Plant-based dietary patterns and risk of esophageal cancer:A prospective cohort study spanning 17 years

Objective: Plant-based diets have multiple health benefits for cancers;however, little is known about the association between plant-based dietary patterns and esophageal cancer(EC).This study presents an investigation of the prospective associations among three predefined indices of plant-based dietary patterns and the risk of EC.Methods: We performed endoscopic screening for 15,709 participants aged 40-69 years from two high-risk areas of China from January 2005 to December 2009 and followed the cohort until December 31, 2022. The overall plant-based diet index(PDI), healthful plant-based diet index(h PDI), and unhealthful plant-based diet index(u PDI), were calculated using survey responses to assess dietary patterns. We applied Cox proportional hazard regression to estimate the multivariable hazard ratios(HRs) and 95% confidence intervals(95% CIs) of EC across 3plant-based diet indices and further stratified the analysis by subgroups.Results: The final study sample included 15,184 participants in the cohort. During a follow-up of 219,365person-years, 176 patients with EC were identified. When the highest quartile was compared with the lowest quartile, the pooled multivariable-adjusted HR of EC was 0.50(95% CI, 0.32-0.77) for h PDI. In addition, the HR per 10-point increase in the h PDI score was 0.42(95% CI, 0.27-0.66) for ECs. Conversely, u PDI was positively associated with the risk of EC, and the HR was 1.80(95% CI, 1.16-2.82). The HR per 10-point increase in the u PDI score was 1.90(95% CI, 1.26-2.88) for ECs. The associations between these scores and the risk of EC were consistent in most subgroups. These results remained robust in sensitivity analyses.Conclusions: A healthy plant-based dietary pattern was associated with a reduced risk of EC. Emphasizing the healthiness and quality of plant-based diets may be important for preventing the development of EC.

Association of frailty and malnutrition with overall survival in adults with gastrointestinal cancer:A prospective cohort study

Background:Themortality burden of patients with gastrointestinalmalignancies is increasing worldwide,suggesting the need formore effective prognostic indicators.This study utilized a prospective cohort to(1)analyze the relationship between frailty and malnutrition and their association with the overall survival(OS)in adults with gastrointestinal cancer and(2)explore which specific frailty-related factors most significantly affect the OS.Methods:Participants diagnosed with gastrointestinal cancer from 2013 to 2018 who were enrolled in the Investigation on Nutrition Status and Clinical Outcome of Common Cancers study were identified.Malnutrition was determined using the Patient-Generated Subjective Global Assessment,whereas frailty was assessed using the FRAIL scale.The main outcome measured was the all-cause mortality.Multivariable-adjusted logistic regression was used to analyze the cross-sectional link between the nutritional status and frailty.Univariate and multivariate Cox regression analyses were conducted to explore the longitudinal association of these with the OS.Results:Among the 4,361 patients enrolled in the study,1,136 deaths were observed over a median follow-up of 43.4 months.Malnourished patients had a significantly higher risk of frailty than well-nourished patients(OR=6.25,95%CI=5.23–7.51).Frailty and malnutrition independently predicted the OS,with frailty showing an HR of 1.50(95%CI=1.33–1.69)and malnutrition showing an HR of 1.51(95%CI=1.31–1.74).Patientswith both frailty andmalnutrition had the highest all-causemortality risk(HR=1.82,95%CI=1.55–2.14)compared with patients with neither risk factor.Mortality rates rose with the accumulation of additional frailty-related factors.Conclusions:Malnutrition and frailty are interrelated prognostic factors in patients with gastrointestinalmalignancies,and their simultaneous presence worsens the patient outcomes.Higher scores for resistance and ambulation are major factors associated with a poorer outcome.Future large-scale prospective studies with repeated measurements are necessary to further explore the complex associations among frailty,malnutrition,and the prognosis in patients with gastrointestinal cancer.

Development of diabetic complications and influencing factors among 32653 type 2 diabetes patients:retrospective cohort study using a multi-state Markov

Background:Patients with type 2 diabetes are at high risk for developing multiple chronic complications.However,there is a lack of studies of the cumulative number of diabetic complications in China.Methods:A retrospective cohort study was performed from 2009 to 2021.Type 2 diabetes patients who were first diagnosed after the age of 35 years between January 1,2009,and December 31,2017,were included.Five states were defined according to the number of chronic complications:no(S0),one(S1),two(S2),three(S3),and four or more complications(S4).A multi-state Markov model was constructed to estimate transition probability,transition intensity,mean sojourn time,and the possible factors for each state.Results:The study included 32653 type 2 diabetes patients(mean age,59.59 years;15929(48.8%)male),and mean follow-up time of 7.75 years.In all,4375 transitions were observed.The 12-year transition probability of from state S0 to S1 was the lowest at 16.4%,while that from S2 to S3 was the highest,at 45.6%.Higher fasting blood glucose,lower high-density lipoprotein cholesterol,higher total cholesterol,and an unhealthy diet were associated with higher risk of progression from S0 to S1.Being female,less than 60 years old,weekly physical activity,and vegetarian diet decreased this risk.Being female and less than 60 years old reduced the likelihood of transition from S1 to S2,whereas lower high-density lipoprotein cholesterol increased this likelihood.Conclusions:Following the occurrence of two complications in type 2 diabetes patients,the risk for accumulating a third complication within a short time is significantly increased.It is important to take advantage of the stable window period when patients have fewer than two complications,strengthen the monitoring of blood glucose and blood lipids,and encourage patients to maintain good living habits to prevent further deterioration.

Real-world 10-year retrospective study of the guidelines for diagnosis and treatment of primary liver cancer in China

BACKGROUND Hepatocellular carcinoma(HCC) is a common malignant tumor worldwide. Many regions across the world have issued various HCC diagnosis and treatment protocols to improve the diagnosis and targeted treatment of patients with HCC. However, real-world studies analysing the practice, application value, and existing problems of the China Liver Cancer(CNLC) staging system are scarce.AIM To analyze the current situation and problems associated with the Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China.METHODS We collected the medical records of all patients with HCC admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2011 to December 31, 2019, and recorded the hospitalization information of those patients until December 31, 2020. All information on the diagnosis and treatment of the target patients was recorded, and their demographic and sociological characteristics, CNLC stages, screening situations, and treatment methods and effects were analyzed. The survival status of the patients was obtained from follow-up data.RESULTS This study included the medical records of 3022 patients with HCC. Among these cases, 304 patients were screened before HCC diagnosis;their early-stage diagnosis rate was 69.08%, which was significantly higher than that of patients with HCC who were diagnosed without screening and early detection(33.74%). Herein, patients with no clinical outcome at discharge were followed up, and the survival information of 1128 patients was obtained. A Cox model was used to analyse independent risk factors affecting overall survival, which were revealed as age > 50 years, no screening, alpha-fetoprotein > 400 ng/mL, Child–Pugh grade B, and middle and late CNLC stages. Based on the Cox model survival analysis, in our study, patients with HCC identified via screening had significant advantages in overall and tumorfree survival after hepatectomy.CONCLUSION Early diagnosis and treatment can be achieved by screening groups at high risk for HCC based on the guidelines;however, real-world compliance is poor.

Ambient Temperature and Risk of Outpatient Chronic Pharyngitis Visits:A Time-series Analysis in Xinxiang,China

Chronic pharyngitis(CP)is a prevalent medical condition in the field of otorhinolaryngology characterized by persistent inflammation of the pharyngeal mucosa,submucosa,and lymphoid tissue.The etiology of CP is multifactorial,with noninfectious factors such as personal habits(e.g.,smoking and drinking).

Integration of Theory and Practice in Medical Morphology Curriculum in Postgraduate Training:A Flipped Classroom and Case-based Learning Exercise

Objective:The integration of training in theory and practice across the medical education spectrum is being encouraged to increase student understanding and skills in the sciences.This study aimed to determine the deciding factors that drive students'perceived advantages in class to improve precision education and the teaching model.Methods:A mixed strategy of an existing flipped classroom(FC)and a case-based learning(CBL)model was conducted in a medical morphology curriculum for 575 postgraduate students.The subjective learning evaluation of the individuals(learning time,engagement,study interest and concentration,and professional integration)was collected and analyzed after FC-CBL model learning.Results:The results from the general evaluation showed promising results of the medical morphology in the FC-CBL model.Students felt more engaged by instructors in person and benefited in terms of time-saving,flexible arrangements,and professional improvement.Our study contributed to the FC-CBL model in Research Design in postgraduate training in 4 categories:1)advancing a guideline of precision teaching according to individual characteristics;2)revealing whether a learning background is needed for a Research Design course to guide setting up a preliminary course;3)understanding the perceived advantages and their interfaces;and 4)barriers and/or improvement to implement the FC-CBL model in the Research Design class,such as a richer description of e-learning and hands-on practice.Conclusion:Undertaking a FC-CBL combined model could be a useful addition to pedagogy for medical morphology learning in postgraduate training.

Lifestyle improvement and the reduced risk of cardiovascular disease:the China-PAR project

BACKGROUND The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease(CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project(Prediction for Atherosclerotic Cardiovascular Disease Risk in China).METHODS A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors(LFs)(smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios(HRs) and corresponding 95% confidence intervals(CIs). The risk advancement periods(RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage(PAR%) were also calculated.RESULTS A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1healthy LFs, maintaining 3–4 healthy LFs was associated with a 40% risk reduction of incident CVD(HR = 0.60, 95% CI: 0.45–0.79)and delayed CVD risk by 6.31 years(RAP:-6.31 [-9.92,-2.70] years). The PAR% of maintaining 3–4 unhealthy LFs was 22.0%compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2to 3–4 was associated with a 23% lower risk of CVD(HR = 0.77, 95% CI: 0.60–0.98).CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

Global pattern and determinants of coronavirus disease 2019(COVID-19)vaccine coverage and progression:a global ecological study

Background:Understanding and minimizing existing global coronavirus disease 2019(COVID-19)vaccination disparities is critical to global population health and eliminating health inequities.The study aims to investigate the disparities of vaccination coverage and progression and the associated economic and educational determinants to inform global COVID-19 vaccination strategies.Methods:COVID-19 vaccination coverage data from 206 countries used in the study were derived from“Our World in Data”website.After obtaining the vaccination coverage indicators,we fitted the progression indicators for vaccination.Correlation and multiple linear regression analysis were used to examine the effects of gross domestic product(GDP)per capita,Gini index,education,and their interactions on the coverage and progression of the COVID-19 vaccination.Results:The coverage of COVID-19 vaccination ranged from less than 30 doses to more than 150 doses per hun­dred people,from less than 15%to more than 75%for proportion of people vaccinated,from less than 15%to more than 60%for proportion of people fully vaccinated.Similarly,the progression of vaccination ranged from less than 0.1 to more than 0.6 for progression of total number of doses,from less than 0.1 to more than 0.3 for progression of proportion of people vaccinated,and from less than 0.1 to more than 0.4 for progression of propor­tion of people fully vaccinated.GDP per capita and education were positively associated with the coverage and progression,while Gini index was negatively associated with the coverage and progression.Negative interaction between GDP per capita and education was also observed for coverage(0=-0.012 to-0.011,P<0.05)and progression(0=-0.012 to-0.011,P<0.05).Conclusions:Substantial geographic disparities existed for the coverage and progression of COVID-19 vaccination.

Exploring the potential mechanisms of luteolin against ulcerative colitis and colorectal cancer via network pharmacology and molecular docking

Background:Patients diagnosed with ulcerative colitis(UC)are known to have an increased susceptibility to colorectal cancer(CRC).However,the shared underlying mechanisms between UC and CRC remain unclear.Given the therapeutic potential of luteolin in both UC and CRC,this study aims to elucidate the molecular targets and mechanisms through which luteolin exerts its effects against these diseases.Methods:The GeneCards database,DisGENet database,and Gene Expression Omnibus database were utilized to analyze the targets associated with UC and CRC.Subsequently,the Traditional Chinese Medicine Systems Pharmacology and SwissTargetPrediction databases were employed to identify luteolin-related targets.The identified luteolin-related targets were then mapped to official gene symbols using the UniProt database.The Cytoscape 3.9.0 software was utilized to construct a network of luteolin-associated targets.Venn diagram analysis was performed to identify common targets among UC,CRC,and luteolin.The common targets were further analyzed using the STRING database to construct a protein-protein interaction network.The“cytoHubba”plugin in Cytoscape 3.9.0 was employed to identify hub targets within the PPI network.Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on the hub targets.Finally,molecular docking using AutoDock and PyMOL software was performed to assess the binding affinity between luteolin and the hub targets.Results:Luteolin was found to interact with a total of 149 pharmacological targets,while UC and CRC were associated with 1232 and 3278 targets,respectively.Forty-six common targets were identified among luteolin,UC,and CRC.Through the application of seven different algorithms,seven hub targets were identified,TP53,AKT1,TNF,SRC,EGFR,and MMP9.Bioinformatics enrichment analysis revealed 49 enriched pathways through Kyoto Encyclopedia of Genes and Genomes analysis,while Gene Ontology analysis yielded a total of 245 biological processes,4 cellular components,and 7 molecular functions.Molecular docking simulations demonstrated a good binding affinity between luteolin and the hub targets.Conclusion:This study identified multiple potential pharmacological targets and elucidated various biological pathways through which luteolin may exert its therapeutic effects in the treatment of UC and CRC.These findings provide a solid theoretical foundation for further experimental investigations in the treatment of UC and CRC.

Genetic Variations and Nonalcoholic Fatty Liver Disease:Field Synopsis,Systematic Meta-Analysis,and Epidemiological Evidence

Objective To systematically summarize the published literature on the genetic variants associated with nonalcoholic fatty liver disease(NAFLD).Methods Literature from Web of Science,PubMed,and Embase between January 1980 and September 2022 was systematically searched.Meta-analyses of the genetic variants were conducted using at least five data sources.The epidemiologic credibility of the significant associations was graded using the Venice criteria.Results Based on literature screening,399 eligible studies were included,comprising 381 candidate gene association,16 genome-wide association,and 2 whole-exome sequencing studies.We identified 465 genetic variants in 173 genes in candidate gene association studies,and 25 genetic variants in 17 genes were included in the meta-analysis.The meta-analysis identified 11 variants in 10 genes that were significantly associated with NAFLD,with cumulative epidemiological evidence of an association graded as strong for two variants in two genes(HFE,TNF),moderate for four variants in three genes(TM6SF2,GCKR,and ADIPOQ),and weak for five variants in five genes(MBOAT7,PEMT,PNPLA3,LEPR,and MTHFR).Conclusion This study identified six variants in five genes that had moderate to strong evidence of an association with NAFLD,which may help understand the genetic architecture of NAFLD risk.

Changes in the Non-targeted Metabolomic Profile of Three-year-old Toddlers with Elevated Exposure to Polycyclic Aromatic Hydrocarbons

Objective To investigate changes in the urinary metabolite profiles of children exposed to polycyclic aromatic hydrocarbons(PAHs)during critical brain development and explore their potential link with the intestinal microbiota.Methods Liquid chromatography-tandem mass spectrometry was used to determine ten hydroxyl metabolites of PAHs(OH-PAHs)in 36-month-old children.Subsequently,37 children were categorized into low-and high-exposure groups based on the sum of the ten OH-PAHs.Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify non-targeted metabolites in the urine samples.Furthermore,fecal flora abundance was assessed by 16S rRNA gene sequencing using Illumina MiSeq.Results The concentrations of 21 metabolites were significantly higher in the high exposure group than in the low exposure group(variable importance for projection>1,P<0.05).Most of these metabolites were positively correlated with the hydroxyl metabolites of naphthalene,fluorine,and phenanthrene(r=0.336–0.531).The identified differential metabolites primarily belonged to pathways associated with inflammation or proinflammatory states,including amino acid,lipid,and nucleotide metabolism.Additionally,these distinct metabolites were significantly associated with specific intestinal flora abundances(r=0.34–0.55),which were mainly involved in neurodevelopment.Conclusion Higher PAH exposure in young children affected metabolic homeostasis,particularly that of certain gut microbiota-derived metabolites.Further investigation is needed to explore the potential influence of PAHs on the gut microbiota and their possible association with neurodevelopmental outcomes.

Molecular Investigation of Theileria in Ixodid Ticks from Changzhi,Shanxi Province,China

Theileria is a tick-borne intracellular protozoan that typically parasitizes erythrocytes,lymphocytes,and macrophages and causes acute clinical symptoms in host animals,including high fever,anemia,jaundice,and swelling of superficial lymph nodes[1].Theileriosis can lead to high mortality rates,and its rising global prevalence has resulted in significant economic losses to livestock husbandry and the national economy[2].

Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing

Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

Understanding the educational inequalities in suicide attempts and their mediators:a Mendelian randomisation study

Background Educational inequalities in suicide have become increasingly prominent over the past decade.Elucidating modifiable risk factors that serve as intermediaries in the impact of low educational attainment on suicide has the potential to reduce health disparities.Aims To examine the risk factors that mediate the relationship between educational attainment and suicide attempts and quantify their contributions to the mediation effect.Methods We conducted a two-sample Mendelian randomisation(MR)analysis to estimate the causal effect of educational attainment on suicide attempts,utilising genome-wide association study summary statistics from the Integrative Psychiatric Research(iPSYCH;6024 cases and 44240 controls)and FinnGen(8978 cases and 368299 controls).We systematically evaluated 42 putative mediators within the causal pathway connecting reduced educational attainment to suicide attempts and employed two-step and multivariable MR to quantify the proportion of the mediated effect.Results In the combined analysis of iPSYCH and FinnGen,each standard deviation(SD)decrease in genetically predicted educational attainment(equating to 3.4 years of education)was associated with a 105%higher risk of suicide attempts(odds ratio(OR):2.05;95%confidence interval(Cl):1.81 to 2.31).0f the 42 risk factors analysed,the two-step MR identified five factors that mediated the association between educational attainment and suicide attempts.The respective proportions of mediation were 47%(95%Cl:29%to 66%)for smoking behaviour,36%(95%Cl:0%to 84%)for chronic pain,49%(95%Cl:36%to 61%)for depression,35%(95%Cl:12%to 59%)for anxiety and 26%(95%Cl:18%to 34%)for insomnia.Multivariable MR implicated these five mediators collectively,accounting for 68%(95%Cl:40%to 96%)of the total effect.Conclusions This study identified smoking,chronic pain and mental disorders as primary intervention targets for attenuating suicide risk attributable to lower educational levels in the European population.

Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions:Findings from Global Burden of Disease Study

Objective:China is one of the countries with the heaviest burden of gastric cancer(GC)in the world.Understanding the epidemiological trends and patterns of GC in China can contribute to formulating effective prevention strategies.Methods:The data on incidence,mortality,and disability-adjusted life-years(DALYs)of GC in China from1990 to 2019 were obtained from the Global Burden of Disease Study(2019).The estimated annual percentage change(EAPC)was calculated to evaluate the temporal trends of disease burden of GC,and the package Nordpred in the R program was used to perform an age-period-cohort analysis to predict the numbers and rates of incidence and mortality in the next 25 years.Results:The number of incident cases of GC increased from 317.34 thousand in 1990 to 612.82 thousand in2019,while the age-standardized incidence rate(ASIR)of GC decreased from 37.56 per 100,000 in 1990 to 30.64 per 100,000 in 2019,with an EAPC of-0.41[95%confidence interval(95%CI):-0.77,-0.06].Pronounced temporal trends in mortality and DALYs of GC were observed.In the next 25 years,the numbers of new GC cases and deaths are expected to increase to 738.79 thousand and 454.80 thousand,respectively,while the rates of incidence and deaths should steadily decrease.The deaths and DALYs attributable to smoking were different for males and females.Conclusions:In China,despite the fact that the rates of GC have decreased during the past three decades,the numbers of new GC cases and deaths increased,and will continue to increase in the next 25 years.Additional strategies are needed to reduce the burden of GC,such as screening and early detection,novel treatments,and the prevention of risk factors.

Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer

BACKGROUND Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR]= 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. CONCLUSION The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.

Performance of common imaging techniques vs serum biomarkers in assessing fibrosis in patients with chronic hepatitis B: A systematic review and meta-analysis

BACKGROUND Noninvasive biomarkers have been developed to predict hepatitis B virus(HBV)related fibrosis owing to the significant limitations of liver biopsy.Both serum biomarkers and imaging techniques have shown promising results and may improve the evaluation of liver fibrosis.However,most of the previous studies focused on the diagnostic effects of various imaging techniques on fibrosis in all chronic liver diseases.AIM To compare the performance of common imaging methods and serum biomarkers for prediction of significant fibrosis caused only by HBV infection.METHODS A systematic review was conducted on the records available in PubMed,EMBASE,and the Cochrane Library electronic databases until December 2018.We systematically assessed the effectiveness of two serum biomarkers and three imagine techniques in predicting significant fibrosis solely caused by HBV infection.The serum biomarkers included aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis index based on the 4 factors(FIB-4).The three imaging techniques included acoustic radiation force impulse(ARFI),FibroScan,and magnetic resonance elastography(MRE).Three parameters,the area under the summary receiver operating characteristic curve(AUSROC),the summary diagnostic odds ratio,and the summary sensitivity and specificity,were used to examine the accuracy of all tests for liver fibrosis.RESULTS Out of 2831 articles evaluated for eligibility,204 satisfied the predetermined inclusion criteria for this current meta-analysis.Eventually,our final data contained 81 studies.The AUSROCs of serum biomarkers of APRI and FIB-4 were both 0.75.For imaging techniques(ARFI,FibroScan,and MRE),the areas were 0.89,0.83,and 0.97,respectively.The heterogeneities of ARFI and FibroScan were statistically significant(I2>50%).The publication bias was not observed in any of the serum biomarkers or imaging methods.CONCLUSION These five methods have attained an acceptable level of diagnostic accuracy.Imaging techniques,MRE in particular,demonstrate significant advantages in accurately predicting HBV-related significant fibrosis,while serum biomarkers are admissible methods.

Tripartite motif.containing 3(TRIM3)inhibits tumor growth and metastasis of liver cancer

Background:Reduced expression of tripartite motif-containing 3(TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma.In our previous research,we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma(HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients.However,the role of TRIM3 in liver cancer remains unknown.This study aimed to investigate the function of TRIM3 in liver cancer cells.Methods:The protein levels of TRIM3 in five liver cancer cell lines(SK-Hep1,Hep3 B,Huh7,HepG2,Bel-7402) and one normal liver cell line(L02) were detected with Western blotting.HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3(LV-TRIM3),whereas Huh7 and Hep3 B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA(siTRIM3).The functions of TRIM3 in the proliferation,colony formation,cell cycle,migration,invasion,and apoptosis of the above cell lines were examined.The effect ofTRIM3 on tumor growth and metastases in nude mice was also investigated.Results:TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection,which further reduced proliferation,colony formation,migration,and invasion of both cell lines.Cell cycle analysis showed that TRIM3 overexpression induced G_0/G_1 phase arrest in HepG2 and Bel-7402 cells.Moreover,apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3.Contrarily,silencing TRIM3 expression in Huh7 and Hep3 B cells by siTRIM3 led to significantly decreased percentages of both cells in the G_0/G_1 phase and promoted cell proliferation,colony formation,migration,and invasion.In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis.Conclusions:TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G_0/G_1 phase.

Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome

BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).However,the metabolic profile and pathophysiology of IBS are still unclear.We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments,including the IBS Symptom Severity System(IBS-SSS),an Italian modified version of the Bowel Disease Questionnaire,the Bristol Stool Form Scale(BSFS),the Hospital Anxiety and Depression Scale,and the Visceral Sensitivity Index.Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator.Fecal metabolites,including amino acids and organic acids,were measured by targeted metabolomics approaches.Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content,more psychological symptoms and increased visceral hypersensitivity compared with the controls.In fecal metabolites,His[IBS-D:0.0642(0.0388,0.1484),HC:0.2636(0.0780,0.3966),P=0.012],Ala[IBS-D:0.5095(0.2826,0.9183),HC:1.0118(0.6135,1.4335),P=0.041],Tyr[IBS-D:0.1024(0.0173,0.4527),HC:0.5665(0.2436,1.3447),P=0.018],Phe[IBS-D:0.1511(0.0775,0.3248),HC:0.3967(0.1388,0.7550),P=0.028],and Trp[IBS-D:0.0323(0.0001,0.0826),HC:0.0834(0.0170,0.1759),P=0.046]were decreased in IBS-D patients,but isohexanoate[IBS-D:0.0127(0.0060,0.0246),HC:0.0070(0.0023,0.0106),P=0.028]was significantly increased.Only Tyr was mildly correlated with BSFS scores in all subjects(r=-0.347,P=0.019).A possible potential biomarker panel was identified to correlate with IBS-SSS score(R2 Adjusted=0.693,P<0.001).In this regression model,the levels of Tyr,Val,hexanoate,fumarate,and pyruvate were significantly associated with the symptom severity of IBS-D.Furthermore,visceral sensation,including abdominal pain and visceral hypersensitivity,was correlated with isovalerate,valerate and isohexanoate.CONCLUSION Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.

Clinicopathological features and survival analysis of gastroenteropancreatic neuroendocrine neoplasms: a retrospective study in a single center of China

Objective： To investigate the clinicopathological features, survival and prognostic factors for gastroenteropancreatic neuroendocrine neoplasms（GEP-NENs） in a Chinese population.Methods： We investigated 154 consecutive patients（88 males, 66 females; median age 56 years, age range 9-86 years） diagnosed with GEP-NENs between 2001 and 2013 at The Affiliated Hospital of Qingdao University. Demographic, clinical and pathological variables and survival data were retrieved.Results： The pancreas was the most common site of involvement（63/154, 40.9%）. Tumor size varied from 0.3 to 16.0 cm（median, 1.2 cm）. The patients were followed up for a median period of 22 months（range, 1-157 months）. The estimated 3- and 5-year overall survival（OS） rates for all patients were 84.0% and 81.9%, respectively. Multivariate analysis showed that larger tumor size, lymphatic metastases and distant metastases were significant predictors for poor survival outcome.Conclusions： Our data provide further information on the clinicopathological features of GEP-NENs in China. Additionally, we identified tumor size, lymphatic metastases and distant metastases as independent prognostic factors for long-term survival.