BACKGROUND:Osteoporosis is a common systemic metabolic disease, leading to increased bone fragility and risk of fractures. Research has shown that Adenosine triphosphate (ATP) synthase, H+transporting, mitochondrial F1 complex, alpha subunit 1 (ATP5A1), a crucial component in ATP production, is inhibited in dexamethasone (DEX)-induced osteoblasts. Therefore, this study aimed to investigate the molecular mechanism underlying the inhibitory impact of DEX on osteogenic differentiation in rat bone marrow mesenchymal stem cells (BMSCs). METHODS:Rat BMSCs were treated with varying concentrations of DEX for 14 days, followed by subsequent analyses. The expression levels of calpastatin (CAST), calpain 1 (CAPN1), and ATP5A1 were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting analyses. Furthermore, osteogenic marker proteins and ATP activity were evaluated employing Western blotting analysis and enzyme-linked immunosorbent assay (ELISA). Moreover, to determine the regulatory role of DEX on the CAST-CAPN1 axis, overexpression plasmids for CAST (oe-CAST) and CAPN1 (oe-CAPN1) were constructed. Additionally, osteogenic differentiation and ATP activity in BMSCs were analyzed using qRT-PCR, Western blotting, Alizarin Red S staining, and ELISA. RESULTS:With increasing concentrations of DEX, the expression of the CAST-CAPN1-ATP5A1 axis in BMSCs was significantly altered (p < 0.05). DEX downregulated the levels of osteogenic markers, including Runt-Related Transcription Factor 2 (RUNX2), alkaline phosphatase (ALP), and osteopontin (OPN), while reducing ATP activity (p < 0.05). However, oe-CAST partially mitigated the inhibitory effects of DEX on osteogenic differentiation and ATP activity (p < 0.05). In contrast, oe-CAPN1 exacerbated the effects of DEX and reversed the regulatory impact of CAST (p < 0.05). CONCLUSION:DEX inhibits osteogenic differentiation and reduces ATP activity in BMSCs by modulating the CAST-CAPN1 axis.

RATIONALE:Open anterior hip dislocation resulting in vascular injury is extremely rare and is a severe orthopedic emergency that can potentially lead to limb necrosis and even life-threatening consequences. PATIENT CONCERNS:A 51-year-old woman presented to our hospital with an open anterior dislocation of the left hip secondary to a fall from height. The patient had a severe infection in the left inguinal area; at presentation, there was dislocation of the femoral head lasting for the past 5 days. Doppler ultrasound revealed left common femoral vein thrombosis. DIAGNOSES:The patient was diagnosed with a multiple-injury patient with an acetabular fracture, femoral head fracture, and open anterior dislocation of the hip with vascular injury and infection. INTERVENTIONS:After placement of an inferior vena cava filter, the reduction was performed under general anesthesia. The common femoral artery ruptured during the process. After suturing, continuous drainage was maintained. During the subsequent treatment, the infection gradually eroded the common femoral artery and formed a pseudoaneurysm. Lower limb vascularity was restored by autologous saphenous vein grafting, repeated debridement, and sensitive antibiotics. OUTCOMES:The infection of the patient was gradually controlled, and the lower limb was successfully preserved. During the 1-year follow-up, the patient returned to normal life without disability. LESSONS:From this rare case, we suggest that a therapeutic approach should be evaluated after adequate exclusion of deep vein thrombosis to prevent thromboembolic events. Moreover, gentle reduction operation, thorough debridement, and timely infection control are essential to prevent complications and improve the functional prognosis of patients.

IntroductionDespite the biomechanical advantages of the Femoral Neck System (FNS), improvements in postoperative complication rates have not been significant. This study evaluated the effects of different FNS positions on the biomechanical stability of Pauwels type III femoral neck fractures (FNFs) using finite element analysis (FEA).MethodsPauwels type III FNF models fixed with different FNS positions were constructed using various bolt lengths, bolt positions, and axis–bolt angles. Biomechanical parameters, including stiffness, maximum implant von Mises stress (MIVS), maximum interfragmentary shear stress (MISS), and maximum interfragmentary gap (MIG), were analyzed by simulating early postoperative weight-bearing. Entropy scoring was used to rank the performance of different fixation positions to determine the optimal FNS implantation position.ResultsCompared with that of the standard model, the biomechanical stability changed when FNS positioning was altered. Among all the evaluated parameters, MIG had the highest weight (60.04%). In the lateral view, fracture fixation was most stable when the bolt was rotated 5° anteriorly relative to the femoral neck axis (composite score = 0.87). However, stability was poorer when the bolt was rotated 9° inward relative to the femoral neck axis (composite score = 0.13).DiscussionThe MIG is an important biomechanical parameter for assessing the stability of different FNS positions when treating FNFs. Shortening the distance between the bolt and the subchondral bone, upward movement, external rotation, and anterior rotation of the bolt can help improve the stability of the FNS in the treatment of Pauwels III FNFs.

Plate fixation is a common treatment option for radial head fractures (RHFs). Due to the benefits of less invasiveness and fewer complications of internal fixation, the application of small-diameter headless compression screws (HCSs) to treat RHFs has become a new trend. This study aimed to compare the mechanical stability of four distinct internal fixation protocols for transversely unstable RHFs via finite element analysis. Using computed tomography data from 10 patients, we developed 40 patient-specific FE models of transversely unstable RHFs fixed by parallel, crossed, and tripod HCSs and mini-T plate (MTP). Under simulated physiological loading of the elbow joint, the construct stiffness, displacement, and von Mises stresses were evaluated and verified by a biomechanical experiment. Under shear loading, the MTP group exhibited lower construct stiffness, larger displacement, and higher Von Mises stress than the HCSs group. The stiffness of tripod HCSs was greater than parallel and crossed screw fixation techniques. There was a strong relationship between apparent bone density and construct stiffness (R = 0.98 to 0.99). In the treatment of transversely unstable RHFs, HCSs have superior biomechanical stability than MTP. The tripod technique was also more stable than parallel and crossed fixation.

Background High shear force is a major factor detrimental to the healing of vertical femoral neck fractures. In addition to firm fixation, reduction quality is crucial for postoperative stability. The present study aimed to compare the biomechanical stability of the newly invented femoral neck system and three inverted-triangle cannulated compression screws treatments for non-anatomical reduction of Pauwels type-III femoral neck fractures. Methods A total of 18 non-anatomical reduction Pauwels type-III femoral neck fracture finite element models were fabricated and fixed using three inverted-triangle cannulated compression screws or the femoral neck system. A 1950-N force was applied to the femoral head to simulate the physiological load during a single-leg stance. Parameters of the maximum total deformation, the interfragmentary gap, and the maximum von Mises stress of the implants and the proximal femur were analyzed. Findings The results of the maximum total deformation, interfragmentary gap, and maximum von Mises stress of the implants in the negative-negative buttress model fixed by the femoral neck system were the largest among all groups (3.58 mm, 0.252 mm, and 729.68 MPa, respectively). In contrast, the anatomical-anatomical reduction model fixed by three inverted-triangle cannulated compression screws demonstrated the minimum total deformation, interfragmentary gap, and minimum von Mises stress of implants (1.107 mm, 0.09 mm, and 189.83 MPa, respectively). Interpretation Anatomical reduction or positive buttress in femoral neck fractures should be recommended during fracture reduction. The femoral neck system showed weaker biomechanical stability than three inverted-triangle cannulated compression screws in treating Pauwels type-III femoral neck fractures.

Bioactive glass-coated hierarchical porous tricalcium phosphate ceramics were constructed as both bone scaffolds and drug delivery devices to treat S. aureus-infected bone defects.

目的 分析多层螺旋CT(MSCT)扫描对外伤性腕关节损伤患者临床诊治价值.方法 选取本院2017年2月至2018年5月收治的34例外伤性腕关节损伤患者作为研究对象,分析MSCT检查和X线对腕关节骨折或脱位的显示情况.结果 34例外伤性腕关节患者经MSCT检查共发现39处骨折或脱位,并经长期随访或手术证实.其中舟状骨骨折10处,头状骨骨折7例,三角骨骨折5例,豆状骨骨折5例,大多角骨骨折4例,月骨周围脱位8例;经X线检查共发现32处骨折或脱位,7处漏诊.34例患者中行开放复位术治疗患者7例,行手术复位术治疗患者23例,其余4例患者行单纯固定.结论 MSCT检查可有效提高外伤性腕关节损伤的诊断准确率,其三维重建技术能明确可疑骨折和脱位,可为临床医师手术方案的制定和选择提供可靠的依据.

It is significant to use functional biomaterials to rationally engineer microenvironments for in situ bone regeneration in the field of bone tissue engineering. To this end, we constructed the gypsum-coated β-tricalcium phosphate (G-TCP) scaffolds by combing a three-dimensional printing technique and an epitaxial gypsum growth method. In vitro simulation experiments showed that the as-prepared scaffolds could establish a dynamic and weakly acidic microenvironment in a simulated body liquid, in which the pH and the calcium ion concentration always changed due to the gypsum degradation and growth of bone-like apatite nanoplates on the scaffold surfaces. The cell experiments confirmed that the microenvironment established by the G-TCP surfaces promoted rapid osteogenic differentiation and proliferation of bone marrow mesenchymal stem cells (BM-MSCs). In vivo experiments confirmed that the G-TCP scaffolds had high bioactivity in modulating in situ regeneration of bone, and the bioactivity of the G-TCP scaffolds was endowed by correct pore structures, degradation of gypsum, and growth of a bone-like apatite layer. The microenvironment established by the gypsum degradation could stimulate tissue inflammation and recruit white blood cells and BM-MSCs and thus accelerating native healing cascades of the bone defects via a bone growth/remodeling-absorption cycle process. Furthermore, in vivo experiments demonstrated that after the bone defects had healed completely, the as-prepared scaffolds also degraded completely within 24 weeks.

Mesenchymal stem cells (MSCs) are a promising regenerative medicine. The roles of miRNAs in osteogenic differentiation of bone marrow MSCs (BM-MSCs) remained less reported. Forkhead Box O3 (FOXO3) and alkaline phosphatase (ALP) levels in the BM-MSCs were measured on 3, 7, and 14 days after osteogenic differentiation. After transfection of FOXO3 overexpression plasmids or siFOXO3 into BM-MSCs, factors related to osteogenic differentiation or cell autophagy were determined. Besides, 3-methyladenine or rapamycin, as well as miR-223-3p mimic or inhibitor were applied to further determine the effect of FOXO3 in BM-MSCs. FOXO3 and ALP levels were increased in a time-dependent manner with osteogenic differentiation, supported by Alizarin Red Staining. Furthermore, up-regulated FOXO3 increased levels of ALP and factors related to osteogenic differentiation by increasing levels of autophagy-related factors. FOXO3, targeted by miR-223-3p, reversed the effects of miR-223-3p on factors related to BM-MSC autophagy and osteogenic differentiation. Down-regulated miR-223-3p expression promoted osteogenic differentiation of BM-MSCs by enhancing autophagy via targeting FOXO3, suggesting the potential of miR-223-3p as a therapeutic target for enhancing bone functions.

目的 分析维生素D辅助股骨近端防旋髓内钉(proximal femoral nail anti-rotation,PFNA)内固定治疗老年股骨转子间骨折的远期疗效.方法 选取2018年1月至2019年6月四川大学华西医院骨科收治的老年股骨转子间骨折患者60例为研究对象,按照随机数字表法将其分为对照组和研究组,每组各30例.研究组患者采取维生素D辅助PFNA内固定治疗,对照组患者采取PFNA内固定治疗.随访1年,比较两组患者治疗总有效率、简明健康状况调查表(short-form health survey-36,SF-36量表)评分、Harris髋关节评分(Harris hip score,HHS)及血清骨形态发生蛋白质-7(bone morphogenetic protein-7,BMP-7)、25-羟维生素D3[25-hydroxyvitamin D3,25(OH)D3]水平.结果 治疗后12个月,研究组患者治疗总有效率显著高于对照组(χ2=4.320,P=0.038);两组患者SF-36量表各项评分均显著高于本组治疗前(均P<0.05),且研究组患者上述评分均显著高于对照组(均P<0.01).治疗后1、2、3、6、12个月,研究组患者HHS、血清BMP-7和25(OH)D3水平均显著高于同期对照组(均P<0.05).随着随访时间的延长,研究组患者HHS、血清BMP-7和25(OH)D3水平升高幅度均显著大于对照组(均P<0.05).结论 维生素D辅助PFNA内固定能够明显提高老年股骨转子间骨折患者血清BMP-7和25(OH)D3水平,对改善髋关节功能具有良好的远期疗效.

In this study, we obtained the RNA expression data of murine skin tissues of control, and UVB irradiated groups. After the re-annotation of lncRNAs, a gene expression similarity analysis was done by WGCNA. The target mRNA prediction of lncRNAs, miRNAs, and ceRNA regulatory networks were constructed by five lncRNAs, 14 miRNAs and 54 mRNAs, respectively. Based on the ceRNA network of UVB-induced skin lesions, it was evident that the dysregulation of Meg3 has critical effects on the UVB-induced inflammatory lesion of murine skin tissues. The overexpression of Meg3 after UVB irradiation was observed in primary murine skin fibroblasts, and the up-regulated Meg3 expression was related to the activation of the inflammatory cytokines. These functional experiments demonstrated that the RNA silencing of Meg3 in murine skin fibroblasts could suppress the expression of the cytokines (in vitro) and UVB-induced skin lesions (in vivo). Moreover, the Meg3 functioned as a competing endogenous RNA (ceRNA) that acted as a sponge for miR-93-5p and thereby modulated the expression of Epiregulin (Ereg). Our results proved that Meg3 was involved in UVB-induced skin inflammation and that the ceRNA networks, which includes miR-93-5p and Ereg, could prove to be a potential therapeutic target for UVB-induced skin damage.

Long non-coding RNAs (lncRNAs) are novel players in intervertebral disc degeneration (IDD) and show multiple functions. LncRNA lincRNA-SLC20A1 (SLC20A1) is aberrantly expressed in IDD. However, the role of SLC20A1 in degenerative nucleus pulposus (NP) cells and its underlying mechanism are unclear. The expressions of SLC20A1, miR-31-5p, and MMP3 were determined using RT-qPCR and western blotting. Extracellular matrix (ECM) degradation was evaluated by ECM-related genes collagen II, aggrecan, and ADAMTS4 using western blotting and an enzyme-linked immunosorbent assay (ELISA). The target binding between miR-31-5p and SLC20A1 or matrix metalloproteinase (MMP3) was predicted based on the miRcode or starBase websites and confirmed using a luciferase reporter assay and an RNA pull-down assay. SLC20A1 expression is upregulated in NP tissues from IDD patients, and this expression promotes ADAMTS5 expression and represses collagen II and aggrecan expression in degenerative NP cells derived from IDD patients. Mechanically, SLC20A1 acts as a competing endogenous RNA (ceRNA) to negatively regulate miRNA-31-5p (miR-31-5p) expression. Moreover, MMP3 is a downstream target for miR-31-5p and is positively modulated by SLC20A1 in degenerative NP cells. Similar to the SLC20A1 effect in human NP cells, the downregulation of miR-31-5p facilitates ECM degradation as well. On the contrary, miR-31-5p upregulation abolishes the promoting role of SLC20A1 in degenerative NP cells, the effect of which is then blocked by the ectopic expression of MMP3. The upregulation of SLC20A1 aggravates ECM degradation in degenerative human NP cells by targeting the miR-31-5p/MMP3 axis, suggesting that the SLC20A1/miR-31-5p/MMP3 pathway can contribute to IDD progression.

Herein, we describe a convenient approach for the preparation of a polymeric micelle using doxorubicin (DOX) conjugated trimethyl-chitosan (TMC) with Beclin-1 siRNA (Si-Beclin1/DOX-TMC). This micelle displayed a potent capacity for autophagy inhibition and reversed drug-resistance to DOX in BIU-87/ADR cell lines. The Si-Beclin1/DOX-TMC micelle was highly cytotoxic to both drug-sensitive BIU-87 and drug-resistant BIU-87/ADR cells. Its capacity to reverse drug-resistance was dependent upon upregulation of autophagy levels in BIU-87/ADR cells. DOX was conjugated to TMC via a pH-sensitive Schiff base, which responded to the acidic lysosome microenvironment and resulted in the cytoplasmic release of DOX. The structure of DOX conjugation to the TMC polymeric micelle was characterized by NMR, GPC, TEM and DLS. DOX release profiles in different pH environment were determined by HPLC. Cellular uptake, changes to nuclei morphology and formation of autophagosomes were observed using a fluorescence microscope. Finally, in vivo antitumor activity of systemic Si-Beclin1/DOX-TMC micelle administration was evaluated in BIU-87/ADR xenograft models and Si-Beclin1/DOX-TMC micelles showed significantly suppressed tumor growth.

OBJECTIVE To determine the influence factors for limb salvage of bone fracture patients with hyperpotassemia caused by Wenchuan earthquake, to discuss the clinical symptom and to improve the clinical treatment. METHODS The clinical symptom, drug therapy, limb incision decompression, hemodialysis, and limb salvage of hyperpotassemia caused by earthquake were analyzed by logistic regression. RESULTS All the 37 patients received drug therapy: 9 patients received incision and decompression singlely,8 received hemodialysis singlely,and the other 20 received decompression and hemodialysis simultaneously. The concentration of potassium decreased from (6.25 +/- 0.91) mmol/L to (4.47+/-0.65) mmol/L,with significant difference (P<0.05). Five patients with Gustilo III grade open injury received amputation at the concentration of potassium of (6.13+/-0.78) mmol/L, while the concentration of potassium for the other 32 patients was (6.25+/-0.31) mmol/L. There was no significant difference between them(P>0.05). Logistic regression analysis found the time of compression, the time before incision and decompression, and the time before hemodialysis were the main factors to affect limb salvage. The OR value of these factors was 4.394, 3.793 and 5.432;while the P value was 0.013, 0.047, and 0.015, respectively. CONCLUSION Decreasing the time of compression, appropriate incision and decompression, and hemodialysis help improve the result of limb salvage in hyperpotassemia patients with bone fracture caused by earthquake.

[Objective]To discuss the injury severity and treatment of 236 patients with upper limb injuries in Wenchuan Earthquake.[Method]The basic informations of patients with upper limb injures in Wenchuan Earthquake,and the injury mechanisms,clinical symptoms and treatment were collected and analyzed.[Result]In 236 cases of patients with upper limb injuries,there were 208 patients,378 cases with fracture,and 64 cases with open fracture.There were 35 cases of clavicle fracture,31 cases of scapula fracture,113 cases of humerus fracture,46 cases of ulna fracture,87 cases of radial fracture and 66 cases of carpometacarpai phalangeal fracture.Fifty cases received debridement and suture,60 cases received fracture reduction and internal fixation and 7 cases received external fixation.Totally,19 limbs were carried on amputation,and only one patient died of hyperkalemia and combined injury.[Conclusion]Analysis of patients with injury mechanisms,clinical symptoms and treatment can provide advices for rescuing and treating of patients with upper limb injuries in earthquake or other disaster cases.