BACKGROUND:In recent years,numerous studies have shown that autophagy and mitophagy play an important role in the regulation of bone metabolism.Under non-physiological conditions,mitophagy breaks the balance of bone metabolism and triggers metabolism disorders,which affect osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells,etc. OBJECTIVE:To summarize the mechanism of mitophagy in regulating bone metabolic diseases and its application in clinical treatment. METHODS:PubMed,Web of Science,CNKI,WanFang and VIP databases were searched by computer using the keywords of"mitophagy,bone metabolism,osteoblasts,osteoclasts,osteocytes,chondrocytes,bone marrow mesenchymal stem cells"in English and Chinese.The search time was from 2008 to 2023.According to the inclusion criteria,90 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Mitophagy promotes the generation of osteoblasts through SIRT1,PINK1/Parkin,FOXO3 and PI3K signaling pathways,while inhibiting osteoclast function through PINK1/Parkin and SIRT1 signaling pathways.Mitophagy leads to bone loss by increasing calcium phosphate particles and tissue protein kinase K in bone tissue.Mitophagy improves the function of chondrocytes through PINK1/Parkin,PI3K/AKT/mTOR and AMPK signaling pathways.Modulation of mitophagy shows great potential in the treatment of bone diseases,but there are still some issues to be further explored,such as different stages of drug-activated mitophagy,and the regulatory mechanisms of different signaling pathways.

Objective To investigate the clinical features and treatment of anti-myelin oligodendrocyte glycoprotein-IgG associated disorders （MOGAD） and the risk factors for recurrence and poor long-term prognosis. Methods A total of 91 patients who were diagnosed with MOGAD in The First Affiliated Hospital of Zhengzhou University from January 2018 to March 2023 were enrolled，and their clinical features and auxiliary examinations were analyzed，as well as the risk factors for recurrence and long-term prognosis. Results Among the 91 patients，69 experienced the first attack of MOGAD，and there were 39 female patients and 47 children （aged<18 years）. The proportion of patients with acute disseminated encephalomyelitis among children was significantly higher than that among adults （42.6% vs 18.2%，P=0.012），while the proportion of patients with transverse myelitis among adults was significantly higher than that among children （29.5% vs 2.1%，P<0.001）. The proportion of patients receiving hormones combined with immunoglobulins during hospitalization among children was significantly higher than that among adults （36.2% vs 11.4%，P=0.006），and the children had a significantly better Expanded Disability Status Scale （EDSS） score than the adults at discharge [1（0，1） vs 2（0，4.75），P=0.007]. Visual impairment was an independent risk factor for increased recurrence risk （OR=4.215，95%CI 1.236-14.377，P=0.022）. A higher EDSS score at discharge （OR=5.05，95%CI 1.27-20.07，P=0.021） and a higher number of attacks （OR=9.235，95%CI 1.352-63.10，P=0.023） were independent factors for poor long-term prognosis，while a steroid maintenance time of >5 weeks at initial diagnosis （OR=0.001，95%CI 0.00-0.33，P=0.001） was an independent factor for improving long-term prognosis. Conclusion For patients newly diagnosed with MOGAD，especially those with a high EDSS score at discharge and features indicating a high risk of recurrence （such as visual impairment），it is recommended that they receive an appropriate course of steroid maintenance treatment after acute-stage treatment.
Recurrence ; Prognosis

Primary biliary cholangitis （PBC） is a liver autoimmune disease with a strong genetic tendency characterized by the degeneration and necrosis of bile duct epithelial cells， and it is often observed in middle-aged and elderly women. With the continuous development of genome-wide association studies， the genetic susceptibility of PBC has attracted more and more attention. This article elaborates on the research advances in the genetic susceptibility genes closely associated with PBC， in order to provide effective targets for the treatment of PBC.

Primary biliary cholangitis （PBC） is a chronic autoimmune disease of cholestasis in which immune factors lead to progressive small bile duct destruction， cholestasis， and eventually liver fibrosis， liver cirrhosis， and even liver failure. Macrophages， as a group with functional heterogeneity， play different roles in the whole disease process of PBC. This article summarizes the possible ways by which macrophages are involved in the pathogenesis of PBC and discusses their impact on the disease and the potential therapeutic targets of macrophages. It is pointed out that macrophages are mainly involved in innate immunity in PBC injury and are associated with gut microbiota dysbiosis， and they are also associated with cholestasis， liver fibrosis， and liver cirrhosis in the later stages of the disease.

Primary biliary cholangitis(PBC)is a persistent inflammatory autoimmune liver disease characterized by inflammatory injury and cholestasis in the small intrahepatic bile ducts.At present,the exact pathogenesis of PBC remains unknown,but a consensus has been reached on the fact that PBC is the result of the synergistic effect of various factors.In the cascade of immune and inflammatory reactions associated with PBC,macrophages appear as essential immune cells and actively participate in the damage to bile duct epithelial cells.This article introduces the origin and heterogeneity of macrophages in PBC and reviews the potential role of macrophages in the pathogenesis of PBC.

Acute symptomatic seizures secondary to autoimmune encephalitis refers to seizures that occur during the active stage of immune-mediated encephalitis,and autoimmune-related epilepsy refers to disorders with an immune etiol-ogy and a long-term predisposition to unprovoked seizures.Both diseases often have poor response to antiepileptic drugs,and early identification of immune etiology and initiation of immunotherapy may help patients achieve a good prognosis.However,there are no guidelines for the use of drugs in patients with different types of symptomatic seizures,and there is also a lack of diagnostic criteria and treatment principles for autoimmune-related epilepsy.This article reviews and dis-cusses the two diseases from the aspects of possible pathogenesis,clinical manifestations,and recommended treatment methods,so as to provide a theoretical basis for diagnosis and treatment and help to determine future research directions.

The impact of prenatal exposure to a mixture of heavy metals on birth weight in newborns has been a topic of ongoing interest. In this study, 258 mothers and infants from the New Hampshire Birth Cohort Study (NHBCS) were selected as the study subjects, and the concentrations of seven heavy metals in the placenta, including Aluminum (Al), Cobalt (Co), Chromium (Cr), Nickel (Ni), Plumbum (Pb), Selenium (Se) and Arsenic (As) were collected. And the birth weight of newborns, the relevant covariates of mothers and newborns were collected. Three analytical methods, Weighted Quantile Sum (WQS) regression, Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) were employed. After adjusting for maternal gestational age, pre-pregnancy BMI, smoking status, education level, parity, gestational age and newborn gender, the combined three methods showed that the total effect of mixed exposure of seven heavy metals on birth weight was negative. Specifically, the WQS analysis revealed that Se had the greatest impact on birth weight, followed by Al. The QGC results showed that the heavy metal associated with the reduction of birth weight was mainly Se and Al in female and male infants, respectively. The BKMR analysis demonstrated a negative combined effect of the seven heavy metals on birth weight in both male and female infants, with Se having the highest posterior inclusion probabilities (PIPs) for female infants (0.45), and Al having the highest PIPs for male infants (0.64) after stratification by gender. In summary, mixed exposure to heavy metals during pregnancy was associated with a decrease in newborn birth weight. Furthermore, there are gender effects with Se and Al associated with decreased birth weight in female and male infants, respectively. These findings provide a theoretical basis for the development of public health policies aimed at preventing adverse pregnancy outcomes and improving the health of newborns.

AIM:To predict the mechanism of Sanguis draconis flavones(SDF)in the prevention and treat-ment of myocardial ischemia reperfusion injury(MIRI)based on network pharmacology and molecular docking methods.METHODS:The main chemical constituents of SDF were collected through literature search,and the targets of key con-stituents were screened by using the SwissTargetPrediction and TargetNet databases.Disease targets were also screened based on GeneCards,OMIM,TTD and PharmGkb databases,then targets were intersected with Cytoscape to construct the"drug-key constituent-target"network diagram,and the core target was obtained through visualization and analysis by Cytoscape software.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were analyzed by the Metascape platform.By utilizing AutoDock Vina software and Pymol,molecular docking between core compounds and core targets was carried out.Further,animal experiments were performed to explore the pharmacodynamic mechanism of SDF.RESULTS:The active constituents of SDF included loureirin B and loureirin A,which were mapped to 391 targets.A total of 3 096 MIRI disease targets were obtained from the database,af-ter intersection,172 intersection targets were obtained,and 56 core targets were acquired through analysis.The core relat-ed pathways included the cancer pathway and cell death signaling pathway.The results of molecular docking verified the strong binding activity between key constituents and key targets.Animal experiments demonstrated that SDF effectively prevented and treated MIRI,significantly inhibited the arachidonic acid 15-lipoxygenase(ALOX15)mRNA and protein expression,and reduced the myocardial infarction size after MIRI.CONCLUSION:SDF may play a positive role in the treatment of MIRI,which may be related to the regulation of the ALOX15 factor.

Aim To investigate how chili-derived exosome-like nanovesicle(CDELN)inhibited ox-LDL uptake and reduced ox-LDL-induced intracellular cholesterol accumulation.Methods CDELN were isolated and purified using tissue crushing,differential centrifugation,ultracentrifugation and sucrose density gradient centrifugation.Ox-LDL was used to stimulate THP-1-derived macrophages for 24 hours to establish a foam cell model in vitro,and the effect of CDELN on macrophage foam and its mechanism were further studied.Confocal laser microscopy was used to detect the uptake of CDELN and DiL-acetylated low density lipoprotein(DiL-ac-LDL)by THP-1 macrophages.Oil red O staining was used to detect intracellular cholesterol content and the positive area of oil red 0 staining in cells was analyzed to evalu-ate the effect of intracellular lipid accumulation.RT-qPCR and Western blot were used to detect mRNA and protein levels of scavenger receptor A(SRA)and cluster of differentiation 36(CD36),lectin-like oxidized low density lipoprotein recep-tor-1(LOX-1),ATP-binding cassette transporter A1/G1(ABCA1/G1).The expression of mitogen-activated protein ki-nase(MAPK)pathway proteins including p-ERK,p-p38 MAPK and p-c-Jun,were also analyzed.Results CDELN were exosome-like nanovesicles with uniform size and double membrane,rich in protein and nucleic acids,which can be taken up by macrophages.The results of DiL-ac-LDL uptake showed that CDELN could inhibit cholesterol uptake of mac-rophages.Oil red 0 staining showed that CDELN could reduce ox-LDL-induced intracellular cholesterol accumulation.RT-qPCR and Western blot showed that CDELN could significantly reduce mRNA levels of matrix metalloprotein-9(MMP-9),SRA,CD36 and LOX-1 and protein levels of p-ERK,SRA,CD36 and LOX-1 in ox-LDL-induced THP-1-derived macro-phages.Treatment with the p-ERK agonist Yoda1 diminished the protective effect of CDELN.Conclusion CDELN can significantly inhibit macrophage foam cell formation,and this effect may be associated with the inhibition of phosphoryl-ation levels of ERK1/2 in the MAPK pathway.

Objective To investigate the association between cardiovascular autonomic function and voiding symptoms in Parkinson disease(PD)patients.Methods We reviewed PD patients from the Department of Neurology of Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)between November 2020 and July 2023.Patients with PD were diagnosed by movement disorder specialists and received motor symptoms assessment based on Movement Disorders Society-Unified Parkinson's Disease Rating Scale part Ⅲ(MDS-UPDRS Ⅲ).We included those patients who underwent 24-hour ambulatory blood pressure monitoring(ABPM),ultrasound measured post void residual(PVR)and uroflowmetry.Subjects were divided into two groups:PD patients with nocturnal hypertension(PD-NH)group and PD patients without nocturnal hypertension(PD-nNH)group,according to the average nocturnal blood pressure.General clinical features,clinical assessments and urinary evaluations were compared between the two groups.We calculated average real variability(ARV)and examined its correlation factors using generalized linear models.Results Among the total of 87 PD patients,46(52.87% )were found to have nocturnal hypertension(NH).The PD-NH group exhibited more PVR[1.00(0.00,21.25)mL]compared to the PD-nNH group[0.00(0.00,5.50)mL](P<0.05).Additionally,generalized linear model analysis which scale response is Gamma with log link showed in PD patients,ARV of 24-hour diastolic blood pressure was correlated with PVR(OR=1.003,95% CI:1.001-1.005,P=0.008)and sex(male,OR=1.234,95% CI:1.050-1.451,P=0.011).Conclusion Our study demonstrates the association between cardiovascular autonomic function and voiding symptoms in PD.