Detection of p21WAF1/Cip1 in brain metastases

The p21^WAF1/Cip1 (p21) protein, a negative regulator of G₁ checkpoint control, was overexpressed in the majority of human gliomas. To investigate whether p21 expression in brain metastases from various systemic origins is similar to that in gliomas and whether p21 expression is regulated differently in brain metastases and in corresponding primary tumors, we used immunohistochemical staining to examine the expression of p21 in paraffin-embedded sections prepared from primary colon and breast carcinomas and from metastatic brain tumors that originated from colon, breast, lung, and kidney cancers and from melanoma. Our results showed that 56% (28 of 50) of the brain metastases samples have more than 1% p21-positive staining cells compared with 87% of primary gliomas reported previously. Among the samples analyzed, p21 expression in brain metastases from breast carcinomas was much higher than in primary breast carcinomas. In contrast, p21 expression in brain metastases from colon carcinomas was less than primary colon carcinomas. The results from this pilot study suggest that p21 expression is regulated differently in metastatic and primary tumors.     

黄芪、前胡、白蒺藜对培养的肺动脉平滑肌细胞增殖及胶原分泌的影响

目的:寻找抑制肺动脉高压肺血管重建的药物。方法:体外培养的肺动脉平滑肌细胞(PASMC)加入中药制剂黄芪口服液、前胡口服液、白蒺藜口服液分别大、小两个剂量(大剂量10mg/ml,小剂量1mg/ml)干预,并掺入~3H-胸腺嘧啶脱氧核糖核苷(`3H-TdR),~3H-脯氨酸(~3H-Pro)检测每分钟液闪值(cpm),反映 PASMC 增殖及胶原合成分泌的改变。结果:~3H-TdR掺入值在加入黄芪、前胡、白蒺藜口服液后,无论大、小剂量,PASMC 均被抑制(P<0.001);对~3H-pro 的掺入值,在加入黄芪、前胡口服液后,大剂量、小剂量皆有阻抑作用(P<0.01和 P<0.05),白蒺藜只在大剂量时有作用(P<0.01)。结论:中药制剂黄芪、前胡、白蒺藜口服液可不同程度地阻抑 PASMC 的增殖和胶原合成过程,可能对肺动脉高压肺血管结构的重建起一定防治作用。     

IMAF方案治疗复杂转移性乳腺癌疗效观察

为了评价异环磷酰胺，美斯纳，阿霉素和５－氟脲嘧啶联治疗复发转移性乳癌的疗效。对乳腺癌根治术后接受常规ＣＭＦ辅助化疗和放疗后，在２ａ内出现复发转移的２６例患者应用ＩＭＡＦ方案化疗。结果完全缓解４例，部分缓解１２例，总有效率为６１．５％。毒副反应主要为恶性心呕吐、骨髓抑制，脱发和镜下血尿。结果表明ＩＭＡＦ方案是治疗复发转移性乳腺癌疗效较好的方案。     

妊娠期大鼠摄入氟化物对子代鼠血液和骨氟浓度的影响

目的:观察孕期大鼠摄入不同剂量的氟之后,对子代鼠血液和骨氟浓度及软骨细胞和骨关节结构的影响,以探索通过妊娠期母体给氟预防乳牙龋齿的新途径。方法:给妊娠SD大鼠分别用N aF按1 m g/kg体重、10 m g/kg体重和50 m g/kg体重灌胃至分娩,并用0.9%N aC l灌胃作为对照组。结果:①实验组各组子鼠血清中的氟化物含量均较对照组高(P<0.01);并且与母鼠摄入的氟剂量呈正相关。②在中、高剂量组子鼠上肢骨骨氟的含量明显高于对照组。③在高剂量组子鼠的上肢骨切片中可见软骨细胞和关节结构的破坏。结论:①妊娠期母体摄入的氟化物可进入其子体体内。②当母鼠摄入的氟化物剂量过高时,可引起骨组织的毒性损害。     

社区美沙酮维持治疗对海洛因成瘾者吸毒行为影响的初步研究

目的 了解四川省西昌市社区美沙酮维持治疗对海洛因成瘾者吸毒行为的影响情况。方法于2004—05／07，以社区为基础招募海洛因成瘾者，调查其社会人口学、毒品使用及共用注射器具行为特征，了解社区美沙酮维持治疗（MMT）对吸毒行为的影响情况。结果 在调查的海洛因成瘾者中参加过MMT的为30．4％（105／346），参加MMT时间的中位数为49d。在控制社会人口学等因素后，多因素Logistic分析结果显示，MMT与海洛因成瘾者近3个月吸毒行为的关系有统计学意义的变量为：静脉吸毒频率（OR：0．40；95％CI：0．24～0．66）、海洛因口吸频率（OR：3．06；95％CI：1．87～5．00）、海洛因混合其他毒品使用频率（OR：0．43；95％CI：0．26～0．73）、共用针头或注射器（OR：0．03；95％CI：0．01-0．13）、共用洗针头或注射器用水（OR：0．06；95％CI：0．01～0．24）和共用吸毒器皿（OR：0．02；95％CI：0．00～0．18）。结论 研究结果表明我国第一批海洛因成瘾者美沙酮维持治疗试点项目在减少吸毒人群毒品使用和艾滋病相关高危吸毒行为等方面具有明显的效果。     

大蒜素对大鼠心室肌细胞L-型钙通道的影响

目的:探讨大蒜素对大鼠心室肌细胞L-型钙通道的作用.方法:用急性酶解法获得大鼠的单个心肌细胞,用标准的全细胞膜片钳技术记录钙通道电流.结果:5、50、250和500μmol/L大蒜素分别抑制钙电流4.4%、26.91%、38.06%、72.90%.250μmol/L大蒜素能使心肌细胞钙电流-电压曲线明显上移,峰电流密度从(7.17±0.65)pA/pF减少至(4.44±0.52)pA/pF(n=15,P<0.05),但激活电位、峰电位和翻转电位无明显改变(P>0.05).大蒜素能使钙电流失活曲线明显左移(P<0.05).大蒜素对钙电流激活曲线、失活再复活曲线和频率依赖性无明显影响(P>0.05).结论:大蒜素呈浓度依赖性地抑制心肌细胞L-型钙通道.     

Constructing Large Scale Cohort for Clinical Study on Heart Failure with Electronic Health Record in Regional Healthcare Platform: Challenges and Strategies in Data Reuse

Regional healthcare platforms collect clinical data from hospitals in specific areas for the purpose of healthcare management. It is a common requirement to reuse the data for clinical research. However, we have to face challenges like the inconsistence of terminology in electronic health records (EHR) and the complexities in data quality and data formats in regional healthcare platform. In this paper, we propose methodology and process on constructing large scale cohorts which forms the basis of causality and comparative effectiveness relationship in epidemiology. We firstly constructed a Chinese terminology knowledge graph to deal with the diversity of vocabularies on regional platform. Secondly, we built special disease case repositories (i.e., heart failure repository) that utilize the graph to search the related patients and to normalize the data. Based on the requirements of the clinical research which aimed to explore the effectiveness of taking statin on 180-days readmission in patients with heart failure, we built a large-scale retrospective cohort with 29647 cases of heart failure patients from the heart failure repository. After the propensity score matching, the study group (n=6346) and the control group (n=6346) with parallel clinical characteristics were acquired. Logistic regression analysis showed that taking statins had a negative correlation with 180-days readmission in heart failure patients. This paper presents the workflow and application example of big data mining based on regional EHR data.     

G3BP1 interacts with YWHAZ to regulate chemoresistance and predict adjuvant chemotherapy benefit in gastric cancer

BACKGROUND A large proportion of gastric cancer patients are susceptible to chemoresistance, while the underlying mechanism remains obscure. Stress granules (SGs) play a self-defence role for tumour cells in inhibiting chemotherapy-induced apoptosis. As an SG assembly effector, G3BP1 (Ras-GTPase-activating protein SH3 domain-binding protein) has been reported to be overexpressed in gastric cancer; thus, here we aim to explore its potent roles in gastric cancer chemoresistance.METHODS Kaplan–Meier analysis was used to compare survival rates in gastric cancer patients with different G3BP1 expression. The influence of G3BP1 on gastric cancer cell chemoresistance and apoptosis were evaluated by in vitro and in vivo approaches. The interaction between G3BP1 and YWHAZ was assessed by immunohistochemistry, immunoprecipitation and immunofluorescence.RESULTS G3BP1 was associated with the poor outcome of gastric cancer patients who received adjuvant chemotherapy. G3BP1 knockdown significantly increased the sensitivity of gastric cancer cells to chemotherapy drugs. Mechanically, cell apoptosis and pro-apoptotic-associated molecules were significantly elevated upon G3BP1 depletion. Gene co-expression network analyses identified YWHAZ as the critical interlayer of G3BP1; as a result, G3BP1 interacted with YWHAZ to sequester Bax into the cytoplasm. Clinically, G3BP1^highYWHAZ^high gastric cancer patients displayed the worst outcome compared with other patients after chemotherapy.CONCLUSIONS The expression of G3BP1 and YWHAZ could predict the adjuvant chemotherapy benefit in gastric cancer patients.Subject terms: Gastric cancer, Cell death