A? plays a crucial role in Alzheimer's Disease and the soluble A? oligomers have been recognized as the emerging neurotoxins,which ultimately cause memory impairment and neuronal loss through different mechanisms.The development of novel drugs targeting A? oligomers indicates new and promising therapy approaches for AD.The pathological roles as the proximal toxins in AD and the compounds,targeting soluble A? oligomers,which are currently in preclinical and early clinical development,are reviewed.

Objective To determine the situation of contraceptive use and impact factors among reproductive-age women seeking abortion in Kunming which was in the southwest of China in order to provide information for improving contraceptive use. Methods A hospital-based study was conducted among 397 women of reproductive age, seeking abortion in hospitals of different levels in Kunming from June 2011 to December 2011. They were face to face interviewed by the trained investigators with the questionnaires. Results Among 397 women, 229 cases (57.7%) had experienced induced abortion. Abortion accounted for 61.7% of married women, and unmarried accounted for 39.3%. About 36.3%never used any contraceptives, and only 21.4%of respondents used contraceptives at every intercourse. The main contraceptive before this pregnancy was condom (68.9%) . The use of contraceptives was mainly decided by couple (73.4%) . Multivariate logistic regression analysis indicated that respondents' age, educational level and access to contraceptives in hospital were associated with the use of contraceptive. Conclusion Premarital pregnancy and low rate of contraception are the main reason for induced abortion. Fewer reproductive-age women seeking abortion use contraceptives. It is necessary to increase their awareness of contraception and abortion related knowledge, provide feasible contraceptive to enable women to avoid unwilling pregnancy. Further more, it is important to promote male involvement in contraception.

Objective:To measure with Zhejiang province as an example the situation of the self-evaluation health management service capability of primary medical staff in county-level medical alliances.Methods:A self-evaluation scale for health management service capability by primary medical staff was customized, covering 5 dimensions of professional attitude, interpersonal communication ability, comprehensive knowledge integration ability, professional practice ability and professional development ability, as well as 29 items. In July-September 2019, medical alliances were selected from three counties/cities based on economic development as the survey targets, and a total of 264 primary medical staff were surveyed. Quantitative data were described in mean and standard deviation, while qualitative data were described in composition ratio, and the differences were compared by Kruskal-Willis test.Results:The self-evaluation scoring of health management service capability of the primary medical staff was (59.75±18.64) points, and the average scoring of the items was (2.06±0.64) points. The scoring of knowledge integration (1.98±0.70)and professional practical ability (2.03±0.67) were lower than the average scoring of the items; gender and occupation type of primary medical staff present statistical significances in the self-evaluation scoring of health management service capability.Conclusions:Given the health management service capabilities of primary medical staff, they still need to upgrade their knowledge integration and professional practice capabilities. County-level medical alliances should enhance their training of health management knowledge and skills, promote doctor-nurse collaboration in health management services to broaden the depth of primary health management services.

Chuanxiong Rhizoma (CX, the dried rhizome of Ligusticum wallichii Franch.), a well-known traditional Chinese medicine, is clinically used for treating cardiovascular, cerebrovascular and hepatobiliary diseases. Cholestatic liver damage is one of the chronic liver diseases with limited effective therapeutic strategies. Currently, little is known about the mechanism links between CX-induced anti-cholestatic action and intercellular communication between cholangiocytes and hepatic stellate cells (HSCs). The study aimed to evaluate the hepatoprotective activity of different CX extracts including the aqueous, alkaloid, phenolic acid and phthalide extracts of CX (CX_AE, CX_AL, CX_PA and CX_PHL) and investigate the intercellular communication-related mechanisms by which the most effective extracts work on cholestatic liver injury. The active compounds of different CX extracts were identified by UPLC-MS/MS. A cholestatic liver injury mouse model induced by bile duct ligation (BDL), and transforming growth factor-β (TGF-β)-treated human intrahepatic biliary epithelial cholangiocytes (HIBECs) and HSC cell line (LX-2 cells) were used for in vivo and in vitro studies. Histological and other biological techniques were also applied. The results indicated that CX_AE, CX_AL and CX_PHL significantly reduced ductular reaction (DR) and improved liver fibrosis in the BDL mice. Meanwhile, both CX_AE and CX_PHL suppressed DR in injured HIBECs and reduced collagen contraction force and the expression of fibrosis biomarkers in LX-2 cells treated with TGF-β. CX_PHL suppressed the transcription and transfer of plasminogen activator inhibitor-1 (PAI-1) and fibronectin (FN) from the 'DR-like' cholangiocytes to activated HSCs. Mechanistically, the inhibition of PAI-1 and FN by CX_PHL was attributed to the untight combination of the acetyltransferase KAT2A and SMAD3, followdd by the suppression of histone 3 lysine 9 acetylation (H3K9ac)-mediated transcription in cholangiocytes. In conclusion, CX_PHL exerts stronger anti-cholestatic activity in vivo and in vitro than other CX extracts, and its protective effect on the intracellular communication between cholangiocytes and HSCs is achieved by reducing KAT2A/H3K9ac-mediated transcription and release of PAI-1 and FN.

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal