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Long-term hepatitis B surface antigen kinetics after nucleos(t)ide analog discontinuation in patients with noncirrhotic chronic hepatitis B

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Liver Research 2024年第3期8卷 179-187页

作者： Lina Wu Jiadi Lai Qiumin Luo Yeqiong Zhang Chaoshuang Lin Dongying Xie Youming Chen Hong Deng Zhiliang Gao Liang Peng Wenxiong Xu department of infectious diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Guangdong Key Laboratory of Liver disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Key Laboratory of Tropical disease Control Ministry of EducationSun Yat-sen UniversityGuangzhouGuangdongChina

Background and aim Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA *** Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation ***,clinical,and laboratory data were collected and analyzed after NA *** Ninety-six patients who finished 5 years of follow-up were *** remained undetectable in 29 patients with end of treatment(EOT)HBsAg *** 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9%)patients with an estimated annual incidence of HBsAg seroclearance of 3.6%.Patients with EOT HBsAg levels of≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of>1000 IU/mL(33.3%vs.5.4%).The proportion of patients with HBsAg≤1000 IU/mL increased during *** regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/*** optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/*** Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg seroclearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of≤1000 IU/mL during 5 years of follow-up after NA *** monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

关键词： Hepatitis B virus(HBV) Chronic hepatitis B(CHB) Hepatitis B surface antigen(HBsAg) Nucleos(t)ide analogs(NAs) Quantitative HBsAg Kinetics

Evaluating short-term and long-term liver fibrosis improvement in hepatitis C patients after DAA treatment

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Journal of Biomedical Research 2024年第5期38卷 464-472,I0001,I0002页

作者： Yifan Wang Xinyan Ma Yanzheng Zou Ming Yue Meiling Zhang Rongbin Yu Hongbo Chen Peng Huang department of infectious disease Jurong Hospital Affiliated to Jiangsu UniversityJurongJiangsu 212400China department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjingJiangsu 211166China department of infectious diseases the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

Despite achieving a high cure rate with the direct-acting antivirals(DAAs)in hepatitis C treatment,further research is needed to identify additional benefits of the DAA *** current study evaluated liver fibrosis improvement in 848 hepatitis C patients treated with DAAs,who also achieved sustained virologic *** the fibrosis-4(FIB-4)index,patients were categorized based on their baseline fibrosis levels,and the improvement in fibrosis was analyzed in both short-term(9-26 weeks)and long-term(≥36 weeks)*** results showed a significant decrease in the FIB-4 index,indicating an improvement in liver fibrosis,in 63.0%and 67.6%of the patients during the short-term and long-term follow-up,***-term improvement was associated with factors including ribavirin usage,blood cholinesterase levels,alanine transaminase levels,albumin levels,and the baseline FIB-4 index,while long-term improvement was associated with factors such as aspartate transaminase levels,total protein level,and the baseline FIB-4 *** current study emphasizes the importance of continuous assessment and post-treatment monitoring of liver fibrosis,which will provide crucial insights for enhancing patient care in hepatitis C management.

关键词： chronic hepatitis C sustained virologic response direct-acting antivirals liver fibrosis

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

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World Journal of Gastroenterology 2024年第9期30卷 1237-1249页

作者： Yue-Hong Kong Mei-Ling Xu Jun-Jun Zhang Guang-Qiang Chen Zhi-Hui Hong Hong Zhang Xiao-Xiao Dai Yi-Fu Ma Xiang-Rong Zhao Chen-Yang Zhang Rong-Zheng Chen Peng-Fei Xing Li-Yuan Zhang Center for Cancer Diagnosis and Treatment The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Radiotherapy&Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina Institution of Radiotherapy&Oncology Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Radiology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Nuclear Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Clinical Laboratory The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Pathology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line *** human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in *** SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 *** had not developed any grade 2 or above treatment-related adverse events at any *** of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no *** PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

关键词： Pancreatic ductal adenocarcinoma PRaG 3.0 therapy Human epidermal growth factor receptor 2 Novel combination therapy Case report

SARS-CoV-2 immunity in animal models

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Cellular & Molecular Immunology 2024年第2期21卷 119-133页

作者： Zhao Chen Yaochang Yuan Qingtao Hu Airu Zhu Fenghua Chen Shu Li Xin Guan Chao Lv Tian Tang Yiyun He Jinling Cheng Jie Zheng Xiaoyu Hu Jingxian Zhao Jincun Zhao Jing Sun State Key Laboratory of Respiratory disease National Clinical Research Centre for Respiratory DiseaseNational Centre for Respiratory MedicineGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong 510182China GMU-GIBH Joint School of Life Sciences Guangzhou Medical UniversityGuangzhou 510000China Guangzhou National Laboratory GuangzhouGuangdong 510005China Shanghai Institute for Advanced Immunochemical Studies School of Life Science and TechnologyShanghaiTech UniversityShanghai 201210China Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518005China

The COVID-19 pandemic,which was caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has become a worldwide health crisis due to its ***-CoV-2 infection results in severe respiratory illness and can lead to significant complications in affected *** complications encompass symptoms such as coughing,respiratory distress,fever,infectious shock,acute respiratory distress syndrome(ARDS),and even multiple-organ *** models serve as crucial tools for investigating pathogenic mechanisms,immune responses,immune escape mechanisms,antiviral drug development,and vaccines against ***,various animal models for SARS-CoV-2 infection,such as nonhuman primates(NHPs),ferrets,hamsters,and many different mouse models,have been *** model possesses distinctive features and *** this review,we elucidate the immune response elicited by SARS-CoV-2 infection in patients and provide an overview of the characteristics of various animal models mainly used for SARS-CoV-2 infection,as well as the corresponding immune responses and applications of these models.A comparative analysis of transcriptomic alterations in the lungs from different animal models revealed that the K18-hACE2 and mouse-adapted virus mouse models exhibited the highest similarity with the deceased COVID-19 ***,we highlighted the current gaps in related research between animal model studies and clinical investigations,underscoring lingering scientific questions that demand further clarification.

关键词： COVID-19 SARS-CoV-2 animal models immune response

Single-cell transcriptomic analysis reveals transcript enrichment in oxidative phosphorylation,fluid sheer stress,and inflammatory pathways in obesity-related glomerulopathy

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Genes & diseases 2024年第4期11卷 314-326页

作者： Yinyin Chen Yushun Gong Jia Zou Guoli Li Fan Zhang Yiya Yang Yumei Liang Wenni Dai Liyu He Hengcheng Lu department of Nephrology Hunan Provincial People's HospitalThe First Affliated Hospital of Hunan Normal UniversityHunan Clinical Research Center for Chronic Kidney DiseaseChangshaHunan 410000China department of Nephrology The Second Xiangya Hospital of Central South UniversityHunan Key Laboratory of Kidney Disease and Blood PurificationChangshaHunan 410011China Cardiovascular Research Institute of Jiangxi Province Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeNanchangJiangxi 330006China

Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal *** have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene *** define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA *** report for the first time that immune cells,including T cells and B cells,are decreased in ORG *** analysis indicated that SPP1 was significantly up-regulated in T cells and B *** gene is related to inflammation and cell *** of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress ***,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and ***,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.

关键词： Fluid shear stress Inflammation Obesity-related glomerulopathy Oxidative phosphorylation Single-cell RNA seq

Optimal Timing of Antiretroviral Therapy Initiation in Acquired Immunodeficiency Syndrome-Associated Toxoplasmic Encephalitis:A Prospective Observational Multicenter Study in China

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infectious diseases & Immunity 2024年第1期4卷 4-9页

作者： Yao Li Haidong Jiang Yanming Zeng Yanqiu Lu Siyuan Chen Yulin Zhang Zhongsheng Jiang Tongtong Yang Shuiqing Liu Yaokai Chen department of infectious diseases Chongqing Public Health Medical CenterChongqing 400036China Center for infectious diseases Beijing Youan HospitalCapital Medical UniversityBeijing 100069China department of infectious diseases Liuzhou People's HospitalLiuzhou 545006GuangxiChina department of infectious disease The Public Health Clinical Center of ChengduChengdu 610066SichuanChina department of infectious disease Guiyang Public Health Clinical CenterGuiyang 550004GuizhouChina

Background:Toxoplasmic encephalitis(TE)is the most frequent cause of expansive brain lesions among patients with acquired immunodeficiency syndrome(AIDS).However,the optimal timing of antiretroviral therapy(ART)initiation in these patients remains *** study aims to investigate the differences in outcomes of ART initiation at different times,in order to help clarify the treatment timing of AIDS-associated ***:This multicenter prospective observational study included 87 patients recruited from 11 research centers in China(from March 2019 to December 2022).Of the patients,38 were assigned to the early ART group(initiating ART within 2 weeks after anti-Toxoplasma treatment initiation),and the remaining 49 patients received deferred ART(initiating ART at least 2 weeks after anti-Toxoplasma treatment initiation).The main outcomes includedmortality and emergence of immune reconstitution inflammatory syndrome(IRIS).Human immunodeficiency virus(HIV)-1 viral load and CD4^(+)T-cell counts at weeks 24 and 48 were ***:The number of deaths(1 vs.5,P=0.225)and incidence of IRIS(2.6%vs.0,P=0.437)were not significantly different between the early and deferred ART groups at week *** ART initiation did not contribute significantly to HIV-1 viral load control(<50 copies/mL,n=8 vs.n=3 at week 24,P=0.142;n=7 vs.n=7 atweek 48,P=1.000).The median CD4^(+)T-cell counts between the two groups were not significantly different,either at week 24(155 vs.91 cells/mm^(3),P=0.837)or atweek 48(181 vs.146 cells/mm^(3),P=0.219).Conclusion:In patients with AIDS-associated TE,early ART initiation was not significantly different from deferred ART initiation in terms of incidence of mortality,IRIS,and HIV virological and immunological *** registration:This study was registered(registration number:ChiCTR1900021195)as one of 12 clinical trials under the title of a general project at the Chinese Clinical Trial Registry(***)on February 1,***

关键词： HIV Toxoplasma gondii Timing of antiretroviral therapy Virological outcome Immunological response

Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2018-2037页

作者： Li Wang Wei-Hua Gong department of Emergency The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina department of Surgery The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310052Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive *** to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant *** than 60%of GC are linked to infection with Helicobacter pylori(***),a gram-negative,active,microaerophilic,and helical *** parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane ***,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between *** infection-related GC and *** To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination *** Gene expression profiles of GC patients and those with ***-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)*** FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox *** predictive ability of the FRGPI was validated in the GEO ***,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and *** Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and ***-associated *** FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk *** FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease ***,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI *** hub genes were also conf

关键词： Ferroptosis Gastric cancer Helicobacter pylori infection Immune checkpoint protein Prognostic model Ferroptosis-related gene prognostic index

CRISPR/Cas9 system and its applications in nervous system diseases

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Genes & diseases 2024年第2期11卷 675-686页

作者： Haibin Jiang Mengyan Tang Zidi Xu Yanan Wang Mopu Li Shuyin Zheng Jianghu Zhu Zhenlang Lin Min Zhang The second School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China The First School of Medicine Wenzhou Medical UniversityWenzhouZhejiang 325035China department of Pediatrics The Second School of MedicineThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China Key Laboratory of Perinatal Medicine of Wenzhou WenzhouZhejiang 325027China Key Laboratory of Structural Malformations in Children of Zhejiang Province WenzhouZhejiang 325000China Zhejiang Provincial Clinical Research Center for Pediatric disease WenzhouZhejiang 325027China

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system is an acquired immune system of many bacteria and archaea,comprising CRISPR loci,Cas genes,and its associated *** system can recognize exogenous DNA and utilize the Cas9 protein's nuclease activity to break DNA double-strand and to achieve base insertion or deletion by subsequent DNA *** recent years,multiple laboratory and clinical studies have revealed the therapeutic role of the CRISPR/Cas9 system in neurological *** article reviews the CRISPR/Cas9-mediated gene editing technology and its potential for clinical application against neurological diseases.

关键词： CRISPR/Cas9 Gene editing Mutation Neurological diseases Therapeutics

Pulmonary rehabilitation protocols in urgent lung transplantation patients

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World Journal of Emergency Medicine 2024年第1期15卷 47-51页

作者： Fei Zeng Lingyun Cai Luyao Guo Meijuan Lan Jiangshuyuan Liang Peipei Gu Nursing department the Second Affi liated Hospital of Zhejiang University School of MedicineHangzhou 310009China

BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex *** aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant ***:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January *** were retrieved from electronic medical records at our lung transplant ***:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and *** mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±*** Nutritional Risk Screening 2002(NRS 2002)scores were≥*** was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,*** total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 *** patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.

关键词： Urgent lung transplantation End-stage lung disease Extracorporeal membrane oxygenation Invasive respiratory support Pulmonary rehabilitation.