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Objective:To evaluate the influence of 25-hydroxyvitamin D[25(OH)D]on dyslipidemia in elderly female patients with type 2 diabetes(T2DM)mellitus aged 60 or over.Methods:We retrospectively reviewed the clinical records of 175 type 2 diabetic older women meeting the inclusion criteria, admitted to the Department of Endocrinology, Beijing Chuiyangliu Hospital, between January and December 2020, with an average age of 66(63, 70)years.According to the diagnostic criteria of dyslipidemia(cholesterol ≥6.2 mmol/L, high density lipoprotein cholesterol <1.0 mmol/L, low-density lipoprotein cholesterol ≥4.1 mmol/L or triglycerides ≥2.3 mmol/L), 110 participants(62.9%)were divided into a dyslipidemia group and 65 participants(37.1%)were assigned into a normal blood lipid group.Logistic regression was employed to investigate factors influencing dyslipidemia.Spearman correlation analysis was employed to analyze the correlation between serum 25(OH)D and blood lipid indexes.Results:The median serum 25(OH)D level of the 175 subjects was 10.92(8.1, 15.2)μg/L.For the dyslipidemia group, it was 9.1(5.8, 12.9)μg/L, lower than 11.9(8.4, 22.6)μg/L in the normal blood lipid group.The proportion of people with hypertension in the dyslipidemia group was higher than in the normal blood lipid group.The dyslipidemia group also had higher BMI, waist circumference and homocysteine levels( P<0.05). Results of multivariate logistic regression analysis demonstrated that hypertension, waist circumference, and homocysteine were significant risk factors for dyslipidemia in elderly women with T2DM, whereas serum 25(OH)D was a protective factor( P<0.05). Correlation analysis results identified that cholesterol and low density lipoprotein cholesterol were inversely correlated to 25(OH)D while high density lipoprotein cholesterol was positively correlated to it( P<0.05). Conclusions:There is a serious deficiency of serum 25(OH)D in older women with T2DM.25(OH)D is protective factor in elderly T2DM women against dyslipidemia.Clinicians should pay attention to vitamin D deficiency in patients during diagnosis and treatment and correct the deficiency.
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Objective:To establish a new nurse standardized training management index system based on training transfer theory, and to provide reference for objective evaluation of standardized training management for new nurses.Methods:From August 2020 to April 2021, guided by the theory of training transfer, the standardized training management indexs for new nurses were preliminarily drawn up through literature review, semi-structured interviews. The Delphi method was used to conduct two rounds of expert consultation.Results:The effective questionnaire recovery rate of the two rounds of expert consultation was 92.00% (23/25) and 95.65% (22/23), respectively. The expert authority coefficients were 0.904 and 0.905, respectively. Kendall′s harmony coefficients were 0.228 and 0.250, respectively, both P<0.01. The final index system of standardized training management for new nurses based on training transfer theory included 4 first-level indexes, 14 second-level indexes and 59 third-level indexes. Conclusions:The new nurse standardized training management index system based on training transfer theory is scientific and reliable. It provides a tool for evaluating standardized training management of new nurses and a reference for perfecting the training management system of new nurses.
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Objective:To investigate the effect of B7-H3 gene on the biological function of fibr-oblastlike synoviocytes (FLS) in osteoarthritis (OA).Methods:Synovial tissue of five cases of OA and synovial tissue of 4 normal knee were obtained, and the primary cell lines were isolated and cultured. The expression of B7-H3 in OA synovial tissue and primary OA-FLS were studied by immunohi-stochemistry, real time-poly merase chain reaction (PCR) and FACS. According to sites 996 and 1041 of B7-H3, corresponding siRNA was designed and the expression of B7-H3 in FLS was silenced and down-regulated. The inhibition of B7-H3 and its protein in target cells was determined by Western blot and FACS. The migration and invasion ability of B7-H3 in target cells were analyzed by scratch assay and Transwell assay. CCK8 assay was used to detect cell proliferation ability, and CBA assay was used to detect cytokines and chemokines in cell culture supernatant. GraphPad Prism 8.0 software was used to analyze the experimental data. The normal distribution data was expressed as mean±standard deviation ( Mean± SD). The comparison between data was performed by T test, and P<0.05 was considered statistically significant. Results:The abnormally high expression of B7-H3 in fibro-blast-like synoviocytes of OA was detected. Compared with siNC, si996 and si1041 inhibited the expression of B7-H3 in OA-FLS. In the Transwell migration experiment, the mean cells number of random view in the siNC group, the si996 group, and the si1041 group indicating decreased migration ability of OA-FLS [siNC vs si996 (100.3±3.7) /view vs (48.7±1.2) /view, t=13.24, P<0.001; siNC vs si1041 (100.3±3.7) /view vs (59.7±1.9) /view, t=9.80, P<0.001). In the Transwell invasion experiment, the mean cells number of random view in the siNC group, in the si996 group, and in the si1041 group indicating decreased invasion ability of OA-FLS [siNC vs si996 (127.3±5.6) /view vs (39.7±3.3) /view, t=13.49, P<0.001; siNC vs si1041 (127.3±5.6) /view vs (57.3±1.9) /view, t=11.85, P<0.001]. The secretion of IL-6 [siNC vs si996 (248±21) pg/ml vs (111±12) pg/ml, t=24.08, P=0.002; siNC vs si1041 (248±21) pg/ml vs (46±5) pg/ml, t=13.21, P=0.006], IL-8 [siNC vs si996 (118.1±15.6) pg/ml vs (47.1±5.4) pg/ml, t=6.68, P=0.022; siNC vs si1041 (118.1±15.6) pg/ml vs (10.0±1.3) pg/ml, t=13.08, P=0.006], CXCL8 [siNC vs si996 (178.8±6.4) ng/ml vs (83.2±2.7) ng/ml, t=13.77, P=0.005; siNC vs si1041 (178.8±6.4) ng/ml vs (93.5±2.8) ng/ml, t=12.23, P=0.007] and CCL2 [siNC vs si996 [(184.1±5.1) ng/ml vs (109.4±5.9) ng/ml, t=9.57, P=0.011; siNC vs si1041 (184.1±5.1) ng/ml vs (97.1±1.5) ng/ml, t=16.39, P=0.004] was decreased . Conclusion:B7-H3 may regulate the migration, invasion, cytokine secretion and other biological functions of OA-FLS, providing clues for further study of B7-H3's involvement in the pathogenesis of OA.
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Objective:To investigate the effect of empagliflozin on diabetic kidney disease in db/db mice and the potential mechanisms.Methods:db/db mice were randomly divided into db/db group and Empa group. C57BL/6J mice were used as normal control group. We measured the level of serum biochemistry and inflammatory cytokines. Pathological changes of kidney were observed by pathological staining. The protein expression levels of NLRP3, cleaved caspase-1 and GSDMD were detected.Results:Compared with db/db group, the level of fasting blood glucose, blood lipids, serum biochemistry, and urinary protein-to-creatinine ratio in Empa group were significantly decreased ( P<0.05). HE staining and Masson staining showed that empagliflozin could significantly improve glomerular pyknosis and renal interstitial fibrosis in db/db mice. Meanwhile, the expressions of NLRP3, cleaved caspase-1, and GSDMD protein were down-regulated ( P<0.05). Conclusion:Empagliflozin improves kidney damage in diabetic model mice, and the possible mechanism is to inhibit the cell pyroptosis signal pathway of NLRP3/caspase-1/GSDMD.
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Objective:To evaluate the short-term prognostic value of model for end-stage liver disease (MELD) combined with high density lipoprotein-cholesterol (HDL-C) in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF).Methods:From December 2015 to December 2018, 182 patients with HBV-ACLF who were treated in Henan Provincial People′s Hospital were included. Prognosis and clinical data including HDL-C, total bilirubin, international standardized ratio (INR), creatinine of patients within 24 hours after admission were collected and analyzed retrospectively.The values of MELD were calculated. The binary logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients.The receiver operator characteristic curve (ROC) and MedCalc 15.2 software were used to assess the predictive value of MELD, HDL-C and MELD-HDL-C model for prognosis. Kaplan-Meier survival curve was performed to analyze the prognosis of patients in different groups.Results:Sixty patients were divided into the death group and 122 patients were divided into the survival group according to the prognosis during hospitalization and 90 days after discharge. The MELD score of patients in the survival group was 21(19, 24), which was significantly lower than that in the death group (29(25, 34)), and the HDL-C value of patients in the survival group was significantly higher than that in the death group (0.3 (0.1, 0.6) mmol/L vs 0.2(0.1, 0.5) mmol/L). The differences were both statistically significant ( Z=-6.290 and -4.087, respectively, both P<0.01). Multivariate logistic regression analysis showed that MELD score and HDL-C value were the independent risk factors for 90-day mortality in patients with HBV-ACLF(odds ratio ( OR)=1.432, 95% confidence interval ( CI)1.271-1.613; OR=0.584, 95% CI 0.487-0.700, respectively; both P<0.01). Areas under the ROC of MELD, HDL-C and MELD-HDL-C scoring models were 0.775, 0.782 and 0.878, respectively. MELD-HDL-C scoring model was superior to both MELD and HDL-C , and the differences were both statistically significant ( Z=3.944 and 3.104, respectively, both P<0.01). When the MELD-HDL-C Youden′s index was set at 0.72, the optimal threshold was 24.69. Patients with MELD-HDL-C score≥24.69 had lower survival rate than patients with MELD-HDL-C score<24.69, and the difference was statistically significant ( χ2=142.900, P<0.01). Conclusion:MELD, HDL-C and MELD-HDL-C scoring systems could predict the short-term prognosis in patients with HBV-ACLF, and the predictive value of MELD-HDL-C has the superiority.
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One thousand and forty-six patients with type 2 diabetes mellitus (T2DM) aged >18 years from 11 community health service centers in Beijing Chaoyang district were enrolled in the study. The body weight, height, fasting plasma glucose level and glycosylated hemoglobin A1c (HbAlc) were measured. A door-to-door questionnaire survey on the use of oral antidiabetic drugs and insulin was conducted between January to December 2017. Of 1 046 T2DM patients, 182 (17.4%) received lifestyle intervention, 257 (24.6%) used single oral antidiabetic drug (OAD), 326 (31.2%) with combined OAD, and 281(26.9%) with insulin and OAD. The average HbA1c in T2DM patients with lifestyle intervention, single OAD drug, combined OAD, and insulin and OAD were (8.1±2.3)%, (7.6±2.0)%, (7.8±2.0)%, and (8.7±2.1)%, respectively (F=18.35, P<0.01). Proportions of the T2DM patients with HbAlc lower than 7.0% were 45.1%, 55.6%, 43.6% and 36.8% in groups, respectively (χ2=55.55, P<0.01). Patients with single or combined OAD aged 18-<45 years had a worse HbA1c control than those aged 45-<65 years and≥65 years. It was found that 59.4%, 52.6%and 30.8%of the patients receiving one OAD, two OADs and three or more OADs achieved glucose control target. The proportion of drug use was 62.6% for α-glucosidase inhibitors, 50.8% for metfomain, 32.5% for insulin, 18.2% for sulfonylureas, 4.9% for glinides, 3.2% for thiazolidinediones and 3.1% for dipeptidyl peptidase-Ⅳs. Among the combined treatment regimens, metfomain+a-glucosidase inhibitors was the most frequently used as compared with α-glucosidase inhibitors+sulfonylureas and metfomain+sulfonylureas. The survey showed that the target-reaching rate of HbA1c was 44.9%, and α-glucosidase inhibitors were frequently used for patients with T2DM in community health service centers in Beijing Chaoyang district south medical alliance.
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From January 2016 to June 2017, 1 002 outpatients with T2DM were recruited in Chuiyangliu Hospital (core hospital) and eleven community health service centers in Chaoyang district in Beijing. A questionnaire survey was conducted, the survey items included demographic information, complications of T2DM, comorbidities and status of treatments. Among 1 002 patients, there were 525 cases from the Southern Medical Consortium core hospital and 477 from the Southern Medical Consortium community health centers. The control rates of glycosylated hemoglobin, fasting blood glucose, 2 h postprandial glucose were 54.1%, 49.5% and 54.6%, respectively. The blood glucose control rates in lifestyle intervention, single OAD and multiple OAD groups of core hospital were all higher than those in corresponding groups of community health centers (P<0.05). There were 115 patients managed with lifestyle interventions only and 887 patients with medications, in whom 533 were treated with oral antidiabetic drugs (OAD) and 354 cases were treated with insulin+OAD. The use rates of metformin in the core hospital and in community health service centers were 58.3% and 35.4%, the use rates of insulin were 48.4% and 24.2%, respectively. The blood sugar control of patients in community health centers is less satisfactory than that in core hospital of Chaoyang District South Medical Consortium in Beijing. The communication and cooperation between core hospitals and community health service centers should be further strengthened for better management of T2DM patients.
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From January 2016 to June 2017, 1002 outpatients with T2DM were recruited in Chuiyangliu Hospital (core hospital) and eleven community health service centers in Chaoyang district in Beijing. A questionnaire survey was conducted, the survey items included demographic information, complications of T2DM, comorbidities and status of treatments. Among 1002 patients,there were 525 cases from the Southern Medical Consortium core hospital and 477 from the Southern Medical Consortium community health centers. The control rates of glycosylated hemoglobin, fasting blood glucose, 2 h postprandial glucose were 54.1％, 49.5％ and 54.6％, respectively. The blood glucose control rates in lifestyle intervention, single OAD and multiple OAD groups of core hospital were all higher than those in corresponding groups of community health centers (P<0.05). There were 115 patients managed with lifestyle interventions only and 887 patients with medications, in whom 533 were treated with oral antidiabetic drugs (OAD) and 354 cases were treated with insulin+OAD. The use rates of metformin in the core hospital and in community health service centers were 58.3％and 35.4％, the use rates of insulin were 48.4％and 24.2％, respectively. The blood sugar control of patients in community health centers is less satisfactory than that in core hospital of Chaoyang District South Medical Consortium in Beijing. The communication and cooperation between core hospitals and community health service centers should be further strengthened for better management of T2DM patients.
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One thousand and forty-six patients with type 2 diabetes mellitus (T2DM) aged ＞18 years from 11 community health service centers in Beijing Chaoyang district were enrolled in the study.The body weight,height,fasting plasma glucose level and glycosylated hemoglobin A 1c (HbAlc) were measured.A door-to-door questionnaire survey on the use of oral antidiabetic drugs and insulin was conducted between January to December 2017.Of 1 046 T2DM patients,182 (17.4％) received lifestyle intervention,257 (24.6％) used single oral antidiabetic drug (OAD),326 (31.2％) with combined OAD,and 281(26.9％) with insulin and OAD.The average HbA1c in T2DM patients with lifestyle intervention,single OAD drug,combined OAD,and insulin and OAD were (8.1±2.3) ％,(7.6±2.0) ％,(7.8±2.0) ％,and (8.7±2.1) ％,respectively (F=18.35,P＜0.01).Proportions of the T2DM patients with HbAlc lower than 7.0％ were 45.1％,55.6％,43.6％ and 36.8％ in groups,respectively (x2=55.55,P＜0.01).Patients with single or combined OAD aged 18-＜45 years had a worse HbA1c control than those aged 45-＜65 years and≥65 years.It was found that 59.4％,52.6％and 30.8％of the patients receiving one OAD,two OADs and three or more OADs achieved glucose control target.The proportion of drug use was 62.6％ for α-glucosidase inhibitors,50.8％ for metfomain,32.5％ for insulin,18.2％ for sulfonylureas,4.9％ for glinides,3.2％ for thiazolidinediones and 3.1％ for dipeptidyl peptidase-Ⅳs.Among the combined treatment regimens,meffomain+a-glucosidase inhibitors was the most frequently used as compared with α-glucosidase inhibitors + sulfonylureas and metfomain + sulfonylureas.The survey showed that the target-reaching rate of HbA1c was 44.9％,and α-glucosidase inhibitors were frequently used for patients with T2DM in community health service centers in Beijing Chaoyang district south medical alliance.
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Objective@#To recognize the efficacy and safety of paritaprevir/ritonavir-ombitasvir combined with dasabuvir (OBV/PTV/RTV+DSV) in the treatment of genotype 1b chronic hepatitis C.@*Methods@#Patients with genotype 1b chronic hepatitis C who were admitted to the People's Hospital of Henan Province, Huashan Hospital of Shanghai and the Fifth Medical Center of the General Hospital of the People's Liberation Army of China between November 2017 to August 2018 were enlisted. All patients received OBV/PTV/RTV+DSV antiviral therapy. HCV RNA levels were measured at baseline, weeks 1, 2, 3, 4, 8, 12, and 24, then 12 weeks, and 24 weeks after completion of treatment; patients’ comorbidity, concomitant medications, and clinical adverse events were recorded.@*Results@#108 patients were enrolled in the study, with an average age of 49.1 years, 44 patients were male (40.8%), 96.3% (104/108) were newly diagnosed, and four patients had previous treatment history, of whom three were treated with IFN and one with IFN + DAA. Ninety-eight cases completed 12 weeks treatment and 89 cases were in follow up for 12 weeks, after discontinuation of the drug. Overall, 89 cases (100%) achieved SVR12.One patient treated with PR and DAA had HCV RNA level of 869175 IU/mL at 4 weeks of treatment, which was significantly higher than the baseline HCV RNA level (301776IU/ML), and was judged as failure of treatment; and follow-up was discontinued. Of all enrolled patients, 19 (17.6%) had underlying diseases and 15 (13.9%) had combined medications. During treatment, adverse events (AE) occurred in 11 patients (10.1%). The main adverse events were pruritus and elevated bilirubin.@*Conclusion@#Combined antiviral therapy (OBV/PTV/RTV+DSV) of 12 weeks are highly effective with good safety profile in the treatment of Chinese patients with genotype 1b chronic hepatitis C.
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Objective To evaluate glucose metabolism in elderly inpatients with primary hypertension. Methods Based on the results of the oral glucose tolerance test (OGTT) ,130 elderly patients with primary hypertension were divided into the normal glucose tolerance (NGT )group ,the impaired fast glucose(IFG)group ,the impaired glucose tolerance(IGT)group and the type 2 diabetes mellitus (T2DM )group.Clinical characteristics and morbidity were compared among the groups. Results Among patients with grade 1 ,2 or 3 hypertension ,14(32.6％ ) ,9(20.5％ )and 7(16.3％ )had NGT ,3(7.0％ ) ,5(11.4％ )and 4(9.3％ )had IFG ,16(37.2％ ) ,18(40.8％ )and 19(44.2％ )had IGT , and 10 (23.2％ ) ,12 (27.3％ ) and 13 (30.2％ ) had T2DM ,respectively.Moreover ,there was a significant difference in levels of 2 hours postprandial blood glucose between patients with grade 1 hypertension and those with grade 3 hypertension in the T2DM group(P< 0.05). Conclusions Abnormal glucose metabolism and diabetes mellitus are highly prevalent in elderly inpatients with essential hypertension.
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Objective To investigate the expression of T cell immunoglobulin and mucindomain-containing molecule-3 (TIM3) on PBMCs,and the plasma concentrations of soluble forms of Galetcin9 and their clinical relationship with rheumatoid arthritis (RA).Methods Peripheral blood samples were collected from 39 patients,25 osteoarthritis (OA) patients and 20 healthy subjects (HC).The expressions of TIM3 on peripheral blood mononuelear cells (PBMCs) were detected by flow cytometry.The concentrations of soluble Galetcin9 were assessed by enzyme linked immunosorbent assay (ELISA).And the relationship between their expression levels and clinical manifestations were analyzed.Levene F test was used for statistical analysis,normal distribution data were compared by t test and Pearson correlation analysis,while Mann-Whitney U test and Spearman correlation analysis were used for non-normal distribution data.Results The expression of TIM3 on CD4+ T cells was significantly higher than that of the HC [(14.7±3.2)％ vs (5.1±0.8)％,t=2.339,P=0.022 7],while there was no statistical difference between the RA group and the OA group [(14.7±3.2)％ vs (5.8±0.4)％,t=1.928,P=0.058 9].The expression of TIM3 was significantly correlated with the concentration of RF in the serum and the corresponding DAS28 score (r=0.325 8,P=0.043 0;r=0.407 5,P=0.010 0).The expression of TIM3 on CD8 + T cells in RA patients was significantly higher than that in the HC and OA [(21.1±3.4)％ vs (8.3±1.5)％,t=2.531,P=0.0142;(21.1±3.4)％ vs (10.7±1.0)％,t=2.314,P=0.024 0] which was significantly correlated with the concentration of RF in serum and the corresponding DAS28 score (r=0.451 5,P=0.003 9;r=0.524 1,P=0.000 6) as well.However,the expression of TIM3 on CD56+ NK cells was not significantly different from that of either OA or HC[(56.4±3.4)％ vs (50.6±3.8)％,t=1.047,P=0.299 8;(56.4± 3.4)％ vs (56.1±3.4)％,t=0.048,P=0.961 9],the concentration of serum RF and the corresponding DAS28 score were not significantly related.We also found that plasma Galectin 9 concentrations in RA patients were significantly higher than those of OA patients [(4.24±0.22) ng/ml vs (3.15±0.18) ng/ml,t=3.187,P=0.024] and healthy subjects [(4.24±0.22) ng/ml vs (2.55±0.14) ng/ml,t=5.567,P＜0.01],which was correlated with RF and DAS28 (r=0.479 2,P=0.002 0;r=0.353 0,P=0.027 5) while there was no correlation with CRP (r=0.176 3,P=0.283 1).Conclusion The upregulated expressions of TIM3 on peripheral lymphocytes and the high levels of plasma concentration of soluble Galectin 9 are closely correlated with the severity of the disease,suggesting that TIM3/Galectin 9 pathway may play a critical role in the pathogenesis of RA.
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Objective To explore the efficacy and safety of daclatasvir (DCV ) combined with asunprevir (ASV) for chronic genotype 1b (GT1b) hepatitis C .Methods Twenty-nine GT1b hepatitis C patients who were treated with DCV combined ASV in Henan Provincial People′s Hospital from September 2017 to November 2017 were included .Hepatitis C virus (HCV ) RNA levels were tested before treatment ,1 week ,2 weeks ,3 weeks ,4 weeks ,8 weeks ,12 weeks and 24 weeks after treatment , and 12 weeks after the end of the treatment .The comorbidities ,combined use of drugs and adverse clinical events were registered .T test was used to compare the measurement data with normal distribution and M (P25,P75) was used for measurement data with non-normal distribution .Results A total of 29 patients with GT1b were included ,with 4 cirrhosis cases and 25 non cirrhotic cases .Seven patients had history of previous interferon and ribavirin combination treatment .There were 9 patients with comorbidity and 7 patients with combined medication . Finally , 25 patients completed a 24-week course of antiviral treatment ;3 patients were lost to follow-up ,and 1 patient withdrew after 16weeks of antiviral treatment because of a virus rebound .Of the 26 followed up patients ,25 achieved sustained virological response at 12-week (SVR12 ) , and one patient failed .And the HCV RNA NS5A resistance-associated variants (RAV) were detected in the patients with treatment failure .No severe adverse clinical events occurred in 26 patients .Conclusions DCV combined with ASV is effective and safe in the treatment of GT 1b chronic hepatitis C .However , the effect of RAV on therapeutic efficacy should be concerned during the treatment .
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Objective:To analyze the clinicopathological features, diagnosis, and treatment of anorectal malignant melanoma (ARMM), and to explore its prognostic factors and misdiagnosis. Methods:A total of 36 patients with ARMM were enrolled in this study from January 2000 to November 2016 in Nanfang Hospital, Zhujiang Hospital, and Guangdong Provincial Hospital of Traditional Chinese Medicine. Results: The clinical manifestations of ARMM were not specific. The odds of misdiagnosis were as high as 52.8% in this study. The 1-and 3-year survival rates were 75%and 35%, respectively, with median survival time of 24.51 months. Survival rate was correlated with tumor size, invasion depth, clinical stage, and lymph node metastasis (P<0.05), but was not related to patient age and gender. The median survival time of the three groups of patients (surgery alone, surgery-based combination therapy, untreated) were 39.21, 26, and 15 months. The difference was not statistically significant. No difference in survival was found between patients under-going abdominoperineal resection and wide local excision. Conclusion:ARMM has poor prognosis and is easily misdiagnosed as a ma-lignant tumor. The prognostic factors are tumor size, invasion depth, clinical stage, and lymph node metastasis. Surgical treatment can extend survival. To avoid misdiagnosis and prolong survival, early diagnosis and early treatment are recommended.
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Objective To explore the molecular mechanisms of hepatic stimulator substance (HSS) gene knockout in promoting the development and progression of nonalcoholic steatohepatitis (NASH).Methods NASH model mice (n=20) with HSS wild-type (HSS+/+) or HSS gene knockout (HSS-/-) were constructed using modified choline-deficient diet (CD-diet),untreated C57BL6-HSS-/-and C57BL6-HSS+/+ mice (n=20) were considered as control.Ten mice of each group were killed at month 1 and 2,respectively.The levels of triglyceride (TG) and total cholesterol (TC) in liver were measured using ELISA method.Histopathology and collagen deposition in liver tissue were observed using HE staining and Masson staining,respectively.Lipid content in liver tissue was observed and calculated using oil red O staining.The levels of mRNA and proteins of peroxisome proliferators activated receptor gama coactivator 1 alpha (PGC-1α),mitochondrial transcription factor A (TFAM),transcription factor-E2 related factor α (Nrf2),[-loop,dynamin-related protein 1 (Drp1),mitochondrial fission 1 protein (Fis1),mitofusins 1 (Mfn1),autophagy related gene 3 (Atg3) in liver tissue were detected using Real-time PCR and Western blot,respectively.Content of malonaldehyde (MDA),cyclooxygenase Ⅳ (COX Ⅳ) and adenosine tirphosphate (ATP) were measured using kits,and the activity of respiratory chain complex Ⅴ and cytochrome C oxidase in liver tissue were measured using spectrophotometry.the comparison between groups was done by t test.Results The levels of HSS mRNA and protein in mice-HSS-/-were 0.154± 0.04 and 0.08± 0.01,respectively,which were both significantly lower than those in mice-HSS+/+ (0.952 ± 0.08 and 1.362±-0.130,respectively),and t he differences had statistical significance (t =10.244 and 10.375,respectively,both P＜0.05).One month and 2 months after NASH modeled,TC contents in mice-HSS-/ were (248.6±21.5) μmol/g and (217.4±18.0) μmol/g,respectively,which were both remarkably higher than those in mice-HSS+/+ [(153.5 ± 11.2) μmol/g and (140.8 ±7.5) μmol/g,respectively],and the differences had statistical significance (t=15.270 and 10.524,respectively,both P＜0.05).The results form HE staining,oil red O staining and Masson staining indicated that fat deposition,collage deposition and inflammation in liver tissues of mice-HSS-/-were severer than those in mice-HSS+/+.One month after NASH modeled,protein levels of Drp1,Fis1,Mfn1 and Atg3 in liver tissues of mice-HSS-/ were all significantly decreased compared with those in mice-HSS+/+,and the differences had statistical significance (t=10.705,24.072,9.892 and 17.540,respectively,all P＜ 0.05).Two months after NASH modeled,protein levels of Drp1,Fis1,Mfn1and Atg3 in liver tissues of mice-HSS-/ were all significantly decreased compared with those in mice-HSS+/+,and the differences had statistical significance (t=125.378,15.926,34.330 and 13.437,respectively,all P＜0.05).One month after NASH modeled,mRNA levels of Drp1,Fis1,Mfn1 and Atg3 in liver tissues of mice-HSS-/-were all significantly decreased compared with those in mice-HSS+/+,the differences had statistical significance (t=36.337,40.825,33.508 and 28.104,respectively,all P＜0.05).Two months after NASH modeled,mRNA levels of Drp1,Fis1,Mfn1 and Atg3 in liver tissues of mice-HSS-/-were all significantly decreased compared with those in mice-HSS+/+,and the differences had statistical significance (t=35.210,42.375,27.753 and 20.560,respectively,all P＜0.05).The protein levels of PGC-1α,TFAM,Nrf2 and D-loop in liver of C57BL6-HSS-/-group were lower than those in liver of C57BL6-HSS+/+ group,and the differences had statistical significance (one month:t=20.548,31.036,19.445 and 10.974,respectively;two months:t=9.887,13.330,22.375 and 18.903,respectively,all P＜0.05).The mRNA levels of PGC-1α,TFAM,Nrf2 and D-loop in liver of C57BL6-HSS-/-group were all lower than those in C57BL6-HSS+/+ group,and the differences had statistical significance (one month:t=9.087,12.582,21.451 and 7.774,respectively;two months:t=23.758,17.924,9.924 and 15.209,respectively,all P＜0.05).One month and 2 months after NASH modeled,the levels of ATP mRNA in liver of C57BL6-HSS / group were both significantly lower than those in C57BL6-HSS+/+,and the differences had statistical significance 0=43.775 and 28.375,respectively,both P＜0.05);the levels of COXⅣ mRNA in liver of C57BL6-HSS / group were 0.142 ± 0.06 and 0.068± 0.001,respectively,which were both significantly lower than those in C57BL6-HSS+/+ group (0.255± 0.08 and 0.172 ±0.06,respectively),and the differences had statistical significance (t=28.337 and 19.782,respectively,both P＜0.05);the levels of MDA mRNA in liver of C57BL6-HSS-/-group were 0.973 ±0.112 and 1.253±0.054,respectively,which were both significantly lower than those in C57BL6-HSS+/+ group (0.366±0.02 and 0.872±0.05,respectively),and the differences had statistical significance (t=8.357 and 6.582,respectively,both P＜0.05).Conclusion Deletion of HSS accelerates NASH progression via inhibiting mitochondrial fusion,which leads to dysfunction of mitochondrial respiratory chain and inhibition of fatty acid oxidation.
ABSTRACT
Objective:To analyze PD-L2 expression on monocytes of peripheral blood cells in systemic lupus erythematosus ( SLE) and it′s correlation with the degree of disease activity .Methods:Peripheral blood of 26 cases of SLE patiens and 38 cases of healthy controls were collected .Peripheral blood mononuclear cells ( PBMC) were isolated and realtime PCR was carried on to analyze the PD-L2 gene expression.At the same time flow cytometry was performed to analyze the CD 14 and PD-L2 expression.Results:PD-L2 was significantly up-regulated on monocytes in RA patients than in healthy controls and had correlation with the disease activity and the SLEAI score.Conclusion:These findings help to clarify the function of PD-L2,including its potential role as a biomarker for SLE .
ABSTRACT
Objective To investigate the expression of inducible co-stimulator (ICOS) and inducible co-stimulator ligand (ICOSL) on PBMCs,and the plasma concentrations of soluble forms of ICOSL and their clinical relationship with systemic lupus erythematosus (SLE) patients.Methods Peripheral blood samples were collected from 45 SLE patients and 39 healthy subjects (HC).The expressions of ICOS and ICOSL on peripheral blood mononuclear cells (PBMCs) were detected by flow cytometry.The concentrations of soluble ICOSL were assessed by measured by enzyme linked immunosorbent assay (ELISA).And the relationship between their expression levels and patients' clinical manifestations were analyzed.Levene F test was used for statistical analysis,the comparison between groups was conducted using t test,and the correlation between two variables were tested by Pearson correlation analysis.Results The expression of ICOS on CD4+ and CD8+ T cells were significantly higher than that of the HC [(19.1±1.7)％ vs (14.0±1.5)％,t=2.156,P=0.035],[(10.0± 1.0)％ vs (6.4±1.0)％,t=2.587,P=0.012].The expression of ICOSL on CD14+ mononuclear cells in SLE patients was significantly higher than that in the HC group [(2.94±0.88)％ vs (0.89 ±0.21)％,t=2.152,P=0.04].Plasma ICOSL concentrations in patients with active SLE were significantly higher than those of patients with inactive SLE [(362±25) ng/ml vs (278±15) ng/ml,t=2.356,P=0.025].We also found a significant negative correlation between the soluble ICOSL expression and the surface ICOSL expression on both mononuclear cells and B cells (r=-0.4243,P=0.022;r=-0.4099,P=0.025).MMPI induced an evident reduction in sICOSL levels released from the cells,which was statistically significant in comparison with untreated cells (P＜0.05).Conclusion The up-regulated expressions of ICOS and ICOSL on peripheral lymphocytes and the high levels of plasma concentration of soluble ICOSL are closely correlated with the severity of the disease,suggesting that ICOS/ICOSL pathway may play a critical role in the pathogenesis of SLE.
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[Abstract ] Objective C reactive protein (CRP), an in-flammatory maker, increased significantly among diabetes mellitus and other metabolic diseases.Meanwhile, adiponectin plays a vital role in anti-atherogenic, anti-inflammatory and anti-diabetic poten-tials.Further, it decreased in diabetes mellitus.To investigate the effects of C-reactive protein in the expression of high-molecular-weight adiponectin ( HMWA) and adiponectin multimerization. Methods The fully differentiated 3T3-L1 cells were respectively treated with 50μg/mL CRP for 0 h、6 h、12 h and 24 h , and different doses of CRP with 0μg/mL、5μg/mL、25μg/mL、50μg/mL for 24 h.The expres-sion of HMWA was further detected by Western blot.Additionally, the mRNA expressions of adiponectin assembly related genes ( Ero1-L、DsbA-L、ERp44 ) were detected by Real time PCR after 50μg/mL CRP treatment for 24 h. Results After 24 h treatment, 25μg/mL CRP and 50μg/mL CRP resulted in a substantial reduction ( [70 ±7]%vs [44 ±7]%, P<0.05) while 5μg/mL CRP revealed no change.With the dose of 50μg/mL CRP treated, the ex-pression of HWMA were both inhibited after the 12 h and 24 h CRP treatment ([71 ±6]%vs [48 ±11]%, P<0.05), but for the 6 h CRP treatment group, HWMA remained unchanged.Additionally, CRP inhibited Ero1-L(86 ±10)%and DsbA-L(72 ±6)%gene expression and upregulated the expression of ERp44(141 ±23)%. Conclusion CRP decreases HMWA expression in a dose and time-dependent manner and inhibits the multimerization of adiponectin, thus weaken the benefits of adiponectin in diabetes.
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Objective To explore the regulation mechanism for miR - 125a - 5P in epidermal growth factor receptor(EGFR)signaling pathway in medulloblastoma. Methods The potential targets of miR - 125a - 5P in the EGFR signaling pathway were predicted by TargetScan and Sanger software,there were 3 groups:control group,non -sense group and miR - 125a - 5P group. Their relationship,between miR - 125a - 5P and cyclin - dependent kinase in-hibitor 2B( CDKN2B),E2F transcription factor 3( E2F3),mitogen - activated protein kinase 14( MAPK14)and growth factor receptor - bound protein 10(GRB10),were tested by luciferase experiments. After miR - 125a - 5P oligo-nucleotide was transfected to D341 cells,miR - 125a - 5P level was detected by reverse transcription polymerase chain reaction. Then the thiazolyl blue tetrazolium bromide assay was used to draw the cell growth curves,and Transwell assay was used to detect cell migration ability. The expression levels of GRB10,EGFR,phosphatidylinositol 3 - kinase(PI3K) and Ras were tested by Western blot method. Results The results of luciferase experimental results showed that GRB10 was the only target gene of miR - 125a - 5P. After miR - 125a - 5P being transfected,the D341 cell prolifera-tion obviously declined markedly. Compared with control group[(38. 16 ± 7. 47)% ]and the non - sense group [(36. 79 ± 8. 94)% ],cell migration rate in the miR - 125a - 5P group was lowest[(13. 59 ± 4. 41)% ],and there was a significant difference among 3 groups(χ2 = 11. 495,P < 0. 05);in the miR - 125a - 5P group,the expression level of EGFR increased 1. 67 times,GRB10,PI3K and Ras levels were reduced to 23% ,61% and 42% . Conclusion miR - 125a - 5P can inhibit tumor growth by silenced GRB10 expression targeting EGFR downstream signaling pathways in medulloblastoma.
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Objective:To investigate the expression of inducible costimulatory ( ICOS) and inducible costimulatory ligand ( ICOSL) on peripheral blood mononuclear cells ( PBMCs ) and their clinical relationship with rheumatoid arthritis ( RA ) patients.Methods:Peripheral blood samples were collected from 85 RA patients and 50 HC in this study.Expression of ICOS and ICOSL on PBMC from the subjects were detected by flow cytometry and real-time polymerase chain reaction( RT-PCR).The alteration of ICOS and ICOSL were observed after hormone therapy in 15 patients with RA and the relationship between their expression level and patients′clinical manifestations were analysed.Results:The ICOS and ICOSL mRNA level of RA patients′PBMCs were significantly higher than that in HC.The expression level of ICOS on CD4+T cells was higher than than that in HC[(7.08±4.72)% vs (3.01+1.39)%,P<0.0001].The expression of ICOSL on monocytes[(5.77±3.45)%vs (3.64±1.43)%,P<0.05] and B cells [(5.78± 4.52)%vs (3.97±1.63)%,P<0.05] were significantly elevated in RA patients.In RA patients with active disease,however,ICOSL expression on monocytes and B cells were increased as compared with those in inactive RA patients [ ( 5.45 ±3.50 )% vs ( 4.04 ± 1.55)%,P=0.036],[(6.59 ±5.74)%vs (5.63±4.30)%,P=0.016].Furthermore,after receiving immunosuppressive therapy, the expressions of ICOS and ICOSL were notably reduced as compared with pre-therapy levels on PBMCs from patients [ ( 5.45 ±3.50)%vs (4.04±1.55)%,P=0.036],[(6.59 ±5.74)%vs (5.63±4.30)%,P=0.016].Conclusion:The high levels of ICOS and ICOSL expression were closely correlated with the degree of disease and therapeutic response,suggesting that ICOS/ICOSL pathway may play a critical role in pathogenesis of RA.