Clinical Focus ›› 2024, Vol. 39 ›› Issue (3): 227-233.doi: 10.3969/j.issn.1004-583X.2024.03.005
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Gong Sijing1, Yang Yushu2, Guo Huifang2, Ding Meng2, Wang Wei2, Gao Lixia2()
Received:
2024-01-08
Online:
2024-03-20
Published:
2024-06-12
Contact:
Gao Lixia
E-mail:27100287@hebmu.edu.cn
CLC Number:
Gong Sijing, Yang Yushu, Guo Huifang, Ding Meng, Wang Wei, Gao Lixia. Analysis of the clinical value for anti-Ro52 and anti-Ro60 antibodies in connective tissue disease[J]. Clinical Focus, 2024, 39(3): 227-233.
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URL: https://huicui.hebmu.edu.cn/EN/10.3969/j.issn.1004-583X.2024.03.005
组别 | 例数 | 年龄 (岁) | 男性 [例(%)] | 临床症状[例(%)] | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
发热 | 关节肿痛 | 肌痛/肌无力 | 皮疹 | 口干/眼干 | 光过敏 | 胸闷/气短 | 头晕/头痛 | ||||
Ro52+Ro60-组 | 94 | 53.10±15.68 | 11(11.7) | 20(27.0) | 32(43.2) | 38(51.4) | 24(32.9) | 24(32.9) | 2(2.7) | 25(34.2) | 3(4.1) |
Ro52-Ro60+组 | 80 | 45.75±17.06* | 7(8.8) | 5(19.2) | 13(50.0) | 4(15.4)* | 4(15.4) | 15(57.7) | 1(3.8) | 4(15.4)* | 0 |
Ro52+Ro60+组 | 251 | 42.39±14.77* | 18(7.2) | 21(17.8) | 47(40.2) | 36(30.5)* | 27(23.5) | 81(68.6)* | 1(0.9) | 20(17.2)* | 8(7.0) |
Ro52-Ro60-组 | 360 | 51.76±16.66#△ | 77(21.4)*#△ | 44(17.1) | 195(75.6)*#△ | 77(29.6)* | 60(23.2) | 53(20.5)#△ | 6(2.3) | 52(20.1) | 9(3.5) |
F/χ2值 | 20.496 | 27.541 | 3.856 | 55.170 | 16.677 | 4.229 | 86.479 | 1.389 | 9.210 | 3.627 | |
P值 | <0.05 | <0.05 | 0.277 | <0.01 | 0.001 | 0.238 | <0.01 | 0.708 | 0.027 | 0.305 |
Tab.1 The basic features and clinical features of patients with different anti-Ro52 and anti-Ro60 antibodies
组别 | 例数 | 年龄 (岁) | 男性 [例(%)] | 临床症状[例(%)] | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
发热 | 关节肿痛 | 肌痛/肌无力 | 皮疹 | 口干/眼干 | 光过敏 | 胸闷/气短 | 头晕/头痛 | ||||
Ro52+Ro60-组 | 94 | 53.10±15.68 | 11(11.7) | 20(27.0) | 32(43.2) | 38(51.4) | 24(32.9) | 24(32.9) | 2(2.7) | 25(34.2) | 3(4.1) |
Ro52-Ro60+组 | 80 | 45.75±17.06* | 7(8.8) | 5(19.2) | 13(50.0) | 4(15.4)* | 4(15.4) | 15(57.7) | 1(3.8) | 4(15.4)* | 0 |
Ro52+Ro60+组 | 251 | 42.39±14.77* | 18(7.2) | 21(17.8) | 47(40.2) | 36(30.5)* | 27(23.5) | 81(68.6)* | 1(0.9) | 20(17.2)* | 8(7.0) |
Ro52-Ro60-组 | 360 | 51.76±16.66#△ | 77(21.4)*#△ | 44(17.1) | 195(75.6)*#△ | 77(29.6)* | 60(23.2) | 53(20.5)#△ | 6(2.3) | 52(20.1) | 9(3.5) |
F/χ2值 | 20.496 | 27.541 | 3.856 | 55.170 | 16.677 | 4.229 | 86.479 | 1.389 | 9.210 | 3.627 | |
P值 | <0.05 | <0.05 | 0.277 | <0.01 | 0.001 | 0.238 | <0.01 | 0.708 | 0.027 | 0.305 |
组别 | 例数 | 细胞因子(ng/L) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IL-1β | IL-2 | IL-12p70 | IL-17 | IFN-α | IFN-γ | TNF-α | ||||||||||||
Ro52+Ro60-组 | 94 | 8.39(2.76, 21.14) | 2.24(1.39, 3.73) | 1.14±0.63 | 2.30(1.37, 3.76) | 3.17(1.46, 7.26) | 6.83(2.40, 9.29) | 3.68(1.88, 5.29) | ||||||||||
Ro52-Ro60+组 | 80 | 6.43(2.60, 16.00) | 1.15(0.83, 1.52)* | 0.95±0.38 | 1.66(0.86, 1.74)* | 1.94(1.26, 3.79)* | 5.46(1.00, 9.53) | 2.86(1.43, 4.07) | ||||||||||
Ro52+Ro60+组 | 251 | 8.87(3.33, 20.97) | 1.79(1.09, 2.71)# | 1.19±0.56# | 1.53(1.05, 2.64)*# | 2.85(1.64, 5.46)# | 7.02(3.21, 11.66)# | 2.81(1.52, 4.79) | ||||||||||
Ro52-Ro60-组 | 360 | 8.74(2.66, 16.44) | 1.44(0.99, 2.09)*△ | 1.13±0.57# | 1.34(0.94, 1.91)*△ | 1.76(1.24, 2.58)*△ | 5.51(1.95, 10.17)△ | 3.25(1.60, 5.62) | ||||||||||
χ2/F/H值 | 4.077 | 45.406 | 3.093 | 40.924 | 49.390 | 8.370 | 5.365 | |||||||||||
P值 | 0.253 | <0.01 | 0.027 | <0.01 | <0.01 | 0.033 | 0.147 | |||||||||||
组别 | 免疫指标(g/L) | 自身抗体[例(%)] | ||||||||||||||||
IgG | IgM | IgA | C3 | C4 | RF | 抗CCP抗体 | ANA | 抗SSB抗体 | ||||||||||
Ro52+Ro60-组 | 12.70(10.95, 15.20) | 1.15(0.89, 1.45) | 2.86(2.23, 3.60) | 0.82±0.19 | 0.17(0.12, 0.24) | 27(40.3) | 10(27.8) | 90(95.7) | 2(2.1) | |||||||||
Ro52-Ro60+组 | 13.60(10.55, 17.60) | 1.00(0.70, 1.59) | 2.93(2.19, 4.05) | 0.63±0.27* | 0.12(0.08, 0.18)* | 18(29.5) | 9(32.1) | 80(100.0) | 7(8.9) | |||||||||
Ro52+Ro60+组 | 18.40(13.63, 22.68)*# | 0.91(0.72, 1.17)* | 2.84(2.15, 3.78) | 0.65±0.3* | 0.13(0.07, 0.19)* | 127(62.7)*# | 24(25.3) | 249(99.6)* | 116(46.4)*# | |||||||||
Ro52-Ro60-组 | 12.40(10.60, 15.80)△ | 0.99(0.67, 1.38)* | 2.55(1.95, 3.33) | 0.89±0.32#△ | 0.20(0.13, 0.26)#△ | 147(51.8)#△ | 119(57.8)*△ | 276(78.4)*#△ | 0*#△ | |||||||||
χ2/F/H值 | 105.940 | 12.112 | 4.701 | 37.540 | 79.812 | 33.323 | 34.739 | 86.948 | 357.394 | |||||||||
P值 | <0.01 | 0.007 | 0.195 | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 |
Tab.2 Comparison of laboratory data of patients with different anti-Ro52 and anti-Ro60 antibodies
组别 | 例数 | 细胞因子(ng/L) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IL-1β | IL-2 | IL-12p70 | IL-17 | IFN-α | IFN-γ | TNF-α | ||||||||||||
Ro52+Ro60-组 | 94 | 8.39(2.76, 21.14) | 2.24(1.39, 3.73) | 1.14±0.63 | 2.30(1.37, 3.76) | 3.17(1.46, 7.26) | 6.83(2.40, 9.29) | 3.68(1.88, 5.29) | ||||||||||
Ro52-Ro60+组 | 80 | 6.43(2.60, 16.00) | 1.15(0.83, 1.52)* | 0.95±0.38 | 1.66(0.86, 1.74)* | 1.94(1.26, 3.79)* | 5.46(1.00, 9.53) | 2.86(1.43, 4.07) | ||||||||||
Ro52+Ro60+组 | 251 | 8.87(3.33, 20.97) | 1.79(1.09, 2.71)# | 1.19±0.56# | 1.53(1.05, 2.64)*# | 2.85(1.64, 5.46)# | 7.02(3.21, 11.66)# | 2.81(1.52, 4.79) | ||||||||||
Ro52-Ro60-组 | 360 | 8.74(2.66, 16.44) | 1.44(0.99, 2.09)*△ | 1.13±0.57# | 1.34(0.94, 1.91)*△ | 1.76(1.24, 2.58)*△ | 5.51(1.95, 10.17)△ | 3.25(1.60, 5.62) | ||||||||||
χ2/F/H值 | 4.077 | 45.406 | 3.093 | 40.924 | 49.390 | 8.370 | 5.365 | |||||||||||
P值 | 0.253 | <0.01 | 0.027 | <0.01 | <0.01 | 0.033 | 0.147 | |||||||||||
组别 | 免疫指标(g/L) | 自身抗体[例(%)] | ||||||||||||||||
IgG | IgM | IgA | C3 | C4 | RF | 抗CCP抗体 | ANA | 抗SSB抗体 | ||||||||||
Ro52+Ro60-组 | 12.70(10.95, 15.20) | 1.15(0.89, 1.45) | 2.86(2.23, 3.60) | 0.82±0.19 | 0.17(0.12, 0.24) | 27(40.3) | 10(27.8) | 90(95.7) | 2(2.1) | |||||||||
Ro52-Ro60+组 | 13.60(10.55, 17.60) | 1.00(0.70, 1.59) | 2.93(2.19, 4.05) | 0.63±0.27* | 0.12(0.08, 0.18)* | 18(29.5) | 9(32.1) | 80(100.0) | 7(8.9) | |||||||||
Ro52+Ro60+组 | 18.40(13.63, 22.68)*# | 0.91(0.72, 1.17)* | 2.84(2.15, 3.78) | 0.65±0.3* | 0.13(0.07, 0.19)* | 127(62.7)*# | 24(25.3) | 249(99.6)* | 116(46.4)*# | |||||||||
Ro52-Ro60-组 | 12.40(10.60, 15.80)△ | 0.99(0.67, 1.38)* | 2.55(1.95, 3.33) | 0.89±0.32#△ | 0.20(0.13, 0.26)#△ | 147(51.8)#△ | 119(57.8)*△ | 276(78.4)*#△ | 0*#△ | |||||||||
χ2/F/H值 | 105.940 | 12.112 | 4.701 | 37.540 | 79.812 | 33.323 | 34.739 | 86.948 | 357.394 | |||||||||
P值 | <0.01 | 0.007 | 0.195 | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 | <0.01 |
组别 | 例数 | pSS是否合并ILD | PM/DM是否合并ILD | RA是否合并ILD | SLE是否合并ILD | SSc是否合并ILD | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
是 | 否 | 是 | 否 | 是 | 否 | 是 | 否 | 是 | 否 | ||||||
Ro52+Ro60-组 | 94 | 9(9.6) | 8(8.5) | 28(29.8) | 12(12.8) | 5(5.3) | 5(5.3) | 6(6.4) | 15(16.0) | 4(4.2) | 2(2.1) | ||||
Ro52-Ro60+组 | 80 | 8(10.0) | 6(7.5) | 0 | 0 | 5(6.2) | 3(3.8) | 8(10.0) | 48(60.0) | 2(2.5) | 0 | ||||
Ro52+Ro60+组 | 251 | 28(11.2) | 58(23.1) | 9(3.5) | 3(1.2) | 3(1.2) | 12(4.8) | 12(4.8) | 123(49.0) | 1(0.4) | 2(0.8) | ||||
Ro52-Ro60-组 | 360 | 10(2.8) | 12(3.3) | 30(8.3) | 31(8.6) | 46(12.8) | 122(33.9) | 21(5.8) | 79(21.9) | 8(2.3) | 1(0.3) | ||||
χ2值 | 5.166 | 5.711 | 7.242 | 9.798 | 4.593 | ||||||||||
P值 | 0.160 | 0.058 | 0.065 | 0.020 | 0.204 |
Tab.3 Relationship between anti-Ro52 and Ro60 antibodies and ILD in different diseases
组别 | 例数 | pSS是否合并ILD | PM/DM是否合并ILD | RA是否合并ILD | SLE是否合并ILD | SSc是否合并ILD | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
是 | 否 | 是 | 否 | 是 | 否 | 是 | 否 | 是 | 否 | ||||||
Ro52+Ro60-组 | 94 | 9(9.6) | 8(8.5) | 28(29.8) | 12(12.8) | 5(5.3) | 5(5.3) | 6(6.4) | 15(16.0) | 4(4.2) | 2(2.1) | ||||
Ro52-Ro60+组 | 80 | 8(10.0) | 6(7.5) | 0 | 0 | 5(6.2) | 3(3.8) | 8(10.0) | 48(60.0) | 2(2.5) | 0 | ||||
Ro52+Ro60+组 | 251 | 28(11.2) | 58(23.1) | 9(3.5) | 3(1.2) | 3(1.2) | 12(4.8) | 12(4.8) | 123(49.0) | 1(0.4) | 2(0.8) | ||||
Ro52-Ro60-组 | 360 | 10(2.8) | 12(3.3) | 30(8.3) | 31(8.6) | 46(12.8) | 122(33.9) | 21(5.8) | 79(21.9) | 8(2.3) | 1(0.3) | ||||
χ2值 | 5.166 | 5.711 | 7.242 | 9.798 | 4.593 | ||||||||||
P值 | 0.160 | 0.058 | 0.065 | 0.020 | 0.204 |
组别 | 例数 | IgG(g/L) | IgA(g/L) | IgM(g/L) | C3(g/L) | C4(g/L) | ANA[例(%)] | |||
---|---|---|---|---|---|---|---|---|---|---|
CTD不合并ILD组 | 542 | 16.52±9.60 | 3.14±1.52 | 1.22±0.80 | 0.75±0.34 | 0.16±0.10 | 482(88.9) | |||
CTD合并ILD组 | 243 | 15.60±7.36 | 3.06±1.54 | 1.34±0.92 | 0.84±0.29 | 0.20±0.10 | 213(87.7) | |||
t/χ2值 | 1.278 | 0.605 | 1.626 | 3.501 | 3.821 | 0.338 | ||||
P值 | 0.202 | 0.545 | 0.104 | <0.01 | <0.01 | 0.561 | ||||
组别 | 抗体[例(%)] | 抗SSB抗体[例(%)] | ||||||||
Ro52+ Ro60- | Ro52- Ro60+ | Ro52+ Ro60+ | Ro52- Ro60- | 阴性 | 阳性 | |||||
CTD不合并ILD组 | 42(7.7) | 57(10.5) | 198(36.5) | 245(45.3) | 441(81.4) | 100(18.6) | ||||
CTD合并ILD组 | 52(21.4) | 23(9.5)* | 53(21.8)* | 115(47.3)*△ | 217(89.3) | 25(10.7) | ||||
t/χ2值 | 37.824 | 8.286 | ||||||||
P值 | <0.01 | 0.004 |
Tab.4 Comparison of immune indicators in CTD patients with ILD versus without ILD
组别 | 例数 | IgG(g/L) | IgA(g/L) | IgM(g/L) | C3(g/L) | C4(g/L) | ANA[例(%)] | |||
---|---|---|---|---|---|---|---|---|---|---|
CTD不合并ILD组 | 542 | 16.52±9.60 | 3.14±1.52 | 1.22±0.80 | 0.75±0.34 | 0.16±0.10 | 482(88.9) | |||
CTD合并ILD组 | 243 | 15.60±7.36 | 3.06±1.54 | 1.34±0.92 | 0.84±0.29 | 0.20±0.10 | 213(87.7) | |||
t/χ2值 | 1.278 | 0.605 | 1.626 | 3.501 | 3.821 | 0.338 | ||||
P值 | 0.202 | 0.545 | 0.104 | <0.01 | <0.01 | 0.561 | ||||
组别 | 抗体[例(%)] | 抗SSB抗体[例(%)] | ||||||||
Ro52+ Ro60- | Ro52- Ro60+ | Ro52+ Ro60+ | Ro52- Ro60- | 阴性 | 阳性 | |||||
CTD不合并ILD组 | 42(7.7) | 57(10.5) | 198(36.5) | 245(45.3) | 441(81.4) | 100(18.6) | ||||
CTD合并ILD组 | 52(21.4) | 23(9.5)* | 53(21.8)* | 115(47.3)*△ | 217(89.3) | 25(10.7) | ||||
t/χ2值 | 37.824 | 8.286 | ||||||||
P值 | <0.01 | 0.004 |
组别 | 例数 | 年龄(岁) | 性别[例(%)] | CRP (mg/L) | ESR (mm/h) | 铁蛋白 (μg/L) | IL-2 (ng/L) | IL-4 (ng/L) | IL-5 (ng/L) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
女性 | 男性 | ||||||||||||||||||
CTD不合并ILD组 | 542 | 45.11±16.53 | 478(88.2) | 64(11.8) | 25.38±42.62 | 49.90±32.49 | 273.72±291.95 | 3.01±4.20 | 1.74±1.67 | 3.95±7.19 | |||||||||
CTD合并ILD组 | 243 | 55.46±14.38 | 194(79.8) | 49(20.2) | 27.13±40.68 | 49.03±35.42 | 266.92±282.34 | 3.63±8.00 | 1.93±1.78 | 4.05±4.77 | |||||||||
t/χ2值 | 8.436 | 9.508 | 0.527 | 0.328 | 0.249 | 1.304 | 1.265 | 0.173 | |||||||||||
P值 | <0.01 | 0.002 | 0.599 | 0.743 | 0.804 | 0.193 | 0.206 | 0.863 | |||||||||||
组别 | IL-6 (ng/L) | IL-8 (ng/L) | IL-10 (ng/L) | IL-17 (ng/L) | IL-12p70 (ng/L) | IL-1β (ng/L) | IFN-α (ng/L) | IFN-γ (ng/L) | TNF-α (ng/L) | ||||||||||
CTD不合并ILD组 | 27.60±45.83 | 18.68±52.87 | 3.67±6.98 | 2.97±5.52 | 2.66±13.70 | 22.67±40.04 | 8.78±20.28 | 16.17±37.18 | 5.01±5.88 | ||||||||||
CTD合并ILD组 | 25.33±43.24 | 14.90±27.63 | 3.20±3.89 | 3.44±7.42 | 1.64±1.53 | 22.83±34.81 | 7.92±15.56 | 17.73±36.96 | 5.24±5.17 | ||||||||||
t/χ2值 | 0.581 | 0.934 | 0.881 | 0.891 | 1.025 | 0.047 | 0.519 | 0.489 | 0.457 | ||||||||||
P值 | 0.562 | 0.350 | 0.379 | 0.374 | 0.306 | 0.963 | 0.604 | 0.625 | 0.648 |
Tab.5 Comparison of basic features and inflammatory index between CTD with ILD and without ILD
组别 | 例数 | 年龄(岁) | 性别[例(%)] | CRP (mg/L) | ESR (mm/h) | 铁蛋白 (μg/L) | IL-2 (ng/L) | IL-4 (ng/L) | IL-5 (ng/L) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
女性 | 男性 | ||||||||||||||||||
CTD不合并ILD组 | 542 | 45.11±16.53 | 478(88.2) | 64(11.8) | 25.38±42.62 | 49.90±32.49 | 273.72±291.95 | 3.01±4.20 | 1.74±1.67 | 3.95±7.19 | |||||||||
CTD合并ILD组 | 243 | 55.46±14.38 | 194(79.8) | 49(20.2) | 27.13±40.68 | 49.03±35.42 | 266.92±282.34 | 3.63±8.00 | 1.93±1.78 | 4.05±4.77 | |||||||||
t/χ2值 | 8.436 | 9.508 | 0.527 | 0.328 | 0.249 | 1.304 | 1.265 | 0.173 | |||||||||||
P值 | <0.01 | 0.002 | 0.599 | 0.743 | 0.804 | 0.193 | 0.206 | 0.863 | |||||||||||
组别 | IL-6 (ng/L) | IL-8 (ng/L) | IL-10 (ng/L) | IL-17 (ng/L) | IL-12p70 (ng/L) | IL-1β (ng/L) | IFN-α (ng/L) | IFN-γ (ng/L) | TNF-α (ng/L) | ||||||||||
CTD不合并ILD组 | 27.60±45.83 | 18.68±52.87 | 3.67±6.98 | 2.97±5.52 | 2.66±13.70 | 22.67±40.04 | 8.78±20.28 | 16.17±37.18 | 5.01±5.88 | ||||||||||
CTD合并ILD组 | 25.33±43.24 | 14.90±27.63 | 3.20±3.89 | 3.44±7.42 | 1.64±1.53 | 22.83±34.81 | 7.92±15.56 | 17.73±36.96 | 5.24±5.17 | ||||||||||
t/χ2值 | 0.581 | 0.934 | 0.881 | 0.891 | 1.025 | 0.047 | 0.519 | 0.489 | 0.457 | ||||||||||
P值 | 0.562 | 0.350 | 0.379 | 0.374 | 0.306 | 0.963 | 0.604 | 0.625 | 0.648 |
因素 | 回归系数 | 标准误 | Wald χ2值 | P值 | OR值 | 95%CI | |
---|---|---|---|---|---|---|---|
下限 | 上限 | ||||||
年龄 | 0.038 | 0.006 | 45.784 | <0.01 | 1.038 | 1.027 | 1.050 |
性别(以女性为对照) | 0.449 | 0.228 | 3.868 | 0.049 | 1.567 | 1.002 | 2.453 |
抗体(以Ro52+Ro60-为对照) | 22.487 | <0.01 | |||||
Ro52-Ro60+ | -0.933 | 0.337 | 7.658 | 0.006 | 0.393 | 0.203 | 0.762 |
Ro52+Ro60+ | -1.209 | 0.271 | 19.867 | <0.01 | 0.298 | 0.175 | 0.508 |
Ro52-Ro60- | -1.061 | 0.250 | 18.003 | <0.01 | 0.346 | 0.212 | 0.565 |
常量 | -1.819 | 0.364 | 24.993 | <0.01 | 0.162 |
Tab.6 Logistic regression analyses of CTD patients with ILD
因素 | 回归系数 | 标准误 | Wald χ2值 | P值 | OR值 | 95%CI | |
---|---|---|---|---|---|---|---|
下限 | 上限 | ||||||
年龄 | 0.038 | 0.006 | 45.784 | <0.01 | 1.038 | 1.027 | 1.050 |
性别(以女性为对照) | 0.449 | 0.228 | 3.868 | 0.049 | 1.567 | 1.002 | 2.453 |
抗体(以Ro52+Ro60-为对照) | 22.487 | <0.01 | |||||
Ro52-Ro60+ | -0.933 | 0.337 | 7.658 | 0.006 | 0.393 | 0.203 | 0.762 |
Ro52+Ro60+ | -1.209 | 0.271 | 19.867 | <0.01 | 0.298 | 0.175 | 0.508 |
Ro52-Ro60- | -1.061 | 0.250 | 18.003 | <0.01 | 0.346 | 0.212 | 0.565 |
常量 | -1.819 | 0.364 | 24.993 | <0.01 | 0.162 |
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[1] | Zhang Jiahong, Zhou Shuhong, Zhou Jing, Wang Huijuan. Clinical observation of thalidomide in treatment of connective tissue disease associated interstitial lung disease [J]. Clinical Focus, 2019, 34(7): 622-625. |
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