Carnosic acid induces autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells

The therapeutic goal of cancer treatment is now geared towards triggering tumour‐selective cell death with autophagic cell death being required for the chemotherapy of apoptosis‐resistant cancer. In this study, Carnosic acid (CA), a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), significantly induced autophagic cell death in HepG2 cells. Ca treatment caused the formation of autophagic vacuoles produced an increasing ratio of LC3‐II to LC3‐I in a time‐ and dose‐dependent manner but had no effect on the levels of autophagy‐related protein ATG6 and ATG13 expression. Autophagy inhibitors, 3‐methyladenine (3‐MA), chloroquine and bafilomycin A1, or ATG genes silencing in HepG2 cells significantly inhibited CA‐induced autophagic cell death. The CA treatment decreased the levels of phosphorylated Akt and mTOR without any effects on PI3K or PTEN. Most importantly, overexpression of Akt and knockdown of PTEN attenuated autophagy induction in CA‐treated cells. Taken together, our results indicated that CA induced autophagic cell death through inhibition of the Akt/mTOR pathway in human hepatoma cells. These findings suggest that CA has a great potential for the treatment of hepatoma via autophagic induction. Copyright © 2014 John Wiley & Sons, Ltd.     

急性冠状动脉综合征患者对氯吡格雷反应的变异性与再发心血管事件的关系

目的探讨急性冠状动脉综合征（ACS）患者对氯吡格雷的反应变异性与再发心血管事件的关系。方法ACS患者入院第1天或经皮冠状动脉介入术前服用负荷剂量氯吡格雷（300mg／d）,第2天起服用维持剂量（75mg／d）,同时口服阿司匹林（100mg／d）,共服用1年。检测患者服用负荷剂量氯吡格雷前和服用后24h最大血小板聚集率（MAR）并计算血小板聚集抑制率（IPA）。根据IPA将患者分为对氯吡格雷无反应组、低反应组和反应组。分别在服药第1、3、6、12个月末进行随访,记录患者出现再发心血管事件（包括心血管死亡、急性和亚急性支架血栓、再发ACS和缺血性中风）的情况。用Kaplan—Meier生存分析法比较3组患者再发心血管事件的累积发生率。结果2009年10月至2013年3月在东南大学附属中大医院心内科住院的190例ACS患者纳入研究,男性111例,女性79例,平均年龄（66．1±7．8）岁。氯吡格雷无反应组53例、低反应组46例、反应组91例。3组患者性别构成、合并危险因素及合并用药的差异均无统计学意义（均P〉0．05）,氯吡格雷无反应组平均年龄[（69．1±7．8）岁]大于反应组[（64．3±7．4）岁]（P〈0．05）,无反应组1、3、6、12个月再发心血管事件累积发生率[11．3％（6／53）、20．8％（11／53）、22．6％（12／53）、35．8％（19／53）]均明显高于反应组[1．1％（1／91）、1．1％（1／91）、2．2％（2／91）、9．9％（9／91）]（均P〈0．05）。Kaplan—Meier生存分析显示氯吡格雷无反应组再发心血管事件累积发生率明显高于低反应组（P〈0．05）与反应组（P〈0．01）。结论ACS患者对氯吡格雷反应的变异性与再发心血管事件可能有关。对使用氯吡格雷的患者应检测MAR与IPA,以减少或避免发生再发心血管事件。     

Interleukin 1 beta (IL-1 beta) processing in murine macrophages requires a structurally conserved homologue of human IL-1 beta converting enzyme.

Murine interleukin 1 beta (IL-1 beta) convertase (mICE) was identified in cytosolic extracts of peritoneal exudate cells (PECs) and macrophage cell lines. mICE cleaves both the human and mouse IL-1 beta precursors (pIL-1 beta) at sites 1 and 2 but fails to cleave a human pIL-1 beta (Asp116 to Ala) mutant at site 2, indicating that Asp is required to the left of the scissile bond. Ac-Tyr-Val-Ala-Asp-amino-4-methyl coumarin, patterned after site 2 of human pIL-1 beta, is a fluorogenic substrate for mICE, while the tetrapeptide aldehyde Ac-Tyr-Val-Ala-Asp-CHO is a potent inhibitor (Ki = 3 nM) that prevents generation and release of mature IL-1 beta by PECs (IC50 = 7 microM). Cloning of a full-length 1.4-kb cDNA shows that mICE is encoded as a 402-aa proenzyme (p45) that can be divided into a prodomain (Met1-Asp122), followed by a p20 subunit (Gly123-Asp296), a connecting peptide (Ser297-Asp314), and a p10 subunit (Gly315-His402). At the amino acid level, p45, p20, and p10 are 62%, 60%, and 81% identical with human IL-1 beta convertase (hICE). The active site Cys284 lies within a completely conserved stretch of 18 residues; however, Ser289 in hICE, which aligns with the catalytic region of serine and viral cysteinyl proteases, is absent from mICE. Expression in Escherichia coli of a truncated cDNA encoding Asn119-His402 generated active enzyme, which was autocatalytically processed at three internal Asp-Xaa bonds to generate a p20 subunit (Asn119-Asp296) complexed with either p11 (Ala309-His402) or p10. Recombinant mICE cleaves murine pIL-1 beta accurately at the Asp117-Val118 bond. The striking similarities of the human and murine enzymes will make it possible to assess the therapeutic potential of hICE inhibitors in murine models of disease.     

Endoscopic mask innovation and protective measures changes during the coronavirus disease-2019 pandemic: Experience from a Chinese hepato-biliary-pancreatic unit

Endoscopy is widely used as a clinical diagnosis and treatment method for certain hepatobiliary and pancreatic diseases. However, due to the distinctive epidemiological characteristics of severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease-2019 (COVID-19), healthcare providers are exposed to the patient's respiratory and gastrointestinal fluids, rendering endoscopy a high risk for transmitting a nosocomial infection. This article introduces preventive measures for endoscopic treatment enacted in our medical center during COVID-19, including the adjustment of indications, the application of endoscope protective equipment, the design and application of endoscopic masks and splash-proof films, and novel recommendations for bedside endoscope pre-sterilization.     

预见性护理对儿童白癜风自体表皮移植患者围术期感染发生率的影响

 目的:研究预见性护理对儿童白癜风自体表皮移植患者围术期感染发生率的影响。方法：将2017年9月-2018年9月在我院进行白癜风自体表皮移植手术患儿(72例)随机分为观察组与对照组,每组各36例,对照组给予常规护理,观察组在对照组基础上实施预见性护理措施。比较两组患儿术后至创口愈合期间的换药次数和创口愈合时间、围术期感染发生率以及患儿家属满意度。结果：对照组术后至创口愈合期间的换药次数为（6.02±0.60）次、创口愈合时间为（9.74±0.91）d,观察组术后至创口愈合期间的换药次数为（5.35±0.48）次、创口愈合时间为（8.78±0.75）d,观察组明显优于对照组,差异有统计学意义（t值分别为5.23、4.89,P值均＜0.05）。对照组围术期感染率为30.56%,观察组围术期感染率为8.33%,观察组低于对照组,差异有统计学意义（ X²=5.68,P＜0.05）。观察组家属对护理服务中护理人员态度、护理技术、护理专业度的满意度评分均高于对照组,差异有统计学意义（t值分别为2.33、2.29、2.45,P值均＜0.05）。结论：儿童白癜风自体表皮移植患者实施预见性护理效果明显,值得临床推广应用。     

超低剂量下不同迭代重建技术在肺动脉成像中的优化

目的 探讨不同迭代重建技术在超低剂量肺动脉成像中的应用价值。方法 对30例临床疑似肺动脉栓塞患者行CT肺动脉成像,扫描采用80 kV管电压并开启自动管电流调制技术,分别采用滤波反投影法(FBP)、iDOSE⁴、迭代模型重建(IMR)重建图像。采用5分制评价肺动脉主干及其分支的图像质量,测量计算图像噪声值、SNR、CNR,记录CT容积剂量指数(CTDIvol)、剂量长度乘积(DLP)、计算有效剂量(ED)。比较不同重建技术图像噪声、SNR、CNR及主观图像质量。结果 30例患者的平均体质量指数(BMI)为(25.12±2.48)kg/m²;平均CTDIvol为(0.78±0.28)mGy;平均DLP为(30.46±11.34)mGy·cm,平均ED为(0.43±0.16)mSv。IMR、iDOSE⁴、FBP图像噪声依次增高(P<0.05),SNR、CNR依次降低(P<0.05),CT值差异无统计学意义(P>0.05)。IMR、iDOSE⁴图像的主观评分显著高于FBP(P<0.05);IMR、iDOSE⁴图像可诊断率高于FBP(P<0.05),IMR图像优良率高于iDOSE⁴(P<0.05)。结论 采用80 kV联合IMR可保证肺动脉成像较高的图像质量,同时大大降低患者辐射剂量。