Inmunodeficiencias secundarias relacionadas con la presencia de autoanticuerpos anticitocinas / Secondary immunodeficiencies related to the presence of anti-cytokine autoantibodies

Resumen Los autoanticuerpos anticitocinas (ACAA) han sido reportados como causa importante de inmunodeficiencias secundarias. Altos títulos de autoanticuerpos neutralizantes pueden causar susceptibilidad a diferentes enfermedades infecciosas potencialmente mortales. Por ejemplo, se ha informado que autoanticuerpos neutralizantes contra IFNγ se correlacionan con susceptibilidad a infecciones micobacterianas y patógenos fúngicos intracelulares. Autoanticuerpos contra IL-6 se detectaron en pacientes con abscesos subcutáneos y celulitis estafilocócica recurrente; asimismo, pacientes con criptococosis, nocardiosis y proteinosis alveolar pulmonar fueron positivos a autoanticuerpos contra GM-CSF. También se ha establecido una relación entre los autoanticuerpos contra IL-17 e IL-22 y las infecciones crónicas por Candida en mucosas, que se han identificado en pacientes con poliendocrinopatía autoinmune tipo 1 o timoma. Recientemente se han reportado autoanticuerpos contra interferón tipo I durante el inicio de COVID-19 aguda. Estos ACAA se asemejan a defectos genéticos en citocinas o en sus rutas de señalización. Por ello, pueden considerarse fenocopias de inmunodeficiencias primarias. De esta forma, la detección de ACAA podría ser importante en el diagnóstico, particularmente en pacientes con enfermedades de aparición tardía, para decidir los tratamientos apropiados. Esta revisión presenta una descripción general de la comprensión actual de las inmunodeficiencias secundarias asociadas a ACAA.

Abstract Anti-cytokine autoantibodies (ACAA) have been reported to be an important cause of secondary immunodeficiencies. High titers of neutralizing autoantibodies may cause susceptibility to different life-threatening infectious diseases. For example, neutralizing autoantibodies against IFNγ have been reported to be correlated with susceptibility to mycobacterial infections and intracellular fungal pathogens. Autoantibodies against IL-6 were detected in patients with subcutaneous abscesses and recurrent staphylococcal cellulitis; on the other hand, patients with cryptococcosis, nocardiosis, and pulmonary alveolar proteinosis were positive for autoantibodies to GM-CSF. A relationship has also been established between autoantibodies against IL-17 and IL-22 and chronic mucosal Candida infections, which have been identified in patients with APECED or thymoma. Autoantibodies against type-I IFN have been recently reported during the onset of acute COVID-19. These ACAAs resemble genetic defects in cytokines or their signaling pathways. Therefore, they may be considered to be primary immunodeficiencies phenocopies. Consequently, the detection of ACAA could be important in the diagnosis of patients, particularly in the case of late-onset diseases, in order to decide appropriate treatments. This review presents an overview of current understanding of ACAA-associated secondary immunodeficiencies.

Long-read sequencing revealed alterations of microbial relationship between tongue coating and gastric mucosa in patients with gastric intestinal metaplasia / 数字中医药（英文）

Objective@#To explore the microbial correlation between oral tongue coating (TC) and gastric mucosa (GM) in patients with gastric intestinal metaplasia (GIM).@*Methods@#The present study recruited 1360 volunteers for upper gastrointestinal cancer screening. The microbiota in TC and GM were profiled by long-read sequencing of full-length 16S rRNA gene. The microbial diversity, community structure, and linear discriminant analysis effect size (LEfSe) were analyzed by the software Visual Genomics. SparCC correlation analysis was used to construct the commensal network and the graphical display was conducted by R software.@*Results@#The population included 44 patients with precancerous GIM, and 28 matched controls with negative rapid urease test (RUT) and non-symptomatic chronic superficial gastritis (CSG). No significant difference in diversity was observed between GIM patients and controls in TC or GM microbiota (P > 0.05). Patients had a higher percentage of 41 – 60 co-occurring operational taxonomic units (OTUs) between TC and GM than controls (34.1% vs. 25.0%) (P < 0.05). The LEfSe showed that TC Prevotella melaninogenica and three gastric Helicobacter species (i.e., Helicobacter pylori, Helicobacter pylori XZ274, and Helicobacter pylori 83) were enriched in patients with GIM. Furthermore, GIM patients with positive RUT had a lower percentage of co-occurring OTUs over 20 (P < 0.05), and lower abundances of gastric Veillonella, Pseudonocardia, and Mesorhizobium than those with negative RUT (P < 0.05). The commensal network between TC and GM was more complex in GIM patients than in controls. GIM patients with positive RUT demonstrated more bacterial correlations between TC and GM than those with negative RUT. Finally, the serum ratio of PG-I/II was negatively correlated with three gastric Helicobacter species (Helicobacter pylori, Helicobacter pylori XZ274, and Helicobacter pylori 83) in patients with negative RUT (P < 0.05), and negatively correlated with two TC species (Fusobacterium nucleatum subsp. nucleatum and Campylobacter showae) in patients with positive RUT (P < 0.05).@*Conclusion@#The development of GIM potentiated the commensal network between oral TC and GM, providing microbial evidence of the correlation between TC and the stomach.

JAK inhibition ameliorated experimental autoimmune encephalomyelitis by blocking GM-CSF-driven inflammatory signature of monocytes

Monocytes are key effectors in autoimmunity-related diseases in the central nervous system (CNS) due to the critical roles of these cells in the production of proinflammatory cytokines, differentiation of T-helper (Th) cells, and antigen presentation. The JAK-STAT signaling is crucial for initiating monocytes induced immune responses by relaying cytokines signaling. However, the role of this pathway in modulating the communication between monocytes and Th cells in the pathogenesis of multiple sclerosis (MS) is unclear. Here, we show that the JAK1/2/3 and STAT1/3/5/6 subtypes involved in the demyelination mediated by the differentiation of pathological Th1 and Th17 and the CNS-infiltrating inflammatory monocytes in experimental autoimmune encephalomyelitis (EAE), a model for MS. JAK inhibition prevented the CNS-infiltrating CCR2-dependent Ly6Chi monocytes and monocyte-derived dendritic cells in EAE mice. In parallel, the proportion of GM-CSF+CD4+ T cells and GM-CSF secretion were decreased in pathological Th17 cells by JAK inhibition, which in turns converted CNS-invading monocytes into antigen-presenting cells to mediate tissue damage. Together, our data highlight the therapeutic potential of JAK inhibition in treating EAE by blocking the GM-CSF-driven inflammatory signature of monocytes.

Application of GM(1,1) model modified with seasonal factors in prediction of PM2.5 concentration in Shanghai / 公共卫生与预防医学

Objective To explore PM2.5 concentration modeling and prediction based on the monthly average concentrations of PM2.5 in Shanghai since 2015, and to provide new ideas about PM2.5 prediction methods. Methods The seasonal factors were introduced into the Grey Model (GM). GM(1,1) model modified with seasonal factors was established and compared with seasonal autoregressive integrated moving average model (ARIMA) model. The data of 2015-2021 was used for modeling and prediction, and the data from January to October in 2022 was used as a validation set to evaluate the prediction effectiveness. The monthly average PM2.5 concentrations in Shanghai from November to December in 2022 were predicted. Results Seasonal ARIMA model showed RMSE=4.02 and MAPE=15.50% in the validation set, while GM(1,1) model modified with seasonal factors showed RMSE=3.30 and MAPE=11.59%. GM(1,1) model modified with seasonal factors predicted the monthly average PM2.5 concentrations in Shanghai from November to December in 2022 to be 24.99 and 34.83μg/m3, respectively. Conclusion The prediction effect of GM(1,1) model modified with seasonal factors has better predictive performance than seasonal ARIMA model. The grey prediction model modified with seasonal factors can be considered when predicting seasonal time series such as the concentration of PM2.5.

Evaluation of the effect of intrathecal GM1 in 24, 48, and 72 hours after acute spinal cord injury in rats

Abstract Objective The aim of this study was to evaluate the best timing and feasibility of intrathecal application of sodium monosialoganglioside (GM1) after spinal cord contusion in Wistar rats as an experimental model. Methods Forty Wistar rats were submitted to contusion spinal cord injury after laminectomy. The animals were randomized and divided into four groups: Group 1 - Intrathecal application of GM1 24 hours after contusion; Group 2 - Intrathecal application of GM1 48 hours after contusion; Group 3 - intrathecal application of GM1 72 hours after contusion; Group 4 - Sham, with laminectomy and intrathecal application of 0.5 mL of 0.9% saline solution, without contusion. The recovery of locomotor function was evaluated at seven different moments by the Basso, Beattie, and Bresnahan (BBB) test. They were also assessed by the horizontal ladder, with sensory-motor behavioral assessment criteria, pre-and postoperatively. Results This experimental study showed better functional scores in the group submitted to the application of GM1, with statistically significant results, showing a mean increase when evaluated on known motor tests like the horizontal ladder and BBB, at all times of evaluation (p < 0.05), especially in group 2 (48 hours after spinal cord injury). Also, fewer mistakes and slips over the horizontal ladder were observed, and many points were achieved at the BBB scale analysis. Conclusion The study demonstrated that the intrathecal application of GM1 after spinal cord contusion in Wistar rats is feasible. The application 48 hours after the injury presented the best functional results.

Coexistencia infrecuente de la enfermedad de Tay-Sachs, coartación aórtica y reflujo vesicoureteral de grado V / Rare coexistence of Tay-Sachs disease, coarctation of the aorta and grade V vesicoureteral reflux

La enfermedad de Tay-Sachs es una enfermedad metabólica hereditaria neurodegenerativa. Existen cuatro tipos según el inicio de los síntomas clínicos: infantil, infantil de inicio tardío, juvenil y adulto. El tipo infantil tiene el peor pronóstico. Recientemente, se describieron diferentes anomalías que acompañan a los trastornos metabólicos e influyen en el pronóstico. Presentamos el caso de un lactante con enfermedad de Tay-Sachs junto con coartación aórtica y reflujo vesicoureteral bilateral (RVU) de grado V. Se realizó el seguimiento del paciente en el consultorio externo de Cardiología Pediátrica. En la ecografía abdominal, se observó ectasia pielocalicial, y se detectó reflujo vesicoureteral bilateral de grado V en la cistouretrografía miccional. No se ha informado previamente la coexistencia de estas anomalías. Este caso pone de manifiesto que no se deben subestimar las anomalías del examen neurológico en los pacientes con una cirugía cardíaca reciente, porque podría perderse la oportunidad de diagnosticar enzimopatías congénitas.

Tay-Sachs disease is a neurodegenerative inherited metabolic disease. There are four forms classified by the time of first clinical symptoms: infantile, late infantile, juvenile and adult. Infantile form has the poorest prognosis. Lately, different abnormalities which accompany metabolic disorders and affect the prognosis have been described. We present an infant with Tay-Sachs disease accompanied by coarctation of the aorta and bilateral grade V vesicoureteral reflux (VUR). The patient was followed up in the outpatient clinic of Pediatric Cardiology. The abdominal ultrasonography showed pelvicalyceal ectasia; bilateral grade V VUR in voiding cystourethrography was found. This coexistence has not been previously reported. This case emphasizes that abnormalities in the neurological examination of cardiac postsurgical patients should not be underestimated because the opportunity to diagnose inborn errors of metabolism could be missed.

Clinical and genetic characteristics of 2 cases with infantile GM1 gangliosidosis / 中华实用儿科临床杂志

Objective:To analyze clinical and genetic characteristics of 2 cases with infantile GM1 gang-liosidosis.Methods:Clinical data of 2 cases with infantile GM1 gangliosidosis in the Department of Rehabilitation, Tianjin Children′s Hospital from May 2019 to June 2019 were retrospectively analyzed.Results:The major manifestations of 2 cases included infantile onset, psychomotor retardation and retrogression, blundering face, sensitive to sound, gingival hyperplasia, abnormal eruption of teeth, hypotonia or dystonia, bone dysplasia, and skin abnormalities.Case 1 had hepatosplenomegaly, corneal opacity and multiple joint contractures.Case 2 had fundus cherry erythema and epileptic seizure.Biochemical results showed that alkaline phosphatase and aspartate transaminase significantly increased, and alanine transaminase was normal.Cranial nuclear magnetic imaging showed poor myelin sheath in the white matter in both cases, and case 1 also had symmetric signal changes in the thalamus.Whole exon sequencing showed that case 1 had deletion mutation of 3p22.3 (33137821-33138587)×1 in the exon of GLB1 gene, which has not been previously reported. Conclusions:The clinical spectrum of infantile GM1 gangliosidosis is broad.Both cases in this study have skin abnormalities, which are relatively rare.Multiple joint contractures in case 1 have not been previously reported, and considered as a new phenotype.The deletion mutation of 3p22.3 (33137821-33138587)×1 in the exon of GLB1 gene in case 1 is a newly detected mutation, which expands the genetic profile of infantile GM1 gangliosidosis.

Effects of ganglioside GM1 and erythropoietin on spinal cord injury in mice: Functional and immunohistochemical assessments

ABSTRACT Objectives: To evaluate the functional and immunohistochemical effects of ganglioside GM1 and erythropoietin following experimental spinal cord injury. Methods: Thirty-two male BALB/c mice were subjected to experimental spinal cord injury using the NYU Impactor device and were randomly divided into the following groups: GM1 group, receiving standard ganglioside GM1 (30 mg/kg); erythropoietin group, receiving erythropoietin (1000 IU/kg); combination group, receiving both drugs; and control group, receiving saline (0.9%). Animals were evaluated according to the Basso Mouse Scale (BMS) and Hindlimb Mouse Function Score (MFS). After euthanasia, the immunohistochemistry of the medullary tissue of mice was analyzed. All animals received intraperitoneal treatment. Results: The GM1 group had higher BMS and MFS scores at the end of the experiment when compared to all other groups. The combination group had higher BMS and MFS scores than the erythropoietin and control groups. The erythropoietin group had higher BMS and MFS scores than the control group. Immunohistochemical tissue analysis showed a significant difference among groups. There was a significant increase in myelinated axons and in the myelinated axon length in the erythropoietin group when compared to the other intervention groups (p < 0.01). Conclusion: Erythropoietin and GM1 have therapeutic effects on axonal regeneration in mice subjected to experimental spinal cord injury, and administration of GM1 alone had the highest scores on the BMS and MFS scales.

LncRNA Gm13568 regulates the activation of A1 astrocytes and affects the EAE process in mice / 中华微生物学和免疫学杂志

Objective:To investigate the effects of long non-coding RNA (lncRNA) Gm13568 on the activation of A1 astrocytes and the progress of experimental autoimmune encephalomyelitis (EAE) in mice.Methods:A recombinant lentiviral vector (LV-Inhibit-Gm13568) carrying astrocyte-specific promoter of glial fibrillary acidic protein (GFAP) was established to inhibit the function of endogenous Gm13568. A control vector (LV-ctrl) was established as well. The recombinant vectors were packaged. C57BL/6 mice were injected with 1×10 7 transforming units of viral suspension via the tail vein and 7 d after the injection, myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55) was used to establish the mouse model of EAE. Four groups, PBS group, EAE group, LV-ctrl+ EAE group and LV-Inhibit-Gm13568+ EAE group, were included in this study. Clinical signs of the mice were monitored daily in a double-blinded manner. The mice were sacrificed 23 d after the EAE model was established and the spinal cord tissues were collected. The expression of Serping 1, C3, Srgn and H2-T23 at mRNA level was detected by real-time PCR. Changes in the expression of IL-6, TNF-α, macrophage chemotactic protein-1 (MCP-1) and interferon-inducible protein-10 (IP-10) were measured. Western blot was used to investigate the expression of GFAP and Notch1 in spinal cord tissues and the phosphorylation of signal transduction and transcription activator 3 (STAT3). The expression of Notch1 intracellular domain (NICD) and GFAP in spinal cord tissues was detected by immunofluorescence. Furthermore, the infiltration of inflammatory cells and the demyelination of spinal cord were observed using HE and Luxol fast blue (LFB) staining methods. Results:Compared with PBS group, A1 astrocytes were activated and Notch1 expression was significantly up-regulated in EAE group and LV-ctrl+ EAE group. The clinical score of mice in LV-Inhibit-Gm13568+ EAE group was decreased from an average score of 3.5 to less than 1 on 23 d after antigen induction and the clinical symptoms were alleviated as compared with the mice in LV-ctrl+ EAE group. Meanwhile, the activation of A1 astrocytes was down-regulated, and the production of inflammatory cytokines and chemokines was also reduced. The expression of Notch1, GFAP and NICD at protein level and the phosphorylation of STAT3 were significantly reduced. Moreover, the infiltration of inflammatory cells and demyelination of spinal cord tissues were alleviated significantly.Conclusions:LncRNA Gm13568 might regulate the activation of A1 astrocytes via the Notch1/STAT3 pathway, thus affecting the production of inflammatory cytokines and chemokines and participating in the process of EAE.

Death and prediction analysis of adult hematological malignancies in Shenzhen / 白血病·淋巴瘤

Objective:To investigate the characteristics of death, tendency and the prediction of Shenzhen residents with adult hematological malignancies from 2017 to 2020.Methods:The surveillance data of hematological malignancies from 2017 to 2020 and the demographic data in Shenzhen were collected from Shenzhen death cause monitoring system and Shenzhen Center for Disease Control and Prevention, respectively. The data of the 7th national demographic data in 2020 were set as the standardized population data. Crude mortality rate (CMR), standardized mortality rate (SMR) and annual percentage change (APC) of mortality were calculated by using Joinpoint software. The grey model GM(1,1) was built to predict the mortality of adult hematological malignancies in Shenzhen between 2021 and 2025.Results:From 2017 to 2022, the male CMR of hematological malignancies was 1.15/100 000 to 1.85/100 000, and the SMR was 2.24/100 000 to 2.44/100 000; the female CMR of hematological malignancies was 0.81/100 000 to 1.75/100 000, and the SMR was 1.67/100 000 to 1.90/100 000. There were no statistically significant differences in the annual CMR and SMR between male and female hematological malignancies (all P > 0.05), and the annual change trend of CMR and SMR was not significant. The APC of male and female CMR was 27.28% and 12.70%, respectively (χ 2 = 0.01, P = 0.939); the APC of male and female SMR was 1.12% and 4.77%, respectively (χ 2 = 0.91, P = 0.318). The death causes of hematological malignancies were successively acute myeloid leukemia (AML), lymphoma, multiple myeloma, acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) plus chronic myelomonocytic leukemia (CMML), chronic lymphoblastic leukemia (CLL) plus chronic myelogenous leukemia (CML). The CMR of patients with hematological malignancies aged 18-40 years was low, the CMR began to rise in patients above 40 years, especially the rapid increase at the age of 60 years, reaching the peak at the age of 80 years or above. The shortest median time of all kinds of hematological malignancies from the onset of disease to the death was found in AML group (8 months, range 0.1-168 months), the longest time was in CLL+CML group (24 months, range 0.1-300 months). Infection was the most direct cause of death, followed by single organ failure. GM(1,1) model had the better predictive effects and the total SMR would increase from 2021 to 2025 (4.52/100 000, 4.76/100 000, 5.01/100 000, 5.28/100 000 and 5.57/100 000, respectively). Conclusions:The incidence of hematological malignancies in Shenzhen residents over 40 years old is on the increase. The trend of adult hematological malignancies in Shenzhen will rise predicted by GM (1,1) grey model.

Granulocyte-Macrophage colony stimulating factor in asthmatic patients infected with respiratory syncytial virus

@#Introduction: It is estimated that at least 30 to 40% of asthma attacks in adults are related to respiratory infections with viruses. The majority of asthma-related viruses include respiratory syncytial virus (RSV), rhinovirus, and parainfluenza. Inflammatory cytokines are supposed to play a vital role in causing inflammation of the respiratory tract as regulators of proliferation, chemotaxis, and activation of inflammatory cells. Objectives: The aim of this study is to assess the role of Granulocyte Macrophage-Colony Stimulating Factor (GMCSF) in asthmatic airway hyper-responsiveness associated with RSV infections. Materials and Methods: Forty five asthmatic cases and 45 healthy individuals were studied in a cross-sectional design. All asthmatics underwent symptom score assessment.GMCSF concentrations in sputum and RSV-IgM/IgG in serum samples were measured for all participants by Enzyme Linked Immuno-Sorbent Assay (ELISA). Results: The GM-CSF concentration level was significantly higher in asthmatics (270.27± 194.87pg/mL) especially among moderate and severe disease with mean concentration of 197.33±98.47 and 521.08± 310.04 respectively, compared to healthy controls (22.20±21.27 pg/ mL) (p=0.0001). The sputum level of GM-CSF in asthmatics is highly significant associated with positive anti-RSV IgG sera which represents 35/45(77.8%) with mean GM-CSF concentration of (276.99± 86.42) compared with controls at about 31/45 (68.9%) with GM-CSF mean concentration of (22.84±23.47). On the other hand, positive anti-RSV IgM in asthma cases was 8 out of 45(17.8 %) with GM-CSF mean concentration of (307.25± 306.65). Furthermore, GM-CSF sputum level was significantly correlated with eosinophil count especially in moderate and severe asthma. Conclusions: This study revealed that GM-CSF level is associated with eosinophilia and indicates asthma severity that might be evident during RSV infection .The distinctive GM-CSF features observed in the sputum from asthmatics with RSV may be useful as a diagnostic methods to help match patients with antibody therapy.

Guillain-Barré syndrome with GM3 antibody positive: a case report / 中华神经科杂志

Guillain-Barré syndrome is an autoimmune disease, and its pathogenesis is believed to be closely related to the appearance of ganglioside antibodies, while GM3 ganglioside antibodies have been reported rarely. This article reports a case of Guillain-Barré syndrome associated with GM3 antibody positive. The patient was a 58-year-old female. The chief complaint was "weakness of both lower limbs for 10 days, incomplete closure of the right eyelid for eight days, and incomplete closure of the left eyelid with dizziness for one day". The serum anti-GM3 antibody was positive, and her symptoms improved after treatment with gamma globulin.

Evaluation and application of an efficient plant DNA extraction protocol for laboratory and field testing / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Nucleic acids in plant tissue lysates can be captured quickly by a cellulose filter paper and prepared for amplification after a quick purification. In this study, a published filter paper strip method was modified by sticking the filter paper on a polyvinyl chloride resin (PVC) sheet. This modified method is named EZ-D, for EASY DNA extraction. Compared with the original cetyl trimethylammonium bromide (CTAB) method, DNA extracted by EZ-D is more efficient in polymerase chain reaction (PCR) amplification due to the more stable performance of the EZ-D stick. The EZ-D method is also faster, easier, and cheaper. PCR analyses showed that DNA extracted from several types of plant tissues by EZ-D was appropriate for specific identification of biological samples. A regular PCR reaction can detect the EZ-D-extracted DNA template at concentration as low as 0.1 ng/μL. Evaluation of the EZ-D showed that DNA extracts could be successfully amplified by PCR reaction for DNA fragments up to 3000 bp in length and up to 80% in GC content. EZ-D was successfully used for DNA extraction from a variety of plant species and plant tissues. Moreover, when EZ-D was combined with the loop-mediated isothermal amplification (LAMP) method, DNA identification of biological samples could be achieved without the need for specialized equipment. As an optimized DNA purification method, EZ-D shows great advantages in application and can be used widely in laboratories where equipment is limited and rapid results are required.

GM1 gangliosidosis: a case report / Gangliosidose GM1: um relato de caso

RESUMEN La gangliosidosis GM1 es un trastorno lisosomal caracterizada por la acumulación de gangliósido GM1 (glucoesfingolípido) en el sistema nervioso central (SNC) y visceral, debido a la deficiencia de la enzima beta-galactosidase (hidrolasa lisosomal). Afecta principalmente al SNC y las vísceras y produce importantes anomalías esqueléticas, que a menudo ocurren con la presencia de linfocitos vacuolados en la muestra de la sangre periférica o médula ósea. Tiene tres formas de presentación, lo que dificulta aún más su identificación debido al amplio espectro clínico. El presente estudio tiene como objetivo describir un caso de gangliosidosis GM1 en un paciente masculino, nacido a las 38 semanas. Hasta el momento, no existe un tratamiento efectivo para la gangliosidosis GM1, es decir, el portador de la enfermedad solo recibe medidas sintomáticas y paliativas. Por tanto, el diagnóstico precoz de la enfermedad es de suma importancia, ya que su única forma de prevención, actualmente, es a través del consejo genético.

Pioderma gangrenoso paraneoplásico en una paciente con recaída de leucemia mieloide aguda / Paraneoplastic bullous pyoderma gangrenosum occurring in a patient with a relapse of an acute myeloid leukemia

Resumen El pioderma gangrenoso ampolloso fue descrito por primera vez en 1972. Se presenta el caso de una paciente con pioderma gangrenoso asociado a una recaída de leucemia mieloide aguda y se hace una revisión de la literatura sobre el tema.

Abstract Bullous pyoderma gangrenosum was first described by Perry in 1972. We present a case of a patient with paraneoplastic pyoderma gangrenosum associated to relapse of an acute myelogenous leukemia and we review the literature on pyoderma gangrenosum.

Immunohistochemical identification of GM-CSF in testis of rats with oligozoospermia with the intervention of Cuscuta chinensis flavonoids / Identificación inmunohistoquímica de GM-CSF en testículos de ratas con oligozoospermia con la intervención de flavonoides de Cuscuta chinensis

Oligozoospermia is a common infertility disease, and the incidence rate is increasing year by year. Cuscuta chinensis is a commonly used medicine for the treatment of oligozoospermia in Chinese medicine. Flavonoids are its main component. GM-CSF is a multifunctional cytokine that plays an important role in the inflammatory response. In this paper, we performed HE staining and immunohistochemical staining on the testis of rats with oligozoospermia. We intend to study the expression changes of GM-CSF in rats with oligospermia and the effect of flavonoids on the expression of GM-CSF in testis of rats with oligozoospermia.

La oligozoospermia es una enfermedad común de infertilidad, con una tasa de incidencia que aumenta año tras año. Cuscuta chinensis es un medicamento de uso común para el tratamiento de la oligozoospermia en la medicina china. Los flavonoides son su componente principal. GM-CSF es una citocina multifuncional que tiene un rol importante en la respuesta inflamatoria. En este trabajo, realizamos tinción con hematoxilina y eosina y tinción inmunohistoquímica en testículos de ratas con oligozoospermia. TNuestro objetivo fue estudiar los cambios de expresión de GM-CSF en ratas con oligozoospermia y el efecto de los flavonoides en la expresión de GM-CSF en testículos de ratas con oligozoospermia.

In silico analysis of the effects of disease-associated mutations of b-hexosaminidase A in Tay–Sachs disease

Tay–Sachs disease (TSD), a deficiency of b-hexosaminidase A (Hex A), is a rare but debilitating hereditary metabolic disorder. Symptoms include extensive neurodegeneration and often result in death in infancy. We report an in silico study of 42 Hex A variants associated with the disease. Variants were separated into three groups according to the age of onset: infantile (n=28), juvenile (n=9) and adult (n=5). Protein stability, aggregation potential and the degree of conservation of residues were predicted using a range of in silico tools. We explored the relationship between these properties and the age of onset of TSD. There was no significant relationship between protein stability and disease severity or between protein aggregation and disease severity. Infantile TSD had a significantly higher mean conservation score than nondisease associated variants. This was not seen in either juvenile or adult TSD. This study has established that the degree of residue conservation may be predictive of infantile TSD. It is possible that these more highly conserved residues are involved in trafficking of the protein to the lysosome. In addition, we developed and validated software tools to automate the process of in silico analysis of proteins involved in inherited metabolic diseases. Further work is required to identify the function of well-conserved residues to establish an in silico predictive model of TSD severity

Tay-Sachs disease / Enfermedad de Tay-Sachs

Abstract Introduction: Lysosomal storage disease is caused by the deficiency of a single hydrolase (lysosomal enzymes). GM2 gangliosidoses are autosomal recessive disorders caused by deficiency of β-hexosaminidase and Tay-Sachs disease (TSD) is one of its three forms. Objective: To perform a review of the state of the art on TSD and describe its definition, epidemiology, etiology, physiopathology, clinical manifestations, as well as advances regarding its diagnosis and treatment. Materials and methods: A literature search was carried out in PubMed using the MeSH terms "Tay-Sachs Disease". Results: after the initial search was conducted, 1 233 results were retrieved, of which 53 articles were finally selected. TSD is caused by the deficiency of the lysosomal enzyme β-hexosaminidase A (HexA), and is characterized by neurodevelopmental regression, hypotonia, hyperacusis and cherry-red spots in the macula. Research on molecular pathogenesis and the development of possible treatments has been limited, consequently there is no treatment established to date. Conclusion: TSD is an autosomal recessive neurodegenerative disorder. Death usually occurs before the age of five. More research and studies on this type of gangliosidosis are needed in order to find an adequate treatment.

Resumen Introducción. La deficiencia de una sola hidrolasa (enzimas lisosomales) da como resultado una enfermedad de almacenamiento lisosomal. Las gangliosidosis GM2 son trastornos autosómicos recesivos causados por la deficiencia de β-hexosaminidasa. La enfermedad de Tay-Sachs (TSD, por sus siglas en inglés) es una de las tres presentaciones de este tipo de gangliosidosis. Objetivo. Realizar una revisión del estado del arte de la TSD describiendo su definición, epidemiología, etiología, fisiopatología, manifestaciones clínicas y actualidades en su diagnóstico y tratamiento. Materiales y métodos. Se realizó una búsqueda bibliográfica en PubMed utilizando como único término MeSH "Tay-Sachs Disease". Resultados. Se encontraron 1 233 publicaciones y se seleccionaron 53 artículos. La TSD es originada por la deficiencia de la enzima lisosomal β-hexosaminidasa A (HexA) y se caracteriza por regresión del neurodesarrollo, hipotonía, hiperacusia y manchas maculares rojo cereza. La investigación de la patogenia molecular y el desarrollo de posibles tratamientos han sido limitados y en la actualidad no se cuenta con uno plenamente establecido. Conclusiones. La TSD es un trastorno neurodegenerativo autosómico recesivo y por lo general la muerte se produce antes de los 5 años de edad. Son necesarias más investigaciones y estudios sobre este tipo de gangliosidosis con el fin de encontrar un tratamiento adecuado.

Clinical and CLB1 gene mutations analysis of GM1 gangliosidosis in a patient / 中华神经科杂志

Objective@#To investigate the clinical and CLB1 gene mutation characteristics of GM1 gangliosidosis patient.@*Methods@#The clinical data of one GM1 gangliosidosis patient from Children′s Hospital Affiliated to Zhengzhou University in March 2018 were reviewed and analyzed. The patient was diagnosed by gene detection and enzymatic activity.@*Results@#The patient is a 4 years and 1 month old boy, mainly presented psychomotor retrogression. His β-galactosidase activity was low (8.0 nmol·g-1·min-1). Two splice site mutations (c.458-2A(IVS4)>G and c.1068+5G(IVS10)>A) of patient′s CLB1 gene were screened by targeted next generation sequencing. The results of Sanger sequencing showed that the mutations are compound heterozygous and both are first reported. The mutation c.1068+5G(IVS10)>A was derived from patient′s mother, and the other one is de nove.@*Conclusion@#GM1 gangliosidosis is a rare neurodegenerative disease, which could be accurately diagnosed by the next generation sequencing and enzyme assay.

Prediction of maternal and child health care indicators in China based on GM(1,1) model / 中华疾病控制杂志

Objective To study the predictive effect of model ［GM(1,1)］ in China’s maternal and child health indicators, and to predict the future maternal and child health indicators in a short-term, and provide a scientific basis for the gradual improvement of maternal and child health care services in China. Methods The maternal mortality rate (MMR), neonatal mortality rate (NMR), infant mortality rate (IMR) and under-five mortality rate (U5MR) were collected from 2008 to 2017 in China. Models were established and MATLAB 2018b software was used for predictive analysis. Results The prediction models of maternal mortality rate, neonatal mortality rate, infant mortality rate and under-five mortality rate were as follows: x