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??Objective??To investigate the clinical features and risk factors of multidrug-resistant bloodstream infection in children with acute leukemia. Methods??The clinical data of 121 blood culture-positive patients with acute leukemia admitted from January 1??2013 to September 30??2018 to Department of Pediatrics??Zhujiang Hospital of Southern Medical University were analyzed retrospectively. Results??Of the 121 patients with acute leukemia infected with bacterial bloodstream??55 were in the multidrug-resistant??MDR?? group and 66 in the non-multidrug-resistant??non-MDR?? group. There were 31 gram-positive bacteria in the MDR group. The top three strains were coagulase-negative Staphylococci??Staphylococcus aureus and Streptococcus mutans. Escherichia coli was the main strain of gram-negative bacteria. Logistic analysis suggested that MDR bloodstream infection was more likely to occur in the patiens with AML??P??0.038??OR 2.505??95%CI 1.036—6.058?? and at induction chemotherapy stage??P??0.038??OR 2.226??95%CI 1.045—4.774??. Other high-risk factors included neutropenic dysplasia ??7 d before fever??P??0.003??OR 3.36??95%CI 1.520—7.428????hemoglobin ??70 g/L??P??0.122??OR 1.897??95%CI 0.842—4.274????and platelet??20 g/L??P??0.005??OR 2.995??95%CI 1.388—6.464??. The fever duration and antibiotic course in the MDR group were longer than those in the non-MDR group??and the procalcitoni and C-reactive protein were higher in the MDR group. The empirical treatment of the MDR group was less effective??and the transfer rate for ICU and mortality rate were higher. Conclusion??AML??induction chemotherapy??neutrophil deficiency time before fever ??7 days ??hemoglobin??70 g/L and platelet??20×109/L are risk factors for MDR bloodstream infection. The inflammation response is severe MDR bloodstream infections??which may result in longer anti-infective treatments and a worse prognosis.     

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肝胆管结石病具有高结石残留率、高结石复发率、高并发症发生率的特点。术前缺乏详细而全面的评估以及手术方式、手术时机选择不当是导致结石残留和复发的主要原因。以肝脏和胆道三维重建、仿真手术、个体化分段技术为核心的数字医学技术的临床应用,可帮助提高术前诊断的精确率、制定合理的手术方案、实现肝胆管结石的精准手术,有效降低结石残留率和复发率。外科导航手术联合微创和介入技术而形成的数字化微创外科技术将成为肝胆管结石治疗的另一重要手段,有望进一步提高肝胆管结石的外科治疗水平。     

Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma

The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.     

Nicotine contributes to the neural stem cells fate against toxicity of microglial-derived factors induced by Aβ via the Wnt/β-catenin pathway

Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of β-amyloid peptide (Aβ). The viability, proliferation, differentiation, apoptosis of NSCs and underlying mechanisms associated with Wnt signaling pathway were investigated. The results showed that Aβ could directly damage NSCs. Furthermore, concomitant to elevated levels of TNF-α, IL-1β derived from microglias, the NSCs had been damaged more severely with the upregulation of Axin 2, p-β-catenin and the downregulation of β-catenin, p-GSK-3β, microtubule-associated protein-2, choline acetyltransferase. However, addition of 10 μmol/L nicotine before microglias treated with Aβ was beneficial to protect the NSCs against neurotoxicity of microglial-derived factors induced by Aβ, which partially rescued proliferation, differentiation and inhibited apoptosis of NSCs via activation of Wnt/β-catenin pathway. Taken together, these data imply that low concentration nicotine attenuates NSCs injury induced by microglial-derived factors via Wnt signaling pathway. Thus, treatment with nicotinic acetylcholine receptor agonist provides a promising research field for neural stem cell fate and therapeutic intervention in neuroinflammation diseases.     

下颌骨整形手术后突发窒息的可能原因分析及防治

目的：总结行气管内全麻经口内入路下颌骨整形术的患者术后出现突发性呼吸困难、窒息的主要原因。方法：回顾性分析2007年7月～2012年6月在全麻下经口内入路下颌骨整形术患者的临床资料。结果：本组714例术后患者中,28例患者术后出现呼吸困难症状,22例予保守治疗,6例予以二次手术探查止血,均痊愈出院。结论：防止下颌骨整形术术后窒息,除了要注意术中手术操作外,更重要的是加强术后病情观察及对窒息的应急处理。     

Efficacy and safety of selective internal radiotherapy versus sorafenib for intermediate-locally advanced hepatocellular carcinoma: a systematic review and meta-analysis

Background: Sorafenib (SOR) is recommended for locally advanced and metastatic hepatocellular carcinoma (HCC), but the tolerability of SOR is unsatisfactory. Selective internal radiotherapy (SIRT) has shown efficacy in intermediate-locally advanced HCC patients. This meta-analysis aimed to compare the efficacy and safety of SIRT and SOR in the treatment of intermediate-locally advanced HCC.

Methods: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases for eligible studies. The endpoints evaluated included the overall survival (OS), disease control rate (DCR), objective response rate (ORR) and grade≥3 adverse events (AEs).

Results: Six studies were included in this analysis. The OS was similar between the two groups (HR 1.06, 95%CI 0.93–1.20; P = 0.40). There was no difference in the DCR between the two groups (RR 1.13, 95%CI 0.87–1.46; P = 0.35). However, the ORR in the SIRT group was significantly higher than that in the SOR group (RR 4.10, 95%CI 1.92-8.76; P = 0.0003). The incidence rate of grade≥3 AEs was higher in the SOR group.

Conclusions: In patients with intermediate-locally advanced HCC, SIRT and SOR result in similar survival rates. The improved toxicity profile of SIRT may help when choosing between the two treatments.     

VEGF-PLGA controlled-release microspheres enhanced angiogenesis in encephalomyosynangiosis-based chronic cerebral hypoperfusion

Treatments enhancing angiogenesis for chronic cerebral hypoperfusion (CCH) are still in the research stage. Although encephalomyosynangiosis (EMS) is a common indirect anastomosis for the treatment of CCH, the effectiveness to promote angiogenesis is not satisfactory. Vascular endothelial growth factors (VEGF) is a cytokine found to specifically act directly on vascular endothelial cells, promote neovascularization, and enhance capillary permeability. However, the short half life and unstable property of VEGF underlies the need to explore available delivery system. In this study, poly (lactide-co-glycolide) (PLGA) was used to prepare VEGF controlled-release microspheres. In vitro and in vivo analysis of release kinetics showed that the microspheres could release VEGF continuously within 30 days. Then, modified chronic cerebral hypoperfusion rat model was established by ligation of bilateral internal carotid artery and one vertebral artery. At 14 days after ischemia, the EMS and the VEGF microspheres injection were performed. At 30 days after the injection, the result of Morris water maze displayed that combinating VEGF microspheres and EMS significantly ameliorated cognitive deficit after ischemia. We observed that combinating VEGF microspheres and EMS could further significantly increase cerebral blood flow. We speculated that this enhancement of cerebral blood flow was attributed to more angiogenesis induced by combination of VEGF microspheres and EMS, which verified by more collateral circulation with cerebral angiography and higher expression of CD31 or α-SMA. Our study demonstrated that combinating VEGF-PLGA controlled-release microspheres could significantly promote angiogenesis in EMS-based CCH rats model, providing new ideas for clinical treatment of CCH.