Perimenopausal syndrome and hypertension during perimenopause in South China: prevalence, relationships and risk factors.

BACKGROUND: More than 2 billion women are experiencing the menopausal transition in China, and some of these women have hypertension. Limited studies has focused on perimenopausal syndrome and hypertension in a specific population, so we aimed to investigate the prevalence of perimenopausal syndrome and hypertension and to analyse their relationships and risk factors in perimenopausal women in South China. METHODS: This cross-sectional study included 3553 women aged 40 to 60 years from South China. We collected medical report, lifestyle, blood sample, general condition questionnaire, and modified Kupperman index (mKMI) data. Multivariate logistic regression analysis was performed to identify risk factors for perimenopausal syndrome and hypertension during perimenopause. RESULTS: The prevalence of hypertension in perimenopause patients was 16.58%, and the prevalence of perimenopausal syndrome was 9.9%. Compared with women without hypertension during perimenopause, women with HTN during perimenopause had an increased risk of perimenopausal syndrome (26.4% vs. 8.7%, P < 0.001). Lipid levels and urinary tract infections were risk factors for hypertension and perimenopausal syndrome, in addition to the presence of breast nodules, the intake of snacks at night, high-salt diets, red meat and sugar-sweetened beverages, and a history of smoking and drinking for perimenopausal syndrome and the presence of gestational hypertension and diabetes for hypertension. CONCLUSION: We concluded that perimenopausal syndrome and HTN are common in perimenopausal women in South China, and the associations between them are strong and positive. Perimenopausal syndrome shares some common risk factors with HTN during perimenopause, such as BMI and dyslipidaemia. Therefore, gynaecological endocrinologists in China should consider screening for perimenopausal syndrome in hypertensive perimenopausal women, and appropriate management of perimenopause is needed to alleviate these conditions.

Association of serum 25-hydroxyvitamin D with the incidence of 16 cancers, cancer mortality, and all-cause mortality among individuals with metabolic syndrome: a prospective cohort study.

PURPOSE: The relationship between vitamin D levels and cancer incidence and mortality in individuals with metabolic syndrome (MetS) remains poorly explored. Herein, we aimed to determine the association between 25-hydroxyvitamin D [25(OH)D] concentrations and the risk of 16 cancer incidence types and cancer/all-cause mortality in patients with MetS. METHODS: We enrolled 97,621 participants with MetS at recruitment from the UK Biobank cohort. The exposure factor was baseline serum 25(OH)D concentrations. The associations were examined using Cox proportional hazards models, which were displayed as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Over a median follow-up period of 10.92 years for cancer incidence outcomes, 12,137 new cancer cases were recorded. We observed that 25(OH)D concentrations were inversely related to the risk of colon, lung, and kidney cancer, and HRs (95% CI) for 25(OH)D ≥ 75.0 vs. < 25.0 nmol/L were 0.67 (0.45-0.98), 0.64 (0.45-0.91), and 0.54 (0.31-0.95), respectively. The fully adjusted model revealed a null correlation between 25(OH)D and the incidence of stomach, rectum, liver, pancreas, breast, ovary, bladder, brain, multiple myeloma, leukemia, non-Hodgkin lymphoma, esophagus, and corpus uteri cancer. Over a median follow-up period of 12.72 years for mortality outcomes, 8286 fatalities (including 3210 cancer mortalities) were documented. An "L-shaped" nonlinear dose-response correlation was detected between 25(OH)D and cancer/all-cause mortality; the respective HRs (95% CI) were 0.75 (0.64-0.89) and 0.65 (0.58-0.72). CONCLUSION: These findings emphasize the importance of 25(OH)D in cancer prevention and longevity promotion among patients with MetS.

TcpC inhibits toll-like receptor signaling pathway by serving as an E3 ubiquitin ligase that promotes degradation of myeloid differentiation factor 88.

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.

Sodium tanshinone IIA sulfonate protects rat myocardium against ischemia-reperfusion injury via activation of PI3K/Akt/FOXO3A/Bim pathway.

AIM: To investigate the mechanisms underlying the protective effects of sodium tanshinone IIA sulfonate (STS) in an ischemia-reperfusion (I/R)-induced rat myocardial injury model. METHODS: Male SD rats were iv injected with STS, STS+LY294002 or saline (NS) for 15 d. Then the hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. Cardiac function, infarction size and area at risk were assessed. Cell apoptosis was evaluated with TUNEL staining, DNA laddering and measuring caspase-3 activity. In addition, isolated cardiomyocytes of neonatal rats were pretreated with the above drugs, then exposed to H2O2 (200 mol/L) for 1 h. Cell apoptosis was detected using flow cytometric assay. The levels of p-Akt, p-FOXO3A and Bim were examined with immunoblotting. RESULTS: Compared to NS group, administration of STS (20 mg/kg) significantly reduced myocardial infarct size (40.28%±5.36% in STS group vs 59.52%±7.28% in NS group), and improved the myocardial function as demonstrated by the increased values of dp/dtmax, LVDP and coronary flow at different reperfusion time stages. Furthermore, STS significantly decreased the rate of apoptotic cells (15.11%±3.71% in STS group vs 38.21%±7.83% in NS group), and reduced caspase-3 activity to nearly a quarter of that in NS group. Moreover, STS significantly increased the phosphorylation of Akt and its downstream target FOXO3A, and decreased the expression of pro-apoptotic gene Bim. Co-treatment with the PI3K inhibitor LY294002 (40 mg/kg) partially countered the protective effects induced by STS treatment. In isolated cardiomyocytes, STS exerted similar protective effects as shown in the ex vivo I/R model. CONCLUSION: STS pretreatment reduces infarct size and improves cardiac function in an I/R-induced rat myocardial injury model via activation of Akt/FOXO3A/Bim-mediated signal pathway.

[Deep sarcoma of the penis: a report of 2 cases and review of the literature].

OBJECTIVE: To investigate the clinical characteristics, diagnosis, treatment and prognosis of deep sarcoma of the penis. METHODS: The pathological and clinical data of 2 cases of deep sarcoma of the penis were analyzed retrospectively and the literature reviewed. RESULTS: Both of the cases were treated by total penectomy. Epithelioid angiosarcoma of the penis was confirmed by postoperative pathology in one patient, who died of pulmonary metastasis in the eighth month after the operation; and epithelioid sarcoma of the penis was confirmed in the other, who died of brain metastasis in the second month after the operation. CONCLUSION: Deep sarcoma of the penis is rare but can be diagnosed pathologically. Total penectomy is the main option for its treatment. Node dissection, with poor prognosis, is not recommended unless adenopathy is palpable.