Tumor-specific lytic path “hyperploid progression mediated death”: Resolving side effects through targeting retinoblastoma or p53 mutant

A major advance was made to reduce the side effects of cancer therapy via the elucidation of the tumor-specific lytic path “hyperploid progression-mediated death” targeting retinoblastoma (Rb) or p53-mutants defective in G1 DNA damage checkpoint. The genetic basis of human cancers was uncovered through the cloning of the tumor suppressor Rb gene. It encodes a nuclear DNA-binding protein whose self-interaction is regulated by cyclin-dependent kinases. A 3D-structure of Rb dimer is shown, confirming its multimeric status. Rb assumes a central role in cell cycle regulation and the “Rb pathway” is universally inactivated in human cancers. Hyperploidy refers to a state in which cells contain one or more extra chromosomes. Hyperploid progression occurs due to continued cell-cycling without cytokinesis in G1 checkpoint-defective cancer cells. The evidence for the triggering of hyperploid progression-mediated death in RB-mutant human retinoblastoma cells is shown. Hence, the very genetic mutation that predisposes to cancer can be exploited to induce lethality. The discovery helped to establish the principle of targeted cytotoxic cancer therapy at the mechanistic level. By triggering the lytic path, targeted therapy with tumor specificity at the genetic level can be developed. It sets the stage for systematically eliminating side effects for cytotoxic cancer therapy.     

肿瘤坏死因子-α-308基因对导管相关性脓毒症患者病情的影响

目的探究肿瘤坏死因子-α(Tumornecrosis factor-α,TNF-α)-308基因对导管相关性脓毒症(Catheter related sepsis,CRS)患者病情的影响,旨在为临床治疗CRS提供科学依据。方法选取2017年7月-2018年10月于浙江大学医学院附属杭州市第一人民医院接受治疗的86例CRS患者为研究对象,按照是否并发多器官功能障碍综合征将患者分为试验组和对照组,对照组共48例,未并发多器官功能障碍综合征,试验组共38例,并发多器官功能障碍综合征,分析两组患者TNF-α-308基因多态性差异,使用多因素Logistic回归分析CRS患者并发多器官功能障碍综合征的危险因素。结果试验组GA基因型频率34.21%、AA基因型频率50.00%、高G等位基因频率18.42%均高于对照组,GG基因型频率52.63%、A等位基因频率28.95%均低于对照组,差异均具有统计学意义(P<0.05);多因素Logistic回归分析结果显示,低GG基因型频率、低G等位基因频率、高GA基因型频率、高AA基因型频率、高A等位基因频率是CRS患者并发多器官功能障碍综合征的危险因素(P<0.05)。结论TNF-α-308基因与CRS患者病情密切相关,GG基因型频率和G等位基因频率降低,GA基因型频率、AA基因型频率、A等位基因频率升高会加重患者的病情,增加多器官功能障碍综合征的发生风险,临床上应该加以重视。     

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

门诊和病房电脑鼠标细菌污染情况调查

目的调查门诊和普通病房电脑鼠标不同时段的细菌污染情况。方法随机抽取某院门诊及普通病房的各16个电脑鼠标，分别于8∶00、10∶30、13∶00、15∶30进行采样，样本接种培养后对菌落计数并筛查多重耐药菌。结果32个鼠标共计采样128次，最高菌落数达121 CFU/cm2，平均菌落数为23.9 CFU/cm2。随着时间的推移，同一鼠标的细菌计数逐渐增多。不同时段门诊和病房的电脑鼠标菌落数比较，在10∶30、13∶00、15∶30三个时间点，病房鼠标的菌落数均高于门诊（均P≤0.05）。64个病房电脑鼠标标本中检出耐甲氧西林金黄色葡萄球菌（MRSA）和耐碳青霉烯类鲍曼不动杆菌（CRAB）各1株。结论加强鼠标日常清洁消毒及监测工作非常重要，应增加清洁消毒频率或更换长效消毒剂，加强病房环境的清洁消毒。     

非手术治疗破裂型腰椎间盘突出症5年随访研究

目的:探讨非手术治疗破裂型腰椎间盘突出症的近中期疗效及预后转归。方法:选取2011年2月至2014年2月接受非手术治疗的75例单节段破裂型腰椎间盘突出症患者进行前瞻性研究,男53例,女22例;年龄18～58(35.62±9.96岁);病程5 d～6个月,平均(46.45±40.66) d。突出节段:L_(3,4) 4例,L_(4,5) 29例,L_5S_1 42例。放射痛左侧46例,右侧29例。选取治疗前,治疗后3个月、6个月、1年、2年、5年6个时间点对患者JOA评分、直腿抬高角度(SLRT)、指地距统计分析。计算末次随访时(治疗后5年)JOA改善率,根据JOA评分评定疗效;分析治疗前、末次随访(治疗后5年)椎间盘突出物体积变化,计算突出物体积吸收率,观察突出物吸收情况;分析JOA改善率与突出物吸收率之间关系。结果:71例患者完成随访,非手术治疗后3个月、6个月、1年、2年、5年JOA评分、SLRT、指地距与治疗前比较,差异有统计学意义(P0.05)。治疗后5年与6个月、治疗后5年与2年、治疗后2年与6个月JOA评分比较,差异无统计学意义(P0.05),其余各时间点两两比较,差异均有统计学意义(P0.05);治疗后5年与6个月、治疗后5年与2年、治疗后2年与6个月SLRT、指地距比较,差异亦无统计学意义(P0.05),其余各时间点两两比较,差异均有统计学意义(P0.05)。末次随访JOA改善率为(62.69±2.47)%,按照JOA评分评定疗效,结果优26例,良26例,可14例,差5例,优良率73.24%;突出物体积由起始的(1 981.73±588.72) mm3减少至(1 011.82±395.47) mm3,总体吸收率(45.65±2.83)%,突出物发生明显吸收24例,部分吸收26例,未吸收19例,增大2例。JOA改善率与突出物吸收率作Spearman秩相关分析,发现两者呈中等以上正相关(r=0.679,P0.001)。结论:非手术治疗破裂型腰椎间盘突出症可取得良好疗效,明确了破裂型腰椎间盘突出症的病情特点及预后转归,同时部分患者发生"重吸收"现象。