A Nomogram Model for Prediction of Mortality Risk of Patients with Dangerous Upper Gastrointestinal Bleeding:A Two-center Retrospective Study

Objective:This study aimed to establish a nomogram model to predict the mortality risk of patients with dangerous upper gastrointestinal bleeding(DUGIB),and identify high-risk patients who require emergent therapy.Methods:From January 2020 to April 2022,the clinical data of 256 DUGIB patients who received treatments in the intensive care unit(ICU)were retrospectively collected from Renmin Hospital of Wuhan University(n=179)and the Eastern Campus of Renmin Hospital of Wuhan University(n=77).The 179 patients were treated as the training cohort,and 77 patients as the validation cohort.Logistic regression analysis was used to calculate the independent risk factors,and R packages were used to construct the nomogram model.The prediction accuracy and identification ability were evaluated by the receiver operating characteristic(ROC)curve,C index and calibration curve.The nomogram model was also simultaneously externally validated.Decision curve analysis(DCA)was then used to demonstrate the clinical value of the model.Results:Logistic regression analysis showed that hematemesis,urea nitrogen level,emergency endoscopy,AIMS65,Glasgow Blatchford score and Rockall score were all independent risk factors for DUGIB.The ROC curve analysis indicated the area under curve(AUC)of the training cohort was 0.980(95%CI:0.962-0.997),while the AUC of the validation cohort was 0.790(95%CI:0.685-0.895).The calibration curves were tested for Hosmer-Lemeshow goodness of fit for both training and validation cohorts(P=0.778,P=0.516).Conclusion:The developed nomogram is an effective tool for risk stratification,early identification and intervention for DUGIB patients.

Proton pump inhibitor for non-erosive reflux disease:A meta-analysis

AIM:To evaluate the efficacy,safety and influential factors of proton pump inhibitor(PPI)treatment for non-erosive reflux disease(NERD).METHODS:PubMed,MEDLINE,EMBASE and the Cochrane Library were searched up to April 2013 to identify eligible randomized controlled trials(RCTs)that probed into the efficacy,safety and influential factors of PPI treatment for NERD.The rates of symptomatic relief and adverse events were measured as the outcomes.After RCT selection,assessment and data collection,the pooled RRs and 95%CI were calculated.This meta-analysis was performed using the Stata 12.0 software(Stata Corporation,College Station,Texas,United States).The level of evidence was estimated by the Grading of Recommendations Assessment,Development and Evaluation system.RESULTS:Seventeen RCTs including 6072 patients met the inclusion criteria.The results of the metaanalysis showed that PPI treatment was significantly superior to H2receptor antagonists(H2RA)treatment(RR=1.629,95%CI:1.422-1.867,P=0.000)and placebo(RR=1.903,95%CI:1.573-2.302,P=0.000)for the symptomatic relief of NERD.However,there were no obvious differences between PPI and H2RA(RR=0.928,95%CI:0.776-1.110,P=0.414)or PPI and the placebo(RR=1.000,95%CI:0.896-1.116,P=0.997)regarding the rate of adverse events.The overall rate of symptomatic relief of PPI against NERD was 51.4%(95%CI:0.433-0.595,P=0.000),and relief was influenced by hiatal hernia(P=0.030).The adverse rate of PPI against NERD was 21.0%(95%CI:0.152-0.208,P=0.000),and was affected by hiatal hernia(P=0.081)and drinking(P=0.053).CONCLUSION:PPI overmatched H2RA on symptomatic relief rate but not on adverse rate for NERD.Its relief rate and adverse rate were influenced by hiatal hernia and drinking.

Mitochondrial pathway mediated by reactive oxygen species involvement in α-hederin-induced apoptosis in hepatocellular carcinoma cells

AIM To investigate the antitumor activity of α-hederin in hepatocellular carcinoma(HCC) cells and its underlying mechanisms in vitro and in vivo.METHODS SMMC-7721, Hep G-2 and Huh-7 HCC cells were cultured in vitro and treated with α-hederin(0, 5 μmol/L, 10 μmol/L, 15 μmol/L, 20 μmol/L, 25 μmol/L, 30 μmol/L, 35 μmol/L, 40 μmol/L, 45 μmol/L, 50 μmol/L, 55 μmol/L, or 60 μmol/L) for 12 h, 24 h, or 36 h, and cell viability was then detected by the Cell Counting Kit-8. SMMC-7721cells were treated with 0, 5 μmol/L, 10 μmol/L, or 20 μmol/L α-hederin for 24 h with or without DL-buthionineS,R-sulfoximine(2 mmol/L) or N-acetylcysteine(5 mmol/L) pretreatment for 2 h, and additional assays were subsequently performed. Apoptosis was observed after Hoechst staining. Glutathione(GSH) and adenosine triphosphate(ATP) levels were measured using GSH and ATP Assay Kits. Intracellular reactive oxygen species(ROS) levels were determined by measuring the oxidative conversion of 2',7'-dichlorofluorescin diacetate. Disruption of the mitochondrial membrane potential was evaluated using JC-1 staining. The protein levels of Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, apoptosis-inducing factor and cytochrome C were detected by western blotting. The antitumor efficacy of α-hederin in vivo was evaluated in a xenograft tumor model.RESULTS The α-hederin treatment induced apoptosis of HCC cells. The apoptosis rates in the control, low-dose α-hederin(5 μmol/L), mid-dose α-hederin(10 μmol/L) and highdose α-hederin(20 μmol/L) groups were 0.90% ± 0.26%, 12% ± 2.0%, 21% ± 2.1% and 37% ± 3.8%, respectively(P < 0.05). The α-hederin treatment reduced intracellular GSH and ATP levels, induced ROS, disrupted the mitochondrial membrane potential, increased the protein levels of Bax, cleaved caspase-3, cleaved caspase-9, apoptosis-inducing factor and cytochrome C, and decreased Bcl-2 expression. The α-hederin treatment also inhibited xenograft tumor growth in vivo. CONCLUSION The α-hederin saponin induces apoptosis of HCC cells via the mitochondrial pathway mediated by increased intracellular ROS and may be an effective treatment for human HCC.

Cooperative inhibitory effect of sinomenine combined with5-fluorouracil on esophageal carcinoma

AIM:To investigate the inhibitory effects of sinomenine(SIN)combined with 5-fluorouracil(5-FU)on esophageal carcinoma in vitro and in vivo.METHODS:Esophageal carcinoma(Eca-109)cells were cultured in DMEM.The single or combined growth inhibition effects of SIN and 5-FU on the Eca-109 cells were examined by measuring the absorbance of CCK-8dye in living cells.Hoechst 33258 staining and an Annexin V/PI apoptosis kit were used to detect the percentage of cells undergoing apoptosis.Western blotting was used to investigate the essential mechanism underlying SIN and 5-FU-induced apoptosis.SIN at 25mg/kg and 5-FU at 12 mg/kg every 3 d,either combined or alone,was injected into nude mice and tumor growth inhibition and side effects of the drug treatment were observed.RESULTS:SIN and 5-FU,both in combination and individually,significantly inhibited the proliferation of Eca-109 cells and induced obvious apoptosis.Furthermore,the combined effects were greater than those of the individual agents(P<0.05).Annexin V/PI staining and Hoechst 33258 staining both indicated that the percentage of apoptotic cells induced by SIN and 5-FU combined or alone were significantly different from the control(P<0.05).The up-regulation of Bax and downregulation of Bcl-2 showed that the essential mechanism of apoptosis induced by SIN and 5-FU occurs via the mitochondrial pathway.SIN and 5-FU alone significantly inhibited the growth of tumor xenografts in vivo,and the combined inhibition rate was even higher(P<0.05).During the course of chemotherapy,no obvious side effects were observed in the liver or kidneys.CONCLUSION:The combined effects of SIN and 5-FU on esophageal carcinoma were superior to those of the individual compounds,and the drug combination did not increase the side effects of chemotherapy.

Hugl-1 induces apoptosis in esophageal carcinoma cells both in vitro and in vivo

AIM: To determine whether the human giant larvae homolog 1 gene (Hugl-1/Llg1/Lgl1) exerts tumor suppressor effects in esophageal cancer. METHODS: We constructed a Hugl-1 expression plasmid, pEZ-M29-Hugl1, for gene transfection. We transfected the pEZ-M29-Hugl1 plasmid into Eca109 esophageal cancer cell lines with Lipofectamine 2000 to overexpress Hugl-1. Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the effects of the plasmid on Hugl-1 expression. In vitro cell proliferation and apoptosis were examined separately by cell counting Kit-8 (CCK-8) assay, flow cytometry, and Western blotting before and after the transfection of the plasmid into Eca109 cells. Cell cycle distribution was assessed with flow cytometry. The effect of Hugl-1 overexpressing on tumor growth in vivo was performed with a xenograft tumor model in nude mice. Expression of Hugl-1 in xenograft tumor was analyzed by immunohistochemistry.The transferase-mediated dUTP nick end-labeling (TUNEL) technique was performed to detect and quantitate apoptotic cell. RESULTS: The transfection efficiency was confirmed with real-time RT-PCR and Western blotting. Our results show that compared with control groups the mRNA levels and protein levels of Hugl-1 in pEZ-M29-Hugl1-treated group were remarkably increased (P < 0.05). The CCK-8 assay demonstrated that the growth of cells overexpressing Hugl-1 was significantly lower than control cells. Cell cycle distribution showed there was a G 0 /G 1 cell cycle arrest in cells overexpressing Hugl-1 (64.09% ± 3.14% vs 50.32% ± 4.60%, 64.09% ± 3.14% vs 49.13% ± 2.24%). Annexin V-fluorescein isothiocyanate revealed that apoptosis was significantly increased in cells overexpressing Hugl-1 compared with control group (17.33% ± 4.76% vs 6.90% ± 1.61%, 17.33% ± 4.76% vs 6.27% ± 0.38%). Moreover, we found that Hugl-1 changes the level of the anti-apoptotic protein Bcl-2 and the proapoptotic protein Bax and the activation of both caspase-3 and caspase-9. With a TUNEL assay, we found that Hugl-1 markedly increased the apoptosis rate of Eca109 cells in vivo (60.50% ± 9.11% vs 25.00% ± 12.25%). It was shown that Hugl-1 represents a significantly more effective tumor suppressor gene alone in a xenograft tumor mouse model. This data suggest that Hugl-1 inhibited tumor growth and induced cell apoptosis in vivo . CONCLUSION: These results suggest that Hugl-1 induces growth suppression and apoptosis in a human esophageal squamous cell carcinoma cell line both in vitro and in vivo .

糖尿病性黄斑水肿与肾小球滤过率的相关性

目的:观察2型糖尿病患者肾小球滤过率(eGFR)与糖尿病性黄斑水肿(DME)之间的关系。方法:选取2015-05/2017-05抚顺市眼病医院糖尿病眼病专科门诊在社区筛查的2型糖尿病患者912例,进行眼底照相、空腹血糖、糖化血红蛋白、肾功能等检查,应用我国eGFR课题协作组改良的简化MDRD方程估算eGFR。结果:选取的912例2型糖尿病患者中无DME、轻度DME、中度DME、重度DME患者分别为815例、29例、21例、47例,随着DME病情的加重,患者eGFR逐渐降低(F=8. 87,P<0. 001)。Logistic回归分析显示, eGFR降低是DME发生的危险因素,且eGFR每下降20. 3mL/(min·1. 73m2)(1个标准差),发生DME的风险增加1. 84倍,肾功能受损及肾功能不全者发生DME的风险是肾功能正常者的1. 60及2. 46倍。结论:eGFR为DME发生的危险因素,与DME严重程度相关,临床治疗中应关注DME患者肾功能情况。

Overexpression of pim-3 and protective role in lipopolysaccharide-stimulated hepatic stellate cells

AIM: To investigate pim-3 expression in hepatic stellate cells(HSCs) stimulated by lipopolysaccharide(LPS), and its protective effect on HSCs. METHODS: Rat HSC-T6 cells were stimulated by LPS. The effect of LPS on proliferation and apoptosis of HSC-T6 cells was investigated by methyl thiazoyltetrazolium(MTT) assay and flow cytometry after annexin V-fluorescein isothiocyanate/propidium iodide double staining. pim-3 m RNA and protein were detected by reverse transcriptase polymerase chain reaction and Western blotting at 48 h when HSC-T6 cells were stimulated with 1 μg/m L LPS for 0, 3, 6, 12, 24 and 48 h. The cells without stimulation served as controls. To study the effect of pim-3 kinase on HSC-T6 cells, si-pim3(si RNA against pim-3) was transfected into HSC-T6 cells. HSC-T6 cells were subjected to different treatments, including LPS, si-pim3, or si-pim3 plus LPS, and control cells were untreated. Protein expression of pim-3 was detected at 48 h after treatment, and cell proliferation at 24 and 48 h by MTT assay. Apoptosis was detected by flow cytometry, and confirmed with caspase-3 activity assay.RESULTS: LPS promoted HSC-T6 cell proliferation and protected against apoptosis. Significantly delayed upregulation of pim-3 expression induced by LPSoccurred at 24 and 48 h for m RNA expression(pim-3/β-actin RNA, 24 or 48 h vs 0 h, 0.81 ± 0.20 or 0.78 ± 0.21 vs 0.42 ± 0.13, P < 0.05), and occurred at 12 h and peaked at 24 and 48 h for protein expression(pim-3/GAPDH protein, 12, or 24 or 48 h vs 0 h, 0.68 ± 0.12, 1.47 ± 0.25 or 1.51 ± 0.23 vs 0.34 ± 0.04, P < 0.01). pim-3 protein was ablated by si-pim3 and upregulated by LPS in HSC-T6 cells at 48 h after treatment(pim-3/GAPDH: si-pim3, si-pim3 plus LPS or LPS vs control, 0.11 ± 0.05, 0.12 ± 0.05 or 1.08 ± 0.02 vs 0.39 ± 0.03, P < 0.01). Ablation of pim-3 by si-pim3 in HSC-T6 cells partly abolished proliferation(OD at 24 h, si-pim3 group or si-pim3 plus LPS vs control, 0.2987 ± 0.050 or 0.4063 ± 0.051 vs 0.5267 ± 0.030, P < 0.01; at 48 h 0.4634 ± 0.056 or 0.5433 ± 0.031 vs 0.8435 ± 0.028, P < 0.01; si-pim3 group vs si-pim3 plus LPS, P < 0.01 at 24 h and P < 0.05 at 48 h), and overexpression of pim-3 in the LPS group increased cell proliferation(OD: LPS vs control, at 24 h, 0.7435 ± 0.028 vs 0.5267 ± 0.030, P < 0.01; at 48 h, 1.2136 ± 0.048 vs 0.8435 ± 0.028, P < 0.01). Ablation of pim3 with si-pim3 in HSC-T6 cells aggravated apoptosis(si-pim3 or si-pim3 plus LPS vs control, 42.3% ±1.1% or 40.6% ± 1.3% vs 16.8% ± 3.3%, P < 0.01; si-pim3 vs si-pim3 plus LPS, P > 0.05), and overexpression of pim-3 in the LPS group attenuated apoptosis(LPS vs control, 7.32% ± 2.1% vs 16.8% ± 3.3%, P < 0.05). These results were confirmed by caspase-3 activity assay.CONCLUSION: Overexpression of pim-3 plays a protective role in LPS-stimulated HSC-T6 cells.

TNF-a-308 polymorphism and risk of digestive system cancers:A meta-analysis

AIM:To evaluate the association between the tumour necrosis factor alpha-308(TNF-a-308)gene polymorphism and the risk of digestive system cancers.METHODS:All eligible case-control studies published up to December 2012 were identified by searching PubMed,Web of Science,Embase and China National Knowledge Internet without language restrictions.The risk of digestive system cancers associated with the TNF-a-308 polymorphism was estimated for each study using odds ratio(OR)together with its 95%CI,respectively.Cochrane Collaboration RevMan 5.1 was used to perform the analysis.Aχ2-test-based Q statistic test and an I2test were performed to assess the betweenstudy heterogeneity.When the Q test was significant(P<0.05)or I2>50%,the random effects model was used,otherwise the fixed effects model was used.RESULTS:Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included.Overall,a significant association was found between the TNF-a-308 polymorphism and the risk of digestive system cancers[dominant model:OR=1.23,95%CI:1.09-1.39,(G/A)vs(G/G):OR=1.15,95%CI:1.02-1.28,(A/A)vs(G/G):OR=1.44,95%CI:1.19-1.73,recessive model:OR=1.38,95%CI:1.15-1.66].Furthermore,when the analysis was stratified by ethnicity,similar results were observed in both the Asian and Caucasian populations,except for the dominant model and heterozygote comparisons in the Asian population[dominant model:OR=1.24,95%CI:0.99-1.56,(G/A)vs(G/G):OR=1.09,95%CI:0.96-1.24].When the cancer type subgroups were examined,similar results were detected in gastric and hepatocellular carcinomas;however,no significant association was observed among other digestive system cancers.CONCLUSION:The TNF-a-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas,but not colorectal,pancreatic,or oesophageal cancer,in the Asian population.

视网膜分支动脉阻塞视力预后相关因素分析

目的:研究视网膜分支动脉阻塞(branch retinal artery occlusion,BRAO)患眼视力预后的相关因素分析。方法:选取2015-06/2017-06来我院就诊并诊断为视网膜分支动脉阻塞的患者68例。收集患者的年龄、性别、发病时间等基本信息及初诊时最佳矫正视力、眼底彩色照相、频域OCT及OCTA等眼科检查结果。OCTA检查采用RTVue XRAVANTI仪进行。选择视网膜血流成像扫描模式,扫描区域分别为黄斑区3mm×3mm。随访时间为6mo,随访时检查最佳矫正视力。结果:患者就诊时基线视力:轻度视力损害(≥0. 5)为69%,中度视力损害(0. 1～0. 4)为24%,重度视力损害(<0. 1)为7%;随访预后视力的轻、中、重度损害分别为75%、19%、6%。影响预后视力的相关因素分析:就诊时基线视力(r=0. 776,P<0. 001)、浅层视网膜毛细血管黄斑区拱环存留度(r=-0. 003,P<0. 001)、深层视网膜毛细血管黄斑区拱环存留度(r=-0. 003,P<0. 001)、黄斑区浅层毛细血管密度(r=-0. 034,P=0. 029)及黄斑区深层毛细血管密度(r=-0. 014,P=0. 012)与预后视力密切相关。性别、年龄、就诊时间、黄斑中心凹厚度、视网膜动脉受阻位置(颞上或颞下)以及是否发现明确视网膜血管动脉栓子与预后视力无相关性(r=-0. 273、0. 01、0、0. 82、0. 41、0. 109,均P>0. 05)。结论:BRAO患眼黄斑拱环存留度、黄斑区毛细血管密度和发病早期视力与预后视力密切相关。

Microstructure and texture evolution of 6016 aluminum alloy during hot compressing deformation

Microstructure and texture in 6016 aluminum alloy during hot compression were researched with a uni- axial compression experiment. Through the electron back- scattered diffraction （EBSD） and X-ray diffraction （XRD） analysis technology, it is shown that the subgrain nucle- ation and recrystallization occur in 6016 aluminum alloy during hot compressing, and strong rolling textures such as （110） fiber texture, Brass, S, and Goss form. With the deformation passes increasing, （110） fiber texture, Brass and S are enhanced. In the heat preservation stage after deformation, recrystallization continues until heat preser- vation for 60 s, and a duplex microstructure of deformation and recrystallization grains is built. At the beginning of heat preservation, recrystallization grains with the Goss texture and random orientation are formed in original grains with S or Brass texture, which makes the volume fraction of S and Brass texture decrease. Then, the complex grain growth process makes the volume fraction of Brass, S, and Goss texture increase, while that of random orien- tation decrease.

Superplasticity of 6016 aluminum alloy at elevated temperatures

The high-temperature plastic deformation be- haviors of 6016 aluminum alloy were investigated with the temperatures ranging from 420 to 540 ℃ and the strain rates ranging from 0.001 to 1.000 s-1. The results show that 6016 aluminum alloys possess superplasticity at 500 ℃ with the strain rates ranging from 0.001 to 0.010 s-1. The grain boundary sliding （GBS） is the main mechanism of superplastic deformation of 6016 aluminum alloy. In addition, a great number of O-type cavities, almost no V type, occur in the microstructure of superplastic deformed 6016 aluminum alloy. The dislocations gather near the grain boundaries to coordinate GBS deformation. The second-phase particles effectively prevent the growth of the recrystallized grains or plastic deformation grains and pin the moving dislocations during deformation.