Harnessing GMNP-loaded BMSC-derived EVs to target miR-3064-5p via MEG3 overexpression: Implications for diabetic osteoporosis therapy in rats.

Diabetic osteoporosis (DO) is a significant complication of diabetes, characterized by a decrease in bone mineral density and an increase in fracture risk. Magnetic nanoparticles (GMNPs) have emerged as potential drug carriers for various therapeutic applications. This study investigated the molecular mechanism of GMNPs loaded with bone marrow mesenchymal stem cell (BMSC) derived extracellular vesicles (EVs) overexpressing MEG3 target miR-3064-5p to induce NR4A3 for treating DO in rats. Initial analysis was carried out on GEO datasets GSE7158 and GSE62589, revealing a notable downregulation of NR4A3 in osteoporotic samples. Subsequent in vitro studies demonstrated the effective uptake of BMSC-EVs-MEG3 by osteoblasts and its potential to inhibit miR-3064-5p, activating the PINK1/Parkin signaling pathway and thus promoting mitochondrial autophagy, osteoblast proliferation, and differentiation. In vivo, experiments using DO rat models further substantiated the therapeutic efficacy of GMNPE-EVs-MEG3 in alleviating osteoporosis symptoms. In conclusion, GMNPs loaded with BMSC-EVs, through the delivery of MEG3 targeting miR-3064-5p, can effectively promote NR4A3 expression, activate the PINK1/Parkin pathway, and thereby enhance osteoblast proliferation and differentiation, offering a promising treatment for DO.

[Early effectiveness of Ti-Robot assisted femoral neck system for minimally invasive treatment of elderly Garden type â ¡ and â ¢ femoral neck fractures].

Objective: To investigate the early effectiveness of the Ti-Robot assisted femoral neck system (FNS) in the treatment of elderly Garden type Ⅱ and Ⅲ femoral neck fractures. Methods: A retrospective analysis was conducted on the clinical data of 41 elderly patients with Garden type Ⅱ and Ⅲ femoral neck fractures who were admitted between December 2019 and August 2022 and met the selection criteria. Among them, 21 cases were treated with Ti-Robot assisted FNS internal fixation (study group), and 20 cases were treated solely with FNS internal fixation (control group). There was no significant difference in baseline data, including gender, age, side, cause of injury, time from injury to surgery, fracture Garden classification, and fracture line classification, between the two groups ( P>0.05). Surgical effectiveness was evaluated based on parameters such as operation time (including incision time and total operation time), reduction level, number of dominant pin insertions, intraoperative fluoroscopy frequency, incision length, whether to extend the incision, need for assisted reduction, postoperative hospital stay, fracture healing time, incidence of osteonecrosis of the femoral head, postoperative visual analogue scale (VAS) score at 1 day, and Harris hip score at last follow-up. Results: The study group showed significantly shorter incision time, fewer dominant pin insertions, fewer instances of extended incisions, fewer intraoperative fluoroscopy frequency, and smaller incisions than the control group ( P<0.05). There was no significant difference in total operation time, reduction level, and assisted reduction frequency between the two groups ( P>0.05). Both groups achieved primary wound healing postoperatively, with no complications such as incision leakage or skin infection. All patients were followed up 12-24 months with an average of 14.6 months. Fractures healed in both groups, with no significant difference in healing time ( P>0.05). There was no significant difference in postoperative hospital stay between the two groups ( P>0.05). The study group showed significantly better VAS score at 1 day after operation and Harris hip score at last follow-up when compared to the control group ( P<0.05). No complication such as internal fixation failure, fracture displacement, or hip joint varus occurred in both groups during the follow-up. Osteonecrosis of the femoral head occurred in 1 patient of the control group, while no was observed in the study group, and the difference in the incidence of osteonecrosis of the femoral head between the two groups was not significant ( P=0.488). Conclusion: Compared to sole FNS internal fixation treatment, Ti-Robot assisted FNS internal fixation for elderly Garden typeⅡ and Ⅲ femoral neck fractures can reduce incision time, achieve minimally invasive and accurate nail implantation, and decrease intraoperative fluoroscopy frequency, leading to improved postoperative hip joint function recovery.

Clinical study of modified INFIX combined with sacroiliac joint screws for pelvic instable injuries.

OBJECTIVE: The INFIX technique is becoming one of the most commonly performed surgical procedures for anterior pelvic ring instability injuries. The purpose of this article is to compare the clinical outcomes of modified anterior subcutaneous internal fixation (M-INFIX) with conventional anterior subcutaneous internal fixation (C-INFIX) for anterior pelvic ring instability injuries. PATIENTS AND METHODS: A retrospective analysis of 36 cases of unstable pelvic injuries treated operatively at our institution, 20 of which were treated with C-INFIX and 16 with M-INFIX. Data collected included age, gender, ISS score, fracture typing, operative time, operative bleeding, postoperative complications, fracture healing time, Matta score, Majeed score, and follow-up time. Statistical sub-folding of each variable between the two groups was performed. RESULTS: There was no statistical difference between the C-INFIX and M-INFIX groups in terms of age, gender, ISS (Injury Severity Score), follow-up time, fracture typing, fracture healing time, and Majeed score (P > 0.05). the M-INFIX had a significantly lower incidence of postoperative complications than the C-INFIX group, especially in the incidence of Lateral femoral cutaneous nerve (LFCN) injury (P < 0.05). In contrast, the M-INFIX group had statistically higher operative time, intraoperative bleeding, and Matta score than the C-INFIX group (P < 0.05). CONCLUSION: This study was based on a modified application of the surgical experience with C-INFIX and showed better clinical outcomes in terms of complication rates and quality of repositioning than the conventional surgical approach. These findings indicate that further analytical studies of this study would be valuable.

[Application and research progress of artificial intelligence technology in trauma treatment].

Objective: To review the application and research progress of artificial intelligence (AI) technology in trauma treatment. Methods: The recent research literature on the application of AI and related technologies in trauma treatment was reviewed and summarized in terms of prehospital assistance, in-hospital emergency care, and post-traumatic stress disorder risk regression prediction, meanwhile, the development trend of AI technology in trauma treatment were outlooked. Results: The AI technology can rapidly analyze and manage large amount of clinical data to help doctors identify patients' situation of trauma and predict the risk of possible complications more accurately. The application of AI technology in surgical assistance and robotic operations can achieve precise surgical plan and treatment, reduce surgical risks, and shorten the operation time, so as to improve the efficiency and long-term effectiveness of the trauma treatment. Conclusion: There is a promising future for the application of AI technology in the trauma treatment. However, it is still in the stage of exploration and development, and there are many difficulties of historical data bias, application condition limitations, as well as ethical and moral issues need to be solved.

[Study on application of ultrasonic bone curette in anterior cervical spine surgery].

Objective: To investigate the effect of ultrasonic bone curette in anterior cervical spine surgery. Methods: A clinical data of 63 patients with cervical spondylosis who were admitted between September 2019 and June 2021 and met the selection criteria was retrospectively analyzed. Among them, 32 cases were operated with conventional instruments (group A) and 31 cases with ultrasonic bone curette (group B). There was no significant difference between the two groups (P>0.05) in gender, age, surgical procedure, surgical segment and number of occupied cervical space, disease type and duration, comorbidities, and preoperative Japanese Orthopaedic Association (JOA) score, cervical dysfunction index (NDI), and pain visual analogue scale (VAS) score. The operation time, intraoperative bleeding, postoperative drainage, postoperative hospital stay, and the occurrence of postoperative complications were recorded in both groups. Before operation and at 1, 3, and 6 months after operation, the JOA score and NDI were used to evaluate the function and the postoperative JOA improvement rate was calculated, and VAS score was used to evaluate the pain improvement. The anteroposterior and lateral cervical X-ray films were taken at 1, 3, and 6 months after operation to observe whether there was any significant loosening and displacement of internal fixators. Results: Compared with group A, group B had shorter operation time and postoperative hospital stay, less intraoperative bleeding and postoperative drainage, and the differences were significant (P<0.05). All incisions healed by first intention in the two groups, and postoperative complications occurred in 5 cases (15.6%) in group A and 2 cases (6.5%) in group B, showing no significant difference (P>0.05). All patients were followed up 6-12 months (mean, 7.9 months). The JOA score and improvement rate gradually increased in groups A and B after operation, while the VAS score and NDI gradually decreased. There was no significant difference in VAS score between 3 months and 1 month in group B (P>0.05), and there were significant differences between the other time points of each indicator in the two groups (P<0.05). At 1, 3, and 6 months after operation, the JOA score and improvement rate in group B were better than those in group A (P<0.05). X-ray films examination showed that there was no screw loosening or titanium plate displacement in the two groups after operation, and the intervertebral cage or titanium mesh significantly sank. Conclusion: Compared with traditional instruments, the use of ultrasonic bone curette assisted osteotomy in anterior cervical spine surgery has the advantages of shorter operation time, less intraoperative bleeding, less postoperative drainage, and shorter hospital stay.

Disc regeneration by injectable fucoidan-methacrylated dextran hydrogels through mechanical transduction and macrophage immunomodulation.

Modulating a favorable inflammatory microenvironment that facilitates the recovery of degenerated discs is a key strategy in the treatment of intervertebral disc (IVD) degeneration (IDD). More interestingly, well-mechanized tissue-engineered scaffolds have been proven in recent years to be capable of sensing mechanical transduction to enhance the proliferation and activation of nucleus pulposus cells (NPC) and have demonstrated an increased potential in the treatment and recovery of degenerative discs. Additionally, existing surgical procedures may not be suitable for IDD treatment, warranting the requirement of new regenerative therapies for the restoration of disc structure and function. In this study, a light-sensitive injectable polysaccharide composite hydrogel with excellent mechanical properties was prepared using dextrose methacrylate (DexMA) and fucoidan with inflammation-modulating properties. Through numerous in vivo experiments, it was shown that the co-culture of this composite hydrogel with interleukin-1ß-stimulated NPCs was able to promote cell proliferation whilst preventing inflammation. Additionally, activation of the caveolin1-yes-associated protein (CAV1-YAP) mechanotransduction axis promoted extracellular matrix (ECM) metabolism and thus jointly promoted IVD regeneration. After injection into an IDD rat model, the composite hydrogel inhibited the local inflammatory response by inducing macrophage M2 polarization and gradually reducing the ECM degradation. In this study, we propose a fucoidan-DexMA composite hydrogel, which provides an attractive approach for IVD regeneration.

The effect of virtual reality technology on anti-fall ability and bone mineral density of the elderly with osteoporosis in an elderly care institution.

OBJECTIVE: To explore the impact of virtual reality (VR) training on anti-fall ability and bone mineral density (BMD) among elderly patients admitted to a healthcare institution. METHODS: People (aged 50) with osteoporosis in an elderly care institution in Anhui Province June 2020 to October 2021 were selected and randomly divided into VR group (n = 25) and control group (n = 25). In VR group, the virtual reality rehabilitation training system was used for training, while control group was treated with traditional fall prevention exercise intervention. The changes of Berg Balance Scale (BBS), timed up and go test (TUGT), functional gait assessment (FGA), bone mineral density (BMD) and falls during 12 months of training were compared between the two groups. RESULTS: BBS and FGA were positively correlated with BMD of the lumbar vertebrae and femoral neck, and TUGT was negatively correlated with BMD of the lumbar vertebrae and femoral neck. After 12 months of training, the BBS score, TUGT evaluation and FGA evaluation of the two groups were significantly improved compared with those prior to training (P < 0.05). However, there was no significant difference in the lumbar spine and femoral neck BMD between the two groups 6 months after the intervention. The femoral neck and lumbar spine BMD of the VR group improved, and it was significantly higher than that of the control group 12 months after the intervention. Nevertheless, there was no significant difference in terms of the incidence of adverse events between the two groups. CONCLUSION: VR training can improve anti-fall ability and increase femoral neck and lumbar spine BMD and can effectively prevent and reduce the risk of injury among elderly people with osteoporosis.

Combined pelvic and acetabular injuries: clinical features and treatment strategies of a unique injury pattern.

BACKGROUND: To explore the clinical characteristics of patients with unstable pelvic fractures combined with acetabular fractures and to discuss the treatment strategies for such patients to help guide treatment. METHODS: We retrospectively assessed 24 patients admitted to our hospital from June 2018 to June 2022 with unstable pelvic fractures combined with acetabular fractures, including 15 male patients and 9 female patients with a mean age of 44.8 years. According to the Tile pelvic fracture classification, 15 cases were type B, and 9 cases were type C. The acetabular fractures were classified using the Letournel-Judet classification. There were 8 transverse fractures, 4 transverse and posterior wall fractures, 3 anterior and posterior hemitransverse fractures, 6 both-column fractures, 2 T-shaped fractures and 1 anterior column fracture. We recorded the cause of the patient's injury and vital signs on admission and assessed the patient's treatment strategy and prognosis. RESULTS: All patients completed the surgery successfully, and the follow-up ranged from 6 to 42 months, with a mean of 23 months. The healing time for pelvic fractures ranged from 11 to 21 weeks, with a mean of 14.8 weeks, and the postoperative displacement of the posterior pelvic ring ranged from 1.2 to 9.0 mm, with a mean of 3.5 mm. The final clinical outcome at follow-up was evaluated using the Majeed scale: excellent in 11 cases, good in 10 cases and fair in 3 cases; the excellent rate was 87.5%. The time to healing of the acetabular fracture ranged from 13 to 25 weeks, with a mean of 15.9 weeks, and the postoperative displacement of the acetabular fracture ranged from 0.6 to 5.2 mm, with a mean of 1.9 mm. Hip function was assessed at the final follow-up using a modified Merle D' Aubigné and Postel scale: there were 9 excellent, 11 good and 4 acceptable scores; an excellent rate of 83.3% was achieved. CONCLUSION: Patients with unstable pelvic fractures combined with acetabular fractures suffer severe trauma and complex mechanisms of injury. Treatment needs to be individualized, taking into account the patient's physiological status, fracture classification and degree of displacement.

The impact of Allgower-Donati suture pattern and postoperative sweet foods on wound suture breakage in experimental rats.

Background: Wound gnawing and/or scratching in rats often occurs in experimental models, causing suture breakage and wound dehiscence, and consequently affecting experimental results and wasting resources. This study aimed to investigate the impact of the combined postoperative use of the Allgower-Donati (A-D) suture pattern and sweet foods on suture breakage, inflammation, and healing in wounds. Materials and methods: Sprague Dawley (SD) rats (n = 48) were treated for linear wounds on the back by four procedures: simple suture, simple suture with postoperative sweet foods, A-D suture, and A-D suture with postoperative sweet foods. Additionally, CD68 immunofluorescence and CD31 immunohistochemistry were used to analyze wound inflammation and vascularization, respectively, on postoperative day 7. Sirius red staining was used to assess collagen deposition on postoperative day 14. Results: Gnawing and scratching of wound sutures were significantly reduced in treated rats (P < 0.01). Neovascularization and collagen deposition were significantly increased (P < 0.001), and inflammatory responses were significantly reduced (P < 0.001) in animals receiving AD sutures and postoperative sweet foods. CD31/CD68 analyses showed that A-D suture and postoperative sweet foods regulated wound angiogenesis and attenuated wound inflammation. Conclusions: Sweet food provision after A-D suture union surgery could reduce wound gnawing and/or scratching, suture breakage, incisional dehiscence, wound inflammation, and promote wound healing in rats.

A comparison of functional and radiological outcome of combine compression antegrade intertrochanteric nail (InterTan) and proximal femoral nail anti-rotation II (PFNA-II) in elderly patients with intertrochanteric fractures.

Objective: To compare the functional and radiological outcome of combine compression interlocking intramedullary nail (InterTan) and proximal femoral nail anti-rotation II (PFNA-II) in the treatment of elderly patients with intertrochanteric fractures. Methods: As a retrospective cohort study, records of 88 patients with intertrochanteric fractures treated in our hospital from January 1st, 2019 to July 31st, 2021 were retrospectively reviewed. According to treatment records, it included 45 patients treated with InterTan (Group-A) and 43 patients treated with PFNA-II (Group-B). The operation safety and functional rehabilitation of the two groups were compared and analyzed. Results: This study included 88 patients with intertrochanteric fractures (mean [SD] age, 68.72 [0.10] years at baseline), of whom 52 (59.09%) were males and 36 (40.91%) were females. Operation time and intraoperative blood loss in Group-B were less than Group-A, while fracture healing time was shorter in Group-A. The fracture separation distance was measured four weeks after the operation. The widening rate of the fracture line in Group-A was lower than Group-B (4.4% vs.18.6%; P<0.05). The incidence of complications in Group-A was lower than Group-B (4.4% vs.18.6%; P<0.05). At three, six and twelve months after the operation, the Harris hip score of the two groups was higher than at discharge (P<0.05), with no significant difference between groups (P>0.05). Conclusions: We found no significant difference in the functional outcome in elderly patients with intertrochanteric fractures treated with InterTan and PFNA-II. Early fracture healing and reduced complication rate however has been noted with InterTan.

Extracellular vesicles derived from bone marrow mesenchymal stem cells loaded on magnetic nanoparticles delay the progression of diabetic osteoporosis via delivery of miR-150-5p.

Extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) are emerged as carriers of therapeutic targets against bone disorders, yet its isolation and purification are limited with recent techniques. Magnetic nanoparticles (MNPs) can load EVs with a unique targeted drug delivery system. We constructed gold-coated magnetic nanoparticles (GMNPs) by decorating the surface of the Fe3O4@SiO2 core and a silica shell with poly(ethylene glycol) (PEG)-aldehyde (CHO) and examined the role of BMSC-EVs loaded on GMNPs in diabetic osteoporosis (DO). The osteoporosis-related differentially expressed miR-150-5p was singled out by microarray analysis. DO models were then established in Sprague-Dawley rats by streptozotocin injection, where poor expression of miR-150-5p was validated in the bone tissues. Next, GMNPE was prepared by combining GMNPs with anti-CD63, after which osteoblasts were co-cultured with the GMNPE-BMSC-EVs. The re-expression of miR-150-5p facilitated osteogenesis in osteoblasts. GMNPE could promote the enrichment of EVs in the bone tissues of DO rats. BMSC-EVs delivered miR-150-5p to osteoblasts, where miR-150-5p targeted MMP14 and consequently activated Wnt/ß-catenin pathway. This effect contributed to the enhancement of osteoblast proliferation and maturation. Furthermore, GMNPE enhanced the EV-based delivery of miR-150-5p to regulate the MMP14/Wnt/ß-catenin axis, resulting in promotion of osteogenesis. Overall, our findings suggest the potential of GMNP-BMSC-EVs to strengthen osteoblast proliferation and maturation in DO, showing promise as an appealing drug delivery strategy against DO. 1. GMNPs-BMSCs-EVs-miR-150-5p promotes the osteogenesis of DO rats. 2. miR-150-5p induces osteoblast proliferation and maturation by targeting MMP14. 3. Inhibition of MMP14 activates Wnt/ß-catenin and increases osteogenesis. 4. miR-150-5p activates the Wnt/ß-catenin pathway by downregulating MMP14.

[Modified internal fixator combined with sacroiliac screws in treatment of Tile C1.3 pelvic fracture].

Objective: To investigate the effectiveness of modified internal fixator (INFIX) to fix the anterior pelvic ring for Tile C1.3 pelvic fracture by comparing with the traditional INFIX. Methods: The patients with Tile C1.3 pelvic fractures admitted between April 2018 and June 2021 were taken as the study objects. Of them, 55 cases were included in the study according to the selection criteria. During operation, the anterior pelvic ring was fixed with the modified INFIX in 30 cases (modified group) and with the traditional INFIX in 25 cases (control group). The posterior pelvic ring in 55 cases was fixed with sacroiliac screws. There was no significant difference between the two groups in gender, age, cause of injury, time from injury to operation, and combined injury ( P>0.05). The operation time, intraoperative blood loss, and complications were recorded and compared between the two groups. The X-ray film was taken to evaluate the reduction of the anterior pelvic ring after operation, grade the reduction according to the Matta scoring standards, and observe the fracture healing and healing time. The function was evaluated according to Majeed scoring standards during follow-up. Results: The operation time of the modified group was significantly longer than that of the control group ( Z=-3.837, P<0.001), but there was no significant difference in the intraoperative blood loss between the two groups ( t=-1.831, P=0.076). All patients were followed up 12-18 months (mean, 14 months). X-ray film reexamination showed that the excellent and good rate of Matta scoring for anterior pelvic ring reduction in the modified group was 88.00%, which was significantly better than that in the control group (63.33%) ( χ 2=4.373, P=0.037). All fractures healed, and the fracture healing time of the modified group and the control group was (12.04±3.59) and (14.83±4.83) weeks respectively, with a significant difference ( t=2.401, P=0.020). At last follow-up, the excellent and good rates of Majeed scoring were 80.00% in the modified group and 76.67% in the control group, with no significant difference ( χ 2=0.089, P=0.766). In the modified group, 2 cases (8%) had complications, all of which were incision infection above pubic symphysis. In the control group, 9 cases (30%) had complications, including 5 cases of lateral femoral cutaneous nerve injury, 2 cases of femoral nerve paralysis, and 2 cases of delayed fracture healing. The incidence of complications was significantly lower in the modified group than in the control group ( χ 2=4.125, P=0.042). Conclusion: Compared with the traditional INFIX, the modified INFIX to fix the anterior pelvic ring for Tile C1.3 pelvic fracture has fewer complications, better stability, shorter fracture healing time, and lower risk of nerve injury.

3D PRINTING APPLICATION IN BONE DEFECT AREA MEASUREMENT ON PATIENTS WITH DEVELOPMENTAL DYSPLASIA OF THE HIP.

Objectives: Evaluate the application value of 3D printing technology in measuring acetabular bone defect area in adult patients diagnosed with developmental dysplasia of the hip (DDH). Methods: 23 cases of DDH requiring total hip replacement surgery were enrolled in this study. Preoperative examination confirmed the standard pelvic plain films Crowe, including 3 cases of Crowe I, 7 Crowe II, and 13 Crowe III. The 3D printing technology was used to print the hip model before the operation. Based on the pre-printed model, pre-operative planning and surgical procedures were established. The area of the acetabular bone defects was measured, the selected size prosthesis was recorded, and the surgery was performed (group A). The actual acetabular bone defect area and the prosthesis size were also recorded (group B). Results: The comparative results indicated that the actual acetabular defect area measured intraoperatively and the area measured using the 3D printing technology did not significantly differ for all participants (all P>0.05). Conclusion: Preoperative model can accurately measure the acetabular bone defect area for DDH. It is significant to develop individualized implants for DDH patients treated with the 3D printing technique. Level of Evidence IV: Case series .

Objetivos: Avaliar o potencial da aplicação da tecnologia de impressão 3D na medição da área de defeito ósseo acetabular em pacientes adultos diagnosticados com displasia do desenvolvimento do quadril (DDH). Métodos: 23 casos de DDH que requereram cirurgia de substituição total do quadril foram incluídos neste estudo. O exame pré-operatório confirmou os filmes pélvicos padrão Crowe, incluindo 3 casos de Crowe I, 7 Crowe II, e 13 Crowe III. A tecnologia de impressão 3D foi utilizada para imprimir o modelo de quadril antes da operação. Com base no modelo pré-impresso, o planejamento pré-operatório e os procedimentos cirúrgicos foram estabelecidos. A área dos defeitos ósseos acetabulares foi medida, a prótese de tamanho selecionado foi registrada, e a cirurgia foi realizada (grupo A). A área do defeito ósseo acetabular real e o tamanho da prótese também foram registrados (grupo B). Resultados: Os resultados comparativos indicaram que a área real do defeito acetabular medida intraoperativamente e a área medida usando a tecnologia de impressão 3D não diferiu significativamente para todos os participantes (todos P>0,05). Conclusão: O modelo pré-operatório pode medir com precisão a área de defeito ósseo acetabular para DDH. É relevante desenvolver implantes individualizados para pacientes com DDH tratados com a técnica de impressão 3D. Nível de Evidência IV: Série de casos .

Identification of Diagnostic Genes and Effective Drugs Associated with Osteoporosis Treatment by Single-Cell RNA-Seq Analysis and Network Pharmacology.

Background: Osteoporosis is a common bone metabolic disease with increased bone fragility and fracture rate. Effective diagnosis and treatment of osteoporosis still need to be explored due to the increasing incidence of disease. Methods: Single-cell RNA-seq was acquired from GSE147287 dataset. Osteoporosis-related genes were obtained from chEMBL. Cell subpopulations were identified and characterized by scRNA-seq, t-SNE, clusterProfiler, and other computational methods. "limma" R packages were used to identify all differentially expressed genes. A diagnosis model was build using rms R packages. Key drugs were determined by proteins-proteins interaction and molecular docking. Results: Firstly, 15,577 cells were obtained, and 12 cell subpopulations were identified by clustering, among which 6 cell subpopulations belong to CD45+ BM-MSCs and the other subpopulations were CD45-BM-MSCs. CD45- BM-MSCs_6 and CD45+ BM-MSCs_5 were consider as key subpopulations. Furthermore, we found 7 genes were correlated with above two subpopulations, and F9 gene had highest AUC. Finally, five compounds were identified, among which DB03742 bound well to F9 protein. Conclusions: This work discovered that 7 genes were correlated with CD45-BM-MSCs_6 and CD45+ BM-MSCs_5 subpopulations in osteoporosis, among which F9 gene had better research value. Moreover, compound DB03742 was a potential inhibitor of F9 protein.

[Effectiveness analysis of modified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering in treatment of diabetic foot].

Objective: To investigate the effectiveness of modified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering in the treatment of diabetic foot (DF). Methods: The clinical data of 22 DF patients treated with modified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering between October 2019 and December 2021 were retrospectively analyzed. There were 13 males and 9 females with an average age of 61.3 years (range, 41-74 years). The duration of diabetes mellitus was 8-30 years, with an average of 12.5 years, and the duration of DF was 10-42 days, with an average of 28.2 days. There were 2 cases of grade 3 and 20 cases of grade 4 according to Wagner classification. CT angiography was performed on both lower extremities of the patients, and the blood vessels of the affected extremities were narrowed to varying degrees and the blood supply was poor. The preoperative skin temperature of affected foot was (28.27±0.91)°C, the ankle brachial index (ABI) was 0.42±0.11, and the visual analogue scale (VAS) score was 7.7±0.6. Preoperative size of DF ulcer ranged from 2.5 cm×2.0 cm to 3.5 cm×3.0 cm. The skin temperature of affected foot, ABI, VAS score, and skin wound healing of the affected foot were recorded and compared between before operation and at 3 months after operation. Results: All patients were followed up 3-18 months, with an average of 10.5 months. The infection of 1 patient with Wagner grade 4 did not improve significantly after operation, and there was a trend of further deterioration, and the amputation of the left leg was finally performed at 22 days after operation.The remaining 21 patients recovered well after operation, the external fixator was removed at 1 month after operation, the wound healed at 3 months after operation, and there was no recurrence of ulcer in situ or other sites during follow-up. At 3 months after operation, the skin temperature of affected foot was (31.76±0.34)°C, the ABI was 0.94±0.08, and the VAS score was 2.1±0.3, which significantly improved when compared with those before operation ( t=25.060, P<0.001; t=32.412, P<0.001; t=-51.746, P<0.001). Conclusion: Modified tibial transverse bone transport technique combined with vancomycin calcium phosphate bone cement local filling and covering for DF patients can effectively improve the blood supply of the affected limb, promote wound healing, and improve effectiveness.

[Experimental study of resveratrol-solid lipid nanoparticles in promotion of osteogenic differentiation of bone marrow mesenchymal stem cells].

Objective: To investigate the effect of solid lipid nanoparticles (SLNs) on enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro by resveratrol (Res), and provide a method for the treatment of bone homeostasis disorders. Methods: Res-SLNs were prepared by high-temperature emulsification and low-temperature solidification method, and then the 2nd-3rd generation BMSCs from Sprague Dawley rat were co-cultured with different concentrations (0, 0.1, 1, 5, 10, 20 µmol/L) of Res and Res-SLNs. The effects of Res and Res-SLNs on the cell viability of BMSCs were detected by cell counting kit 8 (CCK-8) and live/dead cell staining; the effects of Res and Res-SLNs on the osteogenic differentiation of BMSCs were detected by alkaline phosphatase (ALP) staining and alizarin red S (ARS) staining after osteogenic differentiation induction, and the optimal concentration of Res-SLNs for gene detection was determined. Anti-osteocalcin (OCN) immunofluorescence staining and real-time fluorescent quantitative PCR (RT-qPCR) were used to detect the effect of Res and Res-SLNs on osteoblast-related genes (ALP and OCN) of BMSCs. Results: Live/dead cell staining showed that there was no significant difference in the number of dead cells between Res and Res-SLNs groups; CCK-8 detection showed that the activity of BMSCs in Res group was significantly reduced at the concentration of 20 µmol/L (P<0.05), while Res-SLNs activity was not affected by Res concentration (P>0.05). After osteogenic differentiation, the staining intensity of ALP and ARS in both groups was dose-dependent. The percentage of ALP positive staining area and the percentage of mineralized nodule area in Res group and Res-SLNs group reached the maximum at the concentrations of 10 µmol/L and 1 µmol/L, respectively (P<0.05), and then decreased gradually; the most effective concentration of Res-SLNs was 1 µmol/L. The expression of OCN and the relative expression of ALP and OCN mRNA in Res-SLNs group were significantly higher than those in Res group (P<0.05). Conclusion: Encapsulation of SLNs can improve the effect of Res on promoting osteogenesis, and achieve the best effect of osteogenic differentiation of BMSCs at a lower concentration, which is expected to be used in the treatment of bone homeostasis imbalance diseases.

Physiology-Inspired Multilayer Nanofibrous Membranes Modulating Endogenous Stem Cell Recruitment and Osteo-Differentiation for Staged Bone Regeneration.

Bone regeneration involves a cascade of sophisticated, multiple-staged cellular and molecular events, where early-phase stem cell recruitment mediated by chemokines and late-phase osteo-differentiation induced by pro-osteogenic factors play the crucial roles. Herein, enlightened by a bone physiological and regenerative mechanism, the multilayer nanofibrous membranes (PLLA@SDF-1α@MT01) consisting of PLLA/MT01 micro-sol electrospun nanofibers as intima and PLLA/PEG/SDF-1α electrospun nanofibers as adventitia are fabricated through micro-sol electrospinning and manual multi-layer stacking technologies. In vitro releasing profiles show that PLLA@SDF-1α@MT01 represents the rapid release of stromal cell-derived SDF-1α (SDF-1α) in the outer layers, while with long-term sustained release of MT01 in the inner layer. Owing to interconnected porosity like the natural bone extracellular matrix and improved hydrophilia, PLLA@SDF-1α@MT01 manifests good biocompatibility both in vitro and in vivo. Furthermore, PLLA@SDF-1α@MT01 can promote bone marrow mesenchymal stem cells (BMSCs) migration by amplifying the SDF-1α/CXCR4 axis and stimulating BMSCs osteo-differentiation via activating the MAPK pathway in vitro. PLLA@SDF-1α@MT01, with a programmed dual-delivery system, exhibits the synergetic promotion of bone regeneration and vascularization by emulating key characteristics of the staged bone repair in vivo. Overall, PLLA@SDF-1α@MT01 that mimics the endogenous cascades of bone regeneration can enrich the physiology-mimetic staged regenerative strategy and represent a promising tissue-engineered scaffold for the bone defect.

Selenium nanoparticles derived from Proteus mirabilis YC801 alleviate oxidative stress and inflammatory response to promote nerve repair in rats with spinal cord injury.

Microbial biotransformation and detoxification of biotoxic selenite into selenium nanoparticles (SeNPs) has emerged as an efficient technique for the utilization of selenium. SeNPs are characterized by high bioavailability and have several therapeutic effects owing to their antioxidant, anti-inflammatory and neuroprotective activities. However, their influence on microenvironment disturbances and neuroprotection after spinal cord injury (SCI) is yet to be elucidated. This study aimed to assess the influence of SeNPs on SCI and explore the underlying protective mechanisms. Overall, the proliferation and differentiation of neural stem cells were facilitated by SeNPs derived from Proteus mirabilis YC801 via the Wnt/ß-catenin signaling pathway. The SeNPs increased the number of neurons to a greater extent than astrocytes after differentiation and improved nerve regeneration. A therapeutic dose of SeNPs remarkably protected the integrity of the spinal cord to improve the motor function of the hind limbs after SCI and decreased the expression of several inflammatory factors such as tumor necrosis factor-α and interleukin-6 in vivo and enhanced the production of M2-type macrophages by regulating their polarization, indicating the suppressed inflammatory response. Besides, SeNPs reversed the SCI-mediated production of reactive oxygen species. In conclusion, SeNPs treatment holds the potential to improve the disturbed microenvironment and promote nerve regeneration, representing a promising therapeutic approach for SCI.

Mechanically enhanced composite hydrogel scaffold for in situ bone repairs.

High-efficiency repair of critical bone defects is a pressing problem in clinical practice. However, most biological replacement materials do not simultaneously satisfy the dual requirements of mechanical strength and cell compatibility. In this study, chitosan methacryloyl (CSMA) and ß-tricalcium phosphate (ß-TCP) were subjected to photo-crosslinking to form the CSMA/ß-TCP composite hydrogel, which has strong mechanical properties contributing to bone regeneration. In addition, its scaffold can alter the morphology of bone marrow mesenchymal stem cells (BMSCs), promote their proliferation, enhance the expression of alkaline phosphatase (ALP), and augment the nodular deposition of calcium. Meanwhile, the expressions of osteogenic proteins (ALP, osteocalcin, and osteopontin) were upregulated and the regulatory mechanism of the Hippo signaling pathway was verified. Moreover, animal experiments have confirmed that CSMA/ß-TCP has adequate biocompatibility and bone regeneration. These results demonstrate the immense potential of the CSMA/ß-TCP composite hydrogel in bone regeneration therapy.

[Treatment of Wehbe-Schneider typesâ B and â ¡B bony mallet fingers with one-stage closed reduction and elastic compression fixation with double Kirschner wires].

Objective: To investigate the effectiveness of one-stage closed reduction and elastic compression fixation with double Kirschner wires for Wehbe-Schneider types ⅠB and ⅡB bony mallet fingers. Methods: Between May 2017 and June 2020, 21 patients with Wehbe-Schneider type ⅠB and ⅡB bony mallet fingers were treated with one-stage closed reduction and elastic compression fixation using double Kirschner wires. There were 15 males and 6 females with an average age of 39.2 years (range, 19-62 years). The causes of injury were sports injury in 9 cases, puncture injury in 7 cases, and sprain in 5 cases. The time from injury to admission was 5-72 hours (mean, 21.0 hours). There were 2 cases of index finger injury, 8 cases of middle finger injury, 9 cases of ring finger injury, and 2 cases of little finger injury. The angle of active dorsiflexion loss of distal interphalangeal joint (DIPJ) was (40.04±4.02)°. According to the Wehbe-Schneider classification standard, there were 10 cases of typeⅠB and 11 cases of type ⅡB. The Kirschner wire was removed at 6 weeks after operation when X-ray film reexamination showed bony union of the avulsion fracture, and the functional exercise of the affected finger was started. Results: The operation time was 35-55 minutes (mean, 43.9 minutes). The length of hospital stay was 2-5 days (mean, 3.4 days). No postoperative complications occurred. All patients were followed up 6-12 months (mean, 8.8 months). X-ray films reexamination showed that all avulsion fractures achieved bony union after 4-6 weeks (mean, 5.3 weeks). Kirschner wire was removed at 6 weeks after operation. After Kirschner removal, the visual analogue scale (VAS) score of pain during active flexion of the DIPJ was 1-3 (mean, 1.6); the VAS score of pain was 2-5 (mean, 3.1) when the DIPJ was passively flexed to the maximum range of motion. The angle of active dorsiflexion loss of affected finger was (2.14±2.54)°, showing significant difference when compared with preoperative angle (t=52.186, P<0.001). There was no significant difference in the active flexion angle between the affected finger (79.52±6.31)° and the corresponding healthy finger (81.90±5.36)° (t=1.319, P=0.195). At 6 months after operation, according to Crawford functional evaluation criteria, the effectiveness was rated as excellent in 11 cases, good in 9, and fair in 1, with an excellent and good rate of 95.24%. Conclusion: For Wehbe-Schneider typesⅠB and ⅡB bony mallet fingers, one-stage closed reduction and elastic compression fixation with double Kirschner wires can effectively correct the deformity and has the advantages of simple surgery, no incision, and no influence on the appearance of the affected finger.