Clinical characteristics and risk factors of juvenile dermatomyositis with relapses / 中华风湿病学杂志

Objective:To analyze the clinical characteristics and risk factors of juvenile dermatomyositis (JDM) with relapses by comparing clinical features, treatment and disease course among JDM patients with and without relapses.Methods:A retrospective analysis of 102 JDM patients from Children's Hospital of Nanjing Medical University between March 2017 and March 2021 was carried out. Patients were divided into two groups based on whether a JDM relapse had occurred or not. Initial clinical features, laboratory tests and treatment were compared between the two groups. T-test or Mann-Whitney U test was used for measurement data, chi-square test or fisher exact probability was used for count data. The features associated with risk of relapses were analyzed by multivariate logistic regression. Results:Among 102 children with JDM, twenty patients (19.6%) relapsed during drug reduction or after drug withdrawal. The mean duration to the first relapse was 3.24 years (range: 9 months to 7 years). Myositis specific antibodies (MSA) were positive for 8 (40.0%) patients with relapses. With 5 cases were anti-nuclear matrix protein 2 positive, 2 cases were anti-transcription interme-diary factor 1 gamma positive, 1 case was anti-signal recognition particle (SRP) positive, the other 12 cases were MSA negative. By binary logistic regression analysis, we found that peripheral calcinosis [ OR(95% CI)=17.54(1.55, 198.64), P=0.021], and interstitial lung disease [ OR(95% CI)=3.83(1.27, 11.59), P=0.017] were independently related to JDM with relapses. Fifty-three patients (51.9%) received methylpre-dnisolone pulse therapy for initial treatment and 13 (65.0%) patients with relapses received methylprednisolone pulse for initial treatment. There was no significant difference between the two groups ( χ2=1.70 , P=0.193). Tumor necrosis factor alpha antagonist combined with methotrexate (MTX) had achieved good results in clinical treatment in children with relapses. Conclusion:The risk of relapses is high in children with JDM. Calcinosis and interstitial lung disease at disease onset can predict a relapsing disease course. Aggressive treatment is urgently demanded for patients with JDM, especially those with relapses.

Pharmacoeconomic evaluation of empagliflozin in the treatment of heart failure with reduced ejection fraction / 中国药房

OBJECTIVE To conduct the pharmacoeconomic evaluation of empagliflozin in the treatment of heart failure with reduced ejection fraction （HFrEF），and to provide evidence-based reference for rational drug use and medical and healthy decision-making. METHODS A Markov model was used to perform a cost-effectiveness analysis of the regimen of empagliflozin in the treatment of HFrEF ，and to evaluate the cost and effectiveness of standard treatment plan plus empagliflozin （empagliflozin group）vs. standard treatment plan （standard treatment group ）. Clinical parameters were obtained from the EMPEROR-Reduced study；cost and utility data came from the published literatures. The cycle of the model was 1 month and the simulation time was 20 years. Single-factor sensitivity analysis and probability sensitivity analysis were performed to validate the results of cost-effectiveness analysis. RESULTS Compared with the standard treatment group ，each additional quality-adjusted life year in the empagliflozin group cost 37 995.94 yuan more ，which was less than China ’s 1 time GDP per capita in 2020（72 447 yuan）. The results of single factor sensitivity analysis showed that steady-state hospitalization rate of 2 groups was the most important factor affecting the incremental cost-effectiveness ratio . The results of probability sensitivity analysis showed that when the willingness-to-pay threshold （WTP）was 1 time GDP per capita in 2020（72 447 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 58.8％；when the WTP was 3 times GDP per capita in 2020（217 341 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 63.8％. CONCLUSIONS Compared with standard treatment plan alone，standard treatment plan plus empagliflozin is more cost-effective in the treatment of HFrEF. However ，the economic probability is not high.

Successful treatment of refractory systemic'onset juvenile idiopathic arthritis with tocilizumab: a retrospective analysis of 25 cases / 中华风湿病学杂志

Objective To investigate the efficacy and safety of tocilizumab inpatients with refractory systemic'onset juvenile idiopathic arthritis (SoJIA),and to provide a new option for the treatment of this severe disease.Methods We retrospectively studied 25 cases of hospitalized patients with refractory SoJIA treated withtocilizumab,of whom 22 had data that fit for analysis,from May 2005 to February 2016.Data of 22 cases were collected retrospectively from physicians in charge of the patients.Children with SoJIA were treated with nonsteroidal antiinflammatory drugs (NSAIDs),Glucocorticoid (GC),methotrexate,cyclosporin A,etanerceptetc before,but still in high disease activity due to inadequate response were involved.Weretrospective analyzedthe laboratory test results like C'reactive protein (CRP),Erythrocyte sedimentation rate (ESR),Ferritin and other inflammatory index.Improvement of pain,fever,rash,hepatosplenomegaly and lymphadenectasis of active SoJIA (disease course ≥6 months,and inadequate response to NSAIDs and GC) after tocilizumab treatment (Body weight ≥30 kg,8 mg/kg;Body weight＜30 kg,12 mg/kg,per 4 weeks) were analyzed.Safety data of 22 cases were collected throughout the treatment period including neutropenia,infections,anaphylaxis and elevated liver enzymes etc.We also retrospectively analyzedthe dose change of GC and the long'term effect.Dichtomous paramenters were compared teween groups using thex2 test.Continuous parameters were compared using the analysis of uariance.Results In comparison to the indices before the treatment,the level of CRP [(8.7±2.2) mg/L vs (111.6±74.4) mg/L,F=5.192,P=0.002],ESR [(6.4±6.3) mm/1 h) vs (65.6±24.3) mm/1 h,F=50.393,P=0.000],white blood cell (WBC) [(8.4±2.5)×109/L vs (17.6±8.6)×109/L,F=9.321,P=0.000],Neutrophil count [(4.9±2.4)×109/L vs.(14.4±8.7)×109/L,F=10.541,P=0.000],blood platelet (PLT) [(269.5±79.2)×109/L vs (405.4± 145.3)×109/L,F=5.704,P=0.000] and globulin [(19.2±4.1) g/L vs (30.1±3.8) g/L,F=22.896,P=0.000] decreased rapidly and hemoglobin [(118.3±9.0) g/L vs (108.5±9.8) g/L,F=4.693,P=0.002] increased significantly at 24 weeks after Tocilizumab (TCZ) treatment.Clinical manifestationssuch as fever,rash,hepatosplenomegaly,joint swelling and pain were significantly improved.GC dose [(1.25±3.8) mg·kg-1·d-1 vs (16.2±12.8) mg·kg-1·d-1,F=8.21,P=0.000] were significantly reduced after TCZ treatment (P＜0.05);American College of Rheumatology (ACR) Pedi 30/50/70/90 was improved after TCZ treatment.Adverse events occurred in 3 cases of 25 children,who were not included in the statistical analysis group.Conclusion This retrospective case series has demonstrated the efficacy of tocilizumab in SoJIA,low incidence of adverse reactions.Further studies are needed to be developed because this case series haslimited sample size.

Recognition of macrophage activation syndrome / 中华实用儿科临床杂志

Macrophage activation syndrome (MAS)is a serious potentially life -threatening complication seen primarily in patients with systemic onset juvenile idiopathic arthritis (sJIA).Clinical symptoms include persis-tent fever,liver and spleen lymph node enlargement,cytopenia,hyperferritinemia,hypofibrinogenemia,hypertriglyceri-demia,coagulation disorders,and hemophagocytosis can be seen in the bone marrow.This article summarizes the characteristics of MAS occurring in the context of sJIA and discuss the recent advances in classification systems and management.

Observations on the Therapeutic Effect of Acupuncture on Tourette's Syndrome / 上海针灸杂志

ObjectiveTo investigate the clinical efficacy of acupuncture in treating Tourette's syndrome.MethodEighty patients were allocated, using a random number table, to a treatment group of 40 cases and a control group of 40 cases. The treatment group received acupuncture and the control group, Western drug treatment.ResultThe YGTSS score decreased significantly in the two groups of patients after treatment(P<0.01). After treatment, the range of decrease in the YGTSS tic score was larger in the treatment group than in the control group; there was a statistically significant difference (P<0.05). The total efficacy rate was higher in the treatment group than in the control group (P<0.05). The incidences of adverse reactions were significantly lower in the treatment group than in the control group.ConclusionThe effect and safety of treatment for Tourette's syndrome are higher in the treatment group than in the control group.

Severe hepatic injury for predicting the development of macrophage activation syndrome in systemic juvenile idiopathic arthritis / 中华风湿病学杂志

Objective To analyze the clinical features and laboratory data of 10 patients with macrophage activation syndrome (MAS) complicating systemic onset juvenile idiopathic arthritis (soJIA),which were characterized by acute severe liver injury.Methods Data of 10 patients with soJIA/MAS from Nanjing Children's Hospital were collected retrospectively.The clinical features,laboratory findings,treatment,outcomes and prognosis were analyzed.Results In the total 10 patients,female (6/10) outnumbered male.Their age ranged from 1.5 to 9.5 years old (average 5.2±2.6).The most remarkable clinical manifestations were severe liver injury without systemic features,representing as hepatomegaly (10/10),splenomegaly (2/10) and strikingly increased transaminase (10/10,median:ALT 1 445 U/L,AST 885 U/L).Central nervous system dysfunction and hemorrhages were recorded in 20％ of the patients.Two patients had pulmonary infection.Laboratory data showed that platelet count was less than normal or precaution value (10/10,≤262×10g/L).Hyperferritinaemia (10/10,median:17 329 mg/ml) and soluble CD25 elevation (median:3 140 U/ml) were common in the soJIA/MAS patients.Evidence of macrophage hemophagocytosis was found in 90％ of the patients (9/10) who underwent bone marrow aspiration.Pathological findings of liver biopsy from 1 patient revealed massive infiltration of mononuclear cells in the portal tracts.Nearly all patients (9/10) received intravenous pulse methylprednisolone therapy,combined with cyclosporine A and high-dose intravenous immunoglobulin.Eight patients had good outcome.Only 2 patients were complicated with severe interstitial lung disease during 12-months follow-up.Conclusion MAS should be considered when patients with soJIA represents acute severeliver injury without systemic features combined with other laboratory data.Intravenous pulse methylprednisolone and cyclosporine A therapy may improve the prognosis of soJIA/MAS.

Clinical features and long - term follow - up of neonatal lupus erythematosus / 中华实用儿科临床杂志

Objective To investigate the clinical features and long - term prognosis of neonatal lupus erythe-matosus(NLE)and to improve the understanding of NLE. Methods The clinical manifestations and related serologi-cal tests of NLE children diagnosed from June 2010 to January 2014 were analyzed. Regular follow - up was carried out to detect the general condition,rash,blood routine,urine routine,liver and kidney function,complement,red blood cell sedimentation rate(ESR),auto antibodies,electrocardiogram,and ultrasound cardiogram. Results Among the 11 NLE cases,there were 6 male and 5 female patients. All had lesions on skin,3 cases had hematologic changes,7 cases were had liver damage,and 4 cases had heart impairment. The antinuclear antibody and anti - sjogren sydrome A/ Ro antigen (SSA/ Ro)were positive in all the patients. The anti - sjogren sydrome B antigen was positive in 5 patients. The anti -double stands deoxyribonucleic acid antibody was positive in 4 patients. Antibody against U1 - ribonudeoprotein was positive in 3 patients,and the level of ESR was higher in 5 patients. The antinuclear antibody and anti - SSA/ Ro anti-body were positive in all mothers. Only 1 mother had no symptom before pregnancy,7 patients had SLE,3 patients had sjogren syndrome. Seven patients received protect liver enzyme treatment,3 cases of glucocorticoid therapy,and 1 case had combined intravenous treatment with gamma globulin. Among the 11 cases,10 cases were followed up for 10 months to 4 years,while 1 case died from complete bundle branch block after 5 weeks of birth. At 1 year old,10 cases of cuta-neous lupus damage had liver damage were resorted to normal,and the rheumatic autoimmune related autoantibodies of 9 cases turned to be negative,but 1 case was diagnosed as Kawasaki disease when she was 1 year old. Conclusions One of the most common clinical manifestations of NLE was damage of skin,had the liver and blood system abnormity were common but usually not serious. Heart disease especially complete atrioventricular block was less. The long - term follow - up for children with NLE is necessary,and the majority of the prognosis is good,as only a few have the possibi-lity of developing other autoimmune diseases.

Measurement of plasma endotoxin and procalcitonin after endoscopic treatment of esophagogastric varices in liver cirrhotic patients and the clinical significance / 中华消化内镜杂志

Objective To study the changes of plasma endotoxin and procalcitonin in patients with esophagogastric varices and provide a theoretical basis for prophylactic antibiotics after endoscopic treatment. Methods Fifty cases of patients with esophageal and gastric varices accepted the endoscopic treatment.The patients were divided into antibiotic group (32 cases)and non-antibiotic group (18 cases).The plasma endotoxin and procalcitonin were measured before and on the first day and 7th day after endoscopic treatment.Results The plasma levels of endotoxin and procalcitonin were not significantly different on the first and 7th day after endoscopic treatment compared with preoperative levels in antibiotic group.But in non-antibiotic group,the levels significantly increased on 7th day after endoscopic treatment compared with preoperative levels (P <0.05).And in patients of Child-Pugh A grade,the level of plasma procalcitonin significantly increased on 7th day after endoscopic treatment compared with preoperative levels (P <0.01), but the procalcitonin was not significantly different on the first and 7th day after operation.And in patients of Child-Pugh B and C grades,the levels of plasma endotoxin and procalcitonin significantly increased on the 7th day(P <0.01).Conclusion The levels of plasma endotoxin and procalcitonin in non-antibiotic group increase after endoscopic treatment,which suggests the risk of infection.Prophylactic antibiotics after endo-scopic treatment should be considered for the patients of Child-Pugh B and C grades.

Construction of c-myb Antisense RNA Recombinant Retroviral Vector and Establishment of Its Packaging Cell Line PA317 / 中山大学学报(医学科学版)

【Objective】To construct the c-myb antisense RNA recombinant retroviral vector and its packaging cell line.【Methods】The segment of c-myb gene was cloned into pUC19 with TA cloning method after amplication by RT-PCR,and then was subcloned into retroviral vector pDOR.The recombinant retroviral vector named pDOR-myb was transfected into retroviral package cell line PA317 after selection with G418.【Results】Sequencing data indicated that the c-myb gene was exactly identical to the sequence in the GenBank.The segment of c-myb gene was inserted directionally into pDOR.Resistant colonies were obtained and the titers of pDOR-myb were 5.2×104～9.5×104 CFU/mL.【Conclusion】The recombinant retroviral vector containing c-myb gene is successfully constructed and its packaging cell line PA317/pDOR-myb was established.

Construction of a phage display library of human single-chain Fv antibodies from peripheral blood lymphocytes of people with positive serum antibody against hepatitis B virus core protein / 中华传染病杂志

Objective To construcr a phage display library of human single-chain Fv antibodies from peripheral blood lymphocytes of people with positive serum antibody against hepatitis B virus core protein. Methods The heavy chain and light chain variable region gene of human immunoglobulin were amplified individually by RT-PCR from peripheral blood Lymphocytes mRNA of patients with positive serum hepatitis B virus core protein antibody and randomly combined through a DNA linker encoding the peptide (Gly 4Ser) 3 to construct single-chain variable fragments (ScFv)gene. In the presence of helper phage M13KO7, the ScFv were displayed on the surface of recombinant phages. Results Repertoire antibody library was obtained with 10 6 clonies resistant to ampicillin and kanamycin. Conclusions A typical phage display library of human single-chain Fv antibodies has been constructed Using RT-polymerase chain reaction (RT-PCR) and phage display technique, human single-chain Fv antibodies can be screened from this library.

Effects of c-myb antisense RNA on the proliferation and collagen Ⅰ gene expression in cultured hepatic stellate cells / 中国病理生理杂志

98%. In the pDOR-myb infected HSCs, c-myb expression levels, the cell proliferation, and ? 1-Ⅰ collagen mRNA expression were repressed significantly. CONCLUSIONS: c-myb plays a key role in the activation and proliferation of HSC. c-myb antisense RNA can inhibit cell proliferation and ? 1-Ⅰ collagen mRNA expression in the infected HSC. These data suggest that inhibition of c-myb gene expression would be a potential way for the treatment of liver fibrosis.

Construction of human anti-HBc ScFv eukaryotic expression vector and expression of anti-HBc ScFv in HepG2 cells / 中国病理生理杂志

AIM: To construct an eukaryotic expression vector of human single-chain variable fragment ~against hepatitis B virus core protein (anti-HBc ScFv) and detect its expression in HepG2 cells. METHODS: Anti-HBc ScFv genes were amplified from the plasmids abstracted from positive clone and inserted into pEGFP-c1 vector that contained green fluorescent protein gene. The recombinant plasmids were transfected into HepG2 cells, and resistant clones were obtained by G418 selection. The expression of the gene of fusion protein was determined by fluorescent invert microscope and ELISA. RESULTS: Recombinant plasmids were successfully constructed. The plasmid transfected HepG2 cells were obtained by G418 selection. Specific fluorescence was observed in HepG2 cells 48 hours after transfection. ELISA analysis confirmed the expression of anti-HBc ScFv in the cells. CONCLUSION: The construction of human anti-HBc ScFv eukaryotic expression vector and its expression in HepG2 cells lay the foundation for advanced research of intracellular anti-HBc ScFv.

Investigation on the function and morphometrics of cultured primary rat ~hepatocytes / 中国病理生理杂志

AIM: To investigate the function and morphological changes of long-term cultured primary rat hepatocytes. METHODS: Rat primary hepatocytes were isolated by two-step in situ collagenase perfusion method, and then were purified by density and grade centrifugal method with Percoll. Cell viability was observed by 0.4% trypan blue. The hepatocytes were seeded into 6 wells plate with HepatoZYME-SFM medium. ALT, AST, albumin and urea levels in the supernatant were measured, CYPⅠA1 was detected with EROD method. RESULTS: (2-3)?108 cells per whole liver were obtained with viability and purity above 90% after purified with Percoll. Hepatocytes cultured in HepatoZYME-SFM grew well with normal hepatocyte morphometrics. ALT, AST levels in the supernatant decreased after 3-day culture, and kept at a stable level after 6-9 days. Albumin secretion and urea synthesis were maintained at high levels in 18 days, while CYPⅠA 1 enzyme activity was only detected in 3-6 days. CONCLUSIONS: Percoll was used to increase the viability and purity of freshly isolated rat hepatocytes. Hepatocyte morphometrics and their biological synthesized function are effectively maintained in HepatoZYME-SFM medium.

Screening,identifying and sequencing of human single-chain variable fragment specific to hepatitis B virus core protein / 中国病理生理杂志

AIM: To Screen and identify human single-chain variable fragment (ScFv) specific to hepatitis B virus core protein and determine its gene sequence. METHODS: The recombinant phages were panned by HBcAg coated in a 96-pore plate and 48 clones were identified specific to HBc after three rounds of panning. The specificity of ScFv from the positive clone was determined by ELISA. Then, the soluble ScFv was expressed in E.coli. HB2151 and secreted in the supernatant. Subsequently, SDS-PAGE and dot blot were performed to identify the ScFv in the supernatant and cell lysate. The gene of ScFv specific to hepatitis B virus core protein was sequenced. RESULTS: The ScFv screened from phage antibodies has a specific combination character with hepatitis B virus core antigen. Soluble ScFv was confirmed to express in E.coli. HB2151 and secrete in the supernatant. The sequence of ScFv gene conformed to that of heavy chain and kappa chain of human immunoglubulin. CONCLUSION: Human ScFv specific to hepatitis B virus core protein has been identified by means of the phage display technology, and its gene sequence has been determined.