Obatoclax potentiates the cytotoxic effect of cytarabine on acute myeloid leukemia cells by enhancing DNA damage

Resistance to cytarabine and anthracycline‐based chemotherapy is a major cause of treatment failure for acute myeloid leukemia (AML) patients. Overexpression of Bcl‐2, Bcl‐xL, and/or Mcl‐1 has been associated with chemoresistance in AML cell lines and with poor clinical outcome of AML patients. Thus, inhibitors of anti‐apoptotic Bcl‐2 family proteins could be novel therapeutic agents. In this study, we investigated how clinically achievable concentrations of obatoclax, a pan‐Bcl‐2 inhibitor, potentiate the antileukemic activity of cytarabine in AML cells. MTT assays in AML cell lines and diagnostic blasts, as well as flow cytometry analyses in AML cell lines revealed synergistic antileukemic activity between cytarabine and obatoclax. Bax activation was detected in the combined, but not the individual, drug treatments. This was accompanied by significantly increased loss of mitochondrial membrane potential. Most importantly, in AML cells treated with the combination, enhanced early induction of DNA double‐strand breaks (DSBs) preceded a decrease of Mcl‐1 levels, nuclear translocation of Bcl‐2, Bcl‐xL, and Mcl‐1, and apoptosis. These results indicate that obatoclax enhances cytarabine‐induced apoptosis by enhancing DNA DSBs. This novel mechanism provides compelling evidence for the clinical use of BH3 mimetics in combination with DNA‐damaging agents in AML and possibly a broader range of malignancies.     

糖尿病手部坏疽的综合治疗11例报告

目的评估糖尿病手部坏疽综合治疗的临床效果。方法共收治糖尿病手部坏疽患者11例,自发现病变至诊治时间平均为6.2周,术前MHQ评分为61.3±7.5(55~71)分。均接受综合治疗,包括血糖控制、抗炎、清创截肢和术后处理等。结果本组11例随访12~18个月,平均13.2个月。患肢创面均完全愈合,除病变手指外,余指活动正常。术后MHQ评分为84.2±8.9(81~91)分。患侧握力为健侧的69%~83%。结论糖尿病手部坏疽的治疗需采用综合手段,在控制血糖及排除手术禁忌证后,应尽早行截指或者清创手术。     

芒针对脊髓损伤大鼠运动功能和炎症水平的影响

目的探究芒针深刺秩边穴对大鼠脊髓损伤后运动功能的影响及可能作用机制。方法选择健康雄性Wister大鼠81只,随机分为正常组、模型组和芒针组(正常组9只,其余两组各36只),采用改良Allen's造模法制备大鼠脊髓中度损伤模型,模型组不做特殊处理,芒针组采用芒针深刺秩边穴,每日1次,每次30 min。分别于术后1 d、3 d、5 d、7 d行BBB(Basso-Beattie-Bresnahan)运动功能评分;术后1 d、3 d、5 d、7 d取受损段脊髓组织行酶联免疫吸附测定(ELISA)、实时荧光定量PCR(RT-qPCR)和苏木素-伊红染色(HE染色)。结果术后5 d和7 d,芒针组大鼠BBB评分高于模型组,差异有统计学意义(P<0.01);脊髓损伤后,模型组和芒针组大鼠脊髓组织中高迁移率族蛋白B1(HMGB1)、核转录因子kB(NF-kB)、白介素-6(IL-6)含量及HMGB1mRNA、NF-kBmRNA、IL-6mRNA水平显著升高(P<0.05);受损的脊髓组织松散,灰质中有许多空洞形成,伴有炎性细胞浸润。芒针治疗后,芒针组大鼠脊髓组织中HMGB1、NF-kB、IL-6含量及HMGB1mRNA、NF-kBmRNA、IL-6mRNA水平较模型组降低,且在3 d、5 d、7 d差异有统计学意义(P<0.05);受损部位的空洞及炎性细胞逐渐减少。结论脊髓损伤后,炎症因子的大量聚集引起级联性炎症反应,影响大鼠运动功能的恢复。芒针的抗炎机制可能包括抑制HMGB1的表达,降低NF-kB信号通路的传导,下调促炎因子IL-6的分泌。     

新疆昌吉地区哈萨克族冠心病人群指长比分析

目的：通过直接测量的方法，对新疆地区明确诊断为冠心病的哈族人群的指长比进行分析，并探讨哈萨克族指长比与冠心病的相关性。方法：抽取新疆昌吉地区50名通过冠脉造影证实明确诊断为冠心病的哈萨克族人群，同时选择50例排除冠心病的哈萨克族健康人群，采用人体测量学方法测量左右双手第2～5指长度，并对指长比进行分析。结果：新疆昌吉地区哈萨克族人群指长比均呈现2D：3D〈2D：4D〈：3D：4D〈2D：5D〈：4D：5D〈：3D：5D的趋势，冠心病组左手2D：4D及3D：4D明显高于对照组。结论：左手2D：4D和3D：4D可能是新疆哈萨克族冠心病早期筛查的重要指标之一。     

铜绿假单胞菌上清液诱导J774细胞凋亡过程中Fas蛋白的表达

<正>铜绿假单胞菌(pseudomonas aeruginosa,PA)是医院内感染最常见的致病菌,一旦感染,治疗困难。巨噬细胞是机体重要的免疫防御细胞,细菌侵袭机体组织,首先要避免被巨噬细胞等机体免疫细胞的吞噬、清除。因此激发巨噬细胞凋亡对细菌而言很重要。近来研究显示,PA以剂量依赖和时间依赖的方式诱导U937巨噬细胞凋亡,且与线粒体途径有关[1]。本研究采用J774细胞作为巨噬细胞的模型[2],通过观察PA上清液诱导J774细胞凋亡过程中Fas蛋白的表达,进一步探讨PA上清液诱导J774细胞凋亡的致病机制,为开发新型抗感染药物提供重要的理论依据。     

非综合征型聋患儿及其家庭成员常见耳聋基因变异分析

目的分析深圳地区非综合征型耳聋患者及其相关高危人群中常见耳聋基因变异位点的分布，为分子诊断、遗传咨询及流行病学研究提供依据。方法应用基质辅助激光解析电离飞行质谱方法，对深圳地区1~6岁语前聋患儿71例及其听力正常的家庭成员（耳聋高危人群）145例，和作为对照听力的正常人群200例进行GJB2、SLC26A4、GJB3及MT RNR1基因的20个变异位点的检测。结果常见耳聋基因热点变异的检出率在语前聋患儿中为37%（26/71），在高危人群中为28%（40/145），在正常健康人群中为4.5%（9/200）；GJB2热点变异检出率在语前聋患儿中为18%（13/71），在高危人群中为12%（17/145），在正常人群中为2%（4/200）；SLC26A4检出率在语前聋患儿中为18%（13/71），在高危人群中为16%（23/145），在正常人群中为2.5%（5/200）。语前聋患儿组和耳聋高危人群组之间GJB2和SLC26A4变异检出率没有统计学意义（P=0.209），但两者都显著比正常人群高（P均<0.0001）；语前聋患儿中GJB2和SLC26A4变异纯合子和复合杂合子占18%（13/71），耳聋高危人群和正常人群中均未发现纯合子和复合杂合子，与语前聋患儿组比较有统计学意义（P<0.0001）。GJB3和MT RNR1变异在语前聋患儿、高危人群和正常人群中均未发现。结论GJB2和SLC26A4纯合和复合杂合变异是深圳地区语前聋患儿的重要致病原因，其中最常见的变异位点是GJB2:c.235delC和SLC26A4:c.919 2A>G。对于仅检出单杂合变异的耳聋患儿，可进行相应基因的测序，进一步明确分子诊断。     

The value of tumor microenvironment of metastasis in gastric cancer

目的 研究胃癌中是否存在肿瘤微环境转移(tumor microenvironment of metastasis,TMEM)及其与胃癌血道转移的相关性.方法 采用免疫组化双染法同时标记巨噬细胞和内皮细胞,计数26例远处转移及其配对26例无远处转移胃癌组织中TMEM密度.结果 (1)TMEM存在于胃癌组织中;(2)TMEM与分化程度、临床分期明显相关(P<0.001,P=0.006),与肿瘤大小、Lauren分型、淋巴结转移等其他临床病理特点无关(P均＞0.05);(3)TMEM与有无远处转移呈正相关(P<0.001).结论 证实胃癌中存在TMEM,TMEM密度可以预测胃癌血道转移,有望成为评估胃癌血道转移危险性的新预测指标.     

播散性浅表性光线性汗孔角化症21例临床病理分析

目的探讨播散性浅表性光线性汗孔角化症临床和组织病理学特点。方法回顾性分析本科1995年1月～2012年1月间断收治的21例播散性浅表性光线性汗孔角化症患者的临床和组织病理学资料。结果 21例患者中男女比例为1.1∶1(男11例,女10例)。20岁前发病者13例(61.91%),(20～50)岁7例(33.33%),>50岁1例(4.76%),平均发病年龄18.36岁。皮损位于曝光部位,累及面部者10例(47.62%),累及颈部者9例(42.86%),累及上肢者19例(90.48%),累及下肢者7例(33.33%),累及躯干者6例(28.57%)。其中4例有家族史(占19.05%)。3例合并有系统疾病。组织病理资料分析均可见典型的角化不全柱,其下方颗粒层减少或消失。结论播散性浅表性光线性汗孔角化症20岁前发病多见,男女发病率大致相当,皮损位于暴露部位。组织学上以表皮角质层内典型的角化不全柱伴其下方颗粒层减少或消失为特征。     

Online Shopping Behavior Study Based on Multi-granularity Opinion Mining: China Versus America

With the development of e-commerce, many products are now being sold worldwide, and manufacturers are eager to obtain a better understanding of customer behavior in various regions. To achieve this goal, most previous efforts have focused mainly on questionnaires, which are time-consuming and costly. The tremendous volume of product reviews on e-commerce Web sites has seen a new trend emerge, whereby manufacturers attempt to understand user preferences by analyzing online reviews. Following this trend, this paper addresses the problem of studying customer behavior by exploiting recently developed opinion mining techniques. This work is novel for three reasons. First, questionnaire-based investigation is automatically enabled by employing algorithms for template-based question generation and opinion mining-based answer extraction. Using this system, manufacturers are able to obtain reports of customer behavior featuring a much larger sample size, more direct information, a higher degree of automation, and a lower cost. Second, international customer behavior study is made easier by integrating tools for multilingual opinion mining. Third, this is the first time an automatic questionnaire investigation has been conducted to compare customer behavior in China and America, where product reviews are written and read in Chinese and English, respectively. Our study on digital cameras, smartphones, and tablet computers yields three findings. First, Chinese customers follow the Doctrine of the Mean and often use euphemistic expressions, while American customers express their opinions more directly. Second, Chinese customers care more about general feelings, while American customers pay more attention to product details. Third, Chinese customers focus on external features, while American customers care more about the internal features of products.