The sensitivity to inter-subject variability of the bridging vein entry angles for prediction of acute subdural hematoma

Acute subdural hematoma (ASDH) is one of the most frequent traumatic brain injuries (TBIs) with high mortality rate. Bridging vein (BV) ruptures is a major cause of ASDH. The KTH finite element head model includes bridging veins to predict acute subdural hematoma due to BV rupture. In this model, BVs were positioned according to Oka et al. (1985). The aim of the current study is to investigate whether the location and entry angles of these BVs could be modelled using data from a greater statistical sample, and what the impact of this improvement would be on the model’s predictive capability of BV rupture.From the CT angiogram data of 78 patients, the relative position of the bridging veins and their entry angles along the superior sagittal sinus was determined. The bridging veins were repositioned in the model accordingly. The performance of the model, w.r.t. BV rupture prediction potential was tested on simulations of full body cadaver head impact experiments. The experiments were simulated on the original version of the model and on three other versions which had updated BV positions according to mean, maximum and minimum entry angles.Even though the successful prediction rate between the models stayed the same, the location of the rupture site significantly improved for the model with the mean entry angles. Moreover, the models with maximum and minimum entry angles give an insight of how BV biovariability can influence ASDH.In order to further improve the successful prediction rate, more biofidelic data are needed both with respect to bridging vein material properties and geometry. Furthermore, more experimental data are needed in order to investigate the behaviour of FE head models in depth.     

A first-in-human,randomized, double-blind,single- and multiple-dose,phase I study of recombinant human thymosin β4 in healthy Chinese volunteers

The study evaluated the safety, tolerability, pharmacokinetics (PK) and anti-drug antibody (ADA) of the recombinant human thymosin β4 (NL005) for single and multiple intravenous injections in healthy subjects. Seven cohorts, with 54 healthy subjects, were given a single intravenous dose of NL005 or placebo and were observed for 28 days. The cohorts received ascending doses of either 0.05, 0.25, 0.5, 2.0, 5.0, 12.5 or 25.0 μg/kg in the single-dose trial. A total of 30 healthy subjects were randomly enrolled in the multiple-dose trial, and 3 cohorts (0.5, 2.0 and 5.0 μg/kg) were administered once human thymosin β4 daily for 10 days and observed for 28 days. The adverse events were mild to moderate in intensity. There were no dose-limiting toxicities or serious adverse events. The plasma concentration, maximum peak concentration (C_max) and AUC of each dose group increased with the increase in the dose. The tendency of terminal clearance in each dose group was consistent, and there was no obvious accumulation after continuous administration. Thus, the drug can be concluded to be well tolerated and safe in healthy people and suitable for use in a clinical study for the treatment of acute myocardial infarction.     

Focus on the legislative approach to short half life radioactive hospital waste releasing

PurposeWe propose to summarize the advancements introduced by the new Directive 2013/59/Euratom concerning the concept of clearance, for which the radioactive medical waste represents a typical candidate. We also intend to spotlight disputable points in the regulatory scheme in force in Italy, as well to make a contribution to evaluate whether the practice of patients' urine storing, stated by it, can be regarded to be proper.MethodsWith directing our interest to radionuclides used in Nuclear Medicine, we first present an overview of how the clearance concept, and that of exemption closely related to it, have been developed from the previous Directive 96/29 to the new one; then we describe the implementation of these concepts in the Italian legislation. Subsequently we estimate the exposure due both to keeping the effluent on site and to direct discharging it to the environment.ResultsIn line with a well established international consensus, the Directive 2013/59 drives simple and harmonized regulation of clearance. On the contrary, some complexity and lack of consistency can be found in the framework of the national legislation affecting the radioactive medical waste handling. In addition the practice of excreta storing is disputed not to be really beneficial.ConclusionThe opportunity should be taken to make the whole system of these requirements simpler and more consistent and effective when it is revised to transpose the new Directive.     

Autophagy genes coordinate with the class II PI/PtdIns 3-kinase PIKI-1 to regulate apoptotic cell clearance in C. elegans

Phagocytosis and autophagy are two lysosome-mediated cellular degradation pathways designed to eliminate extracellular and intracellular constituents, respectively. Recent studies suggest that these two processes intersect. Several autophagy proteins have been shown to participate in clearance of apoptotic cells, but whether and how the autophagy pathway is involved is unclear. Here we showed that loss of function mutations in 19 genes acting at overlapping or distinct stages of autophagy caused increased numbers of cell corpses in C. elegans embryos. In contrast, genes that mediate specific clearance of P granules or protein aggregates through autophagy are dispensable for cell corpse removal. We showed that defective autophagy impairs phagosome maturation and that autophagy genes act in parallel to the class II phosphoinositide (PI)/phosphatidylinositol (PtdIns) 3-kinase PIKI-1 to regulate phagosomal PtdIns3P in a similar manner as VPS-34. Our data indicate that autophagy may coordinate with PIKI-1 to promote phagosome maturation, thus ensuring efficient clearance of apoptotic cells.     

微创血肿清除与侧脑室引流术治疗小脑出血

目的：观察不同软通道微创手术方式治疗小脑出血的临床疗效。方法：高血压脑出血25例分成软通道微创血肿清除组（n=14）和侧脑室引流组（n=11）。以治疗后28天SSS和死亡率作为判断疗效的标准,比较两组的疗效。2组患者在入院时和入院后7 d行（格拉斯哥昏迷量表,Glasgow coma scale,GCS）评分,入院时和入院后14d及28d行（斯勘的纳维亚卒中量表,Scandinavianstroke scale,SSS）评分。结果：治疗组手术后SSS评分14d（t=3.65 P〈0.01）及30d（t=4.01,P〈0.01）,治疗组明显优于对照组。两组总有效率比较有显著差异（P〈0.05）。结论：软通道微创血肿清除术疗效优于单纯侧脑室引流术,其作为治疗小脑出血的微创治疗技术总体上是安全、有效的,明显降低了患者死亡率,提高了患者生存质量。     

Pharmacokinetic Analysis of Free Radicals by in vivo BCM (Blood Circulation Monitoring)-ESR Method

In pharmacokinetic studies, a variety of analytical method including radioisotopic detection and HPLC (high performance liquid chromatography) has been used. In the present investigation, we developed in vivo BCM (Blood Circulation Monitoring)-ESR method, which is a new technique with a conventional X-band ESR spectrometer for observing stable free radicals in the circulating blood of living rats under anaesthesia. Both 5–(PROXYL derivatives) and 6–(TEMPO derivatives) membered nitroxide spin probes with various types of substituent functional group were used. After physicochemical properties of the spin probes such as hyperfine coupling constant (A-value), g-value and partition coefficient as well as chemical stability of the compounds in the fresh blood were obtained, the in vivo BCM-ESR method was performed in normal rats. Several pharmacokinetic parameters such as half-life of the probes, distribution volume, total body clearance and mean residence time were obtained and discussed in terms of their chemical structures. In addition, clearance of a spin probe was related to the urine concentration. The BCM-ESR method was found to be very useful to observe free radicals at the real time. By time-dependent ESR signal decay of spin probes, pharmacokinetic parameters were obtained.     

Basic fibroblast growth factor accelerates myelin debris clearance through activating autophagy to facilitate early peripheral nerve regeneration

The successful removal of damaged myelin sheaths during Wallerian degeneration (WD) is essential for ensuring structural remodelling and functional recovery following traumatic peripheral nerve injury (PNI). Recent studies have established that autophagy involves myelin phagocytosis and cellular homoeostasis, and its disorder impairs myelin clearance. Based on the role of basic fibroblast growth factor (bFGF) on exerting neuroprotection and angiogenesis during nerve tissue regeneration, we now explicitly focus on the issue about whether the therapeutic effect of bFGF on supporting nerve regeneration is closely related to accelerate the autophagic clearance of myelin debris during WD. Using sciatic nerve crushed model, we found that bFGF remarkedly improved axonal outgrowth and nerve reconstruction at the early phase of PNI (14 days after PNI). More importantly, we further observed that bFGF could enhance phagocytic capacity of Schwann cells (SCs) to engulf myelin debris. Additionally, this enhancing effect is accomplished by autophagy activation and the increase of autophagy flux by immunoblotting and immune-histochemical analyses. Taken together, our data suggest that the action of bFGF on modulating early peripheral nerve regeneration is closely associated with myelin debris removal by SCs, which might result in SC-mediated autophagy activation, highlighting its insight molecular mechanism as a neuroprotective agent for repairing PNI.     

哌拉西林他唑巴坦与头孢哌酮钠舒巴坦治疗COPD合并铜绿假单胞菌感染的疗效和安全性对比

摘要 目的：对比哌拉西林他唑巴坦与头孢哌酮钠舒巴坦治疗慢性阻塞性肺疾病（COPD）合并铜绿假单胞菌感染的疗效和安全性。方法：选择2017年1月至2020年1月我院呼吸科住院治疗的60例COPD合并铜绿假单胞菌感染患者纳入研究,通过抽签法分为A组和B组,各30例。A组在常规治疗基础上给予哌拉西林他唑巴坦,B组在常规治疗基础上给予头孢哌酮钠舒巴坦,均持续治疗7 d。比较A组和B组患者的临床疗效、一般治疗情况、血清实验室指标、血气指标的变化及不良反应。结果：治疗后7 d,A组患者的临床疗效、细菌清除率结果分别为93.33%、83.33%,B组为90.00%、76.67%,差异无统计学意义（P＞0.05）;A组体温正常时间、白细胞计数（WBC）正常时间、肺部炎症病灶消失时间、住院时间分别为（2.68±0.47）d、（5.05±0.53）d、（9.21±1.30）d、（10.02±1.94）d,均明显短于B组的（3.31±0.51）d、（6.52±0.60）d、（10.37±1.88）d、（11.69±1.61）d,差异均有统计学意义（P＜0.05）;治疗后3 d时,A组患者的WBC、C反应蛋白（CRP）、降钙素原（PCT）分别为（10.38±1.75）×109/L、（9.75±1.55）mg/L、（1.94±0.31）μg/L,均明显低于B组的（12.10±2.18）×109/L、（11.18±1.64）mg/L、（2.26±0.29）μg/L,治疗后7 d时,A组患者的WBC、CRP、PCT分别为（6.29±1.40）×109/L、（5.91±0.77）mg/L、（0.86±0.20）μg/L,均明显低于B组的（7.55±1.37）×109/L、（7.04±1.29）mg/L、（1.17±0.34）μg/L,差异均有统计学意义（P＜0.05）;A组患者的动脉血氧饱和度（SaO2）、血氧分压（PaO2）分别为（92.11±3.06）%、（68.37±5.13）mmHg,均明显高于B组的（88.64±3.18）%、（62.84±3.20）mmHg,二氧化碳分压（PaCO2）为（44.12±3.03）mmHg,明显低于B组的（48.49±4.21）mmHg,差异均有统计学意义（P＜0.05）。结论：哌拉西林他唑巴坦与头孢哌酮钠舒巴坦对COPD合并铜绿假单胞菌感染患者均具有较好的抗菌效果及安全性,但哌拉西林他唑巴坦可缩短恢复时间,临床应用价值更高。