E6E7 regulates the HK2 expression in cervical cancer via GSK3ß/FTO signal.

BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide. Hexokinase 2 (HK2) is responsible for phosphorylating glucose into glucose-6-phosphate, which is required for tumorigenesis and metastasis. METHODS: E6E7 and FTO were exogenously expressed, and their effects on HK2 mRNA and protein levels were detected by RT-qPCR and Western blot. RESULTS: The exogenous expression of E6E7 in SiHa and C33A cells up-regulated the mRNA and protein levels of intracellular HK2, up-regulated the total m6A levels, changed the expression of m6A proteins and activated the GSK3ß transcription. The expression levels of METTL3 and WTAP were enhanced, whereas the expression of FTO and ALKBH5 were decreased. In addition, FTO down-regulated the mRNA and protein levels of HK2. FTO overexpression partially inhibited the up-regulated expression of HK2 caused by E6E7. Furthermore, FTO overexpression increased the level of HK2 pre-mRNA in the nucleus and decreased the level of mature HK2 mRNA in the cytoplasm. We also found that GSK3ß overexpression enhanced FTO ubiquitination and decreased FTO protein levels. CONCLUSION: This study found that E6E7 oncogene activates the transcription of GSK3ß; GSK3ß can promote the ubiquitination-proteasomal degradation of FTO and reduce the level of FTO protein; FTO inhibits the maturation and translation of HK2 mRNA by retaining HK2 pre-mRNA in the nucleus.

Evaluation of the drug effect and rational use of antiseptic drugs in outpatient and emergency department of hospital.

With the popularization and application of antiseptic drugs, the abuse of antiseptic drugs and various unreasonable applications have also become a serious medical problem. The prescriptions of antibiotics in our hospital were randomly selected for statistical analysis. Further, we analyzed the various situations of the use of antibiotics in outpatient department, and calculated the DDDs of different drugs based on the defined daily dose (DDD). The results showed that there were 403 unreasonable prescriptions, accounting for 24.9% of the drug prescriptions. The main problems of irrational prescriptions were unsuitable drugs, non indications and improper frequency of administration, which accounted for 27.1%, 21.3% and 18.3%. It is suggested that the quality department of the hospital should strengthen the special training for rational use of antimicrobial agents, intervene in time and effectively, and gradually change post evaluation into prevention and intervention in advance.

Synergistic effect of metformin and medroxyprogesterone 17­acetate on the development of endometrial cancer.

Accumulating data indicate that insulin resistance and unopposed estrogen are important risk factors of endometrial cancer (EC). Medroxyprogesterone 17­acetate (MPA) has been used in the treatment of EC for many years. However, the therapeutic effect of this agent on EC has not been satisfactory. 36 arMetformin was recently reported to be a promising agent for the treatment of malignant diseases including EC. However, information on the synergistic effect of the two agents in EC is limited. With the aim to evaluate the synergistic effect of metformin and MPA, we conducted the present study in vitro and in vivo. We found that the combined application of metformin and MPA significantly inhibited the proliferation of the Ishikawa cells and arrested the cells in the G0/G1 phase. Furthermore, the apoptosis rate of the Ishikawa cells was significantly increased. In the animal study, the development of the xenograft tumors was significantly suppressed by the combined application of the two agents. Further investigation revealed that the synergistic inhibitory effect of the two agents on EC can be at least partly, explained by the decreased expression of cyclin D1 and cyclin E. The results of the current study provide novel insights into the treatment of EC.

Risk factors of acute myocardial infarction in middle-aged and adolescent people (< 45 years) in Yantai.

BACKGROUND: Yantai is a developed medium-sized coastal city in Eastern China, having a population of 1.6845 million. With the development of economy, some middle-aged and adolescent people (< 45 years) devote themselves to work and suffer from greater stress, which makes them ignore their own health. Moreover, they have unhealthy lifestyles and lack the knowledge of cardiovascular risk factors. OBJECTIVES: To identify the risk factors for first acute myocardial infarction in middle-aged and adolescent people in Yantai, a developed medium-sized coastal city in Eastern China. METHODS: A total of 154 consecutive patients with first acute myocardial infarction (< 45 years), were enrolled in case group, and 462 patients without myocardial infarction were enrolled in control group. Three controls with the same sex and age were matched to each case. The risk factors were identified with univariate and multivariate analysis. RESULTS: Unhealthy food habit (eating seafood and meanwhile drinking beer), hypertension, current smokers, self-perceived stress, diabetes mellitus, obesity, sleep insufficience, hypercholesterolaemia and fatigue were independent risk factors for first acute myocardial infarction (P < 0.05). CONCLUSIONS: Besides those recognized risk factors for cardiovascular disease (hypertension, hypercholesterolemia, diabetes mellitus and smoking), eating seafood and meanwhile drinking beer, self-perceived stress, sleep insufficience, obesity and fatigue were also the risk factors for first acute myocardial infarction in middle-aged and adolescent people in Yantai.