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.].

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.

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.

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.

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.

Anti-NMDA Receptor Encephalitis: Retrospective Analysis of 15 Cases, Literature Review, and Implications for Gynecologists.

Background: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is a rare form of autoimmune encephalitis caused by anti-NMDA receptor antibodies. This disease mainly affects women of childbearing age and is commonly associated with ovarian teratoma. However, the relationship between anti-NMDA receptor encephalitis and ovarian teratoma and the role of anti-NMDA receptor antibody in the relationship remain unclear. Objectives: This study aimed to describe 15 cases of anti-NMDA receptor encephalitis (5 with ovarian teratoma), review literature, and reinforce the gynecologist's knowledge of this disorder. Methods: Clinical data of 15 patients from January 2015 to December 2020 admitted to The Second Hospital of Hebei Medical University were collected and analyzed. The diagnosis of anti-NMDA receptor encephalitis was based on the presence of anti-NMDA receptor antibodies in cerebrospinal fluid (CSF) and/or serum. Laparoscopic teratoma removal was performed in patients with ovarian teratoma. All patients had received immunotherapy. In addition, a review of the literature was performed to reinforce the gynecologist's knowledge of this disorder. Results: A total of 15 patients with anti-NMDA receptor encephalitis were screened, of whom 5 patients were confirmed with ovarian teratoma by pathology. The most common symptoms of anti-NMDAR encephalitis with teratoma are fever (5/5, 100%), seizure (5/5, 100%), mental and behavioral disorders (4/5, 80%), and decreased consciousness (4/5, 80%). Conversely, the most common symptoms of patients without teratoma were neuropsychiatric symptoms, including headache (6/10, 60%) and mental and behavioral disorders (7/10, 70%). All patients underwent immunotherapy, including steroids, intravenous immunoglobulin (IVIG), plasma exchange, and cyclophosphamide, and 4 out of 5 patients with ovarian teratomas underwent surgical treatment. All patients had a good outcome after systemic, surgical, and immunotherapy treatment. No patient who underwent surgical treatment developed a recurrence. Conversely, 2 of 10 patients without teratoma developed an anti-NMDA receptor encephalitis recurrence. Conclusions: Patients with anti-NMDA encephalitis show severe mental and neurological symptoms. Resection of teratoma is beneficial to the relief or disappearance of symptoms and has a good prognosis. This disorder should be fully recognized by gynecologists, who play an important role in diagnosis and treatment.

Pterostilbene Protects the Optic Nerves and Retina in a Murine Model of Experimental Autoimmune Encephalomyelitis via Activation of SIRT1 Signaling.

Optic neuritis and retinal damage are common manifestations of multiple sclerosis (MS). Pterostilbene (PT) has been used to treat multiple diseases for its anti-inflammatory, anti-apoptosis and neuroprotective activities. This study aimed to investigate whether PT exerts a therapeutic effect on optic neuritis and retinal damage triggered by MS. Here, experimental autoimmune encephalomyelitis (EAE), an experimental model for MS, was induced in female C57BL/6 mice by immunizing with MOG35-55 peptide and treating with pertussis toxin. The mice were intraperitoneally injected with 20 mg/kg and 40 mg/kg PT once daily for 25 days at 24 h post immunization. We found that PT alleviated EAE severity and delayed EAE onset. Moreover, PT mitigated EAE-induced optic nerves and retinal inflammation, as indicated by the decreased Iba-1+ and GFAP+ cells and mRNA levels of interleukin-6, tumor necrosis factor-α and interleukin-1ß and the increased Iba-1+sirtuin 1 (SIRT1)+ and GFAP+SIRT1+ cells in the optic nerves and retina. PT also protected the optic nerves against demyelination and axonal loss and the retina against disorders in retinal morphology and apoptosis of retinal ganglion cells. High-dose PT had a more significant effect on protection of the optic nerves and retina in EAE than low-dose PT. In addition, PT activated SIRT1 signaling in the optic nerves and retina. Notably, EX-527, an inhibitor of SIRT1, reversed the effect of high-dose PT on the optic nerves and retina, indicating that PT exerted the protective effect via activating SIRT1 signaling. This study provides a potential candidate for treating MS.

Liraglutide attenuate central nervous inflammation and demyelination through AMPK and pyroptosis-related NLRP3 pathway.

AIMS: Multiple sclerosis (MS) still maintains increasing prevalence and poor prognosis, while glucagon-like peptide-1 receptor (GLP-1R) agonists show excellent neuroprotective capacities recently. Thus, we aim to evaluate whether the GLP-1R agonist liraglutide (Lira) could ameliorate central nervous system demyelination and inflammation. METHODS: The therapeutic effect of Lira was tested on experimental autoimmune encephalitis (EAE) in vivo and a microglia cell line BV2 in vitro. RESULTS: Lira administration could ameliorate the disease score of EAE mice, delay the disease onset, ameliorate pathological demyelination and inflammation score in lumbar spinal cord, reduce pathogenic T helper cell transcription in spleen, restore phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) level, autophagy level, and inhibit pyroptosis-related NLR family, pyrin domain-containing protein 3 (NLRP3) pathway in lumbar spinal cord. Additionally, cell viability test, lactate dehydrogenase release test, and dead/live cell staining test for BV2 cells showed Lira could not salvage BV2 from nigericin-induced pyroptosis significantly. CONCLUSION: Lira has anti-inflammation and anti-demyelination effect on EAE mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK pathway, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro. Our study provides Lira as a potential candidate for Multiple Sclerosis treatment.