Explore the vast range of titles available.

In recent years, outbreaks of Marek’s disease (MD) have been frequently reported in vaccinated chicken flocks in China. Herein, we have demonstrated that four Marek’s disease virus (MDV) isolates, HN502, HN302, HN304, and HN101, are all pathogenic and oncogenic to hosts. Outstandingly, the HN302 strain induced 100% MD incidence, 54.84% mortality, and 87.10% tumor incidence, together with extensive atrophy of immune organs. Pathotyping of HN302 was performed in comparison to a standard very virulent (vv) MDV strain Md5. We found that both CVI988 and HVT vaccines significantly reduced morbidity and mortality induced by HN302 or Md5 strains, but the protection indices (PIs) provided by these two vaccines against HN302 were significantly lower (27.03%) or lower (33.33%) than that against Md5, which showed PIs of 59.89% and 54.29%, respectively. These data suggested that HN302 possesses a significant higher virulence than Md5 and at least could be designated as a vvMDV strain. Together with our previous phylogenetic analysis on MDV-1 meq genes, we have presently suggested HN302 to be a typical highly virulent MDV variant belonging to an independent Chinese branch. To our knowledge, this is the first report to provide convincible evidence to identify a pathogenic MDV variant strain with a higher virulence than Md5 in China, which may have emerged and circulating in poultry farms in China for a long time and involved in the recent MD outbreaks.

Background Aicardi-Goutieres syndrome (AGS) is an inflammatory disorder belonging to the type I interferonopathy group. The clinical diagnosis of AGS is difficult, which can lead to a high mortality rate. Overall, there is a lack of large-sample research data on AGS in China. We aim to summarize the clinical characteristics of Chinese patients with AGS and provide clues for clinical diagnostic. Methods The genetic and clinical features of Chinese patients with AGS were collected. Real-time polymerase chain reaction was used to detect expression of interferon-stimulated genes ( ISGs ) . Results A total of 23 cases were included, consisting of 7 cases of AGS1 with three prime repair exonuclease 1 mutations, 3 of AGS2 with ribonuclease H2 subunit B ( RNASEH2B ) mutations, 3 of ASG3 with RNASEH2C , 1 of AGS4 with RNASEH2A mutations, 2 of AGS6 with adenosine deaminase acting on RNA 1 mutations, and 7 of AGS7 with interferon induced with helicase C domain 1 mutations. Onset before the age of 3 years occurred in 82.6%. Neurologic involvement was most common (100%), including signs of intracranial calcification which mainly distributed in the bilateral basal ganglia, leukodystrophy, dystonia, epilepsy, brain atrophy and dysphagia. Intellectual disability, language disability and motor skill impairment were also observed. Skin manifestations (60.87%) were dominated by a chilblain-like rash. Features such as microcephaly (47.62%), short stature (52.38%), liver dysfunction (42.11%), thyroid dysfunction (46.15%), positive autoimmune antibodies (66.67%), and elevated erythrocyte sedimentation rate (53.85%) were also found. The phenotypes of 2 cases fulfilled the diagnostic criteria for systemic lupus erythaematosus (SLE). One death was recorded. ISGs expression were elevated. Conclusions AGS is a systemic disease that causes sequelae and mortality. A diagnosis of AGS should be considered for patients who have an early onset of chilblain-like rash, intracranial calcification, leukodystrophy, dystonia, developmental delay, positive autoimmune antibodies, and elevated ISGs , and for those diagnosed with SLE with atypical presentation who are nonresponsive to conventional treatments. Comprehensive assessment of vital organ function and symptomatic treatment are important.

Background Monogenic lupus is defined as systemic lupus erythematosus (SLE)/SLE-like patients with either dominantly or recessively inherited pathogenic variants in a single gene with high penetrance. However, because the clinical phenotype of monogenic SLE is extensive and overlaps with that of classical SLE, it causes a delay in diagnosis and treatment. Currently, there is a lack of early identification models for clinical practitioners to provide early clues for recognition. Our goal was to create a clinical model for the early identification of pediatric monogenic lupus, thereby facilitating early and precise diagnosis and treatment for patients. Methods This retrospective cohort study consisted of 41 cases of monogenic lupus treated at the Department of Pediatrics at Peking Union Medical College Hospital from June 2012 to December 2022. The control group consisted of classical SLE patients recruited at a 1:2 ratio. Patients were randomly divided into a training group and a validation group at a 7:3 ratio. A logistic regression model was established based on the least absolute shrinkage and selection operator to generate the coefficient plot. The predictive ability of the model was evaluated using receiver operator characteristic curves and the area under the curve (AUC) index. Results A total of 41 cases of monogenic lupus patients and 82 cases of classical SLE patients were included. Among the monogenic lupus cases (with a male-to-female ratio of 1:1.05 and ages of onset ranging from birth to 15 years), a total of 18 gene mutations were identified. The variables included in the coefficient plot were age of onset, recurrent infections, intracranial calcifications, growth and developmental delay, abnormal muscle tone, lymphadenopathy/hepatosplenomegaly, and chilblain-like skin rash. Our model demonstrated satisfactory diagnostic performance through internal validation, with an AUC value of 0.97 (95% confidence interval = 0.92–0.97). Conclusions We summarized and analyzed the clinical characteristics of pediatric monogenic lupus and developed a predictive model for early identification by clinicians. Clinicians should exercise high vigilance for monogenic lupus when the score exceeds − 9.032299. Graphical abstract

Background Recombinant human growth hormone (rhGH) therapy has shown to improve height and body composition in children with Prader–Willi syndrome (PWS), the evidence of early rhGH treatment on motor and mental development is still accumulating. This study explored the time effect on psychomotor development, anthropometric indexes, and safety for infants and young children with PWS. Methods A phase 3, single-arm, multicenter, self-controlled study was conducted in six sites. Patients received rhGH at 0.5 mg/m 2 /day for first four weeks, and 1 mg/m 2 /day thereafter for up to 52 weeks. Motor development was measured using Peabody Developmental Motor Scales-second edition, mental development using Griffiths Development Scales-Chinese (GDS-C). Height standard deviation score (SDS), body weight SDS, and body mass index (BMI) SDS were also assessed. Results Thirty-five patients were enrolled totally. Significant improvements were observed in height, body weight, and BMI SDS at week 52; GDS-C score showed significant improvement in general quotient (GQ) and sub-quotients. In a linear regression analysis, total motor quotient (TMQ), gross motor quotient (GMQ), and fine motor quotient were negatively correlated with age; however, treatment may attenuate deterioration of TMQ and GMQ. Changes in GQ and locomotor sub-quotient in < 9-month group were significantly higher than ≥ 9-month group. Mild to moderate severity adverse drug reactions were reported in six patients. Conclusion Fifty-two-week treatment with rhGH improved growth, BMI, mental development, and lessened the deterioration of motor function in infants and young children with PWS. Improved mental development was more pronounced when instituted in patients < 9 months old.

Classical swine fever (CSF) is a severe acute infectious disease that results from classical swine fever virus (CSFV) infection, which leads to serious economic losses in the porcine industry worldwide. In recent years, numerous studies related to the immune escape mechanism of the persistent infection and pathogenesis of CSFV have been performed. Remarkably, several independent groups have reported that apoptosis, autophagy, and pyroptosis play a significant role in the occurrence and development of CSF, as well as in the immunological process. Apoptosis, autophagy, and pyroptosis are the fundamental biological processes that maintain normal homeostatic and metabolic function in eukaryotic organisms. In general, these three cellular biological processes are always understood as an immune defense response initiated by the organism after perceiving a pathogen infection. Nevertheless, several viruses, including CSFV and other common pathogens such as hepatitis C and influenza A, have evolved strategies for infection and replication using these three cellular biological process mechanisms. In this review, we summarize the known roles of apoptosis, autophagy, and pyroptosis in CSFV infection and how viruses manipulate these three cellular biological processes to evade the immune response.

Objective To report the clinical features of patients with systemic lupus erythematosus (SLE) associated with thrombotic thrombocytopenic purpura (TTP). Their diagnosis, treatment, and prognosis were also discussed. Methods A total of 25 TTP-SLE pediatric patients were included in this study. Their clinical symptoms, laboratory findings, disease activity, and renal biopsy were retrospectively reviewed. Results The median age of the patient cohort was 14 years old. Nine patients were first diagnosed with SLE, followed by the diagnosis of TTP-SLE, whereas 15 patients were diagnosed with TTP and SLE concurrently. All the 25 TTP-SLE patients had decreased platelet count and microangiopathic hemolytic anemia. Fever, rash, edema and neurological symptoms were the main clinical symptoms. Fragmentation of erythrocytes on blood smear and increased LDH were found in all patients. Nineteen patients (76%) had impaired renal function. Renal biopsy showed that most of the patients had lupus nephritis class IV (20%) and TMA (20%). 13 patients (52%) were treated with glucocorticoids in combination with immunosuppressive agent, and 10 patients (40%) were treated with plasma exchange combined with glucocorticoids plus immunosuppressive agent. One patient died due to lung infection; others had disease remission. Fifteen patients had follow-up regularly, and their conditions were stable. Conclusion Patients with TTP-SLE often had moderate to severe lupus disease activity. Testing of LDH level and blood smear should be performed when kidney and neurological symptoms arise in children with SLE. The use of combination therapy, glucocorticoids plus immunosuppressive agent, provided satisfactory clinical outcome. Patients with refractory TTP-SLE will also need plasma exchange therapy.

Background Familial hypercholesterolemia (FH) is an inherited disorder mainly marked by increased low-density lipoprotein cholesterol (LDL-C) concentrations and a heightened risk of early-onset arteriosclerotic cardiovascular disease (ASCVD). This study seeks to characterize the genetic spectrum and genotype‒phenotype correlations of FH in Chinese pediatric individuals. Methods Data were gathered from individuals diagnosed with FH either clinically or genetically at multiple hospitals across mainland China from January 2016 to June 2024. Results In total, 140 children and adolescents (mean age of 6.00 years) with clinically and genetically diagnosed FH were enrolled in the study, with 87 distinct variants identified in the LDLR , APOB and PCSK9 genes. Among the variants, 11 variants were newly identified worldwide, with 9 classified as “pathogenic” or “likely pathogenic”, and 2 classified as “variants of uncertain significance”. Additionally, the 5 most common variants in the study were c.1448G > A (p.W483*), c.1879G > A (p.A627T), c.1216C > A (p.R406R), and c.1747C > T (p.H583Y) in the LDLR gene, as well as c.10579C > T (p.R3527W) in the APOB gene, accounting for 49.29% (69/140) of all patients. These variants are primarily observed in the Asian or Chinese population and are distinct from those present in Caucasian groups. In this cohort, 105 patients were diagnosed with heterozygous FH (HeFH), while 35 were diagnosed with homozygous FH (HoFH). Finally, only 28.57% of the patients (40/140) were using lipid-lowering medications with 33.33% of HoFH patients initiating treatment after the age of 8. Additionally, only 3 compound heterozygous patients (2.14%) underwent liver transplantation because of significantly high lipid levels. Conclusion This study reveals the variable genotypes and phenotypes of children with FH in China and illustrates that the genotypes in the Chinese population differ from those in Caucasians, providing a valuable dataset for the clinical genetic screening of FH in China. Furthermore, the older age at diagnosis and treatment highlights the underdiagnosis and undertreatment of Chinese FH pediatric patients, suggesting that early identification should be improved through lipid or genetic screening, and that more timely and regular pharmacological treatments should be implemented.

Gallid alphaherpesvirus 2 (GaHV2) is an oncogenic avian herpesvirus inducing Marek’s disease (MD) and rapid-onset T-cell lymphomas. To reveal molecular events in MD pathogenesis and tumorigenesis, the dynamic splenic transcriptome of GaHV2-infected chickens during early infection and pathogenic phases has been determined utilizing RNA-seq. Based on the significant differentially expressed genes (DEGs), analysis of gene ontology, KEGG pathway and protein-protein interaction network has demonstrated that the molecular events happening during GaHV2 infection are highly relevant to the disease course. In the ‘Cornell Model’ description of MD, innate immune responses and inflammatory responses were established at early cytolytic phase but persisted until lymphoma formation. Humoral immunity in contrast began to play a role firstly in the intestinal system and started at late cytolytic phase. Neurological damage caused by GaHV2 is first seen in early cytolytic phase and is then sustained throughout the following phases over a long time period. During the proliferative phase many pathways associated with transcription and/or translation were significantly enriched, reflecting the cell transformation and lymphoma formation. Our work provides an overall view of host responses to GaHV2 infection and offers a meaningful basis for further studies of MD biology.

The inflatable leading edge (ILE) is explored as a dynamic stall control concept. A fluid-structure interaction (FSI) numerical method for the elastic membrane structure is constructed based on unsteady Reynolds-averaged Navier-Stokes (URANS) and a mass-spring-damper (MSD) structural dynamic model. Radial basis function- (RBF-) based mesh deformation algorithm and Laplacian and optimization-based mesh smoothing algorithm are adopted in flowfield simulations to achieve the pitching oscillation of the airfoil and to ensure the mesh quality. An airfoil is considered at a freestream Mach number of 0.3 and chord-based Reynolds number of 3.92×106. The airfoil is pitched about its quarter-chord axis at a sinusoidal motion. The numerical results indicate that the ILE can change the radius of curvature of the airfoil leading edge, which could reduce the streamwise adverse pressure gradient and suppress the formation of dynamic stall vortex (DSV). Although the maximum lift coefficient of the airfoil is slightly reduced during the control process, the maximum drag and pitching moment coefficients of the airfoil are greatly reduced by up to 66% and 75.2%, respectively. The relative position of the ILE has a significant influence on its control effect. The control laws of inflation and deflation also affect the control ability of the ILE.

Background This study aimed to evaluate the clinical features of posterior reversible encephalopathy syndrome (PRES) in children. Methods The medical records of 31 patients from five medical centers who were diagnosed with PRES from 2001 to 2013 were retrospectively analyzed. In the 31 patients, 16 were males, and 15 females, with a median age of 7 years (3–12 years). Patients younger than 10 years accounted for 74.2% of the 31 patients. Results Seizure, the most common clinical sign, occurred in 29 of the 31 patients. Visual disturbances were also observed in 20 patients. Cerebral imaging abnormalities were bilateral and predominant in the parietal and occipital white matter. In this series, three patients died in the acute phase of PRES. One patient had resolution of neurologic presentation within one week, but no apparent improvement in radiological abnormalities was observed at eight months. One patient showed gradual recovery of both neurologic presentation and radiological abnormalities during follow-up at eight months. One patient developed long-term cortical blindness. All of the PRES patients with hematologic tumor had a worse prognosis than those without hematologic tumor. Conclusions Seizure is a prevalent characteristic of children with PRES. Poor prognosis can be seen in PRES patients with hematologic tumor.