HNRNPA1-induced spliceopathy in a transgenic mouse model of myotonic dystrophy.

Studies on myotonic dystrophy type 1 (DM1) have led to the RNA-mediated disease model for hereditary disorders caused by noncoding microsatellite expansions. This model proposes that DM1 disease manifestations are caused by a reversion to fetal RNA processing patterns in adult tissues due to the expression of toxic CUG RNA expansions (CUG) leading to decreased muscleblind-like, but increased CUGBP1/ETR3-like factor 1 (CELF1), alternative splicing activities. Here, we test this model in vivo, using the mouse poly(CUG) model for DM1 and recombinant adeno-associated virus (rAAV)-mediated transduction of specific splicing factors.

A Novel Mutation of Mitochondrial T14709C Causes Myoclonic Epilepsy with Ragged Red Fibers Syndrome in a Chinese Patient.

Background: Myoclonic epilepsy with ragged red fibers (MERRF) syndrome is characterized by myoclonus, generalized epilepsy, cerebellar ataxia, and ragged red fibers (RRFs) in the muscle. T-to-C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNA) gene has previously been associated with maternally inherited diabetes and deafness. However, the association between MERRF and mitochondrial T14709C mutation (m.

Identification of Seven Novel Mutations in the Acid Alpha-glucosidase Gene in Five Chinese Patients with Late-onset Pompe Disease.

Background: Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene (GAA). A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease (LOPD) who carried novel GAA gene mutations.

A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb-girdle Muscle.

Background: Congenital myasthenic syndromes (CMSs) are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare.

A novel thymidine phosphorylase mutation in a Chinese MNGIE patient.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder associated with mitochondrial alterations. MNGIE is characterized by severe gastrointestinal dysmotility, cachexia, ophthalmoplegia, ptosis, peripheral neuropathy, and leukoencephalopathy. The condition is caused by mutation of the TYMP gene.

Oculopharyngeal Weakness, Hypophrenia, Deafness, and Impaired Vision: A Novel Autosomal Dominant Myopathy with Rimmed Vacuoles.

Background: Myopathies with rimmed vacuoles are a heterogeneous group of muscle disorders with progressive muscle weakness and varied clinical manifestations but similar features in muscle biopsies. Here, we describe a novel autosomal dominant myopathy with rimmed vacuoles in a large family with 11 patients of three generations affected.

Methods: A clinical study including family history, obstetric, pediatric, and development history was recorded.

D-dimers (DD) in CVST.

Objective: We were interested in further confirming whether D-dimers (DD) are indeed elevated in cerebral venous sinus thrombosis (CVST) as reported in those studies.

Methods: CVST patients who had a plasma D-dimer test (139 cases) were included and divided into two groups: elevated D-dimer group (EDG) (>0.5 μg/mL; 65 cases) and normal D-dimer group (NDG) (≤0.

Increased Expression of the NOD-like Receptor Family, Pyrin Domain Containing 3 Inflammasome in Dermatomyositis and Polymyositis is a Potential Contributor to Their Pathogenesis.

Background: Dermatomyositis (DM) and polymyositis (PM) are common inflammatory myopathies whose immunopathogenic mechanisms remain poorly understood. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome is a type of cytoplasmic multiprotein inflammasome and is responsible for the activation of inflammatory reactivations. Responding to a wide range of exogenous and endogenous microbial or sterile stimuli, NLRP3 inflammasomes can cleave pro-caspase-1 into active caspase-1, which processes the pro-inflammatory cytokines pro-interleukin (IL)-1β and pro-IL-18 into active and secreted IL-1β and IL-18.

A new modified animal model of myosin-induced experimental autoimmune myositis enhanced by defibrase.

Introduction: We investigated the effect of defibrase (a proteolytic enzyme extraction of Agkistrodon halys venom) on experimental autoimmune myositis (EAM) in guinea pigs and explored the option of using a modified pig model of EAM to enhance the study of this disease.

Material And Methods: Guinea pigs were divided into 3 groups: group A (control group) was immunized with complete Freund adjuvant (CFA), then received 6 injections of saline weekly; group B (EAM group) was immunized with partially purified rabbit myosin emulsified with CFA, then received an injection of saline; group C (EAM + defibrase group) was immunized with purified rabbit myosin emulsified with CFA, then received an injection of defibrase. The animals were observed for their general health condition and the body weight was measured daily.

[Regulatory T cells in the treatment of autoimmune myositis in mice: efficacy and mechanism].

Objective: To investigate effect of CD4(+) CD25(+) Foxp3(+) Tregs in the treatment of autoimmune myositis (EAM) in mice and explore the possible mechanisms.

Methods: Mouse models of EAM were divided randomly into model group and treatment group, and the latter received infusion of CD4(+) CD25(+) Foxp3(+) Tregs separated from normal mouse spleen by magnetic activated cell sorting. The changes of muscle pathology was observed, and the expression of PD-1 and CTLA-4 in spleen CD4(+) CD25(+) Foxp3(+) Tregs was analyzed using flow cytometry; peripheral blood IL-10 and TGF-β levels were tested using double antibody sandwich ELISA.

Complement membrane attack complex is related with immune-mediated necrotizing myopathy.

This study is to investigate the expression of complement membrane attack complex (C5b-9) in the skeletal muscle of patients with necrotizing myopathy (NM), and to investigate the relationship between C5b-9 and NM. Thirteen patients with NM and control patients with polymyositis and muscular dystrophy were enrolled in this study. Examinations including creatine kinase (CK) and L-lactate dehydrogenase (LDH) in the serum, electromyogram and muscle pathological examination were performed.

Clinical and pathological features of patients with nemaline myopathy.

Nemaline myopathy (NM) is a rare congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. This study aimed to summarize and analyze retrospectively the clinicopathological features of 28 patients with NM. Among the 28 patients, 15 were classified as of the typical congenital type, manifested as lower- or four-limb weakness as the first symptom and slowly progressive course.

Incidence and risk factors of pleural effusions in patients with POEMS syndrome.

Information regarding the characteristics of pleural effusions in patients with POEMS syndrome is limited. The aim of this study was to describe the incidence and risk factors of pleural effusions in patients with POEMS syndrome and characterize the pleural fluid biochemistry in those patients. A retrospective review of 96 patients with POEMS syndrome was conducted.

The characteristics of ascites in patients with POEMS syndrome.

The characteristics of ascites in patients with POEMS syndrome, which comprise polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes, are unknown. We described the frequency of ascites at presentation of POEMS syndrome and further evaluated for the pathogenesis and nature of the ascites. One hundred and six consecutive patients with POEMS syndrome in Chinese PLA General Hospital were evaluated for the presence of ascites, and the cellular and biochemical characteristics of the ascitic fluids were assessed.

Chinese specific characteristics of sporadic Creutzfeldt-Jakob disease: a retrospective analysis of 57 cases.

Objective: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal and transmissible neurodegenerative disorder. However, no studies have reported Chinese specific characteristics of sCJD. We aimed to identify differences in sCJD between Chinese patients and patients from other countries.

Electrophysiological characteristics of polyneuropathy in POEMS syndrome: comparison with CIDP.

Objective: The purpose of this study was to evaluate the electrophysiological characteristics of polyneuropathy in POEMS syndrome.

Methods: A total 46 patients with POEMS syndrome and 46 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) were included in this study. Six nerve conduction parameters including (1) motor conduction velocity, distal compound muscle action potential; (2) conduction block and temporal dispersion; (3) motor distal latency; (4) F wave; and (5) sensory conduction velocity were reviewed for the subjects in both POEMS and CIDP groups.

Comparison of diffusion-weighted MRI with 18F-fluorodeoxyglucose-positron emission tomography/CT and electroencephalography in sporadic Creutzfeldt-Jakob disease.

18F-fluorodeoxyglucose-positron emission tomography/CT (18F-FDG PET/CT) scanning may be a useful tool for early diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), as it may reveal lowered cellular glucose transport and metabolism in the cortex, cerebellum and basal ganglia. The aim of the present study was to compare the findings from PET/CT, MRI and electroencephalography (EEG) for patients with sCJD, to explore whether typical sites or reliable patterns of regional metabolic change could be found and to evaluate the results of diagnostic imaging in the light of clinical symptomatology. Five patients with biopsy-confirmed sCJD and nine with probable sCJD (aged 36-68 years) were evaluated using PET/CT, diffusion-weighted (DW)-MRI and EEG.

Dural enhancement detected by magnetic resonance imaging reflecting the underlying causes of cerebral venous sinus thrombosis.

Dural enhancement detected by magnetic resonance imaging is a common finding in patients with cerebral venous sinus thrombosis (CVST) and is usually interpreted as a change secondary to CVST. We report two cases of CVST with intense and diffuse dural enhancement that resulted from pachymeningitis in one patient and spontaneous intracranial hypotension in another. Pachymeningitis and spontaneous intracranial hypotension were also determined to be the underlying causes of CVST.

[GNE gene mutation analysis in 5 patients with distal myopathy with rimmed vacuoles].

Objective: To investigate GNE gene mutations in 5 Chinese patients with distal myopathy with rimmed vacuoles (DMRV).

Methods: Five patients with typical clinical and pathological features of DMRV were studied. All the 11 coding exons and the flanking intron sequences of GNE gene were amplified by PCR and sequenced.

Optimal cut-off values for tumor markers in cerebrospinal fluid with ROC curve analysis.

To select optimal cut-off values of tumor markers in cerebrospinal fluid for the diagnosis of meningeal carcinomatosis, the concentrations of CEA, CA125, CA153, CA199, CA724, CYFRA21-1, AFP and NSE were determined by means of double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) in 21 MC patients, 25 cancer patients without leptomeningeal disease (group one) and 45 meningitis patients (group two) using the Roche E170 modular immunoassay analyzer. Optimal cut-off values were selected based on a receiver-operating characteristic curve. The results showed that CA125 and CEA in CSF were optimal diagnostic indices distinguishing between MC patients and cancer patients without leptomeningeal disease.

[Familial and sporadic distal myopathy with rimmed vacuoles: comparison of the clinical, pathological, laboratory test and follow-up data].

Objective: To compare the clinical, pathological, laboratory test and follow-up data between familial and sporadic patients with distal myopathy with rimmed vacuoles (DMRV) and discuss the characteristics of this disorder in Chinese population.

Methods: The clinical and pathological features, laboratory data and follow-up results of 33 sporadic and 4 familial cases of pathologically confirmed DMRV were summarized and compared retrospectively.

Results: The patients age, onset age, or disease duration showed no significant difference between sporadic and familial cases; the onset pattern and affected muscle groups were also similar, but the sporadic cases showed more frequent dysmorphic features than the familial cases.

[Clinical analysis of 47 misdiagnosed cases of atypical tuberculous meningitis].

Objective: To improve the differential diagnosis of tuberculous meningitis (TBM) and reduced potential misdiagnosis of TBM.

Methods: The clinical data of 47 misdiagnosed cases of TBM between January, 1994 and June, 2009 were investigated retrospectively. The clinical presentations and causes for the misdiagnoses were analyzed.

[Value of tumor markers in the cerebrospinal fluid in the diagnosis of meningeal carcinomatosis].

Objective: To assess the diagnostic value of tumor markers in the cerebrospinal fluid (CSF) for meningeal carcinomatosis (MC).

Methods: Twenty-one MC patients (including 13 adenocarcinoma and 8 non-adenocarcinoma patients), 72 patients with tuberculous meningitis (TBM) and 23 with primary intracerebral tumors (PIT) were enrolled in this study. Blood and CSF tumor markers including CEA, CA125, CA15-3, CA19-9, CA72-4, CYFRA21-1, AFP and NSE were measured by Roche E170 electrochemiluminescence analyzer and sandwich assay.