OBJECTIVETo build 3D-pharmacophore model of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors using distance comparisons method and design novel EGFR inhibitors.

METHODSThirteen typical EGFR inhibitors were selected, and their biologically active conformations were obtained by using DOCK5.0 program, then 3D-pharmacophore model of EGFR inhibitors was built using distance comparisons method.

RESULTSValidation of the 3D-pharmacophore model was carried out and novel structures with potential inhibitory activity were selected by means of 3D-searching and docking method.

CONCLUSIONThis method can improve hit rate of lead compounds discovery and can be used to design novel EGFR inhibitors.

Drug Design ; Enzyme Inhibitors ; Epidermal Growth Factor ; metabolism ; Models, Chemical ; Protein-Tyrosine Kinases ; antagonists & inhibitors ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; chemistry ; Structure-Activity Relationship

Adolescent ; Adolescent Development ; Child ; Child Development ; China ; epidemiology ; Female ; Humans ; Male ; Obesity ; epidemiology ; Prevalence

OBJECTIVE:To establish the method for the content determination of 4 active components in Compound xiaosuanzao chewable tablets.METHODS:HPLC-ELSD method was adopted.The determination was performed on a Grace Brava C18-BDS column with mobile phase consisted of acetonitrile-water (gradient elution) at the flow rate of 1.0 mL/min.The column temperature was 25 ℃,and sample size was 20 μL.The drift tube temperature is 100 ℃,and the carrier gas flow rate is 2.9 L/min.RESULTS:The linear ranges of betulic acid,betulinol,pachymic acid and glycyrrhizic acid were 44.50-890.0 μg/mL (r=0.999 3),20.28-405.6 μg/mL (r=0.999 7),20.50-656.0 μg/mL(r=0.999 7) and 10.50-336.0 μg/mL(r=0.999 6),respectively.RSDs of precision,stability and reproducibility were all lower than 3.0％.The recoveries were 99.44％-101.12％ (RSD=0.57％,n=6),99.41％-100.39％ (RSD=0.34％,n=6),99.31％-100.46％ (RSD=0.51％,n=6),98.96％-101.19％ (RSD=0.84％,n=6),respectively.CONCLUSIONS:The method is simple,precise,stable and reproducible,and can be used for simultaneous determination of 4 active components in Compound xiaosuanzao chewable tablets.

OBJECTIVETo evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-β1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population.

METHODSThe subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension.

RESULTSThe frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05).

CONCLUSIONSNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.

Aged ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases ; genetics ; Receptors, Transforming Growth Factor beta ; genetics

Animals ; Chemokine CCL2 ; analysis ; genetics ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Drug Therapy, Combination ; Fatty Acids, Monounsaturated ; administration & dosage ; Indoles ; administration & dosage ; Kidney ; drug effects ; physiopathology ; Male ; NF-kappa B ; analysis ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; administration & dosage ; Transcription Factor RelA ; Valine ; administration & dosage ; analogs & derivatives ; Valsartan

The purpose of this study was to investigate the epidemiological characteristics and risk factors of influenza in Hainan province,to provide evidence to support influenza prevention and control efforts.Pathogen monitoring data of influenza-like illness(ILI)in six national sentinel hospitals in Hainan province from 2013 to 2021 were analyzed in SPSS 20.0 software.A total of 50 415 ILI cases were detected during the 2013-2021 season,of which 5 581 were positive for influenza viruses,with a positivity rate of 11.07％.The dominant strains were type B,type A(H1N1)pdm09 and type A(H3N2).The positivi-ty rate of influenza virus was highest in people 5-14 years of age(17.56％)and lowest in people 0-4 years of age(7.32％).Influenza activity showed both a summer peak and a winter-spring peak in the 2014-2016,2017-2018 and 2019-2020 sea-sons,and was concentrated in April to September,with a maximum peak of 53.64％,and in November to March of the next year,with a peak of 47.30％.The 2013-2014,2016-2017 and 2018-2019 seasons showed only a winter-spring peak concen-trated between October and March of the next year,with a maximum peak of 54.17％,but no obvious summer peak.The pre-dominant influenza viruses during the eight surveillance seasons varied among H1N1,H3N2 and type B.The positive detection rate of influenza virus steeply declined during the 2020-2021 season:the positive detection rate was only 0.25％,and no obvi-ous epidemic period was observed.The intensity of influenza epidemic varied among monitoring years,and the dominant strains changed rapidly in Hainan Province.People 5-14 years of age were the key population affected.Summer,winter and spring were the key periods for influenza prevention and control.Etiological surveillance of influenza should continue to be strength-ened,the roles of health education and publicity should be emphasized,and the dual measures of influenza vaccination and non-drug intervention should be actively promoted to decrease the occurrence of influenza.

Objective To investigate the bacteriostatic activity of five hemostatic dressings for war injury to provide references for the development of novel hemostatic dressings.Methods The bacteriostatic ratios of Combat Gauze made of kaolin and four kinds of dressings made of chitosan including Celox Rapid Gauze,Celox Gauze,ChitoGauze and a self-developed dressing against S.aureus and E.coli were explored according to GB/T 20944.2-2007.The bacteriostatic time and activity were inferred by investigating the growth of S.aureus under simulated conditions.Results Combat Gauze had the hemostatic ratios lower than 20％against both S.aureus and E.coli within 24 h.The hemostatic ratios of Celox Rapid Gauze,Celox Gauze,ChitoGauze and the self-developed dressing against S.aureus were all higher than 90％after 30 min action,while the ratios of the four dressings against E.coli were slightly different and changed with the prolongation of the time of action:after 30 min action only Celox Rapid Gauze had the hemostatic ratio higher than 90％;after 3 h action,ChitoGauze had a low ratio of 35％while the other dressings were all higher than 95％;after 24 h action the four dressings all had the ratios higher than 99％.Celox Rapid Gauze,Celox Gauze,ChitoGauze and the self-developed dressing all significantly inhibited the growth of S.aureus within 15 h and the time for S.aureus to reach the threshold of clinical infection under simulated conditions was 18,15,24 and 15 h,respectively.Conclusion Combat Gauze is not effective in inhibiting S.aureus and E.coli,while Celox Rapid Gauze,Celox Gauze,ChitoGauze and the self-developed dressing behave well with Celox Rapid Gauze gaining high compre-hensive bacteriostatic activity and ChitoGauze having the longest bacteriostatic time against S.aureus.

To investigate the correlation of serum long noncoding RNA-metastasis associated lung adenocarcinoma transcript 1(LncRNA MALAT1) and serum amyloid A(SAA) with diabetic kidney disease. Retrospective research was used, and 40 patients with type 2 diabetes and 80 patients with type 2 diabetic kidney disease patients who were treated in Tianjin Medical University Chu Hsien-I Memorial Hospital from August 2021 to February 2022 were selected, and 40 healthy subjects were selected during the same period. Reverse transcription-polymerase chain reaction(RT-PCR) was used to detect serum LncRNA MALAT1. SAA were detected with enzyme linked immunosorbent assay (ELISA). Automatic biochemistry analyzer was used to detect serum creatinine (CREA) and low-density lipoprotein cholesterol(LDL-C),automatic blood glucose analyzer to detect serum fasting plasma glucose (FPG), automatic glycated hemoglobin analyzer to detect hemoglobin A1C (HbA1c), and automatic immunoassay analyzer to detect urinary albumin to creatinine ratio(UACR). Differences between groups were compared by t test and analysis of variance. Pearson analysis was used to analyze the correlation between MALAT1, SAA and other indicators. Receiver operating characteristic curve(ROC) was used to evaluate the auxiliary diagnostic value of MALAT1 and SAA for diabetic kidney disease. The results showed that MALAT1 and SAA in the diabetic kidney disease with mass albuminuria group were higher than those in the type 2 diabetes mellitus group (q=8.57, P<0.01; q=11.09, P<0.01) and the diabetic kidney disease with microalbuminuria group (q=3.96, P<0.05; q=7.85, P<0.01). MALAT1 had a high correlation with UACR, CREA, SAA, HbA1c and FPG (r value was 0.706, 0.643, 0.578, 0.553, and 0.524, all P<0.01), and SAA had a high correlation with UACR, HbA1c and FPG (r value was 0.664, 0.617, and 0.595, all P<0.01). ROC curve analysis of the diagnostic value of LncRNA MALAT1 and protein SAA for diabetic kidney disease showed that the areas under curve (AUC) were 0.741 and 0.744, respectively. The combined diagnostic value of the two was the greatest (AUC=0.801). In summary, MALAT1 and SAA were elevated in the serum of patients with type 2 diabetes. Their concentrations in the serum of group with diabetic kidney disease were higher than that in the type 2 diabetes group, and the serum concentrations of MALAT1 and SAA in group with mass albuminuria are higher than the group with microalbuminuria. MALAT1 and SAA were both closely related to UACR and HbA1c, and there is a correlation between them. Both of them may have ancillary diagnostic value for diabetic kidney disease.
Humans ; RNA, Long Noncoding/metabolism* ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies/urine* ; Retrospective Studies ; Glycated Hemoglobin ; Serum Amyloid A Protein ; Albuminuria

This paper aims to systematically analyze the peptides and proteins from Asini Corii Colla(ACC) through shotgun proteomics. After high-pH reversed-phase fractionation, the proteins and peptides in the hydrolysate of ACC were further separated by nano LC-Q-Exactive-MS/MS under the following conditions: Thermo Scientific EASY column(100 μm×2 cm, 5 μm, C_(18)) as precolumn, Thermo Scientific EASY column(75 μm×100 mm, 3 μm, C_(18)) for solid phase extraction, gradient elution with 0.1% formic acid in water(mobile phase A) and 84% acetonitrile in water containing 0.1% formic acid(mobile phase B), and MS in positive ion mode. Based on Uniprot_Equus caballus, MS data, and literature, 2 291 peptides were identified from ACC by MaxQuant, with 255 Maillard reactions(AML, CML, CEL)-modified peptides identified for the first time. Through alignment, the peptides were found to belong to 678 equine proteins. In conclusion, the combination of nano LC-Q-Exactive-MS/MS and shotgun proteomics achieved rapid and accurate identification of the proteins and peptides in ACC, which provides the key information and new insights for further investigation of chemicals and effective substances in ACC.
Animals ; Chromatography, Liquid ; Horses ; Peptides ; Proteins ; Proteomics ; Tandem Mass Spectrometry

Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.
COVID-19/epidemiology* ; Contact Tracing ; Humans ; Incidence ; Nucleic Acids ; Prospective Studies ; SARS-CoV-2