Comparison of ESIN and other minimally invasive techniques for anterior pelvic ring injury: a finite element analysis and case-control study.

OBJECT: A novel technique, percutaneous elastic stable intramedullary nail fixation (ESIN), proposed by our team for the treatment of anterior pelvic ring injury. Finite element analysis and retrospective case-control study were used to compare biomechanical properties and clinical outcomes between ESIN and other techniques. METHODS: Four groups of finite element models of pelvic anterior ring injury were simulated, including ESIN (model A), retrograde transpubic screw fixation (RTSF, model B), subcutaneous internal fixator (model C), and external fixator (model D), and a vertical downward load of 500 N was applied to the S1 vertebral endplate. Stress and displacement distributions of intact pelvis, displacement distributions of pubic fracture fragments, and stress distributions of fixation devices were analysed. Then 31 patients with anterior pelvic ring injury (15 in the ESIN group and 16 in the RTSF group) were reviewed. Clinical outcomes were evaluated at the final follow-up. Postoperative complications were also recorded. RESULTS: Under 500N loading, the intact stability of the pelvis was compared as follows: model B (20.58 mm, 121.82 MPa), model A (20.80 mm, 129.97 MPa), model C (22.02 mm, 141.70 MPa), and model D (22.57 mm, 147.06 MPa). The regional stability of superior pubic ramus was compared as follows: model B (9.48 mm), model A (10.16 mm), model C (10.52 mm), and model D (10.76 mm). All 31 patients received follow-up at least 12 months postsurgery (range 12-20 months). Age, sex, injury mechanism, fracture type, time between the injury and operation, American Society of Anesthesiologists score, intraoperative blood loss, hospital stay, follow-up period, time to union, and Majeed scores did not differ significantly between the two groups ( P >0.05). However, the differences in the duration of unilateral surgery, unilateral intraoperative fluoroscopy and one-time success rate were significant ( P <0.05). CONCLUSIONS: With sufficient biomechanical stability and minimally invasive advantage, the percutaneous technique using ESIN can be used to successfully treat anterior pelvic ring injuries. In addition, advantages over RTSF include a shorter duration of surgery, reduced requirement for intraoperative fluoroscopy, and a higher one-time success rate. ESIN therefore constitutes a good alternative to RTSF.

Engineered exosomes derived from miR-132-overexpresssing adipose stem cells promoted diabetic wound healing and skin reconstruction.

The tissue reconstruction of diabetic wounds mainly depends on the proliferation and remodelling of cutaneous cells around wounds and the transplantation of random skin flaps, however, the proliferation of cells or survival of skin flaps are difficult due to the severe inflammation and other problems caused by diabetes. The stem cell-derived exosomes loaded with miRNA can be an effective therapeutic strategy for promoting diabetic wound healing. Therefore, in this study, the engineered exosomes derived from miR-132-overexpressing adipose stem cells (miR-132-exo) was obtained for promoting the healing of diabetic wounds and skin flaps. In vitro, the miR-132-exo promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). In vivo, streptozotocin (STZ) induced diabetic mice were used to create full-thickness skin wounds and random skin flaps to further investigate the healing effect of miR-132-exo. The results showed miR-132-exo evidently enhanced the survival of skin flaps and promote diabetic wound healing, through reducing local inflammation, promoting angiogenesis and stimulating M2-macrophages polarization mediated by NF-κB signaling pathway. These novel findings demonstrated that engineered miR-132-exo can be a potent therapeutic for treating diabetic wounds and inflammatory-related disease.

Experimental study on the repair of ureteral functional regeneration with highly bioactive extracellular matrix stent.

BACKGROUND: The research of extracellular matrix stent (ECM) has made some progress in the repair of urethra and bladder defects. OBJECTIVES: To observe the effects of highly bioactive ECM scaffold on the regeneration and repair of defects in long-segment ureteral replacement. MATERIAL AND METHODS: An animal model of long-segment ureteral defect was established and four-layer tubular highly bioactive ECM materials were prepared. After the ureteral defect was repaired through surgery, the rabbits in the negative control group were administered a non-bioactive stent, and rabbits in the observation group were treated with an ECM stent. RESULTS: Comparison of macro-indicators: The negative control group had a higher infection rate, a lower survival rate and more complications than the observation group (p < 0.05). The frequency of ureteral peristalsis in the negative control group was lower than in the observation group. In addition, the rate of urinary dysfunction was higher, and the ratio of ureteral diameter was lower in the negative control group than in the observation group (all p < 0.05). Comparison of histopathology: Three months after the operation, the vascular, smooth muscle and mucous membrane of the ureter in the observation group regenerated to close to normal ureteral tissue. There was no significant difference between the ureter regeneration in the repair area and the normal ureter tissue in the observation group 3 months after the operation. The number of regenerated muscle fibers in the observation group was significantly higher than that of the negative control group. Compared with the negative control group, the fibrous capsule was thicker, the percentages of CD31, CD3, CD68, CD80+, and CD163+ were higher, the scope of new smooth muscle fiber was expanded, fusion with the host muscle fibers was higher, and the neuromuscular junction (NMJ) structure was stronger in the observation group (all p < 0.05). CONCLUSIONS: A highly bioactive ECM stent can better regenerate the local anatomical structure and physiological function.

TRPC3 deficiency attenuates high salt-induced cardiac hypertrophy by alleviating cardiac mitochondrial dysfunction.

Long-term high salt intake leads to cardiac hypertrophy, but the mechanism remains elusive. Transient receptor potential channel, canonical 3(TRPC3), located in mitochondria, regulates mitochondrial calcium and reactive oxygen species(ROS) production. Herein, we investigated whether TRPC3 participates in high salt-induced cardiac hypertrophy by impairing cardiac mitochondrial function. High salt treatment increased the expression of mitochondrial TRPC3 in cardiomyocytes, accompanied by enhanced mitochondrial calcium uptake and elevated ROS production. Inhibition of TRPC3 significantly reduced high salt-induced ROS generation, promoted ATP production by stimulating oxidative phosphorylation, and increased enzyme activity in mitochondria in cardiomyocytes. Additionally, TRPC3 deficiency inhibited high salt-induced cardiac hypertrophy in vivo. A long-term high salt diet increased cardiac mitochondrial TRPC3 expression, elevated expression of cardiac hypertrophic markers atrial natriuretic peptide (ANP),brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC) and decreased ATP production and mitochondrial complex I and II enzyme activity in a TRPC3-dependent manner. TRPC3 deficiency antagonises high salt diet-mediated cardiac hypertrophy by ameliorating TRPC3-mediated cardiac mitochondrial dysfunction. TRPC3 may therefore represent a novel target for preventing high salt-induced cardiac damage.

Enhanced Mitochondrial Transient Receptor Potential Channel, Canonical Type 3-Mediated Calcium Handling in the Vasculature From Hypertensive Rats.

BACKGROUND: Mitochondrial Ca2+ homeostasis is fundamental to the regulation of mitochondrial reactive oxygen species (ROS) generation and adenosine triphosphate production. Recently, transient receptor potential channel, canonical type 3 (TRPC3), has been shown to localize to the mitochondria and to play a role in maintaining mitochondrial calcium homeostasis. Inhibition of TRPC3 attenuates vascular calcium influx in spontaneously hypertensive rats (SHRs). However, it remains elusive whether mitochondrial TRPC3 participates in hypertension by increasing mitochondrial calcium handling and ROS production. METHODS AND RESULTS: In this study we demonstrated increased TRPC3 expression in purified mitochondria in the vasculature from SHRs, which facilitates enhanced mitochondrial calcium uptake and ROS generation compared with Wistar-Kyoto rats. Furthermore, inhibition of TRPC3 by its specific inhibitor, Pyr3, significantly decreased the vascular mitochondrial ROS production and H2O2 synthesis and increased adenosine triphosphate content. Administration of telmisartan can improve these abnormalities. This beneficial effect was associated with improvement of the mitochondrial respiratory function through recovering the activity of pyruvate dehydrogenase in the vasculature of SHRs. In vivo, chronic administration of telmisartan suppressed TRPC3-mediated excessive mitochondrial ROS generation and vasoconstriction in the vasculature of SHRs. More importantly, TRPC3 knockout mice exhibited significantly ameliorated hypertension through reduction of angiotensin II-induced mitochondrial ROS generation. CONCLUSIONS: Together, we give experimental evidence for a potential mechanism by which enhanced TRPC3 activity at the cytoplasmic and mitochondrial levels contributes to redox signaling and calcium dysregulation in the vasculature from SHRs. Angiotensin II or telmisartan can regulate [Ca2+]mito, ROS production, and mitochondrial energy metabolism through targeting TRPC3.

Enhanced Store-Operated Calcium Entry in Platelets is Associated with Peripheral Artery Disease in Type 2 Diabetes.

BACKGROUND/AIMS: Platelet dysfunction plays an important role in thrombosis in diabetes with peripheral artery disease (PAD). Store-operated calcium entry (SOCE) and stromal interaction molecule 1 (STIM1) regulate platelet activity by modulating calcium influx. We hypothesized that enhanced SOCE in platelets is associated with diabetes with PAD. METHODS: We studied the activity of platelets from healthy participants and from type 2 diabetic patients. Platelet calcium influx and protein expression of STIM1 and sarcoendoplasmic reticulum Ca2+-ATPase 3 (SERCA3) were investigated. RESULTS: Compared with platelets from diabetic patients without PAD, platelets from diabetic patients with PAD exhibited significantly increased SOCE . Menthol administration completely inhibited calcium influx in platelets from diabetic patients without PAD, but this effect was blunted in those from diabetic patients with PAD. Furthermore, the increase in SOCE was correlated with the ankle brachial index (ABI) in diabetic patients. High glucose significantly up-regulated STIM1 and SERCA3 protein expression and induced the phosphorylation of phospholipase C (PLC) in platelets from healthy participants. This effect was attenuated in the presence of menthol or U73122, an inhibitor of PLC. Similarly, significant increases in STIM1 and SERCA3 protein expression were found in platelets from diabetic patients compared to those from healthy participants. CONCLUSION: Platelets from diabetic patients with PAD exhibited enhanced Store-operated calcium influx, which was associated with elevated STIM1/SERCA3 expression via a PLC-dependent pathway and was inhibited by menthol.