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Although many cytokine pathways are important for dendritic cell (DC) development, it is less clear what cytokine signals promote the function of mature dendritic cells. The signal transducer and activator of transcription 4 (STAT4) promotes protective immunity and autoimmunity downstream of proinflammatory cytokines including IL-12 and IL-23. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), Stat4-/- mice are resistant to the development of inflammation and paralysis. To define whether STAT4 is required for intrinsic signaling in mature DC function, we used conditional mutant mice in the EAE model. Deficiency of STAT4 in CD11c-expressing cells resulted in decreased T cell priming and inflammation in the central nervous system. EAE susceptibility was recovered following adoptive transfer of wild-type bone marrow-derived DCs to mice with STAT4-deficient DCs, but not adoptive transfer of STAT4- or IL-23R-deficient DCs. Single-cell RNA-sequencing (RNA-seq) identified STAT4-dependent genes in DC subsets that paralleled a signature in MS patient DCs. Together, these data define an IL-23-STAT4 pathway in DCs that is key to DC function during inflammatory disease.
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Células Dendríticas , Encefalomielite Autoimune Experimental , Interleucina-23 , Fator de Transcrição STAT4 , Transdução de Sinais , Animais , Fator de Transcrição STAT4/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Interleucina-23/metabolismo , Interleucina-23/imunologia , Camundongos , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Camundongos Knockout , Esclerose Múltipla/imunologia , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/imunologia , Inflamação/metabolismo , Inflamação/imunologia , Transferência Adotiva , Camundongos Endogâmicos C57BL , Humanos , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Fast radio bursts (FRBs) are immensely energetic millisecond-duration radio pulses. Observations indicate that nearby FRBs can be produced by old stellar populations, as suggested by the localization of the repeating source FRB 20200120E in a globular cluster of M81. Nevertheless, the burst energies of FRB 20200120E are significantly smaller than those of other cosmological FRBs. Here, we report the detection of a bright burst from FRB 20200120E in 1.1 - 1.7 GHz, with a fluence of approximately 30 Jy ms, which is more than 42 times larger than the previously detected bursts near 1.4 GHz frequency. It reaches one-third of the energy of the weakest burst from FRB 20121102A and is detectable at a distance exceeding 200 Mpc. Our finding bridges the gap between nearby and cosmological FRBs and indicates that FRBs hosted in globular clusters can be bright enough to be observable at cosmological distances.
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Borrelia burgdorferi (B. burgdorferi), an extracellular spirochetal pathogen, elicits a type-I interferon (IFN-I) response that contributes to the pathology of Lyme disease, including the development and severity of Lyme arthritis. However, the specific Pathogen-Associated Molecular Patterns (PAMPs) of B. burgdorferi responsible for triggering the IFN-I response are not well understood. Previous studies have identified an unknown, nuclease-resistant component in B. burgdorferi culture supernatants that significantly stimulates the IFN-I response, but its identity remains unknown. In this study, we reveal that B. burgdorferi secretes cyclic-di-adenosine monophosphate (c-di-AMP) as a key extracellular PAMP, inducing the host IFN-I response in macrophages. Using genetically manipulated B. burgdorferi strains, we demonstrate a requirement of c-di-AMP for stimulating IFN-I response by macrophages ex vivo. Additionally, infecting mice with B. burgdorferi alongside exogenous c-di-AMP resulted in a markedly increased IFN-I response in mouse tissues. Furthermore, inactivation or inhibition of the host STING signaling pathway significantly reduced the IFN-I response, indicating that c-di-AMP-induced IFN-I production is STING-dependent. Our findings identify c-di-AMP as a crucial PAMP secreted by B. burgdorferi to elicit the host IFN-I response via activation of STING signaling pathway, suggesting that targeting c-di-AMP production could represent a novel therapeutic strategy against Lyme arthritis.
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Gallbladder polyp is a common disease of gallbladder, the incidence of gallbladder polyp in China is about 5%~10%, and the trend is increasing year by year. The patients with gallbladder polyps had no obvious clinical symptoms, which was more than that found by ultrasonography during physical examination. At present, the diameter of gallbladder polyps>10 mm is still used by clinicians as the main surgical indication for cholecystectomy. According to the data, about 80% to 90% of gallbladder polyps are cholesterol type polyps and benign gallbladder polyps. For these patients whose gallbladder is removed due to benign gallbladder polyps, we consider that we can continue to observe or retain the gallbladder, without having to bear the adverse consequences that may be caused by gallbladder removal. Based on the literature analysis at home and abroad, this paper discusses the surgical treatment of gallbladder polyps and the results of postoperative pathological diagnosis, and reminds the majority of clinicians to be careful when removing gallbladder polyps.
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Colecistectomia , Doenças da Vesícula Biliar , Pólipos , Humanos , Pólipos/cirurgia , Doenças da Vesícula Biliar/cirurgia , Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/cirurgiaAssuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Estudos Retrospectivos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fator de Transcrição PAX8/metabolismo , Fator de Transcrição PAX8/genética , Fator de Transcrição PAX2/metabolismo , Fator de Transcrição PAX2/genética , Racemases e Epimerases/metabolismo , Racemases e Epimerases/genética , Nefrectomia , SeguimentosRESUMO
Texture and sensory studies at various temperatures are important in evaluating and improving the functionality of butter. While literature is scarce, we evaluated and compared the effect of temperature (5-25°C) on the texture, rheological and sensory properties of commercial butter samples (salted, unsalted, cultured, and spreadable) from the New Zealand market. In addition, the instrumental analyses were compared with the sensory evaluation, to understand the possibility of using instrumental analysis to evaluate consumer liking for different butters. Butter type, temperature, and their type-temperature interaction exhibited significant differences for all instrumental textural parameters. As expected, higher temperature produced softer butter that was more spreadable, liquid-like, less adhesive, less cohesive, had lower storage modulus (G') and lower loss modulus (Gâ³) with the melting of milk fat crystals; however, the rate of change varied for the different butter samples. We have established meltability as the parameter for evaluating butter selection for different applications. The spreadable butter sample exhibited the lowest hardness and G', and highest spreadability (p < .05) at all temperatures, owing to its low solid fat content and the abundance of low-melting triglycerides. The cultured butter sample had the highest melting point, owing to compositional differences. The instrumental and sensory texture analyses were highly correlated, indicating the comparative effectiveness of both approaches for studying the effects of different temperatures on butter textural properties. Overall, our findings provide detailed reference to the dairy industry for butter manufacture, considering variation in fatty acid composition, texture analysis, rheology, and sensory analysis, over the range of storage/usage temperatures.
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Manteiga , Reologia , Temperatura , Nova Zelândia , Humanos , Manteiga/análise , Comportamento do Consumidor , Paladar , Manipulação de Alimentos/métodos , Adulto , Dureza , Feminino , AnimaisRESUMO
Utilizing spin pumping, we present a comparative study of the spin-charge conversion in RuO_{2}(101) and RuO_{2}(110) films. RuO_{2}(101) shows a robust in-plane crystal-axis dependence, whereas RuO_{2}(110) exhibits an isotropic but stronger one. Symmetry-based analysis and first-principles calculations reveal that the spin-charge conversion in RuO_{2}(110) originates from the inverse spin Hall effect (ISHE) due to nodal lines splitting. In RuO_{2}(101), the ISHE also dominates although the inverse spin splitting effect (ISSE) may coexist. These findings, in sharp contrast to previously attributed ISSE, are further corroborated by the reciprocal relation between the spin pumping and the spin-torque ferromagnetic resonance measurements.
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Objective: To understand the utilization and characteristics of outpatient services for pneumoconiosis patients within two weeks in Chongqing, and analyze the influencing factors, so as to provide reference for relevant policy making. Methods: From October 2020 to October 2022, 1771 pneumoconiosis patients who met the inclusion criteria were selected by multi-stage stratified random cluster sampling. A questionnaire survey was conducted on their basic situation, utilization of outpatient services within two weeks, treatment for pneumoconiosis-related symptoms, and selection of medical service institutions using χ(2)-test and logistic regression analysis. Results: All the 1771 pneumoconiosis patients were male, with the average age of (56.1±10.19) years old. In the pneumoconiosis patients were treated in outpatient department within 2 weeks.40.0% (204/510) of aged 41~50 years Rural patients accounted for 87.8% (448/510) ; 65.1% (332/510) of silicosis patients, 37.5% (191/510) of stage II patients, 75.1% (383/510) of patients did not continue to engage in dust work after diagnosis of pneumoconiosis, and 57.1% (291/510) of patients never had work-related injury insurance at work. The outpatient rate within two weeks of pneumoconiosis related assistance and subsistence allowance was 17.6% (90/510) and 12.5% (64/510), respectively. The average self-health score of the patients was (52.9±16.2). 28.2% of the patients had purchased work-related injury insurance; Among the 1204 patients who received the treatment within two weeks, 42.2% were in the outpatient department, 20.7% were in the inpatient department, and 36.9% were self-buyers. There was a significant difference between the different treatment methods of the patients (χ(2)=27.53, P<0.05). There was a significant difference in patients from different residence choosing to visit different medical institutions (χ(2)=13.97, P<0.05). The stage of pneumoconiosis, presence of complications, presence of work injury insurance, self-health score, and whether he/she has been hospitalized in the past year are the important factors affecting the outpatient treatment of pneumoconiosis patients. Conclusion: The utilization of outpatient service of pneumoconiosis patients is influenced by demographic sociology, social support and disease characteristics. The quality of occupational disease medical service in primary health institutions should be strengthened so that pneumoconiosis patients can get convenient and effective treatment. Establish a more perfect social security support system to reduce the disease burden of pneumoconiosis patients.
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Assistência Ambulatorial , Pacientes Ambulatoriais , Pneumoconiose , Humanos , Pessoa de Meia-Idade , Masculino , Pneumoconiose/terapia , Pneumoconiose/epidemiologia , Inquéritos e Questionários , Pacientes Ambulatoriais/estatística & dados numéricos , Assistência Ambulatorial/estatística & dados numéricos , Adulto , Idoso , China/epidemiologia , Silicose/terapia , Silicose/epidemiologiaRESUMO
Objective: To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma. Methods: A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor. Results: â A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group (P=0.016). â¡Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group (P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower (P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group (P=0.002), whereas the incidence of grade 3 diarrhea was lower (P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea (P=0.506), and neither group experienced grade 5 diarrhea. ⢠The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). â£No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⤠All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group (P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group (P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group (P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups (P=0.396). ⥠The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively (P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively (P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively (P=0.373) . Conclusion: In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Transplante Autólogo , Humanos , Mieloma Múltiplo/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Estudos Retrospectivos , Criopreservação , Mobilização de Células-Tronco Hematopoéticas/métodos , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute liver injury induced by lipopolysaccharide (LPS) and D-GalN in mice. METHODS: Adult male C57BL/6J mice with or without LPS/D-GaIN-induced acute liver injury were given intraperitoneal injections of rSj-Cys or PBS 30 min after modeling (n=18), and serum and liver tissues samples were collected from 8 mice in each group 6 h after modeling. The survival of the remaining 10 mice in each group within 24 h was observed. Serum levels of ALT, AST, TNF-α and IL-6 of the mice were measured, and liver pathologies was observed with HE staining. The hepatic expressions of macrophage marker CD68, Bax, Bcl-2 and endoplasmic reticulum stress (ERS)-related proteins were detected using immunohistochemistry or immunoblotting, and TUNEL staining was used to detect hepatocyte apoptosis. RESULTS: The survival rates of PBS- and rSj-Cys-treated mouse models of acute liver injury were 30% and 80% at 12 h and were 10% and 60% at 24 h after modeling, respectively; no death occurred in the two control groups within 24 h. The mouse models showed significantly increased serum levels of AST, ALT, IL-6 and TNF-α and serious liver pathologies with increased hepatic expressions of CD68 and Bax, lowered expression of Bcl-2, increased hepatocyte apoptosis, and up-regulated expressions of ERS-related signaling pathway proteins GRP78, CHOP and NF-κB p-p65. Treatment of the mouse models significantly lowered the levels of AST, ALT, IL-6 and TNF-α, alleviated liver pathologies, reduced hepatic expressions of CD68, Bax, GRP78, CHOP and NF-κB p-p65, and enhanced the expression of Bcl-2. In the normal control mice, rSj-Cys injection did not produce any significant changes in these parameters compared with PBS. CONCLUSION: rSj-Cys alleviates LPS/D-GalN-induced acute liver injury in mice by suppressing ERS, attenuating inflammation and inhibiting hepatocyte apoptosis.
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Apoptose , Cistatinas , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Hepatócitos , Inflamação , Camundongos Endogâmicos C57BL , Schistosoma japonicum , Animais , Camundongos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Masculino , Hepatócitos/metabolismo , Hepatócitos/efeitos dos fármacos , Cistatinas/farmacologia , Fígado/patologia , Fígado/metabolismo , Lipopolissacarídeos , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Proteínas Recombinantes/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Galactosamina , Antígenos CD/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Molécula CD68RESUMO
To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage â ¢ to â £. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.
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Perfuração Intestinal , Humanos , Masculino , Feminino , Criança , Estudos Retrospectivos , Adolescente , Pré-Escolar , Lactente , Prognóstico , Perfuração Intestinal/etiologia , Linfoma de Células B , Linfoma de Burkitt , Trato Gastrointestinal , Linfoma não Hodgkin , Linfoma Difuso de Grandes Células BRESUMO
Acute carbon monoxide poisoning can cause hypoxic injury to multiple organs. Neurological impairment and cardiac dysfunction are common manifestations of severe poisoning patients, but hemorrhagic complications are rare in clinic. The clinical diagnosis and treatment of a case of massive intrathecal hematoma of the rectus abdominis secondary to acute severe carbon monoxide poisoning was reported. The pathophysiological mechanism and treatment strategy of rectus sheath hematoma secondary to acute severe carbon monoxide poisoning was analyzed, in order to improve the understanding of hemorrhagic complications of carbon monoxide poisoning. This case suggests that for patients with a history of cardiovascular disease and taking anticoagulants, clinicians should be alert for the risk of bleeding when making medical decisions.
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Intoxicação por Monóxido de Carbono , Hematoma , Reto do Abdome , Humanos , Intoxicação por Monóxido de Carbono/complicações , Masculino , Hematoma/etiologia , Hematoma/induzido quimicamente , Pessoa de Meia-Idade , Doença Aguda , AdultoRESUMO
OBJECTIVE: Low cardiac output syndrome (LCOS) is a dangerous postoperative complication in patients with acute type A aortic dissection (ATAAD). This study aims to develop and evaluate a nomogram model that can reliably identify risk variables for postoperative LCOS in elderly patients suffering from ATAAD. PATIENTS AND METHODS: In this retrospective study, a total of 310 elderly patients with ATAAD admitted to Fujian Medical University Union Hospital were included and categorized into the LCOS and non-LCOS groups. Stepwise logistic regression was used to analyze independent predictors of LCOS, and a nomogram was constructed. The best clinical decision points were found using decision analysis and a clinical impact curve. RESULTS: Postoperative LCOS occurred in 22 (7.1%) of elderly patients with ATAAD. Independent risk factors for postoperative LCOS were age, smoking history, aortic cross-clamp (ACC), coronary heart disease (CHD), and preoperative shock. The nomogram constructed based on the identified risk factors showed good performance. CONCLUSIONS: Our results suggest that preventive treatment can be administered when needed when the risk of LCOS in older patients with ATAAD after surgery is >60%. This study contributes to developing a methodology that may improve therapeutic decision-making in older patients and provides insights for assessing the risk of LCOS.
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Dissecção Aórtica , Baixo Débito Cardíaco , Nomogramas , Humanos , Idoso , Dissecção Aórtica/cirurgia , Feminino , Masculino , Estudos Retrospectivos , Baixo Débito Cardíaco/diagnóstico , Baixo Débito Cardíaco/etiologia , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisAssuntos
Aromatase , Ginecomastia , Humanos , Ginecomastia/genética , Masculino , Criança , Aromatase/genética , Anastrozol , Sequenciamento do Exoma , Nitrilas , Triazóis/uso terapêutico , Fenótipo , Mutação , Mama/anormalidades , Mama/patologia , LinhagemRESUMO
Modifiers of Huntington's disease (HD) include mismatch repair (MMR) genes; however, their underlying disease-altering mechanisms remain unresolved. Knockout (KO) alleles for 9 HD GWAS modifiers/MMR genes were crossed to the Q140 Huntingtin (mHtt) knock-in mice to probe such mechanisms. Four KO mice strongly ( Msh3 and Pms1 ) or moderately ( Msh2 and Mlh1 ) rescue a triad of adult-onset, striatal medium-spiny-neuron (MSN)-selective phenotypes: somatic Htt DNA CAG-repeat expansion, transcriptionopathy, and mHtt protein aggregation. Comparatively, Q140 cortex also exhibits an analogous, but later-onset, pathogenic triad that is Msh3 -dependent. Remarkably, Q140/homozygous Msh3-KO lacks visible mHtt aggregates in the brain, even at advanced ages (20-months). Moreover, Msh3 -deficiency prevents striatal synaptic marker loss, astrogliosis, and locomotor impairment in HD mice. Purified Q140 MSN nuclei exhibit highly linear age-dependent mHtt DNA repeat expansion (i.e. repeat migration), with modal-CAG increasing at +8.8 repeats/month (R 2 =0.98). This linear rate is reduced to 2.3 and 0.3 repeats/month in Q140 with Msh3 heterozygous and homozygous alleles, respectively. Our study defines somatic Htt CAG-repeat thresholds below which there are no detectable mHtt nuclear or neuropil aggregates. Mild transcriptionopathy can still occur in Q140 mice with stabilized Htt 140-CAG repeats, but the majority of transcriptomic changes are due to somatic repeat expansion. Our analysis reveals 479 genes with expression levels highly correlated with modal-CAG length in MSNs. Thus, our study mechanistically connects HD GWAS genes to selective neuronal vulnerability in HD, in which Msh3 and Pms1 set the linear rate of neuronal mHtt CAG-repeat migration to drive repeat-length dependent pathogenesis; and provides a preclinical platform for targeting these genes for HD suppression across brain regions. One Sentence Summary: Msh3 and Pms1 are genetic drivers of sequential striatal and cortical pathogenesis in Q140 mice by mediating selective CAG-repeat migration in HD vulnerable neurons.
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Objective: To summarize the genotype and clinical phenotype of children with WWOX gene related developmental and epileptic encephalopathy (DEE). Methods: Case series studies. The clinical data of 12 children with WWOX gene related DEE who were admitted to the Neurological Department of Children's Medical Center, Peking University First Hospital from June 2019 to December 2023 were analyzed. The children's characteristics of gene variation, clinical phenotype, auxiliary examination results, treatment and prognosis were analyzed. Results: Among 12 children with WWOX gene related DEE, there were 7 boys and 5 girls, the age of seizure onset ranged from 10 days to 6 months (median 1.8 months). Multiple seizure types were observed, including focal seizures in 10 cases, epileptic spasms in 9 cases, tonic seizures in 4 cases, myoclonic seizures in 1 case. Among 12 cases, 9 cases had multiple seizure types. All 12 cases showed microcephaly and global developmental delay. Video electroencephalography showed slowed background activity in 6 cases, hyperarrhythmia in 6 cases, multifocal discharges in 6 cases, and focal discharges in 1 case. Epileptic spasms were detected in 8 cases, tonic seizures in 4 cases and myoclonic seizures in 1 case. Brain magnetic resonance imaging showed bilateral frontotemporal subarachnoid space widening in 5 cases, deep sulci in 3 cases, bilateral ventricular enlargement in 2 cases, callosal hypoplasia in 5 cases, and delayed white matter myelination in 3 cases. The phenotypes of 12 cases were consistent with the diagnosis of DEE, and 8 of them were diagnosed with infantile epileptic spasm syndrome. All the WWOX gene variants in 12 cases were complex heterozygous variants, including 20 variants, 11 variants and 1 large intragenic WWOX gene deletion (p.Ala149Thr, p.Arg156Ser, p.R167Tfs*8, p.Leu186Val, c.605+5G>A, p.Trp218*, p.His263Arg, p.Leu275fs*19*1, p.N285Kfs*10, p.Ser304Tyr, p.Met326Arg, loss1 exon2-8) had not been reported previously. The age of last follow-up ranged from 11 months to 5 years and 3 months. During the follow-up, 1 case died at the age of 1 year and 10 months, 2 cases were seizure-free, and 9 cases still had seizures after multiple anti-seizure medications. Conclusions: The seizure onset age of children with WWOX gene related DEE is usually less than 6 months, and some of them in neonate. The common seizure types include focal seizures and epileptic spasms. Children usually have microcephaly and global developmental delay. WWOX gene related DEE usually has drug refractory epilepsy.
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Eletroencefalografia , Genótipo , Mutação , Fenótipo , Oxidorredutase com Domínios WW , Humanos , Oxidorredutase com Domínios WW/genética , Masculino , Feminino , Lactente , Espasmos Infantis/genética , Epilepsia/genética , Epilepsia/diagnóstico , Recém-Nascido , Imageamento por Ressonância Magnética , Convulsões/genética , Microcefalia/genética , Deficiências do Desenvolvimento/genética , Pré-Escolar , Proteínas Supressoras de Tumor/genéticaRESUMO
Allergic diseases are affected by both genetic background and environmental factors.In recent years, many studies have shown that allergic diseases are closely related to the gut microbiome.This article will elaborate on the composition of gut microbiome in early life and its relationship with allergies, the mechanism of action, and the influence of gut microbiome colonization on the atopic march, in order to improve the understanding of the relationship between allergy prevention or treatment and gut microbiome in children, and provide new ideas for the early prevention of allergic diseases and the early intervention of allergic processes.
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Hipersensibilidade , Humanos , Hipersensibilidade/microbiologia , Microbiota , Criança , Microbioma Gastrointestinal , Trato Gastrointestinal/microbiologiaRESUMO
Objective: To explore the distribution of allergen-specific IgE (sIgE) for children with atopic dermatitis in Tianjin City and provide the evidences of clinical diagnosis and treatment. Methods: A retrospective cross-sectional study was conducted to analyze the children who were suspected of atopic dermatitis and tested for serum sIgE in the Tianjin Children's Hospital from March 2021 to February 2023. Using first detection results only, a total of 1 841 serum samples were tested for twenty common allergens. The method was the enzyme-linked immune capture assay. The allergen epidemiological characteristics were statistically analyzed by Chi square test based on the children's characteristics and factors such as different sexes, ages and seasons by the mass data. Results: Among the 1 841 cases, the results showed that 1 247 (67.73%) were sensitized to at least 1 allergen-sIgE, comprising to 49.86% (918/1 841) to food allergen-sIgE and 47.96% (883/1 841) to aeroallergen-sIgE. The top three food allergens-sIgE were egg 32.10% (591/1 841), milk 25.91% (477/1 841) and wheat flour 14.61% (269/1 841); the top three positive rates of aeroallergens-sIgE were house dust 24.33% (448/1 841), alternaria 20.59% (379/1 841) and dermatophagoides farinae 14.83% (273/1 841). The positive rates of food allergens-sIgE were the highest in the 1-3 years old group (64.11%, 434/677) (χ2=122.854, P<0.001), while the positive rates of aeroallergens-sIgE were higher in the 11-14 years old group (71.26%, 62/87) (χ2=134.968, P<0.001). No seasonal difference was revealed in the overall positive rate of food allergen-sIgE and aeroallergen-sIgE (χ2=4.047, P=0.256; χ2=7.549, P=0.056). The positive rates of soybean-sIgE and milk-sIgE were the highest in summer (χ2=11.329, P=0.010; χ2=28.720, P<0.001), whereas alternaria-sIgE and mugwort-sIgE were the highest in summer and autumn, respectively (χ2=8.462, P=0.037; χ2=10.641, P=0.014). Among the 1 841 cases, 32.21% were sensitized to three or more allergens-sIgE. The sIgE concentration levels of egg, milk and house dust were mainly level 1 to 2, and the proportions of level 3 and above were all under 15%; although the positive rates of crab, shrimp, and peanut were low, the proportions of grade 3 and above were all beyond 30%. Children sensitized to alternaria, dermatophagoides farinae, mugwort, and cat dander had higher sIgE concentration levels, which were 68.07%, 49.45%, 56.57% and 47.83% respectively. Conclusions: This study can reflect the epidemic characteristics of allergen-sIgE in children with atopic dermatitis in Tianjin region to a certain extent. Allergen-sIgE positivity in patients differed by age, and there were seasonal differences and grade distribution differences in the positive rates of some allergens-sIgE. It is necessary to reasonably avoid the high-risk allergens according to the epidemiological characteristics and clinical symptoms, which provide valuable information for the prevention, diagnosis and treatment of atopic dermatitis.
Assuntos
Alérgenos , Dermatite Atópica , Imunoglobulina E , Humanos , Dermatite Atópica/imunologia , Estudos Transversais , Alérgenos/imunologia , Criança , Estudos Retrospectivos , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Pré-Escolar , Masculino , Feminino , China , Adolescente , Lactente , Hipersensibilidade Alimentar/imunologiaRESUMO
Persistent Organic Pollutants (POPs) have the characteristics of resistance to environmental degradation, bioaccumulation and long-distance migration potential. Maternal exposure to POPs during pregnancy can enter the fetal blood circulation through the placental barrier, and have a potential impact on the functional development of the nervous system of the offspring. This in turn leads to the occurrence and development of neurological defects and diseases in adulthood. The purpose of this paper is to elucidate the effects of exposure to three major POPs (organochlorine compounds, perfluoroalkyl and polyfluoroalkyl substances, and polybrominated diphenyl ethers) during pregnancy on the functional development of the nervous system (social emotions, cognition, language, exercise, and adaptability) in children, and to provide reference for subsequent studies.