OBJECTIVE To study the relationship between HLA-DRB1*03 genes and expression of cytokine IL-18 in chronic hepatitis B patients.METHODS A total of 153 chronic hepatitis B patients and 138 normal healthy people were detected.HLA-DRB1*03 alleles were conducted in all the patients with polymerase chain reaction-sequence specific primer(PCR-SSP),and IL-18 was detected by ELISA.RESULTS Thirty-four individuals with chronic hepatitis B patients were HLA-DRB1*03 genes positive,the frequency was 22.22%,which was higher than the frequency of HLA-DRB1*03 in heathy individuals.The average level of IL-18 in chronic hepatitis B patients with HLA-DRB1*03 negatives was significantly higher than in HLA-DRB1*03 positives.CONCLUSIONS HLA-DRB1*03 closely relates with susceptibility to chronic hepatitis B.In chronic hepatitis B patients,the average level of Th1 cytokines in HLA-DRB1*03 negatives is higher than that in HLA-DRB1*03 positives.

OBJECTIVE:To prepare anti-tumor drug H6(lactone compound)polymeric micelles,and to investigate its in vitro anti-tumor effects. METHODS:Using mPEG2000-PCL4000 as carrier,H6/mPEG2000-PCL4000 micelles were prepared. Using particle size, PDI and 48 h whether to produce precipitation as indexes,feeding ratio,H6 concentration,volume ratio of organic solvent were screened. The encapsulation efficiency and drug-loading amount of micelle were all detected. MTT assay was used to detect the tox-icity of micelles and H6 solution to human non-small cell lung cancer cell A549 and human lung cancer cell H460. RESULTS:The screened formulation was as follows as feeding ratio of 1∶25,H6 concentration of 2 mg/mL,the ratio of ethanol to chloroform of 1∶1(V/V). The parameters of prepared H6/mPEG2000-PCL4000 micelles were as follows as particle size of(40.74±0.116 3)nm,PDI of(0.101±0.006),encapsulation efficiency of(94.87±0.016 3)%,drug-loading amount of(7.07±0.001 5)%(n=3). IC50 of mi-celles and H6 solution to A549 cell were 15.62 and 12.57 nmol/L;IC50 of micelles and H6 solution to H460 cell were 27.68 and 15.19 nmol/L. CONCLUSIONS:H6/mPEG2000-PCL4000 micelles are prepared successfully and show in vitro anti-tumor effects.

Objective To design and testify a novel strategy for acquiring mimetic epitope mapping by screening for a phage random peptide library using polyclonal anti keratin autoantibodies (AK auto Ab). Methods AK auto Ab were isolated and purified from pooled human sera by keratin affinity column in which keratin had been linked with CNBr Sepharose 4B,then biotinylated by the biotin ester. A 15 mer phage random peptide library was biopanned for 3 cycles and positive clones were identified by ELISA,competition assay and DNA sequencing. ResultsBy sequence comparison 23 positive clones were selected randomly and three epitopes were confirmed. Among the three epitopes SLSPMPTTNRR was the dominant epitope. The phages carrying positive clones reacted with AK auto Ab specifically and keratin could prevent interaction between AK auto Ab and positive phages. Conclusion The designed strategy is successfully applied in acquiring epitopes of polyclonal autoantibodies to keratin, which could provide a new approach for the discovery of epitope mapping which binds to natural autoantibodies.

OBJECTIVE:To establish the detection method for anti-inflammatory compound HB0314 in plasma of rats,and study on its pharmacokinetic characteristics in rats in vivo. METHODS:UPLC-MS/MS was performed on the column of Waters Ac-quity UPLCTM BEH C18 with mobile phase of 0.1% formic acid aqueous solution(A)-methanol(B)by gradient elution(0-2 min, 70%-90% B) at flow rate of 0.25 mL/min,column temperature was 30 ℃,and injection volume was 5 μL. Electrospray ion source was used,capillary voltage was 3 kV,ion source temperature was 150 ℃,desolvation gas temperature was 450 ℃,desol-vent air flow volume was 600 L/h,cone air flow volume was 45 L/h,and the inner standard was tetrahydropalmatine. 12 rats were randomly divided into iv group and ig group,6 in each group. Rats were intravenously injected and intragastrically administrated HB0314 solution 5,10 mg/kg. Sample blood 0.4 mL were taken from the jugular vein blood before administration and after 5,15, 30,60,120,240,360,480,600,720,1440 min of administration to determine the HB0314 plasma concentration. DAS 2.0 software was used to calculate the pharmacokinetic parameters and absolute bioavailability. RESULTS:The linear range of HB0314 was 1-1000 ng/mL(r=0.9955),and the lower limit of quantification was 1 ng/mL. RSDs of extra-day and daytime precision,sta-bility were not higher than 8.45%(n=5);recovery were 68.21%-90.29%(RSD≤11.20%,n=5),and matrix effects were 82.63%-106.90%(RSD≤6.75%,n=5). After intravenous injection and intragastric administration,AUC0-24 h were (270.267 ± 21.164), (252.755 ± 26.169)μg·h/L (n=6);t1/2z were (8.722 ± 2.266),(11.877 ± 4.517) h (n=6);and absolute bioavailability was 56.79%. CONCLUSIONS:The method is rapid,simple,and can be used for the determination of HB0314 content in plasma of rats. HB0314 shows high oral absolute bioavailability in rats in vivo,indicating that post-dosage form design may be considered as oral anti-inflammatory drugs.

OBJECTIVETo explore the mechanism underlying changes in microvascular reactivity in single- and double-transgenic mice.

METHODSPeripheral vascular reactivity to the vasodilators, acetylcholine and sodium nitroprusside, on perfused microvasculature of the hind footpad was investigated using nontransgenic mice, single-transgenic mice expressing the human APP-C100 (TgC100. WT or TgC100. V717F) and double-transgenic mice coexpressing human APP-C100 and human SOD(1) (G93A) genes.

RESULTSSingle TgC100 and double Tg mice C100/SOD(1) (G93A) at 2 - 3 months old showed a statistical decrease of 28% in blood flux compared to nontransgenic control mice. In addition, vasodilative responsiveness was markedly reduced to 34% in 8 - 9 months old TgC100 mice compared to control mice. There was no significant difference in the profile of vasodilative reaction between TgC100. WT and TgC100. V717F mice. TgC100 and double Tg mice also had higher levels of A beta peptide in plasma than nontransgenic mice (P < 0.01).

CONCLUSIONSThe present study suggests that the altered reactivity of the microvasculature may be mediated by circulating soluble A beta peptides. The mechanisms underlying the vasoactivity of circulating A beta in TgC100 and double Tg mice may involve both the endothelium and nonendothelium.

Acetylcholine ; pharmacology ; Amyloid beta-Peptides ; blood ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Blood Flow Velocity ; drug effects ; Hindlimb ; blood supply ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Mice, Transgenic ; Mutation ; Nitroprusside ; pharmacology ; Peptide Fragments ; blood ; Superoxide Dismutase ; genetics ; metabolism ; Vasodilator Agents ; pharmacology

Objective: To study the associations between variants of mTORC1 of PI3K/AKT/mTOR pathway and colorectal cancer. Methods: In this hospital-based case-control study, at the First Affiliated Hospital, Xinjiang Medical University from 2000 to 2013, 665 primary colorectal cancer cases and 695 cancer-free controls were genotyped at 10 potentially functional single nucleotide polymorphism (SNPs) loci of mTORC1 (mTOR: rs1034528, rs2295080; Raptor: rs1062935, rs3751934; mLST8: rs3160, rs26865; DEPTOR: rs2271900, rs4871827; AKT1S1: rs2290774, rs2353005) to assess their associations with risk of colorectal cancer by Logistic regression analysis. Results: In single-locus analysis, found a significantly decreased risk of colorectal cancer associated with mLST8 rs26865 by recessive genetic model, especially in populations of ≤68 years of age (OR=0.64; 95%CI=0.43-0.96, P=0.031), female (OR=0.61; 95%CI=0.38-0.99, P=0.046), non-smoking (OR=0.55; 95%CI=0.35-0.87, P=0.010). mTOR rs1034528 CC genotypes were associated with higher risk of colorectal cancer in >68-year-old populations (OR=3.34; 95%CI=1.12-9.91, P=0.030). Raptor rs3751934 CA/AA genotypes were associated with lower colorectal cancer risk in population of body mass index(BMI)>25 kg/m² (OR=0.68; 95%CI=0.47-0.98, P=0.038); and AKT1S1 rs2290774 CC genotypes were associated with lower colorectal cancer risk in non-smoking population (OR=0.67; 95%CI=0.45-0.99, P=0.048). Furthermore, found that populations carrying more than two low-risk genotypes were associated with lower colorectal cancer risk, compared with that of populations carrying less than two low-risk genotypes (OR=0.74, 95%CI=0.58-0.95, P=0.017), especially in population of ≤68 years of age, male and BMI>25 kg/m^2, and non-smoking. Conclusions SNPs of mTORC1-related genes individually or jointly contribute to colorectal cancer susceptibility in Chinese. Further studies of larger cohorts are needed to validate the findings.

Microphthalmia-associated transcription (MiT) family translocation related renal cell carcinoma (RCC) is an important type of renal cell carcinoma, which was included in the new classification of renal tumors by the World Health Organization (WHO) as an independent subtype in 2016. This type of renal cell carcinoma mainly includes Xp11.2 translocation /TFE3 gene fusions associated with renal cell carcinoma and T (6; 11)(p21; q12)/TFEB gene fusion-associated renal cell carcinoma, which has similar clinical features, histology, immunohistochemistry, and molecular genetics, but is significantly different from other renal cell carcinomas. In this review, the clinicopathology and genetics of MiT family translocation associated renal cell carcinoma were reviewed in order to provide guidance and help to the clinical and pathologic work.