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Article(id=1323941239233577195, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1323941237702668764, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202506454, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1750780800000, receivedDateStr=2025-06-25, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1793581789072, onlineDateStr=2026-11-02, pubDate=1765296000000, pubDateStr=2025-12-10, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1793581789072, onlineIssueDateStr=2026-11-02, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1793581789072, creator=13701087609, updateTime=1793581789072, updator=13701087609, issue=Issue{id=1323941237702668764, tenantId=1146029695717560320, journalId=1227665162245664772, year='2025', volume='52', issue='23', pageStart='4225', pageEnd='4416', issueExtLink='null', onlineDate='null', pubDate='1765296000000', pubDateStr='2025-12-10', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1793581788707, creator='13701087609', updateTime=1793581887795, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext={EN=IssueExt(id=1323941653374959780, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1323941237702668764, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1323941653374959781, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1323941237702668764, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null, downloadFileDto=null}, startPage=4269, endPage=4276, ext={EN=ArticleExt(id=1323941242194755820, articleId=1323941239233577195, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=The positive association between circadian syndrome and metabolic dysfunction-associated steatotic liver disease: an analysis of the NHANES database, columnId=1240413921954295836, journalTitle=Modern Preventive Medicine, columnName=Epidemiology and Statistical Methods, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the association between circadian syndrome (CircS) and metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

Utilizing data from the 2017—2020 US National Health and Nutrition Examination Survey (NHANES), 2 060 adults aged ≥20 years were included. MASLD was diagnosed based on vibration-controlled transient elastography (CAP ≥274 dB/m) and metabolic risk criteria. CircS was defined as meeting ≥4 components (abdominal obesity,dyslipidemia, hypertension, hyperglycemia, sleep duration ≤6 h/day, depressive symptoms). Multivariable logistic regression was used to analyze the association between CircS, the number of CircS components, and MASLD [odds ratio (OR) and 95%confidence interval(CI)], adjusting for demographic and lifestyle confounders. Subgroup analyses were performed, and a MASLD risk prediction nomogram was constructed using LASSO-selected variables.

Results

Among the participants, 786 (38.2%) had MASLD and 839 (40.7%) had CircS. The fully adjusted model revealed a significant positive association between CircS and MASLD (OR=3.95, 95% CI: 3.19-4.90). The number of CircS components showed a dose-response relationship with the presence of MASLD (P for trend <0.05), with individuals having ≥6 components exhibiting the highest odds of MASLD (OR=8.35, 95% CI: 5.27-13.50). Subgroup analysis indicated a stronger association in younger adults aged <50 years (OR=5.69,95% CI: 4.12-7.87). The nomogram incorporating CircS demonstrated moderate predictive ability (training set AUC=0.715).

Conclusion

This study is the first to reveal an independent positive association between CircS and MASLD, particularly pronounced in younger adults, with a dose-response relationship. CircS may serve as a potential association marker for MASLD,suggesting that interventions targeting circadian rhythm disruption could represent a novel prevention and management strategy.

, authors=Jia-li HUANG, Hong LIU, authorsList=Jia-li HUANG, Hong LIU, authorCompany=null, correspAuthors=Hong LIU, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1323941243788591347, articleId=1323941239233577195, tenantId=1146029695717560320, journalId=1227665162245664772, language=CN, title=基于NHANES数据库的昼夜节律综合征与代谢功能障碍相关脂肪变性肝病的正相关性分析, columnId=1228016567632462653, journalTitle=现代预防医学, columnName=流行病与统计方法, runingTitle=null, highlight=null, articleAbstract=
目的

探讨昼夜节律综合征（circadian syndrome,CircS）与代谢功能障碍相关脂肪变性肝病（metabolic dysfunction-associated steatotic liver disease, MASLD）的相关性。

方法

基于2017-2020年美国国家营养健康调查（National Health and Nutrition Examination Survey，NHANES）数据，纳入2 060名≥20岁成人。MASLD依据振动控制瞬态弹性成像（CAP≥274 dB/m）及代谢风险标准诊断。CircS定义为满足 ≥4项组分（腹型肥胖、血脂异常、高血压、高血糖、睡眠≤6h/d、抑郁症状）。采用多变量logistic回归分析CircS及其组分数量与MASLD的关联（OR值及95% CI），调整人口学及生活方式等混杂因素。进行亚组分析并构建基于LASSO筛选变量的MASLD风险预测列线图。

结果

786人（38.2%）患MASLD，839人（40.7%）存在CircS。完全调整模型显示CircS与MASLD患病呈显著正相关（OR=3.95, 95% CI: 3.19～4.90）。CircS组分数量与MASLD患病呈剂量-反应正相关（P趋势<0.05），拥有≥6个组分者其MASLD患病几率最高（OR=8.35, 95% CI:5.27～13.50）。亚组分析提示年龄<50岁人群关联更强（OR=5.69, 95% CI: 4.12～7.87）。包含CircS的列线图预测效能中等（训练集曲线下面积=0.715）。

结论

本研究首次揭示CircS与MASLD患病之间存在独立正相关，尤其在年轻人群中关联显著，且存在剂量-反应关系。CircS可作为识别MASLD的一个潜在关联标志物，提示干预昼夜节律紊乱或为防治新策略。

, authors=黄嘉丽, 刘红, authorsList=黄嘉丽, 刘红, authorCompany=null, correspAuthors=刘红, authorNote=

黄嘉丽（1999—），女，硕士，医师，研究方向：代谢功能障碍相关脂肪变性肝病与炎症性肠病

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刘红，E-mail：
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黄嘉丽（1999—），女，硕士，医师，研究方向：代谢功能障碍相关脂肪变性肝病与炎症性肠病

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Frontiers in Physiology, 2024, 15: 1301450., articleTitle=Association between circadian syndrome and chronic diarrhea: a cross-sectional study of NHANES 2005-2010 data, refAbstract=null)], funds=null, companyList=[AuthorCompany(id=1323941244073804020, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, xref=null, ext=[AuthorCompanyExt(id=1323941244082192629, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, companyId=1323941244073804020, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China), AuthorCompanyExt(id=1323941244094775542, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, companyId=1323941244073804020, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=首都医科大学附属北京世纪坛医院消化内科，　北京　100038)])], figs=[ArticleFig(id=1323941245445341449, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Figure 1, caption=Participant selection flowchart, figureFileSmall=GzC4UB2kpaQ9TjoQItDwEQ==, figureFileBig=i023bGa3R/3xQsZcTK8czw==, tableContent=null), ArticleFig(id=1323941245525033226, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=图1, caption=研究样本筛选流程图, figureFileSmall=GzC4UB2kpaQ9TjoQItDwEQ==, figureFileBig=i023bGa3R/3xQsZcTK8czw==, tableContent=null), ArticleFig(id=1323941245726359819, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Figure 2, caption=LASSO regression analysis was used to screen the factors most associated with MASLD, and the results of the predictive modeling were based on this, figureFileSmall=LpjFwFRZU12rgKjiAimi+Q==, figureFileBig=2OEd9Br26GIQG2+5xGZpdQ==, tableContent=null), ArticleFig(id=1323941245827023116, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=图2, caption=采用 LASSO 回归分析筛选与MASLD最相关的因素及基于此构建预测模型

注：A为LASSO 回归系数图；B为交叉验证图；C为基于 LASSO 回归筛选出的关键饮食因素构建的列线图模型；D为用于评估本研究中列线图模型诊断效能的 ROC 曲线。

, figureFileSmall=LpjFwFRZU12rgKjiAimi+Q==, figureFileBig=2OEd9Br26GIQG2+5xGZpdQ==, tableContent=null), ArticleFig(id=1323941245919297805, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Figure 3, caption=Calibration curve of the internal validation model using the bootstrap method, figureFileSmall=wPMxl6waxms0nlR6y5apig==, figureFileBig=oZfSmhlVGYT6b2NdtnQl3w==, tableContent=null), ArticleFig(id=1323941245982212366, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=图3, caption=Bootstrap 法内部验证模型的校准曲线, figureFileSmall=wPMxl6waxms0nlR6y5apig==, figureFileBig=oZfSmhlVGYT6b2NdtnQl3w==, tableContent=null), ArticleFig(id=1323941246049321231, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Table 1, caption=

Baseline characteristics comparison of the MASLD group versus the non-MASLD group ［n（%）， M （P25， P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
特征MASLD（n=786）非MASLD（n=1 274）统计量P值
年龄（岁）53 (40, 64)46 (32, 61)-6.304<0.001
性别4.8750.027
男性399 (50.8)583 (45.8)
女性387 (49.2)691 (54.2)
种族34.977<0.001
墨西哥裔美国人134 (17.0)127 (10.0)
其他西班牙人70 (8.9)131 (10.3)
非西班牙白人312 (39.7)451 (35.4)
非西班牙黑人161 (20.5)349 (27.4)
非西班牙亚裔70 (8.9)142 (11.1)
其他39 (5.0)74 (5.8)
教育水平18.524<0.001
小于9年级学历43 (5.5)67 (5.3)
9～11年级学历76 (9.7)111 (8.7)
高中毕业生/ 同等学历或以下200 (25.4)258 (20.3)
部分大学教育或副学士学位287 (36.5)442 (34.7)
大学本科及以上学历180 (22.9)396 (31.1)
家庭年收入与贫困比2.5120.296
<1.3187 (23.8)306 (24.0)
1.3～3.5320 (40.7)478 (37.5)
> 3.5279 (35.5)490 (38.5)
婚姻状况26.616<0.001
已婚或同居526 (66.9)726 (57.0)
丧偶/离婚/分居154 (19.6)270 (21.2)
从未结婚106 (13.5)278 (21.8)
高血压113.865<0.001
是454 (57.8)438 (34.4)
否332 (42.2)836 (65.6)
糖尿病157.765<0.001
是279 (35.5)156 (12.2)
否507 (64.5)1 118 (87.8)
冠心病2.4250.119
是38 (4.8)44 (3.5)
否748 (95.2)1 230 (96.5)
吸烟状况12.046<0.001
是355 (45.2)477 (37.4)
否431 (54.8)797 (62.6)
久坐行为10.7880.001
轻度519 (66.0)928 (72.8)
中重度267 (34.0)346 (27.2)
高强度或中等强度身体活动20.893<0.001
是49 (6.2)159 (12.5)
否737 (93.8)1 115 (87.5)
昼夜节律综合征220.556<0.001
是481 (61.2)358 (28.1)
否305 (38.8)916 (71.9)
昼夜节律综合征成分236.719<0.001
≤3305 (38.8)916 (71.9)
4196 (24.9)189 (14.8)
5210 (26.7)138 (10.8)
≥675 (9.5)31 (2.4)
BMI（kg/m2）33 (29, 38)27 (23, 30)-21.619<0.001
ALT（U/L）21 (15, 32)16 (12, 22)-12.843<0.001
AST（U/L）20 (16, 25)19 (15, 22)-4.275<0.001
UA（μmol/L）345 (286, 405)303 (250, 357)-10.629<0.001
Cr（μmol/L）74 (61, 88)74 (64, 88)-1.6290.103
TC （mmol/L）4.71 (4.09, 5.48)4.60 (4.01, 5.33)-2.1620.031
), ArticleFig(id=1323941246233870608, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=表1, caption=

MASLD组与非 MASLD 组的基本特征对比［n（%），M（P25，P75）］

, figureFileSmall=null, figureFileBig=null, tableContent=
特征MASLD（n=786）非MASLD（n=1 274）统计量P值
年龄（岁）53 (40, 64)46 (32, 61)-6.304<0.001
性别4.8750.027
男性399 (50.8)583 (45.8)
女性387 (49.2)691 (54.2)
种族34.977<0.001
墨西哥裔美国人134 (17.0)127 (10.0)
其他西班牙人70 (8.9)131 (10.3)
非西班牙白人312 (39.7)451 (35.4)
非西班牙黑人161 (20.5)349 (27.4)
非西班牙亚裔70 (8.9)142 (11.1)
其他39 (5.0)74 (5.8)
教育水平18.524<0.001
小于9年级学历43 (5.5)67 (5.3)
9～11年级学历76 (9.7)111 (8.7)
高中毕业生/ 同等学历或以下200 (25.4)258 (20.3)
部分大学教育或副学士学位287 (36.5)442 (34.7)
大学本科及以上学历180 (22.9)396 (31.1)
家庭年收入与贫困比2.5120.296
<1.3187 (23.8)306 (24.0)
1.3～3.5320 (40.7)478 (37.5)
> 3.5279 (35.5)490 (38.5)
婚姻状况26.616<0.001
已婚或同居526 (66.9)726 (57.0)
丧偶/离婚/分居154 (19.6)270 (21.2)
从未结婚106 (13.5)278 (21.8)
高血压113.865<0.001
是454 (57.8)438 (34.4)
否332 (42.2)836 (65.6)
糖尿病157.765<0.001
是279 (35.5)156 (12.2)
否507 (64.5)1 118 (87.8)
冠心病2.4250.119
是38 (4.8)44 (3.5)
否748 (95.2)1 230 (96.5)
吸烟状况12.046<0.001
是355 (45.2)477 (37.4)
否431 (54.8)797 (62.6)
久坐行为10.7880.001
轻度519 (66.0)928 (72.8)
中重度267 (34.0)346 (27.2)
高强度或中等强度身体活动20.893<0.001
是49 (6.2)159 (12.5)
否737 (93.8)1 115 (87.5)
昼夜节律综合征220.556<0.001
是481 (61.2)358 (28.1)
否305 (38.8)916 (71.9)
昼夜节律综合征成分236.719<0.001
≤3305 (38.8)916 (71.9)
4196 (24.9)189 (14.8)
5210 (26.7)138 (10.8)
≥675 (9.5)31 (2.4)
BMI（kg/m2）33 (29, 38)27 (23, 30)-21.619<0.001
ALT（U/L）21 (15, 32)16 (12, 22)-12.843<0.001
AST（U/L）20 (16, 25)19 (15, 22)-4.275<0.001
UA（μmol/L）345 (286, 405)303 (250, 357)-10.629<0.001
Cr（μmol/L）74 (61, 88)74 (64, 88)-1.6290.103
TC （mmol/L）4.71 (4.09, 5.48)4.60 (4.01, 5.33)-2.1620.031
), ArticleFig(id=1323941246313562385, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Table 2, caption=

Baseline characteristics comparison of the CircS group versus the non-CircS group ［M （P25， P75）， n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
CircS（n=839）非CircS（n=1 221）统计量P值
年龄（岁）60 (45, 69)42 (29, 56)-18.288<0.001
性别0.5100.475
男392 (46.7)590 (48.3)
女447 (53.3)631 (51.7)
种族13.5970.018
墨西哥裔美国人102 (12.2)159 (13.0)
其他西班牙人83 (9.9)118 (9.7)
非西班牙白人337 (40.2)426 (34.9)
非西班牙黑人210 (25.0)300 (24.6)
非西班牙亚裔65 (7.7)147 (12.0)
其他42 (5.0)71 (5.8)
教育水平25.396<0.001
小于9年级学历55 (6.6)55 (4.5)
9 ～11 年级85 (10.1)102 (8.4)
高中毕业生/ 同等学历或以下204 (24.3)254 (20.8)
部分大学教育或副学士学位308 (36.7)421 (34.5)
大学本科及以上学历187 (22.3)389 (31.9)
家庭年收入与贫困比5.1280.080
< 1.3211 (25.1)282 (23.1)
1.3 ～ 3.5339 (40.4)459 (37.6)
> 3.5289 (34.4)480 (39.3)
婚姻状况61.102<0.001
已婚或同居514 (61.3)738 (60.4)
丧偶/离婚/分居225 (26.8)199 (16.3)
从未结过婚100 (11.9)284 (23.3)
高血压529.611<0.001
是609 (72.6)283 (23.2)
否230 (27.4)938 (76.8)
糖尿病304.551<0.001
是336 (40.0)99 (8.1)
否503 (60.0)1 122 (91.9)
冠心病55.924<0.001
是66 (7.9)16 (1.3)
否773 (92.1)1 205 (98.7)
吸烟状况20.999<0.001
是389 (46.4)443 (36.3)
否450 (53.6)778 (63.7)
久坐行为2.5670.109
轻度573 (68.3)874 (71.6)
中重度266 (31.7)347 (28.4)
高强度或中等强度身体活动22.281<0.001
是53 (6.3)155 (12.7)
否786 (93.7)1 066 (87.3)
MASLD220.556<0.001
是481 (57.3)305 (25.0)
否358 (42.7)916 (75.0)
BMI（kg/m2）31 (28, 37)27 (23, 31)-16.173<0.001
ALT（U/L）19 (14, 28)16 (12, 24)-6.191<0.001
AST（U/L）19 (16, 24)19 (16, 23)-1.4830.138
UA（μmol/L）333 (280, 399)303 (250, 363)-7.702<0.001
Cr（μmol/L）76 (64, 91)73 (63, 85)-3.304<0.001
TC（mmol/L）4.63 (3.93, 5.48)4.71 (4.09, 5.35)-0.8010.423
), ArticleFig(id=1323941246384865554, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=表2, caption=

CircS组与非CircS组的基线特征对比［M（P25，P75），n（%）］

, figureFileSmall=null, figureFileBig=null, tableContent=
CircS（n=839）非CircS（n=1 221）统计量P值
年龄（岁）60 (45, 69)42 (29, 56)-18.288<0.001
性别0.5100.475
男392 (46.7)590 (48.3)
女447 (53.3)631 (51.7)
种族13.5970.018
墨西哥裔美国人102 (12.2)159 (13.0)
其他西班牙人83 (9.9)118 (9.7)
非西班牙白人337 (40.2)426 (34.9)
非西班牙黑人210 (25.0)300 (24.6)
非西班牙亚裔65 (7.7)147 (12.0)
其他42 (5.0)71 (5.8)
教育水平25.396<0.001
小于9年级学历55 (6.6)55 (4.5)
9 ～11 年级85 (10.1)102 (8.4)
高中毕业生/ 同等学历或以下204 (24.3)254 (20.8)
部分大学教育或副学士学位308 (36.7)421 (34.5)
大学本科及以上学历187 (22.3)389 (31.9)
家庭年收入与贫困比5.1280.080
< 1.3211 (25.1)282 (23.1)
1.3 ～ 3.5339 (40.4)459 (37.6)
> 3.5289 (34.4)480 (39.3)
婚姻状况61.102<0.001
已婚或同居514 (61.3)738 (60.4)
丧偶/离婚/分居225 (26.8)199 (16.3)
从未结过婚100 (11.9)284 (23.3)
高血压529.611<0.001
是609 (72.6)283 (23.2)
否230 (27.4)938 (76.8)
糖尿病304.551<0.001
是336 (40.0)99 (8.1)
否503 (60.0)1 122 (91.9)
冠心病55.924<0.001
是66 (7.9)16 (1.3)
否773 (92.1)1 205 (98.7)
吸烟状况20.999<0.001
是389 (46.4)443 (36.3)
否450 (53.6)778 (63.7)
久坐行为2.5670.109
轻度573 (68.3)874 (71.6)
中重度266 (31.7)347 (28.4)
高强度或中等强度身体活动22.281<0.001
是53 (6.3)155 (12.7)
否786 (93.7)1 066 (87.3)
MASLD220.556<0.001
是481 (57.3)305 (25.0)
否358 (42.7)916 (75.0)
BMI（kg/m2）31 (28, 37)27 (23, 31)-16.173<0.001
ALT（U/L）19 (14, 28)16 (12, 24)-6.191<0.001
AST（U/L）19 (16, 24)19 (16, 23)-1.4830.138
UA（μmol/L）333 (280, 399)303 (250, 363)-7.702<0.001
Cr（μmol/L）76 (64, 91)73 (63, 85)-3.304<0.001
TC（mmol/L）4.63 (3.93, 5.48)4.71 (4.09, 5.35)-0.8010.423
), ArticleFig(id=1323941246464557331, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Table 3, caption=

Logistic regression analysis of the association between CircS and MASLD

, figureFileSmall=null, figureFileBig=null, tableContent=
变量模型 1模型2模型3
OR95% CIP值OR95% CIP值OR95% CIP值
CirsS
否——————
是4.043.35～4.88<0.0014.113.33～5.07<0.0013.953.19～4.90<0.001
CircS成分（个）
≤3——————
43.112.46～3.95<0.0013.132.43～4.03<0.0012.972.30～3.85<0.001
54.573.56～5.88<0.0014.833.68～6.37<0.0014.623.50～6.12<0.001
≥67.274.73～11.40<0.0017.825.00～12.49<0.0018.355.27～13.50<0.001
P趋势值<0.001<0.001<0.001
), ArticleFig(id=1323941246661689620, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=表3, caption=

CircS和MASLD之间的关系logistic回归分析结果

, figureFileSmall=null, figureFileBig=null, tableContent=
变量模型 1模型2模型3
OR95% CIP值OR95% CIP值OR95% CIP值
CirsS
否——————
是4.043.35～4.88<0.0014.113.33～5.07<0.0013.953.19～4.90<0.001
CircS成分（个）
≤3——————
43.112.46～3.95<0.0013.132.43～4.03<0.0012.972.30～3.85<0.001
54.573.56～5.88<0.0014.833.68～6.37<0.0014.623.50～6.12<0.001
≥67.274.73～11.40<0.0017.825.00～12.49<0.0018.355.27～13.50<0.001
P趋势值<0.001<0.001<0.001
), ArticleFig(id=1323941246741381397, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=EN, label=Table 4, caption=

Association between CircS and MASLD in different subgroups

, figureFileSmall=null, figureFileBig=null, tableContent=
亚组OR (95% CI)P值P交互值
年龄（岁）0.003
<505.69 (4.12～7.87)<0.001
≥ 503.00 (2.28～3.95)<0.001
性别0.496
男性3.82 (2.81～5.18)<0.001
女性3.93 (2.88～5.35)<0.001
种族0.993
墨西哥裔美国人5.37 (2.74～10.52)<0.001
其他西班牙人3.04 (1.49～6.21)0.002
非西班牙白人4.08 (2.88～5.77)<0.001
非西班牙黑人3.32 (2.13～5.17)<0.001
非西班牙亚裔4.80 (2.20～10.48)<0.001
其他3.82 (1.28～11.44)0.016
教育水平0.856
小于9年级学历5.61 (1.85～17.07)0.002
9～11年级学历5.18 (2.51～10.69)<0.001
高中毕业生/ 同等学历或以下4.36 (2.69～7.04)<0.001
部分大学教育或副学士学位4.39 (3.03～6.36)<0.001
大学本科及以上学历2.97 (1.97～4.46)<0.001
婚姻状况0.111
已婚或同居3.54 (2.71～4.61)<0.001
丧偶/离婚/分居3.74 (2.33～6.00)<0.001
从未结过婚6.95 (3.78～12.78)<0.001
吸烟状况0.407
是5.08 (3.62～7.13)<0.001
否3.52 (2.65～4.67)<0.001
久坐行为0.753
轻度4.06 (3.13～5.27)<0.001
中重度3.90 (2.66～5.74)<0.001
高强度或中等强度身体活动0.212
是3.82 (3.06～4.76)<0.001
否6.97 (2.62～18.53)<0.001
), ArticleFig(id=1323941246821073174, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1323941239233577195, language=CN, label=表4, caption=

不同亚组中CircS 和MASLD的关系

, figureFileSmall=null, figureFileBig=null, tableContent=
亚组OR (95% CI)P值P交互值
年龄（岁）0.003
<505.69 (4.12～7.87)<0.001
≥ 503.00 (2.28～3.95)<0.001
性别0.496
男性3.82 (2.81～5.18)<0.001
女性3.93 (2.88～5.35)<0.001
种族0.993
墨西哥裔美国人5.37 (2.74～10.52)<0.001
其他西班牙人3.04 (1.49～6.21)0.002
非西班牙白人4.08 (2.88～5.77)<0.001
非西班牙黑人3.32 (2.13～5.17)<0.001
非西班牙亚裔4.80 (2.20～10.48)<0.001
其他3.82 (1.28～11.44)0.016
教育水平0.856
小于9年级学历5.61 (1.85～17.07)0.002
9～11年级学历5.18 (2.51～10.69)<0.001
高中毕业生/ 同等学历或以下4.36 (2.69～7.04)<0.001
部分大学教育或副学士学位4.39 (3.03～6.36)<0.001
大学本科及以上学历2.97 (1.97～4.46)<0.001
婚姻状况0.111
已婚或同居3.54 (2.71～4.61)<0.001
丧偶/离婚/分居3.74 (2.33～6.00)<0.001
从未结过婚6.95 (3.78～12.78)<0.001
吸烟状况0.407
是5.08 (3.62～7.13)<0.001
否3.52 (2.65～4.67)<0.001
久坐行为0.753
轻度4.06 (3.13～5.27)<0.001
中重度3.90 (2.66～5.74)<0.001
高强度或中等强度身体活动0.212
是3.82 (3.06～4.76)<0.001
否6.97 (2.62～18.53)<0.001
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黄嘉丽 , 刘红
现代预防医学 | 流行病与统计方法 2025,52(23): 4269-4276
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现代预防医学 |流行病与统计方法 2025 , 52 (23) : 4269 -4276
基于NHANES数据库的昼夜节律综合征与代谢功能障碍相关脂肪变性肝病的正相关性分析
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黄嘉丽（1999—），女，硕士，医师，研究方向：代谢功能障碍相关脂肪变性肝病与炎症性肠病

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黄嘉丽（1999—），女，硕士，医师，研究方向：代谢功能障碍相关脂肪变性肝病与炎症性肠病

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黄嘉丽, 刘红
作者信息
  • 首都医科大学附属北京世纪坛医院消化内科，　北京　100038
通讯作者:
刘红，E-mail：
作者简介:

黄嘉丽（1999—），女，硕士，医师，研究方向：代谢功能障碍相关脂肪变性肝病与炎症性肠病

The positive association between circadian syndrome and metabolic dysfunction-associated steatotic liver disease: an analysis of the NHANES database
Jia-li HUANG, Hong LIU
Affiliations
  • Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
出版时间: 2025-12-10 doi: 10.20043/j.cnki.MPM.202506454
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摘要
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目的

探讨昼夜节律综合征（circadian syndrome,CircS）与代谢功能障碍相关脂肪变性肝病（metabolic dysfunction-associated steatotic liver disease, MASLD）的相关性。

方法

基于2017-2020年美国国家营养健康调查（National Health and Nutrition Examination Survey，NHANES）数据，纳入2 060名≥20岁成人。MASLD依据振动控制瞬态弹性成像（CAP≥274 dB/m）及代谢风险标准诊断。CircS定义为满足 ≥4项组分（腹型肥胖、血脂异常、高血压、高血糖、睡眠≤6h/d、抑郁症状）。采用多变量logistic回归分析CircS及其组分数量与MASLD的关联（OR值及95% CI），调整人口学及生活方式等混杂因素。进行亚组分析并构建基于LASSO筛选变量的MASLD风险预测列线图。

结果

786人（38.2%）患MASLD，839人（40.7%）存在CircS。完全调整模型显示CircS与MASLD患病呈显著正相关（OR=3.95, 95% CI: 3.19～4.90）。CircS组分数量与MASLD患病呈剂量-反应正相关（P趋势<0.05），拥有≥6个组分者其MASLD患病几率最高（OR=8.35, 95% CI:5.27～13.50）。亚组分析提示年龄<50岁人群关联更强（OR=5.69, 95% CI: 4.12～7.87）。包含CircS的列线图预测效能中等（训练集曲线下面积=0.715）。

结论

本研究首次揭示CircS与MASLD患病之间存在独立正相关，尤其在年轻人群中关联显著，且存在剂量-反应关系。CircS可作为识别MASLD的一个潜在关联标志物，提示干预昼夜节律紊乱或为防治新策略。

昼夜节律综合征  /  代谢功能障碍相关脂肪变性肝病  /  NHANES  /  风险预测模型
Objective

To investigate the association between circadian syndrome (CircS) and metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

Utilizing data from the 2017—2020 US National Health and Nutrition Examination Survey (NHANES), 2 060 adults aged ≥20 years were included. MASLD was diagnosed based on vibration-controlled transient elastography (CAP ≥274 dB/m) and metabolic risk criteria. CircS was defined as meeting ≥4 components (abdominal obesity,dyslipidemia, hypertension, hyperglycemia, sleep duration ≤6 h/day, depressive symptoms). Multivariable logistic regression was used to analyze the association between CircS, the number of CircS components, and MASLD [odds ratio (OR) and 95%confidence interval(CI)], adjusting for demographic and lifestyle confounders. Subgroup analyses were performed, and a MASLD risk prediction nomogram was constructed using LASSO-selected variables.

Results

Among the participants, 786 (38.2%) had MASLD and 839 (40.7%) had CircS. The fully adjusted model revealed a significant positive association between CircS and MASLD (OR=3.95, 95% CI: 3.19-4.90). The number of CircS components showed a dose-response relationship with the presence of MASLD (P for trend <0.05), with individuals having ≥6 components exhibiting the highest odds of MASLD (OR=8.35, 95% CI: 5.27-13.50). Subgroup analysis indicated a stronger association in younger adults aged <50 years (OR=5.69,95% CI: 4.12-7.87). The nomogram incorporating CircS demonstrated moderate predictive ability (training set AUC=0.715).

Conclusion

This study is the first to reveal an independent positive association between CircS and MASLD, particularly pronounced in younger adults, with a dose-response relationship. CircS may serve as a potential association marker for MASLD,suggesting that interventions targeting circadian rhythm disruption could represent a novel prevention and management strategy.

Circadian syndrome  /  Metabolic dysfunction-associated steatotic liver disease  /  NHANES  /  Risk prediction model
黄嘉丽, 刘红. 基于NHANES数据库的昼夜节律综合征与代谢功能障碍相关脂肪变性肝病的正相关性分析. 现代预防医学, 2025 , 52 (23) : 4269 -4276 . DOI: 10.20043/j.cnki.MPM.202506454
Jia-li HUANG, Hong LIU. The positive association between circadian syndrome and metabolic dysfunction-associated steatotic liver disease: an analysis of the NHANES database[J]. Modern Preventive Medicine, 2025 , 52 (23) : 4269 -4276 . DOI: 10.20043/j.cnki.MPM.202506454
正文
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代谢功能障碍相关脂肪变性肝病（metabolic dysfunction-associated steatotic liver disease, MASLD）定义为至少存在一种心脏代谢风险因素的情况下肝脏中脂质的过度积累[1]。MASLD过去称为非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）、代谢功能障碍相关脂肪性肝病（metabolic dysfunction-associated fatty liver disease, MAFLD），现已成为全球慢性肝病的主要形式，到2040年成人患病率预计将增加到55%以上[2]。MASLD的发病机制呈现多因素交互特征，现有证据表明其涉及胰岛素抵抗（insulin resistance, IR）、代谢紊乱、氧化应激及肠道菌群失调等多种因素[1,3]。
昼夜节律是一种内在调节机制，对肝脏代谢的调节有着深远的影响。肝脏的生物钟受下丘脑视交叉上核(suprachiasmatic nucleus，SCN)主生物钟的调控，通过调控肝脏自身的基因表达、代谢活动及能量消耗等途径维持局部和全身稳态[4]。自然昼夜节律的破坏对健康产生负面影响，可导致代谢紊乱、炎症、心血管、神经和恶性疾病的风险增加[5-7]。鉴于昼夜节律紊乱与代谢综合征核心组分（如肥胖、血糖异常、血脂异常、高血压）以及睡眠障碍、情绪障碍等存在密切关联，研究者逐渐提出了整合这些因素的新概念——昼夜节律综合征（circadian syndrome,CircS），用以综合评估昼夜节律失调对代谢健康的整体影响[6,8]。肝脏生物钟失调已被证实促进代谢综合征及MASLD发生[6,8]。
尽管如此，CircS作为一个整体性概念，其与MASLD患病风险之间的直接关联尚未在人群研究中得到充分探讨。 因此，本研究旨在基于2017-2020年美国国家健康与营养调查（National Health and Nutrition Examination Survey,NHANES）数据，采用横断面研究设计，探讨CircS与MASLD之间的关联，以期为MASLD的防治提供新思路。
1　材料与方法
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1.1　研究人群
我们选定2017-2020年周期的连续NHANES数据，涉及15 560名参与者，排除缺乏MASLD诊断数据、缺乏定义CircS成分以及协变量的数据，最终纳入了2 060人。见图1。
1.2　 研究变量
本研究中的肝脂肪变性通过影像学振动控制瞬态弹性成像（vibration-controlled transient elastography,VCTE）定义，在2017-2020周期中，NHANES技术人员使用带有中型（M）和超大型（XL）探头的FibroScan ® 502 V2 Touch（Echosens）进行了VCTE从而测得控制衰减指数（compensated attenuation parameter，CAP）。MASLD 的定义基于排除大量饮酒、病毒性肝炎等肝脏疾病，满足CAP≥274 dB/m，且满足以下条件之一[1,9]：（1）身体质量指数（body mass index，BMI）≥25 kg/m2或男性腰围 ≥94 cm、女性腰围≥80 cm的个体;（2）空腹血糖水平≥100 mg/dl（5.6mmol/L） 或糖化血红蛋白（glycated hemoglobin,HbA1c）水平≥5.7%，或有2型糖尿病诊断史或目前正在治疗2型糖尿病;（3）血压水平≥130/85 mm Hg 或目前正在治疗高血压;（4）甘油三酯水平≥1.70 mmol/L（150mg/dl）或接受降脂治疗的个体;（5） 高密度脂蛋白胆固醇（high-density lipoprotein cholesterol,HDL-C）水平低，男性<1.0 mmol/L（40 mg/dl）、女性<1.3 mmol/L（50 mg/dl），或接受降脂治疗者。
CircS根据以下诊断标准定义为≥4个组成部分[5]：（1）女性腰围≥88 cm，男性腰围≥102 cm；（2）甘油三酯≥150 mg/dl或使用降脂药物；（3）HDL-C水平降低（男性<40 mg/dl，女性<50 mg/dl）或使用降脂药物；（4）血压升高（收缩压≥130 mm Hg或舒张压≥85 mm Hg）或使用降压药；（5）空腹血糖≥100 mg/dl或使用降糖药物；（6）睡眠时间≤6 h/d；（7）抑郁症状（患者健康问卷-9[PHQ-9] 评分≥10）。
1.3　协变量
本研究考虑的这些协变量包括年龄、性别、种族、教育程度、收入贫困比（poverty income ratio,PIR）、婚姻状态、BMI、VCTE、丙氨酸氨基转移酶、天冬氨酸转氨酶、尿酸、血清肌酐、总胆固醇、丙型肝炎 RNA、丙型肝炎抗体、乙型肝炎表面抗原、吸烟、饮酒、肝炎、高血压、糖尿病、冠心病、肝病和久坐行为。
1.4　统计方法
连续变量根据正态性检验结果，以（均值±标准差）或中位数（四分位距）描述，组间比较分别采用两独立样本t检验或秩和检验。分类变量采用频数（构成比）进行描述，采用χ2检验进行组间差异比较，当期望频数小于5时则采用Fisher精确检验。构建三个多变量logistic回归模型以评估CircS与MASLD的关联，计算比值比（odds ratio,OR）及其95%置信区间（confidence interval,CI）。模型1属于基础模型，未纳入任何调整因素；模型2引入性别、年龄、种族作为调整变量；模型3则在模型2的基础上进一步调整了PIR、教育水平、婚姻状态、吸烟、久坐行为、剧烈或中等运动量。本文还采用分层因素展开亚组分析与交互作用检验，分层因素涵盖性别、年龄、种族、教育程度、婚姻状态、吸烟状况、久坐行为、剧烈或中等运动量等关键维度。采用最小绝对收缩和选择算子（least absolute shrinkage and selection operator,LASSO）回归筛选与MASLD相关的预测变量（包括所有协变量及CircS）。通过10折交叉验证确定最优惩罚参数λ（lambda），设置最大迭代次数为1 000次，见图1A。基于LASSO回归筛选出的6个显著预测因子（种族、婚姻状态、吸烟状态、久坐行为、中高强度体力活动、CircS），构建预测MASLD风险的列线图模型。在训练集中通过绘制受试者工作特征（receiver operating characteristic,ROC）曲线并计算曲线下面积 （area under the curve,AUC）评估列线图模型区分MASLD的能力.
所有统计分析均使用R软件（版本4.2.2）进行，主要应用glmnet包（LASSO回归）、rms包（列线图构建与验证）等。
2　结果
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2.1　研究人群的基线特征
本研究共纳入2 060名研究对象，其中786名（38.2%）诊断为MASLD，1 274名（61.8%）为非MASLD。参与者年龄≥20岁，中位年龄49岁，男性占47.7%，女性占52.3%。基线特征比较见表1。与非MASLD组相比，MASLD组参与者年龄更大，男性比例更高，且高血压、糖尿病、冠心病患病率以及当前吸烟率均显著更高（P<0.05）。此外，MASLD组CircS患病率显著高于非MASLD组（P<0.05）。按CircS状态分组的特征见表2。总体CircS患病率为40.7%，CircS患者中MASLD患病率显著高于非CircS患者（P<0.05）。
2.2　Circs和MASLD之间的关系
CircS与MASLD的关联分析结果见表3。模型1（未调整）显示CircS与MASLD患病显著正相关（OR=4.04, 95% CI: 3.35～4.88）。调整年龄、性别、种族后（模型2），关联强度略有上升（OR=4.11, 95% CI: 3.33～5.07）。进一步调整社会经济及行为因素后（模型3），正相关依然显著（OR=3.95, 95% CI: 3.19～4.90）。CircS组分数量与MASLD患病呈显著剂量反应关系（P趋势<0.05）。与CircS组分≤3个的个体相比，拥有≥6个组分的个体其MASLD患病优势最高（OR=8.35, 95% CI: 5.27～13.50）。
2.3　亚组分析
基于模型3进行亚组分析及交互作用检验，见表4。亚组分析显示，在年龄<50岁的参与者中，CircS与MASLD的关联最强（OR=5.69, 95% CI:4.12～7.87, P<0.001）。交互作用检验表明，年龄分层（<50岁 vs. ≥50岁）对CircS与MASLD的关联存在显著交互效应（P交互<0.05）。而在性别、种族、教育程度、婚姻状态、吸烟状况、久坐行为、中高强度体力活动等分层因素上，未观察到显著的交互作用（P交互 >0.05），提示CircS与MASLD的正相关在这些亚组间相对稳定。
2.4　LASSO 回归和列线图模型
将全部样本按7:3随机分为训练集（n=1 442）和验证集（n=618）。采用LASSO回归筛选MASLD预测变量。LASSO系数收缩路径见图2A。通过10折交叉验证确定最优惩罚参数λ（λ=0.0260），其对应的模型平均误差最小，见图2B。最终筛选出6个预测因子：种族、婚姻状态、吸烟状态、久坐行为、中高强度体力活动、CircS。基于这些因子构建MASLD风险预测列线图，见图2C。在训练集中，模型区分MASLD的ROC的AUC为0.715(95% CI: 0.688～0.742)，验证集AUC为0.731（95% CI: 0.691～0.772），见图2D。Bootstrap法（1 000次重复抽样）内部验证的校准曲线显示预测风险与实际风险具有良好的一致性，见图3。
3　讨论
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既往研究多聚焦于MASLD与单一风险因素（如代谢综合征、睡眠不足或抑郁）的关联。相比之下，本研究创新性地将代谢综合征核心组分、睡眠障碍及抑郁症状整合于CircS这一统一框架内，探讨其与MASLD的整体关联。基于美国NHANES 2017-2020大样本横断面数据，本研究首次揭示了CircS与MASLD患病之间存在独立正相关，且这种关联在年龄<50岁的年轻人群中尤为显著。值得注意的是，CircS组分数量的增加与MASLD患病呈显著剂量反应关系。
昼夜节律紊乱对代谢健康的负面影响已被广泛证实。多种因素，如不良睡眠习惯、夜间人造光（artificial light at night,ALAN）暴露、轮班工作及遗传易感性等，均可导致内源性昼夜节律与外环境光暗周期失同步，引发昼夜节律紊乱[10]，其与代谢综合征、糖尿病、抑郁症及心血管疾病等风险的增加密切相关[11-13]。大量研究证实昼夜节律紊乱与代谢综合征及其核心组分（肥胖、高血压、高血糖、血脂异常）密切相关[6-7,14-15]。动物研究表明，ALAN暴露可扰乱下丘脑SCN主生物钟及外周（如肝脏、脂肪组织）生物钟节律，改变摄食模式，导致体重增加和代谢紊乱[16]。在人类中，昼夜节律紊乱同样被证实与肝脏脂肪变性、炎症反应激活及纤维化进展密切相关[17]。其潜在的分子机制可能涉及生物钟对肝脏代谢的精细调控：核心时钟基因（如CLOCK, BMAL1）通过节律性调控脂质代谢关键转录因子（如SREBP, PPAR）的表达以维持肝脏脂质稳态[18-20]；同时，胆汁酸合成与代谢的关键酶也受时钟基因的节律性调控[21]，节律紊乱可致胆汁酸代谢失衡，促进脂肪肝形成。
此外，CircS与MASLD的关联可能部分通过肠道菌群介导。研究显示，睡眠不足等导致昼夜节律紊乱的因素可显著降低肠道菌群多样性，导致厚壁菌门与拟杆菌门比值（F/B）升高，伴有潜在有益菌减少和潜在有害菌增加，加剧肠道炎症及通透性[22-23]。肠道菌群失调已被公认可通过肠-肝轴等多种机制促进MASLD的发生发展[24-25]。
随着CircS概念的提出及其作为评估昼夜节律紊乱综合影响的指标被接受，其与其他疾病的关联研究日益增多。例如，Shi等[5,26]发现CircS在中美人群中预测心血管疾病的价值优于传统代谢综合征；Feng等[7]报道CircS与胆结石风险呈正相关，尤其在女性和体力活动不足者中；Ding等[27]则发现CircS与美国成人慢性腹泻风险增加相关，尤其在高血压患者中。然而，CircS与MASLD的直接关联尚未在人群研究中得到充分探讨。 本研究的优势在于利用具有全国代表性的NHANES数据库，首次量化了CircS与MASLD的关联强度及剂量反应模式，提示CircS可能作为识别MASLD高危人群的一个新颖且简便的临床指标。但未来需在不同人群（如不同种族、地域）中验证此关联的普适性。
本研究存在一定局限性：首先，横断面设计无法推断CircS与MASLD的因果关系，仅能揭示二者之间的关联性。其次，睡眠时长依赖自我报告，抑郁症状评估采用PHQ-9≥10分（对应中度以上抑郁）而非临床诊断，且未使用体动记录仪等客观监测昼夜节律相位。最后，本研究的CircS定义中PHQ-9临界值设定为10分，可能低估了轻度抑郁障碍的影响。未来研究需结合体动记录仪、暗光褪黑素起始时间等客观昼夜节律标志物以及标准化临床抑郁评估，并通过前瞻性队列进一步探讨CircS与MASLD的纵向关联及潜在因果方向。
总之，本研究发现CircS与MASLD存在独立正相关，尤其在年轻人群中关联显著，且存在剂量反应关系。这为MASLD的早期筛查提供了新思路，推荐对CircS人群（尤其年轻个体）可考虑进行肝脂肪变性评估。基于已有的生物学通路证据，干预昼夜节律紊乱（如限制夜间光暴露、维持规律睡眠-觉醒周期）或许可作为防治MASLD的潜在策略。

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2025年第52卷第23期
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doi: 10.20043/j.cnki.MPM.202506454
  • 接收时间：2025-06-25
  • 首发时间：2026-11-02
  • 出版时间：2025-12-10
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    首都医科大学附属北京世纪坛医院消化内科，　北京　100038

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species		 占总种数比例
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total species (%)		 属
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Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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