AIM:To compare the diagnostic yield of capsule endoscopy (CE) with that of double-balloon enteroscopy (DBE). METHODS:Pubmed,Embase,Elsevier ScienceDirect,the China Academic Journals Full-text Database,and Cochrane Con...AIM:To compare the diagnostic yield of capsule endoscopy (CE) with that of double-balloon enteroscopy (DBE). METHODS:Pubmed,Embase,Elsevier ScienceDirect,the China Academic Journals Full-text Database,and Cochrane Controlled Trials Register were searched for the trials comparing the yield of CE with that of DBE. Outcome measure was odds ratio (OR) of the yield. Fixed or random model method was used for data analysis. RESULTS:Eight studies (n = 277) which prospectively compared the yield of CE and DBE were collected. The results of meta-analysis indicated that there was no difference between the yield of CE and DBE 170/277 vs 156/277,OR 1.21 (95% CI:0.64-2.29). Based on sub analysis,the yield of CE was significantly higher than that of double-balloon enteroscopy without combination of oral and anal insertion approaches 137/219 vs 110/219,OR 1.67 (95% CI:1.14-2.44),P < 0.01),but not superior to the yield of DBE with combination of the two insertion approaches 26/48 vs 37/48,OR 0.33 (95% CI:0.05-2.21),P > 0.05). A focused meta-analysis of the fully published articles concerning obscure GI bleeding was also performed and showed similar results wherein the yield of CE was significantly higher than that of DBE without combination of oral and anal insertion approaches 118/191 vs 96/191,fixed model:OR 1.61 (95% CI:1.07-2.43),P < 0.05) and the yield of CE was significantly lower than that of DBE by oral and anal combinatory approaches 11/24 vs 21/24,fixed model:OR 0.12 (95% CI:0.03-0.52),P < 0.01). CONCLUSION:With combination of oral and anal approaches,the yield of DBE might be at least as high asthat of CE. Decisions made regarding the initial approach should depend on patient's physical status,technology availability,patient's preferences,and potential for therapeutic endoscopy.展开更多
AIM To establish a classification method for differential diagnosis of colorectal ulcerative diseases, especially Crohn's disease(CD), primary intestinal lymphoma(PIL) and intestinal tuberculosis(ITB).METHODS We s...AIM To establish a classification method for differential diagnosis of colorectal ulcerative diseases, especially Crohn's disease(CD), primary intestinal lymphoma(PIL) and intestinal tuberculosis(ITB).METHODS We searched the in-patient medical record database for confirmed cases of CD, PIL and ITB from 2008 to 2015 at our center, collected data on endoscopic ultrasound(EUS) from randomly-chosen patients who formed the training set, conducted univariate logistic regression analysis to summarize EUS features of CD, PIL and ITB, and created a diagnostic classification method. All cases found to have colorectal ulcers using EUS were obtained from the endoscopy database and formed the test set. We then removed the cases which were easily diagnosed, and the remaining cases formed the perplexing test set. We re-diagnosed the cases in the three sets using the classification method, determined EUS diagnostic accuracies, and adjusted the classification accordingly. Finally, the re-diagnosing and accuracy-calculating steps were repeated.RESULTS In total, 272 CD, 60 PIL and 39 ITB cases were diagnosed from 2008 to 2015 based on the in-patient database, and 200 CD, 30 PIL and 20 ITB cases were randomly chosen to form the training set. The EUS features were summarized as follows: CD: Thickened submucosa with a slightly high echo level and visible layer; PIL: Absent layer and diffuse hypoechoic mass; and ITB: Thickened mucosa with a high or slightly high echo level and visible layer. The test set consisted of 77 CD, 30 PIL, 23 ITB and 140 cases of other diseases obtained from the endoscopy database. Seventy-four cases were excluded to form the perplexing test set. After adjustment of the classification, EUS diagnostic accuracies for CD, PIL and ITB were 83.6%(209/250), 97.2%(243/250) and 85.6%(214/250) in the training set, were 89.3%(241/270), 97.8%(264/270) and 84.1%(227/270) in the test set, and were 86.7%(170/196), 98.0%(192/196) and 85.2%(167/196) in the perplexing set, respectively.CONCLUSION The EUS features of CD, PIL and ITB are different. The diagnostic classification method is reliable in the differential diagnosis of colorectal ulcerative diseases.展开更多
BACKGROUND Hepatic steatosis commonly occurs in some chronic liver diseases and may affect disease progression.AIM To investigate the performance of controlled attenuation parameter(CAP)for the diagnosis of hepatic st...BACKGROUND Hepatic steatosis commonly occurs in some chronic liver diseases and may affect disease progression.AIM To investigate the performance of controlled attenuation parameter(CAP)for the diagnosis of hepatic steatosis in patients with autoimmune liver diseases(AILDs).METHODS Patients who were suspected of having AILDs and underwent liver biopsy were consistently enrolled.Liver stiffness measurement(LSM)and CAP were performed by transient elastography.The area under the receiver operating characteristic(AUROC)curve was used to evaluate the performance of CAP for diagnosing hepatic steatosis compared with biopsy.RESULTS Among 190 patients with biopsy-proven hepatic steatosis,69 were diagnosed with autoimmune hepatitis(AIH),18 with primary biliary cholangitis(PBC),and 27 with AIH-PBC overlap syndrome.The AUROCs of CAP for the diagnosis of steatosis in AILDS were 0.878(0.791-0.965)for S1,0.764(0.676-0.853)for S2,and 0.821(0.716-0.926)for S3.The CAP value was significantly related to hepatic steatosis grade(P<0.001).Among 69 patients with AIH,the median CAP score was 205.63±47.36 dB/m for S0,258.41±42.83 dB/m for S1,293.00±37.18 dB/m for S2,and 313.60±27.89 dB/m for S3.Compared with patients with nonalcoholic fatty liver disease(NAFLD)presenting with autoimmune markers,patients with AIH concomitant with NAFLD were much older and had higher serum IgG levels and LSM values.CONCLUSION CAP can be used as a noninvasive diagnostic method to evaluate hepatic steatosis in patients with AILDs.Determination of LSM combined with CAP may help to identify patients with AIH concomitant with NAFLD from those with NAFLD with autoimmune phenomena.展开更多
The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influe...The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various factors.This manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ICIs.Additionally,this study introduced a visual predictive model to estimate the prognosis of GC patients.If confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.展开更多
Acute appendicitis is a common surgical emergency.It is commonly caused by obstruction of the appendiceal lumen due to fecaliths,tumors,or lymphoid hyperplasia.For over a century,appendectomy has been the primary trea...Acute appendicitis is a common surgical emergency.It is commonly caused by obstruction of the appendiceal lumen due to fecaliths,tumors,or lymphoid hyperplasia.For over a century,appendectomy has been the primary treatment for acute appendicitis.Abraham Groves performed the first open appendectomy in 1883.In 1983,Kurt Semm completed the first laparoscopic appendectomy,heralding a new era in appendectomy.However,appendectomy is associated with certain complications and a rate of negative appendectomies.Studies have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson’s disease,but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer,gallstones,and cardiovascular disease.With the recognition that the appendix is not a vestigial organ and the advancement of endoscopic technology,Liu proposed the endoscopic retrograde appendicitis therapy.It is an effective minimally invasive alternative for treating uncomplicated acute appendicitis.Our team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of appendicitis.This article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment.展开更多
BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value...BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.展开更多
Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and im...Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.展开更多
BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylatio...BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.展开更多
BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CR...BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CRC.AIM To investigate the effect of indole-3-acetaldehyde(IAAD)on CRC.METHODS The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests.Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide.Invasiveness was investigated using the transwell assay.Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream genes.The PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String database.RESULTS IAAD reduced tumorigenesis in a syngeneic mouse model.In CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the nucleus.The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of AhR.IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells.At low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell invasion.In addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC;however,at high concentrations(≥25μmol/L),it can also promote epithelial-mesenchymal transition and invasion in CRC cells.IAAD activates AhR and directly binds MMP9,ACE,PARP1,MMP2,and MPO,which partly reveals why it has a bidirectional effect.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS)...BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.展开更多
BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the...BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.展开更多
Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained f...Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double c...BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double center retrospective study included 530 patients diagnosed with AIG from July 2019 to July 2023.We collected clinical,biochemical,serological,and demographic data were of each patient.Logistic regression analyses,both multivariate and univariate,were conducted to pinpoint independent risk factors for GPs in patients with AIG patients.Receiver operating characteristic curves were utilized to establish the optimal cutoff values,sensitivity,and specificity of these risk factors for predicting GPs in patients with AIG.RESULTS Patients with GPs had a higher median age than those without GPs[61(52.25-69)years vs 58(47-66)years,P=0.006].The gastrin-17 levels were significantly elevated in patients with GPs compared with those without GPs[91.9(34.2-138.9)pmol/mL vs 60.9(12.6-98.4)pmol/mL,P<0.001].Additionally,the positive rate of parietal cell antibody(PCA)antibody was higher in these patients than in those without GPs(88.6%vs 73.6%,P<0.001).Multivariate and univariate analyses revealed that PCA positivity[odds ratio(OR)=2.003,P=0.017],pepsinogen II(OR=1.053,P=0.015),and enterochromaffin like cells hyperplasia(OR=3.116,P<0.001)were significant risk factors for GPs,while pepsinogen I was identified as a protective factor.CONCLUSION PCA positivity and enterochromaffin like cells hyperplasia are significant risk factor for the development of GPs in patients with AIG.Elevated gastrin-17 levels may also play a role in this process.These findings suggest potential targets for further research and therapeutic intervention in managing GPs in patients with AIG.展开更多
AIM: To investigate the resistance of Helicobacter pylori (H. pylori ) to 6 commonly used antibiotics from 2000 to 2009 in Shanghai. METHODS: A total of 293 H. pylori strains were collected from 2000 to 2009 in Shangh...AIM: To investigate the resistance of Helicobacter pylori (H. pylori ) to 6 commonly used antibiotics from 2000 to 2009 in Shanghai. METHODS: A total of 293 H. pylori strains were collected from 2000 to 2009 in Shanghai and tested for their susceptibility to metronidazole, clarithromycin, amoxicillin, furazolidone, levofloxacin and tetracycline using agar dilution. RESULTS: The resistant rates of H. pylori to clarithromycin (8.6%, 9.0% and 20.7%) and levofloxacin (10.3%, 24.0% and 32.5%) increased from 2000 to 2009 in Shanghai. The resistant rate of H. pylori to metronidazole remained stable (40%-50%). Only one strain of H. pylori isolated in 2005 was resistant to tetracycline. All strains were sensitive to amoxicillin and furazolidone.The resistant rate of H. pylori to antibiotics was not related with the sex, age and clinical outcome of patients. CONCLUSION: Resistance of H. pylori to antibiotics plays an important role in making treatment strategies against H. pylori -associated diseases.展开更多
AIM To investigate the expression of multiplegenes and the behavior of cellular biology ingastric cancer(GC)and other gastric mucosallesions and their relations to Helicobacter pylori(H.pylori)infection,tumor stag...AIM To investigate the expression of multiplegenes and the behavior of cellular biology ingastric cancer(GC)and other gastric mucosallesions and their relations to Helicobacter pylori(H.pylori)infection,tumor staging andhistological subtypes.METHODS Three hundred and twenty-sevenspecimens of gastric mucosa obtained viaendoscopy or surgical resection,and ABCimmunohistochemical staining were used todetect the expression of p53,p16,Bcl-2 andCOX-2 proteins.H.pylori was determined byrapid urea test combined with pathologicalstaining or<sup>14</sup>C urea breath test.Cellular image analysis was performed in 66 patients withintestinal metaplasia(IM)and/or dysplasia(Dys).In 30 of them,both cancer and theparacancerous tissues were obtained at the timeof surgery.Histological pattern,tumor staging,lymph node metastasis,grading ofdifferentiation and other clinical data werestudied in the medical records.RESULTS p16 expression of IM or Dys wassignificantly lower in positive H.pylori chronicatrophic gastritis(CAG)than those withnegative H.pylori(CAG:54.8% vs 88.0%,IM:34.4% vs 69.6%,Dys:23.8% vs 53.6%,allP【0.05),Bcl-2 or COX-2 expression of IM orDys in positive H.pylori cases was significantlyhigher than that without H.pylori(Bcl-2:68.8%vs23.9%,90.5% vs 60.7%;COX-2:50.0% vs10.8%,61.8% vs 17.8%;all P【0.05).Themean number of most parameters of cellularimage analysis in positive H.pylori group wassignificantly higher than that in negative H.pylori group(Ellipser:53±14,40±12μm,Area<sub>1</sub>:748±572,302±202 μm<sup>2</sup>,Area<sub>2</sub>:3050±1661,1681±1990 μm<sup>2</sup>,all P【0.05;Ellipseb:79±23,58±15 μm,Ratio<sub>1</sub>:22%±5%,13%±4%,Ratio<sub>2</sub>:79%±17%,53%±20%,all P【0.01).There was significant correlation between Bcl-2and histologic pattern of gastric carcinoma,andbetween COX-2 and tumor staging or lymph nodemetastasis(Bcl-2:75.0% vs 16.7%;COX-2:76.0% vs 20.0%,79.2% vs 16.7%;allP【0.05).CONCLUSION p1l6, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/ progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infection. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.展开更多
Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive...Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.展开更多
AIM: To explore whether clinician-patient communication affects adherence to psychoactive drugs in functional dyspepsia(FD) patients with psychological symptoms. METHODS: A total of 262 FD patients with psychological ...AIM: To explore whether clinician-patient communication affects adherence to psychoactive drugs in functional dyspepsia(FD) patients with psychological symptoms. METHODS: A total of 262 FD patients with psychological symptoms were randomly assigned to four groups. The patients in Groups 1-3 were given flupentixol-melitracen(FM) plus omeprazole treatment. Those in Group 1 received explanations of both the psychological and gastrointestinal(GI) mechanisms of the generation of FD symptoms and the effects of FM. In Group 2, only the psychological mechanisms were emphasized. The patients in Group 3 were not given an explanation for the prescription of FM. Those in Group 4 were given omeprazole alone. The primary endpoints of this study were compliance rate and compliance index to FM in Groups 1-3. Survival analyses were also conducted. The secondary end points were dyspepsia and psychological symptom improvement in Groups 1-4. The correlations between the compliance indices and the reductions in dyspepsia and psychological symptom scores were also evaluated in Groups 1-3.RESULTS: After 8 wk of treatment, the compliance rates were 67.7% in Group 1, 42.4% in Group 2 and 47.7% in Group 3(Group 1 vs Group 2, P = 0.006; Group 1 vs Group 3, P = 0.033). The compliance index(Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.024) with the FM regimen was significantly higher in Group 1 than in Groups 2 and 3. The survival analysis revealed that the patients in Group 1 exhibited a significantlyhigher compliance rate than Groups 2 and 3(Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.018). The improvement in dyspepsia(Group 1 vs Group 2, P < 0.05; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01) and psychological symptom scores(anxiety: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01; depression: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.01; Group 1 vs Group 4, P < 0.01) in Group 1 were greater than those in Groups 2-4. The compliance indices were positively correlated with the reduction in symptom scores in Groups 1-3. CONCLUSION: Appropriate clinician-patient communication regarding the reasons for prescribing psychoactive drugs that emphasizes both the psychological and GI mechanisms might improve adherence to FM in patients with FD.展开更多
AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer.METHODS: A prospective study was con...AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer.METHODS: A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods.RESULTS: For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P < 0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P < 0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P < 0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P < 0.001; OLGIM: 83.6% vs 57.8%, P < 0.001).CONCLUSION: OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer.展开更多
AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web o...AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web of Knowledge.The clinical trials that compared the benefit of mosapride plus PPI treatment with that of PPI monotherapy were analyzed.The rate of responders was evaluated by the pooled relative risk(PRR)and improvement in symptom scores was assessed by single effect size of a standardized mean,while Hedges’g was used as the effect size.Pooled effect sizes with 95%CIs were calculated using a fixed-effects model.Between-study heterogeneity was assessed using Q test and I2analyses.In addition,studies that assessed the additional efficacy of mosapride in PPI-resistant patients were also reviewed.RESULTS:This systematic review included information on a total of 587 patients based on 7 trials.Four trials compared the efficacy of combination therapy of mosapride plus a PPI with that of PPI monotherapy.The statistical analysis for the effect of additional mosapride showed equivocal results(PRR=1.132;95%CI:0.934-1.372;P=0.205;Hedges’g=0.24;95%CI:0.03-0.46;P=0.023).No heterogeneity and publication bias were found among the studies.Three openlabeled trials assessed the additional efficacy of mosapride in PPI-resistant patients.However,since these trials did not set the control group,the results may be considerably biased.CONCLUSION:Mosapride combined therapy is not more effective than PPI alone as first-line therapy.Whether it is effective in PPI-resistant patients needs to be determined.展开更多
文摘AIM:To compare the diagnostic yield of capsule endoscopy (CE) with that of double-balloon enteroscopy (DBE). METHODS:Pubmed,Embase,Elsevier ScienceDirect,the China Academic Journals Full-text Database,and Cochrane Controlled Trials Register were searched for the trials comparing the yield of CE with that of DBE. Outcome measure was odds ratio (OR) of the yield. Fixed or random model method was used for data analysis. RESULTS:Eight studies (n = 277) which prospectively compared the yield of CE and DBE were collected. The results of meta-analysis indicated that there was no difference between the yield of CE and DBE 170/277 vs 156/277,OR 1.21 (95% CI:0.64-2.29). Based on sub analysis,the yield of CE was significantly higher than that of double-balloon enteroscopy without combination of oral and anal insertion approaches 137/219 vs 110/219,OR 1.67 (95% CI:1.14-2.44),P < 0.01),but not superior to the yield of DBE with combination of the two insertion approaches 26/48 vs 37/48,OR 0.33 (95% CI:0.05-2.21),P > 0.05). A focused meta-analysis of the fully published articles concerning obscure GI bleeding was also performed and showed similar results wherein the yield of CE was significantly higher than that of DBE without combination of oral and anal insertion approaches 118/191 vs 96/191,fixed model:OR 1.61 (95% CI:1.07-2.43),P < 0.05) and the yield of CE was significantly lower than that of DBE by oral and anal combinatory approaches 11/24 vs 21/24,fixed model:OR 0.12 (95% CI:0.03-0.52),P < 0.01). CONCLUSION:With combination of oral and anal approaches,the yield of DBE might be at least as high asthat of CE. Decisions made regarding the initial approach should depend on patient's physical status,technology availability,patient's preferences,and potential for therapeutic endoscopy.
文摘AIM To establish a classification method for differential diagnosis of colorectal ulcerative diseases, especially Crohn's disease(CD), primary intestinal lymphoma(PIL) and intestinal tuberculosis(ITB).METHODS We searched the in-patient medical record database for confirmed cases of CD, PIL and ITB from 2008 to 2015 at our center, collected data on endoscopic ultrasound(EUS) from randomly-chosen patients who formed the training set, conducted univariate logistic regression analysis to summarize EUS features of CD, PIL and ITB, and created a diagnostic classification method. All cases found to have colorectal ulcers using EUS were obtained from the endoscopy database and formed the test set. We then removed the cases which were easily diagnosed, and the remaining cases formed the perplexing test set. We re-diagnosed the cases in the three sets using the classification method, determined EUS diagnostic accuracies, and adjusted the classification accordingly. Finally, the re-diagnosing and accuracy-calculating steps were repeated.RESULTS In total, 272 CD, 60 PIL and 39 ITB cases were diagnosed from 2008 to 2015 based on the in-patient database, and 200 CD, 30 PIL and 20 ITB cases were randomly chosen to form the training set. The EUS features were summarized as follows: CD: Thickened submucosa with a slightly high echo level and visible layer; PIL: Absent layer and diffuse hypoechoic mass; and ITB: Thickened mucosa with a high or slightly high echo level and visible layer. The test set consisted of 77 CD, 30 PIL, 23 ITB and 140 cases of other diseases obtained from the endoscopy database. Seventy-four cases were excluded to form the perplexing test set. After adjustment of the classification, EUS diagnostic accuracies for CD, PIL and ITB were 83.6%(209/250), 97.2%(243/250) and 85.6%(214/250) in the training set, were 89.3%(241/270), 97.8%(264/270) and 84.1%(227/270) in the test set, and were 86.7%(170/196), 98.0%(192/196) and 85.2%(167/196) in the perplexing set, respectively.CONCLUSION The EUS features of CD, PIL and ITB are different. The diagnostic classification method is reliable in the differential diagnosis of colorectal ulcerative diseases.
基金Supported by National Natural Science Foundation of China,No.81470842 and No.81770572.
文摘BACKGROUND Hepatic steatosis commonly occurs in some chronic liver diseases and may affect disease progression.AIM To investigate the performance of controlled attenuation parameter(CAP)for the diagnosis of hepatic steatosis in patients with autoimmune liver diseases(AILDs).METHODS Patients who were suspected of having AILDs and underwent liver biopsy were consistently enrolled.Liver stiffness measurement(LSM)and CAP were performed by transient elastography.The area under the receiver operating characteristic(AUROC)curve was used to evaluate the performance of CAP for diagnosing hepatic steatosis compared with biopsy.RESULTS Among 190 patients with biopsy-proven hepatic steatosis,69 were diagnosed with autoimmune hepatitis(AIH),18 with primary biliary cholangitis(PBC),and 27 with AIH-PBC overlap syndrome.The AUROCs of CAP for the diagnosis of steatosis in AILDS were 0.878(0.791-0.965)for S1,0.764(0.676-0.853)for S2,and 0.821(0.716-0.926)for S3.The CAP value was significantly related to hepatic steatosis grade(P<0.001).Among 69 patients with AIH,the median CAP score was 205.63±47.36 dB/m for S0,258.41±42.83 dB/m for S1,293.00±37.18 dB/m for S2,and 313.60±27.89 dB/m for S3.Compared with patients with nonalcoholic fatty liver disease(NAFLD)presenting with autoimmune markers,patients with AIH concomitant with NAFLD were much older and had higher serum IgG levels and LSM values.CONCLUSION CAP can be used as a noninvasive diagnostic method to evaluate hepatic steatosis in patients with AILDs.Determination of LSM combined with CAP may help to identify patients with AIH concomitant with NAFLD from those with NAFLD with autoimmune phenomena.
基金Supported by National Nature Science Foundation of China,No.82320108022Shanghai Rising-Star Program,No.21QA1409000Shanghai Frontier Research Base of Disease and Syndrome Biology of Inflammatory Cancer Transformation,No.2021KJ03-12.
文摘The emergence of immunotherapy,particularly immune checkpoint inhibitors(ICIs),represents a groundbreaking approach to treating gastric cancer(GC).However,the prognosis of GC patients receiving ICI treatment is influenced by various factors.This manuscript identified sarcopenia and myosteatosis as independent prognostic factors impacting the outcomes of GC patients treated with ICIs.Additionally,this study introduced a visual predictive model to estimate the prognosis of GC patients.If confirmed by further studies,this observation could provide valuable insights to propel the advancement of personalized clinical medicine and the integration of precision medicine practices.
基金Supported by the Construction Fund of Key Medical Disciplines of Hangzhou,No.0020200026Key R&D Program of Zhejiang Province,No.2023C03054.
文摘Acute appendicitis is a common surgical emergency.It is commonly caused by obstruction of the appendiceal lumen due to fecaliths,tumors,or lymphoid hyperplasia.For over a century,appendectomy has been the primary treatment for acute appendicitis.Abraham Groves performed the first open appendectomy in 1883.In 1983,Kurt Semm completed the first laparoscopic appendectomy,heralding a new era in appendectomy.However,appendectomy is associated with certain complications and a rate of negative appendectomies.Studies have suggested controversy over the impact of appendectomy on the development of inflammatory bowel disease and Parkinson’s disease,but an increasing number of studies indicate a possible positive correlation between appendectomy and colorectal cancer,gallstones,and cardiovascular disease.With the recognition that the appendix is not a vestigial organ and the advancement of endoscopic technology,Liu proposed the endoscopic retrograde appendicitis therapy.It is an effective minimally invasive alternative for treating uncomplicated acute appendicitis.Our team has developed an appendoscope with a disposable digital imaging system operated through the biopsy channel of a colonoscope and successfully applied it in the treatment of appendicitis.This article provides an overview of the progress in endoscopic treatment for acute appendicitis and offers a new perspective on the future direction of appendiceal disease treatment.
基金Supported by National Nature Science Foundation of China,No.82060450,No.82360517,No.81460374,and No.31460304Nature Science Foundation of Jiangxi Province of China,No.20232BAB206086,No.20192BAB205072,No.20203BBGL73206,No.2017BCB23086,No.2017BAB205062,and No.20181BAB205050.
文摘BACKGROUND The TGF-β/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis.SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer.AIM To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer.METHODS This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years(median age 65)between July 2006 and April 2007.Patients were followed up until death or the study ended(median follow-up duration of 28.5 mo).The samples were used to generate tissue microarrays(TMAs)for immunohistochemical(IHC)staining.The expressions of TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 in gastric cancer(GC)tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients.Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015.The relationship between TGF-β1,pSMAD3C(S423/425),pSMAD3L(S204),and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient.The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test.A survival curve was generated using the Kaplan-Meier survival analysis.RESULTS TGFβ-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent noncancerous tissue.The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site[pSMAD3C(S423/425):51.0%and pSMAD3L(S204):31.6%].High expression of pSMAD-3L(S204)was significantly correlated with larger tumors(P=0.038)and later N stages(P=0.035).Additionally,high expression of VEGFR-1 was closely correlated with tumor size(P=0.015)and pathological grading(P=0.013).High expression of both pSMAD3L(S204)and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival(OS).Multivariate analysis indicated that high expression of pSMAD3L(S204)and VEGFR-1 were independent risk factors for prognosis in GC patients.VEGFR-1 protein expression was correlated with TGF-β1(r=0.220,P=0.029),pSMAD3C(S423/425)(r=0.302,P=0.002),and pSMAD3L(S204)(r=0.201,P=0.047),respectively.Simultaneous overexpression of pSMAD3L(S204)and VEGFR-1 was associated with poor OS in gastric cancer patients.CONCLUSION Co-upregulation of pSMAD3L(S204)and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis,and pSMAD3L(204)may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.
基金Supported by National Natural Science Foundation of China,No.82320108022,No.82322076 and No.82104466.
文摘Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.
文摘BACKGROUND Both N6-methyladenosine(m6A)methylation and autophagy are considered relevant to the pathogenesis of ulcerative colitis(UC).However,a systematic exploration of the role of the com-bination of m6A methylation and autophagy in UC remains to be performed.AIM To elucidate the autophagy-related genes of m6A with a diagnostic value for UC.METHODS The correlation between m6A-related genes and autophagy-related genes(ARGs)was analyzed.Finally,gene set enrichment analysis(GSEA)was performed on the characteristic genes.Additionally,the expression levels of four characteristic genes were verified in dextran sulfate sodium(DSS)-induced colitis in mice.RESULTS GSEA indicated that BAG3,P4HB and TP53INP2 were involved in the inflammatory response and TNF-αsignalling via nuclear factor kappa-B.Furthermore,polymerase chain reaction results showed significantly higher mRNA levels of BAG3 and P4HB and lower mRNA levels of FMR1 and TP53INP2 in the DSS group compared to the control group.CONCLUSION This study identified four m6A-ARGs that predict the occurrence of UC,thus providing a scientific reference for further studies on the pathogenesis of UC.
基金Supported by Zhejiang Provincial Natural Science Foundation of China,No.LTGD23C040008,No.LBY23H200006,and No.LQ22H030004.
文摘BACKGROUND Colorectal cancer(CRC)has a high incidence and mortality.Recent studies have shown that indole derivatives involved in gut microbiota metabolism can impact the tumorigenesis,progression,and metastasis of CRC.AIM To investigate the effect of indole-3-acetaldehyde(IAAD)on CRC.METHODS The effect of IAAD was evaluated in a syngeneic mouse model of CRC and CRC cell lines(HCT116 and DLD-1).Cell proliferation was assessed by Ki-67 fluorescence staining and cytotoxicity tests.Cell apoptosis was analysed by flow cytometry after staining with Annexin V-fluorescein isothiocyanate and propidium iodide.Invasiveness was investigated using the transwell assay.Western blotting and real-time fluorescence quantitative polymerase chain reaction were performed to evaluate the expression of epithelial-mesenchymal transition related genes and aryl hydrocarbon receptor(AhR)downstream genes.The PharmMapper,SEA,and SWISS databases were used to screen for potential target proteins of IAAD,and the core proteins were identified through the String database.RESULTS IAAD reduced tumorigenesis in a syngeneic mouse model.In CRC cell lines HCT116 and DLD1,IAAD exhibited cytotoxicity starting at 24 h of treatment,while it reduced Ki67 expression in the nucleus.The results of flow cytometry showed that IAAD induced apoptosis in HCT116 cells but had no effect on DLD1 cells,which may be related to the activation of AhR.IAAD can also increase the invasiveness and epithelial-mesenchymal transition of HCT116 and DLD1 cells.At low concentrations(<12.5μmol/L),IAAD only exhibited cytotoxic effects without promoting cell invasion.In addition,predictions based on online databases,protein-protein interaction analysis,and molecular docking showed that IAAD can bind to matrix metalloproteinase-9(MMP9),angiotensin converting enzyme(ACE),poly(ADP-ribose)polymerase-1(PARP1),matrix metalloproteinase-2(MMP2),and myeloperoxidase(MPO).CONCLUSION Indole-3-aldehyde can induce cell apoptosis and inhibit cell proliferation to prevent the occurrence of CRC;however,at high concentrations(≥25μmol/L),it can also promote epithelial-mesenchymal transition and invasion in CRC cells.IAAD activates AhR and directly binds MMP9,ACE,PARP1,MMP2,and MPO,which partly reveals why it has a bidirectional effect.
基金Supported by Hebei Traditional Chinese Medicine Scientific Research Project,No.2023223.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a global popular malignant tumor,which is difficult to cure,and the current treatment is limited.AIM To analyze the impacts of stress granule(SG)genes on overall survival(OS),survival time,and prognosis in HCC.METHODS The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma(TCGA-LIHC),GSE25097,and GSE36376 datasets were utilized to obtain genetic and clinical information.Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach,and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression,respectively.The prognostic model’s receiver operating characteristic(ROC)curve was produced and plotted utilizing the time ROC software package.Nomogram models were constructed to predict the outcomes at 1,3,and 5-year OS prognostications with good prediction accuracy.RESULTS We identified seven SG genes(DDX1,DKC1,BICC1,HNRNPUL1,CNOT6,DYRK3,CCDC124)having a prognostic significance and developed a risk score model.The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group(P<0.001).The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort.Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle,RNA editing,and other biological processes.CONCLUSION Based on the impact of SG genes on HCC prognosis,in the future,it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.
基金Supported by The Medical and Health Research Project of Zhejiang Province,No.2023KY1105the Traditional Chinese Medical and Health Research Project of Zhejiang Province,No.2022ZB328.
文摘BACKGROUND Intrahepatic cholestasis of pregnancy(ICP)is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy.Short-chain fatty acids(SCFAs),prominent metabolites of the gut microbiota,have significant connections with various pregnancy complications,and some SCFAs hold potential for treating such complications.However,the metabolic profile of SCFAs in patients with ICP remains unclear.AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings.METHODS Maternal serum and cord blood samples were collected from both patients with ICP(ICP group)and normal pregnant women(NP group).Targeted metabolomics was used to assess the SCFA levels in these samples.RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups.Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group,mirroring the pattern seen in maternal serum.Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs[r(Pearson)=0.88,P=7.93e-95].In both maternal serum and cord blood,acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups(variable importance for the projection>1).Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP,with caproic acid exhibiting the highest diagnostic efficacy(area under the curve=0.97).CONCLUSION Compared with the NP group,significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group,although they displayed distinct patterns of change.Furthermore,the SCFA levels in maternal serum and cord blood were significantly positively correlated.Notably,certain maternal serum SCFAs,specifically caproic and acetic acids,demonstrated excellent diagnostic efficiency for ICP.
基金supported by grants from Zhejiang Provincial Ten-Thousand Talents Plan(grant number:2021R52020)the Horizon 2020 Program of the European Union(grant number:856620).
文摘Objective:To provide the most up-to-date data on the burden of malignant mesothelioma(MM)and the projections through 2029 in China.Methods:Data on patients diagnosed with MM from China during 1990-2019 were obtained from the Global Burden of Disease(GBD)2019 database,including annual cases and deaths data and age-standardized rates of incidence,mortality,and disability-adjusted life-years(DALYs)associated with MM among different age groups.Temporal trends during 1990-2019 were analyzed by the Joinpoint regression models using 95%confidence interval(CI),while the projections through 2029 were calculated by the Bayesian age-period-cohort model.Data on the production and consumption of asbestos in China were obtained from the United States Geological Survey on Mineral Commodity Summaries during 1996-2023.Results:We observed a significant elevation in incident new cases and deaths over the last 3 decades,increasing from 1193 in 1990 to 2815 in 2019 for incident cases and from 1134 in 1990 to 2773 in 2019 for death cases.We found a roughly 6%increase in the proportion of incident cases for those aged>70 years(30%in 2019 versus 24%in 1990),while for the proportion of deaths similar elevation for those aged>70 years was found.Additionally,men had significantly higher DALYs due to MM across age groups compared with women.Asbestos consumption in China dramatically dropped since 2012 and reached the bottom in 2017 with 230 kilotons.By 2029,the projected age-standardized rate for incidence and mortality is expected to reach 1.2 per million for both.Conclusion:We found,for the first time using GBD data on the Chinese population,that the burden of MM has been significantly increasing in China over the last three decades and will continue to increase in the upcoming decade,suggesting an urgent need for a complete ban on chrysotile asbestos in China.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
基金Supported by the Health Technology Project of Pudong New District Health Commission,No.PW2020D-12.
文摘BACKGROUND The relationship between autoimmune gastritis(AIG)and gastric polyps(GPs)is not well understood.AIM To explore the clinical characteristics and risk factors of AIG with GPs in patients.METHODS This double center retrospective study included 530 patients diagnosed with AIG from July 2019 to July 2023.We collected clinical,biochemical,serological,and demographic data were of each patient.Logistic regression analyses,both multivariate and univariate,were conducted to pinpoint independent risk factors for GPs in patients with AIG patients.Receiver operating characteristic curves were utilized to establish the optimal cutoff values,sensitivity,and specificity of these risk factors for predicting GPs in patients with AIG.RESULTS Patients with GPs had a higher median age than those without GPs[61(52.25-69)years vs 58(47-66)years,P=0.006].The gastrin-17 levels were significantly elevated in patients with GPs compared with those without GPs[91.9(34.2-138.9)pmol/mL vs 60.9(12.6-98.4)pmol/mL,P<0.001].Additionally,the positive rate of parietal cell antibody(PCA)antibody was higher in these patients than in those without GPs(88.6%vs 73.6%,P<0.001).Multivariate and univariate analyses revealed that PCA positivity[odds ratio(OR)=2.003,P=0.017],pepsinogen II(OR=1.053,P=0.015),and enterochromaffin like cells hyperplasia(OR=3.116,P<0.001)were significant risk factors for GPs,while pepsinogen I was identified as a protective factor.CONCLUSION PCA positivity and enterochromaffin like cells hyperplasia are significant risk factor for the development of GPs in patients with AIG.Elevated gastrin-17 levels may also play a role in this process.These findings suggest potential targets for further research and therapeutic intervention in managing GPs in patients with AIG.
基金Supported by National Natural Science Foundation of China,No. 30770112Shanghai Leading Academic Discipline Project, No. Y0205
文摘AIM: To investigate the resistance of Helicobacter pylori (H. pylori ) to 6 commonly used antibiotics from 2000 to 2009 in Shanghai. METHODS: A total of 293 H. pylori strains were collected from 2000 to 2009 in Shanghai and tested for their susceptibility to metronidazole, clarithromycin, amoxicillin, furazolidone, levofloxacin and tetracycline using agar dilution. RESULTS: The resistant rates of H. pylori to clarithromycin (8.6%, 9.0% and 20.7%) and levofloxacin (10.3%, 24.0% and 32.5%) increased from 2000 to 2009 in Shanghai. The resistant rate of H. pylori to metronidazole remained stable (40%-50%). Only one strain of H. pylori isolated in 2005 was resistant to tetracycline. All strains were sensitive to amoxicillin and furazolidone.The resistant rate of H. pylori to antibiotics was not related with the sex, age and clinical outcome of patients. CONCLUSION: Resistance of H. pylori to antibiotics plays an important role in making treatment strategies against H. pylori -associated diseases.
基金the Natural Science Foundation of the Educational Committee of Jiangsu Province,No.125FA9608.
文摘AIM To investigate the expression of multiplegenes and the behavior of cellular biology ingastric cancer(GC)and other gastric mucosallesions and their relations to Helicobacter pylori(H.pylori)infection,tumor staging andhistological subtypes.METHODS Three hundred and twenty-sevenspecimens of gastric mucosa obtained viaendoscopy or surgical resection,and ABCimmunohistochemical staining were used todetect the expression of p53,p16,Bcl-2 andCOX-2 proteins.H.pylori was determined byrapid urea test combined with pathologicalstaining or<sup>14</sup>C urea breath test.Cellular image analysis was performed in 66 patients withintestinal metaplasia(IM)and/or dysplasia(Dys).In 30 of them,both cancer and theparacancerous tissues were obtained at the timeof surgery.Histological pattern,tumor staging,lymph node metastasis,grading ofdifferentiation and other clinical data werestudied in the medical records.RESULTS p16 expression of IM or Dys wassignificantly lower in positive H.pylori chronicatrophic gastritis(CAG)than those withnegative H.pylori(CAG:54.8% vs 88.0%,IM:34.4% vs 69.6%,Dys:23.8% vs 53.6%,allP【0.05),Bcl-2 or COX-2 expression of IM orDys in positive H.pylori cases was significantlyhigher than that without H.pylori(Bcl-2:68.8%vs23.9%,90.5% vs 60.7%;COX-2:50.0% vs10.8%,61.8% vs 17.8%;all P【0.05).Themean number of most parameters of cellularimage analysis in positive H.pylori group wassignificantly higher than that in negative H.pylori group(Ellipser:53±14,40±12μm,Area<sub>1</sub>:748±572,302±202 μm<sup>2</sup>,Area<sub>2</sub>:3050±1661,1681±1990 μm<sup>2</sup>,all P【0.05;Ellipseb:79±23,58±15 μm,Ratio<sub>1</sub>:22%±5%,13%±4%,Ratio<sub>2</sub>:79%±17%,53%±20%,all P【0.01).There was significant correlation between Bcl-2and histologic pattern of gastric carcinoma,andbetween COX-2 and tumor staging or lymph nodemetastasis(Bcl-2:75.0% vs 16.7%;COX-2:76.0% vs 20.0%,79.2% vs 16.7%;allP【0.05).CONCLUSION p1l6, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/ progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infection. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.
基金Supported by Collaborative Research Fund(CUHK3/CRF/12RHKU3/CRF11R)of the Research Grant Council Hong Kong+2 种基金National Basic Research Program of China,973 Program,No.2013CB531401CUHK Focused Investments Scheme B to HY LanTheme-based Research Scheme of the Hong Kong Re-search Grants Council,No.T12-403-11
文摘Chronic hepatitis B(CHB)virus infection is a global public health problem,affecting more than 400 million people worldwide.The clinical spectrum is wide,ranging from a subclinical inactive carrier state,to progressive chronic hepatitis,cirrhosis,decompensation,and hepatocellular carcinoma.However,complications of hepatitis B virus(HBV)-related chronic liver disease may be reduced by viral suppression.Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon,entecavir,or tenofovir,but the optimal treatment for an individualpatient is controversial.The indications for treatment are contentious,and increasing evidence suggests that HBV genotyping,as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response.The likelihood of achieving a sustained virological response is also increased by extending treatment duration,and using combination therapy.Hence the paradigm for treatment of CHB is constantly evolving.This article summarizes the different indications for treatment,and systematically reviews the evidence for the efficacy of various antiviral agents.It further discusses the shortcomings of current guidelines,use of rescue therapy in drug-resistant strains of HBV,and highlights the promising clinical trials for emerging therapies in the pipeline.This concise overview presents an updated practical approach to guide the clinical management of CHB.
基金Supported by National Natural Science Foundation of China,No.81470812,No.81270463,No.31171106,and No.81070302(to Chen SL)
文摘AIM: To explore whether clinician-patient communication affects adherence to psychoactive drugs in functional dyspepsia(FD) patients with psychological symptoms. METHODS: A total of 262 FD patients with psychological symptoms were randomly assigned to four groups. The patients in Groups 1-3 were given flupentixol-melitracen(FM) plus omeprazole treatment. Those in Group 1 received explanations of both the psychological and gastrointestinal(GI) mechanisms of the generation of FD symptoms and the effects of FM. In Group 2, only the psychological mechanisms were emphasized. The patients in Group 3 were not given an explanation for the prescription of FM. Those in Group 4 were given omeprazole alone. The primary endpoints of this study were compliance rate and compliance index to FM in Groups 1-3. Survival analyses were also conducted. The secondary end points were dyspepsia and psychological symptom improvement in Groups 1-4. The correlations between the compliance indices and the reductions in dyspepsia and psychological symptom scores were also evaluated in Groups 1-3.RESULTS: After 8 wk of treatment, the compliance rates were 67.7% in Group 1, 42.4% in Group 2 and 47.7% in Group 3(Group 1 vs Group 2, P = 0.006; Group 1 vs Group 3, P = 0.033). The compliance index(Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.024) with the FM regimen was significantly higher in Group 1 than in Groups 2 and 3. The survival analysis revealed that the patients in Group 1 exhibited a significantlyhigher compliance rate than Groups 2 and 3(Group 1 vs Group 2, P = 0.002; Group 1 vs Group 3, P = 0.018). The improvement in dyspepsia(Group 1 vs Group 2, P < 0.05; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01) and psychological symptom scores(anxiety: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.05; Group 1 vs Group 4, P < 0.01; depression: Group 1 vs Group 2, P < 0.01; Group 1 vs Group 3, P < 0.01; Group 1 vs Group 4, P < 0.01) in Group 1 were greater than those in Groups 2-4. The compliance indices were positively correlated with the reduction in symptom scores in Groups 1-3. CONCLUSION: Appropriate clinician-patient communication regarding the reasons for prescribing psychoactive drugs that emphasizes both the psychological and GI mechanisms might improve adherence to FM in patients with FD.
文摘AIM: To assess the predictive value of Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) stages in gastric cancer.METHODS: A prospective study was conducted with 71 patients with early gastric cancer (EGC) and 156 patients with non-EGC. All patients underwent endoscopic examination and systematic biopsy. Outcome measures were assessed and compared, including the Japanese endoscopic gastric atrophy (EGA) classification method and the modified OLGA method as well as the modified OLGIM method. Helicobacter pylori (H. pylori) status was determined for all study participants. Stepwise logistic regression modeling was performed to analyze correlations between EGC and the EGA, OLGA and OLGIM methods.RESULTS: For patients with EGC and patients with non-EGC, the proportions of moderate-to-severe EGA cases were 64.8% and 44.9%, respectively (P = 0.005), the proportions of OLGA stages III-IV cases were 52.1% and 22.4%, respectively (P < 0.001), and the proportions of OLGIM stages III-IV cases were 42.3% and 19.9%, respectively (P < 0.001). OLGA stage and OLGIM stage were significantly related to EGA classification; specifically, logistic regression modeling showed significant correlations between EGC and moderate-to-severe EGA (OR = 1.95, 95% CI: 1.06-3.58, P = 0.031) and OLGA stages III-IV (OR = 3.14, 95%CI: 1.71-5.81, P < 0.001), but no significant correlation between EGC and OLGIM stages III-IV (P = 0.781). H. pylori infection rate was significantly higher in patients with moderate-to-severe EGA (75.0% vs 54.1%, P = 0.001) or OLGA/OLGIM stages III-IV (OLGA: 83.6% vs 55.8%, P < 0.001; OLGIM: 83.6% vs 57.8%, P < 0.001).CONCLUSION: OLGA classification is optimal for EGC screening. A surveillance program including OLGA stage and H. pylori infection status may facilitate early detection of gastric cancer.
基金Supported by National Natural Science Foundation of China,No.31171106,No.81070302 and No.81270463
文摘AIM:To assess the potential benefits of mosapride plus proton pump inhibitors(PPIs)in the treatment of gastroesophageal reflux disease.METHODS:A literature search was performed through MEDLINE,EMBASE,and the ISI Web of Knowledge.The clinical trials that compared the benefit of mosapride plus PPI treatment with that of PPI monotherapy were analyzed.The rate of responders was evaluated by the pooled relative risk(PRR)and improvement in symptom scores was assessed by single effect size of a standardized mean,while Hedges’g was used as the effect size.Pooled effect sizes with 95%CIs were calculated using a fixed-effects model.Between-study heterogeneity was assessed using Q test and I2analyses.In addition,studies that assessed the additional efficacy of mosapride in PPI-resistant patients were also reviewed.RESULTS:This systematic review included information on a total of 587 patients based on 7 trials.Four trials compared the efficacy of combination therapy of mosapride plus a PPI with that of PPI monotherapy.The statistical analysis for the effect of additional mosapride showed equivocal results(PRR=1.132;95%CI:0.934-1.372;P=0.205;Hedges’g=0.24;95%CI:0.03-0.46;P=0.023).No heterogeneity and publication bias were found among the studies.Three openlabeled trials assessed the additional efficacy of mosapride in PPI-resistant patients.However,since these trials did not set the control group,the results may be considerably biased.CONCLUSION:Mosapride combined therapy is not more effective than PPI alone as first-line therapy.Whether it is effective in PPI-resistant patients needs to be determined.