Anti-tumor pharmacology of natural products targeting mitosis

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer’s main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.     

RNA干扰抑制Nogo-A基因表达及对PC12细胞凋亡的影响

为研究Nogo-A基因沉默对细胞凋亡的影响,本文构建了靶向Nogo-A的短发夹样RNA(short hairpin RNA,shRNA)真核表达载体并经脂质体转染到培养的PC12细胞。分别以逆转录聚合酶链反应(RT-PCR)和免疫印迹法检测转染48h后Nogo-A mRNA及蛋白表达的变化。在转染后不同时间应用四甲基偶氮唑盐(MTT)法检测细胞增殖活性,用原位末端标记(TUNEL)法及流式细胞仪检测细胞凋亡率。结果显示:由shRNA产生的小干扰RNA(siRNA)可有效抑制PC12细胞Nogo-A基因的表达。Nogo-A siRNA处理组细胞的增殖活性增加、凋亡率明显下降。本结果提示,Nogo-A基因可能与细胞凋亡有关。     

Evaluation of efficacy and safety of esmolol in treating patients with septic shock: A protocol for systematic review and meta-analysis

Background:In septic shock cases, tachycardia and a hyperdynamic hemodynamic profile are characteristics of the condition. It has been reported that using beta antagonist esmolol constitutes a form of treatment to reduce heart rate to improve diastolic filling time and elevate cardiac output, which reduces vasopressor support. Still, there are controversial results. Therefore, in this study, the primary objective is to perform a meta-analysis by systematically evaluating the efficiency and security of using esmolol to treat septic shocks.Methods:A systematic literature search for relevant randomized controlled trials that report evaluations on the efficiency and safety of using esmolol to treat septic shock patients from their inception to February 2022 will be conducted in three databases containing publications in Chinese language (WanFang, Chinese BioMedical Literature Database, and China National Knowledge Infrastructure) and four databases containing English language publications (Cochrane Library, PubMed, Web of Science, and EMBASE). The screening of the relevant studies will be performed by a pair of authors independently, and the screening involves examining the title, abstract and full-text stages, data extraction, and bias risk assessment. The results are summarized through the fixed-effects and random-effects models, the respective models will be utilized for data pooling according to the heterogeneity of studies that will be included. Moreover, publication bias is assessed if more than ten studies are considered.Results:The results are a high-quality synthesis of the most recent evidence for esmolol usage in septic shock treatment.Conclusion:Up-to-date evidence will be provided through the results of this systematic review related to assessing the efficacy and safeness of esmolol usage in treating septic shock.Ethics and dissemination:Ethical permissions are not required as prepublished data are used.OSF registration number:DOI 10.17605/OSF.IO/SKEZ7     

Penetration and Cratering of Steel Target by Jets from Titanium Alloy Shaped Charge Liners

In order to enlarge the crater diameter of shaped charge jet penetration into steel targets, this paper investigates the penetration and cratering characteristics of steel targets by shaped charge jets from titanium alloy liners. Titanium alloy shaped charge liners are prepared separately with mechanical processing and selective laser melting (SLM), and pulsed X-ray radiography is used to identify jet formation characteristics. Jet formation is numerically simulated by AUTODYN-3D, and steel target penetration tests are carried out at a short jet stand-off distance. The results show that AUTODYN-3D can realistically simulate jet formation from titanium alloy liners and that the SLM-processed liner exhibits better penetration performance than the mechanically processed liner. The existing cratering formula of jet penetration is modified to make it consistent with the aperture variations of jet penetration from titanium alloy-lined shaped charges at a short stand-off distance. The findings of this study are expected to provide technical and theoretical support for research on the penetration characteristics of the jets from titanium alloy-lined shaped charges.     

K252a对腺样囊性癌培养中许旺细胞生长的阻断作用

目的观察并探讨K252a在体外坐骨神经长出的许旺细胞对腺样囊性癌细胞趋化生长中的影响。方法采用细胞培养技术,将经神经营养素的高亲和受体Trk特异性阻断剂K252a预处理的小鼠坐骨神经与腺样囊性癌细胞共培养（设24组）,以正常小鼠坐骨神经与腺样囊性癌细胞共培养为对照组（设24组）;结果与对照组相比,经K252a预处理的坐骨神经与腺样囊性癌细胞共培养长出的许旺细胞增生组数及趋化性生长组数X^2值分别为14．03、26．32,P值均小于0．025,说明两组之间的差异非常显著,许旺细胞丧失趋化性及细胞增生未被促进。结论K252a在许旺细胞对腺样囊性癌细胞趋化生长中的阻断作用间接地表明神经营养素可促进许旺细胞增生及向腺样囊性癌细胞趋化迁移,这可能是腺样囊性癌嗜神经性重要机制之一。     

PCR-GeneScan法检测遗传性聋相关基因GJB2 235 delC和mtDNA A1555G突变

目的:检测GJB2 235delC杂合突变和mtDNA A1555G突变。方法:对120例样本进行诊断试验,其中测序GJB2 235delC杂合突变样本16例,mtDNA A1555G突变17例。用PCR方法对目标片段进行扩增,PCR产物在3100DNA sequencer(ABI)上聚丙烯酰胺胶毛细管电泳,GeneScan、GeneMarker软件数据分析。结果:120例样本均得到检测结果,检出GJB2 235delC杂合突变样本17例,mtDNA A1555G突变17例,1例正常样本误诊为235delC杂合突变而出现假阳性。结论:PCR-GeneScan技术可以同时检测2种不同基因的突变,单管多重PCR和GeneScan荧光标记法结合是同时检测多种突变一种新的思路,而且可能是一种有效的方法。     

IPSS-V/S在TUVP术后下尿路症状评估的临床价值

目的：探讨国际前列腺症状评分的排尿期/储尿期评分比值（international prostatic symptom score-voiding/storage sub－score ratio,IPSS-V/S）在经尿道前列腺汽化电切术（transurethral electrovaporization prostatectomy,TUVP）术后下尿路症状（lower urinary tract symptoms,LUTS）再评估的临床价值。方法：回顾性分析了2015年1月至2016年12月期间234例接受TUVP的良性前列腺增生（benign prostatic hyperplasia,BPH）患者的国际前列腺症状评分（international prostatic symptom score,IPSS）等临床资料。按照IPSS-V/S比值将患者分为A组（IPSS-V/S≤1,80例）和B组（IPSS-V/S>1,154例）。术后6个月再次评估IPSS,储尿期症状评分（international prostatic symptom score-storage,IPSS-S）,排尿期症状评分（international prostatic symptom score-voiding,IPSS-V）和生活质量评分（quality of life,QOL）。结果：234例患者术后6个月IPSS和QOL较术前明显降低,差异有统计学意义（t=33.0,P=0.000;t=34.3,P=0.000）。术后6个月B组患者IPSS改善程度明显优于A组[（12.36±3.67）分 vs. （8.20±3.21）分]（t=8.96,P=0.000）。其中A组术后6个月IPSS-S明显高于B组[（9.61±2.88）分 vs. （5.55±2.63）分]（t=10.8,P=0.000）;而2组患者术后6个月时IPSS-V对比无统计学差异（t=1.56,P=0.120）。虽然A组术后6个月的QOL明显改善[（3.59±0.91）分 vs.（5.19±0.55）分]（t=14.8,P=0.000）,但是基本满意及以上者仅占13.75%,明显低于B组的70.78%。A组术后6个月IPSS-S各症状评分均有一定改善,改善程度从高到低依次为尿急评分、尿频评分和夜尿评分,其中夜尿评分改善率最低,仅为36.3%（29/80）,是A组患者IPSS及QOL改善较小的重要原因。结论：相比IPSS,IPSS-V/S更能准确反映TUVP术后疗效,LUTS排尿期症状改善明显优于储尿期症状。对于以夜尿症为主的BPH/LUTS患者,TUVP对患者QOL改善有限,需要引起临床医师重视。     

Function and Significance of Very Low Density Lipoprotein Receptor Subtype Ⅱ

To explore the functions of very low density lipoprotein receptor (VLDL-R) subtype Ⅱ in lipoprotein metabolism and foam cells formation, the recombinant plasmid with the two subtypes cDNA was constructed respectively, the ldl A7 cell lines were transfected and two cell lines expressing VLDL-R were obtained: one stably expressing the VLDLR with the O-linked sugar region (type Ⅰ VLDLR) and the other without the O-linked sugar region (type Ⅱ VLDLR). In the study on binding of VLDLR to their nuclein labeled natural ligands (VLDL and β-VLDL), it was found that surface binding of^125I-VLDL or ^125I-β-VLDL of ldl-A7 cells transfected with type Ⅰ VLDLR recombinant (ldl-A7-VRI) was more higher than that of ldl-A7 cells transfected with type Ⅱ VLDLR recombinant (ldl-A7 VRⅡ). After being incubated with VLDL for different time, the contents of triglyceride and total cholesterol in cells were mensurated, and the formation of foam cells and accumulation of lipid in cells was observed by oil-red O staining. The results showed that the contents of triglyceride and total cholesterol in IdI-A7-VR Ⅰ were much higher than those in ldl-A7-VR Ⅱ, and IdI-A7-VR Ⅰ could transform into foam cells notably. It was suggested that type Ⅰ VLDLR binds with relative higher affinity to VLDL and β-VLDL, and internalizes much more lipoprotein into cells. As a result, we can conclude that type Ⅰ VLDLR plays a more important role in lipoprotein metabolism and foam cells formation than type Ⅱ VLDLR。     

美国的医疗差错报告制度及借鉴意义

准确掌握和统计医疗差错信息,对促进医疗安全有着积极意义.简要地回顾了美国医疗差错报告制度实行的概况,希望对促进我国医疗事故报告制度的建设有所借鉴.