Depleting ANTXR1 suppresses glioma growth via deactivating PI3K/AKT pathway.

Gliomas are commonly known as primary brain tumors and associated with frequent recurrence and an unsatisfactory prognosis despite extensive research in the underlying molecular mechanisms. We aimed to examine the role of ANTXR1 in glioma tumorigenesis and explore its downstream regulatory mechanism. ANTXR1 expression in clinical specimens and its relationship with some pathological characteristics were detected using immunohistochemical staining. After silencing/upregulating ANTXR1 through lentiviral transfection in glioma cell lines, qRT-PCR and western blotting were used to examine mRNA and protein levels, and cell phenotype was also detected. ANTXR1-knockdown and -overexpression cells were then processed by AKT activator and PI3K inhibitor, respectively, to verify downstream PI3K/AKT pathway regulated by ANTXR1. Xenograft nude mice models were constructed to verify the role of ANTXR1 in vivo. We found overexpression of ANTXR1 in both cell lines in comparison with those in normal brain tissues. Glioma cell growth and migratory ability were dramatically impaired as a result of silencing ANTXR1 by shANTXR1 lentiviruses. ANTXR1 blockade also accelerated cell apoptosis and held back cell cycle via targeting G2 phrase during cell mitosis. In vivo xenograft models verified in vitro findings above. Further exploration disclosed that AKT activator promoted anti-tumor effects mediated by ANTXR1 knockdown, while PI3K inhibitor limited pro-tumor effects mediated by ANTXR1 overexpression, indicating that ANTXR1 functioned in glioma cells through regulating PI3K/AKT pathway. ANTXR1 could play an indispensable role in glioma tumorigenesis via activating PI3K/AKT-mediated cell growth. Our study provides a theoretical basis for targeting ANTXR1 as a molecular target in glioma clinical therapeutics.

Magnetic resonance imaging image analysis of the therapeutic effect and neuroprotective effect of deep brain stimulation in Parkinson's disease based on a deep learning algorithm.

In order to study the therapeutic neuroprotective effect of deep brain stimulation (DBS) in Parkinson's disease (PD), based on the deep learning algorithm, this study combines with magnetic resonance imaging (MRI) image analysis technology to study the clinical efficacy of DBS in the surgical treatment of PD and the neuroprotective and neurological recovery effects after surgery. Establish a deep learning algorithm model based on MRI image analysis technology, comparison of UPDRS motor status assessment and the improvement of daily life ability before and after DBS surgery, evaluate the accuracy rate and the detection speed of the model. The models constructed in this study have an accuracy rate of more than 90% in the PD detection test, and the detection speed of the algorithm model under the condition of big data is between 60 and 200 ms. DBS significantly improve a series of clinical symptoms in patients with PD. The deep learning algorithm model based on MRI image analysis technology in this paper has a certain effect. DBS operation can improve the symptoms of PD, and has the effect of neuroprotection and neurological recovery.

LncRNA miR-17-92a-1 cluster host gene (MIR17HG) promotes neuronal damage and microglial activation by targeting the microRNA-153-3p/alpha-synuclein axis in Parkinson's disease.

Long noncoding RNAs (lncRNAs) have been regarded as modulators of neurodegenerative diseases. Here, we addressed the role of lncRNA miR-17-92a-1 cluster host gene (MIR17HG) in Parkinson's disease (PD). C57BL/6 mice and SH-SY5Y cells were intervened with 6-hydroxydopamine (6-OHDA) to set up PD models in vivo and in vitro. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was implemented to compare the expression of MIR17HG and miR-153-3p. Cell viability and apoptosis were estimated by 3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) and Western blot (WB). The expression of alpha-synuclein (α-syn, SNCA) in BV2 was validated by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) generation and lactate dehydrogenase (LDH) and superoxide dismutase (SOD) activity were evaluated using commercially available kits. Bioinformatics analysis, the dual-luciferase reporter assay, RNA immunoprecipitation (RIP) and qRT-PCR were conducted to demonstrate the interactions between miR-153-3p, MIR17HG, and alpha-synuclein (SNCA). MIR17HG was up-regulated while miR-153-3p was down-regulated in PD patients, mouse models and cells. Inhibiting MIR17HG attenuated neuronal apoptosis, microglial activation and SNCA expression in PD mice. Conditioned medium from 6-OHDA-treated SH-SY5Y cells intensified microglial inflammation, while inhibition of MIR17HG or overexpression of miR-153-3p restrained the inflammatory responses. MIR17HG's function was enforced by sponging miR-153-3p and releasing the attenuation of the putative targets of miR-153-3p and SNCA. Overall, MIR17HG, by targeting miR-153-3p and up-regulating SNCA, stimulates neuronal apoptosis and microglial inflammation in PD.

LncRNA FEZF1-AS1 aggravates cell proliferation and migration in glioblastoma.

OBJECTIVES: Glioblastoma (GBM) represents the commonest malignant glioma. Long non-coding RNA (lncRNA) FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been validated to play an oncogenic role in multiple human malignancies, while its function in GBM has not been largely reported. We aim to identify the regulatory mechanism of FEZF1-AS1 in GBM. MATERIALS & METHODS: The expression pattern of FEZF1-AS1 was firstly figured out in GBM cells using RT-qPCR. Then, functional assays were conducted to examine the influence FEZF1-AS1 had on the biological properties of GBM cells. The downstream targets of FEZF1-AS1 were predicted and the underlying regulatory mechanism was determined by mechanism assays. RESULTS: FEZF1-AS1 possessed high expression in GBM cells. Down-regulation of FEZF1-AS1 suppressed GBM cell proliferation, migration and invasion while inducing cell apoptosis. With the help of bioinformatics prediction and mechanism assays, FEZF1-AS1 was found to bind to miR-363-3p and NOB1 was determined to be the downstream gene. Finally, results of rescue assays verified that the suppressive function of FEZF1-AS1 inhibition on GBM development were restored by miR-363-3p depletion or overexpression of NOB1. CONCLUSION: FEZF1-AS1 had oncogenic function in the advancement of GBM by targeting miR-363-3p/NOB1, which made FEZF1-AS1 a potential biomarker for GBM treatment.

High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma.

BACKGROUND: PYD and CARD domain-containing (PYCARD) was upregulated in TMZ-resistant cell lines and glioma tissue and was correlated with poor prognosis, its role in glioma is unclear known. The aim of this study was to elucidate the relationship between PYCARD and glioma based on Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and Chinese Glioma Genome Atlas (CGGA) databases. METHODS: Glioma-resistant cells were compared with parental cells based on the GSE53014 and GSE113510 data sets. The relationship between PYCARD, tumor microenvironment, and long noncoding RNAs (lncRNAs) was assessed using logistic regression. Moreover, Kaplan-Meier and Cox regression were used to analyze the relationship between PYCARD expression and survival rate. Gene set enrichment analysis (GSEA) was also used to determine the biological function of PYCARD and lncRNAs. Cell viability and cell migration assays were used to evaluate the ability of cells to migrate and proliferate. Finally, we analyzed the expression patterns of PYCARD genes in a wide range of cancers. RESULTS: Elevated expression of PYCARD promoted glioma cell proliferation and migration. PYCARD expression was significantly positively associated with gamma delta T cells but negatively correlated with M2 macrophages in glioblastoma multiforme (GBM). Likewise, PYCARD expression was significantly positively associated with monocytes but negatively associated with activated mast cells in low grade glioma (LGG). We also found that 3 PYCARD-related lncRNAs in GBM and 4 PYCARD-related lncRNAs in LGG had a predictive value for glioma patients. The pan-cancer analysis showed that PYCARD expression was higher in most cancer groups. CONCLUSIONS: High expression of PYCARD is an independent predictor of unfavorable prognosis and chemotherapy resistance in glioma.

Downregulation of microRNA-15b-5p Targeting the Akt3-Mediated GSK-3ß/ß-Catenin Signaling Pathway Inhibits Cell Apoptosis in Parkinson's Disease.

Parkinson's disease (PD) is an incurable progressive disorder resulting from neurodegeneration, and apoptosis is considered a dominant mechanism underlying the process of neurodegeneration. MicroRNAs (miRNAs), which are small and noncoding RNAs involved in many a biological process like apoptosis and regulation of gene expressions, have been found in postmortem brain samples of patients with PD, as well as in vitro and in vivo models of PD. To explore the impact of miR-15b-5p and Akt3 on apoptosis in the progression of PD, the method of quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed, and the analysis result showed upregulated expression of miR-15b-5p and downregulated expression of Akt3 in the serum of PD patients, MPP+-induced SH-SY5Y cells, and the brain tissues of MPTP-induced mice. Meanwhile, the dual-luciferase reporter assay was used to demonstrate the regulator-target interaction between miR-15b-5p and Akt3; flow cytometry and spectrophotometry revealed that transfection of miR-15b-5p mimic and si-Akt3 increased the rate of apoptosis and caspase-3 activity, whereas transfecting the miR-15b-5p inhibitor and Akt3-overexpression plasmid repressed the rate of apoptosis and caspase-3 activity in the MPP+-induced SH-SY5Y cell model and the MPTP-induced mouse model. Additionally, analysis of western blotting (WB) assays in vivo and in vitro revealed that proapoptosis proteins (Bax, caspase-3, GSK-3ß, and ß-catenin) showed markedly upregulated expression in the miR-15b-5p inhibitor and si-Akt3-overexpression groups, while the expression of an antiapoptosis gene (i.e., Bcl2) was downregulated. These analysis results indicate that downregulation of miR-15b-5p by targeting the Akt3-mediated GSK-3ß/ß-catenin signaling pathway would repress cell apoptosis in PD in vivo and in vitro. It is expected that the research findings would help find new therapeutic targets for treatment of PD.

COX10-AS1 Facilitates Cell Proliferation and Inhibits Cell Apoptosis in Glioblastoma Cells at Post-Transcription Level.

Glioblastoma (GBM) is an invasive cancer with poor prognosis in patients. Researching on molecular functions in GBM has attracted more and more attention. Actin gamma 1 (ACTG1) was reported as a pathogenic gene in skin cancer and colorectal cancer. Present study was designed to explore the biological role and underlying mechanism of ACTG1 in GBM cells. It was uncovered that ACTG1 presented high expression trends in GBM cells. Moreover, ACTG1 suppression hindered cell proliferation and boosted cell apoptosis in GBM. Then, according to the results of bioinformatics analysis and mechanism assays including RIP, RNA pull down and luciferase reporter assay, ACTG1 was verified to be targeted by miR-361-5p in GBM. Next, COX10-AS1 (COX10 antisense RNA 1) was identified as an endogenous sponge for miR-361-5p in GBM. Moreover, COX10-AS1 acted as a competing endogenous RNA (ceRNA) to positively regulate ACTG1 expression via sponging miR-361-5p. The following rescue assays demonstrated that COX10-AS1 promoted GBM cell proliferation and inhibited GBM cell apoptosis through ACTG1 up-regulation at a miR-361-5p dependent way. On the whole, present study uncovered a novel ceRNA pattern in which COX10-AS1 sponged miR-361-5p to elevate ACTG1 expression, therefore accelerating tumorigenesis in GBM. The findings suggested new promising targets for GBM treatment.

Circular RNA SMO sponges miR-338-3p to promote the growth of glioma by enhancing the expression of SMO.

Glioma is one of the most common tumors in the brain and complete cure still a challenge. The present research aimed to investigate the molecular mechanism of circular RNA SMO (circSMO742) in glioma, via targeting miR-338-3p and regulating SMO expression. QRT-PCR was utilized to examine the expression profiles of circSMO742 and microRNA-338-3p (miR-338-3p) in glioma. SMO protein in glioma was tested via western blot. RNA pulldown assay and dual luciferase reporter assays were used to explore the targeting correlation between RNAs. MTT assay, transwell assays and flow cytometry were used to investigate cell proliferation, migration and invasion, and apoptosis, respectively. Tumor xenograft was done to ascertain the effect of circSMO742 knocking down on tumor growth. CircSMO742 and SMO were highly expressed in glioma tissues, while miR-338-3p expression was reduced. CircSMO742 together with SMO could promote cells proliferation, migration and invasion while inhibit cells apoptosis, whereas miR-338-3p showed negative impacts on the cell activity. Knocking down of circSMO742 suppressed glioma growing in vivo. CircSMO742 promoted glioma growth by sponging miR-338-3p to regulate SMO expression. Our research revealed a new molecular mechanism of glioma growth and provide a fresh perspective on circRNAs in glioma progression.

Geniposide Attenuates Post-Ischaemic Neurovascular Damage via GluN2A/AKT/ ERK-Dependent Mechanism.

BACKGROUND/AIMS: Calcium-permeable ionotropic NMDAR-mediated hyperactivity is regarded as the critical factor in modulating the development of ischaemic stroke. Recently, there has been increasing interest in preventing post-stroke neuronal death by focusing on intervening in the function of subpopulations of NMDARs and their downstream signalling. Geniposide, an iridoid glycoside, has been found to have cytoprotective functions in various conditions. However, it is still unclear whether and how geniposide affects neuronal insult under experimental stroke. METHODS: We demonstrate that dose-dependent geniposide significantly decreased the infarct volume in tMCAO models. RESULTS: A medium level of geniposide improved anti-apoptotic functions and inhibited BBB leakage/haemorrhage via elevating GluN2A-containing NMDAR expression in tMCAO rats. Importantly, these effects could be eliminated by co-treatment of geniposide with the GluN2A antagonist NVP but not the GluN2B inhibitor ifenprodil. Moreover, geniposide's protection was due to the enhancement of GluN2A-dependent survival signals, including pAKT, pERK and PSD-95. CONCLUSION: The results suggest that geniposide protects neurons against post-ischaemic neurovascular injury through the activation of GluN2A/AKT/ERK pathways. As a very promising natural agent, geniposide may be a future therapeutic for stroke patients.

Surgical outcome of thoracic myelopathy caused by ossification of ligamentum flavum.

Ossification of the ligamentum flavum (OLF) may result in thoracic myelopathy (TM) because of the spinal canal narrowing. The aim of this study was to investigate clinical outcomes of symptomatic thoracic OLF treated using posterior decompressive laminectomy. We made a retrospective review of patients who underwent posterior decompressive laminectomy from 2007 through 2016 for symptomatic TM caused by OLF. Thirty-three patients who had surgery for TM caused by OLF that was diagnosed based on clinical, radiologic, and pathologic evaluations. All patients had undergone decompressive laminectomy and excision of the OLF. The clinical course was evaluated according to modified JOA scores. Magnetic resonance imaging was used to determine the number of vertebral segments demonstrating OLF, the level of thoracic cord involvement, and spine lesions coexisting with OLF. Results showed the neurological status improved at follow up (70.82±32.22months) from a preoperative mean Japanese Orthopaedic Association score of 7.03±1.29 points to 9.52±0.83 points at the last follow up (p<0.01). Recovery outcomes were excellent in 8 patients, good in 22 patients, fair in 2 patients and poor in 1 patient. Surgical complications, which resolved after appropriate and prompt treatment, including cerebrospinal fluid leakage in 4 patient, immediate postoperative neurologic deterioration in 2 patient, and wound infection in 4 patient. Our findings suggest that posterior decompressive laminectomy with or without instrumented fusion is an effective treatment for symptomatic thoracic OLF, which provides satisfactory clinical improvement.

Muscle MRI findings in a one-year-old girl with merosin-deficient congenital muscular dystrophy type 1A due to LAMA2 mutation: A case report.

The objective of the present study was to characterize the muscle magnetic resonance imaging (MRI) features of a 1-year-old girl with merosin-deficient congenital muscular dystrophy type 1A (MDC1A). Beginning as an infant, this patient exhibited severe hypotonia and proximal weakness, as well as delays in developmental milestones. Her serum creatine kinase levels at 3 months, 8 months and 1 year were 2,959, 1,621 and 1,659 U/l, respectively. Brain MRI indicated symmetric, mild T1WI low, mild T2WI and FLAIR high radial patterns in the white matter of the Cornu posterius of the ventricular lateral. Gene sequencing demonstrated a heterozygous frame-shift mutation in the LAMA2 gene, consisting of an AG deletion at nucleotides 2049-2050 (LAMA2 c.2049_2050delAG). Lower limb muscle MRI presented obvious fatty infiltration of the muscles and muscle atrophy during the early stage of the disease. The gluteus maximus, erector spinae, vastus intermedius, vastus lateralis, adductor magnus, soleus and gastrocnemius muscles were involved, whereas the piriformis, obturator internus, pectineus, adductor longus, adductor brevis and sartorius muscles presented mild or no involvement. Fatty infiltration of the erector spinae was observed during the early stage of the disease. As an additional tool in the differential diagnosis of muscle disorders, muscle MRI can delay the need for muscle biopsy.

Betulinic Acid Induces Apoptosis in Differentiated PC12 Cells Via ROS-Mediated Mitochondrial Pathway.

Betulinic acid (BA), a pentacyclic triterpene of natural origin, has been demonstrated to have varied biologic activities including anti-viral, anti-inflammatory, and anti-malarial effects; it has also been found to induce apoptosis in many types of cancer. However, little is known about the effect of BA on normal cells. In this study, the effects of BA on normal neuronal cell apoptosis and the mechanisms involved were studied using differentiated PC12 cells as a model. Treatment with 50 µM BA for 24 h apparently induced PC12 cell apoptosis. In the early stage of apoptosis, the level of intracellular reactive oxygen species (ROS) increased. Afterwards, the loss of the mitochondrial membrane potential, the release of cytochrome c and the activation of caspase-3 occurred. Treatment with antioxidants could significantly reduce BA-induced PC12 cell apoptosis. In conclusion, we report for the first time that BA induced the mitochondrial apoptotic pathway in differentiated PC12 cells through ROS.

The SG13S114 polymorphism of the ALOX5AP gene is associated with ischemic stroke in Europeans: a meta-analysis of 8062 subjects.

The association between ALOX5AP SG13S114 polymorphism and ischemic stroke (IS) susceptibility has extensively been investigated, especially in white populations; however, the results were inconclusive. Here, we perform a meta-analysis to clarify the effect of SG13S114 variant on the IS risk in Europeans. The Web of Science, PubMed, EMBASE, and Medline were searched up to August 1st, 2016. Data were extracted and the odd ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed-effects or random-effects model. In total, 8 case control studies involved 8062 subjects were finally included in this meta-analysis. We observed a significantly decreased IS risk in persons carrying an A allele at the SG13S114 polymorphism compared with those with a T allele (A vs T, OR = 0.856, 95% CI = 0.797-0.919, p < 0.001). In addition, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. In addition, the publication bias was not detected using the funnel plot and Egger's tests. In summary, the present meta-analysis suggested that the A allele at the ALOX5AP SG13S114 polymorphism is a protective factor for the IS in the Europeans. In addition, further studies with large sample size are needed to validate the association, as well as in other ethnic groups.

GlyT1 Inhibitor NFPS Exerts Neuroprotection via GlyR Alpha1 Subunit in the Rat Model of Transient Focal Cerebral Ischaemia and Reperfusion.

BACKGROUND/AIMS: Glycine is a strychnine-sensitive inhibitory neurotransmitter in the central nervous system (CNS), especially in the spinal cord, brainstem, and retina. The objective of the present study was to investigate the potential neuroprotective effects of GlyT1 inhibitor N [3-(4'-fluorophenyl)-3-(4'-phenylphenoxy) propyl] sarcosine (NFPS) in the rat model of experimental stroke. METHODS: In vivo ischaemia was induced by transient middle cerebral artery occlusion (tMCAO). The methods of Western Blotting, Nissl Staining and Morris water maze methods were applied to analyze the anti-ischaemia mechanism. RESULTS: The results showed that high dose of NFPS (H-NFPS) significantly reduced infarct volume, neuronal injury and the expression of cleaved caspase-3, enhanced Bcl-2/Bax, and improved spatial learning deficits which were administered three hours after transient middle cerebral artery occlusion (tMCAO) induction in rats, while, low dose of NFPS (L-NFPS) exacerbated the injury of ischaemia. These findings suggested that low and high dose of NFPS produced opposite effects. Importantly, it was demonstrated that H-NFPS-dependent neuronal protection was inverted by salicylate (Sal), a specific GlyR x0251;1 antagonist. Such effects could probably be attributed to the enhanced glycine level in both synaptic and extrasynaptic clefts and the subsequently altered extrasynaptic GlyRs and their subtypes. CONCLUSIONS: These data imply that GlyT1 inhibitor NFPS may be a novel target for clinical treatment of transient focal cerebral ischaemia and reperfusion which are associated with altered GlyR alpha 1 subunits.

Adipose-Derived Stem Cells Expressing the Neurogenin-2 Promote Functional Recovery After Spinal Cord Injury in Rat.

Neurogenin2 (Ngn2) is a proneural gene that directs neuronal differentiation of progenitor cells during development. This study aimed to investigate whether the use of adipose-derived stem cells (ADSCs) over-expressing the Ngn2 transgene (Ngn2-ADSCs) could display the characteristics of neurogenic cells and improve functional recovery in an experimental rat model of SCI. ADSCs from rats were cultured and purified in vitro, followed by genetically modified with the Ngn2 gene. Forty-eight adult female Sprague-Dawley rats were randomly assigned to three groups: the control, ADSCs, and Ngn2-ADSCs groups. The hind-limb motor function of all rats was recorded using the Basso, Beattie, and Bresnahan locomotor rating scale for 8 weeks. Moreover, hematoxylineosin staining and immunohistochemistry were also performed. After neural induction, positive expression rate of NeuN in Ngn2-ADSCs group was upon 90 %. Following transplantation, a great number of ADSCs was found around the center of the injury spinal cord at 1 and 4 weeks, which improved retention of tissue at the lesion site. Ngn2-ADSCs differentiated into neurons, indicated by the expression of neuronal markers, NeuN and Tuj1. Additionally, transplantation of Ngn2-ADSCs upregulated the trophic factors (brain-derived neurotrophic factor and vascular endothelial growth factor), and inhibited the glial scar formation, which was indicated by immunohistochemistry with glial fibrillary acidic protein. Finally, Ngn2-ADSCs-treated animals showed the highest functional recovery among the three groups. These findings suggest that transplantation of Ngn2-overexpressed ADSCs promote the functional recovery from SCI, and improve the local microenvironment of injured cord in a more efficient way than that with ADSCs alone.

Decompressive craniectomy for the treatment of malignant infarction of the middle cerebral artery.

Early decompressive craniectomy (DC) has been shown to reduce mortality in malignant middle cerebral artery (MCA) infarction, whereas efficacy of DC on functional outcome is inconclusive. Here, we performed a meta-analysis to estimate the effects of DC on malignant MCA infarction and investigated whether age of patients and timing of surgery influenced the efficacy. We systematically searched PubMed, Medline, Embase, Cochrane library, Web of Science update to June 2014. Finally, A total of 14 studies involved 747 patients were included, of which 8 were RCTs (341 patients). The results demonstrated that early DC (within 48 h after stroke onset) decreased mortality (OR = 0.14, 95%CI = 0.08, 0.25, p<0.0001) and number of patients with poor functional outcome (modified Rankin scale (mRS)>3) (OR = 0.38, 95%CI = 0.20, 0.73, p = 0.004) for 12 months follow-up. In the subgroup analysis stratified by age, early DC improved outcome both in younger and older patients. However, later DC (after 48h after stroke onset) might not have a benefit effect on lowering mortality or improving outcome in patients with malignant infarction. Together, this study suggested that decompressive surgery undertaken within 48 h reduced mortality and increased the number of patients with a favourable outcome in patients with malignant MCA infarction.

[Values of serum copper and serum free copper in the diagnosis and monitoring of Wilson's disease and its carriers].

OBJECTIVE: To explore the values of serum copper and serum free copper in the diagnosis of Wilson's disease (WD), its carrier and viral hepatitis and explore the guiding significance of monitoring serum copper in the treatment of WD. METHODS: A total of 80 WD patients (hepatic type, n = 60; encephalic type, n = 20), 30 carriers, 20 patients with viral hepatitis were enrolled and their levels of serum copper were determined. The neural symptoms were scored by modified Young grade. Hemogram, hepatic functions, blood clotting functions, serum copper and urinary copper were tested throughout all 8 courses of treatment with sodium dimercaptopropane sulfonate (DMPS). The patients were treated with zinc after discharging. All data were analyzed. RESULTS: The free serum copper increased in the patients with WD (0.17 mg/L ± 0.04 mg/L), carriers (0.13 mg/L ± 0.03 mg/L) and severe viral hepatitis (0.12 mg/L). A slight increase was also observed in the WD carriers. The level of serum copper was correlated with hepatic functions but not with the severity of neural symptoms. The serum copper increased in the patients with no improvement of neural symptoms. However, the serum copper decreased in the WD patients with the improvement of neural symptoms. The serum copper was stabilized at approximately 0.2 mg/L during the long-term treatment period. CONCLUSION: There is auxiliary diagnosis significance of serum copper in the determination of WD. Hepatic functions in hepatic type WD affect the level of serum copper. The serum copper of encephalic type WD can not indicate the severity of neural symptoms. The elevated level of serum copper indicates a poor prognosis. The serum copper is an effective marker in monitoring the development and therapeutic efficacy of the disease.