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*

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Head ; Humans ; Skull Base ; Solitary Fibrous Tumors/surgery* ; Virtual Reality

OBJECTIVE: To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival. METHODS: Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3 RESULTS: The ratio of CD3 CONCLUSION Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.
Bone Marrow ; China ; Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Medicine ; Prescriptions ; Th17 Cells ; Vascular Endothelial Growth Factor A

OBJECTIVE: To detect the level of vascular endothelial growth factor (VEGF) in bone marrow of patients with non-M3 acute leukemia (AL), and estimate its relationship with prognosis. METHODS: From January 2016 to December 2019, 114 patients with AL in department of Hematology, Wuwei People's Hospital were selected as study group, and 25 healthy volunteers were enrolled as control group. The concentration of VEGF in bone marrow was detected by ELISA. The patients were divided into high and low concentration group according to the level of VEGF. The overall survival (OS) and event-free survival (EFS) were compared among different groups. RESULTS: The level of VEGF in patients with AL was significantly higher than that in the control group. The median OS and EFS in the low concentration group was 34.5 and 32 months, respectively, while, in the high concentration group was 30 and 26 months, respectively. The differences between the two groups were statistically significant (P=0.010). There were significant differences in OS rate (P=0.035) and EFS rate (P=0.026) between low and high concentration group. Multivariate analysis showed that high VEGF concentration was an independent risk factor affecting OS (HR=2.619, 95%CI 1.070-6.406, P=0.035) and EFS (HR=2.221, 95%CI 1.074-4.552, P=0.031) in AL patients. CONCLUSION VEGF highly expresses in the bone marrow of patients with AL at initial diagnosis and relapse, and shows adverse effects on the prognosis.
Bone Marrow ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute ; Prognosis ; Vascular Endothelial Growth Factor A

OBJECTIVETo explore the feasibility and the attention of perioperative management of goat lumbar fusion model for individualized 3D printing technology.

METHODSAccording to preoperative X-ray and CT three dimensional reconstruction data of 10 males Boer goat's lumbar(1-2 years old, weight 35-45 kg), the preoperative open height were determined, meanwhile, according to the theoretical entry point of nails, the length of steel plate, arc, and setting position, screw length for reference were determined, the lumbar lateral anterior plate was designed and 3D-printed. Goats lied on the right side, under the general anesthesia, the lumbar vertebrae of the goats and the adjacent intervertebral disc were resected, and the titanium cage after the bone graft was implanted into the goat, the 3D-print lateral bone plate was fixed. After operation, feeding, fluid infusion, anti infection, postoperative complications management, respiratory digestion perioperative management were performed.

RESULTSThe 10 models for goats were successful in results. Postoperative X-ray film and three-dimensional reconstruction of CT showed that titanium cage and bone plate were in good position and reliable. Three months after the operation, CT 3D reconstruction and micro-CT of the goat were observed, and the fusion of the spine was observed. Imaging studies showed that the fusion of the lateral bone plate fixation titanium cage was both at the end of the titanium cage and the dense bone trabecular formation between the vertebral bodies.

CONCLUSIONSThe 3D printing technology sets up the goat lumbar spinal fusion model successfully, which is a kind of effective, more successful, reliable and stable method, perioperative management. The method is scientific, practical, and more humanized, to ensure that lumbar lateral successfully implanted the nail plate of lateralanterior internal fixation system, with reduction of occurrence of surgical complications.

OBJECTIVETo investigate whether Tpeak-Tend interval (Tp-e) and Tp-e/QT ratio are associated with malignant ventricular arrhythmia in patients with implantable cardioverter-defibrillator (ICD) for primary prevention.

METHODSA cohort of 68 consecutive patients with chronic heart failure undergoing standard ICD for primary prevention indications (NYHA function class II-III, left ventricular ejection fraction ≤35%, systolic cardiomyopathy without prior malignant ventricular arrhythmia) were enrolled in this study. The patients were followed up for 18-48 months and were divided into high-risk group and low-risk group according to the occurrence of the endpoint events of sudden cardiac death (SCD), ventricular tachycardia (VT), or ventricular fibrillation (VF). Electrocardiographic and echocardiographic characteristics, Tp-e, and Tp-e/QT ratio were analyzed in all cases before ICD implantation.

RESULTSDuring the follow-up, ICD shock for sustained ventricular tachycardia or ventricular fibrillation occurred in 11 patients; nonsustained ventricular tachycardia (NSVT) that did not require therapy was detected by ICD in 7 patients (high-risk group, 18 cases). ICD did not detect ventricular tachycardia or ventricular fibrillation in 50 patients (low-rsk group). Compared with the low-rsik group, the high-risk group had an increased Tp-e/QT ratio (0.27±0.04 vs 0.22±0.05 P<0.01) and an increased Tp-e (105±15 vs 90±17 ms P<0.01). ROC analysis revealed that a Tp-e/QT ratio ≥0.255 had a sensitivity of 72.2% and a specificity of 65.9%, and a Tp-e ≥103 ms had a sensitivity of 66.7% and a specificity of 67.9% for predicting VT and VF in these patients.

CONCLUSIONIncreased Tp-e and Tp-e/QT ratio are associated with increased risks of ventricular arrhythmias in patients with ICD for primary prevention.

Death, Sudden, Cardiac ; prevention & control ; Defibrillators, Implantable ; Electrocardiography ; Heart Failure ; therapy ; Humans ; Primary Prevention ; ROC Curve ; Tachycardia, Ventricular ; prevention & control ; Ventricular Fibrillation ; Ventricular Function, Left

OBJECTIVETo assess the experimental and clinical data regarding the effects of electromagnetic fields (EMFs) on fracture non-union.

DATA SOURCESThe English language literature regarding EMFs on fracture non-union were searched using MEDLINE, Web of Science and Embase, for the period January 2006 to June 2011. The search terms were electromagnetic fields and non-union/bone marrow stem cells (BMSCs)/bone.

STUDY SELECTIONArticles were included in the review if they were related to the use of EMFs on BMSCs or bone tissue. Papers without full manuscripts available were excluded.

RESULTSThe basic and clinical research in this field, while somewhat limited, supports the insightful application of EMFs to ameliorate disability due to fracture non-union.

CONCLUSIONSFurther basic and clinical research to validate the use of EMFs in facilitating function and bone reparative processes in fracture non-union is required.

Animals ; Bone Regeneration ; physiology ; Electromagnetic Fields ; Humans

OBJECTIVETo evaluate the value of pedicle parameter obtained by the reformation images on multi-slice spiral CT (MSCT) in the surgical treatment of lumbar spondylolisthesis.

METHODSFrom January 2009 to March 2010, 60 patients with lumbar spondylolisthesis failing in conservative treatment were enrolled into the study and divided into experimental and control group randomly (each group with 30 patients). There were 26 males and 34 females ranging in age from 18 to 59 years with an average of (42.60 +/- 9.36) years. The experimental group was examined with volumetric scanning on MSCT before operation. Reformation such as multiplanar reconstruction (MPR) and volume rendering (VR) were carried out at the work station. Transverse section angle (TSA), sagittal section angle (SSA), pedicle length (PL), pedicle width (PW) and pedicle height (PH) were measured on different images and pedicle screws were implanted according pedicle parameter. In control group, the pedicle screws were implanted according to conventional anatomic landmark. Preparative time of screw canal and accuracy of screw were compared between two groups.

RESULTSA hundred fifty-six screws were inserted in experiment group,143 screws were excellent, 11 good, and 2 poor. A hundred fifty screws were inserted in control group, 101 screws were excellent, 26 good, and 23 poor. There was significant difference in accuracy of screw between two groups (P < 0.001). The preparative time of screw canal in experiment group was (66.20 +/- 7.31) s, and was shorter than that of control group [(104.11 +/- 9.51) s, P < 0.001)].

CONCLUSIONAbundant information and parameter could be obtained with the MSCT reconstruction images. The images and parameters could make a perfect operative strategy before operation, adjust the direction of pedicle screws during operation, avoid and decrease operative complications effectively.

Adolescent ; Adult ; Bone Screws ; Female ; Humans ; Lumbar Vertebrae ; diagnostic imaging ; surgery ; Male ; Middle Aged ; Spondylolisthesis ; diagnostic imaging ; surgery ; Tomography, Spiral Computed ; methods