Large bone defects are still a persistent challenge in orthopedics. The availability limitations and associated complications of autologous and allogeneic bone have prompted an increasing reliance on tissue engineering and regenerative medicine. In this study, we developed an injectable scaffold combining an acellular extracellular periosteal matrix hydrogel with poly(d,l-lactate-co-glycol-acetate) microspheres loaded with the E7 peptide and miR217 (miR217/E7@MP-GEL). Characterization of the composites included morphological analysis by scanning electron microscopy, degradation and swelling tests, in vitro and in vivo biological evaluation, and the biological activity evaluation of mesenchymal stem cells (MSCs) through their effects on cell recruitment, proliferation, and osteogenic differentiation. The designed hydrogels demonstrated good physical and chemical properties that are cytocompatible and suitable for cell recruitment. In vitro studies confirmed the high biological activity of the release agent, which markedly enhanced the proliferation and osteogenic differentiation of MSCs. In vivo application to a rat model of a femur defect exhibited a significant increase in bone volume and density over 7 weeks, resulting in enhanced bone regeneration. Acellular periosteum-based hydrogels combined with the E7 peptide and miR217-loaded poly(d,l-lactate-co-glycol-acetate) microspheres can promote effective bone regeneration through the recruitment, proliferation, and osteogenic differentiation of MSCs, which provides a promising approach for the treatment of large bone defects.

In the past decade, the use of green synthesis methods to prepare nanoparticles (NPs) has become a promising alternative to traditional chemical and physical methods. The synthesis of silver nanoparticles (AgNPs) using biological resources is not only simple, economical, and fast, but also environmentally friendly, effectively reducing energy consumption and pollution. This study developed an eco-friendly and non-toxic method for the green biosynthesis of AgNPs using Ginkgo biloba seed extract (GBSE), as a reducing and stabilizing agent. This method was optimized through single factor experiments and response surface methodology. The optimal reaction temperature, ratio, and time for GBSE-AgNPs were determined to be 94.725°C, 23.165 (v/v), and 235.890 min, respectively. The synthesized NPs with uniform distribution had a size of 17.95 ± 1.17 nm. The atomic percentage of Ag element is 19.87%, and the mass percentage is 65.53%. It has been proven that the Ag crystal structure of GBSE-AgNPs is face centered cubic, and the silver element is in a zero-valence state. Further research was conducted on the antibacterial properties of GBSE-AgNPs against Staphylococcus aureus and Escherichia coli and demonstrated good antibacterial performance. Meanwhile, the GBSE-AgNPs also exhibit excellent inhibitory ability against common pathogenic fungi (Aspergillus fumigatus, Aspergillus niger, Aspergillus flavus, and Penicillium marneffei). Compared with GBSE, GBSE-AgNPs possess better antioxidant potential. In addition, it has been also demonstrated that GBSE-AgNPs exhibit excellent inhibitory effects on gastric cancer cell line SGC-7901, causing apoptosis of SGC-7901. Therefore, the green synthesis and eco-friendly GBSE-AgNPs have significant antioxidant, antibacterial, antifungal, and anticancer properties, providing new possibilities for the widespread application of GBSE-AgNPs.

Skin infections present a major clinical challenge, as bacterial invasion and inflammation can complicate wound healing. Therefore, bacterial infections must be treated while the accompanying inflammation and oxidative stress are regulated. Owing to the ongoing global increase in bacterial resistance, in this study, hydrogel co-loaded with bio-antimicrobial peptides and copper ions is designed, which exhibits antimicrobial, anti-inflammatory, and antioxidant properties. the proposed, sodium alginate@copper hydrogel (SA@Cu) is formed through the cross-linking of sodium alginate and Cu2+. Melittin (MEL) is then loaded to prepare a SA@Cu-MEL hydrogel. We optimised the sodium alginate and Cu2+ and MEL concentrations in SA@Cu-MEL hydrogels using Response Surface Methodology method. The proposed SA@Cu-MEL hydrogel exhibits significant antibacterial activity against Staphylococcus aureus and Escherichia coli, as well as good mechanical properties, self-healing ability, and MEL slow-release behaviour. Additionally, the SA@Cu-MEL hydrogel reduces inflammatory responses, promotes macrophage polarisation to the anti-inflammatory M2 type, and facilitates NIH cell proliferation and migration. In rat models, SA@Cu-MEL significantly accelerated wound healing, enhancing angiogenesis and collagen deposition. The optimised hydrogel not only reduces MEL toxicity but also amplifies its antibacterial and anti-inflammatory effects. Therefore, the proposed hydrogel has promising potential application in the treatment of infected skin wounds.

Osteoarthritis (OA) has become a common degenerative joint disease, lacking clinical means to alleviate this disease. Melittin, taken from natural honeybee venom, possesses outstanding anti-inflammatory properties and has great potential to treat OA. However, its high toxicity and hemolytic properties limit its application. In this work, a biocompatible hydrogel was prepared from extracellular matrix (ECM) of rib cartilage, possessing fibrous mesh structure characteristics, which was beneficial for melittin loading. It was found that the use of ECM hydrogel loaded with melittin can reduce the intrinsic toxicity of melittin and prolong the release behavior, simultaneously. Thein vitrostudy demonstrated that melittin-hydrogel could effectively inhibit phosphorylation-ERK/JNK, prevent the exacerbation of TNF-α-induced apoptosis in ATDC5 cells, and reduce their inflammatory markers, effectively alleviating OA and preventing cartilage degradation. Subsequently,in vivostudies have demonstrated that injecting melittin-hydrogel into the joint cavity of OA mice can effectively reduce cartilage degeneration. These findings suggest that melittin-hydrogel plays a critical role in the development of OA and may provide a therapeutic option for the treatment of OA disease.

Objective: To assess whether systemic lupus erythematosus (SLE) may be genetically causally associated with migraine, including the two primary subtypes: migraine with aura (MWA) and migraine without aura (MWoA). Background: The association between SLE and migraine has been investigated extensively. Previous studies have shown a higher prevalence of migraine in patients with SLE, although the exact relationship remains unclear. This study investigated the potential causal association between SLE and migraine using the powerful analytical tool of Mendelian randomization (MR). Methods: We performed two-sample MR analysis of publicly available summary statistic datasets using inverse variance-weighted (IVW), weighted median, and MR-Egger methods based on an SLE genome-wide association study (GWAS; 5201 cases; 9066 controls; the exposure frequency is 36.5%) as an exposure and migraine GWAS (15,905 cases; 264,662 controls) in individuals with European ancestry as outcomes, focusing on the two migraine subtypes MWA (6780 cases; 264,662 controls) and MWoA (5787 cases; 264,662 controls). Thepleiotropy and heterogeneity were performed. Results: We selected 42 single-nucleotide polymorphisms from SLE GWAS as instrumental variables (IVs) for SLE on migraine, and 41 SNP IVs for SLE on MWA or MWoA. The IVW (odds ratio [OR] = 1.01, 95% confidence interval [CI] = [0.99, 1.03], p = 0.271), weighted median (OR = 1.00, 95% CI = [0.97, 1.03], p = 0.914), and MR-Egger (OR = 1.04, 95% CI = [0.99, 1.09], p = 0.153) methods showed no causal effect of SLE on migraine. A causal effect of SLE was observed on MWA (IVW: OR = 1.05, 95% CI = [1.02, 1.08], p = 0.001; weighted median: OR = 1.05, 95% CI = [1.01, 1.10], p = 0.018; MR-Egger: OR = 1.07, 95% CI = [1.01, 1.14], p = 0.035 and p(IVW) < 0.017 [Bonferroni correction]) but not MWoA (IVW: OR = 0.99, 95% CI = [0.96, 1.02], p = 0.331; weighted median: OR = 0.98, 95% CI = [0.94, 1.03], p = 0.496; MR-Egger: OR = 1.02, 95% CI = [0.95, 1.09], p = 0.652). The results showed no significant pleiotropy or heterogeneity. Conclusion: Our MR analysis demonstrated the complex relationship between SLE and migraine, suggesting a potential effect of SLE on the risk of MWA but not MWoA. These findings can aid in the development of improved subtype-specific management of migraine in patients with SLE.

BACKGROUND Tibial avulsion fractures of the posterior cruciate ligament (PCL) are challenging to treat and compromise knee stability and function. Traditional open surgery often requires extensive soft tissue dissection, which may increase the risk of morbidity. In response to these concerns, arthroscopic techniques have been evolving. The aim of this study was to introduce a modified arthroscopic technique utilizing an M-shaped suture fixation method for the treatment of tibial avulsion fractures of the PCL and to evaluate its outcomes through a case series. AIM To evaluate the effects of arthroscopic M-shaped suture fixation on treating tibia avulsion fractures of the PCL. METHODS We developed a modified arthroscopic M-shaped suture fixation technique for tibia avulsion fractures of the PCL. This case series included 18 patients who underwent the procedure between January 2021 and December 2022. The patients were assessed for range of motion (ROM), Lysholm score and International knee documentation committee (IKDC) score. Postoperative complications were also recorded. RESULTS The patients were followed for a mean of 13.83 ± 2.33 months. All patients showed radiographic union. At the final follow-up, all patients had full ROM and a negative posterior drawer test. The mean Lysholm score significantly improved from 45.28 ± 8.92 preoperatively to 91.83 ± 4.18 at the final follow-up (P < 0.001), and the mean IKDC score improved from 41.98 ± 6.06 preoperatively to 90.89 ± 5.32 at the final follow-up (P < 0.001). CONCLUSION The modified arthroscopic M-shaped suture fixation technique is a reliable and effective treatment for tibia avulsion fractures of the PCL, with excellent fracture healing and functional recovery.

Background Systemic Lupus Erythematosus (SLE) and Osteoporosis are two prevalent medical conditions. Previous studies have suggested a possible correlation between SLE and osteoporosis, though the underpinning causal relationship remains largely unknown. The current study aimed to elucidate the causal association between SLE and osteoporosis by employing a Mendelian randomization (MR) approach. Methods We performed two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger methods on publicly available summary statistics datasets using a SLE genome-wide association study (GWAS) as an exposure and osteoporosis GWASs in people with East Asia ancestry as outcomes. The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, and the Cochran's Q test. Results We selected 26 single-nucleotide polymorphisms from a SLE GWAS as instrumental variables for osteoporosis. The IVW (p < 0.05) method results support a potential association between SLE and osteoporosis. MR-Egger intercept (p = 0.82) and MR-PRESSO global test (p = 0.80) did not suggest evidence of horizontal or directional pleiotropy. Cochran's Q test (p = 0.78) showed that there was no heterogeneity between IVs. Conclusion The results of MR analysis indicated that SLE is likely associated with an increased risk of osteoporosis incidence. Our findings highlight the need for increased awareness the potential risk of osteoporosis among SLE patients.

The treatment of infectious bone defects has become a troublesome issue in orthopedics. The disease requires effective anti-infective and bone-reconstruction therapeutic functionalities. In this study, we prepared a novel antibacterial material (vancomycin-impregnated periosteal extracellular matrix [Van-PEM]) by embedding vancomycin in a periosteal extracellular matrix (PEM)-derived hydrogel via physical stirring for the treatment of infectious bone defects. The microstructure, porosity, degradation, and release properties of this antibacterial hydrogel were characterized. The in vitro hemolytic reaction, cytotoxicity, osteogenic ability, and antibacterial properties were also carefully studied. The results showed that the Van-PEM hydrogel possessed a fibrous network structure with high porosity. Moreover, the hydrogel demonstrated slow degradation in vitro and could release vancomycin for at least 1 week. The hydrogel showed no cytotoxicity and possessed good biocompatibility with blood cells. It also promoted osteogenesis and exerted a significant bactericidal effect. Subsequently, the anti-infection and bone-healing abilities of the antibacterial hydrogel were investigated in a rat model of infectious calvarial defects, and the infectious skull defect was successfully cured in vivo. Therefore, Van-PEM hydrogels may represent a promising therapeutic approach for treating infectious bone defects.

Abstract Background The reconstruction of tendons with large defects requires grafts with high mechanical strength and is often hindered by complications such as infection and adhesion. Hence, grafts combining the advantages of mechanical resilience and antibacterial/antiadhesion activity are highly sought after. Methods The silver nanoparticles (GA-Ag NPs) synthesized from gallic acid and silver nitrate were attached to a decellularized extracellular matrix (Decellularized Tendon crosslinking GA-AgNPs, DT-Ag). We examined the histological structure, mechanical property, morphology, Zeta potential, cytotoxicity, antibacterial properties, antioxidant and anti-inflammatory properties, and ability of the DT-Ag to treat tendon defects in animals. Results Approximately 108.57 ± 0.94 μg GA-Ag NPs loaded per 50 mg DT, the cross-linked part of GA-Ag NPs was 65.47 ± 0.57%, which provided DT-Ag with long-lasting antibacterial activity. Meanwhile, GA endowed DT-Ag with good antioxidant and anti-inflammatory activities. Additionally, The DT-Ag facilitated M2 macrophage polarization, and suppressed fibrin deposition by hindering fibroblast adhesion. Mormore, the main advantages of DT-Ag, namely its long-lasting antibacterial activity (tested using Escherichia coli and Staphylococcus aureus as models) and the ability to prevent tissue adhesion were confirmed in vivo. Conclusion The fabricated multifunctional tendon graft was highly hydrophilic, biocompatible, and mechanically resilient, and concluded to be well suited for dealing with the main complications of surgical tendon reconstruction and has bright application prospects. Graphical Abstract

Background We compared the clinical efficacy of mini-open reduction and autologous bone grafting ( G M ) and closed reduction ( G C ) using intramedullary nailing for the treatment of tibial shaft fractures. Methods This retrospective study included 70 tibial shaft fractures treated with G M or G C between January 2018 and December 2021. The demographic characteristics and clinical outcomes were compared between the two treatment methods. Results This study included 70 patients who were followed-up for 12.4 months. In total, 31 and 39 patients were treated with G M and G C , respectively. The operative duration was significantly shorter for G M (95.2 ± 19.3 min) than for G C (105.5 ± 22.2 min, p = 0.0454). The number of radiation times was significantly lower for G M (14.7 ± 6.3) than for G C (22.2 ± 9.2, p < 0.005). There were no statistically significant differences between the groups in terms of the wound complication or infection rates. The malunion and nonunion rates were high after G C than after G M , but there are no significant differences between the groups. Conclusions Closed reduction and intramedullary nailing remains the first choice for tibial shaft fractures. G M is a safe and effective treatment worth considering. Future prospective randomized controlled trials are warranted.

MicroRNAs (miRNAs) are regulatory small noncoding RNAs that play a key role in several types of cancer. It has been reported that miR-331-3p is involved in the development and progression of various cancers, but there are few reports regarding osteosarcoma (OS). The public GEO database was used to analyze the survival difference of miR-331-3p in OS organizations. The level of cell proliferation assay was assessed by CCK-8 and colony formation. First, transwell and wound-healing assays were used to detect the transfer and invasion ability of miR-331-3p in OS. Second, TargetScan, miRDBmiR, TarBase, and dual-luciferase reporter gene assays were used to determine SOCS1 as a targeted regulator. Third, Western blot and immunohistochemistry were used to detect the expression of protein levels. Finally, a mouse model of subcutaneously transplantable tumors is used to evaluate the proliferation of OS in vivo. The low expression of miR-331-3p was negatively correlated with the overall survival of OS patients. Overexpression of miR-331-3p significantly inhibited cell proliferation, metastasis, and invasion. Moreover, miR-331-3p affected the occurrence and development of osteosarcoma by targeting the SOCS1/JAK2/STAT3 signaling pathway. Therefore, miR-331-3p reduces the expression of SOCS1 by combining with its 3′UTR, thereby activating the JAK2/STAT3 signaling pathway to regulate the progression of OS. This provides a new theoretical basis for the treatment of osteosarcoma.

Background Osteosarcoma (OS) has become one of the highest mortality cancers in the world due to its late diagnosis, rapid metastasis and rapid recurrence. MicroRNAs can regulate a variety of signaling pathwas involved in cancer development, such as cell proliferation, apoptosis and migration. Objective In this study, we studied the biological effects and molecular regulation of mir-23b-5p on human osteosarcoma cells. Methods The proliferation of mir-23b-5p in osteosarcoma was measured by CCK8 method and EDU method. In addition, the target population was screened through the database, and the luciferase reporter gene was used to determine the association between miRNA and target gene TMEM127. We verified this result by Western blot. Results We found that mir-23b-5p promotes the progression of osteosarcoma by regulating TMEM127. Conclusions The results of this study show that mir-23b-5p affects the proliferation, metastasis and invasion of OS by targeting TMEM127.

A 17-year-old man with recurrent abdominal pain for 8 years was diagnosed with Crohn's disease (CD) with perforation. After surgery, the patient's abdominal pain persisted despite treatment with azathioprine, adalimumab, and infliximab. Laboratory testing revealed a positive fecal occult blood test, markedly elevated fecal calprotectin (698 µg/g) and slightly elevated plasma C-reactive protein (CRP) level (8.5 mg/L). Colonoscopy showed an anastomotic ulcer and stricture. The patient was treated with an intravenous infusion of cyclophosphamide and oral thalidomide. After 6 months, his abdominal pain had disappeared and the inflammatory markers had returned to normal. Colonoscopy showed the anastomotic ulcer had disappeared but the stricture had worsened. Thalidomide therapy was maintained; however, after another 6 months, the patient again experienced abdominal pain and his inflammatory markers were significantly elevated (CRP 14 mg/L, fecal calprotectin 1376 µg/g). Computed tomographic enterography (CTE) showed the anastomotic stricture and thickened bowel wall without a fistula.

Background Hydrogels loaded with antimicrobial agents have been widely used for treating infected wound defects. However, hydrogels derived from a porcine dermal extracellular matrix (PADM), containing silver nanoparticles (AgNPs), have not yet been studied. Therefore, we investigated the therapeutic effect of an AgNP-impregnated PADM (AgNP-PADM) hydrogel on the treatment of infected wounds. Methods An AgNP-PADM hydrogel was synthesized by embedding AgNPs into a PADM hydrogel. We examined the porosity, moisture retention, degradation, antibacterial properties, cytotoxicity, antioxidant properties, and ability of the PADM and AgNP-PADM hydrogels to treat infected wounds in animals. Results The PADM and AgNP-PADM hydrogels were pH sensitive, which made them flow dynamically and solidify under acidic and neutral conditions, respectively. The hydrogels also exhibited porous network structures, satisfactory moisture retention, and slow degradation. Additionally, the AgNP-PADM hydrogel showed a slow and sustained release of AgNPs for at least 7 days without the particle size changing. Thus, the AgNPs exhibited adequate antibacterial ability, negligible toxicity, and antioxidant properties in vitro. Moreover, the AgNP-PADM hydrogel promoted angiogenesis and healed infected skin defects in vivo. Conclusions The AgNP-PADM hydrogel is a promising bioderived antibacterial material for clinical application to infected wound dressings.

BACKGROUND Guillain-Barré syndrome (GBS) is a rare disorder that typically presents with ascending weakness, pain, paraesthesias, and numbness, which mimic the findings in lumbar spinal stenosis. Here, we report a case of severe lumbar spinal stenosis combined with GBS. CASE SUMMARY A 70-year-old man with a history of lumbar spinal stenosis presented to our emergency department with severe lower back pain and lower extremity numbness. Magnetic resonance imaging confirmed the diagnosis of severe lumbar spinal stenosis. However, his symptoms did not improve postoperatively and he developed dysphagia and upper extremity numbness. An electromyogram was performed. Based on his symptoms, physical examination, and electromyogram, he was diagnosed with GBS. After 5 d of intravenous immunoglobulin (0.4 g/kg/d for 5 d) therapy, he gained 4/5 of strength in his upper and lower extremities and denied paraesthesias. He had regained 5/5 of strength in his extremities when he was discharged and had no symptoms during follow-up. CONCLUSION GBS should be considered in the differential diagnosis of spinal disorder, even though magnetic resonance imaging shows severe lumbar spinal stenosis. This case highlights the importance of a careful diagnosis when a patient has a history of a disease and comes to the hospital with the same or similar symptoms.

Dehuai Zeng, Shenzhen University, China Qihai Zhou, Southwestern University of Finance and Economics, China Yongjun Chen, Guangdong University of Business Studies, China Luo Qi, Wuhan Institute of Technology, China Zhihua Zhang, Wuhan Institute of Physical Education China Yong Ma, Wuhan Institute of Physical Education China Zhenghong Wu, East China Normal University, China Chen Jing, Wuhan University of Technology, China Xiang Kui, Wuhan University of Technology, China Li Zhijun, Wuhan University of Technology, China Zhang Suwen, Wuhan University of Technology, China Shufang Li, Beijing University, China Tianshu Zhou, George Mason University, USA Bing Wu, Loughborough University, UK Huawen Wang, Wuhan University, China Zhihai Wang, Beijing Jiaotong University, China Ronghuai Huang, Beijing Normal University, China Xiaogong Yin, Wuhan University, China Jiaqing Wu, Guangdong University of Business Studies, China Xiaochun Cheng, Middlesex University, UK Jia Luo, Wuhan University of Science and Technology Zhongnan Branch, China Toshio Okamoto, University of Electro-Communications, Japan Kurt Squire, University of Wisconsin-Madison, USA Xianzhi Tian, Wuhan University of Science and Technology Zhongnan Branch, China Alfredo Tirado-Ramos, University of Amsterdam, Amsterdam Bing Wu, Loughborough University, UK Yanwen Wu, Central China Normal University, China Harrison Hao Yang, State University of New York at Oswego, USA Dehuai Zeng, Shenzhen University, China Weitao Zheng, Wuhan University of Technology, China Qihai Zhou, Southwestern University of Finance and Economics, China Tianshu Zhou, George Mason University, USA Shao Xi, Nanjing University of Posts and Telecommunication, China Xueming Zhang, Beijing Normal University, China Peide Liu, Shandong Economic University, China Qian Yin, Beijing Normal University, China Zhigang Chen, Central South University, China