BACKGROUND:This study aims to guide the diagnosis and treatment of hepatolenticular degeneration (also named Wilson's disease, WD) and aid multidisciplinary clinicians in making reasonable and personalized treatment regimens. OBJECTIVES:The authors aim to establish a systemic structure for Chinese Multidisciplinary Expert Consensus on Diagnosis and Treatment of Hepatolenticular Degeneration. METHODS:We collaborated with experts from relevant branches of the Chinese Medical Association and multiple disciplines, along with statistical experts, to formulate this consensus. It is based on advancements in basic and clinical research on Wilson's disease, both domestically and internationally. RESULTS:It mainly consists of clinical manifestations, diagnosis, differential diagnosis, management, and prognosis in the context of Multi-Department treatment (MDT) in China. CONCLUSION:This Chinese consensus incorporates four decades of institutional experience with thousands of Chinese Wilson's disease (WD) inpatients, as well as decades of international inpatient cases from East to West. It is hoped that this consensus will garner broader attention from clinicians worldwide.

Wilson disease is a rare neurogenetic disorder that receives significant attention due to its manifestations, such as jaundice, cirrhosis, tremor, dystonia, and others. However, the impact of Wilson disease on sexual function has been overlooked. In this study, we aimed to investigate current status of sexual dysfunction in Wilson disease. In this study, we investigated the sexual function status and possible influencing factors of 245 Wilson disease patients by questionnaire. Our study identified sexual dysfunction as a prevalent issue in Wilson disease patients, with an overall prevalence of 49.0 %, of which 33.9 % in males and 63.7 % in females, both higher than the prevalence of sexual dysfunction in the normal Chinese population. Compared with non-sexual dysfunction patients, sexual dysfunction was more common in the older age group, females, less educated, rural residence, no occupation, lower income, taking sedatives/antipsychotics, and high SIS scores (P < 0.05). Our binary logistic regression analysis revealed that older age (OR: 1.103, 95 %CI: 1.058-1.151, P < 0.001), being female (OR: 5.900,95 %CI: 2.966-11.736, P < 0.001), and the use of antipsychotics or sedatives (OR: 3.277,95 %CI: 1.065-10.077, P < 0.05) were all positively linked with an increased risk of sexual dysfunction. Despite the well-known symptoms of Wilson disease, sexual dysfunction is also a frequent issue in Wilson disease patients, necessitating further attention.

Methods:We retrospectively screened individuals with serum Cp ≥ 140 mg/L from 1032 WD patients who were hospitalised for the first time. Logistic regression analyses were performed in a case-control study between the WD cohort and another liver disease cohort to explore the independent risk factors for WD diagnosis and establish a regression model to identify them. The follow-up medical records of the WD cohort were subjected to mixed-effects model analysis in a longitudinal study to discover factors associated with Cp normalisation.Results:Eighty-six WD patients and their 353 medical records and another 98 non-WD liver disease patients were included in the present study. Cp normalisation was significantly associated with the copper burden and liver function indexes, such as urinary copper, γ-glutamyltransferase, and albumin (p ≤ 0.001). Logistic regression analysis showed that age and serum creatinine (p ≤ 0.001) were independent risk factors associated with WD. The AUC value of the regression model in the total cohort was 0.926 (p ≤ 0.001). At a cutoff value of ≥0.617 and ≥-1, the positive and negative predictive values were both 90.8% for WD.Conclusion:Increased serum Cp in WD patients is related to excessive copper burden and hepatic injury, and common tests can effectively distinguish WD patients from other liver injury patients.

Background:Hepatolenticular degeneration (HLD) is an inherited disorder caused by the mutation in the adenosine triphosphatase copper transporting β gene (ATP7B). W aimed to explore the genetic changes in HLD using bioinformatics analysis.Methods:The study was conducted in Nepal, in 2019. The GSE107323 dataset was downloaded and the differentially expressed lncRNAs (DElncRNAs) as well as differentially expressed genes (DEGs) induced by ATP7B knockout (KO) and copper toxicity were clustered using Mfuzz clustering analysis. LncRNAs and genes with high coexpression (correlation coefficient > 0.9) and pathways involving the DEGs were used to construct the lncRNA-gene-pathway network.Results:ATP7B KO and ATP7B KO + copper induced 51 overlapping DEGs and 687 overlapping DElncRNAs, respectively. Mfuzz analysis identified four clusters, including two clusters of consistently upregulated and downregulated DEGs/DElncRNAs. The lncRNA-gene-pathway network consisted of 13 DElncRNAs, 10 DEGs, and two pathways, including "hsa04630: Jak-STAT signaling pathway" and "hsa04920: Adipocytokine signaling pathway". Eight downregulated genes, including erythropoietin (EPO), insulin receptor substrate 1 (IRS1), and PPARG coactivator 1 alpha (PPARGC1A), and two upregulated genes (cardiotrophin-like cytokine factor 1 and cyclin D3) were involved in the two pathways. These genes were targeted by multiple lncRNAs, including PCAT6 and MALAT1.Conclusion:Collectively, the differentially expressed lncRNA-mRNA axes play crucial roles in HLD pathogenesis through mediating cell proliferation and inflammation. Moreover, the EPO, IRS1, or PPARGC1A genes were potent therapeutic targets for HLD.

Objective To analyze the clinical features of patients with hepatolenticular degeneration(HLD)com-plicated by hepatic myelopathy(HM).Methods A retrospective analysis was performed on the clinical features,auxil-iary examinations,diagnosis and treatment,and outcomes of 5 patients diagnosed with HLD complicated by HM in our hospital from January 2018 to February 2023,and the relevant literature was reviewed.Results Among the 5 patients,4 were male and 1 was female;the age of onset of HM ranged from 16 to 32 years.All 5 patients had manifestations of de-compensated cirrhosis,and 3 patients had a history of transjugular intrahepatic portosystemic shunt(TIPS).The spinal MRI showed abnormal signals in the thoracic cord in 2 patients.Electromyography showed abnormalities in 3 patients,and electroencephalography showed significantly slower background brain waves in 4 patients.Two patients underwent liver transplantation,and 2 patients received endovascular treatment.One patient died of upper gastrointestinal bleeding;the other 4 patients had varying degrees of recovery.Conclusion The prevalence of HLD complicated by HM is very low.High copper status,hyperammonemia,TIPS,anemia,hypoproteinemia,and portal hypertension are directly associ-ated with HM.

Gerstmann-Sträussler-Scheinker syndrome (GSS) is a rare genetic prion disease caused by a mutation in the prion protein (PRNP) gene. It is typically characterized by progressive cerebellar ataxia and slowly progressive dementia. We present a case study of the GSS from China in which a 45-year-old male with a progressive gait and balance disorder developed cerebellar ataxia onset but was misdiagnosed as spinocerebellar ataxia (SCA) for 2 years. The patient's clinical, electrophysiological, and radiological data were retrospectively analyzed. Examination revealed ataxia, dysarthria, muscle weakness, areflexia in lower limbs, including a pyramidal sign, whereas cognitive decline was insignificant. His late mother had a similar unsteady gait. An electroencephalogram (EEG) showed normal findings, and 14-3-3 protein was negative. A brain MRI was performed for global brain atrophy and ventricular enlargement. Positron emission tomography-computed tomography (PET-CT) (18F-fluoro-2-deoxy-d-glucose, FDG) images showed mild to moderate decreased glucose metabolism in the left superior parietal lobe and left middle temporal lobe. According to genetic testing, his younger brother also had the P102L variant in the PRNP gene. This single case adds to the clinical and genetic phenotypes of GSS.

目的 探究NR3C1、MTHFR和IGFBP3基因多态性及DNA甲基化状态与激素性股骨头坏死(SONFH)之间的关系.方法 本病例对照研究中,选自合肥及周边地区包括79例短期冲击或长期口服糖皮质激素治疗SONFH的患者为病例组,114例服用糖皮质激素但未发生SONFH的患者为对照组.评估两组NR3C1、MTHFR和IGFBP3基因中的5个单核苷酸多态性(SNPs),这些SNPs由iMLDR进行基因分型.采用MethylTarget技术检测阳性位点(CpG位点)的甲基化水平,利用e QTLD技术分析以上3个基因的SNPs与甲基化水平的相互作用.结果 病例组与对照组相比,rs3110697 A/G基因型携带者患病风险低;在隐性遗传模型下,rs3110697 A 等位基因携带者患病风险低;CpG 位点 IGFBP3_2-143、MTHFR_1-36、MTHFR_1-77、MTHFR_1-139、MTHFR_2-42、NR3C1_2-163、NR3C1_4-47甲基化水平差异显著,差异有统计学意义(P＜0.05);共有10对SNPs与甲基化位点线性回归检验差异有统计学意义(P＜0.05).结论 SONFH是一种多基因病,其3个关联基因NR3C1、MTHFR和IGFBP3中的SNPs与DNA甲基化水平均存在广泛交互作用,有助于进一步建立SONFH基因调控模型指导临床诊疗.

经颅磁刺激(transcranial magnetic stimulation,TMS)技术目前日趋成熟,应用较为广泛,而神经系统变性疾病诊断及治疗均比较困难,TMS的发展及应用为神经系统变性疾病的诊断及治疗提供了重要的价值.本文就TMS的原理及应用方法给予简介总结,并针对常见的神经系统变性疾病如PD、AD、MND等的TMS相关应用如动物实验、在诊断及治疗中的价值加以综述,以便更多的同道了解及应用.

目的探讨心脏磁共振(CMR)在评估肝豆状核变性(WD)心肌受累中的应用价值.资料与方法回顾性收集2022年4—6月于安徽医科大学第一附属医院行CMR检查的12例WD患者作为研究组,同时纳入年龄、性别、体重指数、体表面积与研究组匹配的12例健康志愿者作为对照组.收集受试者的临床基线资料、心电图及CMR结果.CMR定量参数包括左心室射血分数、左心室舒张末期容积指数、左心室每搏输出量指数、左心室T1值、T2值、细胞外容积分数、右心室射血分数、右心室舒张末期容积指数、右心室每搏输出量指数,比较两组CMR定量参数的差异.结果1例WD患者左心室室间隔处可见心肌裂.12例WD患者中,心肌延迟增强阳性2例,均位于室间隔右心室插入部.WD患者初始T1值[(1092.4±50.3)ms]、T2值[(53.8±2.0)ms]与细胞外容积分数[(31.7±3.5)％]较对照组[(1039.8±38.1)ms、(51.0±2.7)ms、(25.8±1.0)％]均显著升高(t=2.893、2.904、5.635,P均<0.05).研究组与对照组左心室射血分数、左心室舒张末期容积指数、左心室每搏输出量指数、右心室射血分数、右心室舒张末期容积指数、右心室每搏输出量指数比较,差异均无统计学意义(t=0.322、0.520、0.665、0.913、0.731、0.828,P均>0.05).结论CMR对于早期发现WD心肌受累具有一定的价值,可作为WD患者疑似心脏受累检查的重要方法.

Objective To observe the changes of serum superoxide dismutase（SOD） activity in patients with hepatolenticular degeneration（HLD）, and to analyze the correlation of SOD activity with age, duration of disease, uric acid and 24 h urine copper.Method A retrospective analysis of 500 inpatients with HLD who were hospitalized.Referring to the HLD classification standard formulated by Yang Renmin et al in 2015, the gender, age, duration of disease, clinical classification, liver classification and clinical grade of the enrolled patients were counted.In addition, the serum SOD activity level, uric acid（UA） level and 24-hour urinary copper of the enrolled patients before copper complexation treatment, as well as the 24-hour urinary copper on the second day of the first course of treatment with sodium dimercaptopropanesulfonate.The differences in serum SOD activity levels of HLD patients with different gender, age, duration of disease, clinical classification, liver classification and clinical grade were analyzed and compared, and their correlation with serum SOD activity levels of patients was also analyzed.Results Among the 500 HLD patients, 25 had decreased serum SOD activity levels, and 136 had elevated serum SOD activity levels, with a total abnormal rate of 32.2%.There was no significant difference in serum SOD activity levels between males andfemales（P＞0.05）.There were significant differences in serum SOD activity levels among HLD patients with different age groups, duration of disease groups, clinical classification, liver classification and clinical grades（P＜0.05）.Among them, the serum SOD activity level of patients in the age group of 1-10 years was the highest, while that in the age group of 51-60 years was the lowest; the serum SOD activity level was the highest in patients with a course of 6-10 years, and the lowest in patients with a course of 21-30 years; the serum SOD activity levels were highest in patients with presymptomatic type, and lowest in patients with brain-visceral type; the level of serum SOD activity in patients with mild liver damage was the highest, and that in patients with liver nodule type was the lowest, and the serum SOD activity level of patients gradually decreased with the severity of liver damage; the serum SOD activity level of patients with clinical grade 0 was the highest, and that of patients with grade Ⅳ was the lowest, and the serum SOD activity level of patients gradually decreased with the increase of clinical grade.Spearman correlation analysis showed that: the serum SOD activity level of HLD patients was negatively correlated with age, disease course and 24 h urinary copper（P＜0.05）, and positively correlated with UA（P＜0.05）.Conclusion There were abnormal changes of SOD activity in HLD patients.The serum SOD activity of HLD patients was negatively correlated with age, duration of disease and 24-hour urinary copper, and positively correlated with UA.In addition, the level of serum SOD activity was affected by the degree of disease damage in HLD patients.With the aggravation of disease damage in HLD patients, the level of serum SOD activity decreased gradually.Observation of serum SOD activity in HLD patients has considerable clinical guidance value for the preliminary judgment of the severity of the disease in patients.

目的 总结分析Wilson病并发自身免疫性甲状腺疾病的临床特征,探究其可能的发病机制.方法 回顾性分析5例Wilson病合并自身免疫性甲状腺疾病病例,采集一般人口学信息,分析总结其临床表现,实验室检查及影像学特征,并检索学习相关文献,分析其可能发病机制.结果 5例患者病变涉及肝脏,CNS及甲状腺等多个器官,组织,临床表现以神经、精神症状为主.实验室检查示铜蓝蛋白减低,24 h尿铜显著增高,甲状腺球蛋白抗体和(或)甲状腺过氧化物酶抗体升高.甲状腺超声显示弥漫性改变.头颅MRI表现为双侧豆状核、丘脑等部位异常信号.经过驱铜、抗甲状腺或补充甲状腺素等治疗,随访期患者症状表现得到不同程度改善,但甲状腺激素水平及相关抗体仍异常.结论 Wilson病可引起自身免疫功能紊乱.Wil-son病可并发自身免疫性甲状腺疾病,二者合病临床表现复杂.铜代谢障碍可能参与二者合病.

肝豆状核变性(hepatolenticular degeneration)又称威尔逊病(Wilson disease, WD),是一种常染色体隐性遗传铜代谢障碍疾病[1].1912年金尼尔·威尔逊(Kinnier Wilson)系统描述该病是一种"进行性豆状核变性(progressive lenticular degeneration)伴有肝硬化的家族性神经病变".Ciarla(1916年)在意大利神经病理学杂志首次使用"Wilson disease"的名称,Hall (1921年)指出WD是隐性遗传病,并使用了"肝豆状核变性"(Dégénérescence Hépato-lenticulaire)的术语.1985年Frydman等将WD基因定位于13 号染色体, 1993 年Petrukhin、Bull 和Tanzi 等确定为13 号染色体长臂上( 13q14 . 3 )的ATP7B 基因,编码140 kD 铜转运 P 型 ATP 酶[2].现已明确 WD 由于铜转运 ATP7B 酶功能缺陷,导致铜蓝蛋白合成减少、胆道排铜障碍,肝脏、脑、肾和角膜等组织器官过量铜蓄积,出现进行性肝损害、锥体外系症状、精神症状、角膜色素环( Kayser-Fleischer ring , K-F 环)等.WD 通常在青少年期发病,是迄今少数几种可治疗的神经遗传病之一[3].

目的:分析104例痉挛性斜颈的临床特点、A型肉毒毒素的临床疗效及其与临床特点相关性.方法:回顾分析我院2012年1月至2019年12月住院的符合痉挛性斜颈诊断标准的患者104例,统计患者临床特点;分析A型肉毒毒素疗效在不同性别、年龄、体质指数、教育年限、病程、临床分型、注射次数、注射总量、平均每次注射剂量、注射方式各方面的差异性及治疗后不良反应的发生情况.结果:痉挛性斜颈患者男:女=1∶1.36,年龄以40～50岁为主,且以40 ～ 50岁发病较多,病程(56.84±82.19)个月,发病到确诊间隔时间(22.75±57.44)个月,疾病早期易误诊为颈椎病;易合并精神情绪类疾病;其病因与劳累、情绪异常、饮酒和相关部位的外伤等有关,69.23％的患者在日常生活中起病,64.42％患者情绪激动、劳累或者行走时症状明显;A型肉毒毒素治疗有效率97.22％,A型肉毒毒素疗效与年龄、性别、体质指数、教育年限、病程、临床分型、注射次数、注射总量、平均每次注射剂量之间均无统计学差异(P＞0.05);不良反应发生率10.58％.结论:痉挛性斜颈女性多于男性,年龄多在40～50岁;痉挛性斜颈的临床诊断较困难,病程长,发病多与劳累、情绪等因素有关,早期应防止误诊.A型肉毒毒素治疗痉挛性斜颈有效率较高且不良反应较少,多次注射未见疗效明显降低,但是否有其他影响因素不能肯定.

目的 探讨良性家族性婴儿癫痫(BFIE)的临床特点.方法 回顾性分析1例PRRT2基因突变和双侧额区放电的BFIE患者的临床资料,并进行文献复习.结果 BFIE主要临床表现为局灶性癫痫发作,PRRT2为主要致病基因.发作间歇期EEG多无异常,局灶性放电部位多为额区.本病预后良好,多数抗癫痫药物对本病有效.结论 婴儿期以局灶性癫痫起病,如丛集性发作,且智力、运动发育正常,需结合基因和EEG检查,考虑BFIE可能.

目的 探讨线粒体脑肌病伴乳酸血症和卒中样发作(MELAS)综合征的临床症状、EEG、影像学及肌肉病理特点,以提高对其认识及诊断的正确率.方法 回顾性分析6例基因确诊的MELAS综合征患者的临床资料,分析其临床表现、EEG、影像学、肌肉病理特点.结果 6例患者中男性4例,女性2例,年龄最大者43岁,最小者4岁,平均起病年龄(15.00±13.10)岁.临床主要表现为痫性发作(100％)、卒中样发作(50.0％)、形体矮小(50.0％)、认知功能下降(66.7％)、共济失调(33.3％)、血乳酸增高(83.3％)等;6例EEG检查示4例顶、枕、颞区局灶性癫痫样放电,2例广泛性δ波,其中1例伴弥漫性1.5～2.0 Hz多棘慢、慢棘慢波发放.影像学检查:头颅MRI示4例顶、枕、颞区呈长T1、长T2改变,DWI高信号改变伴脑室扩大、脑沟裂增宽,2例未见明显异常;1例磁共振波谱分析(MRS)示左枕区乳酸峰升高,N-乙酰天门冬氨酸峰减低.肌活检:5例见蓬毛样红纤维,5例CCO染色见强烈反应性血管增生现象(SSVs);3例SDH染色见SSVs.结论 MELAS综合征的临床多表现为癫痫、卒中、发育迟缓、智能减低等.EEG多表现为背景异常、局灶性放电,发作期可见多种发作图形,且局灶性放电部位多与影像学病灶一致.头颅MRI多显示病灶位于大脑半球后部,顶、枕、颞多见,不按脑血管分布.MRS可出现N-乙酰天门冬氨酸峰下降和乳酸峰升高.肌肉病理多见蓬毛样红纤维及SSVs.

Wilson's disease (WD) is an inherited disease caused by mutations in ATP7B and is characterized by the pathological accumulation of copper in the liver and brain. Common clinical manifestations of WD include a wide range of liver disease and neurological symptoms. In some patients, psychiatric symptoms may be the only manifestation at the time of diagnosis. The clinical features of WD are highly variable and can mimic any disease of internal medicine. Therefore, for unexplained medical diseases, the possibility of WD should not be ignored. Early diagnosis and treatment can improve the prognosis of WD patients and reduce disability and early death. Gene sequencing is becoming a valuable method to diagnose WD, and if possible, all WD patients and their siblings should be genetically sequenced. Copper chelators including D-penicillamine, trientine, and dimercaptosuccinic acid can significantly improve the liver injury and symptoms of WD patients but may have a limited effect on neurological symptoms. Zinc salts may be more appropriate for the treatment of asymptomatic patients or for the maintenance treatment of symptomatic patients. High-quality clinical trials for the drug treatment of WD are still lacking, therefore, individualized treatment options for patients are recommended. Individualized treatment can be determined based on the clinical features of the WD patients, efficacy and adverse effects of the drugs, and the experience of the physician. Liver transplantation is the only effective method to save patients with acute liver failure or with severe liver disease who fail drug treatment.

Background: The false increase of ceruloplasmin (Cp) in some Wilson’s disease (WD) patients, which overlaps with those in non-WD liver disease patients, decrease the diagnostic accuracy. The aims of our study was to understand the factors affecting WD patients’ Cp normalization, and develop a model using routine predictors to identify WD patients with ambiguous serum Cp. Results: The mixed effects model analysis which executed in longitudinal study revealed that the WD patients’ Cp normalization were significantly associated with the copper burden and liver function indexes, like urinary copper treated with dimercaptopropansulfonate sodium ( P =0.000), aspartate aminotransferase ( P =0.011), γ-glutamyltransferase ( P =0.000), albumin ( P =0.000). Multivariate logistic regression analysis in case-control study showed age (P=0.000) and serum creatine ( P =0.000) were independent risk factors associated with WD. Based on their regression coefficients, a simplified WD index was derived: 0.001 × age [yr] × Creatine [umol/L] . The AUC value of WD index in total cohort were 0.923 ( P =0.000). At a WD index cutoff value of ≤ 1.9 and ≤ 2.5, the positive and negtive predictive value are 88.2% and 89.9% for WD, respectively. Conclusions: The increase of serum Cp in WD patients is related to their excessive copper burden and hepatic injury, common tests can effectively foretell those WD patients with nearly normal serum Cp from other liver injury patients.

目的:研究肝豆状核变性(WD)患者心理弹性水平并分析其相关影响因素.方法:抽取123例WD患者,收集患者一般资料,采用心理弹性量表(CD-RISC)、社会支持量表(SSRS)、一般自我效能感量表(GSES)展开调查.结果:WD患者心理弹性总分(56.78±15.75),单因分析显示,年龄、职业、收入、一般自我效能感水平及社会支持水平是影响WD患者心理弹性的因素;进一步logistics多因素回归分析显示,年龄(OR=2.164,P＜0.05,95％CI 1.120～4.181)、一般自我效能感(OR=6.155,P＜0.001,95％CI 2.373～15.964)及社会支持(OR= 2.232,P＜0.05,95％CI 1.059～4.703)为其心理弹性水平的独立影响因素.Pearson相关分析显示WD患者心理弹性与一般自我效能、社会支持均呈正相关(r = 0.587、0.514,P＜0.01).结论:WD患者心理弹性水平较低,而对于年龄小,社会支持水平及自我效能感低的WD群体需给予更多的干预措施以提高其心理弹性.

多巴胺反应性肌张力障碍(dopa-responsive dystonia,DRD)是一种十分罕见的遗传性肌张力障碍疾病,其患病率为(0.5～1.0)/1000000[1].其临床表现十分复杂,导致临床早期治疗极困难,误诊率较高,致使不少患者被误诊而辍学、肢体残疾,很多病例直至生活不能自理方才明确诊治,部分患者确诊时已遗留明显的后遗症[2].已判定出DRD疾病的重要致病基因有GCH1基因、TH基因和SPR基因.其中最常见致病基因为GCH1基因,但仍有约33.3％患者未发现该基因编码区存在异样.TH基因和SPR基因突变引发的DRD少见.截至目前,在国内外已报道的研究中,TH突变基因上发现的突变主要以纯合子突变为主要形式,杂合子突变存在少数[3].本文现报道1例散发的TH杂合子突变所致病例,并结合相关文献进行分析,以加深临床医生对该病的发病机制、临床表现及遗传学基础的了解,以进一步提升临床诊断水平,以免误诊误治.

铜稳态失调引发的功能障碍涉及多种疾病,铜维持生命不仅需要细胞中铜的稳态调节,而且需要铜转运到与其相应的配体中,避免氧化应激反应.线粒体也受到生物钟的控制,如果这些机制不能正常运行,将会导致铜的过剩或缺乏引起各种疾病.在肝主疏泄昼夜节律的调控下人体的五脏是应自然界四时阴阳消长而变化的时间自稳调节系统,在这一系列转化过程中,肝是五脏应时而变的内在推动力.因此,以Wilson病为疾病模型尝试从现代医学细胞生物学层面,结合时间医学相关研究结果与肝主疏泄功能和铜稳态平衡结合进行交叉研究以阐明肝主疏泄对线粒体铜稳态昼夜节律调控的科学内涵,对揭示铜稳态失调相关疾病机体整体调节规律的深层内涵具有重要意义.