Background: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. Methods: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. Results: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. Conclusion The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

Objective To investigate the effect of manual therapy based on surface electromyography on knee osteoarthritis(KOA)in the older people. Methods A total of 106 outpatient with unilateral KOA were selected from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,from August,2023 to June,2024,and were randomly divided into control group(n=53)and experimental group(n=53).The control group accepted routine manual therapy,and the experimental group accepted manual therapy based on the analysis of average electromyography(AEMG).They were assessed with Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),Visual An-alogue Scale(VAS)for pain,Tinetti Balance and Gait Score,and 6-minute walk test(6-MWT)distances before and after treatment. Results One case dropped down in each group.Before treatment,AEMG decreased in the rectus femoris,medial femoris and medial head of gastrocnemius on the affected side in the experimental group(|Z|>8.647,P<0.001),and it increased in the lateral femoris,semitendinosus and biceps femoris(|Z|>4.808,P<0.001).The scores of WOMAC,VAS,Tinetti Balance and Gait Score,and distances of 6-MWT improved in both groups after treat-ment(|t|>3.987,P<0.001),and improved more in the experimental group than in the control group,except the VAS score(|t|>2.213,P<0.05). Conclusion Manual therapy focusing on activation of rectus femoris,medial femoris and medial head of gastrocnemius,inhibition of the lateral femoris,semitendinosus and biceps femoris,and releasing the tension of the medial and lateral collateral ligaments,according to the results of surface electromyography,can alleviate the pain of the KOA in the older people and improve the mobility of the knee.

OBJECTIVE To systematically review the efficacy and safety of kidney -tonifying Chinese patent medicine combined with phosphodiesterase type 5（PDE5）inhibitors in the treatment of erectile dysfunction （ED），and to provide evidence - based reference for clinical medication . METHODS Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，VIP， China Biomedical Literature Database ，CNKI and Wanfang database ，randomized controlled trials （RCTs）of kidney -tonifying Chinese patent medicine combined with PDE 5 inhibitors（trial group ）versus PDE 5 inhibitors or kidney -tonifying Chinese patent medicine alone （control group ）were collected . The search period was from the establishment of the database to February 15，2022. After literature screening and data extraction ，the risk of bias assessment tool recommended in Cochrane System Reviewer ’s Handbook 6.1.0 was used to evaluate the quality of the included literature ；Stata 16.0 software was used for network meta -analysis； and the funnel plot was used for publication bias analysis . RESULTS A total of 23 RCTs were included ，with a total of 2 417 patients， involving 8 kinds of Chinese patent medicines ， including Congrong yishen granule ，Canrong zhutian capsule ， Compound xuanju capsule ， Huanshao capsule ， Shanhaidan granule， Shengjing capsule ， Shisanwei ziyin zhuangyang capsule，Shugan yiyang capsule . The results of network meta analysis showed that in terms of total effective rate ，Compound xuanju capsule combined with PDE 5 inhibitor，Shengjing capsule combined with PDE 5 inhibitor，Shugan yiyang capsule combined with PDE 5 inhibitor had higher total effective rate ；in terms of international index of erectile function 5，the scores of Compound xuanju capsule combined with PDE 5 inhibitor，Congrong yishen granule combined with PDE 5 inhibitor，and Canrong zhutian capsule combined with PDE 5 inhibitor were higher ；in terms of safety ，the incidence of adverse drug reactions caused by Huanshao capsule ，Shanhaidan granule and Shugan yiyang capsule were lower . CONCLUSIONS Kidney-tonifying Chinese patent medicine combined with PDE 5 inhibitor can improve the erectile function of ED patients and reduce the occurrence of adverse drug reactions . In terms of efficacy and safety ，Compound xuanju capsule combined with PDE 5 inhibitor is the best .