ABSTRACT
Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy is one of the subtypes of immune-mediated necrotizing myopathy. Anti-HMGCR antibodies induce complement activation,subsequently resulting in myofiber necrosis,regeneration with autophagy abnormalities and mitochondrial changes. The age of onset is from children to adulthood. Some patients have a history of exposure to statins. Most patients are subacute onset. The patients with chronic progressive process, are more like muscular dystrophy. The main symptoms are proximal symmetrical weakness of limbs and usually accompanied with extra-muscle symptoms. The MRI showed muscle edema in all patients and fatty infiltrates in some patients. Myositis-specific auto-antibodies and muscle biopsies play key roles in diagnosis of HMGCR myopathy. Corticosteroids and immunosuppressants were first line therapy. Pediatric patients or patients with chronic course are usually refractory, and the efficacy of different combinations of immunosuppressants needs to be further investigated.
ABSTRACT
Objective:To summarize the clinical, pathological and muscle magnetic resonance imaging (MRI) features of human immunodeficiency virus (HIV)-associated nemaline myopathy (NM; HIV-NM).Methods:The present patient was a 23-year-old man with HIV infection who developed progressive proximal weakness and atrophy for more than 10 months. He was admitted to the Department of Neurology of Beijing Ditan Hospital in early June 2021. Electromyography showed myogenic findings. The serum creatine kinase was 202.4 U/L. CD 4+ count was 585×10 6/L. Serum monoclonal immunoglobulin (M protein) was negative. The patient underwent MRI examination of bilateral thigh muscles, biopsy of left biceps brachii and gene detection. The clinical, pathological and muscle MRI changes of HIV-NM were summarized based on the literature review. Results:MRI examination of bilateral thigh muscles showed edema changes. Muscle biopsy showed nemaline structures in some muscle fibers, accompanied by fiber atrophy and regeneration. No gene mutation related to clinical phenotype was found by second-generation sequencing. After intravenous immunoglobulin combined with prednisone, the patient′s weakness symptoms were significantly improved. A total of 17 cases of HIV-NM (including the present case) were identified in the literature, who were aged (33.7±9.1) years. Fifteen were males and two were females. All patients developed proximal limb weakness. Creatine kinase was normal or slightly elevated. Serum monoclonal protein was positive in 3 cases (3/7). Immunosuppressive therapy was effective.Conclusions:The main clinical characteristics of HIV-NM are progressive proximal limb weakness and muscle atrophy. The muscle pathology shows a large number of nemaline structures in atrophic muscle fibers. Muscle edema can be seen on muscle MRI. This is the first report of HIV-NM in China, which may be a special subtype of immune myopathy.
ABSTRACT
Objective:To summarize the characteristics of neuralgia in Fabry disease and explore the effects of genders and alpha-galactosidase A (GLA) gene mutation types on neuralgia.Methods:Questionnaires and Brief Pain Inventory evaluations were conducted on the recruited patients diagnosed as Fabry disease in Department of Neurology, Peking University First Hospital from January 2001 to April 2020. The characteristics of the neuralgia were summarized, and the portrait of neuralgia between male and female patients, and the patient groups carrying truncated mutations and non-truncated mutations of GLA gene was compared.Results:A total of 93 patients with Fabry disease were enrolled. The incidence of neuralgia was 91.4% (85/93),and the average onset age of pain was 9 years. The average remission age was 20 years with the remission incidence of 22.8% (18/79). Pain attack on extremities [96.5%(82/85)] was the most common form. The neuralgia relieving rate of male patients [17.5%(11/63)] was lower than that of females (7/16, χ2=5.01, P=0.025).Brief Pain Inventory scores showed that the degree of most severe pain attack within 24 hours of male patients (4.16±3.20) was higher than that of females (2.07±2.02, t=3.03, P=0.004),and the impact of pain on daily life [male 4 (7) vs female 0 (4), Z=-2.33, P=0.020], walking ability [male 5 (8) vs female 0 (2), Z=-2.87, P=0.004], daily work [male 5 (8) vs female 0 (2), Z=-3.10, P=0.002], relationship [male 2 (6) vs female 0 (3), Z=-2.67, P=0.008] and interests [male 4 (8) vs female 0 (3), Z=-2.81, P=0.005] of male patients was also higher than female patients. The truncated mutation group [1 (2)] only showed higher score on the current pain level than the non-truncated mutation group [0(0), Z=-2.89, P=0.003]. Conclusions:The neuralgia in Chinese patients with Fabry disease showed high incidence and early onset. Male patients presented more severe pain than female which led to a greater impact on life, while the type of GLA gene mutation had less impact on neuralgia.
ABSTRACT
Objective:Upper gastrointestinal bleeding (UGIB) is a common gastrointestinal disease in the emergency department. Identifying low-risk patients suitable for outpatient treatment is the focus of clinical and research. A simple predictive model was developed to identify patients with UGIB who could safely avoid hospitalization, thus providing a feasible basis for triage by emergency physicians.Methods:A retrospective cohort study was conducted on patients with UGIB treated at Zhongda Hospital Southeast University from January 2015 to December 2020. Baseline demographic data and clinical parameters at the initial presentation were recorded. Multivariate logistic regression model was performed to identify predictors of safe discharge.Results:Six hundred and twelve patients (45.9%) were not safely discharged. There were significant differences in age, Charlson comorbidity index, systolic blood pressure, pulse rate, hemoglobin, albumin, blood urea nitrogen, creatinine and international normalized ratio between the safe discharge group and the non-safe discharge group ( P<0.05). Using multivariate logistic regression analysis, a total of 7 variables were included in the clinical prediction model of UGIB risk stratification: Charlson comorbidity index > 2, systolic blood pressure < 90 mmHg, hemoglobin < 10 g/dL, blood urea nitrogen ≥6.5 mmol/L, albumin <30 g/L, pulse ≥100 beats/min and international normalized ratio ≥1.5. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting unsafe discharge were 98.37%, 24.10%, 52.3%, and 94.6%, respectively, with the best cutoff value ≥1. The area under the receiver operating characteristic (AUROC) curve was 0.822, which was significantly higher than Glasgow Blatchford score (GBS) 0.786 (95% CI: 0.752-0.820, P< 0.01) and AIMS65 0.676 (95% CI: 0.638-0.714, P< 0.01). Conclusions:The predictive model has a reliable predictive value, which can provide references for emergency medical staff to triage patients with UGIB, thereby reducing medical expenses and having certain social and economic benefits.
ABSTRACT
Objective:To determine the clinical, pathological and imaging phenotypes of pediatric patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) myopathy to explore its diagnostic strategies.Methods:The clinical features of 10 pediatric patients with anti-HMGCR myopathy in the Department of Neurology, Peking University First Hospital from July 2014 to July 2021 were collected. Muscle biopsies were performed in all patients, with histological, enzymatic histochemical and immunohistochemical staining.Results:The male to female ratio was 6∶4, the age of onset was 3-16 (8.3±3.7) years, 2 cases had subacute onset, and 8 cases experienced chronic progressive onset. All patients presented with neck and proximal muscular weakness of all limbs. Skin rash was observed in 2 cases. Serum creatine kinase was 998-27 981 U/L. The electromyography results were available from 6 cases, who experienced myogenic changes. The muscle magnetic resonance imaging was performed in 5 cases and revealed muscle edema predominantly in posterior compartment of thigh, with mild fatty infiltrate in 2 cases. An initial diagnosis was limb-girdle muscular dystrophy in 7 cases, but with subsequently negative genetic testing. Muscle biopsies revealed scattered necrotic fibers and regenerating fibers, complement deposition in sarcolemma basement-membrane areas of non-necrotic fibers and a few of lymphocyte infiltrate in all specimens. Moreover, a high frequency of major histocompatibility complex Ⅰ expression in muscle fibers was observed in 9 cases, proliferation of connective tissue of endomysium in 8 cases, muscle fiber hypertrophy in 4 cases and vacuoles in 2 cases.Conclusions:Pediatric anti-HMGCR myopathy is frequently misdiagnosed as muscular dystrophy. Systematic consideration of anti-HMGCR myopathy and testing for myositis specific antibody in children with genetically unconfirmed muscular dystrophy may help the differential diagnosis.
ABSTRACT
Purpose@#Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. @*Materials and Methods@#AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. @*Results@#AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. @*Conclusion@#AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.
ABSTRACT
Objective@#To analyze the diagnostic value of skeletal muscle biopsy in patients with rhabdomyolysis.@*Methods@#Clinical and pathological data of 26 patients with rhabdomyolysis from January 2002 to December 2018 undergoing muscle biopsy were collected.@*Results@#Eighteen males and 8 females were finally recruited with median age of 6-73 (37.3±19.6) years. The average time from onset to biopsy was 44 days (median course was 30 days). All patients had acute manifestations with muscle pain and/or weakness. Serum creatine kinase was between 1 648-92 660 U/L. Muscle biopsies showed nonspecific changes in 12 cases (a few with type 2 muscle fiber atrophy, slight deposition of lipid droplets), 10 cases with necrotizing myopathy (muscle fiber necrosis and regeneration). Toxic neurogenic damages were seen in 2 cases (type 1 and type 2 angular atrophic muscle fibers with group change), lipid storage disease in 1 case (lipid droplets deposit significantly) and idiopathic inflammatory myopathy in 1 case (muscle fiber necrosis and regeneration, with lymphocyte infiltration). The etiology of non-specific pathological changes included short-term strenuous exercise in 6 patients, poisoning in two, chronic kidney disease in one, viral infection in one, hypothyroidism in one and unknown reason in one. As to patients with necrotizing myopathy, seven were poisoning or drug-related, one with hyperthyroidism, two with unknown reason.@*Conclusions@#Among the numerous causes of rhabdomyolysis, exercise usually links nonspecific skeletal muscle changes and poisoning or drug-related disorders are commonly associated with necrotic myopathy. Rhabdomyolysis induced by primary myopathy is rare.
ABSTRACT
Objective To explore muscular pathological features in 6 types of connective tissue diseases except polymyositis and dermatomyositis.Methods We collected 53 patients who were diagnosed as connective tissue diseases with mnscle involvement and were performed muscle biopsies in our department from January,2010 to December,2016.The myopathological features were analyzed.Results Fifty-three cases including 6 systemic sclerosis cases,12 systemic lupus erythematosus cases,7 rheumatoid arthritis cases,13 Sj(o)gren's syndrome (SS) cases,5 mixed connective tissue disease cases,l0 overlap syndrome cases.Thirtyfive out of 53(66％)cases were in accordance with inflammatory myopathies changes.The main histopathologic categories were necrotizing myopathy (3/4) in systemic sclerosis,nonspecific myositis (4/5) in systemic lupus erythematosus,nonspecific myositis (4/9) and necrotizing myopathy (3/9) in SS,nonspecific myositis and necrotizing myopathy (3/8) in overlap syndrome.The most common pathological features were muscle fiber atrophy (50/53,94％),microangiopathy (40/53,75％),myofiber necrosis/regeneration (36/53,68％),C5b-9 deposits in sarcolemma (30/48,63％),diffuse major histocompatibility complex (MHC)-Ⅰ expressing in sarcolemma and endochylema area within myofibers (27/52,52％).Conclusion Necrotizing myopathy and nonspecific myositis are the most common histo-pathological categories in connective tissue diseases except polymyositis and der-matomyositis.Muscle fiber atrophy,microangiopathy,and necrosis/regeneration are the most prevalent pathologic features.
ABSTRACT
Objective The aim of the present study is to evaluate the reliability and validity of the Mandarin version of the PP (MPP) .Methods The first step in the establishment was to translate the original English version into mandarin version with the method of cross -culture translation .The reliability was performed with the internal consistency analysis and test -retest reliability .The validity was performed for the content validity and structure va-lidity .The samples were from 80 Chinese CI children ,and 43 parents answered this questionnaire again 1 month lat-er to evaluate the test -retest reliability .The average age at cochlear implantation were 26 ± 14 months ,ranging from 7 months to 68 months ,the average duration of CI use were 10 ± 7 months ,ranging from 0 month to 24 months .Results The reliability analysis indicates that the Cronbach'sαcoefficient was 0 .797 ,except for the well-being and happiness ,education ,whose coefficients are respectively 0 .303 ,and 0 .341 ,all of the other sundomainscoefficient were greater than 0 .5 ,indicating the internal consistency was good .Test -retest reliability of the scale Cronbach'sαwas satisfactory .All subdomains and total score of the scale coefficients were greater than 0 .70(P<0 .01) .The validity analysis indicated that the pearson correlation coefficients among the total scale and the 8 subdo-mains were 0 .395~0 .992 ,the correlation coefficients among each subdomains were 0 .09~0 .654 ,which confirmed with the psychological characteristics ,proving its good structure validity .Conclusion The Chinese version of the PP show s good reliability and validity and can be used to evaluation the quality of life in mandarin CI children.
ABSTRACT
Objective To summarize clinical phenotypes and pathological characteristics in myopathies with tubular aggregates (TAs).Methods We reviewed 5 697 patients who performed muscle biopsies in our department between January 2001 and July 2015.We collected the cases with TAs and made classification based on their clinical diagnoses and pathological changes.Results Fifty-seven patients (1.00％) showed TAs in muscle specimens,including 50 (87.72％) males and 7 (12.28％) females.According to clinical,neurophysiological,pathological and genetic analysis,the diagnoses included 23 (40.35％) cases of periodic paralysis,7 (12.28％) cases of chronic alcohol intoxication,6 (10.53％) cases of congenital myasthenic syndrome,5 (8.77％) cases of exercise-induced cramps,3 (5.26％) cases of necrotizing myopathy,1 (1.75％) case of stromal interaction molecule 1-associated myopathy,limbgirdle muscular dystrophy 2E,myotonic dystrophy,myotonia congenita,paramyotonia congenitia,hypothyroid myopathy respectively.Other cases of unknown cause included unclassified distal myopathy,external ophthalmoplegia,white matter lesions,mental retardation,stroke,early onset weakness,pulmonary arterial hypertension.Besides TAs,pathological changes also included necrosis of muscle fibers (3 cases,5.26％),neurogenic changes (3 cases,5.26％) and muscular dystrophic changes (1 case,1.75％).Conclusions Our results indicated that TAs are usually found in males and could present in many types of hereditary or acquired neuromuscular disease as independent or accompanying changes.Periodic paralysis,chronic alcohol intoxication and congenital myasthenic syndrome are 3 major diseases causing myopathies with TAs.
ABSTRACT
Objective To analyze membrane attack complex (MAC) expression in different types of idiopathic inflammtory myopathy (IIM).Methods We enrolled 57 cases of dermatomyositis (DM) , 37 cases of polymyositis (PM) ,9 cases of sporadic inclusion body myositis (sIBM) and 15 cases of autoimmune necrotizing myopathy with anti-signal recognition particle antibodies (SRP-ANM) in Department of Neurology at Peking University First Hospital from 2011 to 2014, and used x2 test or Fisher exact test to analyze MAC expression in muscle fibers and endomysial capillaries respectively.Results The total MAC expression in DM, PM, sIBM and SRP-ANM was 75.4％ (43/57), 86.5％ (32/37), 4/9 and 13/15 respectively.The MAC expression in muscle fibers was 50.9％ (29/57), 81.1％ (30/37) , 3/9 and 13/15 respectively.The MAC expression in endomysial capillaries was 49.1％ (28/57) , 24.3％ (9/37) , 1/9 and 6/15 respectively.The MAC expression in muscle fibers and endomysial capillaries of sIBM was less than other types of IIM.The MAC expression in muscle fibers of PM and SRP-ANM was higher than DM and sIBM, but there was no statistically significant difference between PM and SRP-ANM.The MAC expression in endomysial capillaries of DM and SRP-ANM was higher than PM and sIBM, while there was no statistically significant difference between DM and SRP-ANM (x2 =0.397, P =0.574).The MAC expression in four types of IIM had regional distribution, of which 11.6％ (5/43) of DM showed bundle distribution.Conclusion There are differences in the damage of MAC in various types of IIM, the damage of MAC in SRP-ANM indicated the pattern of both DM and PM.
ABSTRACT
Objective To investigate the effect of α-galactosidase A (GLA) gene mutation on cell autophagy and to elucidate its mechanism preliminarily.Methods Two families were diagnosed by ultrastructural pathological examination,GLA gene activity test and GLA gene mutation screening.Mutant type recombinant expression plasmid of two pedigrees (pcDNA3.1-GFP-ex1 (EX1 group),pcDNA3.1-GFP-ex3 (EX3 group)) and wild type recombinant expression plasmid of GLA (pcDNA3.1-GFP-GLA,GLA group) were constructed.Hela cell line (control group) was transiently transfected with recombinant expression plasmid according to lipofectin transfection.The relative gene expression of Beclin-1 was measured with real-time PCR,and protein expression level of LC3-Ⅱ/LC3-Ⅰ,Beclin-1 and P62/SQSTM1 was examined by Western blotting.Results The LC3 protein values of groups EX1,EX3,GLA and control were 1.495 ± 0.064,1.490 ± 0.020,1.285 ± 0.021,1.260 ± 0.042,respectively;P62/ SQSTM1 values were 0.555 ± 0.086,0.480 ± 0.084,0.785 ± 0.439,0.980 ± 0.278,respectively;Beclin-1 mRNA 2-△Ct values were 0.011 ±0.003,0.008 ±0.002,0.005 ±0.001,0.003 ±0.001,respectively;Beclin-1 protein values were 1.178 ±0.098,1.209 ±0.092,0.931 ±0.100,0.796 ±0.184,respectively.Compared with the wide type group,the level of LC3-Ⅱ/LC3-Ⅰ protein was significantly higher in the mutant type groups(t =5.118,4.984;P =0.007,0.008),though no statistically significant difference was found in the expression levels of P62/SQSTM1 (t =1.052,1.400;P =0.323,0.199).Besides,the expression levels of Beclin-1 mRNA (t =3.800,2.445;P =0.005,0.040) and protein (t =2.424,2.729;P =0.042,0.026) were significantly higher in the mutant type groups.Conclusions GLA gene mutation can induce cell autophagic dysfunction,and signaling pathway of autophagic activation may be Beclin-1 dependent.