Objective To investigate the effect of fluctuant high blood glucose on the pathology profile and BCL-2,BAX expression in neurons of the hippocampus from diabetic rats.Methods The diabetic rat models were developed by injection with l% streptozotocin(STZ),followed by insulin administration.Regular insulin was used to set up fluctuant high glucose group model.After 12 experimental weeks,the expression of Fas protein in hippocampus was checked by immunohistochemistry,pathological changes and ultrastructure were observed by using light microscopy and electron microscopy in three groups.Results Compared with those in N group,the expression of BCL-2 in pyramidal cells of diabetic rat's hippocampus was lower,while that of BAX was higher(P

Objective:To explore the independent risk factors and early diagnosis of dermatomyositis (DM) with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody.Methods:A total of 223 DM patients admitted to the Department of Rheumatology and Immunology, Affiliated Hospital of Xuzhou Medical University from January 2012 to June 2021 were retrospectively analyzed, according to whether the anti-MDA5 antibody was positive or not, the patients were divided into anti-MDA5 antibody positive group ( n= 34) and anti-MDA5 antibody negative group ( n=189). The demographic data, clinical manifestations and laboratory test results of the two groups were compared. The risk factors of DM patients with positive anti-MDA5 antibody were analyzed by binary Logistic regression, and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive value of various risk factors for anti-MDA5 antibody positive DM patients. Results:The incidence of skin ulcer [20.6%(7/34) vs 9.0%(17/189), χ2=4.03, P=0.045], the positive rate of anti-Ro52 antibody [61.8%(21/34) vs 21.2%(40/189), χ2=23.90, P<0.001], the incidence of interstitial lung disease (ILD) [91.2% (31/34) vs 38.6%(73/189), χ2=31.98, P<0.001] and rapidly progressive interstitial lung disease (RP-ILD) [67.6%(23/34) vs 5.3%(10/189), χ2=88.87, P<0.001], the levels of D-dimer [1.87(1.23, 2.56) μg/ml vs 1.15(0.59, 1.29) μg/ml, χ2=4.68, P<0.001] and serum ferritin (SF) [931.65(579.12, 1 160.43) ng/ml vs 507.40(200.40, 588.55) ng/ml, χ2=5.60, P<0.001] in the anti-MDA5 antibody positive group were higher than those in the anti-MDA5 antibody negative group, wherease the creatine kinase (CK) level in the anti-MDA5 anti-body positive group was significantly lower than that in the anti-MDA5 antibody negative group [85.50(61.25, 1 55.00) U/L vs 263.00(66.50, 1 111.14) U/L, χ2=3.08, P=0.002]. Multivariate Logistic regression analysis showed that positive anti-Ro52 antibody [ OR(95% CI)=5.027(1.632, 15.483), P=0.005], increased D-dimer level [ OR(95% CI)=1.665(1.124, 2.466), P=0.011], occurrence of ILD [ OR(95% CI)=10.071(2.061, 49.207), P=0.004] and RP-ILD[ OR(95% CI)=10.91(3.294, 36.134), P<0.001] were independent risk factors for anti-MDA5 antibody positive DM patients. The ROC curve showed that the areas under the curve (95% CI) of anti-Ro52 antibody, D-dimer, ILD and RP-ILD were 0.703(0.615, 0.791), 0.752(0.661, 0.843)], 0.763(0.703, 0.822), 0.812(0.730, 0.893) respectively. The P value of all these parameters were <0.001 and their value in predicting anti-MDA5 antibody positive DM was high. Conclusion:Positive anti-Ro52-Ab, increased D-dimer level, presence of ILD and RP-ILD are independent risk factors for anti-MDA5 antibody positive DM patients, and they have certain early diagnostic value for DM patients with positive anti-MDA5 antibody.

Objective:To investigate the clinical features and prognosis of male with anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody.Methods:The clinical data of 246 patients with DM and anti-MDA5 autoantibodies hospitalized by Jiangsu Myositis Cooperation Group from 2017 to 2020 were collected and retrospectively analyzed. Chi-square test was performed to compared between counting data groups; Quantitative data were expressed by M ( Q1, Q3), and rank sum test was used for comparison between groups; Single factor survival analysis was performed by Kaplan-Meier method and Log rank test; Cox regression analysis were used for multivariate survival analysis. Results:①The male group had a higher proportion of rash at the sun exposure area [67.1%(47/70) vs 52.8%(93/176), χ2=4.18, P=0.041] and V-sign [50.0%(35/70) vs 30.7%(54/176), χ2=8.09, P=0.004] than the female group. The male group had higher levels of creatine kinase [112(18, 981)U/L vs 57 (13.6, 1 433)U/L, Z=-3.50, P<0.001] and ferritin [1 500 (166, 32 716)ng/ml vs 569 (18, 14 839)ng/ml, Z=-5.85, P<0.001] than the female group. The proportion of ILD [40.0%(28/70) vs 59.7%(105/176), χ2=7.82, P=0.020] patients and the red blood cell sedimentation rate[31.0(4.0, 101.5)mm/1 h vs 43.4(5.0, 126.5)mm/1 h, Z=-2.22, P=0.026] in the male group was lower than that of the female group, but the proportion of rapidly progressive interstitial lung disease (PR-ILD) [47.1%(33/70) vs 31.3%(55/176), χ2=5.51, P=0.019] was higher than that of the female group. ②In male patients with positive anti-MDA5 antibodies,the death group had a shorter course of disease[1.0(1.0, 3.0) month vs 2.5(0.5,84) month, Z=-3.07, P=0.002], the incidence of arthritis [16.7%(4/24) vs 42.2%(19/45), χ2=4.60, P=0.032] were low than those in survival group,while aspartate aminotransferase (AST)[64(22.1, 565)U/L vs 51(14,601)U/L, Z=-2.42, P=0.016], lactate dehydrogenase (LDH) [485(24,1 464)U/L vs 352(170, 1 213)U/L, Z=-3.38, P=0.001], C-reactive protein (CRP) [11.6(2.9, 61.7) mg/L vs 4.95(0.6, 86.4) mg/L, Z=-1.96, P=0.050], and ferritin levels [2 000(681, 7 676) vs 1 125 (166, 32 716)ng/ml, Z=-3.18, P=0.001] were higher than those in the survival group, and RP-ILD [95.8%(23/24) vs 22.2%(10/45), χ2=33.99, P<0.001] occurred at a significantly higher rate. ③Cox regression analysis indicated that the course of disease LDH level, and RP-ILD were related factors for the prognosis of male anti-MDA5 antibodies [ HR (95% CI)=0.203(0.077, 0.534), P=0.001; HR (95% CI)=1.002(1.001, 1.004), P=0.003; HR (95% CI)=95.674 (10.872, 841.904), P<0.001]. Conclusion:The clinical manifestations of male anti-MDA5 antibody-positive patients are different from those of female. The incidence of ILD is low, but the proportion of PR-ILD is high. The course of disease, serum LDH level, and RP-ILD are prognostic factors of male anti-MDA5 antibody-positive patients.

BACKGROUNDLupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Although there have been substantial improvements in LN treatment over the last decade, the outcome remains unoptimistic in a considerable percentage of patients. The aim of this study was to evaluate the efficacy and safety of mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase, as induction treatment for active LN in comparison with mycophenolate mofetil (MMF) and intravenous cyclophosphamide (CYC).

METHODSNinety patients with active LN were observed. Thirty patients were given MZR orally at the dose of 300 mg every other day. Thirty patients took MMF at 2 g per day in two divided doses. Thirty patients received CYC intravenously 0.5 g every 2 weeks. Therapeutic effects and adverse events (AEs) were evaluated at the end of 24-week treatment. One-way analysis of variance (ANOVA) followed by Dunn's test was applied to compare the difference among the groups. For comparing categorical data between two groups, χ(2) test was employed.

RESULTSEarly responses at week 12 were achieved by 73.3%, 90.0%, and 96.7% in MZR, MMF, and CYC groups, respectively. There was no significant difference in the complete remission rates (22.7%, 24.0%, and 25.0%, respectively) or overall response rates (68.2%, 72.0%, and 75.0%, respectively) among the three groups at week 24. The most prominent drop-down of Systemic Lupus Erythematosus Disease Activity Index scores was observed in MMF or CYC group, and the decline of health assessment questionnaire scores in MZR or MMF group was more prominent than that in the CYC group at week 12. Serum complement 3 (C3) or C4 levels were elevated in all groups after the treatments. CYC was more effective in inhibiting anti-double-stranded DNA antibody, while MZR was more effective in inhibiting antinuclear antibody. The incidences of AEs in patients treated with CYC were significantly higher than those in patients treated with MZR or MMF (24.2% for CYC vs. 3.3% for MZR, and 2.6% for MMF, P = 0.01).

CONCLUSIONSMZR is well tolerated and has an effect similar to MMF in the induction therapy of active LN. MZR may serve as an alternative approach for LN patients.

Administration, Intravenous ; Adolescent ; Adult ; Aged ; Cyclophosphamide ; administration & dosage ; therapeutic use ; Enzyme Inhibitors ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lupus Nephritis ; drug therapy ; Male ; Middle Aged ; Mycophenolic Acid ; administration & dosage ; therapeutic use ; Ribonucleosides ; administration & dosage ; therapeutic use ; Treatment Outcome ; Young Adult