There are still controversies between surgical treatment and conservative treatment for multiple rib fractures (MRFs). No consensus has been reached concerning the indications and timing of surgery. In this meta-analysis, we aimed to determine the optimal treatment for MRFs. Six databases (PubMed, Medline, Embase, Cochrane, Cnki, Wanfang Database) were retrieved for all eligible randomized controlled trials (RCTs) published before January 2020. MRFs were treated either with operative reduction and internal fixation or conservative treatment. The pertinent data were retrieved. The quality of RCTs was evaluated by the modified Jadad rating scale and meta-analysis was performed using RevMan 5.3 software. Seven RCTs involving 538 MRFs patients (260 were treated surgically vs. 278 conservatively) were included in this meta-analysis. Compared with conservative treatment, surgical treatment resulted in shorter length of hospital stay (WMD -8.48; 95% CI -11.34 to -5.63; P < 0.001), length of ICU stay (WMD -5.72; 95% CI -7.31 to -4.13; P < 0.001) and duration of mechanical ventilation (WMD -4.93; 95% CI -8.79 to -1.07; P = 0.01), with a lower risk of complications including pneumonia (RR 0.40; 95% CI 0.30 to 0.53; P < 0.001) and chest wall deformity (RR 0.07; 95% CI 0.03 to 0.14; P < 0.001). The sensitivity analysis carried out by excluding one study with significant heterogeneity showed that the rate of tracheostomy was lower in the surgical group than in the conservative group (RR 0.44; 95% CI 0.28 to 0.71; P = 0.0008). For patients with MRFs, surgical treatment resulted in faster recovery, a lower risk of complications and better prognosis than conservative treatment.

A S252W mutation of fibroblast growth factor receptor 2 (FGFR2), which is responsible for nearly two-thirds of Apert syndrome (AS) cases, causes retarded development of the skeleton and skull malformation resulting from premature fusion of the craniofacial sutures. We utilized a Fgfr2^+/S252W mouse (a knock-in mouse model mimicking human AS) to demonstrate decreased bone mass due to reduced trabecular bone volume, reduced bone mineral density, and shortened growth plates in the long bones. In vitro bone mesenchymal stem cells (BMSCs) culture studies revealed that the mutant mice showed reduced BMSC proliferation, a reduction in chondrogenic differentiation, and reduced mineralization. Our results suggest that these phenomena are caused by up-regulation of p38 and Erk1/2 phosphorylation. Treatment of cultured mutant bone rudiments with SB203580 or PD98059 resulted in partial rescue of the bone growth retardation. The p38 signaling pathway especially was found to be responsible for the retarded long bone development. Our data indicate that the S252W mutation in FGFR2 directly affects endochondral ossification, resulting in growth retardation of the long bone. We also show that the p38 and Erk1/2 signaling pathways partially mediate the effects of the S252W mutation of FGFR2 on long bone development.

Vascular hyperpermeability induced by lipopolysaccharide (LPS) is a common pathogenic process in cases of severe trauma and sepsis. Vascular endothelial cadherin (VE-cad) is a key regulatory molecule involved in this process, although the detailed mechanism through which this molecule acts remains unclear. We assessed the role of clathrin-mediated and caveolae-mediated endocytosis of VE-cad in LPS-induced vascular hyperpermeability in the human vascular endothelial cell line CRL-2922 and determined that vascular permeability and VE-cad localization at the plasma membrane were negatively correlated after LPS treatment. Additionally, the loss of VE-cad at the plasma membrane was caused by both clathrin-mediated and caveolae-mediated endocytosis. Clathrin-mediated endocytosis was dominant early after LPS treatment, and caveolae-mediated endocytosis was dominant hours after LPS treatment. The caveolae-mediated endocytosis of VE-cad was activated through the LPS-Toll-like receptor 4 (TLR4)-Src signaling pathway. Structural changes in the actin cytoskeleton, specifically from polymerization to depolymerization, were important reasons for the switching of the VE-cad endocytosis pathway from clathrin-mediated to caveolae-mediated. Our findings suggest that clathrin-mediated and caveolae-mediated endocytosis of VE-cad contribute to LPS-induced vascular hyperpermeability, although they contribute via different mechanism. The predominant means of endocytosis depends on the time since LPS treatment.

Multidrug-resistant Pseudomonas aeruginosa is one of the most life-threatening pathogens for global health. In this regard, phage encoded lytic proteins, including endolysins and virion-associated peptidoglycan hydrolases (VAPGH), have been proposed as promising antimicrobial agents to treat P. aeruginosa. Most dsDNA phages use VAPGH to degrade peptidoglycan (PG) during infection, and endolysin to lyse the host cells at the end of lytic cycle. By contrast, dsRNA phage encodes only one lytic protein, which is located in the viral membrane to digest the PG during penetration, and also serves as an endolysin to release the phage. Currently, there are only seven sequenced dsRNA phages, and phiYY is the only one that infects human pathogen P. aeruginosa. In this study, dsRNA phage phiYY encoded lysin, named Ply17, was cloned and purified. Ply17 contains a PG-binding domain and a lysozyme-like-family domain. Ply17 exhibited a broad antibacterial activity against the outer membrane permeabilizer treated Gram-negative bacteria. The best lytic activity was achieved at 37^∘C, pH 7.5, in the presence of 0.5 mM EDTA. Moreover, it could effectively lyse Gram-positive bacteria directly, including Staphylococcus aureus. Therefore, dsRNA phage encoded Ply17 might be a promising new agent for treating multidrug-resistant pathogens.

With the widespread adoption of advanced tourniquets, the mortality rate of limb wound hemorrhage has decreased significantly, and non-compressible torso hemorrhage has gradually occupied the leading position of potentially preventable death, both in military and civilian circumstances. With the emergence of novel hemostatic devices and materials, strategies for the management of non-compressible torso hemorrhage have changed significantly. This review summarizes the current treatment strategies and types of equipment for non-compressible torso hemorrhage and suggests future research directions, hoping to provide a comprehensive review for the medical personnel and researchers engaging in this field.