ISSN 1004-4140
CN 11-3017/P

不同预后重症新型冠状病毒感染者临床及胸部CT影像分析

王杏, 袁丽波, 王伟, 柳娇娇, 李宏军, 陈步东

王杏, 袁丽波, 王伟, 等. 不同预后重症新型冠状病毒感染者临床及胸部CT影像分析[J]. CT理论与应用研究, 2023, 32(3): 303-312. DOI: 10.15953/j.ctta.2023.053.
引用本文: 王杏, 袁丽波, 王伟, 等. 不同预后重症新型冠状病毒感染者临床及胸部CT影像分析[J]. CT理论与应用研究, 2023, 32(3): 303-312. DOI: 10.15953/j.ctta.2023.053.
WANG X, YUAN L B, WANG W, et al. Clinical and Imaging Analysis of Patients with Severe and Critical Coronavirus Disease 2019 with Different Prognosis[J]. CT Theory and Applications, 2023, 32(3): 303-312. DOI: 10.15953/j.ctta.2023.053. (in Chinese).
Citation: WANG X, YUAN L B, WANG W, et al. Clinical and Imaging Analysis of Patients with Severe and Critical Coronavirus Disease 2019 with Different Prognosis[J]. CT Theory and Applications, 2023, 32(3): 303-312. DOI: 10.15953/j.ctta.2023.053. (in Chinese).

不同预后重症新型冠状病毒感染者临床及胸部CT影像分析

基金项目: 北京市自然科学基金-海淀原始创新联合基金资助项目(基于机器学习2019-nCOV影像免疫空间组学特征模型及临床应用(L222097))。
详细信息
    作者简介:

    王杏: 女,硕士,首都医科大学附属北京佑安医院主治医师,主要从事传染及感染疾病影像的相应研究,E-mail:wangxingmri@163.com

    通讯作者:

    李宏军: 男,医学博士,教授、主任医师、博士研究生导师、博士后导师,首都医科大学附属北京佑安医院医学影像学中心主任,主要从事传染病放射学,E-mail:lihongjun00113@126.com

    陈步东: 男,医学博士,主任医师、硕士研究生导师,首都医科大学附属北京佑安医院放射科副主任,主要从事胸部疾病影像诊断,E-mail:budongchen@sina.com

  • 中图分类号: R  814;R  563.1

Clinical and Imaging Analysis of Patients with Severe and Critical Coronavirus Disease 2019 with Different Prognosis

  • 摘要: 目的:分析不同预后的重型及危重型新冠肺炎患者影像及临床资料,为临床决策提供帮助。方法:收集重型及危重型新冠肺炎患者的临床资料和胸部CT,临床资料包括:血常规、C反应蛋白、降钙素原(PCT)、肝肾功能、D-二聚体(D-Dimer)、心肌酶、B型氨基端利钠肽原(LNTP)、有无基础病史,比较不同预后两组新冠肺炎患者胸部CT影像及各项指标差异,对两组存在显著差异性的相关指标做二元logistic回归分析。结果:入组118例患者,死亡组68例,生存组50例,死亡组年龄大于生存组,死亡组咳痰与纳差症状的比例更高;与生存组比较,死亡组在白细胞计数(WBC)、中性粒细胞绝对值(NEUT)、单核细胞绝对值(MONO)、红细胞计数(RBC)、血红蛋白(HGB)、红细胞比积(HCT)、肾小球滤过率异常、降钙素原(PCT)、D-Dimer、肌酸激酶同工酶(CK-MB)、肌钙蛋白(TNI)、B型氨基端利钠肽原(LNTP)异常的比例更高;相对于生存组,死亡组的WBC、NEUT及百分率、中性粒细胞/淋巴细胞比值(NLR)、红细胞体积分布宽度(RDW-CV)、红细胞体积分布宽度SD(RDW-SD)、PCT、D-Dimer、肌酸激酶(CK)、CK-MB、肌红蛋白(MYO)、TNI、LNTP值明显升高,而淋巴细胞百分率(%LYMPH)、单核细胞百分率(%MONO)、平均红细胞血红蛋白浓度(MCHC)、肾小球滤过率明显减低。年龄、RBC、肾小球滤过率、CK-MB、MYO、LNTP是提示预后结果的主要因素;与生存组比较,死亡组患者新冠病毒感染肺炎的影像无明显差异,但初始胸部CT病变范围较大,多超过50%;生存组肺部CT病变较多位于肺外周及胸膜下,伴随病程死亡组病变多表现为进展或加重。结论:新冠病毒感染患者的年龄、血常规、肝肾功能、心肌功能、血凝状态、炎性反应物指标、肺部病变范围及进展情况是提示疾病严重程度及预后不良的重要因素;年龄、RBC、肾小球滤过率、CK-MB、MYO、LNTP的异常是提示重型及危重型患者致死性结果的主要危险因素;结合临床及实验室检查综合评估,胸部CT检查及随访是不能缺少的判断疾病严重程度及预后的重要评估方法。
    Abstract: Objective: This study aimed to analyze imaging and clinical data of patients with severe and critical coronavirus disease 2019 (COVID-19) with different prognoses and provide help for clinical decision-making. Method: Clinical data and chest imaging computed tomography (CT) of patients with severe and critical COVID-19 were collected. Clinical data included: blood routine indexes, C-reactive protein, procalcitonin (PCT), the indexes of liver and kidney function, D-Dimer, myocardial enzyme, B-type amino terminal natriuretic peptide (LNTP), and whether there was any underlying medical history. The chest CT images and various indexes of patients with different prognoses of COVID-19 were compared. The relevant indicators with significant differences between the two groups were analyzed using binary logistic regression. Results: A total of 118 patients were enrolled, including 68 in the death group and 50 in the survival group. The age of the death group was longer, and the proportion of sputum and poor tolerance was higher than that of the survival group. Compared with the survival group, in the death group, there was a higher abnormal proportion of leukocyte count (WBC), neutrophil absolute value, monocyte absolute value, red blood cell count (RBC), hemoglobin, erythrocyte ratio, abnormal glomerular filtration rate, PCT, D-Dimer, creatine kinase isoenzyme (CK), troponin (TNI), LNTP. Compared with the survival group, WBC, NEUT and percentage, neutrophil/lymphocyte ratio, erythrocyte volume distribution width, erythrocyte volume distribution width standard deviation, PCT, D-Dimer, CK, CK-MB, myoglobin (MYO), TNI and LNTP were significantly increased in the death group, while the lymphocyte percentage, monocyte percentage, mean RBC hemoglobin concentration (MCHC), and glomerular filtration rate were significantly lower. Compared with the survival group, there was no significant difference in the imaging signs of COVID-19 infection in the death group, but the scope of initial chest CT lesions was larger, with more than 50%. In the survival group, more CT lesions were located in the periphery of the lung and subpleura, while in the death group, more lesions showed progression or aggravation. Age, RBC, glomerular filtration rate, CK-MB, MYO, and LNTP were the main factors that suggested prognostic outcomes. Conclusion: Age, blood routine, liver and kidney function, myocardial function, hemagglutination status, inflammatory reactant index, and lung lesion extent and progression of patients infected with COVID-19 are important factors indicating the severity of the disease and poor prognosis. Abnormal increases in leukocyte and neutrophilic granulocyte, CRP, PCT, D-dimer, and myocardial markers might be the main factors that better predict fatal outcomes in severe and critical patients. Abnormalities in age, RBC, glomerular filtration rate, CK-MB, MYO, and LNTP were the main factors indicating fatal outcomes in severe and critically ill patients. Combined with the comprehensive evaluation of clinical and laboratory examinations, imaging findings and follow-up are indispensable methods to evaluate the severity and prognosis of the disease.
  • 新型冠状病毒(简称“新冠病毒”)感染由新型严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)引起,2019年发现以来迅速在世界范围内蔓延,成为全球关注的公共卫生事件。大多数新冠感染患者的临床表现是轻症的,但少数患者仍会发展为重型及危重型病危及生命[1],对重型及危重型患者的疾病控制具有高度重要性。

    本研究分析不同预后的重型及危重型患者临床及影像特点,以期为临床诊治及决策提供帮助。

    收集首都医科大学附属北京佑安医院2022年11月1日至2023年2月1日的新型冠状病毒感染重型及危重型患者118例,其中男性78例,女性40例,年龄42~94岁,平均年龄(74.63±12.83)岁,中位数为76岁,所有患者咽拭子新冠病毒核酸检测均为阳性。就诊时确诊为重型新冠病毒感染者为108例,危重型10例,诊断标准依据新型冠状病毒感染诊疗方案(试行第十版)。根据预后的不同结果,分为生存组和死亡组,生存组50例,死亡组68例。

    收集患者在院期间的临床资料,包括性别、年龄、临床症状、合并基础疾病情况、实验室检查结及胸部CT检查。所有实验室检查均为入院后首次检查结果。实验室检查指标主要为血常规、肝肾功能相关指标、C反应蛋白、降钙素原、D-Dimer、心肌酶指标、B型氨基端利钠肽原(LNTP)等。

    所有患者均行胸部CT平扫常规检查,采用GE公司Light speed 64排VCT进行扫描。管电压120 kV,采用管电流自动调制技术,NI值设置为10,范围30~500 mA,扫描层厚5 mm,层间距5 mm,探测器宽度40 mm,螺距1.375,球管旋转时间0.6 s/r。

    图像均由两位具有5年以上工作经验的影像科医师进行独立阅片分析,确定肺内病变的分布、累及范围、表现特征、肺外表现及变化情况等,如果意见不一致时,由第3位高级职称影像科医师决定。死亡组有10例患者被排除(1例患者为肺孢子菌肺炎,1例患者为转移瘤,8例初诊时为外院CT检查无法获取),生存组有14例患者被排除(1例为肺癌伴肺转移,13例初诊时为外院CT检查无法获取)。

    使用SPSS 23软件对不同预后患者的临床指标及影像学表现进行统计学分析。符合正态分布的计量资料采用双样本t检验,不符合正态分布的计量资料采用非参数检验,计数资料采用卡方检验;对两组存在显著差异性的相关指标做二元logistic回归分析。P<0.05为差异具有统计学意义。

    本研究中患者多为男性,大部分为60岁以上老人,占比约83.9%,死亡组和生存组患者在性别上无统计学差异,年龄具有统计学差异。

    患者就诊时的临床症状多表现为发热、咳嗽及咳痰,其次为喘憋乏力,基础病史多为高血压及糖尿病,与生存组相比,死亡组的咳痰与纳差症状比例更高(表1)。

    表  1  不同预后两组新型冠状病毒感染者临床特征对比
    Table  1.  Comparison of clinical features between the two groups of patients with different prognosis
    项目组别统计检验
    死亡组(n=68)生存组(n=50)$\chi^2 $P
      男性/女性(人数)46/2231/180.1710.679
      年龄/岁78.00±12.0270.04±12.58-3.416 0.001
      症状/例(%)  发热50(73.5)40(80.0)0.6670.414
      高热11(16.1)11(22.0)0.6440.422
      畏寒5(7.3)0(0.0)3.8390.050
      咽痛7(10.2)2(4.0)1.6200.203
      咳嗽26(38.2)16(32.0)0.4890.485
      咳痰24(35.2)8(16.0)5.4270.020
      咳血2(2.9)1(2.0)0.1030.748
      气促3(4.4)1(2.0)0.5120.474
      喘憋16(23.5)10(20.0)0.2090.648
      呼吸不畅9(13.2)2(4.0)2.9070.088
      乏力18(26.4)6(12.0)3.7240.054
      纳差6(8.8)0(0.0)4.6480.031
      胸痛3(4.4)0(0.0)2.2630.132
      胸闷9(13.2)3(6.0)1.6510.199
      基础疾病/例(%)  高血压43(63.2)31(62.0)0.0190.891
      糖尿病23(33.8)15(30.0)0.1930.660
      冠心病8(11.8)7(14.0)0.1300.719
      恶性肿瘤3(4.4)1(2.0)0.5120.474
      免疫抑制(移植术
      后、化疗等)
    4(5.9)2(4.0)0.2120.646
      肺心病1(1.5)0(0.0)0.7420.389
      肝病(肝炎,肝硬
      化,肝衰竭等)
    4(5.9)5(10.0)0.6930.405
      外科手术史20(29.4)19(38.0)0.0770.782
    下载: 导出CSV 
    | 显示表格

    两组患者的实验室检查多表现为血常规异常、转氨酶升高、肾小球滤过率下降、氧分压下降、血氧饱和度下降、肺动脉氧分压与吸氧浓度的比值降低、CRP升高、PCT升高、D-Dimer升高、部分心肌酶升高、LNTP升高。与生存组比较,死亡组在WBC、NEUT、MONO、RBC、HGB、HCT、肾小球滤过率、PCT、D-Dimer、CK-MB、TNI及LNTP异常的比例更高(表2)。

    表  2  不同预后两组新型冠状病毒感染者实验室指标变化情况比较
    Table  2.  Comparison of the changes of laboratory indexes in the two groups with different prognoses
    项目组别统计检验
    死亡组(n=68)生存组(n=50)$\chi^2 $P
      WBC升高/例(%)53(77.9)18(36.0)21.552<0.001
      NEUT升高/例(%)56(82.4)27(54.0)11.5590.003
      LYMPH降低/例(%)47(69.1)38(76.0)0.8400.657
      MONO升高/例(%)25(36.8)8(16.0)8.2150.016
      %NEUT升高/例(%)59(86.8)37(74.0)3.8130.149
      %LYMPH减低/例(%)62(91.2)44(88.0)1.4350.488
      %MONO正常/例(%)39(57.4)34(68.0)2.7610.251
      RBC减低/例(%)57(83.8)38(56.0)12.9500.002
      HGB减低/例(%)57(83.8)29(58.0)9.7220.002
      HCT减低/例(%)61(89.7)0(0.0)96.061<0.001
      NLR升高/例(%)63(92.6)45(90.0)0.2600.610
      RDW-SD升高/例(%)19(27.9)34(68.0)12.8680.002
      PLT正常/例(%)24(35.3)8(16.0)7.5380.053
      ALT升高/例(%)23(33.8)17(34.0)0.0000.984
      AST升高/例(%)39(59.4)25(50.0)0.6280.428
      eGFR减低/例(%)62(91.2)28(56.0)19.700<0.001
      SO2(%)≤93%/例(%)50(75.8)37(77.1)5.3920.056
      P/F index≤30 mmHg/例(%)37(56.1)36(73.5)3.6760.055
      CRP升高/例(%)66(97.1)44(88.0)3.7410.053
      PCT升高/例(%)63(92.6)27(45.0)34.667<0.001
      D-Dimer升高/例(%)56(86.2)33(68.8)4.9990.025
      CK升高/例(%)22(36.7)6(24.0)1.2820.258
      CK-MB升高/例(%)14(23.3)2(4.7)6.6630.010
      MYO升高/例(%)52(86.7)15(93.8)0.6070.436
      TNI升高/例(%)50(83.3)14(34.1)25.385<0.001
      LNTP升高/例(%)60(95.2)32(76.2)8.4280.004
    注:WBC为白细胞计数,NEUT为中性粒细胞绝对值,LYMPH为淋巴细胞绝对值,MONO为单核细胞绝对值,%NEUT为中性粒细胞百分率,%LYMPH为淋巴细胞百分率,%MONO为单核细胞百分率,RBC为红细胞计数,HGB为血红蛋白,HCT为红细胞比积,NLR为中性粒细胞/淋巴细胞比值,RDW-SD为红细胞体积分布宽度SD,PLT为血小板计数,ALT为丙氨酸氨基转移酶,AST为天门冬氨酸氨基转移酶,eGFR为肾小球滤过率,SO2为血氧饱和度,P/F index为肺动脉氧分压与吸氧浓度的比值,CRP为C反应蛋白,PCT为降钙素原,D-Dimer为D二聚体,CK为肌酸激酶,CK-MB为肌酸激酶同工酶,MYO为肌红蛋白,TNI为肌钙蛋白,LNTP为B型氨基端利钠肽原。
    下载: 导出CSV 
    | 显示表格

    两组患者的实验室结果值比较(表3):相对于生存组,死亡组的WBC、NEUT及百分率、NLR、RDW-CV、RDW-SD、PCT、D-Dimer、CK、CK-MB、MYO、TNI、LNTP明显升高,%LYMPH、%MONO、MCHC、肾小球滤过率明显减低。通过二元logistic回归分析发现年龄、RBC、肾小球滤过率、CK-MB、MYO、LNTP是提示预后结果的主要因素(表4)。

    表  3  不同预后两组新型冠状病毒感染者实验室检查比较
    Table  3.  Comparison of laboratory indexes between the two groups with different prognoses
    项目组别统计检验
    死亡组(n=68)生存组(n=50)Z/FP
      WBC/(×109L)13.86±6.1211.56±21.90-4.670<0.001
      NEUT/(×109/L)12.23±6.027.20±4.22-4.621<0.001
      LYMPH/(×109/L)0.912±0.753.84±21.36-0.2210.825
      MONO/(×109/L)0.57±0.490.45±0.31-0.9150.360
      %NEUT/%86.10±10.0079.96±15.02-2.9630.003
      %LYMPH/%9.03±9.4513.55±14.00-3.1540.002
      %MONO/%4.30±2.985.61±3.28-2.3100.021
      RBC/(×1012/L)3.08±1.123.76±0.902.0290.157
      HGB/(g/L)94.47±29.12114.56±28.000.3080.580
      HCT/%29.40±9.0434.53±7.591.3820.242
      NLR24.34±33.9111.84±11.97-3.3770.001
      MCV/FL97.59±10.0992.68±7.721.5810.211
      MCH/pg35.80±34.6330.59±3.02-0.1090.913
      MCHC/(g/L)324.90±52.82330.16±21.05-3.4650.001
      RDW-CV/%14.89±2.6013.55±3.25-4.524<0.001
      RDW-SD/FL50.96±9.7545.03±9.22-4.316<0.001
      PLT/×109/L161.88±98.87209.36±101.180.1120.738
      ALT/(U/L)184.43±626.4350.72±61.22-0.2490.803
      AST/(U/L)276.62±800.0453.06±47.39-1.8190.069
      eGFR/(mL/min/1.73 m250.67±39.5480.89±31.50-5.065<0.001
      pO2/mmHg67.18±25.3158.02±15.48-1.3810.167
      SO2/%101.02±92.4188.58±9.82-0.8780.380
      P/F index/mmHg324.65±117.98282.22±69.21-1.3860.166
      CRP/(mg/L)86.37±45.2659.40±41.201.0210.314
      PCT/(ng/mL)6.63±14.802.58±13.30-5.370<0.001
      D-Dimer/(ug/L)4281.21±5628.422713.70±6835.12-3.709<0.001
      CK/(U/L)711.10±1295.57136.56±292.62-3.986<0.001
      CK-MB/(ng/mL)4.58±8.091.93±5.60-4.263<0.001
      MYO/(ng/mL)1190.55±2064.71128.31±173.14-5.701<0.001
      TNI/(ng/mL)0.89±2.120.13±0.31-5.070<0.001
      LNTP/(pg/mL)9821.78±21583.976934.55±32028.09-4.840<0.001
    注:WBC为白细胞计数,NEUT为中性粒细胞绝对值,LYMPH为淋巴细胞绝对值,MONO为单核细胞绝对值,%NEUT为中性粒细胞百分率,%LYMPH为淋巴细胞百分率,%MONO为单核细胞百分率,RBC为红细胞计数,HGB为血红蛋白,HCT为红细胞比积,NLR为中性粒细胞/淋巴细胞比值,MCV为平均红细胞体积,MCH为平均红细胞血红蛋白含量,MCHC为平均红细胞血红蛋白浓度,RDW-CV为红细胞体积分布宽度,RDW-SD为红细胞体积分布宽度SD,PLT为血小板计数,ALT为丙氨酸氨基转移酶,AST为天门冬氨酸氨基转移酶,eGFR为肾小球滤过率,pO2为氧分压,SO2为血氧饱和度,P/F index为肺动脉氧分压与吸氧浓度的比值,CRP为C反应蛋白,PCT为降钙素原,D-Dimer为D二聚体,CK为肌酸激酶,CK-MB为肌酸激酶同工酶,MYO为肌红蛋白,TNI为肌钙蛋白,LNTP为B型氨基端利钠肽原。
    下载: 导出CSV 
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    表  4  临床实验室检查指标的logistic回归分析结果
    Table  4.  Logistic regression analysis results of clinical laboratory examination indicators
    项目B标准误瓦尔德OR值OR值95% CIP
     年龄/岁0.2760.1244.9051.3171.032~1.6810.027
     WBC/(×109/L)27.87617.0212.6821.277 E+120.004~3.935 E+260.101
     NEUT/(×109/L)-27.39416.9732.6050.0000.000~354.9650.107
     LYMPH/(×109/L)-30.46518.5442.6990.0000.000~358.0190.100
     MONO/(×109/L)-10.0928.9031.2850.0000.000~1568.4270.257
     %NEUT/%3.0761.6283.56921.681 0.891~527.4640.059
     %LYMPH/%3.5901.8763.66236.224 0.917~1431.4890.056
     %MONO/%1.0080.6262.5962.7410.804~9.3460.107
     RBC/(×1012/L)-34.05117.0493.9890.0000.000~0.5290.046
     HGB/(g/L)-1.0390.6772.3550.3540.094~1.3340.125
     HCT/%6.9673.6963.5541061.421 0.758~1485479.3240.059
     NLR-0.0060.0240.0660.9940.949~1.0410.797
     MCHC/(g/L)0.1430.1351.1261.1540.886~1.5020.289
     RDW-CV/%1.8281.8201.0086.2190.175~220.4470.315
     RDW-SD/(FL)-1.1730.7632.3630.3090.069~1.3810.124
     eGFR/(mL/min/1.73 m20.0900.0424.6661.0951.008~1.1880.031
     CRP/(mg/L)-0.0110.0190.3090.9890.953~1.0270.579
     PCT/(ng/mL)-0.3440.2122.6290.7090.468~1.0740.105
     D-Dimer/(ug/L)0.0000.0001.9571.0000.999~1.0000.162
     CK/(U/L)-0.0030.0021.9000.9970.992~1.0010.168
     CK-MB/(ng/mL)0.4330.2552.8781.5420.935~2.5430.090
     MYO/(ng/mL)0.0240.0124.4571.0251.002~1.0480.035
     TNI/(ng/mL)4.1294.0611.03462.119 0.022~177947.7980.309
     LNTP/(pg/mL)0.0000.0004.3921.0001.000~1.0000.036
    注:WBC为白细胞计数,NEUT为中性粒细胞绝对值,LYMPH为淋巴细胞绝对值,MONO为单核细胞绝对值,%NEUT为中性粒细胞百分率,%LYMPH为淋巴细胞百分率,%MONO为单核细胞百分率,RBC为红细胞计数,HGB为血红蛋白,HCT为红细胞比积,NLR为中性粒细胞/淋巴细胞比值,MCHC为平均红细胞血红蛋白浓度,RDW-CV为红细胞体积分布宽度,RDW-SD为红细胞体积分布宽度SD,eGFR为肾小球滤过率,CRP为C反应蛋白,PCT为降钙素原,D-Dimer为D二聚体,CK为肌酸激酶,CK-MB为肌酸激酶同工酶,MYO为肌红蛋白,TNI为肌钙蛋白,LNTP为B型氨基端利钠肽原。
    下载: 导出CSV 
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    两组患者发病到检查时间比较无统计学差异(表5),以排除检查时间不同导致影像学表现的偏移。患者的胸部CT表现特征为病变多分布于肺外周或胸膜下的片状或斑片状磨玻璃影(图1图2),部分伴实变(图2),小叶间隔增厚呈“铺路石征”,肺内血管穿行于磨玻璃影病灶内呈“血管增粗征”,多数患者胸膜增厚,胸部淋巴结肿大、胸腔及心包积液较为少见,上述特征两组患者中表现无明显统计学差异。

    图  1  男性,67岁,死亡患者,肺部CT显示双肺多发磨玻璃影,小叶间隔增厚呈“铺路石征”(三角形),血管穿行于病灶内呈“血管增粗征”(白色箭号)
    Figure  1.  A 67-year-old male patient (died). A lung CT showed multiple ground glass shadows in both lungs, thickened interlobular septum as a "paving stone sign" (triangle) and blood vessels passing through the lesion as a "thickened vessel sign" (white arrow)
    图  2  男性,66岁,死亡患者。行肺部CT平扫检查,显示病变多位于双肺胸膜下,初始病变范围未超过50%,但病变明显进展
    Figure  2.  A 66-year-old male patient (died). A lung CT scan was performed on day 1, 6, and 15 of admission. The lesions were mostly subpleural in both lungs, and the initial lesions did not exceed 50%, but the lesions progressed significantly
    表  5  不同预后两组新型冠状病毒肺炎影像特征对比
    Table  5.  Comparison of imaging features of the two groups with different prognosis of novel coronavirus pneumonia
    项目级别统计检验
    死亡组(n=58)生存组(n=36)$Z/\chi^2 $P
     发病到CT检查时间/d9.86±6.5012.14±6.90-1.863 0.062
     就诊时病变超过>50%/例(%)33(56.8)12(33.3)4.5800.032
     病灶多位于肺外周或胸膜下/例(%)27(46.6)26(72.2)6.3400.010
     磨玻璃影/例(%)50(86.2)33(91.7)0.9700.325
     实变影/例(%)39(67.2)24(66.7)0.1140.736
     铺路石征/例(%)24(41.4)18(50.0)0.7880.375
     血管穿行于病灶内,伴血管增粗/例(%)32(55.2)23(63.9)0.8540.355
     胸膜增厚/例(%)54(93.1)32(88.9)0.1810.670
     淋巴结肿大/例(%) 6(10.3)1(2.8)1.7900.181
     胸腔积液/例(%)24(41.4) 6(16.7)5.9660.015
     心包积液/例(%)1(1.7)1(2.8)0.1270.721
     病变复查/例n=33*n=28*24.820 <0.001
     进展/例(%)27(81.8) 6(21.4)
     好转/例(%) 5(15.2)22(78.6)
     变化不大/例(%)1(3.0)0(0.0)
     病变进展范围超过50%/例(%)11(33.3)0(0.0)3.6670.056
    注:*-死亡组及生存组排除25例和8例没有CT复查图像。
    下载: 导出CSV 
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    与生存组比较,死亡组患者就诊时病变范围较大,多超过50%(图1),生存组肺部CT病变较多位于肺外周及胸膜下,且伴随病程死亡组病变多表现为进展或加重(图2表4)。但也可以看到死亡组也存在初始病变范围未超过50%者和病变好转者(图2图3),但最终仍然发展为预后不良的结果;生存组也有初始病变范围较多和疾病有进展者(图4图5),生存组患者一般进展范围不大,有的伴部分好转(图5)。

    图  3  男性,72岁,死亡患者,入院第13天胸部CT检查(b)显示病变较入院第1天(a)有好转
    Figure  3.  A 72-year-old male patient (died). Chest CT examination on day 13 of admission (b) showed less lesion than that on day 1 (a)
    图  4  男性,68岁,生存患者,入院第10天胸部CT检查(b)显示病变较入院第1天(a)有好转
    Figure  4.  A 68-year-old patient (survived). Chest CT examination on day 10 of admission (b) showed less lesion than that on day 1 (a)
    图  5  男性,89岁,生存患者,入院第7天(b)胸部CT复查显示病变较入院第1天(a)有进展,左肺上叶部分病变有吸收
    Figure  5.  An 89-year-old patient (survived). Chest CT reexamination on day 7 of admission (b) showed progressive lesions than that on day 1 (a), with partial remission of lesions in the left upper lobe

    新冠病毒感染于2020年由世卫组织命名为“2019冠状病毒病”,病毒在人群传播过程中频繁发生基因突变,截至2022年底已存在5个变异株,在2022年初奥密克戎变异株迅速取代Delta变异株并迅速流行,本研究患者考虑均为奥密克戎变异株感染。此前有研究报告称,奥密克戎感染者最常见的症状是流涕、头痛、疲劳、打喷嚏和喉咙痛[2],本研究患者主要症状为发热、咳嗽、咳痰、喘憋乏力等,推测由于患者年龄偏大,且多有基础疾病,感染新冠病毒后,肺部受累,继而发展为重型及危重型,无显著的上呼吸道感染症状。死亡组患者年龄大于生存组,且年龄是影响不良预后的危险因素之一,与文献[3]报道一致。基础疾病被认为是进展为重症患者的危险因素,本研究均为重型及危重型患者,大部分伴有基础疾病,这与研究并不冲突,但相对于生存组,死亡组无明显差异性,可能由于基础疾病并非致死的关键性原因,且入组患者基础疾病的严重程度也不十分清楚。

    死亡组患者的血常规指标显著异常于生存组,主要表现为白细胞及中性粒细胞指标升高,其次为淋巴细胞下降。白细胞及中性粒细胞的增多说明死亡组患者存在严重的感染炎症反应,多数研究表明WBC的显著增加可能意味着临床恶化和不良结局的风险增加[4]。新冠肺炎患者肺尸检显示,肺泡腔内存在中性粒细胞[5-7],通过产生细胞因子,在过度炎症反应中起着关键作用[8],中性粒细胞的变化可能与新冠病毒感染肺炎患者的肺损伤密切相关[9]。本研究死亡组淋巴细胞百分率显著减低,与多数研究一致[10-13],提示对病毒感染的免疫反应不足。中性粒细胞的增加和/或淋巴细胞的减少意味NLR的增加,有研究表明重症患者较非重症患者的NLR值更高[14-15],且NLR的变化与疾病进展相关[16]。本研究单核细胞升高的患者比例死亡组高于生存组,但其升高的占比不多(36.8%及16%),推测其影响不良预后的意义不大。新冠病毒感染对红细胞影响机制不十分清楚[17],有研究发现在新冠病毒感染者中存在自身免疫性溶血性贫血[18]。无论何种原因,患者出现贫血均可提示不良进展。本研究死亡组红细胞及血红蛋白指标的下降,且显示红细胞计数是显示不良预后的危险因素,均提示其死亡风险的增加。

    急性期炎症反应失调可伴随细胞因子的大量释放,导致单个或多个器官功能受损。研究表明在新冠病毒感染晚期,死亡患者的纤维蛋白相关标志物(D-Dimer和FDP)水平中度或显著升高,提示存在凝血激活和继发性高纤溶症[19],弥散性血管凝血可进展为与器官功能障碍相关的败血症并导致死亡。本研究死亡组除肝脏转氨酶外,CRP、PCT、D-Dimer、肾小球滤过率、心肌损伤指标在异常比例和数值与生存组显著不同,提示这些相关标志物可能是提示疾病不良预后的重要相关因素,并进一步发现肾小球滤过率、CK-MB、MYO及LNTP指标的异常成为预测其不良后果的危险因素。AST升高在两组患者的比例并不低(59.4%、50%),但两组比较无显著差异,有研究显示死亡患者的肝损伤晚于心肌及肾脏损伤[20],推测可能因此,肝功能尽管是提示疾病进展为重症的重要指标之一,但还未来及发生严重的肝脏损伤,就已经出现了致死的心脏及肾脏功能衰竭。

    新冠病毒感染肺部组织病理学改变为弥漫性肺泡损伤和渗出性肺泡炎,表现为透明膜、微血管血栓栓塞、毛细血管充血、间质水肿、炎性细胞浸润[21]。由于肺泡腔内有浆液性/纤维性渗出液充填,可表现为肺内的磨玻璃密度影,随疾病发展,可伴有不同密度的实变影;肺泡间隔充血水肿,形成小叶间隔增厚,在磨玻璃密度影的映衬下呈典型的铺路石征(图1);病灶内可见血管穿行,由于血管内皮受损,血管轮廓模糊增粗呈“血管增粗征”(图1)。

    本研究所有患者均表现为新冠病毒感染肺炎的特征影像学表现,影像学表现高度提示死亡组病变范围更广。新冠病毒感染肺炎通常不伴有胸腔积液及胸膜增厚,无淋巴结肿大特征[21],本研究两组患者处于重症及危重症时期,胸膜增厚比例很高,胸腔积液在死亡组患者中出现比例高,少数病例可见淋巴结增大,推测可能继发或伴发其他感染。根据疾病进展情况,新冠肺炎分为早期、进展期、重症期及恢复期[22],通常疾病出现症状约1周后早期病变演变为双侧且弥漫分布,约2周后磨玻璃影混浊伴发实变,3周过后多为磨玻璃影及索条影并逐步好转,可见本研究患者均为重症肺炎,处于进展期及重症期,这也是成为预后不良的主要原因之一。

    从结果上来看,死亡组较生存组初始肺部病变范围多超过50%,伴随病程,死亡组肺部病变进展更多(图2),生存组好转较多,以上均表明初始病变超过50%且进展可提示严重的不良后果。本研究中死亡组也存在初始病变范围未超过50%者和病变好转者(图2图3),但最终仍然发展为预后不良的结果;生存组也有初始病变范围较多和疾病有进展者(图4图5),不过生存组患者一般进展范围不是很大,有的伴部分好转,因此病变进展的范围可能也是与疾病不同预后的结果相关,有待于以后扩大样本量及收集更详细的资料进一步分析。对于重型和危重型患者,肺部影像改变可能有助于风险分层和疾病进展及改善的后续评估,但不能作为提示病变致死的独立因素,需结合患者临床及相关实验室检查综合分析。

    综上所述,新冠病毒感染的年龄、血常规、肝肾功能、心肌功能、血凝状态、炎性反应物指标及肺部病变范围及进展情况是提示疾病严重程度及预后不良的重要因素。本研究显示年龄、RBC、肾小球滤过率、CK-MB、MYO、LNTP的异常是提示重型及危重型患者致死性结果的主要危险因素;胸部CT表现及随访是不能缺少的判断疾病严重程度及预后的重要评估方法,但需要结合临床及实验室检查综合评估。

    本研究总结了重型及危重型新冠病毒感染患者不同预后的临床、实验室检查及胸部CT特征,以期为重症患者的疾病监测和评估提供重要信息。

  • 图  1   男性,67岁,死亡患者,肺部CT显示双肺多发磨玻璃影,小叶间隔增厚呈“铺路石征”(三角形),血管穿行于病灶内呈“血管增粗征”(白色箭号)

    Figure  1.   A 67-year-old male patient (died). A lung CT showed multiple ground glass shadows in both lungs, thickened interlobular septum as a "paving stone sign" (triangle) and blood vessels passing through the lesion as a "thickened vessel sign" (white arrow)

    图  2   男性,66岁,死亡患者。行肺部CT平扫检查,显示病变多位于双肺胸膜下,初始病变范围未超过50%,但病变明显进展

    Figure  2.   A 66-year-old male patient (died). A lung CT scan was performed on day 1, 6, and 15 of admission. The lesions were mostly subpleural in both lungs, and the initial lesions did not exceed 50%, but the lesions progressed significantly

    图  3   男性,72岁,死亡患者,入院第13天胸部CT检查(b)显示病变较入院第1天(a)有好转

    Figure  3.   A 72-year-old male patient (died). Chest CT examination on day 13 of admission (b) showed less lesion than that on day 1 (a)

    图  4   男性,68岁,生存患者,入院第10天胸部CT检查(b)显示病变较入院第1天(a)有好转

    Figure  4.   A 68-year-old patient (survived). Chest CT examination on day 10 of admission (b) showed less lesion than that on day 1 (a)

    图  5   男性,89岁,生存患者,入院第7天(b)胸部CT复查显示病变较入院第1天(a)有进展,左肺上叶部分病变有吸收

    Figure  5.   An 89-year-old patient (survived). Chest CT reexamination on day 7 of admission (b) showed progressive lesions than that on day 1 (a), with partial remission of lesions in the left upper lobe

    表  1   不同预后两组新型冠状病毒感染者临床特征对比

    Table  1   Comparison of clinical features between the two groups of patients with different prognosis

    项目组别统计检验
    死亡组(n=68)生存组(n=50)$\chi^2 $P
      男性/女性(人数)46/2231/180.1710.679
      年龄/岁78.00±12.0270.04±12.58-3.416 0.001
      症状/例(%)  发热50(73.5)40(80.0)0.6670.414
      高热11(16.1)11(22.0)0.6440.422
      畏寒5(7.3)0(0.0)3.8390.050
      咽痛7(10.2)2(4.0)1.6200.203
      咳嗽26(38.2)16(32.0)0.4890.485
      咳痰24(35.2)8(16.0)5.4270.020
      咳血2(2.9)1(2.0)0.1030.748
      气促3(4.4)1(2.0)0.5120.474
      喘憋16(23.5)10(20.0)0.2090.648
      呼吸不畅9(13.2)2(4.0)2.9070.088
      乏力18(26.4)6(12.0)3.7240.054
      纳差6(8.8)0(0.0)4.6480.031
      胸痛3(4.4)0(0.0)2.2630.132
      胸闷9(13.2)3(6.0)1.6510.199
      基础疾病/例(%)  高血压43(63.2)31(62.0)0.0190.891
      糖尿病23(33.8)15(30.0)0.1930.660
      冠心病8(11.8)7(14.0)0.1300.719
      恶性肿瘤3(4.4)1(2.0)0.5120.474
      免疫抑制(移植术
      后、化疗等)
    4(5.9)2(4.0)0.2120.646
      肺心病1(1.5)0(0.0)0.7420.389
      肝病(肝炎,肝硬
      化,肝衰竭等)
    4(5.9)5(10.0)0.6930.405
      外科手术史20(29.4)19(38.0)0.0770.782
    下载: 导出CSV

    表  2   不同预后两组新型冠状病毒感染者实验室指标变化情况比较

    Table  2   Comparison of the changes of laboratory indexes in the two groups with different prognoses

    项目组别统计检验
    死亡组(n=68)生存组(n=50)$\chi^2 $P
      WBC升高/例(%)53(77.9)18(36.0)21.552<0.001
      NEUT升高/例(%)56(82.4)27(54.0)11.5590.003
      LYMPH降低/例(%)47(69.1)38(76.0)0.8400.657
      MONO升高/例(%)25(36.8)8(16.0)8.2150.016
      %NEUT升高/例(%)59(86.8)37(74.0)3.8130.149
      %LYMPH减低/例(%)62(91.2)44(88.0)1.4350.488
      %MONO正常/例(%)39(57.4)34(68.0)2.7610.251
      RBC减低/例(%)57(83.8)38(56.0)12.9500.002
      HGB减低/例(%)57(83.8)29(58.0)9.7220.002
      HCT减低/例(%)61(89.7)0(0.0)96.061<0.001
      NLR升高/例(%)63(92.6)45(90.0)0.2600.610
      RDW-SD升高/例(%)19(27.9)34(68.0)12.8680.002
      PLT正常/例(%)24(35.3)8(16.0)7.5380.053
      ALT升高/例(%)23(33.8)17(34.0)0.0000.984
      AST升高/例(%)39(59.4)25(50.0)0.6280.428
      eGFR减低/例(%)62(91.2)28(56.0)19.700<0.001
      SO2(%)≤93%/例(%)50(75.8)37(77.1)5.3920.056
      P/F index≤30 mmHg/例(%)37(56.1)36(73.5)3.6760.055
      CRP升高/例(%)66(97.1)44(88.0)3.7410.053
      PCT升高/例(%)63(92.6)27(45.0)34.667<0.001
      D-Dimer升高/例(%)56(86.2)33(68.8)4.9990.025
      CK升高/例(%)22(36.7)6(24.0)1.2820.258
      CK-MB升高/例(%)14(23.3)2(4.7)6.6630.010
      MYO升高/例(%)52(86.7)15(93.8)0.6070.436
      TNI升高/例(%)50(83.3)14(34.1)25.385<0.001
      LNTP升高/例(%)60(95.2)32(76.2)8.4280.004
    注:WBC为白细胞计数,NEUT为中性粒细胞绝对值,LYMPH为淋巴细胞绝对值,MONO为单核细胞绝对值,%NEUT为中性粒细胞百分率,%LYMPH为淋巴细胞百分率,%MONO为单核细胞百分率,RBC为红细胞计数,HGB为血红蛋白,HCT为红细胞比积,NLR为中性粒细胞/淋巴细胞比值,RDW-SD为红细胞体积分布宽度SD,PLT为血小板计数,ALT为丙氨酸氨基转移酶,AST为天门冬氨酸氨基转移酶,eGFR为肾小球滤过率,SO2为血氧饱和度,P/F index为肺动脉氧分压与吸氧浓度的比值,CRP为C反应蛋白,PCT为降钙素原,D-Dimer为D二聚体,CK为肌酸激酶,CK-MB为肌酸激酶同工酶,MYO为肌红蛋白,TNI为肌钙蛋白,LNTP为B型氨基端利钠肽原。
    下载: 导出CSV

    表  3   不同预后两组新型冠状病毒感染者实验室检查比较

    Table  3   Comparison of laboratory indexes between the two groups with different prognoses

    项目组别统计检验
    死亡组(n=68)生存组(n=50)Z/FP
      WBC/(×109L)13.86±6.1211.56±21.90-4.670<0.001
      NEUT/(×109/L)12.23±6.027.20±4.22-4.621<0.001
      LYMPH/(×109/L)0.912±0.753.84±21.36-0.2210.825
      MONO/(×109/L)0.57±0.490.45±0.31-0.9150.360
      %NEUT/%86.10±10.0079.96±15.02-2.9630.003
      %LYMPH/%9.03±9.4513.55±14.00-3.1540.002
      %MONO/%4.30±2.985.61±3.28-2.3100.021
      RBC/(×1012/L)3.08±1.123.76±0.902.0290.157
      HGB/(g/L)94.47±29.12114.56±28.000.3080.580
      HCT/%29.40±9.0434.53±7.591.3820.242
      NLR24.34±33.9111.84±11.97-3.3770.001
      MCV/FL97.59±10.0992.68±7.721.5810.211
      MCH/pg35.80±34.6330.59±3.02-0.1090.913
      MCHC/(g/L)324.90±52.82330.16±21.05-3.4650.001
      RDW-CV/%14.89±2.6013.55±3.25-4.524<0.001
      RDW-SD/FL50.96±9.7545.03±9.22-4.316<0.001
      PLT/×109/L161.88±98.87209.36±101.180.1120.738
      ALT/(U/L)184.43±626.4350.72±61.22-0.2490.803
      AST/(U/L)276.62±800.0453.06±47.39-1.8190.069
      eGFR/(mL/min/1.73 m250.67±39.5480.89±31.50-5.065<0.001
      pO2/mmHg67.18±25.3158.02±15.48-1.3810.167
      SO2/%101.02±92.4188.58±9.82-0.8780.380
      P/F index/mmHg324.65±117.98282.22±69.21-1.3860.166
      CRP/(mg/L)86.37±45.2659.40±41.201.0210.314
      PCT/(ng/mL)6.63±14.802.58±13.30-5.370<0.001
      D-Dimer/(ug/L)4281.21±5628.422713.70±6835.12-3.709<0.001
      CK/(U/L)711.10±1295.57136.56±292.62-3.986<0.001
      CK-MB/(ng/mL)4.58±8.091.93±5.60-4.263<0.001
      MYO/(ng/mL)1190.55±2064.71128.31±173.14-5.701<0.001
      TNI/(ng/mL)0.89±2.120.13±0.31-5.070<0.001
      LNTP/(pg/mL)9821.78±21583.976934.55±32028.09-4.840<0.001
    注:WBC为白细胞计数,NEUT为中性粒细胞绝对值,LYMPH为淋巴细胞绝对值,MONO为单核细胞绝对值,%NEUT为中性粒细胞百分率,%LYMPH为淋巴细胞百分率,%MONO为单核细胞百分率,RBC为红细胞计数,HGB为血红蛋白,HCT为红细胞比积,NLR为中性粒细胞/淋巴细胞比值,MCV为平均红细胞体积,MCH为平均红细胞血红蛋白含量,MCHC为平均红细胞血红蛋白浓度,RDW-CV为红细胞体积分布宽度,RDW-SD为红细胞体积分布宽度SD,PLT为血小板计数,ALT为丙氨酸氨基转移酶,AST为天门冬氨酸氨基转移酶,eGFR为肾小球滤过率,pO2为氧分压,SO2为血氧饱和度,P/F index为肺动脉氧分压与吸氧浓度的比值,CRP为C反应蛋白,PCT为降钙素原,D-Dimer为D二聚体,CK为肌酸激酶,CK-MB为肌酸激酶同工酶,MYO为肌红蛋白,TNI为肌钙蛋白,LNTP为B型氨基端利钠肽原。
    下载: 导出CSV

    表  4   临床实验室检查指标的logistic回归分析结果

    Table  4   Logistic regression analysis results of clinical laboratory examination indicators

    项目B标准误瓦尔德OR值OR值95% CIP
     年龄/岁0.2760.1244.9051.3171.032~1.6810.027
     WBC/(×109/L)27.87617.0212.6821.277 E+120.004~3.935 E+260.101
     NEUT/(×109/L)-27.39416.9732.6050.0000.000~354.9650.107
     LYMPH/(×109/L)-30.46518.5442.6990.0000.000~358.0190.100
     MONO/(×109/L)-10.0928.9031.2850.0000.000~1568.4270.257
     %NEUT/%3.0761.6283.56921.681 0.891~527.4640.059
     %LYMPH/%3.5901.8763.66236.224 0.917~1431.4890.056
     %MONO/%1.0080.6262.5962.7410.804~9.3460.107
     RBC/(×1012/L)-34.05117.0493.9890.0000.000~0.5290.046
     HGB/(g/L)-1.0390.6772.3550.3540.094~1.3340.125
     HCT/%6.9673.6963.5541061.421 0.758~1485479.3240.059
     NLR-0.0060.0240.0660.9940.949~1.0410.797
     MCHC/(g/L)0.1430.1351.1261.1540.886~1.5020.289
     RDW-CV/%1.8281.8201.0086.2190.175~220.4470.315
     RDW-SD/(FL)-1.1730.7632.3630.3090.069~1.3810.124
     eGFR/(mL/min/1.73 m20.0900.0424.6661.0951.008~1.1880.031
     CRP/(mg/L)-0.0110.0190.3090.9890.953~1.0270.579
     PCT/(ng/mL)-0.3440.2122.6290.7090.468~1.0740.105
     D-Dimer/(ug/L)0.0000.0001.9571.0000.999~1.0000.162
     CK/(U/L)-0.0030.0021.9000.9970.992~1.0010.168
     CK-MB/(ng/mL)0.4330.2552.8781.5420.935~2.5430.090
     MYO/(ng/mL)0.0240.0124.4571.0251.002~1.0480.035
     TNI/(ng/mL)4.1294.0611.03462.119 0.022~177947.7980.309
     LNTP/(pg/mL)0.0000.0004.3921.0001.000~1.0000.036
    注:WBC为白细胞计数,NEUT为中性粒细胞绝对值,LYMPH为淋巴细胞绝对值,MONO为单核细胞绝对值,%NEUT为中性粒细胞百分率,%LYMPH为淋巴细胞百分率,%MONO为单核细胞百分率,RBC为红细胞计数,HGB为血红蛋白,HCT为红细胞比积,NLR为中性粒细胞/淋巴细胞比值,MCHC为平均红细胞血红蛋白浓度,RDW-CV为红细胞体积分布宽度,RDW-SD为红细胞体积分布宽度SD,eGFR为肾小球滤过率,CRP为C反应蛋白,PCT为降钙素原,D-Dimer为D二聚体,CK为肌酸激酶,CK-MB为肌酸激酶同工酶,MYO为肌红蛋白,TNI为肌钙蛋白,LNTP为B型氨基端利钠肽原。
    下载: 导出CSV

    表  5   不同预后两组新型冠状病毒肺炎影像特征对比

    Table  5   Comparison of imaging features of the two groups with different prognosis of novel coronavirus pneumonia

    项目级别统计检验
    死亡组(n=58)生存组(n=36)$Z/\chi^2 $P
     发病到CT检查时间/d9.86±6.5012.14±6.90-1.863 0.062
     就诊时病变超过>50%/例(%)33(56.8)12(33.3)4.5800.032
     病灶多位于肺外周或胸膜下/例(%)27(46.6)26(72.2)6.3400.010
     磨玻璃影/例(%)50(86.2)33(91.7)0.9700.325
     实变影/例(%)39(67.2)24(66.7)0.1140.736
     铺路石征/例(%)24(41.4)18(50.0)0.7880.375
     血管穿行于病灶内,伴血管增粗/例(%)32(55.2)23(63.9)0.8540.355
     胸膜增厚/例(%)54(93.1)32(88.9)0.1810.670
     淋巴结肿大/例(%) 6(10.3)1(2.8)1.7900.181
     胸腔积液/例(%)24(41.4) 6(16.7)5.9660.015
     心包积液/例(%)1(1.7)1(2.8)0.1270.721
     病变复查/例n=33*n=28*24.820 <0.001
     进展/例(%)27(81.8) 6(21.4)
     好转/例(%) 5(15.2)22(78.6)
     变化不大/例(%)1(3.0)0(0.0)
     病变进展范围超过50%/例(%)11(33.3)0(0.0)3.6670.056
    注:*-死亡组及生存组排除25例和8例没有CT复查图像。
    下载: 导出CSV
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  • 收稿日期:  2022-03-13
  • 修回日期:  2023-03-28
  • 录用日期:  2023-03-29
  • 网络出版日期:  2023-05-03
  • 发布日期:  2023-05-30

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