Preoperative prediction of lymphovascular and perineural invasion in gastric cancer using spectral computed tomography imaging and machine learning

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are important prognostic factors for gastric cancer(GC)that indicate an increased risk of metastasis and poor outcomes.Accurate preoperative prediction of LVI/PNI status could help clinicians identify high-risk patients and guide treatment deci-sions.However,prior models using conventional computed tomography(CT)images to predict LVI or PNI separately have had limited accuracy.Spectral CT provides quantitative enhancement parameters that may better capture tumor invasion.We hypothesized that a predictive model combining clinical and spectral CT parameters would accurately preoperatively predict LVI/PNI status in GC patients.AIM To develop and test a machine learning model that fuses spectral CT parameters and clinical indicators to predict LVI/PNI status accurately.METHODS This study used a retrospective dataset involving 257 GC patients(training cohort,n=172;validation cohort,n=85).First,several clinical indicators,including serum tumor markers,CT-TN stages and CT-detected extramural vein invasion(CT-EMVI),were extracted,as were quantitative spectral CT parameters from the delineated tumor regions.Next,a two-step feature selection approach using correlation-based methods and information gain ranking inside a 10-fold cross-validation loop was utilized to select informative clinical and spectral CT parameters.A logistic regression(LR)-based nomogram model was subsequently constructed to predict LVI/PNI status,and its performance was evaluated using the area under the receiver operating characteristic curve(AUC).RESULTS In both the training and validation cohorts,CT T3-4 stage,CT-N positive status,and CT-EMVI positive status are more prevalent in the LVI/PNI-positive group and these differences are statistically significant(P<0.05).LR analysis of the training group showed preoperative CT-T stage,CT-EMVI,single-energy CT values of 70 keV of venous phase(VP-70 keV),and the ratio of standardized iodine concentration of equilibrium phase(EP-NIC)were independent influencing factors.The AUCs of VP-70 keV and EP-NIC were 0.888 and 0.824,respectively,which were slightly greater than those of CT-T and CT-EMVI(AUC=0.793,0.762).The nomogram combining CT-T stage,CT-EMVI,VP-70 keV and EP-NIC yielded AUCs of 0.918(0.866-0.954)and 0.874(0.784-0.936)in the training and validation cohorts,which are significantly higher than using each of single independent factors(P<0.05).CONCLUSION The study found that using portal venous and EP spectral CT parameters allows effective preoperative detection of LVI/PNI in GC,with accuracy boosted by integrating clinical markers.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer

BACKGROUND Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide.Neoadjuvant chemoradiotherapy(nCRT)is standard for locally advanced rectal cancer(LARC).Except for pathological examination after resection,it is not known exactly whether LARC patients have achieved pathological complete response(pCR)before surgery.To date,there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes.AIM To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC.METHODS Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed.Patients were categorized into pCR and non-pCR groups.Univariate analysis(using the χ^(2) test or Fisher’s exact test)and logistic multivariate regression analysis were used to study clinical predictors affecting pCR.The 5-year disease-free survival(DFS)and overall survival(OS)rates were calculated using Kaplan-Meier analysis,and differences in survival curves were assessed with the log-rank test.RESULTS Univariate analysis showed that pretreatment carcinoembryonic antigen(CEA)level,lymphocyte-monocyte ratio(LMR),time interval between neoadjuvant therapy completion and total mesorectal excision,and tumor size were correlated with pCR.Multivariate results showed that CEA≤5 ng/mL(P=0.039),LMR>2.73(P=0.023),and time interval>10 wk(P=0.039)were independent predictors for pCR.Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates(94.7%vs 59.7%,P=0.002)and 5-year OS rates(95.8%vs 80.1%,P=0.019)compared to the non-pCR group.Tumor deposits(TDs)were significantly correlated with shorter DFS(P=0.002)and OS(P<0.001).CONCLUSION Pretreatment CEA,LMR,and time interval contribute to predicting nCRT efficacy in LARC patients.Achieving pCR demonstrates longer DFS and OS.TDs correlate with poor prognosis.

Predictors of portal vein thrombosis after splenectomy in patients with cirrhosis

BACKGROUND Portal vein thrombosis(PVT)is a commonthsn complication after splenectomy in patients with cirrhosis.However,the predictors of postoperative PVT are not known.AIM To investigate the predictors of PVT after splenectomy in patient with cirrhosis.METHODS A total of 45 patients with cirrhosis who underwent splenectomy were consecutively enrolled from January 2017 to December 2018.The incidence of PVT at 1 months,3 months,and 12 months after splenectomy in patients with cirrhosis was observed.The hematological indicators,biochemical and coagulation parameters,and imaging features were recorded at baseline and at each observation point.The univariable,multivariable,receiver operating characteristic curve and timedependent curve analyses were performed.RESULTS The cumulative incidence of PVT was 40.0%,46.6%,and 48.9%at 1 months,3 months,and 12 months after splenectomy.Multivariable analysis showed that portal vein diameter(PVD)≥14.5 mm and monthsdel end-stage liver disease(MELD)score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy(P<0.05).Time-dependent curve showed that the cumulative incidence of PVT was significantly different between patients with MELD score≤10 and>10(P<0.05).In addition,the cumulative incidence of PVT in the PVD≥14.5 mm group was significantly higher than that in the PVD<14.5 mm group(P<0.05).CONCLUSION Wider PVD and MELD score>10 were independent predictors of PVT at 1 months,3 months,and 12 months after splenectomy in patient with cirrhosis.

Establishment of a prediction model for severe acute radiation enteritis associated with cervical cancer radiotherapy

BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors.Radiation enteritis(RE)leads to radiotherapy intolerance or termination of radiotherapy,which negatively impacts the therapeutic effect and seriously affects the quality of life of patients.If the incidence of RE in patients can be predicted in advance,and targeted clinical preventive treatment can be carried out,the side effects of radiotherapy in cervical cancer patients can be significantly reduced.Furthermore,accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan.AIM To analyze the relationships between severe acute RE(SARE)of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively.METHODS We included 50 cervical cancer patients who received volumetric modulated arc therapy(VMAT)from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University.Clinical and dose-volume histogram factors of patients were collected.Logistic regression analysis was used to evaluate the predictive value of each factor for SARE.A nomogram to predict SARE was developed(SARE scoring system≥3 points)based on the multiple regression coefficients;validity was verified by an internal verification method.RESULTS Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy.The main adverse reactions were diarrhea,abdominal pain,colitis,anal swelling,and blood in the stool.There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups(P>0.05).There were significant differences in the small intestine V_(20),V_(30),V_(40),and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery(P<0.05).Univariate and multivariate analyses revealed anal bulge rating(OR:14.779,95%CI:1.281-170.547,P=0.031)and disease activity index(DAI)score(OR:53.928,95%CI:3.822-760.948,P=0.003)as independent predictors of SARE.CONCLUSION Anal bulge rating(>0.500 grade)and DAI score(>2.165 points)can predict SARE.The nomogram shows potential value in clinical practice.

Safety and effectiveness of lurasidone in the treatment of Chinese schizophrenia patients:An interim analysis of post-marketing surveillance

BACKGROUND Schizophrenia is a psychiatric disorder characterized by chronic or recurrent symptoms.Lurasidone was licensed in China in 2019 for the treatment of adult schizophrenia in adults with a maximum dose of 80 mg/d.However,post-market surveillance(PMS)with an adequate sample size is required for further validation of the drug’s safety profile and effectiveness.AIM To conduct PMS in real-world clinical settings and evaluate the safety and effectiveness of lurasidone in the Chinese population.METHODS A prospective,multicenter,open-label,12-wk surveillance was conducted in China's Mainland.All patients with schizophrenia from 10 sites who had begun medication with lurasidone between September 2019 and August 2022 were eligible for enrollment.Safety assessments included adverse events(AEs),adverse drug reactions(ADRs),extrapyramidal symptoms(EPS),akathisia,use of EPS drugs,weight gain,and laboratory values as metabolic parameters and the QTc interval.The effectiveness was assessed using the brief psychiatric rating scale(BPRS)from baseline to the end of treatment.RESULTS A total of 965 patients were enrolled in the full analysis set and 894 in the safety set in this interim analysis.The average daily dose was 61.7±19.08 mg(mean±SD)during the treatment.AEs and ADRs were experienced by 101 patients(11.3%)and 78 patients(8.7%),respectively,which were mostly mild.EPS occurred in 25 individuals with a 2.8%incidence,including akathisia in 20 individuals(2.2%).Moreover,59 patients received drugs for treating EPS during the treatment,with an incidence of 6.6%which dropped to 5.4%at the end of the treatment.The average weight change was 0.20±2.36 kg(P=0.01687)with 0.8%of patients showing a weight gain of≥7%at week 12 compared with that at the baseline.The mean values of metabolic parameters and the QTc interval at baseline and week 12 were within normal ranges.The mean changes in total BPRS scores were-8.9±9.76(n=959),-13.5±12.29(n=959),and-16.8±13.97(n=959)after 2/4,6/8,and 12 wk,respectively(P<0.001 for each visit compared with the baseline)using the last-observation-carried-forward method.CONCLUSION The interim analysis of the PMS of adult patients with schizophrenia demonstrate the safety and effectiveness of lurasidone in the Chinese population.No new safety or efficacy concerns were identified.

Evaluation of polygenic risk score for risk prediction of gastric cancer

Genetic variations are associated with individual susceptibility to gastric cancer.Recently,polygenic risk score(PRS)models have been established based on genetic variants to predict the risk of gastric cancer.To assess the accuracy of current PRS models in the risk prediction,a systematic review was conducted.A total of eight eligible studies consisted of 544842 participants were included for evaluation of the performance of PRS models.The overall accuracy was moderate with Area under the curve values ranging from 0.5600 to 0.7823.Incorporation of epidemiological factors or Helicobacter pylori(H.pylori)status increased the accuracy for risk prediction,while selection of single nucleotide polymorphism(SNP)and number of SNPs appeared to have little impact on the model performance.To further improve the accuracy of PRS models for risk prediction of gastric cancer,we summarized the association between gastric cancer risk and H.pylori genomic variations,cancer associated bacteria members in the gastric microbiome,discussed the potentials for performance improvement of PRS models with these microbial factors.Future studies on comprehensive PRS models established with human SNPs,epidemiological factors and microbial factors are indicated.

脉络膜厚度与黄斑裂孔的相关性

目的:探究脉络膜厚度与黄斑裂孔的相关性,为黄斑裂孔的诊断与治疗提供理论依据。方法:本研究观察对象为2015-06/2016-06于我院眼科治疗的40例单眼特发性黄斑裂孔患者以及40例正常体检人员,将特发性黄斑裂孔患者患眼(40眼)设为A组、健侧眼(40眼)设为B组,40例正常体检人员40只正常眼设为C组,通过增强深部成像的相干光断层扫描(enhanced depth image optical coherence tomography,EDIOCT)对黄斑中心凹,黄斑中心凹外1、3mm上下鼻颞四方位9个点的脉络膜厚度进行测定,分别记为SFCT、SCT_(1mm)、SCT3mm、ICT_(1mm)、ICT3mm、NCT_(1mm)、NCT_(3mm)、TCT_(1mm)、TCT3mm,并对SFCT与年龄的关系进行相关性分析。结果:A、B组平均SFCT无显著性差异,C组显著高于A、B组,差异有统计学意义(P<0.05);A、B组SCT_(1mm)、SCT3mm、ICT_(1mm)、ICT3mm、NCT_(1mm)、NCT_(3mm)、TCT_(1mm)、TCT3mm比较,差异无统计学意义(P>0.05),且C组各测量点脉络膜厚度均显著高于A、B组,差异有统计学意义(P<0.05);与年龄的相关性分析发现,A、B组SFCT与年龄无明显相关性(r=-0.065,P=0.148;r=-0.057,P=0.658),C组SFCT与年龄呈负相关(r=-0.343,P=0.041)。结论:特发性黄斑裂孔的发病机制可能与其脉络膜厚度明显降低有关,对侧健眼较正常人群脉络膜厚度也明显降低。

大型综合医院眼眶病专业门诊疾病谱分析及诊治经验

目的:观察眼眶病专业门诊患者疾病谱变化和疾病分布特点,介绍眼眶门诊疾病的诊治流程和方法;明确眼眶病专业的工作重点和社会需求。方法:前瞻性观察研究。设计登记表,记录本治疗组门诊眼眶病患者性别、年龄、门诊诊断。眼眶病共分为七大类,统计分析七大类疾病的构成比、男女比例、发病年龄,以及优势病种的亚类和前三位常见疾病。介绍本院眼眶病专业门诊的诊治流程。结果:2021-04-01/12-31本治疗组门诊登记眼眶病患者共1059例。最常见的是甲状腺相关眼病325例(30.7%),其他依次是眼眶肿瘤282例(26.6%)、眼眶外伤213例(20.1%)、眼眶炎症205例(19.4%),眼眶血管畸形、先天性和遗传性病和其他3类眼眶疾病共34例(3.2%)。病理诊断:眼眶肿瘤良性150例(72.8%),前三位分别是血管淋巴管瘤、眼眶囊肿和神经源性肿瘤;恶性56例(27.2%),前三位分别是眶淋巴瘤、泪腺腺样囊性癌和横纹肌肉瘤。眼眶外伤最常见的是眼眶爆裂骨折,其次是视神经损伤、眼眶软组织挫伤。眼眶炎症中非感染性占89.8%,感染性占10.2%。结论:眼眶病疾病谱有所变化,常见和优势病种依次是甲状腺相关眼病、眼眶肿瘤、眼眶外伤和眼眶炎症,共占96.8%,是眼眶病专业门诊医师的主要工作内容。应根据疾病谱变化合理配置眼眶病专业的医疗资源,适应社会发展需求。

Long noncoding RNA RP4 functions as a competing endogenous RNA through miR-7-5p sponge activity in colorectal cancer

AIM To investigate the role of long noncoding RNA(lnc RNA) RP4 in colorectal cancer.METHODS Lentivirus-mediated lnc RNA RP4 overexpression and knockdown were performed in the colorectal cancer cell line SW480. Cell proliferation, tumor growth, and early apoptosis were evaluated by a cell counting kit-8 assay, an in vivo xenograft tumor model, and annexin V/propidium iodide staining, respectively. Analysis of the lnc RNA RP4 mechanism involved assessment of the association of its expression with mi R-7-5 p and the SH3 GLB1 gene. Western blot analysis was also performed to assess the effect of lnc RNA RP4 on the autophagy-mediated cell death pathway and phosphatidylinositol-3-kinase(PI3 K)/Akt signaling.RESULTS Cell proliferation, tumor growth, and early apoptosis in SW480 cells were negatively regulated by lnc RNA RP4. Functional experiments indicated that lnc RNA RP4 directly upregulated SH3 GLB1 expression by acting as a competing endogenous RNA(ce RNA) for mi R-7-5 p. This interaction led to activation of the autophagy-mediated cell death pathway and de-repression of PI3 K and Akt phosphorylation in colorectal cancer cells in vivo.CONCLUSION Our results demonstrated that lnc RNA RP4 is a ce RNA that plays an important role in the pathogenesis of colorectal cancer, and could be a potential therapeutic target for colorectal cancer treatment.

Hydrological daily rainfall-runoff simulation with BTOPMC model and comparison with Xin'anjiang model

A grid-based distributed hydrological model, the Block-wise use of TOPMODEL （BTOPMC）, which was developed from the original TOPMODEL, was used for hydrological daily rainfall-runoff simulation. In the BTOPMC model, the runoff is explicitly calculated on a cell-by-cell basis, and the Muskingum-Cunge flow concentration method is used. In order to test the model＇s applicability, the BTOPMC model and the Xin＇anjiang model were applied to the simulation of a humid watershed and a semi-humid to semi-arid watershed in China. The model parameters were optimized with the Shuffle Complex Evolution （SCE-UA） method. Results show that both models can effectively simulate the daily hydrograph in humid watersheds, but that the BTOPMC model performs poorly in semi-humid to semi-arid watersheds. The excess-infiltration mechanism should be incorporated into the BTOPMC model to broaden the model＇s applicability.

In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni

AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract(CDAE) in carbon tetrachloride(CCl4)-induced liver damage in rats.METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl(DPPH), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)(ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate(FTC) and thiobarbituric acid(TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAEagainst CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1(CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor(Nrf2), heme oxygenase-1(HO-1), NAD(P)H quinine oxidoreductase 1(NQO1), and γ-glutamylcysteine synthetase catalytic subunit(γ-GCSc) protein expression was measured by Western blot.RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation(P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE(160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes(P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression.CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.

On the energy conservation and critical velocities for the propagation of a "steady-shock" wave in a bar made of cellular material

The propagation of shock waves in a cellular bar is systematically studied in the framework of continuum solids by adopting two idealized material models, viz. the dynamic rigid, perfectly plastic, locking （D-R-PP-L） model and the dynamic rigid, linear hardening plastic, locking （D-R-LHP-L） model, both considering the effects of strain-rate on the material properties. The shock wave speed relevant to these two models is derived. Consider the case of a bar made of one of such material with initial length L 0 and initial velocity v i impinging onto a rigid target. The variations of the stress, strain, particle velocity, specific internal energy across the shock wave and the cease distance of shock wave are all determined analytically. In particular the ＂energy conservation condition＂ and the ＂kinematic existence condition＂ as proposed by Tan et al. （2005） is re-examined, showing that the ＂energy conservation condition＂ and the consequent ＂critical velocity＂, i.e. the shock can only be generated and sustained in R-PP-L bars when the impact velocity is above this critical velocity, is incorrect. Instead, with elastic deformation, strain-hardening and strain-rate sensitivity of the cellular materials being considered, it is appropriate to redefine a first and a second critical impact velocity for the existence and propagation of shock waves in cellular solids. Starting from the basic relations for shock wave propagating in D-R-LHP-L cellular materials, a new method for inversely determining the dynamic stress-strain curve for cellular materials is proposed. By using e.g. a combination of Taylor bar and Hopkinson pressure bar impact experimental technique, the dynamic stress-strain curve of aluminum foam could bedetermined. Finally, it is demonstrated that this new formulation of shock theory in this one-dimensional stress state can be generalized to shocks in a one-dimensional strain state, i.e. for the case of plate impact on cellular materials, by simply making proper replacements of the elastic and plastic constants.

Rh-incompatible hemolytic disease of the newborn in Hefei

BACKGROUND Anti-D antibody is not the common cause of Rh-isoimmunization in Chinese neonatal jaundice.Recent change in national population policy has followed by an increase in Rh-isoimmunization related hemolytic disease of the newborn(HDN).Unfortunately,regional status of Rh-HDN is unavailable.We hypothesize that Rh-HDN in our region is most commonly due to anti-E antibody.AIM To investigate the prevalence of hemolytic disease of the newborn due to Rhisoimmunization in Hefei City.METHODS Retrospective review of data obtained from Children’s Hospital of Anhui and Hefei Blood Center between January 2017 and June 2019.Status of minor blood group antibody was studied in the corresponding mothers.RESULTS Totally 4138 newborns with HDN admitted during the study period and 116(2.8%)received blood exchange transfusion(BET).Eighteen newborns(0.43%)with proven Rh-incompatible HDN were identified.All were not the first-born baby.Thirteen mothers were RhD(+)(72%)and five were RhD(-).The distribution of Rh-related antibodies in mothers was ten anti-E(55%),five anti-D(27%),and for one anti-C,anti-c,and anti-E/c(6%)each.Thirteen(72.2%)were qualified for BET,relative risk for BET was 28.9 as compared to other types of HDN,but only 10 received due to parenteral refusal.All(100%)RhD related HDN received BET which is not significantly different from RhE related HDN(81.8%).CONCLUSION As expected,all Rh-incompatible HDN newborns were not the first-born.Contrary to the Caucasian population,anti-D induced HDN is not the most common etiology.In our region,anti-E(11/18,61%)is the most common cause of Rh-HDN.

Reduced genome size of Helicobacter pylori originating from East Asia

Helicobacter pylori(H.pylori),a major pathogen colonizing the human stomach,shows great genetic variation.Comparative analysis of strains from different H.pylori populations revealed that the genome size of strains from East Asia decreased to 1.60 Mbp,which is significantly smaller than that from Europe or Africa.In parallel with the genome reduction,the number of protein coding genes was decreased,and the guaninecytosine content was lowered to 38.9%.Elimination of non-essential genes by mutations is likely to be a major cause of the genome reduction.Bacteria with a small genome cost less energy.Thus,H.pylori strains from East Asia may have proliferation and growth advantages over those from Western countries.This could result in enhanced capacity of bacterial spreading.Therefore,the reduced genome size potentially contributes to the high prevalence of H.pylori in East Asia.

Salubrinal protects against tunicamycin and hypoxia induced cardiomyocyte apoptosis via the PERK-eIF2a signaling pathway

Objectives This study examined the protective effect of salubrinal and the mechanism underlying this protection against tunicamycin （TM）- and hypoxia-induced apoptosis in rat cardiomyocytes. Methods Neonatal rat cardiomyocytes were cultured from the ventricles of l-day-old Wistar rats. Cells were exposed to different concentrations of salubrinal （10, 20, and 40 gmol/L） for 30 min followed by TM treatment or hypoxia for 36 h. Apoptosis was measured by a multiparameter HCS （high content screening） apoptosis assay, TUNEL assay and flow cytometry. The phosphorylation of eukaryotic translation initiation factor 2 subunit alpha （eIF2c0 and the expression of cleaved caspase-12 were determined by Western blotting. C/EBP homologous protein （CHOP） was detected by immunocytochemistry. Results HCS, TUNEL assays and flow cytometry showed that salubrinal protected cardiomyocytes against apoptosis induced by TM or hypoxia. Western blotting showed that salubrinal protected cardiomyocytes against apoptosis by inducing eIF2ct phosphorylation and down-regulating the expression of the endoplasmic reticulum stress-mediated apoptotic proteins, CHOP and cleaved caspase-12. Conclusions Our study suggests that salubrinal protects rat cardiomyocytes against TM- or hypoxia-associated apoptosis via a mechanism involving the inhibition of ER stress-mediated apoptosis.

Decreased expression of miR-133a correlates with poor prognosis in colorectal cancer patients

AIM: To investigate microRNA-133a (miR-133a) expression in colorectal cancer (CRC) and its relationship with tumorigenesis and disease prognosis.

Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer

AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman's correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.

Relatedness of Helicobacter pylori populations to gastric carcinogenesis

Helicobacter pylori （H. pylorl） is a Gram-negative bac- terium that infects half of the human population. The infection is associated with chronic inflammation of the gastric mucosa and peptic ulcers. It is also a major risk factor for gastric cancer. Phylogenetic analysis of global strains reveals there are seven populations of H. pylori, including hpAfrical, hpAfrica2, hpEastAsia, hpEurope, hpNEAfrica, hpAsia2 and hpSahul. These populations are consistent with their geographical origins, and pos- sibly result from geographical separation of the bac- terium leading to reduced bacterial recombination in some populations. For each population, H. pylori has evolved to possess genomic contents distinguishable from others. The hpEurope population is distinct in that it has the largest genome of 1.65 mbp on average, and the highest number of coding sequences. This confers its competitive advantage over other populations but at the cost of a lower infection rate. The large genomic size could be a cause of the frequent occurrence of the deletion of the cag pathogenicity island in H. pylori strains from hpEurope. The incidence of gastric cancer varies among different geographical regions. This can be attributed in part to different rates of infection of H. pylori. Recent studies found that different popula- tions of H, pylori vary in their carcinogenic potential and contribute to the variation in incidence of gastric cancer among geographical regions. This could be related to the ancestral origin of H, pylori. Further studies are indi- cated to investigate the bacterial factors contributing to differential virulence and their influence on the clinical features in infected individuals.

Participation of microbiota in the development of gastric cancer

There are a large number of bacteria inhabiting the human body,which provide benefits for the health.Alterations of microbiota participate in the pathogenesis of diseases.The gastric microbiota consists of bacteria from seven to eleven phyla,predominantly Proteobacteria,Firmicutes,Bacteroidetes,Actinobacteria and Fusobacteria.Intrusion by Helicobacter pylori(H.pylori)does not remarkably interrupt the composition and structure of the gastric microbiota.Absence of bacterial commensal from the stomach delays the onset of H.pylori-induced gastric cancer,while presence of artificial microbiota accelerates the carcinogenesis.Altered gastric microbiota may increase the production of N-nitroso compounds,promoting the development of gastric cancer.Further investigation of the carcinogenic mechanisms of microbiota would benefit for the prevention and management of gastric cancer.

Influence of severity and types of astigmatism on visual acuity in school-aged children in southern China

AIM： To investigate the influence of astigmatism on visual acuity in school-aged children, and to define a cutoff for clinically significant astigmatism. METHODS： This is a population-based, cross-sectional study. Among 5053 enumerated children aged 5-15 y in Guangzhou, 3729（73.8%） children aged 7-15 with successful cycloplegic auto-refraction（1% cyclopentolate） and a reliable visual acuity measurement were included. Ocular measurement included external eye, anterior segment, media and fundus and cycloplegic auto-refraction. Primary outcome measures included the relationship between severity and subtypes of astigmatism and the prevalence of visual impairment. Three criteria for visual impairment were adopted： best-corrected visual acuity（BCVA） ≤0.7, uncorrected visual acuity（UCVA） ≤0.5 or 〈0.7 in the right eye.RESULTS： Increases of cylinder power was significantly associated with worse visual acuity（UCVA： β=0.051, P〈0.01; BCVA： β=0.025, P〈0.001）. A substantial increase in UCVI and BCVI was seen with astigmatism of 1.00 diopter（D） or more. Astigmatism ≥1.00 D had a greater BCVI prevalence than cylinder power less than 1.00 D（OR=4.20, 95%CI： 3.08-5.74）, and this was also true for hyperopic, emmetropic and myopic refraction categories. Oblique astigmatism was associated with a higher risk of BCVI relative to with the rule astigmatism in myopic refractive category（OR=12.87, 95%CI： 2.20-75.38）.CONCLUSION： Both magnitude and subtypes of astigmatism influence the prevalence of visual impairment in school children. Cylinder ≥1.00 D may be useful as a cutoff for clinically significant astigmatism.