Background:Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study.Methods:Five thousand one hundred and twenty-five NSCLC patients' pathology samples were collected, and EGFR, KRAS, BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR, KRAS, BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis.Results:EGFR, KRAS, BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments.Conclusions:EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and ‘second drug-resistant mutations', T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment.

We suggest that activation of GPER exerts an inhibitory effect on colonic motility by promoting NO release from myenteric nitrergic nerves. These results raise a possibility that GPER may be involved in mediating the inhibitory effect of estrogen on colonic motor functions, via a non-genomic, neurogenic mechanism.

ABSTRACT. Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCRrestriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors ) and 2.35 (95%CI: 1.15-16601 CYP1A1 and GSTM1 polymorphisms and bone tumor susceptibility ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 16600-16607 (2015) 4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence.

Simple acute hematoma can lead to temporary change of morphology and biochemistry. Application of HA can reduce damage of hemarthrosis on cartilaginous and shorten the cartilage recovery time.

Abstract:The aim of this systematic review is to assess whether metformin could change the concentration of serum homocysteine (Hcy) with and without simultaneous supplementation of B-group vitamins or folic acid. A literature search was conducted in PubMed, EmBase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) reporting the concentration of serum Hcy in metformin-treated adults. Meta-analysis was applied to assess the association between metformin and the changes of Hcy concentration. Twelve publications were included in this study. In the overall analysis, metformin administration was not statistically associated with the change of Hcy when compared with the control treatment (mean difference (MD), 0.40 µmol/L; 95% confidence interval (CI), −0.07~0.87 µmol/L, p = 0.10). In the subgroup analysis, metformin was significantly associated with an increased concentration of Hcy in the absence of exogenous supplementation of folic acid or B-group vitamins (MD, 2.02 µmol/L; 95% CI, 1.37~2.67 µmol/L, p < 0.00001), but with a decreased concentration of serum Hcy in the presence of these exogenous supplementations (MD, −0.74 µmol/L; 95% CI, −1.19~−0.30 µmol/L, p = 0.001). Therefore, although the overall effect of metformin on the concentration of serum Hcy was neutral, our results suggested that metformin could increase the concentration of Hcy when exogenous B-group vitamins or folic acid supplementation was not given.

tient stay were linked. Their overall survival data were presented as product-limit survival probabilities. Results: There were 240 to 290 new cases annually between 2006 and 2011. The raw incidence rate was about 1.1 to 1.26 per 100,000 persons,. The age adjusted incidence rate was around 1.5 per 100,000 persons. This was much lower than that the overall incidence in the US (21.1 per 100,000 per year). But it was similar to that of Asia-Pacific islanders in the US. The proportion of death between 2006 and 2011 were 28.8% and 21.9% among males and females respectively. This was different from the US population, whose 5 year survival was 91.3%. The population composition of the US was different from that in Taiwan and thus cannot be compared directly. About 29% of Taiwan patients were farmers. The mortality of farmers (36.5%) was slightly higher than that of non-farmers (22.4%). After controlling for age and sex, the hazard ratio of farmer vs. non-farmers was 1.136. Their age of diagnosis was much higher than the non-farmers: 82% and 34% for farmers and non-farmers diagnosed at age 65 and above, respectively. ConClusions: Malignant melanoma is found to be a rare but deadly disease in Taiwan. One reason for low survival probability was that farmers delayed the diagnosis to old age. It is suggested to screen farmers in early age.

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