BACKGROUND:Recurrence and metastasis are the main causes of disease deterioration in colorectal cancer (CRC) patients, yet efficient therapeutic strategies are lacking. Natural compounds for efficient antitumour therapeutics are becoming increasingly prominent. Kaempferol, one of the main components of flavonoids in plants, displays a variety of pharmacological activities. Our preliminary experiments suggested that kaempferol could inhibit CRC metastasis and is significantly associated with the β-catenin signalling pathway. Moreover, we also defined the regulatory roles of JMJD2C in β-catenin signalling in our previous work.PURPOSE:This study aims to reveal the mechanism by which kaempferol inhibits CRC progression and regulates the JMJD2C/β-catenin signalling pathway.METHODS:The migratory capabilities of CRC cells after kaempferol intervention were measured by scratch wound healing and transwell assays. Circ_0000345 knockdown CRC stable cell lines were generated by lentivirus infection. The possible mechanism of kaempferol on circ_0000345 was verified by molecular-protein docking and verification program cellular thermal shift assay (CETSA). A dual luciferase reporter gene assay was carried out for the targeting relationship among circ_0000345, miR-205-5p and JMJD2C. Fluorescence in situ hybridization (FISH) was performed to determine the expression of circ_0000345 in tumour tissues. A pulmonary metastatic model of CRC in vitro was built to assess the antimetastatic effect and mechanism of kaempferol in vivo.RESULTS:In vitro, kaempferol inhibits the ability to migrate of CRC cells by reducing the activation of the JMJD2C/β-catenin signalling pathway. MiR-205-5p is a key bridge for kaempferol to inhibit the expression of JMJD2C. The function of miR-205-5p is impeded by circ_0000345, which shows higher expression levels in human metastatic CRC tissues than nonmetastatic CRC tissues, and its formation is regulated by the RNA-binding proteins HNRNPK and HNRNPL. Mechanistically, kaempferol physically interacts with HNRNPK and HNRNPL to suppress JMJD2C by downregulating the expression of circ_0000345. In vivo, kaempferol suppresses CRC lung metastasis. Kaempferol inhibits the activation of JMJD2C/β-catenin signalling through reducing the expression of circ_0000345 in the CRC lung metastasis model.CONCLUSION:Circ_0000345 enhances activation of the JMJD2C/β-catenin signalling pathway through miR-205-5p to promote CRC metastasis. Kaempferol inhibits CRC metastasis through the circ_0000345-mediated JMJD2C/β-catenin signalling pathway, and this effect is influenced as a direct consequence of the binding of kaempferol with HNRNPK and HNRNPL. This provides promising therapeutic and/or adjuvant agents for advanced CRC and sheds light on the multifaceted role of phytomedicine in cancer.

Background: Recurrence and metastasis are the main causes of disease deterioration in colorectal cancer (CRC) patients, yet efficient therapeutic strategies are lacking. Natural compounds for efficient antitumour therapeutics are becoming increasingly prominent. Kaempferol, one of the main components of flavonoids in plants, displays a variety of pharmacological activities. Our preliminary experiments suggested that kaempferol could inhibit CRC metastasis and is significantly associated with the 8 -catenin signalling pathway. Moreover, we also defined the regulatory roles of JMJD2C in 8 -catenin signalling in our previous work. Purpose: This study aims to reveal the mechanism by which kaempferol inhibits CRC progression and regulates the JMJD2C/ 8 -catenin signalling pathway. Methods: The migratory capabilities of CRC cells after kaempferol intervention were measured by scratch wound healing and transwell assays. Circ_0000345 knockdown CRC stable cell lines were generated by lentivirus infection. The possible mechanism of kaempferol on circ_0000345 was verified by molecular-protein docking and verification program cellular thermal shift assay (CETSA). A dual luciferase reporter gene assay was carried out for the targeting relationship among circ_0000345, miR-205-5p and JMJD2C. Fluorescence in situ hybridization (FISH) was performed to determine the expression of circ_0000345 in tumour tissues. A pulmonary metastatic model of CRC in vitro was built to assess the antimetastatic effect and mechanism of kaempferol in vivo . Results: In vitro , kaempferol inhibits the ability to migrate of CRC cells by reducing the activation of the JMJD2C/ 8 -catenin signalling pathway. MiR-205-5p is a key bridge for kaempferol to inhibit the expression of JMJD2C. The function of miR-205-5p is impeded by circ_0000345, which shows higher expression levels in human metastatic CRC tissues than nonmetastatic CRC tissues, and its formation is regulated by the RNA-binding proteins HNRNPK and HNRNPL. Mechanistically, kaempferol physically interacts with HNRNPK and HNRNPL to suppress JMJD2C by downregulating the expression of circ_0000345. In vivo , kaempferol suppresses CRC lung metastasis. Kaempferol inhibits the activation of JMJD2C/ 8 -catenin signalling through reducing the expression of circ_0000345 in the CRC lung metastasis model.

目的:观察脐部敷贴通便膏联合服用乳果糖口服溶液对晚期癌痛阿片类药物相关性便秘(OIC)患者的临床疗效.方法:将129例晚期癌痛OIC患者按照随机数字表法随机分为治疗组68例和对照组61例,对照组予乳果糖口服溶液口服,治疗组在对照组治疗的基础上加用通便膏脐部敷贴,2组均治疗14?d后进行疗效观察.比较2组患者治疗前后粪便性状评分(BSFS评分)、便秘情况评分(CCS评分)、生活质量评分(PAC-QOL评分)、中医证候积分等指标改变情况,治疗后比较2组患者中医证候疗效.结果:治疗后治疗组患者BSFS评分、CCS评分、PAC-QOL评分均较治疗前明显降低(P<0.01),且均明显低于同期对照组(P<0.01,P<0.05);治疗后对照组患者BSFS评分较治疗前略有下降,但差异无统计学意义(P>0.05),CCS评分、PAC-QOL评分均明显低于治疗前(P<0.05,P<0.01).治疗后治疗组患者排便不尽感、肠鸣、腹胀、矢气等单项证候评分以及总分均明显低于治疗前(P<0.01),且均明显低于同期对照组(P<0.01);对照组患者除矢气外,其余单项证候评分及总分均明显低于治疗前(P<0.05,P<0.01).治疗组患者中医证候总有效率为98.53％,明显高于对照组的50.82％(P<0.01).结论:在乳果糖口服溶液治疗的基础上加用通便膏脐部敷贴能进一步改善晚期癌痛OIC患者的粪便性状、便秘程度和临床症状,提高患者的生活质量.

目的 探讨扶正胶囊联合化疗治疗脾虚湿阻型大肠癌的临床价值.方法 选取 2020 年 1 月至 2022 年 11 月我院收治的 60 例脾虚湿阻型大肠癌患者.随机分为对照组和观察组各 30 例.对照组给予单纯化疗治疗,观察组给予扶正胶囊联合化疗治疗.比较两组患者治疗前后肿瘤标志物、免疫功能指标、中医证候积分、生活质量及不良反应发生情况.结果 治疗后,观察组血清CEA、CA199 水平显著低于对照组(P<0.05).观察组治疗后CD3+、CD4+、CD4+/CD8+高于对照组,CD8+低于对照组(P<0.05).治疗后,观察组中医证候积分显著低于对照组(P<0.05).治疗后,观察组结直肠癌生活质量专用量表(QLQ-CR38)症状评分显著低于对照组,功能评分显著高于对照组(P<0.05).观察组胃肠道反应、骨髓抑制发生率显著低于对照组(P<0.05).结论 扶正胶囊联合化疗治疗脾虚湿阻型大肠癌,可有效抑制肿瘤标志物表达,改善机体免疫功能,减轻临床症状,改善中医证候积分,减少化疗不良反应发生,提升患者生活质量.

目的 观察温阳助运方联合甲地孕酮治疗胃阳虚型Ⅲ-Ⅳ期癌性厌食的疗效.方法 选取2020年10月—2023年4月于南京中医药大学附属苏州市中医医院肿瘤科住院治疗的胃阳虚型Ⅲ-Ⅳ期癌性厌食患者104例,按照随机数字表法分为治疗组53例和对照组51例.对照组在肿瘤治疗的基础上口服醋酸甲地孕酮分散片;治疗组在对照组治疗基础上加服温阳助运方,2组疗程均为2周.比较2组食欲状况及生活质量[肿瘤患者食欲症状问卷(CASQ)、厌食/恶液质评价量表(A/CS-12)]、中医症状评分、中医证候疗效、机体营养状况及不良反应发生情况.结果 治疗后2组患者CASQ评分及A/CS-12评分均明显升高(P＜0.05);与对照组比较,治疗组治疗后CASQ评分及A/CS-12评分升高更明显(P＜0.05).治疗后对照组胃脘胀满、神疲乏力、恶心呕吐、食欲不振、口淡等症状评分降低(P＜0.05);治疗组治疗后胃脘胀满、畏寒肢冷、神疲乏力、食欲不振、口淡、呕吐清水、恶心呕吐、大便稀溏、夜尿频多等症状评分降低(P＜0.05),且优于对照组(P＜0.05).治疗组总有效率为84.91%,优于对照组的31.37%(P＜0.05).治疗后治疗组前白蛋白明显升高(P＜0.05),而对照组总蛋白、白蛋白、前白蛋白均明显下降(P＜0.05).2组不良反应发生率差异无统计学意义(P＞0.05).结论 温阳助运方联合甲地孕酮能显著改善胃阳虚型Ⅲ-Ⅳ期癌性厌食患者的厌食症状及胃阳虚症状,提高患者生活质量,改善机体营养状态,安全性良好,值得临床推广运用.

目的 评价金复康口服液联合辅助化学药物治疗(简称"化疗")干预早期非小细胞肺癌(NSCLC)根治术后的临床疗效.方法 采用前瞻性、随机、对照的研究方法,纳入198例Ⅰb至Ⅱb期早期NSCLC根治术后中医辨证为气阴两虚证的患者为研究对象,区组随机分为对照组(98例)和试验组(100例),对照组接受4周期术后标准辅助化疗,试验组在辅助化疗的同时联合金复康口服液治疗.比较2组患者治疗后中医症状积分、体力评分及无病生存率等方面的差异.结果 中医症状积分方面,试验组患者咳嗽、咳痰、气短、胸痛、神疲乏力、食欲不振、口干咽燥、自汗盗汗、失眠、夜尿频多等症状积分小于对照组患者(P<0.05,P<0.01).2组体力评分在治疗后均较治疗前好转(P<0.05),且试验组体力评分好转率高于对照组(P<0.05).试验组12、24、36个月的无病生存率分别为90.9％、84.4％和83.1％,对照组分别为88.1％、82.0％和77.3％,试验组各时间点的无病生存率均高于对照组,但差异无统计学意义.结论 金复康口服液联合术后辅助化疗可降低患者中医症状积分,改善NSCLC相关症状及术后体力状态,并在一定程度上延缓患者疾病的进展.

目的:基于循环肿瘤细胞(CTC)比较单纯化疗与金复康口服液联合化疗治疗Ⅰb～Ⅱb期非小细胞肺癌(NSCLC)术后患者的疗效差异.方法:采用多中心随机对照研究方法,纳入144例Ⅰb～Ⅱb期NSCLC术后患者,随机分为治疗组72例与对照组72例,对照组患者给予含铂双药化疗方案治疗,治疗组患者在对照组治疗基础上给予金复康口服液口服.21～28 d为1个化疗周期,共治疗4个周期.分别于化疗前、化疗中(第2周期化疗后)、化疗后(第4周期化疗后)及化疗结束后1年、1.5年、2年,检测所有患者的CTC计数,并于化疗前检测所有患者的肿瘤标志物及免疫指标水平.采用重复测量分析探讨CTC变化趋势,采用Spearman分析法对CTC计数与肿瘤标志物、免疫指标水平进行相关性分析,采用多因素线性回归对CTC计数与免疫指标水平进行相关性分析.结果:研究中,3例患者被剔除,最终纳入统计分析者治疗组70例、对照组71例.①对照组患者的CTC计数在化疗期间下降,但在化疗结束后出现反弹,治疗组患者的CTC计数在化疗中及化疗后均持续下降,无反弹趋势.②Ⅱb期患者化疗结束后1年CTC计数治疗组低于对照组(P＜0.05),其他观察时点组间差异均无统计学意义(P＞0.05).③相关性分析结果显示,CTC计数与癌胚抗原(CEA)、CD8+T淋巴细胞水平呈正相关(P＜0.05).结论:金复康口服液联合化疗可在一定程度上降低Ⅰb～Ⅱb期NSCLC术后患者外周血CTC计数,并在一定程度上抑制化疗结束后CTC计数的反弹趋势,尤其对Ⅱb期患者效果更显著.

目的:观察消积通络散治疗晚期肺癌的临床疗效.方法:将符合入组标准的60例晚期肺癌患者,随机分为治疗组和对照组各30例,在最佳支持治疗的基础上,治疗组予辨证施治并加用消积通络散,对照组予辨证施治,经过3个月治疗后,比较2组的临床疗效.结果:在提高生存质量、改善患者症状等方面,治疗组显著优于对照组,且未见明显毒副作用.结论:消积通络散可用于治疗晚期肺癌.

目的:探讨非小细胞肺癌患者外周血循环肿瘤细胞(circulating tumor cells,CTC)与临床特征及凝血功能的相关性.方法:应用观察性研究的方法,收集多中心284例确诊为原发性非小细胞肺癌患者的外周血CTC,研究CTC与性别、年龄、TNM分期、病理类型等临床特征的相关性;同时对患者血小板、凝血功能进行检测,研究CTC表达与凝血功能的相关性.结果:CTC阳性率在性别、年龄间差异无统计学意义;不同的TNM分期患者的CTC阳性差异显著(P<0.05),CTC阳性率与TNM分期呈正相关(r=0.137,P<0.05).CTC阳性肺癌患者的凝血酶原时间(prothrom-bin time,PT)水平降低(P<0.05),CTC阳性率与PT呈负相关(r=-0.128,P<0.05);有远处转移的患者纤维蛋白降解产物(fibrin degradation products,FDP)、纤维蛋白原(fibrinogen,FIB)、PT水平均显著高于无远处转移的患者(P<0.05),凝血酶时间(thrombin time,TT)水平显著低于无远处转移患者,相关性检验显示FDP、FIB、PT与转移呈正相关(P<0.05),TT与转移呈负相关(r=-0.281,P<0.05).结论:CTC与非小细胞肺癌TNM分期相关,CTC阳性患者存在凝血功能异常,凝血功能异常可能促进非小细胞肺癌循环肿瘤细胞的远处转移.

近年来,肺癌成为全球发病率、病死率急剧增长的癌症之一,是全球男性癌症相关死亡的主要原因,也是女性中仅次于乳腺癌的死亡原因[1].肺癌按病理类型可分为小细胞肺癌和非小细胞肺癌,其中非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)最为常见,包括鳞癌、腺癌、大细胞癌,约占肺癌总数的80％ ～ 85％[2],根据2015年第7版NCCN临床实践指南:对于大多数可耐受手术的NSCLC患者首选手术治疗.Ⅰ期、Ⅱ期和部分Ⅲa期可行手术完全性切除,Ⅰa完全切除术后患者5年生存率约为77％,Ⅲa期下降至23％[3],影响其生存率的主要原因是局部复发和远处转移[4].目前,铂类联合第3代细胞毒性药物的化疗方案仍然是临床上一线化疗的标准方案[5].目前已证实手术切除后的非小细胞肺癌术后辅助化疗是有益的[6],Ⅰb-Ⅲa期完全性切除后的NSCLC患者采取术后辅助化疗是标准方案,将患者的5年生存率提高5％[7].研究分析发现,Ⅱ期及Ⅲa期患者术后化疗的获益较明显[8-9],选择个体化的辅助化疗方案才是治疗成功的关键[10-11].

非小细胞肺癌是肺癌中最常见组织学类型，是发病率、死亡率均较高的恶性肿瘤。晚期非小细胞肺癌一线治疗后，为稳定病情在耐药产生前进行化疗药物或靶向药物维持治疗，取得了一定的进展，而化疗药物在维持治疗中维持治疗期的副反应发生率较高，靶向药物对EGFR野生型患者生存获益有待进一步研究。中医药维持治疗在提高生存质量、延长无进展生存期和/或总生存期方面可使患者获益。 Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. It is a malignant tumor with high incidence rate and mortality rate. After the first-line chemotherapy for advanced NSCLC, some progress have been made in maintenance treatment consists of either chemotherapy or targeted therapy to stabilize the condition, before the drug resistance. However, there is a high incidence of various side reactions of maintenance chemotherapy. Further studies are needed to confirm the survival benefit of the patient with wild type EGFR genes. Traditional Chinese medical treatment on maintenance therapy offers great benefits to patients that include improve quality of life and prolong progression free survival and/or overall survival.