1.CD38/p53/ME1 axis promotes T cell senescence during HIV infection via suppression of mitochondrial function
Xin ZHONG ; Chengbo SONG ; Dingning LIU ; Mei LIU ; Yajing FU ; Yongjun JIANG ; Haibo DING ; Zining ZHANG
Chinese Journal of Microbiology and Immunology 2025;45(4):269-276
Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.
2.Value of dual-energy CT quantitative parameters combined with clinical features in diagnosis of stages T2 and T3 colorectal cancer
Ni FANG ; Xin WEI ; Weijuan CHEN ; Mei FENG ; Lingjing ZHANG ; Yuexi LIU ; Qi LAI ; Xuan DING ; Xinjie LIU ; Wei JIANG ; Han YU
Journal of Army Medical University 2025;47(2):177-185
Objective To investigate the diagnostic value of our regression model based on quantitative parameters of dual-energy CT and clinical features for stages T2 and T3 colorectal cancer.Methods A cross-section study was performed on 91 patients with colorectal cancer confirmed by postoperative pathology in our hospital from January 2022 to November 2023.All of them underwent dual-energy CT examination.According to the pathological T staging criteria of Chinese Colorectal Cancer Diagnosis and Treatment Standard(2020 Edition),they were divided into T2 group(n=43)and T3 group(n=48).Univariate analysis was used to compare the differences in quantitative CT parameters and clinical features between the 2 groups,and the obtained significant variables were employed to construct diagnosis models by univariate or multivariate logistic regression analysis.The area under receiver operating characteristic curve(AUC)of the CT parametric model and the model combined with clinical features was compared to evaluate the efficacy of diagnosing T2 and T3 stages.Results Univariate analysis showed that carcinoembryonic antigen(CEA),N stage,tumor location,tumor longest diameter(LD),CT value of virtual noncontrast(CT-VNC),fat fraction,electron density(Rho)and dual energy index(DEI)were significantly different between the T2 and T3 groups(P<0.05).Multivariate logistic regression analysis found that N stage,tumor location,LD,fat fraction and DEI were independent risk factors for the diagnosis of stage T3.The AUC value of the model of above CT parameters in diagnosing stage T3 colorectal cancer was 0.671(95%CI:0.558~0.783),and the AUC value of the combined model of above CT parameters and clinical features was 0.886(95%CI:0.815~0.957),and statistical difference was observed in the AUC value between the combined model and the CT parametric model(P<0.01).Conclusion The regression model constructed with dual-energy CT quantitative parameters combined with clinical features has high value in the preoperative diagnosis of stages T2 and T3 colorectal cancer before surgery.
3.A Randomized Controlled Clinical Study on the Treatment of Knee Osteoarthritis with Cold-Dampness Arthralgia Obstruc-tion by Shangke Lengtong Patch
Li ZHANG ; Liang DING ; Zhengquan HUANG ; Wei MEI ; Runlin XING ; Songjiang YIN ; Peng WU ; Xi-aochen LI ; Zhenyuan MA ; Nongshan ZHANG ; Jun MAO ; Peimin WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(3):393-398
OBJECTIVE To explore the effectiveness and possible mechanism of Shangke Lengtong Patch in treating knee osteo-arthritis with cold-dampness arthralgia obstruction.METHODS A total of 70 patients who met the inclusion criteria of knee osteoar-thritis with cold-dampness arthralgia obstruction in the Orthopedics Department of Affiliated Hospital of Nanjing University of Chinese Medicine from November to December 2024 were randomly divided into an experimental group and a control group,with 35 cases in each group.During the treatment,1 case dropped out of the experimental group,3 cases dropped out of the control group,and 1 case was discontinued.The experimental group was treated with Shangke Lengtong Patch,and the control group was treated with Compound Nanxing Zhitong Ointment.The WOMAC scores and TCM syndrome scores of the two groups before and after treatment were compared to comprehensively evaluate the clinical efficacy.The changes in the expression levels of CGRP,substance P,HMGB1,IL-1β,CX-CL12,and CXCR4 in the serum of the two groups were detected by ELISA.RESULTS After 3,7,and 14 d of treatment,the WOMAC scores and TCM syndrome scores of the two groups were significantly reduced(P<0.05,P<0.01),and the score of aggrava-ted cold in the experimental group was better than that in the control group at 7 d of treatment(P<0.05);after 14 d of treatment,the expression levels of CGRP,substance P,HMGB1,IL-1β,CXCL12,and CXCR4 in the serum of the two groups were significantly re-duced(P<0.05),and there was no statistical difference between the two groups.CONCLUSION Shangke Lengtong Patch can sig-nificantly relieve the pain symptoms of knee osteoarthritis patients with cold-dampness arthralgia obstruction and improve the joint func-tion of patients.It may improve synovial inflammation by inhibiting the HMGB1/CXCL12/CXCR4 pathway,thereby exerting a thera-peutic effect.
4.The therapeutic effects of newly formulated Tadalafil tablets on rats with pathological cardiac hypertrophy through regulation of NF-κB signaling pathway
Xue-di ZHANG ; Ye-ding SONG ; Li-mei LI ; Hao-yan CHEN ; Hua-sui CUI ; Zheng-gang ZHAO ; Zi-jian ZHAO ; Yun-ping MU ; Fang-hong LI
Chinese Pharmacological Bulletin 2025;41(8):1485-1492
Aim To investigate the therapeutic effects of a newly developed Tadalafil tablets on pathological myocardial hypertrophy induced by abdominal aortic constriction(AAC)in rats,as well as its influence on the activation of the NF-κB signaling pathway in myo-cardial cells.Methods SD rats were randomly divid-ed into 4 groups:the sham operation group(Sham),the model group(AAC),the tadalafil new tablet treat-ment group(N-Tad,5 mg·kg-1),and the positive control drug treatment group(Cialis,10 mg·kg-1g).The AAC model group and treatment group rats under-went blunt dissection and constrictive ligation of the abdominal aorta at the left renal artery branch point during surgery,while the Sham group rats only had their arteries separated without any constrictive liga-tion.Rats in the treatment groups received either N-Tad or Cialis via gavage three days after modeling,while rats in the sham group and the model group re-ceived physiological saline daily for 8 weeks.Small an-imal ultra-high-resolution echocardiography and hemo-dynamic assessment were applied to evaluate left ven-tricular function in each group of rats,and the calcula-tion of the left ventricular mass index was conducted.By employing Western blot and RT-PCR.we assessed the impact of this treatment on the expression of the hy-pertrophy factor atrial natriuretic peptide(ANP),phosphorylated NF-κB p65 protein(p-NF-κB p65),and phosphorylated IκB-α in the left heart tissue of rats and in H9c2 cardiomyocytes.Results Compared to the Sham group,the AAC rats exhibited a significant decrease in left heart function,an increase in left ven-tricular mass index,and a notable increase in ANP and p-p65 expression in the left heart tissue(P<0.05).Both N-Tad and Cialis treatments could significantly enhance left ventricular function,decrease left ventric-ular mass index,and inhibit the expression of ANP and phosphorylated NF-κB p65 in rats with myocardial hy-pertrophy(P<0.05).Notably,the therapeutic effect of low-dose N-Tad was comparable to that of high-dose Cialis.At the cellular level,Tadalafil significantly in-hibited the activation of the NF-κB signaling pathway and reduced the expression of associated proteins in H9c2 cardiomyocytes.Conclusions N-Tad can sig-nificantly inhibit p65 and IκB-α phosphorylation,and the activation of the NF-κB signaling pathway,reduce ANP expression,and improve pathological myocardial hypertrophy,as well as mitigate left heart function damage caused by abdominal aortic constriction.
5.Investigation of the Mechanism of Cold Hyperalgesia in KOA Mice Relieved by Shangke Lengtongtie Based on HMGB1/CX-CL12/CXCR4 Signaling Axis
Yibao WEI ; Li ZHANG ; Taiyang LIAO ; Lishi JIE ; Zhenyuan MA ; Peng WU ; Zhengquan HUANG ; Li ZHANG ; Liang DING ; Wei MEI ; Runlin XING ; Songjiang YIN ; Xiaochen LI ; Nongshan ZHANG ; Jun MAO ; Pei-min WANG
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(2):195-202
OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.
6.Purification effect of air aerosols in digestive endoscope cleaning and disinfection room under different ventilation and disinfection modes
Sijin YAN ; Yan SONG ; Feng LU ; Shiwen HUANG ; Jiayan DING ; Mei HUANG ; Xiaofang FU ; Lina ZHAO ; Yan ZHANG ; Haiqun BAN
Chinese Journal of Nosocomiology 2025;35(13):2040-2044
OBJECTIVE To investigate the changes of air aerosols in the digestive endoscope cleaning and disinfec-tion room under real working conditions and observe the purification effects of aerosols under different ventilation and disinfection modes.METHODS Under the real working conditions(with both the air conditioner and recircu-lating air disinfection machine under the working mode),the air samples were collected every 1 hour from 8:00 to 16:00 from the digestive endoscope cleaning and disinfection room of Ren Ji Hospital,Shanghai Jiao Tong U-niversity School of Medicine from May 2023 to Oct.2023;the contents of particulate matters(PM)and microor-ganisms in the air were detected.At the busiest moment of the cleaning and disinfection room,the air was respec-tively sampled from the cleaning and disinfection room with the working condition modes of air condition systems,recirculating air disinfection machine or natural ventilation before the starting of systems and after the work for 0.5 hour,1 hour and 2 hours.The contents of PMs and microorganisms were detected.RESULTS The PM0.5 con-centrations during various time periods met the Grade 9 ISO clean room standard(≤35,200 particles/L)under the real working conditions,and the content of airborne viable particles also conformed to the Class Ⅲ environmental requirements(≤500 CFU/m3).All of the three ventilation and disinfection methods showed certain effects on purification of the con-tents of PM0.5 and microorganisms after the ventilation for 2 hours,the contents of PMs and microorganisms of the air disinfection machine group decreased most remarkably,followed by the air conditioner group,the natural ventilation group the least.There were no significant differences in the PM concentration and the content of microorganisms among the three groups at the time points;there were only significant differences in the PM concentration and the content of mi-croorganisms of the air disinfection machine group after the ventilation for 2 hours,0.5 hour and 1 hour(P<0.05).CONCLUSIONS Both the air conditioning systems and recirculating air disinfection machine under the working con-dition mode have certain effect on purification of the contents of PM and microorganisms,and the specific effect need to be further studied.The implementation of multicenter dynamic surveillance with the help of intelli-gent techniques may provide reference for the optimization of ventilation and disinfection strategies.
7.Analysis of factors influencing social isolation in elderly people with chronic diseases based on socio-ecological system theory
Liyuan JIA ; Mei YOU ; Lulu ZHANG ; Yuqin JIANG ; Yuan DING ; Yiling LIU ; Xiaohan MAO ; Annuo LIU
Chinese Journal of Modern Nursing 2025;31(14):1903-1907
Objective:To understand the status and influencing factors of social isolation in elderly individuals with chronic diseases.Methods:A multi-stage sampling method was used to select elderly individuals from eight communities or villages in Hefei from July to September 2022. The study employed a general information survey, the Lubben Social Network Scale (LSNS-6) , the Geriatric Depression Scale (GDS-15) , the Social Support Rating Scale (SSRS) , and the Personal Social Capital Scale 16 (PSCS-16) . Binary Logistic regression analysis was used to explore the factors influencing social isolation in elderly individuals with chronic diseases.Results:A total of 1 133 elderly individuals were surveyed, among which 538 had chronic diseases. Among the 538 elderly individuals with chronic diseases, 209 were socially isolated, resulting in a social isolation rate of 38.8%. Binary Logistic regression analysis revealed that living area, fear of falling, depression, social capital, and social support were significant factors influencing social isolation ( P<0.05) . Conclusions:The social isolation rate among elderly individuals with chronic diseases is high. Special attention should be given to elderly individuals living in rural areas, those who fear falling, and those experiencing depression. Additionally, improving social capital and social support can help alleviate social isolation in these elderly individuals.
8.Purification effect of air aerosols in digestive endoscope cleaning and disinfection room under different ventilation and disinfection modes
Sijin YAN ; Yan SONG ; Feng LU ; Shiwen HUANG ; Jiayan DING ; Mei HUANG ; Xiaofang FU ; Lina ZHAO ; Yan ZHANG ; Haiqun BAN
Chinese Journal of Nosocomiology 2025;35(13):2040-2044
OBJECTIVE To investigate the changes of air aerosols in the digestive endoscope cleaning and disinfec-tion room under real working conditions and observe the purification effects of aerosols under different ventilation and disinfection modes.METHODS Under the real working conditions(with both the air conditioner and recircu-lating air disinfection machine under the working mode),the air samples were collected every 1 hour from 8:00 to 16:00 from the digestive endoscope cleaning and disinfection room of Ren Ji Hospital,Shanghai Jiao Tong U-niversity School of Medicine from May 2023 to Oct.2023;the contents of particulate matters(PM)and microor-ganisms in the air were detected.At the busiest moment of the cleaning and disinfection room,the air was respec-tively sampled from the cleaning and disinfection room with the working condition modes of air condition systems,recirculating air disinfection machine or natural ventilation before the starting of systems and after the work for 0.5 hour,1 hour and 2 hours.The contents of PMs and microorganisms were detected.RESULTS The PM0.5 con-centrations during various time periods met the Grade 9 ISO clean room standard(≤35,200 particles/L)under the real working conditions,and the content of airborne viable particles also conformed to the Class Ⅲ environmental requirements(≤500 CFU/m3).All of the three ventilation and disinfection methods showed certain effects on purification of the con-tents of PM0.5 and microorganisms after the ventilation for 2 hours,the contents of PMs and microorganisms of the air disinfection machine group decreased most remarkably,followed by the air conditioner group,the natural ventilation group the least.There were no significant differences in the PM concentration and the content of microorganisms among the three groups at the time points;there were only significant differences in the PM concentration and the content of mi-croorganisms of the air disinfection machine group after the ventilation for 2 hours,0.5 hour and 1 hour(P<0.05).CONCLUSIONS Both the air conditioning systems and recirculating air disinfection machine under the working con-dition mode have certain effect on purification of the contents of PM and microorganisms,and the specific effect need to be further studied.The implementation of multicenter dynamic surveillance with the help of intelli-gent techniques may provide reference for the optimization of ventilation and disinfection strategies.
9.Research progress of transmissible gastroenteritis vaccine
Mei LIU ; Longlong WANG ; Mingqing SHAO ; Shengmei PANG ; Kaiyang ZHANG ; Peng DAI ; Guowei DING ; Qiangde DUAN
Chinese Journal of Veterinary Science 2025;45(7):1535-1542
Transmissible gastroenteritis(TGE)is a highly contagious gastrointestinal disease of pigs caused by the transmissible gastroenteritis virus(TGEV).It results in severe diarrhea and high mortality in suckling piglets.As no specific treatment available,vaccination is considered to be one of the most cost-effective measures for preventing and controlling TGE.However,the immune protection provided by vaccines based on traditional TGEV strains is becoming inadequate due to the continuous emergence of strong and new strains of the virus,which poses a serious threat to the pig industry's health and development.Therefore,the development of new vaccines with im-proved efficiency and broad-spectrum coverage is urgently needed.This paper aims to summarize the pathogenic structural characteristics of TGEV,discuss the latest advancements in TGEV vac-cine research and development,and propose future strategies for the development of highly effec-tive TGEV vaccines.The findings of this paper can serve as a valuable reference for effectively pre-venting and controlling TGE in clinical practice.
10.CD38/p53/ME1 axis promotes T cell senescence during HIV infection via suppression of mitochondrial function
Xin ZHONG ; Chengbo SONG ; Dingning LIU ; Mei LIU ; Yajing FU ; Yongjun JIANG ; Haibo DING ; Zining ZHANG
Chinese Journal of Microbiology and Immunology 2025;45(4):269-276
Objective:To investigate the role of the CD38/p53/ME1 axis in regulating T cell mitochondrial function and senescence during HIV infection.Methods:The expression of CD38 on T cells was examined in HIV-infected individuals receiving antiretroviral therapy(ART), untreated HIV-infected individuals, and HIV-negative healthy controls. Flow cytometry was used to compare senescence markers and mitochondrial function between CD38 + and CD38 - T cells. Malic enzyme 1(ME1) mRNA levels were measured by qRT-PCR in T cells treated with the CD38 inhibitor 78c. Mitochondrial function and senescence were assessed in T cells treated with an ME1 inhibitor. The regulatory mechanism of CD38-mediated ME1 downregulation was further explored. Results:Compared to healthy controls, T cells from HIV-infected individuals exhibited significantly elevated CD38 expression, which persisted despite ART. CD38 + T cells showed increased senescence (CD28 -CD57 + subset) and mitochondrial dysfunction[depolarization and reactive oxygen species(ROS) accumulation]. CD38 inhibition upregulated ME1 mRNA level ( P<0.05). ME1 suppression led to mitochondrial impairment (reduced membrane potential and elevated ROS) and senescence in T cells. Mechanistically, CD38 depletion increased NAD + levels and SIRT1 activity, while SIRT1/p53 inhibition rescued ME1 expression, suggesting CD38 regulates ME1 via the NAD + /SIRT1/p53 axis. Conclusions:The CD38/p53/ME1 axis drives T cell senescence in HIV infection by disrupting mitochondrial function. Targeting this pathway may ameliorate CD38-associated T cell dysfunction and immune aging.

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