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*

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Recent studies have shown that the physiological homeostasis of oral mucosal cells is regulated by the circadian clock.Dis-ruption or dysfunction of the circadian clock is closely associated with the development of oral squamous cell carcinoma(OSCC).Research based on the circadian clock offers a novel perspective on the pathogenesis and therapeutic strategies for OSCC.However,there is current-ly limited research on this topic,and people generally have insufficient understanding and recognition of the circadian clock.Given the complexity and challenges of circadian clock which is the fourth dimension of medical research,we organize relevant experts based on summarizing the current research results of circadian clock in the pathogenesis and precision diagnosis and treatment of OSCC,combining the scientific principles of the circadian clock's role and their long-term research experience,then summarizes and recommends the con-sensus opinions for the research of circadian clock in the pathogenesis mechanism and precision diagnosis and treatment of human OSCC,with the hope of providing guidance for the basic research and clinical application of circadian clock or circadian rhythm in the pathogene-sis mechanism and precision diagnosis and treatment of oral and maxillofacial squamous cell carcinoma.

Neck dissection and reconstruction are two important aspects of oral cancer treatment.There are various surgical methods for neck dissection and reconstruction,but all of them are performed by open surgery.This article reports a full endoscopic neck dis-section through the retroauricular hairline approach,the radical resection of the intraoral tumor and the repair of the defect by superfi-cial circumflex iliac artery perforator flap with in situ vascular anastomosis intraorally.The incision is located in the hairline,hidden and invisible,and there is no exposed surgical scar on the neck after surgery.This paper introduces the technique of scarless neck dissection combined with free skin flap repair for the treatment of oral cancer and discusses its advantages and disadvantages.

Objective:To investigate the effect of early selective reduction of twin pregnancies or spontaneous reduction on the improvement of clinical outcome in IVF-ET treatment.Methods:The clinical data of 6535 cycles(6535 cases)of single or twin pregnancy obtained from fresh and frozen-thawed embryo transfer(FET)of IVF or ICSI-ET in the Department of Reproductive Medicine,Women and Children's Hospital Affiliated to Xiamen Univer-sity from November 2011 to December2021 were analyzed retrospectively,The propensity score matching(PSM)method(1∶4)was used to include the study subjects.The surgical reduction group and the spontaneous single-ton group were included in 128 cycles and 510 cycles,respectively.The spontaneous reduction group and the ini-tial singleton group were included in 511 cycles and 2038 cycles,respectively.The pregnancy outcomes of each groups were compared.Results:After PSM,the number of transferred embryos in the surgical and spontaneous reduction group was higher than that in the initial singleton group.The gestational week of delivery was earlier than that of the initial singleton group,and the birth weight of the newborn was lower than that in the initial single-ton group.The rate of premature delivery and low birth weight was higher than that in the initial singleton group,and the difference was statistically significant(P＜0.05).The incidence of pregnancy complications(postpartum hemorrhage,gestational diabetes,hypertensive disorders of pregnancy)and the rate of cesarean section were not significantly different(P＞0.05).The abortion rate and neonatal birth defect rate were missing after adjusting the PSM model.According to the calculation before adjustment,the early abortion rate of the surgical reduction group and the spontaneous reduction group were significantly lower than that in the initial singleton group(P＜0.05),and the late abortion rate of the spontaneous reduction group was lower than that in the initial singleton group,the difference was statistically significant(P＜0.05).There was no significant difference in the neonatal birth defect rate between the surgical/spontaneous reduction group and the initial singleton group(P＞0.05).Conclusions:Patients with multiple pregnancies caused by assisted reproductive technology(ART)may have a relatively poor prognosis in the perinatal period even if the effect of early pregnancy reduction surgery or spontaneous reduction is limited.Reducing the number of embryos transferred cannot completely reverse the pregnancy outcome.Limiting the number of embryos transferred is the fundamental solution to the adverse outcomes of ART assisted pregnancy.

Objective:To compare the application effect of remote intelligent rehabilitation system and conventional rehabilitation in rehabilitation of patients with rotator cuff injury following minimally invasive arthroscopic surgery.Methods:A retrospective cohort study was used to analyze the clinical data of 47 patients with rotator cuff injury admitted to Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January to July 2022, including 18 males and 29 females; aged 45-65 years [(56.7±6.3)years]. All patients underwent minimally invasive arthroscopic surgical repair of rotator cuff rupture. After surgery, 25 patients underwent self-rehabilitation with conventional education (conventional rehabilitation group), and 22 patients underwent systematic rehabilitation with remote intelligent rehabilitation system (remote rehabilitation group). Constant shoulder score, University of California at Los Angeles (UCLA) shoulder score, self-rating anxiety scale (SAS) score, self-rating depression scale (SDS) score and visual analog score (VAS) were compared between the two groups on the day of admission, 4, 8, 12 weeks after surgery and at the last follow-up. Shoulder MRI was applied at 6 weeks after surgery to compare the degree of intra-articular effusion and bone marrow edema between the two groups. The shoulder range of motion of the two groups was compared at 12 weeks after operation. The satisfaction with the rehabilitation of the two groups was compared at the last follow-up.Results:All the patients were followed up for 6-10 months [(8.5±2.2)months]. There was no significant difference in Constant shoulder score, UCLA shoulder score, SAS score, SDS score and VAS between the two groups on the day of admission (all P>0.05). There was no significant difference in Constant score, UCLA score and SAS score between the two groups at 4 weeks after surgery (all P>0.05). The values of SDS score and VAS at 4 weeks after surgery were (31.8±6.6)points and (3.6±1.1)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(40.5±5.6)points and (4.7±1.3)points] (all P<0.05). The values of Constant score, UCLA score, SAS score, SDS score and VAS at 8 weeks after surgery were (62.5±5.5)points, (18.5±3.3)points, (20.5±4.7)points, (22.5±4.6)points and (2.5±0.6)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(41.3±4.7)points, (15.3±3.1)points, (28.5±4.8)points, (38.5±3.7)points and (3.3±1.3)points] ( P<0.05 or 0.01). The values of Constant score, UCLA score, SAS score and SDS score at 12 weeks after surgery were (85.4±6.4)points, (32.2±3.8)points, (13.6±2.8)points and (18.4±3.9)points in the remote rehabilitation group, which were better than those in the conventional rehabilitation group [(60.3±6.7)points, (25.2±4.1)points, (21.5±4.9)points and (26.7±6.6)points] (all P<0.05), while there was no significant difference in VAS between the two groups ( P>0.05). At the last follow-up, there were no significant differences in Constant score, UCLA score, SAS score, SDS score and VAS between the two groups (all P>0.05). MRI of the shoulder joint at 6 weeks after surgery indicated that the degree of intra-articular effusion in the shoulder joint and bone marrow edema of the proximal humerus in the remote rehabilitation group was significantly reduced than that in the conventional rehabilitation group. At 12 weeks after surgery, the remote rehabilitation group had better shoulder range of motion than the conventional rehabilitation group ( P<0.05 or 0.01). At the last follow-up, the satisfaction with the rehabilitation of the remote rehabilitation group was better than that of the conventional rehabilitation group ( P<0.01). Conclusion:For patients with rotator cuff injury who undergo minimally invasive arthroscopic surgery, postoperative application of remote intelligent rehabilitation system, in comparison with the conventional rehabilitation system, can help to facilitate shoulder function recovery, anxiety and depression improvement and pain relief in the early stage, reduce shoulder soft tissue and bone marrow edema of the shoulder, and increase shoulder range of motion and patients′ satisfaction with the rehabilitation.

In order to obtain virus-like particles (VLPs) for prevention of bovine viral diarrhea virus 1 (BVDV-1), the C-E^rns-E1-E2 region was cloned into a pFastBacDaul vector for generating the recombinant Bacmid-BVDV-1 in DH10Bac Escherichia coli. The recombinant baculovirus Baculo-BVDV-1 was produced by transfecting the Sf9 cells with Bacmid-BVDV-1. The expressed protein and the assembled VLPs were determined by immunofluorescence, Western blotting and electron microscopy. Guinea pigs were immunized with inactivated VLPs coupled with the Montanide ISA-201 adjuvant. The immunogenicity of VLPs was evaluated by monitoring the humoral immune response with neutralizing antibody titer determination, as well as by analyzing the cell-mediated immune response with lymphocyte proliferation assay. The protective efficacy of VLPs was evaluated by challenging with 10⁶ TCID₅₀ virulent BVDV-1 strain AV69. The results showed that the recombinant Baculo-BVDV-1 efficiently expressed BVDV structural protein and form VLPs in infected Sf9 cells. The immunization of guinea pigs with VLPs resulted in a high titer (1:144) of neutralizing antibody, indicating an activated cellular immunity. Significantly lower viral RNA in the blood of the post-challenged immunized guinea pigs was observed. The successful preparation of BVDV VLPs with insect cell expression system and the observation of the associated immunogenicity may facilitate further development of a VLPs-based vaccine against BVD.
Animals ; Antibodies, Viral ; Diarrhea ; Diarrhea Virus 1, Bovine Viral ; Guinea Pigs ; Mineral Oil ; Viral Envelope Proteins ; Viral Vaccines

Objective:To investigate the effect of passive motion and immobilization on shoulder function early after arthroscopic repair of rotator cuff tears.Methods:A retrospective case-control study was conducted to analyze the clinical data of 78 patients with rotator cuff tear admitted to Xinhua Hospital, Shanghai Jiaotong University School of Medicine from January 2016 to December 2017. There were 36 males and 42 females, aged 35-78 years [(62.7±3.2)years]. There were 36 patients with medium-sized tears (1-3 cm), 31 with small tears (<1 cm), and 11 with partial articular supraspinatus tendon avulsion (PASTA). All patients underwent arthroscopic rotator cuff repair. Forty-three patients started rehabilitation exercise immediately after operation (motion group). Thirty-five patients were immobilized with shoulder abduction brace for 6 weeks, and started rehabilitation exercise at week 7 (immobilization group). The range of motion, visual analogue pain score (VAS), simplified shoulder joint function test (SST) and Constant shoulder joint score were compared between the two groups before surgery, 6 weeks, 3 months and 12 months after surgery. The healing results were assessed by ultrasound 12 months after surgery. Complications were observed.Results:All the patients were followed up for 12-16 months [(13.7±1.3)months]. There were 7 patients with shoulder joint stiffness in each group (motion group: 16%, immobilization group: 20%) ( P<0.05). There were no significant differences between the two groups in VAS, SST or Constant score at postoperative 6 weeks, 3 months and 12 months ( P>0.05). The forward flexion and external rotation with the arm at the side in immobilization group was (124.9±12.9)° and 25(20, 30)° at postoperative 6 weeks, significantly improved in motion group [(136.6±16.7)°, 30(25, 40)°] ( P<0.05). There were no significant differences between the two groups in forward flexion and external rotation with the arm at the side at postoperative 3 and 12 months ( P>0.05). There were no significant differences between the two groups in internal rotation at postoperative 6 weeks, 3 months, and 12 months ( P>0.05). All rotator cuffs were healed verified by ultrasound at postoperative 12 months. No infection or implant displacement occurred after operation. Conclusions:For arthroscopic repair of medium-sized tears, small tears and PASTA, early postoperative rehabilitation exercises have advantage in improving range of motion only at early stage when compared to immobilization, which disappears with time. Moreover, the two methods have no significant differences in improving postoperative pain and shoulder function.

Objective:To identify potential risk factors of varus collapse after unstable proximal humerus fracture treated with locking plates.Methods:A retrospective case series study was conducted on data of 146 patients with unstable proximal humerus fracture stabilized by locking plates at Xinhua Hospital, Shanghai Jiaotong University School of Medicine from January 2008 through December 2014. These patients were classified into varus collapse group ( n=39) and non-varus collapse group ( n=107) according to the occurrence of varus collapse. The gender, age, bone mineral density, cause of injury, fracture Neer classification, fracture type (varus or valgus), surgical timing, surgical techniques (medial support, cancellous bone graft, suture augmentation), number of humeral head screws and reduction quality were recorded. Potential risk factors were evaluated using univariate analysis and multivariate Logistic regression. The subjective reliability analysis was performed for Neer classification and medial fracture assessments. Results:Varus collapse group had higher ratio of osteoporosis, varus fracture, lack of medial column support, absence of suture augmentation and varus malreductin compared to non-varus collapse group ( P<0.05). While the two groups had no significant differences in gender, age, fracture classification, allogeneic cancellous bone transplantation and number of humeral head screws ( P>0.05). Moreover, the Logistic regression analysis indicated that osteoporosis, varus fracture, lack of medial column support, absence of suture augmentation and varus malreduction were major independent risk factors for varus collapse in proximal humerus fractures ( P<0.05). Among these risk variables, the lack of medial column support showed the strongest correlation of varus collapse after proximal humerus fractures treated with locking plates ( OR=9.62), and varus malreduction was another remarkable risk factor ( OR=8.39). The reliability of Neer classification and medial fracture assessments between interobservers and intraobservers was good. Conclusion:The risk factors for varus collapse after unstable proximal humerus fracture treated with locking plate are osteoporosis, varus fracture, lack of medial column support, absence of suture augmentation and varus malreduction.