Objective To explore the effects of mitogen-activated protein kinase (MAPK) pathway by estradiol induced vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in endometrial cancer Ishikawa cells.Methods The experiments were divided into 4 groups:E2 group (Ishikawa cells treated with 1 p mol/L estradiol for 30 minutes); inhibitor group:including Ishikawa cells treated with 10 μmol/L Bibf1 120 (Bibf1 120 group),or treated with 2.5 μmol/L Ponatinib (Ponatinib group),or treated with 10 p mol/L U0126 (U0126 group) for 60 minutes; inhibitor + E2 group:including Ishikawa cells treated with 10 μmol/L Bibf1120 (Bibf1120 + E2 group),or treated with 2.5 μmol/L Ponatinib (Ponatinib + E2 group),or treated with 10 μmol/L U0126 (U0126+ E2 group) for 60 minutes following incubation with 1 μmol/L estradiol for 30 minutes; control group:only adding the culture medium without serum DMEM.(1) Western blot analysis was used to detect phosphorylation extracellular signal-regulated kinase 1/2(p-ERK 1/2) protein expression with stimulation in different concentrations of estradiol (0.01,0.1,1,10,100 μmol/L).(2) Quantitative fluorescent reverse transcription (qRT)-PCR and western blot analysis was used to test the level of mRNA and protein of VEGF,bFGF,MAPK kinase 1/2 (MEK1/2),extracellular signal-regulated kinase 1/2 (ERK1/2),p-ERK1/2 and phosphorylation MEK1/2 (p-MEK1/2).Flow cytometry were used to examine the cell cycle,and transwell chamber assay were used to detect the cell migration in different groups.Results The expression of the p-ERK1/2 protein at 0.01,0.1,1,10,100 μ mol/L were 0.16±0.03,0.10±0.03,0.41 ±0.04,0.19±0.03,0.19±0.03,there were significantly higher than that in control group(0.05±0.00,P＜0.05),and which was more obvious at the concentration of 1 μmol/L estradiol.The expression level of VEGF,bFGF mRNA and protein in E2 group were higher than those in the control group (P＜O.05).VEGF mRNA and protein in Bibf1120+E2 group were higher than those in E2 group.The expression of MEK1/2,ERK1/2 mRNA protein in E2 group were higher than those in control group (P＜0.05).The expression of MEK1/2,ERK1/2 mRNA or p-MEK1/2,p-ERK1/2 protein in Bibf1120 + E2 group,Ponatinib+E2 group or U0126+E2 group were lower than those in E2 group(all P＜0.05).Percentage of G1 phase [(53.6±3.2)％] and S phase[(29.2±4.2)％] in E2 group was significantly different with those in control group respectively(P＜0.05).Percentage of G1 phase[(66.8±2.6)％,(63.1±2.6)％ and (63.3±0.4)％] and S phase [(25.4±1.9)％,(25.0±3.8)％ and(23.8±0.5)％] in U0126+E2 group,Bibf1120+E2 group or Ponatinib +E2 group was also significantly different with those in control group (all P＜0.05); percentage of G1 phase and S phase in U0126+E2 group was significant difference with those in Bibf1120+E2 group or ponatinib+E2 group (P＜0.05).The number of cell colony in E2 group (110± 17) was more than those in control group (65±8) ;the number of cell colony in U0126+E2 group(28±4),Bibf1120+E2 group(38±5) or Ponatinib+E2group(42±6) were significant different with those in E2 group (P＜0.05),the number of cell colony in U0126+E2 group was significant difference with those in Bibf1 120+E2 group or Ponatinib+E2 group (all P＜0.05).The results shown that the abilities of proliferation and cell migration were significantly increased in cells after estradiol stimulation.Conclusion Estradiol inducing the production of VEGF and bFGF could activate MAPK pathway through ER-independent manner,further promote development.

Objective:Guiding hospitals to strengthen the emphasis on clinical medical research, promote hospital discipline construction, to improve the quality of medical services and clinical innovation capacities.Methods:Starting from different user groups, combines the experience of the knowledge base of the library construction institution of Grade-A Tertiary Hospital and the cooperation experience with various functional departments, this paper analyzes the functional structure of the institutional repository according to the problems faced in the actual work to explore the difficulties during the construction process.Results:The construction of the Institutional Repository of hospitals for different users is imminent. In addition to the use of Institutional Repository to improve the utilization of intelligence and information resources, the construction of institutional repository on the evaluation of science and technology influence can also promote the development of hospital disciplines.Conclusions:A solution method is proposed, based on the background of scientific and technological influence evaluation, the future construction direction of the institutional repository.

OBJECTIVETo describe the incidence and related risk factors of fatty liver disease in the general population of Northwest China.

METHODSThe study was a cross-sectional survey with multiplestage stratified cluster and random sampling. All participants were 18 years or older and resided in northwest provinces of China.Demographic and behavioral data was gathered by questionnaire.Clinical data such as height, body weight, waist circumference, biochemical function (standard tests) and liver status (ultrasonographic examination) were also collected.

RESULTSAmong the 2 300 total study participants, 1 523 were habitual drinkers (total drinking rate: 66.2%). This population of drinkers was composed almost exclusively of males. There were 201 cases of alcoholic liver disease (total prevalence:8.7%), represented by mild alcoholic injury (prevalence: 4.2%), alcoholic fatty liver (3.8%), alcoholic hepatitis (0.5%), and alcoholic cirrhosis (0.3%).When examined according to provinces of residence, the prevalence of alcoholic liver disease followed this pattern: Shaanxi (14.0%), Gansu (8.6%), and Xinjiang autonomous region (5.0%). Of the total 337 cases of nonalcoholic fatty liver disease (total prevalence: 14.7%), the prevalence by province was: Shaanxi (18.5%), Gansu (10.3%), and Xinjiang autonomous region (16.6%). Individuals with alcoholic liver disease had significantly higher mean age (years), body weight, body mass index (BMI), waist circumference, average daily alcohol intake, and level of aspartate aminotransferase (AST), and alanine aminotraasferase (ALT) (vs. Those with no liver disease, P less than 0.05). Individuals with nonalcoholic fatty liver disease had significantly higher mean age (years), height, body weight, BMI, waist circumference, level of AST and ALT, and presence of obesity, abdominal obesity, hyperlipidemia, diabetes mellitus and hypertension (vs. Those with no liver disease, P less than 0.05). Multiple logistic regression demonstrated that alcoholic liver disease was closely related to age, sex, and average daily alcohol intake. The prevalence of nonalcoholic fatty liver disease was positively correlated to age, female sex, hyperlipidemia, diabetes mellitus, and BMI.

CONCLUSIONThe drinking-rate and prevalence of fatty liver disease is high in Northwest China, but the most prevalent type is nonalcoholic fatty liver disease.Fatty liver disease is closely related to age, sex, average daily alcohol intake, hyperlipidemia, diabetes mellitus, and BMI.

Aspartate Aminotransferases ; Body Mass Index ; Body Weight ; China ; Cross-Sectional Studies ; Diabetes Mellitus ; Fatty Liver ; Female ; Humans ; Hyperlipidemias ; Hypertension ; Logistic Models ; Male ; Obesity ; Prevalence ; Risk Factors ; Surveys and Questionnaires ; Waist Circumference

Tertiary lymphoid structures (TLS) are ectopic lymphoid structures in cancers that are largely associated with favourable prognosis. However, the prognostic value of TLSs in oral squamous cell carcinoma (OSCC) is largely unknown, and the association between tumour infiltrating lymphocytes (TILs) and TLSs has been rarely explored in OSCC. In this study, associated markers of TLS, including peripheral node address (PNAd) in high endothelial venules, CD20 in B cells and CD3 in T cells, were examined in 168 OSCC patients, and survival analysis was performed between TLS-positive and TLS-negative cohorts. We detected the presence of TILs by staining CD8+ cytotoxic T cells and CD57+ NK cells as well. TLSs appeared as highly organized structures in 45 (26.8%) cases. TLS-positive patients had a better 5-year overall survival (OS) rate (88.9% vs. 56.1%, P < 0.001) and relapse-free survival (RFS) rate (88.9% vs. 63.4%, P = 0.002). Moreover, the presence of TLS was an independent prognostic factor for both the 5-year OS rate (hazard ratio [HR] = 3.784; 95% confidence interval [CI], 1.498-9.562) and RFS rate (HR = 3.296; 95% CI, 1.279-8.490) in multivariate analysis. Furthermore, a higher density of CD8+ T cells and CD57+ NK cells was found in TLS-positive sections than in TLS-negative counterparts (P < 0.001), and their combination provided a higher predictive accuracy (AUC = 0.730; 95% CI, 0.654-0.805). In conclusion, our results suggest that TLS is an independent positive prognostic factor for OSCC patients. These findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.