Multiple recombinant antigens of Clonorchis sinensis for serodiagnosis of human clonorchiasis

Antigenic proteins from Clonorchis sinensis have been previously purified and evaluated for their antigenicity to enable the serodiagnosis of clonorchiasis. Though they were of high specificity, molecularly defined proteins were reported to be less sensitive as single antigens than crude antigen. To resolve this issue, 11 clones were selected by immunoscreening an adult C. sinensis cDNA library using infected human sera. Mixed antigens were prepared using recombinant proteins of positive clones and investigated for antigenicity by immunoblotting against C. sinensis- and helminth-infected patient sera. A mixed antigen of recombinant 28 and 26 kDa glutathion S-transferases (Cs28GST and Cs26GST) produced 76% sensitivity and 95% specificity. Furthermore, a triple mix of recombinant Cs26GST and Cs28GST with vitelline precursor protein pushed up the sensitivity to 87% and maintained specificity at 95%. It is proposed that multiple antigen mixes should be further studied to develop rapid serodiagnostic test kits for the serodiagnosis of human clonorchiasis.     

Time-dependent oxidative stress and histopathological changes in <Emphasis Type="Italic">Cyprinus carpio</Emphasis> L. exposed to microcystin-LR

Microcystins (MCs) are produced by cyanobacteria in aquatic environments and are a potential risk to aquatic organisms. Increasing evidence suggests that oxidative stress may play an important role in the toxicity mechanism of MCs on fish, but most studies were based on relatively high concentrations. In this study, the effect of time-dependent oxidative stress in livers of Cyprinus carpio L. (C. carpio) exposed to 10 μg l⁻¹ of microcystin-LR (MC-LR) for 0–14 days was investigated. MC-LR induced histopathological changes in liver and gills were also assessed after 14 days exposure. Electron paramagnetic resonance (EPR) spectrum was used to directly investigate the reactive oxygen species (ROS) in fish liver and results showed that hydroxyl radical (^∙OH) was significantly induced at 0.5 day and then tended to decline with an increase of exposure period. As a response of antioxidant, catalase (CAT) activity increased slightly at first and then decreased with exposure period. A pronounced promotion of glutathione-S-transferase (GST) indicated that the conjugation reaction of MC-LR and GSH occurred. A time-dependent decrease of reduced glutathione (GSH) with an increase of oxidized glutathione (GSSG) level suggested GSH was involved in detoxification of MC-LR in the liver. Oxidative damage was evidenced by the significant increase of malondialdehyde (MDA) level at 2–6 days. After 14 days exposure, a series of pathological changes, like partially dissolved parenchymal architecture, vacuolar degeneration, necrosis, hemorrhage and slight inflammatory cells infiltration in fish liver tissues could be observed. Scanning electron microscopic (SEM) studies showed that dissolved MC-LR could also result in pathological changes like partial broken epithelial cells, deformed taste buds and loose gill filament and lamella in gill tissues. These results suggest that although a restoring response occurred, C. carpio could still be adversely affected by MC-LR at 10 μg l⁻¹.     

血清皮质醇、醛固酮水平在男性伪装精神病司法鉴定中的变化特点

目的:探讨血清皮质醇(COR)、醛固酮(ALD)水平在暴力违法精神疾病司法鉴定中对伪装精神病(诈病)的诊断与鉴别作用。方法:将男性暴力违法(被控故意杀人和伤害)者作为研究对象,分别比较完全责任能力伪装精神疾病组(简称诈病组)、无精神病无诈病表现完全责任能力组(简称完全组)、精神分裂症限定责任能力组(简称限定组)、精神分裂症无责任能力组作为对照组(简称对照组)血清COR、ALD水平。结果:(1)鉴定前后COR、ALD水平自身对照比较:诈病组COR、ALD水平差异均有极显著性(P<0.001);完全组COR有差异(P<0.05),ALD降低但无统计学意义(P>0.05);限定组COR有差异(P<0.05),ALD差异有显著性(P<0.01);对照组COR、ALD均降低,但无统计学差异(P>0.05)。(2)诈病组血清COR、ALD水平下降率高于其他组,差异均有显著性(P<0.001)。(3)鉴定前诈病组COR、ALD水平与其他组比较差异均有极显著性(P<0.001);完全组与限定组比较COR无差异(P>0.05),ALD有差异(P<0.05);完全组与对照组比较COR无差异(P>0.05),ALD差异有极显著性(P<0.001);限定组与对照组比较COR无差异(P>0.05),ALD差异有显著性(P<0.01)。(4)鉴定后诈病组与完全组比较:COR高于完全组差异有极显著性(P<0.001);ALD高于完全组,但差异无显著性(P>0.05)。诈病组与限定组比较:COR高于限定组差异有显著性(P<0.01);ALD高于限定组差异有极显著性(P<0.001)。诈病组与对照组比较:COR高于对照组,差异有显著性(P<0.05);ALD高于对照组,差异有极显著性(P<0.001)。结论:血清COR、ALD水平在应激层面对伪装精神疾病的诊断与鉴别以及对不同责任能力的判定具有一定的客观参考价值。     

Disease Activity Score 28 (DAS28) using C-reactive protein underestimates disease activity and overestimates EULAR response criteria compared with DAS28 using erythrocyte sedimentation rate in a large observational cohort of rheumatoid arthritis patients in Japan

OBJECTIVES: To compare disease activity and the improvement of disease activity evaluated between by Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) and by DAS28 using C-reactive protein (DAS28-CRP) in Japanese patients with rheumatoid arthritis (RA). METHODS: Data from 3073 RA patients registered in the large cohort database (NinJa: National Database of Rheumatic Diseases by iR-net in Japan) of 2003 was used to calculate DAS28-ESR and DAS28-CRP and disease activities were evaluated. Improvements in disease activities were also evaluated according to the European League Against Rheumatism (EULAR) response criteria in 1482 RA patients whose DAS28-ESR and DAS28-CRP could be calculated from data for both 2002 and 2003. RESULTS: The mean value of DAS28-CRP (3.59, SD 1.25) was significantly smaller than that of mean DAS28-ESR (4.31, SD 1.32) (p < 0.0001). The number of patients who satisfied the criteria of remission was 297 (9.7%) in DAS28-ESR versus 705 (22.9%) in DAS28-CRP and the number of patients with high disease activity was 842 (27.4%) versus 357 (11.6%) for DAS28-ESR and DAS28-CRP, respectively; there was a significant difference between the two (p < 0.0001). Change of respective DAS28 was significantly correlated (DeltaDAS28-ESR -0.05, SD 1.14 versus DeltaDAS28-CRP -0.10, SD 1.10) (p < 0.0001); however, the number of "good response" patients was significantly different (p < 0.03) between DAS28-ESR (97 patients, 6.5%) and DAS28-CRP (136 patients, 9.2%). CONCLUSIONS: DAS28-CRP significantly underestimated disease activity and overestimated the improvement in disease activity compared with DAS28-ESR. DAS28-CRP should be evaluated using different criteria from that for DAS28-ESR.     

Inhibition of pacemaker currents by nitric oxide via activation of ATP-sensitive K+ channels in cultured interstitial cells of Cajal from the mouse small intestine

We investigated the role of nitric oxide (NO) in pacemaker activity and signal mechanisms in cultured interstitial cells of Cajal (ICC) of the mouse small intestine using whole cell patch-clamp techniques at 30°C. ICC generated pacemaker potential in the current clamp mode and pacemaker currents at a holding potential of –70 mV. (±)-S-nitroso-N-acetylpenicillamine (SNAP; a NO donor) produced membrane hyperpolarization and inhibited the amplitude and frequency of the pacemaker currents, and increased resting currents in the outward direction. These effects were blocked by the use of glibenclamide (an ATP-sensitive K⁺ channel blocker), but not by the use of 5-hydroxydecanoic acid (a mitochondrial ATP-sensitive K⁺ channel blocker). Pretreatment with ODQ (a guanylate cyclase inhibitor) almost blocked the NO-induced effects. The use of cell-permeable 8-bromo-cyclic GMP also mimicked the action of SNAP. However, the use of KT-5823 (a protein kinase G inhibitor) did not block the NO-induced effects. Spontaneous [Ca²⁺]_i oscillations in ICC were inhibited by the treatment of SNAP, as seen in recordings of intracellular Ca²⁺ ([Ca²⁺]_i). These results suggest that NO inhibits pacemaker activity by the activation of ATP-sensitive K⁺ channels via a cyclic GMP dependent mechanism in ICC, and the activation of ATP-sensitive K⁺ channels mediates the inhibition of spontaneous [Ca²⁺]_i oscillations.     

2019年CHINET三级医院细菌耐药监测

目的监测国内主要地区医疗机构临床分离菌对抗菌药物的敏感性。方法对国内主要地区36所三级医院临床分离菌采用纸片扩散法或自动化仪器法按CHINET统一监测方案进行抗菌药物敏感性试验。按CLSI文件标准判断结果。结果收集2019年1-12月上述医院临床分离菌共249 758株,其中革兰阳性菌占29.0%,革兰阴性菌占71.0%。金黄色葡萄球菌、表皮葡萄球菌和其他凝固酶阴性葡萄球菌(除假中间葡萄球菌和施氏葡萄球菌)中甲氧西林耐药株的检出率分别为31.4%、82.4%和78.3%。甲氧西林耐药株(MRSA、MRSE和MRCNS)对绝大多数抗菌药物的耐药率均显著高于甲氧西林敏感株(MSSA、MSSE和MSCNS)。MRSA中有92.6%的菌株对甲氧苄啶-磺胺甲噁唑敏感;MRSE中有89.0%的菌株对利福平敏感;未发现万古霉素耐药株。肠球菌属中粪肠球菌对多数测试抗菌药物的耐药率均显著低于屎肠球菌,两者中均有少数万古霉素耐药株。2019年儿童和成人中分离的肺炎链球菌中PSSP(95.2%和95.3%)所占比例较2018年有所上升,PISP和PRSP的检出率有所下降。除肺炎克雷伯菌对碳青霉烯类的耐药率为27.6%外,肠杆菌科细菌对碳青霉烯类抗生素仍高度敏感,多数菌属的耐药率低于10%。2005-2019年15年的监测数据显示肺炎克雷伯菌对亚胺培南和美罗培南的耐药率呈持续上升趋势(3.0%和2.9%对25.3%和26.8%)。此外,不动杆菌属对亚胺培南和美罗培南的耐药率分别为73.6%和75.1%;铜绿假单胞菌对上述两药的耐药率分别为27.5%和23.5%。结论临床分离菌对常用抗菌药物的耐药率仍呈增长趋势,尤其是碳青霉烯类耐药革兰阴性杆菌。为应对严峻的全国细菌耐药形势,需各相关部门协作以遏制细菌耐药。     

miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression

Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.     

NSAIDs致上消化道出血的临床特点分析

目的探讨非甾体抗炎药(NSAIDs)致上消化道出血的临床特点。方法对2008年10月至2010年10月NSAIDs组和非NSAIDs组上消化道出血患者的临床资料进行分析。结果 NSAIDs组与非NSAIDs组在病变性质和病灶数目上比较差异具有统计学意义(P<0.05或P<0.01)。NSAIDs组胃溃疡和复合溃疡发病率高于非NSAIDs组(P<0.05)。结论 NSAIDs是诱发或导致上消化道出血的明确原因,应加强对其临床特点的认识,合理应用的同时采取措施减少其不良反应的发生。