布地奈德对脂多糖诱导大鼠急性肺损伤的影响

目的探讨布地奈德对脂多糖(LPS)诱导大鼠急性肺损伤的影响。方法将30只雄性Sprague Dawley大鼠随机分为3组:对照组、LPS组和布地奈德组,每组10只。采用经气管插管给予LPS(5 mg/kg)制备大鼠急性肺损伤模型;布地奈德组给予LPS 24 h后经气道给予布地奈德(500μg/kg)。3组均于48 h后测定肺水清除率,称量肺湿干重比,采用酶联免疫吸附试验测定支气管肺泡灌洗液中白细胞介素1β的水平,HE染色观察肺组织病理学改变,免疫组织化学法观察细胞间黏附分子1的表达。结果与LPS组相比,布地奈德干预后,肺组织结构破坏明显减轻,炎症细胞浸润减少,肺水清除率提高(P值均<0.01),肺湿干重比降低(P<0.05),支气管肺泡灌洗液中蛋白含量及中性粒细胞、巨噬细胞等的渗出减少(P<0.05或P<0.01),细胞间黏附分子1表达减少。结论布地奈德对LPS诱导的急性肺损伤大鼠具有肺保护作用,其机制考虑与减少细胞炎症反应、减少炎症因子对内皮细胞的活化、加强肺水清除作用有关。     

局部治疗联合EGFR-TKIs在晚期耐药肺腺癌中的临床应用研究

目的探讨表皮细胞生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)使用后耐药进展的肺腺癌患者给予局部治疗(冷冻消融、支气管动脉栓塞)联合EGFR-TKIs的临床疗效。方法回顾性分析2012年3月至2018年10月应急总医院经病理证实并完成随访的原发性EGFR敏感突变型晚期肺腺癌患者,进展后再行EGFR基因检测为T790M阴性,继续应用EGFR-TKIs的同时联合局部治疗,分别统计PFS1(从使用EGFR-TKIs到疾病进展时间)、PFS2(从冷冻消融到疾病进展时间)、OS(总生存期)、OS1(冷冻消融后的生存期),及冷冻消融后的并发症情况。分析OS及PFS的统计学相关影响因素。结果32例符合入组标准的晚期肺腺癌患者,PFS1平均时间为(12.4±8.6)个月。其中14例患者冷冻消融前行支气管动脉栓塞治疗,共消融病灶38个。PFS2为(6.7±2.9)个月。OS为(31.5±13.5)个月,其中OS1为(15.5±7.6)个月。统计分析显示PFS1与PFS2与OS存在显著相关性(P<0.05),靶向治疗进展后至氩氦冷冻消融的时间与患者的OS及OS1存在相关性,支气管动脉栓塞联合氩氦消融治疗后并发症主要为气胸及肺内出血,对症处理后均可缓解。结论EGFR-TKIs耐药进展后晚期肺腺癌中,EGFR-TKIs继续使用并联合冷冻消融等局部治疗可延长患者生存,并发症少,取得临床获益。     

How Can I Manage Thrombocytopenia in Hemodialysis Patient? A Review

Hemodialysis (HD) is the most important treatment for patients with end‐stage renal disease (ESRD). Thrombocytopenia is a potential treatment complication related to dialysis. Under normal circumstances, the platelet count would slightly decrease within the first hour of HD, but get restored towards the end of procedure. In most patients, the platelet count can be maintained within the normal range, and the occurrence of thrombocytopenia is relatively rare in clinical practice. Therefore, the possibility of thrombocytopenia in HD patients is often ignored. Moreover, thrombocytopenia might be misdiagnosed and mistreated. At present, almost all articles on the subject, apart from some case reports, focus on pseudothrombocytopenia and heparin‐induced thrombocytopenia. In this review, we summarized various underlying causes, mechanisms, and diagnostic approaches to thrombocytopenia in HD patients. The review aims to provide a guide for clinicians interested in the causes and adequate treatment of thrombocytopenia.     

Causes of Death after Congenital Heart Surgery in Children

Background: This retrospective cohort study aimed to explore the causes of death in children with congenital heart disease (CHD) after cardiac surgery in one of the biggest cardiac centers for children with CHD in China. Methods: A total of 26,856 children undergoing cardiac surgery from January 1, 2012 to December 31, 2019 were included. Based on the clinical data, the causes of death were divided into ten categories and further compared among different periods, types of CHD and surgical procedures. Results: Of all patients, 513 (1.9%) died (median age 162 d, median weight 5.6 kg). The mortality in 2016–2019 was lower than that in 2012–2015 (1.4 ± 0.3% vs. 2.5 ± 0.3%, p = 0.005). A total of 42.5% of children died of heart failure, and 32.9% died of residual anatomic defects. Patients with transposition of the great arteries tended to die from residual anatomic defects (21.9%), while those with double-outlet right ventricle (20%) and single ventricle (20%) tended to die from pulmonary hypertension (PH) (p = 0.006). After biventricular repair, children tended to die from heart failure (90.4%), while after single-ventricle repair, children tended to die from PH (50%) (p < 0.0001). There is a negative correlation between mortality and the ECMO implantation rate (r = −0.898, p = 0.002). Conclusions: Heart failure and residual anatomic defects were the main causes of death after cardiac surgery. The cause of death patterns differed among CHD types and surgical strategies. ECMO may be a life-saving tool when other conventional therapies do not work.     

Expression of chemokine receptor-4 in bone marrow mesenchymal stem cells on experimental rat abdominal aortic aneurysms and the migration of bone marrow mesenchymal stem cells with stromal-derived factor-1

This study investigated the expression and role of chemokine receptor-4 (CXCR4) in bone marrow mesenchymal stem cells (BMSCs) from experimental rats with abdominal aortic aneurysms (AAA) for migration of BMSCs. Sprague–Dawley rats were divided into an experimental group and control group (n = 18 each). AAA was induced with 0.75 M solution infiltrate for 30 minutes, after which the abdomen was rinsed and closed. Saline was used in place of CaCl₂ in the control group. CD34 and CD29 were detected by flow cytometry, the gene and protein expression of CXCR4 were detected by real-time polymerase chain reaction and western blot, respectively. The migration of BMSCs with stromal-derived factor-1 was detected by Transwell chamber. CD34 expression was negative and CD29 expression was positive. The gene and protein expression of CXCR4 were significantly higher in experimental group than them in control group (p < 0.05), the migration ability of BMSCs from the experimental group was significantly higher than that from the control group (p < 0.05). Stromal-derived factor -1/CXCR4 can enhance the migration of BMSCs in vitro in a rat AAA model.     

Synthesis,biocompatible, and self-assembly properties of poly (ethylene glycol)/lactobionic acid-grafted chitosan

Polymers with targeted ligands are widely used as the anti-cancer drug delivery materials. For applications of chitosan as an anti-liver cancer drug delivery, poly (ethylene glycol)/lactobionic acid-grafted chitosan (PEG/LA-CS) was prepared and investigated since lactobionic acid can be specifically recognized by the hepatocytes. The structure of the PEG/LA-CS was characterized by Fourier transform infrared spectrometry and elemental analysis. The self-assembly behaviors of the PEG/LA-CS were monitored by steady-state fluorescence spectroscopy and electronic transmission microscope. The protein adsorption of the PEG/LA-CS was detected with bovine serum albumin (BSA) by electrochemical impedance spectroscopy. The results showed that the PEG/LA-CS almost did not adsorb protein. To study the effects of PEG/LA-CS on the structure of BSA, the interactions between the PEG/LA-CS and BSA were detected by ultraviolet spectrum, fluorescence spectrum, and circular dichroism. All the data gave one result that BSA maintained its original folded confirmation in PEG/LA-CS solution. The hemocompatibility of PEG/LA-CS was investigated by observing the effects of PEG/LA-CS on the hemolysis rate and the plasma recalcification time (PRT). The results showed that the PRT was prolonged greatly and the hemolysis rate was less than 5%. Furthermore, PEG/LA-CS also showed good cytocompatibility with K562, Hep G2, and LO2 cells. Therefore, the PEG/LA-CS is believed to have great potential for producing injectable anti-liver cancer drug delivery.     

Characterization of the biological properties and complete genome sequence analysis of a cattle-derived rabies virus isolate from the Guangxi province of southern China

In this study, a street rabies virus isolate, GXHXN, was obtained from the brain of one rabid cattle in Guangxi province of southern China. To characterize the biological properties of GXHXN, we first evaluated its pathogenicity using 4-week-old adult mice. GXHXN was highly pathogenic with a short incubation period and course of disease. Its LD₅₀ of 10^?6.86/mL is significantly higher than the LD₅₀ of 10^?5.19/mL of GXN119, a dog-derived rabies virus isolate. It also displayed a higher neurotropism index than the rRC-HL strain. However, the relative neurotropism index of GXHXN was slightly lower than that of GXN119. Analyzing antigenicity using anti-N and anti-G monoclonal antibodies (MAbs), all tested anti-N MAbs reacted similarly to GXHXN, CVS, and rRC-HL, but the reaction of anti-N MAbs to GXHXN was slightly different from GXN119. Moreover, 2/11 tested anti-G mAbs showed weaker reactivity to GXHXN than rRC-HL, whereas 4/11 showed stronger reactivity to GXHXN than CVS and GXN119, indicating that the structures of G might differ. In order to understand its genetic variation and evolution, the complete GXHXN genome sequence was determined and compared with the known 12 isolates from other mammals. A total of 42 nucleotide substitutions were found in the full-length genome, including 15 non-synonymous mutations. The G gene accounts for the highest nucleotide substitution rate of 0.70 % in ORF and an amino acid substitution rate of 0.95 %. Phylogenetic trees based on the complete genome sequence as well as the N and G gene sequences from 37 known rabies isolates from various mammals demonstrated that the GXHXN is closely related to the BJ2011E isolate from a horse in Beijing, the WH11 isolate from a donkey in Hubei, and isolates from dogs in the Fujian and Zhejiang provinces. These findings will be helpful in exploring the molecular mechanisms underlying interspecies transmission and the genetic variation of the rabies virus in different mammal species.