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*

Following the principles of evidence-based medicine,in accordance with the structure and drafting rules of standardized documents,based on literature research,according to the characteristics of chronic cough in children and issues that need to form a consensus,the TCM Guidelines for Diagnosis and Treatment of Chronic Cough in Children was formulated based on the Delphi method,expert discussion meetings,and public solicitation of opinions.The guideline includes scope of application,terms and definitions,eti-ology and diagnosis,auxiliary examination,treatment,prevention and care.The aim is to clarify the optimal treatment plan of Chinese medicine in the diagnosis and treatment of this disease,and to provide guidance for improving the clinical diagnosis and treatment of chronic cough in children with Chinese medicine.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Human breast milk oligosaccharides are a kind of complex carbohydrates widely existing in human breast milk, which is the third major nutrient in human breast milk and is closely related to the growth and development of infants and some diseases.More than 200 different functional oligosaccharides have been identified for their role in regulating intestinal flora, regulating immunity and promoting brain development.This article reviews the structural composition, biological function, application and development trend of breast milk oligosaccharides, to provide reference for the application of oligosaccharides in functional food.

Cardiomyopathy, Dilated/metabolism* ; Humans ; Microfilament Proteins/metabolism* ; Models, Cardiovascular ; Mutation ; Myocytes, Cardiac ; Pluripotent Stem Cells/metabolism* ; Transcription Factors/metabolism* ; Troponin T/metabolism*

Ischemic stroke is a major health crisis causing high mortality and morbidity. The key treatment relies on the rapid intervention to dissolve thrombus, to reduce bleeding side effect and re-canalize clotted blood vessels using clot lysis drugs. Tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke, but it has many limitations in clinical use. In recent years, the development of thrombolytic drugs and treatment strategies based on tPA has been progressed rapidly. Here we review the recent progress in this field, including the contributions from us and others, to promote the future development of novel thrombolytic drugs.
Brain Ischemia/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Humans ; Research/trends* ; Stroke/drug therapy* ; Thrombolytic Therapy/trends* ; Tissue Plasminogen Activator/therapeutic use*

Objective:To investigate the oncological efficacy and functional evaluation of total elbow arthroplasty (TEA) for the reconstruction of tumor around elbow joint.Methods:A retrospective case series study was made on the clinical data of 26 patients who underwent total elbow joint replacement after tumor resection in Beijing Jishuitan Hospital from June 1988 to June 2019. According to the inclusion and exclusion criteria, 23 patients were enrolled in the final study, there were 14 males and 9 females, the mean and median age was 37.6±19.9 and 35.0 years respectively. 23 patients included 3 cases of giant cell tumor, 4 cases of metastatic cancer, 4 cases of Ewing's sarcoma, 2 cases of osteosarcoma, 2 cases of aneurysmal bone cyst, 1 angiosarcoma, 1 primary malignacy in giant cell tumor, 1 low-grade central osteosarcoma, 1 parosteosarcoma, 1 synovial sarcoma, 1 plasma cell myeloma, 1 tendon sheath giant cell tumor and 1 case of mixed tumor. There were 6 cases of benign tumor, 4 cases of low grade sarcoma and 13 cases of high grade malignancy. With 19 cases of distal humerus, 3 cases of proximal ulna and 1 case of elbow. Each patient underwent tumor resection followed by restrictive tumor prosthesis and semi-restrictive of coonrad-morrey prosthesis were used for reconstruction.The duration of the operation, the amount of blood loss, epidemiological data, reconstruction length, oncology parameter, complications and functional evaluation were enrolled and statistical analyzed.Results:The mean length of the osteotomy followed by reconstruction was 12.5±3.9 cm, the mean operative time was 154.1±50.1 minutes, and the mean bleeding was 262.2±100.9 ml. Thirteen patients were treated with customized tumor limited prosthesis while 10 patients with Coonrad-Morrey semi-limited prosthesis. The 5-year survival rates of 23 patients was 64.3%, benign tumors, low-grade and high-grade malignancies were 100%, 100% and 39.7%, respectively. Three cases of lung cancer and three cases of Ewing's sarcoma died during the follow-up period (6/23, 26.1%), one case of giant cell tumor and one case of synovial sarcoma developed local recurrence (2/23, 8.7%). The median range of motion for the elbow increased from 35 to 85 degrees ( t=-13.787, P<0.05), the median NRS score decreased from 5.0 to 0.5 ( t=14.391, P<0.05). Postoperative complications occurred in 9 cases (9/23, 39.1%), the recent complications were nerve injury in 4 cases and infection in 1 case, late complications were prosthesis loosening and failure in 4 cases, the 5 year survival rate of prosthesis was 82.0%. The mean and median MSTS 93 score was 84.5%±11.0% and 88.3% respectively. Conclusion:The local control around the elbow is satisfactory after tumor resection. Total elbow arthroplasty can relieve pain and significantly improve function.

Objective:To investigate the predicting value of cardiac serum troponin I (cTnI) levels for the clinical outcome of patients with aneurismal subarachnoid hemorrhage (aSAH) after endovascular coil embolization.Methods:Patients with aSAH treated with endovascular coil embolization in the Department of Neurology, Fujian Provincial Hospital from January 2017 to December 2019 were enrolled retrospectively. The baseline data, clinical grade, serum cTnI and N-terminal-pro B-type natriuretic peptide (NT-proBNP) levels, electrocardiogram, aneurysm characteristics, endovascular treatment status, and complications of the patents were collected. The outcomes were evaluated by the modified Rankin Scale (mRS) at 90 d after onset. Poor outcome was defined as >2 points. Multivariate logistic regression analysis was used to identify the independent risk factors for poor outcomes. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of serum cTnI levels for poor outcomes. Results:A total of 316 patients were enrolled, among them, 256 had good outcomes (81.01%), 60 had poor outcomes (18.99%) and 13 died (4.11%). Forty-seven patients (14.87%) had elevated serum cTnI levels. The proportion of patients with elevated serum cTnI levels in the poor outcome group was significantly higher than that in the good outcome group (45% vs. 7.81%; P<0.001). Compared with the good outcome group, the Glasgow Coma Scale score of the poor outcome group was lower, and the Hunt-Hess grades and Fisher grades were higher ( P<0.001). The proportion of patients with elevated NT-proBNP levels and abnormal electrocardiogram in the poor outcome group (all P<0.001) were also significantly higher than those in the good outcome group. The proportion of receiving stent-assisted coil embolization, cerebrospinal fluid replacement and ventricular drainage, as well as the incidence of complicated with cerebral infarction, hydrocephalus, seizure and rebleeding in the poor outcome group were significantly higher than those in the good outcome group (all P<0.01). Multivariate logistic regression analysis showed that after adjusting for other confounding factors, Hunt-Hess grading 3-5 (odds ratio [ OR] 6.615, 95% confidence interval [ CI]2.158-20.278; P=0.001), Fisher grading 3-4 ( OR 3.719, 95% CI 1.479-9.352; P=0.005), cerebral infarction ( OR 15.814, 95% CI 4.978-50.235; P<0.001), rebleeding ( OR 13.324, 95% CI 2.092-84.881, P=0.006) and elevated serum cTnI levels ( OR 3.874, 95% CI 1.406-10.672; P=0.009) were significantly and independently associated with the poor outcomes, which could independently predict the poor outcomes after the onset of aSAH at 90 d. The area under the ROC curve for serum cTnI levels predicting poor outcomes was 0.747 (95% CI 0.666-0.828; P<0.001). The best cut-off value was 0.025 μg/L, the sensitivity and specificity were 60.0% and 87.9%, respectively. Conclusion:The elevated serum cTnI levels have certain predictive value for the poor outcomes of patients with aSAH after endovascular coil embolization.

Objective To observe the clinical efficacy of irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the second-line treatment of advanced colorectal cancer. Methods The clinical data of 19 patients with advanced colorectal cancer who were admitted to the Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College from October 2014 to December 2017 were retrospectively analyzed, and these patients failed the first-line chemotherapy regimen. All patients were treated with irinotecan plus capecitabine or tegafur-gimeracil-oteracil potassium. The patient's short-term efficacy, adverse reactions, progression-free survival, and overall survival were analyzed. Results After treatment, the efficacy in 18 of the 19 patients with advanced colorectal cancer was evaluable, including partial remission in 3 patients, stable disease in 13 patients, and disease progression in 2 patients. The objective remission rate was 16.7％ (3/18), the disease control rate was 88.9％ (16/18), the median progression-free survival time was 7.6 months, and the median overall survival time was 23.3 months. All of the patients were well tolerated , and the grade 4 adverse reaction was presented as grade 4 neutropenia (1 case), grade 3 leukopenia (2 cases) and thrombocytopenia (1 case), grade 2 diarrhea (1 case), and grade 1 diarrhea (3 cases), and grade 1-2 liver injury (3 cases) and nephrotoxicity (2 cases). Conclusion Irinotecan combined with capecitabine or tegafur-gimeracil-oteracil potassium in the treatment of advanced colorectal cancer is effective and safe, which is worthy of clinical promotion.