Reduced serum IgG galactosylation is associated with increased inflammation during relapses of neuromyelitis optica spectrum disorders.

Background and Objective: Post-translational modifications of antibodies, with a specific focus on galactosylation, have garnered increasing attention in the context of understanding the pathogenesis and therapeutic implications of autoimmune diseases. However, the comprehensive scope and the clinical significance of antibody galactosylation in the context of Neuromyelitis Optica Spectrum Disorder (NMOSD) remain enigmatic.The primary aim of this research was to discern disparities in serum IgG galactosylation levels between individuals in the acute stage of NMOSD relapse and their age- and sex-matched healthy counterparts. Methods: A total of fourteen untreated NMOSD patients experiencing an acute relapse phase, along with thirteen patients under medication, were enrolled, and an additional twelve healthy controls of the same age and gender were recruited for this investigation. Western blot and lectin enzyme techniques were used to determine the level of IgG galactosylation in the serum samples from these subjects. The expression of CD45+, CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD16+CD56+ in peripheral blood leukocytes was measured by flow cytometry. The enzyme-linked immunosorbent assay (ELISA) was also used to quantify the amounts of IgG. Magnetic particle luminescence assays are used to detect cytokines. Robust statistical analysis was executed to ascertain the potential associations between IgG galactosylation and the aforementioned immune indices. Results: In the context of NMOSD relapses, serum IgG galactosylation exhibited a notable decrease in untreated patients (0.2482 ± 0.0261), while it remained comparatively stable in medicated patients when contrasted with healthy controls (0.3625 ± 0.0259) (p=0.0159). Furthermore, a noteworthy inverse correlation between serum IgG galactosylation levels and the Expanded Disability Status Scale (EDSS) score during NMOSD relapse was observed (r=-0.4142; p=0.0317). Notably, IgG galactosylation displayed an inverse correlation with NMOSD relapse among peripheral blood CD45+, CD3+, CD3+CD8+, CD19+ cells, as well as with IL-6 and IL-8. Nevertheless, it was not determined whether IgG galactosylation and CD3+CD4+ T cells or other cytokines are statistically significantly correlated. Conclusion: Our research identified reduced IgG galactosylation in the serum of NMOSD patients during relapses, significantly correlated with disease severity, thereby providing a novel target for the diagnosis and treatment of NMOSD in the realm of medical research.

Association between FOXP3 polymorphisms and expression and neuromyelitis optica spectrum disorder risk in the Northern Chinese Han population.

Background: Forkhead box P3 (FOXP3) plays a critical role in the pathogenesis of autoimmune disorders. In the present study, we genotyped three single-nucleotide polymorphisms, namely, rs2232365, rs3761548, and rs3761549, to determine the relationship between FOXP3 polymorphisms and neuromyelitis optica spectrum disorder (NMOSD) susceptibility among the Northern Chinese Han population. Materials and methods: We genotyped single nucleotide polymorphisms at loci of the FOXP3 gene (rs2232365, rs3761548, and rs3761549136) in 136 NMOSD patients and 224 healthy subjects using the multiplex SNaPshot technique. Allele, genotype, and haplotype frequencies were compared. qPCR was used to analyze the mRNA expression levels of FOXP3 in the peripheral blood mononuclear cells of 63 NMOSD patients and 35 healthy subjects. Non-parametric tests were used to test the FOXP3 mRNA expression across the different groups. Results: The minor allele frequency (MAF) of G in rs2232365 was markedly lower in the NMOSD group than in the control group (odds ratio [OR] = 0.57, 95% confidence interval [95% CI]: 0.41-0.79, p = 0.001). Using genetic (codominant, dominant, and recessive) models and performing haplotype analyses, the MAF of G in rs2232365 was shown to be associated with protection against NMOSD in this population. Furthermore, haplotype analysis revealed that the haplotype GCT and the rs2232365, rs3761548, and rs3761549 alleles predicted protection against NMOSD (OR = 0.63, 95% CI = 0.41-0.97, p = 0.038). The proportions of the three genotypes of rs2232365 (p = 0.001) were not significantly different between the moderate-to-severe (Expanded Disability Status Scale (EDSS) ≥ 3 points) and mild (EDSS < 3 points) groups. Evidently, the proportion of patients with the AA genotype (64.3%) among the rs2232365 patients was significantly greater in the moderate-to-severe group than in the mild group (36.4%). However, the proportion of patients with the GG genotype (15.2%) among the rs2232365 patients was significantly greater in the mild group than in the moderate-to-severe group (2.9%). The mRNA expression of FOXP3 was markedly greater in the NMOSD group than in the control group (p = 0.001). Nevertheless, acute non-treatment patients exhibited lower FOXP3 mRNA expression than healthy controls and patients in the remission group (p = 0.004 and 0.007, respectively). Conclusion: FOXP3 polymorphisms and haplotypes are related to NMOSD susceptibility among the Han Chinese population. The minor allele G of FOXP3 rs2232365 and the haplotype GCT are associated with protection against NMOSD. The GG genotype may decrease the severity of NMOSD, whereas the AA genotype is related to moderate-to-severe NMOSD. FOXP3 mRNA expression is greater in patients with NMOSD than in healthy controls. However, it is decreased in acute non-treatment patients compared with healthy controls.

Interferon Regulatory Factor 5 Gene Polymorphisms and mRNA Expression Levels Are Associated with Neuromyelitis Optica Spectrum Disorder.

Interferon regulatory factor 5 (IRF5) is a critical transcription factor in the toll-like receptor signaling pathway. It is associated with autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. However, the relationship between the functional single nucleotide polymorphisms (SNPs) of IRF5 and its mRNA expression level in patients with neuromyelitis optica spectrum disorder remains unclear. The present study aimed to investigate the relationship between polymorphisms and mRNA expression levels of the IRF5 gene with the incidence of neuromyelitis optica spectrum disorder (NMOSD) in northern Chinese Han people. Two loci of the IRF5 gene (rs2004640 and rs2280714) of 164 patients with NMOSD and 269 healthy subjects were genotyped using the multiple SNaPshot technique. The frequencies of alleles, genotypes, and haplotypes were compared. Stratified analysis was performed according to age, sex, AQP4 status, onset age, and Expanded Disability Status Scale (EDSS) score. The IRF5 mRNA levels in peripheral blood mononuclear cells (PBMCs) of 64 NMOSD patients (32 patients in the acute stage and 32 patients in the remission stage) and 35 healthy subjects were detected by real-time PCR. The association of SNP polymorphisms with the mRNA expression level was determined by nonparametric tests. Allele and genotype frequency distributions of rs2004640 showed significant differences between both groups. Compared to healthy controls, the frequency of rs2004640 T allele markedly increased in patients (OR = 1.51, 95% CI = 1.09-2.08, P = 0.005). Minor allele T and GT genotype of rs2004640 that significantly increases the risk of NMOSD were discovered using genetic inheritance models (codominant, dominant, and overdominant) and haplotype analyses. Subsequent haplotype analyses revealed that the major haplotype "T-A" containing the risk alleles (the SNP sequence of the alleles was rs2004640 and rs2280714) had adverse effects on NMOSD. Based on the stratification analysis according to the EDSS score, the GT genotype frequency in the EDSS ≥ 4 group (38.2%) was markedly lower than that in the EDSS < 4 group (61.8%) (OR = 0.32, 95% CI = 0.15-0.68, P = 0.0054), with a significant difference. The IRF5 mRNA expression level was increased in NMOSD patients compared to that in normal subjects. IRF5 gene polymorphisms may be tightly associated with the genesis and progression of NMOSD in northern Chinese Han people. IRF5 mRNA expression was increased in patients with NMOSD and significantly increased in patients with acute phase. Perhaps IRF5 expression levels can be used as a predictor of disease activity in the future.

Corrigendum to "3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration" [Bioact. Mater. 31 (January 2024) 18-37].

[This corrects the article DOI: 10.1016/j.bioactmat.2023.07.004.].

Deciphering prognostic indicators in AQP4-IgG-seropositive neuromyelitis optica spectrum disorder: An integrative review of demographic and laboratory factors.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a group of inflammatory diseases affecting the central nervous system, characterized by optic neuritis and myelitis. The complex nature of NMOSD and varied patient response necessitates personalized treatment and efficient patient stratification strategies. OBJECTIVE: To provide a comprehensive review of recent advances in clinical and biomarker research related to aquaporin-4 (AQP4)-immunoglobulin G (IgG)-seropositive NMOSD prognosis and identify key areas for future research. METHODS: A comprehensive review and synthesis of recent literature were conducted, focusing on demographic factors and laboratory investigations. RESULTS: Demographic factors, such as age, ethnicity, and sex, influence NMOSD prognosis. Key biomarkers for NMOSD prognosis include homocysteine, antinuclear antibodies, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, thyroid hormone levels, neurofilament light chain levels, and serum glial fibrillary acidic protein might also predict NMOSD attack prognosis. CONCLUSION: Further investigation is required to understand sex-related disparities and biomarker inconsistencies. Identification and understanding of these factors can aid in the development of personalized therapeutic strategies, thereby improving outcomes for NMOSD patients. Future studies should focus on unifying research design for consistent results.

3D-printed tri-element-doped hydroxyapatite/ polycaprolactone composite scaffolds with antibacterial potential for osteosarcoma therapy and bone regeneration.

The resection of malignant osteosarcoma often results in large segmental bone defects, and the residual cells can facilitate recurrence. Consequently, the treatment of osteosarcoma is a major challenge in clinical practice. The ideal goal of treatment for osteosarcoma is to eliminate it thoroughly, and repair the resultant bone defects as well as avoid bacterial infections. Herein, we fabricated a selenium/strontium/zinc-doped hydroxyapatite (Se/Sr/Zn-HA) powder by hydrothermal method, and then employed it with polycaprolactone (PCL) as ink to construct composite scaffolds through 3D printing, and finally introduced them in bone defect repair induced by malignant osteosarcoma. The resultant composite scaffolds integrated multiple functions involving anti-tumor, osteogenic, and antibacterial potentials, mainly attributed to the anti-tumor effects of SeO32-, osteogenic effects of Sr2+ and Zn2+, and antibacterial effects of SeO32- and Zn2+. In vitro studies confirmed that Se/Sr/Zn-HA leaching solution could induce apoptosis of osteosarcoma cells, differentiation of MSCs, and proliferation of MC3T3-E1 while showing excellent antibacterial properties. In vivo tests demonstrated that Se/Sr/Zn-HA could significantly suppress tumors after 8 days of injection, and the Se/Sr/Zn-HA-PCLs scaffold repaired femoral defects effectively after 3 months of implantation. Summarily, the Se/Sr/Zn-HA-PCLs composite scaffolds developed in this study were effective for tumor treatment, bone defect repair, and post-operative anti-infection, which provided a great potential to be a facile therapeutic material for osteosarcoma resection.

Methyl-CpG-Binding Protein 2 Emerges as a Central Player in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

MECP2 and its product methyl-CpG binding protein 2 (MeCP2) are associated with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), which are inflammatory, autoimmune, and demyelinating disorders of the central nervous system (CNS). However, the mechanisms and pathways regulated by MeCP2 in immune activation in favor of MS and NMOSD are not fully understood. We summarize findings that use the binding properties of MeCP2 to identify its targets, particularly the genes recognized by MeCP2 and associated with several neurological disorders. MeCP2 regulates gene expression in neurons, immune cells and during development by modulating various mechanisms and pathways. Dysregulation of the MeCP2 signaling pathway has been associated with several disorders, including neurological and autoimmune diseases. A thorough understanding of the molecular mechanisms underlying MeCP2 function can provide new therapeutic strategies for these conditions. The nervous system is the primary system affected in MeCP2-associated disorders, and other systems may also contribute to MeCP2 action through its target genes. MeCP2 signaling pathways provide promise as potential therapeutic targets in progressive MS and NMOSD. MeCP2 not only increases susceptibility and induces anti-inflammatory responses in immune sites but also leads to a chronic increase in pro-inflammatory cytokines gene expression (IFN-γ, TNF-α, and IL-1ß) and downregulates the genes involved in immune regulation (IL-10, FoxP3, and CX3CR1). MeCP2 may modulate similar mechanisms in different pathologies and suggest that treatments for MS and NMOSD disorders may be effective in treating related disorders. MeCP2 regulates gene expression in MS and NMOSD. However, dysregulation of the MeCP2 signaling pathway is implicated in these disorders. MeCP2 plays a role as a therapeutic target for MS and NMOSD and provides pathways and mechanisms that are modulated by MeCP2 in the regulation of gene expression.

A Novel Method for Treating Distal Radius Diaphyseal Metaphyseal Junction Fracture in Children.

BACKGROUND The treatment of distal radius diaphyseal metaphyseal junction (DMJ) fracture in children is a clinical problem; several treatments are available, but none are very effective. Therefore, this study aimed to report a novel method for treating this fracture using limited open reduction and transepiphyseal intramedullary fixation with Kirschner wire. MATERIAL AND METHODS From January 2018 to December 2019, a total of 15 children (13 boys and 2 girls) with distal radius DMJ fractures with a mean age of 10 years (range: 6-14 years) were included in the study. The operation time, incision length, and X-ray radiation exposure were precisely recorded. All children were followed up regularly. At the final follow-up, clinical outcomes were evaluated according to Price criteria, and complications were recorded. RESULTS The mean operation time of the 15 children was 21.4 min, and the mean incision length was 1.9 cm. The intraoperative X-ray was performed 3.7 times on average. The mean radiographic union of fracture was 4.7 weeks, and the mean time to remove the Kirschner wire was 4.8 weeks for radial instrumentation and 4.7 months for ulnar instrumentation. According to the Price grading evaluation system, clinical outcome was excellent in 14 cases and good in 1 case. Moreover, there were no major complications related to loss of reduction, malunion, nonunion, and physeal arrest of the distal radius. CONCLUSIONS Limited open reduction and transepiphyseal intramedullary fixation with Kirschner wire are effective for treating distal radius DMJ fracture in children, which has the advantages of simple surgical procedures, short operation time, small incision, and less radiation exposure, making it an excellent choice for treating this fracture.

The efficacy of GnRH-a followed by SanJieZhenTong capsules in long-term management of endometriosis: Study protocol for a multicenter, double-blinded, double-dummy randomized clinical trial.

Background: Endometriosis is a common benign gynecological disorder with high risk of recurrence and adverse impact on fertility-sparing. This study aims to evaluate the effectiveness and safety of SanJieZhenTong Capsules, a traditional Chinese medicine, in the long-term management of endometriosis postoperatively. Methods: and analysis: A prospective, double-blinded, double-dummy parallel-group randomized controlled trial will be conducted at three university-based medical centers in China. A total of 600 patients with rAFS III-IV endometriosis diagnosed by laparoscopy will be enrolled. After fundamental treatment (gonadotropin-releasing hormone agonists injection starts on the first day of menstruation postoperatively, and repeats 3 times every 28 days), participants will be randomly allocated to the oral contraceptive group (oral contraceptive + dummy A) or SanJieZhenTong Capsules group (SanJieZhenTong Capsules + dummy B) in a 1:1 ratio. All participants will be treated and followed up for 52 weeks. The primary outcome is a recurrence rate based on endometriosis-related symptoms, physical examination, and/or ultrasound/MRI findings. The secondary outcome includes changes in quality of life and organic function outcome via the 36-item Short-Form scores and gastrointestinal function score. Conclusion: The current trial could provide rigorous evidence on SanJieZhenTong Capsules application in the long-term management of advanced-stage endometriosis.

Risk factor analysis for tibial tubercle avulsion fractures in children.

PURPOSE: Tibial tubercle avulsion fractures (TTAFs) are rare in children, particularly bilateral TTAFs. This study aimed to elucidate the associating factors of TTAF, and compare the risk factor profiles of unilateral and bilateral injuries, thus provide clinical theoretical basis for reducing the occurrence of TTAFs. METHODS: TTAF paediatric patients who were hospitalized between April 2017 and November 2022 were retrospectively analysed. Children who presented for physical examination during the same period were randomly selected, and were age- and sex-matched as controls. A subgroup analysis based on endocrine function was also performed. A risk factor analysis for bilateral TTAF was performed as well. Data were collected via medical records and a questionnaire. All variables were assessed for association with TTAF using univariate and multiple logistic regression analyses. RESULTS: A total of 64 TTAF patients and controls were respectively included. Multivariate analysis demonstrated BMI (P = 0.000，OR = 3.172), glucose (P = 0.016，OR = 20.878), and calcium (P = 0.034，OR = 0.000) as independent associating factors of TTAF. Subgroup analysis showed significant differences in oestradiol (P = 0.014), progesterone (P = 0.006) and insulin levels (P = 0.005) between the TTAF and control groups. Bilateral TTAF was found to significantly associate with a history of knee joint pain (P = 0.026). CONCLUSION: High BMI, hyperglycaemia, and low calcium levels were found as independent risk factors for TTAF in children. In addition, decreased oestradiol, elevated progesterone, and insulin resistance were identified as potential risk factors for TTAF. A history of knee pain may be suggestive of bilateral TTAF.

Tissue engineering in growth plate cartilage regeneration: Mechanisms to therapeutic strategies.

The repair of growth plate injuries is a highly complex process that involves precise spatiotemporal regulation of multiple cell types. While significant progress has been made in understanding the pathological mechanisms underlying growth plate injuries, effectively regulating this process to regenerate the injured growth plate cartilage remains a challenge. Tissue engineering technology has emerged as a promising therapeutic approach for achieving tissue regeneration through the use of functional biological materials, seed cells and biological factors, and it is now widely applied to the regeneration of bone and cartilage. However, due to the unique structure and function of growth plate cartilage, distinct strategies are required for effective regeneration. Thus, this review provides an overview of current research on the application of tissue engineering to promote growth plate regeneration. It aims to elucidates the underlying mechanisms by which tissue engineering promotes growth plate regeneration and to provide novel insights and therapeutic strategies for future research on the regeneration of growth plate.

Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders.

BACKGROUNDS: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease with significant female preponderance. X inactive specific transcript (XIST) is a long non-coding RNA (lncRNA) and a key regulator of X-chromosome inactivation which is related to the sex-bias of autoimmunity. And Th17 cell proportion was significantly elevated in NMOSD according to our previous study. OBJECTIVES: This study aimed to explore the expression levels of lncRNA XIST-KDM6A-TSAd pathway in lymphocytes of female NMOSD patients, and investigate its possible relationship with pathogenesis of NMOSD. METHODS AND RESULTS: The study enrolled 30 acute-phase untreated female NMOSD patients and 30 age-matched female healthy controls, their lymphocytes were collected for experiments. Microarray as well as validation experiments showed lncRNA XIST was significantly downregulated in the NMOSD group. And the levels of lysine demethylase 6A (KDM6A) decreased in NMOSD and showed significant positive correlation with XIST. The levels of T cell-specific adapter (TSAd) mRNA and protein levels were significantly lower in NMOSD. And Chromatin immunoprecipitation assay demonstrated that NMOSD had more H3K27me3 modification than control at TSAd promoter region. CONCLUSIONS: The present study introduced a potential pathway that following lncRNA XIST downregulation, which process may promote Th17 differentiation in NMOSD. These findings shed new light on the immune regulation mechanism about lncRNA XIST and related epigenetic features, which may contribute to develop female-specific treatment plans.

Injectable hydrogel loaded with bilayer microspheres to inhibit angiogenesis and promote cartilage regeneration for repairing growth plate injury.

Introduction: The repair and regeneration of growth plate injuries using tissue engineering techniques remains a challenge due to large bone bridge formation and low chondrogenic efficiency. Methods: In this study, a bilayer drug-loaded microspheres was developed that contains the vascular endothelial growth factor (VEGF) inhibitor, Bevacizumab, on the outer layer and insulin-like growth factor-1 (IGF-1), a cartilage repair factor, on the inner layer. The microspheres were then combined with bone marrow mesenchymal stem cells (BMSCs) in the gelatin methacryloyl (GelMA) hydrogel to create a composite hydrogel with good injectability and biocompatibility. Results: The in vitro drug-release profile of bilayer microspheres showed a sequential release, with Bevacizumab released first followed by IGF-1. And this hydrogel simultaneously inhibited angiogenesis and promoted cartilage regeneration. Finally, in vivo studies indicated that the composite hydrogel reduced bone bridge formation and improved cartilage regeneration in the rabbit model of proximal tibial growth plate injury. Conclusion: This bilayer microsphere-based composite hydrogel with sequential controlled release of Bevacizumab and IGF-1 has promising potential for growth plate injury repair.

3D bioprinted hydrogel/polymer scaffold with factor delivery and mechanical support for growth plate injury repair.

Introduction: Growth plate injury is a significant challenge in clinical practice, as it could severely affect the limb development of children, leading to limb deformity. Tissue engineering and 3D bioprinting technology have great potential in the repair and regeneration of injured growth plate, but there are still challenges associated with achieving successful repair outcomes. Methods: In this study, GelMA hydrogel containing PLGA microspheres loaded with chondrogenic factor PTH(1-34) was combined with BMSCs and Polycaprolactone (PCL) to develop the PTH(1-34)@PLGA/BMSCs/GelMA-PCL scaffold using bio-3D printing technology. Results: The scaffold exhibited a three-dimensional interconnected porous network structure, good mechanical properties, biocompatibility, and was suitable for cellchondrogenic differentiation. And a rabbit model of growth plate injury was appliedto validate the effect of scaffold on the repair of injured growth plate. The resultsshowed that the scaffold was more effective than injectable hydrogel in promotingcartilage regeneration and reducing bone bridge formation. Moreover, the addition ofPCL to the scaffold provided good mechanical support, significantly reducing limbdeformities after growth plate injury compared with directly injected hydrogel. Discussion: Accordingly, our study demonstrates the feasibility of using 3D printed scaffolds for treating growth plate injuries and could offer a new strategy for the development of growth plate tissue engineering therapy.

miR-485 regulates Th17 generation and pathogenesis in experimental autoimmune encephalomyelitis through targeting STAT3.

Experimental autoimmune encephalomyelitis (EAE) is an induced autoimmune disease widely used as an animal model for multiple sclerosis, which is mainly characterized by demyelination, axonal loss, as well as neurodegeneration of central nervous system (CNS). T-helper (Th) 17 cell that generate interleukin-17 (IL-17) plays a key role in its pathogenesis. Their activity and differentiation are tightly regulated by some cytokines and transcription factors. Certain microRNAs (miRNAs) are involved in the pathogenesis of various autoimmune disorders, including EAE. Our research detected a novel miRNA that can regulate EAE. According to the results, during EAE, the expression of miR-485 notably lowered, and STAT3 was significantly increased. It was discovered that miR-485 knockdown in vivo upregulated Th17-associated cytokines and aggravated EAE, while the overexpressed miR-485 down-regulated Th17-associated cytokines and mitigated EAE. The up-regulation of miRNA-485 in vitro inhibited Th17-associated cytokines expression within EAE CD4+ T cells. Furthermore, as revealed by target prediction and dual-luciferase reporter assays, miR-485 directly targets STAT3, a gene that encodes a protein responsible for Th17 generation. Overall, miR-485 exert vital functions in Th17 generation and EAE pathogenesis.

Modified radial tongue-shaped flap following stepwise surgical release for Benson type I camptodactyly of the 5th digit.

To investigate the outcomes of the modified radial tongue-shaped flap following stepwise surgery release for treating Benson type I camptodactyly of the 5th digit. A retrospective analysis involving patients with Benson type I camptodactyly of the 5th digit was performed. A total of 8 patients with 12 affected digits were included. Extent of surgical release depended on the degree of soft tissue contracture. Skin release, subcutaneous fascial release, and flexor digitorum superficialis tenotomy were performed in all 12 digits, sliding volar plate release in 2 digits, and intrinsic tendon transfer in 1 digit. The mean total passive motion of proximal interphalangeal joint significantly increased from 32.5° ± 16° to 86.3° ± 20.4°, while mean total active motion significantly increased from 22° ± 10.5° to 73.8° ± 27.5° (P < 0.05). Treatment outcomes were excellent in 6 patients, good in 3, moderate in 2, and poor in 1. Scar hyperplasia occurred in 1 patient. The radial tongue-shaped flap allowed for full coverage of the volar skin defect, and was considered aesthetically favorable. In addition, the stepwise surgical approach not only achieved good curative effects, but also allowed for individualization of treatment.

Mesenchymal stem cell-derived exosomal microRNA-367-3p alleviates experimental autoimmune encephalomyelitis via inhibition of microglial ferroptosis by targeting EZH2.

Multiple sclerosis (MS) is an autoimmune, inflammatory demyelinating disorder of the central nervous system. Accumulating evidence has underscored the therapeutic potential of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSC-Exos) containing bioactive compounds in MS. Herein, the current study sought to characterize the mechanism of BMSC-Exos harboring miR-367-3p both in BV2 microglia by Erastin-induced ferroptosis and in experimental autoimmune encephalomyelitis (EAE), a typical animal model of MS. Exosomes were firstly isolated from BMSCs and identified for further use. BV2 microglia were co-cultured with miR-367-3p-containing BMSC-Exos, followed by an assessment of cell ferroptosis. Mechanistic exploration was furthered by the interaction of miR-367-3p and its downstream regulators. Lastly, BMSC-Exos harboring miR-367-3p were injected into EAE mice for in vivo validation. BMSC-Exos carrying miR-367-3p restrained microglial ferroptosis in vitro. Mechanistically, miR-367-3p could bind to Enhancer of zeste homolog 2 (EZH2) and restrain EZH2 expression, leading to the over-expression of solute carrier family 7 member 11 (SLC7A11). Meanwhile, over-expression of SLC7A11 resulted in Glutathione Peroxidase 4 (GPX4) activation and ferroptosis suppression. Ectopic expression of EZH2 in vitro negated the protective effects of BMSC-Exos. Furthermore, BMSC-Exos containing miR-367-3p relieved the severity of EAE by suppressing ferroptosis and restraining EZH2 expression in vivo. Collectively, our findings suggest that BMSC-Exos carrying miR-367-3p brings about a significant decline in microglia ferroptosis by repressing EZH2 and alleviating the severity of EAE in vivo, suggesting a possible role of miR-367-3p overexpression in the treatment strategy of EAE. AVAILABILITY OF DATA AND MATERIALS: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Risk factors for femoral overgrowth after femoral shortening osteotomy in children with developmental dysplasia of the hip.

Objective: Developmental dysplasia of the hip (DDH) refers to a series of deformity of acetabulum and proximal femur and abnormal relationship between them, it represents the most common hip disease in children. Overgrowth and limb length discrepancy (LLD) was common complication in children undergoing femoral shortening osteotomy. Therefore, the purpose of this study was to explore the risk factors of overgrowth after femoral shortening osteotomy in children with DDH. Methods: We included 52 children with unilateral DDH who underwent pelvic osteotomy combined with femoral shortening osteotomy between January 2016 and April 2018, including seven males (six left and one right hip) and 45 females (33 left and 12 right hips) with an average age of 5.00 ± 2.48 years, and an average follow-up time of 45.85 ± 6.22 months. The amount of overgrowth and limb length discrepancies (LLDs) were calculated. The risk factors of femoral overgrowth ≥1 cm and LLD ≥ 1 cm were analyzed. Results: There were statistical differences in age (p < 0.001) and operation duration (p = 0.010) between the two groups with femoral overgrowth <1 cm and ≥1 cm. There was a statistical difference in operation duration (p < 0.001) between the two groups. Age (p < 0.001) was an independent influencing factor of femoral overgrowth in children with unilateral DDH after pelvic osteotomy and femoral shortening osteotomy, and a risk factor (p = 0.008) of LLD in these children. Conclusion: The overgrowth and LLD of children with developmental dislocation of hip after pelvic osteotomy and femoral shortening osteotomy are significantly related to age. There was no significant difference between different pelvic osteotomies for femoral overgrowth in children. Therefore, surgeons should consider the possibility of LLD after femoral shortening osteotomy in children of a young age.

Exosomal miR-23b-3p from bone mesenchymal stem cells alleviates experimental autoimmune encephalomyelitis by inhibiting microglial pyroptosis.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system and is marked by inflammation and damage to the myelin sheath surrounding nerve fibers. Recent studies have highlighted the therapeutic value of exosomes (Exos) obtained from bone marrow mesenchymal stem cells (BMSCs) in MS treatment. These BMSC-Exos contain biologically active molecules that show promising results in preclinical evaluations. The aim of this study was to investigate the mechanism of BMSC-Exos containing miR-23b-3p in both LPS-stimulated BV2 microglia and in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Exos were isolated from BMSCs, and their effects were evaluated in vitro by co-culturing with BV2 microglia. The interaction between miR-23b-3p and its downstream targets was also explored. The efficacy of BMSC-Exos was further verified in vivo by injecting the Exos into EAE mice. The results showed that BMSC-Exos containing miR-23b-3p reduced microglial pyroptosis in vivo by specifically binding to and suppressing the expression of NEK7. In vivo, BMSC-Exos containing miR-23b-3p alleviated the severity of EAE by decreasing microglial inflammation and pyroptosis via the repression of NEK7. These findings provide new insights into the therapeutic potential of BMSC-Exos containing miR-23b-3p for MS.

Network pharmacology and experimental validation to explore the potential mechanism of Sanjie Zhentong Capsule in endometriosis treatment.

Purpose: Sanjie Zhentong Capsule (SZC) is gradually becoming widely used in the treatment of endometriosis (EMs) and has demonstrated an excellent curative effect in the clinic. However, the active components and mechanisms of Sanjie Zhentong Capsule (SZC) in the treatment of endometriosis (EMs) remain unclear, and further research is needed to explore the effects of Sanjie Zhentong Capsule (SZC). Materials and methods: First, a drug target database of Sanjie Zhentong capsule (SZC) was established by consulting the TCMSP database and related literature. An endometriosis (EMs) disease target database was then established by consulting the GeneCards, OMIM and Drug Bank databases. The overlapping genes of SZC and EMs were determined, and protein-protein interactions (PPIs), gene ontology (GO) and Kyoto Gene and Genome Encyclopedia (KEGG) analyses were performed to predict the potential therapeutic mechanisms. Molecular docking was used to observe whether the key active ingredients and targets predicted by network pharmacology had good binding energy. Finally, in vitro experiments such as CCK-8, flow cytometry and RT-PCR assays were carried out to preliminarily verify the potential mechanisms. Results: Through the construction of a pharmacological network, we identified a total of 28 active components in SZC and 52 potential therapeutic targets. According to GO and KEGG enrichment analyses, the effects of SZC treatment may be related to oxidative stress, steroid metabolism, apoptosis and proliferation. We also experimentally confirmed that SZC can regulate the expression of steroid hormone biosynthesis-related genes, inhibit ectopic endometrial stromal cell (EESC) proliferation and oxidative stress, and promote apoptosis. Conclusion: This study explored the potential mechanism of SZC in the treatment of EMs through network pharmacology and experiments, providing a basis for further future research on SZC in the treatment of EMs.