Clinical study of different interventional treatments for primary hepatocellular carcinoma based on propensity-score matching

BACKGROUND Transcatheter arterial chemoembolization(TACE)is the main treatment for patients with primary hepatocellular carcinoma(PHC)who miss the opportunity to undergo surgery.Conventional TACE(c-TACE)uses iodized oil as an embolic agent,which is easily washed by blood and affects its efficacy.Drug-eluting bead TACE(DEB-TACE)can sustainably release chemotherapeutic drugs and has a long embolization time.However,the clinical characteristics of patients before the two types of interventional therapies may differ,possibly affecting the conclusion.Only a few studies have compared these two interventions using propensity-score matching(PSM).AIM To analyze the clinical effects of DEB-TACE and c-TACE on patients with PHC based on PSM.METHODS Patients with PHC admitted to Dangyang People’s Hospital(March 2020 to March 2024)were retrospectively enrolled and categorized into groups A(DEB-TACE,n=125)and B(c-TACE,n=106).Sex,age,Child-Pugh grade,tumor-node-meta-stasis stage,and Eastern Cooperative Oncology Group score were selected for 1:1 PSM.Eighty-six patients each were included post-matching.Clinical efficacy,liver function indices(aspartate aminotransferase,alanine aminotransferase,total bilirubin,and albumin),tumor serum markers,and adverse reactions were compared between the groups.RESULTS The objective response and disease control rates were significantly higher in group A(80.23%and 97.67%,respectively)than in group B(60.47%and 87.21%,respectively)(P<0.05).Post-treatment levels of aspartate aminotransferase,alanine aminotransferase,and total bilirubin were lower in group A than in group B(P<0.05),whereas post-treatment levels of albumin in group A were comparable to those in group B(P>0.05).Post-treatment levels of tumor serum markers were significantly lower in group A than in group B(P<0.05).Patients in groups A and B had mild-to-moderate fever and vomiting symptoms,which improved with conservative treatment.The total incidence of adverse reactions was significantly higher in group B(22.09%)than in group A(6.97%)(P<0.05).CONCLUSION DEB-TACE has obvious therapeutic effects on patients with PHC.It can improve liver function indices and tumor markers of patients without increasing the rate of liver toxicity or adverse reactions.

Upadacitinib for refractory ulcerative colitis with primary nonresponse to infliximab and vedolizumab:A case report

BACKGROUND Many patients with ulcerative colitis(UC)do not respond well to,or tolerate conventional and biological therapies.There is currently no consensus on the treatment of refractory UC.Studies have demonstrated that the selective Janus kinase 1 inhibitor upadacitinib,a small-molecule drug,is effective and safe for treating UC.However,no studies have revealed that upadacitinib is effective in treating refractory UC with primary nonresponse to infliximab and vedolizumab.CASE SUMMARY We report the case of a 44-year-old male patient with a chief complaint of bloody diarrhoea with mucus and pus,in addition to dizziness.The patient had recurrent disease after receiving mesalazine,prednisone,azathioprine,infliximab and vedolizumab over four years.Based on the endoscopic findings and pathological biopsy,the patient was diagnosed with refractory UC.In particular,the patient showed primary nonresponse to infliximab and vedolizumab.Based on the patient’s history and recurrent disease,we decided to administer upadacitinib.During hospitalisation,the patient was received upadacitinib under our guidance.Eight weeks after the initiation of upadacitinib treatment,the patient’s symptoms and endoscopic findings improved significantly.No notable adverse reactions have been reported to date.CONCLUSION Our case report suggests that upadacitinib may represent a valuable strategy for treating refractory UC with primary nonresponse.

Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model

BACKGROUND Colon cancer(CC)is one of the most common malignant tumors in the gastrointestinal system.Overall,CC had the third highest incidence but the second highest mortality rate globally in 2020.Nowadays,CC is mainly treated with capecitabine chemotherapy regimen,supplemented by radiotherapy,immunotherapy and targeted therapy,but there are still limitations,so Chinese medicine plays an important role.AIM To investigate the effects of invigorating-spleen and anticancer prescription(ISAP)on body weight,tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)signaling pathway in CC mice model.METHODS The CC mice model were established and the mice were randomly divided into 5 groups,including the control group,capecitabine group,the low-dose,mediumdose and high-dose groups of ISAP,with 8 mice in each group,respectively.After 2 weeks of intervention,the body weight and tumor inhibition rate of mice were observed,and the expression of RAS,ERK,phosphorylated ERK(p-ERK),C-MYC and matrix metalloproteinase 2(MMP2)proteins in the tissues of tumors were detected.RESULTS Compared with the control group,the differences of body weight before and after treatment was much smaller in the groups of ISAP,with the smallest difference in the high-dose group of ISAP,while the capecitabine group had the greatest difference,indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice.The expression of RAS protein was decreased in the low-and medium-dose groups of ISAP,and the change of p-ERK was significant in the medium-and high-dose groups of ISAP.MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP.There were no significant changes in ERK in the ISAP group compared to the capecitabine group,while RAS,MMP2,and C-MYC protein expression were reduced in the ISAP group.The expression level of C-MYC protein decreased after treated with ISAP,and the decrease was the most significant in the medium-dose group of ISAP.CONCLUSION ISAP has a potential inhibiting effect on transplanted tumor in mice,and could maintain the general conditions,physical strength and body weight of mice.The expression levels of RAS,p-ERK,MMP2 and c-myc were also decreased to a certain extent.By inhibiting the expression of upstream proteins,the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased.Therefore,it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.

Relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine fetal distress

BACKGROUND By comprehensively analyzing the blood flow parameters of the umbilical and middle cerebral arteries,doctors can more accurately identify fetal intrauterine distress,as well as assess its severity,so that timely interventions can be implemented to safeguard the health and safety of the fetus.AIM To identify the relationship between ultrasound parameters of the umbilical and middle cerebral arteries and intrauterine distress.METHODS Clinical data of pregnant women admitted between January 2021 and January 2023 were collected and divided into the observation and control groups(n=50 each),according to the presence or absence of intrauterine distress.The ultrasound hemodynamic parameters of the uterine artery(UtA),fetal middle cerebral artery(MCA),and umbilical artery(UmA)were compared with neonatal outcomes and occurrence of intrauterine distress in the two groups.RESULTS Comparison of ultrasonic hemodynamic parameters,resistance index(RI),pulsatility index(PI),and systolic maximal blood flow velocity of UmA compared to diastolic blood flow velocity(S/D),revealed higher values of fetal MCA,PI,and S/D of UmA in pregnant women with UtA compared to controls(P<0.05),while there was no difference between the two groups in terms of RI(P<0.05)The incidence of a neonatal Apgar score of 8-10 points was lower in the observation group(66.7%)than in the control group(90.0%),and neonatal weight(2675.5±27.6 g)was lower than in the control group(3117.5±31.2 g).Further,cesarean section rate was higher in the observation group(70.0%)than in the control group(11.7%),and preterm labor rate was higher in the observation group(40.0%)than in the control group(10.0%).The incidence of fetal distress,neonatal growth restriction and neonatal asphyxia were also higher in the observation group(all P<0.05).CONCLUSION Fetal MCA,UmA,and maternal UtA hemodynamic abnormalities all develop in pregnant women with intrauterine distress during late pregnancy,which suggests that clinical attention should be paid to them,and monitoring should be strengthened to provide guidance for clinical intervention.

Metabolic syndrome and acute pancreatitis:Current status and future prospects

Rising incidence of a complicated disorder with a multifarious etiology is acute pancreatitis.Growing numbers of cases of acute pancreatitis are linked to obesity,hyperlipidemia,hyperglycemia,hypertension,and other metabolic diseases.Trends driven by better living standards and unhealthy lifestyle choices both in China and abroad.Furthermore common diagnosis for many patients is metabolic syndrome.Predicting the adverse effect of metabolic syndrome on the severity and prognosis of acute pancreatitis is a main focus of present clinical research.Our next studies seek to investigate the fundamental causes of this link and create preventative plans meant to lower the incidence of pancreatitis linked to meta-bolic syndrome and enhance the prognosis.

Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Crossroads:Pathogenic role and therapeutic targets of neutrophil extracellular traps in rheumatoid arthritis

Rheumatoid arthritis(RA)is a prevalent autoimmune disease whose main features include chronic synovial inflammation,bone destruction,and joint degeneration.Neutrophils are often considered to be the first responders to inflammation and are a key presence in the inflammatory milieu of RA.Neutrophil extracellular traps(NETs),a meshwork of DNA-histone complexes and proteins released by activated neutrophils,are widely involved in the pathophysiology of autoimmune diseases,especially RA,in addition to playing a key role in the neutrophil innate immune response.NETs have been found to be an important source of citrullinated autoantigen antibodies and inflammatory factor release,which can activate RA synovial fibroblasts(FLS)and cause joint damage.This article reviews the role of NETs in the pathophysiology of RA,demonstrating the application of multiple molecules with various therapies,with a view to informing the discovery and development of novel biomarkers and therapeutic targets for RA.

Artificial intelligence applications in ophthalmic optical coherence tomography:a 12-year bibliometric analysis

AIM:To explore the current application and research frontiers of global ophthalmic optical coherence tomography(OCT)imaging artificial intelligence(AI)research.METHODS:The citation data were downloaded from the Web of Science Core Collection database(WoSCC)to evaluate the articles in application of AI in ophthalmic OCT published from January 1,2012 to December 31,2023.This information was analyzed using CiteSpace 6.2.R2 Advanced software,and high-impact articles were analyzed.RESULTS:In general,877 articles from 65 countries were studied and analyzed,of which 261 were published by the United States and 252 by China.The centrality of the United States is 0.33,the H index is 38,and the H index of two institutions in England reaches 20.Ophthalmology,computer science,and AI are the main disciplines involved.

Prevalence of Helicobacter pylori infection in China from 2014-2023:A systematic review and meta-analysis

BACKGROUND Helicobacter pylori(H.pylori)stands as the predominant infectious agent linked to the onset of gastritis,peptic ulcer diseases,and gastric cancer(GC).Identified as the exclusive bacterial factor associated with the onset of GC,it is classified as a group 1 carcinogen by the World Health Organization.The elimination of H.pylori plays a crucial role in the primary prevention of GC.While the prevalence has declined in recent decades,H.pylori infection is still highly prevalent in China,accounting for a significant part of the disease burden of GC.Therefore,updated prevalence information for H.pylori infection,especially regional and demographic variations in China,is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for H.pylori control.AIM To methodically evaluate the occurrence of H.pylori infection throughout China and establish a reference point for subsequent investigations.METHODS A systematic review and meta-analysis was conducted following established guidelines,as detailed in our methodology section.RESULTS Our review synthesized data from 152 studies,covering a sample of 763827 individuals,314423 of whom were infected with H.pylori.We evaluated infection rates in China's Mainland and the combined prevalence of H.pylori was 42.8%(95%CI:40.7-44.9).Subgroup analysis indicated the highest prevalence in Northwest China at 51.3%(95%CI:45.6-56.9),and in Qinghai Province,the prevalence reached 60.2%(95%CI:46.5-73.9).The urea breath test,which recorded the highest infection rate,showed a prevalence of 43.7%(95%CI:41.4-46.0).No notable differences in infection rates were observed between genders.Notably,the prevalence among the elderly was significantly higher at 44.5%(95%CI:41.9-47.1),compared to children,who showed a prevalence of 27.5%(95%CI:19.58-34.7).CONCLUSION Between 2014 and 2023,the prevalence of H.pylori infection in China decreased to 42.8%,down from the previous decade.However,the infection rates vary considerably across different geographical areas,among various populations,and by detection methods employed.

Combining systemic inflammatory response index and albumin fibrinogen ratio to predict early serious complications and prognosis after resectable gastric cancer

BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.

Present situation of minimally invasive surgical treatment for early gastric cancer

Minimally invasive surgery is a kind of surgical operation,which is performed by using professional surgical instruments and equipment to inactivate,resect,repair or reconstruct the pathological changes,deformities and wounds in human body through micro-trauma or micro-approach,in order to achieve the goal of treatment,its surgical effect is equivalent to the traditional open surgery,while avoiding the morbidity of conventional surgical wounds.In addition,it also has the advantages of less trauma,less blood loss during operation,less psychological burden and quick recovery on patients,and these minimally invasive techniques provide unique value for the examination and treatment of gastric cancer patients.Surgical minimally invasive surgical techniques have developed rapidly and offer numerous options for the treatment of early gastric cancer(EGC):endoscopic mucosal resection(EMR),underwater EMR(UEMR),endoscopic submucosal dissection(ESD),endoscopic full-thickness resection(EFTR),endoscopic submu-cosal excavation(ESE),submucosal tunnel endoscopic resection,laparoscopic and endoscopic cooperative surgery(LECS);Among them,EMR,EFTR and LECS technologies have a wide range of applications and different modific-ations have been derived from their respective surgical operations,such as band-assisted EMR(BA-EMR),conven-tional EMR(CEMR),over-the-scope clip-assisted EFTR,no-touch EFTR,the inverted LECS,closed LECS,and so on.These new and improved minimally invasive surgeries are more precise,specific and effective in treating different types of EGC.

Textual research on Xu Chunfu's life

Xu Chunfu was a famous medical expert in the Ming Dynasty, who authored the Gu Jin Yi Tong Da Quan and the Yi Xue Zhi Nan Jie Jing Liu Shu. This paper uses the Xu family genealogy, literature catalog, historical records to study the Xu family’s life and deeds. Xu Chunfu was born in the second year of the Jiajing reign of the Ming Dynasty (1523) and passed away in the 24th year of the Wanli reign of the Ming Dynasty (1596). He served as an official in the Tai Hospital for about 20 years. His work Gu Jin Yi Tong Da Quan was written around the 43rd year of the Jiajing reign of the Ming Dynasty (1556), with a lower limit of the fifth year of the Longqing reign of the Ming Dynasty (1571), and the initial engraving time was not earlier than the eighth year of the Wanli reign of the Ming Dynasty (1580). This paper corrects the shortcomings and errors in previous research, and provides a comprehensive and systematic examination of Xu Chunfu’s life and works.

Clinical significance of different periampullary diverticulum classifications for endoscopic retrograde cholangiopancreatography cannulation

BACKGROUND Different types of periampullary diverticulum(PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography(ERCP) cannulation,but the clinical significance of the two current PAD classifications for cannulation is limited.AIM To verify the clinical value of our newly proposed PAD classification.METHODS A new PAD classification(Li-Tanaka classification) was proposed at our center.All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared.RESULTS A total of 3564 patients with native papillae were enrolled, including 967(27.13%)PAD patients and 2597(72.87%) non-PAD patients. In the Li-Tanaka classification, type Ⅰ PAD patients exhibited the highest difficult cannulation rate(23.1%, P = 0.01), and type Ⅱ and Ⅳ patients had the highest cannulation success rates(99.4% in type Ⅱ and 99.3% in type Ⅳ, P < 0.001). In a multivariableadjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio(OR) = 1.87, 95% confidence interval(CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group,the difficulty of cannulation in the type Ⅰ PAD group according to the Li-Tanaka classification was greater(OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower(OR = 0.27, 95%CI: 0.11-0.66, P < 0.001),while it was higher in the type Ⅱ PAD group(OR = 4.44, 95%CI: 1.61-12.29, P <0.01).CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Chinese herbal medicine and COVID-19: quality evaluation of clinical guidelines and expert consensus and analysis of key recommendations

Objective:To systematically review the clinical practice guidelines(CPGs)for the treatment of patients with coronavirus disease 2019(COVID-19)using Chinese herbal medicine(CHM),assess the methodological quality as well as clinical credibility and implementability of specific recommendations,and summarize key recommendations.Methods:As of April 2022,we conducted a comprehensive search on major electronic databases,guideline websites,academic society websites,and government websites to assess the methodological quality and clinical applicability of the included CPGs using the Appraisal of Guidelines for Research and Evaluation(AGREE)II tool and Evaluation-Recommendations EXcellence(AGREE-REX)instructions,respectively.Results:The search yielded 61 CPGs,which were mostly published in 2020;moreover,98.4%of the CPGs were published in China.Only five CPGs achieved a high-quality AGREE II rating;further,six CPGs could be directly recommended,with most of the CPGs still showing much room for improvement.CPGs had a low overall score in the AGREE-REX evaluation,with the domains of clinical applicability,values and preferences,and implementability being standardized in 21.80%±12.56%,16.00%±11.81%,and 31.33%±14.55%of the CPGs,respectively.Five high-quality CPGs mentioned 56 Chinese herbal formulas.Half of the recommendations had moderate or strong evidence level in the GRADE evaluation.The most frequently recommended herbal medicines were Lianhua Qingwen granule/capsule and Jinhua Qinggan granule;however,the strength of recommendation for each prescription varied across CPGs and populations.Conclusions:The overall quality of current CPGs for COVID-19 for CHM still needs to be improved;moreover,the strength of the evidence remains to be standardized across CPGs.

Impact of preoperative therapy on surgical outcomes of laparoscopic total gastrectomy for gastric/gastroesophageal junction cancer

Objective: As laparoscopic surgery is widely applied for primarily treated gastric cancer(GC)/gastroesophageal junction cancer(GEJC) and gains many advantages, the feasibility of laparoscopic total gastrectomy(LTG) for GC/GEJC patients who have received preoperative therapy(PT) has come to the fore. This study aims to analyze the safety and feasibility of LTG after PT for GC/GEJC patients.Methods: We retrospectively analyzed the data of 511 patients with GC/GEJC undergoing LTG, of which 405received LTG(LTG group) and 106 received PT+LTG(PT-LTG group) at Nanfang Hospital between June 2018and September 2022. The surgical outcomes were compared between the two groups.Results: The surgical duration was significantly longer in the PT-LTG group(P<0.001), while the incidence of intraoperative complications(P=1.000), postoperative complications(LTG group vs. PT-LTG group: 26.2% vs.23.6%, P=0.587), the classification of complication severity(P=0.271), and postoperative recovery was similar between two groups. Notably, the incidence of anastomotic complications of esophagojejunostomy was also comparable between the two groups(LTG group vs. PT-LTG group: 5.9% vs. 5.7%, P=0.918). The univariate and multivariate analysis confirmed that positive proximal margin [positive vs. negative: odds ratio(OR)=14.094, 95%confidence interval(95% CI): 2.639-75.260, P=0.002], rather than PT, has an impact on anastomotic complications after LTG(OR=0.945, 95% CI: 0.371-2.408, P=0.905).Conclusions: PT did not increase the surgical risk of LTG for GC/GEJC. Therefore, considering the positive effect of PT on long-term survival, the broader application of PT and LTG for GC/GEJC is supported by our findings.

MiR-520f-3p inhibits epithelial-mesenchymal transition of colorectal cancer cells by targeting Yes-associated protein 1

Background:Colorectal cancer(CRC)is one of the most common malignancies.Early diagnosis is the key to effective treatment of CRC.Since microRNAs(miRNAs)can be used as biomarkers of CRC,the objective of this work was to examine the effect of miR-520f-3p,which targets YAP1(Yes-associated protein 1),on the ability of CRC cells to proliferate,invade,migrate,and undergo epithelial-mesenchymal transition(EMT).Methods:A miR-520f-3p mimic was used to overexpress miR-520f-3p in HT29 cells.To establish the tumor-bearing mouse model,transfected HT29 cells were subcutaneously implanted into BALB/c-nu nude mice,and YAP1 and miR-520f-3p levels were determined using qRT‒PCR.The viability,invasion ability,and migration ability of cells were evaluated by CCK-8,Transwell,and wound healing assays.Apoptosis was detected by flow cytometry and TUNEL assays.The regulatory link between miR-520f-3p and the YAP1 gene was examined by dual-luciferase reporter assay.Tumor tissues with positive Ki-67 expression were identified by immunohistochemistry.Vimentin,E-cadherin,and YAP1 expression were evaluated by western blotting.Results:MiR-520f-3p overexpression could inhibit proliferation,invasion,migration,and EMT and induce apoptosis in HT29 cells.YAP1 was found as a target of miR-520f-3p.The inhibitory effects of miR-520f-3p on proliferation,invasion,migration,and EMT may be reversed by overexpressing YAP1.In tumor-bearing mice,miR-520f-3p overexpression reduced the Ki-67 level,increased apoptosis,and prevented tumor development and spread.Conclusion:By targeting YAP1,miR-520f-3p may be capable of suppressing CRC cell proliferation,invasion,migration,and EMT,providing a novel therapeutic target for the disease.

Gut microbiome and metabolic-associated fatty liver disease:Current status and potential applications

Metabolic-associated fatty liver disease(MAFLD)is one of the most common chronic liver diseases worldwide.In recent years,the occurrence rate of MAFLD has been on the rise,mainly due to lifestyle changes,high-calorie diets,and imbalanced dietary structures,thereby posing a threat to human health and creating heavy social and economic burdens.With the development of 16S sequencing and integrated multi-omics analysis,the role of the gut microbiota(GM)and its metabolites in MAFLD has been further recognized.The GM plays a role in digestion,energy metabolism,vitamin synthesis,the prevention of pathogenic bacteria colonisation,and immunoregulation.The gut-liver axis is one of the vital links between the GM and the liver.Toxic substances in the intestine can enter the liver through the portal vascular system when the intestinal barrier is severely damaged.The liver also influences the GM in various ways,such as bile acid circulation.The gut-liver axis is essential in maintaining the body’s normal physiological state and plays a role in the onset and prognosis of many diseases,including MAFLD.This article reviews the status of the GM and MAFLD and summarizes the GM characteristics in MAFLD.The relationship between the GM and MAFLD is discussed in terms of bile acid circulation,energy metabolism,micronutrients,and signalling pathways.Current MAFLD treat ments targeting the GM are also listed.

Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis

BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AGI),but its specific mechanism is not completely understood,and few clinical reports are available.AIM To explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODS In our prospective clinical trial,48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment,whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin.AGI grade,sequential organ failure assessment score,acute physiology and chronic health evaluation II score,D-dimer,activated partial thromboplastin time(APTT),anti-Xa factor,interleukin-6,tumour necrosis factor-α,HPA,syndecan-1(SDC-1),LC3B(autophagy marker),intestinal fatty acid binding protein,D-lactate,motilin,gastrin,CD4/CD8,length of intensive care unit(ICU)stay,length of hospital stay and 28-d survival on the 1^(st),3^(rd) and 7^(th) d after treatment were compared.Correlations between HPA and AGI grading as well as LC3B were compared.Receiver operator characteristic(ROC)curves were generated to evaluate the diagnostic value of HPA,intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTS Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group(P<0.05).In addition,intestinal fatty acid-binding protein,D-lactate,AGI grade,motilin,and gastrin levels and sequential organ failure assessment score were significantly decreased(P<0.05)in the intervention group.However,LC3B,APTT,anti-Xa factor,and CD4/CD8 were significantly increased(P<0.05)in the intervention group.No significant differences in interleukin-6,tumour necrosis factor-α,d-dimer,acute physiology and chronic health evaluation II score,length of ICU stay,length of hospital stay,or 28-d survival were noted between the two groups(P>0.05).Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade.ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSION HPA has great potential as a diagnostic marker for S-AGI.Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms.The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.

Cancerous inhibitor of protein phosphatase 2A enhances chemoresistance of gastric cancer cells to oxaliplatin

BACKGROUND Cancerous inhibitor of protein phosphatase 2A(CIP2A)is a newly discovered oncogene.It is an active cell proliferation regulatory factor that inhibits tumor apoptosis in gastric cancer(GC)cells.CIP2A is functionally related to chemoresistance in various types of tumors according to recent studies.The underlying mechanism,however,is unknown.Further,the primary treatment regimen for GC is oxaliplatin-based chemotherapy.Nonetheless,it often fails due to chemoresistance of GC cells to oxaliplatin.AIM The goal of this study was to examine CIP2A expression and its association with oxaliplatin resistance in human GC cells.METHODS Immunohistochemistry was used to examine CIP2A expression in GC tissues and adjacent normal tissues.CIP2A expression in GC cell lines was reduced using small interfering RNA.After confirming the silencing efficiency,3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium and flow cytometry assays were used to evaluate cell proliferation and apoptosis caused by oxaliplatin treatment.Further,the key genes and protein changes were verified using realtime quantitative reverse transcription PCR and Western blotting,respectively,before and after intervention.For bioinformatics analysis,we used the R software and Bioconductor project.For statistical analysis,we used GraphPad Prism 6.0 and the Statistical Package for the Social Sciences software version 20.0(IBM,Armonk,United States).RESULTS A high level of CIP2A expression was associated with tumor size,T stage,lymph node metastasis,Tumor Node Metastasis stage,and a poor prognosis.Further,CIP2A expression was higher in GC cells than in normal human gastric epithelial cells.Using small interfering RNA against CIP2A,we discovered that CIP2A knockdown inhibited cell proliferation and significantly increased GC cell sensitivity to oxaliplatin.Moreover,CIP2A knockdown enhanced oxaliplatin-induced apoptosis in GC cells.Hence,high CIP2A levels in GC may be a factor in chemoresistance to oxaliplatin.In human GC cells,CIP2A regulated protein kinase B phosphorylation,and chemical inhibition of the protein kinase B signaling pathway was significantly associated with increased sensitivity to oxaliplatin.Therefore,the protein kinase B signaling pathway was correlated with CIP2Aenhanced chemoresistance of human GC cells to oxaliplatin.CONCLUSION CIP2A expression could be a novel therapeutic strategy for chemoresistance in GC.

A retrospective study on professor Gui-Qi Xuan’s experience in traditional Chinese medicine treatment on attention-deficit hyperactivity disorder: based on data mining and network pharmacology

Background:To investigate the clinical medication approach of Professor Guiqi Xuan(Prof.Xuan)in treating pediatric patients with attention-deficit hyperactivity disorder(ADHD)and the potential mechanism of the core herbal prescription.Methods:Following medical record information pretreatment,the Traditional Chinese Medicine(TCM)inheritance computing platform system V3.0 was utilized to analyze the standardized data.The associate rules were summarized to identify the core prescription for treating ADHD.The extracted core herbal prescription’s active compounds and potential targets were used to establish a protein-protein interaction network of active ingredient-disease targets.Cytoscape 3.9.1 software was used to analyze the network’s topological parameters to obtain the key active ingredients and their targets.The Bioconductor data package of R4.0.2 was used to analyze the gene ontology biological functions and Kyoto Encyclopedia of Genes and Genomes pathways of key targets.Results:Two hundred and twenty-seven entries derived from TCM record information were selected.Through data mining,it was found that 62.5%of pediatric patients had short-tempered behavior,nearly half had sleep problems,and 30%-40%had picky eating and polyphagia issues.The highest-frequency syndrome type was kidney deficiency and liver hyperactivity.Deficiency,fire,phlegm,and dyspeptic food were the main pathological factors for ADHD.Prof.Xuan’s treatment of ADHD mainly focused on replenishing kidney essence and subduing Yang(active,external,ascending,warm,bright,functional and excited pertain to Yang).The core herbal prescription for ADHD included Yuan-zhi,Yi-zhi,Gui-jia,Bai-shao,Long-chi,Ci-shi,Shi-chang-pu,Yu-jin,Fu-shen,and Huang-jing.The protein-protein interaction network showed that MAOA,ADRB2,FOS,MAOB,and SLC6A3 were the five key targets essential in treating ADHD with core herbal prescriptions.The gene ontology biological function of crucial targets mainly involved G protein-coupled amine receptor activity,catecholamine binding,and neurotransmitter transmembrane transporter activity.Analysis of Kyoto Encyclopedia of Genes and Genomes pathways showed that the dopaminergic synapse signaling and neuroactive ligand-receptor interaction pathways were significantly enriched and may be the primary routes for the main treatment of ADHD.Conclusion:Prof.Xuan’s treatment of ADHD has achieved satisfactory clinical effects by supplementing the kidney,replenishing the essence,opening the orifices,nourishing the Yin(static,internal,descending,cold,dim,organic,depressed and pertain to Yin),and subduing the Yang.The major prescription predominantly affects catecholamine binding,neuroactive ligand-receptor interaction,G protein-coupled amine receptor function,and signaling pathways for dopaminergic synapses.Our findings showed that the methodology and software used in this research could explore and analyze the mechanism behind Prof.Xuan’s clinical medication rule for treating ADHD in children.