电离辐射致肠道急性损伤的中医病机探讨

电离辐射所致的肠道急性损伤在临床普遍存在,轻者出现纳差、食欲不振、消化不良;重者出现持续的腹痛腹泻,常伴黏液、脓血,肛门坠痛、里急后重,甚至出现梗阻、糜烂、溃疡、穿孔等症。结合电离辐射的中医病因学特点,电离辐射致肠道急性损伤的中医基本病机为:邪盛伤正,气血乏源,虚实夹杂;升降失常,泌别失职,传导失司;“热”“湿”“毒”“瘀”蕴结,损伤血络;屏障缺失,易于恶化。据证立法,方从法出,有的放矢,这不仅为电离辐射导致的肠道急性损伤寻找有效的中医药防治措施提供了理论依据,也进一步拓展了中医药理论的应用范围,因此具有重要的临床价值和实践意义。     

完全肿瘤细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移的病例筛选策略

目的:构建肿瘤细胞减灭程度(completeness of cytoreduction,CC)预测模型,为肿瘤细胞减灭术(cytoreductive surgery,CRS)加腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌腹膜转移(gastric cancer with peritoneal metastasis,GCPM)提供病例筛选方法。方法:比较完全CRS(complete CRS,CCRS)组和不完全CRS(incomplete CRS,ICRS)组患者基本临床病理特征和治疗参数,通过逻辑回归模型筛选CC独立预测因子,精准预测CCRS可能性。结果:125例患者纳入本研究,其中CC0组52例(41.6%),中位总生存期为30.0(95%CI:16.8~43.3)个月;CC1-3组73例,中位总生存期7.3(95%CI:5.7~8.8)个月,差异有统计学意义(P<0.001),而CC1、CC2和CC3组间中位总生存期差异无统计学意义(P>0.05)。因此,CC0定义为CCRS组,CC1-3定义为ICRS组,构建并优化了以腹膜转移时相(OR=14,95%CI:2.0~97.9,P=0.008)、术前肿瘤标志物(OR=6.5,95%CI:2.1~37.8,P=0.037)和腹膜癌指数(OR=1.5,95%CI:1.3~1.8,P<0.001)预测ICRS的多因素回归模型和预测列线图,内部验证显示,ROC曲线下面积为0.985,列线图显示预测准确度、一致性良好。根据列线图结果将患者分为4个亚组,设定CCRS预测概率≥50%,同时性且术前肿瘤标志物正常组、同时性且术前肿瘤标志物异常组、异时性且术前肿瘤标志物正常组、异时性且术前肿瘤标志物异常组腹膜癌指数界值点分别为:≤16、≤12、≤10和≤5。结论:CCRS+HIPEC可延长部分经选择的GCPM患者生存期,以腹膜癌指数为核心,联合腹膜转移时相和术前肿瘤标志物的病例筛选策略,可有效选择高概率实现CCRS的患者接受CCRS+HIPEC治疗。     

In vitro and in vivo synergistic efficacy of ceritinib combined with programmed cell death ligand‐1 inhibitor in anaplastic lymphoma kinase‐rearranged non‐small‐cell lung cancer

Both ceritinib (CER) and programmed cell death (PD)‐1/PD ligand‐1 (PD‐L1) have brought significant breakthroughs for anaplastic lymphoma kinase (ALK)‐rearranged non‐small‐cell lung cancer (NSCLC). However, the overall clinical efficacy of either CER or PD‐1/PD‐L1 inhibitor monotherapy has been limited to a large extent. In addition, the antitumor effect of combined CER and PD‐L1 inhibitor in ALK‐rearranged NSCLC is not fully understood. In H2228 cells, we examined the tumor killing effect of CER plus PD‐L1 inhibitor in vitro by quantitative RT‐PCR, flow cytometry, ELISA, western blot analysis, PBMC coculture system, and plasmid and transfection experiments. A Ba/F3 (EML4‐ALK‐WT) xenograft mouse model was also utilized to further evaluate the synergistic anticancer effects of CER and PD‐L1 inhibitor in vivo. The coculture system of PBMCs with H2228 cells promotes the expression of PD‐L1 and phospho‐ERK, and combined treatments facilitate lymphocyte proliferation and activation, inhibit PD‐L1 expression, and enhance lymphocyte cytotoxicity and cell death. In the in vivo NSCLC xenograft model, the volumes of tumors treated with CER and PD‐L1 inhibitor in combination were significantly smaller than those treated with CER or PD‐L1 alone. The relative tumor growth inhibitions were 84.9%, 20.0%, and 91.9% for CER, PD‐L1 inhibitor, and CER plus PD‐L1 groups, respectively. Ceritinib could synergize with PD‐1/PD‐L1 blockade to yield enhanced antitumor responses along with favorable tolerability of adverse effects. Ceritinib and PD‐L1 inhibitor combined produced a synergistic antineoplastic efficacy in vitro and in vivo, which provides a key insight and proof of principle for evaluating CER plus PD‐L1 blockade as combination therapy in clinical therapeutic practice.     

疏肝法联合滋阴补肾汤治疗IVF-ET 周期卵巢低反应临床研究

目的:疏肝法联合滋阴补肾汤对辅助生殖技术体外受精-胚胎移植(IVF-ET)周期卵巢低反应患者子宫内膜容受性、促性腺激素使用量及妊娠结局的影响。方法:将符合纳入标准的IVF-ET周期卵巢低反应患者180例按照随机分组原则,分为联合组、疏肝法组、对照组3组。对照组患者采用控制性超排卵治疗;疏肝法组患者采用疏肝法配合控制性超排卵治疗;联合组患者采用疏肝法联合滋阴补肾汤配合控制性超排卵治疗。分别对3组GnRH-a启动使用剂量、使用天数以及使用总剂量,使用人绒毛膜促性腺激素当天血清雌二醇(E_2)、黄体生成素(LH)、孕酮(P)水平,子宫内膜容受性,妊娠成功率和不良妊娠结局进行对比观察。结果:3组GnRH-a启动使用剂量、使用天数、使用总剂量、使用人绒毛膜促性腺激素当天E2、P、LH水平,子宫内膜全层厚度和子宫形态之间,差异均有统计学意义(P0.05)。经两两比较,联合组GnRH-a启动使用剂量、使用天数以及使用总剂量显著低于对照组及疏肝法组(P0.05),联合组患者的使用人绒毛膜促性腺激素当天E2、P、LH水平和子宫内膜全层厚度显著高于对照组及疏肝法组(P0.05),联合组临床妊娠率71.67%,高于疏肝法组51.67%及对照组41.67%(P0.05);3组畸形、流产、早产、胎停育等情况,差异均有统计学意义(P0.05),且联合组妊娠异常情况明显低于对照组及疏肝法组(P0.05)。结论:疏肝法联合滋阴补肾汤对IVF-ET周期卵巢低反应患者,可有效改善患者子宫内膜容受性,降低促性腺激素使用量,提高和改善妊娠成功率和妊娠结局。     

Statins use and its impact in EGFR‐TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor‐tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population‐based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non‐statins and 41 statins users who had undergone EGFR‐TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan‐Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non‐statins group (4‐y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%‐81.4% vs. 85.5%; 95% CI, 78.5%‐98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29‐0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41‐0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR‐TKIs and played a synergistic anticancer role.