Objective To assess the clinical efficacy of TiRobot‐assisted percutaneous cannulated screw fixation in the treatment of femoral neck fractures. Methods From September 2015 to July 2017, 26 patients with unilateral femoral neck fractures were treated with TiRobot‐assisted percutaneous cannulated screw fixation. The femoral necks were fixed using three cannulated screws with robot assistance applying the following procedure: image acquisition, path planning, and needle and screw placement. The results of the treatment, including operation duration, frequency of fluoroscopy use, implant placement accuracy, intraoperative bleeding, total drilling, surgical complications, fracture healing time, fracture healing rate, and Harris scores at the last follow‐up, were recorded and compared with 23 similar patients who underwent conventional manual positioning surgery. Results A total of 147 cannulated screws were placed in all patients. The TiRobot group had shorter operation duration (62.6 ± 8.7 min vs 72.4 ± 10.3 min) and fracture healing time (5.1 ± 2.4 months vs 5.9 ± 2.8 months) than the conventional group ( P > 0.05). The robot group had significantly less use of fluoroscopy (26.5 ± 7.4 times vs 51.3 ± 9.4 times), intraoperative bleeding (8.2 ± 5.3 mL vs 36.4 ± 12.5 mL), and total drilling (9.4 ± 4.2 times vs 18.3 ± 9.1 times) than the conventional group (all P < 0.05). The screw parallelism was significantly improved (24.0 ± 0.6 points vs 21.5 ± 1.2 points) and the neck‐width coverage (72.0 ± 6.7 mm 2 vs 53.8 ± 10.4 mm 2 ) was significantly enlarged compared to the conventional group ( P < 0.05). Only three guiding needles were used to penetrate the femoral head during manual insertion in the TiRobot group, which was significantly lower than that in the conventional group (3/78, 3.8% vs 9/69, 13.0%; P < 0.05). Other complications such as wound infection, vascular or nerve injury, screw loosening, and secondary screw displacement, did not occur in the two groups. There was no significant difference between the two groups in fracture healing rate (88.4% vs 82.6%) and Harris scores at the last follow up (88.2 ± 3.6 points vs 87.3 ± 4.7 points; P > 0.05). Conclusion TiRobot‐assisted percutaneous cannulated screw fixation of femoral neck fractures is advantageous over conventional surgery with manual positioning due to easier manipulation, more accurate screw insertion, less invasion, and less radiation exposure, suggesting that it is a better method to stabilize femoral neck fra...

No abstract

BackgroundThe therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration.MethodsWe used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2′-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models.ResultsWe found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p.ConclusionsBlue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p.Graphical abstract

No abstract

Background: Post-ischemic angiogenesis is critical for blood flow recovery and ischemic tissue repair. N6-methyladenosine (m6A) plays essential roles in numerous biological processes. However, the impact and connected mechanism of m6A on post-ischemic angiogenesis are not fully understood. Methods: AlkB homolog 5 (ALKBH5) was screened out among several methyltransferases and demethylases involved in dynamic m6A regulation. Cardiac microvascular endothelial cells (CMECs) angiogenesis and WNT family member 5A (WNT5A) stability were analyzed upon ALKBH5 overexpression with adenovirus or knockdown with small interfering RNAs in vitro. The blood flow recovery, capillary, and small artery densities were evaluated in adeno-associated virus (AAV)-ALKBH5 overexpression or ALKBH5 knockout (KO) mice in a hind-limb ischemia model. The same experiments were conducted to explore the translational value of transient silencing of ALKBH5 with adenovirus. Results: ALKBH5 was significantly upregulated in hypoxic CMECs and led to a global decrease of m6A level. ALKBH5 overexpression further reduced m6A level in normoxic and hypoxic CMECs, impaired proliferation, migration, and tube formation only in hypoxic CMECs. Conversely, ALKBH5 knockdown preserved m6A levels and promoted angiogenic phenotypes in hypoxic but not in normoxic CMECs. Mechanistically, ALKBH5 regulated WNT5A expression through post-transcriptional mRNA modulation in an m6A-dependent manner, which decreased its stability and subsequently impeded angiogenesis in hypoxic CMECs. Furthermore, ALKBH5 overexpression hindered blood flow

Cardiac fibrosis is a common pathological feature of many cardiovascular diseases. The regulatory mechanisms of miRNAs in cardiac fibrosis are still unknown. Previous studies on miR-214-3p in cardiac fibroblasts reached contradictory conclusions. Thus the role of miR-214-3p in cardiac fibrosis deserves further exploration. Using a combination of in vitro and in vivo studies, we identified miR-214-3p as an important regulator of cardiac fibrosis, and the proliferation and activation of cardiac fibroblasts. We demonstrated that the expression of miR-214-3p is down-regulated in TGF-β1-treated myofibroblasts and transverse aortic constriction (TAC)-induced murine model. Additionally, miR-214-3pflox/flox/FSP1-cre mice and miR-214-3pwt/wt/FSP1-cre mice were subjected to TAC operation or sham operation, and the conditional knockout of miR-214-3p in cardiac fibroblasts aggravates TAC-induced cardiac fibrosis. In vitro, our results indicate that miR-214-3p is an important repressor for fibroblasts proliferation and fibroblast-to-myofibroblast transition by functionally targeting NOD-like receptor family CARD domain containing 5 (NLRC5). In conclusion, our findings show that the deficiency of miR-214-3p exacerbates cardiac fibrosis and reveal a novel miR-214-3p/NLRC5 axis in the regulation of cardiac fibrosis.

No abstract

Background Circulating long noncoding RNA (lncRNA) plays a vital role in clinical disease diagnosis and prognosis. Here, we evaluate the role of a lncRNA, named growth arrest specific 5 (GAS5), in atrial fibrillation (AF). Methods Expression of GAS5 was measured by qRT‐PCR. Diagnostic and prognostic values of GAS5 were assessed by the receiver operating characteristics curve (ROC), Kaplan–Meier (KM) and Cox regression analyses. Results A total of 173 participants were enrolled in this study. Circulating GAS5 expression was significantly down‐regulated in AF patients. This change occurred prior to enlargement of the left atrial volume and was strongly associated with AF progression, which demonstrates the potential use of GAS5 as an early biomarker. The area under the ROC curve (AUC) was 0.858 (95% CI 0.789‐0.926, P < .001). Seventy of the 85 AF patients received radiofrequency catheter ablation (RFCA), and 22 (31.4%) had relapsed by the 1‐year follow‐up. The KM analysis (log‐rank test, P = .031) and multivariable Cox analysis (HR = 0.127, 95% CI 0.026‐0.616; P = .01) revealed that GAS5 has a role in predicting recurrence after RFCA. Conclusion Circulating lncRNA GAS5 is a potential biomarker for AF diagnosis and prognosis. Down‐regulation of GAS5 occurs prior to left atrial enlargement and can be used for the prognosis of AF progression and recurrence.