OBJECTIVE:To study the effect of irbesartan and losartan on pharmacokinetics of cyclosporin A(CsA)in rabbits. METHODS: 12 rabbits were randomly divided into two groups(n=6). In self-controlled study,plasma concentration of CsA in rabbits of two groups before and after treating with combination of irbesartan and losartan were determined and pharmacokinetics parameters were examined. RESULTS: After combination of irbesartan or losartan,the Cmax and AUC0～24 of CsA were significantly increased(P

We established a stable Chinese hamster ovary (CHO-S) cell line for recombinant human VEGF165-expressing. We co-transfected GS-expression vector and rhVEGF165 expression plasmid into CHO-S cells, and selected the highest VEGF165-expressing clone as the working cell line to express VEGF165 protein. After 7-day fed-batch culture in a 5 L bioreactor and 3 steps chromatographic purification, we got the rhVEGF165 protein for series of binding and biological activity examination. The production was over 50 mg/L. The purified rhVEGF165 protein was functionally active with a half-maximal Human Umbilical Vein Endothelial Cells (HUVEC) growth-enhancing effect concentration of 1.94 ng/mL. It was slightly better than commercially available Escherichia coli expressing rhVEGF165. So we expressed successfully rhVEGF165 protein in high-level and obtained the fully active rhVEGF165 protein in large quantity.
Animals ; Bioreactors ; CHO Cells ; Cell Proliferation ; drug effects ; Cricetinae ; Cricetulus ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Recombinant Proteins ; biosynthesis ; genetics ; isolation & purification ; Transfection ; Vascular Endothelial Growth Factor A ; biosynthesis ; genetics

A total of 100 HIN1 flu real-time-PCR positive throat swabs collected from fever patients in Zhejiang,Hubei and Guangdong between June and November 2009,were provided by local CDC laboratories.After MDCK cell culture,57 Influenza A Pandemic (H1N1) viruses were isolated and submitted for whole genome sequencing.A total of 39 HA sequences,52 NA sequences,36 PB2 sequences,31 PB1 sequences,40 PA sequences,48 NP sequences,51 MP sequences and 36 NS sequences were obtained,including 20 whole genome sequences.Sequence comparison revealed they shared a high degree of homology (96％～99％) with known epidemic strains (A/Califomia/04/2009(H1N1).Phylogenetic analysis showed that although the sequences were highly conserved,they clustered into a small number of groups with only a few distinct strains.Site analysis revealed three substitutions at loop 220 (221-228) of the HA receptor binding site in the 39 HA sequences:A/Hubei/86/2009 PKVRDQEG→PKVRDQEA,A/Zhejiang/08/2009 PKVRDQEG→PKVRDQER,A/Hubei/75/2009PKVRDQEG→PKVRDQGG,the A/Hubei/75/2009 was isolated from an acute case,while the other two were from patients with mild symptoms.Other key sites such as 119,274,292 and 294 amino acids of NA protein,627 of PB2 protein were conserved.Meanwhile,all the M2 protein sequences possessed the Ser32Asn mutation,suggesting that these viruses were resistant to adamantanes.Comparison of these sequences with other H1N1 viruses collected from the NCBI database provides insight into H1N1 transmission and circulation patterns.

Objective:To investigate the feasibility of "twelve-section ultrasonic screening diagnosis method" in screening for neonatal complex congenital heart disease (CHD) in primary hospitals.Methods:This is a prospective study. A total of 71 580 newborns were screened for CHD using the "twelve-section ultrasonic screening diagnosis method" from four pilot units in Hebei province, which were Bo'ai Hospital of Huanghua Development Zone, Traditional Chinese Medicine Hospital of Fengning County, Maternity & Child Healthcare Hospital of Tang Country, and Maternity & Child Healthcare Hospital of Rongcheng Country, from November 2015 to December 2019. Another 262 children with CHD were enrolled, including 39 with complex CHD. These cases received ultrasonography at four pilot units above and then were transferred to CHD Screening Diagnosis and Treatment Center of Hebei Children's Hospital (our center) prior to the implementation of "twelve-section ultrasonic screening diagnosis method" from June 2012 to June 2014, who were all confirmed by surgery. Set the diagnosis results of our center as the gold standard, the sensitivity, specificity, and diagnostic consistency rate in screening for complex CHD cases were calculated. Receiver operating characteristic (ROC) analysis and Chi-square test were used to compare and analyze the sensitivity for screening neonatal complex CHD before and after implementing the method. The screening results of complex CHD after implementing the method between the pilot units and our center as well as between the four pilot units were compared and analyzed using Chi-square test. Results:A total of 553 (0.77%) CHD cases were detected by the "twelve-section ultrasound screening diagnosis method", including 66 cases of complex CHD and 487 cases simple CHD. Among the cases screened using the method, there were three false negative cases (one case with total anomalous pulmonary venous drainage, one with abnormal coronary artery originating from pulmonary artery, and one with atresia of distal to the left subclavian artery, aortic arch and left aortic arch of double-arch), one false positive case (false echo loss of aortopulmonary septal that was misdiagnosed as aortopulmonary septal defect), five cases of misdiagnosis (one common pulmonary venous atresia case that was misdiagnosed as total anomalous pulmonary venous drainage, one persistent stenosis of the fifth aortic arch that was misdiagnosed as coarctation of aorta, one pulmonary artery sling that was misdiagnosed as absence of left pulmonary artery, one severe coarctation of aorta that was misdiagnosed as interruption of aortic arch, and one aortic isthmus atresia that was misdiagnosed as coarctation of aorta), and all were complex CHD cases. A total of 68 cases (12.3%) of complex CHD were confirmed by our center. The overall sensitivity, specificity, and diagnostic consistency rate of screening were 95.6% (65/68), 99.8% (484/485), and 86.8% (59/68), respectively and the area under ROC curve was 0.98. Before the implementation, the overall sensitivity, specificity, and diagnostic coincidence rates of ultrasonic screening for complex CHD were 69.2%(27/39), 95.5%(213/223), and 61.5% (24/39), respectively, and the area under ROC curve was 0.82. The sensitivity of complex CHD screening was significantly increased after implementing the method ( χ2=14.28, P<0.05). There was no significant statistical significance in the sensitivity for screening complex CHD after the implementation between the pilots and our center or between the four pilots (all P>0.05). Conclusions:"Twelve-section ultrasonic screening diagnosis method" is suitable for the screening of neonatal complex CHD in hospitals at the county level. However patients with some special types of complex CHD are recommended to be transferred for a more accurate diagnosis.

Objective:To investigate the diagnostic method and value of echocardiography in screening right patent ductus arteriosus(PDA) of infants.Methods:This was a prospective study.Thirty-one infants with right PDA diagnosed by ultrasound and confirmed by prenatal ultrasonography, electronic computed tomography angiography, angiocardiography and/or surgery in Hebei Children′s Hospital from April 2014 to May 2022 were collected as research subjects, and the association of right ductus arteriosus with aortic arch anomalies and complex cardiac malformations were summarized. The diagnostic method and value of ultrasonic screening were summed up.Results:Of the 31 cases, 30 cases were correctly diagnosed by ultrasound and 1 case was misdiagnosed, who was a left aortic arch descending to the right, a crossover variation of the right and left pulmonary arteries, and a rightward displacement of the ductus arteriosus. Among these cases diagnosed correctly, 27 cases (including 24 cases with right aortic arch and 3 cases with left aortic arch) presented that ductus arteriosus was open and its ostium of pulmonary artery end was located in the proximal right pulmonary artery in views of parasternal short-axis view of great vessels at cardiac base with the combination of two dimensions and color Doppler flow imaging. Other 3 cases of right aortic arch were all single ventricle with transposition of the great artery. Due to the parallel relationship of the two great arteries, the standard parasternal short-axis view of great vessels could not be obtained, and the right ductus arteriosus was found in the high parasternal views.In all of the 27 cases with right aortic arch and right ductus arteriosus, high parasternal views showed that one end of the ductus arteriosus was connected to the right aortic arch isthmus and the other end was connected to the right pulmonary artery. In all of the 3 cases with left aortic arch and right ductus arteriosus, the high parasternal views showed that one end of the ductus arteriosus was connected to the right subclavian artery and the other end was connected to the right pulmonary artery. Among the 27 cases with right aortic arch, 16 cases were accompanied with mirror image branches, 9 cases of which had complex cardiac malformations; 10 cases were associated with aberrant left subclavian artery, 1 case of which had complex cardiac malformations; 1 case was with isolated left subclavian artery, and without complex cardiac malformations. All 3 cases of left aortic arch were accompanied with isolated right subclavian artery and none of them were associated with complex cardiac malformations. Clinical outcomes of 30 cases with right PDA: 14 cases underwent ductus arteriosus ligation due to thick ductus or other heart malformations. In other 16 cases, 4 cases were closed spontaneously, 9 cases had persistent small ductus arteriosus, and 3 cases were lost to follow-up.Conclusions:Right ductus arteriosus is mostly related to the right aortic arch, and those with mirror image branches are prone to complex cardiac malformations; cases of left aortic arch with right ductus arteriosus are tend to accompany isolated right subclavian artery. Ultrasound has an important application in the screening and diagnosis of right PDA.

Objective: To find out the characteristics and regularity trend of influenza activity according to the analyses of influenza surveillance data in Yangzhou from 2012 to 2017, and to provide scientific supports for predicting and controlling the pandemic outbreak of influenza effectively. Methods: The influenza samples were collected from Northern Jiangsu People′s Hospital, Yangzhou First People's Hospital and Gaoyou People’s Hospital, using fluorescent RT-PCR method to detect influenza virus nucleic acid and classifying influenza virus subtypes. Finally, the surveillance data from January, 2012 to December, 2017 of influenza like illness (ILI) cases of Yangzhou were analyzed. Results: Totally 18 083 throat swabs of ILI specimens were collected from 2012—2017 in Yangzhou, 1 983 samples were positive (10.97%), the difference in positive rates of adjacent years was statistically significant (χ²=167.93, P<0.001). In Yangzhou city, influenza virus kept activative in whole year. The influenza epidemic season was winter-spring and summer, accounting for 83.61% of all positive cases, with type A influenza prevalent throughout all year and type B influenza mainly prevalent in spring and winter, each subtype showed alternating prevalence. The influenza virus infection occurred in every age group. The highest positive rate was 16.33% in the age group of 10-19 years and the lowest was 8.52% in the age group of 20-29 years among all detected age groups. Conclusions From 2012 to 2017, the epidemic of influenza in Yangzhou was obviously seasonal and all the subtypes of influenza were in prevalent status alternately. The high-risk groups of Influenza were infants and teenagers who under the age of 19 years. So a long-term influenza surveillance is much needed for the early warning and forecasting the spread of influenza.

Background Pesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. Objective To evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. Methods This study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑₂OPs, ∑₂PYRs, and ∑₂NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. Results The median creatinine-adjusted concentrations of ∑₂OPs, ∑₂PYRs, and ∑₂NEOs in this study were 419.77, 2.95, and 20.36 nmol·g⁻¹, respectively. The multiple linear regression results showed that the urinary concentration of ∑₂OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑₂PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑₂NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑₂PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑₂NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑₂NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑₂NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). Conclusion The women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.

Background Per- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. Objective To analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. Methods Based on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable. Results Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). Conclusion Although differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.