ABSTRACT
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.
ABSTRACT
OBJECTIVE@#To investigate the inhibitory effect of ketogenic diet (KD) on growth of neuroblastoma in mice.@*METHODS@#BALB/c-nu mouse models bearing neuroblastoma xenografts were established by subcutaneous injection of human neuroblastoma cell line (SH-SY5Y). When the tumor volume reached 250 mm3, the mice were randomized into SD group with standard diet and PBS treatment, KD group with ketogenic diet and PBS treatment, and CP+KD group with ketogenic diet and cyclophosphamide (60 mg·kg·day) treatment, =8. The tumor volume, body weight, blood glucose, ketone body (β-Hydroxybutyrate) levels, and hepatic steatosis in the mice were assessed. The expressions of caspase-3 and caspase-8 were detected by Western blotting, and Ki67 expresison was detected using immunohistochemistry (IHC). Transmission electron microscopy (TEM) was employed for the autophagosomes, and the autophagic protein Beclin1, LC3A/B and P62 were detected by IHC and Western blotting.@*RESULTS@#On day 28 post tumor cell injection, the mice in KD and CP+KD groups could prolong the overall survival rates than that in SD group ( < 0.001). On day 22 post the injection, the tumor volume in KD group was smaller than that in SD group ( < 0.05); on 16, 19, and 22 day post the injection, the tumor volume in CP+KD group was smaller than that in SD group ( < 0.01). The mice in SD group showed greater body weight on day 19 and higher blood glucose level on day 13 post the injection than those in the other two groups ( < 0.05). Blood ketone level and hepatic steatosis score were higher and glucose ketone index (GKI) was lower in KD and CP+KD groups than those in SD group (all < 0.05). The expressions of Ki67 and apoptotic proteins were detected in the tumor tissues of all groups. TEM revealed more autophagosomes in the tumor tissues of KD group than that of SD group. P62 expression was lowered ( < 0.01) and Beclin1 and LC3A/B expressions were up-regulated in the tumor tissues of KD group ( < 0.05), which is consisitent with IHC.@*CONCLUSIONS@#KD has a strong anti-tumor effect in the xenograft mouse model possibly by regulating cell autophagy.