The management of bone defects caused by trauma and nonunion continues to represent a substantial clinical challenge in the management of orthopaedic trauma patients. A variety of treatment options have been described and reported in the literature. The relative rarity of these injuries means that high level, comparative evidence to guide their management is sparse. As such, treatment decisions must be based on knowledge of the available evidence, contemporary fracture management principles, and consideration of patient and surgeon factors. This article reviews the available evidence for the different treatment options available for the management of bone defects.

Brown adipose tissue dissipates energy in the form of heat. Recent studies have shown that adult humans possess both classical brown and beige adipocytes (brown-like adipocytes in white adipose tissue, WAT), and stimulating brown and beige adipocyte formation can be a new avenue to treat obesity. Angiotensin II (AngII) is a peptide hormone that plays important roles in energy metabolism via its angiotensin type 1 or type 2 receptors (AT1R and AT2R). Adipose tissue is a major source of AngII and expresses both types of its receptors, implying the autocrine and paracrine role of AngII in regulating adipose functions and self-remodeling. Here, based on the in vitro studies on primary cultures of mouse white adipocytes, we report that, AT2R activation, either by AngII or AT2R agonist (C21), induces white adipocyte browning, by increasing PPARγ expression, at least in part, via ERK1/2, PI3kinase/Akt and AMPK signaling pathways. It is also found that AngII–AT2R enhances brown adipogenesis. In the in vivo studies on mice, administration of AT1R antagonist (ZD7155) or AT2R agonist (C21) leads to the increase of WAT browning, body temperature and serum adiponectin, as well as the decrease of WAT mass and the serum levels of TNFα, triglycerides and free fatty acids. In addition, AT2R-induced browning effect is also observed in human white adipocytes, as evidenced by the increased UCP1 expression and oxygen consumption. Finally, we provide evidence that AT2R plays important roles in hormone T3-induced white adipose browning. This study, for the first time, reveals the browning and brown adipogenic effects of AT2R and suggests a potential therapeutic target to combat obesity and related metabolic disorders.

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Background: Previous studies have acknowledged Tai Chi and Qigong exercise could be potential effective treatments for reducing depression and anxiety in both healthy and clinical populations. However, there is a scarcity of systematic reviews summarizing the clinical evidence conducted among individuals with substance use disorders. This study tries to fill up this gap. Methods: A systematic search using Medline, EMbase, PsychINFO, Eric, SPORTDiscus, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL), the Chinese National Knowledge Infrastructure (CNKI), Wanfang, and the Chinese Scientific Journal (VIP) databases was initiated to identify randomized controlled trials (RCTs) and nonrandomized comparison studies (NRS) assessing the effect of Tai Chi and Qigong versus various comparison groups on depression and anxiety related outcomes. Study quality was evaluated using a Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR-NPT) designed for nonpharmacological trial. Results: One RCT and six NRS with a total of 772 participants were identified. Some of them were metaanalyzed to examine the pooled effects based on different types of intervention and controls. The results of meta-analyses suggested the effect of Tai Chi was comparable to treatment as usual (TAU) on depression (standardized mean difference (SMD) = − 0.17[− 0.52, 0.17]). Qigong exercise appears to result in improvement on anxiety compared to that of medication (SMD =-1.12[− 1.47, − 0.78]), and no treatment control (SMD =-0.52[− 0.77, − 0.27]). Conclusion: The findings suggest potentially beneficial effect of Qigong exercise on symptoms of anxiety among individuals with drug abuse. Considering the small number and overall methodological weakness of included studies and lack of RCTs, results should be interpreted with caution and future rigorously designed RCTs are warranted to provide more reliable evidence.

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Background Rhabdomyolysis (RM) is a common complication of exertional heat stroke (EHS) and constitutes a direct cause of death. However, the mechanism underlying RM following EHS remains unclear. Methods The murine EHS model was prepared by our previous protocol. RNA sequencing is applied to identify the pathological pathways that contribute to RM following EHS. Inhibition of the acyl‐CoA synthetase long‐chain family member 4 (ACSL4) was achieved by RNA silencing in vitro prior to ionomycin plus heat stress exposure or pharmacological inhibitors in vivo prior to heat and exertion exposure. The histological changes, the iron accumulation, oxidized phosphatidylethanolamines species, as well as histological evaluation and levels of lipid metabolites in skeletal muscle tissues were measured. Results We demonstrated that ferroptosis contributes to RM development following EHS. Ferroptosis inhibitor ferrostatin‐1 administration once EHS onset significantly ameliorated the survival rate of EHS mice from 35.357% to 52.288% within 24 h after EHS (P = 0.0028 compared with control) and markedly inhibited RM development induced by EHS. By comparing gene expression of between sham heat rest (SHR) (n = 3) and EHS (n = 3) mice in the gastrocnemius (Gas) muscle tissue, we identified that Acsl4 mRNA expression is elevated in Gas muscle tissue of EHS mice (P = 0.0038 compared with SHR), so as to its protein levels (P = 0.0001 compared with SHR). Followed by increase in creatine kinase (CK) and myoglobin (MB) levels, the labile iron accumulation, decrease in glutathione peroxidase 4 (GPX4) expression, and elevation of lipid peroxidation products. From in vivo and in vitro experiments, inhibition of Acsl4 significantly improves muscle cell death caused by EHS, thereby ameliorating RM development, followed by reduction in CK and MB levels by 30–40% (P < 0.0001; n = 8–10) and 40% (P < 0.0001; n = 8–10), restoration of GPX4 expression, and decrease in lipid peroxidation products. Mechanistically, ACSL4‐mediated RM seems to be Yes‐associated protein (YAP) dependent via TEA domain transcription factor1/TEA domain transcription factor4. Conclusions These findings demonstrate an important role of ACSL4 in mediating ferroptosis activation in the development of RM following EHS and suggest that targeting ACSL4 may represent a novel therapeutic strategy to limit the skeletal muscle cell death and prevent RM after EHS.

BackgroundPectoral (PECs) block was first described by Blanco et al for postoperative analgesia in breast surgery. It was proposed to be an easier and safer alternative to thoracic epidural or paravertebral block (PVB). In this systematic review and meta-analysis, we compare the perioperative analgesic efficacy and adverse events of PECs block and PVB.MethodsWe systematically searched PubMed, Central, EMBASE, CINAHL, Google Scholar, Web of Science citation index, US clinical trials register, Wanfang database, as well as recent conference abstracts, for clinical studies comparing the two techniques. Analgesic efficacy was assessed according to the time to first rescue analgesia and 24 hours opioid consumption. Adverse events from the trials were recorded and reported descriptively.ResultsThe literature search was last updated on 20 February 2020. We identified a total of 10 randomized controlled trials (RCTs) comparing PECs to PVB with 252 and 250 patients, respectively. There was no difference in 24 hours opioid consumption between PECs and PVB. There was no significant difference in the time to rescue analgesia between the two cohorts. The most common adverse event noted was postoperative nausea and vomiting). Trial sequence analysis indicate that further studies are unlikely to alter the conclusion regarding opioid requirement.ConclusionOur systematic review suggests that PECs and PVB are comparable in postoperative analgesia efficacy for mastectomy, and further studies are unlikely to alter the conclusion. The choice of technique should, therefore, be based on practitioner skill and institutional guidelines.PROSPERO registration numberCRD42020165137.

Exertional heat stroke (EHS) is a life-threatening disease characterized by high mortality and incidence of rhabdomyolysis (RM). It would therefore be valuable to establish a stable EHS-induced RM model that accurately reflects the clinical characteristics of EHS patients and provides an objective animal model for further study of the pathogenesis of RM. In the current study, 8∼9-week-old, male, wild-type C57BL/6J mice, at the stage of sexual maturity, were randomly divided into four groups: the EHS group, the classical heat stroke (CHS) group, the sham heat exercise group, and sham heat rest group. The survival rate of mice was determined under relatively high levels of temperature and humidity (37.5 • C, 65% relative humidity (RH); 37.5 • C, 70% RH; 39.5 • C, 65% RH; and 39.5 • C, 70% RH) as well as a high core temperature (Tc; 42, 42.5, and 43 • C). Results showed that the environmental condition of 39.5 • C and 65% RH was most suitable for EHS modeling. The end point of EHS evaluation was exhaustion or an individual's core temperature reaching 43 • C. The survival rate of mice in the EHS group within 24 h under these conditions was 37.34%, which is consistent with the high mortality characteristics noted in EHS patients. Severe RM was observed in the EHS group by H&E staining and transmission electron microscopy. Creatine kinase levels in the EHS group mostly exceeded 10,000 U/L, which was approximately 10 times higher than that in the sham heat rest group. Renal tubules of the EHS group exhibited severe necrosis, and calcium overload in the skeletal muscles of this group was also observed using intravital 2photon microscopy. In conclusion, we made improvements to a stable EHS-induced RM animal model to truly reflect the clinical characteristics of EHS patients. This new model should be helpful in the further study of RM pathogenesis.