1.Risk factors for the prognosis of rheumatoid arthritis-associated interstitial lung disease: a multicenter retrospective clinical study
Ning CHEN ; Longxin MA ; Chaoyue DIAO ; Jie GAO ; Dongbao ZHAO
Chinese Journal of Rheumatology 2023;27(3):171-177,c3-1
Objective:To explore the impact of clinical features, serological indicators, and pulmonary function test (PFT) on the prognosis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD).Methods:Clinical data of RA-ILD patients who were diagnosed by HRCT and were followed up in Changhai Hospital or Yancheng First People's Hospital from 2011 to 2021 were collected Respiratory functional impairment of the patients was evaluated according to the changes of HRCT score and PFT, and the patients were divided into progressive group and stable group. COX survival analysis and ROC curve were used to determine the factors related to the progression of RA-ILD.Results:Finally 98 RA-ILD patients were included. The mean age of ILD onset was (62.9±12.1) years old, the median course of RA was 7.0 (1.0, 15.3)years, and the median follow-up time was 36.5 months (14.0, 79.5). There were 49 cases in the progressive group, and the clinical characteristics and laboratory tests of the two groups were compared. The results showed that: progressive time [(23(8.5,43.0)months vs 63(32.5,90.9) months, Z=-4.55, P=0.001)], HRCT score [(115(109,135) vs 111(105,116), Z=-2.70, P=0.007)], forced vital capacity(FVC) predicted [(70.1±15.7)% vs (80.8±19.7)%, t=2.12, P=0.039)], diffusing capacity of the lungs for CO(DLCO) predicted [(57.5±16.3)% vs (83.4±18.8)%, t=4.87, P=0.001)], male [(44.9% vs 18.4%, χ2=7.97, P=0.005)], UIP pattern [(36(73.5%) vs 9(18.4%), χ2=29.96, P<0.001)], RF>200 U/ml[(21(65.6%) vs 18(41.9%), χ2=4.15, P=0.042)], anti-CCP>75 U/ml [(42(91.3%) vs 35(71.4%), χ2=6.10, P=0.013], all had significantly different between the two groups. In multivariate analyses, UIP[ HR(95% CI)=3.25(1.62,6.50), P<0.001], anti-CCP antibody >75 U/ ml[ HR(95% CI)=3.85 (1.20,12.33), P=0.023] and smoking [ HR (95% CI): 5.74(1.10, 30.13), P=0.039] were significantly correlated with the progression of pulmonary fibrosis in RA-ILD patients. PFT was performed in only 44 patients with RA-ILD. The univariate analyses and ROC curve suggested that DLCO predicted [ HR (95% CI)=1.04 (1.02,1.06), P<0.001] was a significant risk factor for the progression of RA-ILD, and the area under curve (AUC) of DLCO was 0.845 [95% CI=(0.729,0.961)]. Conclusion:UIP pattern, high titer of anti-CCP antibody, smoking, and reduced DLCO predicted % may be potential predictors for poor prognosis of RA-ILD patients.
2.Seneciphylline induced the autophagy of cervical cancer cells via MEK/ERK1/2 regulation
Jingfan MA ; Yan ZHANG ; Ganping YE ; Qiliang WEI ; Longxin QIU
Journal of China Pharmaceutical University 2018;49(5):616-623
The purpose of this study was to explore the effects of seneciphylline on the proliferation and autophagy of cervical cancer HeLa and Caski cells and the possible mechanisms of autophagy. MTT assay was used to evaluate the effect of seneciphylline on the proliferation of cervical cancer cells. Immunofluorescence assay was applied to investigate the formation of autophagosomes in GFP-LC3/HeLa and GFP-LC3/Caski cells. The effect of seneciphylline on the expression of autophagy-related proteins was checked by Western blotting. In addition, fluorescence colocation assay was used to detect the fusion of autophagosomes and lysosomes. Human cervical cancer subcutaneous xenografts in nude mice were used to evaluate the effect of seneciphylline on the growth of the tumor in vivo. Results showed that HeLa cells proliferation was inhibited by seneciphylline in a dose- and time- dependent manner. Seneciphylline could induce formation of autophagosomes, increase the expression of LC3-II and decrease the expression of P62, suggesting that seneciphylline induced autophagy in HeLa and Caski cells. Compared with seneciphylline alone, seneciphylline combined with later-stage autophagy inhibitor chloroquine significantly increased the expression of LC3-II and P62. Moreover, and fluorescence colocation assay showed that autophagosomes induced by seneciphylline could colocate with lysosomes, indicating that seneciphylline could induce the complete autophagy flux. Compared with seneciphylline alone, seneciphylline combined with earlier-stage autophagy inhibitor 3MA significantly increased the expression of LC3-II and significantly decreased HeLa and Caski cells viability, suggesting that seneciphylline induced protective autophagy. Compared with seneciphylline alone, seneciphylline combined with MEK inhibitor significantly decreased the expression of P-ERK1/2 and formation of autophagosomes, suggesting that autophagy induced by seneciphylline activated MEK/ERK1/2 signal pathway. In addition, seneciphylline showed a significant inhibitory effect on growth of human cervical cancer cells subcutaneous xenografts.
3.Clinical characteristics and prognosis of male dermatomyositis patients with positive anti-melanoma differentiation associated gene 5 antibody
Yitian SHI ; Fenghong YUAN ; Ting LIU ; Wenfeng TAN ; Ju LI ; Min WU ; Zhanyun DA ; Hua WEI ; Lei ZHOU ; Songlou YIN ; Jian WU ; Yan LU ; Dinglei SU ; Zhichun LIU ; Lin LIU ; Longxin MA ; Xiaoyan XU ; Yinshan ZANG ; Huijie LIU ; Tianli REN
Chinese Journal of Rheumatology 2024;28(1):44-49
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.