1.The associations of obesity phenotypes with the risk of hypertension and its transitions among middle-aged and older Chinese adults
Ziyue SHENG ; Shang LOU ; Jin CAO ; Weidi SUN ; Yaojia SHEN ; Yunhan XU ; Ziyang REN ; Wen LIU ; Qian YI ; Peige SONG
Epidemiology and Health 2023;45(1):e2023043-
OBJECTIVES:
This study aimed to investigate the associations of obesity phenotypes with hypertension stages, phenotypes, and transitions among middle-aged and older Chinese.
METHODS:
Using the 2011-2015 waves of the China Health and Retirement Longitudinal Study, we conducted a cross-sectional analysis included 9,015 subjects and a longitudinal analysis included 4,961 subjects, with 4,872 having full data on the hypertension stage and 4,784 having full data on the hypertension phenotype. Based on body mass index and waist circumstance, subjects were categorized into 4 mutually exclusive obesity phenotypes: normal weight with no central obesity (NWNCO), abnormal weight with no central obesity (AWNCO), normal weight with central obesity (NWCO), and abnormal weight with central obesity (AWCO). Hypertension stages were classified into normotension, pre-hypertension, stage 1 hypertension, and stage 2 hypertension. Hypertension phenotypes were categorized as normotension, pre-hypertension, isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). The association between obesity phenotypes and hypertension was estimated by logistic regression. A comparison between different sexes was conducted by testing the interaction effect of sex.
RESULTS:
NWCO was associated with normal→stage 2 (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.11 to 3.42), maintained stage 1 (OR, 1.62; 95% CI, 1.14 to 2.29), and normal→ISH (OR, 1.39; 95% CI, 1.05 to 1.85). AWCO was associated with normal→stage 1 (OR, 1.75; 95% CI, 1.40 to 2.19), maintained stage 1 (OR, 2.77; 95% CI, 2.06 to 3.72), maintained stage 2 (OR, 2.80; 95% CI, 1.50 to 5.25), normal→ISH (OR, 1.56; 95% CI, 1.20 to 2.02), and normal→SDH (OR, 2.54; 95% CI, 1.72 to 3.75). An interaction effect of sex existed in the association between obesity phenotypes and hypertension stages.
CONCLUSIONS
This study highlights the importance of various obesity phenotypes and sex differences in hypertension progression. Tailored interventions for different obesity phenotypes may be warranted in hypertension management, taking into account sex-specific differences to improve outcomes.
2.TLR4 and IFN - γ Activated Mesenchymal Stem Cells Improve Schistosomiasis Liver Fibrosis by Regulating Macrophage Polarization
Yaojia REN ; Fang CHEN ; Wanxian HUANG ; Zhongdao WU ; Junxia LEI
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(3):410-419
ObjectiveTo investigate whether co-activated mesenchymal stem cells(MSCs) exert therapeutic effects against schistosomiasis by modulating macrophage polarization. MethodsTwenty adult male Balb/c mice were randomly divided into four groups: uninfected, infected, MSC-treated, and MSCTLR4+IFN-γ-treated groups. The Schistosoma japonicum infection model was established via abdominal patch method with cercariae. At week 5 post-infection, praziquantel was administered orally for antiparasitic treatment. At week 6, mice received either MSCs treatments (with or without pre-activation) or no treatment. Body weight changes were monitored weekly. Hepatic pathological alterations were evaluated via HE and Masson staining. RT-qPCR was used to assess α-SMA and collagen (Col-I, Col-Ⅲ) mRNA levels to quantify fibrosis. The mRNA levels of hepatic inflammatory cytokines and matrix metalloproteinases(MMP) were analyzed to explore fibrotic mechanisms. The expressions of i-Nos and Arg-1 in liver tissues were detected by RT-qPCR, and the ratio of M1 or M2 macrophages was detected by immunofluorescence staining, aiming to analyze the correlation between MSCs treatment and macrophage polarization. An in vitro co-culture system validated direct MSC-macrophage interactions. ResultsCompared with the infected group, the MSCTLR4+IFN-γ group exhibited increased body weight gain (P< 0.01), reduced hepatic granulomatous lesion area (P< 0.001), and decreased α-SMA, Col-I, and Col-Ⅲ mRNA levels (P< 0.01). Additionally, the MSCTLR4+IFN-γ group showed reduced TNF-α and IL-1β expression (P< 0.05), as well as elevated MMP2, Mmp9, and MMP13 levels (P< 0.01). The MSCTLR4+IFN-γ group showed higher expression of M2 marker Arg-1 mRNA compared with the infection group (P < 0.001) , while the expression of M1 marker i-Nos decreased (P< 0.05). Immunofluorescence confirmed a lower i-Nos+ cell ratio (P< 0.05) and higher F4/80+CD206+ cell ratio (P< 0.000 1) in the MSCTLR4+IFN-γ group compared with the infection group. In vitro co-culture experiments further demonstrated that MSCTLR4+IFN-γ promoted Arg-1 expression, suppressed pro-inflammatory cytokine i-Nos and TNF-α levels, consistent with ELISA results. ConclusionsThis study reveals that TLR4 and IFN-γ co-activated MSCs alleviate Schistosoma japonicum-induced hepatic fibrosis, potentially through modulating macrophage polarization toward the M2 phenotype. This mechanism may suppress inflammation and enhance extracellular matrix degradation, providing a therapeutic strategy for schistosomiasis-associated liver fibrosis.