Metabolic disorders and hepatitis: Insights from a Mendelian randomization study

BACKGROUND Hepatitis is a systemic disease that often results in various comorbidities.Meta-bolic disorders,the most common comorbidities in clinical practice,were selected for this study.AIM To investigate the causal relationship between comorbidities and hepatitis trea-tment outcomes.METHODS A total of 23583378 single nucleotide polymorphisms from 1248743 cases and related summaries of genome-wide association studies were obtained from online public databases.A two-sample Mendelian randomization(MR)was performed to investigate causality between exposure[type 2 diabetes mellitus(T2D),hyperlipidemia,and hypertension]and outcome(chronic hepatitis B or C in-fections).RESULTS The data supported the causal relationship between comorbidities and hepatitis infections,which will affect the severity of hepatitis progression and will also provide a reference for clinical researchers.All three exposures showed a link with progression of both hepatitis B(T2D,P=0.851;hyperlipidemia,P=0.596;and hypertension,P=0.346)and hepatitis C(T2D,P=0.298;hyperlipidemia,P=0.141;and hypertension,P=0.035).CONCLUSION The results of MR support a possible causal relationship between different ex-posures(T2D,hyperlipidemia,and hypertension)and chronic hepatitis progression;however,the potential mechanisms still need to be elucidated.

Correlation between diabetic retinopathy and Helicobacter pylori infection: a cross-sectional retrospective study

AIM:To explore the correlation between diabetic retinopathy(DR)and Helicobacter pylori(Hp)infection,based on data from a physical examination population.METHODS:This cross-sectional retrospective analysis included data of 73824 health examination participants from December 2018 to December 2019.Participants were divided into the diabetic group and non-diabetic group,nondiabetic retinopathy(NDR)group,non-proliferative diabetic retinopathy(NPDR)group,proliferative diabetic retinopathy(PDR)group,and Hp infection group.Gender,age,body mass index(BMI),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),glycated hemoglobin A1c(HbA1c),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and Hp data were recorded to compare the degree of DR lesions and Hp infection.Logistic regression analysis was used to evaluate the correlation between DR and Hp infection.RESULTS:There was a statistically significant difference between the diabetic and non-diabetic group(χ2=94.17,P<0.0001).Logistic regression analysis showed that male sex,age,BMI,SBP,TG,LDL-C,and Hp infection were independent risk factors for DR.There was no correlation between the degree of DR lesions and Hp infection(ρ=-0.00339,P=0.7753).Age[odds ratio(OR)=1.035,95%CI:1.024,1.046,P<0.0001]and SBP(OR=1.009,95%CI:1.004,1.015,P=0.0013)were independent risk factors for the degree of DR.CONCLUSION:There is a significant correlation between DR and Hp infection in the physical examination population.Hp infection is a risk factor for DR,and there is no significant difference between Hp infection and DR of different pathological degrees.Actively eradicating Hp may be of help to prevent DR.

Mutation-associated transcripts reconstruct the prognostic features of oral tongue squamous cell carcinoma

Tongue squamous cell carcinoma is highly malignant and has a poor prognosis.In this study,we aimed to combine whole-genome sequencing,whole-genome methylation,and whole-transcriptome analyses to understand the molecular mechanisms of tongue squamous cell carcinoma better.Oral tongue squamous cell carcinoma and adjacent normal tissues from five patients with tongue squamous cell carcinoma were included as five paired samples.After multi-omics sequencing,differentially methylated intervals,methylated loop sites,methylated promoters,and transcripts were screened for variation in all paired samples.Correlations were analyzed to determine biological processes in tongue squamous cell carcinoma.We found five mutated methylation promoters that were significantly associated with mRNA and lncRNA expression levels.Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade,which is associated with cancer progression and the development of drug resistance during treatment.The prognostic signature models constructed based on WDR81 and HNRNPH1 and combined clinical phenotype-gene prognostic signature models showed high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings.We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs.Collectively,changes in transcript levels affect the prognosis of tongue squamous cell carcinoma patients.

Occurrence of Boerhaave's syndrome after diagnostic colonoscopy:what else can emergency physicians do?

Dear editor,Boerhaave’s syndrome is a barogenic tear of the esophagus,typically at the gastroesophageal junction,caused by a sudden increase in intraluminal pressure in the distal esophagus.[1]In recent years,the number of Boerhaave’s syndrome cases has increased,and a growing proportion of clinicians have recognized this rare but life-threatening disease.

Clinical and genetic diagnosis of autosomal dominant osteopetrosis typeⅡin a Chinese family:A case report

BACKGROUND Osteopetrosis is a rare genetic disorder characterized by increased bone density due to defective bone resorption of osteoclasts.Approximately,80%of autosomal dominant osteopetrosis type II(ADO-II)patients were usually affected by heterozygous dominant mutations in the chloride voltage-gated channel 7(ClCN7)gene and present early-onset osteoarthritis or recurrent fractures.In this study,we report a case of persistent joint pain without bone injury or underlying history.CASE SUMMARY We report a 53-year-old female with joint pain who was accidentally diagnosed with ADO-II.The clinical diagnosis was based on increased bone density and typical radiographic features.Two heterozygous mutations in the ClCN7 and Tcell immune regulator 1(TCIRG1)genes by whole exome sequencing were identified in the patient and her daughter.The missense mutation(c.857G>A)occurred in the CLCN7 gene p.R286Q,which is highly conserved across species.The TCIRG1 gene point mutation(c.714-20G>A)in intron 7(near the splicing site of exon 7)had no effect on subsequent transcription.CONCLUSION This ADO-II case had a pathogenic CLCN7 mutation and late onset without the usual clinical symptoms.For the diagnosis and assessment of the prognosis for osteopetrosis,genetic analysis is advised.

Diagnostic and classification value of immune-related lncRNAs in dilated cardiomyopathy

Background:Various physiological mechanisms are linked to dilated cardiomyopathy(DCM)development,including oxidative stress,immune irregularities,inflammation,fibrosis,and genetic changes.However,precise molecular drivers of DCM,especially regarding abnormal immune responses,remain unclear.This study investigates immune-related long non-coding RNAs(lncRNAs)in DCM’s diagnostic and therapeutic potential.Methods:GSE141910,GSE135055,and GSE165303 datasets were acquired from the GEO database.LASSO,SVM-RFE,and random forest algorithms identified DCM-associated immune-related lncRNAs.Diagnostic capabilities were assessed by Nomogram and receiver operating characteristic(ROC)curves.Multivariate linear regression explored lncRNA correlations with ejection fraction.Single-sample gene set enrichment analysis(ssGSEA)gauged immune cell infiltration/functions.Functional enrichment analyses were performed using Gene set variation analysis(GSVA),gene ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG).Consensus clustering categorized DCM cases.Results:Ten immune-related lncRNAs emerged:C10orf71-AS1,FHAD1-AS1,SCIRT,FNDC1-AS1,MELTFAS1,LOC101928834,GDNF-AS1,DCXR-DT,C3orf36,and LOC107985323.These lncRNAs,tied to immunomodulation,showed promising DCM diagnostic accuracy.Adjusted for confounders,they independently correlated with ejection fraction.Using lncRNA expression,DCM patients were grouped into subtypes.Subtype C1 displayed a higher level of immune cell infiltration and immune checkpoint expression compared to subtype C2,emphasizing the variations in the immune microenvironment.Conclusion:This study identifies ten immune-related lncRNAs for further exploration in DCM diagnosis and subtyping.Based on expression patterns,we propose two potential DCM subtypes.Notably,findings are preliminary and hypothesis-generating,demanding validation and further investigation.This research provides insights into DCM diagnosis and classification.

Association between the Lung Immune Prognostic Index and mortality in patients with idiopathic inflammatory myopathy-associated interstitial lung disease

Objective:To explore the association between the Lung Immune Prognostic Index(LIPI)and 1-year all-cause mortality in patients with idiopathic inflammatory myopathy related interstitial lung disease(IIM-ILD).Methods:Patients who were diagnosed with IIM-ILD at West China Hospital,Sichuan University from January 2008 to December 2021 were retrospectively included and categorized into three groups based on LIPI.Univariable and multivariable Cox proportional hazards models were conducted to explore potential association between the LIPI and patients'mortality.Results:A total of 1116 patients were screened,and 830 were included in this study.The multivariable Cox analysis showed that,compared with patients with poor LIPI,the hazard ratio(HR)for all-cause 1-year mortality was 0.22(95%CI 0.05-0.93,P=0.04)for patients in the good LIPI group(LDH<250 IU/L and dNLR<3).After excluding patients lost to follow-up within one year,a similar result was found for LIPI(HR 0.20,95%CI 0.05-0.86;P=0.03).Conclusions:Good LIPI was independently associated with decreased risk of all-cause 1-year mortality in patients with IIM-ILD.This easy-to-obtain index might be served as a potential marker for assessing the prognosis of IIM-ILD.

Endoscopic submucosal tunnel dissection for early esophageal squamous cell carcinoma in patients with cirrhosis:A propensity score analysis

BACKGROUND Although early esophageal squamous cell carcinoma(EESCC)with cirrhosis is a relatively rare clinical phenomenon,the management of EESCC in cirrhotic patients continues to be a challenge.AIM To evaluate the feasibility,safety,efficacy and long-term survival outcomes of endoscopic submucosal tunnel dissection(ESTD)for treating EESCC in patients with cirrhosis.METHODS This was a single-center retrospective cohort study.We examined 590 EESCC patients who underwent ESTD between July 14,2014,and May 26,2021,from a large-scale tertiary hospital.After excluding 25 patients with unclear lesion areas or pathological results,the remaining 565 patients were matched at a ratio of 1:3 by using propensity score matching.A total of 25 EESCC patients with comorbid liver cirrhosis and 75 matched EESCC patients were ultimately included in the analysis.Parametric and nonparametric statistical methods were used to compare the differences between the two groups.The Kaplan–Meier method was used to create survival curves,and differences in survival curves were compared by the log-rank test.RESULTS Among 25 patients with liver cirrhosis and 75 matched noncirrhotic patients,there were no significant differences in intraoperative bleeding(P=0.234),30-d post-ESTD bleeding(P=0.099),disease-specific survival(P=0.075),or recurrence-free survival(P=0.8196).The mean hospitalization time and costs were significantly longer(P=0.007)and higher(P=0.023)in the cirrhosis group than in the noncirrhosis group.The overall survival rate was significantly lower in the cirrhosis group(P=0.001).CONCLUSION ESTD is technically feasible,safe,and effective for patients with EESCC and liver cirrhosis.EESCC patients with Child-Pugh A disease seem to be good candidates for ESTD.

Noncirrhotic portal hypertension due to peripheral T-cell lymphoma,not otherwise specified:A case report

BACKGROUND Peripheral T-cell lymphoma(PTCL),an aggressive and rare disease that belongs to a heterogeneous group of mature T-cell lymphomas,develops rapidly and has a poor prognosis.Early detection and treatment are essential to improve patient cure and survival rates.Here,we report a rare case of PTCL with clinical presentation of noncirrhotic portal hypertension,which provides a basis for early vigilance of lymphomas in the future.CASE SUMMARY A 65-year-old Chinese woman was admitted to our hospital because of abdominal distension for 3 months and pitting oedema of both lower limbs for 2 months.Physical examinations and associated auxiliary examinations showed the presence of hepatosplenomegaly,and her hepatic venous pressure gradient was 10 mmHg.Immunohistochemical analysis of the liver biopsy confirmed the diagnosis of PTCL.The patient underwent combination therapy with dexamethasone,VP-16,and chidamide.Unfortunately,after 41 days of chemotherapy,the patient died of multiple organ failure.CONCLUSION PCTL accompanied by noncirrhotic portal hypertension is rarely reported.This case report discusses the diagnosis of a patient according to the literature.

Precision medicine in inflammatory bowel disease

Inflammatory bowel disease(IBD)is an incurable disease characterized by remission-relapse cycles throughout its course.Both Crohn's disease(CD)and ulcerative colitis(UC),the two main forms of IBD,exhibit tendency to develop complications and substantial heterogeneity in terms of frequency and severity of relapse,thus posing great challenges to the clinical management for IBD.Current treatment strategies are effective in different ways in induction and maintenance therapies for IBD.Recent advances in studies of genetics,pharmacogenetics,proteomics and microbiome provide a strong driving force for identifying molecular markers of prognosis and treatment response,which should help clinicians manage IBD patients more effectively,and then,improve clinical outcomes and reduce treatment costs of patients.In this review,we summarize and discuss precision medicine in IBD,focusing on predictive markers of disease course and treatment response,and monitoring indices during therapeutic drug monitoring.

Safety, immunogenicity and protective effectiveness of heterologous boost with a recombinant COVID-19 vaccine (Sf9 cells) in adult recipients of inactivated vaccines

Vaccines have proven effective in protecting populations against COVID-19,including the recombinant COVID-19 vaccine(Sf9 cells),the first approved recombinant protein vaccine in China.In this positive-controlled trial with 85 adult participants(Sf9 cells group:n=44;CoronaVac group:n=41),we evaluated the safety,immunogenicity,and protective effectiveness of a heterologous boost with the Sf9 cells vaccine in adults who had been vaccinated with the inactivated vaccine,and found a post-booster adverse events rate of 20.45%in the Sf9 cells group and 31.71%in the CoronaVac group(p=0.279),within 28 days after booster injection.Neither group reported any severe adverse events.Following the Sf9 cells vaccine booster,the geometric mean titer(GMT)of binding antibodies to the receptor-binding domain of prototype SARS-CoV-2 on day 28 post-booster was significantly higher than that induced by the CoronaVac vaccine booster(100,683.37 vs.9,451.69,p<0.001).In the Sf9 cells group,GMTs of neutralizing antibodies against pseudo SARS-CoV-2 viruses(prototype and diverse variants of concern[VOCs])increased by 22.23–75.93 folds from baseline to day 28 post-booster,while the CoronaVac group showed increases of only 3.29–10.70 folds.Similarly,neutralizing antibodies against live SARS-CoV-2 viruses(prototype and diverse VOCs)increased by 68.18–192.67 folds on day 14 post-booster compared with the baseline level,significantly greater than the CoronaVac group(19.67–37.67 folds).A more robust Th1 cellular response was observed with the Sf9 cells booster on day 14 post-booster(mean IFN-γ+spot-forming cells per 2×105 peripheral blood mononuclear cells:26.66 vs.13.59).Protective effectiveness against symptomatic COVID-19 was approximately twice as high in the Sf9 cells group compared to the CoronaVac group(68.18%vs.36.59%,p=0.004).Our study findings support the high protective effectiveness of heterologous boosting with the recombinant COVID-19 vaccine(Sf9 cells)against symptomatic COVID-19 of diverse SARS-CoV-2 variants of concern,while causing no apparent safety concerns.

Investigating association between gut microbiota and sarcopenia-related traits:a Mendelian randomization study

Background Observational studies have indicated a potential link between gut microbiota and sarcopenia.However,the underlying mechanisms and a causal relationship have not been established.Thus,the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits,including low hand-grip strength and appendicular lean mass(ALM),to shed light on the gut–muscle axis.Methods To investigate the potential impact of gut microbiota on low hand-grip strength and ALM,we utilized a two-sample Mendelian randomization(MR)approach.Summary statistics were obtained from genome-wide association studies of gut microbiota,low hand-grip strength,and ALM.The primary MR analysis employed the random-effects inverse-variance weighted(IVW)method.To assess the robustness,we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier(MR-PRESSO)test to detect and correct for horizontal pleiotropy,as well as the MR-Egger intercept test and leave-one-out analysis.Results Alcaligenaceae,Family XIII,and Paraprevotella were positively associated with the risk of low hand-grip strength(P-values<0.05).Streptococcaceae were negatively associated with low hand-grip strength(P-values<0.05).Eight bacterial taxa(Actinomycetales,Actinomycetaceae,Bacteroidaceae,Porphyromonadaceae,Prevotellaceae,Bacteroides,Marvinbryantia,and Phascolarctobacterium)were associated with a higher risk of ALM(P-values<0.05).Eubacterium fissicatena group was negatively associated with ALM(P-values<0.05).Conclusion We found several gut microbiota components causally associated with sarcopenia-related traits.Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota,contributing to a better understanding of the gut–muscle axis.

Evaluation and prospect of scientific research capacity ranking for community healthcare centres in China

The National Health and Family Planning Commission of the People's Republic of China has proposed to improve the medical capacity of general practitioners and the establishment of general practice in recent health reform.For the first time,the ability to conduct scientific research was included in this reform,which demands community healthcare centres(CHCs)to strengthen their research capacity.The evaluation of community scientific research capacity has become an important endeavour to promote the implementation of research in CHCs.Since 2016,our research team has been working on an evaluation system and has published the scientific research capacity ranking for the top 100 CHCs in China.The latest released ranking of scientific research capacities of China CHCs has aroused great attention in the country.

Precision prevention of monkeypox

Dear Editor,Recently,the World Health Organization(WHO)declared monkeypox as a Public Health Emergency of International Concern(PHEIC),another one after the last PHEIC of COVID-19 announced in early 2020.1 Unlike the new SARS-CoV-2 virus that has multiple variants,monkeypox virus is a DNA virus first identified in 1958 with no evidence of significant mutation of its sequence.