OBJECTIVE To investigate the dynamic changes in urine metabolic profiles in rats induced by D-galactose (D-Gal),and to study the correlations between the differential metabolites and behavior indicators using the proton nuclear magnetic resonance (1H-NMR)-based metabonomics.METHODS Subcutaneous injection of D-Gal 100 mg· kg-1 for 10 weeks was adopted in the model group.The sample of urine was collected at day 0 (dO),d14,d28,d42,d56 and d70.NMR metabonomics technique was used for acquisition of data,which was analyzed by multivariate statistical analysis.The ability of learning and memory were measured by Morris water maze test from d70.After the behavioral test,the rats were sacrificed and the hippocampus was observed by hematoxylin-eosin staining.RESULTS Principal component analysis (PCA) results revealed that there was considerable difference between the model group and the normal control group at d70.According to the varible importance plot (VIP) calculation and S-plot scores,a total of 12 metabolites were screened and identified as potential biomarkers at d70.The differences of metabolites and Morris water maze test were subjected to correlation analysis,and the results showed that the levels of choline,lactate and dimethylglycine in the model group were significantly increased and negatively correlated with the times of crossing the platform (r =-0.90,-0.50 and-0.52;n=10).Formate was significantly negatively correlated with the time spent in the target area (r =-0.51,n=10),but choline and formate were significantly positively correlated with the escape latency (r =0.72 and 0.53;n=10).However,the levels of creatine and taurine decreased in the model group,which was significantly positively correlated to the times of acrossing platforms (r =0.89 and 0.71;n=10),while alanine was significantly positively correlated to the time spent in the target area(r =0.74,n=10).Taurine,alanine and creatine were significantly negatively correlated with the escape latency (r =-0.66,-0.50 and-0.85;n=10).The correlations between the differential metabolites and the behavioral indicators were further proved.CONCLUSION The metabolic profile changes in urine from D-Gal induced aging model rats are significantly correlated with impairement of ability in learning and memory.1H-NMR metabonomics in urinary metabolic profile changes may be used as an evaluation index in the D-Gal induced aging rats model.

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg(-1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, β-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.

Objective In this paper,we analyzed the initial review projects of clinical research during past five years in a hospital,which aims to summarize the experience and analysis existent problems,in order to provide a reference for the future hospital ethics review.Methods Summarizing and analyzing the meeting records during past five years,which were also in the field of the initial review projects of clinical research.Results Clinical trials of drug and divice,and clinical research projects exist in varying degrees of problems,which express in these two aspects:research design and ethical rational.Conclusions Ethics Committee should stengthen review the following two parts,the scientific of research project and the informed consent form.Improve their own system constantly,and ensure the efficient operation of the Ethics Committee.

T lymphocyte subpopulation and level of soluble interleuckin 2 receptor in peripheral bloodand serum of primary hepatocellular carcinoma and donor were tested.The results show that de-crease of T lymphocyte subpopulations is related with increase of level of soluble interleuckin2 re-ceptor in patients with primary hepatocellular carcinoma.

Objective To predict clinical chemotherapy sensitivity of primary ovarian cancer by jointing adenosine triphosphate(ATP) - tumor chemo-sensitivity assay(TCA) method in vitro and detection of drug resistance genes, provide reference for clinical treatment. Methods Forty-seven primary epithelial ovarian tumor samples were collected from the patients who received cytoreductive surgery. Viable ovarian cancer cells obtained from malignant tissue were tested for their sensitivity to carboplatin (CBP), cisplatin (DDP), paclitaxel(PTX) and CBP + PTX using ATP-TCA method in vitro; at same time, real-time quantitative PCR was used to analysis BRCA1 and ERCC1 mRNA relative expression in forty-six specimens (1 frozen tumor samples mRNA were not detected due to serious degradation). The relationship between ATP-TCA test results, clinical indicators, and the effectiveness of the joint prediction on clinical chemosensitivity by combining these two methods were statistically analyzed using chi-square test. Results (1)The results showns that three programs of DDP,CBP and PTX + CBP were significantly related with clinical results(P<0.05) in vitro, in which the compliance rate in PTX + CBP program was the highest 83%(39/47) ,and the predictive sensitivity, predictive specificity, positive predictive value, negative predictive value and predictive accurate rate were 90%,71%,84% and 80% ,respectively.PTX + CBP combined in vitro test results was also related with residual tumor size and neoadjuvant chemotherapy, which was more prone to drug resistance with residual tumor larger than 2 cm (P = 0. 023) and with neoadjuvant chemotherapy (P = 0.011). (2) BRCA1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was 0.673 ± 2.143 and - 1.436 ± 2.594 (P=0.008), ERCC1 mRNA expression levels in the clinical-resistant group and the clinical-sensitive group was -0.529 ± 1.982 and - 3.188 ±2.601 (P =0.001). There were also significant correlation among the expression levels of BRCA1 ,ERCC1 mRNA and clinical efficacy (P<0.01). (3)ATP-TCA and detection of drug resistance genes combined to predict the clinical application of PTX + CBP resistance may occur in 8/9 cases. Conclusions ATP-TCA may be an ideal method of in vitro drug sensitivity testing method, which could effectively predict clinical chemotherapy sensitivity. Combination of the drug-resistant associated genes detection method and the ATP-TCA method can increase the predictive effectiveness of ovarian cancer chemosensitivity and guide individual chemotherapy of ovarian cancer.

[摘 要] 目的：探讨肿瘤坏死因子受体相关蛋白1（TRAP1）在结肠癌组织和细胞中的表达及其与临床病理特征和患者预后的关系和相关分子机制。方法：通过TCGA和GEO数据全面分析TRAP1在结肠癌中的表达及其与临床病理特征和患者预后的关系，选取2020年10月至2021年03月间在山西医科大学第一医院手术切除的10例结肠癌组织及相应癌旁组织标本，用IHC染色法检测中国人结肠癌组织中TRAP1的表达进行验证，运行R包（survival和survminer）进行Kaplan-Meier生存分析；在线分析TRAP1蛋白的信号肽及穿膜结构域，通过基因富集分析软件进行GO分析和KEGG分析。培养结肠癌SW480和SW620细胞，将si-NC和si-TRAP1转染结肠癌细胞，实验分为空白对照组、si-NC组和si-TRAP1组，采用qPCR法检测转染后各组结肠癌细胞中TRAP1的表达，FCM检测转染后各组细胞的细胞周期和凋亡情况。结果：与癌旁组织比较，TRAP1在结肠癌组织中呈高表达（P<0.01），TRAP1表达水平与淋巴结转移有关联（P<0.05），TRAP1高表达组结肠癌患者5年OS率较低（P<0.05）。TRAP1蛋白属于细胞质蛋白，功能富集结果显示TRAP1及其相关分子与细胞周期、核糖体生物发生等信号通路有关（均P<0.01），TRAP1高表达组的结肠癌代谢重编程基因簇和线粒体蛋白输入基因簇水平升高（均P<0.01）。敲减TRAP1后，结肠癌细胞周期阻滞于G1期，细胞凋亡水平显著升高（均P<0.01）。结论：TRAP1在结肠癌组织中呈高表达，且与患者淋巴结转移和低OS率相关联，敲减TRAP1可阻滞结肠癌细胞周期并促进其凋亡。