Enhancing clinical skills in pediatric trainees: a comparative study of ChatGPT-assisted and traditional teaching methods.

BACKGROUND: As artificial intelligence (AI) increasingly integrates into medical education, its specific impact on the development of clinical skills among pediatric trainees needs detailed investigation. Pediatric training presents unique challenges which AI tools like ChatGPT may be well-suited to address. OBJECTIVE: This study evaluates the effectiveness of ChatGPT-assisted instruction versus traditional teaching methods on pediatric trainees' clinical skills performance. METHODS: A cohort of pediatric trainees (n = 77) was randomly assigned to two groups; one underwent ChatGPT-assisted training, while the other received conventional instruction over a period of two weeks. Performance was assessed using theoretical knowledge exams and Mini-Clinical Evaluation Exercises (Mini-CEX), with particular attention to professional conduct, clinical judgment, patient communication, and overall clinical skills. Trainees' acceptance and satisfaction with the AI-assisted method were evaluated through a structured survey. RESULTS: Both groups performed similarly in theoretical exams, indicating no significant difference (p > 0.05). However, the ChatGPT-assisted group showed a statistically significant improvement in Mini-CEX scores (p < 0.05), particularly in patient communication and clinical judgment. The AI-teaching approach received positive feedback from the majority of trainees, highlighting the perceived benefits in interactive learning and skill acquisition. CONCLUSION: ChatGPT-assisted instruction did not affect theoretical knowledge acquisition but did enhance practical clinical skills among pediatric trainees. The positive reception of the AI-based method suggests that it has the potential to complement and augment traditional training approaches in pediatric education. These promising results warrant further exploration into the broader applications of AI in medical education scenarios.

Causal links between sedentary behavior, physical activity, and psychiatric disorders: a Mendelian randomization study.

BACKGROUND: Studies suggest a correlation between excessive sedentary behavior, insufficient physical activity, and an elevated likelihood of experiencing psychiatric disorder. Nonetheless, the precise influence of sedentary behavior and physical activity on psychiatric disorder remains uncertain. Hence, the objective of this research was to investigate the possible causal relationship between sedentary behavior, physical activity, and the susceptibility to psychiatric disorder (depression, schizophrenia and bipolar disorder), utilizing a two-sample Mendelian randomization (MR) approach. METHODS: Potential genetic instruments related to sedentary leisure behaviors were identified from the UK Biobank database, specifically a summary-level genome-wide association study (GWAS) involving 422,218 individuals of European descent. The UK Biobank database also provided the GWAS data for physical activity. Primary analysis was performed using inverse variance weighting (IVW) to assess the causal relationship between sedentary behavior, physical activity, and the risk of psychiatric disorder (depression, schizophrenia and bipolar disorder). Sensitivity analysis was conducted using Cochran's Q test, the MR-Egger intercept test, the MR-pleiotropy RESidual sum and outlier test, leave-one-out analysis, and funnel plot analysis. RESULTS: According to the IVW analysis, there was a significant association between genetically predicted leisure television watching and an increased risk of depression (odds ratio [OR] = 1.027, 95% confidence interval [CI]: 1.001-1.053; P = 0.04). The IVW analysis also indicated that there was a decreased risk of depression associated with fraction accelerations of > 425 milligravities, as measured by accelerometers (OR = 0.951, 95%CI: 0.914-0.989; P = 0.013). The other MR methods obtained consistent but non-significant results in the same direction. However, there was no evidence of a causal association between genetic liability for moderate-to-vigorous physical activity, accelerometer-assessed physical activity, computer use, or driving and the risk of depression. Furthermore, IVW analysis has also found that driving has a slight effect in reducing the risk of schizophrenia (OR = 0.092, 95%CI: 0.010-0.827; P = 0.033), while leisure television viewing has a significant protective effect against the onset of bipolar disorder (OR = 0.719, 95%CI: 0.567-0.912; P = 0.006). CONCLUSION: The study provides compelling evidence of a link between depression, bipolar disorder, and excessive TV watching. Furthermore, it suggests that higher accelerometer-assessed fraction accelerations of > 425 milligravities can serve as a genetic protective factor against depression. To mitigate the risk of developing depression, it is advisable to reduce sedentary activities, particularly television watching, and prioritize engaging in vigorous physical exercise.

Association of dietary inflammatory index with obesity among children and adolescents in the United States NHANES cohort: a population-based study.

BACKGROUND: Childhood obesity has become a huge challenge to childhood health, and there is a lack of understanding about the relationship between dietary inflammatory index (DII) and childhood obesity. The main objective of this study was to analyze the potential link between DII and obesity among children and adolescents residing in the United States. METHODS: A cross-sectional analysis was performed using data obtained from the National Health and Nutrition Examination Survey between 2009 and 2018. In total, 12,454 participants were included in the analysis. DII was calculated based on dietary data from the first day of the 24-hour dietary recall. Logistic regression was used to analyze the association between DII and obesity, as well as central obesity defined by the waist-to-height ratio of 0.5 or higher or waist circumference ≥ 90th percentile for age and sex. RESULTS: The mean dietary inflammation index was 2.05 (SE = 0.02), with higher levels in children than in adolescents (P = 0.01). According to our findings, the prevalence of central obesity was higher among adolescents (38.0%) than among children (31.4%). The adolescents in the third quartile of DII have a higher risk of overweight/obesity (OR = 1.46, 95% CI: 1.24-1.71) after adjusting for age, sex, and race. This positive association remained significant even after physical activity was added to the model. Concerning central obesity, the adolescents in the highest quartile of DII have a higher risk, independent of demographic characteristics and physical activity. However, no significant association was observed among children. CONCLUSIONS: The dietary inflammation index was positively associated with overweight/obesity and central obesity among adolescents in the United States after adjusting for confounding factors. These findings highlight the importance of promoting anti-inflammatory diets in adolescents to prevent obesity and its associated complications.

Global burden of myocarditis and cardiomyopathy in children and prediction for 2035 based on the global burden of disease study 2019.

Background: Myocarditis and cardiomyopathy are commonly occurring cardiovascular diseases that seriously threaten children's health. It was urgent to update the global incidence and mortality of childhood myocarditis and cardiomyopathy, and to predict the incidence rate of 2035 by the Global Burden of Disease database. Methods: The Global Burden of Disease study data from 1990 to 2019 in 204 countries and territories were used to determine: global incidence and mortality rates of childhood myocarditis and cardiomyopathy from 0 to 19 by five age groups; relationship between sociodemographic index (SDI) and incidence and mortality rates by age group; and, based on an age-period-cohort model, the projected incidence of childhood myocarditis and cardiomyopathy for 2035. Results: From 1990 to 2019, global age-standardized incidence rate decreased by 0.1% (95% UI 0.0-0.1) to 7.7% (95% UI 5.1-11.1). Boys had higher age-standardized incidence of childhood myocarditis and cardiomyopathy than girls [9.12, (95% UI 6.05-13.07) vs. 6.18, (95% UI 4.06-8.92)]. Childhood myocarditis and cardiomyopathy affected 121,259 (95% UI 80,467-173,790) boys and 77,216 (95% UI 50,684-111,535) girls in 2019. At the regional level, SDI changes in most areas showed no meaningful difference. In East Asia and high-income Asia Pacific, increased SDI was associated with decreased and increased incidence rate, respectively. In 2019, 11,755 (95% UI 9,611-14,509) children died from myocarditis and cardiomyopathy worldwide. Age-standardized mortality rate decreased significantly by 0.4% (95% UI 0.2-0.6)-0.5% (95% UI 0.4-0.6). Number of deaths from childhood myocarditis and cardiomyopathy in 2019 was highest in the <5-year-old group [7,442 (95% UI 5,834-9,699)]. Myocarditis and cardiomyopathy incidence in 10-14- and 15-19-year-olds is projected to increase by 2035. Conclusion: Global data on childhood myocarditis and cardiomyopathy from 1990 to 2019 showed a decreasing trend in incidence and mortality, and an increasing trend in older children, especially in high SDI regions.

Hypertension crisis as the first symptom of renovascular hypertension in children.

BACKGROUND: Renovascular hypertension (RVH) is one of the main causes of hypertensive crisis (HTN-C). It is characterized by acute onset and severe disease, and early diagnosis and treatment are difficult. The objective was to describe the characteristics of RVH and factors associated with RVH leading to HTN-C in children. At present, there are few clinical studies on RVH in children with large cases in China. METHODS: This study retrospectively analyzed the clinical data of inpatient children with RVH. Patients were divided into non-hypertensive crisis (non-HTN-C) group, and HTN-C group according to the first symptoms and blood pressure. Further, HTN-C were classified as hypertensive urgency (HTN-U) or hypertensive emergency (HTN-E). RESULTS: Fifty-four pediatric cases (41 boys and 13 girls) were included. 83.3% of the RVH cases were ≥ 6 years old. Three cases were classified into the non-HTN-C group. Of the 51 HTN-C cases, 18 cases were grouped as HTN-U and 33 as HTN-E. The HTN-U group were mainly asymptomatic (50.0%, 9/18) while the HTN-E group mainly presented with neurological symptoms (72.7%, 24/33). The number of unknown etiology children was 32 (59.2%). The top three known etiologies were Takayasu's arteritis (50.0%, 11/22), congenital renal dysplasia (27.3%, 6/22) and fibromuscular dysplasia (13.6%, 3/22). As for the target organ damage of RVH, patients had a higher prevalence of left ventricular hypertrophy (71.4%, 35/49) and retinopathy (77.8%, 21/27). CONCLUSIONS: Most RVH patients with HTN-C as the first symptoms, especially for males over 6 years old, should be assessed for RVH even if they were asymptomatic. Most asymptomatic patients with RVH already had target organ damage, and symptomatic patients even developed life-threatening complications. As preventive measures, routine monitoring of BP during children's physical examinations is advised.

Prediction of Immune Infiltration Diagnostic Gene Biomarkers in Kawasaki Disease.

Kawasaki disease (KD) is characterized by disorder of immune response with unknown etiology. Immune cells may be closely related to the onset of KD. The focus of this research was to evaluate the significance of the infiltration of immune cells for this disease and find possible diagnostic biomarkers for KD. The Gene Expression Omnibus database was utilized to retrieve two freely accessible gene expression patterns (GSE68004 and GSE18606 datasets) from human KD and control specimens. 114 KD, as well as 46 control specimens, were searched for obtaining differentially expressed genes (DEGs). Candidate biological markers were determined utilizing the support vector machine recursive feature elimination and the least absolute shrinkage and selection operator regression model analysis. To assess discriminating capacity, the area under the receiver operating characteristic curve (AUC) was computed. The GSE73461 dataset was utilized to observe the biomarkers' expression levels and diagnostic significance in KD (78 KD patients and 55 controls). CIBERSORT was employed to assess the composition profiles of the 22 subtypes of immune cell fraction in KD on the basis of combined cohorts. 37 genes were discovered. The DEGs identified were predominantly involved in arteriosclerotic cardiovascular disease, atherosclerosis, autoimmune disease of the urogenital tract, and bacterial infectious disease. Gene sets related to complement and coagulation cascades, Toll-like receptor signaling pathway, Fc gamma R-mediated phagocytosis, NOD-like receptor signaling pathway, and regulation of actin cytoskeleton underwent differential activation in KD as opposed to the controls. KD diagnostic biomarkers, including the alkaline phosphatase (ALPL), endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2 (EDEM2), and histone cluster 2 (HIST2H2BE), were discovered (AUC = 1.000) and verified utilizing the GSE73461 dataset (AUC = 1.000). Analyses of immune cell infiltration demonstrated that ALPL, EDEM2, and HIST2H2BE were linked to CD4 memory resting T cells, monocytes, M0 macrophages, CD8 T cells, neutrophils, and memory CD4 T cells. ALPL, EDEM2, and HIST2H2BE could be utilized as KD diagnostic indicators, and they can also deliver useful information for future research on the disease's incidence and molecular processes.

Duchenne Muscular Dystrophy With Low Acidic α-Glucosidase Activity: Two Case Reports and Literature Review.

Background: Pompe disease is usually considered in children with elevated creatine kinase (CK) levels and decreased acidic α-glucosidase (GAA) enzyme activity. However, there are exceptions, such as GAA pseudo deficiency alleles, which result in lower GAA enzyme activity but do not cause Pompe disease. Here, we report two cases presenting with high CK levels and low GAA activity who were ultimately diagnosed with Duchenne muscular dystrophy (DMD). Case Presentation: Case 1 patient was a 2-month-old boy who presented with an extremely high serum CK level (5,480∼11,880 U/L) and low GAA activity (2.72 nmol/1 h/mg). The whole-exome sequencing did not find the pathogenic GAA gene mutation, however, there was a DMD gene hemizygous variation (c. 7657C > T, p. Arg2553Ter) inherited from his mother, which was verified by the first-generation sequencing. Further genetic analysis of GAA identified two homozygous pseudo deficiency alleles (c.1726G > A, p. Gly576Ser and c.2065G > A, p. Glu689Lys), which were believed to induce the patient's low GAA activity. Therefore, the boy was diagnosed with DMD, although he had extremely low GAA activity. Case 2 patient was also a 2-month-old boy presenting with a significant increase in CK level (12,408∼24,828 U/L). His blood GAA activity (colorimetric method) was 9.02 nmol/1 h/mg. Similarly, his whole-exome sequencing did not find the pathogenic mutation of the GAA gene, but a DMD gene hemizygous variation (c.5571del, p. Lys1857AsnfsTer8), hence he was diagnosed with DMD as well. Regarding GAA activity, the case 2 patient was not as low as the case 1 patient, mainly because his two GAA pseudo deficiency alleles were heterozygous. Conclusion: Pompe disease is usually screened in infants with high CK levels. We should be aware that pseudo deficiency alleles can cause low GAA activities but not Pompe disease. Genetic tests would be helpful to distinguish cases with GAA pseudo deficiency alleles from patients with some muscular disorder diseases such as DMD.

Clinical Characteristics of Hospitalized Pediatric Patients With Hypertensive Crisis-A Retrospective, Single-Center Study in China.

Background: A hypertensive crisis is a medical emergency that causes acute damage to multiple organs. However, the etiology, clinical features, and prognosis of hypertensive crisis in Chinese children remain relatively unknown. The purpose of this study was to analyze the clinical characteristics of pediatric hypertensive crisis patients from a single center in China. Methods: We analyzed data from 70 children with hypertensive crisis between January, 2000, and January, 2022. The patients were divided into two groups: those diagnosed with a hypertensive emergency (n = 46) and those diagnosed with hypertensive urgency (n = 24). Baseline etiologies and risk factors were compared between the two groups. The following data were collected and analyzed: age, sex, weight, height, family history of hypertension, blood pressure, clinical manifestations of hypertensive crisis, underlying causes, biochemical indicators, and antihypertensive drugs. Results: The major symptoms of hypertensive crisis were headache (n = 31, 44.29%), followed by visual symptoms (n = 15, 21.43%), and dizziness (n = 13, 18.57%). Further analysis showed that the incidence of convulsions was significantly higher in patients with hypertensive emergency than those with hypertensive urgency (χ2 = 5.38, p = 0.02). The leading underlying causes were renal disease (n = 34, 48.57%), followed by vascular disease (n = 11, 15.71%), essential hypertension (n = 9, 12.86%), oncological disease (n = 9, 12.86%), central nervous system disease (n = 3, 4.29%), endocrine and metabolic diseases (n = 2, 2.86%), and other (one case with lead poisoning, one case with histiocytosis). End-organ damage occurred in 46 patients with hypertensive crisis, including retinal damage (n = 20, 43.48%), brain damage (n = 19, 41.30%), heart damage (n = 15, 32.61%), and renal damage (n = 3, 6.52%). Hypertensive crisis was most common among children aged 7-12 years. Among children aged 13-18 years, hypertensive urgency was more common than hypertensive emergency. The incidence of dyslipidemia, elevated serum creatinine, and elevated uric acid did not differ significantly between the two groups. Most patients with hypertensive crisis need combined antihypertensive therapy (n = 60, 85.71%). There were no cases of mortality. Conclusions: Hypertensive crisis is caused by secondary diseases, especially renal disease and vascular disease, in the majority of pediatric patients. Combination therapy with antihypertensive agents and treatment of secondary etiology results in a good prognosis.

Haploinsufficiency of A20 in a Chinese child caused by loss-of-function mutations in TNFAIP3: A case report and review of the literature.

Case Presentation: A 3-year-and-6-month-old child was reported to have recurrent high fever with generalized lymph node enlargement and significant elevation of inflammatory markers such as C-reactive protein and procalcitonin in tests. Later, whole exome sequencing determined that the child's disease was haploinsufficiency of A20 (HA20). Results: After immunosuppressive therapy, the child's symptoms improved significantly, and the inflammatory markers dropped to the normal range. Conclusion: Because of the characteristics of HA20, this disease is often underdiagnosed and misdiagnosed in clinical practice. By reporting this case of HA20 in a child, we hope to increase the awareness of this disease in the clinic.

Stent implantation in severe aortic coarctation in a pediatric patient with Turner syndrome: Case report and literature review.

Background: Turner syndrome is a rare systemic disease and a significant proportion of these patients experience aortic coarctation. Selection of optimal therapy for aortic coarctation in patients with Turner syndrome is difficult due to the pathologic change of the systemic vessel. Case presentation: We report one successful case of covered stent implantation for the treatment of severe native coarctation of the aorta in a 15-year-old patient with Turner syndrome weighing 36 kg. A covered stent was implanted in this patient. After the stent implantation, the peak systolic pressure gradient immediately decreased from 48 mmHg to 14 mmHg. The aortic diameter at the coarctation site increased from 3 mm to 10 mm after stenting. A femoral arterial complication occurred in this case, and we stabilized the situation finally. Results: During a follow-up of 3 years, no restenosis of aortic coarctation was observed and the patient no longer experienced hypertension. The dissection of the right femoral artery remained stable. Conclusion: A covered stent implantation for severe aortic coarctation in patients with Turner syndrome could be safe and effective. However, caution should be taken when using the technique to prevent complications.

Case Report: Talaromyces marneffei Infection in a Chinese Child With a Complex Heterozygous CARD9 Mutation.

Talaromyces marneffei (TM) infection is rarely seen in clinical practice, and its pathogenesis may be related to deficiency in antifungal immune function. Human caspase recruitment domain-containing protein 9 (CARD9) is a key molecule in fungal immune surveillance. There have been no previous case reports of TM infection in individuals with CARD9 gene mutations. Herein, we report the case of a 7-month-old Chinese boy who was admitted to our hospital with recurring cough and fever with a papular rash. A blood culture produced TM growth, which was confirmed by metagenomic next-generation sequencing. One of the patient's sisters had died of TM septicaemia at 9 months of age. Whole exome sequencing revealed that the patient had a complex heterozygous CARD9 gene mutation with a c.1118G>C p.R373P variation in exon 8 and a c.610C>T p.R204C variation in exon 4. Based on the culture results, voriconazole antifungal therapy was administered. On the third day of antifungal administration, his temperature dropped to within normal range, the rash gradually subsided, and the enlargement of his lymph nodes, liver, and spleen improved. Two months after discharge, he returned to the hospital for a follow-up examination. His general condition was good, and no specific abnormalities were detected. Oral voriconazole treatment was continued. Unexplained TM infection in HIV-negative individuals warrants investigation for immune deficiencies.

Sitosterolemia With Atherosclerosis in a Child: A Case Report.

Introduction: Sitosterolemia is a rare condition in children and is often misdiagnosed as familial hypercholesterolemia. Serious complications can result if not treated promptly and effectively. When pediatric patients are diagnosed with sitosterolemia, vascular, and cardiac studies are important to evaluate for the presence of atherosclerosis. Few cases of severe atherosclerotic heart disease in children with sitosterolemia have been reported, making this case worthy of presentation. Case Presentation: Here, we report a case of sitosterolemia in an 8-year-old child. The patient presented with severe hypercholesterolemia and xanthoma. He was diagnosed two and a half years prior with familial hypercholesterolemia because his father had elevated cholesterol levels. After conventional treatment, the patient was dissatisfied with lipid level control and visited our hospital for further management. Genetic tests of the patient and parents found mutations in intron 7 (NM 022436.2, c.904+1G>A) and intron 9 (NM 022436.2, C. 1324+1de1G) of ABCG5. The 7 intron mutation was from his mother, and the 9 intron mutation was from his father. The patient was diagnosed with sitosterolemia. Results: The child was treated with ezetimibe, a low plant sterol diet, and clopidogrel anticoagulant therapy. After 3 months of treatment, the blood lipid level was significantly lower. Conclusion: Genetic testing should be completed as soon as possible to avoid misdiagnosis in children with abnormally elevated hypercholesterolemia who have a family history of elevated cholesterol. In addition, clinicians should rule out great arterial lesions and be vigilant in evaluating patients for systemic arterial disease and atherosclerosis.

A prognostic model for melanoma patients on the basis of immune-related lncRNAs.

The prognosis of melanoma patients is highly variable due to multiple factors conditioning immune response and driving metastatic progression. In this study, we have correlated the expression of immune-related lncRNAs with patient survival, developed a prognostic model, and investigated the characteristics of immune response in the diverse groups. The gene expression profiles and prognostic information of 470 melanoma patients were downloaded from TCGA database. Significantly predictive lncRNAs were identified by multivariate Cox regression analyses, and a prognostic model based on these variables was constructed to predict survival. Kaplan-Meier curves were plotted to estimate overall survival. The predictive accuracy of the model was evaluated by the area under the ROC curve (AUC). Principal component analysis was used to observe the distribution of immune-related genes. CIBERSORT and ESTIMATE were used to evaluate the composition of immune cells and the immune microenvironment. Eight immune-related lncRNAs were determined to be prognostic by multivariate COX regression analysis. The patient scores were calculated and divided into high- and low-risk groups. The model could effectively predict the prognosis in patients of different stages. The AUC of the model is 0.784, which was significantly higher than that of the other variables. There were significant differences in the distribution of immune-related genes between two groups; the immune score and immune function enrichment score were higher in the low risk group.

Treatment Option for Abernethy Malformation-Two Cases Report and Review of the Literature.

Background: Abernethy malformation is a rare vascular anomaly of the portal venous system, which is also known as congenital portosystemic shunts (CPSS). The clinical manifestations of this anomaly can be serious, including hepatopulmonary syndrome(HPS), which can lead to significant hypoxemia and cyanosis. Case Presentation: This study reports two cases of patients with Abernethy Malformation. Case 1 was a 6-year-old boy whose blood oxygen saturation was 78%. Case 2 was a 6-year-old girl who had a history of open heart surgery and residual cardiac left to right shunt, whose blood oxygen saturation was 83%. These two children had unexplained cyanosis and were diagnosed with pulmonary arteriovenous fistula by contrast echocardiography with agitated saline. A selective retrograde catheter angiography confirmed the presence of a portosystemic shunt. Case 1 was a type I Abernethy malformation and did not receive any specific treatment and could only wait for liver transplantation. Case 2 was with type II Abernethy and underwent transcatheter closure of the CPSS. A 20mm-diameter, 14mm-long Vascular Plug (SHSMA Inc, Shanghai, China) was used to occlude the shunt. Results: In case 1, the boy developed deteriorating cyanosis and dyspnea on exertion. In case 2, the exercise tolerance of the patient improved after shunt closure. During a follow-up of 3 years, her blood oxygen saturation increased from 83 to 98%. Conclusion: The results indicate that children with unexplained cyanosis require special attention since these patients may have Abernethy malformation, and part of them could be treated by transcatheter occlusion with a good outcome. The key to treatment is how it is diagnosed and carefully assessed.

A Chromosomal Inversion of 46XX, inv (6) (p21.3p23) Connects to Congenital Heart Defects.

Congenital heart defects (CHDs) represent the most common human birth defects. Ventricular septal defect (VSD) is the most common subtype of CHDs. It has been shown that about 20-40% of VSDs are closely related to chromosomal aneuploidies or Mendelian diseases. In this study, we report a pedigree with VSD associated with a balanced paracentric inversion of chromosome 6, inv (6)(p21.3p23), a rarely reported CHD-associated chromosomal abnormality related to the fragile site at 6p23. We have found that the major clinical features of the proband include CHDs (ventricular septal defect, severe pulmonary hypertension, tricuspid regurgitation, and patent foramen ovale), severe pneumonia, and growth retardation. Our study reports a rare chromosomal abnormality connected to CHDs, which may represent a new genetic etiology for VSD.

Prognostic value of immune cell infiltration in bladder cancer: A gene expression-based study.

The present study aimed to analyse the relationship between tumour-infiltrating immune cells (TIICs) and the prognosis of bladder cancer (BC). In the present study, an established computational method (CIBERSORT) was used to analyse the gene expression profile of BC from 409 patients to infer the number of infiltrating immune cells among 22 immune cell subsets. The relationship between each cell type and overall survival (OS) was further analysed. Single-sample GSEA and ESTIMATE algorithms were performed to evaluate the composition of immune microenvironment in each immune cluster. A significant difference in immune cell infiltration between BC and bladder tissue was observed. Increased natural killer and CD8+ T cell infiltration was associated with longer OS, whereas a higher percentage of M0 macrophages among the total immune cells was associated with shorter OS. The number of M0 macrophages increased with increasing BC stage, whereas the percentage of activated memory CD4+ and CD8+ T cells decreased. Patients with BC were divided into three subgroups by hierarchical cluster analysis of immune cells, and each cluster was associated with distinct survival and immune characteristics. The data indicated differences in the cellular composition of TIICs in patients with BC. Moreover, these TIICs were shown to be potential drug targets and reliable prognostic indicators.

Beta Blocker Therapy for Congenital Hepatic Arteriovenous Fistula in Two Neonates.

Introduction: Hepatic arteriovenous fistula (HAVF) is an abnormal communication between the hepatic arteries and hepatic veins. This condition is treated mainly using interventional closure and surgery. However, these procedures are associated with many postoperative complications and high mortality. Propranolol and other beta blockers have been used widely and effectively to treat infantile hemangiomas. However, no reports describe the use of these drugs to treat congenital HAVF. Case Description:Here, we present two cases in which beta blocker therapy was used to treat congenital HAVF in neonates. In both cases, antenatal examinations revealed cardiac enlargement and hepatic space-occupying lesions. After birth, both patients rapidly presented with respiratory distress, cyanosis, and heart failure. Echocardiography suggested enlargement of the right heart, widening of the pulmonary artery, and severe pulmonary arterial hypertension, and hepatic examinations revealed HAVF. Results:After admission, the patients were treated with dopamine, milinone, and furosemide for heart failure. However, their conditions worsened, as indicated by nod-like breathing and cyanosis. Endotracheal intubation and ventilator-assisted breathing and a small dose of oral propranolol (1 mg/kg/d) were initiated. The patients' conditions improved, as indicated by decreases in levels of the N-terminal pro-hormone BNP, and the ventilators were removed. The propranolol dose was increased gradually to 2 mg/kg/d. After 2 weeks of propranolol treatment, the neonate in case 2 developed bronchospasm, which improved after propranolol treatment ended and metoprolol treatment was initiated. Liver imaging performed 8-9 months after beta blocker therapy suggested the disappearance of the arteriovenous fistulae in case 2, and close to disappearing of the arteriovenous fistulae in case 1. Conclusion:Propranolol and metoprolol can effectively treat HAVF in infants, an observation consistent with that found in earlier studies that have shown beta blockers are a valid medical treatment option for infantile hemangioma. However, future studies should explore the underlying potential mechanism.

A new therapy in Epstein-Barr virus-associated lymphoproliferative disease: a case report and a revision of the literature.

BACKGROUND: Systemic chronic active Epstein-Barr virus infection is an extremely rare childhood disease. Since chronic active Epstein-Barr virus infection can trigger the onset of Epstein-Barr virus-associated lymphoproliferative disease. The clinical manifestations of the disease vary according to the site of involvement; therefore, management may be challenging. Currently, there are no standardized guidelines for treating Chronic active Epstein-Barr virus infection effectively. CASE PRESENTATION: We report a case of chronic active Epstein-Barr virus infection in a 5-year-old Chinese boy with intestinal, vascular, and neurological involvement. At age of 2 years and 7 months old, he had hepatomegaly and been diagnosed with Epstein-Barr virus infection. After treatment, he showed some clinical improvement. At age of 3 years and 3 months old, he presented with recurrent fever and diarrhea. Then he received methylprednisolone for 1 year and his symptoms ameliorated. At the age of 5 years, his symptoms recurred and had gastrointestinal hemorrhage and developed polyuria, frequent convulsions and hyponatremia. He was transferred to our hospital for further management. He was unconscious on admission and was diagnosised Epstein-Barr virus-lymphoproliferative disorder, based on the results in situ hybridization of EBV-encoded miRNA in sigmoid colon. Three-dimensional CT angiography demonstrated an aneurysm in the right internal carotid artery. Abdominal CT showed dilatation of vessels in part of the intestinal wall. He was also diagnosised Epstein-Barr virus encephalitis based on the elevated Epstein-Barr virus antibody titers and presence of Epstein-Barr virus DNA in the Cerebrospinal Fluid. A repeated duodenal artery embolization and symptomatic therapy could not control the hemorrhage after admission. He subsequently received treatment with ganciclovir, glucocorticoid, thalidomide, and propranolol. Hemorrhage was controlled in 5 days; his symptoms improved. The fever did not recur and the CSF pressure was also normalized. A follow-up CT at 3 months after admission showed regression of the aneurysm in the right internal carotid artery and the vascular lesion in the duodenum. DISCUSSION AND CONCLUSIONS: A new treatment protocol including thalidomide and propranolol resulted in a marked improvement in his clinical symptoms, and shows promise as a novel and effective therapeutic approach for Chronic active Epstein-Barr virus infection-associated lymphoproliferative disorder.

Down Regulation of c-FLIPL Enhance PD-1 Blockade Efficacy in B16 Melanoma.

Immune checkpoint blockade of programmed cell death protein 1 (PD-1) had an impressive long-lasting effect in a portion of advanced-stage melanoma patients, however, this therapy failed to induce responses in several patients; how to increase the objective response rate is very important. Cellular FLICE-inhibitory protein (c-FLIP) could inhibit apoptosis directly at the death-inducing signaling complex of death receptors and is also considered to be the main cause of immune escape. The overexpression of c-FLIPL occurs frequently in melanoma and its expression is associated with the prognosis. We found that the level of c-FLIPL expression was associated with the PD-1 blockade response rate in melanoma patients. Thus, we performed this research to investigate how c-FLIPL regulates immunotherapy in melanoma. We demonstrate that down regulation of c-FLIPL enhances the PD-1 blockade efficacy in B16 melanoma tumor model. Down regulation of c-FLIPL could increase the tumor apoptosis and enhance the antitumor response of T cells in the lymphocyte tumor cells co-culture system. Moreover, knockdown of c-FLIPL could decrease the expression of PD-L1 and recruit more effector T cells in the tumor microenvironment. Our results may provide a new combined therapeutic target for further improving the efficacy of PD-1 blockade in melanoma.

Amiodarone-Related Pure Red Cell Aplastic Anemia and Hypothyroidism in a Child With Total Anomalous Pulmonary Venous Connection.

Introduction: Amiodarone is an effective anti-arrhythmic drug, but there are many clinical side effects that limit its application. There are no case reports of amiodarone-related pure red cell aplastic anemia (PRCA). Case Presentation: Here, we present a case of amiodarone-related PRCA and hypothyroidism in a 7-month-old boy. The patient had a total anomalous pulmonary venous connection (the cardiac type) and had undergone cardiac surgery at the age of 2 months. Eleven days after the operation, atrial tachycardia was observed. Amiodarone was administered orally (15 mg/kg.d), following which the arrhythmia was under control. Subsequently, the patient was prescribed amiodarone (5 mg/kg.d) and discharged. Regular medical consultations were not conducted as required. At 7 months of age (5 months after the operation), the patient returned to the hospital for re-examination. The electrocardiogram showed intermittent sinus bradycardia, occasional junctional escape beats, hemoglobin 7.9 g/DL, and thyroid function-TSH 9.660 uIU/mL. Results: Amiodarone was discontinued. Thyroxine was administered orally. Subsequently, the heart rate improved and TSH returned to normal levels. Nutritional therapy was recommended based on a diagnosis of nutrition-related anemia. A re-visit at 9 months of age showed that the weight was 6 kg, but the routine blood test indicated that hemoglobin was 5.9 g/DL with positive cell anemia and low reticulocyte count. Bone marrow cytology examination suggested PRCA. The hemoglobin level was gradually restored after treatment with prednisone. Conclusion: The use of amiodarone in small infants and young children and its side effects should be carefully monitored. The potential mechanism of amiodarone-related PRCA needs further study.