Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

BACKGROUND/OBJECTIVES: Previous research has shown maternal betaine supplementation alleviates fetal-derived hepatic steatosis. Therefore, this study examined the anti-inflammatory effect of maternal betaine intake in offspring mice and its mechanism.MATERIALS/METHODS: Female C57BL/6J mice and their offspring were randomly divided into 3 groups according to the treatment received during gestation and lactation: control diet (CD), fatty liver disease (FLD), and fatty liver disease + 1% betaine (FLD-BET). The FLD group was given a high-fat diet and streptozotocin (HFD + STZ), and the FLD-BET group was treated with HFD + STZ + 1% betaine. After weaning, the offspring mice were given a normal diet for 5 weeks and then dissected to measure the relevant indexes. RESULTS: Compared to the CD group, the offspring mice in the FLD group revealed obvious hepatic steatosis and increased serum levels of alanine aminotransferase, interleukin (IL)-6, and tumor necrosis factor (TNF)-α; maternal betaine supplementation reversed these changes. The hepatic mRNA expression levels of IL-6, IL-18, and Caspase-1 were significantly higher in the FLD group than in the CD group. Maternal betaine supplementation reduced the expression of IL-1β, IL-6, IL-18, and apoptosis-associated speck-like protein containing C-terminal caspase recruitment domain (ASC). Maternal betaine supplementation also reversed the increasing protein expressions of nitric oxide dioxygenase-like receptor family pyrin domain containing 3 (NLRP3), ASC, Caspase-1, IL-1β, and IL-18 in offspring mice exposed to HFD + STZ. Maternal betaine supplementation decreased the homocysteine (Hcy) and s-adenosine homocysteine (SAH) levels significantly in the livers. Furthermore, the hepatic Hcy concentrations showed significant inverse relationships with the mRNA expression of TNF-α, NLRP3, ASC, and IL-18. The hepatic SAH concentration was inversely associated with the IL-1β mRNA expression. CONCLUSIONS The lipotropic and anti-inflammatory effect of maternal betaine supplementation may be associated with the inhibition of NLRP3 inflammasome in the livers of the offspring mice.

Objective To evaluate cardiovascular benefits in patients with type 2 diabetes mellitus treated with the marketed 11 sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like polypeptide-1 (GLP-1) receptor agonism by Bayesian network meta-analysis system. Methods MEDLINE, Embase and Cochrane Library were searched from the establishment of the database to 18 July 2020. The endpoint of the study was adverse cardiovascular events. The effect measures were hazard ratios (HR) and 95% credible intervals (CI). Results Compared with placebo, empagliflozin, canagliflozin, dapagliflozin, albiglutide, dulaglutide, exenatide, liraglutide, semaglutide reduced the risk of major adverse cardiovascular events in patients with type 2 diabetes with HR and 95% CI ranging between 0.75(0.60-0.95)~0.90(0.82-0.99); The risk of heart failure was reduced by empagliflozin, canagliflozin, dapagliflozin and ertugliflozin, with HR and 95%CI ranging between 0.64(0.49-0.82)~0.74(0.65-0.85); Empagliflozin, canagliflozin, dapagliflozin, exenatide, liraglutide and oral semaglutide reduced the incidence of all-cause mortality with HR and 95%CI ranging between 0.52(0.33-0.84)~0.89(0.80-0.99); Empagliflozin, canagliflozin, liraglutide and oral semaglutide can reduce the risk of cardiovascular death events, with HR and 95% CI ranging between 0.54(0.30-0.95)~0.83(0.71-0.96) . Conclusion The order of the cardiovascular benefits of SGLT-2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes mellitus complicated with atherosclerotic cardiovascular disease are canagliflozin (the best), empagliflozin, dulaglutide, liraglutide; for patients with type 2 diabetes and heart failure. The order of the cardiovascular benefits for patients with type 2 diabetes and heart failure are empagliflozin, canagliflozin, ertugliflozin, and dapagliflozin.

Objective:To summarize the evidence of diet management in patients with chronic kidney disease (CKD) in stage 3-5 D, so as to provide a reference for clinical nursing.Methods:After establishing evidence-based nursing questions, according to the "6S evidence model", the evidence on diet management of patients with CKD in stage 3-5 D was searched by computer, including computer decision support system evidence, guidelines, best evidence summary and systematic review. The search time limit was from the establishment of the database to September 2020. The guideline quality assessment was independently completed by two research nurses and a doctor of nephrology. The quality assessment of non-guideline article was independently completed by two research nurses, and an evidence-based instructor participated in decision-making. The evidence was extracted, evaluated and graded using the Joanna Briggs Institute (JBI) 2014 version of the intervention research evidence pre-grading system.Results:A total of 19 articles that met the requirements were included, including 5 guidelines, 8 systematic reviews, 4 randomized controlled trials, 1 clinical decision, and 1 national standard. A total of 22 pieces of the best evidence on diet management of patients with CKD in stage 3-5 D were summarized from three aspects, namely, diet/nutrition assessment, diet management, teamwork and education.Conclusions:The best evidence of diet management in patients with CKD in stage 3-5 D provides a certain reference for clinical practice, so as to improve the quality of diet management in patients with CKD and the clinical outcomes of patients.

Type 2 diabetes is a high risk factor for atherosclerotic cardiovascular disease. Studies have found that SGLT-2 inhibitor and GLP-1 receptor agonists have cardiovascular protective effects in patients with type 2 diabetes and cardiovascular disease. Therefore, from the aspects of cardiovascular safety test and its Meta-analysis and net-like Meta-analysis, the research progress of cardiovascular safety of SGLT-2 inhibitors and GLP-1 receptor agonists is summarized.

Objective To review and analysis the clinical manifestations, occurrence rules, treatment and outcomes of adverse drug reactions caused by anlotinib in order to provide reference for safety and reasonable use of anlotinib in clinical practice. Methods The cases reports of anlotinib were searched in Web of Science, Pubmed, Wiley Online Library, CNKI, Wanfang and VIP. The basic patient information, adverse reaction time, characters, treatment, outcomes and involved systems or organs were collected and analyzed. Results A total of 20 cases were collected, 10 females and 10 males, with a median age of 63.5(36～76 years old). Adverse drug reactions mostly occurred within 2 months after the medication. 52 cases occurred in total, involving 9 systems/organs, of which blood and lymphatic system disorders (all were hypertension) were the most common (21.2%). Conclusion After the administration of anlotinib, the incidence rate of adverse reactions in the cardiovascular system is relatively high. The medication process should be closely monitored, and attention should be paid to monitoring the potential adverse reactions mentioned in the instructions.

In order to strengthen the integration of reform system and build a comprehensive integration of openness and innovation, the medical device registrar system has become the institutional choice to promote the reform of the medical approval system and the innovation and development of the industry. The system allows scientific researchers, R&D institutions and enterprises to become applicants for medical device registration and to consign the production of samples and products, thus realizing the separation of market license and production license, and breaking the binding relationship between registration and production in current regulations. The medical device registrar system has laid a theoretical foundation for remolding the management system of medical devices, and has also made practical exploration for improving the reform of the medical devices supervision system, so it has important theoretical and practical significance.
Device Approval ; Industry ; Licensure ; Registries

Objective:To analyze the sleep quality before treatment and related risk factors of sleep disorder in patients with nasopharyngeal carcinoma (NPC). Methods: Totally 143 patients first diagnosed as nasopharyngeal carcinoma were selected [ average age (43 ± 10) years, 100 males and 43 females] in a NPC ward of one hospital, the Chinese version of Pittsburgh Sleep Quality Index (PSQI, total score ＞ 5 diagnosed as sleep disorder) was used to investigate the sleep quality before treatment, and the logistic regression analysis was used to analyze related factors of the sleep disorder before treatment Results: The rate of sleep disorder was 50.3％. The logistic regression analysis showed that age was a risk factor of sleep disorder before treatment in patients with NPC (OR = 1.04, 95％ CI: 1.01-1.08), while gender, culture degree, clinical stage, body mass index were not correlated with sleep disorder (Ps＞0.05). Conclusion: It suggests that patients with NPC may have a higher incidence of sleep disorder before treatment, and older patients may be more prone to pre-treatment sleep disorder.

Objective To explore the cognition and demand status of order oriented nursing talents in different hospitals in Xinjiang,so as to provide a scientific basis for establishing the model in Xinjiang. Methods Using qualitative research methods and purposive sampling, 12 nursing directors from different grades of hospitals in North and South Xinjiang were selected and semi structured in-depth interviews were conducted from September 2016 to October 2016. Colaizzi phenomenological seven step analysis method was used to analyze the data and get the theme. Results Through analysis, the three themes of different types of hospitals in Xinjiang were put forward: there are different levels of hospitals in order to model the demand of nursing personnel training;different levels of hospital nursing students'needs of different orders;the hospital expects to establish order type talent training hospital-school cooperation steering committee. Conclusions Xinjiang area hospitals of different levels to construct the pattern of the urgent need for the"order"of nursing personnel training,to meet the needs of nursing professionals of different levels of hospitals, so as to improve the overall level of nursing staff, to provide quality health services along the Silk Road and the surrounding countries.

Objective To explore the incidence and risk factors of common complications in PICC patients during chemotherapy in Xinjiang.Methods A prospective study was conducted.The patients with PICC were treated with PICC from April 2016 to April 2017 were followed up for 10 months. The incidence of PICC complication and the influencing factors were observed dynamically during chemotherapy.Results The incidence of PICC complication was 13.6%(42/208)during chemotherapy in Xinjiang patients.The incidence of PICC was higher in the third chemotherapy cycle and the incidences of the first and sixth chemotherapy cycles were lower. Age, valve type, number of punctures, maintenance time>7d, and living conditions were the influencing factors of PICC complications(P＜0.05). Conclusions The incidence of common complications of PICC in cancer patients during chemotherapy is high in Xinjiang region.The risk factors of complications include age＜18 years,number of open-end PICCs,increased number of punctures, maintenance time>7d and living conditions for rural areas. Clinical nurses should give personalized health guidance on the causes of complications in different patients to reduce the occurrence of complications of PICC,and improve the quality of PICC use.