In the central nervous system (CNS), the myelin sheath, a specialized membrane structure that wraps around axons, is formed by oligodendrocytes through a highly coordinated spatiotemporal developmental program. The process begins with the directed differentiation of neural precursor cells into oligodendrocyte precursor cells (OPCs), followed by their migration, proliferation, differentiation, and maturation, ultimately leading to the formation of a multi-segmental myelin sheath structure. Recent single-cell sequencing research has revealed that this process involves the temporal regulation of over 200 key genes, with a regulatory network composed of transcription factors such as Sox10 and Olig2 playing a central role. The primary function of the myelin sheath is to accelerate nerve signal transmission and protect nerve fibers from damage. Its insulating properties not only increase nerve conduction speed by 50-100 times but also ensure the long-term functional integrity of the nervous system by maintaining axonal metabolic homeostasis and providing mechanical protection. The pathological effects of myelin sheath injury exhibit a cascade amplification pattern: acute demyelination leads to action potential conduction block, while chronic lesions may cause axonal damage and neuronal death in severe or long-term cases, ultimately resulting in irreversible neurological dysfunction with neurodegenerative characteristics. Multiple sclerosis (MS) is a neurodegenerative disease characterized by chronic inflammatory demyelination of the CNS. Clinically, the distribution of lesions in MS exhibits spatial heterogeneity, which is closely related to differences in the regenerative capacity of oligodendrocytes within the local microenvironment. Emerging evidence suggests that astrocytes form a dynamic “neural-immune-metabolic interface” and play a multidimensional regulatory role in myelin development and regeneration by forming heterogeneous populations composed of different subtypes. During embryonic development, astrocytes induce the targeted differentiation of OPCs in the ventricular region through the Wnt/β-catenin pathway. In the mature stage, they secrete platelet-derived growth factor AA (PDGF-AA) to establish a chemical gradient that guides the precise migration of OPCs along axonal bundles. Notably, astrocytes also provide crucial metabolic support by supplying energy substrates for high-energy myelin formation through the lactate shuttle mechanism. In addition, astrocytes play a dual role in myelin regulation. During the acute injury phase, reactive astrocytes establish a triple defense system within 72 h: upregulating glial fibrillary acidic protein (GFAP) to form scars that isolate lesions, activating the JAK-STAT3 regeneration pathway in oligodendrocytes via leukemia inhibitory factor (LIF), and releasing tumor necrosis factor-stimulated gene-6 (TSG-6) to inhibit excessive microglial activation. However, in chronic neurodegenerative diseases, the phenotypic transformation of astrocytes contributes to microenvironmental deterioration. The secretion of chondroitin sulfate proteoglycans (CSPGs) inhibits OPC migration via the RhoA/ROCK pathway, while the persistent release of reactive oxygen species (ROS) leads to mitochondrial dysfunction and the upregulation of complement C3-mediated synaptic pruning. This article reviews the mechanisms by which astrocytes regulate the development and regeneration of myelin sheaths in the CNS, with a focus on analyzing the multifaceted roles of astrocytes in this process. It emphasizes that astrocytes serve as central hubs in maintaining myelin homeostasis by establishing a metabolic microenvironment and signaling network, aiming to provide new therapeutic strategies for neurodegenerative diseases such as multiple sclerosis.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.

Objective To summarize the epidemiological and clinical features of infectious diseases of the central nervous system(CNS)by a single-center analysis.Methods A retrospective analysis was conducted on the data of 1247 cases of CNS infectious diseases diagnosed and treated in the First Medical Center of PLA General Hospital from 2001 to 2020.Results The data for this group of CNS infectious diseases by disease type in descending order of number of cases were viruses 743(59.6％),Mycobacterium tuberculosis 249(20.0％),other bacteria 150(12.0％),fungi 68(5.5％),parasites 18(1.4％),Treponema pallidum 18(1.4％)and rickettsia 1(0.1％).The number of cases increased by 177 cases(33.1％)in the latter 10 years compared to the previous 10 years(P<0.05).No significant difference in seasonal distribution pattern of data between disease types(P>0.05).Male to female ratio is 1.87︰1,mostly under 60 years of age.Viruses are more likely to infect students,most often at university/college level and above,farmers are overrepresented among bacteria and Mycobacterium tuberculosis,and more infections of Treponema pallidum in workers.CNS infectious diseases are characterized by fever,headache and signs of meningeal irritation,with the adductor nerve being the more commonly involved cranial nerve.Matagenomic next-generation sequencing improves clinical diagnostic capabilities.The median hospital days for CNS infectious diseases are 18.00(11.00,27.00)and median hospital costs are ￥29,500(￥16,000,￥59,200).The mortality rate from CNS infectious diseases is 1.6％.Conclusions The incidence of CNS infectious diseases is increasing last ten years,with complex clinical presentation,severe symptoms and poor prognosis.Early and accurate diagnosis and standardized clinical treatment can significantly reduce the morbidity and mortality rate and ease the burden of disease.

Objective To evaluate the bioequivalence and safety of the test formulation dapagliflozin tablets(10 mg)compared to the reference formulation in healthy adult subjects under fasting and fed conditions.Methods A single-center,randomized,open-label,two-period,two-sequence,crossover study design was employed.A total of 68 subjects were enrolled,with 32 subjects in the fasting group and 36 subjects in the fed group.Each subject received a single oral dose of either the test or reference formulation 10 mg.Plasma concentrations of dapagliflozin were measured using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 8.2 to assess the bioequivalence of the two formulations and their safety.Results Key pharmacokinetic parameters of the test and reference formulations in the fasting group were as follows:Cmax were(195.08±58.24)and(200.22±45.20)ng·mL-1;tmax were 0.67 and 0.67 h;AUC0_t were(553.52±97.82)and(552.47±106.07)ng·h·mL-1;AUC0-∞ were(580.40±103.79)and(579.42±111.23)ng·h·mL-1.In the fed group,the parameters were:Cmax were(123.38±39.50)and(125.80±39.05)ng·mL-1;tmaxwere 2.00 and 2.50 h;AUC0-t were(606.05±129.44)and(596.73±131.97)ng·h·mL-1;AUC0-∞ were(637.12±138.77)and(629.38±136.81)ng·h·mL-1.The 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t and AUC0-∞ for the test and reference formulations were within the bioequivalence range of 80.00％to 125.00％.The incidence of adverse drug events was 3.23％in the fasting group and 5.56％in the fed group.Conclusion The test formulation of dapagliflozin tablets is bioequivalent to the reference formulation in healthy Chinese subjects and has a good safety profile.

Objective Cognitive impairment(CI)in older individuals has a high morbidity rate worldwide,with poor diagnostic methods and susceptible population identification.This study aimed to investigate the relationship between different retinal metrics and CI in a particular population,emphasizing polyvascular status. Methods We collected information from the Asymptomatic Polyvascular Abnormalities Community Study on retinal vessel calibers,retinal nerve fiber layer(RNFL)thickness,and cognitive function of 3,785 participants,aged 40 years or older.Logistic regression was used to analyze the relationship between retinal metrics and cognitive function.Subgroups stratified by different vascular statuses were also analyzed. Results RNFL thickness was significantly thinner in the CI group(odds ratio:0.973,95%confidence interval:0.953-0.994).In the subgroup analysis,the difference still existed in the non-intracranial arterial stenosis,non-extracranial carotid arterial stenosis,and peripheral arterial disease subgroups(P<0.05). Conclusion A thin RNFL is associated with CI,especially in people with non-large vessel stenosis.The underlying small vessel change in RNFL and CI should be investigated in the future.

AIM To identify the chemical components of Longmu Qingxin Mixture by UPLC-Q-TOF-MS and study its material basis for the treatment of attention deficit hyperactivity disorder.METHODS The sample was detected by mass spectrometry in positive and negative ion mode on a Waters CORTECS? UPLC? T3 chromatographic column.The data were analyzed with Peakview 1.2 software and matched with the Natural Products HR-MS/MS Spectral Library 1.0 database,and the components were identified in combination with literature reports.The material basis of Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder was analysed according to the identified components.RESULTS Forty chemical components were identified,including 11 flavonoids,6 monoterpene glycosides,4 triterpene saponins,3 phenolic acids,6 alkaloids etc.,which mainly derived from Radix Astragali,Radix Paeoniae Alba,Radix Scutellariae,licorice root,Ramulus Uncariae cum,etc.,baicalein,formononetin,astragaloside Ⅳ and rhynchophylline may be the material basis for the therapeutic effect of Longmu Qingxin Mixture.CONCLUSION UPLC-Q-TOF-MS can quickly identify the chemical components of Longmu Qingxin Mixture.Flavonoids,triterpene saponins and alkaloids may be the material basis for Longmu Qingxin Mixture for the treatment of attention deficit hyperactivity disorder,which can provide the basis for its material basis research,quality standard establishment and pharmacological study of the dismantled formula.

Objective To investigate the impacts of LINC00943 on proliferation,apoptosis,and invasion of esophageal squamous cell carcinoma(ESCC)cells by regulating the miR-126-5p/HOXB2 axis.Methods QRT-PCR was applied to detect the expression of LINC00943 in 45 ESCC tissues and cell lines;The effects of LINC00943 knockdown on the proliferation,apoptosis and invasion of KYSE30 cells were detected by MTT assay,flow cytometry and Transwell chamber.Western blot was applied to detect the expression of proliferating cell nuclear antigen(PCNA),Bcl-2 associated X protein(Bax),anti apoptotic factor B cell lymphomatoma-2(Bcl-2),cleaved caspase-3,matrix metalloproteinase-2(MMP-2),MMP-9,and HOXB2;dual luciferase reporter gene experiment was applied to verify the relationship between miR-126-5p and LINC00943 and HOXB2;the ESCC nude mouse in vivo model was constructed and separated into si-NC and si-LINC00943 groups,the tumor mass and volume were measured,qRT-PCR was applied to detect the expression of miR-126-5p in transplanted tumor tissue,immunohistochemistry was applied to detect the expression of HOXB2 protein in transplanted tumor tissue,and TUNEL staining was applied to detect cell apoptosis in tumor tissue.Results The expression of LINC00943 mRNA increased in ESCC tissues and cell lines(P＜0.05);Compared with the si-NC group,the proliferation activity,migration and invasion cell number,HOXB2,PCNA,MMP-2,MMP-9 and Bcl-2 protein expression of KYSE30 cells in the si-LINC00943 group were decreased,and the expression of miR-126-5 p,Bax,Cleaved Caspase-3 and apoptosis rate were increased(P＜0.05);downregulation of miR-126-5p was able to weaken the inhibitory effect of LINC00943 knockdown on the malignant behavior of KYSE30 cells(P＜0.05);dual luciferase reporter gene experiment confirmed the targeted regulatory relationship between miR-126-5p and LINC00943,and miR-126-5p and HOXB2(P＜0.05);The ESCC nude mouse model was constructed in vivo and divided into si-NC and si-LINC00943 groups.The tumor mass,tumor volume,expression of miR-126-5p and HOXB2 in transplanted tumor tissues and apoptosis rate of tumor cells were measured.(P＜0.05).Conclusion LINC00943 is highly expressed in ESCC tissues and cell lines.Knocking down LINC00943 may inhibit the expression of HOXB2 by up-regulating the expression of miR-126-5p,promote the apoptosis of ESCC cells,and inhibit their proliferation,migration and invasion.

Objective To explore the risk factors related to afterload mismatch(AM)after transcatheter mitral valve repair(MitraClip).Methods This was a retrospective cohort study.48 patients hospitalized in the Department of Cardiovascular Medicine,the First Affiliated Hospital of Sun Yat-sen University from December 2021 to December 2023,who underwent MitraClip due to severe mitral regurgitation(MR)were included.Preoperative clinical data,laboratory tests,and preoperative and postoperative color Doppler echocardiographic examination results of surgical patients were collected.AM was defined as the left ventricular ejection fraction(LVEF)decreased by 15％or more after surgery compared with the one before(dLVEF≤-15％).Patients were divided into AM group and non-AM group according to whether afterload mismatch occurred.Univariate and multivariate logistic regression were used to analyze the risk factors of postoperative AM.Results Among 48 patients who underwent MitraClip,14 of them(29.2％)developed afterload-mismatched.For those without AM,their overall LVEF was improved after the operation;for patients in both AM group and non-AM group,their overall left ventricular end-diastolic diameter(LVEDd),left ventricular end-diastolic diameter volume index(LVEDVi)was reduced compared with the preoperative ones.Univariate regression analysis showed that C-reactive protein levels(OR 1.98,95％CI 1.02-3.83),platelets(OR 2.22,95％CI 1.08-4.53),systemic immune inflammation index(OR 1.96,95％CI 1.03-3.71)were associated with an increased risk of AM in patients undergoing MitraClip(all P＜0.05),while those with larger right atrial diameter(OR 0.35,95％CI 0.13-0.93)or moderate to severe tricuspid regurgitation(OR 0.19,95％CI 0.05-0.81)were less likely to develop into AM(both P＜0.05),which is still satisfied after adjustment.Conclusions For patients who underwent MitraClip,C-reactive protein levels,platelets and systemic immune inflammation index(SII)are associated with an increased risk of afterload mismatched,while those with larger right atrial diameter or moderate to severe tricuspid regurgitation were less likely to develop into AM.

Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.