Cellular immune responses are crucial in determining outcomes of the hepatitis B virus (HBV) infection. Ineffective immune responses enable persistent HBV infection and contribute to progressive liver disease. Understanding the mechanisms underlying immunological HBV tolerance and restoring functional adaptive immune responses is essential for successful chronic hepatitis B (CHB) treatment. This study examined the dysregulated immune responses and immunopathological cell states associated with CHB using single-cell RNA sequencing of peripheral blood mononuclear cells to investigate immune cell composition and transcriptional differences between patients with CHB and healthy donors. Phenotypic alterations in the lymphoid and myeloid compartments were observed following HBV infection. T cell immune profiling in patients with CHB showed enrichment of exhausted CD8+ T cells, impaired cytotoxicity of effector CD8+ T cells, and increased regulatory T cell (Treg) suppressive activity. Immature neutrophils and a unique CD14+ monocyte subset (myeloid-derived suppressor cells) exhibited potent immunosuppressive abilities. A novel population of CD14+CD163+VSIG4+ M2-like macrophages with immunosuppressive and anti-inflammatory phenotypes was enriched in a patient with severe CHB and liver failure, indicating a potential contribution to dysfunctional immune responses. Our study demonstrated immune exhaustion and evasion in chronic HBV infection, elucidating its immunopathological features and suggesting new therapeutic strategies for immune-mediated disorders and unresolved chronic HBV infection.

At present, the disease burden of drug-resistant tuberculosis (DR-TB) is still heavy in the world. In this study, we aimed to evaluate the success rate of DR-TB patients after standardized treatment and to analyze the risk factors for poor outcomes in Zhejiang, China. From 2017 to 2021, all culture-confirmed tuberculosis (TB) patients were prospectively enrolled from three designated TB hospitals in Zhejiang, China. Demographic surveys were conducted in all patients, and drug susceptibility of TB strains was tested by fluorescent polymerase chain reaction probe melting curve analysis (MeltPro). DR-TB patients were treated with WHO recommended standardized treatment according to the type of drug resistance, and the outcomes were thoroughly monitored and tracked until June 2023. Binary logistic regression model was used to analyze the related risk factors of poor outcomes in patients with DR-TB. The patients' socio-demographic information, comorbidities, fever, antibiotic use, laboratory test results, lung imaging characteristics and drug resistance characteristics were included in the analysis. A simple TB severity score was developed according to the WHO definition and applied to the analysis. Among 1013 patients with confirmed TB, 779 were sensitive to all of the tested drugs (rifampicin, isoniazid, ethambutol, streptomycin and fluoroquinolones), and 234 were resistant to at least one tested drug. Among the 234 DR-TB patients in the study, 50 patients had poor outcomes (23 cases of failure, 13 cases of death, and 14 patients lost to follow-up), 158 patients were successfully treated (125 cases were cured and 33 cases completed treatment), and 26 were referred to other provinces. The overall treatment success rate was 76.0

Hepatocellular carcinoma (HCC) is a primary liver malignancy with high mortality rates and poor prognosis. Recent advances in high-throughput sequencing and bioinformatic technologies have greatly enhanced the understanding of the genetic and epigenetic changes in liver cancer. Among these changes, RNA methylation, the most prevalent internal RNA modification, has emerged as a significant contributor of the development and progression of HCC. Growing evidence has reported significantly abnormal levels of RNA methylation and dysregulation of RNA-methylation-related enzymes in HCC tissues and cell lines. These alterations in RNA methylation play a crucial role in the regulation of various genes and signaling pathways involved in HCC, thereby promoting tumor progression. Understanding the pathogenesis of RNA methylation in HCC would help in developing prognostic biomarkers and targeted therapies for HCC. Targeting RNA-methylation-related molecules has shown promising potential in the management of HCC, in terms of developing novel prognostic biomarkers and therapies for HCC. Exploring the clinical application of targeted RNA methylation may provide new insights and approaches for the management of HCC. Further research in this field is warranted to fully understand the functional roles and underlying mechanisms of RNA methylation in HCC. In this review, we described the multifaceted functional roles and potential mechanisms of RNA methylation in HCC. Moreover, the prospects of clinical application of targeted RNA methylation for HCC management are discussed, which may provide the basis for subsequent in-depth research on RNA methylation in HCC.

Background Vasculogenic mimicry, a novel neovascularization pattern of aggressive tumors, is associated with poor clinical outcomes.Objective The aim of this research was to establish a new model, termed VC score, to predict the prognosis, Tumor Microenvironment (TME) components, and immunotherapeutic response in Hepatocellular Carcinoma (HCC).Methods The expression data of the public databases were used to develop the prognostic model. Consensus clustering was performed to confirm the molecular subtypes with ideal clustering efficacy. The high- and low-risk groups were stratified utilizing the VC score. Various methodologies, including survival analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Tumor Immune Dysfunction and Exclusion scores (TIDE), Immunophenoscore (IPS), and nomogram, were utilized for verification of the model performance and to characterize the immune status of HCC tissues. GSEA was performed to mine functional pathway information.Results The survival and immune characteristics varied between the three molecular subtypes. A five-gene signature (TPX2, CDC20, CFHR4, SPP1, and NQO1) was verified to function as an independent predictive factor for the prognosis of patients with HCC. The high-risk group exhibited lower Overall Survival (OS) rates and higher mortality rates in comparison to the low-risk group. Patients in the low-risk group were predicted to benefit from immune checkpoint inhibitor therapy and exhibit increased sensitivity to immunotherapy. Enrichment analysis revealed that signaling pathways linked to the cell cycle and DNA replication processes exhibited enrichment in the high-risk group.Conclusion The VC score holds the potential to establish individualized treatment plans and clinical management strategies for patients with HCC.

Digestive tract tumors are heterogeneous and involve the dysregulation of multiple signaling pathways. The Janus kinase-signal transducer and activator of transcription (JAK–STAT) pathway plays a notable role in the oncogenesis of digestive tract tumors. Typically activated by pro-inflammatory cytokines, it regulates important biological processes, such as cell growth, differentiation, apoptosis, immune responses, and inflammation. The aberrant activation of this pathway manifests in different forms, including mutations in JAKs, overexpression of cytokine receptors, and sustained STAT activation, and contributes to promoting the malignant characteristics of cancer cells, including uncontrolled proliferation, resistance to apoptosis, enhanced invasion and metastasis, angiogenesis, acquisition of stem-like properties, and drug resistance. Numerous studies have shown that aberrant activation of the JAK-STAT pathway is closely related to the development and progression of digestive tract tumors, contributing to tumor survival, angiogenesis, changes in the tumor microenvironment, and even immune escape processes. In addition, this signaling pathway also affects the sensitivity of digestive tract tumors to chemotherapy and targeted therapy. Therefore, it is crucial to comprehensively understand the oncogenic mechanisms underlying the JAK-STAT pathway in order to develop effective therapeutic strategies against digestive tract tumors. Currently, several JAK–STAT inhibitors are undergoing clinical and preclinical trials as potential treatments for various human diseases. However, further investigation is required to determine the role of this pathway, as well as the effectiveness and safety of its inhibitors, especially in the context of digestive tract tumors. In this review, we provide an overview of the structure, classic activation, and negative regulation of the JAK-STAT pathway. Furthermore, we discuss the pathogenic mechanisms of JAK-STAT signaling in different digestive tract tumors, with the aim of identifying potential novel therapeutic targets.

Digestive system tumors have been reported in more than 25% of all cancer cases worldwide, bringing a huge burden on the healthcare system. RNA methylation modification—an important post-transcriptional modification—has become an active research area in gene regulation. It is a dynamic and reversible process involving several enzymes, such as methyltransferases, demethylases, and methylation reader proteins. This review provides insights into the role of three major methylation modifications, namely m6A, m5C, and m1A, in the development of digestive system tumors, specifically in the development of tumor immune microenvironment (TIME) of these malignancies. Abnormal methylation modification affects immunosuppression and antitumor immune response by regulating the recruitment of immune cells and the release of immune factors. Understanding the mechanisms by which RNA methylation regulates digestive system tumors will be helpful in exploring new therapeutic targets.

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. Since the tricarboxylic acid cycle is widely involved in tumor metabolic reprogramming and cuproptosis, investigating related genes may help to identify prognostic signature of patients with HCC. Data on patients with HCC were sourced from public datasets, and were divided into train, test, and single-cell cohorts. A variety of machine learning algorithms were used to identify different molecular subtypes and determine the prognostic risk model. Our findings revealed that the risk score (TRscore), based on the genes OGDHL, CFHR4, and SPP1, showed excellent predictive performance in different datasets. Pathways related to cell cycle and immune inflammation were enriched in the high-risk group, whereas metabolism-related pathways were significantly enriched in the low-risk group. The high-risk group was associated with a greater number of mutations of detrimental biological behavior and higher levels of immune infiltration, immune checkpoint expression, and anti-cancer immunotherapy response. Low-risk patients demonstrated greater sensitivity to erlotinib and phenformin. SPP1 was mainly involved in the interaction among tumor-associated macrophages, T cells, and malignant cells via SPP1–CD44 and SPP1–(ITGA5 + ITGB1) ligand-receptor pairs. In summary, our study established a prognostic model, which may contribute to individualized treatment and clinical management of patients with HCC.

Objective: Mass screening for HIV and preexposure prophylaxis (PrEP) may be effective measures for reducing the probability of HIV transmission. Our study aimed to determine the cost-effectiveness of preliminary screening in the general population, PrEP for HIV-negative spouses in serodiscordant couples, or both approaches in Zhejiang Province. Design: From a policy-maker's perspective, a Markov model was constructed to compare four strategies over a 30-year horizon. Methods: In the Markov model, the implementation intensities of the strategies varied from 50 to 100%. Different strategies were evaluated by the reduction of unfavorable clinical outcomes, saved life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). Results: The PrEP-screening strategy reduced the most unfavorable clinical outcomes and saved the most life-years and QALYs from 2023 to 2052. It always gained the maximum QALYs and NMB, while its ICER was always lower than the willingness-to-pay (WTP). The NMB of the PrEP-screening strategy gradually increased as the implementation intensity increased. Conclusion: With adequate manpower and policies, we suggest implementing the PrEP-screening strategy in Zhejiang Province, suggesting that the broader the population coverage of the strategy, the better. In addition, the PrEP strategy is an alternative.

The etiologies of infectious diseases (IDs) of classic fever of unknown origin (FUO) are multitudinous. Different etiologies affect medication decisions. Here, we have made an attempt to predict the types of etiology on the basis of a machine learning (ML) model for IDs of classic FUO for adults. Ten years clinical data of 408 classic FUO were retrospectively collected from August 2012 to August 2022 in Huzhou Central Hospital. A total of 256 adult patients with ID of classic FUO were divided into four subgroups for clinical characteristic analysis. Random forest (RF), light gradients boosting (Light GBM), and extreme gradient boosting (XGBoost) were used to construct prediction models of 10-fold cross validation. The micro average and weighted average of F1 score were calculated to evaluate the performance of the models. SHapley Additive exPlanations (SHAP) was used to explain the relationship between features and the predicted results. Clinical characteristic analysis showed that 25 indices were statistically different (P <0.05). RF, LightGBM and XGBoost models, were constructed on the basis of these indices. Among them, the XGBoost model showed the best performance (micro-F1=0.7129，weighted-F1=0.6618). The areas under the ROC curve of the four subgroups were 0.7477, 0.7162, 0.9200 and 0.7500, respectively. C-reactive protein (CRP), N%, C3, and C4 with high SHAP values were positively correlated with the bacterial ID model output, which was used to distinguished other causes. Bacterial infections were the main cause of IDs. The XGBoost model could be regarded as an auxiliary tool to predict the etiological types of IDs of classic FUO, improve the etiological diagnostic rate, and provide evidence for clinical drug application.

BACKGROUND:Our study aimed to compare the predictive performance of different hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B patients receiving entecavir or tenofovir, including discrimination, calibration, negative predictive value (NPV) in low-risk, and proportion of low-risk. METHODS:We conducted a systematic literature research in PubMed, EMbase, the Cochrane Library, and Web of Science before January 13, 2022. The predictive performance was assessed by area under receiver operating characteristic curve (AUROC), calibration index, negative predictive value, and the proportion in low-risk. Subgroup and meta-regression analyses of discrimination and calibration were conducted. Sensitivity analysis was conducted to validate the stability of the results. RESULTS:We identified ten prediction models in 23 studies. The pooled 3-, 5-, and 10-year AUROC varied from 0.72 to 0.84, 0.74 to 0.83, and 0.76 to 0.86, respectively. REAL-B, AASL-HCC, and HCC-RESCUE achieved the best discrimination. HCC-RESCUE, PAGE-B, and mPAGE-B overestimated HCC development, whereas mREACH-B, AASL-HCC, REAL-B, CAMD, CAGE-B, SAGE-B, and aMAP underestimated it. All models were able to identify people with a low risk of HCC accurately. HCC-RESCUE and aMAP recognized over half of the population as low-risk. Subgroup analysis and sensitivity analysis showed similar results. CONCLUSION:Considering the predictive performance of all four aspects, we suggest that HCC-RESCUE was the best model to utilize in clinical practice, especially in primary care and low-income areas. To confirm our findings, further validation studies with the above four components were required.

Methods:We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation.Results:Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥-1, the positive and negative predictive values were both 90.8% for WD.Conclusion:Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.

目的:探讨以医疗剧衍生的情景模拟联合CBL教学法在感染科本科教育中的应用效果.方法:选择在感染科轮转的110名本科医学生,每组各55人,试验组采用情景模拟联合CBL的教学模式,对照组采用传统教学模式,比较两组学生考核成绩和教学评价.结果:试验组学生最终考核成绩和教学评价均显著高于对照组(P＜0.05).结论:以医疗剧衍生的情景模拟联合CBL教学法能够提高教学质量和学生的考核成绩,值得推广.

新冠肺炎疫情防控情形下,我国高校都在积极探索和实践"停课不停学",身处世界各地的高校留学生教学面临着巨大挑战;同时,疫情防控措施的实施与影响也让人们重新审视传染病学的重要性.近年来,留学生传染病学的教学内容和教学方式在线上教学方面的问题逐渐显现.浙江大学医学院针对丰富传染病学教学内容、创新传染病学线上教学方式等相关问题进行了剖析,同时对进一步加强全英文传染病学教学进行了探讨,以使留学生的传染病学线上教学能够满足新形势下的临床实际需求,提高留学生传染病学的教学水平,促进留学生教学质量的不断提高.

Background This study aimed to estimate hepatitis B incidence and chronicity risk in rural adults in China under the background of eliminating viral hepatitis. Methods Hepatitis B surface antigen (HBsAg) screening was conducted every 2 years in demonstration areas since 2011. Individuals with baseline HBsAg-negative were included. Incidence was calculated as the number of HBsAg-positive cases divided by the total person-times. HBsAg-positive individuals were followed up to study the persistent infection (> 6 months), chronic infection (> 12 months), and recovery with hepatitis B surface antibody (anti-HBs). The chi-square test and cox proportional regression analysis were performed. Results There were 8,942 incident cases over 2,138,532 person-years, yielding an average incidence of 0.42 per 100 person-years. HBV incidence decreased rapidly in both genders and all age groups and then kept stable. Male gender, low population density, low gross domestic product per capita, and islanders were associated with higher incidence. Of the positive cases, 4,989 (55.8%) patients were followed up. The persistent infection, chronic infection, and recovery with anti-HBs rates were 32.3%, 31.0%, and 31.4%, respectively. Persistent or chronic infection was more common in younger adults and males, while seroconversion had no concern with gender or age. Conclusions HBV incidence in adult rural residents was decreasing and stayed low. The chronicity rate was relatively high and protective antibodies were induced in only one third. The importance of population-based screening and vaccination for susceptible individuals should be addressed.

目的 探究在课程思政视域下传染病临床教学路径重构设计和实施效果.方法 从改革传染病临床教学路径,提升与思政教育课堂的协同性和利用信息化手段增加传染病临床思政教学方式多样性等几方面着手,将思政教育融汇贯通于传染病临床教学中.并通过问卷调查法明确重构设计的成效及不足.结果 以线下形式累计发放调查问卷20份,回收有效问卷20份.问卷第一部分对重构的教学路径效果整体评估,从思政教育的深度与广度、教学形式的生动性多样性两方面调研,100％受访者认为对提高思政水平有较大帮助,其中非常有帮助占60.00％,比较有帮助占40.00％.问卷第二部分对重构的教学路径不足之处评估,50.00％受访者认为时事整合欠缺,40.00％认为整合深度广度尚有进步空间,20.00％认为"互联网+"技术的个性化教学手段应用尚需加强.结论 新时代医学教育应培养德才兼备,全面发展的医学拔尖创新人才和领导者.将与国运民生紧密相连的传染病学临床教学与思政教育融合有着重要的社会意义.

Background Bibliometric have been widely applied to the evaluation of academic productivity. However, those of individuals or institutions on a specific disease have not been explored. The aim of the present study is to conduct a bibliometric analysis of particular rare disease and investigate whether those doctors and hospitals with higher index screened by this method specialize in this disease. Methods A representative rare disease, Wilson disease (WD), was searched on Clarivate Analytics’ Web of Science and Elsevier’s Scopus, which was published in English between 1 January 2001 and 31 December 2020. Clinical authors and medical institutions with the most papers were screened, and their total number of publications and citations, h-index and g-index were computed and then ranked by h-index. Results A total of 6856 and 6193 papers and 200 and 160 authors were got from WoS and Scopus, respectively. Scopus provided 160 institutions. The above bibliometric indices were calculated in 100 researchers and 80 institutions, and top 30 authors (Top-30a) and top 20 institutions (Top-20i) of them based on the h-index were listed in the tables. Top-30a came from seven specialties and 13 countries whose median (interquartile range) h-index was 14 (12–19.5) (range 10–28) which was located between associate and full professors in some other disciplines. Top-20i was distributed in 13 countries whose mean ± standard deviation of the h-index was 15 ± 4.9 (range 10–27). Conclusions The related specialists and medical institutions of WD screened by specific disease bibliometric analysis are eminent and credible and benefit WD patients to obtain reliable medical treatment. This model may be suitable for other rare diseases.

Despite the achievements obtained worldwide in the control of tuberculosis in recent years, many countries and regions including China still face challenges such as low diagnosis rate, high missed diagnosis rate, and delayed diagnosis of the disease. The discovery strategy of tuberculosis in China has changed from "active discovery by X-ray examination" to "passive discovery by self-referral due to symptoms", and currently the approach is integrated involving self-referral due to symptoms, active screening, and physical examination. Active screening could help to identify early asymptomatic and untreated cases. With the development of molecular biology and artificial intelligence-assisted diagnosis technology, there are more options for active screening among the large-scale populations. Although the implementation cost of a population-based active screening strategy is high, it has great value in social benefits, and active screening in special populations can obtain better benefits. Active screening of tuberculosis is an important component of the disease control. It is suggested that active screening strategies should be optimized according to the specific conditions of the regions to ultimately ensure the benefit of the tuberculosis control.

This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.

医学教育创新发展对高校附属医院临床医师(简称临床医师)提出了新要求,临床医师需要树立新理念、明确新定位、丰富新内涵.本研究通过文献查阅、访谈,并结合团队多年医学教育实践的经验,对当前临床医师参与医学教育中存在的问题进行剖析,探讨临床医师参与医学教育的经验和成效,提出临床医师助推医学创新发展的思考和建议.

炎症性肠病(IBD)是一类以肠道慢性炎症为特征的疾病,包括克罗恩病(CD)和溃疡性结肠炎(UC),其发病率在全球呈上升趋势.IBD的病因尚未完全明确,相关研究主要集中于遗传学、宿主免疫反应、肠道菌群和环境因素等方面.近年来,随着测序技术的发展,越来越多的研究提示,肠道真菌可能在IBD的发生发展中发挥多方面作用.本文主要对IBD患者的肠道真菌改变及其作用机制进行综述.