约10%~30%的新发结直肠癌患者会出现急性肠梗阻,传统急诊手术治疗存在术后并发症高、死亡率高、生存质量低等不足。肠道支架置入联合限期手术作为一种新型治疗策略,展现出显著优势。肠道支架可迅速解除梗阻,改善患者症状,降低手术风险,为肿瘤微创切除创造条件,同时为新辅助化疗提供可能,但其潜在并发症如出血、移位、再梗阻及肠穿孔等也不容忽视,且长期安全性及对肿瘤结局的影响尚不明确。文章综述了肠道支架治疗梗阻性结直肠癌的治疗现状、争议及研究进展,旨在为临床研究和实践提供参考依据。
Approximately 10% to 30% of patients with newly diagnosed colorectal cancer present with acute intestinal obstruction.Traditional emergency surgical intervention is characterized by high rates of postoperative complications,elevated mortality,and diminished quality of life.Combined stent and curative elective surgery(CSCES)has emerged as a novel therapeutic strategy,exhibiting significant clinical benefits.Intestinal stenting can rapidly alleviate obstruction,thereby improving patient symptoms,reducing surgical risks,and facilitating minimally invasive tumor resection.Additionally,it provides an opportunity for neoadjuvant chemotherapy.However,potential complications,including bleeding,stent migration,recurrent obstruction,and intestinal perforation,must be carefully considered.Moreover,the long-term safety and impact on oncologic outcomes remain to be elucidated.This review aims to provide a comprehensive overview of the current status,controversies,and recent advancements in the use of intestinal stents for the treatment of obstructive colorectal cancer,with the goalof informing clinical research and practice.
目的 探讨术前静注艾司氯胺酮在腹腔镜结直肠癌根治术患者中的应用效果。方法 前瞻性分析2024年1月—2025年4月在厦门市中医院行腹腔镜结直肠癌根治术患者的临床资料,根据随机数字表法将患者分为两组:对照组40例,术前5 min予5 mL生理盐水;观察组40例,术前5 min予以0.25 mg/kg艾司氯胺酮(以生理盐水配置成5 mL)。比较围术期指标、炎症因子、负性情绪、疼痛情况、不良反应。结果 观察组的手术时间、麻醉时间、术中出血量分别为(213.54±64.22)min、(240.67±81.26)min、(141.31±45.03)mL,与对照组的(210.43±65.71)min、(244.25±81.33)min、(137.64±42.75)mL比较,差异均无统计学意义(t=0.214、0.197、0.374,P均>0.05),而观察组丙泊酚、瑞芬太尼用量分别为(1 075.52±134.37)mg、(1 267.18±242.26)μg,虽然低于对照组的(1?126.64±150.21)mg、(1 352.50±295.14)μg,但差异也无统计学意义(t=1.604、1.413,P均>0.05);观察组在术后24 h的肿瘤坏死因子-α、白介素-6、C反应蛋白水平分别为(54.52±9.64)pg/mL、(40.08±7.75)pg/mL、(30.38±6.93)mg/L,均低于对照组的(77.31±10.86)pg/mL、(56.35±9.47)pg/mL、(43.73±7.61)mg/L(t=9.926、8.409、8.203,P均<0.05);术后1 d的焦虑、抑郁自评量表评分及术后1 h、6 h、12 h、24 h咳嗽时的疼痛视觉模拟量表评分分别为(51.92±4.41)分、(53.96±4.47)分、(3.59±1.14)分、(3.06±1.01)分、(2.89±0.91)分、(2.57±0.76)分,均低于对照组的(55.06±5.12)分、(57.21±5.19)分、(4.27±1.36)分、(3.68±1.18)分、(3.41±1.06)分、(2.96±0.92)分(t=2.939、3.001、2.423、2.525、2.329、2.067,P均<0.05),但两组术后48 h咳嗽时疼痛视觉模拟量表评分比较差异无统计学意义(P>0.05);两组术后不良反应发生率也无显著差异(P<0.05)。结论 在腹腔镜结直肠癌根治术术前静注艾司氯胺酮可有效降低术后炎症反应水平,减轻术后疼痛,缓解术后负性情绪,且不会增加患者术后不良反应发生率。
Objective To explore the application effect of preoperative intravenous injection of esketamine in patients undergoing laproscopic radical resection of colorectal cancer.Methods The clinical data of patient who underwent laparoscopic radical resection of colorectal cancer in Xiamen Hospital of Traditional Chinese Medicine from January 2024 to April 2025 were retrospectively analyzed.The patients were divided into two groups according to the random number table method:40 cases in the control group were given 5 mL saline,five minutes before operation,40 cases in the observation group were treated with 0.25 mg / kg esketamine(in 5 mL saline)five minutes before operation.The perioperative indicators,inflammatory factors,negative emotions,pain and adverse reactions were compared between two groups.Results The operation time,anesthesia time and intraoperative blood loss of the observation group were(213.54±64.22)min,(240.67±81.26)min and(141.31±45.03)mL,respectively,which were not significantly different from those of the control group(210.43±65.71)min,(244.25±81.33)min and(137.64±42.75)mL(t=0.214,0.197,0.374,all P>0.05).The dosage of propofol and remifentanil in the observation group were(1 075.52±134.37)mg and(1 267.18±242.26)μg,respectively,which were lower than those in the control group of (1126.64±150.21)mg and(1352.50±295.14)μg,but the difference was not statistically significant(t=1.604,1.413,P>0.05).The levels of tumor necrosis factor-α,interleukin-6 and C-reactive protein in the observation group at 24 h after operation were(54.52±9.64)pg / mL,(40.08±7.75)pg / mL and(30.38±6.93)mg / L,respectively,which were lower than those in the control group of (77.31±10.86)pg / ml,(56.35±9.47)pg / mL and 43.73±7.61)mg / L(t=9.926,8.409,8.203,all P<0.05).The scores of Anxiety and Depression Self-Rating Scale at 1 day after operation and the scores of pain visual analogue scale at 1 h,6 h,12 h and 24 h after operation were(51.92±4.41),(53.96±4.47),(3.59±1.14),(3.06±1.01),(2.89±0.91) and(2.57±0.76),respectively,which were lower than those of the control group(55.06±5.12),(57.21±5.19),(4.27±1.36),(3.68±1.18),(3.41±1.06) and(2.96±0.92)(t=2.939,3.001,2.423,2.525,2.329,2.067,P<0.05).However,no significant difference was observed in cough-related VAS scores between the groups at 48 h postoperatively(P>0.05).Adverse event rates showed no significance in two groups(P>0.05).Conclusions Preoperative administration of esketamine in laparoscopic colorectal cancer surgery can attenuate postoperative inflammation,decrease pain,mitigate negative emotions,without increasing the incidence of postoperative adverse reactions.
目的 观察补肾益气方肾俞膏摩治疗结直肠癌康复期癌因性疲乏的临床疗效。方法 收集2023年6月—2024年6月结直肠癌康复期的80例住院及门诊患者,随机平均分为两组。行常规对症支持治疗的为对照组;在常规对症支持治疗上加用补肾益气方肾俞膏摩的为干预组;两组均连续治疗14天。于开始治疗前1天和治疗结束后1天分别进行疗效评估相关指标检测。于治疗前1天、治疗第7天和第14天进行不良反应检测。结果 干预组治疗后Piper评分、中医证候总积分、PSQI评分、KPS评分及免疫功能指标(CD3+ 、CD4+、CD8+ 、CD4+ /CD8+ )较治疗前均有明显改善;干预组发生不良反应少于对照组。结论 补肾益气方肾俞膏摩治疗能够有效改善结直肠癌患者的癌因性疲乏的治疗效果,提高生活质量和免疫功能,减少不良反应。
Objective To observe the clinical observation of Shenshu Tuina combined with Bushen Yiqi herbal ointment in the treatment of cancer-induced fatigue in the convalescent stage of colorectal cancer and evaluate the efficacy.Methods From June 2023 to June 2025,80 inpatients and outpatients of colorectal cancer in the recovery period were collected and randomly divided into two groups.The patients who received routine symptomatic supportive treatment were enrolled as the control group.The intervention group was given Shenshu Tuina combined with Bushen Yiqi herbal ointment on the basis of control group.The relevant indicators for efficacy evaluation were tested one day before treatment and one day after the end of treatment.Adverse reactions were detected on the day before treatment,theseventh day and 14th day during treatment.Results The efficacy evaluation indexes of the intervention group after treatment were obviously improved compared with those before treatment.Adverse reactions occurred less in the intervention group than in the control group.Conclusions Shenshu Tuina combined with Bushen Yiqi herbal ointment can effectively improve the treatment effect of cancer-induced fatigue in patients with colorectal cancer,improve the quality of life and immune function,reduce adverse reactions.
目的 探讨转录因子E盒结合锌指蛋白1(ZEB1)、溶酶体相关膜蛋白5(LAMP5)在结直肠癌组织中的表达水平分析及预后预测价值。方法 选取驻马店市中心医院2018年1月—2020年1月收治的120例结直肠癌患者,分别采取所有患者的结直肠癌组织及癌旁组织进行免疫组化染色,对比ZEB1、LAMP5阳性率。对比不同病理特征结直肠癌患者ZEB1、LAMP5表达水平差异。对所有患者进行4年随访,依照随访结果将患者分为2个亚组,即预后不良组(n=35)和预后良好组(n=85),对比两组患者一般临床特征及ZEB1、LAMP5表达水平,应用Logistic回归分析ZEB1、LAMP5对结直肠癌预后的预测价值。结果 结直肠癌组织ZEB1、LAMP5相对表达量(38.26±5.49、26.77±3.85)与ZEB1、LAMP5阳性率(86.67%、72.22%)高于癌旁组织(15.46±2.54、8.04±1.59、23.33%、15.56%],对比差异有统计学意义(t=41.280,χ2=25.437;t=49.255,χ2=16.071;P<0.05)。不同TNM分期[Ⅰ~Ⅱ期(35.55±4.13)、Ⅲ~Ⅳ期(42.32±4.75)]、淋巴结转移患者[是(44.37±4.28)、否(35.84±3.77)]、肿瘤分化程度[低分化(35.27±4.57)、中高分化(41.34±4.60)]ZEB1相对表达量对比差异有统计学意义(t=-8.281,P<0.001;t=10.746,P<0.001;t=-7.253,P<0.001);不同TNM分期[Ⅱ期(24.88±3.37)、Ⅲ~Ⅳ期(29.61±2.57)]、淋巴结转移[是(30.72±2.19)、否(25.21±3.19)]、肿瘤分化程度[低分化(24.57±3.62)、中高分化(29.04±2.55)]患者LAMP5相对表达量对比差异有统计学意义(t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,<0.001);预后良好组与预后不良组患者性别、年龄、大体类型、肿瘤大小对比差异无统计学意义(P>0.05),预后良好组与预后不良组患者TNM分期、淋巴结转移、肿瘤分化程度、ZEB1、LAMP5阳性比例对比差异有统计学意义(P<0.05);Logistic回归分析显示:淋巴结转移、ZEB1阳性、LAMP5阳性为结直肠癌预后不良独立预测因素(P<0.05)。结论 ZEB1、LAMP5在结直肠癌组织中呈现高表达状态,且与结直肠癌的发生有关,同时ZEB1、LAMP5是结直肠癌预后的独立预测因素,两者有希望成为结直肠癌的治疗靶点。
Objective To investigate the expression levels and prognostic value of transcription factor E-box binding to zinc finger protein 1(ZEB1)and lysosomal associated membrane protein 5(LAMP5)in colorectal cancer tissues. Methods A total of 120 colorectal cancer patients admitted to a hospital from January 2018 to January 2020 were selected.Immunohistochemical staining was performed on the colorectal cancer tissues and adjacent tissues of all patients,and the positivity rates of ZEB1 and LAMP5 were compared.The expression levels of ZEB1 and LAMP5 in colorectal cancer patients with different pathological characteristics were compared.All patients were followed up for 4 years and divided into two subgroups based on the follow-up results,namely the poor prognosis group(n=35)and the good prognosis group(n=85).The general clinical characteristics and expression levels of ZEB1 and LAMP5 were compared between the two groups.Logistic regression analysis was used to evaluate the predictive value of ZEB1 and LAMP5 for the prognosis of colorectal cancer. Results The relative expression level of ZEB 1 and LAMP 5 in colorectal cancer tissues [(38.26±5.49),(26.77±3.85)] and the positive rate of ZEB 1 and LAMP 5(86.67%,72.22%)were significantly higher than that of adjacent tissues [(15.46±2.54),(8.04±1.59),23.33%,15.56%],the contrast difference was statistically significant(t=41.280,χ2=25.437;t=49.255,χ2=16.071;P<0.05).Relative ZEBI expression levels in different TNM stages [I-Ⅱstage(35.55±4.13),Ⅲ-Ⅳstage(42.32±4.75)],lymph node metastasis[Yes(44.37±4.28),No(35.84±3.77)],degree of tumor differentiation [hypodifferentiated(35.27±4.57),and middle or high differentiated(29.04±2.55)],those differences were statistically significant(t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001).The relative expression of LAMP 5 between different TNM stages [I-Ⅱstage(24.88±3.37),Ⅲ-Ⅳstage(29.61±2.57)],lymph node metastasis [yes(30.72±2.19),no(25.21±3.19)],degree of tumor differentiation [hypodifferentiated(24.57±3.62),and middle or high differentiated(29.04±2.55)],the contrast was statistically significant(t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001).There were no differences in gender,age,gross type,and tumor size between the good prognosis group and the poor prognosis group(P>0.05),while there were differences in TNM stages,lymph node metastasis,tumor differentiation degrees,ratio of ZEB 1 and LAMP 5(P<0.05).Logistic regression analysis showed that TNM stage,lymph node metastasis,ZEB 1 positive,and LAMP 5 positive were independent predictive factors of poor prognosis in colorectal cancer(P<0.05). Conclusions ZEB1 and LAMP5 are highly expressed in colorectal cancer tissues and closely related to the occurrence and development of colorectal cancer.ZEB1 and LAMP5 are independent prognostic factors for colorectal cancer,and they have the potential to become therapeutic targets for colorectal cancer.
目的 分析贝伐珠单抗与化疗对晚期结直肠癌患者4种错配修复蛋白(MSH2、MLHI、MSH6、PMS2)水平影响。方法 选择2022年1月—2024年1月江苏省宿迁市中医院肿瘤科102例晚期结直肠癌患者,按抽签法分成两组,即化疗组及联合组,各51例。化疗组应用FOLFOX(亚叶酸钙+奥沙利铂+氟尿嘧啶)方案进行化疗,联合组采取贝伐珠单抗联合FOLFOX方案治疗。对比其肿瘤控制效果、免疫功能及MSH2、MLHI、MSH6和PMS2水平变化,并对比组间不良反应发生率。结果 联合组客观缓解率、疾病控制率高于化疗组(P<0.05);治疗后联合组患者CD4+、CD3+、CD8+、和CD4+/CD8+数值高于化疗组,且两组治疗后均低于治疗前(P<0.05);治疗后两组患者MSH2、MLHI、MSH6和PMS2缺失率对比无统计学意义(P>0.05),但其阳性、阴性表达情况对比差异有统计学意义,联合组MSH2、MLHI、MSH6和PMS2阳性率低于化疗组(P<0.05);两组不良反应发生率对比差异无统计学意义(P>0.05)。结论 对晚期结直肠癌在化疗基础上增加贝伐珠单抗抗肿瘤效果显著,改善其免疫功能,虽无法改善患者错配修复蛋白缺损,但可辅助降低其阳性率,且不影响安全性。
Objective To analyze the effects of bevacizumab and chemotherapy on the levels of four mismatch repair proteins(MSH2,MLHI,MSH6,PMS2)in patients with advanced colorectal cancer. Methods A total of 102 patients with advanced colorectal cancer from the Oncology Department of Suqian Traditional Chinese Medicine Hospital in Jiangsu Province from January 2022 to January 2024 were selected,and were divided into two groups according to the drawing method,namely the chemotherapy group and the combination group,with 51 patients in each group.The chemotherapy group received FOLFOX(calcium folinate+oxaliplatin+fluorouracil)regimen for chemotherapy,while the combination group received bevacizumab combined with FOLFOX regimen for treatment.Tumor control effect,immune function,and changes in MSH2,MLHI,MSH6,and PMS2 levels,and its incidence of adverse reactions were compared.Results The objective remission rate and disease control rate of the combined group were higher than those of the chemotherapy group(P<0.05).After treatment,the CD4+,CD3+,CD8+ and CD4+/CD8+ values in the combination group were higher than those in the chemotherapy group,and those after treatment were lower than those before treatment in both groups(P<0.05).After treatment,there were no significant differences in the deletion rates of MSH2,MLHI,MSH6,and PMS2 between the two groups of patients(P>0.05),but there was a significant difference in their positive and negative expression.The positive rates of MSH2,MLHI,MSH6,and PMS2 in the combination group were lower than those in the chemotherapy group(P<0.05).There was no significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusions Adding bevacizumab on the basis of chemotherapy has a significant anti-tumor effect on advanced colorectal cancer,improving its immune function.Although it cannot improve the mismatch repair protein defect in patients,it can assist in reducing its positivity rate and has high safety.
通过筛查和早期发现,可以降低结直肠癌(CRC)的发病率,有效切除肿瘤病变可以降低CRC的病死率。虽然对CRC的危险因素、发病机制和前体病变的了解已经取得进展,但最近年轻人群CRC发病率升高,原因尚不清楚。在过去十年中,出现了多种侵入性、半侵入性和非侵入性筛查方式。目前对结肠镜检查质量的重视提高了筛查的有效性,人工智能等影像新技术在肿瘤检测中的作用正在迅速显现。而且,CRC有效干预措施,如保肛治疗新术式、靶向治疗及免疫治疗领域的新进展,被证明可以提高CRC患者的生存率。该文旨在总结目前国内外CRC筛查方式和指南的证据,并综述CRC治疗领域的进展。
The incidence of colorectal cancer(CRC)can be reduced through screening and early detection.Effective resection of tumor lesions reduces mortality from CRC.Although progress has been made in understanding the risk factors,pathogenesis and precursor lesions of CRC,the reasons for the recent increase in the incidence of CRC in young adults are largely unknown.A variety of invasive,semi-invasive and non-invasive screening modalities have emerged in the last decade.The current emphasis on the quality of colonoscopy has improved the effectiveness of screening,and the role of new imaging technologies such as artificial intelligence in tumor detection is rapidly emerging.Moreover,there are effective interventions for CRC,such as new surgical modalities for anal preservation therapy,and new advances in the field of targeted therapy and immunotherapy,which have been shown to improve the survival rate of CRC.The aim of this article is to summarize the current evidence on CRC screening modalities and guidelines both nationally and internationally,and to provide an overview of advances in the field of CRC treatment.
目的 探究新斯的明拮抗顺阿曲库铵的时机对患者腹腔镜结直肠癌根治术后肌松残留和早期肺功能的影响。方法 选取于2021年2月—2022年9月在我院行结肠癌根治手术的194例患者为研究对象,以随机数字表法将患者分为空白对照组和试验组,然后结合给予新斯的明治疗时所体现的4个成串刺激(TOF)比值将试验组患者分为试验组A(TOF≤0.1)、试验组B(0.10.8)。对比组间肌松残余情况以及肺功能情况。结果 插管前,试验组A患者TOF比值低于其他组(P<0.01),空白对照组患者TOF比值高于其他组(P<0.01);空白对照组分别与试验组A~E在复苏室接受观察的时间比较,差异无统计学意义(P>0.01);试验组A患者肌松恢复指数低于其他组(P<0.01),空白对照组患者肌松恢复指数高于其他组(P<0.01)。插管前、拔管0.5 h以及拔管24 h时,组间1秒用力呼气容积(FEV1)、用力肺活量(FVC)和FEV1/FVC比较差异无统计学意义(P>0.05)。结论 结直肠癌根治术后给予新斯的明,有助于加快肌松恢复,但不会影响复苏室停留时间与肺功能水平。
Objective To investigate the effect of timing of neostigmine antagonizing cisatracurium on residual muscle relaxation and early lung function in patients underwent laparoscopic radical resection of colorectal cancer.Methods February 2021 to September 2022,194 patients who underwent radical colon cancer surgery in our hospital were selected as the research subjects.The patients were randomly divided into a blank control group and an experimental group using a random number table method.Then,combined with the train-of-four(TOF)ratios observed during neostigmine treatment,the experimental group patients were divided into experimental group A(TOF≤0.1),experimental group B(0.10.8).The residual muscle relaxation and lung function between groups were compared.Results Before intubation,the TOF ratio of patients in experimental group A was lower than that of other groups(P<0.01),while the TOF ratio of patients in the blank control group was higher than that of other groups(P<0.01).There was no significant difference in the observation time between the blank control group and the experimental group A~E in the postanesthesia care unit(P>0.01).The muscle relaxation recovery index of patients in experimental group A was lower than that of other groups(P<0.01),while the muscle relaxation recovery index of patients in the blank control group was higher than that of other groups(P<0.01).There were no significant differences in force expiratory volume in one second(FEV1),forced Vital capacity(FVC)and FEV1/FVC between groups before intubation,0.5 h after extubation and 24 h after extubation(P>0.05).Conclusions Administration of neostigmine after radical surgery for colorectal cancer can accelerate muscle relaxation recovery,but it will not affect the residence time of the postanesthesia care unit and lung function levels.
目的 观察结直肠癌患者使用联合药物FOLFOX化疗前后左心室应变参数的变化。方法 选取健康人30例作为正常组,收集病理确诊为结直肠癌并采用FOLFOX(5-氟尿嘧啶+奥沙利铂+亚叶酸钙)化疗的患者30例,以自身对照做研究,分别在化疗前、化疗1个周期后、化疗6个周期后、化疗12个周期后48 h内完成心脏超声检查,采集左心室的动态图像,获取常规参数:LVEDd、LVEDs、IVSd、LVPWd、LVEDV、LVESV、LVEF、LVFS;三维参数:SPI、SV、CO、LVEDMass、LVESMass、GAS、GRS、GLS、GCS,并比较化疗前后这些数值的变化。结果 正常组与各化疗组相比对,LVEDd、LVEDs、IVSd、LVPWd、LVPW、LVESV、SPI的变化均无统计学意义(P>0.05);LVEF、LVFS、SV、CO在化疗中、后期出现了降低,差异有统计学意义(P<0.05),HR、LVEDMass、LVESMass略升高,差异有统计学意义(P<0.05);化疗后GLS及GAS较化疗前明显减低(P<0.05),其中GAS的ROC曲线下面积为0.883,P<0.001,选30%为诊断界点,灵敏度为86.7%,特异度为80%;GLS的ROC曲线下面积为0.888,P<0.001,选19%为诊断界点,灵敏度为73.3%,特异度为90.0%。结论 三维斑点追踪技术能够早期发现FOLFOX致结直肠癌患者左心室功能的变化,其中LVGLS、LVGAS是有力的观测指标。
Objective To observe the changes of left ventricular strain parameters in patients with colorectal cancer before and after combined chemotherapy with FOLFOX. Methods 30 healthy people were selected as normal group, and 30 patients with pathologically diagnosed colorectal cancer and FOLFOX (5-fluorouracil +oxaliplatin+calcium leucovorin) chemotherapy were collected. Before, after 1 cycle of chemotherapy, after 6 cycles of chemotherapy, and within 48 hours after 12 cycles of chemotherapy, cardiac ultrasound examination was performed, and dynamic images of the left ventricle were collected to obtain conventional parameters: LVEDd, LVEDs, IVSd, LVPWd, LVEDV, LVESV, LVEF, LVFS; three-dimensional parameters: SPI, SV, CO, LVEDMass, LVESMass, GAS, GRS, GLS, GCS, and the changes of these values before and after chemotherapy were compared. Results Compared with the chemotherapy group, the normal group had no statistically significant changes in LVEDd, LVEDs, IVSd, LVPWd, LVPW, LVESV, and SPI (P>0.05); LVEF, LVFS, SV, CO were in the middle and late stages of chemotherapy. There was a decrease, the difference was statistically significant (P<0.05), HR, LVEDMass, LVEESMass were slightly increased, the difference was statistically significant (P<0.05); LGS and GAS after chemotherapy were significantly lower than before chemotherapy (P<0.05), the area under the ROC curve of GAS is 0.883, P=0.000, 30% is selected as the diagnostic boundary, the sensitivity is 86.7%, and the specificity is 80%; the area under the ROC curve of GLS is 0.888, P=0.000, 19% as a diagnostic boundary, the sensitivity is 73.3% and the specificity is 90.0%. Conclusion Three-dimensional speckle tracking technology can detect the changes of left ventricular function in patients with colorectal cancer caused by FOLFOX in early stage, of which LVLGS and LVGAS are powerful observation indicators.
目的 通过生物信息学方法,分析阿司匹林抗结直肠癌的作用机制。方法 在DrugBank 5.1.5中查找阿司匹林的直接作用蛋白靶点(direct protein targets,DPTs);构建阿司匹林DPTs的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并分析相关信号通路;从GEO数据库中获取结直肠癌表达谱芯片数据,筛选中心度最高的20个结直肠癌差异表达基因作为Hub基因;将DPTs相互关联基因与结直肠癌Hub基因求交集,确认阿司匹林抗结直肠癌的潜在作用靶点,分析其在TCGA数据库结肠腺癌样本中的表达情况,并进行GO功能富集分析和KEGG信号通路分析。最终通过RT-PCR和WB实验验证阿司匹林抗结直肠癌的潜在靶点。结果 在DrugBank 5.1.5中确定了11个阿司匹林DPTs,KEGG信号通路分析发现其中6个DPTs(EDNRA,IKBKB,NFKB2,NFKBIA,PTGS2,TP53)与癌症的发生发展有关。将DPTs相关联基因与筛选的20个结直肠癌Hub基因求交集,发现5个基因(CDK1,AURKA,CCNB1,MAD2L1,TPX2)可能是阿司匹林抗结直肠癌的潜在作用靶点,其在TCGA数据库结肠腺癌样本中均表达上调,基因功能主要富集于细胞周期调控。RT-PCR和WB实验结果显示阿司匹林可以降低人结肠癌细胞中CDK1,AURKA,CCNB1,MAD2L1,TPX2的mRNA水平和蛋白表达。结论 CDK1,AURKA,CCNB1,MAD2L1,TPX2可能是阿司匹林抗结直肠癌的潜在靶点,其可能通过影响细胞周期调控发挥抗肿瘤作用。
Objective To analyze the mechanism of aspirin against colorectal cancer(CRC)by bioinformatic analysis. Methods DrugBank 5.1.5 was used to identify direct protein targets (DPTs) of aspirin. The protein-protein interaction (PPI) network of DPTs was constructed and involved signaling pathways were analyzed. CRC-associated gene expression datasets were downloaded from GEO database, and the top twenty differentially expressed genes with the highest degree were screened out as Hub genes. Common genes between the genes associated with the DPTs and the Hub genes of CRC were the potential targets of aspirin against CRC. The potential targets in TCGA database colon adenocarcinoma (COAD) samples were examined. GO functional enrichment analysis and KEGG signaling pathway analysis of the potential targets were performed. The potential targets of aspirin against CRC cells were verified by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Results Eleven DPTs of aspirin were identified in DrugBank 5.1.5. KEGG signaling pathway showed that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2, TP53) were associated with the occurrence and development of CRC. By intersecting 20 Hub genes of CRC with genes associated with the DPTs of aspirin, it was found that 5 genes (CDK1, AURKA, CCNB1, MAD2L1, TPX2) might be the potential targets of aspirin against CRC. They were all up-regulated in TCGA-COAD samples, and the gene functions were mainly enriched in cell cycle regulation. The results of RT-PCR and WB showed that aspirin could down-regulate the mRNA and protein expression levels of CDK1, AURKA, CCNB1, MAD2L1 and TPX2 in human colon cancer cells respectively. Conclusion CDK1, AURKA, CCNB1, MAD2L1 and TPX2 could be potential targets of aspirin against CRC by affecting the progress of cell cycle regulation.
目的 评估中性粒细胞与淋巴细胞比值(NLR)在晚期结直肠癌(CRC)患者化疗疗效及预后的意义。方法 回顾性收集2016年1月—2019年4月期间接受以奥沙利铂为基础的标准一线化疗的晚期不可切除结直肠癌患者50例临床病历资料,并在2个化疗周期后评估化疗疗效;根据入组患者化疗前血液学数据计算中性粒细胞与淋巴细胞比值(NLR),运用受试者工作特征曲线确定的NLR最佳截断值,将患者分为高NLR(≥3.785) 组和低NLR(<3.785) 组,比较高、低NLR与临床病理特征、化疗疗效及无进展生存期(PFS)、总生存期(OS)差异;采用COX回归分析模型分析影响晚期结直肠癌患者PFS、OS的因素。结果 高、低NLR两组肿瘤分化程度(P=0.030)、ECOG评分(P=0.003)、CEA(P=0.011)、CA19-9(P=0.047)比较,差异有统计学意义;高低NLR两组间化疗疗效比较,差异有统计学意义(P<0.001),高NLR组化疗疗效较差;两组中位PFS分别为3.44个月和12.84个月,差异有统计学意义(χ2=39.730,P<0.001),两组中位OS分别为7.59个月和22.32个月,差异有统计学意义(χ2=40.505,P<0.001);Cox回归分析提示NLR高低、CEA水平是PFS、OS的独立预后因素(P<0.05)。结论 高水平NLR与晚期结直肠癌患者化疗疗效不佳和预后不良相关,可作为其化疗疗效及预后监测的指标。
Objective To evaluate the value of neutrophil-lymphocyte ratio (NLR) in the chemotherapy curative effect and prognosis of patients with advanced colorectal cancer (CRC). Methods Retrospective collection of clinical data from 50 patients with advanced unresectable colorectal cancer who received oxaliplatin-based standard first-line chemotherapy between January 2016 and April 2019. Chemotherapy curative effect was evaluated following 2 chemotherapy cycles. Calculation of neutrophil to lymphocyte ratio (NLR) based on pre-chemotherapy hematology data. The receiver operating characteristic curve was used to determine the optimal cutoff value of NLR,according to patients who were divided into groups of high NLR(NLR≥3.785)and low NLR(NLR≥3.785).The differences between high and low NLR and clinicopathological features, efficacy of chemotherapy, progression-free survival (PFS), and total survival (OS) were compared. COX regression analysis mode was used to analysis of factors affecting PFS and OS in patients with advanced colorectal cancer. Results The differences in tumor differentiation (P=0.030), ECOG score (P=0.003), CEA (P=0.011), CA19-9 (P=0.047) in the high and low NLR groups were statistically significant. The differences in chemotherapy between the two groups was statistically significant (P<0.001), and the high NLR group was less effective. The median PFS of the high and low NLR groups were 3.44 months and 12.84 months, respectively, and the difference was statistically significant (χ2=39.730, P<0.001). The median OS of the high and low NLR groups was 7.59 months and 22.32 months, respectively, and the difference was statistically significant (χ2=40.505, P<0.001). Cox regression analysis suggested that NLR levels and CEA levels were independent prognostic factors for PFS and OS(P<0.05). Conclusion High-level NLR is associated with poor chemotherapy response and poor prognosis in patients with advanced colorectal cancer, and was used as an indicator of chemotherapy efficacy and prognosis.