Hepatic cystic lesions include congenital dysplasia,inflammatory cystic lesions,neoplastic cystic lesions and parasitic cystic lesions.As different treatment modalities can be chosen for these lesions,differential dia...Hepatic cystic lesions include congenital dysplasia,inflammatory cystic lesions,neoplastic cystic lesions and parasitic cystic lesions.As different treatment modalities can be chosen for these lesions,differential diagnosis is particularly important[1].Clinical features or imaging findings of cystic lesions of the liver are typical;for instance,liver abscess often shows thick-walled enhancement on contrast-enhanced CT.展开更多
BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has increased in recent clinical practice;however,the relationship between CHB and hepatic steatosis(HS)rema...BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has increased in recent clinical practice;however,the relationship between CHB and hepatic steatosis(HS)remains controversial.AIM To shed light on the potential association between NAFLD and hepatitis B virus(HBV)infection.METHODS We conducted a systematic literature search using multiple databases,including PubMed,the Cochrane Library,Web of Science,and EMBASE,to identify relevant studies.Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis.RESULTS Comprehensive meta-analysis software was used for statistical analysis,which covered 20 studies.The results indicated a lower NAFLD susceptibility in HBVinfected individuals(pooled OR=0.87;95%CI=0.69-1.08;I2=91.1%),with diabetes(P=0.015),body mass index(BMI;P=0.010),and possibly age(P=0.061)as heterogeneity sources.Of note,in four studies(6197 HBV patients),HBV-infected individuals had a reduced NAFLD risk(OR=0.68,95%CI=0.51-0.89,P=0.006).A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients,along with specific biochemical indicators,including BMI,creatinine,uric acid,fasting blood glucose,and homeostasis model assessment of insulin resistance.CONCLUSION HBV infection may provide protection against HS;however,the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.展开更多
BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM T...BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.展开更多
BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment...BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.展开更多
BACKGROUND Cesarean scar pregnancy(CSP)is rare but may result in uterine rupture during pregnancy or massive hemorrhage during abortion procedures.Awareness of this condition is increasing,and most patients with CSP a...BACKGROUND Cesarean scar pregnancy(CSP)is rare but may result in uterine rupture during pregnancy or massive hemorrhage during abortion procedures.Awareness of this condition is increasing,and most patients with CSP are now diagnosed early and can be managed safely.However,some atypical patients are misdiagnosed,and their surgical risks are underestimated,increasing the risk of fatal hemorrhage.CASE SUMMARY A 27-year-old Asian woman visited our institution because of abnormal pregnancy,and she was diagnosed with a hydatidiform mole through transvaginal ultrasound(TVS).Under hysteroscopy,a large amount of placental tissue was found in the scar of the lower uterine segment,and a sudden massive hemorrhage occurred during the removal process.The bilateral internal iliac arteries were temporarily blocked under laparoscopy,and scar resection and repair were rapidly performed.She was discharged in good condition 5 d after the operation.CONCLUSION Although TVS is widely used in the diagnosis of CSP,delays in the diagnosis of atypical CSP remain.Surgical treatment following internal iliac artery temporary occlusion may be an appropriate management method for unanticipated massive hemorrhage during CSP surgery.展开更多
Non-small cell lung cancer(NSCLC)is a malignant tumor with high incidence worldwide.Triptolide(TP),extracted from Tripterygium wilfordii Hook F,exhibits potent broad-spectrum antitumor activity.Although some mechanism...Non-small cell lung cancer(NSCLC)is a malignant tumor with high incidence worldwide.Triptolide(TP),extracted from Tripterygium wilfordii Hook F,exhibits potent broad-spectrum antitumor activity.Although some mechanisms through which TP inhibits NSCLC are well understood,those that involve ribosomal proteins remain yet to be understood.In this study,the transcriptome and proteome were integrated and analyzed.Our data indicated ribosomal protein L4(RPL4)to be a core hub protein in the protein-protein interaction network.RPL4 is overexpressed in NSCLC tissues and cells.Transfection with siRPL4 or TP treatment alone arrested the cell cycle in the G1 phase,induced cell apoptosis,and repressed cell invasion.Compared to treating cells with TP alone or siRPL4,treating them with siRPL4–TP enhanced the inhibition of NSCLC cells.Reduced RPL4 expression reinforced the inhibitory effects of TP on NSCLC cells by disrupting the MDM2-P53 pathway and by altering the expression of PARP1/Snail/cyclin D1.In vivo assays verified that TP induced cell apoptosis and reduced RPL4 expression in xenografts.These findings provide clues to facilitate the development of effective TP-based therapeutic strategies to kill NSCLC cells.展开更多
Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aime...Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aimed to determine the role of m6A-modified methylase complex methyltransferase-like 3(METTL3)in cerebral ischemiareperfusion(I/R)injury.We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar(MA-C)and the brain of middle cerebral artery occlusion(MCAO)model mice.METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation,which increased with METTL3 over-expression.Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis,which was significantly reduced with METTL3 up-regulation.In an MCAO model,METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis,indicating that METTL3 OE treatment could ameliorate brain edema and injury.Thus,METTL3 could be used as a target to treat I/R injury.展开更多
BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings pr...BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.展开更多
BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or m...BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.展开更多
BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.A...BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.展开更多
OBJECTIVE Major depressive disorder(MDD) is a highly heterogeneous mental illness.Further classification may help characterize its heterogeneity.The purpose of this study was to examine metabolomic and brain connectom...OBJECTIVE Major depressive disorder(MDD) is a highly heterogeneous mental illness.Further classification may help characterize its heterogeneity.The purpose of this study was to examine metabolomic and brain connectomic associations with traditional Chinese medicine(TCM) diagnostic classification of MDD.METHODS Fifty unmedicated depressed patients were classified into Liver Qi Stagnation(LQS,n=30) and Heart and Spleen Deficiency(HSD,n=20) subtypes according to TCM diagnosis.Healthy volunteers(n=28) were included as controls.Gas chromatography-mass spectrometry(GC-MS) and diffusion tensor imaging were used to detect serum and urinary metabolomic profiles and whole-brain white matter connectivity,respectively.RESULTS In metabolomic analysis,28 metabolites were identified for good separations between TCM subtypes and healthy controls in serum and urine samples.While both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids and energy metabolism-related metabolites that were differentiated from healthy controls,the LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in the biosynthesis of monoamine and amino acid neurotransmitters.Several metabolites are differentially associated with the two subtypes.In connectomic analysis,The LQS subtype showed significant differences in multiple network metrics of the angular gyrus,middle occipital gyrus,calcarine sulcus,and Heschl′ s gyrus when compared to the other two groups.The HSD subtype had markedly greater regional connectivity of the insula,parahippocampal gyrus,and posterior cingulate gyrus than the other two groups,and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole.The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity.CONCLUSION The LQS subtype may represent an MDD subpopulation mainly characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters,closer associations with stress-related pathophysiology,and aberrant connectivity of the audiovisual perception-related temporal-occipital network,whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbicparalimbic network.Certain metabolomic and connectomic variables are potential biomarkers for TCM diagnostic subtypes which is perhaps an alternative classification for depressive disorders.展开更多
Simultaneous anterior and posterior traumatic dislocations of both hips are very rare. Only 33 cases have been previously reported in the English language literature. Although they were all due to high-energy injuries...Simultaneous anterior and posterior traumatic dislocations of both hips are very rare. Only 33 cases have been previously reported in the English language literature. Although they were all due to high-energy injuries, they were hemodynamically stable and had a stable pelvic ring. We report a unique case of asymmetrical hip dislocations with an unstable pelvic ring and hemodynamic instability. A 40-year-old man was injured in a high-energy motor vehicle accident. He was hemodynamically unstable when he presented in the emergency department. Radiolographs showed asymmetrical dislocations of both hips with an unstable pelvic ring. Under general anesthesia, he had closed reduction of the dislocations of both hips, followed by temporary stabilization with an external fixator. Transcatheter arterial embolization was performed to stop active pelvic bleeding. Delayed open reduction and internal fixation was performed 12 d later with anterior and posterior plates. The patient recovered well with an uneventful post-operative course. Asymmetrical bilateral hip dislocations with pelvic ring instability caused by trauma, as presented in this case, is very rare and potentially life threatening. Prompt treatment can give a good outcome.展开更多
BACKGROUND Pregnancy in the setting of systemic lupus erythematosus can worsen thecondition from the stable to active stage, with quality of life and fertility desirebeing particular concerns. Pregnancy in the active ...BACKGROUND Pregnancy in the setting of systemic lupus erythematosus can worsen thecondition from the stable to active stage, with quality of life and fertility desirebeing particular concerns. Pregnancy in the active stage of systemic lupuserythematosus (ASLE), although rare and complicated to manage, can be treatedfavorably with immunotherapies ifs used properly. Here we report such a successcase.CASE SUMMARY A 31-year-old primigravida patient, diagnosed with SLE seven years ago, wasinduced ASLE after a cold at 21 + weeks. The patient’s vital signs on presentationwere normal. Her laboratory exam was remarkable for significant proteinuria,liver and renal dysfunction, and low C3 and C4 levels. Infectious work-up wasnegative. The patient was diagnosed with ASLE. She was given immunosuppressiveagents (methylprednisolone, gamma globulin and azathioprine etc.)and plasma adsorption therapy, monitoring blood pressure every 8 h, fetal heartrate twice a day, and liver and renal function at least twice a week. Successfulmaternal and fetal outcomes are presented here.CONCLUSION Child-bearing in ASLE has become more promising, even for this difficult case ofASLE with multiple organ damage. Thorough antepartum counseling, cautiousmaternal-fetal monitoring, and multi-organ function monitoring bymultidisciplinary specialties are keys to favorable pregnancy outcomes.展开更多
Herein we reported 5 patients of mass-type intrahepatic cholangiocarcinoma(ICC)misdiagnosed as liver abscess by contrast-enhanced CT,the diagnosis was confirmed through contrast-enhanced ultrasound(CEUS)imaging and pa...Herein we reported 5 patients of mass-type intrahepatic cholangiocarcinoma(ICC)misdiagnosed as liver abscess by contrast-enhanced CT,the diagnosis was confirmed through contrast-enhanced ultrasound(CEUS)imaging and pathology.From January 2015 to January 2018,five patients(1 male and 4 females)were confirmed as ICC by surgical resection or biopsy in Tongde Hospital of Zhejiang Province,with average age of(74.2±5.6)years.These 5 ICC patients were misdiagnosed as liver abscess by contrast-enhanced CT and later on。展开更多
AIM: To evaluate the effects of epidermal growth factor(EGF) on transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT) in human corneal epithelial cells(HCECs). METHODS: HCECs were cu...AIM: To evaluate the effects of epidermal growth factor(EGF) on transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT) in human corneal epithelial cells(HCECs). METHODS: HCECs were cultured and treated with TGF-β1 for establishing the model of EMT in vitro. Biological effect of EGF on TGF-β1-induced EMT was evaluated. Proteins and m RNAs expression changes of E-cadherin, N-cadherin and Fibronectin(EMT-relative markers) after TGF-β1 or TGF-β1 combined EGF treatment were detected by Western blot and RT-PCR, respectively. Viability and migration of HCECs were measured by CCK-8, transwell cell migration assay and cell scratch wound healing assay. Activation of Smad2, ERK, p38, JNK and Akt signaling pathways were evaluated by Western blot. Inhibitors of relevant signaling pathways were added to the HCECs to explore the key signal mechanism.RESULTS: With treatment of TGF-β1 only, three EMTrelative proteins and m RNA expression showed that EMT up-regulated in a concentration-dependent and time-dependent manner, with significantly decreasing cell viability(TGF-β1≥5 ng/m L, P<0.05) and increasing cell migration(TGF-β1≥5 ng/m L, P<0.01). The phosphorylation of Smad2 and p38 was a key process of TGF-β1-induced EMT. Meanwhile, EMT-relative proteins and m RNA expression showed that EGF inhibited TGF-β1-indued EMT, with significantly increasing cell viability(EGF≥10 ng/m L, P<0.01). It was noteworthy that EGF significantly enhanced cell migration although EMT was inhibited(EGF≥10 ng/m L, P<0.01), and the blockage of p38(by SB202190, a p38 inhibitor) was a potential mechanism of this phenomenon. CONCLUSION: EGF inhibits TGF-β1-induced EMT via suppressive p38, and promotes cells proliferation and migration in a non-EMT process by inhibiting p38 pathway.展开更多
Psoriasis is a chronic,non-communicable,painful,disfiguring and disabling disease for which there is no cure,with great negative impact on patients’quality of life(QoL).Diagnosis and treatment with traditional Chines...Psoriasis is a chronic,non-communicable,painful,disfiguring and disabling disease for which there is no cure,with great negative impact on patients’quality of life(QoL).Diagnosis and treatment with traditional Chinese medical technique based on syndrome differentiation has been used in practice for a long time and proven effective,though,up to now,there are only a few available studies about the use of semantic technologies and the knowledge systems that use Traditional Chinese Medicine(TCM)-syndrome differentiation for information retrieval and automated reasoning.In this paper we use semantic techniques based on ontologies to develop a prototypical system for the diagnosis of Psoriasis.For this purpose,a domain ontology is developed for syndrome differentiation of psoriasis vulgaris(PV).This ontology is founded on an adapted version of the general formal ontology(GFO),with the evidence-based clinical practice guideline of TCM for psoriasis vulgaris(Guideline 2013)as the primary data sources.The implemented prototype,called ONTOPV,contains this domain ontology and is aimed at a decision support system for diagnosis and treatment of PV.This system uses a case-database for Case Based Reasoning(CBR),combined with fuzzy pattern recognition.Experimental results show that the ONTOPV realizes the basic functionalities of data collection,querying,browsing and navigation,and supports rule-based knowledge reasoning,and integrates fuzzy pattern recognition.It can provide users with clinical decision support for TCM syndrome differentiation in diagnosis of psoriasis.展开更多
Pancreatic cancer(PC)is the seventh leading cause of cancer death worldwide.The vast majority of patients who have PC develop metastases,resulting in poor treatment effects.Although great progress in therapeutic appro...Pancreatic cancer(PC)is the seventh leading cause of cancer death worldwide.The vast majority of patients who have PC develop metastases,resulting in poor treatment effects.Although great progress in therapeutic approaches has been achieved in recent decades,extensive drug resistance still persists,representing a major hurdle to effective anticancer therapy for pancreatic ductal adenocarcinoma(PDAC).Therefore,there is an urgent need to better understand the drug resistance mechanisms and develop novel treatment strategies to improve patient outcomes.Numerous studies suggest that chemoresistance is closely related to epithelial-mesenchymal transition(EMT)of PDAC cells.Thus,this article summarizes the impact of EMT on PDAC from the perspective of chemotherapy resistance and discusses the possible novel applications of EMT inhibition to develop more effective drugs against PDAC.展开更多
The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsificati...The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation(methazolamide-chitosan-SLNs)prepared was(58.5± 4.5)%,Particle size(247.7 ± 17.3) nm and zeta potential(33.5 ±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosanSLNs is a potential carrier for ophthalmic administration.展开更多
The breakthrough of immune checkpoint inhibitor(ICI)therapy has created extensive opportunities for cancer immunotherapy.Especially,the block of programmed death-1/programmed death ligand 1(PD-L1)axis using ICIs has b...The breakthrough of immune checkpoint inhibitor(ICI)therapy has created extensive opportunities for cancer immunotherapy.Especially,the block of programmed death-1/programmed death ligand 1(PD-L1)axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer(GC).However,in the past decade,single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory,including clinical trials for advanced GC.However,after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs,the objective response rate and progression-free survival of patients with gastric cancer were improved significantly.The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instabilityhigh/mismatch repair deficiency.In this review,the updated data from the latest trial results of combination immunotherapy for GC are presented.Based on the outcome of combination therapy,we discuss its possible molecular mechanism and summarize effective predictive biomarkers.We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.展开更多
BACKGROUND Pericardial rupture caused by blunt chest trauma is rare in clinical practice.Because of its atypical clinical symptoms,and because surgeons are often unfamiliar with the clinical and radiological manifesta...BACKGROUND Pericardial rupture caused by blunt chest trauma is rare in clinical practice.Because of its atypical clinical symptoms,and because surgeons are often unfamiliar with the clinical and radiological manifestations of the injury,preoperative diagnosis is difficult;it is easily misdiagnosed and causes serious consequences.CASE SUMMARY A 60-year-old man,previously healthy,was transported to the emergency room after falling from a great height.Upon arrival,his vital signs were stable.Electrocardiography and echocardiography were performed,and there was no sign of cardiac injury or ischemia.Chest and abdomen computerized tomography revealed pneumopericardium,hemopneumothorax,lung contusion,multiple rib fractures on the right side(Figure 1),and right scapula and clavicle fractures.He was admitted to the inpatient department for further observation after tube thoracostomy.The next day,the patient suddenly experienced rapid arrhythmia(the ventricular rate reached 150-180 beats/min)when turning onto his right side,accompanied by a blood pressure drop to 70/45 mm Hg and a chief complaint of palpitation.Thoracoscopy was performed urgently,and a large vertical tear(8 cm×6 cm)was found in the pericardium.The defect was successfully repaired using a heart Dacron patch.His postoperative condition was uneventful without any fluctuations in vital signs,and he was transferred to the orthopedics department for further surgery on postoperative day 8.CONCLUSION Although the possibility of pericardial rupture combined with cardiac hernia is extremely low,it is one of the causes of cardiogenic shock following blunt trauma.Therefore,clinicians need to be more familiar with its characteristic manifestations and maintain a high degree of vigilance against such injuries to avoid disastrous consequences.展开更多
基金This study was supported by a grant from the Exploration Project of Natural Science Foundation of Zhejiang Province(LY20H180002).
文摘Hepatic cystic lesions include congenital dysplasia,inflammatory cystic lesions,neoplastic cystic lesions and parasitic cystic lesions.As different treatment modalities can be chosen for these lesions,differential diagnosis is particularly important[1].Clinical features or imaging findings of cystic lesions of the liver are typical;for instance,liver abscess often shows thick-walled enhancement on contrast-enhanced CT.
基金Supported by Program of Zhejiang Provincial TCM Sci-tech Plan,No.2024ZL039.
文摘BACKGROUND The prevalence of nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has increased in recent clinical practice;however,the relationship between CHB and hepatic steatosis(HS)remains controversial.AIM To shed light on the potential association between NAFLD and hepatitis B virus(HBV)infection.METHODS We conducted a systematic literature search using multiple databases,including PubMed,the Cochrane Library,Web of Science,and EMBASE,to identify relevant studies.Predefined inclusion criteria were used to determine the eligibility of the studies for further analysis.RESULTS Comprehensive meta-analysis software was used for statistical analysis,which covered 20 studies.The results indicated a lower NAFLD susceptibility in HBVinfected individuals(pooled OR=0.87;95%CI=0.69-1.08;I2=91.1%),with diabetes(P=0.015),body mass index(BMI;P=0.010),and possibly age(P=0.061)as heterogeneity sources.Of note,in four studies(6197 HBV patients),HBV-infected individuals had a reduced NAFLD risk(OR=0.68,95%CI=0.51-0.89,P=0.006).A positive link between hyperlipidemia and metabolic syndrome emerged in hepatitis B patients,along with specific biochemical indicators,including BMI,creatinine,uric acid,fasting blood glucose,and homeostasis model assessment of insulin resistance.CONCLUSION HBV infection may provide protection against HS;however,the occurrence of HS in patients with HBV infection is associated with metabolic syndrome and specific biochemical parameters.
基金Supported by Hangzhou Municipal Bureau of Science and Technology,No.2021WJCY366.
文摘BACKGROUND Aplastic anemia(AA)presents a significant clinical challenge as a life-threatening condition due to failure to produce essential blood cells,with the current the-rapeutic options being notably limited.AIM To assess the therapeutic potential of ginsenoside Rg1 on AA,specifically its protective effects,while elucidating the mechanism at play.METHODS We employed a model of myelosuppression induced by cyclophosphamide(CTX)in C57 mice,followed by administration of ginsenoside Rg1 over 13 d.The invest-igation included examining the bone marrow,thymus and spleen for pathological changes via hematoxylin-eosin staining.Moreover,orbital blood of mice was collected for blood routine examinations.Flow cytometry was employed to identify the impact of ginsenoside Rg1 on cell apoptosis and cycle in the bone marrow of AA mice.Additionally,the study further evaluated cytokine levels with enzyme-linked immunosorbent assay and analyzed the expression of key proteins in the MAPK signaling pathway via western blot.RESULTS Administration of CTX led to significant damage to the bone marrow’s structural integrity and a reduction in hematopoietic cells,establishing a model of AA.Ginsenoside Rg1 successfully reversed hematopoietic dysfunction in AA mice.In comparison to the AA group,ginsenoside Rg1 provided relief by reducing the induction of cell apoptosis and inflammation factors caused by CTX.Furthermore,it helped alleviate the blockade in the cell cycle.Treatment with ginsenoside Rg1 significantly alleviated myelosuppression in mice by inhibiting the MAPK signaling pathway.CONCLUSION This study suggested that ginsenoside Rg1 addresses AA by alleviating myelosuppression,primarily through modulating the MAPK signaling pathway,which paves the way for a novel therapeutic strategy in treating AA,highlighting the potential of ginsenoside Rg1 as a beneficial intervention.
基金the National Natural Science Foundation of China,No.82274547the Major Program of the National Natural Science Foundation of Zhejiang Province,No.LD22C060002+1 种基金the State Administration of Traditional Chinese Medicine of Zhejiang Province,No.GZY-ZJ-KJ-23064the Zhejiang Provincial Research Foundation for Basic Public Welfare Research,No.LGF20H270005.
文摘BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.
基金Supported by Medical Health Science and Technology Project of Zhejiang Province,China,No.2020ZH003。
文摘BACKGROUND Cesarean scar pregnancy(CSP)is rare but may result in uterine rupture during pregnancy or massive hemorrhage during abortion procedures.Awareness of this condition is increasing,and most patients with CSP are now diagnosed early and can be managed safely.However,some atypical patients are misdiagnosed,and their surgical risks are underestimated,increasing the risk of fatal hemorrhage.CASE SUMMARY A 27-year-old Asian woman visited our institution because of abnormal pregnancy,and she was diagnosed with a hydatidiform mole through transvaginal ultrasound(TVS).Under hysteroscopy,a large amount of placental tissue was found in the scar of the lower uterine segment,and a sudden massive hemorrhage occurred during the removal process.The bilateral internal iliac arteries were temporarily blocked under laparoscopy,and scar resection and repair were rapidly performed.She was discharged in good condition 5 d after the operation.CONCLUSION Although TVS is widely used in the diagnosis of CSP,delays in the diagnosis of atypical CSP remain.Surgical treatment following internal iliac artery temporary occlusion may be an appropriate management method for unanticipated massive hemorrhage during CSP surgery.
基金supported by the National Natural Science Foundation of China(Grant Nos.82004007 and 81774026).
文摘Non-small cell lung cancer(NSCLC)is a malignant tumor with high incidence worldwide.Triptolide(TP),extracted from Tripterygium wilfordii Hook F,exhibits potent broad-spectrum antitumor activity.Although some mechanisms through which TP inhibits NSCLC are well understood,those that involve ribosomal proteins remain yet to be understood.In this study,the transcriptome and proteome were integrated and analyzed.Our data indicated ribosomal protein L4(RPL4)to be a core hub protein in the protein-protein interaction network.RPL4 is overexpressed in NSCLC tissues and cells.Transfection with siRPL4 or TP treatment alone arrested the cell cycle in the G1 phase,induced cell apoptosis,and repressed cell invasion.Compared to treating cells with TP alone or siRPL4,treating them with siRPL4–TP enhanced the inhibition of NSCLC cells.Reduced RPL4 expression reinforced the inhibitory effects of TP on NSCLC cells by disrupting the MDM2-P53 pathway and by altering the expression of PARP1/Snail/cyclin D1.In vivo assays verified that TP induced cell apoptosis and reduced RPL4 expression in xenografts.These findings provide clues to facilitate the development of effective TP-based therapeutic strategies to kill NSCLC cells.
基金supported by the Natural Science Foundation of Guangdong Province(Grant No.2020A151501287)the General Project of Science and Technology Innovation Commission of Shenzhen(Grant Nos.JCYJ20210324134800001,JCYJ20190808103401655)+1 种基金Basic Public Welfare Research Project of Zhejiang Province(Grant No.LGF21H090011)the National Natural Science Foundation of China(Grant No.82174132).
文摘Ischemic cerebrovascular disease is a leading cause of death globally and is often exacerbated by cerebral ischemic/reperfusion injury(CIRI).The exact mechanisms underlying I/R injury are unclear.In this study,we aimed to determine the role of m6A-modified methylase complex methyltransferase-like 3(METTL3)in cerebral ischemiareperfusion(I/R)injury.We found that m6A and METTL3 levels increased in OGD/RX-induced mouse astrocytescerebellar(MA-C)and the brain of middle cerebral artery occlusion(MCAO)model mice.METTL3 siRNA treatment reduced OGD-RX-induced MAC cell viability and proliferation,which increased with METTL3 over-expression.Flow cytometry analysis showed that silencing METTL3 significantly enhanced OGD/RX-induced MAC apoptosis,which was significantly reduced with METTL3 up-regulation.In an MCAO model,METTL3 overexpression significantly reduced cerebral infarction area and decreased brain cell apoptosis,indicating that METTL3 OE treatment could ameliorate brain edema and injury.Thus,METTL3 could be used as a target to treat I/R injury.
文摘BACKGROUND This study examines the complex relationships among the neuroendocrine axis,gut microbiome,inflammatory responses,and gastrointestinal symptoms in patients with irritable bowel syndrome(IBS).The findings provide new insights into the pathophysiology of IBS and suggest potential therapeutic targets for improving patient outcomes.AIM To investigate the interactions between the neuroendocrine axis,gut microbiome,inflammation,and gastrointestinal symptoms in patients with IBS.METHODS Patients diagnosed with IBS between January 2022 and January 2023 were selected for the study.Healthy individuals undergoing routine check-ups during the same period served as the control group.Data were collected on neuroendocrine hormone levels,gut microbiome profiles,inflammatory biomarkers,and gastrointestinal symptomatology to analyze their interrelations and their potential roles in IBS pathogenesis.RESULTS IBS patients exhibited significant dysregulation of the neuroendocrine axis,with altered levels of cortisol,serotonin,and neuropeptides compared to healthy controls.The gut microbiome of IBS patients showed reduced diversity and specific alterations in bacterial genera,including Bifidobacterium,Lactobacillus,and Faecalibacterium,which were associated with neuroendocrine disturbances.Additionally,elevated levels of inflammatory markers,such as C-reactive protein,interleukin-6,and tumor necrosis factor-α,were observed and correlated with the severity of gastrointestinal symptoms like abdominal pain,bloating,and altered bowel habits.CONCLUSION The findings suggest that targeting the neuroendocrine axis,gut microbiome,and inflammatory pathways may offer novel therapeutic strategies to alleviate symptoms and improve the quality of life in IBS patients.
文摘BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.
基金Supported by the National Nature Science Foundation of China,No.81273735 and No.82174319the Natural Science Foundation of Guangdong Province,China,No.2021A1515010961+1 种基金the Key-Area Research and Development Program of Guangdong Province,China,No.2020B1111100011the China Postdoctoral Science Foundation,China,No.2023M740859.
文摘BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.
基金National Natural Science Foundation of China(81403502)General Research Fund ofResearch Grants Council of Hong Kong (17124418).
文摘OBJECTIVE Major depressive disorder(MDD) is a highly heterogeneous mental illness.Further classification may help characterize its heterogeneity.The purpose of this study was to examine metabolomic and brain connectomic associations with traditional Chinese medicine(TCM) diagnostic classification of MDD.METHODS Fifty unmedicated depressed patients were classified into Liver Qi Stagnation(LQS,n=30) and Heart and Spleen Deficiency(HSD,n=20) subtypes according to TCM diagnosis.Healthy volunteers(n=28) were included as controls.Gas chromatography-mass spectrometry(GC-MS) and diffusion tensor imaging were used to detect serum and urinary metabolomic profiles and whole-brain white matter connectivity,respectively.RESULTS In metabolomic analysis,28 metabolites were identified for good separations between TCM subtypes and healthy controls in serum and urine samples.While both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids and energy metabolism-related metabolites that were differentiated from healthy controls,the LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in the biosynthesis of monoamine and amino acid neurotransmitters.Several metabolites are differentially associated with the two subtypes.In connectomic analysis,The LQS subtype showed significant differences in multiple network metrics of the angular gyrus,middle occipital gyrus,calcarine sulcus,and Heschl′ s gyrus when compared to the other two groups.The HSD subtype had markedly greater regional connectivity of the insula,parahippocampal gyrus,and posterior cingulate gyrus than the other two groups,and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole.The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity.CONCLUSION The LQS subtype may represent an MDD subpopulation mainly characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters,closer associations with stress-related pathophysiology,and aberrant connectivity of the audiovisual perception-related temporal-occipital network,whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbicparalimbic network.Certain metabolomic and connectomic variables are potential biomarkers for TCM diagnostic subtypes which is perhaps an alternative classification for depressive disorders.
基金Zhejiang Scientific and Technological Plan of Traditional Chinese Medicine,No.2018ZB033Zhejiang Medical and Health Science and Technology Project,No.2018234792
文摘Simultaneous anterior and posterior traumatic dislocations of both hips are very rare. Only 33 cases have been previously reported in the English language literature. Although they were all due to high-energy injuries, they were hemodynamically stable and had a stable pelvic ring. We report a unique case of asymmetrical hip dislocations with an unstable pelvic ring and hemodynamic instability. A 40-year-old man was injured in a high-energy motor vehicle accident. He was hemodynamically unstable when he presented in the emergency department. Radiolographs showed asymmetrical dislocations of both hips with an unstable pelvic ring. Under general anesthesia, he had closed reduction of the dislocations of both hips, followed by temporary stabilization with an external fixator. Transcatheter arterial embolization was performed to stop active pelvic bleeding. Delayed open reduction and internal fixation was performed 12 d later with anterior and posterior plates. The patient recovered well with an uneventful post-operative course. Asymmetrical bilateral hip dislocations with pelvic ring instability caused by trauma, as presented in this case, is very rare and potentially life threatening. Prompt treatment can give a good outcome.
文摘BACKGROUND Pregnancy in the setting of systemic lupus erythematosus can worsen thecondition from the stable to active stage, with quality of life and fertility desirebeing particular concerns. Pregnancy in the active stage of systemic lupuserythematosus (ASLE), although rare and complicated to manage, can be treatedfavorably with immunotherapies ifs used properly. Here we report such a successcase.CASE SUMMARY A 31-year-old primigravida patient, diagnosed with SLE seven years ago, wasinduced ASLE after a cold at 21 + weeks. The patient’s vital signs on presentationwere normal. Her laboratory exam was remarkable for significant proteinuria,liver and renal dysfunction, and low C3 and C4 levels. Infectious work-up wasnegative. The patient was diagnosed with ASLE. She was given immunosuppressiveagents (methylprednisolone, gamma globulin and azathioprine etc.)and plasma adsorption therapy, monitoring blood pressure every 8 h, fetal heartrate twice a day, and liver and renal function at least twice a week. Successfulmaternal and fetal outcomes are presented here.CONCLUSION Child-bearing in ASLE has become more promising, even for this difficult case ofASLE with multiple organ damage. Thorough antepartum counseling, cautiousmaternal-fetal monitoring, and multi-organ function monitoring bymultidisciplinary specialties are keys to favorable pregnancy outcomes.
基金supported by a grant from the Major Research Project of Natural Science Foundation of Zhejiang Province(NO.LSD19H180001)。
文摘Herein we reported 5 patients of mass-type intrahepatic cholangiocarcinoma(ICC)misdiagnosed as liver abscess by contrast-enhanced CT,the diagnosis was confirmed through contrast-enhanced ultrasound(CEUS)imaging and pathology.From January 2015 to January 2018,five patients(1 male and 4 females)were confirmed as ICC by surgical resection or biopsy in Tongde Hospital of Zhejiang Province,with average age of(74.2±5.6)years.These 5 ICC patients were misdiagnosed as liver abscess by contrast-enhanced CT and later on。
基金Supported by the 63th Postdoctoral Science Foundation of China(No.2018M632487)General Natural Science ProjectsDepartment of Education,Zhejiang Province,China(No.Y201636718)
文摘AIM: To evaluate the effects of epidermal growth factor(EGF) on transforming growth factor-beta1(TGF-β1)-induced epithelial-mesenchymal transition(EMT) in human corneal epithelial cells(HCECs). METHODS: HCECs were cultured and treated with TGF-β1 for establishing the model of EMT in vitro. Biological effect of EGF on TGF-β1-induced EMT was evaluated. Proteins and m RNAs expression changes of E-cadherin, N-cadherin and Fibronectin(EMT-relative markers) after TGF-β1 or TGF-β1 combined EGF treatment were detected by Western blot and RT-PCR, respectively. Viability and migration of HCECs were measured by CCK-8, transwell cell migration assay and cell scratch wound healing assay. Activation of Smad2, ERK, p38, JNK and Akt signaling pathways were evaluated by Western blot. Inhibitors of relevant signaling pathways were added to the HCECs to explore the key signal mechanism.RESULTS: With treatment of TGF-β1 only, three EMTrelative proteins and m RNA expression showed that EMT up-regulated in a concentration-dependent and time-dependent manner, with significantly decreasing cell viability(TGF-β1≥5 ng/m L, P<0.05) and increasing cell migration(TGF-β1≥5 ng/m L, P<0.01). The phosphorylation of Smad2 and p38 was a key process of TGF-β1-induced EMT. Meanwhile, EMT-relative proteins and m RNA expression showed that EGF inhibited TGF-β1-indued EMT, with significantly increasing cell viability(EGF≥10 ng/m L, P<0.01). It was noteworthy that EGF significantly enhanced cell migration although EMT was inhibited(EGF≥10 ng/m L, P<0.01), and the blockage of p38(by SB202190, a p38 inhibitor) was a potential mechanism of this phenomenon. CONCLUSION: EGF inhibits TGF-β1-induced EMT via suppressive p38, and promotes cells proliferation and migration in a non-EMT process by inhibiting p38 pathway.
基金This work was partially supported by the National Natural Science Foundation of China(No.82174534)the China Academy of Chinese Medical Sciences Innovation Fund(No.CI2021A05306)the Fundamental Research Funds for the Central Public Welfare Research Institutes(Nos.ZZ13-YQ-021,ZZ13-YQ-126,ZZ150314).
文摘Psoriasis is a chronic,non-communicable,painful,disfiguring and disabling disease for which there is no cure,with great negative impact on patients’quality of life(QoL).Diagnosis and treatment with traditional Chinese medical technique based on syndrome differentiation has been used in practice for a long time and proven effective,though,up to now,there are only a few available studies about the use of semantic technologies and the knowledge systems that use Traditional Chinese Medicine(TCM)-syndrome differentiation for information retrieval and automated reasoning.In this paper we use semantic techniques based on ontologies to develop a prototypical system for the diagnosis of Psoriasis.For this purpose,a domain ontology is developed for syndrome differentiation of psoriasis vulgaris(PV).This ontology is founded on an adapted version of the general formal ontology(GFO),with the evidence-based clinical practice guideline of TCM for psoriasis vulgaris(Guideline 2013)as the primary data sources.The implemented prototype,called ONTOPV,contains this domain ontology and is aimed at a decision support system for diagnosis and treatment of PV.This system uses a case-database for Case Based Reasoning(CBR),combined with fuzzy pattern recognition.Experimental results show that the ONTOPV realizes the basic functionalities of data collection,querying,browsing and navigation,and supports rule-based knowledge reasoning,and integrates fuzzy pattern recognition.It can provide users with clinical decision support for TCM syndrome differentiation in diagnosis of psoriasis.
基金Zhejiang Provincial Nature Science Foundation of China,No.LR20H160001Key R&D projects of Zhejiang Province,No.2020C03G5263593+4 种基金Zhejiang Provincial Ten Thousand Plan for Young Top Talents(2018)Training Objects of Health Innovative Talents of Zhejiang Health(2018)Key Project Co-constructed by Zhejiang Province and Ministry,No.WKJ-ZJ-1916Natural Science Foundation of China,No.81972693,No.81802383,No.81972674,No.81673809 and No.31900543Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project,No.2020ZZ004.
文摘Pancreatic cancer(PC)is the seventh leading cause of cancer death worldwide.The vast majority of patients who have PC develop metastases,resulting in poor treatment effects.Although great progress in therapeutic approaches has been achieved in recent decades,extensive drug resistance still persists,representing a major hurdle to effective anticancer therapy for pancreatic ductal adenocarcinoma(PDAC).Therefore,there is an urgent need to better understand the drug resistance mechanisms and develop novel treatment strategies to improve patient outcomes.Numerous studies suggest that chemoresistance is closely related to epithelial-mesenchymal transition(EMT)of PDAC cells.Thus,this article summarizes the impact of EMT on PDAC from the perspective of chemotherapy resistance and discusses the possible novel applications of EMT inhibition to develop more effective drugs against PDAC.
基金supported by grants from the National Natural Science Foundation of China(81100977)
文摘The present study aimed to develop and optimize chitosan coated solid lipid nanoparticles(chitosan-SLNs)encapsulated with methazolamide. Chitosan-SLNs were successfully prepared by a modified oil-in-water emulsification-solvent evaporation method with glyceryl monostearate as the solid lipid and phospholipid as the surfactant. Systematic screening of formulation factors was carried out. The optimized formula for preparation was screened by orthogonal design as well as Box-Behnken design with entrapment efficiency, particle size and zeta potential as the indexes. The entrapment efficiency of the optimized formulation(methazolamide-chitosan-SLNs)prepared was(58.5± 4.5)%,Particle size(247.7 ± 17.3) nm and zeta potential(33.5 ±3.9) mV. Transmission electron microscopy showed homogeneous spherical particles in the nanometer range. A prolonged methazolamide in vitro release profile was obtained in the optimized chitosan-SLNs suspension compared with methazolamide solution. No ocular damages were observed in the susceptibility test on albino rabbits. The results suggest that the combination of orthogonal design and Box-Behnken design is efficient and reliable in the optimization of nanocarriers, and chitosanSLNs is a potential carrier for ophthalmic administration.
基金Supported by National Natural Science Funds of Young Scientists of China,No.81802944Zhejiang Provincial Public Welfare Technology Application Research Project,No.LGF18H160007+7 种基金Program of Ningbo Medical Research Center for Digestive System Cancer,No.2019A21003Zhejiang Provincial Natural Science Foundation,No.LR20H160001Zhejiang Provincial Ten Thousand Plan for Young Top Talents to Wei Chen(2018)Training Objects of Health Innovative Talents of Zhejiang Health to Wei Chen(2018)Key Project Co-constructed by Zhejiang Province and Ministry,No.WKJZJ-1916National Natural Science Foundation of China,No.81972693,No.81802383,No.81972674,No.81673809,and No.31900543Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project,No.2020ZZ004Projects of Lishui Key Research and Development Plan in Zhejiang Province,No.2017ZDYF12.Conflict-of-interest statement:The authors have no conflict of interest to declare.
文摘The breakthrough of immune checkpoint inhibitor(ICI)therapy has created extensive opportunities for cancer immunotherapy.Especially,the block of programmed death-1/programmed death ligand 1(PD-L1)axis using ICIs has become a new therapeutic strategy to treat advanced gastric cancer(GC).However,in the past decade,single-arm and randomized trials for single-drug ICI therapy showed that the therapeutic effect was not satisfactory,including clinical trials for advanced GC.However,after selecting suitable predictive biomarkers and developing a combination of anti-angiogenic targeted drugs and other chemotherapeutic drugs,the objective response rate and progression-free survival of patients with gastric cancer were improved significantly.The United States Food and Drug Administration has approved treatment with pembrolizumab for patients with advanced GC with PD-L1 expression or microsatellite instabilityhigh/mismatch repair deficiency.In this review,the updated data from the latest trial results of combination immunotherapy for GC are presented.Based on the outcome of combination therapy,we discuss its possible molecular mechanism and summarize effective predictive biomarkers.We also discuss possible problems stemming from results of other clinical trials of ICI treatment and propose other directions for ICI therapy.
基金The 13th Five-Year Key Project for Traditional Chinese Medicine of Zhejiang Province,No.2A11951.
文摘BACKGROUND Pericardial rupture caused by blunt chest trauma is rare in clinical practice.Because of its atypical clinical symptoms,and because surgeons are often unfamiliar with the clinical and radiological manifestations of the injury,preoperative diagnosis is difficult;it is easily misdiagnosed and causes serious consequences.CASE SUMMARY A 60-year-old man,previously healthy,was transported to the emergency room after falling from a great height.Upon arrival,his vital signs were stable.Electrocardiography and echocardiography were performed,and there was no sign of cardiac injury or ischemia.Chest and abdomen computerized tomography revealed pneumopericardium,hemopneumothorax,lung contusion,multiple rib fractures on the right side(Figure 1),and right scapula and clavicle fractures.He was admitted to the inpatient department for further observation after tube thoracostomy.The next day,the patient suddenly experienced rapid arrhythmia(the ventricular rate reached 150-180 beats/min)when turning onto his right side,accompanied by a blood pressure drop to 70/45 mm Hg and a chief complaint of palpitation.Thoracoscopy was performed urgently,and a large vertical tear(8 cm×6 cm)was found in the pericardium.The defect was successfully repaired using a heart Dacron patch.His postoperative condition was uneventful without any fluctuations in vital signs,and he was transferred to the orthopedics department for further surgery on postoperative day 8.CONCLUSION Although the possibility of pericardial rupture combined with cardiac hernia is extremely low,it is one of the causes of cardiogenic shock following blunt trauma.Therefore,clinicians need to be more familiar with its characteristic manifestations and maintain a high degree of vigilance against such injuries to avoid disastrous consequences.