Combined targeted therapy and immunotherapy for cancer treatment

Although targeted therapies and immunotherapies have been effective against several malignancies, the respective monotherapies are limited by low and/or short-term responses. Specific inhibitors of oncogenic signaling pathways and tumor-associated angiogenesis can activate the anti-tumor immune responses by increasing tumor antigen presentation or intratumor T cell infiltration. Additional insights into the effects and mechanisms of targeted therapies on the induction of anti-tumor immunity will facilitate development of rational and effective combination strategies that synergize rapid tumor regression and durable response. In this review, we have summarized the recent combinations of targeted therapies and immunotherapies, along with the associated clinical challenges.     

Does estrogen receptor gene polymorphism play a role in Parkinson's disease?

This study was designed to investigate the frequency of estrogen receptor (ER) gene polymorphism in Chinese patients with Parkinson's disease (PD). Polymerase chain reaction (PCR) method and restriction fragment length polymorphism (RFLP) were used to detect the ER gene polymorphisms in 158 PD patients and 146 healthy controls. In the PD and control groups, “x” accounted for 83.5% and 80.8%, respectively (P > 0.05). “xx” was found in 77.2% of the PD group and in 69.9% of the control group (P > 0.05). The frequency of “p” in the PD and control group was 67.7% and 64.0%, respectively (P > 0.05). “pp” was 51.9% in the PD group and 43.8% in the control group (P > 0.05). “ppxx” was found in 49.4% of the PD and 43.0% of the control subjects (P > 0.05). There was no significant difference in the “x”, “xx”, “p”, “pp” or “ppxx” between males and females within the PD or control groups. In conclusion, we found no significant differences in the genotype or allele frequencies between patients with Parkinson's disease and healthy subjects. These findings suggest that the estrogen receptor gene polymorphism may not play a key role in the pathogenesis PD in Chinese patients.     

严重代谢性碱中毒时CO2潴留的处理

代谢性碱中毒是指细胞外液碱增多和(或)H~+丢失引起血液pH升高,以血浆HCO_3~-原发性增多为特征,动脉血二氧化碳分压(PaCO_2)可代偿性增高,一般极少超过55 mmHg。然而,在极其严重代谢性碱中毒情况下,PaCO_2代偿极限可达60~72 mmHg,但目前国内外鲜有此类报道。本文探讨了我院成功抢救的1例严重代谢性碱中毒患者,以提高对该罕见临床现象的认识。     

TRAIL-R1 polymorphisms and cancer susceptibility: An evidence-based meta-analysis

Published data on the association between tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1 or DR4) polymorphisms rs20575 (C626G), rs2230229 (A1322G) and rs20576 (A683C) and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of nine studies, among which eight articles including 2941 cases and 3358 controls described C626G genotypes, three articles including 736 cases and 668 controls described A1322G genotypes and three studies totalling 1550 cases and 2257 controls described A683C genotypes were involved in this meta-analysis. Overall, all three polymorphisms were associated with cancer susceptibility. For C626G polymorphism, there was no association between C626G polymorphism and the risk of cancer in all genetic models when all the eligible studies were pooled into the meta-analysis. In the subgroup analysis by source of controls, statistically significantly reduced cancer risks were found among groups with population-based controls for CG versus CC (OR = 0.77, 95% CI:0.65–0.91, P_{heterogeneity} = 0.007) and dominant model (OR = 0.84, 95% CI:0.72–0.99, P_{heterogeneity} = 0.409). For A1322G polymorphism, we found it was associated with a significantly elevated cancer risk of all cancer types in different genetic models (homozygote comparison: OR = 2.80, 95% CI:1.16–6.76, P_{heterogeneity} = 0.905; dominant model comparison: OR = 1.57, 95% CI:1.02–2.41, P_{heterogeneity} = 0.167; and recessive model comparison: OR = 1.22, 95% CI:0.94–1.60, P_{heterogeneity} = 0.535). Similar results were obtained from A683C polymorphism (homozygote comparison: OR = 3.21, 95% CI:1.26–8.20, P_{heterogeneity} = 0.012; dominant model comparison: OR = 1.61, 95% CI: 1.09–2.36, P_{heterogeneity} = 0.000; and recessive model comparison: OR = 2.79, 95% CI: 1.17–6.68, P_{heterogeneity} = 0.025). In summary, this meta-analysis suggests that TRAIL-R1 C626G polymorphism is marginally associated with cancer susceptibility, and both TRAIL-R1 A1322G G allele and A683C C allele are associated with increased risk for cancer.     

胰腺结石的诊断与外科治疗(附10例报告)

目的　探讨胰腺结石的外科诊断方法与外科手术方式。方法　对 10例胰腺结石病人的诊治情况进行了回顾性分析。结果　B超诊断结石 6例 ,ERCP检查 4例 ,腹部X线摄片检查3例 ;胰十二指肠切除 2例 ,切开胰管取石、胰管空肠侧侧吻合术 5例 ,囊肿Roux Y吻合术 1例 ,脾胰体尾切除与胰体尾切除各 1例。结论　B超、腹部平片、CT和ERCP对胰腺结石是有效的诊断手段。手术方式的选择取决于胰腺结石的部位、主胰管狭窄程度、是否合并胰腺癌肿与胰腺囊肿、有无慢性胰腺炎与糖尿病情况。     

中华按蚊防御素基因的克隆、原核表达及其重组产物生物活性的初步评价

目的 克隆、原核表达中华按蚊的防御素基因，并对其表达产物的生物学活性进行评价。方法 根据已发表的埃及伊蚊和冈比亚按蚊防御素基因序列设计合成两对引物．以中华按蚊成蚊cDNA为模板进行PCR扩增，将预期片段克隆测序并进行分析；根据表达质粒pET32a( ）上的克隆位点及测序结果设计PCR引物．将截短的基因片段重组入质粒pET32a( )中进行表达．纯化表达产物并进行体外抑菌试验。结果 PCR扩增产物大小约270bp．目的基因的序列与冈比亚按蚊防御素基因同源性为85％；截取其保守功能区域序列(162bp)．构建成功重组表达质粒pET32a( )-tDEF，含重组质粒的转化菌用IPTG诱导表达后，于Mf26000处可见一预期的特异表达带，该蛋白与抗6-His抗体有特异性的反应；琼脂扩散法显示，纯化的重组防御素融合蛋白未出现抑菌环。结论首次克隆了中华按蚊防御素基冈．其截短片段在大肠杆菌中得到了高效可溶性表达，但重组融合蛋白不具备抑菌活性。     

急性髓系白血病中eIF4E高表达与疾病进展相关

本研究检测未治疗、未缓解/复发及缓解期间急性髓系白血病(AML)和其他良性血液病患者骨髓细胞中eIF4E基因表达水平并分析其与疾病进展的关系。采用SYBR Green I荧光定量PCR和相对定量分析法检测30例AML患者(M2型6例,M3型5例,M4型8例,M5型10例,M6型1例),11例AML化疗后完全缓解患者和20例非肿瘤性血液病患者骨髓单个核细胞的eIF4E表达情况,以β2微球蛋白基因(β2M)作为内参,采用公式2-△Ct×100%计算eIF4E基因表达水平。结果表明:AML未治疗及未缓解/复发组患者骨髓细胞eIF4E表达水平(7.098±5.544)%明显高于非肿瘤患者(0.248±0.163)%(P<0.01)和化疗后完全缓解患者(0.964±0.312)%(P<0.01),各AML亚型之间不存在统计学差异,尽管M4、M5亚型的表达水平相对较高。非白血病患者与缓解患者比较,eIF4E表达水平不存在显著性差异。结论:eIF4E基因在急性髓系白血病细胞中出现高表达,并随着疾病的缓解而明显降低,因此eIF4E有可能作为监测白血病进展的一项参数。     

Effects of the total physical activity and its changes on incidence,progression, and remission of hypertension

OBJECTIVESModerate to vigorous physical activity is recommended to prevent hypertension according to the current guidelines. However, the degree to which the total physical activity (TPA) and its changes benefit normotensives and hypertensives is uncertain. We aimed to examine the effects of TPA and its changes on the incidence, progression, and remission of hypertension in the large-scale prospective cohorts.METHODSA total of 73,077 participants (55,101 normotensives and 17,976 hypertensives) were eligible for TPA analyses. During a mean follow-up of 7.16 years (394,038 person-years), 12,211 hypertension cases were identified. TPA was estimated as metabolic equivalents and categorized into quartiles. Cox proportional hazards regression and multivariable logistic regression were used to estimate associations of TPA and changes in TPA with incident hypertension and progression/remission of hypertension.RESULTSCompared with the lowest quartile of TPA, normotensives at the third and the highest quartile had a decreased risk of incident hypertension, with hazard ratios (HRs) of 0.86 [95% confidence interval (CI): 0.81−0.91] and 0.81 (95% CI: 0.77−0.86), respectively. Hypertensives at the highest quartile of TPA demonstrated a decreased risk of progression of hypertension [odds ratio (OR) = 0.87, 95% CI: 0.79−0.95], and an increased probability of hypertension remission (OR = 1.17, 95% CI: 1.05−1.29). Moreover, getting active from a sedentary lifestyle during the follow-up period could reduce 25% (HR = 0.75, 95% CI: 0.58−0.96) risk of incident hypertension, whereas those becoming sedentary did not achieve benefit from initially being active.CONCLUSIONSOur findings indicated that increasing and maintaining TPA levels could benefit normotensives, whereas higher TPA levels were needed to effectively control progression and improve remission of hypertension. Physical activity played undoubtedly an essential role in both primary and secondary prevention of hypertension.     

治疗剂量高压氧对胎鼠及新生鼠视网膜血管的影响

目的:探讨临床治疗剂量高压氧(HBO)对胎鼠及新生鼠视网膜的影响.方法:SD新生大鼠,随机分为实验1～3组、对照组(常压空气组)及ROP模型组各5只,实验1组于孕鼠分娩前单纯予治疗剂量的HBO 5 d(2ATA, 800 mL/L O2,1 h)、实验2组新生大鼠不仅予宫内HBO,且出生后7 d起继续HBO 5 d、实验3组仅予新生鼠7 d HBO(2ATA, 800 mL/L O2,1 h)连续5 d;对照组置于常压空气中;ROP模型组第7 d常压吸氧(800 mL/L)5 d,然后吸空气. 全部新生大鼠于17 d制作视网膜组织切片,计数突破视网膜内界膜的细胞核数目及免疫组织化学方法测定血管内皮生长因子(VEGF)在视网膜的表达.结果:实验1～3组突破视网膜内界膜的细胞核数目与对照组相比,差异无统计学意义(P>0.05),ROP模型组与对照组及实验1～3组相比,差异有统计学意义(37.9±6.1 vs 1.4±0.9, 1.6±1.1, 1.4±0.8, P<0.01). 实验各组及对照组的VEGF的表达均以弱阳性为主,均弱于ROP模型组,差异有统计学意义(P<0.01).结论:临床治疗剂量高压氧对胎鼠及新生鼠视网膜无影响.     

大黄素对烟曲霉菌性角膜炎模型大鼠的抗炎作用机制研究

目的：研究大黄素对烟曲霉菌性角膜炎模型大鼠的抗炎作用机制。

方法：建立烟曲霉菌性角膜炎模型,分为模型组和大黄素组,各8只,正常组10只。大黄素组采取大黄治疗,模型组和正常组采取等体积生理盐水治疗。观察大鼠角膜炎症指数、病理学特征,检测肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、细胞间黏附分子-1(ICAM-1)、过氧化物酶体增殖物激活受体(PPAR)、MAPK、NF-κB蛋白。

结果：大黄素组大鼠角膜炎症指数、角膜炎症细胞计数、TNF-α、IL-6、ICAM-1水平、MAPK、NF-κB蛋白低于模型组,PPAR蛋白表达高于模型组(P<0.05)。

结论：大黄素通过调控PPAR、MAPK、NF-κB蛋白,改善TNF-α、IL-6、ICAM-1炎症因子水平,对烟曲霉菌性角膜炎大鼠起到抗炎作用。