Integrated analysis of single-cell and bulk RNA-seq establishes a novel signature for prediction in gastric cancer

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 singlecell 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.

脊柱不稳定性预测评分系统对OVCF患者椎体强化术后再发骨折的预测价值

目的探究脊柱不稳定性预测评分系统对骨质疏松性椎体压缩性骨折患者(OVCF)椎体强化术后骨折再发的预测效果。方法选取2015年6月-2017年6月该院行椎体强化术的OVCF患者,收集其一般情况和影像学资料,以及随访过程中再发骨折情况和视觉疼痛评分,利用Logistic回归分析骨折再发的危险因素,并对其赋分,构建脊柱不稳定性预测评分系统,计算似然比检测该系统的准确性。结果共纳入342例患者,2例失访,142例患者再发骨折。再发骨折的危险因素包括脊柱后凸角度、椎体后凸角度、椎体高度、强化椎体的数量、骨密度以及骨折部位。根据预测评分系统评分将所有患者分为4组,总体评分<5分组似然比为0.10,总体评分≥15分组似然比为5.84。结论脊柱不稳定性预测评分系统较为准确地预测椎体强化术后OVCF患者的骨折再发风险,可为骨折再发的预防提供理论依据,值得临床深入探究。

早期胃癌内镜黏膜下剥离术后出血危险因素的Meta分析

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 ofScience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(O^R:1.73,95%CI:1.26~2.37)、溃疡阳性(O^R:1.83,95%CI:1.04~3.22)、抗血栓类药物(O^R: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。

Chemotherapy and resection for gastric cancer with synchronous liver metastases

AIM: To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM). METHODS: A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter. RESULTS: Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the Response Evaluation Criteria in Solid Tumors Criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date. CONCLUSION: Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.

Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Lack of association between apolipoprotein C3 gene polymorphisms and risk of nonalcoholic fatty liver disease in a Chinese Han population

AIM:To investigate the association between two polymorphisms of apolipoprotein C3(APOC3)and risk of nonalcoholic fatty liver disease(NAFLD)in a Chinese Han population.METHODS:Genotypes for rs2854116 and rs2854117in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3(PNPLA3)in 390patients with NAFLD and 409 control subjects were determined by sequencing and polymerase chain reaction analysis.Serum lipid profiles were determined using biochemical methods,and an index of insulin resistance(IR,HOMA-IR),serum APOC3 concentrations and total antioxidant status(TAS)were also assessed.RESULTS:No significant differences in genotype and allele frequencies of rs2854116 and rs2854117 were found between the NAFLD population and the controls(P>0.05).The OR for the association between-455Cand-482T allele carriers and the risk of NAFLD were1.06(95%CI:0.72-1.57,P>0.05)and 1.00(95%CI:0.68-1.48,P>0.05),respectively.The variant carriers did not have a significantly increased risk of NAFLD or elevated clinical and biochemical parameters such as APOC3 concentrations,IR(1.42±0.43 vs 1.48±0.52,P>0.05),liver enzymes and TAS(13.94±2.01vs 14.38±1.92,P>0.05)compared with the controls.Moreover,the results were similar when testing was carried out independent of the genetic variation in PNPLA3.CONCLUSION:The two polymorphisms of the APOC3gene are not associated with a risk of NAFLD,or with lipid profiles,IR and oxidative stress in the Chinese Han population.

Specific HLA-DQB1 alleles associated with risk for development of hepatocellular carcinoma:A meta-analysis

AIM:To evaluate the association of human leukocyte antigen(HLA)-DQB1 alleles with hepatocellular carcinoma(HCC) through meta-analysis of published data.METHODS:Case-control studies on HLA-DQB1 allele association with HCC published up to January 2010 were included in the analyses.The odds ratios(ORs) of HLADQB1 allele distributions in HCC patients were analyzed and compared with healthy controls.The meta-analysis software REVMAN 5.0 was applied for investigating heterogeneity among individual studies and for summarizing all the studies.A meta-analysis was performed using fixed-effect or random-effect methods,depending on the absence or presence of significant heterogeneity.Seven case-control studies containing 398 cases and 594 controls were included in the final analysis.RESULTS:Among the five family alleles,two(DQB1*02 and DQB1*03) were found to be significantly associated with the risk of HCC.The combined OR for the association of DQB1*02 and DQB1*03 allele with the risk for HCC was 1.78(95% CI:1.05-3.03,P = 0.03) and 0.65(95% CI:0.48-0.89,P = 0.007),respectively.Among the 13 specific alleles,two(DQB1*0502 and DQB1*0602) were significantly associated with risk of HCC.The combined OR for the association of DQB1*0502 and DQB1*0602 allele with the risk for HCC was 1.82(95% CI:1.14-2.92,P = 0.01) and 0.58(95% CI:0.36-0.95,P = 0.03),respectively.No significant association was established for other HLA-DQB1 family alleles and specific alleles.CONCLUSION:Our results support the hypothesis that specific HLA-DQB1 allele families and alleles might influence the susceptibility or resistance to HCC,although it needs further investigations.

Endoscopic stenting and concurrent chemoradiotherapy for advanced esophageal cancer:A case-control study

AIM:To evaluate the role of endoscopic stenting with or without concurrent 3-dimensional conformal chemoradiotherapy (3D-CRT) in patients with inoperable esophageal cancer.METHODS:Advanced esophageal cancer patients indicated for esophagectomy received esophageal stents.A part of patients completed 3D-CRT after stenting.Efficacy was assessed by endoscopy and computed tomographic scan before and 4 wk after completion of the treatment.The median survival,3D-CRT toxicity and complications were compared between 3D-CRT and control groups.RESULTS:From 1999 to 2008,99 consecutive patients with T3/T4 disease and unsuitable for esophagectomy were placed with esophageal stents.Sixty-seven patients received 3D-CRT,while 36 patients treated withendoscopic stents alone were recruited as controls.After 3D-CRT treatment,the median tumor volume of 3D-CRT patients were reduced significantly from 43.7 ± 10.2 cm 3 to 28.8 ± 8.5 cm 3 (P < 0.05).The complete and partial response rate was 85.1%,and no response was 14.9%.After 3D-CRT,the incidence rate of T2 and T3 disease evident on CT scan increased to 78.4% while T4 decreased from 66.7% to 21.6% (P < 0.05).3DCRT Karnofsky Performance Status improved in 3D-CRT patients compared with the control group (P=0.031).3D-CRT patients had a longer survival than the control group (251.7 d vs 91.1 d,P < 0.05).And the median half-year survival rate in 3D-CRT group (91%) was higher than in the control group (50%,P < 0.05).The most common toxicity was leukocytopenia in the 3D-CRT group (46.7% vs 18.8%,P=0.008).The control group had a higher rate of restenosis than the 3D-CRT group (81.3% vs 9.0%,P < 0.05).The rate of nephrotoxicity was increased in 3D-CRT as compared with the control group (31.3% vs 15.6%,P < 0.05).CONCLUSION:3D-CRT can improve dysphagia in patients with inoperable esophageal carcinoma.3D-CRT combined with stenting results in better survival as compared with endoscopic stents used alone.

联轴器螺栓紧固件的有限元建模仿真和试验分析（英文）

The aim of this paper is to study the stress status of the bolt fastener in coupling under complex load-ings, the research result is greatly beneficial for the analysis of the failure of the screw bolt in coupling. Thethreads in the bolt and nut are modeled with accurately construct helical thread geometry and implanted into theANSYS software. Research shows that the model has the ability to simulate the preload of bolt, equivalent stress ofcoupling under load, and structure stress of the screw bolt in coupling. The finite element results agree with theexperimental observations quantitatively. In addition, the fatigue strength and the self relaxation of the screw boltare more sensitive to the torsional load, which can provide reference for further research on the failure of screw bolt.