The study of Wilson disease in pregnancy management.

INTRODUCTION: Pregnancy management in women with Wilson disease (WD) remains an important clinical problem. This research was conducted to investigate how to avoid worsening of WD symptoms during pregnancy and increase pregnancy success in women with WD by identifying the best pregnancy management approaches in these patients. PATIENTS AND METHODS: The clinical data of 117 pregnancies among 75 women with WD were retrospectively analyzed. Related information of the fetus was also recorded and analyzed. At the same time, regression analysis was performed for data of 22 pregnant women without WD, as normal controls. RESULTS: Of a total of 117 pregnancies among the 75 women with WD and 31 pregnancies among the 22 control womenincluded in this study, there were 108 successful pregnancies and 9 spontaneous abortions. Among the 108 successful pregnancies, 97 women a history of copper chelation therapy before pregnancy; all 97 women stopped anti-copper therapy during pregnancy. The nine women with spontaneous abortion had no pre-pregnancy history of copper displacement therapy. The incidence of lower limb edema was higher in the WD group than in normal controls (P = 0.036). Compared with the control group, there was a higher proportion in the WD group of male infants (P = 0.022) and lower average infant birth weight (t = 3.514, P = 0.001). CONCLUSION: It is relatively safe for women with WD patients to become pregnant. The best management method for pregnancy in women with WD may be intensive pre-pregnancy copper chelation therapy and no anti-copper treatment during pregnancy.

Using time-series Sentinel-1 data for soil prediction on invaded coastal wetlands.

Coastal soils are particularly sensitive to nonnative species invasion. In this context, spatially explicit soil information is essential for improving the knowledge of the role of soil in changing environments, supporting coastal sustainable management. Synthetic-aperture radar (SAR) data provides an attractive opportunity to monitor soil because the acquisition of images is independent of weather and daylight. However, SAR has not been commonly used for soil prediction. In this study, we firstly investigated the temporal variation of vegetation canopy and the soil-vegetation relationship using Sentinel-1 data in an invaded coastal wetland. And then we built 3D models to predict soil properties at multiple depths. A total of 16 Sentinel-1 images were acquired in a growing season. A series of soil physicochemical properties were examined including soil bulk density, texture, organic/inorganic carbon, pH, salinity, total nitrogen, and C/N ratio, relating to three depth layers in the top 1-m depth. Our results showed that time-series Sentinel-1 data can capture temporal characteristics of vegetation, and VH/VV was more sensitive to the vegetation growth than VH and VV. The soil-vegetation relationship captured by time-series SAR data was beneficial to predict soil properties, especially for soil chemical properties. The models provided permissible prediction accuracy, with an average RPD of 0.99. We concluded that the prior understanding of the temporal variation of SAR data is essential for developing practical soil prediction strategy. Our results highlight that SAR has the potential to predict a diverse set of soil properties in coastal wetlands with dense vegetation cover.

Sexual dysfunction in Wilson disease: Prevalence and influencing factors.

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.

Case report: A Chinese patient with spinocerebellar ataxia finally confirmed as Gerstmann-Sträussler-Scheinker syndrome with P102L mutation.

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.

[Epidemiological study of hepatolenticular degeneration at Hanshan County, Anhui Province].

OBJECTIVE: To identify the incidence and morbidity rates of hepatolenticular degeneration (HLD) at Hanshan County, Anhui Province. METHODS: According to the principles of age stratification, cluster and random sampling, a total of 112 810 subjects were screened by cornea slit-lamp examination during the period of November 2008 to October 2009. The subjects were from recruited from schools, factories, communities, institutions and villages at Hanshan County. And they belonged to the age group of 7 - 75 years. At the same time, each subject was evaluated by the clinical examination with regards to the presence of such clinical manifestations as brain, liver, kidney, skin and other organ damage. And the examinations of copper biochemistry and abdominal ultrasound were performed for those subjects with K-F rings or their clinical manifestations suspicious of HLD. In order to confirm or exclude HLD, the penicillamine challenge test (PCT) was performed if necessary. RESULTS: Seven HLD patients had a definite diagnosis of HLD. There were classical Wilson type (n = 1), pseudosclerosis type (n = 1), mental disorder type (n = 1), liver type (n = 1) and presymptomatic (n = 3). The incidence rate was 2.66/100 000 and the prevalence rate 6.21/100 000 at Hanshan County, Anhui Province. CONCLUSION: HLD is a common disease. In order to avoid a misdiagnosis and prevent an incorrect treatment, physicians should pay more attention to this curable disease and try their best to achieve early detection, early diagnosis and early treatment.

Management Perspective of Wilson's Disease: Early Diagnosis and Individualized Therapy.

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.

Exploring the likely relationship between soil carbon change and environmental controls using nonrevisited temporal data sets: Mapping soil carbon dynamics across China.

The prediction of soil organic carbon (SOC) changes in response to environmental change is often limited by a scarcity of revisited temporal data, which constrains scientific understanding and realistic predictions of soil carbon change. The present study improved the potential of nonrevisited temporal data in the prediction of SOC stocks (SOCS) variations. We proposed a method to develop predictions of SOCS change using two independent temporal data sets (pertaining to the 1980s and 2010s) in China based on the digital soil mapping technique. Changes in SOCS over time at the site level were analyzed via the interpolation of missing SOCS values in each data set. Quantitative SOCS change predictions were generated by modeling the relationship between SOCS change and variables that represent changes in climate, vegetation indices, and land cover. The scale-dependent response of SOCS change to these environmental dynamics was assessed. On average, a slight increase was observed from 3.70 kg m-2 in the 1980s to 4.53 kg m-2 in the 2010s. The proposed approach attained moderate accuracy with an R2 value of 0.32 and a root mean squared error (RMSE) of 1.73 kg m-2. We found that changes in climate factors were dominant controls of SOCS change over time at the country scale. At the regional scale, the controlling factors of SOCS change were distinct and variable. Our case study may be of value in the application of independent temporal data sets to analyze soil carbon change on multiple scales. The method may be used to resolve questions of soil carbon change projections and provide an alternative solution to predict likely changes in soil carbon in response to future environmental change when no temporal data are available.

Mechanisms of soil organic carbon storage response to Spartina alterniflora invasion and climate change.

Coastal wetlands have been identified as vital global carbon (C) sinks; however, soil C sequestration in these ecosystems is susceptible to impacts of non-native species invasion and climate change worldwide. Although their potential impacts on soil organic C (SOC) storage have been reported in previous literature, the well-established mechanisms that control SOC storage response, especially in relation to soil depths, is still limited. To fill this knowledge gap, we developed a structural equation model (SEM) to identify mechanisms that account for SOC changes in topsoil (0-0.3 m) and subsoil (0.3-0.6 m) on coastal wetland of the East China Sea, where SOC in both depths increased with exotic Spartina alterniflora invasion. In the initial model, we hypothesized that there were a set of direct and indirect effects of the invasion, climate, and soil physicochemical properties on SOC storage. By evaluating the interactions of these factors, we found relatively complex patterns that vary with depth. For topsoil, the invasion had not only direct effects on SOC storage, but also indirect effects through mediating effects of soil water content (SWC) that was linked to fine soil fractions. For subsoil, the invasion was indirectly related to SOC storage through mediating effects of SOC in topsoil, SWC, and salinity. SOC in subsoil was also affected by temperature. Our results highlight that the response of SOC storage to the invasion and climate change results from the interacting effects of climate-plant-soil system.

Long-term outcomes of a patient with late-onset multiple acyl-CoA dehydrogenase deficiency caused by novel mutations in ETFDH: A case report.

RATIONALE: Late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD) mainly affects the neck extensor muscle group, which has been confirmed by novel mutations in electron-transferring-flavoprotein dehydrogenase (ETFDH). So far, a few cases have been reported with long-term follow-up. Here we report a case of late-onset MADD where the patient was followed up for 8 years during which time he underwent 2 muscle biopsies and 2 pathological examinations and his symptoms were significantly alleviated after appropriate treatments. PATIENT CONCERNS: In September 2009, a 16-year-old male patient was hospitalized due to gradually increasing difficulty in raising his head and weakness in limb muscles over a 6-month period. During the physical examination, the patient's neck extensor muscle strength was grade III-IV. His proximal limb muscle strength was grade IV, and his distal muscle strength was normal. His blood creatine kinase (CK) was 783 U/L. DIAGNOSIS: Muscle biopsy revealed a large number of vacuolar fibers, which were mainly type I fibers. These findings were consistent with the diagnosis of lipid storage myopathy (LSM). ETFDH gene test detected C.736G > A at exon 7 and C.920C > G at exon 8. INTERVENTIONS: Coenzyme Q10 treatment was administered. The first coenzyme Q10 40 mg tid was treated for three months, with the change of coenzyme Q10 20 mg tid for 6 months, followed by the change of coenzyme Q10 10 mg tid for long-term use. OUTCOMES: The patient's condition significantly improved after 3 months. At 7th year follow-up the patient's blood CK was normal, and a second muscle biopsy revealed no muscle vacuolar fibers and no increase in lipid droplets. Subsequently, the patient was withdrawn from the coenzyme Q10 treatment, and the condition of the patient remained normal. LESSONS: Muscle biopsy was the main method used to determine LSM. Treatment with riboflavin should be started when the diagnosis of LSM is definitive. Furthermore, ETFDH gene tests should be performed for further classification. Moreover, coenzyme Q10 may be another effective drug for MADD.

[Effect of Gandou Decoction IV combined with short-term decoppering therapy with sodium dimercapto-sulphonate on serum indexes of hepatic fibrosis in patients with Wilson' s disease].

OBJECTIVE: To observe the effect of Gandou Decoction IV (GDIV) on serum indexes of hepatic fibrosis and liver function in patients with Wilson's disease (WD). METHODS: Sixty-one WD patients were assigned to two groups, 30 patients in the sodium dimercaptosulphonate (DMPS) group and 31 patients in the GD IV group. Both groups received 8 courses of DMPS treatment with 6 days as one course, and the GD IV group was given GD IV additionally. Serum indexes of liver function were examined, serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by double antibody sandwish ABC enzyme-linked immunosorbent assay (ELISA), and serum hyaluronic (HA), laminin (LN), procollagen III (PC III) and collagen type IV (C-IV) were determined by radioimmunoassay (RIA). RESULTS: After treatment, all indexes of hepatic fibrosis and liver function had no significant change in the DMPS group, while in the GD IV group, the serum TIMP-1 level markedly decreased (P <0.05), the ratio of MMP-1/TIMP-1 significantly increased (P <0.01), and serum indexes of liver function markedly decreased (P < 0.05), but the changes in serum levels of HA, LN and PCIII, as well as in serum MMP-1 and C-IV were insignificant (P> 0.05), though they showed a trend of decreasing or increasing, respectively. CONCLUSION: Short-term decopper-ing treatment with DMPS alone has no significant effect on hepatic function and serum fibrosis indexes in WD patients, while combined with GD IV, it can improve liver function and display an anti-fibrosis effect through inhibiting the serum TIMP-1 level and increasing the ratio of MMP-1/TIMP-1.

Pedogenic knowledge-aided modelling of soil inorganic carbon stocks in an alpine environment.

Accurate estimation of soil carbon is essential for accounting carbon cycling on the background of global environment change. However, previous studies made little contribution to the patterns and stocks of soil inorganic carbon (SIC) in large scales. In this study, we defined the structure of the soil depth function to fit vertical distribution of SIC based on pedogenic knowledge across various landscapes. Soil depth functions were constructed from a dataset of 99 soil profiles in the alpine area of the northeastern Tibetan Plateau. The parameters of depth functions were mapped from environmental covariates using random forest. Finally, SIC stocks at three depth intervals in the upper 1m depth were mapped across the entire study area by applying predicted soil depth functions at each location. The results showed that the soil depth functions were able to improve accuracy for fitting the vertical distribution of the SIC content, with a mean determination coefficient of R2=0.93. Overall accuracy for predicted SIC stocks was assessed on training samples. High Lin's concordance correlation coefficient values (0.84-0.86) indicate that predicted and observed values were in good agreement (RMSE: 1.52-1.67kgm-2 and ME: -0.33 to -0.29kgm-2). Variable importance showed that geographic position predictors (longitude, latitude) were key factors predicting the distribution of SIC. Terrain covariates were important variables influencing the three-dimensional distribution of SIC in mountain areas. By applying the proposed approach, the total SIC stock in this area is estimated at 75.41Tg in the upper 30cm, 113.15Tg in the upper 50cm and 190.30Tg in the upper 1m. We concluded that the methodology would be applicable for further prediction of SIC stocks in the Tibetan Plateau or other similar areas.

Current Drug Managements of Wilson's Disease: From West to East.

Wilson's disease (WD), also called hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism characterized by the multiple mutations in the ATP-ase 7B gene of chromosome 13q. About half of the WD patients have neurological or psychiatric symptoms. As WD is a kind of medicable or nearly curable neurodegenerative disease in the field of medicine, early consideration/examination and without delay/ life-long treatment usually lead to better prognoses. The drugs, also named as anticopper agents, are commonly used in clinics including D-penicillamine, trientine, sodium dimercaptosuccinate, dimercaptosuccinic acid, zinc and tetrathiomolybdate. This provides detailed reviews about these medicines.

Precise estimation of soil organic carbon stocks in the northeast Tibetan Plateau.

There is a need for accurate estimate of soil organic carbon (SOC) stocks for understanding the role of alpine soils in the global carbon cycle. We tested a method for mapping digitally the continuous distribution of the SOC stock in three dimensions in the northeast of the Tibetan Plateau. The approach integrated the spatial distribution of the mattic epipedon which is a special surface horizon widespread and rich in organic matter in Tibetan grasslands. Prediction models resulted in high prediction accuracy. An average SOC stock in the mattic epipedon was estimated to be 4.99 kg m(-2) in a mean depth of 14 cm. The amounts of SOC in the mattic epipedon, the upper 30 cm and 50 cm accounted for about 21%, 80% and 89%, respectively, of the total SOC stock in the upper 1 m depth. Compared with previous estimates, our approach resulted in more reliable predictions. The mattic epipedon was proven to be an important factor for modelling the realistic distribution of the SOC stock in Tibetan grasslands. Vegetation-related covariates have the most important influence on the distribution of the mattic epipedon and the SOC stock in the alpine grassland soils of northeast Tibetan Plateau.

Impairment of recognition of disgust in Chinese with Huntington's or Wilson's disease.

The selective involvement of the basal ganglia in recognition of the facial expression of disgust was investigated by examining a group of six symptomatic Huntington's disease patients and 32 Wilson's disease patients in China. Morphed photographs of facial expressions covering happiness-surprise-fear-sadness-disgust-anger were used and the patients were asked to label each photo. Other measures assessed basic cognitive functions and perception of non-emotion facial information, such as perception of gender, age, gaze direction, and recognition of unfamiliar as well as famous people. There was dissociation between the perception of emotions and other facial information, and between impairment of recognition of disgust and other emotions. The basal ganglia are the overlapping substrate involved in both Huntington's and Wilson's disease, although each has its own other lesions. The differentially severe impairment of recognition of disgust in the Chinese Huntington's disease and Wilson's disease patients strengthens the view that basal ganglia are selectively involved in processing the emotion of disgust.

Anticopper efficacy of captopril and sodium dimercaptosulphonate in patients with Wilson's disease.

The aim of this study was to explore and compare initial treatment effects of captopril (Tensiomin) and sodium dimercaptosulphonate (DMPS) on a relatively large series of Wilson's disease inpatients. Two important markers of anticopper efficacy: serum sulphydryl and 24 h urinary copper levels in the patients were evaluated before and after treatment. The patients were randomly subdivided into 4 groups to allow statistical analysis (ANOVA) of the values recorded. The protocol was an open-label study of all the patients treated for 8 weeks (i.e., all the patients except those in the no-drug group), and a further six-month follow-up (post hospitalization) of the 14 patients administered captopril. Several copper-related variables were studied to evaluate the effect of the drugs on copper, and several biochemical and clinical variables were studied to evaluate potential toxic effects. Captopril was found to have a significant anticopper effect and did not markedly raise serum sulphydryl levels within this limited patient sample; the anticopper efficacy of captopril was, however, found to be markedly lower than that of DMPS; DMPS was found to raise the patients' serum sulphydryl and urinary copper levels. Evaluation of data from individual patients revealed evidence of a toxic side effect in only 1 patient, treated with DMPS, who exhibited transiently raised serum alanine aminotransferases, while no serious adverse events, upstanding syncope, irritating cough and leukopenia induced by captopril were noted. The results obtained in this four-group sample suggest that captopril might be a mild anticopper agent for Wilson's disease, possibly relieving the hepatic portal hypertension, but that DMPS has a greater field of anticopper efficiency than captopril. The authors also discuss recent experience of the overall treatment in China.

[Effect of gandou tablet I on neurological electrophysiology in patients of hepatolenticular degeneration].

OBJECTIVE: To observe the influence of Gandou Tablet I (GD I) on neurologic electrophysiology in patients of hepatolenticular degeneration (HLD). METHODS: Vigilance-controlled electroencephalogram (VEEG), electromyogram (EMG) and brain-stem auditory evoked potential (BAEP) in 32 cases of HLD were examined before GD I treatment, and reexamined after 4 weeks of treatment in those with abnormal neurologic electrophysiology. RESULTS: At the same time of clinical symptom improvement after treatment, the abnormal VEEG, EMG and BAEP also improved with the effective rate of 71.43%, 70% and 66.67% respectively, their constitutional ratio were different insignificantly, P > 0.05. The peak latency (PL) of III, V waves and interpeak latency (IPL) of I-III, III-V and I-V waves in patients before treatment were all greatly prolonged, compared with those in the healthy control group (P < 0.05 or 0.01), the IPL of III-V and I-V waves were markedly improved after treatment. CONCLUSION: Neurologic electrophysiologic examination was valuable for complementary diagnosis and therapeutic effect evaluation of HLD. GD I could improve the abnormal neurologic electrophysiologic parameters.

Comparison of long lasting therapeutic effects between succimer and penicillamine on hepatolenticular degeneration.

AIM:To compare the long-term effect of succimer (Suc) with that of penicillamine (Pen) in treating hepatolenticular degeneration (HLD).METHODS:One hundred and twenty patients with HLD were divided into 2 groups. Group A (n =60) received Suc 750mg,po.bid.Group B (n =60) received Pen 250mg, po. qid. The period of maintenance treatment varied from 6 months to 3 years, averaging 1.5 years. Symptoms and therapeutic effects were evaluated by modified Goldstein scale.RESULTS:The total effectiveness of group A in two different periods of treatment were 80% and 85% respectively, higher than those of group B (58% and 59% respectively)(P < 0.05). Suc also had obvious curative effects for the patients who failed in the use of Pen. There were fewer side effect in group A than in group B (P < 0.05). Suc and Pen could increase urinary copper excretion effectively and continually.CONCLUSION:Suc is more effective and safer than Pen. Clinically, it can replace Pen as first-choice drug for long-term maintenance therapy of HLD.

Copper-chelating therapeutic effect in Wilson disease with different clinical phenotypes and polymorphisms of ATP7B gene.

AIM:To investigate the copper-chelating therapeutic effect in Wilson disease (WD) with different clinical phenotypes and polymorphisms of ATP7B gene.METHODS:One hundred and twenty-two WD patients with different clinicalphenotypes were given DMPS intravenously and Gandou copper-chelating tablet orally for one month. The therapeutic effect was judged by modified Goldstein mothod. Exon 18 of ATP7B gene extracted from the DNA of patients and 20 healthy volunteers was amplified with PCR mutation and polymorphism were screened with SSCP technique.RESULTS:Four kinds of abnormal migration bands in PCR-SSCP were observed in 37 WD patients, mutation frequencies of three different disease phenotypes, and curative effect between mutation group and non-mutation group showed no statistically significant difference (P > 0.05), but the total effectiveness rates in patients with Wilson type or pseudosclerosis type were significantly higher than those of patients with hepatic type (X(2) = 6.17, P < 0.05).CONCLUSION:Most WD patients are compound heterozygotes, the patients with different clinical phenotypes have different response to copper-chelating therapy. Specific mutation, at least in part, plays a role in influencing the disease phenotypes and therapeutic effect.