1.The regulatory role of tissue-resident memory T cells in chronic liver diseases and associated therapeutic targets
Jin LIN ; Yu ZENG ; Zhanfei TIAN ; Xiaoli FAN
Journal of Clinical Hepatology 2025;41(5):975-982
Tissue-resident memory T cells (TRM cells) are a subset of memory T cells that reside in tissues, exhibit tissue specificity, and do not recirculate. When potential hazards threaten the liver, such as pathogen invasion (bacteria, viruses, etc.) and excessive autoimmune responses, TRM cells are essential as the first line of immune defense, playing an important role in viral hepatitis, autoimmune liver disease, metabolic dysfunction-associated fatty liver disease, liver cirrhosis, and liver transplantation. Here, we present the immunophenotypes of TRM cells in the liver and their surface markers and transcriptional profiles, aiming to clarify the role of TRM cells in chronic liver diseases and explore their potential function as therapeutic targets in immunotherapy.
2.Pharmacological action of astragaloside Ⅳ in the prevention and treatment of liver diseases and its mechanism
Ke FU ; Shu DAI ; Juan YOU ; Chen YANG ; Xiaoli LI ; Li ZENG ; Shiyun PU
Journal of Clinical Hepatology 2025;41(10):2174-2179
Astragaloside Ⅳ (AS-Ⅳ) is a natural triterpenoid saponin compound derived from Astragalus membranaceus and has shown significant potential in the regulation of liver diseases. This article reviews the latest research advances in AS-Ⅳ in the field of liver diseases in China and globally, and it is found that AS-Ⅳ exerts a liver-protecting effect by regulating lipid metabolism, exerting an anti-tumor/anti-inflammatory/anti-fibrotic effect, and modulating gut microbiota. Its mechanism of action involves multiple signaling pathways, such as AMPK, NLRP3, NF-κB, JAK2/STAT3, and Nrf2. These research findings provide a scientific basis for the development of liver-protecting drugs or functional foods based on the natural product AS-Ⅳ.
3.p300 promotes hepatic lipid accumulation in dyslipidemia by regulating SREBP-1c acetylation
Nyewneh Abdul-Rauf NUHU ; Xiaoli LI ; Lu FANG ; Yongqing CAI ; Fei CHEN ; Lie YUAN ; Xiong YANG ; Qingsong JIANG ; Yinbo LIU ; Chao LIU ; Peiling ZHONG ; Menghua ZENG
Journal of Army Medical University 2025;47(22):2735-2748
Objective To investigate the role of p300 in lipid metabolism disorders.Methods Bioinformatics analysis was performed to analyze the expression patterns of p300 in lipid metabolism disorder-related diseases and its correlation with SREBP-1c and downstream lipid metabolic enzymes.Immunofluorescence assay was used to detect the expression of p300 in the liver tissues of the patients with varying disease severity of non-alcoholic fatty liver disease(NAFLD).A mouse model of lipid metabolism disorder was established in male C57BL/6J mice by feeding high-fat diet(HFD)for 12 weeks.Western blotting was employed to assess p300 expression level in the liver tissues of HFD-fed mice.A cell model of lipid metabolism disorder was established in HepG2/AML-12 cells induced with free fatty acid(FFA).The effects of siRNA-mediated knockdown of p300 was observed to measure the levels of intracellular total cholesterol(TC)and triglyceride(TG),lipid deposition,and production of reactive oxygen species(ROS).Results Clinically,p300 was highly expressed in lipid metabolism disorders,and its level was positively correlated with NAFLD severity(P<0.05).Gene Set Enrichment Analysis(GSEA)revealed that p300 expression was significantly associated with fatty acid metabolism,cholesterol homeostasis,lipogenesis,PPAR signaling pathway,and peroxisome pathway.In vivo,p300 was significantly up-regulated in the livers of HFD-fed mice(P<0.01).In vitro,FFA stimulation markedly increased p300 expression in both HepG2 and AML-12 cells(P<0.01),whereas p300 knockdown significantly reduced intracellular TG and TC levels(P<0.01),attenuated lipid droplet accumulation,and reversed FFA-induced ROS elevation(P<0.01).Furthermore,p300 expression was positively correlated with the expression of SREBP-1c and its downstream key lipid synthesis enzymes.Conclusion p300 may promote hepatic lipid accumulation by acetylating and activating SREBP-1c and regulating downstream lipid metabolic enzymes,thereby affecting lipid synthesis and oxidative stress.These findings suggest that p300 may be a potential therapeutic target for lipid metabolism disorder-related diseases.
4.Mediating role of medical coping strategies in the relationship of perceived social support and resilience in patients with occupational pneumoconiosis
Xiaoli ZENG ; Xinxiang QIU ; Xiaoyuan LIN ; Lvqin WEN ; Yan ZENG
China Occupational Medicine 2024;51(5):544-549
Objective To investigate the mediating role of medical coping strategies in the relationship between perceived social support and resilience among patients with occupational pneumoconiosis (hereinafter referred to as pneumoconiosis). Methods A total of 240 pneumoconiosis patients were selected as the study subjects using the convenience sampling method. The Perceived Social Support Scale, the 10-item Connor-Davidson Resilience Scale and Medical Coping Strategies Questionnaire were used to evaluate their perceived social support, resilience and medical coping strategies. AMOS 26.0 software was used to construct the structural equation model. Results The average scores of perceived social support and resilience were (56.6±0.9) and (20.9±7.5), respectively. The scores for the dimensions of confrontation, avoidance and resignation of medical coping strategies were (20.2±3.6), (11.2±3.1) and (18.1±2.9), respectively. The score of resilience was positively correlated with the score of perceived social support, avoidance dimension and confrontation dimension of medical coping strategies (r=0.260, 0.176, 0.174, all P<0.01). It was negatively correlated with resignation coping (r=-0.292, P<0.01). The results of mediating effect test showed that the total effect of perceived social support on resilience was 0.252 [95% confidence interval (CI) was 0.056-0.448], which mainly affected the resilience by affecting the resignation coping (95%CI: -0.458 to -0.104), with the indirect effect value of 0.120, accounting for 47.6% of the total effect. Conclusion The resilience of pneumoconiosis patients is moderately low. Resignation coping in medical coping strategies plays a mediating role between perceived social support and resilience in pneumoconiosis patients.
5.Analysis of laboratory tests and prevention strategies for hemolytic disease of the fetus and newborn caused by anti-M
Hecai YANG ; Xiaoli MA ; Yonglei LYU ; Dongdong TIAN ; Qunjuan ZENG ; Minglu GENG ; Yi CAO ; Liping WANG
Chinese Journal of Blood Transfusion 2024;37(6):648-653
Objective To analyze the application of serological test results in the diagnosis and treatment of anti-M-in-duced hemolytic disease of the fetus and newborn(HDFN),and to explore HDFN prevention strategies.Methods The se-rological test results of 12 cases of HDFN caused by anti-M diagnosed in our laboratory from January 2017 to December 2023 were retrospectively analyzed,including blood group identification of mothers and children,serum total bilirubin/hemoglo-bin/antibody titer test,and three hemolysis tests in newborns.Clinical data of the children and mothers were collected,in-cluding pregnancy history,blood transfusion history,prenatal antibody testing,history of intrauterine blood transfusion and gestational week of delivery,and the prognosis of the children was followed up.Results All 12 cases of fetal neonatal he-molytic disease due to anti-M were RhD+MN phenotype newborn born to RhD+NN mother,with maternal-fetal incompati-blility in MN blood groups.In the ABO blood group system,ABO incompatibility between mother and child accounted for 41.7%(5/12).None of the mothers had a history of blood transfusion,and the median titer of the test at 4℃was 32,and the median titer at 37℃was 4.The mothers of 3 cases had a history of multiple intrauterine blood transfusions,with an inci-dence of 25%(3/12).One case had an abnormal first pregnancy,with an incidence of 8.3%(1/12),and seven cases had an abnormal pregnancy with a miscarriage,with an incidence of abnormal pregnancy and birth history of 58.3%(7/12).There were 6 cases of premature labor,with an incidence of 50%(6/12).The mothers in three cases underwent regular ob-stetric examination and the specificity of the antibodies was determined,accounting for 25%(3/12).Twelve children had free antibodies with a median titer of 6 at 4℃and 2 at 37℃.Two children had anti-M antibodies that were not reactive at 37℃,with a negative rate of 16.7%(2/12).The positive rate of DAT and elution test was respectively 8.3%(1/12)and 16.7%(2/12)in the children.The median minimum hemoglobin value was 75 g/L,and all 12 children received blood transfusions.The median peak total bilirubin value was 157.5 μmol/L,and none of them reached the threshold for blood ex-change.The rate of delayed anemia was16.7%(2/12),the postnatal mortality rate was8.3%(1/12),and 11 children was free of growth and neurodevelopmental delay in prognosis.Conclusion Anti-M can cause severe HDFN,which can also oc-cur in primigravida.The intensity of antibody titer does not correlate with the severity of the disease,and it is prone to cause delayed anemia,which should be monitored regularly according to the serological characteristics of anti-M and clinical symp-toms,and should be treated timely.
6.Identification of anti-Jra antibodies by serology and mass spectrometry
Zhifa LING ; Xiaoli ZENG ; Xuewen YUAN ; Wei SHEN
Chinese Journal of Blood Transfusion 2024;37(7):827-830
Objective To report the antibody specific identification process of a pregnant woman who had no history of blood transfusion but presented high-frequency anti-Jra antibodies.Methods Antibody screening and identification were performed by saline and indirect Coomb's technique(microcolumn gel card,PEG).ABO,Rh and other blood group anti-gens were identified by saline.Further antibody identification tests were performed by the reaction between cells treated with various enzymes and patient plasma.Jra antigen was identified by human anti-Jraantibody.JR blood type genotyping was per-formed by MALDI-TOF mass spectrometry detection system.Antibody titer in serum was tested.Results The patient′s blood type was O with RhD(+)and CcDEe.The plasma reacted negatively with antibody screening and identification cells by saline,but positively by indirect globulin test.The self-control was negative.The patient′s Jraantigen was negative in sero-logical tests and mass spectrometry blood type genotyping.Mass spectrometry revealed a homozygous nonsense mutation(c.376C>T)in exon4.The anti-Jra antibody titer was1∶2.Conclusion The patient developed high-frequency anti-Jraantibod-ies during pregnancy.
7.Molecular biological analysis of RhD variant blood donors in Zhengzhou
Hecai YANG ; Qunjuan ZENG ; Xiaoli MA ; Yonglei LYU ; Minglu GENG ; Liping WANG
Chinese Journal of Blood Transfusion 2024;37(8):866-871
Objective To investigate the serological characteristics and gene mutation mechanism of RhD variant blood donors in Zhengzhou.Methods From January 2023 to December 2023,1 619 RhD-negative blood donors sent to our labora-tory were selected for the study,and RhD negative confirmation test and RhCE phenotype detection were applied by tube method and microcolumn gel indirect antiglobulin test method.RHD gene amplification and Sanger sequencing were used to detect RhD variant sample genotypes.Results A total of 69 cases of RhD variants were detected in the RhD negative con-firmation test,with a proportion of 4.26%(69/1 619).The RhCE phenotypes were ccEe,Ccee,CcEe and CCee.There were 17 genotypes and 15 phenotypes of the D variant.The RHD?weak partial 15 allele was the most frequent(33 cases),with a frequency of 47.83%(33/69),and the main phenotype was the ccEe.This was followed by the RHD?DVI.3 allele in 20 ca-ses with a frequency of 28.99%(20/69)and the predominant phenotype was Ccee.The RHD?weak partial 15/RHD?01EL.01 heterozygote was found in 3 cases with a frequency of 4.35%(3/69),all with the CcEe phenotype.Other rare genotypes were present in 13 cases with a frequency of 18.84%(13/69).Antibody screening was positive in 3 cases with a frequency of 4.35%(3/69).Two cases of female blood donors,both with history of pregnancy and childbirth,were identified as anti-D;one case of male donor was anti-M.Conclusion The RHD?weak partial 15 genotype was the most common among the RhD variants in blood donors in Zhengzhou,followed by the RHD?DVI.3 genotype.It plays an important role in guarantee-ing the safety of blood supply and guiding precision transfusion.
8.Self-perceived risk of stroke among elderly population in Haikou area
Xufang WEI ; Xiaoli FENG ; Ting HUANG ; Chaokun ZENG ; Kangmeng WANG ; Zhenqiang ZHAO
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):167-170
Objective To investigate the difference between self-perceived risk and objective risk of stroke in the elderly population in Haikou area and explore the related factors in order to deter-mine the role of stroke knowledge in self-perceived risk.Methods A cross-sectional questionnaire survey was conducted on 584 elderly patients who were selected by convenience sampling from those taking physical examination in the First Affiliated Hospital of Hainan Medical College from September 2022 to April 2023.According to the accuracy of self-perceived risk of stroke,they were divided into an under-estimation group(170 cases),an accurate-estimation group(329 cases)and an over-estimation group(85 cases).Their self-perceived risk of stroke was assessed with the Stroke Risk Perception Questionnaire,and the objective risk of stroke was assessed with the Screening Criteria of Stroke High-Risk Group Screening Intervention Project of National Health Commission.Multivariate logistic regression model was used to analyze the factors related to the accuracy of self-perceived risk of stroke.One-way ANOVA was used to analyze the correlation be-tween the accuracy of self-perceived stroke risk and stroke knowledge.Results The participants with low,moderate,and high self-perceived risk of stroke accounted for 75.5%,20.5%and 3.9%,respectively.Compared with the objective risk assessment,the percentages of the participants with self-perceived stroke risk were 29.1%,56.3%and 14.6%,respectively,in the under-,accurate-and over-estimation groups.Significant differences were observed in gender,education level,smoking,drinking,exercise,fatty diet,fruit,overweight or obesity,and dyslipidemia among all groups(P<0.05,P<0.01).Multivariate logistic regression analysis showed that smoking,regular exercise,overweight or obesity and dyslipidemia were associated with accuracy of stroke risk perception in the accurate and the over-estimation groups when the under-estimation group was regarded as control(P<0.01).The total score of stroke knowledge was 6.81±3.63,7.17±3.47 and 8.07± 3.24,respectively in the 3 estimation groups.The accuracy of self-perceived stroke risk was corre-lated with stroke knowledge(F=3.756,P=0.024).Conclusion Targeted health education should be implemented to make the elderly establish correct awareness of stroke risk,promote healthy behaviors and habits,and achieve the goal of early stroke prevention.
9.Epidemiological and genetic characteristics of coxsackievirus B3 in Guangdong Province, 2008-2021
Hanri ZENG ; Huanying ZHENG ; Yong LONG ; Xiaoli CHEN ; Wei ZHANG ; Caixia LI ; Bixia KE ; Xiaoling DENG ; Bosheng LI
Chinese Journal of Microbiology and Immunology 2024;44(7):629-634
Objective:To study the epidemiological and genetic characteristics of coxsackievirus B3 (CVB3) circulating in Guangdong Province from 2008 to 2021.Methods:This study collected the specimens of hand, foot, and mouth disease (HFMD) cases from 2008 to 2021 that were positive for other enteroviruses except for enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and CVA6, as well as the specimens of herpangina and neonatal infection cases from 2020 to 2021. Enteroviruses in these specimens were detected and their types were identified. CVB3 strains were isolated and the entire VP1 sequences of CVB3 strains were amplified and sequenced. The genetic features of CVB3 strains were analyzed using DNAStar 7.1 and MEGA 6.06 software packages.Results:Among 3 484 HFMD cases positive for other enteroviruses from 2008 to 2021, CVB3-positive cases accounted for 1.6% (57/3 484); among 560 cases of herpangina from 2020 to 2021, CVB3-positive cases accounted for 2.1% (12/560); one neonatal infection case in 2021 was positive for CVB3. CVB3-positive cases accounted for 67.1% (47/70) in 2021 and 18.6% (13/70) in 2020, while there were less than five cases in other years. Forty-eight CVB3 strains were isolated and the entire VP1 sequences of 26 CVB3 strains were obtained. Phylogenetic analysis indicated that the CVB3 strains could be divided into eight genotypes (A-H) and the strains of genotypes A, D and E were prevalent in the Chinese mainland. The 26 CVB3 strains isolated in Guangdong Province shared 80.2%-100.0% nucleotide homology, and belonged to two genotypes of D and E, with genotype D prevalent from 2008 to 2017 and genotype E prevalent from 2020 to 2021.Conclusions:CVB3 is prevalent sporadically in Guangdong Province from 2008 to 2017, but the epidemic intensity increased during 2020 and 2021. CVB3 strains of genotypes D and E are prevalent in Guangdong Province during 2008 to 2021, with genotype E being the prevalent genotype during 2020 and 2021.
10.Analysis of three-year retention rate and efficacy of levetiracetam,lamotrigine and valproic acid in patients with newly diagnosed epilepsy
Jie QI ; Jiao ZENG ; Xiaoli ZHANG
Journal of Clinical Neurology 2024;37(4):268-273
Objective Compared the 3-year retention rate and efficacy of levetiracetam(LEV),lamotrigine(LTG)and valproic acid(VPA)in patients with newly diagnosed epilepsy.Methods According to the antiepileptic drugs selected for the first time,323 patients with newly diagnosed epilepsy were divided into the LEV group,LTG group and VPA group.They were followed up for more than 3 years by telephone and outpatient clinic.Results There were significant differences in the single drug retention rate and epileptiform discharge rate among the LEV group,LTG group and VPA group in the first 3 years(all P<0.05).Compared with those in LEV group,the single drug retention rates in LTG group were significantly decreased in the first year and the second year(χ2=6.265,χ2=5.376;all P<0.025),the epileptiform discharge rate were significantly increased in the first year and the second year(χ2=14.011,χ2=8.574;all P<0.025);the single drug retention rate in VPA group were significantly decreased in the second year and the third year(χ2=6.226,χ2=10.112;all P<0.025),the epileptiform discharge rate was significantly increased in the first year,the second year and the third year(χ2=11.504,χ2=14.206,χ2=7.596;all P<0.025).There were significant differences in the survival curve of single drug retention and epileptiform discharge among the LEV group,LTG group and VPA group(χ2=9.349,P<0.05;χ2=7.395,P<0.05).The survival curve of single drug retention in LEV group was significantly higher than that in LTG group(χ2=4.451,P<0.05)and VPA group(χ2=9.464,P<0.05).The survival curve of epileptiform discharge in LEV group was significantly lower than that in VPA group(χ2=7.523,P<0.05).There was no significant difference in drug effective rate and no epileptic seizure rate in the first 3 years between LEV group,LTG group and VPA group(all P>0.05).There was a significant difference in the incidence of adverse drug reactions among the LEV group,LTG group and VPA group(χ2=8.068,P=0.018).Compared with that in LEV group,the incidence of adverse drug reactions in LTG group and VPA group were significantly increased(χ2=6.153,P=0.013;χ2=7.109,P=0.008).The main reasons for drug withdrawal,drug addiction and dressing change in LEV group were unsatisfactory curative effects,while those in LTG group and VPA group were adverse drug reactions.Conclusion The 3-year single drug retention rate of LEV is higher than that of LTG and VPA,and the EEG epileptiform discharge rate and the incidence of adverse drug reactions are significantly reduced,which was more suitable as the first choice for single drug treatment in patients with newly diagnosed epilepsy.

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