1.Dynamics of HIV reservoir and α4β7 cells in patients with different immune reconstitution outcomes during long-term antiretroviral therapy
Lingyu GAO ; Xueji LI ; Yanmei JIAO ; Mengmeng QU ; Zheng XU ; Jijing SHI ; Baopeng YANG ; Luxue ZHANG
Chinese Journal of Microbiology and Immunology 2025;45(4):285-292
Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.
2.Flavones in pomelo peel resist fibril formation of human islet amyloid polypeptide.
Cuiyun GAO ; Zhiruo WAN ; Yan LIU ; Yuting MENG ; Xu CHEN ; Xiaohan TANG ; Lingyu HANG ; Hailong YUAN
Chinese Herbal Medicines 2025;17(1):166-177
OBJECTIVE:
Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated.
METHODS:
The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation.
RESULTS:
The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers.
CONCLUSION
A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.
4.Roles of the glymphatic system in ischemic stroke
Danli QIU ; Shenghai GAO ; Lingyu ZHANG ; Honghong JI ; Pengfei WANG
International Journal of Cerebrovascular Diseases 2025;33(7):528-533
The glymphatic system is an important pathway for fluid drainage and metabolic waste clearance in the central nervous system. Its core mechanism involves the active cerebrospinal fluid-interstitial fluid circulation process mediated by perivascular spaces and aquaporin-4 channels located on astrocytic endfeet. This process is crucial for eliminating neurotoxic substances such as β-amyloid and tau proteins, as well as maintaining homeostasis in the central nervous system. Recent studies have shown that dynamic changes in the glymphatic system are associated with recovery after ischemic stroke. This article elaborates on the role of the glymphatic system in ischemic stroke and evaluates its potential value as a novel therapeutic target, providing new insights for post-stroke treatment strategies.
5.Effect of unilateral or bilateral transcranial direct current stimulation on post-stroke dysphagia
Fei GAO ; Lixu LIU ; Xueyan HU ; Xiaoli WU ; Lingyu YANG ; Yuqi YANG ; Changqing YE ; Xiaoxia DU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):993-999
Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.
6.Effect of unilateral or bilateral transcranial direct current stimulation on post-stroke dysphagia
Fei GAO ; Lixu LIU ; Xueyan HU ; Xiaoli WU ; Lingyu YANG ; Yuqi YANG ; Changqing YE ; Xiaoxia DU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(9):993-999
Objective To investigate the effect of unilateral or bilateral transcranial direct current stimulation(tDCS)on post-stroke dysphagia.Methods From February,2023 to March,2025,27 stroke patients with dysphagia and nasal feeding in Beijing Bo'ai Hos-pital were randomly divided into healthy side stimulation group,bilateral stimulation group and sham stimulation group,with nine cases in each group.All the groups received conventional swallowing training and tDCS,while the healthy side stimulation group stimulated on the healthy side of oropharyngeal cortex;and the bilateral stimu-lation group alternatively stimulated bilateral oropharyngeal cortex,with one hour interval between bilateral stim-ulation;the sham stimulation group stimulated the healthy side of oropharyngeal cortex for 30 seconds and then stop.The course lasted two weeks.The scores of Standard Swallowing Function Assessment Scale(SSA),Modi-fied Mann Assessment of Swallowing Ability(MMASA)and Rosenbek Penetration-Aspiration Scale(PAS)were compared before and after treatment.Results The intra-group effect(F=16.185,P<0.01)was significant in the scores of SSA,the intra-group effect(F=28.650,P<0.01)and interaction effect(F=3.453,P<0.01)were significant in the scores of MMASA,and there was no significant difference in the inter-group effect,intra-group effect and interaction effect in the scores of PAS(P>0.05).Post hoc test showed that there was no significant difference in the scores of SSA,MMASA and PAS among three groups(P>0.05).There was significant difference in the score difference of MMASA be-fore and after treatment among three groups(F=4.698,P<0.05).Post hoc test showed that the score difference of MMAS was more in the healthy side stimulation group than in the bilateral stimulation group and the sham stimulation group(P<0.05),with no significant difference between the bilateral stimulation group and the sham stimulation group(P>0.05).Conclusion tDCS can partly improve post-stroke dysphagia.The healthy side anode stimulation is superior to the alter-nating bilateral hemisphere anode stimulation.
7.Dynamics of HIV reservoir and α4β7 cells in patients with different immune reconstitution outcomes during long-term antiretroviral therapy
Lingyu GAO ; Xueji LI ; Yanmei JIAO ; Mengmeng QU ; Zheng XU ; Jijing SHI ; Baopeng YANG ; Luxue ZHANG
Chinese Journal of Microbiology and Immunology 2025;45(4):285-292
Objective:To investigate immunological non-responders (INRs) and immunological responders (IRs) during long-term antiretroviral therapy (ART), and study the dynamics of HIV reservoir and α4β7 cells in INRs and IRs and their correlation.Methods:Twenty-six patients with chronic HIV infection who received ART for 5 years were included. They were divided into INRs (CD4 + T cell counts≤350 cells/μl, n=9) and IRs (CD4 + T cell counts≥500 cells/μl, n=17) based on immune reconstitution outcomes. The percentages and numbers of α4β7 cells in both groups at baseline, ART 1, 3, and 5 years were detected by flow cytometry, and the levels of HIV DNA and cell-associated HIV RNA were quantified by real-time fluorescent quantitative PCR during the same periods. HIV viral decay, α4β7 cells dynamics, and their correlations with T cells were compared at baseline, ART 1, 3 and 5 years between the two groups. Results:Over 5 years of ART, INRs exhibited higher HIV reservoir levels compared to IRs, but the decline trend was not slow. The counts of α4β7 cell were lower and the growth trend was slow in INRs ( P<0.05). α4β7 cell counts were strongly positively correlated with CD4 + T cell counts at all timepoints (Year 1: r=0.887; Year 3: r=0.878; Year 5: r=0.887; P all <0.001), while showing significantly negative correlations with activated CD38 + HLA-DR + CD4 + T cells (Year 1: r=-0.619, P=0.001), CD38 + HLA-DR + CD8 + T cells (Year 1: r=-0.517; Year 5: r=-0.532; P all <0.01), and PD-1 + CD4 + T cells (Year 1: r=-0.476, Year 5: r=-0.390, P all <0.05). Conclusions:During long-term ART, INRs maintained higher HIV reservoir and lower α4β7 cell counts compared with IRs, and decreased α4β7 cells may be associated with disease progression.
8.Research on the establishment of capability evaluation system and training and exercise models of the national emergency medical rescue team
Dan ZHOU ; Jian YIN ; Caiping GAO ; Lingyu LI ; Liming ZHAO ; Zhongmin LIU
Shanghai Journal of Preventive Medicine 2024;36(3):262-268
ObjectiveTo improve the response capabilities to disasters and prevent major epidemics, it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises, to enhance the overall quality of the teams. MethodsFirst, a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification (IEC) standards of the national emergency medical rescue team. Then, based on the outcome based education (OBE) concept, we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally, an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023, as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators, the five core competencies in the evaluation system, including rescue skills, medical and health knowledge, disaster coping ability, team cooperation ability, and mental resilience training, were positively correlated with the cumulative number of trainings (r=0.71, r=0.76, r=0.81, r=0.84, r=0.96,all P<0.05), indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.
9.Researchon the training model of innovative talents in traditional Chinese medicine with the integration of science and education in local high-level universities
Lanwen GAO ; Ye GAO ; Ronghua ZHANG ; Li YANG ; Huan WANG ; Xiaoyun LI ; Lingyu LI ; Yu CAI
Modern Hospital 2024;24(1):127-129
Traditional Chinese Medicine has a long history and plays a decisive role in the fields of modern medicine and pharmacy.It is an important part of our country's traditional medicine.With the progress of the times,people are paying more and more attention to the innovation and development of traditional Chinese medicine.However,the current traditional Chinese medicine talents trained by major universities cannot meet the needs and requirements of society.This is closely related to the current talent training model of universities.Local high-level universities have unique advantages and potential in cultivating inno-vative talents in traditional Chinese medicine.They can incorporate traditional Chinese medicine culture with local characteristics into the teaching content and practical links of training traditional Chinese medicine talents,and build innovative traditional Chi-nese medicine talents integrating science and education.The training model is more conducive to cultivating top innovative talents that meet the needs of society and and the development of traditional Chinese medicine.This article analyzes and discusses how local high-level universities can develop innovative talent training models that suit the needs of traditional Chinese medicine by combining local characteristics and disciplinary advantages,so as to provide useful reference and inspiration for local high-level u-niversities in cultivating talents in traditional Chinese medicine.
10.Investigation and analysis of hearing function in community-managed patients with diabetes
Yanting NIU ; Lingyu XIN ; Ying GAO ; Bo LIU
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(6):356-359
OBJECTIVE To investigate the awareness rate of diabetic otology diseases and evaluate hearing in patients with diabetes under community management,analyze the characteristics of hearing loss in patients with diabetes,and provide scientific basis for incorporating hearing care into community diabetes management.METHODS From 2018 to 2020,719 patients(1438 ears)with diabetes in a community in Beijing were investigated by questionnaire,medical history collection,specialist physical examination and audiology examination.The results were analyzed statistically.RESULTS 1.The awareness rate of hearing loss was 32.5%(234/719)in patients with diabetes,94.7%(1 362/1 438)reported hearing loss after pure tone hearing examination.Of the 954 ears that reported normal hearing,92.8%(885/954)were found to have varying degrees of hearing loss.2.In the young and middle-aged group(438 ears),89.7%(393/438)had hearing loss,and 80.6%(353/438)had high-frequency hearing loss.Of the 334 ears with normal hearing,88.0%(294/334)had some degree of hearing loss.3.Hearing loss was more severe in patients with diabetes with a disease duration≥10 years than patients with a disease duration<10 years(P<0.05).The degree of hearing loss was more severe in patients with diabetes with hypertension and/or hyperlipidemia(P<0.05).CONCLUSION The self-examination rate of hearing loss in patients with diabetes is low and the incidence is high,especially in young and middle-aged patients.The course and comorbidities of diabetes are risk factors for the development of hearing loss,which should be paid attention to by both doctors and patients.

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