Hatfieldgibson5241
High-grade neuroendocrine tumors (NETs) of the lung consist of small-cell lung cancer (SCLC) and large-cell neuroendocrine carcinoma (LCNEC). Both exhibit aggressive malignancy with poor prognosis. The transformation of lung adenocarcinoma (ADC) to SCLC or LCNEC also contributes to acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). Despite initially being responsive to chemotherapy, high-grade NET patients inevitably develop drug resistance; thus, novel therapeutic targets are urgently needed for these patients. Our study reported that VGF (nerve growth factor inducible), a factor mainly expressed in neurons during neural development, is highly expressed in SCLC and LCNEC as well as in a subset of ADCs, whereas targeting VGF attenuates cancer cell growth and tumor formation. High VGF expression was associated with advanced stage SCLC and predicted poor prognosis in lung ADC. In addition, EGFR-TKI selection enriched VGF expression in TKI-resistant ADC under epigenetic control. The VGF locus possessed the HDAC1 binding site, and treatment of ADC cells with the HDAC1 inhibitor induced VGF expression. High VGF expression was associated with chemoresistance, and silencing VGF induced BMF and BCL2L11 expression and rendered lung cancer cells sensitive to chemotherapy drugs. These findings suggested the potential of VGF as a prognostic factor and therapeutic target in lung cancers with neuroendocrine feature.Chest CT-scan (CT) exceeds chest X-ray (CXR) to diagnose community-acquired pneumonia (CAP) but actual use and results remain unclear. We examine whether CT performed at ED visit improved ED diagnosis of CAP as compared to a final diagnosis of CAP at hospital discharge (gold standard diagnosis for the study), and how it impacts relevant clinical outcomes. This retrospective monocenter observational study was based on the analysis of the hospital database. Patients with a diagnosis of CAP in the ED (ICD-10 codes J110, J111, from J12- to J18-, J440, J690, U0710, and U0711) were included. We compared ED patients who were diagnosed with CAP using CXR and CT. We measured diagnostic consistency, duration of ED visit, percentage of CXR and CT during hospital stay, hospital length-of-stay, ICU admission, and in-hospital mortality. Multivariate analysis was adjusted for CRB65 score by multiple logistic regression analysis for binary outcomes and by multivariate analysis of variance for continuous outcomes. We included 994 ED patients with an initial diagnosis of CAP (751 receiving CXR, 243 receiving CT). CT prescription in the ED increased over time ( P less then 0.001). In patients admitted after ED, CT improved diagnosis consistency for CAP [88.2% vs. 80.9%; difference 7.3% (95% confidence interval 1.2-13.3%)] with a trend for lower hospital length-of-stay [10.2 vs. 12.2 days; difference -2.0 (95% confidence interval -3.9 to -0.1)], but not ICU admission ( P = 0.09) and in-hospital mortality ( P = 0.056). Diagnosis of patients admitted with CAP improved when CT was obtained at ED visit. These results should be reproduced at a larger scale to test whether early CT conserves healthcare resources.Fatty acids (FAs) have diverse functions in cellular activities. The intracellular distribution of FAs is critical for their functions. Imaging of FAs by time-of-flight secondary ion mass spectrometry (TOF-SIMS) has been achieved. However, TOF-SIMS images of FAs so far do not have subcellular distribution due to inadequate sample preparation methods. In this study, we developed a chemical fixation method using glutaraldehyde (GA) with uranyl acetate (UA), which preserved cellular structure and intracellular FA distribution well. Combining GA+UA fixation with sputtering-based methods and unroofing-based methods, respectively, we successfully imaged intracellular lipids with the subcellular distribution.Leukodystrophy (LD) is a group of genetic heterogeneous diseases characterized by primary abnormalities in glial cells and myelin sheath, and it is a common nervous system disease in children and has significant genotype-phenotype correlation. In recent years, the improvement in high-throughput sequencing has changed the diagnostic and therapeutic mode of LD, and elaborative phenotype analysis, such as the collection of natural history and multimodal neuroimaging evaluation during development, also provides important information for subsequent genetic diagnosis. This article reviews LD from the perspective of clinical genetics, in order to improve the awareness of this disease among pediatricians in China.A boy, aged 11 years, was admitted due to intermittent fever for 15 days, cough for 10 days, and "hemoptysis" for 7 days. The boy had fever and cough with left neck pain 15 days ago, and antibiotic treatment was effective. During the course of disease, the boy developed massive "hemoptysis" which caused shock. selleck inhibitor Fiberoptic bronchoscopy revealed a left pyriform sinus fistula with continuous bleeding. In combination with neck and vascular imaging examination results, the boy was diagnosed with internal jugular vein injury and thrombosis due to congenital pyriform sinus fistula infection and neck abscess. The boy was improved after treatment with temperature-controlled radiofrequency ablation for the closure of pyriform sinus fistula, and no recurrence was observed during the follow-up for one year and six months. No reports of massive hemorrhage and shock due to pyriform sinus fistula infection were found in the searched literature, and this article summarizes the clinical features, diagnosis, and treatment of this boy, so as to provide a reference for the early diagnosis of such disease and the prevention and treatment of its complications.A boy, aged 5 years, attended the hospital due to progressive psychomotor regression for 2.5 years. Motor function regression was the main manifestation in the early stage, and brain MRI and whole-exome sequencing (WES) of the family showed no abnormalities. After the age of 4 years and 9 months, the boy developed cognitive function regression, and brain MRI showed cerebellar atrophy. The reanalysis of WES results revealed a compound heterozygous mutation, [NM_000520, c.784C>T(p.His262Tyr]), c.1412C>T(p.Pro471Leu)], in the HEXA gene. The enzyme activity detection showed a significant reduction in the level of β-hexosaminidase encoded by this gene. The boy was diagnosed with juvenile Tay-Sachs disease (TSD). TSD has strong clinical heterogeneity, and cerebellar atrophy may be an important clue for the diagnosis of juvenile TSD. The reanalysis of genetic data when appropriate based on disease evolution may improve the positive rate of WES.
To examine the expression of serum thyroglobulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) in children with immune thrombocytopenia (ITP).
A total of 120 children with ITP who were admitted from October 2019 to October 2021 were enrolled as the ITP group. A total of 60 children without ITP were enrolled as the non-ITP group. According to the clinical classification of ITP, the children in the ITP group were further divided into a newly diagnosed ITP group, a persistent ITP group, and a chronic ITP group. The clinical data were compared between the ITP group and the non-ITP group and between the children with different clinical classifications of ITP. The expression levels of serum TGAb and TPOAb in children with ITP were measured and their association with the clinical classification of ITP was analyzed.
Compared with the non-ITP group, the ITP group had significantly lower levels of CD3
, CD4
, and platelet count (PLT) and significantly higher levels of CD8
, TGAb, and TPOAb (
<0.05). The children with chronic ITP had significantly lower levels of CD3
, CD4
, and PLT and significantly higher levels of CD8
, TGAb, and TPOAb than those with newly diagnosed ITP or persistent ITP (
<0.05). The logistic regression analysis showed that CD3
, CD4
, CD8
, TGAb, and TPOAb were the influencing factors for chronic ITP (
<0.05). A decision curve was plotted, and the results showed that TGAb combined with TPOAb within the high-risk threshold range of 0.0-1.0 had a net benefit rate of >0 in evaluating the clinical classification of ITP in children.
TGAb and TPOAb are abnormally expressed in children with ITP and are associated with the clinical classification of ITP in children.
TGAb and TPOAb are abnormally expressed in children with ITP and are associated with the clinical classification of ITP in children.
To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD.
The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (
=284) and a non-liver damage group (
=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD.
Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (
< liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.
To study the metabolic mechanism of neonatal sepsis at different stages by analyzing the metabolic pathways involving the serum metabolites with significant differences in neonates with sepsis at different time points after admission.
A total of 20 neonates with sepsis who were hospitalized in the Department of Neonatology, Hunan Provincial People's Hospital, from January 1, 2019 to January 1, 2020 were enrolled as the sepsis group. Venous blood samples were collected on days 1, 4, and 7 after admission. Ten healthy neonates who underwent physical examination during the same period were enrolled as the control group. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for the metabonomic analysis of serum samples to investigate the change in metabolomics in neonates with sepsis at different time points.
On day 1 after admission, the differentially expressed serum metabolites between the sepsis and control groups were mainly involved in the biosynthesis of terpenoid skeleton. For the sepsis group, the differentially expressed serum metabolites between days 1 and 4 after admission were mainly involved in pyruvate metabolism, and those between days 4 and 7 after admission were mainly involved in the metabolism of cysteine and methionine. The differentially expressed serum metabolites between days 1 and 7 after admission were mainly involved in ascorbic acid metabolism.
The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.
The metabolic mechanism of serum metabolites varies at different stages in neonates with sepsis and is mainly associated with terpenoid skeleton biosynthesis, pyruvate metabolism, cysteine/methionine metabolism, and ascorbic acid metabolism.
