体外转染Cyclin A2基因对原代大鼠心肌细胞增殖的影响

目的探讨体外转染细胞周期素A2(Cyclin A2)基因对原代大鼠心肌细胞增殖的影响,为心脏再生提供细胞学依据。方法 SD乳鼠12只,分离、培养、鉴定原代乳鼠心肌细胞并分为3组,实验组:转染带有强化绿色荧光蛋白(GFP)和Cyclin A2基因的重组腺病毒(Ad-Cyclin A2-GFP);空病毒组:转染不含目的基因带有GFP的重组腺病毒(Ad-Null-GFP);阴性对照组:未做转染处理,仅加入等量的培养基。利用GFP示踪技术,评估原代心肌细胞转染效率;转染后的细胞继续体外培养3~5d,利用免疫荧光技术分别检测Cyclin A2、磷酸化组蛋白H3(H3P)、心肌肌钙蛋白-T(c Tn T)。结果 1.荧光GFP示踪表明原代心肌细胞的转染效率高达(97±0.74)%;2.免疫荧光标记显示,空病毒组和对照组结果相似;心肌细胞特异性标记蛋白c Tn T分布于细胞质,原代心肌细胞纯度高达(95±0.62)%;心肌细胞Cyclin A2主要在胞核内聚集,少数分布于细胞质。H3P为核蛋白在细胞核内分布。3.转染Cyclin A2后,实验组H3P阳性率明显高于空病毒组和对照组,差异具有统计学意义(P0.05);实验组可见大量多核细胞,以双核为主,伴少量3核细胞。结论腺病毒作为转染载体对原代心肌细胞有很好的侵染效率;Cyclin A2超表达促进原代心肌细胞形成双核。     

血液系统恶性肿瘤患者化疗后合并中性粒细胞减少性肠炎的诊治研究

目的分析成人血液系统恶性肿瘤患者接受强烈化疗后中性粒细胞减少性肠炎（NE）的发生率、危险因素及预后情况。方法收集2004至2013年接受化疗的1804例血液系统恶性肿瘤患者，记录患者血常规、凝血检测和血液生化检测结果，并记录患者年龄、性别、原发病、既往化疗次数、既往化疗方案中是否使用阿糖胞苷、临床症状、肠壁厚度、中性粒细胞最低计数、中性粒细胞缺乏持续时间、NE的治疗方法和预后等，探讨NE起病诱因、临床特征、腹部B超特点、症状的预后意义及化疗药物对发病的影响等。结果1804例患者中226例（12.5%）化疗后合并NE，化疗后10~19d起病，中位起病时间为化疗后第14天。发生NE后26例患者死亡，病死率11.5%。化疗药物包括阿糖胞苷、临床症状≥4项、中性粒细胞缺乏持续超过7d以及B超下肠壁厚度≥10mm的患者病死率相对较高。结论NE是接受强烈化疗的血液系统肿瘤患者的严重的并发症，发生NE后患者病死率较高。     

不同波形低频率电刺激对小鼠海马电点燃癫痫的作用比较

目的观察比较不同脉冲波形的低频率电刺激对海马电点燃癫痫模型小鼠的作用差异。方法采用电点燃刺激法建立小鼠癫痫模型, 观察正弦波、单相方波、双相方波低频率电刺激对模型小鼠癫痫行为发作及后放电持续时间的影响, 并比较不同时间点给予正弦波低频率电刺激的抗癫痫作用。结果与对照组比较, 正弦波低频率电刺激30 s能降低小鼠海马电点燃癫痫发作等级(2.85 ± 0.27 vs 4.75 ±0.12, P < 0.05)、减少大发作概率(53.6% vs 96.5%, P < 0.01) 和缩短后放电持续时间[(16.22 ± 1.69) s vs (30.29 ± 1.12) s, P < 0.01], 而单相方波和双相方波低频率电刺激30 s没有明显的抗癫痫作用。常用的单相方波低频率电刺激15 min能降低小鼠海马电点燃发作等级(3.58 ± 0.16, P < 0.05)、减少大发作概率(66.7%, P < 0.01);但对海马后放电持续时间及大发作持续时间无影响(均 P>0.05)。此外, 电点燃刺激前预先给予或结束后3 s内给予正弦波低频率电刺激具有明显的抗癫痫作用( P < 0.05或 P < 0.01), 而电点燃刺激结束10 s给予正弦波低频率电刺激则无上述抗癫痫作用。 结论低频率电刺激抗癫痫作用受波形参数的影响, 其中正弦波低频率电刺激能有效抑制小鼠海马电点燃癫痫的发作。     

伊伐布雷丁在心血管疾病中的现状与进展

降低心率可能成为心血管疾病治疗的新靶标,伊伐布雷定可通过特异性地抑制If起搏电流通过降低窦房结节律而减慢心率,目前在心血管疾病领域取得了一定的进展,现对其临床应用进行综述。     

Secretion,blood levels and cutaneous expression of TL1A in psoriasis patients

TL1A is a TNF‐like cytokine which has been shown to co‐stimulate TH1 and TH17 responses during chronic inflammation. The expression of this novel cytokine has been investigated in inflammatory disorders like rheumatoid arthritis and inflammatory bowel disease, but little is known about expression and induction in psoriasis. Indeed, the pathogenesis in psoriasis is still not fully understood and it is speculated that cytokines other than TNF‐α are important in subsets of patients. Also, for patients with severe disease that are treated with systemic anti‐TNF‐α blockade, novel candidates to be used as disease and response biomarkers are of high interest. Here, we demonstrate TL1A expression in biopsies from psoriatic lesions. Also, we investigated spontaneous and induced TL1A secretion from PBMCs and blood levels from a cohort of psoriasis patients. Here, increased spontaneous secretion from PBMCs was observed as compared to healthy controls and a small subset of patients had highly elevated TL1A in the blood. Interestingly, activation of PBMCs with various cytokines showed a decreased sensitivity for TL1A activation in psoriasis patients compared to healthy controls.TL1A levels in blood and biopsies could not be correlated with disease activity with this patient cohort. Thus, additional large‐scale studies are warranted to investigate TL1A as a biomarker.     

基于“祛邪为第一要义”从清热化湿论治新型冠状病毒肺炎

结合验案分析,基于"祛邪为第一要义"探讨新型冠状病毒肺炎从清热化湿论治的思路与方法。认为新型冠状病毒肺炎主要是属于"湿热"性质的疫病,治疗应强调清热化湿,以"祛邪为第一要义",辅以扶正。在中医祛邪与扶正理论指导下,通过宣肺平喘、通腑泻热、芳香化湿等治法,祛邪为主,肺肠合治,可以使发热减轻或消退,使大便通畅,从而截断病情进展,避免或减少危重症的发生及死亡的风险;通过清热化湿、疏肝健脾、凉血化瘀等治法,祛邪兼以扶正,肺与肝、脾合调,可以改善肝功能损伤,减少病情加重的风险;通过补气健脾等扶正治法,可以改善患者的精神和体力,促使病毒更快转阴,缩短病程,促进患者早日康复。     

Racial differences in characteristics and prognoses between Asian and white patients with nonsmall cell lung cancer receiving atezolizumab: An ancillary analysis of the POPLAR and OAK studies

This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy.     

女性难治性膀胱过度活动症患者心理弹性及保护性因素研究

目的探讨女性难治性膀胱过度活动症患者心理弹性状况及保护性因素，为改善其身心健康提供依据。方法采用心理弹性量表、症状自评量表、艾森克人格问卷、社会支持量表、焦虑及抑郁量表对80例女性难治性膀胱过度活动症患者进行问卷调查。结果女性难治性膀胱过度活动症患者心理弹性得分为（54.10±8.27）分，显著低于国内常模（P＜0.05）。患者的一般情况（病程、年龄、文化程度）对心理弹性的预测作用不明显（R2=0.14，F=18.10），当社会支持、SCL-90、人格特质、SAS、SDS进入方程后，对患者的心理弹性具有较明显的预测作用（R2=0.67，△R2=0.46，F=115.22）。结论女性难治性膀胱过度活动症患者心理弹性较差，社会支持、SCL-90、人格特质、焦虑抑郁情绪是其重要的影响因素，应重视患者存在的心理问题，发掘心理弹性的保护性因素并积极干预，促进其身心健康。     

LEEP术对绝经后妇女高级别宫颈上皮内瘤变的诊治

目的:探讨绝经后妇女高级别宫颈上皮内瘤变行宫颈环形电切术(LEEP)诊治的临床价值。方法:选择2017年2月-2018年12月于北京妇产医院妇科微创中心因宫颈高级别鳞状上皮内病变(HSIL)行LEEP术的患者共142例,其中绝经组40例,未绝经组102例。收集2组患者的液基薄层细胞学检查(TCT)、高危型人乳头瘤病毒(HPV)检测、阴道镜检查及其活检病理结果、LEEP术后病理结果、切缘病变情况,并将上述检查结果进行组间比较。结果:2组患者阴道镜下宫颈转化区类型比较,差异有统计学意义(χ~2=28.658,P=0.000)。绝经组阴道镜活检与LEEP术后病理符合率为50.00%(20/40),未绝经组符合率为51.96%(53/102),2组差异无统计学意义(χ~2=0.044,P=0.854)。绝经组1例LEEP术后病理升级为宫颈癌,未绝经组1例LEEP术后病理升级为原位腺癌。绝经组术后病理切缘阳性8例(20.00%),未绝经组术后病理切缘阳性16例(15.69%),2组比较差异无统计学意义(χ~2=0.381,P=0.537)。2组患者术后TCT检查比较及高危型HPV感染情况比较,差异均无统计学意义(均P>0.05)。结论:LEEP手术适用于宫颈无明显萎缩的绝经后妇女高级别宫颈上皮内瘤变的诊治,以避免对宫颈病变的漏诊和过度治疗。