Tumor-derived exosomes (TDEs) are key immune regulators in the tumor microenvironment. They have been shown to reshape the immune microenvironment and prevent antitumor immune responses via their immunosuppressive cargo, thereby determining responsiveness to cancer therapy. By delivering suppressive cargo to the immune cells, TDEs directly or indirectly influence the functions and antitumor activities of immune cells. TDE-based therapy is emerging as a cutting-edge and promising strategy for inhibiting tumor progression or enhancing antitumor immunity. Therefore, in this study, we reviewed the mechanism by which TDEs regulate immune cells and their applications in immunotherapy.

BACKGROUND:Short-chain fatty acids exert anti-cancer effects on tumor cells.OBJECTIVE:We aimed to reveal the signaling network altered by butyrate in Gastric Cancer (GC) using small RNA sequencing (sRNA-seq).METHODS:The effects of butyrate on the biological behavior of NCI-N87 and KATO III cells in vitro were assessed by functional assays and half-maximal inhibitory concentrations (IC50) of butyrate in KATO III cells were calculated. sRNA-seq was performed on KATO III cells. Differentially expressed miRNAs (DE-miRNAs) were identified between butyrate treatment and control groups using DESeq2, and miRNA targets were predicted. A protein-protein interaction (PPI) network of DE-miRNA targets was created using Metascape. Key MCODE complexes were identified using the MCODE algorithm and cluster Profiler. The relationship between DE-miRNA and GC overall survival (OS) was evaluated using Kaplan-Meier curves.RESULTS:Butyrate dose-dependently inhibited NCI-N87 and KATO III cell viability. KATO III cells were more sensitive to butyrate than NCI-N87 cells. Butyrate promoted apoptosis and inhibited KATO III cell migration. Total 324 DE-miRNAs were identified in KATO III cells, and 459 mRNAs were predicted as targets of 83 DE-miRNAs. Two key protein complexes were identified in a PPI network of the 459 targets. A key signaling network responding to butyrate was generated using targets in these key complexes and their miRNA regulators. The DE-miRNAs in the key signaling network were related to the OS of GC.CONCLUSION:Butyrate altered the biological behavior of GC cells, which may be achieved by regulating miRNAs and related oncogenic pathways.

Background. Although the effects of methylation of the Ras association domain-containing protein 1 isoform A (RASSF1A) gene in cell-free DNA on the outcomes of patients with different types of cancer have been reported, the results are inconsistent. Objective: To explore the relationships between RASSF1A methylation in cell-free DNA and the outcomes of cancer patients. Methods. The PubMed, Embase, and Web of Science databases were searched for papers related to this topic on December 8, 2021. The retrieved articles were screened by two independent researchers, following which the methodological quality of the selected studies was evaluated using the Newcastle-Ottawa Scale. Additionally, hazard ratios were calculated, and publication bias of the studies was determined using Egger’s test. Results. Nine relevant publications involving a combined total of 1254 patients with different types of cancer were included in this study. The combined results of the random effects models yielded a hazard ratio of 1.73 (95% confidence interval: 1.31, 2.29; P < 0.001 ), which suggested there was a significant association between RASSF1A methylation and overall survival, and patients with an RASSF1A methylation status had a significantly increased risk of total death. Moreover, the Egger test result suggested there was no significant publication bias among the included studies. Conclusions. The methylation of RASSF1A in cell-free DNA in cancer patients was observably associated with an increased risk of poor overall survival.

An extraperitoneal colostomy is not sufficiently effective in preventing parastomal hernias. On the basis of anatomic structures and mechanical principles, we modified this surgical technique by preserving the integrity of the posterior rectus abdominis sheath to prevent parastomal hernia, and we applied it clinically.

MiR-1253 has been reported to play vital roles in a variety of cancers. However, its function in the progression and prognosis of colon cancer remains unclear. Here, the clinical significance and biological function of miR-1253 in the development of colon cancer was investigated. The expression of miR-1253 was identified in colon cancer tissues and cell lines by qRT-PCR. The prognostic value of miR-1253 was evaluated by Kaplan–Meier and Cox regression analysis. The roles of miR-1253 in regulating cell proliferation, migration, and invasion of colon cancer were evaluated in vitro by CCK8 and Transwell assay. It was found that miR-1253 was significantly downregulated in colon cancer tissues and cell lines (P < 0.001). The downregulation of miR-1253 was associated with the TNM stage (P = 0.007) and lymph node metastasis (P = 0.037) of patients. MiR-1253 (HR factor = 2.564, 95% CI = 1.077–6.107, P = 0.033) and TNM stage (HR factor = 2.899, 95% CI = 1.024–8.205, P = 0.045) were identified as independent factors that can predict the prognosis of patients. Functionally, miR-1253 acts as a tumor suppressor that inhibited cell proliferation, migration, and invasion of colon cancer through targeting EZH2. MiR-1253 was identified as a prognostic biomarker and a tumor suppressor of colon cancer.

Purpose: We aimed to screen novel genetic biomarkers for use in a prognostic score (PS) model for the accurate prediction of survival outcomes for patients with colon adenocarcinoma (COAD). Methods: Gene expression and methylation data were downloaded from The Cancer Genome Atlas database, and the samples were randomly divided into training and validation sets for the screening of differentially methylated genes (DMGs) and differentially expressed genes (DEGs). Co-methylated genes were screened using weighted gene co-expression network analysis. Functional enrichment analysis was performed using the Database for Annotation, Visualization, and Integrated Discovery. Univariate and multivariate Cox regression analyses were performed to identify prognosis-related genes and clinical factors. Receiver operating characteristic curve analysis was carried out to evaluate the predictive performance of the PS model. Results: In total, 1434 DEGs and 1038 DMGs were screened in the training set, among which 284 were found to be overlapping genes. For 127 of these overlapping genes, the methylation and expression levels were significantly negatively correlated. An optimal signature from 10 DMGs was identified to construct the PS model. Patients with a high PS seemed to have worse outcomes than those with a low PS. Moreover, cancer recurrence and the PS model status were independent prognostic factors. Conclusion: This PS model based on an optimal 10-gene signature would help in the stratification of patients with COAD and improve the assessment of their clinical outcomes.

Extraperitoneal colostomy is a widely used technique during abdominoperineal resection (APR) operation for lower rectal cancer. This technique has been reported to be effective to prevent the postoperative parastomal hernia in some retrospective studies, however, there is still a certain incidence of parastomal hernia. A modification of the extraperitoneal colostomy technique is described in this paper that keeps posterior rectal sheath intact instead of having a conventional incision, to further reduce the risk of parastomal hernia. Until now, this modified technique has been performed in 15 patients, no occurrence of parastomal hernia was observed.

An early diagnosis and effective prognostic factors would greatly reduce the mortality rate of colorectal cancer (CRC). This research is intended to complete the evaluation of the prognostic value and potential role of miR-1180-3p in CRC. The miR-1180-3p levels were reduced in CRC patients' tissues, blood, and human CRC cell lines. The ability of miR-1180-3p was explored in discrimination of CRC patients and healths and the value in overall survival estimate. The effect of miR-1180-3p dysregulation on the CRC cellular function was investigated. miR-1180-3p is downregulated in CRC tissues, blood and cells than normal ones. This lower expression was correlated with vascular invasion, lymph node metastasis, and TNM stage. With the use of ROC curve, miR-1180-3p showed discriminating ability in CRC patients and healthy subjects. With the result of Kaplan-Meier analysis and multi-multivariate Cox analysis, miR-1180-3p was an independent predictor for CRC patients' overall survival. Utilizing CCK-8, Transwell and matrigel assays, overexpression of miR-1180-3p reduced cancer cell proliferation and mobility, but induced apoptosis, by targeting COL12A1. miR-1180-3p might function as a suppressor in CRC progression and allowed the discovery of a new biomarker for diagnosis, prognosis and therapy target for CRC.

目的 探讨过表达miR-320a对结肠癌HCT116细胞的生物学行为的影响,并初步分析miR-320a对KLF5的调控机制.方法 将miR-320a模拟物转染结肠癌HCT116细胞,建立过表达miR-320a结肠癌HCT116细胞系,采用CCK-8方法检测转染后HCT116细胞增殖能力,Transwell实验检测转染后HCT116细胞侵袭能力.通过网站Targetscan7.2预测KLF5是否为miR-320a的靶基因,双荧光素酶实验进行验证.Western blot检测转染后各组HCT116细胞中KLF5蛋白表达.结果 CCK-8实验结果显示,miR-320a过表达抑制HCT116细胞增殖能力,Transwell实验结果显示,miR-320a过表达抑制HCT116细胞的侵袭能力,Western blot结果显示,上调miR-320a可使HCT116细胞中KLF5蛋白表达下降,TargetScan7.2网站分析及双荧光素酶实验证实KLF5为miR-320a的靶基因.结论 过表达miR-320a可以抑制结肠癌HCT116细胞增殖及侵袭能力,其机制可能与下调KLF5的表达有关.

目的 研究结直肠癌中miR-320a和KLF5的表达,分析二者表达相关性及其临床意义.方法 通过OncomiR公共数据库分析miR-320a在结直肠癌中的表达.通过GEPIA、HPA公共数据库分析结直肠癌中KLF5基因的表达,通过GEPIA分析KLF5表达患者生存期的关系.通过在线预测工具(TargetscanHuman 7.2,miRDB)预测KLF5是否为miR-320a的靶基因.应用实时定量PCR及Western blot在细胞水平检测miR-320a和KLF5的表达,并用CCK8法研究SW480、HCT116细胞的增殖能力.结果 OncomiR分析结果显示,结直肠癌中miR-320a表达下降(P＜0.05);GEPIA分析结果显示,在结直肠癌中,KLF5的mRNA表达增加;HPA分析结果显示,在结直肠癌中,KLF5的蛋白表达水平增加.在结肠腺癌患者中,KLF5的mRNA表达与无病生存期(DFS)显著相关(P＜0.05);在直肠腺癌患者中,KLF5的mRNA表达与总生存期(OS)显著相关(P＜0.05).在线预测网站预测结果显示,在KLF5基因的3'UTR区域,有1处miR-320a的结合位点.实时定量PCR及Western blot结果显示,miR-320a在SW480和HCT116中表达下降,KLF5在SW480和HCT116中表达增加.结论 在结直肠癌中miR-320a呈现低表达,KLF5呈现高表达,miR-320a可能通过靶向KLF5的表达影响结直肠癌的病程.

目的 应用在线公共数据库分析转录因子RUNX1的表达,研究其表达的临床意义.方法 通过Oncomine、GEPIA公共数据库分析结直肠癌中RUNX1基因mRNA的表达情况,通过HPA(Human Protein Atlas)数据库分析RUNX1基因的蛋白表达情况,通过GEPIA分析RUNX1表达与肿瘤病理分期的关系以及RUNX1表达与患者生存期的关系.结果 RUNX1 mRNA和蛋白在结直肠癌表达水平上调,与结直肠癌分期无显著相关.RUNX1表达与结肠癌(COAD)患者总体生存率(OS)和无病生存率(DFS)显著相关,其表达量越高,患者生存期越短;但与直肠癌(READ)患者OS和DFS无显著相关.结论 RUNX1参与结肠癌的发病机制,是治疗结肠癌的潜在靶点.

目的 探索腹腔镜直肠癌根治术治疗高龄患者的疗效.方法 选择2017年5月—2018年5月期间收治的100例高龄直肠癌患者为试验对象,采用数据库随机分为对照组和观察组,各50例,分别进行开腹手术治疗、腹腔镜直肠癌根治术治疗,随后对比两组各项指标.结果 观察组CA199(25.65±3.19)U/mL、CEA(4.36±1.65)ng/mL、AFP(5.17±1.33)ng/mL、CRP(5.19±1.22)mg/L、 并发症发生率(4.00％)、淋巴结转移数目(5.96±0.57)枚、淋巴结清扫数目(10.31±1.39)枚、手术时间(48.95±5.69)min、切口大小(2.37±0.17)cm、开始进食时间(12.19±5.85)h、肠鸣音恢复时间(29.37±5.52)h、 肛门排气时间(10.18±2.52)d、腹胀持续时间(3.49±0.35)d均优于对照组(P<0.05).结论 对高龄直肠癌患者实施腹腔镜直肠癌根治术治疗效果显著,可发挥操作简便、安全性高、疗效高、术后并发症少、恢复快等特点,更利于病情康复,加速胃肠道功能恢复,降低手术风险,改善预后.

目的 研究结肠癌中miR-144与Krüppel样因子12(KLF12)的表达,并探讨二者表达的相关性及其临床意义.方法 通过Oncomine公共数据库分析结直肠癌中KLF12基因mRNA的表达,通过UALCAN、GEPIA公共数据库分析结肠癌中KLF12基因mRNA的表达、通过GEPIA公共数据库分析KLF12表达与肿瘤病理分期的关系以及KLF12表达与患者生存期的关系.通过OncomiR公共数据库分析miR-144在结肠癌中的表达以及miR-144表达与患者生存期的关系.通过在线预测工具(TargetscanHuman 7.2,miRDB)预测KLF12是否为miR-144的靶基因.结果 结肠癌中KLF12 mRNA表达水平下降,与结直肠癌的分期显著正相关,与无病生存率(Disease Free Survival,DFS)显著负相关.miR-144在结肠癌中表达水平升高,在生存组患者表达水平升高.在KLF12基因的3'UTR区域,有3处miR-144的结合位点.结论 miR-144可能通过影响KLF12的表达参与直肠癌的发生、发展.

目的 探究中低位直肠癌患者接受腹腔镜治疗的效果.方法 将中低位直肠癌患者150例,以双盲法进行随机分组,时间为2017年1月-2019年1月,对照组实施开腹手术治疗,试验组则实施腹腔镜手术治疗,分析两组中低位直肠癌患者肛门排气时间、住院时间、手术出血量、手术用时、淋巴结清扫数、并发症发生情况的差异.结果 试验组中低位直肠癌患者的肛门排气时间(1.98±0.75)d、住院时间(5.56±1.19)d、手术出血量(56.89±20.12)ml、手术用时(137.89±35.85)min均低于对照组肛门排气时间(3.71±1.12)d、住院时间(3.71±1.12)d、手术出血量(122.67±56.87)mL、手术用时(180.36±45.71)min,差异有统计学意义(t值分别为11.1150,7.0933,9.4435,6.3314,P值均<0.05);试验组淋巴结清扫数(11.23±0.75)个与对照组淋巴结清扫数(11.30±0.82)个相比,无统计学意义(t值=0.5455,P值>0.05);试验组中低位直肠癌患者的并发症发生率(5.33％),相较于对照组并发症发生率(21.33％),明显更低,差异有统计学意义(χ2值=8.3077,P值<0.05).结论 中低位直肠癌患者接受腹腔镜手术治疗,可较好将淋巴结清除,效果好,且可缩短患者的治疗和康复时间,减少其手术出血量,安全有效.

目的 探讨miR-129对结肠腺癌SW480细胞增殖的影响及可能的机制.方法 采用miR-129模拟物转染结肠腺癌SW480细胞,分为空白对照组(未进行转染)、miR-129阴性对照组(转染无关序列)、miR-129模拟物转染组(转染miR-129模拟物),通过实时定量PCR进行验证,Western blot检测miR-129过表达后SW480细胞RUNX1蛋白的表达.采用CCK-8法检测miR-129对SW480细胞增殖的影响,采用生物信息学网站预测RU NX1是否为miR-129潜在的靶基因,应用双荧光素酶报告基因实验进行验证.结果 miR-129过表达,SW480细胞中RUNX1mRNA和蛋白表达下调,抑制SW480细胞体外增殖,生物信息学分析结果显示RUNX1是miR-129的靶基因之一,双荧光素酶实验证实RUNX1为miR-129的下游靶基因.结论 miR-129通过靶向调控RUNX1抑制结肠腺癌SW480细胞增殖.

目的 研究中性粒细胞/淋巴细胞比值(NLR)与结直肠癌病理因素及预后的关系,为临床预测结直肠癌预后提供依据.方法 回顾性分析2013年1月至2016年1月中国医科大学附属第四医院收治的120例可手术结直肠癌患者的临床资料,收集患者入院2 d的血常规资料,计算NLR.对患者进行随访,随访截至2019年3月30日,采用受试者工作特征(ROC)曲线分析术前NLR对可手术结直肠癌患者死亡率的预测价值.分析NLR与结直肠癌病理特征及预后的关系,采用Cox分析影响结直肠癌患者全因死亡的危险因素.结果 截至随访结束,本组120例患者中有10例失访,随访成功率91.7％(110/120).中位随访时间为55个月.110例中死亡37例,存活73例.ROC曲线显示,NLR预测死亡的最佳临界点为3.1,此时的灵敏度为65.2％,特异度为74.4％.将3.1作为NLR的临界值,将110例患者分为NLR升高组(NLR>3.1)40例和NLR降低组(NLR≤3.1)70例.NLR升高组的年龄、恶性肿瘤家族史比例、肿瘤部位在结肠者及TNM分期为Ⅲ期的比例高于NLR降低组,差异有统计学意义.logistic回归分析显示肿瘤部位为结肠(OR=1.325,95％CI=1.104～2.654,P=0.042)、TNM分期高(OR=1.674,95％CI=1.233～5.987,P=0.032)是术前NLR升高的独立危险因素.NLR升高组的生存率较NLR降低组显著降低,差异有统计学意义(P<0.05).Cox多因素回归分析显示,术前NLR(OR=1.725,95％CI=1.124～6.674)、TNM分期(OR=1.835,95％CI=1.324～8.417)、年龄(OR=1.129,95％CI=1.054～2.215)、肿瘤分化程度(OR=1.378,95％CI=1.114～3.699)、脉管侵犯(OR=1.341,95％CI=1.097～3.241)是结直肠癌患者死亡率的独立影响因素(P<0.05).结论 术前NLR是结直肠癌死亡率的独立影响因素,可用于预测结直肠癌患者预后,NLR升高患者的预后不良.

Objective To investigate how microRNA 24 (miR-24) regulates the development of lung cancer. Methods The levels of miR-24 in 30 cases of lung cancer were detected using real-time PCR, and the relationship between miR-24 levels and overall survival was analyzed. After overexpression or silencing of miR-24 in A549 lung cancer cells, the effect on cell proliferation was observed by the MTT assay. Transwell assays were carried out to observe the effect of miR-24 on cell migration. The effects of miR-24 on the expression of cyclin-dependent kinase (CDK) 4/6 and matrix metalloproteinase (MMP) 2 in A549 cells were examined by Western blotting. Results Survival analysis showed that patients with low miR-24 expression had a shorter survival time. The MTT-based viability assay revealed that overexpression of miR-24 inhibited A549 cell proliferation. Cell proliferation was promoted when miR-24 was inhibited. In the Transwell assay, overexpression of miR-24 significantly inhibited the A549 cell migration, and cell migration increased when miR-24 was inhibited.Western blotting analysis revealed that overexpression of miR-24 could inhibit CDK4/6 and MMP2 production in A549 cells. Inhibition of miR-24 was associated with increased production of CDK4/6 and MMP2 in A549 cells. Conclusion miR-24 can inhibit the proliferation and migration of A549 lung cancer cells.

Objective To explore the effect of noscapine on the biological function of A549 cells and its underlying mechanism. Methods Concentrations of 10 μmol/L and 20 μmol/L of noscapine were used on the A549 cells. The effect of noscapine on their proliferation was observed via the MTT assay. Western blotting and real time PCR were used to detect the effects on Cyclin D1, BCL-2, and MMP2. The Hoechst 33258 staining assay was used to observe the effects of noscapine on the apoptosis of A549 cells. The metastasis of A549 cells was detected by using the Transwell assay. Results The MTT assay showed that the rate of inhibition of cell proliferation after treatment with 10 μmol/L and 20 μmol/L noscapine were (32.98±1.09) ％ and (49.56±3.98) ％, with a significant difference between the values (P ＜ 0.05). Hoechst 33258 staining evinced that noscapine promoted apoptosis, while the Transwell assay displayed that noscapine inhibited A549 cell metastasis. Western blotting and real time PCR indicated that the expression of Cyclin D1, BCL-2, and MMP2 in A549 cells was inhibited by noscapine. Conclusion Noscapine can inhibit the growth and metastasis of the lung cancer cell line A549 and promote the apoptosis of A549 cells. In conclusion, noscapine can potentially be used as a chemotherapeutic drug for lung cancer.

目的:比较自固定补片与缝合补片在Lichtenstein腹股沟疝修补术中应用的效果.方法:计算机检索2010年1月-2019年1月国内外数据库中关于在Lichtenstein无张力疝修补术中应用自固定补片与缝合补片效果比较的随机对照试验(RCT).按照纳入和排除标准筛选文献后,使用Cochrane风险偏倚评估工具进行质量评价,采用Review Manager 5.3统计学软件进行效应量的合并分析.结果:最终纳入14项RCT共3 904例患者,其中自固定补片组1 930例,缝合补片组1 974例.Meta分析结果显示,与缝合补片组比较,自固定补片组的手术时间明显缩短(MD=-5.31,95％ CI=-8.11～-2.51,P=0.000 2),术后切口感染发生率明显降低(RR=0.46,95％ CI=0.26～0.81,P=0.007),但术后疝复发率较高(RR=1.67,95％ CI=1.12～2.48,P=0.01).两组患者的术后慢性腹股沟区疼痛发生率、术区异物感发生率、血肿发生率、血清肿发生率差异均无统计学意义(均P＞0.05).结论:与传统缝合补片在Lichtenstein无张力修补术中应用效果相比,自固定补片具有缩短手术时间和降低术后切口感染发生率的优势,但术后短期(1年内)疝复发率可能升高,但该结论仍需更大样本高质量的研究予以验证.

目的:探讨miR-548d对骨肉瘤细胞增殖和迁移的影响.方法:通过Real time PCR及Western blot检测miR-548d和KRAS在30例骨肉瘤组织以及293、MG63和U2OS细胞中的表达情况.对30例骨肉瘤组织中miR-548d和KRAS含量的相关性进行分析,随后通过报告基因实验印证miR-548d对KRAS的靶向作用.MG63细胞中分别过表达或沉默miR-548d后,通过Western blot实验分析KRAS的变化情况,MTT实验观察miR-548d对细胞增殖的影响,Transwell实验观察miR-548d对其迁移能力的影响.结果:骨肉瘤组织及细胞中miR-548d表达较低,KRAS表达较高.在骨肉瘤组织中miR-548d与KRAS的表达呈负相关.报告基因实验证明miR-548d可以直接打靶KRAS.Western blot指出miR-548d可以抑制KRAS的表达.最后MTT和Transwell实验指出miR-548d可以抑制MG63细胞的增殖与迁移.结论:miR-548d可以通过打靶KRAS抑制骨肉瘤细胞的增殖和迁移.