Objective:To investigate influences of two different HLA-B antigens expressed on K562 cells on receptors expression of NK cells from peripheral blood lymphocytes.Methods:Studied the alteration of the percentage of CD16+CD56+ cells and the percentage of KIR3DL1+ cells before and after PBMC interaction with K562 cells for 24 hours,and also compared the percentage of CD16+CD56+ cells and the percentage of KIR3DL1+ cells after PBMC interaction with two different kind of K562 cells transfected with HLA-B39 and HLA-B51 respectively.Results:After PBMCs were incubated with K562 cells for 24 hours,the percentage of CD16+CD56+ cells and the percentage of KIR3DL1+ cells were both increased.However,after PBMCs were incubated with K562-HLA-B51 cells for 24 hours,the percentage of KIR3DL1+ cells and the percentage of CD16+CD56+ cells were both decreased in comparison with that interaction with K562-HLA-B39 cells.Conclusion:CD16 up-regulation was associated with an up-regulation of inhibitory receptors(KIR3DL1).The interaction between HLA-Bw4 and KIR3DL1 would down-regulate the expression of KIR3DL1.In addition,KIR3DL1 down-regulation was associated with down-regulation of activating receptors(CD16).

Objective To investigate whether MICA gene exon 2,3 and 4 polymorphism is associated with seronegative spondylarthropathies (SpA) or not in Chinese Han population.Methods All 199 B27 positive patients with SpA and 183 randomly ethnically matched healthy controls,and 12 B27 positive controls were enrolled to detect the MICA genotype from its exons 2,3 and 4 by using PCR SSOP method in Shanghai area.Results The MICA007 allele frequency was significantly more in the patient group (18 0%) than in the randomly healthy control group (6 6%) (RR=3 04, P =0 000 045).However,the MICA007 allele frequency was not significantly higher in the B27 positive patient group than in the B27 positive control group.Conclusion The MICA007 allele itself may not be the real disease susceptibility gene involved in the development of ankylosing spondylitis.The increased frequency of MICA007 allele is supposed to be due to a strong linkage disequilibrium between MICA and HLA B genes.

Objective To investigate expressions of phosphorylated c-Jun N-terminal kinase (p-JNK)and P38 mitogen-activated protein kinase(p-P38MAPK)in psoriasis vulgaris lesions. Methods Tissue specimens were obtained from lesions of 30 patients with psoriasis vulgaris and normal skin of 30 healthy human controls. An immunohistochemical study and Western-blot analysis were performed to measure protein expressions of p-JNK and p-P38MAPK in these skin specimens. Results As the immunohistochemical study showed, the expressions of p-JNK and p-P38MAPK(expressed as the average optical density [AOD]value for targeted proteins)were significantly higher in psoriasis vulgaris lesions than in normal skin tissues (p-JNK: 0.663 ± 0.016 vs. 0.333 ± 0.009, t = 44.869, P < 0.001; p-P38MAPK: 0.436 ± 0.011 vs. 0.306 ± 0.010, t = 21.913, P < 0.001). Western-blot analysis also showed increased protein expressions of p-JNK and p-P38MAPK in psoriasis vulgaris lesions compared with normal skin tissues (t = 20.477, 165.084, respectively, both P <0.05). Conclusion The activation of JNK and P38MAPK may be involved in the overproliferation of epidermal cells in psoriasis vulgaris lesions.

OBJECTIVETo detect genetic polymorphism in the exons 2 to 4 of the MICA gene in Chinese Han population in Shanghai, Dai population in Yunnan province and Uygur population in Xinjiang province respectively.

METHODSDNA samples from 183 random healthy individuals in Han population, 41 in Dai population and 66 in Uygur population were genotyped by using the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probing (SSOP) method.

RESULTSIn total, 10, 7 and 9 alleles of MICA were observed in Han, Dai and Uygur population respectively. MICA*008 was the most common allele in the population of both Han and Uygur, whereas MICA*010 was the most popular one in Dai population. Han and Dai had a bit similar distribution pattern (Chi-square=12.809 P=0.046), in contrast with Han to Uygur (Chi-square=58.499 P=0) and Dai to Uygur (Chi-square=49.273 P=0).

CONCLUSIONMICA gene displayed different allele distributions in different populations.

Alleles ; China ; Exons ; genetics ; Gene Frequency ; Genotype ; Geography ; Haplotypes ; Histocompatibility Antigens Class I ; genetics ; Humans ; Linkage Disequilibrium ; Polymorphism, Genetic

OBJECTIVETo investigate the effect of adrenomedullin (ADM) on renal arteriole remodeling and phosphorylation of extracellular signal-regulated protein kinases 1/2 (p-ERK1/2) in spontaneous hypertensive rats (SHR).

METHODSMale SHR (4 weeks old) were randomized into hypertensive group (SHR) and ADM-treated group (ADM) to receive subcutaneous saline and ADM injections (daily dose of 1.0 nmol/kg, 5 days a week), respectively, with age-matched Wistar-Kyota (WKY) rats as the blank control. The systolic blood pressure (SBP) was measured at the end of each week, and histological changes of the renal arterioles were observed using HE and Weigert staining; the expression of P-ERK1/2 in the arterioles was detected with immunohistochemistry and Western blotting.

RESULTSAt 16 and 24 weeks of age, the rats in both SHR and ADM groups showed significantly higher SBP levels than WKY rats (P<0.05), and at 24 weeks, SBP was significantly lower in ADM group than in SHR group (P<0.05). The intima thickness/lumen diameter (IT/LD) ratio of the renal arterioles increased in both SHR and ADM groups at 16 and 24 weeks as compared with that of WKY rats (P<0.05), and for arterioles with an outer diameter <40 µm, the IT/LD ratio was significantly lower at 24 weeks in ADM group than in SHR group (P<0.05). The renal expression of p-ERK1/2, which increased significantly in SHR and ADM groups at 16 and 24 weeks (P<0.05), was significantly lower in ADM group than in SHR group at 24 weeks (P<0.05).

CONCLUSIONSLong-term ADM treatment can control SPB elevation in SHR rats and reduce renal arteriole remodeling by inhibiting the phosphorylation of ERK1/2.

Adrenomedullin ; pharmacology ; Animals ; Arterioles ; drug effects ; Blood Pressure ; Hypertension ; Kidney ; blood supply ; Male ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Vascular Remodeling

Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.

Objective: To explore the clinical value of plasma heme oxygenase 1(HO-1) in the development of non-alcoholic fatty liver disease(NAFLD). Methods: Patients with NAFLD were selected from the Physical examination center and the Department of Traditional and Western Medical Hepatology of Third Hospital of Hebei Medical University. A combination of ultrasound and liver elastography was used to screen NAFLD patients and healthy persons. General clinical characteristics, peripheral blood cell count and liver biochemical test results were collected synchronously, plasma samples were retained, and plasma HO-1 level was detected by enzyme-linked immunosorbent assay. SPSS21.0 statistical software was used for statistical analysis, multivariate logistic regression analyses was used to analyse the independent risk factors affecting the incidence and progression of NAFLD. The diagnostic efficacy of indicators related to development of NAFLD was assessed by the receiver operating characteristic curve(ROC). Results: A total of 328 patients with NAFLD and 113 healthy controls were included. According to the liver biochemical results, the NAFLD group was divided into 148 patients with normal liver enzymes and 180 patients with abnormal liver enzymes. The level of HO-1 in the three groups was 9.09 ± 2.19, 14.38 ± 2.63, 17.00 ± 3.30 ng/ml, and was increased respectively of healthy controls, patients with normal liver enzymes and patients with abnormal liver enzymes. Analyzing plasma HO-1 levels of components associated with metabolic disorders suggests that components without metabolic syndrome(9.83 ± 3.21) < components with 1 metabolic syndrome(13.59 ± 3.72) < components with 2 or more metabolic syndrome(16.09 ± 3.41), P < 0.001. The results of HO-1 level stratification analysis showed that WBC, ALT, AST, GGT, TG increased as HO-1 level increased, and the pairwise difference was statistically significant (P < 0.001). The WBC count of NAFLD is significantly higher than healthy group(6.79 ± 1.62 vs 5.68 ± 1.36, P < 0.001). The univariate and multivariate regression analyses of all the subjects showed that HO-1, TG and BMI were prognostic factors for the occurrence of NAFLD and HO-1, TC, GLU were prognostic factors for the progression of NAFLD, P < 0.05. The ROC analysis showed that HO-1 was reliable markers for predicting the occurrence and progression of NALFD, the sensitivity and specificity were respectively 85.10%, 92.90% and 38.33%, 95.27%. Conclusion Plasma HO-1 can predict the occurrence and progression of NAFLD and is expected to be a novel molecular diagnostic marker for NAFLD and NASH.

Objective To explore the clinical value of plasma heme oxygenase l(HO-l)in the development of non-alcoholic fatty liver disease(NAFLD).Methods Patients with NAFLD were selected from the Physical examination center and the Department of Traditional and Western Medical Hepatology of Third Hospital of Hebei Medical University.A combination of ultrasound and liver elastography was used to screen NAFLD patients and healthy persons.General clinical characteristics,peripheral blood cell count and liver biochemical test results were collected synchronously,plasma samples were retained,and plasma HO-1 level was detected by enzyme-linked immunosorbent assay.SPSS21.0 statistical software was used for statistical analysis,multivariate logistic regression analyses was used to analyse the independent risk factors affecting the incidence and progression of NAFLD.The diagnostic efficacy of indicators related to development of NAFLD was assessed by the receiver operating characteristic curve(ROC).Results A total of 328 patients with NAFLD and 113 healthy controls were included.According to the liver biochemical results,the NAFLD group was divided into 148 patients with normal liver enzymes and 180 patients with abnormal liver enzymes.The level of HO-1 in the three groups was 9.09±2,19,14.38±2.63,17.00±3.30 ng/ml,and was increased respectively of healthy controls,patients with normal liver enzymes and patients with abnormal liver enzymes.Analyzing plasma HO-1 levels of components associated with metabolic disorders suggests that components without metabolic syndrome(9.83±3.21)

Objective To investigate the impact of sample typeon the detection of c-KIT exon 17 mutation in acute myeloid leukemia (AML) patients. Methods A retrospective study was conducted on 51 bone marrow samples collected from 37 AML patients [17 maleand 20 female, with a median age of 33 (range from 1 to 82)] at diagnosis or after treatment from June 2016 to August 2018. Of the 37 cases of AML, 24 were t(8; 21) AML, 11 were inv(16)/t(16;16) AML and 2 were non-CBF-AML. RNA and DNA were simultaneously extracted from every sample. PCR followed by Sanger sequencing were used to screen c-KIT exon 17 mutation, and the comparisons were made between paired cDNA and DNAsamples. Results (1) Of the 51 paired samples, 14 pairs were simultaneously detected positive for c-KITmutation in both of cDNA and DNA samples, but 17 pairs were detected negative in both, and the remaining 20 pairswere only detected positive for the mutation in cDNA but not in DNA, with an inconsistency rate of 39.2％. The positive rate of detecting c-KITmutation was significantly higher in cDNA than in DNA samples (66.7％vs 27.5％,P=0.000073). (2)Inconsistent mutation results between paired cDNA and DNA samples occurred in t(8;21)AML, inv(16)AML and non-CBF-AML patients with the inconsistency rate of 36.4％(12/33), 27.2％(3/11) and 71.4％ (5/7), respectively. (3)The inconsistency rate was significantly higher in samples collected after treatment compared with those collected at diagnosis (72.7％vs 13.8％, P=0.00003). (4) All 5 serially monitored patients with c-KITmutation had inconsistency in mutation detection between cDNA and DNA samples during follow up. Conclusion cDNA improves the detection of c-KIT exon 17 mutation in AML patients compared with DNA, which is especially common after treatment.