肺癌化疗后骨髓抑制研究进展

肺癌作为世界上发病率和死亡率最高的恶性肿瘤之一,至今仍然威胁着人类的生命健康。化疗作为肺癌最基础也是最重要的治疗方式,其最为人熟知的不良反应即骨髓抑制。骨髓抑制会造成化疗患者贫血、出血、免疫机制下降,使得化疗中断或药物减量,影响化疗疗效,严重的骨髓抑制甚至会直接导致患者死亡。本文通过对肺癌患者化疗后发生骨髓抑制的定义、发生机制、治疗方式及危险因素进行阐述,进一步加强对于肺癌化疗后骨髓抑制的认识。     

姜黄素对大鼠视网膜缺血再灌注后细胞凋亡及p53表达的影响

目的 探讨姜黄素对大鼠视网膜缺血再灌注后细胞凋亡及凋亡相关基因p53表达的影响。方法制作大鼠视网膜缺血再灌注模型,并随机分为假手术组（SH组）、缺血再灌注组（IR组）、姜黄素处理组（CU组）和对照组（SC组）,分别于再灌注后2、6、24、72h和7d时观察大鼠视网膜和视网膜毛细血管细胞的凋亡情况,并检测视网膜Caspase-3酶的表达活性及p53基因的表达情况。结果各组模型均制作成功,细胞组织学检查可见CU组损伤明显轻于其他组。CU组视网膜和视网膜毛细血管的细胞凋亡数量均显著多于SH组（均P〈0.01）,但显著少于IR组（P〈0．01）;CU组p53表达水平及Caspase-3酶活性均显著强于SH组（均P〈0.01）,但显著弱于IR组（P〈0．01）。结论姜黄素对大鼠视网膜缺血再灌注损伤具有保护作用,调控凋亡相关基因p53蛋白的表达可能是其作用机制之一。     

Pax-8基因在心脏发育中蛋白表达下调

目的：观察Pax-8基因在ALK3基因敲除小鼠心脏中的蛋白表达情况,探讨Pax-8基因在心脏发育中的作用。方法：基因芯片（microarray）和定量逆转录-聚合酶链反应测定ALK3基因的下游基因,免疫组化法检测13.5 d小鼠胚胎心脏特异性ALK3基因敲除小鼠胚胎中Pax-8蛋白的表达,连续病理切片及HE染色观察刚出生的Pax-8基因敲除小鼠的心脏形态。结果：在心脏特异的ALK3基因敲除小鼠中,转录因子Pax-8基因mRNA的表达水平上被下调7.1倍。免疫组化结果显示：13.5 d小鼠胚胎心脏特异性ALK3基因敲除的纯合子小鼠Pax-8基因在蛋白水平与杂合子相比也明显下调。Pax-8基因敲除小鼠纯合子有明显的室间隔和左心室肥厚,心脏呈球形。结论：Pax-8基因是ALK3基因的下游基因,与心脏发育有密切关系。     

BiPAP无创治疗重度-极重度COPD稳定期患者短期疗效观察

目的：观察无创双水平正压通气（BiPAP）治疗重度-极重度慢性阻塞性肺疾病（COPD）稳定期患者的短期疗效。方法选取50例重度-极重度COPD稳定期患者,其中对照组（25例）给予舒利迭吸入治疗,治疗组在对照组治疗基础上加用BiPAP无创通气治疗。分别于治疗前（0周）及治疗后1、4、12周检测肺活量（VC）、用力肺活量（FVC）、1秒用力呼气容积（FEV1）、最大通气量（MVV）、最大中期呼气流速（MMF）的预计值及残气量/肺总量（RV/TLC）的实测值,并测定6min步行时间（6MWT）及经皮血氧饱和度（SpO2）,评价Borg呼吸困难程度（Borg指数）,观察12周内两组急性加重的患者数。结果与0周比较,治疗组治疗后1、4、12周6MWT、Borg指数及SpO2均发生显著变化（均P＜0.01）;与对照组同时点比较,治疗组治疗后1、4、12周6MWT、Borg指数及SpO2均发生显著变化。与0周比较,对照组仅治疗后1、4周FEV1明显升高,治疗组治疗后1周FVC、FEV1、MVV均发生明显变化,治疗后4、12周各指标均发生明显变化,差异均有统计学意义（P＜0.05或0.01）;与对照组同时点比较,治疗组治疗后1周MVV显著升高,治疗后4、12周FEV1、MVV、MMF、RV/TLC均发生明显变化,差异均有统计学意义（P＜0.05或0.01）。治疗期间,治疗组急性加重发生率明显低于对照组（8.0%、36.0%）,差异有统计学意义（P＜0.05）。结论常规治疗基础上辅以BiPAP更能在短期内改善重度-极重度COPD稳定期患者的肺通气功能,增进氧合,提高活动能力,减少急性发作。     

自发性高血压大鼠缺血再灌注后视网膜毛细血管细胞凋亡及p53基因表达

Objective To investigate the effect of apoptosis-related gene p53 on the apoptosis of retinal capillary cells in rats with spontaneously hypertensive (SHR) after ischemic reperfusion injury. Methods A total of 60 SHR rats were randomly divided into sham group (SHR-SH) and retinal ischemie reperfusion group (SHR-RIR), which were subdivided into 5 subgroups according to the time after RIR: 2, 6, 24, and 72 hours and 7 days, with 6 rats in each subgroup. Another 60 Wistar-Kyoto (WKY) rats were divided into the same groups as the SHR rats as the control. The RIR model was set up. The apoptosis of retinal capillary cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods and the expression of p53 was determined by streptavidin-perosidase (SP) immunohistochemistry. Results The apoptosis rate of retinal capillary cells in the 5 SHR-RIR groups was (8.64±0.56)%, (14.92±0.99)%, (24.72±2.98)%, (16.53±1.80)%, and (7.12±1.10)%,respectively. The expression of p53 in SHR-RIR groups increased at the 2nd hour after RIR, reached the peak at the 24th hour, kept the high level at the 72nd hour, and remained a little at the 7th day, which was significantly different from which in the SHR-SH groups (P<0. 01). The expression of p53 were higher in SHR-IR groups than that in the WKY-RIR groups (P<0. 01). Conclusions p53 may play a part in RIR injury by inducing or promoting apoptosis. The apoptosis of retinal capillary cells after RIR is more severe under the hypertension, and reaches the peak at the 24 hour after RIR.     

Pax-8基因在胚胎心脏发育中的作用

目的： 在心脏特异的骨形态形成蛋白受体IA(the bone morphogenetic protein receptor IA,ALK3)基因敲除小鼠模型中,纯合子的心脏特异ALK3 基因敲除的小鼠死于胚胎中期,同时伴有室间隔缺损。用基因芯片(microarray)法筛选了ALK3 下游基因,并获得下游候选基因（转录因子Pax-8）。为了进一步明确Pax-8基因在胚胎心脏发育中的角色,Pax-8基因在小鼠被系统敲除。方法: 运用实时荧光定量RT-PCR法检测Pax-8基因在小鼠胚胎中的表达情况。运用原位杂交法显示Pax-8基因在小鼠胚胎心脏中的表达部位。TUNEL法检测心肌细胞的凋亡情况,电镜下观察Pax-8基因敲除的小鼠心脏组织发育的病理学异常。结果: 正常胚胎小鼠9.5、10.5、11.5、12.5以及13.5 d的Pax-8基因的表达水平以10.5 d表达最高。胚胎切片的原位杂交显示：转录因子Pax-8 表达在13.5 d的α-MHC Cre+/-,ALK3F/+小鼠整个心脏中。Pax-8基因敲除的小鼠心脏表现出形态改变(心脏呈球形,左心室壁肥厚,室间隔增厚,左室乳头肌肥大),左心室壁和室间隔心肌组织细胞凋亡率明显增高,同时线粒体体积较对照组明显缩小并且数量增多。结论: Pax-8基因是心脏较特异的参与心脏正常发育的ALK3 下游基因,并与心肌细胞凋亡有关。     

自发性高血压大鼠视网膜微血管稀少与细胞凋亡

目的：研究自发性高血压大鼠（SHR）视网膜毛细血管细胞凋亡的发生情况,探讨细胞凋亡与高血压视网膜微血管病变之间的关系,为研究高血压视网膜病变发病机制提供形态学依据。方法：10只雄性自发性高血压大鼠（SHR组）和10只雄性正常血压（WKY）大鼠（WKY组）分别在13周龄和18周龄取眼球做视网膜消化铺片,采用核苷酸末端转移酶介导dUTP缺口翻译法（TUNEL法）检测视网膜微血管细胞凋亡变化情况,HE染色及图像分析,动态观察视网膜微血管形态的改变及测定视网膜毛细血管面积及密度的改变。结果：①TUNEL法标记显示SHR各周龄大鼠视网膜微血管均出现阳性反应细胞,且18周龄大鼠阳性细胞与13周龄大鼠比较明显增多;WKY组大鼠视网膜微血管未见TUNEL阳性细胞。②血管铺片HE染色显示SHR组部分毛细血管闭塞,内皮细胞和周细胞丢失,出现无细胞毛细血管,毛细血管密度较WKY组显著降低。结论：在高血压发展过程中,视网膜毛细血管内皮细胞和周细胞均可发生凋亡,同时伴有微血管稀疏,细胞凋亡可能在高血压视网膜病变的过程中扮演重要的角色。     

自发性高血压大鼠缺血再灌注后视网膜毛细血管细胞凋亡及p53基因表达

Objective To investigate the effect of apoptosis-related gene p53 on the apoptosis of retinal capillary cells in rats with spontaneously hypertensive (SHR) after ischemic reperfusion injury. Methods A total of 60 SHR rats were randomly divided into sham group (SHR-SH) and retinal ischemie reperfusion group (SHR-RIR), which were subdivided into 5 subgroups according to the time after RIR: 2, 6, 24, and 72 hours and 7 days, with 6 rats in each subgroup. Another 60 Wistar-Kyoto (WKY) rats were divided into the same groups as the SHR rats as the control. The RIR model was set up. The apoptosis of retinal capillary cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) methods and the expression of p53 was determined by streptavidin-perosidase (SP) immunohistochemistry. Results The apoptosis rate of retinal capillary cells in the 5 SHR-RIR groups was (8.64±0.56)%, (14.92±0.99)%, (24.72±2.98)%, (16.53±1.80)%, and (7.12±1.10)%,respectively. The expression of p53 in SHR-RIR groups increased at the 2nd hour after RIR, reached the peak at the 24th hour, kept the high level at the 72nd hour, and remained a little at the 7th day, which was significantly different from which in the SHR-SH groups (P<0. 01). The expression of p53 were higher in SHR-IR groups than that in the WKY-RIR groups (P<0. 01). Conclusions p53 may play a part in RIR injury by inducing or promoting apoptosis. The apoptosis of retinal capillary cells after RIR is more severe under the hypertension, and reaches the peak at the 24 hour after RIR.     

新型冠状病毒肺炎17例临床诊治分析

目的交流和积累新型冠状病毒肺炎（COVID-19）的救治经验。方法回顾性分析金华市确诊的17例COVID-19患者的流行病学史、临床症状、实验室检查结果、影像学检查结果和转归情况。结果17例患者中普通型15例,重型2例;起病前均有武汉旅行史或与COVID-19确诊患者接触史。疾病潜伏期为1~11（5.5±3.1）d。最常见症状是发热（94.1%）,其次为干咳（41.2%）,少有咳痰、肌痛、头晕和腹泻症状。白细胞计数在正常值范围内14例,淋巴细胞计数降低7例,C反应蛋白升高7例。早期影像学典型表现为两肺多发斑片影和磨玻璃影。经过治疗11例患者治愈出院,余下6例患者首次咽拭子病毒核酸检测已转阴。结论COVID-19具有很强的传染性,需要科学防控、积极治疗。尽早救治患者一般转归良好。