Mechanisms of Bushen Tiaoxue Granules against controlled ovarian hyperstimulation-induced abnormal morphology of endometrium based on network pharmacology.

Bushen Tiaoxue Granules (BTG) is an empirical Chinese herbal formula that has been used for the treatment of subfertility. The protective effect of BTG on controlled ovarian hyperstimulation (COH)-induced impaired endometrial receptivity has been reported in our previous study. This study aims to explore the mechanisms of BTG on ameliorating abnormal morphology of endometrium based on network pharmacology. Active compounds of BTG were identified via the traditional Chinese medicine systems pharmacology and UPLC-MS technology. The SwissTargetPrediction platform and HERB database were used to screen out the putative targets of BTG. Potential targets of endometrial dysfunction caused by COH were obtained from three GEO databases. Through the STRING database, the protein-protein interaction was carried out according to the cross-common targets of diseases and drugs. GO terms and KEGG pathways enrichment analyses were conducted via the Metascape database. AutoDock Vina was used for docking validation of the affinity between active compounds and potential targets. Finally, in vivo experiments were used to verify the potential mechanisms derived from network pharmacology study. A total of 141 effective ingredients were obtained from TCMSP and nine of which were verified in UPLC-MS. Six genes were selected through the intersection of 534 disease related genes and 165 drug potential targets. Enrichment analyses showed that BTG might reverse endometrial dysfunction by regulating adherens junction and arachidonic acid metabolism. Hematoxylin-eosin staining revealed that BTG ameliorated the loose and edematous status of endometrial epithelium caused by COH. The protein expression of FOXO1A, ß-Catenin and COX-2 was decreased in the COH group, and was up-regulated by BTG. BTG significantly alleviates the edema of endometrial epithelium caused by COH. The mechanisms may be related to adheren junctions and activation of arachidonic acid metabolism. The potential active compounds quercetin, taxifolin, kaempferol, eriodictyol, and isorhamnetin identified from the BTG exhibit marginal cytotoxicity. Both high and low concentrations of kaempferol, eriodictyol, and taxifolin are capable of effectively ameliorating impaired hESC cellular activity.

Burden and attributable risk factors of ischemic stroke in China from 1990 to 2019: an analysis from the Global Burden of Disease Study 2019.

Background: The epidemiologic characteristics and attributable risk factors of ischemic stroke in China have changed over the past three decades. An up-to-date analysis on deaths, disability-adjusted life-years (DALYs), prevalence, incidence, and attributable risk factors of ischemic stroke for China is needed. This study aims to provide a comprehensive analysis of burden and attributable risk factors of ischemic stroke at national level in China by sex from 1990 to 2019. Methods: This is a secondary analysis of the Global Burden of Disease (GBD) study 2019. All data used in this study was derived from the 2019 GBD study. Deaths, DALYs, prevalence, incidence, and attributable risk factors of ischemic stroke in China by sex from 1990 to 2019 were analyzed. Results: From 1990 to 2019, the age-standardized deaths rate decreased by 3.3%, age-standardized DALYs rate decreased by 4%, age-standardized prevalence rate increased by 33.5%, and age-standardized incidence rate of ischemic stroke in China increased by 34.7%. In 2019, ambient particulate matter pollution became an important risk factor, whereas household air pollution from solid fuels was no longer a major risk factor for ischemic stroke in China. Burden of ischemic stroke was higher in China compared to other regions. Ambient particulate matter pollution among men, and diet high in sodium, smoking, household air pollution from solid fuels among women account for the increased deaths/DALYs due to ischemic stroke in China. Conclusion: Our study revealed that great changes have occurred in burden and attributable risk factors of ischemic stroke in China in the past three decades. Distinct sex-specific differences are observed in burden and attributable risk factors.

Highly Efficient Luminescence from a Red Thermally Activated Delayed Fluorescence Emitter with Flexible Conformation of Ancillary Groups.

Robust scaffolds were typically applied in thermally activated delayed fluorescence (TADF) molecules to suppress the non-radiative decay, trigger the fast spin-flipping, and enhance the light out-coupling efficiency. Herein, we disclosed for the first time the positive effect of flexible conformation of ancillary groups on the photophysical properties of TADF emitter. The red TADF emitter Ph-TPA with flexible conformation demonstrated small excited-state structural distortion and low reorganization energy compared to the counterpart Mc-TPA with a rigid macrocycle. Consequently, Ph-TPA showed an excellent photoluminescent quantum yield (PLQY) of 92 % and a state-of-the-art external quantum efficiency (EQE) of 30.6 % at 630 nm. This work could deepen our understanding of structure-property relationships of organic luminophores and help us to rationalize the design of efficient TADF materials.

Association between serum ß2-microglobulin levels and the risk of all-cause and cardiovascular disease mortality in chinese patients undergoing maintenance hemodialysis.

BACKGROUND: The association between serum ß2-microglobulin (ß2M) levels and the risk of all-cause and cardiovascular disease (CVD) mortality and the incidence of cardiovascular events (CVEs) in patients undergoing maintenance hemodialysis (MHD) is inconclusive. Furthermore, no study has been performed in China on the significance of serum ß2M levels in MHD patients. Therefore, this study investigated the aforementioned association in MHD patients. METHODS: In this prospective cohort study, 521 MHD patients were followed at Dalian Municipal Central Hospital affiliated with Dalian University of Technology from December 2019 to December 2021. The serum ß2M levels were categorized into three tertiles, and the lowest tertile served as the reference group. Survival curves were calculated by the Kaplan-Meier method. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. Sensitivity analysis was performed by excluding patients with CVD at baseline. RESULTS: During the follow-up period of 21.4 ± 6.3 months, there were 106 all-cause deaths, of which 68 were caused by CVD. When excluding CVD patients at baseline, there were 66 incident CVEs. Kaplan-Meier analysis revealed that the risk of all-cause and CVD mortality in the highest tertile of serum ß2M levels was significantly higher than that in the lowest tertile (P < 0.05), but not for the CVEs (P > 0.05). After adjusting for potential confounders, serum ß2M levels were positively associated with the risk of all-cause (HR = 2.24, 95% CI = 1.21-4.17) and CVD (HR = 2.54, 95% CI = 1.19-5.43) mortality, and a linear trend was evident (P < 0.05). Besides, the results of sensitivity analysis were consistent with the main findings. However, we didn't observed the significant association between serum ß2M levels and CVEs (P > 0.05). CONCLUSION: The serum ß2M level may be a significant predictor of the risk of all-cause and CVD mortality in MHD patients. Further studies are needed to confirm this finding.

Association between corrected serum calcium levels after dialysis and post-dialysis fatigue risk: a hospital-based case-control study.

OBJECTIVE: Post-dialysis fatigue (PDF) is an important problem in patients undergoing maintenance hemodialysis (MHD); however, evidence of the association between serum calcium after dialysis and the risk of PDF is limited and controversial. We explored this association among patients receiving MHD. METHODS: We carried out a case-control study of patients in the dialysis unit of Dalian Municipal Central Hospital between December 2019 and January 2020, including 340 patients with PDF and 270 patients without PDF. PDF was assessed by a \validated self-administered questionnaire. Clinical variables were tested for multicollinearity using variance inflation factor analysis. Corrected serum calcium levels were categorized into three groups, with the lowest tertile used as the reference category. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for PDF risk were estimated using an unconditional logistic regression model. RESULT: After adjusting for potential confounders, corrected serum calcium levels showed a significant positive association with the risk of PDF (ORT3vs.T1 = 1.61, 95% CI = 1.01-2.58). Notably, after stratification by age, corrected serum calcium was also positively associated with the risk of PDF in patients aged ≥ 65 years (ORT3vs.T1 = 4.25, 95% CI 1.66-11.46). Furthermore, a significant linear trend and interaction were also observed (P < 0.05). DISCUSSION: Higher corrected serum calcium levels after dialysis might increase the risk of PDF among MHD patients. However, further studies are warranted to confirm these findings.

Serum total indoxyl sulfate levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study.

BACKGROUND: The association between serum total indoxyl sulfate (tIS), and cardiovascular disease (CVD) and all-cause mortality is a matter of debate. In the current study we sought to determine the association, if any, between serum tIS, and all-cause and CVD-associated mortality in patients on maintenance hemodialysis (MHD). METHODS: A prospective cohort study was conducted involving 500 MHD patients at Dalian Municipal Central Hospital from 31 December 2014 to 31 December 2020. Serum tIS levels were measured at baseline and classified as high (≥44.16 ng/ml) or low (< 44.16 ng/ml) according to the "X-tile" program. Besides, the associations between continuous serum tIS and outcomes were also explored. Predictors were tested for colinearity using variance inflation factor analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Restricted cubic spline model was performed to assess dose-response relationships between tIS concentration and all-cause and CVD mortality. RESULTS: During a 58-month median follow-up period, 224 deaths (132 CVD deaths) were documented. After adjustment for potential confounders, the serum tIS level was positively associated with all-cause mortality (HR = 1.02, 95% = 1.01-1.03); however, we did not detect a significant association when tIS was a dichotomous variable. Compared with the MHD population with a serum tIS level < 44.16 ng/ml, the adjusted HR for CVD mortality among those with a serum tIS level ≥ 44.16 ng/ml was 1.76 (95% = 1.10-2.82). Furthermore, we also noted the same association when the serum tIS level was a continuous variable. CONCLUSION: The serum tIS level was associated with higher risk of all-cause and CVD mortality among MHD patients. Further prospective large-scale studies are required to confirm this finding.

Dietary supplementation Eucommia ulmoides extract at high content served as a feed additive in the hens industry.

Since numerous natural components in Eucommia ulmoides belong to phytoestrogen, its effect on hens production deserve more attention. To investigate the potential of E. ulmoides extract used as a feed additive, laying performance, egg quality, yolk cholesterol, yolk fatty acids, yolk fatty, yolk volatile components, albumen amino acids, plasma biochemical parameters, intestinal histology, and gut microbiota of hens (n = 120) were determined between basal diet (A) and dietary supplementation low (B), middle (C), and high (D) level E. ulmoides extract for 11 wk. When compared to A group, 2 percentage points elevation in laying rate was observed of D group. Significant up-regulation of immunoglobulin indexes and down-regulation of lipid related indexes in D group were also found if comparison with A group, suggesting that supplementation E. ulmoides extract at a relative high content benefited in immunity enhancing and blood-fat depressing. Meanwhile, obvious variation in albumen amino acids and yolk volatile compounds were inspected as dietary supplementation E. ulmoides extract, especially in D group, implied that the flavor of egg would change under high-level E. ulmoides extract treatment. Besides, villus height and villus height to crypt depth ratio of duodenum, jejunum, and ileum in D group were also significantly higher than that of in A group, indicating high-level E. ulmoides extract contributed to nutrient adsorption via intestinal histology changing. Moreover, the richness, diversity, and composition of gut microbiota in D group also significantly altered with a comparison of A group. These variation caused gut microbiota in D group major enriched in the KEGG pathway of insulin signing pathway, systemic lupus erythematosus, and bacterial invasion of epithelial cells, which were conducive to egg production elevation via facilitating nutrient adsorption, inflammation relieving, blood lipid amelioration, and insulin resistance alleviation. These results indicated that dietary supplementation E. ulmoides extract at high content could serve as a feed additive in the hens industry.

miR-29a regulates vascular neointimal hyperplasia by targeting YY1.

OBJECTIVES: The formation of vascular neointima is mainly related to impairment of the vascular endothelial barrier and abnormal proliferation and migration of smooth muscle cells. The objective of this study was to investigate whether miR-29a exerts any promoting effect on the vascular neointimal hyperplasia and if so, its mechanism. MATERIALS AND METHODS: RT-qPCR was performed to determine expression of miR-29a in vascular smooth muscle cells (VSMC) and vascular neointimal hyperplasia. To further understand its role, we restored its expression in VSMCs by transfection with miR-29a mimics or inhibitors. Effects of miR-29a on cell proliferation were also determined. RESULTS: In this study, we used two kinds of model to observe the role of miR-29a in neointimal hyperplasia induced by carotid ligation or balloon injury. The major findings were that: (i) miR-29a overexpression promoted neointimal hyperplasia induced by carotid ligation; (ii) miR-29a increased proliferation of VSMCs, one aspect of which was by targeting expression of Ying and yang 1 protein (YY1), a negative regulator of Cyclin D1. A further aspect, was by increasing expression of Krüppel-like factor 5, a positive regulator of Cyclin D1, thereby allowing formation a synergistic effect. (iii) Tongxinluo (TXL), a traditional Chinese medicine reduced neointimal formation in ligated vessels by inhibiting VSMC proliferation and migration. CONCLUSIONS: These findings provide a new molecular mechanism of TXL in decreasing neointima hyperplasia.