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.

Respiratory diseases(e.g.,lung inflammation and pulmonary fibrosis)are a serious threat to human health.Mitochondria,organelles unique to eukaryotic cells,not only have important functions in energy production,biosynthesis,and the maintenance of intracellular homeostasis but also act as diverse signaling organelles involved in inflammation,proliferation,differentiation,cell repair,and other processes.The mitochondrial quality control system involves mitochondrial biogenesis,dynamics,and autophagy.Certain pathological mechanisms of respiratory diseases,such as oxidative stress and inflammation,are closely related to the dysregulation of mitochondrial quality control systems.This paper summarizes the progress of research into mitochondrial quality control dysregulation in respiratory diseases(chronic obstructive pulmonary disease,pulmonary fibrosis,acute lung injury,asthma,and bacterial pneumonia)to explore new ideas for the prevention and treatment of respiratory diseases.

Abstract： Schizophrenia is a common serious mental disorder, and genetic and environmental factors jointly contribute to the pathogenesis of schizophrenia. A correlation has been found between atmospheric particulate matter and the risk of schizophrenia, and short-term exposure to fine particulate matter (PM2.5) and inhalable particulate matter (PM10) may pose lagged and cumulative effects on the development of schizophrenia. Based on review of national and international publications, this review summarizes the associations between exposure to PM2.5 and PM10 and the risk of schizophrenia, so as to provide insights into the management of schizophrenia.

Objective: To investigate the mortality and life lost among patients with severe mental illness (SMI) that were registered in Ningbo City from 2016 to 2020, so as to provide the evidence for formulating the SMI control strategy. Methods: All data pertaining to dead SMI patients registered in Ningbo City from 2016 to 2020 were extracted from Ningbo Municipal Mental Health Information Management System. The demographic characteristics and causes of death were analyzed among dead SMI patients, and the life lost was analyzed among dead SMI patients using years of potential life lost (YPLL), years of potential life lost rate (YPLLR) and average years of life lost (AYLL). Results: A total of 3 350 deaths occurred among SMI patients registered in Ningbo City from 2016 to 2020, with mortality of 1 962/105, including 2 490 patients with schizophrenia (74.33%), 1 640 men (48.96%), 1 877 farmers (56.03%), and 2 622 patients with an educational level of primary school and below (78.27%). The dead SMI patients had a median age of 66.8 (interquartile range, 20.1) years at death, and median disease course of 25.8 (interquartile range, 26.7) years. The median age at death was 63.7 (interquartile range, 18.5) years among men, which was significantly lower than that (median, 70.0 years; interquartile range, 19.6 years) among women (χ2=132.633, P<0.001). The patients with mental retardation complicated by mental disorders had the longest disease course (median, 40.3 years; interquartile range, 34.1 years) and the lowest age at death (median, 61.4 years; interquartile range, 21.9 years). Physical disease was identified as the predominant cause of death (2 754 cases, 82.21%), and the YPLL, AYLL and YPLLR due to all causes of death were 44 417.32 person-years, 15.61 years and 6.21‰. The AYLL was significantly greater among men than among women (17.33 vs. 13.75 years; χ2=68.254, P<0.001). The YPLL was 30 156.80 person-years among patients with schizophrenia, and the AYLL was 20.87 years among patients with mental retardation complicated by mental disorders. Conclusions Physical disease was the main cause of death among SMI patients registered in Ningbo City from 2016 to 2020, which posed a great effect on the lifespan among men and patients with schizophrenia and mental retardation complicated by mental disorders.

Objective To investigate the effects of subthreshold micropulse yellow laser (577 nm) on vascular endothelial growth factor (VEGF),nerve growth factor (NGF) and Chemerin expressions in retina of early stage diabetic rats.Methods A total of 40 Brown Norway rats were treated with streptozocin (65 mg · kg-1) to establish the diabetic model.20 diabetic BN rats' right eyes were received subthreshold micropulse yellow laser (577 run) therapy after 2 weeks.The left eyes were used as control group.At 3 days,7 days,14 days,28 days after laser therapy,5 BN rats were randomly chosen to perform RT-PCR and Weston-blot.The expressions of mRNA and protein of VEGF,NGF and Chemerin were analyzed.Results The expression of VEGF mRNA and protein increased in control group at 3 days,7 days,14 days and 28 days (all P ＜ 0.05).Compared with the control group,VEGF mRNA and protein decreased in the subthreshold micropulse yellow laser (577 nm) group (all P ＜ 0.05).The expression of NGF mRNA and protein decreased in the control group at 3 days,7 days,14 days and 28 days (all P ＜ 0.05),however,the difference was not statistically significant between 3 days and 7 days(P ＞0.05).Compared with control group,NGF mRNA and protein increased in the subthreshold micropulse yellow laser (577 nm) group (all P ＜ 0.05),with maximum expression at 14 days.The expression of chemerin mRNA and protein increased at 3 days,7 days,14 days and 28 days in the control group (all P ＜0.05).Compared with the control group,chemerin mRNA and protein decreased in the subthreshold micropulse yellow laser (577 urn) group (all P ＜ 0.05).Conclusion Subthreshold micropulse yellow laser (577 urn) can suppress VEGF,Chemerin expression and upregulate NGF expression in early stage diabetic rats.

Objective:To investigate the pathogenic bacteria distribution and risk factors of pulmonary infection after tracheotomy in patients with stroke coma,and to put forward preventive measures.Methods:96 patients with stroke coma from January 2016 to February 2017 in our hospital were retrospectively analyzed.The incidence of pulmonary infection and distribution of pathogenic bacteria of patients with stroke coma were analyzed.At the same time,the risk factors of pulmonary infection were analyzed by single factor and multiple factors logistic regression analysis,and corresponding preventive measures were put forward.Results:The incidence of pulmonary infection after tracheotomy in 96 patients with stroke coma was 48.96％ (47/96).A total of 104 pathogens were isolated and cultured,including gram negative bacteria 69 strains (66.35％),gram positive bacteria 20 strains (19.23％) and fungus 15 strains (14.42％).Single factor regression analysis results showed that pulmonary infection after tracheotomy in patients with stroke coma was closely related with age,basic diseases,time of tracheotomy,and bed time,use of broad-spectrum antibiotics,smoking history,artificial airway,times of sputum suction and inhalation(P＜0.05),and it was not related to the patient's gender,weight,stroke type (P＞0.05).Multivariate logistic regression analysis showed that age 45 years old,complicated with basic disease,time oftracheotomy 5 d,use of broad-spectrum antibiotics,smoking history and the establishment of artificial airway were risk factors of pulmonary infection after tmcheotomy in patients with stroke coma (P＜0.05).ROC analysis results showed that the critical point (threshold C) oftmcheotomy time was 4.3 days,and the sensitivity and specificity were 0.851 and 0.918 respectively.Conclusion:The main pathogenic bacteria of pulmonary infection after tracheotomy in patients with stroke coma is gram-negative bacteria,age 45 years old,complicated with basic disease,time of tmcheotomy 5d,use of broad-spectrum antibiotics,smoking history and the establishment of artificial airway can lead to pulmonary infection after tracheotomy in patients with stroke coma,and the risk of pulmonary infection in patients with stroke coma will increase considerably after the time of tracheotomy for more than 4.3 days.Targeted measures should be taken to reduce the risk of pulmonary infection according to pathogenic features and risk factors.