1.Sleep Traits and Malignant Risk of Pulmonary Nodules: Evidence Triangulation From Questionnaire, Cohort, and Mendelian Randomization
Xiangyu CHEN ; Yiqiao XUE ; Mengqing LIU ; Yile HU ; Weizuo LIANG ; Hanqing LIU ; Yizheng WANG ; Mingfang ZHAO
Medical Journal of Peking Union Medical College Hospital 2026;17(3):663-676
To investigate the association between sleep-related phenotypes and the risk of malignancy in pulmonary nodules, and to provide complementary evidence from a general population cohort and genetic analyses. This study comprised three parts. Part 1 was a cross-sectional study that consecutively enrolled patients with imaging-confirmed pulmonary nodules at the First Hospital of China Medical University from November 2024 to December 2025. Nine sleep domains were constructed using items from the Pittsburgh sleep quality index (PSQI), with domain severity coded on a 0-6 scale according to the frequency of occurrence. Benign or malignant status of pulmonary nodules was determined based on pathological results or clinical follow-up. Multivariable Logistic regression models with progressive adjustment were constructed. Stratified, interaction, and dose-response analyses (including categorical grouping and restricted cubic splines) were performed focusing on the insomnia symptom domain to explore the association between sleep-related phenotypes and the risk of malignant pulmonary nodules. Part 2 was a prospective cohort study using the China Health and Retirement Longitudinal Study (CHARLS) to investigate the association between sleep duration and incident lung cancer risk in the general population. Part 3 comprised genetic causality analyses, including two-sample Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC), using data from the OpenGWAS database, to assess whether directionally consistent genetic association signals exist between sleep-related phenotypes and lung cancer risk. In the cross-sectional study, a total of 800 patients with pulmonary nodules were included, of whom 288 (36.0%) were in the malignant group. In the continuous-variable main model fully adjusted for baseline confounders, all nine sleep domains, imaging findings, and depression and anxiety status, the severity of the insomnia symptom domain showed a positive association signal with the risk of malignant pulmonary nodules (fully adjusted model: per 1-point increase, In patients with pulmonary nodules, an association signal exists between insomnia-related symptoms and the risk of malignancy, but the dose-response relationship remains unclear. The CHARLS cohort and genetic analyses provide supplementary directional clues for the above associations, albeit with limited statistical strength and result consistency. Definitive conclusions regarding the association between sleep phenotypes and the risk of malignant pulmonary nodules require further validation in prospective studies.
2.Comparison of the Prognostic Value Between CHA2DS2-VASc and R2CHA2DS2-VASc Scores in Patients With Atrial Fibrillation and Heart Failure
Yile LIN ; Shuyan ZHANG ; Zeyue CHEN ; Zhiyu HE ; Dunzheng HAN ; Haobin ZHOU ; Hongliang XUE ; MOK TOI-MENG ; Chen LIU ; Woliang YUAN ; Yugang DONG ; Ailan CHEN
Chinese Circulation Journal 2025;40(7):674-680
Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.
3.Comparison of the Prognostic Value Between CHA2DS2-VASc and R2CHA2DS2-VASc Scores in Patients With Atrial Fibrillation and Heart Failure
Yile LIN ; Shuyan ZHANG ; Zeyue CHEN ; Zhiyu HE ; Dunzheng HAN ; Haobin ZHOU ; Hongliang XUE ; MOK TOI-MENG ; Chen LIU ; Woliang YUAN ; Yugang DONG ; Ailan CHEN
Chinese Circulation Journal 2025;40(7):674-680
Objectives:To investigate the prognostic value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with atrial fibrillation(AF)and heart failure(HF).Methods:Patients with AF and HF from hospitals diagnosed by the Heart Failure Center in Guangdong Province between January 2017 and December 2021 were selected.Major adverse cardiovascular events(MACE)were used as the follow-up endpoint.Statistical methods such as the area under the receiver operating characteristic(ROC)curve(AUC),net reclassification index(NRI),and integrated discrimination improvement(IDI)were applied to evaluate the predictive value of the CHA2DS2-VASc and R2CHA2DS2-VASc scores in patients with AF and HF.Results:A total of 1 839 patients were enrolled in this study,comprising 703 patients in the MACE group and 1 136 patients in the non-MACE group.Compared with the non-MACE group,the MACE group exhibited significantly advanced age,higher prevalence of New York Heart Association class Ⅳ and coronary artery disease,lower diastolic blood pressure and estimated glomerular filtration rate levels,and elevated serum N-terminal pro-B-type natriuretic peptide concentrations(all P<0.05).Additionally,significantly lower proportions of patients in the MACE group received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors,beta-blockers,mineralocorticoid receptor antagonists,or anticoagulant therapy(all P<0.05).Multivariable logistic regression analysis revealed that each 1-point increment in both CHA2DS2-VASc and R2CHA2DS2-VASc scores was associated with approximately 10%increased risk of MACE.ROC curve analysis demonstrated that the AUC values for predicting MACE in AF patients with HF were 0.555(95%CI:0.528-0.582,P<0.001)for CHA2DS2-VASc and 0.576(95%CI:0.549-0.608,P<0.001)for R2CHA2DS2-VASc,indicating marginally superior discriminatory capacity of the R2CHA2DS2-VASc score.Delong's test confirmed statistically significant differences between the two scoring systems(P=0.001).The R2CHA2DS2-VASc score demonstrated a NRI of 0.259(95%CI:0.166-0.352,P<0.001)and an IDI of 0.007(95%CI:0.005-0.010,P<0.001)compared with the conventional CHA2DS2-VASc score.Although the R2CHA2DS2-VASc score exhibited slightly better predictive accuracy and outcome discrimination capacity than the original scoring system,both scores demonstrated suboptimal clinical predictive performance.Conclusions:Both the R2CHA2DS2-VASc and CHA2DS2-VASc scores show suboptimal performance for predicting the risk of MACE in patients with AF and HF,and the predicting performance of R2CHA2DS2-VASc score is marginally superior to CHA2DS2-VASc score in this patient cohort.
4.A profile of cross-reactive neutralizing antibodies against various subtypes of HIV-1 strains in people with HIV-1 infection in Chongqing city
Yi LIN ; Quanhua ZHOU ; Min ZHANG ; Tao WANG ; Fangwei SHEN ; Yile XUE ; Ying WANG ; Ping ZHONG
Chinese Journal of Microbiology and Immunology 2015;(3):167-172
Objective To measure the levels of cross-reactive neutralizing antibodies responding to various subtypes of HIV-1 strains in people with HIV-1 infection in Chongqing and to analyze their character-istics.Methods Two hundred and thirty-six plasma samples were collected from patients with chronic HIV-1 infection in Chongqing city.The single-round-infection assay in TZM-bl cells were performed to screen the plasma samples with cross-reactive neutralizing antibodies against various subtypes of HIV-1 strains by using HIV-1 pseudovirus strains and to measure the 50%inhibitory dose ( ID50 ) .Results Eight-een out of 236 (7.63%) plasma samples were able to neutralize various B subtypes and/or C subtypes of HIV-1 pseudovirus strains, among which 15 plasma samples showed the great ability to neutralize pseudovir-us strains of different subtypes.Conclusion The cross-reactive neutralizing antibodies against various sub-types of HIV-1 strains existed in plasma samples collected from people with chronic HIV-1 infection in Chongqing city.
5.Association of PD-1 expression on CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells with disease progression in HIV-1 infected patients
Qinghua CAO ; Yile XUE ; Ying WANG
Journal of Cellular and Molecular Immunology 2009;25(11):1020-1022
AIM: To investigate whether Programmed death-1 (PD-1) expression on peripheral CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells (Treg) was associated with disease progression in HIV-1-infected patients. METHODS: Peripheral blood from 108 HIV-1-infected patients in distinct disease progression statuses and 27 healthy individuals were collected in the present investigation. PBMCs were isolated by centrifugation on Ficoll-Hypaque, followed by staining with anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE and anti-PD-1-APC. PD-1 expression on Treg was analyzed by four-color staining flow cytometry. CD4~+T cell absolute counts were determined using Multitest CD3/CD4/CD8/CD45 kit and plasma viral loads were detected on NucliSens EasyQ. All data were analyzed using SPSS14.0 software. RESULTS: In peripheral blood of healthy individuals, Treg expressed PD-1 at very low levels (1.72%±0.65%). In contrast, Treg from HIV-1-infected patients showed a significantly increased PD-1 expression (5.33%±2.24%, P<0.01). Moreover, AIDS patients exhibited statistically higher PD-1 expression on Treg (7.87%±2.23%) than newly HIV-1 infected patients (3.22%±1.01%, P<0.05) and patients in progression to AIDS(5.21%±1.72%, P<0.05). PD-1 up-regulation on Treg was closely correlated with reduced CD4~+T cell absolute counts but elevated plasma viral load. CONCLUSION: Overall, we found that PD-1 expression on peripheral Treg was up-regulated and correlated with disease progression in HIV-1-infected patients for the first time. These findings not only extend our understanding of how Treg functions in HIV-1-infected patients but also support the notion that blocking PD-1/PD-L1 interactions may represent a potential therapeutic strategy for HIV-1-infected patients.
6.A molecular epidemioiogical survey of 60 human immunodeficiency viruses-1 infected individuals from Honghe district in Yunnan Province
Yunya XU ; Weimin JIANG ; Leiming ZHOU ; Ping ZHONG ; Yile XUE ; Qichao PAN ; Xinhua WU ; Yan MENG ; Xinhua WENG ; Laiyi KANG
Chinese Journal of Infectious Diseases 2008;26(6):367-370
Objective To investigate the molecular epidemiology of human immunodefieiency viruses (HIV)-1 infected individuals in Honghe district,Yunnan Province and provide the evidence of molecular biology features of HIV-1 infection.Methods HIV-1 pol gene was amplified by reverse transcription-polymerase chain reaction (RT-PCR).Then sequencing and phylogenetic tree analysis were employed tO determine HIV-I subgenotype.The sequence alignment was performed in the database of international drug resistance tO identify resistance-associated mutations.Results The samples from 60 HIV-1 infected individuals were investigated:39 were male,21 were female,with average age 35.5 years old.Thirty-four cases were infected with HIV-I through intravenous drug abuse,12 by sexual contacts,2 were contaminated blood/blood products transfusion and 12 with unknown transmission routes.Phylogenetic analysis revealed that 53 cases (88.3%) were subtype 08-BC,6 (10.0%) were subtype 07-BC and 1 (1.7%) was subtype 01_AE.The total rate of drug resistance associated mutations was 33.3%.The major mutations in protease (PR) and reverse transcriptase (RT) regions accounted for 5.0% and 3 1.7%,respectively.The major mutations in PR region were I541M,V82VFIL,M46MI,which were found in 1 case,respectively.The mutations in RT region were as follows:4 cases were T69D,6 were A62V,1 was D67DE,1 was E44D,3 were V179D,1 was V179E.1 was K238KN,1 was L234T+P236S and 1 was V106E.Conclusions The major transmission route of HIV-I infection in Honghe district,Yunnan Province is through drug injection.The major HIV-1 subtype of HIV-infeeted individuals is 08_BC.PR inhibitor and RT inhibitor drug resistance associated mutations in HlV-1 gene have already existed.
7.Impact of the CD4~+CD25~(nt/hi)CD127~(lo) regulatory T cells on the immune status and disease progression in HIV-1 infected individuals
Mingkui ZHOU ; Yile XUE ; Juli GONG ; Leiming ZHOU ; Xiaohong ZHENG ; Jing GAI ; Fangwei SHEN ; Wei ZHANG ; Zhen NING ; Qing YUE ; Wei LU ; Qichao PAN ; Laiyi KANG ; Ping ZHONG ; Wensi ZHU ; Ying WANG
Chinese Journal of Immunology 1999;0(12):-
Objective:To investigate the impact of the CD4+CD25nt/hiCD127lo regulatory T cell subset frequency on the immune status and disease progression of Chinese HIV-1 infected individuals.Methods:83 untreated HIV-infected individuals and 312 healthy control individuals of four distinct age groups were enrolled in the research. The CD4+ T cell absolute counts, phenotypes and frequency determination of CD4+CD25nt/hiCD127lo Regulatory T cell subsets was performed on freshly obtained whole blood samples by 3-color immune staining flow cytometry. The HIV-1 specific cellular immune function was test at single cell level by ELISpot. The corresponding plasma viral load was determined by NASBA.Results:The frequency of peripheral CD4+CD25nt/hiCD127lo regulatory T cells of HIV infected individuals in distinct disease progression status was dissimilar in China , and significantly increased in contrast to the healthy controls(P

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