Skeletal muscle stem cells (SkMSCs) are essential for muscle regeneration and represent a promising therapeutic target for muscle disorders. However, effective strategies to precisely regulate SkMSC fate by integrating biochemical and mechanical cues remain limited. A decellularized extracellular matrix (ECM) hydrogel replicating the native muscle microenvironment was developed. The hydrogel was loaded with TGFβ1 and applied to SkMSCs in vitro and in Sprague-Dawley rat models. Signaling activation, m6A methylation of integrin mRNA, ERK phosphorylation, and functional outcomes were assessed through molecular and physiological analyses. The TGFβ1-loaded ECM hydrogel significantly enhanced SkMSC proliferation and differentiation by activating ERK signaling. Mechanistically, TGFβ1 promoted m6A methylation of integrin mRNA, leading to sustained ERK phosphorylation. In vivo, ECM hydrogels and TGFβ1 synergistically improved SkMSC function and muscle regeneration via m6A-modulated integrin signaling. This study reveals a novel m6A-mediated pathway that integrates biochemical (TGFβ1) and mechanical (ECM hydrogel) signals to direct SkMSC fate and provides a promising biomaterial-based strategy for treating muscle diseases through microenvironment-mimicking regenerative engineering. Decellularized ECM hydrogel mimics muscle microenvironment. TGFβ1 enhances SkMSC proliferation and differentiation via ERK signaling. TGFβ1 promotes m6A methylation of integrin mRNA, activating ERK. ECM hydrogel and TGFβ1 synergistically improve SkMSC function in rats.

Diabetes-induced skeletal muscle atrophy is closely linked to oxidative stress and chronic inflammation, which severely compromise quality of life. This study aimed to identify effective anti-inflammatory strategies to mitigate muscle degeneration in diabetes. We investigated the molecular mechanism of Ginsenoside CK (Gin), a major bioactive component of ginseng known for its anti-inflammatory properties. Using activity-based protein profiling, we identified never in mitosis A-related kinase 7 (NEK7) as a direct target of Gin. Mechanistically, Gin covalently binds to histidine 262 (H262) of NEK7-an essential residue for NEK7-NLRP3 interaction-thereby disrupting inflammasome formation. In a diabetic mouse model of skeletal muscle atrophy, Gin administration significantly inhibited NEK7-NLRP3 complex formation, reduced interleukin-6 levels, and attenuated muscle atrophy. These findings establish NEK7 as a critical therapeutic target of Gin and suggest that targeting the NEK7-NLRP3 axis may offer a promising strategy for treating inflammation-driven diabetic muscle wasting. Developing novel inhibitors of NEK7-NLRP3 interaction are expected to advance the treatment of inflammation-associated conditions.

Abstract N6-methyladenosine (m6A)-associated mechanisms are involved in cellular metabolic activities; however, their role in skeletal muscle stem cell (SkMSC) senescence is unknown. In this study, m6A RNA modification and METTL3 expression were decreased in aged SkMSCs from mice. Transcriptional analysis of m6A modification further revealed that suppressor of cytokine signaling 3 (SOCS3) was downregulated in aged SkMSCs, and that downregulation of METTL3 promoted SkMSC senescence. In addition, the upregulation of METTL3 alleviated the senescence of SkMSCs. Mechanistically, deletion of m6A modifications promoted senescence and inhibited SOCS3 expression, whereas downregulation of SOCS3 promoted senescence. Moreover, insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) was identified as an important regulator in the recognition and stabilization of m6A modified SOCS3 expression. IGF2BP1 binds to SOCS3 and reinforces its stability by suppressing the phosphorylation of JAK2/STAT3. Therefore, METTL3 inhibits SkMSC senescence through m6A modification-dependent stabilization of SOCS3 expression and inhibition of JAK2-STAT3 signaling. This study thus highlights a novel mechanism underlying SkMSC senescence.

Skeletal muscle is capable of repairing itself after injury to maintain the stability of its own tissue, but this ability declines with aging. Circular RNAs (circRNAs) are involved in cell aging. However, there is little research into their role and underlying mechanisms, especially in skeletal muscle stem cells (SkMSCs). In this study, we assessed circRNA FUT10 expression in aged and adult SkMSCs. We observed that circRNA FUT10 was upregulated in aged SkMSCs compared with that in adult SkMSCs. Furthermore, we identified putative miR-365-3p binding sites on circRNA FUT10, suggesting that this circRNA sponges miR-365a-3p. We also found that HOXA9 is a downstream target of miR-365a-3p and confirmed that miR-365a-3p can bind to circRNA FUT10 and the 3'-untranslated region of HOXA9 mRNA. This finding indicated that miR-365a-3p might serve as a "bridge" between circRNA FUT10 and HOXA9. Finally, we found that the circRNA FUT10/miR365a-3p/HOXA9 axis is involved in SkMSC aging. Collectively, our results show that the circRNA FUT10/miR365a-3p/HOXA9 axis is a promising therapeutic target and are expected to facilitate the development of therapeutic strategies to improve the prognosis of degenerative muscle disease.

Background: The purpose of this study was to illustrate the characteristics of skeletal muscle ECM hydrogels and assess the function and underlying mechanisms of hydrogels combined with TGFβ1 for the myogenesis of skeletal muscle stem cells (SkMSCs). Methods: Six methods were used to obtain extracellular matrix (ECM) from rat skeletal muscle. Hydrogel components and cytocompatibility were assessed by Masson’s trichrome staining, scanning electron microscopy, the sulfated glycosaminoglycan (s-GAG) and bFGF contents and a cell viability assay. Satellite cells were sorted, identified and seeded into skeletal muscle ECM hydrogels with TGFβ1. To determine the function of decellularized aligned skeletal muscle ECM hydrogels with TGFβ1 for the proliferation and differentiation of SkMSCs, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2′-deoxyuridine (EdU) analysis and immunofluorescence staining were conducted. RNA stability assay and Gene set enrichment analysis (GSEA) were used to further investigated the mechanism underlying the function. Results: Our study established a highly efficient method for the decellularization of skeletal muscle and fabricated an ECM hydrogel without cell components that preserves the rich ECM composition. This hydrogel formed a three-dimensional microstructure and showed good biocompatibility. We found that the decellularized aligned ECM scaffold with TGFβ1 promoted SkMSC proliferation and suppressed SkMSC differentiation through extracellular signal-regulated kinase (ERK) signaling. Our study suggested that TGFβ1 increases the m6A methylation of the integrin mRNA 3’UTR, thereby inducing the phosphorylation of ERK and promoting SkMSCs proliferation and differentiation.Conclusions: Our study explored a highly efficient method for the decellularization of skeletal muscle and fabricated an ECM hydrogel with a three-dimensional microstructure and good biocompatibility. Furthermore, we demonstrated that decellularized aligned ECM scaffolds with TGFβ1 promoted SkMSC proliferation and differentiation through enhancing the m6A methylation of the integrin mRNA 3’UTR, which may serve as a potential therapeutic strategy for the acute and chronic muscle injuries

Abstract Background: The purpose of this study was to illustrate the characteristics of skeletal muscle ECM hydrogels and assess the function and underlying mechanisms of hydrogels combined with TGFβ1 for the myogenesis of skeletal muscle stem cells (SkMSCs). Methods: Six methods were used to obtain extracellular matrix (ECM) from rat skeletal muscle. Hydrogel components and cytocompatibility were assessed by Masson’s trichrome staining, scanning electron microscopy, the sulfated glycosaminoglycan (s-GAG) and bFGF contents and a cell viability assay. Satellite cells were sorted, identified and seeded into skeletal muscle ECM hydrogels with TGFβ1. To determine the function of decellularized aligned skeletal muscle ECM hydrogels with TGFβ1 for the proliferation and differentiation of SkMSCs, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 5-ethynyl-2′-deoxyuridine (EdU) analysis and immunofluorescence staining were conducted. RNA stability assay and Gene set enrichment analysis (GSEA) were used to further investigated the mechanism underlying the function. Results: Our study established a highly efficient method for the decellularization of skeletal muscle and fabricated an ECM hydrogel without cell components that preserves the rich ECM composition. This hydrogel formed a three-dimensional microstructure and showed good biocompatibility. We found that the decellularized aligned ECM scaffold with TGFβ1 promoted SkMSC proliferation and suppressed SkMSC differentiation through extracellular signal-regulated kinase (ERK) signaling. Our study suggested that TGFβ1 increases the m6A methylation of the integrin mRNA 3’UTR, thereby inducing the phosphorylation of ERK and promoting SkMSCs proliferation and differentiation.Conclusions: Our study explored a highly efficient method for the decellularization of skeletal muscle and fabricated an ECM hydrogel with a three-dimensional microstructure and good biocompatibility. Furthermore, we demonstrated that decellularized aligned ECM scaffolds with TGFβ1 promoted SkMSC proliferation and differentiation through enhancing the m6A methylation of the integrin mRNA 3’UTR, which may serve as a potential therapeutic strategy for the acute and chronic muscle injuries

BackgroundCircular RNAs (circRNAs) are involved in the occurrence and development of breast cancer bone metastasis. This study aims to identify whether the circRNA DENND4C/ miR145-5p/HOXA9 axis is involved in the regulation of cell invasion and migration and breast cancer progression.MethodscircRNA DENND4C, miR-145-5p and HOXA9 expression was measured in serum samples from healthy volunteers, breast cancer patients without bone metastasis and breast cancer patients with bone metastasis. Moreover, we analyzed the levels of circRNA DENND4C, miR‑145-5p and HOXA9 according to different conditions of differentiation, tumor volume and lymph node metastasis. The online software starBases and the dual-luciferase reporter gene assay were used to predict the relationship miR-145-5p, circRNA DENND4C and HOXA9 mRNA. MTT assays were performed to assess the effect of circRNA DENND4C on proliferation. To assess the proliferation of breast cancer cells among different groups. Statistical significance was determined byStudent's t‑test which was used for comparisons between two groups and one‑way analysis of variance followed by Tukey's post hoc test for comparisons between more than two groups.ResultsThe expression patterns of circRNA DENND4C, miR145-5p and HOXA9 were altered in patients with breast cancer bone metastasis. Notably, the stimulatory effects of circRNA DENND4C overexpression on HOXA9 were eliminated by miR-145-5p upregulation. circRNA DENND4C overexpression promotes proliferation, migration and invasiveness by regulating the miR-145-5p/HOXA9 axis. circRNA DENND4C downregulation suppresses proliferation, cell viability and invasiveness by regulating the miR-145-5p/HOXA9 axis. ConclusionOur study suggest that circRNA DENND4C/miR-145-5p/HOXA9 pathway was involved in tumor growth and bone metastasis in breast cancer. This findings may facilitate the development of potential therapeutic agents to improve the prognosis of patients with breast cancer bone metastasis.

MicroRNA-217-5p (miR-217-5p) has been implicated in cell proliferation; however, its role in skeletal muscle stem cells (SkMSCs) remains unknown. The present study aimed to explore the roles of miR-217-5p in the biological characteristics of SkMSCs. SkMSCs were identified by cell surface markers using flow cytometry. The present study observed that miR-217-5p mimics accelerated the proliferation and suppressed the differentiation in SkMSCs. In addition, the results of the present study revealed that fibroblast growth factor receptor 2 (FGFR2) was a target of miR-217-5p, as miR-217-5p bound directly to the 3′-untranslated region of FGFR2 mRNA, resulting in increased FGFR2 mRNA and protein levels. In addition, the present study suppressed the expression of FGFR2 in SkMSCs using a selective FGFR inhibitor AZD4547 and detected the efficiency of inhibition by reverse transcription-quantitative PCR and western blotting. miR-217-5p levels were positively associated with FGFR2 expression, which was upregulated and accelerated the proliferation of SkMSCs compared with that of the miR-NC group. Collectively, these results demonstrated that miR-217-5p may act as a myogenesis promoter in SkMSCs by directly targeting FGFR2 and may regulate the myogenesis of these cells.

Objective:To explore the therapeutic outcome of rat skeletal muscle extracellular matrix(ECM) hydrogels blended with skeletal muscle stem cells for skeletal muscle defects in a rat model.Methods:From May, 2018 to January, 2020, 5 methods were employed to obtain ECM from rat skeletal muscle. The resulting ECM was evaluated using haematoxylin and eosin (HE) staning and 4-6-diamidino-2-phenylindole (DAPI) staining. The components and structure of hydrogel were assessed by Masson staining and scanning electron microscopy (SEM). Skeletal muscle stem cells were then blended in the hydrogel and MTT was used to observe the growth of cells. Rat skeletal muscle defect models were established and HE staining was used to examine the growth of injured skeletal muscle in each group. Expression of Pax7 and MyoD were detected by immunofluorescence in each group. The function of skeletomuscular tissue was evaluated by electrical stimulation in each group. T test and ONE-WAY analysis of variance were used for data analysis.Results:In this study, a method that caused little damage to skeletal muscle structure and completely removed the cell components was found. This method was employed in the preparation of hydrogel. Masson staining and SEM showed that hydrogel retained the basic structure and some biological factors of skeletal muscle. MTT test showed that hydrogel promoted the proliferation of skeletal muscle stem cells. The experiments in rat skeletal muscle defect models showed that the group treated with stem cells [Specific force was (9.00±2.10) N/cm 2 achieved better outcomes than the other groups (4.06±1.12) N/cm 2 and (5.00±1.60) N/cm 2 in unrepaired group and hyclrogel group, respectively] ( P<0.05) . Conclusion:The results indicated that ECM hydrogel has a good biocompatibility. Furthermore, it was observed that rat skeletal muscle ECM hydrogels blended with skeletal muscle stem cells promoted the repair of muscle defect in a rat model, which would offer a promising strategy for functional muscle repair.

The C5-C6 nerve roots are usually spared from avulsion after brachial plexus injury (BPI) and can thus be used as donors for nerve repair. A BPI rat model with C5-C6 nerve root stumps has been established in our previous work. The aim of this study was to test whether riluzole loaded into a thermosensitive hydrogel could applied locally in the nerve root stumps of this BPI rat model, thus increasing the reparative effect of the nerve root stumps. Nile red (a hydrophobic dye) was used as a substitute for riluzole since riluzole itself does not emit light. Nile red, loaded into a thermosensitive hydrogel, was added to the nerve root stumps of the BPI rat model. Additionally, eighteen rats, with operation on right brachial plexus, were evenly divided into three groups: control (Con), thermosensitive hydrogel (Gel) and thermosensitive hydrogel loaded with riluzole (Gel + Ri) groups. Direct nerve repair was performed after local riluzole release for two weeks. Functional and electrophysiological evaluations and histological assessments were used to evaluate the reparative effect 8 weeks after nerve repair. Nile red was slowly released from the thermosensitive hydrogel and retrograde transport through the nerve root stumps to the motoneurons, according to immunofluorescence. Discernible functional recovery began earlier in the Gel + Ri group. The compound muscle action potential, ChAT-expressing motoneurons, positivity for neurofilaments and S100, diameter of regenerating axons, myelin sheath thickness and density of myelinated fibers were markedly increased in the Gel + Ri group compared with the Con and Gel groups. Our results indicate that the local administration of riluzole could undergo retrograde transportation through C5-C6 nerve root stumps, thereby promoting neuroprotection and increasing nerve regeneration.

AbstractBackgroundThe outcomes for open tibial fractures with severe soft tissue injury are still a great challenge for all the trauma surgeons in the treatment. However, most of the existing open tibial fracture models can only provide minimal soft tissue injury which cannot meet the requirement of severe trauma research. Our goal is to investigate a novel tibial fracture model providing different fractures combined with soft tissue injury for better application in trauma research.MethodsA total of 144 Sprague-Dawley rats were randomly divided into 4 groups. With group 1 as control, the other groups sustained different right tibial fractures by the apparatus with buffer disc settings either 3 mm, 10 mm, or 15 mm. X-ray and computed tomography angiography (CTA) were performed at 6 h to evaluate the fracture patterns and vascular injuries. Peripheral blood and tibialis anterior muscle were harvested at 6 h, 1 day, 3 days, 7 days, 14 days, and 28 days for ELISA and histological analysis.ResultsX-ray and μCT results indicated that different fractures combined with soft tissue injuries could be successfully provided in this model. According to OTA and Gustilo classification, the fractures and soft tissue injuries were evaluated and defined: 36 type I in group 2, 34 type II in group 3, and 36 type III in group 4. The CTA confirmed no arterial injuries in groups 1 and 2, 2 arterial injuries in group 3, and 35 in group 4. ELISA indicated that the levels of pro-inflammatory cytokines TNF-α and IL-1β were significantly higher in group 4 than in other groups, and the levels of anti-inflammatory cytokines TGF-β and IL-10 were significantly higher in surgery groups than in group 1 in later stage or throughout the entire process. HE, Masson, and caspase-3 stains confirmed the most severe inflammatory cell infiltration and apoptosis in group 4 which lasted longer than that in groups 2 and 3.ConclusionsThe novel apparatus was valuable in performing different fractures combined with soft tissue injuries in a rat tibial fracture model with high reproducibility and providing a new selection for trauma research in the future.

Lung cancer is the leading cause of cancer-related deaths worldwide, with 50–70% of patients suffering from bone metastasis. Accumulating evidence has demonstrated that miRNAs are involved in cell proliferation, migration, and invasion in malignancy, such as lung cancer bone metastasis. In the present study, we demonstrated that reduced miR-192-5p and increased TRIM44 levels were associated with the proliferation, migration and invasion of lung cancer. Furthermore, the potential functions of miR-192-5p were explored in A549 and NCI-H1299 cells. We found that miR-192-5p upregulation suppressed tumour behaviours in lung cancer cells. To further investigate whether miR-192-5p is associated with TRIM44, we used TargetScan software to predict the binding site between miR-192-5p and TRIM44. Luciferase activity assays were performed to verify this prediction. In addition, the significant role of miR-192-5p in negatively regulating TRIM44 expression was manifested by our research group. our results suggest that miR-192-5p inhibited the proliferation, migration and invasion of lung cancer through TRIM44.

BACKGROUND: Antagonism of bone sclerosis protein can stimulate osteogenesis and increase bone synthesis and metabolism through the Wnt/β-catenin signaling pathway. OBJECTIVE: To investigate the effects of sclerostin-single chain antibody fragment (Scl-scFv) on the proliferation and osteogenic differentiation of C57BL/6 mouse bone marrow mesenchymal stem cells (BMSCs). METHODS: BMSCs were isolated from C57BL/6 mice using whole bone marrow adherence method. Alizarin red staining was performed at the 14thday of osteogenic induction, and oil red O staining performed at the 7thday of adipogenic induction. Passage 3 BMSCs were cultured with α-MEM complete medium with (experimental) or without (control) 50 μg/L Scl-scFv aScl-scFv. Real-time PCR was used to detect type 1 collagen, alkaline phosphatase, RUNX2, osteopontin, osteocalcin at the 7thday of culture and meanwhile, alkaline phosphatase staining was done; western blot assay was used to detect expression of type 1 collagen and osteopontin proteins, and ELISA was used to detect the level of osteocalcin in the cell supernatant at 4, 7, 10 days of culture. RESULTS AND CONCLUSION: Formation of calcium nodules and orangered oil droplets was obviously visible in the BMSCs after osteogenic and adipogenic induction, respectively. Over time, the absorbance value showed no difference between the experimental and control group. Compared with the control group, the experimental group showed significant increases in mRNA and protein expression of type 1 collagen and osteopontin as well as in protein expression of alkaline phosphatase, RUNX2 and osteocalcin (P < 0.05). Moreover, stronger alkaline phosphatase staining was found in the experimental group relative to the control group. These findings indicate that Scl-scFv has no effect on BMSCs proliferation,but can promote the osteogenic capacity of BMSCs in vitro.

目的 分析D-二聚体(D-D)及纤维蛋白原(fibrinogen,FIB)对老年髋部骨折患者围术期深静脉血栓形成(DVT)的诊断价值.方法 回顾性分析2015年1月至2016年6月我科老年髋部骨折后手术治疗患者169例(年龄＞ 60岁),根据彩色多普勒超声将患者分为无血栓组157例(男43例、女114例,平均年龄78岁)和血栓组12例(男4例、女8例,平均年龄76岁).记录患者性别、年龄、术前制动时间、手术时间、基础疾病,术前、术后1～5 d、术后6～ 10d的血浆D-D值及FIB值.应用SPSS 20.0统计软件,绘制ROC曲线,进行统计学分析.结果 2组患者性别、年龄、术前制动时间、术前和术后6～10d D-D和FIB值的差异均无统计学意义(P＞0.05);2组基础疾病、术后1～5dD-D和FIB值的差异有统计学意义(P＜0.05).根据ROC曲线,单独检测D-D和FIB时,术后1～5 d的D-D值和FIB曲线下最大面积分别为0.801和0.746,位于ROC曲线左上角的值为截断值,血浆D-D＞1 587μg/L和FIB＞4.69g/L,D-D和FIB联合检测时ROC曲线下面积为0.835,联合检测时的敏感性和准确度较单独诊断时高.结论 根据ROC曲线,髋部骨折术后1～5d,D-D＞1 587μg/L和FIB＞4.69 g/L的患者发生DVT的风险较大,应尽早进行相关检查,积极预防和治疗.

Objective To investigate the impact of inhibiting the function of sclerostin by antibodies in tumor cells on MDAMB-231 induced bone metastasis.Methods MDA-MB-231 cells were co-cultured with sclerostin antibody(Sci-Ab).Twenty-four female nude mice aged 6-8 weeks were divided randomly into two groups (n =12).MDA-MB-231 cells (6 × 105) were injected into the bone marrow space.The mice were treated with normal saline (NS) and sclerostin antibody (Sci-Ab),respectively.Thirty-five days after the treatment,all the nude mice were subjected to pathological examination to determine bone metastasis.The bone remodelling activities were compared between PBS treatment group and antibody treatment group using micro-CT analysis.Student's t-test was used for the comparison of quantitative data,and Fisher's exact test was used for the comparison of qualitative data.Results According to MTT assay and Wound Healing,higher Sci-Ab promoted the proliferation and invasion of MDA-MB-231 cells.There were six bone metastasis lesions detected in control group(treated with normal saline),and nine in experimental group(treated with Sci-Ab),but there was no statistically significant difference between the two groups(P =0.30).The bone tumor volume of control group and experimental group was (0.87 ± 0.244) cm3 and (0.73 ± 0.118) cm3,respectively (P =0.35).The survival of experimental group was significantly longer than that of control group(P ＜ 0.05).Micro-CT analysis of the tumor-bearing mice indicated that Sci-Ab was effective in bone protection against breast cancer-induced bone destruction as the bone mineral density (BMD;g/cm2) was significantly increased (P ＜ 0.05).Conclusions Bone metastasis from breast cancer is closely correlated with the sclerostin expression level in tumor cells.Inhibiting the expression of sclerostin can promote proliferation and invasion of MDA-MB-231 cells in vitro and improve the survival of mice in vivo.

BACKGROUND:Sclerostin has been shown to promote bone formation and decrease bone resorption,which provides a new idea for the treatment of osteoporosis.OBJECTIVE:To review the literatures related to sclerostin and osteoporosis,thereby providing theoretical basis for sclerostin applied in the treatment and prevention of osteoporosis,so as to improve the diagnosis and curative efficacy of osteoporosis.METHODS:PubMed database was searched using the keywords of "osteoporosis,sclerostin,sclerosteosis,Wnt/β-catenin,LRP5/6,sclerostin antibody,sclerostin and expertise,romosozumab,blosozumab".Finally,58 pertinent articles were enrolled for analysis.RESULTS AND CONCLUSION:Sclerostin inhibits bone formation,so anti-sclerostin antibody is utilized,and animal experiments and clinical trials have shown that it can promote bone formation and inhibit bone reaorption.Phase Ⅲ trial results potentially signify a significant step in achieving market approval,which support the preclinical and clinical emergence of sclerostin antibody therapies for both osteoporosis and alternative applications.The serum level of sclerostin is found to be closely related to lifestyle,but still need to be studied in depth.Increasing trial results show that sclerostin is the promising therapeutic candidate,which provides a new direction in the prevention and treatment of osteoporosis.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Many patients suffer from bone metastasis. Sclerostin, a key regulator of normal bone remodeling, is critically involved in osteolytic bone diseases. However, its role in breast cancer bone metastasis remains unknown. Here, we found that sclerostin was overexpressed in breast cancer tumor tissues and cell lines. Inhibition of sclerostin by antibody (Scl-Ab) significantly reduced migration and invasion of MDA-MB-231 and MCF-7 cells in a time- and dose-dependent manner. In xenograft model, sclerostin inhibition improved survival of nude mice and prevented osteolytic lesions resulting from tumor metastasis. Taken together, sclerostin promotes breast cancer cell migration, invasion and bone osteolysis. Inhibition of sclerostin may serve as an efficient strategy for interventions against breast cancer bone metastasis or osteolytic bone diseases.

Objective To explore the risk factors for deep venous thrombosis ( DVT ) after knee arthroplasty and the diagnosis value of D-dimer for DVT.Methods A retrospective study was performed on 136 patients ( male 40, female 96 ) undergoing knee replacement surgery between January 2013 and December 2015, whose average age was ( 70.7 ± 10.1 ) years. Ultrasonography was used to assess the DVT occurrence in the lower limbs of the patients. Logistic regression was used to identify the association of DVT and the variables including the gender, age, preoperative braking time, duration of surgery, bed rest time after the surgery, plasma D-dimer concentration, ifbrinogen ( FIB ) concentration and chronic illness.Results The plasma D-dimer level was 1.82 mg / L ( range: 1.53 - 4.53 mg / L ) in the DVT group, which was 0.45 mg / L ( range: 0.21 - 1.22 mg / L ) in the control group. And the differences were statistically signiifcant (P < 0.05 ). Logistic regression analysis showed that plasma D-dimer level, duration of surgery and chronic illness were risk factors for the development of DVT, but further studies should be performed on the association of DVT and the age, gender, preoperative braking time, bed rest time after the surgery and FIB concentration. Receiver operating characteristic ( ROC ) curves showed when the cut-off point of plasma D-dimer was 1.5 mg / L, the sensitivity was 88.9% and the speciifty was 84.7% in the prediction of DVT.Conclusions Duration of surgery and chronic illness are signiifcant risk factors for the development of DVT. When the plasma D-dimer is more than 1.5 mg / L, a higher occurrence rate of DVT should be noticed, and regular review of leg veins and clinical intervention may be necessary.

Objective To explore the causes and prevention strategies of wound complications after operative fixation of calcaneal fracture.Methods A retrospective analysis was performed of the 65 patients with calcaneal fracture who had been treated with operative fixation from January 2008 to January 2013 at our department.They were 38 males and 17 females,19 to 68 years of age (average,45 years).Laterality:29 on the left side and 36 on the right side.According to Sanders classification,16 cases were type Ⅱ,35 type Ⅲ,and 14 type Ⅳ.The duration from injury to surgery ranged from 3 hours to 14 days,averaging 7.1 days.The fractures were treated by the extended lateral approach,internal fixation with plate and bone transplantation.Their postoperative wound complications were documented.Wound complications occurred in 9 cases (13.8％) but did not in the other 56 ones.The 2 groups were compared in terms of age,gender,fracture type,American Society of Anesthesiologists(ASA) grading,fall height,operation time,tourniquet time and other surgery-associated factors to screen out the risk factors associated with wound complications.Results We found that ASA grading Ⅱ or above (OR =8.750,P =0.002),fall height (OR =9.570,P =0.003),operation time (P=0.027),tourniquet time (P-0.020),fime from injury to operation(P=0.004),hospital stay (P =0.013),hypoproteinemia (OR =6.000,P =0.012) were significantly associated with wound complications.Conclusions On the basis of routine treatment,these risk factors should be targeted by prevention measures.The postoperative wound complications after operative fixation of calcaneal fracture can be effectively prevented by careful assessment of soft tissue defects,proper timing for surgery,shortening operation time and tourniquet time,and rational management of postoperative wounds.