The millimeter-scale capsules with controllable morphology,ultra-low permeability and excellent mechanical stability were fabricated by millifluidics.Viscosity of inner phase was adjusted to control the morphology and...The millimeter-scale capsules with controllable morphology,ultra-low permeability and excellent mechanical stability were fabricated by millifluidics.Viscosity of inner phase was adjusted to control the morphology and properties of the capsules.In detail,as the concentration of polyvinyl alcohol(PVA)increased from 0 to 8% in the inner phase of the capsules,the diameter of capsules decreased from 3.33 ± 0.01mm to 2.97 ± 0.01 mm,the shell thickness of capsules decreased from 0.183 ± 0.004 mm to 0.155 ± 0.003 mm.While the capsules had round shape and high sphericity.Notably,the capsules with 2% PVA in the inner phase had remarkably decreased water permeability and good morphological stability.Specifically,the end-time of water losing of the capsules was up to 49 days,while the dehydrated capsules maintained spherical appearance,and crushing force of the capsules was up to 13.73 ± 0.79 N,which ensured stability during processing and transportation.This research provides a new strategy for stable encapsulation of small molecules.展开更多
BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain t...BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia.Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur.IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of IC.CASE SUMMARY The patient was admitted to the hospital with"abdominal pain for half a month and bloody stool with mucous and pus for 3 d"and was diagnosed with"IC".Symptomatic and supportive treatment,such as antibiotics(levofloxacin),acid inhibition and stomach protection,fluid replenishment,and intravenous nutrition,was given.The patient's colonic ulcers were considered to be related to the oral administration of platelet(PLT)-raising capsules;the patient was asked to stop PLT-raising drugs for selective review via colonoscopy,and antibiotics and mesalazine enteric-coated tablets were stopped.Under the guidance of hematology consultation,60 mg of methylprednisolone was given in combination with PLT infusion to increase the PLT.After treatment,the patient's condition stabilized,the patient’s stool turned yellow,the patient’s symptoms improved,and the patient was allowed to leave the hospital.CONCLUSION PLT-raising capsules can lead to IC,so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocyt-INTRODUCTION Ischemic colitis(IC)is also known as colon ischemia(CI)and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon;this process is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia[1].Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur[2,3].The pathogenesis of this disease has not been extensively studied,but increased clotting ability has been recognized as an important factor in the pathogenesis of IC[4].People older than 60 years(especially women)who suffer from certain underlying diseases,such as cardiovascular and cerebrovascular diseases,diabetes,and shock,are the most prone to colon IC.The lesions can involve any segment of the colon,among which the left half of the colon,such as the sigmoid colon,descending colon and spleen region,is the most common site of lesions.This is because the region south of the sigmoid colon is the"watershed region"of the colonic blood supply,where vascular dysplasia may easily cause ischemia.In addition,the left half of the colon is supplied by the inferior mesenteric artery,which is at an acute angle to the abdominal aorta and affects blood perfusion.The rectum is supplied by both the inferior mesenteric artery and the rectal artery,and ischemia is rare.Therefore,the IC lesions were mainly in the left colon,and most of them were of the first pass type.The disease is relatively mild and can be cured after conservative medical treatment,so the prognosis is favorable[5-7].Once ischemia improves,the patient’s condition can recover in a relatively short time,and this condition can be distin-guished from other types of enteritis[5-7],such as infectious colitis,inflammatory bowel disease,pseudomembranous enteritis,diverticulitis,colon cancer,and acute mesenteric ischemia.Clinically,ischemic colitis can be divided into gangrene and nongrene.The latter can also be subdivided into transient and chronic types.Treatment for IC usually includes fasting,gastrointestinal decompression,intravenous nutritional support,improved circulation,fluid resuscitation,empirical use of antibiotics and other symptomatic supportive treatments,and attention should be given to the treatment of the primary disease.Most patients will experience improvements in clinical symp-toms within 1 to 2 d,and patients with complications may require surgery.However,IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of ischemic colitis.展开更多
In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturi...In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturized devices to evaluate the small bowel and colon[pan-intestinal capsule endoscopy(PCE)],makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders.This technology is expected to identify which patients will require conventional invasive endoscopic procedures(colonoscopy or balloon-assisted enteroscopy),based on the lesions detected by the capsule,i.e.,those with an indication for biopsies or endoscopic treatment.The use of PCE in patients with inflammatory bowel diseases,namely Crohn’s disease,as well as in patients with iron deficiency anaemia and/or overt gastrointestinal(GI)bleeding,after a non-diagnostic upper endoscopy(esophagogastroduodenoscopy),enables an effective,safe and comfortable way to identify patients with relevant lesions,who should undergo subsequent invasive endoscopic procedures.The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract,is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract,from mouth-to-anus,meeting the expectations of the early developers of capsule endoscopy.展开更多
BACKGROUND Traditional esophagogastroduodenoscopy(EGD),an invasive examination method,can cause discomfort and pain in patients.In contrast,magnetically controlled capsule endoscopy(MCE),a noninvasive method,is being ...BACKGROUND Traditional esophagogastroduodenoscopy(EGD),an invasive examination method,can cause discomfort and pain in patients.In contrast,magnetically controlled capsule endoscopy(MCE),a noninvasive method,is being applied for the detection of stomach and small intestinal diseases,but its application in treating esophageal diseases is not widespread.AIM To evaluate the safety and efficacy of detachable string MCE(ds-MCE)for the diagnosis of esophageal diseases.METHODS Fifty patients who had been diagnosed with esophageal diseases were pros-pectively recruited for this clinical study and underwent ds-MCE and conven-tional EGD.The primary endpoints included the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for patients with esophageal diseases.The secondary endpoints consisted of visualizing the esophageal and dentate lines,as well as the subjects'tolerance of the procedure.RESULTS Using EGD as the gold standard,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%,86.21%,81.82%,89.29%,and 86%,respectively.ds-MCE was more comfortable and convenient than EGD was,with 80%of patients feeling that ds-MCE examination was very comfortable or comfortable and 50%of patients believing that detachable string v examination was very convenient.CONCLUSION This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD,providing a novel noninvasive method for treating esophageal diseases.展开更多
Objective: To compare the clinical efficacy of conventional Western medicine combined with Qiliqiangxin capsule and western medicine alone in the treatment of chronic heart failure, and to prove that Qiliqiangxin caps...Objective: To compare the clinical efficacy of conventional Western medicine combined with Qiliqiangxin capsule and western medicine alone in the treatment of chronic heart failure, and to prove that Qiliqiangxin capsule combined treatment has more advantages, providing reference for clinical decision-making in the treatment of chronic heart failure. Methods: Randomized controlled trials (RCTs) of conventional Western medicine treatment and Western medicine combined with Qiliqiangxin capsule in the treatment of chronic heart failure were searched in databases such as PubMed, Embase, Webofscience, CNKI, WanFang, VIP, and CBM. The bias risk assessment was conducted using the RCT tool recommended by Cochrane, and then the meta-analysis was performed using RevMan5.4 and Stata17 software. Compare the efficacy evaluation of cardiac function, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), cardiac stroke output (SV), 6-minute walking test (6MWT), and N-terminal proBNP in the conventional western medicine combined with Qiliqiangxin capsule group (hereinafter referred to as the treatment group) and the conventional western medicine group (hereinafter referred to as the control group). Results: A total of 20 RCTs meeting the criteria were included, including 2953 patients, including 1508 in the treatment group and 1445 in the control group. The results of meta-analysis showed that the treatment group had significantly better cardiac function evaluation, LVEF, LVEDD, SV, 6MWT, and NT-proBNP improvement than the control group. Its central functional efficacy evaluation (OR=2.09,95% CI: 1.71-2.55, P<0.001), LVEF (WMD=7.05,95% CI: 5.30-8.79, P<0.00001), LVEDD (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), SV (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), 6MWT (SMD=0.70,95% CI: 0.54-0.87, P<0.00001), NT-proBNP (SMD=-1.95,95% CI: -2.5 2 to 1.38 (P<0.0001), with statistically significant differences. Conclusion: Conventional western medicine combined with Qiliqiangxin capsule can significantly improve the clinical efficacy of heart failure, improve LVEF, LVEDD, SV, and NT-proBNP index, and improve exercise tolerance. It is worth using for reference in the treatment.展开更多
Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced...Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.展开更多
Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal ex...Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.展开更多
Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.T...Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.The purpose of this investigation was to discover the potential mechanisms of YTC ameliorates NAFLD.Methods:In this investigation,a high-fat diet(HFD)was adopted to establish a NAFLD mouse model.Liver samples were stained for oil red O and hematoxylin and eosin staining.The levels of total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in the tissues were also detected.Network pharmacology was analyzed to filter out the key ingredients and targets of effect of YTC for the therapy of NAFLD.Subsequently,free fatty acids(FFA)was applied to induce Aml12 cells for in vitro experiments,and the cell samples were stained with oil red O and assayed for TC,TG,MDA,and SOD contents.At last,the Western blot technique was used to illuminate the pathway by which YTC plays a protective role against NAFLD.Results:Histopathological results demonstrated that YTC ameliorated tissue damage in the HFD-induced mouse model.At the same time,it also reduced the contents of TC,TG,MDA and increased the expression of SOD in the liver tissue of NAFLD mouse model.All of these findings demonstrate that YTC can play a role in the treatment of NAFLD by ameliorating oxidative stress.Network analysis of YTC ameliorates NAFLD mainly by modulating the PI3K-Akt signaling pathway.Follow-up in vitro experiments revealed that FFA caused lipid accumulation in Aml12 cells,which was dramatically reduced by YTC.Meanwhile,YTC could remarkably reduce the FFA-induced elevation of TC,TG,and MDA contents,and reverse the FFA-induced reduction of SOD contents.Western blot was verified for the PI3K-Akt signaling pathway.It was found that FFA could remarkably decrease the expression of p-PI3K,p-Akt,and p-GSK-3βproteins,which could be significantly increased after YTC treatment.Conclusions:The combination of network analysis prediction and experimental verification was used to identify the therapeutic effect of YTC on NAFLD.The protective effect was achieved by YTC through upregulation of PI3K-Akt-GSK-3βpathway.展开更多
[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362...[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.展开更多
Objective:To analyze the effectiveness of applying ShuGan JieYu Capsules(SGJYC)combined with trazodone in patients with post-stroke depression(PSD)with insomnia.Methods:60 cases of PSD with insomnia patients admitted ...Objective:To analyze the effectiveness of applying ShuGan JieYu Capsules(SGJYC)combined with trazodone in patients with post-stroke depression(PSD)with insomnia.Methods:60 cases of PSD with insomnia patients admitted to the hospital from May 2022 to May 2023 were selected and randomly divided into a reference group(trazodone)and a research group(SGJYC combined with trazodone)of 30 cases each.Statistics were analyzed using the Hamilton Depression Rating Scale(HAM-D),Pittsburgh Sleep Quality Index(PSQI),and Activities of Daily Living(ADL)scale before treatment and 4,8,and 12 weeks after treatment.Results:Before treatment,The results of HAM-D,PSQI,and ADL scale studies in the two groups before treatment were not statistically significant(P>0.05);4,8,and 12 weeks after treatment,the results of HAM-D and PSQI studies in the research group were lower than that of the reference group,and the results of ADL scale studies were higher than that of the reference group.There was a significant difference between the groups(P<0.05).The total adverse reaction rate of the research group was lower than that of the reference group,and there was a significant difference between the groups(P<0.05).Conclusion:The combination of SGJYC and trazodone reduced depression in post-stroke patients,corrected insomnia,improved sleep quality,was safe,and had a low rate of adverse reactions.展开更多
The Shima yield criterion used in finite element analysis for nickel-based superalloy powder compact during hot isostatic pressing(HIP) was modified through uniaxial compression experiments. The influence of cylindric...The Shima yield criterion used in finite element analysis for nickel-based superalloy powder compact during hot isostatic pressing(HIP) was modified through uniaxial compression experiments. The influence of cylindrical capsule characteristics on FGH4096M superalloy powder compact deformation and densification behavior during HIP was investigated through simulations and experiments. Results revealed the simulation shrinkage prediction fitted well with the experimental shrinkage including a maximum shrinkage error of 1.5%. It was shown that the axial shrinkage was 1.7% higher than radial shrinkage for a cylindrical capsule with the size of ∮50 mm × 100 mm due to the force arm difference along the axial and radial direction of the capsule. The stress deviated from the isostatic state in the capsule led to the uneven shrinkage and non-uniform densification of the powder compact. The ratio of the maximum radial displacement to axial displacement increased from0.47 to 0.75 with the capsule thickness increasing from 2 to 4 mm. The pressure transmission is related to the capsule thickness, the capsule material performance, and physical parameters in the HIP process.展开更多
BACKGROUND Small intestinal vascular malformations(angiodysplasias)are common causes of small intestinal bleeding.While capsule endoscopy has become the primary diagnostic method for angiodysplasia,manual reading of t...BACKGROUND Small intestinal vascular malformations(angiodysplasias)are common causes of small intestinal bleeding.While capsule endoscopy has become the primary diagnostic method for angiodysplasia,manual reading of the entire gastrointestinal tract is time-consuming and requires a heavy workload,which affects the accuracy of diagnosis.AIM To evaluate whether artificial intelligence can assist the diagnosis and increase the detection rate of angiodysplasias in the small intestine,achieve automatic disease detection,and shorten the capsule endoscopy(CE)reading time.METHODS A convolutional neural network semantic segmentation model with a feature fusion method,which automatically recognizes the category of vascular dysplasia under CE and draws the lesion contour,thus improving the efficiency and accuracy of identifying small intestinal vascular malformation lesions,was proposed.Resnet-50 was used as the skeleton network to design the fusion mechanism,fuse the shallow and depth features,and classify the images at the pixel level to achieve the segmentation and recognition of vascular dysplasia.The training set and test set were constructed and compared with PSPNet,Deeplab3+,and UperNet.RESULTS The test set constructed in the study achieved satisfactory results,where pixel accuracy was 99%,mean intersection over union was 0.69,negative predictive value was 98.74%,and positive predictive value was 94.27%.The model parameter was 46.38 M,the float calculation was 467.2 G,and the time length to segment and recognize a picture was 0.6 s.CONCLUSION Constructing a segmentation network based on deep learning to segment and recognize angiodysplasias lesions is an effective and feasible method for diagnosing angiodysplasias lesions.展开更多
OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar⁃get profiles of the components of BZBS were pre⁃dicted.S...OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar⁃get profiles of the components of BZBS were pre⁃dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich⁃ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further⁃more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec⁃tion analysis.Two Alzheimer′s disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre⁃liminarily verify the anti-AD efficacy and mecha⁃nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat⁃ment of AD.In vitro experiments showed that BZ⁃BS could significantly reduce the release of TNF-αand IL-6 and the expression of COX-2 and PSEN1 in Aβ25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of Aβ25-35 induced SH-SY5Y cells,significantly increased mitochon⁃drial membrane potential,reduced the expres⁃sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU⁃SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu⁃lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further⁃more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun⁃dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.展开更多
Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospray...Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.展开更多
BACKGROUND Although Liu-Wei-Bu-Qi capsule(LBC)inhibits tumor progression by improving the physical condition and immunity of patients with lung cancer(LC),its exact mechanism of action is unknown.AIM To through compou...BACKGROUND Although Liu-Wei-Bu-Qi capsule(LBC)inhibits tumor progression by improving the physical condition and immunity of patients with lung cancer(LC),its exact mechanism of action is unknown.AIM To through compound multi-dimensional network of chemical ingredient-targetdisease-target-protein-protein interaction(PPI)network,the principle of action of Chinese medicine prescription was explained from molecular level.METHODS Network pharmacology and molecular docking simulations were used to analyze the relationship among the main components,targets,and signaling pathways of LBC in treatment of LC.RESULTS From the analysis,360 LBC active ingredient-related targets and 908 LC-related targets were identified.PPI network analysis of the LBC and LC overlapping targets identified 16 hub genes.Kyoto Encyclopedia of Genes and Genomes analysis suggested that LBC can target the vascular endothelial growth factor signaling pathway,Toll-like receptor signaling pathway,prolactin signaling pathway,FoxO signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway in the treatment of LC.Molecular docking simulations showed that quercetin had the best affinity for MAPK3,suggesting that quercetin in LBC may play an important role in the treatment of LC.CONCLUSION The results showed that the active ingredients in LBC can play a crucial role in the treatment of LC by regulating multiple signaling pathways.These results provide insights into further studies on the mechanism of action of LBC in the treatment of LC.展开更多
[Objectives]This study was conducted to establish the quality standard of Danshen Jianxin Capsules.[Methods]Orthogonal design was adopted to optimize the water extraction process by taking the amount of water added,ex...[Objectives]This study was conducted to establish the quality standard of Danshen Jianxin Capsules.[Methods]Orthogonal design was adopted to optimize the water extraction process by taking the amount of water added,extraction time and extraction times as factors,and the content of tanshinone I as the index.Salviae Miltiorrhizae,Notoginseng Radix Et Rhizoma and Radix Astragali in the capsules were qualitatively identified by TLC,and the content of tanshinone I in the capsules was determined by HPLC.[Results]The best water extraction process included the steps of adding 12 times of water each time,extracting the materials twice,for 1 h each time.In TLC identification,the test samples showed spots of the same color at the positions corresponding to tanshinone II A,ginsenoside Rg1,notoginsenoside R1 and astragaloside IV reference samples.[Conclusions]Danshen Jianxin Capsules was prepared by the water extraction method,which is characterized by high efficiency and being suitable for mass production.The quality control method is reliable,fast and accurate,which can effectively control the quality of the product.展开更多
BACKGROUND: Sedative and hypnotic drugs could cure insomnia in a dependent manner, and traditional Chinese medicine has some superiority in treating insomnia. OBJECTIVE: To observe the synergistic action of yinao ca...BACKGROUND: Sedative and hypnotic drugs could cure insomnia in a dependent manner, and traditional Chinese medicine has some superiority in treating insomnia. OBJECTIVE: To observe the synergistic action of yinao capsules with pentobarbital sodium in threshold and sub-threshold dosages in hypnosia and sedation. DESIGN: A completely randomized grouping design and control experiment. SETTING: Pharmacological laboratory, College of Pharmacy, Henan College of Traditional Chinese Medicine. MATERIALS: Totally 200 grade II Kunming mice of 18 - 21 g, either male or female, were used. Yinao capsules, main ingredients of which were turtleback glue, thinleaf milkwort root, Chinese magnoliavine fruit, mythic fungus, tangshen, ginseng and grassleaf sweetflag rhizome, were offered by Chinese-American Huayi Pharmacy, Co.,Ltd. (ratified number: 040901); Kangnaoshuai capsules, main ingredients of which were prepared rehmannia root, tuber fleeceflower root, ginseng, membranous milkvetch root, thinleaf milkwort root, Fushen, grassleaf sweetflag rhizome, spine date seed, lecithin, barbary wolfberry fruit, pueraria root, vitamin E, etc., were produced by Shijiazhuang Siyao, Co.,Ltd. (ratified number: 040964); Pentobarbital sodium was produced by China Medicine (Group) Shanghai Chemical Reagent, Co,.Ltd. (Ratified number: 030816). ZZ-6 mice spontaneous activity apparatus was produced by Chengdu Taimeng Science and Technology, Co.,Ltd. METHODS: The experiment was carried out in the Animal Experimental Center, Henan College of Traditional Chinese Medicine from October to December in 2005. (1) Influence of Yinao capsules on the spontaneous activity of mice: Fifty mice were randomly divided into five groups with 10 mice in each group: Mice in the large, middle and small dosages of Yinao capsules groups were intragastrically infused with Yinao capsules suspension (1.36, 0.68, 0.34 g/kg); Those in the Kangnaoshuai capsules group were infused with Kangnaoshuai suspension (1.12 g/kg); Those in the control group were given physiologic saline of the same volume. The mice were administrated once a day for 7 days continuously, and they were placed into the mice spontaneous activity apparatus after 60 minutes from the last administration, the times of spontaneous activities and the times of arising within 10 minutes were recorded after adaptation for 5 minutes. (2) Synergistic action in hypnosia by Finao capsules with pentobarbital sodium of threshold dosage: Seventy mice were randomly divided into 5 groups as above-mentioned with 14 mice in each group, and they were treated the same as above. They were intraperitoneally injected with 50 mg/kg pentobarbital sodium after 60 minutes from the last administration, then conditions of falling asleep were observed. The disappearance of righting reflex was taken as the index of falling asleep, the latency of falling asleep was the duration from intraperitoneal injection of pentobarbital sodium to fall asleep, the sleeping time was from falling asleep to the disappearance of righting reflex. (3) Synergistic action in hypnosia by Yinao capsules with pentobarbital sodium of sub-threshold dosage: Eighty mice were randomly divided into 5 groups as above-mentioned with 16 mice in each group, and they were treated the same as above. They were intraperitoneally injected with 27 mg/kg pentobarbital sodium after 60 minutes from the last administration. Mice whose righting reflex disappeared for at least 1 minute within 30 minutes were taken as falling asleep, the number of sleeping animals in each group was recorded, and the rate of falling asleep was calculated. MAIN OUTCOME MEASURES: Synergistic action of Yinao capsules with pentobarbital sodium of threshold and sub-threshold dosages in hypnosia and sedation. RESULTS: All the 200 mice were involved in the analysis of results. (1) Influence of Yinao capsules on the spontaneous activity of mice: The times of spontaneous activities within 10 minutes in the large and middle dosage of Yinao capsules groups and Kangnaoshuai capsules group [(138.0±37.0), (156.8±28.3), (133.3±46.1) times] were obviously fewer than those in the control group [(204.3±61.3) times, P 〈 0.05- 0.01]. The arising times within 10 minutes in the middle and small dosages of Yinao capsules groups and Kangnaoshuai capsules group [(30.7 ± 18.3), (26.5± 11.2), (24.2±11.6) times] were obviously fewer than those in the control [(71.7±38.6) times, P 〈 0.01 ]. (2) Synergistic action in hypnosia by Yinao capsules with pentobarbital sodium of threshold dosage: The sleeping latencies in the large and middle dosages of Yinao capsules groups and Kangnaoshuai capsules group [(4.49±1.84), (4.83±1.72), (3.85± 1.94) minutes] were obviously shorter than that in the control group [(6.73 ±2.75) minutes, P 〈 0.05 - 0.01 ]. The sleeping time in the large, middle and small dosages of Yinao capsules groups and Kangnaoshuai capsules group [(89.0± 38.42), (67.21 ±24.07), (66.28±18.94), (84.36±29.81) minutes] were obviously longer than that in the control group [(45.78±20.78) minutes, P 〈 0.05- 0.01]. (3) Synergistic action in hypnosia by Yinao capsules with pentobarbital sodium of sub-threshold dosage: The rates of falling asleep in the large and middle dosages of Yinao capsules groups were higher than that in the control group [56% (9/1 6), 38% (6/1 6), 6% (6/16), P 〈 0.01, 0.05], whereas Kangnaoshuai capsules and small dosage of Yinao capsules had no synergistic action with pentobarbital sodium of sub-threshold dosage (P 〉 0.05). CONCLUSION: Yinao capsules have synergistic action with pentobarbital sodium in hypnosia. Yinao capsules possess obvious sedative and hypnotic effects in a dosage-dependent manner.展开更多
The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in t...The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.展开更多
The present study established a rat model of post-stroke depression using incomplete ischemia induced by unilateral carotid artery ligation in combination with solitary raising and subcutaneous injection of a small do...The present study established a rat model of post-stroke depression using incomplete ischemia induced by unilateral carotid artery ligation in combination with solitary raising and subcutaneous injection of a small dose of reserpine. After intragastric perfusion with 45 mg/100 g, 15 mg/100 g, and 7.5 mg/100 g of Xingnao Jieyu for 7, 14 and 21 days, neuronal morphology in the frontal lobe and hippocampus was improved, depression state and voluntary behaviors were also effectively improved in rats with post-stroke depression. Moreover, the effects of Xingnao Jieyu at a dose of 45 and 15 mg/100 g were similar to the traditional antidepressant Prozac.展开更多
Aiming at the prior medical knowledge that hepatic ascites only occurs in the severe period of liver cirrhosis, and the severe rupture of the liver capsule curve, when ascites occurs visually, can easily lead to the w...Aiming at the prior medical knowledge that hepatic ascites only occurs in the severe period of liver cirrhosis, and the severe rupture of the liver capsule curve, when ascites occurs visually, can easily lead to the wrong location of the liver capsule, a transposed grayscale statistical threshold method is proposed to solve the problem. Realize the identification of liver ascites. By analyzing the visual characteristics of the liver image, the gray value of the upper half of the ultrasound image is counted column by column from a mathematical point of view, the gray distribution curve is drawn, and the relevant threshold is set for corresponding judgment. At the same time, the gray value above the ascites detection boundary is set to zero. The ablation experiment proved that the ascites detection method and post-processing operation proposed in this paper provide effective support for the precise positioning of the liver capsule curve, quantitative analysis and diagnosis of liver cirrhosis in the later stage. The Hessian matrix is sensitive to linear structure to achieve image enhancement. In view of the low accuracy of the existing liver envelope curve detection method and the incomplete quantitative evaluation of liver cirrhosis, it is proposed to use drift iteration under the synergistic effect of multiple filters. A search algorithm extracts the liver capsule.展开更多
文摘The millimeter-scale capsules with controllable morphology,ultra-low permeability and excellent mechanical stability were fabricated by millifluidics.Viscosity of inner phase was adjusted to control the morphology and properties of the capsules.In detail,as the concentration of polyvinyl alcohol(PVA)increased from 0 to 8% in the inner phase of the capsules,the diameter of capsules decreased from 3.33 ± 0.01mm to 2.97 ± 0.01 mm,the shell thickness of capsules decreased from 0.183 ± 0.004 mm to 0.155 ± 0.003 mm.While the capsules had round shape and high sphericity.Notably,the capsules with 2% PVA in the inner phase had remarkably decreased water permeability and good morphological stability.Specifically,the end-time of water losing of the capsules was up to 49 days,while the dehydrated capsules maintained spherical appearance,and crushing force of the capsules was up to 13.73 ± 0.79 N,which ensured stability during processing and transportation.This research provides a new strategy for stable encapsulation of small molecules.
文摘BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia.Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur.IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of IC.CASE SUMMARY The patient was admitted to the hospital with"abdominal pain for half a month and bloody stool with mucous and pus for 3 d"and was diagnosed with"IC".Symptomatic and supportive treatment,such as antibiotics(levofloxacin),acid inhibition and stomach protection,fluid replenishment,and intravenous nutrition,was given.The patient's colonic ulcers were considered to be related to the oral administration of platelet(PLT)-raising capsules;the patient was asked to stop PLT-raising drugs for selective review via colonoscopy,and antibiotics and mesalazine enteric-coated tablets were stopped.Under the guidance of hematology consultation,60 mg of methylprednisolone was given in combination with PLT infusion to increase the PLT.After treatment,the patient's condition stabilized,the patient’s stool turned yellow,the patient’s symptoms improved,and the patient was allowed to leave the hospital.CONCLUSION PLT-raising capsules can lead to IC,so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocyt-INTRODUCTION Ischemic colitis(IC)is also known as colon ischemia(CI)and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon;this process is not significant enough to maintain the metabolic function of cells,leading to intestinal wall ischemia[1].Its main symptoms include abdominal pain,diarrhea,and bloody stool.In severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may occur[2,3].The pathogenesis of this disease has not been extensively studied,but increased clotting ability has been recognized as an important factor in the pathogenesis of IC[4].People older than 60 years(especially women)who suffer from certain underlying diseases,such as cardiovascular and cerebrovascular diseases,diabetes,and shock,are the most prone to colon IC.The lesions can involve any segment of the colon,among which the left half of the colon,such as the sigmoid colon,descending colon and spleen region,is the most common site of lesions.This is because the region south of the sigmoid colon is the"watershed region"of the colonic blood supply,where vascular dysplasia may easily cause ischemia.In addition,the left half of the colon is supplied by the inferior mesenteric artery,which is at an acute angle to the abdominal aorta and affects blood perfusion.The rectum is supplied by both the inferior mesenteric artery and the rectal artery,and ischemia is rare.Therefore,the IC lesions were mainly in the left colon,and most of them were of the first pass type.The disease is relatively mild and can be cured after conservative medical treatment,so the prognosis is favorable[5-7].Once ischemia improves,the patient’s condition can recover in a relatively short time,and this condition can be distin-guished from other types of enteritis[5-7],such as infectious colitis,inflammatory bowel disease,pseudomembranous enteritis,diverticulitis,colon cancer,and acute mesenteric ischemia.Clinically,ischemic colitis can be divided into gangrene and nongrene.The latter can also be subdivided into transient and chronic types.Treatment for IC usually includes fasting,gastrointestinal decompression,intravenous nutritional support,improved circulation,fluid resuscitation,empirical use of antibiotics and other symptomatic supportive treatments,and attention should be given to the treatment of the primary disease.Most patients will experience improvements in clinical symp-toms within 1 to 2 d,and patients with complications may require surgery.However,IC induced by long-term use of certain special drugs is relatively rare in clinical practice.This article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of ischemic colitis.
文摘In 2000,the small bowel capsule revolutionized the management of patients with small bowel disorders.Currently,the technological development achieved by the new models of double-headed endoscopic capsules,as miniaturized devices to evaluate the small bowel and colon[pan-intestinal capsule endoscopy(PCE)],makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders.This technology is expected to identify which patients will require conventional invasive endoscopic procedures(colonoscopy or balloon-assisted enteroscopy),based on the lesions detected by the capsule,i.e.,those with an indication for biopsies or endoscopic treatment.The use of PCE in patients with inflammatory bowel diseases,namely Crohn’s disease,as well as in patients with iron deficiency anaemia and/or overt gastrointestinal(GI)bleeding,after a non-diagnostic upper endoscopy(esophagogastroduodenoscopy),enables an effective,safe and comfortable way to identify patients with relevant lesions,who should undergo subsequent invasive endoscopic procedures.The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract,is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract,from mouth-to-anus,meeting the expectations of the early developers of capsule endoscopy.
基金the Science and Technology Commission of Shanghai,No.18DZ1930309.
文摘BACKGROUND Traditional esophagogastroduodenoscopy(EGD),an invasive examination method,can cause discomfort and pain in patients.In contrast,magnetically controlled capsule endoscopy(MCE),a noninvasive method,is being applied for the detection of stomach and small intestinal diseases,but its application in treating esophageal diseases is not widespread.AIM To evaluate the safety and efficacy of detachable string MCE(ds-MCE)for the diagnosis of esophageal diseases.METHODS Fifty patients who had been diagnosed with esophageal diseases were pros-pectively recruited for this clinical study and underwent ds-MCE and conven-tional EGD.The primary endpoints included the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for patients with esophageal diseases.The secondary endpoints consisted of visualizing the esophageal and dentate lines,as well as the subjects'tolerance of the procedure.RESULTS Using EGD as the gold standard,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%,86.21%,81.82%,89.29%,and 86%,respectively.ds-MCE was more comfortable and convenient than EGD was,with 80%of patients feeling that ds-MCE examination was very comfortable or comfortable and 50%of patients believing that detachable string v examination was very convenient.CONCLUSION This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD,providing a novel noninvasive method for treating esophageal diseases.
基金National Natural Science Foundation of China Regional Science Foundation Project(No.82160887)General Project of Guangxi Natural Science Foundation(No.2021GXNSFAA220111)Guangxi Natural Science Foundation Project Youth Science Foundation Project(No.2021GXNSFBA196018)。
文摘Objective: To compare the clinical efficacy of conventional Western medicine combined with Qiliqiangxin capsule and western medicine alone in the treatment of chronic heart failure, and to prove that Qiliqiangxin capsule combined treatment has more advantages, providing reference for clinical decision-making in the treatment of chronic heart failure. Methods: Randomized controlled trials (RCTs) of conventional Western medicine treatment and Western medicine combined with Qiliqiangxin capsule in the treatment of chronic heart failure were searched in databases such as PubMed, Embase, Webofscience, CNKI, WanFang, VIP, and CBM. The bias risk assessment was conducted using the RCT tool recommended by Cochrane, and then the meta-analysis was performed using RevMan5.4 and Stata17 software. Compare the efficacy evaluation of cardiac function, left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), cardiac stroke output (SV), 6-minute walking test (6MWT), and N-terminal proBNP in the conventional western medicine combined with Qiliqiangxin capsule group (hereinafter referred to as the treatment group) and the conventional western medicine group (hereinafter referred to as the control group). Results: A total of 20 RCTs meeting the criteria were included, including 2953 patients, including 1508 in the treatment group and 1445 in the control group. The results of meta-analysis showed that the treatment group had significantly better cardiac function evaluation, LVEF, LVEDD, SV, 6MWT, and NT-proBNP improvement than the control group. Its central functional efficacy evaluation (OR=2.09,95% CI: 1.71-2.55, P<0.001), LVEF (WMD=7.05,95% CI: 5.30-8.79, P<0.00001), LVEDD (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), SV (WMD=6.73, 95% CI: 3.18-10.29, P=0.0002), 6MWT (SMD=0.70,95% CI: 0.54-0.87, P<0.00001), NT-proBNP (SMD=-1.95,95% CI: -2.5 2 to 1.38 (P<0.0001), with statistically significant differences. Conclusion: Conventional western medicine combined with Qiliqiangxin capsule can significantly improve the clinical efficacy of heart failure, improve LVEF, LVEDD, SV, and NT-proBNP index, and improve exercise tolerance. It is worth using for reference in the treatment.
基金Scientific Research Project of Heilongjiang Provincial Education Department(No.12531608)。
文摘Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.
基金funding from the Basic Research Project of the Education Department of Shaanxi Province(21JC010,21JP035)the Young and Middle-Aged Scientific Research and Innovation Team of the Shaanxi Provincial Administration of Traditional Chinese Medicine(2022SLRHLJ001)the 2023 Central Financial Transfer Payment Local Project“Innovation and Improvement of Five Types of Hospital Preparations,Such as Roumudan Granules”.
文摘Background:The purpose of the study was to investigate the active ingredients and potential biochemical mechanisms of Juanbi capsule in knee osteoarthritis based on network pharmacology,molecular docking and animal experiments.Methods:Chemical components for each drug in the Juanbi capsule were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,while the target proteins for knee osteoarthritis were retrieved from the Drugbank,GeneCards,and OMIM databases.The study compared information on knee osteoarthritis and the targets of drugs to identify common elements.The data was imported into the STRING platform to generate a protein-protein interaction network diagram.Subsequently,a“component-target”network diagram was created using the screened drug components and target information with Cytoscape software.Common targets were imported into Metascape for GO function and KEGG pathway enrichment analysis.AutoDockTools was utilized to predict the molecular docking of the primary chemical components and core targets.Ultimately,the key targets were validated through animal experiments.Results:Juanbi capsule ameliorated Knee osteoarthritis mainly by affecting tumor necrosis factor,interleukin1β,MMP9,PTGS2,VEGFA,TP53,and other cytokines through quercetin,kaempferol,andβ-sitosterol.The drug also influenced the AGE-RAGE,interleukin-17,tumor necrosis factor,Relaxin,and NF-κB signaling pathways.The network pharmacology analysis results were further validated in animal experiments.The results indicated that Juanbi capsule could decrease the levels of tumor necrosis factor-αand interleukin-1βin the serum and synovial fluid of knee osteoarthritis rats and also down-regulate the expression levels of MMP9 and PTGS2 proteins in the articular cartilage.Conclusion:Juanbi capsule may improve the knee bone microstructure and reduce the expression of inflammatory factors of knee osteoarthritis via multiple targets and multiple signaling pathways.
基金This work was supported by Science and Technology Program of Guangyuan city(grant number:23ZDYF0018)Sichuan Science and Technology Program(grant number:2020YFS0523)。
文摘Background:Oxidative stress is one of the key elements in the progression of non-alcoholic fatty liver disease(NAFLD),and Yiqi Tongluo capsule(YTC)have a variety of physiological activities which include antioxidant.The purpose of this investigation was to discover the potential mechanisms of YTC ameliorates NAFLD.Methods:In this investigation,a high-fat diet(HFD)was adopted to establish a NAFLD mouse model.Liver samples were stained for oil red O and hematoxylin and eosin staining.The levels of total cholesterol(TC),triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in the tissues were also detected.Network pharmacology was analyzed to filter out the key ingredients and targets of effect of YTC for the therapy of NAFLD.Subsequently,free fatty acids(FFA)was applied to induce Aml12 cells for in vitro experiments,and the cell samples were stained with oil red O and assayed for TC,TG,MDA,and SOD contents.At last,the Western blot technique was used to illuminate the pathway by which YTC plays a protective role against NAFLD.Results:Histopathological results demonstrated that YTC ameliorated tissue damage in the HFD-induced mouse model.At the same time,it also reduced the contents of TC,TG,MDA and increased the expression of SOD in the liver tissue of NAFLD mouse model.All of these findings demonstrate that YTC can play a role in the treatment of NAFLD by ameliorating oxidative stress.Network analysis of YTC ameliorates NAFLD mainly by modulating the PI3K-Akt signaling pathway.Follow-up in vitro experiments revealed that FFA caused lipid accumulation in Aml12 cells,which was dramatically reduced by YTC.Meanwhile,YTC could remarkably reduce the FFA-induced elevation of TC,TG,and MDA contents,and reverse the FFA-induced reduction of SOD contents.Western blot was verified for the PI3K-Akt signaling pathway.It was found that FFA could remarkably decrease the expression of p-PI3K,p-Akt,and p-GSK-3βproteins,which could be significantly increased after YTC treatment.Conclusions:The combination of network analysis prediction and experimental verification was used to identify the therapeutic effect of YTC on NAFLD.The protective effect was achieved by YTC through upregulation of PI3K-Akt-GSK-3βpathway.
基金Supported by the Science and Medicine Joint Fund Project of Natural Science Foundation of Hunan Province(2022JJ80001).
文摘[Objectives]To investigate the clinical effect of Yinhuang Qingfei capsules in the treatment of asymptomatic and mild/common severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.[Methods]A total of 362 patients with SARS-CoV-2 infection were divided into the treatment group with 242 patients and control group with 120 patients according to their treatment regimen.The patients in the control group were given standard treatment regimen and those in the treatment group were given Yinhuang Qingfei capsules in addition to the treatment in the control group.The two groups were observed in terms of average length of hospital stay,mean time for nucleic acid clearance,TCM syndrome score,and progression to severe/critical illness,and clinical outcome was compared between the two groups.[Results]There was a significant difference in the overall response rate between the treatment group and the control group[97.52%(236/242)vs 95.00%(114/120),P<0.05].Compared with the control group,the treatment group had significantly shorter length of hospital stay and time for nucleic acid clearance(P<0.05).After 7 days of treatment,both groups had a significant change in TCM syndrome score,and there was a significant difference in TCM syndrome score between the two groups(P<0.05);after 15 days of treatment,both groups had a TCM syndrome score of 0.Progression to severe/critical illness was not observed in either group.[Conclusions]Compared with the standard treatment regimen alone,standard treatment regimen combined with Yinhuang Qingfei capsules can effectively shorten the length of hospital stay and time for nucleic acid clearance and improve TCM symptoms in patients with asymptomatic and mild/common SARS-CoV-2 infection.
基金Research Project on Heilongjiang Province Traditional Chinese Medicine No.ZHY2022-057。
文摘Objective:To analyze the effectiveness of applying ShuGan JieYu Capsules(SGJYC)combined with trazodone in patients with post-stroke depression(PSD)with insomnia.Methods:60 cases of PSD with insomnia patients admitted to the hospital from May 2022 to May 2023 were selected and randomly divided into a reference group(trazodone)and a research group(SGJYC combined with trazodone)of 30 cases each.Statistics were analyzed using the Hamilton Depression Rating Scale(HAM-D),Pittsburgh Sleep Quality Index(PSQI),and Activities of Daily Living(ADL)scale before treatment and 4,8,and 12 weeks after treatment.Results:Before treatment,The results of HAM-D,PSQI,and ADL scale studies in the two groups before treatment were not statistically significant(P>0.05);4,8,and 12 weeks after treatment,the results of HAM-D and PSQI studies in the research group were lower than that of the reference group,and the results of ADL scale studies were higher than that of the reference group.There was a significant difference between the groups(P<0.05).The total adverse reaction rate of the research group was lower than that of the reference group,and there was a significant difference between the groups(P<0.05).Conclusion:The combination of SGJYC and trazodone reduced depression in post-stroke patients,corrected insomnia,improved sleep quality,was safe,and had a low rate of adverse reactions.
基金financially supported by Guangdong Province Key Field R&D Program, China (No. 2019B01 0935001)the National Nature Science Foundation of China (No. 51905192)the Fundamental Research Funds for the Central Universities (No. FRT-TP-20-006A2)
文摘The Shima yield criterion used in finite element analysis for nickel-based superalloy powder compact during hot isostatic pressing(HIP) was modified through uniaxial compression experiments. The influence of cylindrical capsule characteristics on FGH4096M superalloy powder compact deformation and densification behavior during HIP was investigated through simulations and experiments. Results revealed the simulation shrinkage prediction fitted well with the experimental shrinkage including a maximum shrinkage error of 1.5%. It was shown that the axial shrinkage was 1.7% higher than radial shrinkage for a cylindrical capsule with the size of ∮50 mm × 100 mm due to the force arm difference along the axial and radial direction of the capsule. The stress deviated from the isostatic state in the capsule led to the uneven shrinkage and non-uniform densification of the powder compact. The ratio of the maximum radial displacement to axial displacement increased from0.47 to 0.75 with the capsule thickness increasing from 2 to 4 mm. The pressure transmission is related to the capsule thickness, the capsule material performance, and physical parameters in the HIP process.
基金Chongqing Technological Innovation and Application Development Project,Key Technologies and Applications of Cross Media Analysis and Reasoning,No.cstc2019jscx-zdztzxX0037.
文摘BACKGROUND Small intestinal vascular malformations(angiodysplasias)are common causes of small intestinal bleeding.While capsule endoscopy has become the primary diagnostic method for angiodysplasia,manual reading of the entire gastrointestinal tract is time-consuming and requires a heavy workload,which affects the accuracy of diagnosis.AIM To evaluate whether artificial intelligence can assist the diagnosis and increase the detection rate of angiodysplasias in the small intestine,achieve automatic disease detection,and shorten the capsule endoscopy(CE)reading time.METHODS A convolutional neural network semantic segmentation model with a feature fusion method,which automatically recognizes the category of vascular dysplasia under CE and draws the lesion contour,thus improving the efficiency and accuracy of identifying small intestinal vascular malformation lesions,was proposed.Resnet-50 was used as the skeleton network to design the fusion mechanism,fuse the shallow and depth features,and classify the images at the pixel level to achieve the segmentation and recognition of vascular dysplasia.The training set and test set were constructed and compared with PSPNet,Deeplab3+,and UperNet.RESULTS The test set constructed in the study achieved satisfactory results,where pixel accuracy was 99%,mean intersection over union was 0.69,negative predictive value was 98.74%,and positive predictive value was 94.27%.The model parameter was 46.38 M,the float calculation was 467.2 G,and the time length to segment and recognize a picture was 0.6 s.CONCLUSION Constructing a segmentation network based on deep learning to segment and recognize angiodysplasias lesions is an effective and feasible method for diagnosing angiodysplasias lesions.
基金Chinese Academy of Engi⁃neering Strategic Consulting Project(2022-XY-45)S&T Program of Hebei(22372502D)+1 种基金Scien⁃tific Research Project of Hebei Provincial Admin⁃istration of Traditional Chinese Medicine(023172)and Scientific Research Project of Hebei Provincial Administration of Traditional Chinese Medicine(2021273)。
文摘OBJECTIVE To explore the new indications and key mechanism of Bazi Bushen capsule(BZBS)by network pharmacology and in vitro experiment.METHODS The potential tar⁃get profiles of the components of BZBS were pre⁃dicted.Subsequently,new indications for BZBS were predicted by disease ontology(DO)enrich⁃ment analysis and initially validated by GO and KEGG pathway enrichment analysis.Further⁃more,the therapeutic target of BZBS acting on AD signaling pathway were identified by intersec⁃tion analysis.Two Alzheimer′s disease(AD)cell models,BV-2 and SH-SY5Y,were used to pre⁃liminarily verify the anti-AD efficacy and mecha⁃nism of BZBS in vitro.RESULTS In total,1499 non-repeated ingredients were obtained from 16 herbs in BZBS formula,and 1320 BZBS targets with high confidence were predicted.Disease enrichment results strongly suggested that BZBS formula has the potential to be used in the treat⁃ment of AD.In vitro experiments showed that BZ⁃BS could significantly reduce the release of TNF-αand IL-6 and the expression of COX-2 and PSEN1 in Aβ25-35-induced BV-2 cells.BZBS reduced the apoptosis rate of Aβ25-35 induced SH-SY5Y cells,significantly increased mitochon⁃drial membrane potential,reduced the expres⁃sion of Caspase3 active fragment and PSEN1,and increased the expression of IDE.CONCLU⁃SIONS BZBS formula has a potential use in the treatment of AD,which is achieved through regu⁃lation of ERK1/2,NF-κB signaling pathways,and GSK-3β/β-catenin signaling pathway.Further⁃more,the network pharmacology technology is a feasible drug repurposing strategy to reposition new clinical use of approved TCM and explore the mechanism of action.The study lays a foun⁃dation for the subsequent in-depth study of BZBS in the treatment of AD and provides a basis for its application in the clinical treatment of AD.
基金supported by research grants from the National Key R&D Program(2019YFD0902003)。
文摘Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.
文摘BACKGROUND Although Liu-Wei-Bu-Qi capsule(LBC)inhibits tumor progression by improving the physical condition and immunity of patients with lung cancer(LC),its exact mechanism of action is unknown.AIM To through compound multi-dimensional network of chemical ingredient-targetdisease-target-protein-protein interaction(PPI)network,the principle of action of Chinese medicine prescription was explained from molecular level.METHODS Network pharmacology and molecular docking simulations were used to analyze the relationship among the main components,targets,and signaling pathways of LBC in treatment of LC.RESULTS From the analysis,360 LBC active ingredient-related targets and 908 LC-related targets were identified.PPI network analysis of the LBC and LC overlapping targets identified 16 hub genes.Kyoto Encyclopedia of Genes and Genomes analysis suggested that LBC can target the vascular endothelial growth factor signaling pathway,Toll-like receptor signaling pathway,prolactin signaling pathway,FoxO signaling pathway,PI3K-Akt signaling pathway and HIF-1 signaling pathway in the treatment of LC.Molecular docking simulations showed that quercetin had the best affinity for MAPK3,suggesting that quercetin in LBC may play an important role in the treatment of LC.CONCLUSION The results showed that the active ingredients in LBC can play a crucial role in the treatment of LC by regulating multiple signaling pathways.These results provide insights into further studies on the mechanism of action of LBC in the treatment of LC.
基金Supported by Self-financed Scientific Research Project of Administration of Traditional Chinese Medicine of Guangxi Zhuang Autonomous Region(GXZYZ20210290)The First Batch of High-level Talent Research Project of Affiliated Hospital of Youjiang Medical University for Nationalities in 2019(Y20196311)Basic Scientific Research Ability Improvement Project for Young and Middle-aged Teachers in Guangxi Universities in 2020(2020KY13034).
文摘[Objectives]This study was conducted to establish the quality standard of Danshen Jianxin Capsules.[Methods]Orthogonal design was adopted to optimize the water extraction process by taking the amount of water added,extraction time and extraction times as factors,and the content of tanshinone I as the index.Salviae Miltiorrhizae,Notoginseng Radix Et Rhizoma and Radix Astragali in the capsules were qualitatively identified by TLC,and the content of tanshinone I in the capsules was determined by HPLC.[Results]The best water extraction process included the steps of adding 12 times of water each time,extracting the materials twice,for 1 h each time.In TLC identification,the test samples showed spots of the same color at the positions corresponding to tanshinone II A,ginsenoside Rg1,notoginsenoside R1 and astragaloside IV reference samples.[Conclusions]Danshen Jianxin Capsules was prepared by the water extraction method,which is characterized by high efficiency and being suitable for mass production.The quality control method is reliable,fast and accurate,which can effectively control the quality of the product.
基金New Century Excellent Person With Ability Hold by Ministry of Education, No.NCET-04-0657Cultivating Project of Advanced School Innovate Person with Ability Hold by Henan Province, No.2004-23
文摘BACKGROUND: Sedative and hypnotic drugs could cure insomnia in a dependent manner, and traditional Chinese medicine has some superiority in treating insomnia. OBJECTIVE: To observe the synergistic action of yinao capsules with pentobarbital sodium in threshold and sub-threshold dosages in hypnosia and sedation. DESIGN: A completely randomized grouping design and control experiment. SETTING: Pharmacological laboratory, College of Pharmacy, Henan College of Traditional Chinese Medicine. MATERIALS: Totally 200 grade II Kunming mice of 18 - 21 g, either male or female, were used. Yinao capsules, main ingredients of which were turtleback glue, thinleaf milkwort root, Chinese magnoliavine fruit, mythic fungus, tangshen, ginseng and grassleaf sweetflag rhizome, were offered by Chinese-American Huayi Pharmacy, Co.,Ltd. (ratified number: 040901); Kangnaoshuai capsules, main ingredients of which were prepared rehmannia root, tuber fleeceflower root, ginseng, membranous milkvetch root, thinleaf milkwort root, Fushen, grassleaf sweetflag rhizome, spine date seed, lecithin, barbary wolfberry fruit, pueraria root, vitamin E, etc., were produced by Shijiazhuang Siyao, Co.,Ltd. (ratified number: 040964); Pentobarbital sodium was produced by China Medicine (Group) Shanghai Chemical Reagent, Co,.Ltd. (Ratified number: 030816). ZZ-6 mice spontaneous activity apparatus was produced by Chengdu Taimeng Science and Technology, Co.,Ltd. METHODS: The experiment was carried out in the Animal Experimental Center, Henan College of Traditional Chinese Medicine from October to December in 2005. (1) Influence of Yinao capsules on the spontaneous activity of mice: Fifty mice were randomly divided into five groups with 10 mice in each group: Mice in the large, middle and small dosages of Yinao capsules groups were intragastrically infused with Yinao capsules suspension (1.36, 0.68, 0.34 g/kg); Those in the Kangnaoshuai capsules group were infused with Kangnaoshuai suspension (1.12 g/kg); Those in the control group were given physiologic saline of the same volume. The mice were administrated once a day for 7 days continuously, and they were placed into the mice spontaneous activity apparatus after 60 minutes from the last administration, the times of spontaneous activities and the times of arising within 10 minutes were recorded after adaptation for 5 minutes. (2) Synergistic action in hypnosia by Finao capsules with pentobarbital sodium of threshold dosage: Seventy mice were randomly divided into 5 groups as above-mentioned with 14 mice in each group, and they were treated the same as above. They were intraperitoneally injected with 50 mg/kg pentobarbital sodium after 60 minutes from the last administration, then conditions of falling asleep were observed. The disappearance of righting reflex was taken as the index of falling asleep, the latency of falling asleep was the duration from intraperitoneal injection of pentobarbital sodium to fall asleep, the sleeping time was from falling asleep to the disappearance of righting reflex. (3) Synergistic action in hypnosia by Yinao capsules with pentobarbital sodium of sub-threshold dosage: Eighty mice were randomly divided into 5 groups as above-mentioned with 16 mice in each group, and they were treated the same as above. They were intraperitoneally injected with 27 mg/kg pentobarbital sodium after 60 minutes from the last administration. Mice whose righting reflex disappeared for at least 1 minute within 30 minutes were taken as falling asleep, the number of sleeping animals in each group was recorded, and the rate of falling asleep was calculated. MAIN OUTCOME MEASURES: Synergistic action of Yinao capsules with pentobarbital sodium of threshold and sub-threshold dosages in hypnosia and sedation. RESULTS: All the 200 mice were involved in the analysis of results. (1) Influence of Yinao capsules on the spontaneous activity of mice: The times of spontaneous activities within 10 minutes in the large and middle dosage of Yinao capsules groups and Kangnaoshuai capsules group [(138.0±37.0), (156.8±28.3), (133.3±46.1) times] were obviously fewer than those in the control group [(204.3±61.3) times, P 〈 0.05- 0.01]. The arising times within 10 minutes in the middle and small dosages of Yinao capsules groups and Kangnaoshuai capsules group [(30.7 ± 18.3), (26.5± 11.2), (24.2±11.6) times] were obviously fewer than those in the control [(71.7±38.6) times, P 〈 0.01 ]. (2) Synergistic action in hypnosia by Yinao capsules with pentobarbital sodium of threshold dosage: The sleeping latencies in the large and middle dosages of Yinao capsules groups and Kangnaoshuai capsules group [(4.49±1.84), (4.83±1.72), (3.85± 1.94) minutes] were obviously shorter than that in the control group [(6.73 ±2.75) minutes, P 〈 0.05 - 0.01 ]. The sleeping time in the large, middle and small dosages of Yinao capsules groups and Kangnaoshuai capsules group [(89.0± 38.42), (67.21 ±24.07), (66.28±18.94), (84.36±29.81) minutes] were obviously longer than that in the control group [(45.78±20.78) minutes, P 〈 0.05- 0.01]. (3) Synergistic action in hypnosia by Yinao capsules with pentobarbital sodium of sub-threshold dosage: The rates of falling asleep in the large and middle dosages of Yinao capsules groups were higher than that in the control group [56% (9/1 6), 38% (6/1 6), 6% (6/16), P 〈 0.01, 0.05], whereas Kangnaoshuai capsules and small dosage of Yinao capsules had no synergistic action with pentobarbital sodium of sub-threshold dosage (P 〉 0.05). CONCLUSION: Yinao capsules have synergistic action with pentobarbital sodium in hypnosia. Yinao capsules possess obvious sedative and hypnotic effects in a dosage-dependent manner.
基金funded by the Key Science and Technology Project of Shaanxi Provincial "13115"Technology Innovation Engineering,No.2010ZDKG-65
文摘The Xingnao Jieyu capsule has been shown to effectively relieve neurologic impairments and les- sen depression. It remains poorly understood whether this capsule can be used to treat post-stroke depression. Thus, in the present study, we established a rat model of post-stroke depression using left middle cerebral artery occlusions in combination of chronic unpredictable stress and solitary housing during development. Experimental rats received intragastric perfusion with 0.82, 0.41, and 0.20 g/kg Xingnao Jieyu capsules separately dissolved in 2 mL distilled water. Fluoxetine served as a positive control. The treatment was conducted over 28 days. Sugar water consumption test, open-field test, real-time fluorescent quantitative PCR and immunohistochemical staining results demonstrated that intragastric perfusion with various doses of Xingnao Jieyu capsules increased sugar water consumption, voluntary behaviors and synaptotagmin mRNA and protein expression in rats with post-stroke depression. These therapeutic effects were similar to those of fluoxetine. These results indicate that Xingnao Jieyu capsules upregulate synaptotagmin expression in hip pocampi of rats with post-stroke depression, and exert antidepressant effects.
基金supported by the Major Program of "13115" Science and Technology Innovation Project (Preclinical study of Xingnao Jieyu capsule), No. 2010ZDKG-65
文摘The present study established a rat model of post-stroke depression using incomplete ischemia induced by unilateral carotid artery ligation in combination with solitary raising and subcutaneous injection of a small dose of reserpine. After intragastric perfusion with 45 mg/100 g, 15 mg/100 g, and 7.5 mg/100 g of Xingnao Jieyu for 7, 14 and 21 days, neuronal morphology in the frontal lobe and hippocampus was improved, depression state and voluntary behaviors were also effectively improved in rats with post-stroke depression. Moreover, the effects of Xingnao Jieyu at a dose of 45 and 15 mg/100 g were similar to the traditional antidepressant Prozac.
文摘Aiming at the prior medical knowledge that hepatic ascites only occurs in the severe period of liver cirrhosis, and the severe rupture of the liver capsule curve, when ascites occurs visually, can easily lead to the wrong location of the liver capsule, a transposed grayscale statistical threshold method is proposed to solve the problem. Realize the identification of liver ascites. By analyzing the visual characteristics of the liver image, the gray value of the upper half of the ultrasound image is counted column by column from a mathematical point of view, the gray distribution curve is drawn, and the relevant threshold is set for corresponding judgment. At the same time, the gray value above the ascites detection boundary is set to zero. The ablation experiment proved that the ascites detection method and post-processing operation proposed in this paper provide effective support for the precise positioning of the liver capsule curve, quantitative analysis and diagnosis of liver cirrhosis in the later stage. The Hessian matrix is sensitive to linear structure to achieve image enhancement. In view of the low accuracy of the existing liver envelope curve detection method and the incomplete quantitative evaluation of liver cirrhosis, it is proposed to use drift iteration under the synergistic effect of multiple filters. A search algorithm extracts the liver capsule.