BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Female ; Humans ; Pregnancy ; Septate Uterus ; Uterus/surgery* ; Hysteroscopy/methods* ; Estrogens ; Tissue Adhesions/surgery* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

Objective:To test and evaluate the reliability and clinical effectiveness of osteoporotic thoracolumbar fracture (OTLF) scoring and classification system.Methods:A multicenter retrospective case series study was conducted to analyze the clinical data of 530 OTLF patients admitted to 8 hospitals including Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to June 2022. There were 212 males and 318 females, aged 55-90 years [(72.6±10.8)years]. There were 4 patients with grade C and 18 with grade D according to American Spinal Injury Association (ASIA) classification. According to the osteoporotic thoracolumbar injury classification and severity (OTLICS) score, all patients had an OTLICS score over 4 points and required surgical treatment. Among them, 410 patients had acute symptomatic OTLF (ASOTLF), including 24 patients with type I, 159 type IIA, 47 type IIB, 31 type IIC, 136 type IIIA, 8 type IIIB, 2 type IV (absence of neurological symptoms) and 3 type IV (presence of neurological symptoms), and 120 patients had chronic symptomatic OTLF (CSOTLF), including 62 patients with type I, 21 type II, 17 type III, 3 type IV (reducible under general anesthesia), 9 type IV (not reducible under general anesthesia), 1 type V (reducible under general anesthesia), 5 type V (presence of neurological symptoms), and 2 type V (not reducible under general anesthesia). Surgical procedures included percutaneous vertebroplasty (PVP), positional repositioning plus PVP, percutaneous kyphoplasty (PKP), posterior open reduction combined with bone graft fusion and bone cement augmented screw internal fixation, posterior open reduction combined with decompression, bone graft fusion and bone cement augmented screw internal fixation, and posterior open reduction combined with osteotomy and orthopedics, bone graft fusion and bone cement augmented screw internal fixation. A weighted Kappa was used to test the interobserver and intraobserver reliability of the OTLICS score, the ASOTLF classification, and the CSOTLF classification. The visual analog scale (VAS), Oswestry disability index (ODI), ASIA classification were compared before, at 1 month after surgery and at the last follow-up. Incidence of postoperative complications was observed.Results:The percentage of mean interobserver agreement for OTLICS staging was 93.4%, with a mean confidence Kappa value of 0.86, and the percentage of mean intraobserver agreement was 93.0%, with a mean confidence kappa value of 0.86. The percentage of mean interobserver agreement for ASOTLF staging was 94.2%, with a mean confidence Kappa value of 0.84, and the percentage of mean intraobserver agreement was 92.5%, with a mean confidence Kappa value of 0.83. The percentage of mean interobserver agreement for CSOTLF subtyping was 91.9%, with a mean confidence Kappa value of 0.80, and the percentage of mean intraobserver agreement was 91.3%, with a mean confidence Kappa value of 0.81. All the patients were followed up for 6-12 months [(9.0±2.1)months]. The VAS and ODI scores were significantly lower in patients with ASOTLF and CSOTLF classifications at 1 month after surgery and at the last follow-up than those before surgery (all P<0.05). The VAS scores in patients with ASOTLF types IIA, IIB, IIC, IIIA, and IV were significantly lower at the last follow-up than that at 1 month after surgery; the ODI scores in patients with ASOTLF types I, IIA, IIB, IIIA, IIIB and IV were significantly lower at the last follow-up than those at 1 month after surgery. The VAS scores in patients with CSOTLF types II, III, IV, and V were significantly lower at the last follow-up than those at 1 month after surgery, and the ODI scores in patients with all CSOTLF types were significantly lower at the last follow-up than those at 1 month after surgery (all P<0.05). Two patients with ASIA grade C recovered to grade D, and the rest recovered to grade E at the last follow-up ( P<0.01). No major vessel or nerve injury or internal fixation failure was found during follow-up. There were 18 patients with cement leakage, none of whom showed relevant clinical symptoms. There were 35 patients with new vertebral fractures, all of whom recovered well after symptomatic treatment. Conclusions:The OTLICS score, ASOTLF classification and CSOTLF classification have a high degree of reliability. Application of stepwise treatment for patients with different levels of injury according to the scoring and classification system can reduce pain, promote recovery of the spinal function, and reduce complications, which is of some significance in guiding the selection of clinical treatment.

Objective To evaluate the radiation protection of “four-in-one” dental X-ray equipment and to investigate the safety interlock of the equipment by measuring the scattered radiation at the position of the patient during operation. Methods A cone-beam CT dental phantom was used to simulate the patient’s head. The intra-oral and extra-oral components of the “four-in-one” X-ray equipment were installed in a 5 m² room. The scattered radiation at patient position was measured using a γ/X-ray survey meter, and the effects of intra-oral and extra-oral components were compared. Results For a 5 m² room, when CBCT was exposed under typical conditions, the dose at the patient's position was 10.70 uSv/h when there was an intra-oral component and 10.60 uSv/h when there was no intraoral component. The intra-oral part did not affect the radiation dose at the patient's position. When the intra-oral component was exposed, the dose rate at the patient's position was 4.05-6.85 uSv/h, and the extra-oral part did not affect the scattered dose of the patient examined with intra-oral components. Conclusion The evaluation of radiation protection of new equipment must comprehensively consider radiation safety and equipment operation safety. The results of this study provide suggestions for clinical radiation protection supervision and evaluation of “four-in-one” dental X-ray equipment.

Objective To investigate the effects of natural killer (NK)-cell-derived miR-30e-3p-containing exosomes (Exo) on esophageal squamous cell carcinoma (ESCC) cell proliferation, apoptosis and invasion. Methods NK cells were isolated and amplified from the peripheral blood of healthy donors, and NK cell-derived Exo was isolated and identified, which were further co-cultured with NEC cells and were randomly grouped into Exo1 and Exo2 groups. Transmission electron microscopy (TEM) was used to observe the morphology and size of exosomes. Western blot analysis was used to detect the expression levels of exosome markers apoptosis related gene 2- interacting protein X(ALIX), tumor susceptibility gene 101(TSG101), CD81 and calnexin. The NC plasmids, mimics and inhibitors of miR030e-3p were respectively delivered into the NK cells, and the corresponding NK cells-derived Exo were co-cultured with NEC cells, which were divided into NC, Exo, mimic and inhibitor groups. CCK-8 assay was used to evaluate cell proliferation, flow cytometry was conducted to determine cell cycle, annexin V-FITC/PI double staining was employed to detect cell apoptosis, and Transwell^TM assay was performed to detect cell invasion abilities. Real-time quantitative PCR was used to detect the expression of miR-23b, miR-422a, miR-133b, miR-124, miR-30e-3p and miR-99a in NCE cells and exosomes. Results The percentages of CD56⁺CD3⁺ cells and CD56⁺CD16⁺ cells in NK cells were (0.071±0.008)% and (90.6±10.6)%, respectively. Exosome isolated from NK cells ranged from 30 nm to 150 nm, and was positive for ALIX, TSG101 and CD81, while negative for calnexin. NK cell-derived Exos inhibited the proliferation, reduced the proportion of S-phase cells and the number of invaded cells of NEC cells, and promoted the apoptosis and the proportion of G1 phase cells. Overexpression of miR-30E-3p in NK cell-derived exosome inhibited the proliferation and invasion of NEC cells, and blocked cell cycle and promoted apoptosis, while knockdown miR-30e-3p in NK cell-derived exosomes did the opposite. Conclusion miR-30e-3p in NK cell-derived exosomes can inhibit the proliferation and invasion of ESCC cells, block their cell cycle and induce their apoptosis.
Humans ; Esophageal Squamous Cell Carcinoma/genetics* ; Esophageal Neoplasms/genetics* ; Exosomes/metabolism* ; Calnexin/metabolism* ; Cell Movement/genetics* ; MicroRNAs/metabolism* ; Cell Proliferation/genetics* ; Killer Cells, Natural ; Cell Line, Tumor ; Apoptosis/genetics*

Objective:To evaluate the efficacy between pedicle screws combined with vertebroplasty (PSV) and pedicle screws combined with intermediate screws (PSIS) for the treatment of osteoporotic thoracolumbar fracture (OTLF).Methods:PubMed, Cochrane Library, Web of Science, CNKI, VIP and Wanfang database were searched for all randomized controlled trial (RCT) or case-control trial (CCT) studies that comparing PSV and PSIS for the treatment of OTLF. Two reviewers independently screened the studies in the light of the inclusion and exclusion criteria, extracted data and evaluated the quality of the included studies. The Meta-analysis was performed using the RevMan 5.4 software. The subjects were divided into PSV group and PSIS group according to different treatment methods. Operation time, intraoperative blood loss, postoperative incision infection rate, postoperative short-, mid- and long-term visual analogue scale (VAS) score, postoperative short- and mid-term Oswestry disability index (ODI), hospitalization time, postoperative short-, mid- and long-term Cobb angle, postoperative short-, mid- and long-term anterior vertebral height ratio (VBH) and implant failure rate were compared between the two groups.Results:A total of 12 studies were enrolled for review, involving 870 subjects (433 in PSV group and 437 in PSIS group). The results showed insignificant difference between the two groups in operation time ( WMD=7.07, 95% CI -4.00, 18.13, P>0.05), intraoperative blood loss ( WMD=0.62, 95% CI -7.19, 8.43, P>0.05), postoperative incision infection rate ( OR=0.65, 95% CI 0.10, 4.08, P>0.05), postoperative short-term Cobb angle ( WMD=-0.19, 95% CI -0.43, 0.05, P>0.05) and postoperative short-term VBH ( WMD=0.91, 95% CI -1.30, 3.13, P>0.05). However, there was significant difference between the two groups in postoperative short-term VAS score ( WMD=-0.59, 95% CI -1.02, -0.15, P<0.05), mid-term VAS score ( WMD=-0.41, 95% CI -0.65, -0.16, P<0.05), long-term VAS score ( WMD=-0.51, 95% CI -0.59, -0.43, P<0.05), postoperative short-term ODI ( WMD=-6.26, 95% CI -9.65, -2.87, P<0.05), postoperative mid-term ODI ( WMD=-2.44, 95% CI -3.43, -1.45, P<0.05), hospitalization time ( WMD=-2.65, 95% CI -4.61, -0.68, P<0.05), postoperative mid-term Cobb angle ( WMD=-1.40, 95% CI -2.41, -0.39, P<0.05), postoperative long-term Cobb angle ( WMD=-1.06, 95% CI -1.59, -0.52, P<0.05), postoperative mid-term VBH ( WMD=3.06, 95% CI 1.31, 4.81, P<0.05), postoperative long-term VBH ( WMD=4.11, 95% CI 2.44, 5.77, P<0.05) and implant failure rate ( OR=2.06, 95% CI 0.11, 0.59, P<0.05). Conclusion:Compared with PSIS, PSV can not reduce the operation time, intraoperative blood loss and incision infection in the treatment of OTLF, but it can significantly relieve pain, improve function, decrease reduce hospitalization time, help to maintain Cobb angle and anterior vertebral height after operation, and reduce implant failure rate.

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.