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Objective:To investigate the characteristics of attention bias in Wilson disease(WD) patients with different levels of state-trait anxiety.Methods:The emotional Stroop paradigm and the state-trait anxiety inventory(STAI) were used to evaluate the anxiety level and the characteristics of attention bias in 49 inpatients with WD.SPSS 25.0 software was used for statistical analysis.Independent sample t-test was used for comparison between the two groups.Multiple linear regression analysis was used to evaluated the influencing factors of attentional bias response time. Results:(1) In WD patients, the response times measured under the positive, negative and neutral words in the high trait anxiety group((867.0±172.1)ms, (877.0±167.7)ms, (898.4±169.8)ms, respectively) were significantly higher than the low trait anxiety group((771.9±128.9)ms, (770.9±110.4)ms, (778.4±120.1)ms, respectively) and the differences were statistically significant( t=-2.183, -2.605, -2.847, all P<0.05). The response times under the positive, negative and neutral word measured in the high state anxiety group((866.9±171.9)ms, (867.8±173.8)ms, (889.8±173.5)ms, respectively) were higher than those of the low state anxiety group((771.9±129.2)ms, (780.4±109.3)ms, (787.3±123.0)ms, respectively) and the differences were statistically significant( t=-2.177, -2.116, -2.378, all P<0.05). (2) Multiple linear regression analysis showed that the total score of trait anxiety ( B=4.584, 4.671, 5.376, P=0.020, 0.015, 0.008) and age ( B=9.314, 7.864, 7.505, P=0.002, 0.008, 0.014) were the influencing factors of response times measured under the positive, negative and neutral emotion words. Conclusion:Anxiety will lead patients with WD to show more negative attention bias, and trait anxiety can significantly predict the characteristics of attention bias.
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Objective To investigate the impulsivity and aggressiveness characteristics of patients with hepatolenticular degeneration (HLD) and its relationship with brain structure.Methods The Chinese version of the Barratt impulsiveness scale,11 version (BIS-1 1-C) and Buss-Perry aggression questionnaire (BPAQ) were assessed in 78 patients with hepatolenticular degeneration(HLD group) and 86 normal adults (health control group).HLD patients were examined by 3.0T magnetic resonance imaging (MRI).The differences in impulsivity and aggressiveness of the two groups were compared,and the relationship was analyzed between impulsivity,aggressiveness and different brain structures in patients with HLD.Results The total impulsive score,unplanned factor score,the total aggressive score and anger factor score of patients with cerebral HLD (61.74±9.82,26.08±5.06,82.71 ± 15.92,20.06± 5.74,respectively) were higher than those in patients with hepatic HLD (56.73±7.11,23.02±4.20,72.84± 11.15,16.64±5.01,respectively),and health control group(52.19±7.53,21.50± 3.93,64.64±9.83,14.27 ±4.38,respectively),and the differences were significant (F=3.193,4.646,11.830,8.270,all P＜0.05).Total impulsive score was positively correlated with aggressive score and physical aggression in HLD group(r=0.299,0.290,both P＜0.05).Unplanned score was positively correlated with aggressive total score (r=0.324) and physical aggression (r=0.320) in HLD group (P＜0.05).Frontal lobe injury was the influencing factor of total impulsive score(B=10.263,95％CI=0.467-19.946,P=0.008),attention score(B=2.837,95％CI=0.382-5.600,P=0.010) and unplanned factor score (B=3.977,95％ CI=0.848-8.502,P=0.046).Thalamus injury was the influencing factor of aggressive total score and its factor score.Caudate nucleus injury was the influencing factor of aggressive total score (B=10.030,95％ CI=3.351-18.039,P=0.017) and physical aggression score (B =4.432,95％ CI=1.193-7.729,P=0.016).Conclusion Patients with HLD have higher impulsive and aggressive tendencies,which are mainly manifested in unplanned impulsive and anger tendencies.Brain injury may be an important factor affecting impulsiveness and aggression in patients with HLD.Impulsiveness is related with frontal lobe injury and aggression to thalamus and caudate nucleus injury.Impulsiveness and aggressiveness in patients with HLD are not caused by damage to isolated brain areas,but are related to damage to multiple brain areas.
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Objective To explore cognitive impairment and related factors in patients with Wilson disease (WD) and to screen the risk factors of cognitive impairment in order to provide evidence for clinical intervention. Methods The Chinese Version Addenbrooke＇s Cognitive Examination-III (ACE-III-C) was used to assess the cognitive function. The WD patients with cognitive impairment were analyzed the difference between those with non-cognitive disorders in the Young scale, Baethel scale and biochemical indicators. Risk factors for cognitive impairment in WD patients were analyzed by multiple linear regression. Results Cognitive impairment occurred in 43 (59.7%) of 72 patients with WD. ACE-III-C total score, attention, memory, language fluency, visual spatial factor scores, Young scores, Barthel scores and serum copper levels were significantly different between patients with cognitive impairment and patients with non-cognitive impairment (P＜0.01). Linear regression analysis showed that serum copper levels were the most important risk factors for ACE-III-C total score and cognitive subfields (P＜0.01). Serum zinc levels as a secondary risk factor of language fluency and visual space (P＜0.05). Age-related participation affected language fluency (P＜0.05). Conclusions Serum copper and zinc levels may be the main risk factors of cognitive impairment. Modulation of serum copper and zinc levels may be the key for intervention to treat cognitive impairment in WD patients.
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Objective To study the effect of high copper on Wnt /β-catenin signaling pathway and oxidative stress. Methods BRL-3A cells were incubated with different concentrations of CuSO4.The cell growth and proliferation wre assessed using MRR method.The production of reactive oxygen species(ROS)and mitochondrial membrane potential (JC-1) were examined usingf flow cytometry. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were detected by microplate reader. The expression of protein was detected by Western Blot. Results①The results of MTT showed that CuSO4inhibited the growth and proliferation of BRL-3A cells in a time- and concentration-dependent manner(P<0.01).②Flow cytometry results showed that CuSO4induced a large amount of ROS and significantly decreased the fluorescence intensity of JC-1 in BRL-3A cells (P<0.01). ③ Microplate reader results showed that CuSO4increased the content of MDA and decreased the activity of SOD (P<0.05).④Western blotting assay showed that CuSO4significantly decreased the total expression levels of β-catenin and p-Ser 9-GSK-3β protein as well as nuclear levels of p-(S33+S37)-β-catenin and c-Myc (P<0.01) and increased expression levels of GSK-3β、DKK1、Dishevelled3 protein in BRL-3A cells. Conclusion High copper can induce oxidative stress and induce Wnt /β-catenin signaling pathway to deactivate liver cells,leading to hepatocellular injury.
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Objective To study the regional cerebral blood flow (rCBF) and correlated factors in patients with hepatolenticular degeneration (HLD).Methods The rCBF of lentiform nucleus,thalamus and other sites in 14 patients with HLD of cerebral type (cerebral type group) and 10 patients with HLD of non-cerebral type (non-cerebral type group) were determined by magnetic resonance-perfusion imaging technology,meanwhile 13 healthy volunteers were selected as control group,and calculated the relative regional cerebral blood flow (rrCBF) for avoiding perfusion time lag.The correlation between the clinical symptom scores,the content of urinary copper,duration and rrCBF in HLD patients were evaluated.Results The rrCBF of cerebral type group in the left and right frontal lobe,temporal lobe,lentiform nucleus,caudate nucleus,thalamus,midbrain,pons and the left hippocampus,cerebellar cortex,dentate nucleus were lower than those of control group (1.91 ±0.35 vs.2.44 ±0.64,1.80 ±0.30 vs.2.37 ±0.65,1.37 ±0.35 vs.2.14 ±0.91,1.58 ±0.52 vs.2.39 ±0.99,1.61 ±0.38 vs.2.59 ±0.74,1.52 ±0.64 vs.2.63 ±0.73,1.88 ±0.32 vs.2.61 ±0.67,1.70 ±0.40 vs.2.35 ±0.50,1.48 ±0.13 vs.2.01 ±0.59,1.46 ±0.38 vs.2.38 ±0.99,1.47 ±0.55 vs.2.02 ±0.72,1.27 ±0.48 vs.1.91 ±0.51,1.24 ±0.38 vs.1.47 ±0.29,1.25 ±0.39 vs.1.53 ±0.37,1.74 ±0.27 vs.2.40 ±0.89,1.79 ±0.50 vs.2.22 ±0.66,2.15 ±0.41 vs.2.64 ± 0.61),and there were significant differences (P ＜ 0.05 or ＜ 0.01).There were no significant differences in the rrCBF of the parietal and occipital lobe,etc between cerebral type group and control group (P ＞ 0.05).The rrCBF of cerebral type group in the left and right lentiform nucleus were lower than those of non-cerebral type group (1.61 ± 0.38 vs.1.94 ± 0.58,1.52 ± 0.64 vs.1.99 ± 0.59),and there were significant differences (P ＜ 0.05).The clinical symptom scores were positively correlated with the rrCBF of the left and right lentiform nucleus in 24 patients with HLD (r =-0.792 and-0.764,P ＜ 0.01),the content of urinary copper and duration had no correlation with the rrCBF of the left and right lentiform nucleus(P ＞ 0.05).Conclusions The rCBF of cerebral type and non-cerebral type HLD is significantly reduced,cerebral type patients have lower rCBF than non-cerebral type patients.The rCBF is correlated with the clinical symptom scores.
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Objective To examine the brain metabolic changes in WD patients receiving copper chelation by us?ing 1H-MRS. Method Thirty-nine patients with WD was randomly divided into four groups: non-brain type group (18 cases), brain type prior-treatment group and short-term treatment group (21 cases), long-term treatment group (20 cases) from short-term treatment group, and 20 healthy volunteers served as a control group. 1H-MRS and MRI were performed on patients on 1.5/MR/MRS system to detect these above-mentioned items before and after treatment. Result The mean of NAA/Cr was significantly lower in the left putamen and head of the caudate nucleus than in the left basal ganglion in the 39 patients with WD. The mean of NAA/Cr and Cho/Cr in the left putamen and basal ganglion was significantly lower in non-brain type group than in control group(P0.05). The mean of NAA/Cr and NAA/Cho in the left putamen and basal ganglion was much higher in long-term treatment group than in brain type group(P<0.01 or P<0.05). The mean of Cho/Cr in the left head of caudate nucleus were much higher after treatment compared with prior-treatment group(P<0.05). The mean of NAA/Cr in the left putamen, head of the left caudate nucleus and basal ganglion in all groups was negatively correlated with course of the disease. Conclusion There are significant differences in brain metabolism among different type of WD. The long-term but not short-term copper chelation significantly improves brain metabolism. NAA/Cr may be used as a non-invasive indicator to examine the efficacy of treatment.
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<p><b>OBJECTIVE</b>To study the clinical and genetic characteristics of twins and siblings affected with Wilson's disease (WD).</p><p><b>METHODS</b>Clinical data and blood samples were collected from the subjects after informed consent was obtained. Genomic DNA was extracted and potential mutations in the exons in ATP7B gene were detected with PCR-DNA sequencing. Short tandem repeat (STR) genotyping was performed to determine the zygosity of the twins.</p><p><b>RESULTS</b>The 5 pairs of twins have all met the diagnostic criteria for WD. STR genotyping has confirmed that 4 pairs were monozygotic twins. 3 pairs of twins had an onset with liver symptoms, the other 2 had an onset with brain symptoms. ATP7B gene mutations were detected in 4 pairs of twins, which have all located in exons 8 and 13. A heterozygous p.R778W mutation in exon 8 and homozygous p.P992L mutation in exon 13 were detected in all patients from one family, whose parents have carried a heterozygous p.R778W mutation and p.P992L heterozygous mutation, respectively, which suggested loss of heterozygosity (LOH). In one family, no mutation was detected in all exons of the ATP7B gene in the patients and their parents. For a triplet, one female was with definite WD and brain symptoms at the onset, one male had subclinical type with WD, whilst another female was completely normal. The triplets and their mother have all carried a p.P992L heterozygous mutation .</p><p><b>CONCLUSION</b>Above results have confirmed an important role for genetic factors in the pathogenesis of WD. In addition to point mutations, LOH is also involved in the pathogenesis for WD.</p>
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Adolescent , Child , Child, Preschool , Female , Humans , Male , Young Adult , Adenosine Triphosphatases , Genetics , Base Sequence , Cation Transport Proteins , Genetics , Copper-Transporting ATPases , Exons , Genotype , Hepatolenticular Degeneration , Diagnosis , Genetics , Loss of Heterozygosity , Mutation , Siblings , TwinsABSTRACT
@#Objective To study the clinical efficacy of electromyography biofeedback on dystonia after hepatolenticular degeneration.Methods 40 patients with dystonia after hepatolenticular degeneration were divided into treatment group (n=20) and control group (n=20).All patients were treated with copper-cleaning, clonazepam and benzhexol hydrochloride etc., and acupuncture. The treatment group wastreated with electromyographic biofeedback in addition. They were assessed with modified Ashworth scale, modified Barthel index, and ankledorsiflexion active range of motion. Results The lower extremities function of all patients improved after treatment (P<0.05) and thetreatment group improved more than the control group (P<0.05). Conclusion Electromyography biofeedback is more effective to improvethe lower extremities function and activity of daily living in patients with hepatolenticular degeneration following dystonia.
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ObjectiveTo study the quality of life of patients with hepatolenticular degeneration (HLD)and analyze the influencing factors.Methods287 patients with HLD and 51 health people were investigated by World Health Organization quality of life assessment instrument brief version (WHOQOL-BREF),Symptom Checklist 90 (SCL-90),Life Satisfaction Index A (LSIA) and variance analysis,t-test and multiple linear regression analysis were analyzed the influencing factors.Results①Scores of WHOQOL-BREF:physical domain(54.64 ± 17.11 ),psychological domain ( 52.09 ± 15.83 ) in patients with HLD were lower than those in the health people (67.30 ± 12.66,58.90 ± 12.75 ) with statistically significant difference (P ＜ 0.01 ) ; social domain ( 51.35± 17.18),the domain of environment(53.54 ± 16.67) in patients with HLD were lower than those in the health people (57.53 ± 14.99,58.42 ± 10.55 ) with statistically significant difference (P ＜ 0.05 ).②The quality of life of the patients with HLD was influenced by LSIA,total score of SCL-90,the attitude toward the doctors,economic status,the attitude toward the disease,residence with statistically significant difference (P ＜ 0.0l ).ConclusionThe quality of life in patients with HLD is lower than that in health people and much factors influence it,so it is necessary to take multi-facet interventions to improve their quality of life.
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@#ObjectiveTo study the clinical efficcacy of combined therapy of acupuncture, transcutaneous electrical nerve stimulation and swallowing function training in the treatment of dysphagia for hepatolenticular degeneration.MethodsSixty patients with dysphagia for hepatolenticular degeneration were divided into three groups: group A treated with acupuncture, transcutaneous electrical nerve stimulation and swallowing function training, group B treated with acupuncture and swallowing function training, and group C treated with transcutaneous electrical nerve stimulation and swallowing function training. The three groups had all been treated for two courses of treatment(30 d).ResultsThe therapeutic effect of group A outweighed groups B and C and the socres of water swallow test and standardized bedside swallowing assessment(SSA) were higher in group A than in groups B and Cafter the first course of treatment(P＜0.01), while there were no significant difference among the three groups (P>0.05) after the second course of treatment.ConclusionCombined therapy of acupuncture, transcutaneous electrical nerve stimulation and swallowing function training is effective to improve the swallowing function of hepatolenticular degeneration following dysphagia.
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Objective To establish a fast and effective gene diagnosis method for Wilson's disease(WD) patients by double PCR-SSCP technology.Methods We amplificated exon8 and exon12 of ATP7B gene by double PCR from genomic DNA of 140 unrelated WD patients and 30 normal controls,then used SSCP technology to screen them.At last we identificated these patients' mutation features by direct sequencing.Results No abnormality shift was found in 30 controls.In 140 patients,we found 7 types of abnormal mobility shifts in 66 cases(47.14%).In subsequent direct sequencing,mutation rate of Arg778Leu/Gln was 37.14%(52/140),and Thr935Met was 12.86%(18/140).Conclusion Double PCR-SSCP diagnosis technology is a effective method which can improve diagnosis rate for Wilson disease.
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Objective:To study the anti-depression mechanism of Chaiyuwendan Decoction(CYWDD).Methods:Rat models were established by separation and chronic unpredictable mild stress(CUMS).Ethology of rats were detected by open-field test and sucrose consumption test,contents of monoamine neurotransmitters were detected by HPLC-ECD.Results:Compared with normal group,the weight,the frequency of crossing,rearing and the contents of consumption to sucrosum water in depressive disorder rats decreased significantly(P
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<p><b>OBJECTIVE</b>To observe the clinical manifestation of 155 patients with hepatolenticular degeneration (HLD) complicated with epilepsy and the therapeutic effect of integrative Chinese and Western medicine treatment on them.</p><p><b>METHODS</b>Clinical manifestation of patients and its relationship with abnormalities in cranial CT and/or MRI were observed. Patients were treated by combined treatment of copper repellent with sodium dimercaptosulfonate 20 mg/kg per day by intravenous dripping, and modified Gandou Decoction (GDD) by oral intake and antiepileptics as well, after treatment for 8-10 courses, the clinical effect, copper levels in urine and serum were compared between groups.</p><p><b>RESULTS</b>In the 155 HLD patients, 96 were complicated with petit mal and 59 with grand mal. In the CT and/or MRI conducted in 72 patients, all showed abnormal images, besides such frequently met images as bilateral symmetrical basal ganglia focal lesion in 65 case-episode (90.3%) and brain atrophy of various degrees in 61 case-episode (84.7%), the massive lesions in cerebral white matter as principal, with the cortex involved, were also found in 54 patients (74%), which were mostly bilateral and symmetric or located in 2 adjecent lobes of brain, the sites of damage, in sequence of occurrence, were frontal lobe, parietal lobe, temporal lobe and callosal gyrus. Brain atrophy was found in all the remained patients without above-mentioned lesions. Abnormal EEG was shown in 29 patients (40.2%), which mainly manifested as theta wave of moderate to high potential and/or short paroxysmal spike-slow or sharp-slow complex wave evoked. The urinary copper level in patients after treatment was 34.5 +/- 21.6 micromol/24 hrs, significantly higher than that before treatment, 4.49 +/- 1.93 micromol/24 hrs (P < 0.01). And the serum copper level in patients also lowered significantly (P< 0.01). Epileptic seizure was controlled completely along with the gradually improving of extrapyramidal symptoms.</p><p><b>CONCLUSION</b>Partial seizure was the most common type of seizure of HLD patient complicated with epilepsy, the next is systemic seizure. Cerebral damage lesion and obvious brain atrophy could be the main etiological factors of HLD complicated with epilepsy, combined copper repellent therapy of integrative Chinese and Western medicine, and antiepileptics produced good clinical effect on the patients.</p>
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Adolescent , Adult , Female , Humans , Male , Anticonvulsants , Therapeutic Uses , Chelating Agents , Therapeutic Uses , Drug Therapy, Combination , Drugs, Chinese Herbal , Therapeutic Uses , Epilepsy , Drug Therapy , Hepatolenticular Degeneration , Drug Therapy , Phytotherapy , Unithiol , Therapeutic UsesABSTRACT
Objective To explore the value of immunofluorescent technique for clinical diagnosing Duchenne muscular dystrophy(DMD),Becker muscular dystrophy(BMD) and Limb-girdle muscular dystrophy(LGMD).Methods Immunofluorescent technique was applied,and the expressions of Dys1,Dys2,Dys3 monoclonal antibodies and ?-,?-,?-sarcoglycan(SG) polyclonal antibodies against dystrophin,?-SG,?-SG,?-SG in musculomembranes of frozen section specimens from 25 patients(10 cases of DMD,4 cases of BMD and 11 cases of LGMD) were detected.Results 10 DMD patients had negative staining of dystrophin,and 4 BMD patients had discontinuous or a patchy positive staining pattern.All LGMD patients had positive dystrophin staining.There was one patient presented negative staining of ?-SG and ?-SG,respectively.Conclusions Detecting of dystrophin by immunofluorescent technique is special and helpful in diagnosing and classifying DMD/BMD.At present,SG may not be used in diagnosing the LGMD patients.
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Objective To explore the level and main functions of P-type ATPase7B in hepatic cells of patients with hepatolenticular degeneration(HLD).Methods The hepatic cells from 5 normal controls and 9 patients with HLD were cultured in vitro. P-type ATPase7B levels in hepatic cells were examined and compared by SDS-PAGE and Western-blot techniques.Results Compared with the controls, 9 patients displayed various changes of electrophoresis strip. Almost normal strips at 155?103 were found in 3 cases, no strip was found in 1 case, and thinner and lighter strips were showed in the remain 5 cases. 6 cases presented abnormal specific reaction strips.Conclusion Mutations of gene ATPase7B in HLD patients cause change of P-type ATPase7B in quantity and quality, thus leads to dysmetabolism of copper.