Objective To discusses the clinical significance of XRCC1 399 and TYMS 5'-translation section enhancement subsequence polymorphism in guidance the postoperative individual chemotherapy for patients with resected non-small cell lung cancer.Methods Retrospectively analyze the results of 150 cases from February 2010to June 2014.Statistical analysis with SPSS 21.0.Results Three of the most common gene type of XRCC1 399 is Arg/Arg(58.7％),Arg/Gln(36.7％) and Gln/Gln(4.6％),respectively.Three of the most common gene type of TYMS is 3R/3R (70.7％),2R/3R (25.3％) and 2R/2R (4.0％),respectively.Conclusion In resected non-small cell lung cancer,XRCC1 399 Arg/Arg genotype is the most common,followed by Arg/Gln type.At the sarne time,TYMS gene type 3R/3R accounted for more than 70％,especially higher percentage of in adenocarcinoma.Neither of these two gene polymorphism is recommended as marker to guide the postoperative individual chemotherapy.

Metagenomic cosmid libraries containing 1.26 x 10(5) clones, covering about 4.8 x 10(6) kb metagenomic DNA of uncultured microorganisms from the contents of buffalo rumens were constructed, and 118 independent clones expressing beta-glucosidase activity were isolated from the libraries. Screening of these clones showed that eight clones expressed relatively higher beta-glucosidase activity at pH 5.0 and 37 degrees C. One out of the eight clones was subcloned. Sequencing analysis showed that an open reading frame (ORF) of 2223 bp, termed umcel3G, potentially encodes a beta-glucosidase. The encoded product shared highest homology with a beta-glucosidase from Bacillus sp. at 60% identity and 73% similarity. The umcel3G was over-expressed in Escherichia coli and the size of the translated product Umcel3G on SDS-PAGE was in agreement with the predicted molecular mass. Zymogram analysis showed that Umcel3G exhibited beta-glucosidase activity, confirming that this ORF encodes a beta-glucosidase. The Umcel3G, purified with Ni-NTA column, exhibited optimal activity at pH 6.0-6.5 and 45 degrees C. Certain ions such as Ca2+, Zn2+ had significant positive effect on the activity of Umcel3G. However, some ions such as Fe3+, Cu2+ gave significant inhibitory effect on the enzyme. The Ni-NTA purified recombinant beta-glucosidase Umcel3G had a specific activity of 22.8 IU/mg at pH4.5, 35 degrees C and at the presence of 5 mmol/L Ca2+, indicating that this enzyme has potential applications in the fermentative production of ethanol by simultaneous saccharification and cofermentation (SSCF) of lignocelluloses.
Animals ; Bacteria ; enzymology ; genetics ; Buffaloes ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Open Reading Frames ; genetics ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification ; metabolism ; Rumen ; microbiology ; beta-Glucosidase ; biosynthesis ; genetics ; isolation & purification

As one of the important liquid biopsies, circulating tumor cells (CTCs) shows more and more clinical values in the treatment of lung cancer such as diagnostic screening, treatment evaluation, postoperative monitoring, and prog-nosis predicting etc.A large number of small pulmonary nodules patients are detected when screening the high risk population of lung cancer. However, small lung nodules are not equal to lung cancer, and 90%-95% of them are benign lesion, therefore, to accurately and correctly differentiate whether it is benign or malignant when patients firstly detected and treat a small pulmo-nary nodule is become a new opportunity and challenge for clinician. With the improvement of CTCs detection technology, whether it will play an important role in early differential diagnosis of lung cancer. And whether it will have clinical significance to early lung cancer surgery operations. These require further researches and explorations so as to achieve clinical transforma-tion in the future.

Background and objectiveSerum carcinoembryonic antigen (CEA) and the soluble fragment of cyto-keratin 19 (CYFAR21-1) are important tumor markers (TMs) in the preoperative examination of patients with non-small cell lung cancer (NSCLC). However, the prognostic role of these markers in NSCLC patients remains controversial. hTe aim of the study was to investigate the clinical signiifcance of serum CEA variances and CYFAR21-1 levels for the prognosis of NSCLC patients following surgery.MethodshTis retrospective study investigated the clinical records and follow-up sessions of 175 patients with NSCLC who accepted surgery and adjuvant chemotherapy. Patients were subdivided into groups based on serum CEA and CYFAR21-1 levels. Survival analysis was conducted usingKaplan-Meier method for each group. hTe prognostic fac-tor was evaluated usingCox proportional hazards model.Results hTe overall survival (OS) of patients with high preopera-tive CEA or CYFAR21-1 levels was lower than that of patients with normal preoperative CEA or CYFAR21-1 levels. hTe OS displayed a signiifcant difference (P=0.001) between groups with high and normal preoperative CYFAR21-1. Compared with groups exhibiting normal preoperative and postoperative levels of CEA or CYFAR21-1, the OS was shorter for groups with high preoperative and postoperative levels of CEA or CYFAR21-1. hTe difference of the paired groups was signiifcant (P<0.05). Compared with the groups with normal preoperative and postoperative levels of CEA and CYFAR21-1, the OS was lower for the groups with high preoperative and postoperative levels of CEA and CYFAR21-1, which indicated a signiifcant difference (P<0.001). hTe CEACYFAR211 (HHHH), CEACYFAR211 (NNHH), CYFAR21-1 (HH), CEA (HH), and male genderwere identiifed as independent prognostic factors (P<0.05).ConclusionhTis study suggested that the prognosis of NSCLC patients was not signiifcantly satisfactory if preoperative and postoperative level of serum CEA or CYFAR21-1 was higher than standard value, especially if the preoperative and postoperative levels of CYFAR21-1 and CEA were higher than the standard values. hTe measurement of preoperative and postoperative levels of CYFAR21-1 and CEA proved helpful for the prognosis of patients with NSCLC.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC₅₀ > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.