Tdentification of a new target region on the long arm of chromosome 7 in gastric carcinoma by loss of heterozygosity

AIM: To define the common deleted region on the long arm of haman chromosome 7q linked to primary gastric carcinomas in Chinese by loss of heterozygosity (LOH)and its clinical significance.METHODS: Nine microsatellite markers distributed over chromosome 7q with an average marker density of 10cM were used to examine 70 primary gastric carcinomas for LOH by PCR amplification. The PCR products were separated by electrophoresis on polyacrylamide gel.Genescan and Genotyper soft-wares were used to analyze LOH.RESULTS: LOH with at least one marker on 7q occurred in 34.3% (12/50) of the tumors. Among them, LOH at D7S486 and D7S798 was higher in 24.0% (24/70) and 19.2% (5/26), respectively. By statistical analysis we also observed an obvious genotype-phenotype correlation on 7q (P＜0.05). The frequency of LOH at D7S486 in patients with lymph node metastasis was significantly higher than that in those without lymph node metastasis (P= 0.015).CONCLUSION: The high incidence of LOH at D7S486and its correlation with poorer prognosis suggest that there might be putative tumor suppressor genes in this region involved in the tumorigenesis and progression of gastric carcinoma.     

风湿性二尖瓣狭窄患者心钠素与血液动力学关系研究

应用超声心动图(M型、二维及多普勒)检查法和放射性免疫测定法,对31例风湿性二尖搏狭窄患者的心房大小、心功能及血液动力学与血浆心钠素浓度之间的关系进行研究。结果显示:血浆心钠素浓度水平,在二尖瓣狭窄组明显高于正常对照组,且与左心房容量、压力、张力及肺动脉压等明显相关。     

血糖,血浆胰岛素水平与血压升高的关系发生于糖尿病之前？

对年龄２５岁～７４岁２０１例糖耐量正常（ＮＯＧＴＴ）、３０７例ＩＧＴ、３６６例新发现ＮＩＤＤＭ，进行Ｐｅｒｓｏｎ单相关分析。年龄、性别、ＢＭＩ、空腹及服糖后血糖、胰岛素（ＩＮＳ）水平分别与血压正相关，调整年龄、性别、ＢＭＩ、血浆胆固醇、抽烟等因素后，ＮＯＧＴＴ及ＩＧＴ血糖与血压相关，ＮＩＤＤＭ者血糖与血压不相关，提示血糖水平对血压的影响发生于糖尿病之前。ＮＯＧＴＴ、ＩＧＴ、和ＮＩＤＤＭ总组，ＮＯＧＴＴ及ＩＧＴ组血浆ＩＮＳ水平与血压不相关，只有年龄小于５０岁，非肥胖的ＮＯＧＴＴ者血浆ＩＮＳ水平与血压相关，提示血浆胰岛素水平对血压的影响发生于年轻非肥胖的糖耐量正常者。     

Activation of fibronectin gene expression by hepatitis B virus x antigen

The development of fibrosis and cirrhosis during chronic hepatitis B virus (HBV) infection correlates with the persistent expression of HBV x antigen (HBxAg), which acts in part, by stimulating selected signal transduction pathways, including nuclear factor kappa B (NF-kappa B). To identify NF-kappa B responsive genes that are differentially expressed in HBxAg-positive cells, HepG2 cells were stably transfected with HBxAg, and then with pZeoSV2 or pZeoSV2-I kappa B alpha. When RNAs from each culture were compared by PCR-select cDNA subtraction, fibronectin (FN) mRNA was shown to be strongly down-regulated by I kappa B alpha. Up-regulated expression of FN and co-expression between FN and HBxAg were observed in liver sections from HBV carriers that were stained for HBxAg and analysed for FN mRNA by in situ hybridization (ISH). In liver cell cultures, HBxAg increased the levels of FN mRNA and protein. This was because of the HBxAg-mediated trans-activation of the FN promoter, which was NF-kappa B-dependent. HBxAg also antagonized the repression of the FN promoter by the tumour suppressor, p53. Hence, the FN gene may be a natural target for HBxAg trans-activation, perhaps through activation of NF-kappa B and inactivation of p53, thereby contributing to the accumulation of FN in the liver over the course of chronic HBV infection.     

An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study

Aim/hypothesis Microalbuminuria represents the earliest clinical evidence of diabetic nephropathy and is a marker of increased cardiovascular morbidity and mortality. Its early detection allows the implementation of individualised and aggressive intervention programmes to reduce cardiovascular risk factors. There is limited information on the prevalence of microalbuminuria among hypertensive type 2 diabetic patients in Asia.Methods This cross-sectional epidemiological study aimed to assess the prevalence of microalbuminuria and macroalbuminuria among consecutively screened hypertensive type 2 diabetic adult patients in 103 centres in 10 Asian countries or regions. Predictive factors for microalbuminuria and macroalbuminuria were characterised using a stepwise logistic regression model.Results A total of 6,801 patients were enrolled and 5,549 patients constituted the per-protocol population (patients with bacteriuria and haematuria were excluded). The prevalence of microalbuminuria was 39.8% (39.2–40.5; 95% CI) and the prevalence of macroalbuminuria was 18.8% (18.2–19.3; 95% CI). Only 11.6% of the patients had systolic and diastolic blood pressure below the 130/80 mm Hg target. In the multivariate analyses, the predictive factors for the presence of microalbuminuria were age, BMI, systolic blood pressure and ethnic origin. The highlighted predictive factors for the presence of macroalbuminuria were age, sex, ethnic origin, BMI, duration of diabetes, presence of diabetic complications, intake of diuretics, intake of calcium channel blockers, diastolic and systolic blood pressure.Conclusions/interpretation The high prevalence (58.6%) of micro or macroalbuminuria observed in these patients is alarming and indicates an impending pandemic of diabetic cardiovascular and renal diseases in Asia with its potential economic consequences.A.Y.T. Wu, F.A. de Leon and M.R. Weir received honoraria for speaking engagements and A. Rouillon is employed by Sanofi-Synthelabo Groupe.     

Emetine inhibits glycolysis in isolated, perfused rat hearts

This work was designed to test whether phosphofructokinase is a target for emetine action on the heart. The effects of 37, μM emetine on the activities of phosphofructokinase and hexokinase were measured in homogenates from perfused hearts. The action of increasing concentrations of emetine was determined in nonperfused heart homogenates. The effect of 37 μM emetine or control solutions on the concentration of fructose-6-phosphate and fructose-1,6-phosphate was measured. The effect of 37 μM emetine or control perfusion on the utilization of fructose-6-phosphate by phosphofructokinase in centrifugation supernatants of homogenates and in reconstituted 27,000g pellets was measured. Double-reciprocal plots of fructose-6-phosphate concentrations vs phosphofructokinase activities were plotted. Emetine decreased phosphofructokinase activity in homogenates from both perfused and nonperfused hearts. Emetine did not inhibit cardiac hexokinase activity. In homogenates from nonperfused hearts, the maximal inhibition with high concentrations of emetine was approx 50%. Emetine perfusion caused a simultaneous increase in the phosphofructokinase substrate fructose-6-phosphate and a decrease in the phosphofructokinase product fructose-1,6-bisphosphate. Phosphofructokinase and, consequently, glycolytic flux appear to be subcellular targets for emetine in the heart. Homogenate centrifugation studies indicate that emetine acts on bound rather than unbound phosphofructokinase. The inhibition may be uncompetitive in nature.     

Desired vancomycin trough concentration to achieve an AUC0‐24/MIC ≥400 in Chinese children with complicated infectious diseases

A vancomycin steady‐state trough concentration (C_min) of 15‐20 mg/L is recommended for achieving a ratio of the 24‐hour area under the curve to the minimum inhibitory concentration (AUC_0‐24/MIC) of ≥400 in adults. Since few paediatric data are available, our objectives were to (a) measure the pharmacokinetic indices of vancomycin and (b) determine the correlation between C_min and AUC_0‐24/MIC in paediatric patients. Population‐based pharmacokinetic modelling was performed for paediatric patients to estimate the individual parameters. The relationship between C_min and the calculated AUC_0‐24/MIC was explored using linear regression and a probabilistic framework. A sensitivity analysis was also conducted using Monte Carlo simulations. Body‐weight significantly influenced the pharmacokinetics of vancomycin. Based on real data and simulations, C_min ranges of 5.0‐5.9 and 9.0‐12.9 mg/L were associated with AUC_0‐24/MIC ≥400 for MIC values of ≤0.5 and ≤1 mg/L, respectively. Vancomycin regimens of 10 and 15 mg/kg every 6 hours achieved a C_min of 5.0‐5.9 mg/L and AUC_0‐24/MIC ≥400 in >90% of the children when MIC was ≤0.5 mg/L. At a MIC of ≤1 mg/L, vancomycin at 15 mg/kg every 6 hours achieved C_min of 9.0‐12.9 mg/L and AUC_0‐24/MIC ≥400 in 2.0‐ and 1.6‐fold as many children compared to a dose of 10 mg/kg every 6 hours, respectively. Vancomycin C_min values of 5.0‐12.9 mg/L were strongly predictive of achieving AUC_0‐24/MIC ≥400, and rational dosing regimens of 10‐15 mg/kg q6h were required in paediatric patients, depending on the pathogen.     

A combination of ssGSEA and mass cytometry identifies immune microenvironment in muscle‐invasive bladder cancer

BackgroundMuscle‐invasive bladder cancer (MIBC) is a heterogeneous disease with varying clinical courses and responses to treatment. To improve the prognosis of patients, it is necessary to understand such heterogeneity.MethodsWe used single‐sample gene set enrichment analysis to classify 35 MIBC cases into immunity‐high and immunity‐low groups. Bioinformatics analyses were conducted to compare the differences between these groups. Eventually, single‐cell mass cytometry (CyTOF) was used to compare the characteristics of the immune microenvironment between the patients in the two groups.ResultsCompared with patients in the immunity‐low group, patients in the immunity‐high group had a higher number of tumor‐infiltrating immune cells and greater enrichment of gene sets associated with antitumor immune activity. Furthermore, positive immune response‐related pathways were more enriched in the immunity‐high group. We identified 26 immune cell subsets, including cytotoxic T cells (Tcs), helper T cells (Ths), regulatory T cells (Tregs), B cells, macrophages, natural killer (NK) cells, and dendritic cells (DCs) using CyTOF. Furthermore, there was a higher proportion of CD45+ lymphocytes and enrichment of one Tc subset in the immunity‐high group. Additionally, M2 macrophages were highly enriched in the immunity‐low group. Finally, there was higher expression of PD‐1 and Tim‐3 on Tregs as well as a higher proportion of PD‐1+ Tregs in the immunity‐low group than in the immunity‐high group.ConclusionIn summary, the immune microenvironments of the immunity‐high and immunity‐low groups of patients with MIBC are heterogeneous. Specifically, immune suppression was observed in the immune microenvironment of the patients in the immunity‐low group.     

miR‐30b‐5p up‐regulation related to the dismal prognosis for patients with renal cell cancer

The diagnosis of renal cell carcinoma (RCC) is often made late since there is no early symptom, which thus results in dismal patient prognosis. As a result, new biomarkers are urgently needed and efforts should be made to identify their functions in predicting RCC prognosis. microRNAs (miRNAs) are a class of small noncoding RNAs that are about 20‐22 nucleotides in length, and they have been demonstrated to function as prognostic markers in numerous tumors. This study aimed to assess the role of miR‐30b‐5p in predicting the prognosis of RCC postoperatively. In this study, RNA was extracted from 284 formalin‐fixed and paraffin‐embedded kidney cancer tissue samples. After cDNA synthesis, real‐time quantitative PCR (RT‐qPCR) was adopted for detecting the relative miR‐30b‐5p level. Then, the Kaplan‐Meier method, Cox regression analysis, and the receiver operating characteristic curve analysis were applied in analyzing the miR‐30b‐5p effect on the prognosis for patients. Our findings indicated that, following adjustment for age, gender, tumor stage, and tumor size, patients with low miR‐30b‐5p expression had remarkably longer overall survival. Thus, the miR‐30b‐5p level might be related to RCC prognosis.     

Comparison of the clinical characteristics of patients with novel coronavirus pneumonia between China and overseas

BackgroundTo explore the clinical manifestation, imaging examination, and serology of patients with novel coronavirus pneumonia (COVID‐19) between China and overseas.MethodsNinety patients with COVID‐19 who admitted to Fuzhou Pulmonary Hospital from January 23, 2020, to May 1, 2020, were included in this retrospective study. They were divided into domestic group and overseas group according to the origin regions. The clinical manifestations, imaging examination, serology, treatment, and prognosis between the two groups were compared and analyzed.ResultsThe clinical manifestations of patients in the two groups mainly included fever (83.1% and 47.4%), cough (62% and 31.6%), expectoration (47.9% and 31.6%), anorexia (28.2% and 47.4%), fatigue (21.1% and 10.5%), and dyspnea (22.5% and 0%). The main laboratory characteristics in the two groups were decreased lymphocyte count, increased lactate dehydrogenase, decreased oxygenation index, decreased white blood cell count, increased erythrocyte sedimentation rate (ESR), and increased C‐reactive protein. The computed tomography (CT) examinations of chest showed bilateral and peripheral involvement, with multiple patch shadows and ground glass shadows. However, pleural effusions were rare.ConclusionFever, cough, and dyspnea are more common in domestic cases than overseas cases. However, patients with COVID‐19 from overseas may have the symptoms of loss of taste and smell that domestic cases do not have.