目的 分析比较左右半结肠癌及直肠癌根治术后患者的生存预后差异及影响因素.方法 选取2004年1月—2016年12月于上海中医药大学附属市中医医院、上海市普陀区中心医院和复旦大学附属肿瘤医院肿瘤科收治的Ⅰ～Ⅲ期结直肠癌根治术后病例1028例,分为右半结肠癌组243例、左半结肠癌组339例和直肠癌组446例,对比3组无疾病生存期(DFS)、总生存期(OS)、复发转移率的差异及其影响生存预后因素.结果 右半结肠癌组、左半结肠癌组和直肠癌组的中位DFS分别为9.13、16.43和52.17个月,3组比较差异有统计学意义(χ2/P=167.362/0.000),中位OS分别为22.93、28.98和60.83个月,3组比较差异有统计学意义(χ2/P=122.748/0.000).复发转移率比较,右半结肠癌组>左半结肠癌组>直肠癌组(χ2/P=172.251/0.000).化疗和中药治疗是OS的保护因素,肿瘤部位是影响OS的危险因素,右半结肠癌影响总生存期的风险是直肠癌的2.004倍(95％CI 1.582～2.540),左半结肠癌影响OS的风险是直肠癌的1.379倍(95％CI 1.082～1.758).中药治疗是DFS的保护因素,肿瘤部位为右半结肠是影响DFS的危险因素[OR(95％CI)=0.794(0.655～0.961),1.365(1.098～1.698)].结论 直肠癌的生存预后明显优于结肠癌,相比左半结肠癌,右半结肠癌患者的生存期更短,复发转移率更高.中药治疗不仅能延长生存期,还能降低结直肠癌术后患者复发转移的风险.

目的 探究散结抑癌方联合贝伐珠单抗对BALB/c裸鼠结肠癌肺转移的影响,以及对血管内皮生长因子(VEGF)蛋白表达的影响.方法 采用经尾静脉注射对数生长期的人源结肠癌HCT116荧光细胞的方法,构建BALB/c裸鼠肺转移模型.将造模成功的20只裸鼠随机分为4组,每组5只.中药组,散结抑癌方灌胃;西药组,贝伐珠单抗腹腔注射;联合组,散结抑癌方灌胃+贝伐珠单抗腹腔注射;对照组,生理盐水灌胃.每周进行1次活体荧光成像观察肿瘤生长情况,记录小鼠体质量.干预4周后取小鼠肺组织,H-E染色观察小鼠结肠癌肺转移情况,免疫组织化学法检测VEGF蛋白表达情况.结果 与干预前比较,对照组在干预后体质量下降最多.干预后,中药组体质量略高于对照组(P>0.05),联合组体质量略高于西药组(P>0.05),联合组和西药组体质量均明显高于对照组(P<0.05).小动物成像定量分析结果显示,干预后中药组、西药组和联合组生物发光光子数均少于对照组(P均<0.05).H-E染色结果指出,对照组转移灶面积最大,转移处最多,联合组转移灶面积最小,转移处最少.免疫组织化学检测结果显示,对照组VEGF蛋白平均阳性细胞率为48.57％,高于中药组(39.91％)、西药组(35.82％)和联合组(29.03％),差异均有统计学意义(P均<0.01).结论 散结抑癌方可以抑制结肠癌肺转移,作用途径可能与VEGF蛋白表达相关.

Objective To analyze the active compounds, potential targets, and diseases of JianPi Fu Recipe (JPFR) based on network pharmacology and bioinformatics and verify the potential biological function and mechanism of JPFR in vitro and in vivo. Methods Network pharmacology databases including TCMSP, TCM-PTD, TCMID, and DrugBank were used to screen the active compounds and potential drug targets of JPFR. Cytoscape 3.7 software was applied to construct the interaction network between active compounds and potential targets. The DAVID online database analysis was performed to investigate the potential effective diseases and involved signaling pathways according to the results of the GO function and KEGG pathways enrichment analysis. To ensure standardization and maintain interbatch reliability of JPFR, High Performance Liquid Chromatography (HPLC) was used to establish a “chemical fingerprint.” For biological function validation, the effect of JPFR on the proliferation and migration of CRC cells in vitro was investigated by CCK-8 and transwell and wound healing assay, and the effect of JPFR on the growth and metastasis of CRC cells in vivo was detected by building a lung metastasis model in nude mice and in vivo imaging. For the potential mechanism validation, the expressions of MALAT1, PTBP-2, and β-catenin in CRC cells and transplanted CRC tumors were detected by real-time PCR, western blot, and immunohistochemical staining analysis. Results According to the rules of oral bioavailability (OB) > 30% and drug-likeness (DL) > 0.18, 244 effective compounds in JPFR were screened out, as well as the corresponding 132 potential drug targets. By the analysis of DAVID database, all these key targets were associated closely with the cancer diseases such as prostate cancer, colorectal cancer, bladder cancer, small cell lung cancer, pancreatic cancer, and hepatocellular carcinoma. In addition, multiple signaling pathways were closely related to JPFR, including p53, Wnt, PI3K-Akt, IL-17, HIF-1, p38-MAPK, NF-κB, PD-L1 expression and PD-1 checkpoint pathway, VEGF, JAK-STAT, and Hippo. The systematical analysis showed that various active compounds of JPFR were closely connected with Wnt/β-catenin, EGFR, HIF-1, TGFβ/Smads, and IL6-STAT3 signaling pathway, including kaempferol, isorhamnetin, calycosin, quercetin, medicarpin, phaseol, spinasterol, hederagenin, beta-sitosterol, wighteone, luteolin, and isotrifoliol. For in vitro experiments, the migration and growth of human CRC cells were inhibited by the JPFR extract in a dose-dependent way, and the expression of MALAT1, PTBP-2, β-catenin, MMP7, c-Myc, and Cyclin D1 in CRC cells were downregulated by the JPFR extract in a dose-dependent way. For in vivo metastasis experiments, the numbers of lung metastasis were found to be decreased by the JPFR extract in a dose-dependent manner, and the expressions of metastasis-associated genes including MALAT1, PTBP-2, β-catenin, and MMP7 in the lung metastases were downregulated dose dependently by the JPFR extract. For the orthotopic transplanted tumor experiments, the JPFR extract could inhibit the growth of orthotopic transplanted tumors and downregulate the expression of c-Myc and Cyclin D1 in a dose-dependent manner. Moreover, the JPFR extract could prolong the survival time of tumor-bearing mice in a dose-dependent manner. Conclusions Through effective network pharmacology analysis, we found that JPFR contains many effective compounds which may directly target cancer-associated signaling pathways. The in vitro and in vivo experiments further confirmed that JPFR could inhibit the growth and metastasis of CRC cells by regulating β-catenin signaling-associated genes or proteins.

新型冠状病毒肺炎(Novel coronavirus pneumonia,简称COVID-19)是指由新型冠状病毒(简称2019-nCoV)引起的以发热、咳嗽、头痛、乏力、呼吸困难等症状为主要临床表现的病毒型肺炎.我国最早的COVID-19患者被发现于武汉,患者从感染到发病通常在14天内,该病毒具有较强的传染性.截止至2020年2月23日,COVID-19患者累计77049例,导致不少于2445位患者死亡.与SARS相比,COVID-19进展快,危重患者多存在肺损伤、肝功能异常、急性呼吸窘迫综合征,最终发展至多器官衰竭、休克.危重COVID-19患者的病理变化机制目前仍未阐释清楚,有学者从COVID-19引起的炎症瀑布揭示COVID-19患者肝功能异常.COVID-19病理发展变化最终需要详实的解剖和病理研究证实.COVID-19给我国造成的危害不亚于2003年我国爆发的SARS.在当前COVID-19防治工作中,仍未形成全球公认最佳疗效的治疗指南,现代医学与传统医学救治措施均有报道.本文将COVID-19的最新中西医防治方法和措施予以汇总,为COVID-19防治工作提供支持.

"络病学说"作为重要的中医基础病机之一,近年来被广泛应用于肿瘤类疾病的临床诊疗中,其对于肿瘤的发生发展以及转移等机制研究与治疗均有理论指导意义."络病"在形态与功能上与现代医学中的肿瘤微血管、微循环概念相似;瘀阻络脉与肿瘤患者血液高凝状态类似,故运用"通络法"抗肿瘤具有充足的理论依据.虫类药是动物药的别称,作为通络药的代表,善于搜刮剔络,在肿瘤的防治中起到了活血化瘀通络、攻毒散结通络、搜风解毒通络以及补益培本通络等作用.通过梳理"络病学说"的起源、发展与成熟阶段的主要思想内涵,整理并总结现代肿瘤治疗中"络病学说"的相关研究与应用,并分析虫类药在通络法中的具体应用,以期为开展中医络病防治肿瘤的临床应用提供理论依据.

消化系统肿瘤的发生是由多种因素引起的抑癌基因或促癌基因发生突变所导致的.NF2基因是一种抑癌因子,其编码Merlin蛋白功能的缺失是造成消化系统肿瘤发生、发展的重要因素.NF2/Merlin通过Hippo/Yap、Wnt/β-catenin、转化生长因子-β(TGF-β)等多条信号通路发挥抗肿瘤作用.该文综述了NF2基因及其表达产物Merlin蛋白在消化系统肿瘤发生、发展过程中的抑制作用,旨在为探究NF2/Merlin的抑癌机制及肿瘤防治方法提供新思路.

目的 系统评价中医药辅助卡培他滨片维持治疗结直肠癌的临床疗效.方法 检索Pubmed、Embase、Cochrane Library、中国知识资源总库(CNKI)、中国学术期刊数据库(万方数据)、中文科技期刊数据库(维普网)及中国重要会议论文全文数据库中医药辅助卡培他滨片维持治疗结直肠癌随机对照试验(RCT),检索时间范围为建库至2018年11月.采用Cochrane偏倚风险评估工具对纳入研究进行质量评价,应用RevMan5.3进行Meta分析.结果 共纳入13项RCT,涉及患者964例.Meta分析结果显示:与对照组比较,试验组明显提高卡氏评分(RR=0.35,95％CI[0.26,0.49],P<0.00001),改善手足综合征(RR=0.55,95％CI[0.38,0.79],P=0.001),减少白细胞降低(RR=0.66,95％CI[0.49,0.89],P=0.006),减轻恶心呕吐(RR=0.51,95％CI[0.36,0.72],P=0.0002),减轻腹泻(RR=0.49,95％CI[0.35,0.68],P<0.0001),增加CD3+、NK细胞计数(RR=5.62,95％CI[3.08,8.16],P<0.05;RR=7.18,95％CI[5.31,9.06],P<0.05).试验组对瘤体有效率与对照组比较差异无统计学意义(RR=0.78,95％CI[0.57,1.05],P=0.10).结论 中医药辅助卡培他滨片维持治疗晚期结直肠癌患者疗效优于单纯化疗,可改善患者生活质量,减轻化疗毒副作用,提高机体免疫力,但尚需更多大样本高质量的RCT验证.