Purpose　 The aim is to establish the HPLC method for the determination of Fluoro-deoxyuridine in plasma.Methods　The Chromatography conditions include: Chromatography column: Nova-pak C18(3.9mm×150mm,4μm), mobile phase: 0.05mol/L sodium phosphate monobasic -methanol-water(0.5∶7∶92.5)， UV detection at 260nm， FUDR was extracted with ethyl acetate. Results　The average recoveries were 96.4%，96.5%，97.8% for concentration 0.23、1.67、20.0μg/ml (n=5).The corresponding reproducibility were RSD 1.61%, 1.98%, 3.17% respectwely for iner-day and RSD 3.56%, 1.90%, 2.63% for the intra-day(n=5). The FUDR concentration was linear with a correlation coefficient of 0.999　4 over the range of 0.099～20.0μg/ml. Conclusion　 The method was sensitive and accurate and suitable for pharmacokinetics and bioavailability study of FUDR.

Objective:To investigate the effects of resistance exercise on mitochondrial function, muscle attenuation and muscle fiber morphology in quadriceps femoris of aged rats.Methods:The 18-month-old male rats were randomly divided into five groups( n=8, each): control(not exercise), 0% weight-bearing, 30% weight-bearing, 50% weight-bearing, and 70% weight-bearing exercise.After maximum resistance running, intermittent race table resistance exercise with 0%, 30%, 50%, 70% maximum load were performed.The treadmill placement slope was 35°, the running speed was 15 m/min, and exercise was performed every other day.At the end of the 8 th week, the mitochondrial membrane potential of quadriceps femoris muscle was measured, cytosol contents of cytochrome C(Cyt c), apoptosis-inducing factor(AIF), and apoptotic protein(Smac/DIABLO)were measured, and the morphology and structure of muscle fibers were observed. Results:Compared with the control group, the mitochondrial ΔΨmt was increased in the 0%, 30%, 50% and 70% maximum load groups, with a significant difference in the increment in the 0%, 30% and 50% maximum load groups( t=7.412, 5.611, 6.213, all P<0.01).Compared with the 0% maximum load group, the percentage of cells with mitochondrial ΔΨmt was statistically significantly decreased in the 30% maximum load group(10.6%)( t=9.356, P<0.05), while the percentage of cells with mitochondrial ΔΨmt was statistically significantly increased in the 70% maximum load group(10.03%)( t=8.341, P<0.05).Compared with the control group, the contents of Cyt c, AIF and Smac/DIABLO in the cytoplasm of quadriceps femoris of aged rats with 8-week resistance exercise were decreased, among which the contents of Cyt c and Smac/DIABLO were statistically significantly decreased in the three groups of 0%, 30%, and 50% maximum load( t=8.324, 7.516, and 6.871, all P<0.05), as well as the decrement in AIF of the three groups of 0%, 30%, and 50% maximum load was statistically significant( t =9.434, 8.78, and 7.342, all P<0.05).Compared with the control group, the vacuolar area of muscle fibers was extremely significantly decreased in the 0%, 30%, and 50% maximum load groups( t =5.567, 6.784, and 7.432, P<0.01); the protein content in the quadriceps femoris muscle was very significantly increased in the 30%, 50%, and 70% maximum load groups( t =7.478, 6.765, and 4.564, all P <0.01).Compared with the 0% maximum load group, the protein content in the quadriceps femoris muscle was very significantly increased in the 30%, 50%, and 70% maximum load groups( t=9.236, 8.342, and 6.456, all P<0.01). Conclusions:Low and medium weight-bearing resistance exercise can improve the mitochondrial function of quadriceps femoris, reduce the femoral quadriceps mitochondria-released proapoptotic proteins Cyt c, AIF, and Smac/DIABLO, and reduce the incidence of quadriceps femoris apoptosis.Low and medium weight-bearing resistance exercise can increase the protein content of muscle fibers, reduce the vacuolar area of muscle fibers, maintain muscle mass, and delay the occurrence of sarcopenia.

Objective:To analyze the effectiveness and immunogenicity of enterovirus-A71(EV-A71) vaccine in immunization program.Methods:A cohort study was conducted in immunization clinics in Jing’an district in Shanghai from October to December 2017. Children who received EV-A71 vaccine based on a 2-dose schedule (on day 0 and day 30) were enrolled as vaccine group and those who received no EV-A71 vaccine were enrolled as control group. After 1-year follow-up, the effectiveness and neutralizing antibody level and the positive results of antibody immunogenicity in vaccine group were analyzed.Results:A total of 3 018 children aged 8-20 months were enrolled, in whom 1 211 were in vaccine group and 1 807 were in control group. The vaccine effectiveness was 100% against EV-A71-associated hand, foot, and mouth disease (HFMD) indicated by 1 year follow-up (95 %CI: -66.99%-100.00%). The geometric mean titer of neutralizing antibody (GMT) was 41.76 (95 %CI: 35.60-49.34) at day 60 and 28.44(95 %CI: 23.59-34.54) at day 365 in 124 children in vaccine group. Conclusions:In children, EV-A71 vaccine elicited EV-A71-specific immune response. Less EV-A71-associated HFMD cases have been observed, further observation is needed.

Abstract OBJECTIVE Oxcarbazepine(OXC) is an antiepileptic drug, which is metabolized to the active 10-monohydroxy derivative(MHD) after oral administration. The half-life period of MHD in children is significantly shorter than that in adults, and the clearance is increased by 30% to 160% compared with that in adults, which indicates that the pharmacokinetics(PK) of MHD in children is obviously different from that in adults, while adults and children exhibit different levels of expression of metabolism enzymes and transporter proteins with the same genotype. At present, there is no study describing the influence of genetic polymorphism of PK-related enzymes on MHD plasma concentrations in children with epilepsy. This study investigates whether the polymorphism of metabolic enzymes and transporter genes have significant effects on MHD plasma concentrations in children with epilepsy in China, so as to provide the reference for individualized application of OXC in pediatric patients. METHODS The plasma samples from pediatric patients with epilepsy aged 0-14 years old at the First Affiliated Hospital of Fujian Medical University who received OXC were prospective collected from June 2021 to June 2023. The MHD blood concentrations of the patients were measured using enzyme amplified immunoassay, and the metabolic enzyme genes UGT2B7 802T>C, UGT1A9 I399C>T, as well as the transporter genes ABCB1 3435C>T and ABCB2 1249G>A polymorphism were detected using dideoxy chain-termination method in epilepsy children. According to Hardy Weinberg's law of genetic balance, the theoretical values of genotype frequency of the patients were calculated, and a Chi-Square test method was used to compare whether there was a significant difference between the theoretical value and the measured value, to examine whether the genotype of the patients included in the study is accordance with the law of genetic balance. One-way ANOVA statistical method was used to analyze the correlation of the four single nucleotide polymorphisms, daily maintenance dosage of OXC, and MHD blood concentrations. Subsequently, Fisher's least significant difference(LSD) test was performed. LSD test is a pairwise comparison of the differences between the mean values of each group, calculated based on the standard error and degrees of freedom to obtain the minimum significant difference between each two groups, while P<0.05 indicated that the difference was significant. RESULTS In this study, 161 trough concentrations were collected from children with epilepsy. The genotype of the included population conformed to the genetic balance law, which indicated that the included patients were representative for the population. Unite analysis of variance showed a significant correlation between the transporter gene ABCB1 3435C>T and MHD blood drug concentration(P<0.05). Subsequently, Fisher's minimum significant difference test was conducted, and MHD plasma concentrations of patients carrying the ABCB1 3435C>T mutation allele were significantly higher than that of non-carriers. No significant association was found between the four single nucleotide polymorphisms and the daily maintenance dosage of OXC, and no significant impact of the other metabolic enzyme and transporter genetic polymorphisms on MHD plasma concentrations was found. CONCLUSION The results of research shows that the ABCB1 3435C>T polymorphism significantly affect the MHD blood concentration of pediatric patients with epilepsy, and the effects of UGT2B7 802T>C, UGT1A9 I399C>T and ABCB2 1249G>A genetic polymorphisms on MHD blood concentration and daily maintenance dosage of OXC are not found. The results suggest that MHD blood concentrations are significantly increased by affecting the expression of the encoded MDR1 transporter protein after ABCB1 3435C>T site mutation, which also may increase the risk of adverse reactions of OXC. The genetic polymorphisms of ABCB1 3435C>T can be detected in children with epilepsy when taking OXC, and the dosage can be adjusted appropriately for patients with genetic mutations. The results of this study can provide the reference for the individualized administration of OXC in clinic.