Wilson's disease （WD） is a copper metabolism disorder caused by mutations in the ATP7B gene， with diverse phenotypes and complex pathogenesis. It is one of the few rare diseases that can achieve good clinical efficacy through standardized treatment. Since there are few systematic reviews of this disease， we summarize the pathogenesis and treatment methods of WD from traditional Chinese and western medicine by reviewing the literature related to WD. In western medicine， ATP7B gene mutation is considered as the root cause of WD， which affects copper transport and causes copper metabolism disorders. The excessive copper deposited in the body will result in oxidative stress， defects in mitochondrial function， and cell death. Western medicine treatment of WD relies mainly on drugs， and copper antagonists are the first choice in clinical practice， which are often combined with hepatoprotective and antioxidant therapy. Surgery is a common therapy for the patients with end-stage WD， and gene therapy provides an option for WD patients. According to the traditional Chinese medicine （TCM） theory， WD is rooted in constitutional deficiency and copper accumulation and triggered by dampness-heat accumulation or phlegm combined with stasis. The patient syndrome varies in different stages of the disease， and thus the treatment should be based on syndrome differentiation. The TCM treatment method of nourishing the liver and kidneys and warming the spleen and kidneys can address the root cause. The methods of clearing heat and drying dampness， resolving phlegm and dispelling stasis， and soothing liver and regulating qi movement can be adopted to treat symptoms. On the basis of syndrome differentiation， special prescriptions for the treatment of WD have been formulated， such as Gandou decoction， Gandouling， and Gandou Fumu decoction， which have been widely used in clinical practice. TCM and western medicine have their own advantages and shortcomings. The integrated Chinese and western medicine complementing with each other demonstrates great therapeutic potential. This paper summarizes the pathogenesis and treatment of WD with integrated Chinese and western medicine， aiming to provide a reference for the clinical diagnosis and treatment of this disease.

ObjectiveTo explore the mechanism and pathway of Gandou Fumu decoction （GDFMD） in the development of liver fibrosis in Wilson's disease （WD）. MethodFirst， 30 TX-j mice were randomly divided into the model group， high-dose， medium-dose， and low-dose GDFMD groups， and penicillamine group， with six mice in each group， and another six wild-type mice were used as the normal group. The high-dose， medium-dose， and low-dose GDFMD groups were intragastrically administered drugs of 13.92， 6.96， 3.48 g·kg^-1. In the penicillamine group， 0.1 g·kg^-1 of penicillamine was given by intragastric administration. The model group and the normal group were given equal volume of normal saline， once a day， for four consecutive weeks. Samples were collected four weeks after gavage， and enzyme-linked immunosorbent assay （ELISA） was used to detect type Ⅲ procollagen peptide （PCⅢ）， collagen type Ⅳ （Col Ⅳ）， hyaluronic acid （HA）， and laminin （LN）. Hematoxylin-eosin （HE）， Masson， and picric acid-Sirus red collagen （Sirus Red） staining were used to observe the histopathological changes of liver fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， immunohistochemistry， and Western blot were used to observe the expressions of α-smooth muscle actin （α-SMA） and collagen type Ⅰ （Col Ⅰ）， which were related to the activation of hepatic stellate cells （HSCs）. The expression of miR-29b-3p was observed by Real-time PCR. The expression of Unc-51-like kinase 1 （ULK1） and its downstream-related factors were observed by Western blot. The downstream genes of miR-29b-3p were verified by the dual luciferase reporter gene detection method. ResultCompared with the normal group， the four items of liver fibrosis （PCⅢ， Col Ⅳ， HA， and LN） in the model group were significantly abnormal （P<0.01）， and the pathology was significantly abnormal. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was up-regulated （P<0.05， P<0.01）， and miR-29b-3p expression was down-regulated （P<0.01）. ULK1， p-ULK1， autophagy-related gene 13 （Atg13）， p-Atg13， Beclin-1， FAK family kinase-interacting protein of 200 kDa （FIP200）， activating molecule in BECN1-regulated autophagy protein 1 （AMBKA1）， and microtubule-associated protein 1 light chain 3Ⅱ/Ⅰ（LC3Ⅱ/Ⅰ） were up-regulated （P<0.05， P<0.01）. p62 protein expression was down-regulated （P<0.01）. Compared with the model group， the four items of liver fibrosis in the high-dose， medium-dose， and low-dose GDFMD groups and the penicillamine group were significantly improve （P<0.01）， and the pathological conditions were improved. The expression of HSC activation-related indicators including α-SMA and Col Ⅰ， as well as α-SMA mRNA and Col Ⅰ mRNA was down-regulated （P<0.05， P<0.01）， and the expression of miR-29b-3p was up-regulated （P<0.01）. ULK1， p-ULK1， Atg13， p-Atg13， Beclin-1， FIP200， AMBKA1， and LC3Ⅱ/Ⅰ were down-regulated （P<0.05， P<0.01）， and p62 protein expression was up-regulated （P<0.01）. The prediction software predicted that there was a binding site between miR-29b-3p and ULK1. The dual-luciferase reporter gene detection method indicated that the luciferase activity of the ULK1-WT plasmid-transfected cell group was reduced when miR-29b-3p mimics were co-cultured （P<0.01）. ConclusionGDFMD can regulate ULK1-mediated autophagy by up-regulating miR-29b-3p and further exert its anti-hepatic fibrosis effect in Wilson's disease.

Objective To investigate the safety and feasibility of peripheral vascular intervention via the ipsilateral transulnar access(TUA)due to failure of transradial access(TRA)puncture.Methods The clinical data of 2546 peripheral vascular interventions via TRA,which were performed at authors'hospital between January 2019 and December 2021,were retrospectively analyzed.Among the 2546 interventions,TRA puncture failed in 37 procedures,and in 27 of these patients the ipsilateral TUA puncture had to be adopted.The puncture success rate,surgical success rate and puncture approach-related complications of TUA of the 27 patients receiving ipsilateral TUA puncture were analyzed.Results The success rate of ipsilateral TUA puncture after TRA puncture failed was 96.3％(26/27),and in one patient transfemoral access(TFA)puncture had to be substituted because of the ulnar artery spasm.The total success rate of interventional procedures was 96.3％(26/27).No serious complications occurred,and the incidence of minor complications was 19.2％(5/26).Conclusion Preliminary results indicate that for the experienced TRA operators,using ipsilateral TUA puncture due to failure of TRA puncture is a safe and feasible strategy choice.

Objective:To analyze the application and regularity of acupoint selection of Sanyinjiao (SP 6) based on data mining.Methods:Search for literatures in CNKI, Wanfang, VIP, and Pubmed, the clinical researches of acupuncture on Sanyinjiao (SP 6) point were selected, according to the inclusion and exclusion criteria, and the retrieval period was from database construction to September 30th, 2021. Excel 2016, SPSS Statistics 25.0, SPSS Modeler 18.0 were used to perform descriptive analysis, association analysis and cluster analysis.Results:After literature screening, a total of 261 literatures were included, involving 73 kinds of diseases, mainly including mental and behavioral disorders, genitourinary diseases, endocrine and nutritional metabolism diseases and nervous system diseases. The most frequently used acupoints in Sanyinjiao (SP 6) compatibility are Zusanli (ST 36), Baihui (GV 20), Guanyuan (CV 4) and Taichong (LR 3), most of which focus on stomach meridian, conception channel, governor channel and bladder meridian. Seven categories were extracted among high-frequency acupoints by cluster analysis. The association rule analysis showed that the commonly used combination of Sanyinjiao (SP 6) were Zusanli (ST 36)-Sanyinjiao (SP 6), Baihui (GV 20)-Sanyinjiao (SP 6), and Guanyuan (CV 4)-Sanyinjiao (SP 6).Conclusions:Sanyinjiao (SP 6) is widely used in clinical application, and it is always compatible with stomach meridian, conception vessel, governor channel acupoints, especially those acupoints on the outer and inner meridians and the upper and lower parts. Sanyinjiao (SP 6) combined with other acupoints can treat diseases of multiple systems, such as insomnia, stroke, anxiety and depression, dysmenorrhea, infertility, etc. Clustering and association analysis found the core compatibility law of Sanyinjiao (SP 6), which can be used as a reference for clinical acupoint selection.

Objective To systematically integrate qualitative studies on health promoting behaviors of stroke patients and provide references for the development of relevant behavioral interventions.Methods Qualitative studies on health promotion behaviors of stroke patients were retrieved from CNKI,Wanfang,China Biomedical Database,VIP,PubMed,Web of Science,the Cochrane Library,and Embase from the inscription to February 2023.The JBI Model of Evidence-Based Healthcare was employed to assess the quality of the acquired literature,with the results treated with meta-integration.Results A total of 9 articles were included in the study.From the literature acquired 49 complete themes were abstracted and 3 novel types of literature were yielded.By meta-integration,11 factors affecting the health promoting behaviors of the stroke patients were concluded,including ability of patients such as physical dysfunction,disease cognition,disease risk management,motivation such as negative emotional distress,positive emotional experience,psychological self-regulation,and opportunity such as family caring degree,iatrogenic support,peer mutual support,access to information,and environmental restrictions.Conclusions The factors influencing health promoting behaviors of stroke patients consist of ability,motivation,and opportunity.Medical staff should care about their mental and physical experience,establishing a multi-social support system and working hard to promote the transformation of their health behaviors.

Hepatolenticular degeneration (HLD) is a rare genetic metabolic disorder of the nervous system with complex and diverse clinical phenotypes and is difficult to diagnose. The common lesions of HLD brain area are basal ganglia, thalamus, cerebellum and other anatomical structures, the classic manifestations of brain magnetic resonance imaging are symmetrical bilateral lenticular nucleus with low signal on T 1WI and high signal on T 2WI, and it is extremely rare for cases with high signal intensity on diffusion weighted imaging (DWI) of the brain stem, bilateral cerebral peduncles, thalamus, and basal ganglia. This article reported a case of HLD with high signal on DWI for clinical reference.

Wilson's disease (WD) is a rare autosomal recessive disorder with a complex pathogenesis involving multiple systems, multiple visceral organs, and the complex copper homeostasis regulation system within the body. The liver is the most common organ for copper deposition, and liver injury is the earliest and most common manifestation of WD; therefore, it is important to find an ideal animal model for WD research. By summarizing the animal models of WD commonly used in the world, this article systematically summarizes the background, liver and nervous manifestations, and application of different models and compares the characteristics of different animal models, so as to provide a reference for the application of various animal models of WD.

To analyze the mediating role of anxiety and depression in perceived social support and fatigue in ICU patients′ families, and to provide a theoretical evidence for alleviating their fatigue status. A total of 223 family members of ICU patients who received treatment at the Affiliated Hospital of Jiangnan University from October 2020 to April 2021 were selected as the study subjects. The general data questionnaire, perceived social support scale (PSSS), generalized anxiety disorder scale (GAD-7), patient health questionnaire (PHQ-9) and fatigue assessment instrument (FAI) were used to conduct a survey. Among 223 family members of ICU patients, 155(69.51%) had fatigue problems. There were statistically significant differences in total fatigue scores of ICU patients′ family members in terms of gender, age, education level, relationship with patients, residence, payment method and per capita monthly income ( P<0.05). Anxiety, depression and fatigue were negatively correlated with perceived social support ( r are -0.353, -0.276 and -0.416, respectively, all P<0.01). Depression and fatigue were positively correlated with anxiety ( r are 0.808 and 0.703, respectively, all P<0.01), and fatigue was also positively correlated with depression ( r= 0.665, P<0.01). Anxiety and depression had a partial mediating effect on perceived social support and fatigue, and the total indirect effect size was 52.64%. Comprehensive intervention on the level of social support, anxiety and depression is helpful to improve the fatigue status of ICU patients′ family members.

Objective:To explore the pathogenic genes, clinical characteristics and treatment follow-up of children with congenital long QT syndrome (LQTS).Methods:Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15, 2011 to April 15, 2021 in Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′ s exact probability method. Results:LQTS-related gene mutations were detected in all the 20 cases, and pathogenic or suspected pathogenic mutations were identified in 18 cases (90.0%). Five LQTS mutation genes were discovered, including KCNQ1, KCNH2, SCN5A, CACNA1C and AKAP9.Eighteen cases (90.0%) had positive symptoms, and 13 cases (65.0%) had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1) was related to exercise, the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1 (JLNS1) with complex heterozygous mutations were exercise or emotional agitation; the causes of syncope in LQTS type 2 (LQT2) were unrelated to exercise; severe exercise in LQTS type 3 (LQT3) resulted in symptoms; and seizure in LQTS type 8 (LQT8) was non-induced.The corrected QT(QTc) interval of 20 cases was (553.1±66.6) ms, with a range of 460-707 ms, among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG) manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders, or between children with syncope and those without syncope (all P>0.05). The follow-up time was (3.4±2.3) years, ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)] and 3 cases did not.By the end of the follow-up, 1 child died, 19 cases survived, and 2 cases of the surviving children lost consciousness. Conclusions:There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.

Objective: : Extracranial supra-aortic dissections (ESADs) with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke. Endovascular stenting to reconstruct non acute phase ESADs (NAP-ESADs) is an alternative to anticoagulant or antiplatelet therapy. However, its feasibility, safety and efficacy of stenting in NAP-ESADs is unclear. This study aims to investigate the long-term outcomes of the feasibility, safety and efficacy of stenting in NAP-ESADs. Methods: : Seventy-four patients with 91 NAP-ESAD vessels with severe stenosis, occlusion and/or pseudoaneurysm presents potential risk of stroke who underwent stent remodeling were enrolled into this respective study from December 2008 to March 2020. Technical success rate, complications, clinical and angiographic results were harvested and analyzed. Results: : Success rate of stent deployment was 99% (90/91) with no procedural mortality or morbidity. Transient ischemic attack occurred in three patients during operation (4.1%, 3/74). Asymptomatic embolisms of distal intracranial vessels were found in two patients (2.7%, 2/74). One hundred and forty-two stents deployed at 85 carotid (135 stents) and six vertebral (seven stents) vessels. Six stent types (Wingspan, 28/135, 20.7%; Solitaire, 10/135, 7.4%; Neuroform, 8/135, 5.9%; LVIS, 2/135, 1.5%; Precise, 75/135, 55.6%; Acculink, 12/135, 8.9%) were deployed at carotid arterial dissection while two types (Wingspan, 5/7, 71.4%; Solitaire 2/7, 28.6%) at vertebral arterial dissection. Digital subtracted angiography (56%, 51/91), computational tomography angiography (41.8%, 38/91) and high resolution magnetic resonance imaging (2.2%, 2/91) were adopted for follow up, with a mean time of 17.2±15.4 months (5–77). All patient modified Rankin Scale scores showed no increase at discharge or follow-up. Angiographically, dissections in 86 vessels in 69 patients (94.5%, 86/91) were completely reconstructed with only minor remnant dissections in four vessels in four patients (4.4%, 4/91). Severe re-stenosis in the stented segment required re-stenting in one patient (1.1%, 1/91). Conclusion : Stent remodeling technique provides feasible, safe and efficacious treatment of ESADs patients with severe stenosis, occlusion and/or pseudoaneurysm.