BACKGROUND:Single-cell sequencing technology provides the capability to analyze changes in specific cell types during the progression of disease. However, previous single-cell sequencing studies on gastric cancer (GC) have largely focused on immune cells and stromal cells, and further elucidation is required regarding the alterations that occur in gastric epithelial cells during the development of GC.AIM:To create a GC prediction model based on single-cell and bulk RNA sequencing (bulk RNA-seq) data.METHODS:In this study, we conducted a comprehensive analysis by integrating three single-cell RNA sequencing (scRNA-seq) datasets and ten bulk RNA-seq datasets. Our analysis mainly focused on determining cell proportions and identifying differentially expressed genes (DEGs). Specifically, we performed differential expression analysis among epithelial cells in GC tissues and normal gastric tissues (NAGs) and utilized both single-cell and bulk RNA-seq data to establish a prediction model for GC. We further validated the accuracy of the GC prediction model in bulk RNA-seq data. We also used Kaplan-Meier plots to verify the correlation between genes in the prediction model and the prognosis of GC.RESULTS:By analyzing scRNA-seq data from a total of 70707 cells from GC tissue, NAG, and chronic gastric tissue, 10 cell types were identified, and DEGs in GC and normal epithelial cells were screened. After determining the DEGs in GC and normal gastric samples identified by bulk RNA-seq data, a GC predictive classifier was constructed using the Least absolute shrinkage and selection operator (LASSO) and random forest methods. The LASSO classifier showed good performance in both validation and model verification using The Cancer Genome Atlas and Genotype-Tissue Expression (GTEx) datasets [area under the curve (AUC)_min = 0.988, AUC_1se = 0.994], and the random forest model also achieved good results with the validation set (AUC = 0.92). Genes TIMP1, PLOD3, CKS2, TYMP, TNFRSF10B, CPNE1, GDF15, BCAP31, and CLDN7 were identified to have high importance values in multiple GC predictive models, and KM-PLOTTER analysis showed their relevance to GC prognosis, suggesting their potential for use in GC diagnosis and treatment.CONCLUSION:A predictive classifier was established based on the analysis of RNA-seq data, and the genes in it are expected to serve as auxiliary markers in the clinical diagnosis of GC.

[This corrects the article DOI: 10.3389/fonc.2021.752504.].

肝硬化是各种肝脏疾病的终末阶段,肝硬化能否逆转已争议多年,越来越多的证据表明,肝硬化在去除病因、得到有效治疗后可发生一定程度的逆转.肝纤维化是各种慢性肝病发展为肝硬化的重要中间环节,具有修复和损伤双重性,肝纤维化可进一步发展为肝硬化甚至肝癌,严重威胁患者生命.因此,肝纤维化逆转的研究对于临床诊治具有重要的指导意义.动物实验是生物医学研究的基本手段之一,也是连接基础研究和临床试验的重要桥梁,本文总结不同动物模型包括化学损伤性肝纤维化逆转模型、胆管结扎肝纤维化逆转模型和非酒精性脂肪性肝纤维化逆转模型等,通过归纳不同动物模型的优点与局限性,为肝纤维化逆转研究提供依据,以更好地指导临床实践.

目的 分析早期胃癌(EGC)内镜黏膜下剥离术后出血(PEB)的危险因素.方法 搜索中国知网、万方、维普数据库、中国生物医学文献数据库、PubMed、Embase、谷歌学术、Cochrane Library和Web of Science等数据库中关于EGC发生PEB的文章,使用纽卡斯尔-渥太华量表(NOS)对获取的文献进行质量评价.结果 共纳入9篇文献,研究对象5719例,发生PEB 282例(4.93％).Meta分析结果显示:男性(OR^:1.73,95％CI:1.26～2.37)、溃疡阳性(OR^:1.83,95％CI:1.04～3.22)、抗血栓类药物(OR^:2.17,95％CI:1.65～2.86)、操作时间(MD:12.48,95％CI:1.72～23.23)、病灶切除大小(MD:5.30,95％CI:3.32～7.29)和浸润深度(O R^:1.53,95％CI:1.04～2.26)是EGC发生PEB的危险因素.结论 男性、术中发现溃疡阳性、使用抗血栓类药物、操作时间、病灶切除大小和浸润深度是EGC发生PEB的独立危险因素,尤其是使用抗血栓类药物治疗的患者,要引起足够的重视.

目的 探讨影响胃癌肝转移(gastric cancer liver metastasis,GCLM)患者预后因素,建立预后列线图并对患者进行危险分层.方法 从SEER(surveillance epidemiology and end results)数据库中收集GCLM患者的临床及病理学资料,通过单因素和多因素COX回归分析筛选出影响患者肿瘤特异性生存期(cancer-specific survival,CSS)的预后因素.建立预后列线图并进行危险分层.通过C指数(C-index)、受试者工作特征(ROC)曲线、校准曲线对列线图进行评估.结果 肿瘤部位、肿瘤直径、病理类型、组织学分级、肝外转移、化疗及原发肿瘤是否手术是影响CSS的独立预后因素(P均<0.05).训练组、内部验证组及外部验证组的C指数分别为0.720、0.724和0.711,均高于TNM分期系统(C指数为0.557).校准曲线结果显示该列线图有较高的预测质量.此外,列线图对不同风险患者的预后有显著的辨别能力.结论 与传统的TNM分期系统比较,列线图能可靠的预测GCLM患者的CSS,且可以成功区分高、中和低危患者.

Background Ras-association domain family (RASSF) members are a set of proteins involved in cell cycle control and apoptosis and they are generally considered as tumor suppressors. Objective The present study aimed to elucidate the expression patterns of RASSFs and their prognostic values in gastric cancer. Methods The Oncomine and UALAN online databases were used for analyzing the expression patterns of RASSFs in gastric cancer patients and Kaplan-Meier online database was used for analyzing the prognostic values of RASSFs. The STRING database was used to establish the protein-protein interaction network. Gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomics (KEGG) enrichment analysis were performed by using clusterProfiler package. Finally, MEXPRESS was used for analyzing DNA methylation. Results It was found that RASSF 1 was upregulated in gastric cancer and associated with a better prognosis, whereas RASSF7 was also upregulated in gastric cancer, but associated with a worse prognosis. Enrichment analysis further explained RASSFs association with Ras by regulation of GTP/GDP binding. RASSF genes showed different methylation levels in gastric cancer. Conclusions In conclusion, RASSF members are differentially expressed in gastric cancer, and could be potential prognostic biomarkers in gastric cancer.

肝静脉压力梯度(HVPG)是诊断门静脉高压症以及判断其严重程度的"金标准",但因其有创性、操作技术难度大,限制了其在临床中的广泛开展.通过非侵入性方法替代HVPG是目前研究的热点,但现有的血清学及影像学方法的准确度仍有待商榷,尚不能在临床中完全替代HVPG.肝活检已在临床中广泛开展多年,是确诊某些肝脏疾病不可或缺的方法.近来研究发现肝穿刺后的病理学指标,如胶原面积、纤维间隔厚度、结节大小、微血管密度及胆管、淋巴管密度和面积等,不仅能判断肝纤维化的严重程度,而且与门静脉压力也有良好的相关性.这对诊断肝硬化门静脉高压症及评估门静脉高压症严重程度提供了新的思路.

消化内镜是诊断和治疗消化道疾病的重要工具,随着消化道肿瘤筛查项目的扩大,越来越多的患者和无症状健康人群将接受消化内镜检查,因此消化内镜的培训尤为重要.传统的基于患者的培训模式将逐渐被更为规范化的培训模式所取代.虚拟现实(VR)模拟器具有客观性、安全性、经济性等优势,其应用有助于逐步推进和完善我国消化内镜医师的规范化培训模式.本文就VR技术在消化内镜培训中的应用和研究进展及其优势、局限性和发展方向作一综述.

BACKGROUND:This retrospective cohort study aimed to evaluate the clinical outcomes of H101 combined with chemotherapy for advanced gastric carcinoma (GC) patients.METHODS:The advanced GC patients, who were treated with H101 and/or chemotherapy, were enrolled and divided into three groups according to treatment method. The clinical characteristics of patients, clinical short-term and long-term outcomes, followed up, and complication were analyzed.RESULTS:A total of 95 patients (30 patients in group A were treated with H101, 33 in group B patients were treated with chemotherapy, 32 patients in group C were treated with H101 combined with chemotherapy) were retrospectively reviewed. The disease control rate (DCR) and overall response rate (ORR) were significantly greater in group C (81.3% and 50.0%) than in groups A (63.3% and 30.0%) and B (66.7% and 33.3%, all p < 0.05). The 1- and 2-year survival rates and progression-free survival were significantly greater in group C than in groups A and B (all p < 0.05). There was no significant difference in complication among the three groups. At dose levels of 0.5 × 1012 vp/day, 1.0 × 1012 vp/day, and 1.5 × 1012 vp/day, complications were not increased as increased of dose.CONCLUSIONS:H101 combined with chemotherapy may be a potential therapeutic option for patients with advanced GC, and prospective studies with proper assessment of toxicity will be needed in the future.

BACKGROUND:Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by the loss of proteins, lymphocytes, and immunoglobulins into the intestinal lumen. Increasing evidence has demonstrated an association between PIL and lymphoma.CASE PRESENTATION:A 54-year-old man with a 20-year history of abdominal distension and bilateral lower limb edema was admitted. Laboratory investigations revealed lymphopenia, hypoalbuminemia, decreased triglyceride and cholesterol level. Colonoscopy showed multiple smooth pseudo polyps in the ileocecal valve and terminal ileum and histological examination showed conspicuous dilation of the lymphatic channels in the mucosa and submucosa. A diagnosis of PIL was made. Three years later colonoscopy of the patient showed an intraluminal proliferative mass in the ascending colon and biopsy examination confirmed a malignant non-Hodgkin lymphoma. Then the patient was been underwent chemotherapy, and his clinical condition is satisfactory.CONCLUSION:Our report supports the hypothesis that PIL is associated with lymphoma development.

目的 对四氯化碳(CCl4)化学损伤性以及胆管结扎(BDL)机械梗阻性大鼠门静脉高压模型进行比较,对两种动物模型在门静脉高压形成过程中的特点进行探讨.方法 CCl4模型分为模型组和对照组,BDL模型分为模型组和假手术组.分别于造模后4周、8周、12周测量门静脉压力、取肝脾组织标本.从大鼠一般情况、门静脉压力数值、大体标本变化、病理形态学、体质量、肝脏湿重、脾脏湿重这几方面对两种动物模型进行比较分析.正态分布的资料以均数±标准差表示,两组比较采用t检验.结果 CCl4组肝脏大体变化以肝叶变形、粘连为主,病理表现为纤维间隔分割肝实质,假小叶形成.而BDL组肝叶形态尚存,肝脏呈深褐色,病理表现为大量胆管增生.就门脉高压形成过程而言,CCl4组门静脉压力呈逐渐升高趋势,与对照组相比,造模8周、12周有统计学差异(P<0.05).BDL组门静脉压力呈现短期迅速升高趋势,造模4周、8周及12周较假手术组均明显升高且有统计学差异(P<0.05).在体质量、肝脏湿重、脾脏湿重这几个指标中,脾脏湿重与门脉压力升高趋势一致.在CCl4组,脾脏质量亦是逐渐增加的.而在BDL组,造模4周脾脏质量较假手术组明显增加,造模8周、12周时较假手术组有统计学差异(P<0.05).结论 两种动物模型门静脉高压形成过程及压力变化趋势不同,本文为深入认识不同原因肝硬化门静脉高压提供了实验依据.

Retraction: "Vinculin promotes gastric cancer proliferation and migration and predicts poor prognosis in patients with gastric cancer," by Mingming Zhang, Pei Liu, Famei Xu, Yuanlong He, Xiangjun Xie, Xiangjun Jiang, J Cell Biochem. 2019; 14107-14115: The above article, published online on 15 April 2019 in Wiley Online Library (), has been retracted by agreement between the the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. The authors collaborated in the investigation initially, but were not available for a final confirmation of the retraction.

目的 探讨早期胃癌及癌前病变内镜下黏膜剥离术(endoscopic submucosal dissection,ESD)术后发生出血的影响因素,并进行风险分层.方法 收集2016年1月至2020年12月于青岛大学附属青岛市市立医院因早期胃癌及癌前病变行ESD治疗的手术病例,分析ESD术后发生出血的影响因素,并对与术后出血相关的影响因素进行赋分,根据评分进行风险分层,分为高危、中危、低危.结果 237例早期胃癌患者经ESD治疗后发生术后出血13例(5.4％).单因素分析显示,切除病灶大小、病变≥2个病灶、胃溃疡史、肝硬化史、恶性肿瘤史、阿司匹林服用史、氯吡格雷服用史、双联抗血小板药物服用史与ESD术后出血有关;多因素分析显示仅胃溃疡病史、切除病灶大小、恶性肿瘤史、双联抗血小板药物服用史是ESD治疗后出血的危险因素.结论 胃溃疡病史、切除病灶大小、恶性肿瘤史、双联抗血小板药物服用史是ESD术后出血的危险因素,对于合并多种危险因素的患者,术前及时评估,ESD术中、术后要引起足够的重视,以预防术后出血.

The present study explored a new downstream regulator of Stat-3 signaling, miR-499-5p and its target gene programmed cell death 4 (PDCD4) in cell survival and metastasis of gastric cancer. Our results showed that miR-499-5p is significantly upregulated in human gastric cancer cell line SGC-7901. We further demonstrated that miR-499-5p promotes gastric cancer cell proliferation and invasion in vitro. Mechanistically, we demonstrated that upregulation of miR-499-5p expression associated with inhibition of PDCD4; STAT3 transcriptional activation by IL-6 is crucial for the upregulation of miR-499-5p expression. These results indicate that the STAT3-miR-499-5p-PDCD4 signaling axis plays an important role in gastric cancer progression and a potentially therapeutic target for gastric cancer treatment.

ObjectiveTo investigate the clinical efficacy and safety of sofosbuvir combined with ribavirin in the treatment of treatment-nave patients with genotype 2 chronic hepatitis C virus (HCV) infection. MethodsTreatment-nave patients with genotype 2 HCV infection were screened in sixteen research centers of China. All patients received sofosbuvir (400 mg/tablet, 1 tablet/d) combined with ribavirin (1000 mg/d for patients with a body weight of ＜75 kg and 1200 mg/d for those with a body weight of ≥75 kg) for 12 weeks and were followed up for 12 weeks after drug withdrawal. The primary outcome measure was sustained virologic response at week 12 of follow-up, and the secondary outcome measures included the proportion of patients with HCV RNA below the lower limit of quantitation at weeks 2, 4, 8, and 12 of treatment and after 4 weeks of drug withdrawal, virological rebound rate at weeks 4, 8, and 12 of treatment, and recurrence rate at weeks 4 and 12 of follow-up. Adverse events were observed during treatment to evaluate drug safety. ResultsA total of 136 subjects were enrolled, among whom 121 had no liver cirrhosis and 15 had compensated liver cirrhosis. The sustained virologic response (SVR) rate was 92.6% (95% confidence interval: 88.3%-97.0%) after 12 weeks of drug withdrawal. At week 8 of treatment, 1 patient experienced virological rebound; after 4 weeks of drug withdrawal, 8 patients experienced virological rebound; after 12 weeks of drug withdrawal, 10 patients experienced virological rebound. Among the 136 subjects, 128 (94.1%) reported 549 cases of treatment-emergent adverse events, among which 243 cases were associated with sofosbuvir and/or ribavirin and were reported in 99 subjects (72.8%). No adverse events leading to the adjustment or discontinuation of sofosbuvir were observed. A total of 7 serious adverse events were reported in 6 patients (4.4%), among which only one (a low echo area in the liver with unknown nature) was considered possibly associated with sofosbuvir and/or ribavirin. No adverse events leading to study discontinuation or death were observed. ConclusionSofosbuvir combined with ribavirin can achieve a high SVR rate in treatment-nave patients with genotype 2 chronic HCV infection, with mild adverse reactions and acceptable safety profile.

背景胃癌(gastric cancer,GC)是常见恶性肿瘤之一,发病率、死亡率均排在全国、乃至全世界前列,是影响人类健康的重要问题.目前仍缺乏GC早期诊断、治疗及GC预后相关的基因靶点.目的探讨母源性表达基因8(maternally expressed gene 8,MEG8)及转谷氨酰胺酶2(transglutaminase 2,TGM2)在GC组织中的表达及临床意义.方法通过荧光定量聚合酶链式反应检测30对GC及癌旁组织中MEG8、TGM2表达情况,分析表达情况与GC患者临床病理特征相关性,通过摘录Oncomine数据库中相关研究数据,分析TGM2表达差异性及与GC患者的生存状态的相关性.结果MEG8在GC组织中的表达量低于癌旁组织(0.462±0.082 vs l.048±0.149),TGM2在GC组织中的表达量高于癌旁组织(1.202±0.143 vs 0.742±0.083),差异具有统计学意义(P＜0.05);MEG8表达与年龄、临床分期有关(P＜0.05),TGM2表达与临床分期有关(P＜O.05);TGM2表达高低与GC患者生存状态无关(P＞0.05).结论MEG8、TGM2参与GC的发生发展过程,可作为GC诊断及预后的潜在靶点.

BackgroundTo determine the safety and efficacy of different doses of tolvaptan for treating Chinese cirrhotic patients with or without hyponatraemia who still had ascites after routine therapy with diuretics.MethodsIn the present placebo-controlled, randomized, double-blinded, multicentre clinical trial, patients with cirrhotic ascites who failed to adequately respond to a combination of an aldosterone antagonist plus an orally administered loop diuretic were randomly placed at a 4:2:1 ratio into 3 groups [the 15 mg/day tolvaptan group (N=301), 7.5 mg/day tolvaptan group (N=153) and placebo group (N=76)] for 7 days of treatment. The effects and safety were evaluated on days 4 and 7. A change in body weight from baseline on day 7 of treatment was the primary endpoint.ResultsThe administration of 7.5 or 15 mg/day tolvaptan significantly decreased body weight from baseline on day 7 of treatment compared to that with placebo treatment (P=0.026; P=0.001). For the secondary endpoints, changes in abdominal circumference from baseline and improvements in ascites were markedly different in the treatment groups and the placebo group on day 7 (P-7.5=0.05, P-15.0=0.002 and P-7.5=0.037, P-15.0=0.003), but there was no difference between the 7.5 mg/day and 15 mg/day dosage groups. The 24-h cumulative urine volume was higher in the 7.5 mg/day and 15 mg/day tolvaptan groups than the placebo group (P=0.002, P<0.001) and was greater in the 15 mg/day tolvaptan group than the 7.5 mg/day tolvaptan group (P=0.004). Sodium serum concentrations were higher in patients with hyponatraemia after tolvaptan treatment, with no significant difference between the two dosage groups. The incidence of serious adverse drug reactions was not different between the groups (P=0.543).ConclusionsTolvaptan treatment at 7.5 mg per day might be a good therapeutic choice for Chinese cirrhotic patients with ascites who did not achieve satisfactory clinical responses to previous treatment regimens with combination therapy with an aldosterone antagonist and an orally administered loop diuretic.Trial registrationNCT01349348. Retrospectively registered May 2011.

Vinculin is a highly conserved protein involved in cell proliferation, migration, and adhesion. However, the effects of vinculin on gastric cancer (GC) remain unclear. Therefore, we aimed to explore the functional role of vinculin in GC, as well as its underlying mechanism. Expression of vinculin in patients with GC was analyzed by real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry. Overall survival was evaluated by the Kaplan-Meier method with the log-rank test. The relationship between vinculin and clinicopathological characteristics of patients with GC was further identified. In addition, we assessed the expression of vinculin in GC cell lines. Besides, vinculin was suppressed or overexpressed by transfection with small interfering (si-vinculin) or pcDNA-vinculin and then cell viability, cell apoptosis, and/or migration was respectively examined by the 3-(4, 5-dimethylthiazole-2-yl)-2, 5-biphenyl tetrazolium bromide assay, flow cytometer, and scratch assay, respectively. Moreover, the cell cycle- and apoptosis-related proteins were detected by Western blot analysis. The expression of vinculin was significantly increased in the GC tissues and cells compared with the nontumor tissues or cells. Vinculin protein positive staining was mainly located in the cell membrane and cytoplasm. Moreover, vinculin was significantly associated with Tumor Node Metastasis (TNM) and poor differentiation. Patients with high vinculin levels had significantly worse overall survival than those with low levels. Suppression of vinculin significantly decreased cell viability and migration and promoted cell apoptosis. However, overexpression of vinculin statistically increased cell viability but had no effects on cell apoptosis. Vinculin promotes GC proliferation and migration and predicts poor prognosis in patients with GC.