Glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH) is a refractory, highly disabling bone disease fundamentally driven by oxidative stress-induced osteoblast damage. While metformin has demonstrated substantial potential in regulating bone metabolism, its precise efficacy and underlying molecular mechanisms in the treatment of GA-ONFH remain to be fully elucidated. The present study comprehensively evaluated the protective efficacy of metformin in antagonizing glucocorticoid-induced cytotoxicity. Combining transcriptomic analyses with multidimensional in vitro assays, we identified the specific glutathione (GSH)-degrading enzyme, CHAC1, as a central downstream target mediating osteoblast injury. Mechanistically, metformin exerts its protective effects by targeting and suppressing the PERK/eIF2α/ATF4 endoplasmic reticulum (ER) stress signaling axis, which significantly downregulates the pathological overexpression of CHAC1. This intervention successfully restores intracellular GSH homeostasis, thereby synergistically blocking both mitochondria-dependent apoptosis and lipid peroxidation-driven ferroptosis cascades. Crucially, in a rat model of GA-ONFH, targeted Chac1 knockdown, exogenous GSH supplementation, or pharmacological blockade of the PERK pathway all successfully rescued osteogenic function and significantly delayed the pathological progression of femoral head necrosis. In conclusion, this study not only highlights the critical role of CHAC1-mediated GSH depletion in determining osteoblast fate, but also provides a robust theoretical foundation for repurposing metformin as an early clinical intervention for GA-ONFH via ER stress suppression and redox homeostasis remodeling.

BACKGROUND The purpose of this study was to analyze the outcomes of revascularization exceeding 12 h after arterial injury at different sites of the lower extremity. MATERIAL AND METHODS From January 2009 to April 2017, 58 patients with 58 lower-limb arterial injuries who underwent revascularization over 12 h after trauma were included in our study. Outcomes measured, including mortality, amputation, complications, and other parameters (gait, length discrepancy, the range of movement of the knee and ankle joint, and muscle wasting) were analyzed. RESULTS External iliac artery injury (EIAI) or femoral artery injury (FAI) was affected in 4 patients, superficial femoral artery injury (SFAI) in 18, and popliteal artery injury (PAI) (including proximal gastrocnemius muscle vascular (PGMV) and proximal gastrocnemius muscle vascular [PGMV]) in 36. The median time of arterial injury was 72 h (interquartile range, 59.5). No mortality was found. Amputations were performed in 16 patients due to non-viable limbs, progressing infection, or muscle necrosis. All patients were followed up (median, 52 months; interquartile range, 5.5). Of the 42 limb-salvage patients, most had a limp, muscle wasting, or ankle and knee dysfunctions, and 26 patients with knee or ankle dysfunction underwent secondary surgery. CONCLUSIONS Although limited recanalization of blood vessels may lead to limb complications or amputations over time, the high success rate of limb salvage still merits the surgeon's best efforts.

Femoral neck fractures often lead to complications such as delayed union or nonunion due to limited blood supply to the femoral head. Enhanced external counterpulsation (EECP) is a non-invasive method that improves peripheral and tissue perfusion. This study aimed to evaluate whether postoperative EECP could promote fracture healing and improve hip function recovery after cannulated screw fixation for femoral neck fractures. This single-center, prospective, randomized controlled trial included patients with acute femoral neck fractures eligible for cannulated screw fixation. Participants were randomized in a 1:1 ratio into two groups using a computer-generated random sequence. Group assignments were sealed in opaque envelopes to ensure allocation concealment. Baseline characteristics were comparable between groups. Three weeks postoperatively, patients in the EECP group underwent daily 1-hour EECP sessions for 7 consecutive weeks, while the control group received standard care without EECP. Color Doppler ultrasound was used to measure the peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistance index (RI) of the medial femoral circumflex artery on the ipsilateral fracture side. Fracture union time, as well as the incidences of avascular necrosis of the femoral head (ANFH) and nonunion, were recorded. The Harris Hip Score (HHS) was assessed at 3, 6, and 12 months postoperatively. A total of 64 patients completed at least 24 months of follow-up, including 31 in the EECP group and 33 in the control group. After the final EECP session, the EECP group demonstrated significantly higher PSV and EDV values compared to the control group (both p < 0.0001; 95

Excessive inflammation, infection, persistent reactive oxygen species (ROS) accumulation, hyperglycemia, and vascular lesions in diabetic chronic wounds severely impair healing. Currently, there is no treatment regimen available to improve the complex microenvironment of such wounds. We have designed a comprehensive microenvironment intervention system, namely the composite dressing CVCeCG. The injectability, self-healing properties, and tissue adhesion of hydrogel make it an ideal physical barrier. The CVCeCG hydrogel incorporates a photothermal therapy (PTT) strategy, enabling photothermal activation of a missile-like bactericidal program to eliminate infections rapidly. Additionally, CVCeCG hydrogel remodels the immune microenvironment, constructs a dynamic regulatory network of epidermal/dermal cells, macrophages, and blood vessels through immune training and metabolic reprogramming. Even after the dressing is removed, it can still promote wound healing and has long-term effects. Furthermore, this hydrogel dressing alleviates wound hypoxia and reduces ROS levels, thereby further mitigating inflammation and promoting tissue repair. In the diabetic rat model with MRSA-infected wounds, the CVCeCG hydrogel significantly eliminated infection, reduced local inflammatory responses and ROS levels, and established a mutually supportive cycle between improved immune microenvironment and angiogenesis, thereby promoting wound healing. In summary, this work provides significant insights into the use of photothermal therapy to eliminate bacteria and improve the immune microenvironment through immune training and metabolic reprogramming, offering new strategies for comprehensively improving the microenvironment of chronic wounds in diabetes. A hydrogel (CMC-PDA/GEL) was created by combining gelatin (GEL) with catechol-modified carboxymethyl cellulose (CMC-DA). Composite hydrogel dressings in CVCeCG were created by adding polycaprolactone microspheres loaded with calcium peroxide (CPO@PCL) or vancomycin (Van@PCL) and cerium oxide nanoparticles (CeNPs) to CMC-PDA/GEL. This hydrogel can mimic missiles to eliminate infections quickly, remodel the local immune microenvironment by training the immune system and metabolic reprogramming, and clear ROS, establishing a comprehensive microenvironment intervention system, which helps wounds heal.

The problems in the current medical equipment measurement work have made many medical institutions begin to consider establishing a convenient, long-term stable and low-cost measurement service model by establishing internal measurement standards, but they have not made further in-depth exploration and the construction of a perfect measurement standard to establish a feasibility evaluation system. This study aims to construct a feasibility evaluation system for establishing measurement standards based on the Group Decision Making-Analytical Hierarchy Processes and provide a reference basis for decision-making in the establishment of measurement standards for medical equipment. A feasibility evaluation system for the establishment of measurement standards based on Group Decision Making-Analytical Hierarchy Processes is constructed, which includes 5 main criteria-level evaluation indicators and 14 sub-criteria-level evaluation indicators. The relative weights of the criteria-level evaluation indicators are calculated by constructing a judgment matrix through pairwise comparisons of the evaluation indicators using the Saaty scale method. Additionally, sensitivity analysis of the constructed model is conducted using the perturbation method. Then, we applied the constructed evaluation system to the feasibility evaluation of establishing measurement standards for eight different types of medical equipment in seven medical institutions. Differences in medical institutions and categories of medical equipment both have an impact on the values of the feasibility indicators for the establishment of measurement standards for medical equipment. The results of this study show that, the feasibility evaluation system for establishing measurement standards based on Group Decision Making-Analytical Hierarchy Processes can transform the problem of exploring the feasibility of establishing measurement standards in medical institutions into a multi-indicator quantitative evaluation problem, making the difficult-to-quantify decision-making process more scientific and objective.

Despite the high incidence of femoral neck fractures, the optimal surgical strategy (open reduction vs. closed reduction) for patients with an irreducible femoral neck fracture (IFNF) remains a controversial topic. Furthermore, there is a lack of consensus regarding the surgical approach to open reduction. The purpose of this study was to introduce a novel open approach for the treatment of IFNF. We retrospectively reviewed 52 patients defined as IFNF who achieved anatomic reduction and definitive fixation through the intertrochanteric line approach. During surgical management, all patients underwent "sandwich mode" bone grafting. Post-operative Garden index and Hip Harris score (HHS) were recorded to assess the quality of femoral neck reduction and hip function. Patients were followed up for fracture healing time, avascular necrosis (AVN), and other complications. All patients were followed up with an average of 32.37 months (range, 24–56 months). The fracture union was achieved in all patients with a mean duration of 4.35 ± 0.85 months. According to the Garden index, 37/52 cases achieved grade I reduction, and 15/52 cases achieved grade II reduction, respectively. Functional outcomes of 52 hips were evaluated by HHS, among which 39 cases were excellent, 7 cases were good, 3 cases were fair, and 3 cases who developed AVN were poor. None of them experienced postoperative Trendelenburg gait, infections, thrombosis, or paresthesia. The intertrochanteric line approach is an effective and safe method for IFNF, providing excellent anatomic reduction, capsular decompression, which yields favorable outcomes in combination with the "sandwich mode" bone graft. More importantly, it has a short learning curve that is readily generalizable, while simultaneously minimizing complications, especially AVN and nonunion.

The regenerative microenvironment after peripheral nerve injury is imbalanced and difficult to rebalance, which is mainly affected by inflammation, oxidative stress, and inadequate blood supply. The difficulty in remodeling the nerve regeneration microenvironment is the main reason for slow nerve regeneration. Traditional drug treatments have certain limitations, such as difficulty in penetrating the blood-nerve barrier and lack of pleiotropic effects. Therefore, there is an urgent need to build multifunctional nerve grafts that can effectively regulate the regenerative microenvironment and promote nerve regeneration. Nitric oxide (NO), a highly effective gas transmitter with diatomic radicals, is an important regulator of axonal growth and migration, synaptic plasticity, proliferation of neural precursor cells, and neuronal survival. Moreover, NO provides potential anti-inflammation, anti-oxidation, and blood vessel promotion applications. However, excess NO may cause cell death and neuroinflammatory cell damage. The prerequisite for NO treatment of peripheral nerve injury is that it is gradually released over time. In this study, we constructed an injectable NO slow-release system with two main components, including macromolecular NO donor nanoparticles (mPEG-P(MSNO-EG) nanoparticles, NO-NPs) and a carrier for the nanoparticles, mPEG-PA-PP injectable temperature-sensitive hydrogel. Due to the multiple physiological regulation of NO and better physiological barrier penetration, the conduit effectively regulates the inflammatory response and oxidative stress of damaged peripheral nerves, promotes nerve vascularization, and nerve regeneration and docking, accelerating the nerve regeneration process.Statement of SignificanceThe slow regeneration speed of peripheral nerves is mainly due to the destruction of the regeneration microenvironment. Neural conduits with drug delivery capabilities have the potential to improve the microenvironment of nerve regeneration. However, traditional drugs are hindered by the blood nerve barrier and cannot effectively target the injured area. NO, an endogenous gas signaling molecule, can freely cross the blood nerve barrier and act on target cells. However, excessive NO can lead to cell apoptosis. In this study, a NO sustained-release system was constructed to regulate the microenvironment of nerve regeneration through various pathways and promote nerve regeneration.

Endoplasmic reticulum (ER) stress exerts significant effects on cell growth, proliferation, migration, invasion, chemoresistance, and angiogenesis in various cancers. However, the impact of ER stress on the outcomes of osteosarcoma patients remains unclear. In this study, we established an ER stress risk model based on The Cancer Genome Atlas (TARGET) osteosarcoma dataset to reflect immune features and predict the prognosis of osteosarcoma patients. Survival analysis revealed significant differences in overall survival among osteosarcoma patients with different ER stress-related risk scores. Furthermore, ER stress-related risk features were significantly associated with the clinical pathological characteristics of osteosarcoma patients and could serve as independent prognostic indicators. Functional enrichment analysis indicated associations of the risk model with cell chemotaxis, leukocyte migration, and regulation of leukocyte migration. Additionally, the ER stress-related risk model suggested the presence of an immunosuppressive microenvironment and immune checkpoint responses. We validated the significance of 7 ER stress-related genes obtained from LASSO regression analysis through RT-qPCR testing on osteosarcoma samples from a local hospital, and inferred the importance of STC2 based on the literature. Subsequently, IHC experiments using samples from 70 osteosarcoma cases and 21 adjacent tissue samples confirmed differential expression of STC2 between cancer and normal tissues, and explored the gene’s expression in pan-cancer and its association with clinical pathological parameters of osteosarcoma. In conclusion, we have proposed an ER stress risk model as an independent prognostic factor and identified STC2 as a novel risk indicator for disease progression, providing a promising direction for further research and treatment of osteosarcoma.

BACKGROUND:By interacting with bone marrow mesenchymal stem cells (BMSCs) and regulating their function through exosomes, bone macrophages play crucial roles in various bone-related diseases. Research has highlighted a notable increase in the number of M1 macrophages in glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). Nevertheless, the intricate crosstalk between M1 macrophages and BMSCs in the glucocorticoid-stimulated environment has not been fully elucidated, and the underlying regulatory mechanisms involved in the occurrence of GA-ONFH remain unclear. METHODS:We employed in vivo mouse models and clinical samples from GA-ONFH patients to investigate the interactions between M1 macrophages and BMSCs. Immunofluorescence staining was used to assess the colocalization of M1 macrophages and BMSCs. Flow cytometry and transcriptomic analysis were performed to evaluate the impact of exosomes derived from normal (n-M1) and glucocorticoid-stimulated M1 macrophages (GC-M1) on BMSC differentiation. Additionally, miR-1a-3p expression was altered in vitro and in vivo to assess its role in regulating adipogenic differentiation. RESULTS:In vivo, the colocalization of M1 macrophages and BMSCs was observed, and an increase in M1 macrophage numbers and a decrease in bone repair capabilities were further confirmed in both GA-ONFH patients and mouse models. Both n-M1 and GC-M1 were identified as contributors to the inhibition of osteogenic differentiation in BMSCs to a certain extent via exosome secretion. More importantly, exosomes derived from GC-M1 macrophages exhibited a heightened capacity to regulate the adipogenic differentiation of BMSCs, which was mediated by miR-1a-3p. In vivo and in vitro, miR-1a-3p promoted the adipogenic differentiation of BMSCs by targeting Cebpz and played an important role in the onset and progression of GA-ONFH. CONCLUSION:We demonstrated that exosomes derived from GC-M1 macrophages disrupt the balance between osteogenic and adipogenic differentiation in BMSCs, contributing to the pathogenesis of GA-ONFH. Inhibiting miR-1a-3p expression, both in vitro and in vivo, significantly mitigates the preferential adipogenic differentiation of BMSCs, thus slowing the progression of GA-ONFH. These findings provide new insights into the regulatory mechanisms underlying GA-ONFH and highlight potential therapeutic targets for intervention.

Due to persistent inflammation and oxidative stress reactions, achieving drug absorption in diabetic wounds is challenging. To overcome this problem, our article presents a composite hydrogel, GelMA-GA/DMOG@GDNP, which consists of gelatin methacryloyl (GelMA) treated with gallic acid (GA) and encapsulating ginseng-derived nanoparticles (GDNPs) loaded with dimethyloxallyl glycine (DMOG). The composite hydrogel demonstrates excellent biocompatibility. In laboratory settings, the hydrogel inhibits the production of nitric oxide synthase 2 (iNOS) in mouse immune cells (RAW264.7 cells), enhances the growth and migration of mouse connective tissue cells (L929 cells) and human endothelial cells (HUVECs), and promotes tube formation in HUVECs. In a rat model of type 1 diabetes-induced wounds, the composite hydrogel attenuates inflammatory reactions, facilitates the formation of fibres and blood vessels, accelerates wound healing, and elucidates specific pathway mechanisms through transcriptome sequencing. Therefore, the GelMA-GA/DMOG@GDNP hydrogel can serve as a safe and efficient wound dressing to regulate the inflammatory response, promote collagen fiber and blood vessel formation, and accelerate wound healing. These findings suggest that utilizing this multifunctional engineered nanoparticle-loaded hydrogel in a clinical setting may be a promising strategy for diabetic wound healing.

Our previous research revealed a close association between the acetylation of peroxisome proliferator-activated receptor γ (PPARγ) histone H3K27 and the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). We preliminarily explored the epigenetic mechanism of steroid-induced avascular necrosis of the femoral head (SANFH) development, but the specific histone deacetylase (HDAC) involved in this regulatory process remains unknown. In this study, we combined cell, animal, and clinical specimen experiments to screen for specific HDAC genes that could regulate BMSC adipogenic differentiation and to explore their roles. The results showed that dexamethasone (DEX) significantly exacerbated the imbalance between the adipogenic and osteogenic differentiation of BMSCs, and there were differences in HDAC expression in the adipogenic differentiation cell models, with histone deacetylase 10 (HDAC10) showing the most significant decrease in expression. Subsequent use of a chromatin immunoprecipitation assay kit and quantitative polymerase chain reaction (ChIP‒qPCR) revealed a decrease in HDAC10 expression at predicted potential sites within the PPARγ promoter, indicating a significant decrease in HDAC10 enrichment in the PPARγ promoter region of BMSCs, thereby promoting sustained PPARγ expression. Additionally, immunohistochemistry of samples collected from mice and humans with SANFH and normal femoral heads revealed an imbalance between adipogenic and osteogenic differentiation in the necrotic area of femoral heads, with a significant decrease in the relative expression of HDAC10 in the necrotic area of femoral heads with SANFH. In summary, we speculate that HDAC10 affects the progression of SANFH by regulating BMSC adipogenic differentiation, a process possibly related to PPARγ histone acetylation. These findings provide a promising direction for the treatment of SANFH.

Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.

Bioinspired strontium magnesium phosphate cements for bone tissue engineering were prepared using a new, facile, environmentally friendly and high yielding (98.5%) precursor method. The bioinspired SMPCs have uniform particle distributions, excellent mechanical strengths and high biocompatibilities. The in vitro responses of bone marrow stromal cells to the SMPCs, including viability, osteogenic differentiation and alkaline phosphatase activity, were evaluated. The results show that the SMPC containing 0.5 mol of strontium (referred to as SMPC-2) has a higher degradation rate and biological activity than magnesium phosphate cements and the other SMPCs. In addition, the synergistic effect of strontium and magnesium ion release from SMPC-2 creates a conducive environment for cell proliferation, mineralized calcium deposition and new bone formation. These observations demonstrate the feasibility of using the new precursor method to generate SMPCs and the utility of these biologically compatible and highly effective cements for bone tissue engineering.

Inflammation stands as a pivotal factor in the pathogenesis of glucocorticoid-associated osteonecrosis of the femoral head (GA-ONFH). However, the vital role played by M1 macrophages, the principal constituents of the inflammatory process, remains largely underexplored. In this study, we employed reverse transcription-quantitative polymerase chain Reaction (RT-PCR), western blot, and flow cytometry to assess the impact of M1-conditioned medium on cultures of mouse bone marrow-derived mesenchymal stem cells (BMSCs) and Murine Long bone Osteocyte-Y4 (MLO-Y4) in vitro. Moreover, we quantified the levels of inflammatory cytokines in the M1-conditioned medium through the employment of an enzyme-linked immunosorbent assay (ELISA). For in vivo analysis, we examined M1 macrophages and investigated the NF-kB signaling pathway in specimens obtained from the femoral heads of animals and humans. We found that the number of M1 macrophages in the femoral head of GA-ONFH patients grew significantly, and in the mice remarkably increase, maintaining high levels in the intramedullary. In vitro, the M1 macrophage-conditioned medium elicited apoptosis in BMSCs and MLO-Y4 cells, shedding light on the intricate interplay between macrophages and these cell types. The presence of TNF-α within the M1-conditioned medium activated the NF-κB pathway, providing mechanistic insight into the apoptotic induction. Moreover, employing a robust rat macrophage clearance model and GA-ONFH model, we demonstrated a remarkable attenuation in TNF-α expression and NF-kB signaling subsequent to macrophage clearance. This pronounced reduction engenders diminished cellular apoptosis and engenders a decelerated trajectory of GA-ONFH progression. In conclusion, our study reveals the crucial involvement of M1 macrophages in the pathogenesis of GA-ONFH, highlighting their indispensable role in disease progression. Furthermore, early clearance emerges as a promising strategy for impeding the development of GA-ONFH.

Objective:To explore the therapeutic effect on transposition of peroneal longus tendon in reconstruction of long segment defects of chronic Achilles tendon.Methods:From November 2013 to November 2018, 17 patients with long segment defects of chronic Achilles tendon(greater than 5.0 cm of defect) were admitted in the Department of Trauma and Micro-orthopaedics of Zhongnan Hospital of Wuhan University. The patients were 14 males and 3 females, aged 19-55 years old, with an average of 34.7 years old. Eleven patients had defects on left Achilles tendon and 6 on the right. The chronic defects lasted over 1-12 months with an average of 3.8 months. The broken ends of the Achilles tendon located at 0-5.0 cm from the insertion point. The defects were at 5.0-9.0 cm in length, after debridement of the broken ends. After thoroughly debridement of the scar tissue over the broken end of an Achilles tendon, an autologous peroneal tendon transposition was performed for reconstruction of an Achilles tendon. Postoperative follow-ups were conducted to observe wound healing and complications. Arner Lindholm score was employed to evaluate the therapeutic efficacy before surgery and at the final follow-up. Ankle-hindfoot score of American Orthopedic Foot and Ankle Society(AOFAS) and Achilles Tendon Total Rupture Score(ATRS) were used to evaluate functional recovery. At the final follow-up, heel raise of single affected foot and the maximum circumference of both calves were observed, gait analyses for plantar stress assessment as well as review of ankle CT and MRI scans were conducted for assessment of therapeutic efficacy. Using t test in SPSS 22.0 software to compare preoperative and postoperative AOFAS and ATRS scores, P<0.05 indicates a statistically significant difference. Results:Wounds healed in one stage, except 1 diabetic patient who had haematoma in the wound after surgery and healed after debridement combined with VSD treatment. All the 17 patients had completed the postoperative follow-up that lasted for 24-48 months, with an average of 33 months. According to Arner Lindholm score for efficacy evaluation, 11 patients were in excellent and 6 in good. The postoperative AOFAS scores increased from 62.94 ± 6.51 before surgery to 93.71 ± 6.15 after the surgery. ATRS increased from 29.00 ± 3.54 before surgery to 92.29 ± 3.02 after the surgery, and the score difference between before and after surgery was staistically significant ( P<0.05). No patient experienced a complication such as Achilles tendon rupture, wound infection or nerve injury. During follow-up, ankle functions recovered well, valgus was found powerful as well as heel raise on single foot. The circumference of the affected calf was smaller than that of the healthy side by no more than 1.5 cm. Gait analysis showed balanced distribution of plantar stress. No corpus callosum formation was found in both of the affected and the healthy feet. No obvious sign of osteoarthritis of ankle showed review in CT scans. Ankle MRI scans showed good continuity of the reconstructed Achilles tendons, which become significantly thicker after the surgery. Conclusion:The transposition of the long peroneal tendon is a relatively simple and effective surgical technique for reconstruction of a chronic Achilles tendon rupture or defect in a longer length or a rupture at the insertion point.

Background: The clinical applications of stromal vascular fraction (SVF) therapy for osteoarthritis (OA) have attracted academic and clinical attention. However, data of the effects of stromal vascular fraction therapy on regeneration of degenerated cartilage are limited in the literature. Meanwhile, there is a great need for a simple and non-invasive evaluation method to analyze the changes of joint cartilage qualitatively and quantitatively in clinical trials. This study entitled “stromal vascular fraction Therapy for Human Knee Osteoarthritis” was registered in ClinicalTrial.gov # NCT05019378.Materials and Methods: We designed and conducted a single center, open labeled clinical phase I/II study, and 6 osteoarthritis patients with both knee cartilage defect I-II were enrolled in this study. The two knees of each patient were randomly assigned to autologous stromal vascular fraction treatment group or non-treatment control group to evaluate the safety and therapeutic effect of stromal vascular fraction therapy for human knee osteoarthritis. We have also established a novel protocol to provide 3D MRI imaging for human knee cartilage enabling us to qualitatively and quantitatively evaluate cartilage degeneration and regeneration in this study.Results: The qualitative and quantitative evaluation of 3D Magnetic Resonance Imaging (MRI) imaging of knee cartilage demonstrated that the stromal vascular fraction therapy reduced the cartilage defects; and significant increase of cartilage value both in defect cartilage area and whole cartilage area of treated group and significant increase of thickness and area of both femoral and tibia cartilage in vertical sections of the stromal vascular fraction treated Group at 12 and 24 W post treatment in cartilage defect I-II osteoarthritis patients.Conclusion: This clinical phase I/II study indicated that stromal vascular fraction therapy is a safe clinical procedure and provided evidence that the stromal vascular fraction therapy significantly facilitated cartilage regeneration, opening the opportunity to a phase III trial investigating authentic efficacy of the procedure. This study is the first qualitative and quantitative evaluation of the efficacy of autologous stromal vascular fraction cellular therapy on cartilage regeneration. Through early and definite diagnosis of knee osteoarthritis patients, and providing safe and efficient therapy to facilitate cartilage regeneration, we will be able to control or reverse cartilage degeneration and completely change the epidemiology of osteoarthritis worldwide.

Objective:To explore intraoperative assessment of blood supply to the femoral head after femoral neck fracture, and the correlation between the blood supply and postoperative osteonecrosis of the femoral head.Methods:A retrospective analysis was performed of the 63 patients with femoral neck fracture who had been treated at Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University by open reduction and internal fixation with hollow compression screws from April 2016 to March 2021. They were 39 males and 24 females with an age of (44.9±13.6) years. There were 42 cases of Garden type Ⅲ and 21 cases of Garden type Ⅳ. Time from injury to operation was (4.1±2.4) days. After internal fixation, a hole was drilled using a 2.0 mm Kirschner wire at 2.0 cm above the femoral head-neck junction to observe the velocity, color, and characteristics of the blood oozing at the drill hole. The patients were divided into a good oozing group of 51 cases in whom bright red blood oozing was observed within 15 seconds after drilling and a poor oozing group of 12 cases in whom dark red blood oozing was observed beyond 15 seconds after drilling. The incidence of postoperative femoral head necrosis, Harris hip score, and visual analogue scale (VAS) for pain were compared between the 2 groups. Single factor and multi factor analyses were conducted using the Cox regression model to analyze the factors influencing postoperative femoral head necrosis in the patients.Results:The 63 patients were followed up for 24 (18, 36) months. The 2 groups were comparable because there was no significant difference in the preoperative general data between them ( P>0.05). Femoral head necrosis was observed in 3 cases in the good oozing group and in 5 cases in the poor oozing group, showing a significant difference between the 2 groups ( P<0.05). The Harris hip score [90.0 (86.0, 92.0)] and the VAS pain score [1.0 (1.0, 2.0)] at 1 year after surgery in the good oozing group were significantly better than those in the poor oozing group [85.5 (71.3, 88.8) and 2.5 (1.0, 3.8)] ( P<0.05). Multivariate Cox regression analysis showed that Garden type Ⅳ ( HR=6.784, 95% CI: 1.324 to 35.664, P=0.023) and intraoperative poor blood oozing ( HR=10.744, 95% CI: 2.359 to 51.774, P=0.003) were risk factors for femoral head necrosis after cannulated compression screw fixation of fractures of displaced femoral neck ( P<0.05). Conclusions:The blood supply to the femoral head after femoral neck fracture can be directly assessed by drilling a hole in the femoral head after open reduction and internal fixation. Intraoperative poor blood oozing is a risk factor for the femoral head necrosis after cannulated compression screw fixation of fractures of displaced femoral neck.

糖皮质激素(GC s )在临床上使用十分广泛,由此诱发的激素性股骨头坏死(GA-ONFH)的发病率逐年上升,发病年龄亦日趋年轻.国内每年报告新发病例在100～200万[1].多数病人罹患后会在2～3年内股骨头塌陷,随后髋关节发生骨性关节炎.大部分病人最终只能选择关节置换.GCs引起 GA-ONFH的发病机制可能与骨髓间充质干细胞(BMSCs)成脂/成骨分化异常、氧化应激、细胞凋亡与自噬、炎症和免疫、外泌体调控、及非编码RN A的异常表达等因素相关.本文主要围绕GA-ONFH致病机制进行综述.

目的 了解新冠病毒感染疫情期间医院重症监护病房(ICU)住院患者医院感染特征,为ICU医院感染管理提供循证依据.方法 采取前瞻性调查法,对某医院ICU新冠病毒感染患者进行医院感染目标性监测.结果 共监测该医院ICU住院患者90例,医院感染发病率14.44％,医院感染发生部位以下呼吸道为主.ICU患者呼吸机相关性肺炎(VAP)发病率21.93‰,导管相关尿路感染(CAUTI)发病率3.42‰,导管相关血流感染(CRBSI)发病率为0.00‰.检出率居前2位的病原菌是鲍曼不动杆菌和肺炎克雷伯菌,构成比分别为60.87％和13.04％.抗菌药物使用居前4位的是卡泊芬净(11.58％)、多黏菌素(10.53％)、替加环素(8.42％)和哌拉西林/他唑巴坦(8.42％).结论 该医院ICU在新冠病毒感染疫情期间,住院患者医院感染以下呼吸道感染为主,VAP发病率高.科学规范呼吸机管理,严格实施CAUTI和CRBSI集束化干预策略、加强手卫生质量管理和恰当应用抗菌药物治疗是减少ICU院内感染的关键.

Abstract Endoplasmic reticulum (ER) stress has a significant impact on cell growth, proliferation, metastasis, invasion, chemotherapy resistance, and angiogenesis in various cancers. However, the effect of ER stress on the outcome of osteosarcoma patients is still unclear. In this study, we established an ER stress risk model based on the Cancer Genome Atlas for osteosarcoma dataset to reflect immune features and predict the prognosis of osteosarcoma patients. Survival analysis showed significant differences in overall survival among osteosarcoma patients with different ER stress-related risk scores. Additionally, ER stress-related risk features were significantly associated with clinical and pathological characteristics of osteosarcoma patients and served as independent prognostic indicators. Functional enrichment analysis revealed that the risk model was associated with cell chemotaxis, leukocyte migration, and regulation of leukocyte migration. Moreover, the ER stress-related risk model indicated the presence of an immunosuppressive microenvironment and immune checkpoint responses in osteosarcoma. In conclusion, we proposed an ER stress risk model that is an independent prognostic factor and indicates general immune features in the microenvironment of osteosarcoma.