Drug degradation poses a significant challenge in the pursuit of effective gene therapies for cancers. Here we have developed a bioactive nanosized composite that utilizes human umbilical cord mesenchymal stem cells (hucMSCs) derived small extracellular vesicles (sEVs), to carry tumor suppressor miR-145 alongside erbium-doped rare earth nanoparticles (ErNPs). This approach not only enhances in vivo delivery but also facilitates real-time fluorescence tracking of nucleic acid drugs in the near infrared (NIR) II window. With this technique, we are able to realize and visualize the effective inhibition of colorectal cancer (CRC) progression in a xenografted murine model. Our results revealed that the efficient loading of miR-145 into sEVs could be achieved through a dynamic combination of sonication and electroporation. The resulting miR-145-encapsulated sEVs (i.e., miRNA@sEVs) exhibited a profound ability to hinder tumor growth by effectively downregulating the expression of fascin actin-bundling protein 1 (FSCN1), both in vitro and in vivo. Additionally, the circulation half-time of miRNA@sEVs was measured to be 4 h and the fluorescence at the tumor sites reached a peak intensity at 8 h after intravenous injection of sEVs particles. Finally, the fluorescent signals of miRNA@sEVs were predominantly localized in the mouse liver and spleen, with substantial accumulation in tumors. Our results illuminated the excellent biosafety of miRNA@sEVs and their high accumulation in tumors, leading to efficient suppression of tumor progression. This research heralds a promising advancement in gene therapy, paving the way for more effective and safer treatment options. Not applicable.

To investigate the optimal closure time of a temporary ileostomy in patients with rectal cancer receiving anus-preserving operation. Patients with rectal cancer were enrolled from the Affiliated Hospital of Jiangsu University from May 2010 to June 2019. The eligible patients were grouped according to their actual ileostomy closure time after stoma creation. Outcomes were complications during stoma closure and complications within one year after stoma closure. This study included 361 qualified subjects, with 108 patients in the 3–5 months group, 133 in the 5–7 months group and 120 in the ≥ 7 months group. Compared with the risk of complications during stoma closure in the 3–5 months group, that in the 5–7 months group was significantly reduced (odds ratio [OR]: 0.36, 95

Objective:At present, renal injury caused by sepsis seriously endangers the health of patients. Our paper proposed to study the protective effects of meloxicam (Mel) in sepsis-induced acute kidney injury (SAKI) and the underlying mechanisms.Methods:The in vitro and in vivo models of SAKI were established using lipopolysaccharide (LPS). Mel was injected intraperitoneally at 60 mg/kg into male C57BL/6 mice 4 hours before LPS injection (10 mg/kg). The HK-2 cells were treated with LPS (1 μg/mL) and Mel (40 μM). The renal function and renal pathological changes as well as renal inflammation and apoptosis were detected in SAKI mice. The inflammation and apoptosis of HK-2 cells induced by LPS were also detected.Results:The treatment of Mel significantly decreased the elevated levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in SAKI mice. In addition, the results of HE staining suggested that Mel significantly reduced kidney damage in SAKI mice. Consistently, Mel reduced the expression of LPS-induced kidney injury markers (NGAL and KIM-1). Moreover, LPS induced the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the kidney, which can be reduced by Mel. Furthermore, Mel effectively reduced the number of apoptotic cells and inhibited the expression of proapoptotic-related proteins (cleaved Caspase-3 and Bax) but increased the antiapoptotic-related protein (Bcl-2) in the kidneys of SAKI mice. Mechanistically, Mel inhibited the phosphorylation of P65 but induced the phosphorylation of AKT and the expression of glycoprotein B of nonmetastatic melanoma (GPNMB). However, knocking down GPNMB can eliminate the anti-inflammatory and antiapoptotic effects of Mel.Conclusion:Mel alleviated sepsis-induced kidney injury by inhibiting kidney inflammation and apoptosis via upregulating GPNMB.

目的:运用生物信息学方法探究GJB3基因在胰腺癌组织中的表达及潜在作用机制,并进一步验证其在胰腺癌组织中的表达水平及其临床意义.方法:利用GEPIA在线数据库分析GJB3在胰腺癌组织中的表达及对预后的影响;从TCGA数据库下载有关GJB3基因的临床样本表达数据,分析GJB3表达与胰腺癌临床病理参数的相关性;采用实时荧光定量PCR法测定15例胰腺癌组织及其癌旁组织中GJB3基因的表达水平,结合数据库临床病理参数分析其表达水平对胰腺癌患者预后的影响.随后通过慢病毒介导的RNA干扰来沉默AsPC-1细胞株中的GJB3表达,进一步检测胰腺癌细胞增殖能力及细胞周期所受到的影响.结果:GJB3在胰腺癌组织中的表达量高于正常胰腺组织(P<0.05).与低表达患者相比,GJB3高表达患者的总体生存期(P<0.05)和无病生存期(P<0.05)较差.GJB3基因的表达与胰腺癌患者的T分期和TNM分期显著相关(P<0.05).GJB3在胰腺癌患者的癌组织中表达水平明显增高(P<0.05).沉默GJB3表达后,胰腺癌AsPC-1细胞的增殖能力受到抑制(P<0.05).结论:GJB3基因在胰腺癌组织中的表达水平显著增高,与胰腺癌不良的预后相关,沉默GJB3能抑制胰腺癌细胞增殖,同时GJB3可能通过影响细胞周期加速胰腺癌的进展.

目的 通过生物信息学及细胞学实验方法,研究长链非编码RNA(LncRNA)PCA3在胃癌发生发展及预后方面的价值.方法 利用癌症基因组图谱(TCGA)和基因型-组织表达数据库(GTEx)中的高通量测序数据,对PCA3的表达及其与临床资料的相关性进行分析.采用肿瘤免疫评估资源(TIMER)数据库分析PCA3在免疫浸润物中的表达及对胃癌患者生存预后的影响.随后通过慢病毒介导的RNA干扰来沉默AGS细胞株中的PCA3表达,并用CCK-8法及Transwell小室法来检测细胞的增殖、迁移及侵袭能力.结果 TCGA及GETx数据库分析发现,PCA3在胃癌组织中的表达水平高于正常胃黏膜组织(P<0.0001),且表达越高,患者的总体生存期越短(P<0.01).相关性分析显示,PCA3的表达与肿瘤T分期及分化程度之间有关联(P<0.05).TIMER数据库分析显示在免疫微环境中高表达PCA3 mRNA的巨噬细胞对胃癌患者生存预后较差(P<0.05).与空白对照组及阴性对照组相比,PCA3的表达降低后,胃癌AGS细胞的增殖、迁移及侵袭能力受到抑制(P<0.05).结论 PCA3可能成为一种新型肿瘤标志物,有助于胃癌的早期诊断及预后评估,对促进胃癌诊治及提高患者预后具有一定的价值.

目的:比较腹腔镜辅助胃癌根治术中功能型助手与支架型助手的作用.方法:回顾分析2017年1月至2019年12月收治的122例行腹腔镜辅助胃癌根治术(全胃切除,食管-空肠Roux-en-Y吻合术)患者的临床资料.其中,60例为支架型助手组(对照组),62例为功能型助手组(研究组).对比分析两组围手术期及近期随访情况.结果:入组患者均顺利完成手术,无围手术期死亡病例.与支架型助手组相比,功能型助手组手术时间短[(208.1±34.8)min vs.(259.4±37.9)min,P<0.001],淋巴结清扫数量多[(30.2±7.4)枚vs.(26.0±6.4)枚,P=0.001],术中出血量少[(115.0±61.9)mL vs.(200.5±71.5)mL,P<0.001],切口短[(6.7±0.8)cm vs.(8.1±0.6)cm,P<0.001],首次进食流质早[(4.7±1.1)d vs.(5.2±1.3)d,P=0.033];两组首次排气时间[(3.8±0.9)d vs.(4.1±1.2)d,P=0.116]、引流管拔除时间[(9.0±2.5)d vs.(8.2±2.8)d,P=0.096]及术后住院时间[(10.7±2.8)d vs.(9.9±2.5)d,P=0.107]差异均无统计学意义.结论:功能型助手在腹腔镜辅助胃癌根治术中优势明显,与支架型助手相比,具有创伤小、出血少、手术时间短、淋巴结清扫更彻底等优势,近期效果显著.

Oxidative stress and neuronal apoptosis are considered crucial therapeutic targets against early brain injury (EBI) after subarachnoid hemorrhage (SAH). Emerging evidence indicates that mitochondrial dysfunction is the main reason for oxidative stress and neuronal apoptosis. MitoNEET, an outer mitochondrial membrane protein, has been shown to regulate mitochondrial function. However, whether mitoNEET activation attenuates oxidative stress and neuronal apoptosis after SAH remains unknown. This study was therefore conducted to verify the neuroprotective role of mitoNEET in EBI after SAH in rats. A total of 93 rats were subjected to an endovascular perforation model of SAH. TT01001, a selective agonist of mitoNEET, was administered intraperitoneally 1 h after SAH induction. Neurological tests, immunofluorescence, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining, dihydroergotamine (DHE) staining, and western blot experiments were performed. The results showed that MitoNEET is expressed in neurons, but significantly decreased at 24 h after SAH induction. Activating mitoNEET with TT01001 significantly improved the neurological deficits, and reduced oxidative stress and neuronal apoptosis as measured by DHE and TUNEL staining, when compared with the SAH+vehicle group. Furthermore, TT01001 treatment decreased the expression of the proapoptotic marker, Bax, while increasing the expression of the antiapoptotic marker, Bcl-2. Together, our results suggested that mitoNEET activation with TT01001 reduced oxidative stress injury and neuronal apoptosis by improving mitochondrial dysfunction in EBI after SAH.

目的 探讨远端胃癌根治术后行残胃-空肠Roux-en-Y(R-Y)吻合的适用情况及其有效性、安全性和经济性.方法 选取胃癌患者84例,根据消化道重建方式的不同分为Roux-en-Y(R-Y)组(n=38)和毕Ⅰ(BillrothⅠ)组(n=46),对比分析两组患者的一般情况、术中情况、术后恢复情况、术后并发症的发生情况及住院总费用.结果 与毕Ⅰ式组相比,R-Y组患者肿瘤体积较大、侵润程度较深、分期较晚,手术时间较长,留置腹腔引流管时间较长,住院费用较高,残胃炎的发生率较小,但进食后腹胀却高于毕Ⅰ式组(P<0.05).结论 R-Y吻合术与毕Ⅰ式吻合术相比各有利弊,当患者肿瘤体积较大、侵润较深、分期较晚时,为更好的达到根治的目的,宜选用R-Y吻合术进行消化道重建.

Oxidative stress and apoptosis of vascular smooth muscle cells (VSMCs) are key to vascular calcification in patients with chronic kidney disease (CKD). The mitochondria-targeted antioxidant, mitoquinone (MitoQ), which reduces oxidative stress and apoptosis, has a protective effect in acute models of renal injury but whether MitoQ can attenuate vascular calcification in CKD patients is unknown. This study was conducted to investigate whether MitoQ can prevent calcification, both in vitro and in vivo. Adenine was used to induce calcification in rats, and inorganic phosphate was used to induce calcification in VSMCs. To elucidate the underlying molecular mechanism, a specific inhibitor of Nrf2, ML385, was used 1 h before MitoQ administration. Histological staining, ELISA, flow cytometry, alizarin red staining and western blotting were used to test this hypothesis. Administration of MitoQ alleviated calcification and oxidative stress. The anti-apoptotic effect of MitoQ was associated with upregulation of Bcl-2, downregulation of Bax, and increased Nrf2 expression. The effects of MitoQ were reversed by treatment with ML385. This study offers evidence that MitoQ attenuates vascular calcification by suppressing oxidative stress and apoptosis of VSMCs through the Keap1/Nrf2 pathway. MitoQ should be further investigated as a potential therapy to prevent vascular calcification in CKD patients.

Introduction Long non-coding RNAs (lncRNAs) have been demonstrated to participate in many biological processes and severs as important regulators during the progression of gastric cancer. Methods Here, we introduced human lncRNA SNHG15 which was highly expressed in gastric cancer and cells. Interestingly, the expression of SNHG15 was correlated with programmed cell death ligand 1 (PD-L1), which promotes the resistance of gastric cancer cells to immune responses. Meanwhile, SNHG15 downregulation suppressed the expression of PD-L1 and resistance of immune responses. Results Further, our results suggested that SNHG15 acted as a competing endogenous RNA (CeRNA) to sponge miR-141, which was downregulated in gastric cancers and negatively correlated to PD-L1. Conclusion Our results suggested that SNHG15 improved the expression of PD-L1 by inhibiting miR-141, which in turn promoted the resistance of stomach cancer cells to the immune responses.

目的 探究血清C反应蛋白(CRP)对直肠癌行腹腔镜手术后吻合口瘘的预测效果.方法 选取2014年1月—2018年11月在江苏大学附属医院行腹腔镜手术的141例患者.其中,发生吻合口瘘的22例患者作为观察组,未发生吻合口瘘的119例患者作为对照组.分析两组手术前后7 d内患者血清CRP水平变化.结果 两组血清CRP水平比较,采用重复测量设计的方差分析,结果:①不同时间点血清CRP有差别(F=116.970,P=0.000);②两组血清CRP有差别(F=241.717,P=0.000);③两组血清CRP变化趋势有差别(F=32.776,P=0.000).行预防性造口组与未行预防性造口组血清CRP水平比较,采用重复测量设计的方差分析,结果:①不同时间点的血清CRP有差别(F=28.057,P=0.000);两组间的血清CRP无差别(F=0.009,P=0.927);③两组血清CRP变化趋势无差别(F=0.029,P=0.993).低位组与高位组血清CRP水平比较,采用重复测量设计的方差分析,结果:①不同时间点血清CRP有差别(F=22.473,P=0.000);②两组血清CRP无差别(F=0.197,P=0.662);③两组血清CRP变化趋势无差别(F=0.017,P=0.997).术后3 d患者ROC曲线下面积最大,达到0.902(95％CI:0.613,1.000).血清CRP临界点为80.13 mg/L,预测吻合口瘘的敏感性为0.821(95％CI:0.648,0.994),特异性为0.859(95％CI:0.733,0.985).结论 直肠癌患者行腹腔镜手术后可以通过其血清CRP水平预测吻合口瘘的发生.

Non-coding RNAs (ncRNAs) have been previously reported to serve an important role in transcription. In addition, several studies have revealed that long ncRNAs (lncRNAs) have a crucial role in human diseases. However, the association between lncRNAs and inflammation-induced intestinal macrophages in the intestinal mucosal barrier has remained elusive. In the present study, intestinal macrophages from healthy Sprague Dawley rats were divided into two groups: The experimental group, consisting of intestinal macrophages treated with 1 mg/l lipopolysaccharide (LPS) and the control group, composed of untreated cells. Differentially expressed (DE) lncRNAs and mRNAs between the control and experimental groups were identified using microarray profiling. The levels of DE mRNAs and lncRNAs were measured by reverse transcription-quantitative PCR (RT-qPCR). Furthermore, Gene Ontology (GO) and pathway enrichment analyses of DE mRNAs and lncRNAs were performed. To identify core regulatory factors among DE lncRNAs and mRNAs, a lncRNA-mRNA network was constructed. A total of 357 DE lncRNAs and 542 DE mRNAs between the LPS-treated and untreated groups were identified (fold-change >1.5; P<0.05). In addition, selected microarray data were confirmed by RT-qPCR. GO analysis of the DE mRNAs indicated that the biological functions of the upregulated mRNAs included inflammatory response, immune response, metabolic process and signal transduction, whereas those of the downregulated mRNAs were metabolic process, cell cycle, apoptosis and inflammatory response. In addition, pathway enrichment analysis of the upregulated mRNAs revealed that the most enriched pathways were the NF-kappa B signaling pathway, B-cell receptor signaling pathway and apoptosis, while the downregulated mRNAs were significantly involved in metabolic pathways, the phosphatidylinositol signaling system, cytokine-cytokine receptor interaction and the Toll-like receptor signaling pathway. The lncRNA-mRNA co-expression network suggested that lncRNAs NONMMUT024673 and NONMMUT062258 may have an important role in LPS-induced intestinal macrophages. The present study identified the DE profiles between LPS- and non-LPS-treated intestinal macrophages. These DE lncRNAs and mRNAs may be used as potential targets for attenuating excessive inflammatory response in intestinal mucosal barrier dysfunction.

目的:探讨YEATS域含蛋白质4(YEATS4)胰腺癌组织中的表达及其与临床意义.方法:用手术切除且病理确诊的80例胰腺癌组织及对应癌旁组织标本构建组织芯片,利用免疫组织化学技术检测YEATS4在胰腺癌及癌旁组织中的表达情况.分析胰腺癌组织中YEATS4的表达与胰腺癌临床病理特征及胰腺癌患者预后的关系.结果:免疫组化结果显示,YEATS4在胰腺癌组织中的阳性表达率明显高于相应癌旁组织(56.25％vs.26.25％,P＜0.05).YEATS4的阳性表达与胰腺癌患者的性别(P=0.037)、TMN分期(P＜0.001)、神经转移(P=0.006)、淋巴结转移(P＜0.001)以及脉管侵犯(P=0.042)明显有关.全组患者中YEATS4蛋白阴性表达患者生存率明显高于其阳性表达患者(x2=7-593,P=0.0059);亚组分析显示,YEATS4蛋白与不良预后的关系仅明显存在于TMN Ⅲ/Ⅳ期、淋巴结转移、神经转移和脉管侵犯患者中(均P＜0.05).YEATS4表达是胰腺癌患者预后的独立危险因素(HR=2.1,95％ CI=1.1～4.2,P=0.026).结论:YEATS4在胰腺癌中的表达量升高,可能参与了胰腺癌的进展,并可能是胰腺癌治疗的潜在预后标记和治疗靶点.

Background To investigate the expression and role of G-protein-signaling modulator 2 (GPSM2) in a CD133+ pancreatic stem cell subset. Materials and methods Pancreatic cancer stem cells (PCSCs) from the cell line PANC-1 were sorted into CD133+ and CD133− subsets by flow cytometry. The tumorigenic potential of the subsets was assessed by subcutaneous tumor formation experiments in nude mice. Differential expression of GPSM2 was examined by real-time quantitative-PCR (qPCR) and Western blotting. To silence GPSM2 expression, a shRNA lentiviral vector targeting GPSM2 was constructed and stably transfected into CD133+ PCSCs. The inhibitory efficiency of the GPSM2 gene was verified by qPCR and Western blotting. The proliferation, colony formation, and migration abilities of the transfected CD133+ pancreatic cancer cells were assessed by MTT, soft agar colony formation, and Transwell assays. Results CD133+ and CD133− cell subsets were successfully isolated from PANC-1 cells. The CD133+ subset subcutaneously formed tumors in nude mice that were significantly bigger (343.05±57.59 mm3 vs 176.86±32.58 mm3, P<0.01) and denser (4.13±0.37 g vs 1.07±0.21 g, P<0.01) than those of the CD133− group. The GPSM2 mRNA and protein expression was significantly higher in CD133+ cells than in CD133− cells. Stable downregulation of GPSM2 expression reduced the proliferation, colony formation, and migration abilities of CD133+ PANC-1 cells (P<0.05). Conclusion The CD133+PANC-1 cells have obvious stem cell characteristics and increased GPSM2 expression. Downregulation of GPSM2 significantly reduces the proliferation and migration ability of the cells. Therefore, GPSM2 may provide an important target for regulating PCSCs.

随着我国综合国力的不断提升,到我国学习临床医学的外国留学生日益增多,留学生教育已成为高等医学教育的重要组成部分.为适应医学留学生胃肠外科教学需要,结合留学生教学实践,本文提出制订合适的教学内容与方法,编写专用英文教材,加强教师英语口语表达能力并加强师生沟通.在传授知识的同时,还应注重临床实践能力的培养和医德医风的教育.实践表明,上述措施对提高教学质量有一定帮助.

目的:探讨叉头框C2(forkhead box C2,FOXC2)在胰腺癌中的表达及其与胰腺癌患者预后的相关性.方法:利用Oncomine数据库分析FOXC2 mRNA在胰腺癌及癌旁组织中的表达;收集112例胰腺患者癌组织及相应癌旁组织,采用qRT-PCR和免疫组织化学染色检测FOXC2的表达,并分析其与临床病理参数的关系.应用Kap-lan-meier法分析FOXC2表达对患者生存时间的影响.结果:Oncomine数据库中FOXC2 mRNA在胰腺癌癌组织中表达明显高于癌旁组织(tBadea=4.074,tPei=3.741,P均<0.05);FOXC2蛋白主要表达于胰腺癌细胞胞核,且癌组织免疫组化评分明显高于癌旁组织(t=7.571,P<0.05);FOXC2 mRNA在胰腺癌组织中表达明显高于癌旁组织(t=13.79,P<0.05);有淋巴结转移的癌组织中FOXC2阳性表达率高于无淋巴结转移的癌组织(χ2=16.998,P<0.01),胰腺癌Ⅲ期FOXC2阳性表达率高于Ⅰ期(χ2=15.688,P<0.001)和Ⅱ期(χ2=10.678,P=0.001).FOXC2阳性组胰腺癌患者的中位生存时间显著短于阴性组(χ2=10.32,P=0.0013),FOXC2阳性表达(HR=2.569,P=0.003)可作为预测胰腺癌预后的独立因素.结论:FOXC2在胰腺癌组织中呈高表达,且与胰腺癌患者的预后高度相关.

Objective To analyze the colonoscopy-assisted laparoscopic surgery in the treatment of early colorectal tumor, and further elevate the application value of them in the treatment of early colorectal cancer. Methods From January, 2014 to May, 2017, a total of 31 early colorectal tumor patients were treated with colonoscopy-assisted laparoscopic surgery in our hospital. Locations of colorectal lesions were explored by colonoscopy. According to the rapid frozen pathological results, laparoscopic surgery was selected. Results All patients were treated with colonoscopy-assisted laparoscopic surgery successfully, with no conversion to laparotomy. Among 22 cases of preoperative diagnosis of stageⅠcolorectal cancer, there were 20 cases of intraoperative and postoperative diagnosis of stageⅠ (13 cases of T1 N0 M0, 7 cases of T2 N0 M0) and 2 cases of stageⅢ ( T2 N1 M0). There were 9 cases of preoperative diagnosis of precancerous lesions, 2 of which were diagnosis of high grade intraepithelial neoplasia and 7 cases were diagnosis of high grade intraepithelial neoplasia with carcinogenesis. 6 cases were under polypectomy at the same time, the rapid frozen pathological results proved to be a low level adenomatoid polyp during the operation, and no additional surgery was performed. All patients were examined by colonoscopy half a year after operation. After that, 1 time a year was reviewed, and tumor markers were monitored at the same time. All patients were followed up 6-42 months, with a median of 32 months. Most of the patients were alive without recurrence except one case died of cerebral infarction 2 years after operation. Conclusion Laparoscopy combined with colonoscopy in treatment of early colorectal tumor has advantages of both endoscopy, especially suitable for lesions with difficult location or complete resection, which can improve surgical accuracy and safety.