Recommendations for the diagnosis and treatment of rheumatic diseases-related hemophagocytic syndrome in China / 中华内科杂志

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

Predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for medium-term outcome in patients with primary gastrointestinal diffuse large B cell lymphoma / 中华核医学与分子影像杂志

Objective:To explore the predictive value of 18F-FDG PET/CT metabolic parameters combined with inflammatory markers for the medium-term efficacy of chemotherapy in patients with primary gastrointestinal diffuse large B cell lymphoma (PGI-DLBCL). Methods:From April 2011 to May 2020, 67 patients (37 males, 30 females, age: 28-85 years) with PGI-DLBCL examined by 18F-FDG PET/CT before chemotherapy in Changhai Hospital, Navy Medical University were retrospectively analyzed. All patients were treated with cyclophosphamide+ doxorubicin+ vincristine+ prednisone (CHOP) or rituximab+ CHOP (R-CHOP) regimens, and the medium-term efficacy was evaluated after 2-4 cycles of chemotherapy. The effect outcome was divided into complete remission (CR) group and non-CR (NCR) group based on the Lugano lymphoma response evaluation criteria. Mann-Whitney U test was used to compare the differences of SUV max, peak of SUV (SUV peak), metabolic tumor volume (MTV), total lesion glycolysis (TLG), platelet/lymphocyte ratio (PLR) and neutrophil/lymphocyte ratio (NLR) between two groups. The independent risk factors of NCR were analyzed by multivariate logistic regression and the binary logistic regression model was established according to the results. The model was tested with external validation data ( n=15). Results:Of 67 PGI-DLBCL patients, 28(41.8%) were CR and 39(58.2%) were NCR. SUV peak, MTV, TLG, PLR and NLR in NCR group (17.3(12.3, 28.1), 73.8(42.9, 141.7) cm 3, 887.5(300.9, 2 075.3) g, 203.9(155.7, 297.1), 3.9(3.0, 4.9)) were significantly higher than those in CR group (9.5(6.2, 15.2), 11.3(4.7, 23.2) cm 3, 85.2(35.5, 214.6) g, 149.3(102.8, 173.1), 2.2(1.8, 4.6); z values: from -6.41 to -2.33, all P<0.05). The logistic regression model was as follows: P=1/(1+ e - x), x=0.100×MTV+ 0.024×PLR-8.064. The prediction accuracy for NCR risk was 86.57%(58/67), with the accuracy of 13/15 tested by external validation data. Conclusion:MTV combined with PLR has a good predictive value for medium-term efficacy of CHOP/R-CHOP chemotherapy in patients with PGI-DLBCL.

Analysis of clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody-positive myopathy / 中华实用儿科临床杂志

Objective:To explore clinical characteristics and treatment of pediatric anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibody-positive myopathy.Methods:Two cases of pediatric anti-HMGCR antibody-positive myopathy admitted to the Department of Neurology, Shenzhen Children′s Hospital from January to July 2020 were retrospectively analyzed for their clinical manifestations, creatine kinase (CK), myositis autoantibody, electromyography (EMG), muscle pathology, muscle magnetic resonance imaging (MRI), and treatment information.Results:Both of them were female cases.Case 1 was 3 years and 11 months old and case 2 was 7 years and 9 months old.They used to be healthy without history of statin use.Case 1 showed chronic onset of the disease, and case 2 had a subacute onset.The main clinical manifestations were progressive symmetric proximal muscle weakness accompanied by myalgia.Case 1 developed skin rash but case 2 did not.Significantly increased CK level was detected in both of them, which increased by 27.3-48.0 and 66.7-77.4 times of the upper limit before treatment in case 1 and case 2, respectively.They were diagnosed as muscular dystrophy at the early stage.EMG results suggested myogenic injuries in 2 cases, and muscle MRI showed extensive muscle edema.The muscle pathology of the 2 cases suggested muscle necrosis with a small amount of inflammatory cell infiltration.After diagnosis, both of them were treated with Methylprednisolone combined with intravenous immunoglobulin.CK decreased significantly but remained high, and muscle weakness was improved but did not return to normal.Oral Prednisone was given after discharge and case 2 was additionally medicated with azathioprine.Conclusions:Compared with adult patients, the clinical characteristics of pediatric anti-HMGCR antibody-positive myopathy are mostly similar.However, children patients usually have no history of statins and are more difficult to treat, less effective and worse prognosis.In addition, children patients are more likely to be diagnosed with " muscular dystrophy" at the beginning of illness.Therefore, idiopathic myositis autoantibody should be examined to confirm the diagnosis for children suspected to be " muscular dystrophy" but not confirmed by genetic examination.

Effects of repetitive transcranial magnetic stimulation on sleep quality in patients with sleep disorder after stroke: systematic review and meta-analysis / 中国基层医药

Objective:To evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) on sleep quality in patients with post-stroke sleep disorder (PSSD).Methods:The clinical randomized controlled trials involving PSSD patients who received rTMS were retrieved from nine medical databases. After excluding duplicated references, screening for independent references and risk evaluation, the remaining references were input into RevMan5.4 software for meta-analysis.Results:Twelve eligible literatures were included in the final analysis. Meta-analysis results revealed that after rTMS intervention, there were significant differences in the following terms between the treatment and control groups (all P < 0.05): Pittsburgh sleep quality index score [MD = -2.60, 95% CI (-3.03, -2.17), P < 0.000 01]; sleep latency [MD = -9.69, 95% CI (- 16.87, - 2.50), P < 0.01], sleep efficiency [MD = 8.90, 95% CI (5.41, 12.39), P < 0.01], number of awakenings [MD = -1.15, 95% CI (- 2.26, - 0.04), P = 0.04], awakening duration [MD = -10.95, 95% CI (- 13.30, -8.61), P < 0.01], and rapid eye movement [MD = 4.54, 95% CI (2.24, 6.85), P < 0.01] in polysomnography; brain-derived neurotrophic factor score [MD = 5.29, 95% CI (2.47, 8.11), P = 0.0002]; clinical curative rate [ OR = 4.46, 95% CI (2.75, 7.23), P < 0.000 01]. Conclusion:rTMS can improve the sleep quality in patients with PSSD, which is worthy of clinical promotion.

Construction of Tre enzyme eukaryotic expression vector and identification of its function in loxLTR sequence-specific recognition / 医学研究生学报

Objective Clearing HIV provirus is the key to cure AIDS .The study was to construct the Tre enzyme eukaryotic expression vector and identify its function in specific recognition of loxLTR sequence in HIV provirus . Methods Tre gene was in-serted into eukaryotic expression vector pcDNA 3.1 gene recombination manipulation by genetic recombination techniques including gene synthesis , PCR, restriction enzyme digestion and ligation .EGFPpA-LoxLTR sequence was inserted into pmCherry-N1 vector and was tested by restriction enzyme digestion , PCR and sequencing .Constructed vectors were electroporated into HeLa cells , then using fluorescence microscopy to observe fluorescence intensity changes . Results PCR, restriction enzyme digestion , electrophoresis and sequencing confirmed that Tre enzyme eukaryotic expression vector had been constructed successfully , and it could specifically recog-nize and cut loxLTR sequence after being transfected into Hela cells . Conclusion Constructed Tre enzyme eukaryotic expression vector can be expressed in Hela cells and specifically recognize loxLTR sequence , which has prepared the experimental ground for fur-ther studies of clearing HIV provirus .

Tamizaje para sífilis en donantes de sangre y reactividad simultánea con otros marcadores en la Fundación Hematológica Colombia / Screening for syphilis in blood donors and simultaneous reactivity with other markers in the Fundación Hematológica Colombia / O rastreamento da sífilis em doadores de sangue e reativida- de simultânea com outros marcadores na Fundação Hemato - logia da Colombia

El presente artículo se propone caracterizar los donantes voluntarios de sangre que presentaron reactividad contra \r\nTreponema pallidum\r\n durante el periodo 2006-2011 y conocer la reactividad simultánea con otros marcadores en un \r\nbanco de sangre colombiano. Para ello, se realizó un estudio retrospectivo de corte transversal en el banco de sangre \r\nFundación Hematológica Colombia, Bogotá (Colombia). La población de estudio estuvo conformada por registros de \r\ndonantes voluntarios de sangre que presentaron reactividad en el tamizaje para \r\nTreponema pallidum\r\n y otros marca\r\n-\r\ndores entre 2006 y 2011.\r\nLa población de estudio estuvo conformada por 11.203 registros de donantes voluntarios de sangre, el promedio de \r\nedad fue de 43,27 ± 12,04 años, de los cuales el 56,2% (n=6.296) pertenecía al género masculino, el 11,1% (n=1.246) \r\nde los sujetos con tamizaje para sífilis presentaron coinfección para los marcadores de reactividad simultánea con \r\nsífilis; el de mayor presentación fue Anti-Core con un 67,7% (n=900), seguido de VIH con 10,3%. La prevalencia de \r\nsífilis del periodo de estudio fue de 1,9%.\r\nEn conclusión, se logró describir claramente las características generales de la población con tamizaje para sífilis, \r\nademás se encontraron datos estadísticamente significativos por género. Es importante conocer este tipo de compor\r\n-\r\ntamiento con el fin de fortalecer los procesos de selección de donantes de sangre y demostrar que la reactividad \r\nsimultánea no es un proceso aislado en un banco de sangre.

Objective: describe voluntary blood donors who showed \r\nreactivity to Treponema pallidum during 2006-2011 and \r\nto identify simultaneous reactivity with other markers \r\nin a Colombian blood bank. Materials and methods: a \r\nretrospective cross-sectional study was performed at the \r\nFundación Hematológica Colombia, Bogotá-Colombia. \r\nThe records of volunteer blood donors that showed reac\r\n-\r\ntivity for screening for Treponema pallidum and other \r\nmarkers of simultaneous screening during 2006-2011 \r\nwere included. Results: A total of 11.203 records of \r\nvoluntary blood donors were included; the mean age was \r\n43.27 ± 12.04 years, 56.2% males (n = 6.296), 11.1% \r\n(n = 1.246) of subjects with syphilis had co-infection \r\nand syphilis screening for markers simultaneous reacti\r\n-\r\nvity with syphilis. The greatest incidence was Anti Core \r\nwith 67.7% (n = 900), followed by HIV with 10.3%, \r\nthe prevalence of syphilis of the study period was 1.9%. \r\nConclusions: the general characteristics of the popula\r\n-\r\ntion with syphilis screening were clearly determined. \r\nThere is a statistically significant difference among the \r\ngenders. It is important to note this kind of behavior in \r\norder to reinforce the processes of blood donor selection, \r\nand to demonstrate that simultaneous reactivity is not an \r\nisolated process in the blood bank.

Objetivo: caracterizar os doadores voluntários de sangue \r\nque apresentaram reatividade contra \r\nTreponema pallidum\r\ndurante 2006-2011 e para conhecer a reatividade simul\r\n-\r\ntânea com outros marcadores em um banco de sangue \r\nna Colombia. Materiais e métodos: foi realizado um \r\nestudo transversal retrospectivo no banco de sangue da \r\nFundação de Hematologia Colombia, Bogotá, Colombia. \r\nA população do estudo consistiu de registros de doadores \r\nde sangue voluntários que apresentaram reatividade para \r\na triagem de Treponema pallidum e outros marcadores \r\ndurante 2006-2011. Resultados: a população do estudo \r\nconsistiu de 11.203 registros de doadores voluntários de \r\nsangue, a idade média foi de 43,27 ± 12,04 anos, sendo \r\nque 56,2% (n = 6.296) pertenciam ao sexo masculino, \r\n11,1% (n = 1.246) dos indivíduos tiveram co-infecção \r\npara os marcadores reatividade simultânea com a sífilis, \r\na maior incidência foi de Anti-Core com 67,7% (n = \r\n900), seguido por HIV com 10,3%, a prevalência de \r\nsífilis do período de estudo foi de 1,9%. Conclusão: foi \r\npossível descrever claramente as características gerais \r\nda população com sífilis também encontramos dados \r\nestatisticamente significativas por sexo. É importante \r\nconhecer esse tipo de comportamento, a fim de fortalecer \r\nos processos de seleção de doadores de sangue e também \r\nmostrar que a reatividade simultânea não é um processo \r\nisolado no banco de sangue.

Mucopolisacaridosis de tipo I Hurler: Informe de un caso / Mucopolysaccharidosis I, Hurler syndrome: A case report

La mucopolisacaridosis de tipo I (MPS I), es una enfermedad genética autosómica recesiva de origen lisosomal, caracterizada por la deficiencia de la enzima a-L-iduronidasa. La deficiencia en el catabolismo de los glucosaminoglucanos resulta en su acumulación en diferentes tejidos y órganos. La incidencia global de la MPS I es de 0,99-1,99/100 000 nacidos vivos. Existen tres presentaciones clínicas: Hurler (grave), Hurler-Scheie (moderada) y Scheie (leve). Presentamos el caso de un niño de 10 años de edad a quien se le diagnosticó MPS I, de variedad grave en el año 2006, mediante medición de la actividad enzimática de a-L-iduronidasa en leucocitos. Este caso es el único con diagnóstico confirmado y tratamiento enzimático hasta el momento, en el Perú. Presenta infecciones respiratorias recurrentes, hernia umbilical, opacidad corneal, rasgos toscos, macroglosia, hipoacusia, rigidez articular, estenosis de la válvula pulmonar leve-moderada, manos en garra, retardo mental y retraso del crecimiento. Recibe terapia de reemplazo enzimático desde el año 2008, mostrando mejoría de los síntomas viscerales, más no del daño neurológico.

Mucopolysaccharidosis I (MPS I) is a rare, recessively inherited, lysosomal storage disorder caused by deficiency on the enzyme a-L-iduronidase. This defect results in accumulation of heparan and dermatan sulfate in different tissues and organs due to a deficiency in the catabolism of glycosaminoglycans. The overall incidence of MPS I is 0.99-1.99/100.000 live births. There are three clinical presentations: Hurler (severe), Hurler Scheie (mild) and Scheie (mild). We report the case of a 10-years-old male patient diagnosed with Hurler syndrome, the severe presentation, 5 years ago by enzyme a-L-iduronidase activity measurement in leukocytes; with a history of recurrent respiratory infections, umbilical hernia, corneal opacity, coarse facial features, macroglossia, hearing loss, stiffness of joints, cardiac compromise, claw hands, mental retardation and stunted growth. After enzyme replacement therapy the patient has shown improvement of visceral symptoms, but the neurological damage continuous in progress.

DNA triplex structures in neurodegenerative disorder, Friedreich’s ataxia.

It is now established that a small fraction of genomic DNA does adopt the non-canonical B-DNA structure or ‘unusual’ DNA structure. The unusual DNA structures like DNA-hairpin, cruciform, Z-DNA, triplex and tetraplex are represented as hotspots of chromosomal breaks, homologous recombination and gross chromosomal rearrangements since they are prone to the structural alterations. Friedreich’s ataxia (FRDA), the autosomal recessive degenerative disorder of nervous and muscles tissue, is caused by the massive expansion of (GAA) repeats that occur in the first intron of Frataxin gene X25 on chromosome 9q13-q21.1. The purine strand of the DNA in the expanded (GAA) repeat region folds back to form the (R∙R*Y) type of triplex, which further inhibits the frataxin gene expression, and this clearly suggests that the shape of DNA is the determining factor in the cellular function. FRDA is the only disease known so far to be associated with DNA triplex. Structural characterization of GAA-containing DNA triplexes using some simple biophysical methods like UV melting, UV absorption, circular dichroic spectroscopy and electrophoretic mobility shift assay are discussed. Further, the clinical aspects and genetic analysis of FRDA patients who carry (GAA) repeat expansions are presented. The potential of some small molecules that do not favour the DNA triplex formation as therapeutics for FRDA are also briefly discussed.

The Characterization of Glucocoritcoid Response Element(GRE) on the Promoter of Thyrotropin-Releasing Hormone(TRH) Gene / 대한내분비학회지

BACKGROUND: We previously demonstrated that the promoter of rat TRH gene has GRE half site (TGTTCT) between -210 bp and -205 bp flanking with similar sequences of TPA response element (TRE), TAGTCA, at a distance of several base pairs from the GRE half site. It promps us to hypothesize that this composite GRE/TRE sequence can provide a site for interaction between glucocorticoid receptor (GR) and c-Jun. Thus, we investigated whether the composite sequence mediates transcriptional regulation induced by dexamethasone (DEX) and 12-O-tetradecanoyl phobol-13-acetate (TPA), and whether it binds GR and c-Jun. METHODS: A luciferase expressing plasmids that contain a part of rat TRH promoter including the composite sequence or their mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX increased the transcriptional activity of the plasmid containing the wild type GRE by 2.5 folds, and TPA increased the transcriptional activity by 4 folds. The simultaneous stimulation with DEX and TPA synergistically increased the transcriptional activity by 10 folds. Two mutants whose GRE half sits were altered showed no responses to DEX, and suppressed the TPA-induced or both agents-induced transcriptional activity by 50%. Two mutants whose TRE-like sites were altered suppressed the DEX-induced transcriptional activity by 20%, TPA-induced trarptional activity by 25%, and both agents-induced transcriptional activity by 50%. Gel retardation assay showed that the composite sequence fonned a complex with GR and its mutants bound to GR with remarkably less affinity. c-Jun also bound to the composite sequence to form two cornplexes with less affinity compared to the AP-1 consensus sequence. The mutants of the TRE-like sequence bound to c-Jun with a significantly lower affinity compared to that of the wild type. Simulateous binding of the composite sequence with GR and c-Jun did not form any larger complex. The complex of GR and the composite sequence was much smaller than that formed by c-Jun, suggesting that GR binds to the composite sequence as a monomer. CONCLUSION: These results suggest that the composite sequence of GRE half site and TRE-like site on the promoter of rat TRH gene provides binding sites for GR and c-Jun, which mediate the interaction between two signal transduction pathways. (J Kor Soc Endocrinol 14:265-277, 1999)

Analysis of Glucocorticoid Response Element and TPA Response Element of Rat Thyrotropin-Releasing Hormine Gene by Site-Directed Mutagenesis / 대한내분비학회지

BACKGROUND: We previously demonstrated that a GRE/TRE composite sequence, which is located between 200 bp and 220 bp relative to the transcriptional start site of rat TRH gene, is responsible for the dexamethasone (DEX)- and TPA-induced transcriptional activation, and the transcriptional activation by DEX is mediated by interaction between glucocorticoid receptor (GR) and a TRE-binding transcriptional factor such as c-Jun. However, a non-specific binding with the transciption factors can not be excluded as the mutants used in the previous report could not inhibit the binding of GR and c-Jun completely, and it remains unclear which one of the two TRE-like sequences is critical for the interaction of the two transcription factors. METHODS: Luciferase expressing plasmids that contain a part of rat TRH promoter including the composite GRE sequence or its mutants were transfected into HeLa cells by Fugene 6. After the cells were incubated overnight with DEX or/and TPA, the luciferase activity was measured in a chemiluminometer. A gel retardation assay was performed after binding of the labeled composite sequence or its mutants with GR and c-Jun. RESULTS: DEX and TPA increased the transcriptional activity of the wild type composite sequence by 3 folds and 4 folds, respectively, and the combined stimulation increased the activity by 10 folds. The mutants of which all 6 nucleotides of the GRE half site were replaced and removed almost did not bind to GR and eould not enhance the transcriptional activity at all in response to DEX. The GRE-deleted mutant bound to c-Jun with a remarkably lower affinity and showed a lower response to TPA, whereas the GRE-replaced mutant bound to c-Jun with a similar affinity and showed a similar response to TPA compared to those of the wild type. In response to the combined simulation with DEX and TPA, the mutants showed 30-40% of the trancriptional activity of the wild type. Basal transcriptional activity of all the TRE mutants was significantly lower than that of the wild type. While they almost could not bind to c-Jun, their binding affinity to GR was comparable to that of the wild type. Whereas the DEX- and TPA-induced transcriptional activity of 5 TRE mutant was 10% and 15% of that of the wild type, it responded to those agents in a similar pattern as the wild type. The 3 TRE mutant and the mutant of both TRE sites did not respond to DEX and TPA. The GRE-deleted mutant hardly formed the DNA-protein complex as did the wild type, while the GRE -replaced mutant could form the complex in a less amount with nuclear extract of HeLa celL CONCLUSION: These results suggest that GRE/TRE composite sequence of rat TRH gene specifically binds to GR and c-Jun, providing a site for interaction between the two transcription factors, and that both TRE sites play an important role in basal transcription, and that the 3 TRE site is more critical in the interaction between GRE and TRE for DEX-induced transcriptional activation. (J Kor Endocrinol 14:278-292, 1999)