A single nuclear polymorphism in let-7g binding site affects the doubling time of thyroid nodule by regulating KRAS-induced cell proliferation.

As an indicator for the malignancy of thyroid nodules (TN), the doubling time of TN was studied in this study to evaluate the effect of rs712 polymorphism on the progression of TN. In addition, we aimed to study the potential molecular mechanisms underlying the pathological effect of rs712 polymorphism upon TN. A Taqman method was used to genotype the patients according to their rs712 polymorphism. Real-time polymerase chain reaction, western blot, Terminal deoxynucleotidyl transferase dUTP nick end labeling assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay was conducted to study the correlation between KRAS expression and the pathological effect of rs712 polymorphism. In-silicon analysis and luciferase assay were utilized to establish the regulatory relationship between let-7g and KRAS. KRAS messenger RNA (mRNA)/protein levels in the GG group were upregulated with a decreased apoptosis index. KRAS mRNA was validated to be a virtual target of let-7g. In addition, the mRNA/protein level of KRAS as well as cell proliferation index was decreased in primary thyroid cancer cells genotyped as TT/TG and transfected with KRAS small interfering RNA (siRNA)/let-7g precursors. The cell apoptosis index was evidently elevated in the KRAS siRNA/let-7g precursors group compared with that in the scramble controls. Moreover, KRAS mRNA/protein only showed slight reduction when GG-genotyped primary thyroid cancer cells were transfected by let-7g precursors. Additionally, let-7g precursors exhibited no significant effect on cell proliferation index or cell apoptosis in GG cells. Rs712 polymorphism T>G in the 3'-untranslated region of KRAS interrupts the interactions between let-7g and KRAS mRNA, leading to a higher cell proliferation index and reduced doubling time of TN.

Comparison of two malnutrition risk screening tools with nutritional biochemical parameters, BMI and length of stay in Chinese geriatric inpatients: a multicenter, cross-sectional study.

OBJECTIVES: The aims of this study were to assess malnutrition risk in Chinese geriatric inpatients using Nutritional Risk Screening 2002 (NRS2002) and Mini-Nutritional Assessment (MNA), and to identify the most appropriate nutritional screening tool for these patients. DESIGN: Cross-sectional study. SETTING: Eight medical centres in Hubei Province, China. PARTICIPANTS: A total of 425 inpatients aged ≥70 years were consecutively recruited between December 2014 and May 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Nutritional risk was assessed using NRS2002, MNA, anthropometric measurements and biochemical parameters within 24 hours of admission. Comorbidities and length of hospitalisation were recorded. Nutritional parameters, body mass index (BMI) and length of hospital stay (LOS) were employed to compare MNA and NRS2002. Kappa analysis was used to evaluate the consistency of the two tools. RESULTS: The average age was 81.2±5.9 years (range, 70-98). The prevalence of undernutrition classified by NRS2002 and MNA was 40.9% and 58.6%, respectively. Patients undergoing malnutrition had lower BMI, haemoglobin, albumin and prealbumin (p<0.05), and longer LOS (p<0.05). The NRS2002 showed moderate agreement (κ=0.521, p<0.001) with MNA. Both tools presented significant correlation with age, BMI and laboratory parameters (p<0.001). In addition, a significant association between both tools and LOS was found (p<0.05). In addition, the NRS2002 was not different from MNA in predicting nutritional risk in terms of the area under the receiver operating characteristic curve (p>0.05). CONCLUSIONS: The results show a relatively high prevalence of malnutrition risk in our sample cohort. We found that NRS2002 and MNA were both suitable in screening malnutrition risk among Chinese geriatric inpatients.