Cardiorespiratory fitness and metabolic risk in Chinese population: evidence from a prospective cohort study.

BACKGROUND: Studies on the association between estimated cardiorespiratory fitness (CRF) and changes in metabolic risk in the Chinese population are limited. This study aims to examine the associations between CRF and changes in metabolic risk. SUBJECTS AND METHODS: We included 4,862 and 2,700 participants recruited from 28 provinces in the China Health and Retirement Longitudinal Study (CHARLS) in the baseline (Wave 1) and follow-up (Wave 4) analyses, respectively. CRF was calculated using sex-specific longitudinal non-exercise equations. Metabolic indicators included systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and fasting plasma glucose (FPG) levels. The metabolic score was calculated as the number of changes in the above metabolic indicators above the 75th percentile of the distribution of changes (equal to or below the 25th percentile for HDL-C). RESULTS: In the baseline analysis, CRF was negatively associated with SBP, DBP, TG, and FPG, and positively correlated with HDL-C after adjusting for age, smoking status, and drinking status (all P < 0.0001) in both males and females. In the follow-up analysis, higher baseline CRF was significantly related to a decrease in SBP, DBP, TG, FPG, and metabolic score (all P < 0.0005), and increased HDL-C (P < 0.0001) after further adjustment for corresponding baseline metabolic indicators. The associations remained significant after stratification by sex, except for the changes in HDL-C levels in females. Furthermore, improved CRF was associated with favorable changes in DBP, TG, HDL-C, FPG, and metabolic scores in all populations and males. Significant associations between changes in CRF and DBP, TG, and FPG levels were found in females. CONCLUSION: Higher baseline CRF and improved CRF were associated with favorable changes in metabolic indicators.

Changes in frailty and incident cardiovascular disease in three prospective cohorts.

BACKGROUND AND AIMS: Previous studies found that frailty was an important risk factor for cardiovascular disease (CVD). However, previous studies only focused on baseline frailty status, not taking into consideration the changes in frailty status during follow-up. The aim of this study was to investigate the associations of changes in frailty status with incident CVD. METHODS: This study used data of three prospective cohorts: China Health and Retirement Longitudinal Study (CHARLS), English Longitudinal Study of Ageing (ELSA), and Health and Retirement Study (HRS). Frailty status was evaluated by the Rockwood frailty index and classified as robust, pre-frail, or frail. Changes in frailty status were assessed by frailty status at baseline and the second survey which was two years after the baseline. Cardiovascular disease was ascertained by self-reported physician-diagnosed heart disease (including angina, heart attack, congestive heart failure, and other heart problems) or stroke. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting for potential confounders. RESULTS: A total of 7116 participants from CHARLS (female: 48.6%, mean age: 57.4 years), 5303 from ELSA (female: 57.7%, mean age: 63.7 years), and 7266 from HRS (female: 64.9%, mean age: 65.1 years) were included according to inclusion and exclusion criteria. The median follow-up periods were 5.0 years in the CHARLS, 10.7 years in the ELSA, and 9.5 years in the HRS. Compared with stable robust participants, robust participants who progressed to pre-frail or frail status had increased risks of incident CVD (CHARLS, HR = 1.84, 95% CI: 1.54-2.21; ELSA, HR = 1.53, 95% CI: 1.25-1.86; HRS, HR = 1.59, 95% CI: 1.31-1.92). In contrast, frail participants who recovered to robust or pre-frail status presented decreased risks of incident CVD (CHARLS, HR = 0.62, 95% CI: 0.47-0.81; ELSA, HR = 0.49, 95% CI: 0.34-0.69; HRS, HR = 0.70, 95% CI: 0.55-0.89) when compared with stable frail participants. These decreased risks of incident CVD were also observed in pre-frail participants who recovered to robust status (CHARLS, HR = 0.66, 95% CI: 0.52-0.83; ELSA, HR = 0.65, 95% CI: 0.49-0.85; HRS, HR = 0.71, 95% CI: 0.56-0.91) when compared with stable pre-frail participants. CONCLUSIONS: Different changes in frailty status are associated with different risks of incident CVD. Progression of frailty status increases incident CVD risks, while recovery of frailty status decreases incident CVD risks.

Estimated cardiorespiratory fitness and incident risk of cardiovascular disease in China.

BACKGROUND: Limited evidence is available on the association between estimated cardiorespiratory fitness (e-CRF) and incidence of cardiovascular disease (CVD) in Chinese population. METHODS: A total of 10,507 adults including 5084 men (48.4%) and 5423 (51.6%) women with a median age of 56.0 (25% quantile: 49, 75% quantile 63) years from the China Health and Retirement Longitudinal Study (CHARLS) was recruited in 2011 as baseline. The CVD incident events were followed-up until 2018. e-CRF was calculated from sex-specific longitudinal non-exercise equations and further grouped into quartiles. Cox proportional models were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for incidence risks of CVD, heart disease and stroke. RESULTS: During a median follow-up of 7 years, a total of 1862 CVD, 1409 heart disease and 612 stroke events occurred. In fully adjusted models, each one MET increment of e-CRF was associated with lower risk of CVD (HR = 0.91, 95%CI = 0.85-0.96 for males, HR = 0.87, 95%CI = 0.81-0.94 for females). Compared with the Quartile (Q)1 group, the HRs (95%CI) of the Q2, Q3 and Q4 groups were 0.84 (0.63-1.03), 0.72 (0.57-0.91) and 0.66 (0.51-0.87) for CVD in males. Females had HRs of 0.79 (0.66-0.96) in Q2, 0.71 (0.57-0.88) in Q3 and 0.58 (0.45-0.75) in Q4 for CVD. The associations between e-CRF and heart disease and stroke were slightly weaker than that for CVD in both males and females. CONCLUSIONS: Higher e-CRF decreases the incident risk of CVD, heart disease and stroke.

F···Br and F···S Heterohalogen-Bond-Directed 2D Self-Assemblies of a Benzothiadiazole Derivative.

Halogen bonding (XB) is of great importance in fabricating a two-dimensional (2D) self-assembly for its adaptive directionality. However, the XBs involving fluorine (F) have barely been studied due to the absence of an σ-hole on F. Here, 2D self-assemblies of a F-substituted 4,7-bis(5-bromo-4-dodecylthiophen-2-yl)-5,6-difluorobenzo[c][1,2,5]thiadiazole (BTZ-BrF) molecule on graphite were investigated using scanning tunneling microscopy (STM) and density functional theory (DFT) calculations. STM experiments revealed that the 2D patterns of BTZ-BrF had a clear solvent and concentration dependence, showing a frame-like pattern in aliphatic acid and aliphatic hydrocarbon solvents at high concentrations. At lower concentrations, a bamboo-like and a wave-like pattern were observed in aliphatic acid, whereas small frame-like and large ladder-like domains at high solution concentrations in aliphatic hydrocarbon were observed. As the concentration further decreased, two linear patterns were observed. DFT calculations suggested that the hetero-XBs of F···Br, F···S, Br···S, and Br···N, the homo-XBs of type-II Br···Br, and the S···S interactions synergistically directed and stabilized the polymorphic 2D architectures. This understanding of intermolecular XBs during the molecular assembly at the molecular level may shed light on the ongoing efforts of regulating nanostructures of multifunctional organics.

CD14 dictates differential activation of mesenchymal stromal cells through AKT, NF-κB and P38 signals.

Mesenchymal stromal cells (MSCs) widely exist in many tissues and have multiple differentiation potential and immunomodulatory capacities. Recently, MSCs have become promising tools for the treatment of various degenerative disorders and autoimmune diseases. The properties of MSCs could be modified in different microenvironments. Thus, it is important to explore the factors controlling MSC function. The presence of Toll-like receptors (TLRs) in MSCs was demonstrated according to previous studies. Consistently, we also illustrated the expression of TLRs in both murine and human MSCs, and displayed that the expression patterns of TLRs in MSCs from different sources. Furthermore, we explored the role of TLR and TLR signaling pathway in MSCs. Interestingly, activation of TLR4-induced expression of cytokines and some specific genes in MSCs. However, MSCs retained much lower mRNA level compared with macrophages. We explored the expression of CD14 in MSCs from different sources, which played a vital role in TLR4 signaling pathway, and found that MSCs are almost negative for CD14. Moreover, only partial activation of TLR4 signaling pathway was observed in MSCs, with no activation of AKT, NF-κB and P38. Here, in the study we defined TLR expression, function and activation in MSCs, which is critical for designing MSC-based therapies.

[In vitro effect of combined traditional Chinese medicine (Changqing capsule) on the tachyzoites of Toxoplasma gondii].

OBJECTIVE: To detect the in vitro effect of the traditional Chinese medicine on the tachyzoites of Toxoplasma gondii. METHODS: Supernatant (1.5 ml) of different doses of the traditional Chinese medicine (Changqing capsule) was collected by normal saline immersion and 2.5 x 10(4) Toxoplasma gondii tachyzoites were added in each paste well for 8 hours. Spiramycin, pyrimethamine and azithromycin in different doses were used as controls. Normal saline was used as negative control. Mice were inoculated with drug-treated tachyzoites intraperitoneally or intragastrically. The normal mice were subcultured after 8 days for 3 generations. RESULTS: The incident number of the infected mice was significantly different among groups with different drugs and doses: 2/60, 16/60, 10/60 and 10/60 in the groups of Changqing capsule, spiramycin, pyrimethamine and azithromycin respectively (P < 0.05). No mice were found incident in groups of high and medium dose Changqing capsule while 2 out of 20 found sick in the low dose group (P < 0.05). The subculture observation showed that 2 and 1 mice in the first generation of the low dose Changqing capsule group inoculated intraperitonelly and intragastrically were found infected respectively. 2 mice of the second generation in low dose spiramycin group and 1 mouse of the third generation in low dose pyrimethamine group were also found infected. CONCLUSION: The in vitro killing effect of the Changqing capsule on the tachyzoites of Toxoplasma gondii is better than the current clinical drugs and shows a positive correlation with the dosages.

[Expressions of Cx43 and Skp2 in epithelial ovarian tumor and their clinical significances].

BACKGROUND & OBJECTIVE: Connexin 43 (Cx43), an important member of connexins family, is frequently down-regulated in neoplastic cells. It has been shown to have gap junction-dependent anti-tumor effect on various tumor cell lines. Recently, it was reported that Cx43 could inhibit tumor growth via down-regulating the expression of S-phase kinase associated protein 2 (Skp2). Skp2, a member of F-box protein family, can specifically recognize, and accelerate the ubiquitin-mediated degradation of several key regulators of G(1) phase progression. This study was to detect expressions of Cx43 and Skp2 in epithelial ovarian tumor, and to explore their correlations to tumorigenesis and development of ovarian cancer. METHODS: Expressions of Cx43 and Skp2 were examined by immunohistochemistry in 81 specimens of epithelial ovarian tumor (13 specimens of adenoma, 12 specimens of borderline adenoma, and 56 specimens of adenocarcinoma). Relationship between expression levels of Cx43 and Skp2, and association of their expression levels with clinicopathologic factors were statistically analyzed. RESULTS: Positive rates of Cx43 in ovarian adenoma, borderline adenoma, and ovarian adenocarcinoma were 84.6% (11/13), 66.7% (8/12), and 33.9% (19/56), respectivelyu expression level of Cx43 in ovarian adenocarcinoma was significantly lower than those in ovarian adenoma (P<0.01), and borderline adenoma (P<0.01). Positive rates of Skp2 in ovarian adenoma, borderline adenoma, and ovarian adenocarcinoma were 0, 0, and 46.3% (26/56), respectivelyu expression level of Skp2 in ovarian adenocarcinoma was significantly higher than those in ovarian adenoma (P<0.01), and borderline adenoma (P<0.01). Moreover, the expression levels of Cx43 and Skp2 were independent of age and histological type, but significantly associated with pathologic grade, clinical stage, and positive lymph node metastasis of ovarian adenocarcinoma. Besides, in ovarian adenocarcinoma, expression level of Cx43 was moderately inversely correlated with that of Skp2 (r=-0.48, P<0.01). CONCLUSIONS: Down-regulation of Cx43, and over-expression of Skp2 are tumor specific, and may play important roles in tumorigenesis, and development of ovarian cancer. Up-regulation of Skp2 may be related with down-regulation of Cx43 in ovarian cancer.

[Expression of cellular FLICE inhibitory protein (cFLIP) in endometrial adenocarcinoma].

BACKGROUND & OBJECTIVE: Cellular FLICE inhibitory protein (cFLIP) is a new-found member of the inhibitors of apoptosis. It has been reported to be overexpressed in various human cancers. We investigated the expression of cFLIP in endometrial adenocarcinoma and its association with clinicopathological features and proliferating cell nuclear antigen-labeling index (PCNA-LI). METHODS: cFLIP and PCNA-LI were determined in endometrial tissue samples including 42 endometrial adenocarcinoma tissues, 20 normal proliferative endometrial tissues, and 40 hyperplastic tissues with (n=10) or without (n=30) atypia by immunohistochemistry. RESULTS: The positive rates of cFLIP expression in normal proliferative samples of endometrium, hyperplastic samples, and endometrial adenocarcinomas were (55.0+/-11.4)%, (72.5+/-7.1)%, and (83.3+/-5.8)%, respectively. Scoring on the basis of the percentage of positive cells and the intensity of positive immunostaining indicated that the expression level of cFLIP was significantly higher in adenocarcinoma than in normal proliferative endometrium (P< 0.01) and hyperplastic endometrium with or without atypia (P< 0.05);but no significant difference was found between the later two groups. PCNA-LI were (12.01+/-2.07)%,(20.26+/-6.99)%, (27.10+/-3.01)%, and (41.65+/-10.16)%, respectively in the adenocarcinoma groups with different cFLIP levels showed as -, +, ++, +++. Statistical analysis showed that cFLIP expression was significantly associated with PCNA-LI (r=0.7471,P< 0.01). In addition, cFLIP expression was also significantly associated with clinical stage (P< 0.05), the presence of invasion to >1/2 myometrium (P< 0.05) and positive lymph node metastasis (P< 0.01) of endometrial adenocarcinomas. CONCLUSION: Overexpression of cFLIP is tumor specific, which may be a late event in the tumor development of endometrial adenocarcinoma.