Background and purpose:Methylene tetrahydrofolate reductase (MTHFR) plays an important role in metabolism of folate and DNA methylation. This study aimed to investigate the relationship between methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism and chemotherapy side effects in advanced non-small cell lung cancer (NSCLC) patients. Methods:A total of 100 patients with advanced NSCLC conifrmed by pathology were included into this study in Zhejiang Cancer Hospital from Jun. 2007 to May. 2009. All patients received the combined chemotherapy of platinum drug and gemcitabine. MTHFR genotypes were determined by allele-specific-PCR technology. Results:In the 100 cases, genotype frequency of MTHFR C677T T/T, T/C and C/C were 20%, 44%and 36%, respectively. Compared with patients of T/T and T/C genotype, patients of C/C genotype were correlated with decreased rate of thrombocytopenia to chemotherapy (P=0.039). No signiifcant differences were observed concerning gastrointestinal toxicity. Conclusion:MTHFR C677T gene polymorphism can be used to predict the adverse reactions to platinum-based chemotherapy in patients with advanced NSCLC.

Objective To investigate the efficacy and safety of Nocardiarubra cell wall skeleton (N-CWS) bladder irrigation in prevention of recurrence after transurethral resection for the treatment of non-muscle invasive bladder cancer (NMIBC).Methods The clinical data of patients with NMIBC treated by N-CWS and epirubicin collected between October 2013 and November 2018 at the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed.All patients underwent TURBT.Among the 118 NMIBC patients,the average age was (65.1 ± 1 1.9) years,and the sex ratio (male/female) was 1.9∶1 (77/41).Patients were divided into two group:N-CWS group (n =55) and epirubicin group (n =63) according to different instillation regimens.N-CWS was given as an instillation of 800 μg in 50 ml of saline and maintained in the bladder for 2 h in the N-CWS group.Epirubicin was given as an instillation of 50 mg in 50 ml of saline and maintained in the bladder for 1 h in the epirubicin group.In the N-CWS group,mean agewas (64.9 ± 12.1) years and 37 (67.3％) were male.Multiple tumors were present in 17 (69.1％) patients.Tumor size was ≤3 cm in 49(89.1％) and 7(12.7％) had a history of NMIBC.Stage was Ta and T1 in 36(65.5％) and 19(34.5％),respectively.Grade 1,Grade 2 and Grade 3 were the primary grades in 38(69.1％),13(23.6％) and 4(7.3％),respectively.Low risk,intermediate risk and high risk were present in 14 patients(25.5％),16 (29.1％) and 25 (45.5％),respectively.In the epirubicin group,mean age was (65.3 ± 11.2) years and 40(63.5％)were male.Multiple tumors were present in 19(30.2％) patients.Tumor size was ≤3 cm in 56(88.9％) and 11 (17.5％) had a history of NMIBC.Stage was Ta and T1 in 37(58.7％) and 26 (41.3％),respectively.Grade 1,Grade 2 and Grade 3 were the primary grades in 44(69.8％),12(19.0％)and 7(11.1％),respectively.Low risk,intermediate risk and high risk were present in 13 (20.6％),19 (30.2％) and 31 (49.2％),respectively.The tumor recurrence,progression and adverse reactions after Intravesical Instillation in both groups were followed up and recorded.No significant differences were found between the two groups.Results A total of 118 patients were followed up.Mean follow-up time was (33.7 ± 5.4) months.25.5％ (14/55) in the N-CWS group vs.42.8％ (27/63) in the epirubicin group had recurrence after 5 years (x2 =3.922,P =0.048).The five-year RFS was higher in the N-CWS group than in the epirubicin group (74.2％ vs.56.5％,P =0.044).No significant difference was found in the progression rate between the two groups(5.5％ vs.7.9％,P =0.867).The incidences of adverse events in the two groups were 16.4％ (9/55) and 19.0％ (12/63),respectively.The N-CWS group had significantly fewer cases with urinary frequency and dysuria than the epirubicin group.No significant differences were found in other side effects.Conclusions Intravesical instillation of N-CWS after NMIBC TURBT was found to be a promising procedure to prevent recurrence and prolong the recurrence-free survival with less side effects.

OBJECTIVETo study the changes in microtubule motor protein expression in the spinal cord and sciatic nerve of rats exposed to carbon disulfide, and to investigate the possible molecular mechanism of changes in axonal transport in carbon disulfide-induced peripheral neuropathy.

METHODSHealthy adult male Wistar rats were randomly divided into one control group and three experimental groups (10 rats per group). The rats in experimental groups were intoxicated by gavage of carbon disulfide at a dose of 200, 400, or 600 mg/kg 6 times a week for 6 consecutive weeks, while the rats in control group were given the same volume of corn oil by gavage. Animals were sacrificed after exposure, with nerve tissue separated. The levels of dynein, dynactin, and kinesin in the spinal cord and sciatic nerve were determined by Western blot.

RESULTSThe content of dynein, dynactin, and kinesin in the sciatic nerve decreased significantly under exposure to carbon disulfide. The levels of dynein in the sciatic nerve were reduced by 23.47% and 33.34% at exposure doses of 400 and 600 mg/kg, respectively. The levels of dynactin in the sciatic nerve of the three experimental groups were reduced by 19.91%, 24.23%, and 41.30%, respectively. The level of kinesin was reduced by 25.98%under exposure to 600 mg/kg carbon disulfide. All the differences were statistically significant (P < 0.01). As compared with the control group, the 600 mg/kg group experienced a 28.24% decrease in level of dynactin in the spinal cord (P < 0.01), but no significant change was observed in the level of dynein or kinesin.

CONCLUSIONCarbon disulfide has an impact on microtubule motor protein expression in nerve tissues, which might be involved in the development of carbon disulfide-induced peripheral neuropathy.

Animals ; Axonal Transport ; drug effects ; physiology ; Carbon Disulfide ; toxicity ; Dynactin Complex ; Male ; Microtubule-Associated Proteins ; metabolism ; Nerve Tissue ; metabolism ; Peripheral Nervous System Diseases ; chemically induced ; metabolism ; Rats, Wistar ; Sciatic Nerve ; metabolism ; Spinal Cord ; metabolism