China special issue on gastrointestinal tumors-Radiological features of pathological complete response in mismatch repair deficient colorectal cancer after neoadjuvant PD-1 blockade: A post hoc analysis of the PICC phase II trial

Neoadjuvant programmed cell death protein 1 (PD-1) blockade exhibits promising efficacy in patients with mismatch repair deficient (dMMR) colorectal cancer (CRC). However, discrepancies between radiological and histological findings have been reported in the PICC phase II trial (NCT 03926338). Therefore, we strived to discern radiological features associated with pathological complete response (pCR) based on computed tomography (CT) images. Data were obtained from the PICC trial that included 36 tumors from 34 locally advanced dMMR CRC patients, who received neoadjuvant PD-1 blockade for 3 months. Among the 36 tumors, 28 (77.8%) tumors achieved pCR. There were no statistically significant differences in tumor longitudinal diameter, the percentage change in tumor longitudinal diameter from baseline, primary tumor sidedness, clinical stage, extramural venous invasion status, intratumoral calcification, peritumoral fat infiltration, intestinal fistula and tumor necrosis between the pCR and non-pCR tumors. Otherwise, tumors with pCR had smaller posttreatment tumor maximum thickness (median: 10 mm vs 13 mm, P = .004) and higher percentage decrease in tumor maximum thickness from baseline (52.9% vs 21.6%, P = .005) compared to non-pCR tumors. Additionally, a higher proportion of the absence of vascular sign (P = .003, odds ratio [OR] = 25.870 [95% CI, 1.357-493.110]), nodular sign (P < .001, OR = 189.000 [95% CI, 10.464-3413.803]) and extramural enhancement sign (P = .003, OR = 21.667 [2.848-164.830]) was observed in tumors with pCR. In conclusion, these CT-defined radiological features may have the potential to serve as valuable tools for clinicians in identifying patients who have achieved pCR after neoadjuvant PD-1 blockade, particularly in individuals who are willing to adopt a watch-and-wait strategy.     

肾透明细胞癌不同CT影像学征象对患者术后康复情况的影响

目的探究肾透明细胞癌不同CT影像学征象对患者术后康复情况的影响。方法选取2010年1月到2014年4月我院收治的50例肾透明细胞癌患者的CT征象,进行T分期,并分析不同CT征象与患者预后关系。结果利用CT征象进行T分期区别主要在T3a期,T3a期分为T3a-CT(10例)和T3a-仅病理(6例),T3a-仅病理CT分期可分为T1期2例,T2期4例;单因素分析显示,肿瘤大小、肿瘤是否侵及肾被膜外、是否侵及肾窦集合系统、是否侵及肾静脉及分支、是否侵及下腔静脉、有无广泛性坏死、是否存在囊性改变、瘤周是否受侵、瘤周是否存在新生血管与5年生存率具有一定相关性(P<0.05);多因素回归分析显示,肿瘤≥7cm、肿瘤穿透肾被膜、肾静脉及分支受侵、下腔静脉受侵、肿瘤无囊变、瘤周受侵及瘤周新生血管是影响肾透明细胞癌预后的独立危险因素(P<0.05)。结论肾透明细胞瘤患者肿瘤大于7cm、肿瘤穿透肾被膜、肾静脉及分支受侵、下腔静脉受侵、肿瘤无囊变、瘤周受侵及瘤周新生血管是影响肾透明细胞癌预后的独立危险因素,肿瘤周围受侵及瘤周新生血管形成可降低患者5年生存率,而肿瘤囊变可作为预测术后康复情况较好的标志之一。     

Constrained empirical-likelihood confidence regions in nonignorable covariate-missing data problems

Missing covariates in regression analysis are a pervasive problem in medical, social, and economic researches. We study empirical-likelihood confidence regions for unconstrained and constrained regression parameters in a nonignorable covariate-missing data problem. For an assumed conditional mean regression model, we assume that some covariates are fully observed but other covariates are missing for some subjects. By exploitation of a probability model of missingness and a working conditional score model from a semiparametric perspective, we build a system of unbiased estimating equations, where the number of equations exceeds the number of unknown parameters. Based on the proposed estimating equations, we introduce unconstrained and constrained empirical-likelihood ratio statistics to construct empirical-likelihood confidence regions for the underlying regression parameters without and with constraints. We establish the asymptotic distributions of the proposed empirical-likelihood ratio statistics. Simulation results show that the proposed empirical-likelihood methods have a better finite-sample performance than other competitors in terms of coverage probability and interval length. Finally, we apply the proposed empirical-likelihood methods to the analysis of a data set from the US National Health and Nutrition Examination Survey.     

氯吡格雷联合前列地尔对急性脑梗死患者疗效、血流动力学及凝血功能水平的影响

目的：探讨氯吡格雷联合前列地尔对急性脑梗死患者的疗效及对患者血流动力学、凝血功能水平的影响。方法：选取2015年6月-2017年6月某院收治的急性脑梗死患者90例，按照随机数字表法分为对照组与观察组，每组各45例。对照组患者在常规治疗基础上给予氯吡格雷治疗，观察组患者在对照组治疗基础上给予前列地尔治疗。比较2组患者临床治疗效果；检测治疗前、后2组患者血浆黏度（PV）、血浆纤维蛋白原（FIB）、血小板聚集率（PAR）、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、D-二聚体（D-D）水平。结果：对照组患者治疗后临床总有效率为64.44%；观察组患者治疗后临床总有效率为86.67%。两者比较差异有显著性（P<0.05）。治疗前，2组患者血流动力学指标PV、FIB、PAR及凝血功能指标PT、APTT、D-D水平比较，差异无显著性（P>0.05）。治疗后，对照组及观察组患者PV、FIB、PAR及D-D水平均明显低于本组治疗前，PT、APTT水平均明显高于本组治疗前；观察组患者治疗后PV、FIB、PAR及D-D水平均明显低于对照组治疗后，PT、APTT水平均明显高于对照组治疗后，差异均有显著性（P<0.05）。结论：氯吡格雷联合前列地尔对急性脑梗死患者具有较好的临床疗效，可通过抑制血小板活性及降低血液黏度，起到改善患者血流动力学水平，调节患者凝血功能的作用。     

重症监护病房患者导尿管相关尿路感染风险评分系统的建立与验证

目的建立并验证重症监护病房(ICU)患者导尿管相关尿路感染(CAUTI)风险评分系统,为ICU降低CAUTI的发生率提供依据。方法对常州市第一人民医院ICU在2017年1月-2018年12月期间1026例留置导尿管患者进行CAUTI目标性监测,利用1∶1简单化随机方法分为模型组和验证组,各513例。根据模型组数据筛选出CAUTI影响因素,建立风险评分系统应用于验证组,计算验证组中每例患者的风险评分。采用模型组和验证组数据建立受试者工作特征曲线图(ROC),根据ROC曲线下面积判断该风险评分系统建立的有效性。结果本研究期间患者发生CAUTI 44例,千日感染率为3.99‰。ICU住院时间、插管日数、未正确固定尿管、未规范执行手卫生是模型组导尿管插管患者CAUTI发生的影响因素(P<0.05)。利用此结果建立CAUTI风险评分系统,发现验证组中的高、中、低风险得分患者CAUTI发生率的差异有统计学意义,得分越高者患CAUTI的风险更高。最终利用该评分系统对模型组及验证组患者绘制ROC曲线,发现二者ROC曲线下面积均接近1,且差异无统计学意义,再次说明该评分系统具有较好的预测效果。结论建立CAUTI风险评分系统,采取针对性的早期干预可降低CAUTI的发生率,为患者提供最优经验治疗。     

汞中毒大鼠QRS时限与Cx43及其Ser368位点磷酸化表达水平研究

目的探讨汞中毒大鼠心电图QRS时限与心肌缝隙连接蛋白43(Cx43)及其Ser368位点磷酸化(pS368Cx43)表达水平。方法40只Wistar大鼠随机分为对照组(0.2ml生理盐水)及氯化汞低、中、高剂量染毒组(33.5、67.0、134.0μg/kg氯化汞溶液)，皮下注射染毒，1次/d。染毒90d后采集大鼠心电图，分析QRS时限改变，采用免疫组织化学染色法和Western blot法检测心室肌组织Cx43、pS368Cx43蛋白的表达情况；分析汞中毒大鼠QRS时限与Cx43及pS368Cx43表达量与分布改变的关系。结果与对照组相比，慢性汞中毒大鼠心电图QRS时限延长(P<0.05)，心室肌组织Cx43、pS368Cx43表达量降低(P<0.05)；Cx43和pS368Cx43在对照组主要分布于闰盘处，汞中毒组分布紊乱，部分呈现侧膜化改变。结论汞中毒大鼠QRS时限延长，其机制可能与汞中毒导致心肌Cx43和pS368Cx43表达降低及分布异常有关。     

养血解毒方对银屑病角质形成细胞紧密连接的调节作用

目的:观察银屑病样小鼠皮损紧密连接蛋白中水闸蛋白(claduin-1,claudin-7),闭锁蛋白(occludin)的表达,明确养血解毒方对银屑病表皮通透屏障的修复作用,为养血解毒方治疗银屑病提供科学依据。方法:将C57BL/6J小鼠随机分为空白组、模型组、甲氨喋呤组、养血解毒方组,制备甲氨喋呤溶液、养血解毒方水煎剂对应灌胃干预,同时小鼠背部剃毛后给予咪喹莫特涂抹诱导银屑病样皮损模型。每日拍照记录皮损形态并对严重程度指数(PASI)评分;水油测试笔检测皮损表皮含水量;苏木素-伊红(HE)染色观察其病理改变、测量表皮厚度;免疫荧光法检测增殖相关的核抗原(Ki67);免疫组化法检测表皮兜甲蛋白(loricrin),真皮中CD3^+T淋巴细胞浸润和紧密连接蛋白claduin-1,claudin-7,occludin的表达;蛋白免疫印迹法(Western blot)检测皮损中claudin-7,occludin的表达。模拟银屑病皮损微环境,建立白细胞介素-17(IL-17,1 mg·L^-1)刺激的角质形成细胞(Hacat)模型,制作养血组分、解毒组分、养血解毒方喷干粉进行干预。采用细胞增殖毒性检测试剂盒-8(CCK-8)法检测药物对Hacat细胞的毒性;细胞免疫荧光法检测药物对角质形成细胞claudin-1,claudin-7,occludin表达的干预作用。结果:与模型组比较,养血解毒方可显著减轻小鼠银屑病样皮损表现,降低PASI评分及皮损表皮厚度(P<0.01),增加皮损区表皮水分含量(P<0.01),减少表皮ki67,loricrin的异常表达和真皮CD3+T细胞浸润(P<0.01),并增加紧密连接蛋白claudin-1,claudin-7,occludin的表达(P<0.05),增加紧密连接结构的完整性;体外研究发现,与模型组比较,养血解毒方组和养血组分组明显升高紧密连接蛋白claudin-1,claudin-7,occludin的表达(P<0.05);与模型组比较,解毒组分组蛋白表达水平无统计学差异。结论:养血解毒方通过调节角质形成细胞间紧密连接的表达抑制其异常的增殖分化过程,进一步恢复破坏的表皮通透屏障,可能是其治疗银屑病的作用机制之一。其中养血解毒方的养血组分对调节紧密连接的修复起主要作用。