Objective:To analyze the trends in refractive error and ocular biological parameters in elementary school students over 5 years, and to investigate the patterns of change before and after myopia onset.Methods:A cohort study was adopted.A total of 1 986 first-grade students from the Anyang Childhood Eye Study were enrolled in this cohort study and their right eye data were taken for analysis, including 1 126 boys and 860 girls.Every year, cycloplegic autorefraction was performed with 1% cyclopentolate eyedrops to obtain the spherical equivalent (SE).The axial length (AL), anterior chamber depth, lens thickness, mean corneal curvature (Km) and other parameters were obtained by ocular biometry.The lens refractive power (LP) was calculated using the Bennett formula.The subjects were assigned to persistent myopia group, non-myopia group and new onset myopia group.According to the age of myopia onset, the new onset myopia group was subdivided into the 8-, 9-, 10-, 11- and 12-year-old myopia groups to compare the differences in refractive error and ocular bioparameters among groups at different time points of follow-up.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2018-030).Written informed consent form was obtained from the guardians of each subject.Results:All children had a gradual SE drift toward myopia and a gradual increase in the AL with age, and there were significant differences in SE and AL between adjacent follow-up ages within the three groups (all at P<0.05).The earlier the onset of myopia, the higher the myopia SE and the longer the AL of the eye at the same follow-up age, the differences in SE between adjacent groups were statistically significant (all at P<0.05), and the differences in AL between adjacent groups at the follow-up age of 8 to 12 years were statistically significant (all at P<0.05).In the nonmyopia group, SE drifted toward emmetropia at a slow and steady rate of (-0.23±0.27)D/year, and AL also increased slowly and steadily at (0.18±0.13)mm/year.In the new onset myopia group, the changes in SE in the third, second, and first years before myopia onset were (-0.32±0.25), (-0.45±0.33), and (-0.98±0.44)D, and the increases in AL were (0.25±0.12), (0.32±0.15), and (0.48±0.19)mm, respectively.Both SE and AL change rates began to accelerate before myopia onset and slowed down after myopia onset, with statistically significant differences in the overall comparison of SE and AL change rates at different time intervals before and after myopia onset (all at P<0.001).The AL at myopia onset in boys was (24.11±0.70)mm, which was longer than (23.60±0.66)mm in girls ( t=159.71, P<0.01).LP decreased with age in all groups, with a faster rate before the age of 9 years and a slower rate after the age of 9 years.The mean decrease rate in LP was (-0.48±0.19), (-0.44±0.20), (-0.49±0.16), (-0.51±0.18), and (-0.48±0.19)D/year in the persistent myopia group and 8~11-year-old myopia group, respectively, which were significantly faster than -0.42±0.17 D/year in 12-year-old myopia group and (0.37±0.15)D/year in nonmyopia group (all at P<0.05).There was no statistically significant difference in Km among groups at different follow-up ages (all at P>0.05). Conclusions:The AL begins to grow at an accelerated rate 3 years before myopia onset, and the increase rate of the AL slows down after the onset of myopia, but it is still significantly faster than that of non-myopic children.In this process, the decrease in LP plays a compensatory role; there is no significant change in corneal curvature.The AL of males at the onset of myopia is longer than that of females at the same age.AL is an important indicator for the prevention and control of myopia.It is important to consider gender differences and to pay more attention to the growth rate when assessing AL.

AIM:This study investigated the protective effects and underlying mechanisms of rosuvastatin(RST)in mitigating high glucose(HG)-induced damage in human umbilical vein endothelial cells(HUVECs),comple-mented by bioinformatics analysis.METHODS:Network pharmacology was employed to identify the potential targets and signaling pathways of RST in treating HG-induced vascular endothelial dysfunction.Molecular docking techniques were used to evaluate the binding affinity of RST to these core targets.The HUVECs were cultured in vitro and assigned into control,HG,and HG+RST(0.01,0.1,1,2,5 and 10 μmol/L)groups.Cell viability was determined using the MTS as-say.Levels of lactate dehydrogenase(LDH)and nitric oxide(NO)were quantified using chemical colorimetric assays.The mRNA levels of endothelial nitric oxide synthase(eNOS),claudin-1(CLDN-1),occludin(OCLN),zonula oc-cludens-1(ZO-1),aldose reductase(AR),Janus kinase 2(JAK2),mitogen-activated protein kinase 1(MAPK1),Ras homologous gene family member A(RHOA)and heat shock proteins 90AB1(HSP90AB1)were assessed by RT-qPCR.Western blot analysis was used to evaluate protein levels of eNOS,OCLN and ZO-1.RESULTS:Network pharmacology analysis suggested that RST may improve HG-induced vascular endothelial dysfunction by influencing the chemokine sig-naling pathway,tyrosine metabolism,MAPK signaling pathway,and hypoxia-inducible factor 1 alpha signaling pathway.The MTS assay indicated that RST significantly enhanced cell viability in an HG environment(P＜0.01)and reduced HG-induced damage in HUVECs.Compared with the control group,the HG group showed a significant increase in LDH levels(P＜0.01)and decreases in NO,eNOS,CLDN-1,OCLN and ZO-1 levels(P＜0.05).Additionally,the mRNA levels of AR,JAK2,MAPK1 and RHOA were elevated(P＜0.01),and HSP90AB1 was reduced in the HG group(P＜0.05).Rel-ative to the HG group,RST treatment significantly decreased LDH levels(P＜0.01)and increased the levels of NO,eNOS,CLDN-1,OCLN and ZO-1(P＜0.01).Moreover,the mRNA levels of AR,JAK2,MAPK1 and RHOA were re-duced(P＜0.01),and HSP90AB1 expression was increased in the HG+RST group(P＜0.01).CONCLUSION:RST ef-fectively attenuates HG-induced endothelial injury.This protective effect is potentially mediated by downregulating AR,JAK2,MAPK1,and RHOA expression and upregulating HSP90AB1 expression.

AIM:This study investigated the protective effects and underlying mechanisms of rosuvastatin(RST)in mitigating high glucose(HG)-induced damage in human umbilical vein endothelial cells(HUVECs),comple-mented by bioinformatics analysis.METHODS:Network pharmacology was employed to identify the potential targets and signaling pathways of RST in treating HG-induced vascular endothelial dysfunction.Molecular docking techniques were used to evaluate the binding affinity of RST to these core targets.The HUVECs were cultured in vitro and assigned into control,HG,and HG+RST(0.01,0.1,1,2,5 and 10 μmol/L)groups.Cell viability was determined using the MTS as-say.Levels of lactate dehydrogenase(LDH)and nitric oxide(NO)were quantified using chemical colorimetric assays.The mRNA levels of endothelial nitric oxide synthase(eNOS),claudin-1(CLDN-1),occludin(OCLN),zonula oc-cludens-1(ZO-1),aldose reductase(AR),Janus kinase 2(JAK2),mitogen-activated protein kinase 1(MAPK1),Ras homologous gene family member A(RHOA)and heat shock proteins 90AB1(HSP90AB1)were assessed by RT-qPCR.Western blot analysis was used to evaluate protein levels of eNOS,OCLN and ZO-1.RESULTS:Network pharmacology analysis suggested that RST may improve HG-induced vascular endothelial dysfunction by influencing the chemokine sig-naling pathway,tyrosine metabolism,MAPK signaling pathway,and hypoxia-inducible factor 1 alpha signaling pathway.The MTS assay indicated that RST significantly enhanced cell viability in an HG environment(P＜0.01)and reduced HG-induced damage in HUVECs.Compared with the control group,the HG group showed a significant increase in LDH levels(P＜0.01)and decreases in NO,eNOS,CLDN-1,OCLN and ZO-1 levels(P＜0.05).Additionally,the mRNA levels of AR,JAK2,MAPK1 and RHOA were elevated(P＜0.01),and HSP90AB1 was reduced in the HG group(P＜0.05).Rel-ative to the HG group,RST treatment significantly decreased LDH levels(P＜0.01)and increased the levels of NO,eNOS,CLDN-1,OCLN and ZO-1(P＜0.01).Moreover,the mRNA levels of AR,JAK2,MAPK1 and RHOA were re-duced(P＜0.01),and HSP90AB1 expression was increased in the HG+RST group(P＜0.01).CONCLUSION:RST ef-fectively attenuates HG-induced endothelial injury.This protective effect is potentially mediated by downregulating AR,JAK2,MAPK1,and RHOA expression and upregulating HSP90AB1 expression.

Objective To investigate the prevalence of hepatitis D virus (HDV) infection among patients with chronic hepatitis B virus (HBV) infection in some regions of China. Methods Serum samples were collected from 3 131 patients with chronic HBV infection in 10 provinces, cities, and autonomous regions of China from March 2021 to June 2022, and anti-HDV IgG ELISA was used for the detection of all serum samples. Nested reverse transcription-polymerase chain reaction (nRT-PCR) was used to detect HDV RNA in anti-HDV IgG-positive samples, and the nRT-PCR amplification products of HDV RNA-positive samples were sequenced and analyzed to determine HDV genotype. The clinical features of anti-HDV IgG-positive patients were analyzed. The Mann-Whitney U rank sum test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results The positive rate of anti-HDV IgG in the 3 131 patients with chronic HBV infection was 0.70% (22/3 131), and that in the patients with chronic HBV infection in Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region, Beijing, and Hunan Province was 1.81% (16/886), 0.88% (2/226), 0.28% (2/708), and 1.00% (2/200), respectively; the patients with chronic HBV infection in Inner Mongolia Autonomous Region had a significantly higher positive rate of anti-HDV IgG than those in Beijing ( P =0.004), and there was no significant difference between the other regions ( P > 0.05). Clinical features of the patients with chronic HBV infection in Inner Mongolia Autonomous Region showed that compared with the anti-HDV IgG-negative group, the anti-HDV IgG-positive group had a significantly higher proportion of patients with Mongol nationality ( P =0.001), abnormal alanine aminotransferase ( P =0.007), or antiviral treatment ( P =0.029), as well as a significantly lower median HBV DNA level ( P =0.030). A total of 19 HDV RNA-positive samples were identified, all of which had HDV genotype 1. Conclusion The prevalence rate of HDV varies greatly across different regions of China, with a higher prevalence rate of HDV in patients with chronic HBV infection from Inner Mongolia Autonomous Region. HDV genotype 1 is the predominant genotype in some provinces and cities of northern China.

Objective: To investigate the effects of embryonic inflammation on the hippocampal synaptosomal-associated protein 25(SNAP-25) level and cognitive function in middle-aged. Methods: During gestational days 15-17, the CD-1 maternal mice received a daily intraperitoneal injection of lipopolysaccharides(LPS, 50 μg/kg) or the equal volume of normal saline, and the corresponding offspring were regarded as LPS group and CON group respectively. At the age of young(3-month-old) and middle-aged(15-month-old), the spatial learning and memory ability was assessed using Morris water maze(MWM), and the expression of hippocampal SNAP-25 protein was detected by immunohistochemical method and Western blot. Results: Compared with the 3-month CON group, the 15-month CON group had longer swimming distance(P<0.01), lower swimming distance percentage(P<0.01) in the target quadrant, and higher hippocampal subregions(CA1, CA3, DG) SNAP-25 levels(P<0.01). The same results were obtained in 15-month LPS group compared with 15-month CON group in learning and memory phase(P<0.05), and higher hippocampal subregions(CA1, DG) SNAP-25 levels(P<0.01). Pearson correlation analysis indicated that the hippocampal CA1 and CA3 subregions SNAP-25 level was positively correlated with the swimming distance, but negatively correlated with the percentage of swimming distance in the target quadrant. Conclusion Embryonic inflammation can accelerate the impairment of spatial learning and memory and the increase of hippocampal CA1 and CA3 subregions SNAP-25 protein in middle-aged CD-1 mice, and there may be a correlation between them.

Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.

Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.

Lianhuaqingwen (LHQW) capsule, a herb medicine product, has been clinically proved to be effective in coronavirus disease 2019 (COVID-19) pneumonia treatment. However, human exposure to LHQW components and their pharmacological effects remain largely unknown. Hence, this study aimed to determine human exposure to LHQW components and their anti-COVID-19 pharmacological activities. Analysis of LHQW component profiles in human plasma and urine after repeated therapeutic dosing was conducted using a combination of HRMS and an untargeted data-mining approach, leading to detection of 132 LHQW prototype and metabolite components, which were absorbed

Objective:To investigate the effect of CD 8+ CD 25+ FoxP3 + regulatory T cell (Treg) expression levels in peripheral blood of pregnant women with premature rupture of fetal membranes(PROM) on immune function of helper T cells (Th) 1/Th2. Methods:Thirty cases of pregnant women with PROM (PROM group), 30 cases of normal pregnant women (normal pregnancy group) and 30 cases of normal non-pregnant women (non-pregnancy group) who treated in Binhai County People′s Hospital from September 2019 to May 2020 were collected. Peripheral blood of each group was collected and the proportion of CD 8+ CD 25+ FoxP3 + Treg was determined by flow cytometry. Peripheral blood mononuclear cells (PBMCs) were extracted and FoxP3 mRNA was determined by polymerase chain reaction (PCR). The levels of Th1-related cytokines interferon-γ (IFN-γ), interleukin (IL)-2, and Th2-related cytokines IL-10 and IL-4 were measured by Luminex liquid phase microarray. The effects of CD 8+ CD 25+ FoxP3 + Tregexpression on Th1/Th2 balance were analyzed. Results:The proportion of CD 8+ CD 25+ FoxP3 + Tregand the expression of FoxP3 mRNA in PROM groupand normal pregnancy group were lower than those in non-pregnancy group: (0.15 ± 0.03) %, (0.35 ± 0.09) % vs. (0.47 ± 0.11) %; 0.89 ± 0.11, 3.15 ± 0.67 vs. 3.75 ± 0.23 , the proportion of CD 8+ CD 25+ FoxP3 + Treg and the expression of FoxP3 mRNA in PROM groupwere lower than those in the normal pregnancy group , and the differences were statistically significant ( P<0.05). The levels of Th1-related cytokines IFN-γ and IL-2 in PROM group and normal pregnancy group were higher than those in non-pregnancy group, the level of Th2-related cytokines IL-4 was lower than that in non-pregnancy group , the levels of IFN-γ and IL-2 in PROM group were higher than those in normal pregnancy group, the level of IL-4 was lower than that in normal pregnancy group , and the differences were statistically significant ( P<0.05). In PROM group, the proportion of CD 8+ CD 25+ FoxP3 + Treg and the expression of FoxP3 mRNA in peripheral blood were negatively correlated with Th1-related cytokines IFN-γ ( r = - 0.413, -0.451, P<0.05) and IL-22 ( r = -0.645, -0.535, P<0.05), and were positively correlated with Th2-related cytokines IL-4 ( r = 0.558, 0.469, P<0.05). Conclusions:The proportion of CD 8+ CD 25+ FoxP3 + Treg in peripheral blood of pregnant women with PROM is lower, and the expression level of related FoxP3 mRNA is lower, which all affecte the Th1/Th2 immune balance and cause Th1 immune drift, which may be the related immune mechanism of PROM.

Objective To investigate the effect of blood glucose levels at admission on the outcomes and hemorrhagic transformation in patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods From December 2013 to January 2017, patients with AIS treated with intravenous thrombolysis at the Department of Neurology, Xuzhou Central Hospital were enrolled retrospectively. According to the blood glucose levels on admission, they were divided into non-hyperglycemic group ( ≤8 mmol/L ) and hyperglycemic group ( > 8 mmol/L). The functional outcome was assessed with the modified Rankin Scale score at 90 d after onset, and 0-2 was defined as good outcome and > 2 was defined as poor outcome. From 24 h to 7 d after treatment, CT scan was performed again to determine whether there was intracranial hemorrhage or not. Multivariate logistic regression analysis was used to identify the independent influencing factors of outcomes after intravenous thrombolysis. Results A total of 323 patients with AIS were enrolled, including 237 (73. 4％) in the non-hyperglycemic group and 86 (26. 6％) in the hyperglycemic group; 238 (73. 7％) in the good outcome group, and 85 (26. 3％) in the poor outcome group; 25 (7. 7％) in the hemorrhagic transformation group, and 298 (92. 3％) in the non-hemorrhagic transformation group. Univariate analysis showed that there were significant differences in the proportions of patients with ischemic heart disease, atrial fibrillation, past history of stroke or TIA, as well as age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and baseline blood glucose between the poor outcome group and the good outcome group (all P < 0. 05). There were significant differences in the proportion of hypertensive patients and baseline NIHSS score between the hemorrhagic transformation group and the non- hemorrhagic transformation group ( all P < 0. 05 ). Multivariate logistic regression analysis showed that hyperglycemia at admission (odds ratio [OR] 2. 239, 95％ confidence interval [CI] 1. 210-4. 143; P = 0. 010)and baseline NIHSS score (OR 3. 528, 95％ CI 2. 451-5. 078; P < 0. 001) were the independent influencing factors of poor outcome; hypertension (OR 0. 410, 95％ CI 0. 173-0. 972; P = 0. 043 ) and baseline NIHSS score (OR 2. 283, 95％ CI 1. 382-3. 772, P = 0. 001 ) were the independent influencing factors of hemorrhagic transformation. Conclusion Hyperglycemia at admission was an independent risk factor for poor outcome in patients with AIS after intravenous thrombolytic therapy, but it was not associated with the risk of hemorrhagic transformation.