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Group 3 innate lymphoid cells (ILC3s) play key roles in intestinal inflammation. Olfactomedin 4 (OLFM4) is highly expressed in the colon and has a potential role in dextran sodium sulfate-induced colitis. However, the detailed mechanisms underlying the effects of OLFM4 on ILC3-mediated colitis remain unclear. In this study, we identify OLFM4 as a positive regulator of IL-22+ILC3. OLFM4 expression in colonic ILC3s increases substantially during intestinal inflammation in humans and mice. Compared to littermate controls, OLFM4-deficient (OLFM4-/-) mice are more susceptible to bacterial infection and display greater resistance to anti-CD40 induced innate colitis, together with impaired IL-22 production by ILC3, and ILC3s from OLFM4-/-mice are defective in pathogen resistance. Besides, mice with OLFM4 deficiency in the RORγt compartment exhibit the same trend as in OLFM4-/-mice, including colonic inflammation and IL-22 production. Mechanistically, the decrease in IL-22+ILC3 caused by OLFM4 deficiency involves the apoptosis signal-regulating kinase 1 (ASK1)- p38 MAPK signaling-dependent downregulation of RAR-related orphan receptor gamma (RORγt) protein. The OLFM4-metadherin (MTDH) complex upregulates p38/RORγt signaling, which is necessary for IL-22+ILC3 activation. The findings indicate that OLFM4 is a novel regulator of IL-22+ILC3 and essential for modulating intestinal inflammation and tissue homeostasis.
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Colitis , Interleucina-22 , Interleucinas , Ratones Noqueados , Animales , Ratones , Interleucinas/metabolismo , Interleucinas/genética , Colitis/genética , Colitis/inducido químicamente , Colitis/metabolismo , Colitis/inmunología , Colitis/patología , Humanos , Linfocitos/inmunología , Linfocitos/metabolismo , Ratones Endogámicos C57BL , Factor Estimulante de Colonias de Granulocitos/metabolismo , Factor Estimulante de Colonias de Granulocitos/genética , Inmunidad Innata , Inflamación/metabolismo , Inflamación/genética , Masculino , GlicoproteínasRESUMEN
Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.
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Disbiosis , Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/microbiología , Disbiosis/metabolismo , Disbiosis/microbiología , Disbiosis/inmunología , Humanos , Ratones , Masculino , Femenino , Animales , Enfermedad del Almacenamiento de Glucógeno Tipo I/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo I/genética , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Modelos Animales de Enfermedad , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologíaRESUMEN
BACKGROUND: Nonpharmacological interventions for COVID-19 could reduce the incidence of children hospitalized in pediatric intensive care units (PICU) and the incidence of children with bacterial infections. This study aimed to evaluate changes in the bacterial profile of children in PICU before and during the COVID-19 pandemics. METHODS: This is a retrospective study, involving clinical data of children with positive bacterial cultures admitted to the PICU respectively in 2019 and 2021. RESULTS: In total 652 children were included in this study. The total number of hospitalized patients and the incidence of bacteria-positive children in 2021 were lower than those in 2019. There were no significant differences in the ratio of Gram-positive bacterial infection, Gram-negative bacteria infection or fungi infection between the two years. The rate of Streptococcus pneumoniae in 2021 was higher than that in 2019(p = 0.127). The incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend(p = 0.002). The distribution of previous underlying diseases in children admitted to PICU with different outcomes of bacterial infection between the two years were homogeneous (p > 0.05). CONCLUSION: After the implementation of COVID-19 isolation, prevention and control measures, the number of hospitalizations and bacterial infections in PICU decreased, which may be due to changes in population's behavior patterns. Meanwhile, the incidence of Haemophilus influenzae in hospitalized patients decreased with a downward trend.
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COVID-19 , Infecciones por Bacterias Grampositivas , Niño , Humanos , SARS-CoV-2 , Estudios Retrospectivos , COVID-19/epidemiología , Pandemias , Unidades de Cuidado Intensivo PediátricoRESUMEN
OBJECTIVES: To analyze the epidemiological characteristics and trends in death after thoracotomy in children with congenital heart disease (CHD). METHODS: The clinical data of children with CHD aged 0-14 years who died after thoracotomy in our hospital from January 1, 2005, to December 31, 2020, were retrospectively collected to analyze the characteristics of and trends in postoperative death. RESULTS: A total of 502 patients (365 males; 72.7%) died from January 1, 2005, to December 31, 2020, with an average of 31 deaths per year. For these patients, the median age was 2.0 months, the median length of hospital stay was 16.0 days, the median postoperative time to death was 5.0 days, and the median risk adjustment in congenital heart surgery-1 (RACHS-1) score was 3.0. 29.5% underwent emergency surgery, 16.9% had postoperative ECMO support, and 15.9% received postoperative blood purification treatment. In the past 16 years, the deaths of children with CHD under 1 year old accounted for 80.5% of all deaths among children with CHD aged 0-14 years, and deaths (349 cases) under 6 kg accounted for 69.5% of all deaths. Age at death, weight, and disease type were characterized by annual changes. CONCLUSIONS: The postoperative deaths of children with CHD mainly occurred in infants and toddlers who weighed less than 6.0 kg, and TGA and PA were the most lethal CHDs. The proportion of deaths has been increasing across the years among patients who are young, have a low body weight, and have complex cyanotic CHD.
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Cardiopatías Congénitas , Masculino , Lactante , Humanos , Estudios Retrospectivos , Cardiopatías Congénitas/cirugía , Tiempo de Internación , Hospitales , ToracotomíaRESUMEN
Invasive pulmonary aspergillosis (IPA) is a serious fungal infection, with a high degree of mortality in immunocompromised individuals. Diagnosis of IPA is challenging in that clinical manifestations are not specific, with sensitivity of traditional detection procedures low. We report a case of IPA in a chronic granulomatous disease (CGD) infant who was initially suspected to have a lung tumor. Aspergillus fumigatus was identified as the pathogen in bronchoalveolar lavage fluid (BALF) by next-generation sequencing (mNGS). The patient recovered rapidly following a change of appropriate antifungal treatment and was discharged. This case highlights the additional value of BALF-mNGS for the diagnosis of pediatric invasive pulmonary fungal infection in immune-deficient children.
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Background: Genetic epilepsy with febrile seizures plus (GEFS+) is a type of epileptic syndrome closely related to heredity factors, which can be caused by gene mutations. However, it still remains unclear how these mutations result in seizures. Previously, we identified a new heterozygous missense mutation of the KCNAB3 gene, H258R, in the GEFS+ family; the electric currents of the human embryonic kidney 293 (HEK293) cells co-expressing Kvß3 (H258R) and Kv1.1 showed obvious inactivation. This study sought to examine the effects of this mutation on the potassium channels in the mammalian brain. Methods: Mutant mice were generated by introducing the human H258R missense mutation within exon 10 at an equivalent position in the mouse KCNAB3 gene via CRISPR/Cas9 and homologous recombination. A patch clamp was used to detect the potassium currents in the pyramidal cells of the hippocampal CA1 region of the mutant mice. The total potassium currents of the pyramidal cells in the hippocampal CA1 region of KCNAB3 [wild-type (WT)] and KCNAB3 (H258R) adult mice were recorded with increased voltage. Results: We found a decreased total potassium current in the H258R group but no significant differences at a maximum voltage (+80 mV; P>0.05). Conclusions: These results suggest that the KCNAB3 mutation reduced hippocampal potassium currents in this mouse model.
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BACKGROUND: Alagille syndrome (ALGS) is an autosomal dominant genetic disorder caused by mutations in the JAG1 or NOTCH2 gene. It is characterized by decreased intrahepatic bile ducts associated with a variety of abnormalities in many other organ systems, such as the cardiovascular, skeletal, and urinary systems. CASE SUMMARY: We report a rare case of ALGS. A 1-month-old male infant presented with sustained jaundice and had a rare congenital heart disease: Total anomalous pulmonary venous connection (TAPVC). Sustained jaundice, particularly with cardiac murmur, caught our attention. Laboratory tests revealed elevated levels of alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, total bilirubin, and total bile acids, indicating serious intrahepatic cholestasis. Imaging confirmed the presence of butterfly vertebra at the seventh thoracic vertebra. This suggested ALGS, which was confirmed by genetic testing with a c.3197dupC mutation in the JAG1 gene. Ursodiol was administered immediately after confirmation of the diagnosis, and cardiac surgery was performed when the patient was 1.5 month old. He recovered well after treatment and was discharged at the age of 3 mo. At the age of two years, the patient returned to our clinic because multiple cutaneous nodules with xanthomas appeared, and their size and number increased over time. CONCLUSION: We report a unique case of ALGS associated with TAPVC and severe xanthomas. This study has enriched the clinical manifestations of ALGS and emphasized the association between JAG1 gene and TAPVC.
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Pneumonia is the leading cause of death in children; the pathogens are often difficult to diagnose. In this study, the performance of metagenomic next-generation sequencing (mNGS) using bronchoalveolar lavage fluid (BALF) samples from 112 children with confirmed pneumonia has been evaluated. mNGS performed a significantly higher positive detection rate (91.07%, 95% confidence interval [CI] 83.80% to 95.40%) and coincidence rate against the final diagnosis (72.32%, 95% CI 62.93% to 80.15%) than that of conventional methods (70.54%, 95% CI 61.06% to 78.58% and 56.25%, 95% CI 46.57% to 65.50%, respectively) (P < 0.01 and P < 0.05, respectively). Bacteria, viruses, and their mixed infections were common in children with pneumonia. Streptococcus pneumoniae was the most common bacterial pathogen in children with pneumonia, while Haemophilus parainfluenzae and Haemophilus influenzae seemed more likely to cause nonsevere pneumonia in children. In contrast, human cytomegalovirus (CMV) infection and the simultaneous bacterial infections could cause severe pneumonia, especially in children with underlying diseases. After adjustments of antibiotics based on mNGS and conventional methods, the conditions improved in 109 (97.32%) children. mNGS of BALF samples has shown great advantages in diagnosing the pathogenic etiology of pneumonia in children, especially when considering the limited volumes of BALF and the previous use of empirical antibiotics, contributing to the timely adjustment of antibiotic treatments, which can potentially improve the prognosis and decrease the mortality. IMPORTANCE Our study indicates high efficiency of mNGS using BALF for the detection of causative pathogens that cause pneumonia in children. mNGS can be a potential diagnostic tool to supplement conventional methods for children's pneumonia.
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Metagenómica , Neumonía , Niño , Humanos , Líquido del Lavado Bronquioalveolar , Sensibilidad y Especificidad , Metagenómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Neumonía/diagnóstico , Neumonía/microbiología , Bacterias/genética , AntibacterianosRESUMEN
Background: Talaromyces marneffei (TM) bloodstream infections are life- threatening in immunocompromised individuals. The lack of specific clinical features for these infections and poor sensitivity associated with routine examination procedures make diagnosis challenging. Untimely diagnosis and delayed antifungal treatment threatens the life of such patients. Case description: We report a case of a TM bloodstream infection, confirmed by the results of blood culture, of a child who was HIV negative and possessed a CD40LG gene mutation. A diagnosis of TM was established by blood metagenomic next-generation sequencing (mNGS) of the patient's blood, which was confirmed by microbiological culture of blood. On admission, this previously healthy male patient was 8-months of age, who presented with recurrent fever and a cough of 6-days in duration. His condition did not improve after antibacterial treatment for 5-days, with significant and recurrent fever and worsening spirit. He was referred to the Department of Pediatrics in our tertiary medical institution with a white blood cell count of 21.5*10â§9/L, C-reactive protein of 47.98 mg/L, and procalcitonin of 0.28 ng/mL. A bloodstream infection was not excluded and blood was collected for microbial culture. The patient received a 1-day treatment of cefoperazone sulbactam and 6-days of imipenem cilastatin. Symptoms did not improve and fever persisted. Blood was submitted for mNGS analysis and within 14-h, 14,352 TM reads were detected with a relative abundance of 98.09%. Antibiotic treatment was immediately changed to intravenous amphotericin B combined with oral itraconazole. The condition of the child gradually improved. Blood culture showed TM on the 7th day after hospitalization, confirming bloodstream infection. After the 13th day of hospital admission, the patient's body temperature dropped close to 38°C and was discharged on the 30th day of hospitalization. Oral itraconazole was prescribed with follow up at the outpatient clinic. Conclusions: HIV-negative patients with CD40LG mutations may be potential hosts for TM. TM infections are rare in children and their detection by conventional microbial culture methods are inadequate for an early diagnosis. mNGS is a rapid detection method that permits early diagnosis of uncommon infectious agents, such as TM, allowing for improved patient outcomes.
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The three-dimensional (3D) printing of a SiO2-filled thermosetting polyimide (SiO2@TSPI) composite with outstanding performance is realized via the direct ink writing (DIW) of polyamide acid (PAA) composite ink and thermal treatment conducted thereafter. The composite ink consists of phenylethynyl-terminated PAA and silica nanoparticles, where the SiO2 nanoparticles serve as the rheology modifier that is necessary for the DIW technique to obtain self-supporting feedstock during 3D printing and the reinforcement filler that is used to enhance the performance of the final composite. As a result, printed parts with complex geometry and robust thermal stability are obtained. Due to the extrusion-based DIW technique, the printed structures exhibit anisotropic mechanical strength that highly depends on printing roads. This simple and convenient means of realizing 3D structures of thermosetting polyimides is a promising strategy in aerospace and other fields.
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Background: Sepsis-associated encephalopathy (SAE) is a common complication in septic patients with a higher ICU and hospital mortality in adults and poorer long-term outcomes. Clinical presentation may range from mild confusion to convulsions and deep coma; however, little is known about SAE in children. We aimed to retrospectively analyze the data for children with sepsis, to illustrate the epidemiology, performance, and adverse outcome, and to evaluate the association between risk factors and SAE in children. Methods: All children with sepsis who were admitted to the Department of Pediatrics, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China from January 2010 to December 2020 were retrospectively analyzed. Results: A total of 210 patients with sepsis were retrospectively assigned to the SAE and non-SAE groups, of which 91 (43.33%) were diagnosed with SAE with a mortality of 6.70% (14/210). Significant differences were observed in the level of white blood platelet, platelets, international normalized ratio, prothrombin time, activated partial thromboplastin time, total protein, Ccr, UREA, blood urea nitrogen, alanine transaminase, aspartate transaminase, creatine kinase, creatine kinase isoenzymes, lactate dehydrogenase, procalcitonin, and lactic acid (p < 0.05). In the risk assessment scales, significant differences were observed in the modified Glasgow Coma score, PCIS, Pediatric Logistic Organ Dysfunction Score 2 (PELOD-2), Pediatric Sequential Organ Failure Assessment Score, and Pediatric Risk of Mortality III (p < 0.05). The incidence of septic shock, acute kidney disease, liver dysfunction, and coagulation disorder were higher in the SAE group (p < 0.05). The mechanical ventilation time ([6.57 d ± 16.86 d] vs. [2.05 d ± 5.79 d]; p < 0.001), CRRT time ([1.74 d ± 6.77 d] vs. [0.11 d ± 0.63 d]; p < 0.001), ICU stay time ([299.90 h ± 449.50 h] vs. [177.67 h ± 245.36 h]); p < 0.001 was longer than that of non-SAE. Both the PCT, Ca2+, septic shock, PELOD-2, and midazolam were identified as independent risk factors, and fentanyl was a protective factor for SAE in pediatric patients (p < 0.05). The main clinical neurological symptoms consisted of agitation, hypnosia, hypnosis alternates agitated, anterior fontanelle full/bulging/high tension, coma, muscle hypertonia, muscle hypotonia, hyperreflexia, focal seizure, and generalized seizure. Conclusions: The incidence of SAE in children was found high and the prognosis poor. In this retrospective study, the identified patients were more susceptible to SAE, with an inflammatory storm with hypocalcemia or septic shock. The use of midazolam will increase the occurrence of SAE, whereas fentanyl will reduce the incidence of SAE, and PELOD-2 may predict the occurrence of SAE.
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Background: CaBP4 encodes Ca2+-binding protein 4, a neuronal Ca2+-binding protein that participates in many cellular processes by regulating the concentration of free Ca2+ ions. De novo CaBP4 variants have been identified as a cause of congenital stationary night blindness (CSNB). However, we recently reported a 4-generation pedigree with 11 individuals diagnosed with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) that were validated with only one novel missense mutation, c.464G>A (p.G155D), in CaBP4. De novo CaBP4 variants have never been reported to be related with ADNFLE. This study aimed to identify whether c.464G>A (p.G155D) in CaBP4 reduced the expression of CaBP4. Methods: In vitro experiments using recombinant protein expressed in human neuron cells were utilized in this study. Real-time polymerase chain reaction (RT-PCR) was performed to evaluate the effect of c.464G>A on CaBP4 mRNA expression. Western blot was performed to assess the effect of c.464G>A on CaBP4 protein expression. Results: According to the RT-PCR and Western blot results, c.464G>A (p.G155D) was associated with an increased expression of CaBP4 mRNA and a reduced expression of CaBP4 protein. Conclusions: These results reveal that c.464G>A (p.G155D) in CaBP4 reduced the expression of CaBP4 by reducing the stability of the CaBP4 protein. Mutations in the CaBP4 gene may be associated with ADNFLE.
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BACKGROUND: To evaluate trends in the in-hospital mortality rate for pediatric cardiac surgery procedures between 2005 and 2017 in our center, and to discuss the mortality characteristics of children's CHD after thoracotomy. METHODS: This retrospective data were collected from medical records of children underwent CHD surgery between 2005 and 2017. RESULTS: A total of 19,114 children with CHD underwent surgery and 444 children died, with the in-hospital mortality was 2.3%. Complex mixed defect CHD had the highest fatality rate (8.63%), left obstructive lesion CHD had the second highest fatality rate (4.49%), right to left shunt CHD had the third highest mortality rate (3.51%), left to right shunt CHD had the lowest mortality rate (χ2 = 520.3,P < 0.05). The neonatal period has the highest mortality rate (12.17%), followed by infant mortality (2.58%), toddler age mortality (1.16%), and preschool age mortality (0.94%), the school age and adolescent mortality rate was the lowest (χ2 = 529.3,P < 0.05). In addition, the fatality rate in boys was significantly higher than that in girls (2.77% versus 1.62%, χ2 = 26.4, P < 0.05). CONCLUSIONS: The mortality rate of CHD surgery in children decreased year by year. The younger the age and the more complicated the cyanotic heart disease, the higher the mortality rate may be.
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Procedimientos Quirúrgicos Cardíacos , Cardiopatías Congénitas , Adolescente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Niño , Preescolar , Femenino , Cardiopatías Congénitas/cirugía , Mortalidad Hospitalaria , Humanos , Lactante , Recién Nacido , Masculino , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: To explore disease-causing gene mutations of epilepsy with febrile seizures plus (EFS+) in Southern Chinese Han population. METHODS: Blood samples and clinical data were collected from 49 Southern Han Chinese patients with EFS+. Gene screening was performed using whole-exome sequencing and panel sequencing for 485 epilepsy-related genes. The pathogenicity of variants was evaluated based on ACMG scoring and assessment of clinical concordance. RESULTS: We identified 10 putatively causative sodium channel gene variants in 49 patients with EFS+, including 8 variants in SCN1A (R500Q appeared twice), one in SCN3A and one in SCN9A. All these missense mutations were inherited from maternal or paternal and were evaluated to be of uncertain significance according to ACMG. The clinical features of patients were in concordance with the EFS+ phenotype of the mutated SCN1A, SCN3A and SCN9A gene. The clinical phenotypes of 11 probands with these gene variants included febrile seizures plus (FS+, n=7), Dravet Syndrome (n=3), FS+ with focal seizures (n=1). Three probands with SCN1A variants (R500Q located in the non-voltage areas, or G1711D in the pore-forming domain) developed severe Dravet syndrome. The affected individuals with the other 6 SCN1A variants located outside the pore-forming domain showed mild phenotypes. Novel SCN3A variant ((D1688Y) and SCN9A variant (R185H) were identified in two probands respectively and both of the probands had FS+. CONCLUSION: The SCN1A, SCN3A, and SCN9A gene mutations might be a pathogenic cause of EFS+ in Southern Chinese Han population.
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Epilepsias Mioclónicas , Epilepsia , Convulsiones Febriles , Pueblo Asiatico/genética , Niño , China , Epilepsias Mioclónicas/complicaciones , Epilepsias Mioclónicas/genética , Epilepsia/complicaciones , Epilepsia/genética , Humanos , Mutación , Canal de Sodio Activado por Voltaje NAV1.1/genética , Canal de Sodio Activado por Voltaje NAV1.3/genética , Canal de Sodio Activado por Voltaje NAV1.7/genética , Linaje , Fenotipo , Convulsiones Febriles/complicaciones , Convulsiones Febriles/genética , Canales de Sodio/genéticaRESUMEN
BACKGROUND: Intellectual developmental disorders (IDD) generally refers to the persistent impairment of cognitive activities and mental retardation caused by physical damage to the brain or incomplete brain development. We aimed to explore its genetic causes. METHODS: In this study, 21 IDD patients were recruited. The Gesell developmental scales (GDS) and Wechsler intelligence scale for children (WISC) were used to assess the impaired level of intellectual development for all probands. A superconducting MRI scanner (Philips AcsNT 3.0 T Philips, Best, The Netherlands) was used to perform a plain MRI scan of the skull on the probands. The whole-exome sequencing was carried out using next-generation sequencing in all probands and their families. RESULTS: Eight had seizures and four had typical characteristics of autism. Pregnancy and delivery were uneventful except for three patients. Moderate IDD (52.4%) accounted for the majority. The abnormal MRI results included ventriculomegaly, pachygyria, broadening external cerebral space, abnormal signal change and agenesis of corpus callosum. Eleven variants were identified, including the variant in CREBBP, MECP2, HCFC1, ATRX, RAB39B, CLCN4, DYRK1A and CASKgenes. The function areas result of gene-positive group were compared to that of gene-negative group. Not significant (p>0.05) items were revealed after this analysis. CONCLUSION: Eleven variants were identified, including the variant in CREBBP, MECP2, HCFC1, ATRX, RAB39B, CLCN4, DYRK1A and CASK genes. The function areas result of gene-positive group were not significantly different from the gene-negative group.
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PURPOSE: The aim of this was to discover disease-causing gene mutations linked to genetic epilepsy with febrile seizures plus (GEFS+) in a family in the Southern Chinese Han population. Of a three-generation pedigree of 18 members in this family, 4 were affected with GEFS+. METHOD: Blood samples of 7 family members-3 affected and 4 unaffected individuals-were collected. Whole-exome sequencing was performed to assess for genetic mutations in two of the affected individuals and two of the unaffected individuals. RESULTS: Fourteen potentially consequential mutations were found in the two affected individuals and were validated with the Sanger sequencing method. Blood DNA tested in polymerase chain reaction with KCNAB3 primers revealed that one novel missense mutation, c.773A>G (p.H258R) in the KCNAB3 gene, which encoded the potassium voltage-gated channel subfamily A regulatory ß subunit 3 (KCNAB3), was shared by all three affected and one unaffected family member. However, this mutation did not appear in 300 unrelated control subjects. According to the bioinformatics tools SIFT and PROVEAN, p.H258R was thought to affect protein function. Functional verification showed that the KCNAB3 mutation could accelerate the inactivation of potassium channels, thus inhibiting potassium current, increasing neuronal excitability, and promoting epileptic convulsion. CONCLUSIONS: These results reveal that mutations in the KCNAB3 gene may be associated with GEFS+.
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Epilepsia Generalizada , Epilepsia , Convulsiones Febriles , Epilepsia/genética , Epilepsia Generalizada/genética , Humanos , Mutación , Mutación Missense , Linaje , Convulsiones Febriles/genética , Canales de Potasio de la Superfamilia ShakerRESUMEN
BACKGROUND: A retrospective study was conducted to summarize the clinical information of childhood infections during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic. METHODS: Children with SARS-CoV-2 infection in 11 hospitals from three provinces of South China were included in the study. Clinical information was collected and compared with children and adults infected by SARS-CoV-2 in Wuhan. RESULTS: In total, 52 children were enrolled, including 28 boys. The median age was 9 years (interquartile range [IQR], 4-12); 44.2% cases were of clustered occurrences, 40.4% patients had fever, 48.1% had cough, and 46.2% had a high lymphocyte count. No abnormalities were found in the liver and kidney function. Also, 82.7% of patients received antiviral therapy, but such therapy did not shorten the time to virus negativity or hospital stay (P = .082). The time to virus negativity was 12.0 days (IQR, 8.0-16.8) and hospital stay was 14.5 days (IQR, 10.3-17.9). Compared with reports in Wuhan, there were more acute upper respiratory tract infection (AURTI) and fewer pneumonia cases (P = .000). Compared with the non-ICU adult COVID-19 in Wuhan, these children's diseases were relatively mild, with fewer complications. CONCLUSIONS: Children with SARS-CoV-2 infection had a mild fever, lymphocyte elevation was more common than reduction, and antiviral treatment had no obvious effect. The overall clinical manifestations were mild, and the prognosis was good.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , SARS-CoV-2 , Adolescente , Adulto , Antivirales/uso terapéutico , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/inmunología , Prueba de COVID-19 , Niño , Preescolar , China/epidemiología , Tos/diagnóstico , Tos/tratamiento farmacológico , Tos/epidemiología , Tos/inmunología , Epidemias , Femenino , Fiebre/diagnóstico , Fiebre/tratamiento farmacológico , Fiebre/epidemiología , Fiebre/inmunología , Humanos , Lactante , Recién Nacido , Tiempo de Internación , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Three-dimensional (3D) printing of poly(dimethylsiloxane) (PDMS) is realized with a two-state curing strategy, i.e., photocuring for additively manufacturing high-precision architectures followed by thermal cross-linking for high-performance objects, taking Sylgard-184 as an example. In the mixture of base and curing agent of Sylgard-184, the photocuring ingredient methacrylated PDMS is incorporated to form hybrid inks with not only high-efficiency UV curing ability but also moderate rheological properties for 3D printing. The inks are then used to additively manufacture high-precision architectures by UV-assisted direct ink writing. Various architectures such as lattices and honeycombs, channels that can be used as microfluidics, and pressure-proof pipes with a feature size of ≈100 µm, can be readily printed. Thereafter, thermal cross-linking at elevated temperature is conducted to obtain the 3D PDMS objects with comparable properties to Sylgard-184. The facile, universal two-stage approach to 3D printing of PDMS can facilitate the development of microfluidics, flexible electronics, soft robots, and so on.
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Dimetilpolisiloxanos/química , Polímeros/química , Impresión Tridimensional , Temperatura , Estructura Molecular , Tamaño de la Partícula , Procesos Fotoquímicos , Propiedades de SuperficieRESUMEN
High-definition and arbitrary grayscale hydrogel paintings that can appear reversibly with hydration/dehydration are realized through spatially grayscale exposure. Spatio-temporally grayscale images are used to guide the exposure of a hydrogel processor to dictate the gradient cross-linking density spatially, which thereafter results in the heterogeneity of hydrogels in swelling ratio, mechanical properties, and especially visible light transmittance, leading to swelling-induced patterns by gradient and local visible light scattering difference based on tunable mesh size and microphase separation. The resultant grayscale hydrogel patterns, with visible light transmittance adjustable, are reversible during hydration (in 1-2 s) and dehydration and possess the feature size of 70 µm and more pattern information compared with previous hydrogel patterning. Uniquely, the patterns can be realized not only on the outmost surface of hydrogels as usual but inside. Combining the unique grayscale exposure with three-dimensional printing technology, arbitrary hydrogel patterns that have plenty of details and even vary at different layers are fabricated readily, indicating its broad potential in smart anti-counterfeiting of security field, mechanics, engineering, and many others.
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PURPOSE: This study aimed to identify disease-causing gene mutations in individuals belonging to the Southern Chinese Han population diagnosed with fever-associated seizures or epilepsy (FASE). METHODS: Blood samples and clinical data were collected from 78 children with FASE. All subjects were screened for mutations using whole-exome sequencing, and mutations were validated using the Sanger sequencing method. RESULTS: Three novelSCN9A heterozygous missense mutations (I775M, R429C and A442T) were noted, which are associated with febrile seizures (FS), febrile seizures plus (FS+) and genetic epilepsy with febrile seizures plus (GEFS+), respectively. The R429C and A442T mutations are located in the large cytoplasmic loop between transmembrane topological domains, whereas I775M is located in the topological domain DIIS2. The I775M and R429C mutations have highly evolutionarily conserved residues and are predicted to affect the SCN9A protein function according to bioinformatics tools. These three mutations were not identified in 300 unrelated control subjects. CONCLUSIONS: Mutations in theSCN9A gene may be linked with FASE.