OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

OBJECTIVE To investigate the effect of hyperoside on high glucose-induced excessive proliferation of retinal endo-thelial cells(RECs)and its possible mechanism.METHODS Diabetic retinopathy(DR)models were established in male Sprague-Dawley(SD)rats.DR rats were treated with low-and high-dose hyperoside(DR+L-HY group and DR+H-HY group).Additional-ly,the normal control(NC)group,DR non-intervention(DR)group and DR+calcium dobesilate intervention(DR+CD)group were set up.The differences in the number of RECs in retinal blood vessels were observed and compared among all groups after intervention.In addition,RECs were inoculated into cell culture plates after normal culture and subculture.They were divided into 5 groups according to different treatments:normal glucose(NG)group,high glucose(HG)group,mannitol(MT)group,high glucose+low concentration of hyperoside(HG+H100)group and high glucose+high concentration of hyperoside(HG+H400)group.The activ-ity,cell migration and tubule formation of RECs in each group were detected and compared by CCK-8,cell migration and tubule for-mation assays.Western blot and qPCR were used to detect the expression of NADPH Oxidase 4(NOX4)and thioredoxin interacting protein(TXNIP)in each group.RESULTS The number of RECs in the DR group was significantly increased compared to the NC group(P<0.01).In contrast,the DR+L-HY,DR+H-HY,and DR+CD groups all showed significant decreases in RECs number compared to the DR group(P<0.05,P<0.01),and the reduction of RECs in the DR+H-HY group was significantly greater than that in the DR+L-HY group(P<0.05).Furthermore,the cell activity,migration number and tube formation number of RECs in the HG group were significantly higher than those in the NG group(P<0.05,P<0.01).The protein and mRNA expression levels of NOX4 and TXNIP in the HG group were also significantly higher than those in the NG group(P<0.01).However,the RECs activity,RECs mi-gration number and tube formation number in the HG+H100 group and the HG+H400 group were significantly lower than those in the HG group(P<0.05,P<0.01).The expression levels of NOX4 and TXNIP in both groups were significantly lower than those in the HG group(P<0.05,P<0.01),and the RECs activity,migration number,tube formation number,and the expression of NOX4 and TXNIP in the HG+H400 group were further significantly decreased compared with those in the HG+H100 group(P<0.01).CONCLU-SION Hyperoside could significantly inhibit the high glucose-induced excessive proliferation of RECs.The mechanism may be relat-ed to the inhibition of NOX4/TXNIP activation in high-glucose environment.

OBJECTIVE To investigate the impact of the methionine synthase reductase （MTRR） rs10380 C＞T gene polymorphism on methotrexate （MTX） plasma concentration， adverse drug reaction， and prognosis in children with intracranial tumors. METHODS Peripheral blood was collected from children with intracranial tumors， and genomic DNA was extracted. The MTRR rs10380 C＞T genotype was analyzed using matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. The association of the MTRR rs10380 C＞T gene polymorphism with the ratio of MTX plasma concentration to dose （C/D ratio）， adverse drug reaction， tumor recurrence， and metastasis was analyzed. Bioinformatics analysis was used to explore the association of the rs10380 genotype and MTRR gene expression and its possible mechanisms. RESULTS A total of 75 children were included in the study. The distribution frequencies of the wild-type CC genotype and C allele of rs10380 were 62.67% and 81.33%， respectively， while the distribution frequencies of the variant CT genotype and T allele were 37.33% and 18.67%， respectively， which were in accordance with Hardy-Weinberg equilibrium（P＞0.05）. The incidence of electrolyte disorders （51.06%） and tumor metastasis rate （57.45%） in children with the CC genotype were significantly higher than those with the CT genotype （P＜0.05）. No significant differences were observed in the 24-hour and 42-hour C/D ratios and recurrence rates between the two genotypes of children （P＞0.05）. Bioinformatics analysis showed that MTRR protein mainly works in conjunction with 10 proteins， including MMAA， and was involved in various biological processes such as sulfur amino acid biosynthesis. CONCLUSIONS The MTRR rs10380 CC genotype may be a risk factor for electrolyte disorders and tumor metastasis in children with intracranial tumors after MTX chemotherapy.

Objective To compare the consistency of liquid chromatography-tandem mass spectrometry(LC-MS/MS)and fully auto-mated chemiluminescent immunoassay(CLIA)methods in measuring plasma aldosterone concentration(PAC)in the elderly patients in intensive care unit(ICU)and to explore the correlation between the levels of aldosterone(ALD)and blood biomarkers.Methods A total of 41 elderly ICU patients were included.PAC was measured using both LC-MS/MS and CLIA methods,followed by methodolo-gy validation and consistency comparison.Meanwhile,a retrospective analysis of the patients'clinical data was conducted,and the cor-relations between ALD and blood biomarkers were analyzed.Results The linear range of the LC-MS/MS method was 15 to 1 500 pg/mL,with a lower limit of quantification of 15 pg/mL.The inter-day and intra-day precisions were both less than 15％,and the re-covery rate was 94％to 99％,with no significant matrix effect.The PAC results detected by CLIA and LC-MS/MS methods were posi-tively correlated(r=0.762 7,P＜0.01),but the consistency between the two methods was poor.Deming regression analysis yielded the equation Y=0.969 6X-16.71,with a slope of 0.970(95％CI:0.890～1.049)and an intercept of-16.71(95％CI:-25.690 to-7.728).Bland-Altman analysis showed that CLIA overestimated PAC by an average of 21.18 pg/mL(95％CI:-25.89 to 68.26 pg/mL)compared to LC-MS/MS,with a bias of 24.02％.In the correlation analysis between ALD and blood biomarkers,ALD showed a significant positive correlation with myoglobin(Mb)(r=0.303,P＜0.05).Conclusion The LC-MS/MS method demonstrated good methodological performance in measuring PAC in the elderly patients in ICU.The consistency between LC-MS/MS and CLIA methods was poor,and the two methods should not be used interchangeably in clinical practice.There was a positive correlation between ALD and Mb,suggesting that ALD may be associated with myocardial injury.

OBJECTIVE To compare the safety of high-dose methotrexate （HD-MTX） via peripherally inserted central catheter （PICC） and totally implantable venous access port （TIVAP） in pediatric patients with malignant brain tumors. METHODS Patients with malignant brain tumors who received HD-MTX via PICCs or TIVAPs in our hospital from July 2018 to April 2022 were retrospectively analyzed. Clinical data were collected to compare differences in blood concentration of methotrexate （MTX），the incidence of adverse events （including adverse drug reactions and catheter-related complications） and length of stay in hospital. Multivariate linear regression was applied to analyze the factors that influenced the blood concentration of MTX. RESULTS A total of 107 patients were included in the study，with 65 patients in the PICC group and 42 patients in the TIVAP group. Blood concentration of MTX at 24 h （C24 h） in TIVAP group was significantly higher than PICC group （[ 126.87±61.99） μmol/L vs. （102.45±48.77） μmol/L，P＜0.05）. There was no significant difference in blood concentration of MTX at 42 h （C42 h），compared with PICC group （P＞0.05）. Results of multivariate linear regression analysis showed that TIVAP was associated with the increase of C24 h（P＜0.05）. No significant differences were observed in the incidence of adverse events and the length of stay in the hospital between 2 groups （P＞0.05）. CONCLUSIONS Risk of adverse events is not increased，although the MTX C24 h level is elevated after administration of TIVAP. TIVAP is a safe choice for HD-MTX therapy with implementing therapeutic drug monitoring.

Objective:To explore whether NSBB is suitable for the primary prevention of liver cirrhosis accompanied by CSPH with no or small esophageal varices.Methods:Relevant literatures were retrieved from Cochrane library, PubMed, EMBASE, SinoMed, CNKI and Wanfang databases until December 12, 2020. All randomized controlled trials (RCTs) on NSBB use for primary prevention of cirrhosis accompanied by CSPH with no or small esophageal varices were collected. The literature was strictly screened according to the established inclusion and exclusion criteria, odds ratio (OR), and 95% confidence interval (CI) combined effect size. The development of esophageal varices and the initial upper gastrointestinal bleeding were the primary outcome measures. Death (with a maximum average follow-up of about five years) and adverse events (adverse drug reactions, etc.) were the secondary outcome measures.Results:A total of 9 RCTs with 1396 cases were included. Meta-analysis results showed that, compared with placebo, NSBB significantly reduced the incidence of liver cirrhosis accompanied by CSPH with no or small esophageal varices to large esophageal varices progression ( OR=0.51, 95% CI: 0.29-0.89, P=0.02), and mortality (with maximum average follow-up of about five years) ( OR=0.64, 95% CI: 0.44-0.92, P=0.02); however, there was no statistically significant difference in the initial upper gastrointestinal bleeding rate between the two groups ( OR=0.82, 95% CI: 0.44-1.52, P=0.53). Adverse event incidence was greater in the NSBB than the placebo group ( OR=1.74, 95% CI: 1.27-2.37, P=0.0005). Conclusions:NSBB use cannot reduce the initial upper gastrointestinal bleeding rate or adverse event incidence in patients with liver cirrhosis accompanied by CSPH with no or small esophageal varices, but it can delay the progression of gastroesophageal varices and reduce patient mortality.

OBJECTIVE:To investigate the correlation of gene polymorphism in peripheral artery disease(PAD)patients with antiplatelet efficacy of clopidogrel. METHODS:Reviewing related domestic and foreign literatures in recent years,the correlation of gene polymorphism in PAD patients with antiplatelet efficacy of clopidogrel was summarized and analyzed. RESULTS&CON-CLUSIONS:At present,a variety of genes associated with clopidogrel antiplatelet efficacy and major adverse cardiovascular events (MACE)have been identified,including cytochrome P450(CYP)2C19,adenosine three phosphate binding cassette B subfamily 1 (ABCB1),paraoxonase 1 (PON1) and adenosine diphosphate P2Y12 receptor (P2Y12),etc. CYP2C19*2,*3 allele may reduce the antiplatelet effect of clopidogrel. Their correlation has been confirmed by a number of studies,and study results are broadly con-sistent. Mutations in the ABCB1 C3435T and PON1 Q192R sites may lead to a lower response to clopidogrel and increase the risk of MACE;but there is a lack of large-scale prospective clinical studies,and the present results are inconsistent. P2Y12 gene poly-morphism in PAD patients has not been found to be significantly associated with clopidogrel efficacy.