Early Radiographic Characteristics of the Lateral Talocalcaneal Angle and its Predictive Significance for Relapse in Patients With Idiopathic Clubfoot Treated With the Ponseti Method.

In order to evaluate the early radiographic characteristics of the lateral talocalcaneal (L-TC) angle in patients with idiopathic clubfoot (ICF) and to investigate its prognostic significance for relapse after initial treatment with the Ponseti method. We retrospectively included 151 patients (96 males and 55 females; 227 feet) with ICF treated at our Institution between January 2005 and December 2014. The age at initial treatment was less than 6 months, and radiographs were obtained within 3 months of the Achilles tenotomy (mean age: 2.3 months; range: 0.77-6.8). All patients were followed up for at least 7 years (range, 7-18). The participants' feet were classified into 3 groups: relapsed (Group A), not relapsed (Group B), and normal foot groups which consisted of healthy feet in patients with unilateral ICF (Group C). All angle measurements were expressed in degrees. Forty-seven ICF feet in 33 patients relapsed, while 180 feet in 118 patients did not, and the age at relapse was 5.92 ± 1.91 years. Seventy-five normal feet were included in Group C. The average L-TC angle in Group A and B patients was 33.57° ± 12.05° and 39.37° ± 12.55°, respectively, while Group C was 49.61° ± 9.11°. A significant difference was found among the 3 groups of patients (F = 31.48, p < .001). The L-TC angle cut-off value below which a recurrence could be predicted was 36.1° (sensitivity, 74.47%). The L-TC angle of ICF patients treated using the Ponseti method were reduced compared to normal feet. An L-TC angle of <36.1° has relative value in predicting ICF relapse.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

Epigenetic Insights Into Necrotizing Enterocolitis: Unraveling Methylation-Regulated Biomarkers.

Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. This study aimed to identify novel methylation-regulated biomarkers in NEC intestinal tissue through multiomics analysis. We analyzed DNA methylation and transcriptome datasets from ileum and colon tissues of patients with NEC. We identify methylation-related differential genes (MrDEGs) based on the rule that the degree of methylation in the promoter region is inversely proportional to RNA transcription. These MrDEGs included ADAP1, GUCA2A, BCL2L14, FUT3, MISP, USH1C, ITGA3, UNC93A and IL22RA1. Single-cell data revealed that MrDEGs were mainly located in the intestinal epithelial part of intestinal tissue. These MrDEGs were verified through Target gene bisulfite sequencing and RT-qPCR. We successfully identified and verified the ADAP1, GUCA2A, IL22RA1 and MISP, primarily expressed in intestinal epithelial villus cells through single-cell data. Through single-gene gene set enrichment analysis, we found that these genes participate mainly in the pathological process of T-cell differentiation and the suppression of intestinal inflammation in NEC. This study enhances our understanding of the pathogenesis of NEC and may promote the development of new precision medicine methods for NEC prediction and diagnosis.

CD14 facilitates perinatal human cytomegalovirus infection in biliary epithelial cells via CD55.

Background & Aims: A high human cytomegalovirus (HCMV) infection rate accompanied by an increased level of bile duct damage is observed in the perinatal period. The possible mechanism was investigated. Methods: A total of 1,120 HCMV-positive and 9,297 HCMV-negative children were recruited, and depending on age, their liver biochemistry profile was compared. Fetal and infant biliary epithelial cells (F-BECs and I-BECs, respectively) were infected with HCMV, and the differences in cells were revealed by proteomic analysis. Protein-protein interactions were examined by coimmunoprecipitation and mass spectrometry analyses. A murine cytomegalovirus (MCMV) infection model was established to assess treatment effects. Results: Perinatal HCMV infection significantly increased the level of bile duct damage. Neonatal BALB/c mice inoculated with MCMV showed obvious inflammation in the portal area with an abnormal bile duct structure. Proteomics analysis showed higher CD14 expression in F-BECs than in I-BECs. CD14 siRNA administration hindered HCMV infection, and CD14-knockout mice showed lower MCMV-induced bile duct damage. HCMV infection upregulated CD55 and poly ADP-ribose polymerase-1 (PARP-1) expression in F-BECs. Coimmunoprecipitation and mass spectrometry analyses revealed formation of the CD14-CD55 complex. siRNA-mediated inhibition of CD55 expression reduced sCD14-promoted HCMV replication in F-BECs. In MCMV-infected mice, anti-mouse CD14 antibody and PARP-1 inhibitor treatment diminished cell death, ameliorated bile duct damage, and reduced mortality. Conclusions: CD14 facilitates perinatal HCMV infection in BECs via CD55, and PARP-1-mediated cell death was detected in perinatal cytomegalovirus-infected BECs. These results provide new insight into the treatment of perinatal HCMV infection with bile duct damage. Impact and implications: Perinatal human cytomegalovirus (HCMV) infection is associated with bile duct damage, but the underlying mechanism is still unknown. We discovered that CD14 expression is increased in biliary epithelial cells during perinatal HCMV infection and facilitates viral entry through CD55. We also detected PARP-1-mediated cell death in perinatal HCMV-infected biliary epithelial cells. We showed that blocking CD14 or inhibiting PARP-1 reduced bile duct damage and mortality in a mouse model of murine cytomegalovirus infection. Our findings provide a new insight into therapeutic strategies for perinatal HCMV infection.

Proteomics Defines Plasma Biomarkers for the Early Diagnosis of Biliary Atresia.

Early diagnosis of biliary atresia (BA) is crucial for improving the chances of survival and preserving the liver function of pediatric patients with BA. Herein, we performed proteomics analysis using data-independent acquisition (DIA) and parallel reaction monitoring (PRM) to explore potential biomarkers for the early diagnosis of BA compared to other non-BA jaundice cases. Consequently, we detected and validated differential protein expression in the plasma of patients with BA compared to the plasma of patients with intrahepatic cholestasis. Bioinformatics analysis revealed the enriched biological processes characteristic of BA by identifying the differential expression of specific proteins. Signaling pathway analysis revealed changes in the expression levels of proteins associated with an alteration in immunoglobulin levels, which is indicative of immune dysfunction in BA. The combination of polymeric immunoglobulin receptor expression and immunoglobulin lambda variable chain (IGL c2225_light_IGLV1-47_IGLJ2), as revealed via machine learning, provided a useful early diagnostic model for BA, with a sensitivity of 0.8, specificity of 1, accuracy of 0.89, and area under the curve value of 0.944. Thus, our study identified a possible effective plasma biomarker for the early diagnosis of BA and could help elucidate the underlying mechanisms of BA.

The Born in Guangzhou Cohort Study enables generational genetic discoveries.

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.

Prognostic Value of Serum Cholinesterase Levels for In-Hospital Mortality among Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Cholinesterase (ChE) is associated with the pathogenesis of chronic obstructive pulmonary disease (COPD), including chronic airway inflammation and oxidation/antioxidant imbalance. However, the relationship between serum ChE levels and survival outcomes of patients hospitalized with acute exacerbations of COPD (AECOPD) is unknown. In this retrospective single-center study, we investigated the ability of the serum ChE level to predict in-hospital death in patients hospitalized with AECOPD. The clinicopathological data, including serum ChE levels as well as clinical and biochemical indicators were extracted for 477 patients from the hospital records and analyzed. Our results demonstrated that AECOPD patients with lower serum ChE levels were associated with increased mortality, frequent hospitalization due to acute exacerbations (AE) in the past year, and longer hospital stay. The optimal cutoff value for the serum ChE level was 4323 U/L. The area under the ROC curve (AUC) values for predicting in-hospital mortality based on the serum ChE level was 0.79 (95% confidence interval (CI), 0.72-0.85). Multivariate logistic regression analysis demonstrated that serum ChE level ≤ 4323 U/L (odds ratio (OR) 9.09, 95% CI 3.43-28.3, p < 0.001), age-adjusted Charlson comorbidity index (aCCI), and the number of hospitalizations due to AE in the past year were independent risk factors for predicting the in-hospital mortality of AECOPD patients. In conclusion, our study demonstrated that low serum ChE levels were associated with significantly higher in-hospital mortality rates of patients hospitalized with AECOPD. Therefore, serum ChE level is a promising prognostic predictor of hospitalized AECOPD patients.