中药标准品对人肺癌耐药细胞A549/DDP的逆转效果研究

目的：研究中药标准品对人肺腺癌耐顺铂细胞株A549/DDP的逆转效果。方法：通过细胞增殖实验研究耐药细胞株（A549/DDP）的耐药倍数和对所选中药标准品的耐受情况。回归分析计算中药标准品对A549/DDP的IC5作为其逆转耐药的工作浓度。研究中药标准品在工作浓度下对A549/DDP耐顺铂的逆转效果。结果：A549/DDP的耐药指数为31.79。A549/DDP对川芎嗪、苦参碱耐受良好。盐酸小檗碱、北豆根碱（蝙蝠葛碱）和冬凌草甲素对A549/DDP细胞增殖均有一定的抑制作用,且存在明显的量效关系,工作浓度时,均能逆转A549/DDP对顺铂的耐受性（P<0.01）。结论：所选的中药标准品能有效逆转A549/DDP对顺铂的耐药性。     

SurViVin在顺铂诱导Panc-1细胞凋亡中的作用

的 :体外观察顺铂是否具有诱导胰腺癌细胞株 (Panc-1)凋亡的作用 ,同时观察在此过程中凋亡抑制蛋白 Survivin的表达变化 ,为探讨胰腺癌的化疗耐药机制提供理论基础。方法 :用人 Panc-1株进行培养传代 ;MTT试验检测顺铂以不同浓度和不同时间对 Panc-1株生长的抑制作用 ;用 RT-PCR检测凋亡过程中 Survivin基因表达的动态变化。结果 :顺铂可明显抑制 Panc-1细胞增殖 ,其增殖抑制率呈浓度和时间依赖性 ;DNA电泳可以观察到凋亡的发生 ,而且呈药物浓度、作用时间依赖关系 ;Survivin表达水平随着顺铂作用浓度的增加而下降 ,当顺铂浓度为 5 0μg/ml时下降最明显 (61% ) ;Survivin c DNA/β-actin c DNA比值与细胞增殖抑制率和细胞凋亡率呈负相关 (P<0 .0 1)。结论 :顺铂可以有效诱导 Panc-1株的细胞凋亡 ,而且 Survivin基因的抑制在顺铂诱导 Panc-1株的细胞凋亡中起重要作用。     

Does hot weather affect work-related injury? A case-crossover study in Guangzhou,China

Background

Despite increasing concerns about the health effects of climate change, the extent to which workers are affected by hot weather is not well documented. This study aims to investigate the association between high temperatures and work-related injuries using data from a large subtropical city in China.

紫杉醇联合顺铂循环式腹腔热灌注化疗对卵巢癌疗效和安全性分析

目的探讨紫杉醇联合顺铂循环式腹腔热灌注化疗对卵巢癌的疗效与安全性。方法回顾性分析我院2011年8月至2013年8月期间收治的96例中晚期卵巢癌患者,根据两种不同治疗方法分为观察组与对照组,每组48例。对照组采用卵巢癌细胞减灭术后予紫杉醇联合铂类全身静脉化疗治疗,观察组采用手术结合紫杉醇联合顺铂循环式腹腔热灌注化疗术,术后予TP方案静脉化疗,对两组患者治疗效果及安全性进行比较。结果观察组治疗有效率为87.50%,对照组治疗有效率为60.42%,两组差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论卵巢癌细胞减灭术后紫杉醇联合顺铂腹腔热灌注化疗辅助静脉化疗对于中晚期卵巢癌患者具有积极的治疗作用,能够有效控制肿瘤进展及恶性腹水,延长患者无进展生存期,提高患者生活质量,且不良反应可耐受。     

中药制剂单用确定性与合用调配性的关键理论技术问题研究

目的:通过分析中药制剂研究特点,明确该学科的长期发展方向,并提出本学科亟待解决的关键问题及对策。方法:根据中药制剂研究的发展轨迹,结合中医药基础理论、现代新药研究技术与本人从事中医药现代化研究经验,从中药制剂发展方向、特点、亟需解决的关键问题与对策等方面进行探讨。结果:建立以结构与作用明确的多成分群为原料,按中医药基础理论或现代网络医药为指导,以来源方便的动、植、矿物为原料,单用确定性(有效、稳定、可控),合用可调性(可预、最优效、最低毒)整体相统一的单个、群体与中药复方制剂体系。在实现上述目标时,需解决成分有效性归属、遗传稳态性与一次投料量、成分间理化性质迁移规律、提取过程动态性与稳态性规律、制备时整体模型受控与紊湍受控规律、体内外的评价规律、微观质量与宏观质量、单用的确定性与合用的调配性等关键技术问题。结论:中药制剂是体现单用确定性与合用调配性高度统一的整体有效成分群制剂。     

艾滋病中医药治疗及其相关问题研究进展

艾滋病（acquired immunodeficiency syndrome,AIDS）严重危及人类生命健康,而西药治疗AIDS采用的高效抗逆转录病毒治疗法（HAART）疗效有限。AIDS的中医药治疗方案可分为4类：单味中药及其有效成分,其研究重点主要为抗艾滋病毒和免疫调节两方面;中药复方;针灸疗法;中西药联合应用治疗,其中中药可起到减毒增效的效果。在中医药治疗AIDS的过程中,疗效评估和患者依从性的相关问题需要被着重考虑。中医药治疗AIDS已经表现出了个体化治疗、价格低廉、毒副作用小等诸多优势,但也存在着缺少中医诊断标准体系、缺少治疗实施方案和临床治疗过程的检测及质量控制等主要问题。通过大力开展对中医药各个领域的研究及其有效成分的提取,进而发现新的有价值的药剂或拓宽设计、合成药物的视野和思路,中医药疗法将在AIDS的治疗中发挥日益重要的作用。     

Efficacy and tolerability of luliconazole cream 1% for dermatophytoses: A Meta‐analysis

We evaluated the efficacy and safety of luliconazole cream 1% in the treatment of dermatophytoses. According to our meta‐analysis, short‐term treatment of luliconazole cream 1% can result in the complete clearance of dermatophytoses. It showed that 1% luliconazole was more effective than controlled drugs or vehicle (week 4: odds ratio = 1.46, 95% confidence interval = 1.12–1.91), and no more adverse events occurred in the 1% luliconazole group (week 4: odds ratio = 1.01, 95% confidence interval = 0.71–1.44). This effect strengthens the evidence for luliconazole cream 1% being more effective than vehicle, 1% terbinafine, 1% bifonazole, and 0.1% or 0.5% luliconazole.     

癫癎所致精神障碍患者87例精神残疾状况分析

目的分析癫癎所致精神障碍患者精神残疾特点、残疾程度及与性别、年龄、精神障碍病程的关系。方法对2009-07—2012-12在我院接受精神残疾评定的癫癎所致精神障碍87例患者,应用第二次全国残疾人抽样调查评定方法和世界卫生组织残疾评定量表Ⅱ(WHO-DASⅡ)总分进行精神残疾评定,然后对一般资料和残疾评定结果进行统计分析。结果 87例患者WHO-DAS II总分为(108.9±11.2)分,以一级残疾(49.4%)和二级残疾(25.3%)为主,相对应的WHO-DASⅡ总分为(121.2±12.3)分和(109.3±10.6)分;不同性别患者之间残疾等级构成差异无统计学意义(P>0.05);60岁以上患者多为一级残疾(P<0.05),占76.2%;精神障碍病程越长则一级残疾的比例越大(P<0.05或P<0.01);精神障碍病程>10a者基本都是三级以上的重度残疾者(P<0.05)。结论癫癎所致精神障碍成为精神残疾致残因素之一,须积极治疗和采取康复措施以减轻或延缓精神残疾的发生。     

RIPK1 activates distinct gasdermins in macrophages and neutrophils upon pathogen blockade of innate immune signaling

Injection of effector proteins to block host innate immune signaling is a common strategy used by many pathogenic organisms to establish an infection. For example, pathogenic Yersinia species inject the acetyltransferase YopJ into target cells to inhibit NF-κB and MAPK signaling. To counteract this, detection of YopJ activity in myeloid cells promotes the assembly of a RIPK1–caspase-8 death–inducing platform that confers antibacterial defense. While recent studies revealed that caspase-8 cleaves the pore-forming protein gasdermin D to trigger pyroptosis in macrophages, whether RIPK1 activates additional substrates downstream of caspase-8 to promote host defense is unclear. Here, we report that the related gasdermin family member gasdermin E (GSDME) is activated upon detection of YopJ activity in a RIPK1 kinase–dependent manner. Specifically, GSDME promotes neutrophil pyroptosis and IL-1β release, which is critical for anti-Yersinia defense. During in vivo infection, IL-1β neutralization increases bacterial burden in wild-type but not Gsdme-deficient mice. Thus, our study establishes GSDME as an important mediator that counteracts pathogen blockade of innate immune signaling.

Gasdermins are a family of recently described pore-forming proteins and are emerging as key drivers of cell death and inflammation. Gasdermins comprise a cytotoxic N-terminal domain connected to an inhibitory carboxyl-terminal domain and are activated upon proteolytic cleavage (1, 2). This cleavage event releases the cytotoxic N-terminal fragment, which creates membrane pores and triggers a form of lytic cell death called pyroptosis (3–6). Gasdermin D (GSDMD) is arguably the best characterized family member to date and is activated upon proteolysis by caspase-1, 4, 5, 8, and 11 and serine proteases (7–14). Active GSDMD promotes host defense by eliminating the replicating niche of intracellular pathogens (15) and inducing the extrusion of antimicrobial neutrophil extracellular traps (NETs) (16). In addition, GSDMD pores act as a conduit for bioactive IL-1β release (17–19), a potent proinflammatory cytokine that similarly requires proteolytic cleavage by caspase-1 or -8 to gain biological activity (20). By contrast, gasdermin E (GSMDE [also known as DFNA5]) is activated by apoptotic caspase-3 and 7 and granzyme B, which drives tumor cell pyroptosis and anti-tumor immunity (21–23). The physiological function of GSDME in primary immune cells and its potential role in host defense remain unresolved and have not been reported.Pathogenic Yersinia are a group of Gram-negative extracellular bacteria that causes disease ranging from gastroenteritis (Yersinia pseudotuberculosis) to plague (Y. pestis). A major mechanism by which pathogenic Yersinia establish systemic infection is by injecting the effector protein YopJ, an acetyltransferase that blocks transforming growth factor beta-activated kinase 1 (TAK1), to inhibit host innate immune signaling and proinflammatory cytokine production (24). To counteract this, detection of YopJ activity by myeloid cells induces the assembly of a cytoplasmic death–inducing complex that comprises receptor-interacting serine/threonine protein kinase 1 (RIPK1), fas-associated protein with death domain, and caspase-8 (24–26). During in vivo infection, RIPK1/caspase-8–dependent cell death in myeloid cells restricts bacterial dissemination and replication at distal sites by inducing proinflammatory cytokine production from uninfected bystander cells (24). More recently, GSDMD was identified as a caspase-8 substrate during Yersinia infection that drives antimicrobial defense in vivo (11, 12, 27). However, whether RIPK1 activates additional substrates to restrict Yersinia infection is unclear and is a focus of this study. Here, we identify GSDME as a substrate activated downstream of RIPK1 that confers host resistance against Yersinia. Gsdme-deficient mice failed to control bacterial replication in the spleen and liver and consequently are more susceptible to Yersinia infection than wild-type (WT) animals. Mechanistically, our data reveal that RIPK1 promotes caspase-3–dependent GSDME activation and IL-1β release in neutrophils, but not macrophages. Neutralization of IL-1β impaired bacterial clearance in WT, but not Gsdme^−/−, animals, indicating that IL-1β is mainly secreted through GSDME pores during Yersinia challenge in vivo.     

老年乳腺癌术后不良事件危险因素及预防的研究现状

该研究以老年患者身心特点为切入点分析易引起老年乳腺癌患者术后住院期间不良事件的潜在危险因素,并归纳了老年患者术后常见在院不良事件包括跌倒、深静脉血栓、切口愈合不良的预防措施和护理要点,为提高医护人员对老年乳腺癌术后住院不良事件的重视,做好危险因素评估,实施全面有效的预防措施,避免不良事件的发生,促进术后康复。