SP-141抑制胃癌细胞增殖、迁移并促进凋亡

目的：探讨MDM2的新型小分子抑制剂SP-141对胃癌细胞株MGC803和BGC823增殖、凋亡以及迁移的影响。方法：胃癌细胞经SP-141处理后,采用CCK-8法、克隆形成实验、流式细胞术、Hoechst染色法和划痕实验分别检测细胞存活率、细胞增殖、周期分布、凋亡以及迁移能力改变。Western blot检测相关分子蛋白质表达水平。结果：TCGA数据库中32对胃癌组织中的MDM2 mRNA表达水平高于癌旁组织（P<0.01）;5种胃癌细胞株均检出MDM2,表达水平差异不大;SP-141抑制MGC803和BGC823的细胞存活率以及克隆形成,诱导其细胞周期阻滞在G2/M期;SP-141增加细胞凋亡发生率,并下调Bcl-2同时上调Bax、Caspase-3剪切体、PARP剪切体的蛋白表达;SP-141抑制细胞迁移并伴有FAK蛋白表达量的下降。结论：MDM2的新型小分子抑制剂SP-141可有效抑制胃癌细胞增殖、迁移并促进细胞凋亡。     

微小 RNA-141-3p靶向调控含 CUE结构域蛋白 2基因对雨蛙素诱导的大鼠胰腺腺泡细胞损伤的影响

目的探讨微小 RNA-141-3p(miR-141-3p)靶向调控含 CUE结构域蛋白 2(CUEDC2)对雨蛙素诱导的大鼠胰腺腺泡细胞损伤的影响。方法 2018年7月至 2019年12月,从美国 ATCC购买大鼠胰腺腺泡细胞 AR42J。100 nm/L雨蛙素(CAE)刺激大鼠胰腺腺泡细胞 AR42J 6 h建立急性胰腺炎细胞模型。实时荧光定量 PCR(qRT-PCR)和蛋白质印迹法(Western blotting)检测雨蛙素干预后AR42J细胞中 miR-141-3p和CUEDC2的表达水平。双荧光素酶报告基因实验和蛋白质印迹法验证 miR-141-3p和CUEDC2的靶向关系。利用脂质体转染法将 miR-141-3p抑制物(anti-miR-141-3p)、miRNA抑制物阴性对照(anti-miR-NC)、CUEDC2过表达载体(pcDNA-CUEDC2)、空载体(pcDNA)分别转染 AR42J细胞,经雨蛙素干预处理后,流式细胞术检测细胞凋亡,蛋白质印迹法检测 B细胞淋巴瘤 /白血病 -2(Bcl-2)和Bcl-2相关 X蛋白(Bax)的表达水平,酶联免疫吸附试验(Elisa)试剂盒检测细胞培养上清中肿瘤坏死因子-α(TNF-α)和白细胞介素 -6(IL-6)水平。结果雨蛙素干预处理后 AR42J细胞中 miR-141-3p的表达水平显著升高［(2.43±0.24)比(1.00±0.09)］,CUEDC2的表达水平显著降低。 miR-141-3p靶向负性调控 CUEDC2表达。与转 anti-miR-NC和雨蛙素协同处理组比较,转染 anti-miR-141-3p和雨蛙素协同处理组 AR42J细胞凋亡率显著增加［(27.48±2.33)%比(15.64±1.51)%］Bax蛋白的表达显著增加, Bcl-2蛋白的表达显著降低, TNF-α［(136.54±14.58)ng/L比( 226.48±20.54)ng/L］和 IL-6［(115.89±11.65)n,g/L比( 193.47± 18.63)ng/L］的分泌显著降低;与转染 pcDNA和雨蛙素协同处理组比较,转染 pcDNA-CUEDC2和雨蛙素协同处理组 AR42J细胞凋亡率显著增加［(23.87±2.35)%比(14.23±1.44)%］,Bax蛋白的表达显著增加, Bcl-2蛋白的表达显著降低, TNF-α［(158.74±15.32)ng/L(236.87±18.66)ng/L］和IL-6［(135.77±14.97)ng/L比(189.67±17.32)ng/L］的分泌显著降低;转染 si-CUEDC2可逆转转染 anti-miR14比1-3p对雨蛙素诱导的大鼠胰腺腺泡细胞损伤的影响。结论抑制 miR-141-3p通过靶向 CUEDC2可促进急性胰腺炎腺泡细胞的凋亡,抑制 TNF-α和IL-6分泌,从而减轻雨蛙素诱导的大鼠胰腺腺泡细胞损伤。     

Regional differences in the control of lipolysis in human adipose tissue

Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.     

Surface Contamination of CT and MRI Equipment—A Potential Source for Transmission of Hospital-Acquired Infections

Hospital-acquired infections (HAIs) are a major problem for health care worldwide. These infections cause additional suffering for the patient and infer major societal costs. There has been extensive research on infection transmission in health care, but to a lesser extent within the field of radiology. The purpose of this study was to identify selected hand-touched surfaces inside and outside the computed tomography (CT) and magnetic resonance imaging (MRI) examination rooms which are prone to contamination and which could represent a risk for transmission of HAI pathogens. We also aimed to examine differences in bacterial contamination between public and private radiology departments. Six public and four private radiology departments participated in the study. Bacterial samples were taken from ten predetermined surfaces inside and outside CT and MRI examination rooms. Sampling was carried out between patients after standard cleaning procedure, using flocked nylon swabs. The swab was applied over a 100 cm² surface, and after cultivation, bacterial colony-forming units (CFU) per cm² were calculated. Bacterial CFU were found on almost all selected surfaces. The highest numbers were found on keyboards, chairs of the patient changing rooms, headphones, and the alarm control/buzzer. There was no significant difference between public and private radiology departments. No multidrug-resistant microorganisms such as methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase–producing Enterobacterales, or carbapenemase-producing Enterobacterales were found in any of the investigated radiology departments. Both the CT and MRI equipment in public and private radiology departments may be potential sources of pathogenic bacteria, and disinfection between patients should be improved.     

黑皮质素受体4激动剂的研究进展

黑皮质素受体4(melanocortin-4 receptor,MC4R)是一种参与中枢调节的G蛋白偶联受体,主要存在于皮质、丘脑、下丘脑、脑干.激活MC4R可产生多种生理功能,因此本文就近年来新发现的外源性MC4R激动剂RM-493、RO27-3225和PT-141的生理功能及其研究进展做一综述,旨在为今后临床用药提...     

Preoperative geriatric assessment and follow-up of patients older than 75 years undergoing elective surgery for suspected colorectal cancer

ObjectivesWe investigated the predictive value of specific tools used in a Comprehensive Geriatric Assessment (CGA) with regard to postoperative outcome in patients 75 years and older undergoing elective colorectal cancer (CRC) surgery. Furthermore, recovery was followed over the first postoperative year using the same assessment tools.Material and MethodsBaseline clinical and CGA variables including functional and nutritional status, pressure sore risk, fall risk, cognition, depression, polypharmacy, comorbidity, and health-related quality-of-life (HRQoL) were prospectively recorded. Outcome variables were postoperative complications and length of stay (LOS). Patients were likewise followed up at one, three and twelve months postoperatively.ResultsForty-nine patients underwent surgery (median age 81 years). Forty-three per cent had ASA (American Society of Anesthesiologists) class 2 47% had ASA class 3. Postoperative complications occurred in 32.7%. Median LOS was eight days. In univariate analyses, none of the parameters tested predicted postoperative complication or LOS. During follow-up, all patients recovered to baseline values apart from HRQoL which was still reduced at three and twelve months (p = .017). Nutritional status had improved twelve months after surgery (p = .011).ConclusionsNo association could be found in this study between the results of a comprehensive geriatric assessment and prolonged length of stay or postoperative complication rate after elective surgery for colorectal cancer. Patients recovered well during the first year after surgery. Quality of life, however, was still lower than prior to surgery.     

人参皂甙Rb1抑制扩张型心肌病发生中的HB-EGF表达和纤维化

目的 HB-EGF过表达可促进心肌纤维化及心肌细胞凋亡,本文研究人参皂甙Rb1对cTnTR141W转基因扩张型心肌病小鼠发病过程中的HB-EGF表达和心肌纤维化的影响. 方法将cTnTR141W转基因小鼠随机分为模型组和人参皂甙Rb1组(70 mg/kg/d),连续给药7个月,取野生型小鼠作为对照组.用Kaplan-Meier法进行生存分析.心脏超声检测心功能及心脏几何构型.计算心重指数.光镜观察心肌细胞及间质变化.Western blot检测心脏HB-EGF,pSTAT3表达水平. 结果 Rb1长期给药能显著改善该模型的心功能和心脏几何构型,将死亡率降低50%.Rb1治疗组心重指数降低11.3%(P<0.05),光镜观察显示Rb1能减轻心肌细胞排列紊乱以及间质纤维化.Western blot结果显示Rb1能够显著降低模型中的HB-EGF及pSTAT3的表达.结论 Rb1抑制心肌病发生中的HB-EGF表达及抑制下游信号pSTAT的激活,并改善扩张型心肌病模型的心功能及心脏重构.     

Genomic and Phenotypic Insights for Toxigenic Clinical Vibrio cholerae O141

Vibrio cholerae remains a major public health threat worldwide, causing millions of cholera cases each year. Although much is known about the evolution and pathogenicity of the O1/O139 serogroups of V. cholerae, information is lacking on the molecular epidemiology of non‒O1/O139 strains isolated from patients who have diarrheal illnesses. We performed whole-genome sequence analysis and in vivo infections to investigate characteristics of V. cholerae O141 isolated from sporadic diarrheal cases in 4 countries. The strains formed a distinct phylogenetic clade distinguishable from other serogroups and a unique multilocus sequence type 42, but interstrain variation suggests that O141 isolates are not clonal. These isolates encode virulence factors including cholera toxin and the toxin-coregulated pilus, as well as a type 3 secretion system. They had widely variable capacities for intestinal colonization in the infant mouse model. We propose that O141 isolates comprise a distinct clade of V. cholerae non‒O1/O139, and their continued surveillance is warranted.