Zhijun Pan

Substantial evidence has demonstrated that the decreased osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is closely related to bone metabolic diseases. Thus, it is very important to develop several potentially useful therapeutic agents to enhance BMSC osteogenesis. Flavonoids show promise in enhancing bone mass. Dihydromyricetin (DMY), a type of flavonoid, has not yet been investigated regarding its effects on BMSC osteogenesis. To investigate the effects of DMY on osteogenesis, human BMSCs were induced with or without DMY. We found that DMY (0.1–50 μm) exhibited no cytotoxic effect on proliferation, but increased alkaline phosphatase activity, osteoblast‐specific gene expression, and mineral deposition. It also enhanced active β‐catenin expression and reduced dickkopf‐1(DKK1) and sclerostin expression. The Wnt/β‐catenin signaling pathway inhibitor (DKK1 and β‐catenin‐specific siRNA) decreased the enhanced bone mineral formation caused by DMY. Taken together, these findings reveal that DMY enhances osteogenic differentiation of human BMSCs partly through Wnt/β‐catenin in vitro.

The migration of mesenchymal stem cells (MSCs) and osteogenic differentiation occupy an important role in fracture healing. High mobility group box 1 (HMGB1), a widely distributed inflammatory factor in fractures, has been confirmed to act as a chemoattractant to MSCs. To investigate the effect of HMGB1 on MSC migration and the underlying mechanism, the synthesis of MSC chemokines, and the consequent activation of signaling pathways following HMGB1 stimulation, were evaluated. A Quantibody® array was performed to determine which chemokines were secreted from MSCs with or without treatment with HMGB1. The results indicated differential chemokine synthesis by MSCs following treatment with HMGB1, including that of CCL4 and CCL13. In addition, the Ras‑associated protein‑1 (Rap1) signaling pathway was markedly activated in the HMGB1‑treated groups, suggesting that HMGB1 may enhance the migrational ability of MSCs via Rap1 activation. Furthermore, HMGB1 was able to promote the secretion of various chemokines derived from MSCs, which would, in turn, increase the mobility of MSCs. Taken together, these results provide a mechanistic basis for developing novel approaches to promote fracture healing.

HSPA1A, which encodes cognate heat shock protein 70, plays important roles in various cellular metabolic pathways. To investigate its effects on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), its expression level was compared between undifferentiated and differentiated BMSCs. Rat HSPA1A overexpression in BMSCs increased osteoblast-specific gene expression, alkaline phosphatase activity and mineral deposition in vitro. Moreover, it upregulated β-catenin and downregulated DKK1 and SOST. The enhanced osteogenesis due to HSPA1A overexpression was partly rescued by a Wnt/β-catenin inhibitor. Additionally, using a rat tibial fracture model, a sheet of HSPA1A-overexpressing BMSCs improved bone fracture healing, as determined by imaging and histological analysis. Taken together, these findings suggest that HSPA1A overexpression enhances osteogenic differentiation of BMSCs, partly through Wnt/β-catenin.

Sutures are an increasing focus of research in knee arthroplasty (KA). Whether knotless barbed sutures (KBS) are safe and efficient in KA remains controversial. The objective of our study is to compare the clinical outcomes of KA according to wound closure method: KBS versus knotted traditional sutures (KTS). To clarify this, we conducted a systematic review and meta-analysis. Nine articles involving 10 studies were included in this study. The dataset consisted of 1729 patients with 1754 KA. Among these, 814 patients’ wounds were closed with KBS and 915 with KTS. Our analysis indicates that KBS is preferable for KA wound closure given its shorter wound closure time and lower total cost; postoperative Knee Society scores and complication rates were similar to those of surgeries using KTS. The subgroup analysis revealed that closure of arthrotomy with KBS appears to be associated with a lower risk of complications. This meta-analysis indicates that use of KBS in KA reduces operative time and cost. KBS is the preferred option for wound closures, including arthrotomy and reattachment of subcutaneous and subcuticular tissues. Given the possible biases, adequately powered and better-designed studies with longer follow-up are required to reach a firmer conclusion.

Increasing evidence indicates that the osteogenic differentiation of mesenchymal stem cells (MSCs) is related to bone formation, heterotopic ossification, and even vascular calcification. Therefore, it is essential to understand the microenvironment that regulates these processes. The Klotho gene plays an important role in tissue mineralization, and its secreted protein functions as a hormone. We investigated the effects of secreted Klotho protein on the osteogenesis of human bone marrow MSC (hBMSCs). To this end, the cells received osteogenic medium with or without Klotho protein. The results showed that osteoblast-specific gene expression and mineral deposition were decreased when MSCs were incubated with Klotho. Klotho reduced the expression of fibroblast growth factor receptor 1 (FGFR1) and phosphorylated extracellular signal-regulated kinase 1/2. However, both MEK and FGFR1 inhibitors delayed bone mineral formation more than Klotho. These data suggest that secreted Klotho protein attenuates the osteogenic differentiation of hBMSCs in vitro through FGFR1/ERK signaling.

The purpose of this study is to compare the rates of urinary tract infection (UTI) and postoperative urinary retention (POUR) in patients undergoing lower limb arthroplasty after either indwelling urinary catheterization or intermittent urinary catheterization. We conducted a meta-analysis of relevant randomized controlled trials (RCT) to compare the rates of UTI and POUR in patients undergoing total joint arthroplasty after either indwelling urinary catheterization or intermittent urinary catheterization. A comprehensive search was carried out to identify RCTs. Study-specific risk ratios (RR) with 95% confidence intervals (CI) were pooled. Additionally, a meta-regression analysis, as well as a sensitivity analysis, was performed to evaluate the heterogeneity. Nine RCTs with 1771 patients were included in this meta-analysis. The results showed that there was no significant difference in the rate of UTIs between indwelling catheterization and intermittent catheterization groups (P>0.05). Moreover, indwelling catheterization reduced the risk of POUR, versus intermittent catheterization, in total joint surgery (P<0.01). Based on the results of the meta-analysis, indwelling urinary catheterization, removed 24-48 h postoperatively, was superior to intermittent catheterization in preventing POUR. Furthermore, indwelling urinary catheterization with removal 24 to 48 hours postoperatively did not increase the risk of UTI. In patients with multiple risk factors for POUR undergoing total joint arthroplasty of lower limb, the preferred option should be indwelling urinary catheterization removed 24-48 h postoperatively. Level I.

To better clinical outcomes, open reduction and internal fixations (ORIFs) have been commonly performed in the case of closed displaced intra-articular calcaneal fractures (CDICFs). Nonetheless, postoperative wound complications remain a significant problem. Therefore, the aim of our study is to summarise relevant evidence investigating the risk factors for postoperative wound complications of CDICFs following ORIFs. A meta-analysis was conducted on relevant clinical studies to identify the risk factors for wound complications of CDICFs after ORIFs. Electronic databases were searched for all relevant studies up to October 2014. The Newcastle-Ottawa scale was used to evaluate the methodological quality, and study-specific odds ratios (ORs) were pooled using the fixed-effects model or random-effects model. Sensitivity analysis and meta-regression analysis was performed to evaluate the heterogeneity. Ten observational studies involving 1559 patients with 1651 fractures were included in this meta-analysis. The results showed that diabetes (OR, 9.76; p < 0.01), no drainage (OR, 5.86; p < 0.01), fracture severity (OR, 3.31; p < 0.01) and bone graft (OR, 1.74; p < 0.01) were the risk factors for wound complications of CDICFs after ORIFs. A trend of more wound complications in patients with a history of smoking was detected. However, female patients, ORIFs performed within 14 days of injury, smoking, hypertension and drinking did not significantly increase the risk of wound complications (p > 0.05). Based on available relevant evidence, bone graft, diabetes, no drainage and fracture severity were all associated with an increased risk of wound complications after ORIF for CDICFs.

The aim of this study is to evaluate the effects of tourniquet release before wound closure for hemostasis or after wound closure in cemented total knee arthroplasty (TKA). We conducted a meta-analysis and review work on relevant clinical outcomes to evaluate the effects of the timing of tourniquet release in cemented TKA. Electronic databases were searched for relevant randomized controlled trials (RCTs) that compared outcomes of tourniquet release before wound closure for hemostasis with tourniquet release after wound closure. The methodological quality of each included RCT was assessed in terms of the 12-item scale. The meta-analysis was performed with STATA 12.0 software. Eleven RCTs involving 651 patients with 670 TKAs were included in this meta-analysis. Of these, 332 patients (342 knees) were in an early tourniquet release group and 319 patients (328 knees) in the late tourniquet release group. The results showed that there were no significant differences in overt blood loss, hemoglobin drop, and blood transfusions, whereas the tourniquet release after wound closure might increase the risks of overall complications and major complications. Tourniquet release before wound closure for hemostasis might reduce the rate of complications, but it could not limit overall blood loss. The current evidences are not enough to indicate that tourniquet release before wound closure is superior to its release after wound closure in cemented TKA.

To investigate the effect and influence factors on knee joint peripheral fractures and/or dislocations with an associated vascular injury through retrospectively study. From March 2002 to November 2007 31 patients with knee joint peripheral fractures and/or dislocations with an associated vascular injury were treated, including 24 males and 7 females with a mean age of 41 years (range from 21 to 62 years). Definite diagnosis of vascular injury by combining colored ultrasonic, CTA, operative exploration with clinical signs, fixing fractures and/or dislocations with fixators, plates and screws, reconstructing blood circulation based on the condition of the vascular injury by vascular repair, homograft vein or artificial vascular grafting separately and analysing the effects of PSI, diagnosis and treatment methods on salvage lower extremities. Successful reconstruction was carried out in 31 cases, however there were 1 death because of mult-fractures and brain injury and 6 amputation, 24 cases successful salvage followed up mean 24.2 months, 6 cases bone nonunion and infected bone defect were cured by delayed bone planting or bone transportation. Ligaments repair reconstruction of 7 cases knee joint dislocation were done in delayed 3 or 4 weeks after first operation, the good functional rate was 71.4%. The patients of PSI under 10 grades in knee joint peripheral fractures and/or dislocations with an associated vascular injury should been carried out treatment, early definite diagnosis and blood circulation reconstruction are the key factors of successful salvage treatment.