肺肠合治法对LPS诱导急性肺损伤大鼠NF-κB炎症通路和巨噬细胞极化的影响

目的 探究肺肠合治法（麻黄汤+大承气汤）对脂多糖（LPS）诱导的急性肺损伤（ALI）大鼠的作用与保护机制。方法 将Wistar大鼠随机分为正常组、模型组、肺肠合治低、中、高剂量组、地塞米松组。通过LPS（10 mg·kg^-1）腹腔注射成功复制ALI大鼠模型。观察与记录各组大鼠一般状态;采用肛温测量法记录各组大鼠造模后0~8 h体温数值;造模后24 h取材,收集血清与肺组织。酶联免疫吸附测定法（ELISA）检测大鼠血清白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）、精氨酸酶-1（Arg-1）含量;蛋白免疫印迹法（Western blot）检测各组大鼠肺组织中核转录因子-κB p65（NF-κB p65）、磷酸化核转录因子-κB p65（p-NF-κB p65）、核转录因子抑制蛋白α（IκBα）、磷酸化核转录因子抑制蛋白α（p-IκBα）蛋白的表达量;免疫荧光双标检测大鼠肺组织经典激活型（M1）巨噬细胞标记物CD80、IL-1β、巨噬细胞标记物F4/80、IL-10表达。结果 与正常组比较,模型组大鼠体温和热效应指数（TRI）显著升高,血清促炎因子TNF-α、IL-1β和抗炎因子IL-10水平显著升高（P<0.01）,肺组织p-NF-κB p65、p-IκBα蛋白表达显著升高（P<0.01）,肺组织巨噬细胞标志物F4/80、M1巨噬细胞标志物CD80和IL-1β的表达显著升高（P<0.01）;与模型组比较,肺肠合治各组和地塞米松组大鼠体温与TRI指数降低（P<0.01）,血清炎症因子TNF-α、IL-1β水平降低（P<0.05,P<0.01）,血清抗炎因子IL-10、Arg-1水平升高（P<0.05,P<0.01）,肺组织p-NF-κB p65、p-IκBα蛋白表达降低（P<0.05,P<0.01）,肺组织M1巨噬细胞标志物CD80、IL-1β表达显著降低和IL-10表达显著升高（P<0.01）,巨噬细胞标志物F4/80表达无明显变化。结论 肺肠合治方剂对ALI大鼠的发热与炎症状态有明显的改善,其机制可能与NF-κB炎症通路被抑制,肺组织巨噬细胞向抗炎表型极化有关。     

艾灸对三阴性乳腺癌移植瘤小鼠生存期的影响及机制研究

目的:观察艾灸对三阴性乳腺癌(TNBC)移植瘤小鼠生存期的影响,并基于对血清外泌体的分析探讨艾灸的干预机制。方法:采用TNBC细胞系皮下移植构建小鼠移植瘤模型,随机分为对照组与实验组; 分析小鼠生存期,绘制生存曲线,并检测血清外泌体。结果:实验组小鼠最长生存期达到53 d,对照组小鼠最长生存期48 d,两组比较差异有统计学意义(P<0.05); 通过透射电镜观察提取物形态,纳米颗粒跟踪分析仪测定粒径分布及浓度,Western blot检测外泌体表面标记蛋白,最终确定该提取物为血清外泌体。两组小鼠血清提取物均有CD63、TSG101表达。两组小鼠外泌体浓度分别为(6.19×10⁹)个/ml、(2.34×10⁹)个/ml,两组比较差异有统计学意义(P<0.01)。结论:艾灸延长三阴性乳腺癌荷瘤小鼠生存期的机制可能与促进相关细胞释放外泌体有关。     

CDK4/6抑制剂耐药机制的研究进展

细胞周期依赖性激酶4/6（cyclin-dependent kinase 4/6,CDK4/6)抑制剂能作用于过度活化的CDK4/6,恢复正常细胞周期,并通过触发免疫,改变肿瘤微环境等发挥抗肿瘤作用。目前,CDK4/6抑制剂的问世极大地改善了激素受体阳性（hormone receptor-positive,HR+）、人表皮生长因子受体2阴性（human epidermal growth factor receptor 2-negative,HER2-)晚期乳腺癌患者的预后,使无进展生存期(progression-free-survival,PFS)增加近一倍,且不良反应可控。尽管如此,这类患者最终仍会因CDK4/6抑制剂耐药而出现疾病进展。CDK4/6抑制剂的耐药机制十分复杂,尚未完全明确。预测其早期耐药或治疗敏感的生物标记物也有待确定。本文对CDK4/6抑制剂治疗的作用机制及耐药机制进行梳理和总结,并对疾病进展后的治疗策略作简要讨论。     

系统性红斑狼疮患者甲皱微循环观察

在系统性红斑狼疮患者的甲皱中可见到非常明显的异常，表现为视野模糊，管袢减少，弯曲，呈螺旋状并分枝，排列紊乱，管经扩张，血流缓慢，袢顶部淤血，袢周有渗出及出血等。     

三阴型乳癌的临床特征及预后探讨

目的探讨三阴型乳癌（TNBC）的临床特征及预后。方法回顾性分析潍坊市人民医院肿瘤外科2000—2008年有完整随访资料97例乳癌病人临床资料,其中经病理学检查证实TNBC者23例。结果 TNBC与肿瘤大小、淋巴结转移、病理类型、组织学分级均有关（χ2=4.169~4.998,P〈0.05）,与病人年龄、月经状况无关。随访的23例TNBC病人中,14例发生复发转移;74例非TNBC病人中,19例发生复发转移,差异具有统计学意义（χ2=9.682,P〈0.05）;TNBC病人中位生存期为38个月,非TNBC病人中位生存期为63个月,差异具有统计学意义（χ2=5.372,P〈0.05）。结论 TNBC有特定的临床特征,其预后明显差于非TNBC。     

老年人胃癌与谷胱甘肽转硫酶P1基因多态性关系的研究

目的 探讨幽门螺杆菌(Hp)感染及谷胱甘肽转硫酶P1(GSTP1)基因多态性与胃癌的关系.方法 选择老年胃癌患者(胃癌组)98例和胃镜检查正常者(对照组)149例,以快速尿素酶试验、13C-尿素呼气试验或活检标本吉姆萨染色(Giemsa)检测Hp感染;通过聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)分析方法检测GSTP1基因型.结果 Hp感染率胃癌组(54.1%)与对照组(40.9%)比较,差异有统计学意义(x2=4.11,P＜0.05);具有GSTP1突变纯和基因型并有Hp感染阳性的人群胃癌发病风险显著增加OR值5.44(1.26～26.79)(x2=7.13,P＜0.01).结论 老年患者Hp感染和GSTP1基因型多态性与胃癌的发病风险有关.

Abstract：

Objective To study the relationships of Helicobacter pylori (Hp) infection and genetic polymorphisms of glutathione s-transferase P1 (GSTP1) with gastric cancer (GC). Methods The 98 patients with GC and 149 controls with normal finding at endoscopy were enrolled for this study. The rapid urease test (RUT), 13C- urea breath test (13C-UBT) and Giemsa staining of biopsy samples were used to check Hp infection. PCR-based restriction fragment length polymorphisms (PCR-RFLP) was used to detect GSTP1 genotype. Results The rate of Hp infection was higher in GC group than in control group (54.1% vs. 40.9%, x2 =4.11, P＜0. 05). The risk of GC would significantly increase in the GSTP1 homozygous mutant gene (MM) group with Hp infection (OR=5.44, 95%CI 1. 26-26. 79, x2=7.13, P＜0.05). Conclusions Hp infection and GSTP1 genetic polymorphisms are associated with gastric cancer risk in the elderly.     

Gender differences in the association between elevated serum uric acid, not diuretic-induced, and cardiovascular disease in untreated hypertension patients

background Studies have been inconsistent regarding whether hyperuricemia, either diuretic- or non diuretic-induced, is an independent risk factor for cardiovascular events. The study investigated the association of cardiovascular disease with diuretic- and non diuretic-induced elevated serum uric acid. MethodsA community-based cross-section study was conducted in 5,235 treated and untreated hypertensive patients aged 40-75 years. Conventional risk factors, serum uric acid and the presence of cardiovascular disease were determined. Hyperuricemia was defined as serum uric acid levels ≥420 μmol/L in men or ≥360 μmol/L in women. ResultsHyperuricemia was more common in men than in women (21.5 % vs. 10.2 %, P < 0.001). After adjustment for age and other conventional risk factors, hyperuricemia was associated with metabolic syndrome, decreased creatinine clearance, and use of diuretics in both genders, as well as age in women and alcohol consumption in men. The presence of coronary artery disease or stroke increased significantly with the increase of quartiles of serum uric acid (8.0 %, 11.0 %, 13.4 %, and 16.8 %, respectively, P < 0.01), and the highest serum uric acid quartile was associated with a 1.8-fold risk for cardiovascular disease (OR: 1.83, 95 % CI: 1.24-2.71) in untreated women. But this association was not observed in untreated men as well as in treated patients using diuretics in both genders. Conclusions Hyperuricemia is markedly associated with metabolic syndrome, decreased creatinine clearance, use of diuretics besides alcohol consumption in men and age in women. Elevated serum uric acid, but not that diuretic-induced, may be associated with increased the risk of cardiovascular disease in untreated hypertensive women.     

胃癌高发区社会心理因素对慢性胃炎发病的影响

目的 探讨胃癌高发区人群慢性胃炎发病和社会心理因素的相关性.方法 以经过确诊的93例慢性浅表性胃炎(CSG)和69例萎缩性胃炎(CAG)患者作为研究对象,健康志愿者作对照组,了解上述人群各项社会心理因素情况.结果 (1)CSG组人际关系敏感、强迫症所占比例明显高于对照组(P均＜0.005),睡眠差高于对照组(P＜0.0...     

高血压及高血压左室肥厚患者心室跨壁复极离散度增加

目的研究高血压以及高血压左室肥厚患者心电图的Tp—Te间期、Tp—Te/QT比率与正常人群的区别,为预测高血压患者的临床不良事件提供依据。方法收集812例体检心电图,分为三组,正常组242例,高血压组270例,高血压左室肥厚组300例,测量V2导联连续3个心动周期的QT间期及Tp—Te间期,取其平均值。结果与正常组(82.14±8.53ms)相比,高血压组(97.98±13.31ms)和高血压左室肥厚组(104.56±12.64ms)的Tp—Te间期显著延长(P<0.01),高血压左室肥厚组Tp—Te间期与高血压组比较也有显著统计学意义(P<0.01)。与正常组(0.22±0.02)相比,高血压组(0.26±0.03)和高血压左室肥厚组(0.27±0.03)的Tp—Te/QT比率显著增大(P<0.01),高血压左室肥厚组Tp—Te/QT比率与高血压组比较也有显著统计学意义(P<0.01)。Tp-Te间期、Tp-Te/QT比率与左室质量指数成正相关(P<0.01),Pearson相关系数r分别为0.37、0.33。结论高血压及高血压左室肥厚患者心电图Tp—Te间期显著延长、Tp—Te/QT比率显著增大,高血压尤...