Role of Hedgehog Signaling Pathways in Multipotent Mesenchymal Stem Cells Differentiation.

Multipotent mesenchymal stem cells (MSCs) have high self-renewal and multi-lineage differentiation potentials and low immunogenicity, so they have attracted much attention in the field of regenerative medicine and have a promising clinical application. MSCs originate from the mesoderm and can differentiate not only into osteoblasts, cartilage, adipocytes, and muscle cells but also into ectodermal and endodermal cell lineages across embryonic layers. To design cell therapy for replacement of damaged tissues, it is essential to understand the signaling pathways, which have a major impact on MSC differentiation, as this will help to integrate the signaling inputs to initiate a specific lineage. Hedgehog (Hh) signaling plays a vital role in the development of various tissues and organs in the embryo. As a morphogen, Hh not only regulates the survival and proliferation of tissue progenitor and stem populations but also is a critical moderator of MSC differentiation, involving tri-lineage and across embryonic layer differentiation of MSCs. This review summarizes the role of Hh signaling pathway in the differentiation of MSCs to mesodermal, endodermal, and ectodermal cells.

Frozen inactivated autograft replantation for bone and soft tissue sarcomas.

Background: The frozen inactivation of autologous tumor bones using liquid nitrogen is an important surgical method for limb salvage in patients with sarcoma. At present, there are few research reports related to frozen inactivated autograft replantation. Methods: In this study, we retrospectively collected the clinical data of patients with bone and soft tissue sarcoma treated with liquid nitrogen-frozen inactivated tumor bone replantation, and analyzed the safety and efficacy of this surgical method. The healing status of the frozen inactivated autografts was evaluated using the International Society of Limb Salvage (ISOLS) scoring system. Functional status of patients was assessed using the Musculoskeletal Tumor Society (MSTS) scale. Results: This study included 43 patients. The average length of the bone defect after tumor resection is 16.9 cm (range 6.3-35.3 cm). Patients with autograft not including the knee joint surface had significantly better healing outcomes (ISOLS scores) (80.6% ± 15% vs 28.2% ± 4.9%, P<0.001) and limb function (MSTS score) (87% ± 11.6% vs 27.2% ± 4.4%, P<0.001) than patients with autografts including the knee joint surface. The healing time of the end of inactivated autografts near the metaphyseal was significantly shorter than that of the end far away from the metaphyseal (9.8 ± 6.3 months vs 14.9 ± 6.3 months, P=0.0149). One patient had local recurrence, one had an autograft infection, five (all of whom had an autograft including the knee joint surface) had joint deformities, and seven had bone non-union. Conclusion: Frozen inactivated autologous tumor bone replantation is safe and results in good bone healing. But this method is not suitable for patients with autograft involving the knee joint surface.

The application of custom 3D-printed prostheses with ultra-short stems in the reconstruction of bone defects: a single center analysis.

Objective: Considering the advantages and widespread presence of 3D-printing technology in surgical treatments, 3D-printed porous structure prostheses have been applied in a wide range of the treatments of bone tumor. In this research, we aimed to assess the application values of the 3D-printed custom prostheses with ultra-short stems for restoring bone defects and maintaining arthrosis in malignant bone tumors of lower extremities in children. Methods: Seven cases of pediatric patients were included in this study. In all cases, the prostheses were porous titanium alloy with ultra-short stems. MSTS 93 (Musculoskeletal Tumor Society) scores were recorded for the functional recovery of the limbs. VAS (Visual analogue scale) scores were utilized to assess the degree of painfulness for the patients. X-ray and MRI (magnetic resonance imaging) were applied to evaluate the bone integration, prostheses aseptic loosening, prostheses fracture, wound healing, and tumor recurrence during follow-up. Results: During follow-up, none of the patients developed any postoperative complications, including prostheses aseptic loosening, prostheses fracture, or tumor recurrence. Radiological examinations during the follow-up showed that prostheses implanted into the residual bone were stably fitted and bone defects were effectively reconstructed. The MSTS 93 scores were 24.9 ± 2.9 (20-28). VAS scores were decreased to 5.8 ± 1.2 (4.0-7.0). No statistically significant differences in leg length discrepancy were observed at the time of the last follow-up. Conclusion: 3D-printing technology can be effectively applied throughout the entire surgical treatment procedures of malignant bone tumors, offering stable foundations for the initial stability of 3D-printed prostheses with ultra-short stems through preoperative design, intraoperative precision operation, and personalized prosthesis matching. With meticulous postoperative follow-up, close monitoring of postoperative complications was ensured. These favorable outcomes indicate that the utilization of 3D-printed custom prostheses with ultra-short stems is a viable alternative for reconstructing bone defects. However, further investigation is warranted to determine the long-term effectiveness of the 3D-printing technique.

Combining nanoparticle albumin-bound paclitaxel with camrelizumab in advanced soft tissue sarcoma: activity, safety, and future perspectives.

Background: It is still uncertain whether Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor have synergistic effects on metastatic soft tissue sarcomas (STSs). The purpose of this study was to evaluate the safety and activity of nab-paclitaxel plus camrelizumab (a PD-1 inhibitor) in patients with advanced STS who had previously failed chemotherapy. Methods: In this single-center, open-label, single-arm phase II clinical trial, patients with advanced (unresectable or metastatic) STS who had previously failed chemotherapy received up to six cycles of nab-paclitaxel plus camrelizumab, whereas camrelizumab treatment was continued for up to 1 year. The median progression-free survival (PFS), objective response rate (ORR) and safety were collected and evaluated. Results: This trial included 40 patients (28 men and 12 women). The overall ORR was 22.5%, and the median PFS was 1.65 months (95% confidence interval [CI], 1.3-2.0 months). Patients with epithelioid sarcoma demonstrated a longer PFS compared with those with other histological subtypes (2.3 months vs. 1.5 months, respectively); however, this difference was not significant. Patients who had received only one line of previous chemotherapy had a significantly longer PFS compared with those who had undergone two or more lines of previous chemotherapy (2.8 months vs. 1.3 months, respectively, p = 0.046). In terms of safety, the toxicity of this combination therapy is mild and no serious adverse events have occurred. Conclusion: Nab-paclitaxel plus camrelizumab exhibited modest activity and mild toxicity in treating epithelioid sarcoma, angiosarcoma, and fibrosarcoma. The overall effectiveness of this treatment regimen for advanced STS is relatively low. Further research on combining nab-paclitaxel with effective drugs, including chemotherapy and targeted agents, for these specific STS subtypes is needed.

DLX2 promotes osteosarcoma epithelial-mesenchymal transition and doxorubicin resistance by enhancing HOXC8-CDH2 axis.

Metastasis and doxorubicin resistance are challenges in the clinical diagnosis and treatment of osteosarcoma, the mechanisms underlying these phenomena remain unclear. In this study, we found that DLX2 is highly expressed in metastatic osteosarcoma and is closely related to clinical prognosis. Knockdown of DLX2 inhibited tumor proliferation and migration in vitro and inhibited tumor growth in vivo. Mechanistically, we found that DLX2 enhanced the repression of CDH2 transcription by binding to HOXC8, thereby promoting the epithelial-mesenchymal transition in osteosarcoma cells. Through subsequent exploration, we found that targeting DLX2/HOXC8 signaling significantly restores the sensitivity of osteosarcoma cells to doxorubicin. In conclusion, our findings demonstrate that DLX2 may enhance the transcriptional regulation of CDH2 through interacting with HOXC8, which in turn promotes epithelial-mesenchymal transition and doxorubicin resistance in osteosarcoma. These findings hold great potential for clinical application and may guide the development of novel targeted therapies for osteosarcoma.

Atomistic Construction of Silicon Nitride Ceramic Fiber Molecular Model and Investigation of Its Mechanical Properties Based on Molecular Dynamics Simulations.

Molecular simulations are currently receiving significant attention for their ability to offer a microscopic perspective that explains macroscopic phenomena. An essential aspect is the accurate characterization of molecular structural parameters and the development of realistic numerical models. This study investigates the surface morphology and elemental distribution of silicon nitride fibers through TEM and EDS, and SEM and EDS analyses. Utilizing a customized molecular dynamics approach, molecular models of amorphous and multi-interface silicon nitride fibers with complex structures were constructed. Tensile simulations were conducted to explore correlations between performance and molecular structural composition. The results demonstrate successful construction of molecular models with amorphous, amorphous-crystalline interface, and mixed crystalline structures. Mechanical property characterization reveal the following findings: (1) The nonuniform and irregular amorphous structure causes stress concentration and crack formation under applied stress. Increased density enhances material strength but leads to higher crack sensitivity. (2) Incorporating a crystalline reinforcement phase without interfacial crosslinking increases free volume and relative tensile strength, improving toughness and reducing crack susceptibility. (3) Crosslinked interfaces effectively enhance load transfer in transitional regions, strengthening the material's tensile strength, while increased density simultaneously reduces crack propagation.

GPX4 is a key ferroptosis biomarker and correlated with immune cell populations and immune checkpoints in childhood sepsis.

Sepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a new-fashioned type of programmed cell death that may have an impact on sepsis development. However, the precise mechanism still needs to be explored. In this paper, Four pediatric sepsis datasets [training datasets (GSE26378 and GSE26440) and validation datasets (GSE11755 and GSE11281)] were chosen through the GEO (Gene Expression Omnibus) database, and 63 differentially expressions of ferroptosis-relation-genes (DE-FRGs) were eventually discovered using bioinformatics investigation. Functional annotation was performed using GO and KEGG pathway enrichment analysis. Then, four Core-FRGs (FTH1, GPX4, ACSL1, and ACSL6) were extracted after the construction of the protein-protein interaction (PPI) network and the research of the MCODE module. Consequently, Hub-FRG (GPX4) was found using the validation datasets, and correlation exploration of immunity populations (neutrophils, r = - 0.52; CD8 T-cells, r = 0.43) and immunity checkpoints (CD274, r = - 0.42) was implemented. The usefulness of GPX4 as a marker in sepsis was assessed in a mouse model of sepsis. The findings demonstrate that GPX4 is a crucial biomarker and a new latent immunotherapy target for the prediction and therapy of pediatric sepsis.

Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma.

Background: Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods. Methods: The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression. Results: A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES. Conlusion: UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.

Experimental Investigations into the Pyrolysis Mechanism and Composition of Ceramic Precursors Containing Boron and Nitrides with Different Boron Contents.

In this work, a novel ceramic precursor containing boron, silicon, and nitrides (named SiBCN) was synthesized from liquid ceramic precursors. Additionally, its pyrolysis, microstructure, and chemical composition were studied at 1600 °C. The results showed that the samples with different boron contents had similar structural composition, and both of the two precursors had stable amorphous SiBN structures at 1400 °C, which were mainly composed of B-N and Si-N and endowed them with excellent thermo-oxidative stability. With the progress of the heating process, the boron contents increased and the structures became more amorphous, significantly improving the thermal stability of the samples in high-temperature environments. However, during the moisture treatment, the introduction of more boron led to worse moisture stability.

[Application of three-dimensional printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors].

Objective: To investigate the clinical application and effectiveness of three-dimensional (3D) printed customized prosthesis with preserved epiphysis and articular surface in the reconstruction of large bone defects in treatment of adolescent femoral malignant tumors. Methods: The clinical data of 10 adolescent patients with femoral primary malignant tumor who met the selection criteria and underwent limb salvage surgery with 3D printed customized prosthesis with preserved epiphysis and articular surface between January 2020 and October 2021 were retrospectively analyzed. There were 6 males and 4 females with an average age of 12.5 years ranging from 7 to 18 years. There were 8 cases of osteosarcoma and 2 cases of Ewing's sarcoma. Enneking stage was Ⅱb. The length of the lesions ranged from 76 to 240 mm, with an average of 138.0 mm. The length of osteotomy (i. e. length of customized prosthesis) ranged from 130 to 275 mm, with an average of 198.5 mm; the distance between distal osteotomy end and epiphyseal line ranged from 0 to 15 mm, with an average of 8.8 mm; the bone defect after osteotomy accounted for 37.36% to 79.02% of the total length of the lesion bone, with a mean of 49.43%. The operation time, intraoperative blood loss, complications, tumor outcome (refered to RESIST1.1 solid tumor efficacy evaluation criteria), and limb length discrepancy were recorded. The Musculoskeletal Cancer Society (MSTS) 93 score was used to evaluate the function at 6 months after operation, and visual analogue scale (VAS) score was used to evaluate the pain before and after operation. Results: The operation was successfully performed in all the 10 patients, and the postoperative pathological results were consistent with the preoperative pathological results. The operation time was 165-440 minutes, with an average of 263 minutes; and the intraoperative blood loss was 100-800 mL, with an average of 350 mL. All patients were followed up 7-26 months, with an average of 11.8 months. No tumor was found on the osteotomy surface; the customized prosthesis were firmly installed and closely matched with the retained articular surface. The tumor outcome of neoadjuvant chemotherapy was stable in 4 cases and partial remission in 6 cases. No local recurrence or distant metastasis was found in 9 cases after postoperative adjuvant chemotherapy; pulmonary metastasis was found in 1 case at 12 months after operation. Two patients had local incision fat liquefaction, superficial infection, and delayed healing at 14 days after operation; 1 patient had local bone absorption at the contact surface of the prosthesis, and the screw and prosthesis did not loosen at 7 months after operation; the other patients had good incision healing, with no infection, prosthesis loosening, fracture, or other complications. At 6 months after operation, the MSTS93 score was 19-28, with an average of 24.1; 8 cases were excellent and 2 cases were good. The VAS score was 0.9±1.0, which significantly improved when compared with before operation (5.9±1.0) ( t=23.717, P<0.001). The height of the patients increased by 1-12 cm, with an average of 4.6 cm. At last follow-up, 4 patients had limb length discrepancy, with a length difference of 1 cm in 2 cases and 2 cm in 2 cases. Conclusion: The application of 3D printed customized prosthesis in the resection and reconstruction of adolescents femoral primary malignant tumors can achieve the purpose of preserving epiphysis and articular surface, and obtain good effectiveness.

[Effectiveness evaluation of three-dimensional printed titanium-alloy prosthesis reconstruction after distal tibia tumor segment resection].

Objective: To evaluate the feasibility and short-term effectiveness of three-dimensional (3D) printed titanium-alloy prosthesis reconstruction after the distal tibia tumor segment resection. Methods: The clinical data of 6 patients with bone defect after distal tibia tumor segment resection treated with 3D printed titanium-alloy prosthesis reconstruction and tibiotalar joint fusion between January 2020 and December 2021 were retrospectively analyzed. There were 2 males and 4 females; the age ranged from 12 to 35 years, with an average of 18.5 years. Among them, 4 cases were osteosarcoma, 1 case was Ewing sarcoma, and 1 case was giant cell tumor of bone. The Enneking staging was stage ⅡA in 3 cases, stage ⅡB in 2 cases, and stage Ⅲ in 1 case. The disease duration was 2-5 months (mean, 3.2 months). All patients received preoperative neoadjuvant therapy, and patients with osteosarcoma and Ewing sarcoma started chemotherapy at3 weeks after operation. The systemic and local tumor conditions and prosthesis conditions were evaluated regularly after operation. The Musculoskeletal Tumor Society (MSTS) score and the American Orthopaedic Foot and Ankle Society (AOFAS) score were used to evaluate the lower extremity and ankle function. Results: All patients were followed up 8-26 months, with an average of 15.6 months. There was no local recurrence and distant metastasis during the follow-up. The ankle joints of 5 cases were all in 90° functional position at last follow-up, and there was no complication such as prosthesis loosening and fracture; the ankle joint fusion was stable, the local bone ingrowth was good, and the daily activities could be completed, but the ankle range of motion was limited and the ankle joint was stiff. The MSTS score ranged from 22 to 26, with an average of 24, and 3 cases were evaluated as excellent and 2 cases were good; the AOFAS score ranged from 71 to 86, with an average of 80.6, and 4 cases were evaluated as good and 1 case was fair. One patient had severe periprosthetic infection at 2 months after operation, resulting in failure of prosthesis implantation, pain in limb movement, and poor ankle function; MSTS score was 12, AOFAS score was 50, and both were evaluated as poor; distraction osteogenesis was performed after removal of prosthesis and infection control, at present, it was still in the process of distraction osteogenesis, and local osteogenesis was acceptable. Conclusion: Using 3D printed titanium-alloy prosthesis and tibiotalar joint fusion to reconstruct the bone defect after distal tibia tumor segment resection has satisfactory mechanical stability and function, and is one of the effective distal tibial limb salvage methods.

PDGFR kinase inhibitor protects against septic death via regulation of BTLA.

Sepsis, defined as life-threatening organ failure caused by a dysregulated host response to severe infection, is a major cause of death among intensive care unit patients. Therapies targeting on immunomodulatory is a new research field in sepsis treatment. B- and T-lymphocyte attenuator (BTLA) is an inhibitory costimulatory factor molecule of B and T lymphocytes. Studies have shown that elevated expression of BTLA in lymphocytes can reduce mortality in sepsis, but its regulatory compounds and the underlying mechanism remains to be elucidated. Here, we show that treatment with CP-673451 significantly decreases mortality of septic mouse. CP-673451 is a PDGFR kinase inhibitor which can promote the expression of BTLA, inhibit the release of chemokines such as CXCL13, and reduce first the chemotaxis of B cells to the peripheral blood and vital organs. CP-673451 also inhibits both the release of cytokines and chemokines such as IL-1ß, IL-6, IL-10, TNF-α, CCL1, CCL2 and CCL7 and reduces both the chemotactic ability of T cells. This suggests that CP-673451 may prevent septic death by inhibiting lymphocyte chemotaxis and alleviating "cytokine storm". In conclusion, our study provides a new therapeutic target and an effective compound for sepsis treatment.

Freestanding Graphene Fabric Film for Flexible Infrared Camouflage.

Graphene films, fabricated by chemical vapor deposition (CVD) method, have exhibited superiorities in high crystallinity, thickness controllability, and large-scale uniformity. However, most synthesized graphene films are substrate-dependent, and usually fragile for practical application. Herein, a freestanding graphene film is prepared based on the CVD route. By using the etchable fabric substrate, a large-scale papyraceous freestanding graphene fabric film (FS-GFF) is obtained. The electrical conductivity of FS-GFF can be modulated from 50 to 2800 Ω sq-1 by tailoring the graphene layer thickness. Moreover, the FS-GFF can be further attached to various shaped objects by a simple rewetting manipulation with negligible changes of electric conductivity. Based on the advanced fabric structure, excellent electrical property, and high infrared emissivity, the FS-GFF is thus assembled into a flexible device with tunable infrared emissivity, which can achieve the adaptive camouflage ability in complicated backgrounds. This work provides an infusive insight into the fabrication of large-scale freestanding graphene fabric films, while promoting the exploration on the flexible infrared camouflage textiles.

Tim-3 regulates sepsis-induced immunosuppression by inhibiting the NF-κB signaling pathway in CD4 T cells.

Immunosuppression in response to severe sepsis remains a serious human health concern. Evidence of sepsis-induced immunosuppression includes impaired T lymphocyte function, T lymphocyte depletion or exhaustion, increased susceptibility to opportunistic nosocomial infection, and imbalanced cytokine secretion. CD4 T cells play a critical role in cellular and humoral immune responses during sepsis. Here, using an RNA sequencing assay, we found that the expression of T cell-containing immunoglobulin and mucin domain-3 (Tim-3) on CD4 T cells in sepsis-induced immunosuppression patients was significantly elevated. Furthermore, the percentage of Tim-3+ CD4 T cells from sepsis patients was correlated with the mortality of sepsis-induced immunosuppression. Conditional deletion of Tim-3 in CD4 T cells and systemic Tim-3 deletion both reduced mortality in response to sepsis in mice by preserving organ function. Tim-3+ CD4 T cells exhibited reduced proliferative ability and elevated expression of inhibitory markers compared with Tim-3-CD4 T cells. Colocalization analyses indicated that HMGB1 was a ligand that binds to Tim-3 on CD4 T cells and that its binding inhibited the NF-κB signaling pathway in Tim-3+ CD4 T cells during sepsis-induced immunosuppression. Together, our findings reveal the mechanism of Tim-3 in regulating sepsis-induced immunosuppression and provide a novel therapeutic target for this condition.

Characterization of a Type VI Secretion System vgrG2 Gene in the Pathogenicity of Burkholderia thailandensis BPM.

Burkholderia thailandensis is a clinically underestimated conditional pathogen in the genus Burkholderia, the pathogenicity of the infection caused by B. thailandensis remains poorly understood. According to previous studies, Type-VI secretion system (T6SS) is a protein secreting device widely existing in Gram-negative bacilli. Valine-glycine repeat protein G (VgrG) is not only an important component of T6SS, but also a virulence factor of many Gram-negative bacilli. In one of our previous studies, a unique T6SS vgrG gene (vgrG2 gene) was present in a virulent B. thailandensis strain BPM (BPM), but not in the relatively avirulent B. thailandensis strain E264 (E264). Meanwhile, transcriptome analysis of BPM and E264 showed that the vgrG2 gene was strongly expressed in BPM, but not in E264. Therefore, we identified the function of the vgrG2 gene by constructing the mutant and complemented strains in this study. In vitro, the vgrG2 gene was observed to be involved in the interactions with host cells. The animal model experiment showed that the deletion of vgrG2 gene significantly led to the decrease in the lethality of BPM and impaired its ability to trigger host immune response. In conclusion, our study provides a new perspective for studying the pathogenicity of B. thailandensis and lays the foundation for discovering the potential T6SS effectors.

Gene expression regulations by long noncoding RNAs and their roles in cancer.

Cancers are deadly diseases. The general mystery of carcinogenesis, primary and acquired drug resistance and distant organ metastasis are still puzzles to be solved. Long noncoding RNAs (lncRNAs) are receiving more and more attention in recent years since their roles in transcriptional regulation have been unveiled. Detailed functional annotations of lncRNAs have showed that their regulatory roles are largely determined by their binding partners. LncRNAs directly bind to DNA, RNA and proteins and regulate gene expression at transcriptional, post-transcriptional and post-translational levels. Here we review the current understanding of molecular functions of lncRNAs, will emphasize on their binding partners and summarize their biological roles in cancer.

Debridement, antibiotics, and implant retention for periprosthetic knee infections: a pooling analysis of 1266 cases.

BACKGROUND: The debridement, antibiotics, and implant retention (DAIR) procedure is an established therapeutic option for periprosthetic knee infections (PKI). However, the efficacy and the indication for this procedure are still controversial. METHODS: All the relevant literatures were systematically reviewed and analyzed. The present study aimed to assess the success rate of DAIR in the management of PKI, identify the factors associated with prognosis of DAIR, and establish a simple algorithm for predicting a high success rate of DAIR. RESULTS: Totally, 33 studies with 1266 cases were included. The overall success rate following DAIR in the management of PKI was 57.11%. In the subgroup analyses, the factors of "the time from symptoms to debridement was < 3 weeks" and "the bacterial species other than methicillin-resistant Staphylococcus aureus" significantly improved the success rate of DAIR and thus were defined as the major criteria. The statistically insignificant factors of "the open debridement and liner exchange" and "the comorbidity of rheumatoid arthritis" were set as the minor criteria. The success rate of DAIR for PKI meeting all the major criteria and no less than one minor criterion was 80.98%, which was significantly higher than the overall success rate of DAIR (p < 0.05). CONCLUSION: PKI cases meeting two major criteria and no less than one minor criterion may confer a high success rate of DAIR. This simple algorithm may contribute to identifying the appropriate PKI patient for DAIR treatment and predicting the prognosis of DAIR.

Risk factors for anterior shoulder instability: a matched case-control study.

BACKGROUND: Anatomic skeletal features of the shoulder play important roles in anterior shoulder dislocation. However, studies on the effect of the humeral structure are few. This case-control study aimed to analyze the risk factors of anterior shoulder instability, including glenoid and humeral factors. METHODS: Anterior shoulder instability was found in 64 of 10,035 individuals who underwent magnetic resonance imaging. Propensity score matching was used to select controls matched for age, sex, height, and weight. We analyzed the glenoid and humeral structural data using conditional logistic regression analysis and identified cutoff points using receiver operating characteristic curve analysis. RESULTS: Significant differences were found between the control and dislocation groups in the depth-to-width ratio (0.119 ± 0.034 vs. 0.105 ± 0.037, P = .021), height-to-width ratio (1.51 ± 0.13 vs. 1.67 ± 0.16, P < .001), humeral head diameter-to-glenoid fossa diameter ratio (1.56 ± 0.11 vs. 1.64 ± 0.20, P < .001), and humeral containing angle (67.3° ± 5.9° vs. 60.4° ± 5.9°, P < .001). The humeral containing angle (odds ratio, 0.95; P = .024) and the glenoid height-to-width ratio (odds ratio, 7.88; P = .002), adjusted for the depth-to-width ratio and diameter ratio, were associated with anterior shoulder instability. The cutoff point for the humeral containing angle was 64° and for the height-to-width ratio was 1.60. CONCLUSIONS: This study revealed significant risk factors for shoulder instability in the Chinese Han population. The humeral containing angle and the glenoid height-to-width ratio were risk factors for anterior shoulder instability.

Mechanical Properties and Porosity of Acrylic Cement Bone Loaded with Alendronate Powder.

Aseptic loosening is the most common complication of joint replacement. Previous studies showed that acrylic bone cement loaded with a commercially-available alendronate powder (APAC) had good promise against wear debris-mediated osteolysis for prevention of aseptic loosening. The purpose of the present study was to investigate the effect of adding alendronate powder to an acrylic bone cement on quasi-static mechanical properties (namely, compressive strength, compressive modulus, tensile strength, and flexural strength), fatigue life, porosity, and microstructure of the cement. The results showed that adding up to 1 wt./wt.% alendronate powder exerted no detrimental effect on any of the quasi-static mechanical properties. However, the fatigue life of APAC decreased by between ~17% and ~27 % and its porosity increased by between ~ 5-7 times compared with corresponding values for the control cement (no alendronate powder added). Fatigue life was negatively and significantly correlated with porosity. Considering that fatigue life of the cement plays a significant role in joint replacement survival, clinical use of APAC cannot be recommended.

Microbubble-Mediated Ultrasound Outweighs Low-Intensity Pulsed Ultrasound on Osteogenesis and Neovascularization in a Rabbit Model of Steroid-Associated Osteonecrosis.

Microbubbles magnify the acoustic pressure of low-intensity pulsed ultrasound (LIPUS) and may enhance its bioeffect for diagnostic and therapeutic purposes. This study compared the effect of this novel microbubble-mediated ultrasound (MUS) with that of the traditional LIPUS on osteogenesis and neovascularization in a rabbit model of steroid-associated osteonecrosis. We hypothesized that MUS might outweigh LIPUS on promoting osteogenesis and neovascularization in steroid-associated osteonecrosis. The bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in the rabbits. The indices of bone mineral density (BMD), trabecular number, maximal loading strength, and mineral apposition rate were analyzed, demonstrating that the animal model of steroid-associated osteonecrosis was successfully established. Both the MUS group (GM) and the LIPUS group (GL) were insonated 20 min daily for six weeks. GM received an extra intracapsular injection of microbubbles before insonation every other day. Fluorescence bone labeling, Micro-CT Analysis, biomechanical test, quantitative real-time PCR, Western blot analysis, and histological evaluation were performed for comparing GM with GL. The results demonstrated a 39% higher mineral apposition rate in GM compared with GL. The BMD and the maximal loading strength of femoral head of GM increased by 4.3% and 27.8% compared to those of GL, respectively. The mRNA and protein expression of BMP-2 and VEGF were also significantly higher in GM. The number of blood vessels of GM was 65% greater than that of GL. MUS is more potent than LIPUS in enhancing osteogenesis, neovascularization, and biomechanical strength of femoral head in the animal model of steroid-associated osteonecrosis. Without increasing the intensity of insonation or the risk of tissue damage, MUS is better for inhibiting the process of steroid-associated osteonecrosis.