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Efficacy and safety of low-dose cyclophosphamide combined with lenvatinib, pembrolizumab and TACE for unresectable hepatocellular carcinoma:A single-center, prospective,single-arm clinical trial

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Chinese Journal of Cancer Research 2024年第2期36卷 114-123页

作者： Yupeng Ren Yuxuan Li Mingbo Cao Yongchang Tang Feng Yuan Gaoyuan Yang Zhiwei He Zheng Shi Xiaorui Su Zhicheng Yao Meihai Deng Department of Hepatobiliary Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Department of General Surgery Qilu HospitalShandong UniversityJinan 250012China Department of Hepatobiliary Surgery the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Hepatobiliary and Pancreatic Surgery the Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China

Objective: Unresectable hepatocellular carcinoma(uHCC) continues to pose effective treatment options. The objective of this study was to assess the efficacy and safety of combining low-dose cyclophosphamide with lenvatinib, pembrolizumab and transarterial chemoembolization(TACE) for the treatment of uHCC.Methods: From February 2022 to November 2023, a total of 40 patients diagnosed with uHCC were enrolled in this small-dose, single-center, single-arm, prospective study. They received a combined treatment of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE. Study endpoints included progression-free survival(PFS), objective response rate(ORR), and safety assessment. Tumor response was assessed using the modified Response Evaluation Criteria in Solid Tumors(mRECIST), while survival analysis was conducted through KaplanMeier curve analysis for overall survival(OS) and PFS. Adverse events(AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events(version 5.0).Results: A total of 34 patients were included in the study. The median follow-up duration was 11.2 [95% confidence interval(95% CI), 5.3-14.6] months, and the median PFS(mPFS) was 15.5(95% CI, 5.4-NA) months.Median OS(mOS) was not attained during the study period. The ORR was 55.9%, and the disease control rate(DCR) was 70.6%. AEs were reported in 27(79.4%) patients. The most frequently reported AEs(with an incidence rate >10%) included abnormal liver function(52.9%), abdominal pain(44.1%), abdominal distension and constipation(29.4%), hypertension(20.6%), leukopenia(17.6%), constipation(17.6%), ascites(14.7%), and insomnia(14.7%). Abnormal liver function(14.7%) had the most common grade 3 or higher AEs.Conclusions: A combination of low-dose cyclophosphamide with lenvatinib, pembrolizumab, and TACE is safe and effective for u HCC, showcasing a promising therapeutic strategy for managing uHCC.

关键词： Hepatocellular carcinoma lenvatinib low-dose cyclophosphamide pembrolizumab transarterial chemoembolization

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Prognostic relevance of ventricular arrhythmias in surgical patients with gastrointestinal tumors

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1787-1795页

作者： Jiao-Jie Xue Su-Tian Hu Chong-Chong Wang Zhi-Chong Chen Shi-Yao Cheng Shu-Qi Yu Hua-Jing Peng Yi-Tao Zhang Wei-Jie Zeng Department of Cardiovascular Internal Medicine Sun Yat-sen University Sixth Affiliated HospitalGuangzhou 510655Guangdong ProvinceChina Department of Cardiovascular Internal Medicine The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510700Guangdong ProvinceChina Department of Ultrasound Fuwai HospitalChinese Academy of Medical Sciences ShenzhenShenzhen 518052Guangdong ProvinceChina Department of Kidney Internal Medicine Sun Yat-sen University First Affiliated HospitalGuangzhou 510062Guangdong ProvinceChina

BACKGROUND Individuals diagnosed with gastrointestinal tumors are at an increased risk of developing cardiovascular diseases.Among which,ventricular arrhythmia is a prevalent clinical concern.This suggests that ventricular arrhythmias may have predictive value in the prognosis of patients with gastrointestinal tumors.AIM To explore the prognostic value of ventricular arrhythmias in patients with gastrointestinal tumors receiving surgery.METHODS We retrospectively analyzed data from 130 patients undergoing gastrointestinal tumor resection.These patients were evaluated by a 24-h ambulatory electrocardiogram(ECG)at the Sixth affiliated hospital of sun yat-sen university from January 2018 to June 2020.Additionally,41 general healthy age-matched and sexmatched controls were included.Patients were categorized into survival and non-survival groups.The primary endpoint was all-cause mortality,and secondary endpoints included major adverse cardiovascular events(MACEs).RESULTS Colorectal tumors comprised 90%of cases.Preoperative ambulatory ECG monitoring revealed that among the 130 patients with gastrointestinal tumors,100(76.92%)exhibited varying degrees of premature ventricular contractions(PVCs).Ten patients(7.69%)manifested non-sustained ventricular tachycardia(NSVT).The patients with gastrointestinal tumors exhibited higher PVCs compared to the healthy controls on both conventional ECG[27(21.3)vs 1(2.5),P=0.012]and 24-h ambulatory ECG[14(1.0,405)vs 1(0,6.5),P35/24 h to all-cause mortality,and NSVT was associated with MACE.However,neither PVC burden nor NSVT independently predicted outcomes according to multivariate analysis.CONCLUSION Patients with gastrointestinal tumors exhibited elevated PVCs.PVCs>35/24 h and NSVT detected by 24-h ambulatory ECG were prognostically significant but were not found to be ind

关键词： Ventricular arrhythmia Gastrointestinal tumor Major adverse cardiovascular events Prognostic Surgery

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Viral hepatitis E:Clinical manifestations,treatment,and prevention

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Liver Research 2024年第1期8卷 11-21页

作者： Qiumin Luo Jia Chen Yeqiong Zhang Wenxiong Xu Ying Liu Chan Xie Liang Peng Department of Infectious Disease 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

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions.In the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)antibodies.Although acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver failure.Moreover,some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis.Proactive screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E.This review focused on the clinical presentation,management,and prevention of hepatitis E.

关键词： Hepatitis E Chronic hepatitis Screening Antiviral therapy Vaccination

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SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike-induced intestinal inflammation

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Precision Clinical Medicine 2024年第1期7卷 84-86页

作者： Zhanyu Li Jianzhong He Yun Yin Lei Tang Ye Liu Olivia Monteiro Famin Zeng Department of Pathology The Fifth Affliated HospitalSun Yat-sen UniversityZhuhai 5190ooChina City university of Macao Macao 999078China Faculty of Medicine Macao University of Science and TechnologyMacao 999078China

Dear Editor,The pathogenesis of COVID-19 in the gastrointestinal(GI)tract is well-documented[1].However,due to a lack of simple animal models,the pathogenic mechanisms of SARS-CoV-2 in the GI tract is not well establi... 详细信息

关键词： pathogenesis gastrointestinal inflammation

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A Prognostic Nomogram with High Accuracy Based on 2D-SWE in Patients with Acute-on-chronic Liver Failure

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Journal of Clinical and Translational Hepatology 2022年第5期10卷 803-813页

作者： Lili Wu Jieyang Jin Taicheng Zhou Yuankai Wu Xinhua Li Xiangyong Li Jie Zeng Jinfen Wang Jie Ren Yutian Chong Rongqin Zheng Department of Medical Ultrasonics Third Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Key Laboratory of Liver Disease ResearchGuangzhouGuangdongChina Department of Gastroenterological Surgery and Hernia Center Sixth Affiliated Hospital of Sun Yat-Sen UniversityGuangdong Institute of GastroenterologyGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesSupported by National Key Clinical DisciplineGuangzhouGuangdongChina Department of Infectious Diseases Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdongChina

Background and Aims:Acute-on-chronic liver failure(ACLF)is associated with very high mortality.Accurate prediction of prognosis is critical in navigating optimal treatment decisions to improve patient survival.This study was aimed to develop a new nomogram integrating two-dimensional shear wave elastography(2D-SWE)values with other independent prognostic factors to improve the precision of predicting ACLF patient outcomes.Methods:A total of 449 consecutive patients with ACLF were recruited and randomly allocated to a training cohort(n=315)or a test cohort(n=134).2D-SWE values,conventional ultrasound features,laboratory tests,and other clinical characteristics were included in univariate and multivariate analysis.Factors with prognostic value were then used to construct a novel prognostic nomogram.Receiver operating curves(ROCs)were generated to evaluate and compare the performance of the novel and published models including the Model for EndStage Liver Disease(MELD),MELD combined with sodium(MELD-Na),and Jin’s model.The model was validated in a prospective cohort(n=102).Results:A ACLF prognostic nomogram was developed with independent prognostic factors,including 2D-SWE,age,total bilirubin(TB),neutrophils(Neu),and the international normalized ratio(INR).The area under the ROC curve(AUC)was 0.849 for the new model in the training cohort and 0.861 in the prospective validation cohort,which were significantly greater than those for MELD(0.758),MELD-Na(0.750),and Jin’s model(0.777,all p<0.05).Calibration curve analysis revealed good agreement between the predicted and observed probabilities.The new nomogram had superior overall net benefit and clinical utility.Conclusions:We established and validated a 2D-SWE-based noninvasive nomogram to predict the prognosis of ACLF patients that was more accurate than other prognostic models.

关键词： Acute-on-chronic liver failure Two-dimensional shear wave elastography Hepatitis B virus Prognosis

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The relationship between zinc deficiency and infectious complications in patients with hepatitis B virus-related acute-on-chronic liver failure

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Gastroenterology Report 2022年第1期10卷 552-558页

作者： Xinhua Li Lu Wang Na He Yeqiong Zhang Jiahui Pang Heping Wang Meng Yu Yongyu Mei Liang Peng Wenxiong Xu Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Key Laboratory of Tropical Disease Control(sun yat-sen university) Ministry of EducationGuangzhouGuangdongP.R.China Department of Diagnostics Second School of Clinical MedicineBinzhou Medical UniversityYantaiShandongP.R.China

Background The prevalence of zinc deficiency is high in patients with chronic liver disease,but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).This study aimed to assess the association between zinc deficiency and infectious complications,and model for end-stage liver disease(MELD)score in patients with HBV-related ACLF.Methods Patients with HBV-related ACLF from the Department of Infectious Diseases of the third affiliated hospital of sun yat-sen university(Guangzhou,China)between January 2019 and December 2019 were retrospectively analysed in this study.Their demographic,clinical,and laboratory data were retrieved from the hospital information system and analysed.The Student’s t-test was used for normally distributed continuous variables between two groups and the Chi-square test was used for categorical data.Univariate and multivariate logistic regression analyses were applied to identify independent parameters.Results A total of 284 patients were included in this study,including 205 liver cirrhosis and 79 non-cirrhosis patients.The proportion of patients with zinc deficiency was the highest(84.5%),followed by subclinical zinc deficiency(14.1%)and normal zinc level(1.4%).Patients in the zinc deficiency group had a higher MELD score than the subclinical zinc deficiency or normal zinc group(P=0.021).Age,total bilirubin,and serum zinc level were independent factors for infection(P_(s)<0.05).The serum zinc level in patients without complications at admission was significantly higher than that in patients with complications(P=0.004).Moreover,the serum zinc level in patients with prothrombin time activity(PTA)of<20%was significantly lower than that in patients with 20%≤PTA<30%(P=0.007)and that in patients with 30%≤PTA<40%(P<0.001).Conclusions Zinc deficiency is common in patients with HBV-related ACLF.Zinc deficiency is closely associated with infectious complications and MELD score in patients with HBV-related

关键词： hepatitis B virus acute-on-chronic liver failure mortality zinc complications

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Efficacy and safety of low-dose thalidomide combined with mesalazine in the treatment of refractory ulcerative colitis in adults

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Gastroenterology Report 2022年第1期10卷 653-655页

作者： Jun-Rong Chen Lei Mai Jia-Chen sun Xiang Peng Min Zhang Min Zhi Department of General Practice The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Gastroenterology The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiGuangdongP.R.China Department of Gastrointestinal Endoscopy The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdongP.R.China

Introduction Inducing and maintaining clinical remission and mucosal healing is essential in the treatment of ulcerative colitis(UC),a nonspecific chronic recurrent inflammatory disorder[1].Mesalazine(5-ASA)is commonly prescribed as a first-line drug for UC.Despite the short-term efficacy of ciclosporin and infliximab,some patients may develop methylprednisolone resistance or dependence[2].

关键词： healing clinical treatment

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Interplays between drugs and the gut microbiome

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Gastroenterology Report 2022年第1期10卷 54-61页

作者： yating Wan Tao Zuo Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongP.R.China Guangdong Institute of Gastroenterology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Center for Gut Microbiota Research The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China

The gut microbiota is considered a key‘metabolic organ’.Its metabolic activities play essential roles complementary to the host metabolic functions.The interplays between gut microbes and commonly used non-antibiotic drugs have garnered substantial attention over the years.Drugs can reshape the gut microorganism communities and,vice versa,the diverse gut microbes can affect drug efficacy by altering the bioavailability and bioactivity of drugs.The metabolismof drugs by gut microbial action or by microbiota–host cometabolism can transform the drugs into various metabolites.Secondary metabolites produced from the gut microbial metabolismof drugs contribute to both the therapeutic benefits and the side effects.In view of the significant effect of the gut microbiota on drug efficiency and clinical outcomes,it is pivotal to explore the interactions between drugs and gut microbiota underlying medical treatments.In this review,we describe and summarize the complex bidirectional interplays between gut microbes and drugs.We also illustrate the gut-microbiota profile altered by non-antibiotic drugs,the impacts and consequences of microbial alteration,and the biochemical mechanism of microbes impacting drug effectiveness.Understanding how the gut microbes interact with drugs and influence the therapeutic efficacy will help in discovering diverse novel avenues of regulating the gut microbes to improve the therapeutic effects and clinical outcomes of a drug in precision.

关键词： gut microbiota microbiome drug metabolism efficacy

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Enhanced recovery nursing and mental health education on postoperative recovery and mental health of laparoscopic liver resection

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世界胃肠外科杂志:英文版(电子版) 2023年第8期15卷 1728-1738页

作者： Dong-Xia Li Wei Ye Yi-Lu Yang Lei Zhang Xiang-Jun Qian Ping-Hua Jiang Department of Pancreatic Hepatobiliary Surgery Department of General SurgeryThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina Department of Orthopedics The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655Guangdong ProvinceChina

BACKGROUND Patients undergoing laparoscopic resection of liver metastases of colorectal cancer are prone to negative emotions and decrease of digestive function.Early nursing and psychological intervention are necessary.AIM To observe the effect of enhanced recovery nursing combined with mental health education on postoperative recovery and mental health of patients undergoing laparoscopic resection of liver metastases of colorectal cancer.METHODS One hundred and twenty patients who underwent laparoscopic resection of liver metastases of colorectal cancer at our hospital between March 2021 and March 2023,were selected as participants.The patients admitted from March 1,2021 to February 28,2022 were set as the control group,and they were given routine nursing combined with mental health education intervention.While the patients admitted from March 1,2022 to March 31,2023 were set as the observation group,they were given accelerated rehabilitation surgical nursing combined with mental health education intervention.The differences in postoperative recovery-related indices,complications and pain degrees,and mental health-related scores were compared between groups.The T lymphocyte subset levels of the two groups were also compared.RESULTS The postoperative exhaust,defecation,eating and drainage time of the observation group were shorter than those of the control group.The pain scores of the observation group were lower than those of the control group at 6,12,24,48,and 72 h after surgery.The cumulative complication rate of the observation group was lower than that of the control group(P<0.05).The CD4+/CD8+in the observation group was higher than that in the control group 3 d after surgery(P<0.05).After intervention,the self-rating depression scale,self-rating anxiety scale,avoidance dimension,and yielding dimension in Medical coping style(MCMQ)scores of the two groups were lower than those prior to intervention,and the scores in the observation group were lower than those in the control group(P<0.05).The face dimension

关键词： Accelerated surgical rehabilitation Mental health education Laparoscopy Liver metastasis of colorectal cancer Gastrointestinal function Mental health

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Analysis of functional hub genes indicates DLGAP5 is linked to lung adenocarcinoma prognosis

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BIOCELL 2023年第11期47卷 2453-2469页

作者： HAOSHENG ZHENG RUIJUN LIN WEIJIE CAI YUZHEN ZHENG XINGPING YANG ZUI LIU FEI QIN YONGJIE CAI XIANYU QIN HONGYING LIAO Department of Thoracic Surgery Thoracic Cancer CenterThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou510655China Department of Thoracic Surgery The First Affiliated Hospital of Shantou University Medical CollegeShantou515041China Department of Microbiology Zhongshan School of MedicineKey Laboratory for Tropical Diseases Control of the Ministry of EducationSun Yat-sen UniversityGuangzhouChina

Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a valuable molecular target for the treatment of LUAD.Methods:Using multiple databases,we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5(DLGAP5)in LUAD.We investigated the genetic variation,functional enrichment,and epigenetic activity of DLGAP5.Furthermore,we evaluated the relationship between the tumor microenvironment(TME)and DLGAP5.Results:Our study identified 10 hub genes in LUAD:CDC45,KIAA0101,DLGAP5,CDT1,NCAPG,CCNB1,CDCA5,CDC20,KIF11,and AURKA.We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD.DLGAP5 exhibited an overall genetic variation frequency of 2%,and its DNA promoter was hypomethylated in LUAD(p<0.05).The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine(m6A)-methylation genes.Additionally,DLGAP5 was primarily associated with the cell cycle in LUAD.Notably,there was a significant favorable association between DLGAP5 and CD274,CTLA4,HAVCR2,and LAG3 in LUAD.Conclusion:DLGAP5 may be a therapeutic target for LUAD,as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME.

关键词： DLGAP5 Lung adenocarcinoma Prognosis Tumor microenvironment Hub genes

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