Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

MicroRNAs(miRNAs)are small non-coding RNAs that are closely associated with the occur-rence and progression of tumors and other diseases.However,miRNAs require high-sensitivity and high-specificity detection due to their low abundance,high sequence homology,and rapid degradation.The RNA-cleaving deoxyribozyme(RCD)is a functional single-stranded DNA molecule that enables specific cleavage of substrates to release miRNAs that can be recycled with the assistance of metal ions,prompting cyclic signal amplification.Recently,developing new methods based on RCD catalytic amplification for miRNA high-sensitivity detection has become the focus of researchers.Based on combing with the various new technologies and materials in miRNA biosensors,this study classifies and reviews the new methods for detecting miRNAs based on deoxyribozyme catalytic amplification developed in recent years.We sepa-rate these miRNA detection strategies into three categories:RCDs combined with DNA self-assembly,i-sothermal amplification,and nanomaterials.We explore the basic principles of each approach,the latest research advancements,and application scenarios in biomedical sensors and medical detection.This re-view provides a foundation and reference for further research of highly sensitive and accurate miRNA de-tection strategies.

This study collected epidemic data of COVID-19 in Zhengzhou from January 1 to January 20 in 2022. The epidemiological characteristics of the local epidemic in Zhengzhou High-tech Zone caused by the SARS-CoV-2 Delta variant were analyzed through epidemiological survey and big data analysis, which could provide a scientific basis for the prevention and control of the Delta variant. In detail, a total of 276 close contacts and 599 secondary close contacts were found in this study. The attack rate of close contacts and secondary close contacts was 5.43% (15/276) and 0.17% (1/599), respectively. There were 10 confirmed cases associated with the chain of transmission. Among them, the attack rates in close contacts of the first, second, third, fourth and fifth generation cases were 20.00% (5/25), 17.86% (5/28), 0.72% (1/139) and 14.81% (4/27), 0 (0/57), respectively. The attack rates in close contacts after sharing rooms/beds, having meals, having neighbor contacts, sharing vehicles with the patients, having same space contacts, and having work contacts were 26.67%, 9.10%, 8.33%, 4.55%, 1.43%, and 0 respectively. Collectively, the local epidemic situation in Zhengzhou High-tech Zone has an obvious family cluster. Prevention and control work should focus on decreasing family clusters of cases and community transmission.
Humans ; SARS-CoV-2 ; COVID-19 ; Epidemics ; Incidence

Objective:To explore the mediating effect of expectations regarding aging between social support and frailty in elderly patients with chronic obstructive pulmonary disease (COPD), so as to promote better health education among medical staff and improve patients′ ability to cope with frailty.Methods:This was a cross-sectional study, the convenience sampling method was used to select 258 elderly COPD patients hospitalized in the Department of Respiratory Medicine and Geriatrics of Xinjiang Uygur Autonomous Region People′s Hospital from November 2021 to April 2022. They were investigated by the general information questionnaire, Fried Scale, Social Support Scale and Expectations Regarding Aging-21. Analyzed the correlation among social support, expectations regarding aging and frailty. AMOS 26.0 was used to investigate the mediating effect of expectations regarding aging between social support and frailty in elderly COPD patients.Results:The score of social support, expectations regarding aging and frailty in elderly patients with COPD was (30.45 ± 5.57), (35.25 ± 6.28) and (2.34 ± 1.71)points, respectively. There was negative correlation between social support and frailty in elderly COPD patients ( r=-0.541, P<0.01), while positive correlation between social support and expectations regarding aging ( r=0.477, P<0.01). The negative correlation between social support and expectations regarding aging ( r=-0.536, P<0.01). Expectations regarding aging played a partial mediating role between social support and frailty, with mediating effect value of -0.229, accounting for 35.39% of the total effect. Conclusions:Expectations regarding aging is a mediator variable between social support and frailty in elderly COPD patients. Health care providers can alleviate or even reverse patients' debilitating condition by improving their expectations regarding aging and social support.

Persistent neurogenesis exists in the subventricular zone (SVZ) of the ventricles and the subgranular zone (SGZ) of the dentate gyrus of the hippocampus in the adult mammalian brain. Adult endogenous neurogenesis not only plays an important role in the normal brain function, but also has important significance in the repair and treatment of brain injury or brain diseases. This article reviews the process of adult endogenous neurogenesis and its application in the repair of traumatic brain injury (TBI) or ischemic stroke, and discusses the strategies of activating adult endogenous neurogenesis to repair brain injury and its practical significance in promoting functional recovery after brain injury.
Adult ; Animals ; Humans ; Brain/physiopathology* ; Hippocampus/physiopathology* ; Mammals/physiology* ; Neurogenesis/physiology* ; Brain Hemorrhage, Traumatic/therapy* ; Ischemic Stroke/therapy* ; Recovery of Function ; Spinal Cord/physiopathology*

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.
Lycium/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Structure-Activity Relationship ; Antioxidants/pharmacology* ; Antineoplastic Agents ; Polysaccharides/chemistry*

Objective:To explore the changes of hip joint function in patients with total hip arthroplasty (THA) within three months after operation, and to explore the impact of fear of falling on hip joint function recovery.Methods:From December 2020 to August 2021, 205 patients with THA after operation in the Xinjiang Uygur Municipal People's Hospital were selected as the study subject by objective sampling. The patients were investigated with the General Information Questionnaire, the Chinese version of Falls Efficacy Scale-International (FES-I) , and the Harris Hip Score after the first activity out of bed, one month and three months after operation. Pearson correlation was used to analyze the correlation between the scores of FES-I in Chinese version and the scores of Harris Hip Score in different periods after operation, and multiple linear regression were used to analyze the influencing factors of hip joint function recovery in different periods after operation.Results:After the first activity out of bed, one month and three months after operation, the FES-I scores of 205 patients after THA were (32.24±6.05) , (30.94±6.04) and (28.48±3.52) respectively, and the scores of Harris Hip Score were (61.49±8.92) , (72.58±5.52) and (89.15±5.70) respectively, and the correlation analysis showed that they were negatively correlated ( r=-0.512, -0.523, -0.549; P<0.05) . The results of multiple linear regression analysis showed that age and fear of falling were the influencing factors for the hip joint function recovery when THA patients got out of bed for the first time after operation ( P<0.05) , which could explain 31.2% of the total variation. Sex, age, number of concomitant diseases and fear of falling were the influencing factors of hip joint function recovery in THA patients one month after operation ( P<0.05) , which could explain 43.7% of the total variation. Sex, age, number of concomitant diseases and fear of falling were the influencing factors of hip joint function recovery in THA patients three months after operation ( P<0.05) , which could explain 36.9% of the total variation. Conclusions:The recovery of hip joint function in THA patients shows an overall upward trend three months after operation. The impact of fear of falling on the recovery of hip joint function in different periods persists. The higher the level of fear of falling, the worse the recovery of hip joint function. Nurses should evaluate the patients' fear of falling at different periods after operation, and strengthen the attention and guidance to patients with high fear of falling, elderly patients, and patients with other diseases, so as to promote the recovery of patients' joint function.

Objective To explore the in vitro and in vivo antimicrobial activity of antipsychotic agent pimozide against Staphylococcus aureus(S.aureu).Methods The minimal inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of pimozide were determined by micro-dilution assay.Biofilm was cultured in 96-well cell culture plate,and the anti-biofilm activity of pimozide was detected by turbidimetry.The effect of pimozide on biofilm was further observed through laser confocal microscopy and SYTO9/PI staining.Combined antimicrobial effect of pimozide and other antimicrobial agents was detected by chessboard dilution method,and cytotoxicity of pimozide was detected by CCK-8 assay kit.A model of skin abscess was constructed,in vivo antimicrobial activity and toxicity of pimozide was tested.Results Pimozide showed significant dose-dependent antimicrobial activity against S.aureu,with a MIC of 8-16 μg/mL.It could significantly inhibit the formation of S.aureu biofilm and disperse the formed biofilm.The combination of pimozide and doxycycline has a synergistic antimicrobial effect in vitro,with a synergistic antimicrobial index of 0.5.It can significantly reduce the bacterial load in mouse abscess tissue in vivo,and reduce the live bacterial count from(8.25±0.13)lgarithmic value of CFU/abscess to(3.31± 0.81)logarithmic value of CFU/abscess(q=3.74,P＜0.05).The cytotoxicity of pimozide was extremely low,with a half inhibitory concentration of 64 μg/mL on cells.Conclusion Pimozide exhibits significant antimicrobial activity in vitro and in vivo with extremely low toxicity,thus is promising for the treatment of S.aureu-related local infection in psychiatric patients.

Objective To locate the distribution of muscle spindles in tibialis anterior (TA) and extensor digitorum longus muscle (EDL) and the anchoring mode of muscle spindles in skeletal muscles, and perform statistics analysis of their morphological character by anatomical parameters. Methods Five adult wild type C57BL/6 mice were sacrificed, and TA and EDL were dissected and frozen with improved ultra-low temperature cryopreservation technology avoiding myofibers damaged by possible ice crystal. Continuous frozen transections were obtained and operated by HE staining, followed by microimaging to spot the muscle spindles location. Some parameters including regions length and cross section area (CSA) of muscle spindles were noticed for the discovery of some general characteristics of spindles by statistics. Results For TA and EDL, the scattered characters of muscle spindles were distributed as follows: the spindles were located at the upper third of the mid-belly of both TA and EDL from caudal to rostral position, while near the enter point to muscle of the deep peroneal nerve in dorsal-ventral orientation. The peripheral of muscle spindles anchored to extrafusal fibers to hold in the muscle. And in term of length, region A, connected with sensory nerve ending, demonstrated a significant correlation with region B, which located at the poles of region A and twined by motor nerve ending (correlation index = 0. 75) when considering the muscle spindles with four intrafusal fibers only. And no correlation was discovered in any others pairwise parameters. Conclusion The scattered diagram of muscle spindles in TA and EDL of C57BL/6 mice might provide anatomic basis for evaluation of lower limb motor function, especially for the spinal cord injury and recovery research. And the correlationship between the length of region A and B might improve exploring the variability of electrophysiological characters.

Objective:To report the efficacy of arthroscopic medullary decompression combined with platelet-rich plasma (PRP) in the treatment of bone marrow edema of the talus.Methods:A retrospective case series study was used to analyze the clinical data of 17 patients with bone marrow edema of the talus admitted to Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to July 2020. There were 11 males and 6 females, with the age range of 15-56 years [(45.7±4.3)years]. All patients were subjected to arthroscopic medullary decompression combined with the administration of PRP. Operation time and wound healing were recorded. Maximum area of bone marrow edema was measured by MRI preoperatively and at 6 and 12 months postoperatively. Ankle range of motion (ROM), visual analog score (VAS) and American Association of Foot and Ankle Surgery (AOFAS) ankle-hindfoot score were measured preoperatively and at 6 and 12 months postoperatively. Complications were also detected.Results:All patients were followed up for 12-41 months [(16.7±2.1)months]. Operation time was 45.2-68.5 minutes [(53.4±12.4)minutes]. All wounds were healed at stage I. The maximum area of bone marrow edema decreased from (28.2±6.9)mm 2 preoperatively to (16.3±5.7)mm 2 at 6 months postoperatively and to (7.1±1.7)mm 2 at 12 months postoperatively (all P<0.01). Ankle ROM increased from (52.2±8.9)° preoperatively to (72.3±3.1)° at 6 months postoperatively and to (83.1±2.8)° at 12 months postoperatively (all P<0.01). VAS decreased from (8.2±0.6)points preoperatively to (6.5±0.4)points at 6 months postoperatively and to (3.1±0.8)points at 12 months postoperatively (all P<0.01). AOFAS ankle-hindfoot score increased from (32.4±4.8)points preoperatively to (54.4±6.5)points at 6 months postoperatively and to (88.7±4.3)points at 12 months postoperatively (all P<0.01). There were significant differences in maximum area of bone marrow edema of the talus, ankle ROM, VAS and AOFAS ankle-hindfoot score at 12 months postoperatively when compared with those at 6 months postoperatively (all P<0.01). One patient showed the symptom of localized skin numbness postoperatively, and improved with nerve nutrition therapy. Conclusion:Arthroscopic medullary decompression combined with PRP therapy for bone marrow edema of the talus presents good short-term clinical benefits in terms of reduced extent of bone marrow edema, improved ankle ROM, attenuated pain, improved ankle joint function and few postoperative complications.