Objective:To investigate the role of pro-inflammatory cytokine IL-17 involved in the pathogenesis of cytomegalovirus hepatitis in vivo.Methods:First of all,disseminated infection model was established.Then,mice were randomly divided into 4 groups:normal control group,MCMV-infected control group,IL-17 blockade group,and isotype control group.Mice were sacrificed on day 7 after infection.The levels of IL-17 protein were detected by Western blot.Hematoxylin eosin (HE) staining was performed to evaluate the pathologic change of the liver.Serum ALT levels were detected by a Roche DPPI biochemical analyzer.The level of serum IL-17 was measured by double antibody sandwich ELISA.The expressions of mRNA of IL-17R,IFN-γand IL-10 in liver were detected by RT-PCR.Results:Compared with MCMV-infected mice and isotype control,the blockade of IL-17 inhibited the expression of IL-17 protein in liver (P＜0.05).The degree of liver damage reduced obviously.The serum ALT was significantly lower [(146±15)vs (102±11)vs (37±12),P＜0.05].The level of serum IL-17 was relatively reduced[(719.76±6.06)vs (722.1±4.62) vs (707.53 ±8.58),P＜0.05].The expression of IFN-γmRNA [(0.56± 0.06)vs (0.55±0.13)vs (0.96±0.2),P＜0.05] and IL-10 mRNA[(0.55±0.073) vs (0.51 ±0.07) vs (0.903 ±0.18),P＜0.05] increased significantly,while that of IL-17R did not change apparently[(0.81±0.16)vs (0.89±0.38) vs (0.87±0.23),P＞0.05].Conclusion:The increased expression of pro-inflammatory cytokine IL-17 is involved in the pathogenesis of immune injury in cytomegalovirus hepatitis.The blockade of IL-17 is helpful to relieve the liver damage and improve the liver function.

Objective To evaluate the role of minimum apparent diffusion coefficient(MinADC) values in peritumoral edema based on magnetic resonance diffusion weighted imaging in the differential diagnosis between primary central nervous system lymphoma(PCNSL) and glioblastoma(GBM).Methods ADC values in peritumoral edema were measured in 16 patients with PCNSL(diffuse large B cell lymphoma) and 31 patients with GBM(WHO grade 4) confirmed by pathology.Regions of interests were manually drawn on ADC maps on peritumoral edema regions to obtain the MinADC value.Independent samples t-test and receiver operating characteristic analysis were performed for statistical analysis.Results The MinADC value [(1.20-1.45)×10 mm/s,mean(1.35±0.68)×10 mm/s] in PCNSL was significantly higher than that in GBM [(0.95-1.31)×10 mm/s,mean(1.12±0.09)×10 mm/s](t=9.977,P=0.000).The area under the receiver operating characteristic curve was 0.986,and the cutoff value of MinADC was 1.245×10 mm/s for the differentiation between PCNSL and GBM,with the best combination of sensitivity(94.1%) and specificity(94.1%).Conclusion MinADC value can be a simple and effective measure for the differential diagnosis between PCNSL and GBM.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP &ge; 140 mmHg and/or diastolic BP &ge; 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVEThis study is to examine the influence of familiarity on energy intake, eating behavior, and concentration of the plasma gut hormones in lean and overweight young male subjects.

METHODSTwenty-eight lean and twenty-eight overweight participants were recruited. Their food consumption was documented and analyzed when they had a test meal while they were paired with friends or strangers at the same weight stature. Their eating behavior was recorded with cameras hidden in the carton, and postprandial plasma gut hormone concentration were measured.

RESULTSCompared with overweight strangers (OS), overweight friends (OF) had increased food consumption, prolonged and decreased number of chews per 10 g food. Compared with OS, postprandial plasma concentration of cholecystokinin-8 was significantly lower in OF group at 30, 60, and 90 min, whereas the concentration of glucagon-like peptide 1 was significantly lower at 60 and 90 min. Plasma ghrelin concentration was significantly higher in the OF group than that in the OS group at 90 and 120 min. No significant differences in gut hormone concentration were observed between lean strangers (LS) and lean friends (LF) groups at all time points.

CONCLUSIONFamiliarity plays an important role in increasing energy intake and in changing of postprandial gut hormone concentration in overweight individuals.

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.