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Effects of Salmonella infection on hepatic damage following acute liver injury in rats

Hepatobiliary & Pancreatic diseases International 2016年第4期15卷 399-405页

作者： Yong-Tao Li Cheng-Bo Yu Dong Yan Jian-Rong Huang Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalZhejiang University School of Medicine

BACKGROUND： Acute liver injury is a common clinical disorder associated with intestinal barrier injury and disturbance of intestinal microbiota. Probiotic supplementation has been reported to reduce liver injury; however, it is unclear whether enteropathogen infection exacerbates liver injury. The purpose of this study was to address this unanswered question using a rat model. METHODS： Oral supplementation with Salmonella enterica serovar enteritidis（S. enteritidis） was given to rats for 7 days. Different degrees of acute liver injury were then induced by intraperitoneal injection of D-galactosamine. The presence and extent of liver injury was assayed by measuring the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and total bilirubin. Histology was used to observe liver tissue damage. Additionally, we measured the changes in plasma endotoxin, serum cytokines and bacterial translocation to clarify the mechanisms underlying intestinal microbiota associated liver ***： The levels of liver damage and endotoxin were significantly increased in the Salmonella infected rats with severe liver injury compared with the no infection rats with severe liver injury（P〈0.01）; The peyer＇s patch CD3＋ T cell counts were increased significantly when the Salmonella infection with severe injury group was compared with the normal group（P〈0.05）. S. enteritidis pretreatment enhanced intestinal barrier impairment and bacterial ***： Oral S. enteritidis administration exacerbates acute liver injury, especially when injury was *** factors of the exacerbation include inflammatory and oxidative stress injuries induced by the translocated bacteria and associated endotoxins, as well as over-activation of the immune system in the intestine and liver.

关键词： acute liver injury Salmonella enteritidis endotoxin cytokine bacterial translocation

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Nasal delivery of broadly neutralizing antibodies protects mice from lethal challenge with SARS-CoV-2 delta and omicron variants

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Virologica Sinica 2022年第2期37卷 238-247页

作者： Jia Lu Qiangling Yin Rongjuan Pei Qiu Zhang Yuanyuan Qu Yongbing Pan Lina Sun Ding Gao Cuiqin Liang Jingwen Yang Wei Wu Jiandong Li Zongqiang Cui Zejun Wang Xinguo Li Dexin Li Shiwen Wang Kai Duan Wuxiang Guan Mifang Liang Xiaoming Yang National Engineering Technology Research center for Combined Vaccines Wuhan Institute of Biological Products Co.Ltd.Wuhan430070China State Key Laboratory for Molecular Virology and Genetic Engineering National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China center for emerging infectious diseases Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China CDC-WIV Joint Research center for emerging diseases and Biosafety Wuhan430071China Institution of infectious diseases Shenzhen Bay LaboratoryShenzhen518107China

Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing *** highlights a critical need to discover new therapeutic agents to overcome the variants *** the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants ***,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 *** broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron *** prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining ***,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron *** findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.

关键词： Coronavirus disease 2019(COVID-2019) Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) Prophylactic protection Omicron variant K18-h ACE2

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Immune recall enhances cross-reactive antibody longevity after a large wave of SARS-CoV-2 breakthrough infection

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Signal Transduction and Targeted Therapy 2024年第9期9卷 3563-3565页

作者： Dan Li Qingfei Chu Kang Li Lanjuan Li Yiming Shao State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China National Key Laboratory of Intelligent Tracking and Forecasting for infectious diseases National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Dear Editor,Although coronavirus disease 2019(COVID-19)is no longer deemed a“Public Health Emergency of International Concern”,the global transmission dynamics of SARS-CoV-2 have shifted due to vaccination,emergency of virus variants,and pre-existing coronavirus immunity.1–3 It remains unclear how cross-reactive and pre-existing humoral immunity might impact the effectiveness of vaccines and antibodies against new viral mutations.4,5 This study seeks to elucidate the cross-reactivity of coronavirus antibodies induced by previously unencountered Omicron BA.5/BF.7 variants in the breakthrough infection(BTI)population.

关键词： immunity infection breakthrough

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Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy

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Science China(Life Sciences) 2021年第1期64卷 152-161页

作者： Guoli Li Jiarui Li Henghui Zhang Yu Zhang Di Liu Yu Hao Junyan Han Juan Du Liuluan Zhu Yongqin Zeng Bei Li Rui Li Chuan Song Fujie Zhang Chen Chen Hongxin Zhao Hui Zeng Institute of infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijing100015China Beijing Key Laboratory of emerging infectious diseases Beijing100015China Clinical and Research center of infectious diseases Beijing Ditan HospitalCapital Medical UniversityBeijing100015China Computational Virology Group Center for Bacteria and Virus Resources and ApplicationWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing101408China

Chronic human immunodeficiency virus(HIV) infection not only causes a gradual loss of CD4~+T cells but also leads to a disturbance of the T cell receptor(TCR) repertoire. In people living with HIV(PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3(CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in *** characterized the TCR V-J pairing profile of na?ve and memory CD4~+T cells in healthy donors, HIV-infected antiretroviral therapy(ART)-na?ve patients and long-term(over5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories(expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-na?ve patients, 14 of the 18 parameters were significantly ***-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual ***, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection.

关键词： acquired immune deficiency syndrome human immunodeficiency virus antiretroviral therapy T cell receptor V-J pairing

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A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang Jia-Jie Zhu Zong-Ming Liu Yu-Xuan Zhang Jia-Jia Chen Ke-Da Chen Zhejiang Chinese Medical University Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term *** competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC *** on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is ***:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in *** function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory *** the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC ***-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment ***:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was *** inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC *** analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC ***:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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Monkeypox outbreak: a novel threat after COVID-19?

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Military Medical Research 2023年第1期10卷 137-138页

作者： Yang Zhang Ji-Yuan Zhang Fu-Sheng Wang Senior Department of infectious diseases the Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China

Dear Editor,Monkeypox is a zoonosis caused by monkeypox virus (MPXV)infection first reported in Central and West Africa[1]. The first outbreak of monkeypox outside of Africa was reported in2003[2].Afterthat,Israel,theUnitedKingdom(UK),Singapore, and other countries have reported monkeypox cases among travelers back from Nigeria since 2018[3].

关键词： Monkeypox Outbreak Zoonosis Human-to-human transmission

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Clinical characteristics of critical patients with pandemic influenza A(H1N1) virus infection in Chengdu,China

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第1期13卷 49-55页

作者： Li-hui DENG1,2,Yi-lan ZENG3,Ping FENG1,Ya-ling LIU3,Li-chun WANG1,2,Yun BAI3,Hong TANG1,2(1center of infectious diseases,West China Hospital of Sichuan University,Chengdu 610041,China)(2Division of infectious diseases,State Key Laboratory of Biotherapy,Sichuan University,Chengdu 610041,China)(3Chengdu infectious Disease Hospital,Chengdu 610041,China) center of infectious diseases West China Hospital of Sichuan University Chengdu 610041 China

Objective： The critical illness of pandemic influenza A （H1N1） virus infection may be associated with relatively poor outcomes. The objective of this study is to describe clinical features and factors associated with the deaths of critical patients. Methods： Medical records of 26 critical patients with H1N1 infection admitted from Sept. 1 to Dec. 31, 2009, were retrospectively reviewed. Diagnosis was established by real-time reverse transcdptase- polymerase chain reaction （RT-PCR） assay. Results： The mean age of the patients was （40.4＋18.4） years and 73.1% of them were male. Clinical manifestations included fever, cough, and sputum production. The laboratory findings included leukocytosis, lymphopenia, C-reaction protein, and lactic dehydrogenase elevation. In this series, 17 subjects survived and 9 died. The parameters between the deaths and survivors were compared, which included acute physiology and chronic health evaluation II （APACHE II） scores （23.8＋10.1 vs. 14.3_＋6.6, P〈0.05）, sequential organ failure assessment （SOFA） scores （13.3_＋3.0 vs. 6.6_＋3.3, P〈0.05）, and multiple organ dysfunction syndrome （MODS） scores （7.4＋2.5 vs. 3.3＋1.7, P〈0.05）. The cases of deaths had higher incidences of cardiovascular failure （100% vs. 41.2%, P〈0.05）, renal failure （55.6% vs. 11.7%, P〈0.05）, encephalopathy （44.4% vs. 5.9%, P〈0.05）, hepatic failure （33.3% vs. 5.9%, P〈0.05）, and septic shock （33.3% vs. 17.6%, P〈0.05）. Conclusions： The critical patients with H1 N1 infection have high APACHE II, SOFA, and MODS scores, which may be associated with an increased risk of death and complex clinical courses.

关键词： Critical illness H1N1 Infection Influenza A virus Mortality

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Predictors of loss of hepatitis B surface antigen in HIV-infected patients

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World Journal of Gastroenterology 2010年第9期16卷 1093-1096页

作者： George Psevdos Jong Hun Kim Jin S Suh Victoria Lee Sharp center for Comprehensive Care Division of Infectious DiseasesSt.Luke's-Roosevelt Hospital Center Division of infectious diseases University of Pittsburgh Medical Center center for Comprehensive Care St.Luke's-Roosevelt Hospital Center

AIM:To study factors associated with loss of hepatitis B surface antigen (HBsAg) in patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV).METHODS:We retrospectively reviewed the medical records of 5681 patients followed up at two New York City HIV clinics from January 1999 to May *** and laboratory parameters including baseline and follow-up HIV viral loads,CD4 cell counts,alanine transaminase levels,demographics,presence of hepatitis C infection,and treatment with highly active antiretroviral therapy dually active against both HIV and HBV infection,were analyzed to determine factors associated with loss of ***:Three hundred and fifty five patients (355/5681,6.84%) were co-infected with HIV and HBV and were *** these,226 patients with more than 12 mo follow-up were included in further analysis to determine factors associated with loss of HBsAg in the long-term *** the univariate analysis,baseline CD4 cell count was associated with loss of HBsAg (P=0.052).Cox regression analysis revealed that loss of HBsAg was associated with baseline CD4 cell count > 500 cells/mm3 (P=0.016,odds ratio:76.174,95% confidence interval:2.233-2598.481).CONCLUSION:Our study showed an interesting association of loss of HBsAg in HIV-HBV co-infected patients with higher CD4 cell count,suggesting that T-cell cytolytic activity against HBV may still be effective in clearing HBV infection.

关键词： Human immunodeficiency virus Hepatitis B Viral antigens Surface antigens

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Application of large language models in disease diagnosis and treatment

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中华医学杂志(英文版) 2025年第2期138卷 130-142页

作者： Yang Xintian Li Tongxin Su Qin Liu Yaling Kang Chenxi Lyu Yong Zhao Lina Nie Yongzhan Pan Yanglin State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research center for Digestive diseases Xijing Hospital of Digestive Diseases Fourth Military Medical University Xi’an Shaanxi China Department of Radiotherapy Xijing Hospital Fourth Military Medical University Xi’an Shaanxi China

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.

关键词： Large language models Artificial intelligence Diagnosis Treatment planning Clinical decision support

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Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-onchronic liver failure:a nationwide prospective multicenter study in China

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Hepatobiliary & Pancreatic diseases International 2016年第3期15卷 275-281页

作者： Jia-Jia Chen Jian-Rong Huang Qian Yang Xiao-Wei Xu Xiao-Li Liu Shao-Rui Hao Hui-Fen Wang Tao Han Jing Zhang Jian-He Gan Zhi-Liang Gao Yu-Ming Wang Shu-Mei Lin Qing Xie Chen Pan Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesFirst Affiliated HospitalZhejiang University School of Medicine Liver Failure Therapy and Research center 302 Hospital of People’s Liberation Army Department of Hepatology Third Central Clinical College of Tianjin Medical University Artificial Liver center You’an HospitalCapital Medical University Department of infectious diseases First Affiliated Hospital of Suzhou University Department of infectious diseases Third Affiliated Hospital of Sun Yat-Sen University Institute of infectious diseases Southwest HospitalThird Military Medical University Department of infectious diseases First Affiliated Hospital of Xi’an Jiaotong University Department of infectious diseases Ruijin HospitalShanghai Jiaotong University School of Medicine Department of infectious diseases Infectious Diseases Hospital Affiliated to Fujian Medical University

BACKGROUND： Plasma exchange （PE）-centered artificial liver support system reduced the high mortality rate of hepa titis B virus （HBV）-related acute-on-chronic liver failure （ACLF）. But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.

关键词： liver failure artificial liver support plasma exchange acute-on-chronic liver failure

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