Association between spontaneous portosystemic shunt and hepatorenal syndrome in liver cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the association between spontaneous portosystemic shunt （SPSS） and hepatorenal syndrome （HRS） in patients with liver cirrhosis. MethodsA retrospective analysis was performed for 93 patients with SPSS from Dezhou Hospital， Qilu Hospital of Shandong University， from January 2015 to January 2022， and the patients were followed up for 12 months with the onset of HRS as the observation endpoint. According to the presence or absence of HRS， the 93 patients with SPSS were divided into HRS group with 38 patients （40.86%） and non-HRS group with 55 patients （59.14%）， and the two groups were compared in terms of clinical data， laboratory data， complication， and shunt diameter. Based on the maximum shunt vein diameter of 1.5 cm， the 93 patients with SPSS were divided into high shunt group with 52 patients （55.91%） and low shunt group with 41 patients （44.09%）， and with the onset of HRS as the observation endpoint， the two groups were compared in terms of the incidence rate of HRS and survival time curve. The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance between two groups， and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic （ROC） curve was used to predict cut-off values， the Kaplan-Meier curve was used for comparison of survival time， and the Log-rank test was used to compare the differences in survival curves. The multivariate Cox regression analysis was used to investigate risk factors. ResultsCompared with the non-HRS group， the HRS group had significant increases in Child-Pugh score， Child-Pugh class， MELD score， serum creatinine， blood urea nitrogen， alanine aminotransferase， aspartate aminotransferase， maximum shunt vein diameter， the incidence rates of hepatic encephalopathy and spontaneous bacterial peritonitis， and the degree of ascites， as well as significant reductions in main portal vein diameter， serum sodium and albumin （all P<0.05）. Compared with the low shunt group， the high shunt group had a significant increase in the incidence rate of HRS （51.92% vs 26.83%， χ²=5.974， P=0.015） and a significant reduction in the time to the onset of HRS （Log-rank P=0.033）. A maximum shunt vein diameter of >1.5 cm （hazard ratio ［HR］=1.123， 95% confidence interval ［CI］： 1.041‍ ‍—‍ ‍1.211， P=0.003）， an increase in MELD score （HR=1.205， 95%CI： 1.076‍ ‍—‍ ‍1.437， P=0.039）， a reduction in serum albumin （HR=0.890， 95%CI： 0.814‍ ‍—‍ ‍0.974， P=0.011）， an increase in the degree of ascites （HR=2.099， 95%CI： 1.066‍ ‍—‍ ‍4.130， P=0.032）， and spontaneous bacterial peritonitis （HR=2.259， 95%CI： 1.020‍ ‍—‍ ‍5.003， P=0.045） were independent risk factors for the onset of HRS in SPSS patients. ConclusionThere is an association between SPSS and HRS， and shunt diameter >1.5 cm was an independent risk factor for HRS in SPSS patients， which should be taken seriously and require early intervention in clinical practice.

Intrathecal delivery of nusinersen using the Ommaya reservoir in a spinal muscular atrophy type 2 patient: a case report / 中华神经科杂志

Ommaya reservoir implantation is generally used in the treatment of hydrocephalus and intraventricular drug administration. Ommaya reservoir implantation in the subarachnoid space of the spinal cord for the intrathecal drug administration has not been carried out in China, and only several reports can be retrieved from PubMed. About 60%-90% of untreated patients with spinal muscular atrophy type 2 (SMA2) who survive to adulthood often have complex scoliosis and joint deformities. Nusinersen is an effective drug for the treatment of SMA2. And the route of administration is intrathecal injection, which is difficult for patients with severe scoliosis. This article summarizes the process of Ommaya reservoir implantation and postoperative drug administration in a patient with complex scoliosis type SMA2, which provides a new method for clinical treatment of this disease.

A case report of hereditary spastic paraplegia type 58 / 中华神经科杂志

Hereditary spastic paraplegia type 58 is rare, caused by pathogenic variations in KIF1C gene. Here, a case diagnosed in Qilu Hospital, Shandong University, was reported. The 15-year-old female suffered tremor in bilateral upper limbs which was aggravated gradually since age 8. Cerebellar ataxia, positive pyramidal tract sign and dystonic tremor were prominent on physical examination. The brain magnetic resonance imaging showed T 2-hyperintense signals in bilateral pyramidal tracts, optic radiations and superior cerebellar peduncles, with mild cerebellar atrophy. Whole exon sequencing revealed the unreported homozygous c.425_426delTG (p.V142Gfs*10) mutation which was presumed pathogenic.

Clinical analysis of a case of central nervous system intravascular lymphoma with multiple intracerebral microbleeds and literature review / 中华神经科杂志

Objective:To investigate the clinicopathological features and imaging differential diagnosis of intravascular large B-cell lymphoma (IVLBCL) in the central nervous system (CNS).Methods:A case of CNS IVLBCL with multiple intracerebral microbleeds (CMBs) diagnosed in the Department of Neurology, Qilu Hospital of Shandong University in 2017 was reported. The clinical and imaging data, histological and immunohistochemical markers were retrospectively analyzed, and the relevant literature was reviewed.Results:The patient was a 31-year-old woman presented with headache and seizures. Cranial magnetic resonance imaging (MRI) showed multifocal lesions involving mainly the cortical and subcortical white matter (bilateral cerebral hemisphere and right cerebellar hemisphere), hyperintense signal on T 2-weighted and fluid-attenuated inversion recovery images, with hypointense signal on T 1-weigthed and diffusion-weighted images and contrast enhancement in some lesions. The susceptibility weighted imaging revealed multifocal cortical or subcortical hypointense lesions, involving mainly the subcortical white matter. Brain magnetic resonance angiography was normal. Brain magnetic resonance venography showed left side transverse sinus was hypoplastic. Cranial magnetic resonance spectroscopy showed decreased N-acetylaspartylglutamate peak, elevated choline peak and inverted lipid double peak. Her symptoms and the lesions once improved after starting steroid treatment. However, CNS recurrence occurred after 1 week of steroid withdrawal. She underwent the biopsy of the right frontotemporal lobe. The pathological examination showed multiple microscopic hemorrhages and edema scattered in the brain tissue. A large number of heterologous mononuclear cells were aggregated in small blood vessels in the parenchyma and meninges. Immunohistochemical analysis revealed that the tumor was negative for Epstein-Barr virus encoded small RNAs, CD 3, CD 10, cytokeratin and CD 138, and positive for CD 20, CD 79α, B-cell lymphoma (BCL)-2, BCL-6, myelocytomatosis oncogene (C-myc) and multiple myeloma oncogene-1 (MUM-1). The Ki67 proliferation index was about 70%. The diagnosis of IVLBCL was confirmed. Conclusions:IVLBCL in CNS is a rare and swiftly progressive disease with poor prognosis. Its clinical symptoms and imaging are nonspecific. Early diagnosis and treatment is critical. Biopsy is the gold standard for diagnosis. Random skin biopsy may be helpful for the early diagnosis. Furthermore, regarding the cause of multiple CMBs, the possibility of IVLBCL should be considered in the differential diagnosis, in addition to the common causes, such as primary angiitis of the CNS and cerebral amyloid angiopathy.

Congenital Myasthenic Syndrome / 罕见病研究

Congenital Myasthenic syndrome (CMS) is a group of partially treatable genetic disorders characterized by dysfunction of neuromuscular junction signaling.With the popularization of high-throughput sequencing and in-depth understanding of the disease in recent years, more than thirty pathogenic genes have been discovered and there is a correlation between genotype and clinical phenotype.Misdiagnosis and missed diagnosis are common in clinical practice. This paper summarized the molecular mechanisms, clinical features, electrophysiologic, pathological features and treatment of main subtypes of CMS to deepen the understanding of the disease.

Relationship between CCL21 and TREM2/DAP12 signaling pathways in spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain / 中华麻醉学杂志

Objective:To evaluate the relationship between CCL21 and triggering receptor expressed on myeloid cells 2 (TREM2)/DNAX-activating protein of 12 kDa (DAP12) signaling pathways in the spinal dorsal horn in remifentanil-induced hyperalgesia in mice with incisional pain.Methods:Thirty-two SPF healthy male C57BL/6J mice, weighing 18-22 g, aged 8-10 weeks, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), CCL21 neutralizing antibody group (group anti-CCL21), remifentanil + incisional pain group (group R+ I), and CCL21 neutralizing antibody + remifentanil + incisional pain group (group anti-CCL21+ R+ I).A CCL21 neutralizing antibody 0.3 μg (diluted to 10 μl in normal saline) was intrathecally injected in anti-CCL21 and anti-CCL21+ R+ I groups twice a day.Normal saline 10 μl was intrathecally injected at the same time point twice a day in C and R+ I groups.Fifteen min after intrathecal injection, normal saline 0.1 ml was injected via the caudal vein for 4 consecutive times at an interval of 15 min in C and anti-CCL21 groups, and remifentanil 10 μg/kg (diluted to 0.1 ml in normal saline) was injected via the caudal vein for 4 consecutive times at an interval of 15 min in R+ I and anti-CCL21+ R+ I groups.The tail-flick latency (TFL) and mechanical paw withdrawal threshold (MWT) were measured at 24 h before remifentanil or normal saline injection (T 0) and 3, 6, 24 and 48 h after stopping injection of remifentanil or normal saline (T 1-4).The mice were sacrificed after the last measurement of pain threshold, and L 4-6 segments of the spinal cord were removed for determination of the expression of TREM2 and DAP12 protein and mRNA (by Western blot or quantitative real-time polymerase chain reaction). Results:Compared with group C, TFL was significantly shortened and MWT was decreased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was up-regulated in group R+ I and R+ I+ anti-CCL21 ( P<0.05), and no significant change was found in the parameters mentioned above in group anti-CCL21 ( P>0.05).Compared with group R+ I, TFL was significantly prolonged and MWT was increased at T 1-4, and the expression of TREM2 and DAP12 protein and mRNA was down-regulated in group anti-CCL21+ R+ I ( P<0.05). Conclusions:CCL21 is involved in remifentanil-induced hyperalgesia by activating TREM2/DAP12 signaling pathways in the spinal dorsal horn of mice with incisional pain.

Clinical analysis of type Ⅱ Alexander disease and literature review / 中华神经科杂志

Objective:To analyze the clinical features, imaging findings and gene test of patients with type Ⅱ Alexander disease.Methods:All the clinical data of three cases with type Ⅱ Alexander disease from August 2018 to June 2020 in the Department of Neurology, Qilu Hospital of Shandong University (Qingdao) and Qilu Hospital of Shandong University were collected, and their clinical and imaging findings were analyzed retrospectively.Results:All the three patients were middle aged and old men with a chronic progressive course, beginning with weakness of one or both lower limbs, followed by dizziness, dysarthria, dysphagia, sphincteral disturbances, constipation and orthostatic hypotension. Three patients all experienced misdiagnosis (hydrarthrosis, cerebral vascular disease, alcoholism, respectively) at early stage of the disease. Cranial magnetic resonance imaging (MRI) showed mild supratentorial periventricular leukodystrophy, which was not specific. Sagittal cranial MRI demonstrated medulla oblongata and upper cervical cord atrophy called “tadpole atrophy”, which had high suggestive value. The results of gene analysis showed heterozygous mutation of glial fibrillary acidic protein gene, which had been reported as pathogenic gene; c.1091C>T (p.A364V) in exon 6, c.722C>T (p.R258C) in exon 4 and c.197G>A (p.R66Q) in exon 1, respectively.Conclusions:Type Ⅱ Alexander disease is an autosomal dominant disease, most with point mutations, rarely with deletion mutations. Type Ⅱ Alexander disease should be suspected when a patient had signs of lower brainstem involvement such as dizziness, ataxia, pyramidal sign, autonomic dysfunction, especially when cranial MRI showed mild supratentorial leukodystrophy, and medulla oblongata and upper cervical cord atrophy.

Clinical research of two cases of late-onset ornithine carbamoyltransferase deficiency / 中华神经科杂志

Objective To explore the clinical characteristics of late-onset ornithine carbamoyltransferase deficiency (OTCD) in order to improve the clinicians' understanding of this disease.Methods The clinical,therapeutic and follow-up data of two patients with late-onset OTCD diagnosed in the Department of Neurology,Qilu Hospital of Shandong University from November 2017 to February 2018 were collected and analyzed.Results Case 1 is a 17-year-old male who was admitted into Qilu Hospital with recurrent dizziness and vomiting for 4 months,sudden mental abnormality and convulsion for 3 days.The liver dysfunction,respiratory alkalosis and hyperammonemia (434 μmol/L) had been found before his admission.His blood ammonia fluctuated obviously from 180 μ mol/L to 2998 μmol/L,though he was given hemodialysis and arginine infusion,and died on the fourth day after admission.Case 2 is a 15-year-old male,complained with recurrent dizziness,vomiting,bluntness and somnolence for 20 days.He was found with hyperammonemia (600 μmol/L) and liver dsyfunction in a local hospital.He was getting better after intravenous administration of arginine and liver protective drugs.After admission,the blood ammonia,liver function and amino acids,acylcarnitine profiling in dried blood spots,and organic acid analysis in urine were normal,and he has not recurred since restriction of protein diet.Brain magnetic resonane imaging of both patients showed cytotoxic edema of bilateral frontal lobe and insular cortex,and their genetic detection both showed c.119G＞A(p.R40H) hemizygous pathogenic mutation of OTC gene inherited from their respective mothers.Conclusion Unexplained hyperammonemia and acute encephalopathy with insular and frontal cortical involvement should be on the alert to the urea cycle disorders,especially OTCD.Early diagnosis and reasonable treatment are the key to changing the prognosis.

Clinical analysis of three cases of listerial rhombencephalitis / 中华神经科杂志

Objective To describe the features of clinical,imaging and cerebral spinal fluid (CSF) of listerial rhombencephalitis to improve the understanding of this disease in clinical practice.Methods All the clinical data of three cases of listerial rhombencephalitis from April to August 2017 in Qilu Hospital were collected and analyzed retrospectively.Results All the three cases were healthy adult women before,with a rapidly progressive course,beginning with fever (38.2-40 ℃),headache accompanied by nausea and vomiting,followed by cranial paralysis,dysphagia and paralysis of the limbs on the 2nd to 5th day of onset,and developed to acute respiratory failure and unconsciousness on the 5th to 8th day of onset.All the three patients were diagnosed with CSF culture positive for Listera monocytogenes on the 3rd to 5th day after admission.The initial CSF lactic acid increased significantly,representing 12.3,12.0 and 10.0 mmol/L respectively;CSF white blood cells were 416× 106/L,760× 106/L and 793× 106/L,respectively,and the protein levels were 0.76 g/L,0.57 g/L and 1.47 g/L,respectively.Brain images showed brain stem was involved in all the three patients,therein cases 1 and 3 with cerebellar hemisphere involved,case 2 with upper cervical spinal cord involved,and case 1 with supratentorial hydrocephalus involved.After treatment with sensitive antibiotics,case 1 recovered,case 2 died,and case 3 lived with dysphagia.Conclusions Listerial rhombencephalitis should be suspected when a patient started with fever and headache,rapidly progressed to cranial nerve paralysis,brainstem symptoms,and acute respiratory failure,especially when the brain imaging suggested brainstem involved with increased white blood cells and apparently elevated lactic acid level of CSF.The earlier the sensitive antibiotics initiated,the better the patients' prognosis.

Unignorable late-onset inborn errors of metabolism of the nervous system / 中华神经科杂志

Inborn errors of metabolism (IEMs) are defined as genetically enzymatic deficiencies or defects in polypeptide or protein involved in cellular metabolism,which include nearly a thousand kinds of genetic-definite disease entities up to now and could develop symptoms and signs at any age,and those whose onset-age is more than 1 years old are named as late-onset IEMs.More than 80％ of IEMs could involve the nervous system,also called IEMs of the nervous system,and most of the late-onset IEM patients will go to the Deparment of Neurology firstly.The treatment aim of IEMs is to correct the metabolic deficiency.The main therapeutic strategies include substrate-limitted intake,enzyme replacement therapy,clearance of the toxic metabolites,cofactor supplement,gene therapy and sympatomatic and support treatment.Many kinds of late-onset IEMs of the nervous system are treatable,and could be healthy living if treated early and correctly.Therefore,it is important to strengthen the understanding of neurologists on the late IEMs of the nervous system,which should not be ignored.

CT manifestations and pathologic characteristics of solitary fibrous tumor of the pleural / 实用放射学杂志

Objective To investigate the CT manifestations and pathology features of solitary fibrous tumors of the pleural (SFTP),to improve diagnostic accuracy of this disease.Methods CT manifestations of 12 cases with SFTP confirmed by surgery were analyzed retrospectively by comparison with the pathological findings.Results The CT images of the 12 cases showed intrathoracic soft-tissue shadow with well-defined margin which was widely connected with pleural.There were 4 cases with mound like and mushroom shape,3 cases with round or oval shape,2 cases with irregular shape growing into the pleural space,3 cases with large mass filling unilateral thoracic cavity,9 cases with pleural tail sign and 1 case with pleural pedicle sign.The plain CT showed homogeneous density in 7 cases,high-low mixed density in 4 cases and with internal calcification in 1 case.After contrast enhancement,5 cases were map like heterogeneous and progressive enhancement,and 4 cases have strip distorted vessel inside or on the edge of the lesion.Conclusion CT manifestations of SFTP have certain characteristics,such as broad base,shaping growth and pleural tail sign,which could be helpful to improve the diagnostic accuracy of SFTP by analyzing carefully.

Myelin-associated glycoprotein associated neuropathies: clinical features and antibody detection / 中华神经科杂志

Objective To investigate the clinical and electrophysiological characteristics of anti-myelin-associated glycoprotein (MAG)-associated peripheral neuropathy, as well as its antibody detection methods, treatment and prognosis. Methods Six cases of IgM paraproteinemia and anti-MAG antibody-associated peripheral neuropathy were summarized. All of the patients came from Peking Union Medical College Hospital and Qilu Hospital since April 2014 to February 2018. The clinical features, electrophysiological characteristics, and auxiliary examinations including anti-MAG antibody results were analyzed, and the treatment and prognosis were followed. Results Of the six patients, five were male and one was female. The age of onset was 50-77 years and the duration was three months to six years. All the six cases suffered from numbness of distal limbs and gradually progressed to the proximal limbs, of which three cases had muscle weakness. Walking instability occurred in five cases. One patient had electricity-like pain in the lower extremities. Reflexes in the four limbs decreased in five cases, and gloves and socks-like deep sensation decreased in six cases. Five patients underwent lumbar puncture and the cerebral spinal fluid protein ranged from 0.75 to 1.33 g/L. Serum monoclonal proteins were found in six patients, of which four were IgM kappa and two were IgG kappa and IgM kappa biclonal. Four cases were diagnosed with monoclonal gammopathy of undetermined significance and two cases were diagnosed with Waldenstr?m's macroglobulinaemia. Abnormal electromyography was detected in all the six cases, suggesting demyelinating peripheral nerve damage with secondary axonal damage, which was sensory predominant and more severe in lower limbs than upper limbs. In all the six cases, anti-MAG-IgM antibodies were all positive by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues. After the diagnosis, three patients underwent RCD (rituxima + dexamethasone + cyclophosphamide) chemotherapy. One patient improved (the modified Rankin scale (mRS) score was 3 before treatment and 2 three years after treatment), one patient was stable, and one patient was still in follow-up. One patient was treated with rituxima, and the condition improved (the mRS score was 3 before treatment and 1 one year after treatment). Conclusions MAG-associated peripheral neuropathy can present a slow progressed distal symmetric sensomotor peripheral neuropathy with predominant sensory symptoms. Electromyography shows demyelinating change. Monoclonal protein is usually IgM kappa. MAG-IgM antibodies detection by indirect immunofluorescence assay based on transfected cells and peripheral nerve tissues can support the diagnosis. RCD chemotherapy may be effective.

Characteristics of clinical manifestations and molecular genetics of late-onset cobalamin C deficiency / 中华神经科杂志

Objective To investigate the characteristics of clinical manifestations and genetics of late-onset cobalamin (cbl) C deficiency,also named as combined methylmalonic acidemia and homocystinemia, cblC type. Methods We reviewed 26 late-onset cblC deficiency patients diagnosed in Qilu Hospital, Shandong University from 2012 to 2017 and analysed the clinical, biochemistry, neuroimaging, follow-up and MMACHC gene data. Results Among the 26 patients, male:female ratio is 11:15, with the age of diagnosis from 4 to 39 years and sibling comorbidity in 4 families. The clinical manifestaions of nervous system included spastic paraplegia,mental and behavior disorder,intelectual decline,epilepsy,ataxia,dystonia and peripheral neuropathy. There were four cases with proteinuria at onset. At first visit, the levels of serum total homocystinuria of all patients were elevated, from 61.4 to 193.4μmol/Lwith methylmalonic acidemia. The neuroimaging data of the 26 cases showed 11 with cerebral atrophy, 10 with thoracic spinal cord atrophy, five with brain parenchymal lesions, three with longitudinal myelopathy which were reversible in follow-up, one with syringomyelia, one with multiple cerebral artery stenosis. In all the cases, cobalamins were supplied parenterally and folate, betaine, L-carnitine, vitamin B6 were supplied orally during acute metabolic crisis, and the symptoms of acute encephalopathy disappeared but symptoms of spastic paraplegia had little improvement. In chronic stage, frequency of intramuscular injection of hydroxocobalamine could be decreased while the index can still be improved. All the 26 cases had definite mutations in MMACHC gene, the most common mutations of which were found to be c.482G>A(15/52) and c. 609G>A(13/52). Conclusions Homocystine is the important biomarker for cblC deficiency. Once diagnosed, parenteral hydroxocobalamin and oral betaine should be supplied for a lifetime with good prognosis. The most common mutations of MMACHC gene in our cases are c. 482G>A and c. 609G>A missense mutations.

Guanosine diphosphate-mannose pyrophosphorylase-B gene mutations causing limb-girdle muscular dystrophy overlapping with congenital myasthenic syndrome / 中华神经科杂志

Objective To report four patients with secondary α-dystroglycanopathy caused by guanosine diphosphate-mannose pyrophosphorylase-B ( GMPPB ) gene mutations and review the literature aiming to analyze the clinical manifestations , muscle image , molecular pathology and genetic characteristics of the disease.Methods The medical history , physical examination , electromyography and other clinical data of four patients with secondary α-dystroglycanopathy from two families were collected and retrospectively reviewed from 2009 to 2017.Case 1 ( proband of pedigree 1) and case 2 ( proband of pedigree 2) were then further analyzed with muscle imaging , muscle pathology and targeted next generation gene sequencing (NGS).Results Four patients came from two families (three from the same pedigree), two males and two females, with an onset age of 17 -18 years.All four cases presented as limb-girdle muscular dystrophy (LGMD) overlapping with congenital myasthenic syndrome (CMS) characterized by evident proximal limb weakness in early adulthood and fluctuating muscle weakness .They all had delayed motor milestone and did not perform well in physical education since childhood . Serum creatine kinase was elevated markedly (1877-5275 U/L).Myogenic changes on electromyography and marked attenuation on three Hz repetitive nerve stimulation were observed in all patients .Muscle MRI showed prominent involvement of bilateral hamstrings in case 1 and case 2.Muscular dystrophic patterns were demonstrated on muscle biopsies . Targeted NGS revealed two compound heterozygous missense mutations in GMPPB for each case .Case 1 carried c.860G>T (p.R287L)/c851T>C (p.V284L).Case 2 and his two affected sisters (case 3 and case 4) carried c.1097A >G ( p.N366S)/c.589G >T ( p.V197F) .All of these mutations were novel variants and pedigree analysis suggested that the two mutations were from parents .Compared with normal controls, immunohistochemistry and Western blotting showed significantly decreased expression of α-dystroglycan in the muscle tissue from case 1 and case 2.The myasthenic symptoms of all four patients were improved to varying degrees after treatment with pyridostigmine bromide . Conclusions Mutations in GMPPB can lead to dysfunction both in muscle and in neuromuscular transmission causing overlapping between LGMD and CMS phenotypes . Cholinesterase inhibitors can partly improve the symptoms of myasthenia in such patients .

Caveolin-associated myopathy: three cases with muscle rippling and a literature review / 中华神经科杂志

Objective To summarize the clinical , pathological and genetic characteristics of three patients with caveolin-3 associated myopathy and review the literatures .Methods The clinical data of three patients with caveolin-3 associated myopathy were investigated .With informed consent , we performed muscle biopsy and genetic analysis of CAV 3 and PTRF genes.Results All the three patients presented with percussion/pressure-induced rapid contraction , percussion-induced muscle mounding and mechanically induced muscle rippling.Besides, case 1 had weakness and atrophy of hand muscles .Case 2, who manifested with muscle hyperexcitability at onset , developed weakness and atrophy of distal part of lower limbs.Case 3 showed normal muscle strength and tone .All of them had myalgia or tenderness .Muscle biopsy revealed mild myogenic changes in two patients and a muscular dystrophic pattern in one . Immunohistochemical staining of caveolin-3 revealed an even deficiency in case 1 and a mosaic deficiency in cases 2 and 3.Gene analysis revealed a missense mutation ( c.80G>A, p.R27Q) in CAV3 gene of case 1. No mutations were identified in cases 2 and 3.Conclusions There is phenotypic variability in patients with caveolin-associated myopathy , including limb-girdle syndrome , rippling muscle disease , distal myopathy , muscle hypertrophy , idiopathic hyperCKemia and cardiomyopathy .Muscle biopsy and caveolin-3 staining should be performed for the above patients with muscle rippling .

Clinical and pathological study of Guillain-Barré syndrome with treatment-related fluctuations / 中华神经科杂志

Objective To investigate the clinical and pathological features of Guillain-Barré syndrome with treatment-related fluctuations (GBS-TRF).Methods Clinical data were obtained from medical records of patients with GBS-TRF during the period 1999 to 2014 in our Hospital.Sural nerve specimens were collected and summarized retrospectively (two cases).Results Eight of 868 cases with GBS had at least one TRF including three chronic hepatitis B patients.The onset of disease was ranged in age from six to 63 years, averaging 34 years.It is more common in men than in women in a ratio of seven to one.Triggering infections occurred in three patients.The initial symptom included weakness of the lower limbs (five cases) and upper extremities (three cases).Sensory symptom was presented in six patients.Five patients had associated respiratory paralysis.None of them had cranial nerve palsy or autonomic dysfunction.The examination of cerebrospinal fluid showed protein and cell separation.Five patients had two attacks, one had three attacks and two had six attacks.The interval between attacks ranged between 14 days and 46 days (mean 23 days).The striking pathologic finding was the presence of sectional selective nerve fiber degeneration (SNFD) with evidence of demyelination.Conclusions Patients with GBS-TRF show similar onset age, preceding infection, cerebrospinal fluid findings, and electrophysiologic characteristics comparing to patients with GBS,while there are more male patients than female patients.SNFD found in sural nerve biopsy reveals ischemic neuropathy, which predicts that injury of arterioles might play an important role in the pathogenesis of GBS-TRF.

A clinical and pathological study of Guillain-Barré syndrome with treatment-related fluctuations / 中华神经科杂志

Objective To investigate the clinical and pathological features of Guillain-Barré syndrome with treatment-related fluctuations ( GBS-TRF ).Methods Clinical data were obtained from medical records of patients with GBS-TRF during the period 1999 to 2014 in our Hospital.Sural nerve specimens were collected and summarized retrospectively ( two cases ).Results Eight of 868 cases with GBS had at least one TRF including three chronic hepatitis B patients.The onset of disease was ranged in age from six to 63 years, averaging 34 years.It is more common in men than in women in a ratio of seven:one.Triggering infections occurred in three patients.The initial symptom included weakness of the lower limbs ( five cases ) and upper extremities ( three cases ).Sensory symptom was presented in six patients.Five patients had associated respiratory paralysis.None of them had cranial nerve palsy or autonomic dysfunction.Five patients had two attacks , one had three attacks and two had six attacks.The interval between attacks ranged between 14 days and 46 days ( mean 23 days ).The striking pathologic finding was the presence of sectional selective nerve fiber degeneration ( SNFD ) with evidence of demyelination.Conclusions Patients with GBS-TRF shows similar onset age , preceding infection , cerebrospinal fluid findings, and electrophysiologic characteristics comparing to patients with GBS ,while there are more male patients than female patients.SNFD found in sural nerve biopsy reveals ischemic neuropathy , which predicts that injury of arterioles might play an important role in the pathogenesis of GBS -TRF.

Activation of the wnt/β-Catenin Signaling Pathway in Polymyositis, Dermatomyositis and Duchenne Muscular Dystrophy

BACKGROUND AND PURPOSE: The wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). METHODS: Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. RESULTS: Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The transcriptional activities of β-catenin/Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. CONCLUSIONS: Our findings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fibrosis.

A novel channel dilator for coronary chronic total occlusion recanalization / 中国介入心脏病学杂志

Objective To assess the efficacy and safety of using a novel channel dilator (the Corsair microcatheter) accompanied with special occlusion guide wires for coronary chronic total occlusion (CTO) recanalization. Methods From 2011 December to 2013 August,we performed 89 cases (the study group) using channel dilator and the new special occlusion guide wires for CTO recanalization. Another 89 CTO lesions treated before using the corsair microcatheter were compared as the control group.We recorded clinical characteristic, outcome of PCI,radiation exposure time, contrast utilization and the procedure time. The MACE rate was monitored during follow up. Results The intracoronary channel dilator accompanied with special occlusion guide wires were inserted into 33 left anterior descending arteries, 17 left circumlfex arteries and 38 right coronary arteries. The success rates of procedure were signiifcantly higher in the study group than in the control group (91% vs. 67.7%, P < 0.05). Procedure and lfuoroscopy time tended to be lower in the study group than in the control group. There were no serious complications related to the catheter and no death case recorded. Conclusions The channel dilator accompanied with special occlusion guide wires may facilitate the conventional approach with a higher success rate in PCI.

Characterization of flavonoids in Millettia nitida vat.hirsutissima by HPLC/DAD/ESI-MSn / 药物分析学报

Millettia nitida var.hirsutissima is a Chinese herbal medicine used for the treatment of gynecological diseases.An HPLC/DAD/ESI-MSn method was established for the rapid separation and characterization of bioactive flavonoids in M.nitida var.hirsutissima.A total of 32 flavonoids were detected,of which 14 compounds were unambiguously characterized by comparing their retention time,UV,and MS spectra with those of the reference standards,and the others were tentatively identified based on their tandem mass spectrometry fragmentation data obtained in the negative ionization mode on line.Nineteen of these compounds characterized were reported from this plant for the first time.