Diabetic retinopathy(DR)is one of the common causes of visual impairment and blindness in adults, which is caused by various pathogenesis. Although the mechanism of DR has not been elucidated yet, the destruction of blood-retinal barrier is a key process. As a highly endothelial-specific factor in promoting the growth of vascular endothelial cell, vascular endothelial growth factor(VEGF)plays a crucial role in the formation of pathological retinal neovascularization and the destruction of blood-retinal barrier. Therefore, a comprehensive understanding of the etiology and pathogenesis of blood-retinal barrier damage promoted by VEGF is critical for exploring the pathogenesis of DR. In this study, the underlying relationship between VEGF and the mechanism of blood-retinal barrier damage, including retinal vascular endothelial cell permeability, vascular inflammatory response, apoptosis, oxidative stress, mitochondrial damage and endoplasmic reticulum stress, with a view to providing a reference for the study in VEGF in the pathogenesis of blood-retinal barrier damage in DR.

To investigate the association of triglyceride to high density lipoprotein-cholesterol ratio (TG/HDL-C) in early pregnancy with the risk of gestational diabetes mellitus (GDM).

Purpose/Significance To investigate the effectiveness of experiential teaching in perinatal healthcare management contin-uing education.Method/Process The perinatal healthcare team of Peking Union Medical College Hospital holds a four-day experiential learning program for 30 maternity-related medical staffs from China.Through the self-administered experiential teaching questionnaire(ETQ)and satisfaction questionnaire,the researchers analyze the participants'post-teaching skill acquisition,clinical application abil-ity and educational needs,as well as their satisfaction with course content,course duration,teaching design,classroom atmosphere,and teaching format,which are quantified with Likert scale.Result/Conclusion The experiential teaching mode shows good teaching effects in perinatal healthcare management continuing education,and has higher application value.In the future,the researchers should combine it with theoretical teaching and carry out more comprehensive and structured periodic learning classes throughout the country,so as to im-prove both the theoretical foundation and practical ability of healthcare workers for better healthcare services for pregnant women.

Objective To investigate the relationship between Notch1 and autophagy under high glucose conditions and to explore the effects of Notch1 inhibitor DAPT and autophagy inhibitor 3-MA on human retinal pigment epithelial cells cultured in high glucose conditions.Methods Via preliminary experiment,25 mmol·L-1 glucose was used as the high glucose culture medium of adult retinal pigment epithelial(ARPE)-19 cells,and 5 mmol·L-1 3-MA was adopted as the au-tophagy inhibitor.ARPE-19 cells cultured in vitro were randomly divided into four groups:control group(treated with 5 mmol·L-1 glucose for 48 h),high glucose group(treated with 25 mmol·L-1 glucose for 48 h),high glucose+DAPT group(treated with 40 μmol·L-1 DAPT for 2 h and then 25 mmol·L-1 glucose for 48 h),and high glucose+3-MA group(treated with 5 mmol·L-1 3-MA for 2 h and then 25 mmol·L-1 glucose for 48 h).A transmission electron microscope was used to observe the ultrastructure of cells in each group.Cell proliferation and migration were observed using Cell Counting Kit-8 and scratch assays.Western blot was used to detect the protein expression levels of Notch1 and autophagy-related proteins LC3 and Beclin1.Reverse transcription-polymerase chain reaction was used to measure the relative messenger ri-bonucleic acid(mRNA)expression levels of Notch1,LC3 and Beclin1 of cells in each group.Results Transmission elec-tron microscope showed that cells in the control group had normal structures,with round or oval nuclei and a few autopha-gosomes.In the high glucose group,cells exhibited slightly obvious injury,with uneven cytoplasm and numerous autolyso-somes.Compared to the control group,ARPE-19 cells in the high glucose group had increased proliferation and migration abilities,and higher mRNA and protein expression levels of Notch1,LC3 and Beclin1(all P＜0.05).Compared to the high glucose group,ARPE-19 cells in the high glucose+DAPT group showed decreased proliferation and migration abilities,and lower mRNA and protein expression levels of Notch1,LC3 and Beclin1(all P＜0.05).The high glucose+3-MA group showed reduced proliferation and migration abilities,as well as decreased mRNA and protein expression levels of LC3 and Beclin1(all P＜0.05)compared to the high glucose group.Conclusion High glucose can activate Notch1 and the auto-phagy process,promoting the proliferation of ARPE-19 cells.In the high glucose+DAPT group and high glucose+3-MA group,the autophagy process is inhibited to a certain extent,thereby restraining cell proliferation.

Objective To investigate if Lycium barbarum polysaccharide(LBP)could inhibit the high glucose-in-duced human retinal microvascular endothelial cell(HRMEC)injury by regulating the NOD-like receptor family pyrin do-main containing protein 3(NLRP3)/Caspase-1 pyroptosis pathway.Methods HRMECs cultured in vitro were randomly divided into the control group(5.5 mmol·L-1 glucose),the high glucose group(55.5 mmol·L-1 glucose),the low LBP group(55.5 mmol·L-1 glucose+100 mg·L-1 LBP),the medium LBP group(55.5 mmol·L-1 glucose+500 mg·L-1 LBP),the high LBP group(55.5 mmol·L-1 glucose+1 000 mg·L-1 LBP),the si-NC group(55.5 mmol·L-1glucose after transfection with 20 pmol·L-1 si-NC)and the si-NLRP3 group(55.5 mmol·L-1 glucose after transfection with 20μmol·L-1si-NLRP3).The Cell Counting Kit-8 was used to detect the proliferation of HRMECs in each group and flow cy-tometry was adopted to measure the pyroptosis of HRMECs in each group.The reverse transcription-polymerase chain reac-tion was used to detect the relative messenger ribonucleic acid(mRNA)expression levels of NLRP3,Caspase-1,nuclear factor(NF)-κB,Gasdermin-D(GSDMD)and vascular endothelial growth factor(VEGF)in the HRMECs of each group,Western blot was adopted to detect the relative protein expression levels of HRMEC pyroptosis-related NLRP3,Caspase-1,NF-κB,GSDMD and VEGF in each group,and enzyme-linked immunosorbent assay was used to detect the interleukin(IL)-1β and IL-18 expression levels in downstream pyroptosis in the HRMEC supernatant of each group.Results Com-pared with the control group,the proliferation rate of HRMECs decreased,the pyroptosis rate increased,the relative mR-NA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF increased,and the expressions of IL-1βand IL-18 increased in the high glucose group(all P＜0.05).Compared with the high glucose group,the proliferation rate of HRMECs increased,the pyroptosis rate decreased,the relative mRNA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF decreased,and the expressions of IL-1β and IL-18 decreased in the si-NLRP3 group(all P＜0.05).There were no significant differences in cell proliferation rate,pyroptosis rate,mRNA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF,as well as levels of IL-1β and IL-18,in the si-NC group compared with the high glucose group(all P＞0.05).Compared with the high glucose group,the medium LBP group and high LBP group had increased proliferation rates,lower pyroptosis rates,and declined mRNA and protein expression levels of NLRP3,Caspase-1,NF-κB,GSDMD and VEGF as well as expressions of IL-1β and IL-18(all P＜0.05).Compared with the high glucose group,there was no significant difference in the proliferation rate of HRMECs and various protein expression levels in the low LBP group(all P＞0.05),and other indicators were consistent with those in the medium LBP group and high LBP group.Conclusion LBP has a protective effect on HRMEC injury induced by high glucose,can promote cell prolif-eration and inhibit pyroptosis,and its mechanism is related to inhibiting the activation of NLRP3/Caspase-1 signaling path-way and reducing the expression of related inflammatory factors.

Objective:To analyze the prevalence of different genotypes of wild measles virus in Fujian province from 2014 to 2019.Methods:The information of suspected measles cases and the throat swab specimens of the cases in Fujian province from 2014 to 2019 were collected. Reverse transcription-polymerase chain reaction was applied to amplify the 450 nucleotides of the 3-terminal of the nucleoprotein gene. Phylogenetic tree was constructed to identify and analyze the target sequence.Results:A total of 1 102 suspected measles cases were reported in Fujian province from 2014 to 2019, with an annual incidence rate of 0.47/100 000. Totally 884 throat swabs were tested in the laboratory, and 179 nucleotide sequences were obtained except vaccine strain. Sequence analysis showed that 110 measles genotypes were H1, 43 were B3 and 26 were D8. Nucleotide homology analysis showed that the H1a genotype measles virus in Fujian province distributed in two branches, divided into nine different sequence variants. Some of the variants were highly homologous (99.8%-100.0%) with the measles strains in other regions and countries. There were six different sequence variants of B3 genotype measles virus in Fujian province. The nucleotide homology between the B3 genotype measles virus in Fujian province and the domestic and foreign prevalent B3 strains was 98.4%-100.0%. The D8 genotype measles strain in Fujian province had five different sequence variants, some of which were highly homologous with the strains from Vietnam, Japan and Thailand.Conclusions:Three different genotypes of measles viruses (H1, B3 and D8) prevailed in Fujian province from 2014 to 2019, among which H1 genotype was still the local endemic genotype, while B3 and D8 genotypes were imported genotypes in Fujian province. The result indicated that although the local cases of measles were less in Fujian province in recent years, the risk of imported cases from abroad was increasing, and the surveillance of imported cases from abroad should be strengthened.

Objective:To investigate the level of mumps virus (MuV) IgG antibody of healthy population and the genotyping of MuV in Fujian province in 2018.Methods:MuV IgG antibody of healthy population was detected by enzyme-linked immunosorbent assay (ELISA). Small hydrophobin (SH) gene of MuV was genotyped in pharyngeal swab and cell cultures of mumps patients using reverse transcription polymerase chain reaction (RT-PCR). The phylogenetic tree by SH sequences was constructed to identify MuV genotype.Results:A total of 4 925 people completed antibody testing, the positive rate of MuV IgG antibody was 78.58%(3780/4925), and the geometric mean concentration (GMC) was 245.83 IU/ml. There was no statistically significant difference in the positive rate of antibodies between people of different genders, while GMC had statistically significant differences ( χ2=4.295, P=0.117; Z=-2.220, P=0.026). There were significant differences in the positive rate of antibodies and GMC between people in different regions and age groups. Especially in infants and 12-15 years old group of people, the MuV IgG antibody positive rate and GMC were at low levels. The antibody positive rate and GMC of people with a history of mumps-containing vaccine (MuCV) immunization were higher than those without a history of MuCV immunization and those with unknown MuCV immunization history ( χ2=259.315, P<0.001; Z=-16.319, P<0.001). Eight strains of MuV were isolated from the mumps outbreak, which were all F genotypes. Conclusion:The immune level of mumps in infants and young children in Fujian province was low, and the 12-15 age group is the focus of attention. The epidemic strains of MuV in Fujian province in 2018 were mainly F genotype strains.

Objective:To evaluate the effects of vaccine switch on the levels of neutralizing antibody (NA) of poliovirus in children aged<12 years.Methods:Subjects aged<12 years from 9 districts in Fujian province were chosen by stratified cluster and complete random sampling method. Blood samples were collected for testing NA of poliovirus by microcell neutralization.Results:A total of 2 134 subjects aged<12 years were selected. The positive rate of NA against PVⅠand Ⅲ were 98.64% and 95.83%; and geometric mean titers (GMTs) were 1∶259.35 and 1∶105.14, respectively. The GMTs presented a trend of decreasing as age increased. Compared to trivalent oral poliovirus vaccine (tOPV), bivalent oral poliovirus vaccine (bOPV) and inactivated poliovirus vaccine (IPV) induced higher GMTs of NA against poliovirusⅠand Ⅲ respectively. Among 182 children aged<5 years, the positive rate of NA against PVⅠ, Ⅱ, Ⅲ were 97.25%, 76.37% and 92.86%. There were statistical differences among the three types ( χ2=44.44, P=0.000). The rate of NA against PVⅡwas significantly lower than those ofⅠand Ⅲ (Ⅱ vs. I: χ2=34.65, P=0.000; Ⅱ vs. Ⅲ: χ2=18.99, P=0.000). And the GMTs of NA against PV Ⅰ, Ⅱ, Ⅲ were 1∶368.96、1∶23.06 and 1∶183.10, which were significantly different ( F=156.54, P=0.000). The GMT of PVⅠwas the highest, PV Ⅲ was the second, PVⅡ was lowest (pairwise comparison showed values of P all were 0.000). The analysis of general linear model showed that the interval between the date of last immunization and the date of sample collection would affect the GMTs of PVⅠand Ⅲ, different vaccine models would affect only the GMT of PV Ⅰ. The age maybe was a confounding factor. But no factors would affect the GMT of PV Ⅱ. Conclusions:After the vaccine switch, the level of NA against PVⅠand PV Ⅲ were still maintaining high level, but the level of PVⅡamong children<5 years was at relatively low level, which indicated that the surveillance should be strengthened.

Objective:We isolated and identified the genotypes and molecular characteristics of the imported B3 measles virus (MeV) in Fujian province in 2018.Methods:Throat swab specimens were collected from clinically diagnosed measles patients and tested for viral RNA, using the real-time reverse transcription-polymerase chain reaction after the RNA extraction. Reverse transcription-polymerase chain reaction method was undertaken to amplify the 634 nucleotide acids of 3-terminal of the nucleoprotein gene. A phylogenetic tree was constructed and similarities in homology assessed.Results:We successfully isolated and obtained two measles virus strains and eighteen viral nucleic acid sequences. The Fujian strains were clustered within the same genotype group of WHO genotype B3 reference strains. Compared to the major circulating measles strain genotype B3 in the world, two Fujian strains MV18-41 and MV18-42 showed 100.0 % nucleic acid homology to HongKong.CHN/35.18 strain which was isolated from Hong Kong in 2018. The remaining 16 Fujian strains showed the highest homology (99.9 %) with the Mvs/Osaka.JPN/38.18/B3 strain isolated from Japan in 2018. Compared with other 23 WHO genotype reference strains, homology on both nucleotide and amino acid of the Fujian strain and the B1 genotype reference strain were the smallest, as 95.1 %-95.4 % and 95.3 %, respectively. The differences of homology between the Fujian strain and H1 genotype reference strain were the largest, as 88.7 %-89.0 % and 87.3 %, respectively. In addition, there were 13 mutation sites between the Fujian strain and the vaccine strain (Shanghai-191) at the 150 amino acid position of carboxy terminus on N protein, However, these sites did not cause functional changes in the protein region. Conclusions:In Fujian province, two strains of B3 genotype measles virus were obtained successfully, which were considered to be new genotype measles virus found in 2018. These findings showed it is necessary to strengthening the monitoring program on imported cases for better control and eliminate the measles virus.

Objective To investigate the association and interaction of heat shock proteins B1 (HSPB1) gene rs2868371 and tumor-suppressor protein p53 (TP53) gene rs1042522 polymorphisms with chromosome damage levels among coke oven workers. Methods We recruited 1 333 male workers from a state-run coke oven plant in Wuhan in September-October 2010. Among them, 949 who had worked in coke oven workplaces, including auxiliary facilities and bottom, side, and top ovens, were nominated as coke oven workers (i.e., exposed), and 384 administrative or medical staff whose workplaces were offices were used as controls. General characteristics and 5 ml of venous blood were collected from each participant. The plasma concentrations of benzo [a] pyrene-diolepoxide (BPDE)-albumin adducts and the lymphocytic micronucleus (MN) frequencies for each individual were detected by ELISA and cytokinesis-block micronucleus assay, respectively. Gene polymorphisms were genotyped using TaqMan assays via quantitative PCR (ABI Prism 7900HT), and the corresponding frequency ratios (FR) with 95%confidence intervals (CI) were computed for all assays. Results In the exposed group, the MN frequencies were higher in HSPB1 rs2868371 GC, CC, and GC+CC genotype carriers ((3.88 ± 2.88)‰, (4.00 ± 2.66)‰, and (3.91 ± 2.83)‰, respectively) than in rs2868371 GG genotype carriers ((3.52±2.67)‰;FR=1.10, 1.13, and 1.11;95%CI:1.02-1.19, 1.02-1.25, and 1.03-1.19, respectively), and the HSPB1 rs2868371C allele was associated with increased MN frequency (Ptrend=0.006). Further, in the exposed group, the MN frequencies were lower in TP53 rs1042522 CG and CG+GG genotype carriers ((3.63±2.61)‰and (3.66±2.61)‰, respectively) than in TP53 rs1042522 CC genotype carriers (3.95 ± 3.06)‰(FR=0.87 and 0.90;95%CI:0.83-0.96 and 0.84-0.97, respectively). The effect of gene-gene interaction between HSPB1, rs2868371, and TP53 rs1042522 on MN frequency was significant among coke oven workers (P=0.001). Further stratified analyses showed that the effects of the HSPB1 rs2868371C allele in increasing MN frequencies were robust in subjects aged>40 years (FR=1.07, 95% CI: 1.01-1.12), those working >20 years (FR=1.08, 95% CI: 1.02-1.14), those with BMI ≤24 kg/m2 (FR=1.07, 95% CI: 1.01-1.13), drinkers (FR=1.09, 95% CI: 1.02-1.16), and workers with higher BPDE-albumin adduct levels (FR=1.07, 95% CI: 1.01-1.13) (Ptrend=0.023, 0.013, 0.029, and 0.020, respectively). The decreasing effect of the TP53 rs1042522 G allele on MN frequencies was robust in subjects aged >40 years (FR=0.94, 95% CI: 0.89-0.99), those with BMI ≤24 kg/m2 (FR=0.94, 95% CI:0.88-0.99), and drinkers (FR=0.94, 95% CI: 0.88-1.00) (Ptrend=0.031, 0.023, and 0.038, respectively). In addition, there were interactions between HSPB1 rs2868371 and age and between HSPB1 rs2868371 and working years in terms of MN frequency (P=0.030 and 0.013, respectively). Conclusion In coke oven workers, the HSPB1 rs2868371 C and TP53 rs1042522 G alleles were associated with increased and decreased chromosome damage levels, respectively, and their interaction effect on chromosome damage levels was significant.