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*

BACKGROUND:Antioxidants can alleviate cellular damage and matrix degradation caused by oxidative stress,protect the structure and function of intervertebral discs,and thus delay the occurrence and development of intervertebral disc degeneration.OBJECTIVE:To review the research status of antioxidants in the treatment of intervertebral disc degeneration.METHODS:The first author searched the articles included in CNKI and PubMed databases.The literature search time was from inception to June 2024.Chinese search terms were"intervertebral disc degeneration,antioxidants,oxidative stress,signaling pathways."English search terms were"antioxidants,oxidative stresses,oxidative DNA damage,intervertebral disc degenerations,degenerative disc disease*,disc degeneration*,signal pathway."Finally,92 articles that met the criteria were selected for review.RESULTS AND CONCLUSION:(1)Antioxidants have multiple roles in the treatment of intervertebral disc degeneration,including reducing oxidative stress,inhibiting inflammatory responses,promoting autophagy,inhibiting apoptosis,and protecting the extracellular matrix.Through the combined effect of multiple pathways,antioxidants are expected to become an important means in the treatment of intervertebral disc degeneration.(2)The nano-hydrogel system can quickly and stably target the delivery of antioxidants to the inside of the intervertebral disc and improve the bioavailability of antioxidants.Therefore,the development of new antioxidants and antioxidant combination treatment strategies carried by nano-hydrogel systems will be the focus of future research.

Post-stroke affective disorders (PSTD) are common complications, which significantly affect neurological function recovery and quality of life in stroke patients. Common PSTD includes post-stroke depression, post-stroke anxiety or post-stroke depression-anxiety co-morbidity, post-stroke apathy, post-stroke mania, and post-stroke anger proneness, with post-stroke depression being the most commonly concerned. PSTD is not easily recognized and intervened clinically due to its hidden nature. At present, clinical identification mainly relies on clinical assessment and psychological scale tests; PTSD intervention mainly includes drug treatment, psychological treatment and physical treatment. This review summarizes the recent advances in these 5 major PSTD subtypes, encompassing their pathophysiological mechanisms, clinical identification criteria, diagnostic approaches, and evidence-based intervention strategies, aiming to provide practical references for optimizing clinical management of PSTD.

Objective To evaluate the efficacy and safety of botulinum toxin A (BTX-A) injection into the external urethral sphincter in combination with sacral neuromodulation (SNM) for the treatment of idiopathic non-obstructive urinary retention (INOUR). Methods A total of 57 INOUR patients treated in our hospital during May 2022 and May 2024 were enrolled. Patients were divided into the BTX (n=30) and combined groups (n=27) according to whether they chose SNM after BTX-A injection. The baseline, postoperative 1-month and 6-month consecutive 3-day voiding diaries, quality of life score (QoL), and post-void residual (PVR), preoperative and postoperative 1-month urodynamic results, and postoperative complications were recorded and compared between the two groups. Results One month after surgery, the average number of voiding frequency per day and PVR were lower in both groups than those before surgery (P<0.05), while the average daily urine volume and maximum flow rate (MFR) were higher (P<0.05). There was no statistically significant difference between the maximum detrusor pressure during micturition in both groups before and after surgery (P>0.05). One month after surgery, the average number of voiding frequency per day, average daily urine volume, PVR, QoL, MFR, bladder compliance (BC), and maximum cystometric capacity (MCC) were better in the combined group than in the BTX group (P<0.05), and the efficiency was higher in the combined group (88.9% vs.63.3%, P<0.05). Six months after surgery, the efficacy of the BTX group returned to the baseline level with no statistically significant difference, whereas the efficacy of the combined group was stable (not different from the postoperative 1-month indicators, but better than the baseline level). During the follow-up, there was no difference in the incidence of complications between the BTX group and combined group [43.3% (13/30) vs. 48.1% (13/27), P>0.05]. Conclusion BTX-A injection into the external urethral sphincter combined with SNM improves the short-term outcomes of INOUR patients and maintains the efficacy 6 months postoperatively, which is a safe and reliable treatment option.

Objective To investigate the correlation between the combined assessment of preoperative 5-factor modified frailty index(mFI-5)and Naples prognostic score(NPS)with overall survival in patients with unresectable hepatocellular carcinoma(uHCC)following interventional therapy.Methods A retrospective cohort study enrolled 292 patients with uHCC who underwent interventional therapy at the Department of Hepatobiliary Pancreatic Surgery of the Second Affiliated Hospital in Army Medical University from October 2017 to December 2021.Patients were stratified into high-risk and low-risk groups based on mFI-5(≥1),NPS(≥3),and CONUT(≥4)scores.Propensity score matching(PSM)was performed to balance baseline characteristics(post-matching n=186).The primary endpoint was overall survival(OS),analyzed using Kaplan-Meier curves with log-rank tests.The predictive performance of combined indicators was evaluated by receiver operating characteristic(ROC)curves,and prognostic factors were assessed via Cox regression analysis.Results After PSM,baseline characteristics(including age,tumor markers,and treatment-related parameters)showed no significant differences between the two groups.Survival analysis demonstrated a 2.252-fold higher risk of death in the mFI-5 plus NPS high-risk group(95%CI:1.60～3.18,P<0.001).The combination of mFI-5 and NPS scores yielded an area under curve(AUC)of 0.718 for predicting 3-year overall survival,significantly outperforming either index alone(P=0.007).Multivariable Cox regression analysis identified that dual positivity for mFI-5 and NPS(HR=1.46;95%CI:1.01～2.11,P=0.044),portal vein tumor thrombosis(HR=1.49;95%CI:1.03～2.16,P=0.035),tumor diameter>5 cm(HR=2.01;95%CI:1.27～3.17,P=0.003),Barcelona clinic liver cancer(BCLC)stage C disease(HR=2.05;95%CI:1.37～3.07,P<0.001)were independent predictors of poor prognosis.Postoperative combination targeted therapy and immunotherapy was associated with significantly reduced mortality risk(HR=0.57;95%CI:0.39～0.81,P=0.002).Conclusion The combination of mFI-5 and NPS scores is significantly associated with overall survival in patients with unresectable hepatocellular carcinoma(uHCC)undergoing locoregional therapy,providing a validated tool for clinical risk stratification and personalized treatment planning.

Medical image recognition is a technology that utilizes computer algorithms to process,analyze and understand medical images,aiming to identify various patterns,targets and objects,thereby aiding doctors in more accurate diagnosis and treatment.Current researches in medical image recognition mainly focuses on medical image classification,lesion location and segmentation,image registration and fusion,content-based image retrieval,as well as three-dimensional reconstruction and visualization.The review provides a summary of the research directions and trends in medical image recognition,introducing concepts and technologies such as deep learning,multimodal fusion,three-dimensional reconstruction and visualization.It also highlights the applications of medical image recognition in medical imaging diagnosis,pathological analysis and radiotherapy planning,while pointing out the existing problems and challenges.Furthermore,the future developments and challenges of medical image recognition technology are put forward for providing a reference for medical image recognition research and clinical medical image analysis.

Background and Aims:The long non-coding RNA SOX2 overlapping transcript(SOX2-OT)is involved in the regulation of cancer cell cycle and proliferation.Bioinformatics analysis has revealed potential binding sites among miR-409-3p,SOX2-OT,and membrane binding protein annexin A2(ANXA2).This study aims to investigate the expression and functional role of the SOX2-OT/miR-409-3p/ANXA2 axis in gastric cancer cells.Methods:qRT-PCR was used to measure the expression levels of SOX2-OT,miR-409-3p,and ANXA2 mRNA in gastric cancer tissues and cell lines.Gastric cancer cells were transfected with SOX2-OT shRNA plasmid(sh-SOX2-OT),co-transfected with sh-SOX2-OT and miR-409-3p inhibitor,or co-transfected with sh-SOX2-OT and ANXA2 overexpression plasmid.The control groups included blank,shRNA-negative control,inhibitor-negative control,and overexpression plasmid-negative control.Expression levels of SOX2-OT,miR-409-3p,and ANXA2 mRNA,cell proliferation,migration/invasion,apoptosis,and protein expression of Ki-67,cleaved caspase-3,Bax,MMP-9,and ANXA2 were assessed.Dual-luciferase reporter assays were conducted to confirm the targeting relationships among miR-409-3p,SOX2-OT,and ANXA2.A xenograft tumor model in nude mice was used to evaluate the effect of SOX2-OT on gastric cancer tumor growth in vivo.Results:SOX2-OT and ANXA2 expression levels were significantly upregulated,while miR-409-3p was downregulated in gastric cancer tissues(vs.adjacent non-cancerous tissues)and gastric cancer cell lines(vs.normal gastric epithelial cells)(all P＜0.05).In gastric cancer cels,knockdown of SOX2-OT led to decreased expression of SOX2-OT and ANXA2 mRNA and increased expression of miR-409-3p(all P＜0.05),and this was accompanied by reduced proliferation and migration/invasion abilities,and increased apoptosis(all P＜0.05);protein levels of ANXA2,Ki-67,and MMP-9 were significantly decreased,whereas cleaved caspase-3 and Bax levels were significantly increased(all P＜0.05).These effects were reversed by co-transfection with the miR-409-3p inhibitor or ANXA2 overexpression plasmid(all P＜0.05).Dual-luciferase assays confirmed the direct targeting relationships among miR-409-3p,SOX2-OT,and ANXA2.In vivo,knockdown of SOX2-OT significantly inhibited tumor growth in nude mice,with reduced SOX2-OT and increased miR-409-3p expression,as well as decreased ANXA2 and Ki-67 protein positivity in xenograft tissues(all P＜0.05).Conclusion:SOX2-OT is upregulated in gastric cancer cells and may promote malignant behaviors by competitively binding miR-409-3p,thereby relieving its inhibition on ANXA2.The SOX2-OT/miR-409-3p/ANXA2 axis may represent a potential molecular target for gastric cancer therapy.

BACKGROUND:Antioxidants can alleviate cellular damage and matrix degradation caused by oxidative stress,protect the structure and function of intervertebral discs,and thus delay the occurrence and development of intervertebral disc degeneration.OBJECTIVE:To review the research status of antioxidants in the treatment of intervertebral disc degeneration.METHODS:The first author searched the articles included in CNKI and PubMed databases.The literature search time was from inception to June 2024.Chinese search terms were"intervertebral disc degeneration,antioxidants,oxidative stress,signaling pathways."English search terms were"antioxidants,oxidative stresses,oxidative DNA damage,intervertebral disc degenerations,degenerative disc disease*,disc degeneration*,signal pathway."Finally,92 articles that met the criteria were selected for review.RESULTS AND CONCLUSION:(1)Antioxidants have multiple roles in the treatment of intervertebral disc degeneration,including reducing oxidative stress,inhibiting inflammatory responses,promoting autophagy,inhibiting apoptosis,and protecting the extracellular matrix.Through the combined effect of multiple pathways,antioxidants are expected to become an important means in the treatment of intervertebral disc degeneration.(2)The nano-hydrogel system can quickly and stably target the delivery of antioxidants to the inside of the intervertebral disc and improve the bioavailability of antioxidants.Therefore,the development of new antioxidants and antioxidant combination treatment strategies carried by nano-hydrogel systems will be the focus of future research.

Background and Aims:The long non-coding RNA SOX2 overlapping transcript(SOX2-OT)is involved in the regulation of cancer cell cycle and proliferation.Bioinformatics analysis has revealed potential binding sites among miR-409-3p,SOX2-OT,and membrane binding protein annexin A2(ANXA2).This study aims to investigate the expression and functional role of the SOX2-OT/miR-409-3p/ANXA2 axis in gastric cancer cells.Methods:qRT-PCR was used to measure the expression levels of SOX2-OT,miR-409-3p,and ANXA2 mRNA in gastric cancer tissues and cell lines.Gastric cancer cells were transfected with SOX2-OT shRNA plasmid(sh-SOX2-OT),co-transfected with sh-SOX2-OT and miR-409-3p inhibitor,or co-transfected with sh-SOX2-OT and ANXA2 overexpression plasmid.The control groups included blank,shRNA-negative control,inhibitor-negative control,and overexpression plasmid-negative control.Expression levels of SOX2-OT,miR-409-3p,and ANXA2 mRNA,cell proliferation,migration/invasion,apoptosis,and protein expression of Ki-67,cleaved caspase-3,Bax,MMP-9,and ANXA2 were assessed.Dual-luciferase reporter assays were conducted to confirm the targeting relationships among miR-409-3p,SOX2-OT,and ANXA2.A xenograft tumor model in nude mice was used to evaluate the effect of SOX2-OT on gastric cancer tumor growth in vivo.Results:SOX2-OT and ANXA2 expression levels were significantly upregulated,while miR-409-3p was downregulated in gastric cancer tissues(vs.adjacent non-cancerous tissues)and gastric cancer cell lines(vs.normal gastric epithelial cells)(all P＜0.05).In gastric cancer cels,knockdown of SOX2-OT led to decreased expression of SOX2-OT and ANXA2 mRNA and increased expression of miR-409-3p(all P＜0.05),and this was accompanied by reduced proliferation and migration/invasion abilities,and increased apoptosis(all P＜0.05);protein levels of ANXA2,Ki-67,and MMP-9 were significantly decreased,whereas cleaved caspase-3 and Bax levels were significantly increased(all P＜0.05).These effects were reversed by co-transfection with the miR-409-3p inhibitor or ANXA2 overexpression plasmid(all P＜0.05).Dual-luciferase assays confirmed the direct targeting relationships among miR-409-3p,SOX2-OT,and ANXA2.In vivo,knockdown of SOX2-OT significantly inhibited tumor growth in nude mice,with reduced SOX2-OT and increased miR-409-3p expression,as well as decreased ANXA2 and Ki-67 protein positivity in xenograft tissues(all P＜0.05).Conclusion:SOX2-OT is upregulated in gastric cancer cells and may promote malignant behaviors by competitively binding miR-409-3p,thereby relieving its inhibition on ANXA2.The SOX2-OT/miR-409-3p/ANXA2 axis may represent a potential molecular target for gastric cancer therapy.