Objective:To study the effects of Tongmai Huazheng Decoction on the fibrosis of lesions in mice with adenomyosis (AM); To explore its mechanism.Methods:The ICR mouse model of adenomyosis was established by using tamoxifen modeling method. The 30 mice successfully modeled were divided into model group, Tongmai Huazheng Decoction group and progesterone group according to the random number table method with 10 mice in each group, and 10 female mice were set as the blank group. Tongmai Huazheng Decoction group was intragastrically administered with Tongmai Huazheng Decoction 30.47 g/kg, once/d; The gestrinone group was intragastrically administered with gestrinone suspension 0.32 mg/kg, twice a week; the blank group and model group were intragastrically administered with 0.1 ml/10 g normal saline, once a day. After 8 weeks of intervention, HE staining was used to observe the pathological changes of uterine tissue; Masson staining was used to observe the degree of uterine tissue fibrosis; immunofluorescence method was used to detect the protein expressions of CollagenⅠ, CollagenⅢ and fibronectin in uterine tissue of each group; Western bolt method was used to detect the protein expressions of TGF-β1 and α-smooth muscle actin (α-SMA) in each group.Results:Compared with the model group, the ratio of collagen fiber area in uterine tissue in Tongmai Huazheng Decoction group and progesterone group decreased ( P<0.05), the immunofluorescence intensity of CollagenⅠ, CollagenⅢ and Fibronectin decreased ( P<0.05), and the expressions of TGF-β1 and α-SMA proteins decreased ( P<0.05). Conclusion:Tongmai Huazheng Decoction can reduce the ratio of collagen fiber area in the uterus of mice with adenomyosis model, downregulate the expression of CollagenⅠ, Collagen Ⅲ, Fibronectin, TGF-β1, and α-SMA proteins, alleviate the degree of fibrosis in adenomyosis lesions, and thus inhibit or slow down disease progression.

BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

ObjectiveTo compare the retest reliability and discriminant validity of dynamic postural stability indices for functional ankle instability (FAI) obtained by different algorithms based on acceleration signals at different positions of human body. MethodsFrom April to June, 2021, 21 subjects with unilateral FAI and 21 subjects with normal ankle were recruited. Three inertial sensors were attached to the waist points, knee and ankle positions. The ground reaction force (GRF) and kinematics data of the subjects in multi-direction single leg landing test were collected synchronously by 3D force plate and inertial sensors. The unbounded third order polynomial (UTOP) fitting method was used to calculate the stability time, and the root mean square was used to caculate the stability index. ResultsMost of the indicators calculated based on acceleration signal correlated with that based on GRF with low coefficient (|r| = 0.116 to 0.368, P < 0.05). The stability time and stability index based on the acceleration signals of different positions of human body showed low to high retest reliability (CMC 0.30 to 0.91). For the females, among the stability time based on acceleration signal, eleven indexes achieved average to very high discriminant validity (AUC = 0.702 to 0.942, P < 0.05); eight of the stability indexes reached general level of discriminant validity (AUC = 0.717 to 0.782, P < 0.05). No algorithms achieved good discriminant effect in male subjects. ConclusionBased on the acceleration signal of waist point in single-leg landing stability test, the stability time calculated by UTOP algorithm can evaluate the dynamic postural stability of female FAI patients with high discriminant validity and medium to high retest reliability.

Hyperandrogenism is a common endocrine pathological state in women, and polycystic ovary syndrome is the main cause. Studies have shown that in addition to affecting reproductive function, hyperandrogenism in women can also interfere with vascular endothelial function, and directly or indirectly increases the risk of atherosclerotic disease by affecting risk factors such as blood pressure, lipids, and glucose. This article reviews the impact of hyperandrogenism on the cardiovascular system of women, aiming at a deeper understanding of the role of androgens in women′s health.

Objective:To analyze the selection status of randomized controlled trial (RCT) outcome indicators of TCM for the treatment of adenomyosis (AM) in the past five years; To provide suggestions for the future studies in this field.Methods:The RCTs of TCM for the treatment of AM were retrieved from the databases of CNKI, Wanfang Data, VIP, CBM, PubMed, Embase, the Cochrane Library, Web of Science, Chinese Clinical Trial Register and ClinicalTrials from the establishment of the database to February 28, 2022. The risk of bias was assessed, and the outcome indicators were classified, described and analyzed, and compared with the international core outcome set (COS) studies.Results:A total of 48 studies were included, of which 47 were from published literature and 1 was from registered clinical trials, involving 4 544 patients and 77 outcome indicators. Among the 47 literatures, the total clinical efficacy rate (63.83%) was the most frequently reported outcome indicator, followed by uterine volume (61.70%). Ultrasound examination was the main outcome index in 1 registered trial. Compared with the international COS study, it was found that the included studies paid attention to the outcome report of pain degree, menstrual status and hematological indicators, the reporting rate of quality of life and economic indicators was low, and the urinary system symptoms and fertility outcome indicators were not reported.Conclusion:In the selection of outcome indicators, RCTs of TCM treatment of AM pay attention to the symptoms and signs outcomes, physical and chemical examination outcomes. However, there were still several problems of the selection of outcome measures: unclear primary and secondary outcome indicator, the use of unreasonable composite outcomes, lack of measurement blindness, insufficient attention to endpoint criteria, and ignoring economic evaluation.

Optimization efforts were devoted to discover novel PDE10A inhibitors in order to improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension (PAH) starting from the previously synthesized inhibitor

Objective: To establish comprehensive understanding of the self-rated health of the Chinese doctors and nurses and probe into their influencing factors. Methods: Data were drawn from a hospital performance survey, which was conducted by the Peking Union School of Public Health from March 18th to April 9th, 2019, among the 144 tertiary public hospitals in 31 provinces, autonomous regions, and municipalities. The survey included a cell-phone based questionnaire filled out by the sampled doctors and nurses, in which they were asked to rate their health using a 5-level Likert scale(from " very poor" to " very good" ). Mann-Whitney U test was used to analyze the differences in self-rated health between doctors and nurses. Chi-square test and two-class multivariate logistic regression were performed to analyze factors affecting self-rated health of the providers. Results: Among the 144 sample hospitals, the proportion of doctors, who rated their health as " healthy" , was 20.30%(4 979/24 529), that of nurses was 28.92%(8 361/28 910). It was worse than that in some developed countries and lower than the general population in China. Multi-variate analysis showed that adequate sleeping time, satisfaction with the work and with the doctor-patient relationship, were positively associated with the level of self-rated health of the sampled doctors and nurses(P<0.05). It was also found that the longer the average weekly working time, the higher the recognition of " the work load is too heavy" , the lower the proportion of doctors and nurses who rated their health as " healthy" (P<0.05). Conclusions Sleep time, job satisfaction, workload and doctor-patient relationship are important factors affecting self-rated health of the Chinese doctors and nurses.

The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPAR agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC values <5 nmol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Compound , the most effective one, gave the IC of 1.1 nmol/L towards PDE9, which is significantly better than the reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding patterns and binding free energy of the designed compounds with PDE9 may explain the structure-activity relationships and provide evidence for further structural modifications.