Article(id=1203033501537890898, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203033494428541350, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.05.0523, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1672675200000, receivedDateStr=2023-01-03, revisedDate=null, revisedDateStr=null, acceptedDate=1679241600000, acceptedDateStr=2023-03-20, onlineDate=1764755138048, onlineDateStr=2025-12-03, pubDate=1685203200000, pubDateStr=2023-05-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764755138048, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764755138048, creator=13701087609, updateTime=1764755138048, updator=13701087609, issue=Issue{id=1203033494428541350, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='5', pageStart='489', pageEnd='626', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764755136353, creator=13701087609, updateTime=1764756085669, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203037476202967229, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203033494428541350, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203037476202967230, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203033494428541350, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=523, endPage=529, ext={EN=ArticleExt(id=1203033501839880809, articleId=1203033501537890898, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Correlation analysis between triacylglycerol levels and the risk of papillary thyroid carcinoma in patients undergoing thyroid nodule surgery, columnId=1203033497192591798, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Special Issue on Risk Factors Related to Thyroid Malignant Nodules, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the correlation between serum triglyceride (TG) levels and papillary thyroid carcinoma (PTC) in patients undergoing thyroid nodule surgery. Methods A retrospective analysis was conducted with the clinical data of 3340 patients with thyroid nodular disease [940 males (28.1%) and 2400 females (71.9%) with age of (44.5±11.4) years]who underwent thyroid nodule surgery and had complete operative blood lipid data in the First Medical Center of PLA General Hospital from January 2016 to December 2020. Based on the postoperative pathological condition, all the patients were divided into PTC group (2867 cases) and benign thyroid nodules group (473 cases). Analyze the general data of the two groups of patients using logistic regression to analyze the correlation between serum TG levels and the risk of PTC, and analyze the risk of PTC in age, gender, BMI, and thyroid autoantibody subgroups. Results Compared with benign nodules group, the serum TG levels of patients in PTC group were significantly higher [1.2(0.8, 1.7) vs. 1.1(0.8, 1.5), P<0.001]. Multivariate binary logistic regression analysis revealed that serum TG levels were associated with an increased risk of PTC disease (adjusted OR=3.067, 95%CI 1.839-5.116, P<0.001). Triglyceride levels were categorized into quartiles, with the lowest quartile serving as a reference. The relative risk for the highest quartile of triglycerides in PTC patients was 2.142(95%CI 1.548-2.965, P<0.001), and this association persisted even when serum triglycerides were within the normal reference range (adjusted OR=3.244, 95%CI 1.440-7.307, P=0.005). Subgroup analysis demonstrated that serum TG were associated with an increased risk of PTC only in patients with negative thyroid autoantibodies and a BMI<28 kg/m2 (P<0.05). Moreover, the risk of PTC was more pronounced in patients under 45 years of age compared with those aged 45 years and older (P for interaction=0.043). Conclusion Elevated serum triglyceride levels were associated with an increased risk of PTC in patients with negative thyroid autoantibodies and BMI<28 kg/m2.

, correspAuthors=Zhao-Hui Lv, authorNote=null, correspAuthorsNote=
* E-mail:
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目的 探讨因甲状腺结节行手术治疗的患者血清三酰甘油(TG)水平与甲状腺乳头状癌(PTC)发生风险的相关性。方法 收集2016年1月-2020年12月在解放军总医院第一医学中心行手术治疗且血脂资料完整的3340例甲状腺结节患者的临床资料进行回顾性分析。其中男940例(28.1%),女2400例(71.9%),年龄(44.5±11.4)岁;PTC 2867例,甲状腺良性结节473例。将所有患者基于术后病理分为良性结节组和PTC组,分析两组患者的一般资料,采用logistic回归分析血清TG水平与PTC发生风险的相关性,并在年龄、性别、BMI、甲状腺自身抗体亚组中分析PTC的发生风险。结果 与良性结节组相比,PTC组血清TG水平明显升高[1.2(0.8, 1.7)vs. 1.1(0.8, 1.5),P<0.001]。Logistic回归分析发现,血清TG水平与PTC发生风险升高有关(调整后OR=3.067,95%CI 1.839~5.116,P<0.001);将所有患者按血清TG水平四分位数进行分组,与最低四分位数组相比,最高四分位数组的PTC发生风险升高(调整后OR=2.142,95%CI 1.548~2.965,P<0.001);即使血清TG水平处于正常参考值范围时该相关性仍然存在(调整后OR=3.244,95%CI 1.440~7.707,P=0.005)。按性别、年龄、BMI、甲状腺自身抗体进行亚组分析发现,仅在甲状腺自身抗体阴性、BMI<28 kg/m2的患者中,血清TG水平与PTC发生风险升高有关(P<0.05);此外,与≥45岁的患者相比,<45岁的患者PTC发生风险更高(P交互=0.043)。结论 在甲状腺自身抗体阴性、BMI<28 kg/m2的甲状腺结节手术人群中,血清TG水平增高与PTC发生风险升高有关。

, correspAuthors=吕朝晖, authorNote=null, correspAuthorsNote=
吕朝晖,E-mail:
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聂智梅,硕士研究生,主要从事内分泌代谢疾病方面的研究

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聂智梅,硕士研究生,主要从事内分泌代谢疾病方面的研究

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聂智梅,硕士研究生,主要从事内分泌代谢疾病方面的研究

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Metabolic reprogramming by the PI3K-Akt-mTOR pathway in cancer[J]. Recent Results Cancer Res, 2016, 207: 39-72., articleTitle=Metabolic reprogramming by the PI3K-Akt-mTOR pathway in cancer, refAbstract=null), Reference(id=1203033513684594859, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, doi=null, pmid=null, pmcid=null, year=2016, volume=20, issue=1, pageStart=13, pageEnd=26, url=null, language=null, rfNumber=[27], rfOrder=31, authorNames=Nozhat Z, Hedayati M, journalName=Mol Diagn Ther, refType=null, unstructuredReference=Nozhat Z, Hedayati M. PI3K/AKT pathway and its mediators in thyroid carcinomas[J]. 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Diabetes, 2005, 54(12): 3458-3465., articleTitle=Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1203033503450493602, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, xref=1, ext=[AuthorCompanyExt(id=1203033503454687907, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, companyId=1203033503450493602, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China), AuthorCompanyExt(id=1203033503463076516, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, companyId=1203033503450493602, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1解放军总医院第一医学中心内分泌科,北京 100853)]), AuthorCompany(id=1203033503538573994, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, xref=2, ext=[AuthorCompanyExt(id=1203033503542768300, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, companyId=1203033503538573994, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2School of Medicine, Nankai University, Tianjin, 300071, China), AuthorCompanyExt(id=1203033503551156908, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, companyId=1203033503538573994, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2南开大学医学院,天津 300071)])], figs=[ArticleFig(id=1203033508953420795, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=EN, label=Tab. 1, caption=

Comparison of characteristics of subjects with thyroid disease between the two groups

, figureFileSmall=null, figureFileBig=null, tableContent=
项目总体(n=3340)良性结节组(n=473)PTC组(n=2867)P
性别[例(%)]   0.432
 940(28.1)126(26.6)814(28.4)
 2400(71.9)347(73.4)2053(71.6)
年龄(岁,$\bar{x}±s$)44.5±11.449.4±12.443.7±11.1<0.001
年龄[例(%)]   <0.001
 <45岁1650(49.4)152(32.1)1498(52.2)
 ≥45岁1690(50.6)321(67.9)1369(47.8)
甲状腺癌家族史[例(%)]   0.263
 3293(98.6)469(99.2)2824(98.5)
 47(1.4)4(0.8)43(1.5)
BMI(kg/m2, $\bar{x}±s$)24.8±3.624.1±3.424.9±3.7<0.001
BMI[例(%)]   <0.001
 <24 kg/m21452(43.5)238(50.3)1214(42.3)
 24~28 kg/m21279(38.3)174(36.8)1105(38.5)
 ≥28 kg/m2609(18.2)61(12.9)548(19.1)
SBP(mmHg, $\bar{x}±s$)126.1±15.5127.7±14.5125.9±15.60.017
DBP(mmHg, $\bar{x}±s$)79.2±10.278.6±10.179.3±10.30.141
ALT[U/L,M(Q1,Q3)]14.6(10.3,21.7)14.3(9.9,19.6)14.7(10.4,22.1)0.017
AST[U/L,M(Q1,Q3)]15.4(13.0,18.7)15.9(13.2,18.8)15.3(12.9,18.6)0.193
ALP(U/L, $\bar{x}±s$)61.8±22.768.2±41.760.8±17.4<0.001
GGT(U/L, $\bar{x}±s$)23.5±24.724.4±35.823.4±22.30.434
FPG(mmol/L, $\bar{x}±s$)4.8±0.74.7±0.64.8±0.70.042
TC(mmol/L, $\bar{x}±s$)4.3±0.84.3±0.84.3±0.80.233
TG[mmol/L,M(Q1,Q3)]1.2(0.8,1.7)1.1(0.8,1.5)1.2(0.8,1.7)<0.001
log10 TG($\bar{x}±s$)0.1±0.20.0±0.20.1±0.2<0.001
HDL-C(mmol/L, $\bar{x}±s$)1.2±0.31.3±0.31.2±0.3<0.001
LDL-C(mmol/L, $\bar{x}±s$)2.8±0.72.7±0.72.8±0.80.256
FT3(pmol/L, $\bar{x}±s$)4.7±0.54.8±0.54.7±0.50.002
FT4(pmol/L, $\bar{x}±s$)15.1±2.114.7±2.015.2±2.1<0.001
TSH[mU/L,M(Q1,Q3)]1.9(1.3,2.8)1.7(1.1,2.5)1.9(1.3,2.8)<0.001
TgAb[例(%)]   <0.001
 阴性2525(75.6)420(88.8)2105(73.4)
 阳性815(24.4)53(11.2)762(26.6)
TPOAb[例(%)]   <0.001
 阴性2655(79.5)421(89.0)2234(77.9)
 阳性685(20.5)52(11.0)633(22.1) 
), ArticleFig(id=1203033509054083073, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=CN, label=表1, caption=

两组甲状腺疾病患者临床资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
项目总体(n=3340)良性结节组(n=473)PTC组(n=2867)P
性别[例(%)]   0.432
 940(28.1)126(26.6)814(28.4)
 2400(71.9)347(73.4)2053(71.6)
年龄(岁,$\bar{x}±s$)44.5±11.449.4±12.443.7±11.1<0.001
年龄[例(%)]   <0.001
 <45岁1650(49.4)152(32.1)1498(52.2)
 ≥45岁1690(50.6)321(67.9)1369(47.8)
甲状腺癌家族史[例(%)]   0.263
 3293(98.6)469(99.2)2824(98.5)
 47(1.4)4(0.8)43(1.5)
BMI(kg/m2, $\bar{x}±s$)24.8±3.624.1±3.424.9±3.7<0.001
BMI[例(%)]   <0.001
 <24 kg/m21452(43.5)238(50.3)1214(42.3)
 24~28 kg/m21279(38.3)174(36.8)1105(38.5)
 ≥28 kg/m2609(18.2)61(12.9)548(19.1)
SBP(mmHg, $\bar{x}±s$)126.1±15.5127.7±14.5125.9±15.60.017
DBP(mmHg, $\bar{x}±s$)79.2±10.278.6±10.179.3±10.30.141
ALT[U/L,M(Q1,Q3)]14.6(10.3,21.7)14.3(9.9,19.6)14.7(10.4,22.1)0.017
AST[U/L,M(Q1,Q3)]15.4(13.0,18.7)15.9(13.2,18.8)15.3(12.9,18.6)0.193
ALP(U/L, $\bar{x}±s$)61.8±22.768.2±41.760.8±17.4<0.001
GGT(U/L, $\bar{x}±s$)23.5±24.724.4±35.823.4±22.30.434
FPG(mmol/L, $\bar{x}±s$)4.8±0.74.7±0.64.8±0.70.042
TC(mmol/L, $\bar{x}±s$)4.3±0.84.3±0.84.3±0.80.233
TG[mmol/L,M(Q1,Q3)]1.2(0.8,1.7)1.1(0.8,1.5)1.2(0.8,1.7)<0.001
log10 TG($\bar{x}±s$)0.1±0.20.0±0.20.1±0.2<0.001
HDL-C(mmol/L, $\bar{x}±s$)1.2±0.31.3±0.31.2±0.3<0.001
LDL-C(mmol/L, $\bar{x}±s$)2.8±0.72.7±0.72.8±0.80.256
FT3(pmol/L, $\bar{x}±s$)4.7±0.54.8±0.54.7±0.50.002
FT4(pmol/L, $\bar{x}±s$)15.1±2.114.7±2.015.2±2.1<0.001
TSH[mU/L,M(Q1,Q3)]1.9(1.3,2.8)1.7(1.1,2.5)1.9(1.3,2.8)<0.001
TgAb[例(%)]   <0.001
 阴性2525(75.6)420(88.8)2105(73.4)
 阳性815(24.4)53(11.2)762(26.6)
TPOAb[例(%)]   <0.001
 阴性2655(79.5)421(89.0)2234(77.9)
 阳性685(20.5)52(11.0)633(22.1) 
), ArticleFig(id=1203033509133774853, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=EN, label=Tab. 2, caption=

Univariate analysis results on the relationship between various indicators and PTC disease in the study population

, figureFileSmall=null, figureFileBig=null, tableContent=
指标OR(95%CI)P
性别 0.432
 1
 0.916 (0.735~1.141)
年龄0.956 (0.947~0.964)<0.001
甲状腺癌家族史 0.270
 1
 1.785 (0.638~4.995)
BMI(kg/m2)1.064 (1.034~1.094)<0.001
SBP(mmHg)0.992 (0.986~0.999)0.017
DBP(mmHg)1.007 (0.998~1.017)0.141
ALT(U/L)1.011 (1.003~1.019)0.010
AST(U/L)1.002 (0.990~1.014)0.733
ALP(U/L)0.986 (0.981~0.991)<0.001
GGT(U/L)0.999 (0.995~1.002)0.436
FPG(mmol/L)1.179 (1.006~1.382)0.041
TC(mmol/L)0.931 (0.829~1.047)0.233
TG(mmol/L)1.180 (1.047~1.330)0.007
log10 TG2.185 (1.431~3.336)<0.001
HDL-C(mmol/L)0.502 (0.376~0.670)<0.001
LDL-C(mmol/L)1.079 (0.946~1.231)0.256
FT3(pmol/L)0.745 (0.617~0.899)0.002
FT4(pmol/L)1.118 (1.065~1.174)<0.001
TSH(mU/L)1.241 (1.128~1.366)<0.001
TgAb <0.001
 阴性1
 阳性2.869 (2.131~3.863)
TPOAb <0.001
 阴性1
 阳性2.294 (1.697~3.101) 
), ArticleFig(id=1203033509221855243, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=CN, label=表2, caption=

各指标与PTC发生风险关系的单因素分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
指标OR(95%CI)P
性别 0.432
 1
 0.916 (0.735~1.141)
年龄0.956 (0.947~0.964)<0.001
甲状腺癌家族史 0.270
 1
 1.785 (0.638~4.995)
BMI(kg/m2)1.064 (1.034~1.094)<0.001
SBP(mmHg)0.992 (0.986~0.999)0.017
DBP(mmHg)1.007 (0.998~1.017)0.141
ALT(U/L)1.011 (1.003~1.019)0.010
AST(U/L)1.002 (0.990~1.014)0.733
ALP(U/L)0.986 (0.981~0.991)<0.001
GGT(U/L)0.999 (0.995~1.002)0.436
FPG(mmol/L)1.179 (1.006~1.382)0.041
TC(mmol/L)0.931 (0.829~1.047)0.233
TG(mmol/L)1.180 (1.047~1.330)0.007
log10 TG2.185 (1.431~3.336)<0.001
HDL-C(mmol/L)0.502 (0.376~0.670)<0.001
LDL-C(mmol/L)1.079 (0.946~1.231)0.256
FT3(pmol/L)0.745 (0.617~0.899)0.002
FT4(pmol/L)1.118 (1.065~1.174)<0.001
TSH(mU/L)1.241 (1.128~1.366)<0.001
TgAb <0.001
 阴性1
 阳性2.869 (2.131~3.863)
TPOAb <0.001
 阴性1
 阳性2.294 (1.697~3.101) 
), ArticleFig(id=1203033509309935631, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=EN, label=Tab. 3, caption=

Association of serum TG levels with PTC in all the subjects

, figureFileSmall=null, figureFileBig=null, tableContent=
TG(mmol/L)模型1模型2模型3
OR(95%CI)POR(95%CI)POR(95%CI)P
log10 TG2.185(1.431~3.336)<0.0012.524(1.546~4.119)<0.0013.067(1.839~5.116)<0.001
Q1(TG<0.81)1(参考值) 1(参考值) 1(参考值)
Q2(0.81≤TG<1.18)1.242(0.954~1.616)0.1071.422(1.078~1.876)0.0131.480(1.115~1.965)0.007
Q3(1.18≤TG<1.69)1.261(0.966~1.644)0.0881.463(1.096~1.953)0.0101.585(1.176~2.136)0.002
Q4(TG≥1.69)1.753(1.32~2.329)<0.0011.905(1.393~2.605)<0.0012.142(1.548~2.965)<0.001
P趋势 0.001 <0.001 <0.001
), ArticleFig(id=1203033509393821715, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=CN, label=表3, caption=

所有患者血清TG水平与PTC发生风险的相关性分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
TG(mmol/L)模型1模型2模型3
OR(95%CI)POR(95%CI)POR(95%CI)P
log10 TG2.185(1.431~3.336)<0.0012.524(1.546~4.119)<0.0013.067(1.839~5.116)<0.001
Q1(TG<0.81)1(参考值) 1(参考值) 1(参考值)
Q2(0.81≤TG<1.18)1.242(0.954~1.616)0.1071.422(1.078~1.876)0.0131.480(1.115~1.965)0.007
Q3(1.18≤TG<1.69)1.261(0.966~1.644)0.0881.463(1.096~1.953)0.0101.585(1.176~2.136)0.002
Q4(TG≥1.69)1.753(1.32~2.329)<0.0011.905(1.393~2.605)<0.0012.142(1.548~2.965)<0.001
P趋势 0.001 <0.001 <0.001
), ArticleFig(id=1203033509498679320, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=EN, label=Tab. 4, caption=

Correlation between normal range of serum TG levels and the risk of PTC occurrence

, figureFileSmall=null, figureFileBig=null, tableContent=
TG(mmol/L)模型1模型2模型3
OR(95% CI)POR(95% CI)POR(95% CI)P
log10 TG1.687(0.837~3.401)0.1442.696(1.227~5.925)0.0143.244(1.440~7.307)0.005
Q1(TG<0.74)1(参考值) 1(参考值) 1(参考值)
Q2(0.74≤TG<1.02)1.235(0.908~1.68)0.1781.377(1.000~1.897)0.0501.433(1.033~1.989)0.031
Q3(1.02≤TG<1.29)1.278(0.938~1.741)0.1201.505(1.079~2.098)0.0161.596(1.131~2.253)0.008
Q4(TG≥1.29)1.169(0.864~1.581)0.3111.409(1.011~1.965)0.0431.514(1.074~2.132)0.018
P趋势 0.302 0.045 0.020
), ArticleFig(id=1203033509586759711, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=CN, label=表4, caption=

正常范围的血清TG水平与PTC发生风险的相关性分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
TG(mmol/L)模型1模型2模型3
OR(95% CI)POR(95% CI)POR(95% CI)P
log10 TG1.687(0.837~3.401)0.1442.696(1.227~5.925)0.0143.244(1.440~7.307)0.005
Q1(TG<0.74)1(参考值) 1(参考值) 1(参考值)
Q2(0.74≤TG<1.02)1.235(0.908~1.68)0.1781.377(1.000~1.897)0.0501.433(1.033~1.989)0.031
Q3(1.02≤TG<1.29)1.278(0.938~1.741)0.1201.505(1.079~2.098)0.0161.596(1.131~2.253)0.008
Q4(TG≥1.29)1.169(0.864~1.581)0.3111.409(1.011~1.965)0.0431.514(1.074~2.132)0.018
P趋势 0.302 0.045 0.020
), ArticleFig(id=1203033509700005920, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=EN, label=Tab. 5, caption=

Correlation between between TG and PTC in different subgroups

, figureFileSmall=null, figureFileBig=null, tableContent=
亚组模型1 [OR(95% CI)]模型2 [OR(95% CI)]模型3[OR(95% CI)]P交互
年龄(岁)   P=0.043
 <45(n=1650)5.652(2.648~12.066)3.215(1.354~7.636)3.564(1.458~8.716)
 ≥45(n=1690)2.291(1.306~4.020)2.094(1.143~3.835)2.496(1.322~4.712)
性别   P=0.824
 男(n=940)3.588(1.553~8.289)2.813(1.086~7.285)3.712(1.342~10.271)
 女(n=2400)1.824(1.088~3.058)2.424(1.351~4.351)2.661(1.451~4.877)
BMI(kg/m2)   P=0.216
 <24(n=1452)1.336(0.703~2.541)2.115(1.030~4.343)2.643(1.234~5.659)
 24~28(n=1279)2.868(1.333~6.169)3.670(1.637~8.228)4.624(1.989~10.748)
 ≥28(n=609)1.179(0.364~3.814)1.089(0.316~3.753)1.030(0.286~3.713)
甲状腺自身抗体   P=0.703
 阴性(n=2297)2.720(1.698~4.355)2.865(1.669~4.920)3.179(1.815~5.570)
 阳性(n=1043)1.676(0.595~4.719)2.285(0.677~7.715)2.684(0.760~9.480)
), ArticleFig(id=1203033509804863525, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203033501537890898, language=CN, label=表5, caption=

不同亚组中血清TG水平与PTC发生风险的相关性

, figureFileSmall=null, figureFileBig=null, tableContent=
亚组模型1 [OR(95% CI)]模型2 [OR(95% CI)]模型3[OR(95% CI)]P交互
年龄(岁)   P=0.043
 <45(n=1650)5.652(2.648~12.066)3.215(1.354~7.636)3.564(1.458~8.716)
 ≥45(n=1690)2.291(1.306~4.020)2.094(1.143~3.835)2.496(1.322~4.712)
性别   P=0.824
 男(n=940)3.588(1.553~8.289)2.813(1.086~7.285)3.712(1.342~10.271)
 女(n=2400)1.824(1.088~3.058)2.424(1.351~4.351)2.661(1.451~4.877)
BMI(kg/m2)   P=0.216
 <24(n=1452)1.336(0.703~2.541)2.115(1.030~4.343)2.643(1.234~5.659)
 24~28(n=1279)2.868(1.333~6.169)3.670(1.637~8.228)4.624(1.989~10.748)
 ≥28(n=609)1.179(0.364~3.814)1.089(0.316~3.753)1.030(0.286~3.713)
甲状腺自身抗体   P=0.703
 阴性(n=2297)2.720(1.698~4.355)2.865(1.669~4.920)3.179(1.815~5.570)
 阳性(n=1043)1.676(0.595~4.719)2.285(0.677~7.715)2.684(0.760~9.480)
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甲状腺结节手术人群三酰甘油水平与甲状腺乳头状癌发生风险的相关性分析
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聂智梅 1 , 胡晓东 1 , 许怀瑾 1, 2 , 李洁菲 1, 2 , 康韶洋 1 , 赵思童 1 , 柳洪宙 1 , 王玉寒 1 , 王安宁 1 , 吕朝晖 1, 2, *
解放军医学杂志 | 甲状腺恶性结节相关危险因素专题研究 2023,48(5): 523-529
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解放军医学杂志 | 甲状腺恶性结节相关危险因素专题研究 2023, 48(5): 523-529
甲状腺结节手术人群三酰甘油水平与甲状腺乳头状癌发生风险的相关性分析
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聂智梅1, 胡晓东1, 许怀瑾1, 2, 李洁菲1, 2, 康韶洋1, 赵思童1, 柳洪宙1, 王玉寒1, 王安宁1, 吕朝晖1, 2, *
作者信息
  • 1解放军总医院第一医学中心内分泌科,北京 100853
  • 2南开大学医学院,天津 300071
  • 聂智梅,硕士研究生,主要从事内分泌代谢疾病方面的研究

通讯作者:

吕朝晖,E-mail:
Correlation analysis between triacylglycerol levels and the risk of papillary thyroid carcinoma in patients undergoing thyroid nodule surgery
Zhi-Mei Nie1, Xiao-Dong Hu1, Huai-Jin Xu1, 2, Jie-Fei Li1, 2, Shao-Yang Kang1, Si-Tong Zhao1, Hong-Zhou Liu1, Yu-Han Wang1, An-Ning Wang1, Zhao-Hui Lv1, 2, *
Affiliations
  • 1Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
  • 2School of Medicine, Nankai University, Tianjin, 300071, China
出版时间: 2023-05-28 doi: 10.11855/j.issn.0577-7402.2023.05.0523
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目的 探讨因甲状腺结节行手术治疗的患者血清三酰甘油(TG)水平与甲状腺乳头状癌(PTC)发生风险的相关性。方法 收集2016年1月-2020年12月在解放军总医院第一医学中心行手术治疗且血脂资料完整的3340例甲状腺结节患者的临床资料进行回顾性分析。其中男940例(28.1%),女2400例(71.9%),年龄(44.5±11.4)岁;PTC 2867例,甲状腺良性结节473例。将所有患者基于术后病理分为良性结节组和PTC组,分析两组患者的一般资料,采用logistic回归分析血清TG水平与PTC发生风险的相关性,并在年龄、性别、BMI、甲状腺自身抗体亚组中分析PTC的发生风险。结果 与良性结节组相比,PTC组血清TG水平明显升高[1.2(0.8, 1.7)vs. 1.1(0.8, 1.5),P<0.001]。Logistic回归分析发现,血清TG水平与PTC发生风险升高有关(调整后OR=3.067,95%CI 1.839~5.116,P<0.001);将所有患者按血清TG水平四分位数进行分组,与最低四分位数组相比,最高四分位数组的PTC发生风险升高(调整后OR=2.142,95%CI 1.548~2.965,P<0.001);即使血清TG水平处于正常参考值范围时该相关性仍然存在(调整后OR=3.244,95%CI 1.440~7.707,P=0.005)。按性别、年龄、BMI、甲状腺自身抗体进行亚组分析发现,仅在甲状腺自身抗体阴性、BMI<28 kg/m2的患者中,血清TG水平与PTC发生风险升高有关(P<0.05);此外,与≥45岁的患者相比,<45岁的患者PTC发生风险更高(P交互=0.043)。结论 在甲状腺自身抗体阴性、BMI<28 kg/m2的甲状腺结节手术人群中,血清TG水平增高与PTC发生风险升高有关。

三酰甘油  /  甲状腺乳头状癌  /  甲状腺结节  /  回顾性研究

Objective To investigate the correlation between serum triglyceride (TG) levels and papillary thyroid carcinoma (PTC) in patients undergoing thyroid nodule surgery. Methods A retrospective analysis was conducted with the clinical data of 3340 patients with thyroid nodular disease [940 males (28.1%) and 2400 females (71.9%) with age of (44.5±11.4) years]who underwent thyroid nodule surgery and had complete operative blood lipid data in the First Medical Center of PLA General Hospital from January 2016 to December 2020. Based on the postoperative pathological condition, all the patients were divided into PTC group (2867 cases) and benign thyroid nodules group (473 cases). Analyze the general data of the two groups of patients using logistic regression to analyze the correlation between serum TG levels and the risk of PTC, and analyze the risk of PTC in age, gender, BMI, and thyroid autoantibody subgroups. Results Compared with benign nodules group, the serum TG levels of patients in PTC group were significantly higher [1.2(0.8, 1.7) vs. 1.1(0.8, 1.5), P<0.001]. Multivariate binary logistic regression analysis revealed that serum TG levels were associated with an increased risk of PTC disease (adjusted OR=3.067, 95%CI 1.839-5.116, P<0.001). Triglyceride levels were categorized into quartiles, with the lowest quartile serving as a reference. The relative risk for the highest quartile of triglycerides in PTC patients was 2.142(95%CI 1.548-2.965, P<0.001), and this association persisted even when serum triglycerides were within the normal reference range (adjusted OR=3.244, 95%CI 1.440-7.307, P=0.005). Subgroup analysis demonstrated that serum TG were associated with an increased risk of PTC only in patients with negative thyroid autoantibodies and a BMI<28 kg/m2 (P<0.05). Moreover, the risk of PTC was more pronounced in patients under 45 years of age compared with those aged 45 years and older (P for interaction=0.043). Conclusion Elevated serum triglyceride levels were associated with an increased risk of PTC in patients with negative thyroid autoantibodies and BMI<28 kg/m2.

triglyceride  /  papillary thyroid carcinoma  /  thyroid nodules  /  retrospective study
聂智梅, 胡晓东, 许怀瑾, 李洁菲, 康韶洋, 赵思童, 柳洪宙, 王玉寒, 王安宁, 吕朝晖. 甲状腺结节手术人群三酰甘油水平与甲状腺乳头状癌发生风险的相关性分析. 解放军医学杂志, 2023 , 48 (5) : 523 -529 . DOI: 10.11855/j.issn.0577-7402.2023.05.0523
Zhi-Mei Nie, Xiao-Dong Hu, Huai-Jin Xu, Jie-Fei Li, Shao-Yang Kang, Si-Tong Zhao, Hong-Zhou Liu, Yu-Han Wang, An-Ning Wang, Zhao-Hui Lv. Correlation analysis between triacylglycerol levels and the risk of papillary thyroid carcinoma in patients undergoing thyroid nodule surgery[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (5) : 523 -529 . DOI: 10.11855/j.issn.0577-7402.2023.05.0523
近年来甲状腺癌发病率逐渐增高,其中肿瘤直径>2 cm的甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和远处转移肿瘤的死亡率呈上升趋势[1],因此早期发现及防治尤为重要。目前,仅儿童时期的电离辐射暴露为甲状腺癌明确的危险因素[2],碘缺乏或碘过量、雌激素及生殖因素、内分泌干扰物质等因素可能导致甲状腺癌发病率增高[3]。围绕代谢综合征(如肥胖、糖代谢异常、脂代谢紊乱)与甲状腺癌风险的相关性分析已成为研究热点。其中,奥地利的一项超过14万例的队列研究发现,甲状腺癌发生风险与血糖水平>5.3 mmol/L呈正相关[4];Kitahara等[5]对22项前瞻性队列研究的2 094 047例患者进行汇总分析发现,身高、体重指数(BMI)、腰围与甲状腺癌的发病率呈正相关;此外,1997年冰岛的一项队列研究发现血清三酰甘油(TG)水平与甲状腺癌存在相关性[6]。此后,陆续出现少量关于血清TG水平与甲状腺癌相关性的研究,但结论并不一致[7-11]。本研究通过回顾性分析解放军总医院第一医学中心甲状腺结节手术人群的临床资料,探讨血清TG水平与PTC发生风险之间的相关性,旨在为PTC的预防和诊治提供依据。
收集2016年1月-2020年12月于解放军总医院第一医学中心行手术治疗的甲状腺结节患者3340例。纳入标准:(1)术前超声提示有甲状腺结节;(2)术后组织病理学提示为良性肿瘤或PTC。排除标准:(1)年龄<18岁;(2)合并糖尿病病史、其他恶性肿瘤病史、服用降脂药物史、甲状腺手术史;(3)甲状腺功能异常;(4)血脂资料缺失。其中,良性肿瘤与PTC术后组织病理分类参考世界卫生组织公布的甲状腺肿瘤分类标准第5版[12],良性肿瘤包括滤泡性腺瘤、滤泡结节性疾病、嗜酸细胞腺瘤等。将术后病理证实为PTC的2867例作为PTC组,术后病理提示为良性肿瘤的473例作为良性结节组。本研究已获解放军总医院第一医学中心医学伦理委员会的审批(伦审第S2022-015-01号)。
收集患者的人口学资料、血清学检查(肝功能、血脂、血糖、甲状腺功能)及术后病理特征等。血清学检查于清晨空腹(至少8 h)采集静脉血检测,采用罗氏Cobas c701全自动生化分析仪检测TG(正常参考值范围为0.4~1.7 mmol/L),血清甲状腺球蛋白抗体(TgAb)和甲状腺过氧化物酶抗体(TPOAb)采用放射免疫法测定(TPOAb≥60 U/ml、TgAb≥60 U/ml为阳性)。根据《中国成人超重和肥胖症预防控制指南》,超重定义为BMI 24~28 kg/m2,肥胖定义为BMI≥28 kg/m2
分析两组患者的临床资料。由于TG为偏态分布,为规范数据分布,将其做log10转换,将研究人群按TG水平四分位数从低到高分为Q1组(TG<0.81 mmol/L)、Q2组(0.81≤TG<1.18 mmol/L)、Q3组(1.18≤TG<1.69 mmol/L)、Q4组(TG≥1.69 mmol/L),采用单因素回归分析确定与PTC有关的影响因素,并检验变量的多重共线性;结合既往研究结果及逐步回归法选择调整的混杂因素,将TG分别作为连续变量及分类变量进行logistic回归分析,并进一步在年龄、性别、BMI、甲状腺自身抗体亚组中分析PTC的发生风险。
采用R4.2.2软件进行统计分析,分析前使用多重插补对数据的缺失值进行分析并插补。对研究人群的特征进行描述性统计,分类变量用例(%)表示,组间比较采用χ2检验;符合正态分布的计量资料以$\bar{x}±s$表示,两组间比较采用t检验;非正态分布的计量资料以M(Q1Q3)表示,组间比较采用Mann-Whitney U检验。采用logistic回归分析TG与PTC发生风险的相关性,并进行亚组分析。P<0.05为差异有统计学意义。
3340例中,男940例(28.1%),女2400例(71.9%),男女比例为1:2.55,年龄(44.5±11.4)岁。与良性结节组相比,PTC组患者年龄较小,高密度脂蛋白胆固醇(HDL-C)、碱性磷酸酶(ALP)、游离三碘甲腺原氨酸(FT3)水平明显降低,BMI、空腹血糖(FPG)、TG、促甲状腺激素(TSH)水平及TgAb、TPOAb阳性率明显增高(P<0.05),而性别、甲状腺癌家族史、胆固醇(TC)水平、舒张压(DBP)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、低密度脂蛋白胆固醇(LDL-C)水平两组差异无统计学意义(P>0.05)(表1)。
单因素分析显示,PTC发生风险与年龄、BMI、收缩压(SBP)、谷丙转氨酶(ALT)、ALP、FPG、TG、HDL-C、FT3、FT4、TSH、TgAb、TPOAb有关,差异有统计学意义(P<0.05),而与性别、甲状腺癌家族史、DBP、AST、GGT、TC、LDL-C无关(P>0.05)(表2)。
在调整年龄、甲状腺癌家族史、BMI、ALP、FPG、TSH、TgAb、TPOAb(模型3)后,logistic回归分析结果显示,log10 TG每增加1个单位,PTC发生风险增加206.7%(OR=3.067,95%CI 1.839~5.116,P<0.001)。与Q1组相比,Q2组的发生风险增高48.0%(OR=1.480,95%CI 1.115~1.965,P=0.007),Q3组增高58.5%(OR=1.585,95%CI 1.176~2.136,P=0.002),Q4组增高114.2%(OR=2.142,95%CI 1.548~2.965,P<0.001),且随着血清TG水平升高,PTC的发生风险呈现上升趋势(P趋势<0.01)(表3)。此外,对血清TG水平处于正常参考值范围(0.4~1.7 mmol/L)的研究人群进行分析,在调整年龄、甲状腺癌家族史、BMI、ALP、FPG、TSH、TgAb、TPOAb(模型3)后,血清TG水平与PTC发生风险呈正相关(OR=3.224,95%CI 1.440~7.307,P=0.005),与Q1组相比,Q4组PTC发生风险增高51.4%(OR=1.514,95%CI 1.074~2.132,P=0.018);且随着血清TG水平升高,PTC发生风险呈现上升趋势(P趋势=0.02)(表4)。
基于年龄、性别、BMI、甲状腺自身抗体对研究人群进行亚组分析,检验不同亚组中血清TG水平与PTC发生风险的相关性,TG进行log10转换。调整年龄、甲状腺癌家族史、BMI、ALP、FPG、TSH、TgAb、TPOAb(模型3)后,结果显示,以年龄45岁为截断值将研究人群分为两个亚组,其中<45岁组(OR=3.564,95%CI 1.458~8.716)较≥45岁组(OR=2.496,95%CI 1.322~4.712)相关性更明显,即TG对PTC的作用受到年龄的明显影响(P交互=0.043);不同性别亚组中,TG与PTC发生风险的相关性稳定存在,且不存在交互作用(P交互=0.824);以BMI 24 kg/m2、28 kg/m2作为截断值将研究人群分为3组,在BMI<24 kg/m2(OR=2.643,95%CI 1.234~5.659)及24≤BMI<28 kg/m2(OR=4.624,95%CI 1.989~10.748)亚组中的相关性稳定存在,而在BMI≥28 kg/m2亚组中无明显相关性(P>0.05),且3组间不存在交互作用(P交互=0.216);将TgAb、TPOAb全阴性作为甲状腺自身抗体阴性组,TgAb、TPOAb任一阳性或全阳性作为甲状腺自身抗体阳性组,结果显示在甲状腺自身抗体阴性组中血清TG水平与PTC发生风险存在相关性(OR=3.179,95%CI 1.815~5.570),而在甲状腺自身抗体阳性组中无明显相关性(OR=2.684,95%CI 0.760~9.480),且两组间不存在交互作用(P交互=0.703)(表5)。
近年来,代谢综合征与甲状腺癌患病率均呈上升趋势。研究发现,高甘油三酯血症产生的脂毒性[13]与甲状腺癌之间的关联具有一定的病理生理基础[14-15]。目前关于血清TG与PTC之间相关性的研究较少。本研究发现,在行甲状腺结节手术的人群中,血清TG水平与PTC发生风险之间存在相关性;随着TG水平升高,PTC发生风险呈上升趋势。这种相关性仅存在于甲状腺自身抗体阴性、BMI<28 kg/m2的患者中,不受性别影响,在年龄<45岁的患者中更为明显;且当血清TG水平处于正常参考值范围时,这种相关性仍然存在。
目前,有关血清TG水平与甲状腺癌发生风险之间的研究有限且结论不一致。倪静等[7]发现,PTC组的TG水平明显高于良性结节组[(1.68±1.10) mmol/L vs. (1.32±1.05) mmol/L,P=0.037],但多因素logistic回归分析发现TG水平与PTC无明显相关性。另一项纳入40例PTC、40例结节性甲状腺肿及40例健康对照的研究发现,PTC患者TG水平明显高于健康对照组[(1.42±0.53) mmol/L vs. (1.05±0.36) mmol/L,P=0.04],推测PTC的发生可能与TG水平升高有关[8]。然而,该研究仅分析了组间差异,无法说明两者间的相关性。冰岛一项针对22 946例既往无肿瘤病史的雷克雅未克居民的队列研究发现,在调整高血压药物使用情况后,TG是男性结直肠肿瘤和甲状腺肿瘤的危险因素[6];另一项来自奥地利的纳入156 153例受试者的队列研究在平均随访10.6年后发现,与TG最低四分位数的研究人群相比,最高四分位数研究人群的甲状腺癌发生风险增高(HR=1.96,95%CI 1.00~3.84)[9]。然而,上述研究均未明确甲状腺癌的具体病理类型,且缺乏既往史如降脂药物和激素用药史及糖尿病史等信息。来自欧洲We-Can项目的队列研究结论也不一致。其中,Borena等[10]的一项探讨TG水平与癌症风险之间关系的研究发现,与TG最低五分位数的研究人群相比,TG最高五分位数研究人群的甲状腺癌发生风险明显增高(RR=3.49,95%CI 1.04~11.57),而Almquist等[11]的一项探讨代谢成分与甲状腺癌发生风险关系的研究发现,TG水平与甲状腺癌无关。但上述研究未考虑甲状腺癌已知的危险因素如甲状腺癌家族史,且未记录患者甲状腺激素状态。
甲状腺激素可直接或间接参与体内血糖、血脂、尿酸等的代谢过程。越来越多的证据表明,甲状腺功能减退与TG水平升高有关[16],且血清TSH水平升高可能使甲状腺癌发生风险增加[17-18]。因此,本研究在纳入受试者时通过FT3、FT4、TSH对甲状腺功能进行分类,并排除了甲状腺功能异常者。此外,Dong等[19]在2022年发表的一项纳入20项队列研究的meta分析发现,糖尿病患者患甲状腺癌的风险增加约30%,其中女性患者增加36%,男性患者增加26%,合并糖尿病病史可能影响PTC的发生风险。因此,本研究在纳入研究人群时排除了合并糖尿病病史的患者,使研究结果可信度更高。
流行病学研究发现,肥胖与甲状腺癌之间存在关联,Shin等[20]于2022年发表的一项纳入13项队列研究538 857例受试者、平均随访时间为15.1年的meta分析发现,与BMI 18.5~22.9 kg/m2组相比,在男性人群中,BMI 25.0~29.9 kg/m2及≥30.0 kg/m2组的甲状腺癌发生风险增高(分别为HR=1.31,95%CI 0.95~1.80;HR=1.84,95%CI 0.89~3.81),而女性人群中,BMI 23.0~24.9 kg/m2组的甲状腺癌发生风险增高(HR=1.26,95%CI 1.07~1.48)。因此,本研究对研究人群进行了BMI亚组分析,发现TG水平与PTC之间的相关性在BMI<24.0 kg/m2的患者中仍然存在,推测TG在癌症中的作用可能部分独立于BMI,而在BMI≥28 kg/m2亚组并未发现相关性,可能与亚组样本量较小有关。韩国的一项研究发现,TgAb阳性是甲状腺恶性肿瘤的独立预测因子(OR=1.61,95%CI 1.12~2.33)[21];贾晓蒙等[22]同样发现TgAb与女性PTC发生风险增高有关。而本研究对甲状腺自身抗体进行亚组分析发现,在甲状腺自身抗体阴性的患者中,TG水平与PTC呈正相关,而自身抗体阳性的患者中该相关性不明显。此外,TG水平与PTC之间的正相关性在不同性别亚组中稳定存在;而对年龄亚组进行分析发现,在年龄<45岁的患者中该相关性较年龄≥45岁的患者更为明显,即TG水平对PTC的作用受到年龄的明显影响,提示年轻患者合并高甘油三酯血症时PTC的发生风险更高,但也有可能是由于本研究人群PTC组的年龄低于良性结节组而造成的偏倚所致。
TG水平与PTC发生风险之间关联的生物学机制尚不清楚,目前认为可能与氧化应激、慢性炎症、胰岛素抵抗等因素有关。生理浓度的活性氧(reactive oxygen species,ROS)作为第二信使参与细胞增殖、基因表达、激素合成等,而高浓度的ROS则可通过DNA碱基修饰、缺失、链断裂等损伤DNA,如损伤发生在与细胞增殖或细胞存活有关的基因,则可能促进癌症的进展;甲状腺本身极易受氧化应激的影响,而TG水平升高可产生过量的ROS[23-24]。高甘油三酯血症或甘油三酯异位沉积破坏靶组织胰岛素信号转导均会引起胰岛素抵抗[25],高胰岛素血症会刺激细胞内信号通路PI3K/Akt/mTOR的持续激活,而该通路的多个组成部分已被证实是癌基因和肿瘤的抑制因子,可调控肿瘤发展过程中的关键通路[26]。有研究发现,PI3K/Akt/mTOR途径在甲状腺癌患者中持续激活[27]。此外,高甘油三酯血症可激活促炎通路IKK/IκB/NF-κB途径[28],而炎症本身也可参与肿瘤的发生、发展。
综上所述,本研究发现,在甲状腺自身抗体阴性、BMI<28 kg/m2的甲状腺结节手术人群中,血清TG水平升高与PTC发生风险增高有关。但本研究仍存在一定的局限性:为回顾性研究,TG水平与PTC之间的因果关系无法证实;基于单中心甲状腺结节手术人群纳入研究对象,且TG的数据缺失较多,可能存在一定的选择偏倚。由于本研究仅从流行病学角度进行分析,未来仍需通过前瞻性研究进一步验证TG与PTC之间的关联并评估其潜在机制。
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2023年第48卷第5期
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doi: 10.11855/j.issn.0577-7402.2023.05.0523
  • 接收时间:2023-01-03
  • 首发时间:2025-12-03
  • 出版时间:2023-05-28
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  • 收稿日期:2023-01-03
  • 录用日期:2023-03-20
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    1解放军总医院第一医学中心内分泌科,北京 100853
    2南开大学医学院,天津 300071

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