The role of mir96 in predicting CTC status and prognostic evaluation in gastric cancer patients.

In this study, 20 patients clinically diagnosed with advanced gastric cancer were selected as subjects. Circulating tumor cells (CTCs) in the peripheral blood of gastric cancer patients were detected and counted by collecting peripheral blood samples at Ningbo No. 2 Hospital and using the Cell Rich TM system combined with a negative enrichment strategy. In addition, routine pathological examination and immunohistochemical staining were performed on surgical specimens, including HER2, EBER, E-cadherin, and vimentin indicators. These indicators were correlated and analyzed with CTC counts and routine clinical tests. At the same time, miRNA groups were performed to explore the miRNAs with or without correlation with CTC and to try to construct a predictive model for CTC status. Tumor tissue from patients whose CTC counts did not match the results of the miRNA prediction model was subjected to second-generation gene sequencing to analyze indicators such as tumor heterogeneity and immune microenvironment. The results of the study showed that CTCs were detected in the peripheral blood of 50% (10/20) of gastric cancer patients using the Cell Rich TM system, serum fibrinogen was negatively correlated with CTC counts, whereas TNM staging elements, HER2 receptor and p53 were not correlated with CTC counts. miRNA assays showed that the expression levels of miR218, miR1207, miR96, miR409, miR149, miR148a, miR155, miR370 and miR223 were significantly different between the two groups of CTC≥2 and CTC<2. Among them, miR-96 showed good efficacy as an indicator for predicting CTC status and assisting in determining the prognosis of gastric cancer. In conclusion, the present study demonstrated that the Cell Rich TM system combined with the negative enrichment strategy can effectively detect CTCs in the peripheral blood of gastric cancer patients and that the expression of miR-96 can be used as an effective indicator to predict CTC status and assist in determining the prognosis of gastric cancer. These findings have important implications for the diagnosis and treatment of gastric cancer and provide new clues for the further study of the tumor immune microenvironment and tumor heterogeneity.

Genome-Wide Analysis of R2R3-MYB Genes and Functional Characterization of SmMYB75 in Eggplant Fruit Implications for Crop Improvement and Nutritional Enhancement.

R2R3-MYB represents a substantial gene family that plays diverse roles in plant development. In this study, 102 SmR2R3-MYB genes were identified from eggplant fruit and classified into 31 subfamilies. Analysis indicated that segmental duplication events played a pivotal role in the expansion of the SmR2R3-MYB gene family. Furthermore, the prediction of miRNAs targeting SmR2R3-MYB genes revealed that 60 SmR2R3-MYBs are targeted by 57 miRNAs, with specific miRNAs displaying varying numbers of target genes, providing valuable insights into the regulatory functions of miRNAs in plant growth, development, and responses to stress conditions. Through expression profile analysis under various treatment conditions, including low temperature (4 °C), plant hormone (ABA, Abscisic acid), and drought stress (PEG, Polyethylene glycol), diverse and complex regulatory mechanisms governing SmR2R3-MYB gene expression were elucidated. Notably, EGP21875.1 and EGP21874.1 exhibited upregulation in expression under all treatment conditions. Transcriptome and metabolome analyses demonstrated that, apart from anthocyanins (delphinidin-3-O-glucoside, cyanidin-3-O-(6-O-p-coumaroyl)-glucoside, and malvidin-3-O-(6-O-p-coumaroyl)-glucoside), overexpression of SmMYB75 could also elevate the content of various beneficial compounds, such as flavonoids, phenolic acids, and terpenes, in eggplant pulp. This comprehensive study enhances our understanding of SmR2R3-MYB gene functions and provides a strong basis for further research on their roles in regulating anthocyanin synthesis and improving eggplant fruit quality.

Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD.

BACKGROUND: Alveolar macrophages (AMs) and AM-produced matrix metalloprotease (MMP)-12 are known to play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The apoptosis inhibitor of the macrophages (AIM)/CD5 molecule-like (CD5L) is a multifunctional protein secreted by the macrophages that mainly exists in the blood in a combined form with the immunoglobulin (Ig)M pentamer. Although AIM has both facilitative and suppressive roles in various diseases, its role in COPD remains unclear. METHODS: We investigated the role of AIM in COPD pathogenesis using porcine pancreas elastase (PPE)-induced and cigarette smoke-induced emphysema mouse models and an in vitro model using AMs. We also analyzed the differences in the blood AIM/IgM ratio among nonsmokers, healthy smokers, and patients with COPD and investigated the association between the blood AIM/IgM ratio and COPD exacerbations and mortality in patients with COPD. RESULTS: Emphysema formation, inflammation, and cell death in the lungs were attenuated in AIM-/- mice compared with wild-type (WT) mice in both PPE- and cigarette smoke-induced emphysema models. The PPE-induced increase in MMP-12 was attenuated in AIM-/- mice at both the mRNA and protein levels. According to in vitro experiments using AMs stimulated with cigarette smoke extract, the MMP-12 level was decreased in AIM-/- mice compared with WT mice. This decrease was reversed by the addition of recombinant AIM. Furthermore, an analysis of clinical samples showed that patients with COPD had a higher blood AIM/IgM ratio than healthy smokers. Additionally, the blood AIM/IgM ratio was positively associated with disease severity in patients with COPD. A higher AIM/IgM ratio was also associated with a shorter time to the first COPD exacerbation and higher all-cause and respiratory mortality. CONCLUSIONS: AIM facilitates the development of COPD by upregulating MMP-12. Additionally, a higher blood AIM/IgM ratio was associated with poor prognosis in patients with COPD. TRIAL REGISTRATION: This clinical study, which included nonsmokers, healthy smokers, and smokers with COPD, was approved by the Ethics Committee of the Hokkaido University Hospital (012-0075, date of registration: September 5, 2012). The Hokkaido COPD cohort study was approved by the Ethics Committee of the Hokkaido University School of Medicine (med02-001, date of registration: December 25, 2002).

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

Comparative transcriptomic analysis of early fruit development in eggplant (Solanum melongena L.) and functional characterization of SmOVATE5.

KEY MESSAGE: Comparative transcriptome analysis of early fruits of long and round eggplants, SmOVATE5, is involved in regulating fruit development. Eggplant, a solanaceous crop that has undergone a long period of domestication, is one of the most important vegetables worldwide. The shape of its fruit is an important agronomic trait and consumers in different regions have different preferences. However, a limited understanding of the molecular mechanisms regulating fruit development and shape has hindered eggplant breeding. In this study, we performed morphological observations and transcriptome analysis of long- and round-fruited eggplant genotypes to understand the molecular regulation during the early development of different fruit shapes. Morphological studies revealed that the two varieties already exhibited distinctly different phenotypes at the initial stage of fruit development before flowering, with rapid fruit enlargement beginning on the sixth day after flowering. Comparative transcriptome analysis identified phytohormone-related genes that were significantly upregulated on the day of flowering, indicating they may be involved in regulating the initial stages of fruit development. Notably, SmARF1 showed a sustained upregulation pattern in both varieties, suggesting that it may promote eggplant fruit growth. In addition, several differentially expressed genes of the SUN, YABBY, and OVATE families are potentially involved in the regulation of fruit development or fruit shape. We demonstrated that the SmOVATE5 gene has a negative regulatory function suppressing plant growth and development. In conclusion, this study provides new insights into the molecular regulatory mechanisms of eggplant fruit development, and the genes identified may provide valuable references for different fruit shape breeding programs.

Structural features on quantitative chest computed tomography of patients with maximal mid-expiratory flow impairment in a normal lung function population.

BACKGROUND: Maximal mid-expiratory flow (MMEF) is an earlier predictor of chronic obstructive pulmonary disease (COPD) development than forced expiratory volume in 1 s (FEV1). Changes of lung structure in patients with MMEF impairment only is still not clear. Therefore, this study aimed to investigate the structural features of patients with decreased MMEF by quantitative computed tomography (QCT) and develop a predictive model for predicting patients with reduced MMEF in normal lung function population. METHODS: In this study, 131 patients with normal spirometry results and available volumetric chest CT images were enrolled and divided into the reduced MMEF group (FEV1/forced expiratory vital capacity (FEV1/FVC) > 0.7, FEV1% predictive values (FEV1%pred) > 80%, MMEF%pred < 80%, n = 52) and the normal MMEF group (FEV1/FVC > 0.7, FEV1%pred > 80%, MMEF%pred ≥ 80%, n = 79). The emphysema, small airway disease and medium-size airway parameters were measured by a commercial software. The differences were investigated in clinical features, spirometrical parameters and QCT parameters between the two groups. A nomogram model was constructed based on the results of the multivariable logistic regression model. Spearman's correlation coefficients were calculated between QCT measurements and spirometrical parameters. RESULTS: There were more males in reduced MMEF group than normal group (P < 0.05). Lung parenchyma parameter (PRMEmph) and airway-related parameters (functional small airway disease (PRMfSAD), luminal area of fifth- and sixth- generation airway (LA5, LA6) were significantly different between the reduced MMEF group and the normal group (20.2 ± 17.4 vs 9.4 ± 6.7, 3.4 ± 3.5 vs 1.9 ± 2.0, 12.2 ± 2.5 vs 13.7 ± 3.4, 7.7 ± 2.4 vs 8.9 ± 2.8, respectively, all P < 0.01). After multivariable logistical regression, only sex (odds ratio [OR]: 2.777; 95% confidence interval [CI]:1.123-3.867), PRMfSAD (OR:1.102, 95%CI:1.045-1.162) and LA6 (OR:0.650, 95%CI:0.528-0.799) had significant differences between the two groups (P < 0.05) and a model incorporating with the three indicators was constructed (area under curve, 0.836). Correlation analysis showed MMEF%pred had mild to moderate correlation with airway-related measurements. CONCLUSION: In normal lung function population, patients with reduced MMEF have potential medium-size and small airway changes, and MMEF%pred is significantly associated with airway-related CT parameters. The nomogram incorporating with sex, PRMfSAD and LA6 has good predictive value and offers more objective evidences in a group with reduced MMEF.

Fabrication and Investigation of the Microwave Absorption of Nonwovens Modified by Carbon Nanotubes and Graphene Flakes.

This study aims to investigate the influences of carbon nanotubes (CNTs) and graphene flakes (GFs) on the microwave absorption performance of nonwovens. Nonwovens were modified with CNTs and GFs through an impregnation method, creating a series of absorption samples with different carbon nanomaterial contents. Then the absorption performance of the samples was tested on both sides in the X-band (8.2~12.4 GHz) and the Ku-band (12~18 GHz) using the arch method. The experimental results showed that the absorption performance of GF-impregnated nonwovens was superior to that of CNT-impregnated nonwovens, and the overall absorption performance in the Ku-band was better than in the X-band. At a CNT content of 5 wt.%, the reflection loss of the impregnated nonwovens on the backside reached a minimum of -14.06 dB and remained below -10 dB in the 17.42~17.88 GHz frequency range. The sample fabricated with 4 wt.% GFs in the impregnation solution exhibited the best absorption performance, with minimum reflection losses of -15.33 dB and -33.18 GHz in the X-band and Ku-band, respectively. When the GFs were at 3 wt.%, the absorption bandwidth below -10 dB reached 4.16 GHz. In contrast to CNT-impregnated nonwovens, the frontside of GF-impregnated nonwovens demonstrated better absorption performance in the Ku-band. The results of this work provide experimental data support for the fabrication and application of microwave absorption materials.

Subtyping preserved ratio impaired spirometry (PRISm) by using quantitative HRCT imaging characteristics.

BACKGROUND: Preserved Ratio Impaired Spirometry (PRISm) is defined as FEV1/FVC ≥ 70% and FEV1 < 80%pred by pulmonary function test (PFT). It has highly prevalence and is associated with increased respiratory symptoms, systemic inflammation, and mortality. However, there are few radiological studies related to PRISm. The purpose of this study was to investigate the quantitative high-resolution computed tomography (HRCT) characteristics of PRISm and to evaluate the correlation between quantitative HRCT parameters and pulmonary function parameters, with the goal of establishing a nomogram model for predicting PRISm based on quantitative HRCT. METHODS: A prospective and continuous study was performed in 488 respiratory outpatients from February 2020 to February 2021. All patients underwent both deep inspiratory and expiratory CT examinations, and received pulmonary function test (PFT) within 1 month. According to the exclusion criteria and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification standard, 94 cases of normal pulmonary function, 51 cases of PRISm and 48 cases of mild to moderate chronic obstructive lung disease (COPD) were included in the study. The lung parenchyma, parametric response mapping (PRM), airway and vessel parameters were measured by automatic segmentation software (Aview). One-way analysis of variance (ANOVA) was used to compare the differences in clinical features, pulmonary function parameters and quantitative CT parameters. Spearman rank correlation analysis was used to evaluate the correlation between CT quantitative index and pulmonary function parameters. The predictors were obtained by binary logistics regression analysis respectively in normal and PRISm as well as PRISm and mild to moderate COPD, and the nomogram model was established. RESULTS: There were significant differences in pulmonary function parameters among the three groups (P < 0.001). The differences in pulmonary parenchyma parameters such as emphysema index (EI), pixel indices-1 (PI-1) and PI-15 were mainly between mild to moderate COPD and the other two groups. The differences of airway parameters and pulmonary vascular parameters were mainly between normal and the other two groups, but were not found between PRISm and mild to moderate COPD. Especially there were significant differences in mean lung density (MLD) and the percent of normal in PRM (PRMNormal) among the three groups. Most of the pulmonary quantitative CT parameters had mild to moderate correlation with pulmonary function parameters. The predictors of the nomogram model using binary logistics regression analysis to distinguish normal from PRISm were smoking, MLD, the percent of functional small airways disease (fSAD) in PRM (PRMfSAD) and Lumen area. It had a good goodness of fit (χ2 = 0.31, P < 0.001) with the area under curve (AUC) value of 0.786. The predictor of distinguishing PRISm from mild to moderate COPD were PRMEmph (P < 0.001, AUC = 0.852). CONCLUSIONS: PRISm was significantly different from subjects with normal pulmonary function in small airway and vessel lesions, which was more inclined to mild to moderate COPD, but there was no increase in pulmonary parenchymal attenuation. The nomogram based on quantitative HRCT parameters has good predictive value and provide more objective evidence for the early screening of PRISm.

Extrarenal Wilms tumor with hypertension and dilated cardiomyopathy in an infant: A report of an unusual case.

While Wilms tumors are the most frequently detected kidney cancer type in children, extrarenal Wilms tumors (ERWTs) remain rare. This report is the first to describe hypertension and dilated cardiomyopathy in a patient with an ERWT. A 6-month-old male infant presented with an abdominal mass and paroxysmal hypertension; echocardiography revealed dilated cardiomyopathy with an ejection fraction of 34%, as well as substantially increased plasma renin activity. Pathology yielded a definitive diagnosis of ERWT. Cardiac function and blood pressure gradually returned to normal after tumorectomy. The early diagnosis of such a tumor together with efficient oncologic treatment are vital to optimal patient outcomes.

Comparative genomic investigation of TCP gene family in eggplant (Solanum melongena L.) and expression analysis under divergent treatments.

KEY MESSAGE: The putative TCP genes and their responses to abiotic stress in eggplant were comprehensively characterized, and SmTCP genes (Smechr0202855.1 and Smechr0602431.1) may be involved in anthocyanin synthesis. The Teosinte branched1/Cycloidea/Proliferating cell factors (TCPs), a family of plant-specific transcription factors, plays paramount roles in a plethora of developmental and physiological processes. We here systematically characterized putative TCP genes and their response to abiotic stress in eggplant. In total, 30 SmTCP genes were categorized into two subfamilies based on the classical TCP conserved domains. Chromosomal location analysis illustrated the random distribution of putative SmTCP genes along 12 eggplant chromosomes. Cis-acting elements and miRNA target prediction suggested that versatile and complicated regulatory mechanisms that control SmTCPs gene expression, and 3 miRNAs (miR319a, miR319b, and miR319c-3p) might act as major regulators targeting SmTCPs. Tissue expression profiles indicated divergent spatiotemporal expression patterns of SmTCPs. qRT-PCR assays demonstrated different expression profiles of SmTCP under 4 °C, drought and ABA treatment conditions, suggesting the possible participation of SmTCP genes in multiple signaling pathways. Furthermore, RNA-seq data of eggplant anthocyanin synthesis coupled with yeast one-hybrid and dual-luciferase assays suggested the involvement of SmTCP genes (Smechr0202855.1 and Smechr0602431.1) in the mediation of anthocyanin synthesis. Our study will facilitate further investigation on the putative functional characterization of eggplant TCP genes and lay a solid foundation for the in-depth study of the involvement of SmTCP genes in the regulation of anthocyanin synthesis.

A light-responsive transcription factor SmMYB35 enhances anthocyanin biosynthesis in eggplant (Solanum melongena L.).

MAIN CONCLUSION: SmMYB35, a light-responsive R2R3-MYB transcription factor, positively regulates anthocyanin biosynthesis in eggplant by binding to the promoters of SmCHS, SmF3H, SmDFR, and SmANS and enhancing their activities. In addition, SmMYB35 interacts with SmTT8 and SmTTG1 to form a MBW complex, thereby enhancing anthocyanin biosynthesis. Eggplant is a vegetable rich in anthocyanins. SmMYB35, a light-responsive R2R3-MYB transcription factor, was isolated from eggplant and investigated for its biological functions. The results suggested that the expression of SmMYB35 was regulated by SmHY5 through directly binding to G-box in the promoter region, and the overexpression of SmMYB35 could increase the anthocyanin content in the stems and petals of the transgenic eggplants. SmMYB35 could also bind to the promoters of SmCHS, SmF3H, SmDFR, and SmANS and enhance their activities. In addition, SmMYB35 interacted with SmTT8 and SmTTG1 to form a MBW complex which enhanced anthocyanin biosynthesis. Taking together, we firstly verified that SmMYB35 promoted anthocyanin biosynthesis in plants. The results provide new insights into the regulatory effects of SmMYB35 on key anthocyanin biosynthetic genes and advance our understanding of the molecular mechanism of light-induced anthocyanin synthesis in eggplants.

Innate lymphoid cells exhibited IL-17-expressing phenotype in active tuberculosis disease.

BACKGROUND: Innate lymphoid cells (ILCs), as an important group of innate immunity, could respond rapidly to Mycobacterium tuberculosis (Mtb) infection. In this research, we studied the phenotypic changes of circulatory ILCs in active tuberculosis (TB) disease. METHODS: We recruited 40 patients with active Mtb infection (TB group) and 41 healthy subjects (NC group), and collected their clinical information and peripheral blood. Circulating ILCs, ILC subsets, dendritic cells (DCs), macrophages, and the production of cytokines in ILCs were tested by flow cytometry (FCM). Enzyme-linked immunosorbent assay (ELISA) was used to detect plasma IL-23. RESULTS: Compared with healthy control, total ILCs (0.73% vs. 0.42%, P = 0.0019), ILC1 (0.55% vs. 0.31%, P = 0.0024) and CD117+ ILC2 (0.02% vs. 0.01%, P = 0.0267) were upregulated in TB group. The total IL-17+ lymphocytes were elevated (3.83% vs. 1.76%, P = 0.0006) while the IL-22+ lymphocytes remained unchanged. Within ILC subsets, ILC3, CD117+ ILC2 and ILC1 in TB group all expressed increased IL-17 (15.15% vs. 4.55%, 19.01% vs. 4.57%, 8.79% vs. 3.87%, P < 0.0001) but similar IL-22 comparing with healthy control. TB group had more plasma IL-23 than NC group (7.551 vs. 5.564 pg/mL, P = 0.0557). Plasma IL-23 in TB group was positively correlated to IL-17+ ILC3 (r = 0.4435, P = 0.0141), IL-17+CD117+ ILC2 (r = 0.5385, P = 0.0021) and IL-17+ ILC1(r = 0.3719, P = 0.0430). TB group also had elevated DCs (9.35% vs. 6.49%, P < 0.0001) while macrophages remained unchanged. Within TB group, higher proportion of IL-17+ ILCs was related to severer inflammatory status and poorer clinical condition. CONCLUSIONS: In active TB disease, circulatory ILCs were upregulated and exhibited IL-17-expressing phenotype. This may expand the understanding of immune reaction to Mtb infection.

Association between severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery after ablation in children.

OBJECTIVE: To investigate the association between the severity of cardiac dysfunction caused by ventricular pre-excitation-led dyssynchrony and cardiac function recovery time after catheter ablation and identify predictors of cardiac function recovery after ablation. METHODS AND RESULTS: A total of 49 children underwent successful ablation (median 2.92 years). This study included 23 patients with mild cardiac dysfunction (left ventricular ejection fraction [LVEF]: 45% ≤ LVEF ≤ 55%), 15 with moderate (30% ≤ LVEF < 45%), and 11 with severe (LVEF <30%). The time for mean LVEF reaching 55% was 0.75, 3, and more than 12 months, respectively. The mean LVEF of children with severe cardiac dysfunction aged ≤6 years normalized within 12 months of follow-up (63.00% ± 1.41%). Mean LVEF of those aged more than 6 years did not normalize at 12 months of follow-up (38.67% ± 10.97%). LVEF recovery time was significantly different between these two age groups (median 11 months vs >12 months, χ2 = 4.55; P = .04). Cox regression analysis showed that preablation smaller left ventricular diastolic diameter (LVDd) Z score and higher LVEF were predictors of cardiac dysfunction recovery time (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.82-0.99, P = .04; HR = 1.09, 95% CI = 1.03-1.15, P = .01). CONCLUSION: Patients with higher LVDd Z scores and lower LVEF tend to have slower improvement in cardiac function after ablation. Patients with LVEF less than 30% and aged more than 6 years need more than 12 months to fully recover, and some might not even completely recover. Early catheter ablation is suggested once ventricular pre-excitation-led cardiac dysfunction is suspected.

CHD4 mediates proliferation and migration of non-small cell lung cancer via the RhoA/ROCK pathway by regulating PHF5A.

BACKGROUND: Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. METHODS: By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. RESULTS: Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CONCLUSIONS: CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

Electrophysiological Characteristics and Outcomes of Radiofrequency Catheter Ablation of Atrial Flutter in Children with or Without Congenital Heart Disease.

There are scarce studies on radiofrequency catheter ablation (RFCA) of atrial flutter (AFL) in the pediatric population. This study therefore aimed to investigate the clinical features and RFCA of AFL in children with or without congenital heart disease. Data from 72 consecutive children (44 males; mean age, 6.1 ± 3.8 [0.9-15.0] years; and mean weight, 23.6 ± 13.9 [8.1-72.0] kg) undergoing RFCA for AFL from 2009 to 2019 were retrospectively reviewed. Thirty-three patients had normal cardiac structure and 39 had congenital heart disease (CHD) of whom 29 had undergone surgical repair and developed AFL at a mean of 3.1 ± 2.5 years later. Fifty-nine patients (84%) presented with persistent AFL. Five patients (7%) had cardiac dysfunction with LVEF of 30-48%, which normalized after ablation. Overall, acute success rate of ablation was 99% and recurrence rate was 18% at 0.5-10 years of follow-up. No procedure-related complications were identified. All 33 patients with normal cardiac structure had cavotricuspid isthmus (CTI)-dependent AFL. Among patients who had undergone corrective surgery for CHD, 15 (52%) had CTI-dependent AFL, 4 (14%) had surgical incisional scar reentrant AFL and the remaining 10 (34%) had both CTI-dependent and scar reentrant AFL. Success rate (100% vs. 97%, P = 1.0000) and recurrence rate (21% vs. 16%, P = 0.7008) were similar between patients with and without CHD. Overall, sick sinus syndrome (SSS) was found in 42% (30/72) of patients with AFL, with an incidence of 39% (13/33) among patients with normal cardiac structure and 59% (17/29) among those who underwent surgery for congenital defects. Permanent pacemakers (PM) were implanted in 53% (16/30) of patients with SSS after ablation. RFCA therefore appeared efficacious and safe for treatment of pediatric AFL. The mechanisms underlying AFL after corrective surgery for CHD are complex, including CTI-dependent macro-reentrant, scar reentrant, or a combination of both. SSS is not rare among pediatric AFL cases, with approximately half of patients needing PM implantation.

Right Atrial Appendage Aneurysm Resection to Cure Aneurysm-Related Atrial Tachyarrhythmia.

Congenital right atrial appendage aneurysm (RAAA) is an extremely rare malformation that can coexist with atrial tachyarrhythmia. There is no consensus on treatment for this condition. This research aimed to investigate the clinical characteristics and efficacy of surgical resection to treat atrial tachyarrhythmia originating from RAAA in children. Four RAAA children diagnosed with atrial tachyarrhythmia at the age of 1-5.25 years weighing 8.3-17.1 kg were discussed in this retrospective study. Patients underwent various treatments, included electrocardiogram (ECG) and echocardiography, antiarrhythmic medication therapy, radiofrequency catheter ablation (RFCA), surgical resection of RAAA and pathological examinations. The results from these treatments along with clinical features of patients were analyzed. The incidence of RAAA in patients with atrial tachycardia originating from the right or left atrial appendages (RAA or LAA) was 7.3% (4/55). The prevalence of RAAA in the RAA was 12.5% (4/32). Atrial tachyarrhythmia was identified both prenatally (26 and 36 weeks of gestational age) and postnatally (1 and 4 months after birth), with two patients per group, respectively. The RAAAs condition in two patients with atrial tachycardia (AT), concomitant atrial flutter (AF) and atrial fibrillation (Af) was identified using echocardiogram. Although, RAAA in two patients with mono AT was unidentified in echocardiogram and failed to be identified in the procedure of RFCA, RAAA was confirmed during surgical resection of the RAA. Multiple pre-surgical antiarrhythmic medications combined therapy used to treat all four patients showed either no effect at all or was only partially effective. The original atrial tachyarrhythmia was successfully abolished after RAAA surgical resection in four patients. AT originating from new foci was established in two patients post-surgically. The conditions of these two patients were successfully reverted and normal sinus rhythm maintained in the application of antiarrhythmic medications. These results confirmed the efficacy of RAAA surgical resection. The pathology study showed cystic dilation in parts of the atrial cavity, fibrosis of the cyst wall, generalized fibrosis of atrial myocardium with myocardium atrophy and cystic dilation. RAAA is prone to misdiagnosis by echocardiogram. Atrial tachyarrhythmia in patients with RAAA is usually resistant to antiarrhythmic medication therapy and RFCA. Surgical resection of RAAA is a safe and effective option that is minimally invasive.

Predictors of Pharmacological Therapy of Ectopic Atrial Tachycardia in Children.

Ectopic atrial tachycardia (EAT) is a relatively common type of supraventricular tachycardia in the pediatric population, and it can be resistant to antiarrhythmic drugs and lead to tachycardia-induced cardiomyopathy (TIC) if not properly managed. The purpose of this study was to determine the predictors of the response to pharmacological therapy in children with EAT. From January 2009 to April 2014, 115 children were admitted to our hospital with a diagnosis of EAT and placed on antiarrhythmic drugs. We examined the clinical history, response to therapy, and follow-up of the children. The incidence of TIC secondary to EAT was 22.6% (n = 26) in children. Incessant EAT accounted for 44.3% of all patients. Control of EAT with antiarrhythmic therapy was achieved in 73.9% (n = 85) of the children. The combination of sotalol and propafenone performed well in controlling EAT in children [complete control in 35 (49.3%) of 71]. The mean time of conversion to sinus rhythm was 24 days, and the mean duration of therapy was 11 months in children with resolution. Multivariate predictors of the control of EAT were age at presentation (OR 0.289, P = 0.038) and tachycardia type (OR 0.276, P = 0.006). TIC occurs in 22.6% of children with EAT. Incessant EAT is more frequently complicated by TIC. Independent factors associated with a good response to pharmacological therapy include a younger age at presentation and non-incessant tachycardia in children with EAT.

Pediatric Dosing of Intravenous Sotalol Based on Body Surface Area in Patients with Arrhythmia.

In a recently published study, we evaluated the efficacy and safety of intravenous sotalol in pediatric patients with incessant tachyarrhythmias and we have found that intravenous sotalol is effective and safe. Our dosing regimen was based on the body weight of the patients. In the US, the recommendation for intravenous sotalol dosing in pediatric patients is based on body surface area (BSA) while taking into consideration the patients' age. The purpose of this paper is to show the correspondence of a body weight-based dosing regimen when expressed for BSA as mg/m2. We evaluated the similarity of a body weight-based dose to that calculated based on BSA using the US labeling recommendations. Of the 83 patients, 5 were newborns (age: 0-30 days), 39 infants and toddlers (age: 1-24 month), 26 young children (age: >2-6 years), 11 older children (age: 6-12 years), and 2 adolescents (age: 14 years). Each received a loading dose of 1 mg/kg intravenous sotalol administered over 10 min followed by a maintenance dose of 4.5 mg/kg/day. There was a close correlation between the sotalol loading doses calculated based on body weight and BSA across the entire age range (r = 0.977, p < 0.001). In most of the age groups, the body weight-based loading doses were lower or equal to the BSA-based doses. Only in the adolescents were the body weight-based doses higher. The maintenance doses given in our study were significantly higher than the BSA-based dose in newborns: 75 ± 6 versus 53 ± 8 mg/m2, p < 0.05; infants/toddlers: 88 ± 14 versus 77 ± 7 mg/m2, p < 0.001; younger children: 113 ± 12 versus 85 mg/m2, p < 0.001; older children: 123 ± 16 versus 85 mg/m2, p < 0.01; and adolescents 157 ± 30 versus 85.5 mg/m2. Despite the rapid administration of the loading dose and the increased maintenance doses, our body weight-based dosing regimen was safe. Only one newborn had significant adverse event (AV block) that resolved spontaneously after discontinuation of the infusion.

Emergency Pacing via the Umbilical Vein and Subsequent Permanent Pacemaker Implantation in a Neonate.

A dying neonate with congenital complete atrioventricular block underwent an emergency temporary pacing via the umbilical vein 1 h after birth. Implantation of a permanent epicardial pacemaker system was performed at the age of 10 days. During the follow-up period of 3 months, the child had been growing well with the VVIR pacemaker.