INTRODUCTIONThe objective of the present study was to review the distribution and incidence of branchial anomalies in an Asian paediatric population and highlight the challenges involved in the diagnosis of branchial anomalies.

METHODSThis was a retrospective chart review of all paediatric patients who underwent surgery for branchial anomalies in a tertiary paediatric hospital from August 2007 to November 2012. The clinical notes were correlated with preoperative radiological investigations, intraoperative findings and histology results. Branchial anomalies were classified based on the results of the review.

RESULTSA total of 28 children underwent surgery for 30 branchial anomalies during the review period. Two children had bilateral branchial anomalies requiring excision. Of the 30 branchial anomalies, 7 (23.3%) were first branchial anomalies, 5 (16.7%) were second branchial anomalies, 3 (10.0%) were third branchial anomalies, and 4 (13.3%) were fourth branchial anomalies (one of the four patients with fourth branchial anomalies had bilateral branchial anomalies). In addition, seven children had 8 (26.7%) branchial anomalies that were thought to originate from the pyriform sinus; however, we were unable to determine if these anomalies were from the third or fourth branchial arches. There was inadequate information on the remaining 3 (10.0%) branchial anomalies for classification.

CONCLUSIONThe incidence of second branchial anomalies appears to be lower in our Asian paediatric population, while that of third and fourth branchial anomalies was higher. Knowledge of embryology and the related anatomy of the branchial apparatus is crucial in the identification of the type of branchial anomaly.

Adolescent ; Branchial Region ; abnormalities ; Branchioma ; congenital ; epidemiology ; Child ; Child, Preschool ; Female ; Hospitals, Pediatric ; Humans ; Incidence ; Infant ; Male ; Retrospective Studies ; Singapore ; epidemiology

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells(ESCs).However,the related mechanisms remain obscure.Here,we show that Npac,a"reader"of histone H3 lysine 36 trimethylation(H3K36me3),is required to maintain mouse ESC(mESC)pluripotency since knockdown of Npac causes mESC differentiation.Depletion of Npac in mouse embryonic fibroblasts(MEFs)inhibits reprogramming efficiency.Furthermore,our chromatin immunoprecipitation followed by sequencing(ChIP-seq)results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs.Interestingly,we find that Npac interacts with positive transcription elongation factor b(p-TEFb),Ser2-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser2P),and Ser5-phosphorylated RNA Pol Ⅱ(RNA Pol Ⅱ Ser5P).Furthermore,depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rifl.Taken together,we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interact-ing with RNA Pol Ⅱ Ser2P and Ser5P.

Objective:To evaluate consistency between 2-fold serial and 4-fold serial diluted neutralization tests against Enterovirus A71 (EV-A71) in estimating titer, Geometric mean titer (GMT), seroprevalence, and seroincidence.Methods:Based on a prospective cohort of 1-9 years old children, mothers and infants established in Anhua County, Hunan Province, during 2013-2018, from which 92 participants with a total of 386 blood specimens were sampled and tested with a 2-fold serial dilution and a 4-fold serial dilution neutralization tests against EV-A71 at the same time. Agreement was estimated using the Bland-Altman method. Stratified analysis was conducted to estimate effect dilution approach on GMT, seroprevalence and seroincidence.Results:The mean difference (0.04, 95% CI:-0.02-0.10) between the two dilution approaches was not significant. However, the limits of agreement (LOA) (-1.12-1.21), with the 95% confidence interval of upper LOA (1.10-1.31) and of lower LOA (-1.22--1.02), significantly exceeded the Clinic accept interval (-1, 1) indicating insufficient agreement between the two approaches in practice. While the dilution approaches did not affect estimates of GMT of the total population and the positive population, and seroincidence with seroconversion only, the differences were 2, 6 and 2%, respectively ( P>0.05). Estimates of seroincidence with at least 4-fold increase and seroconversion/4-fold increase were significantly higher using a 4-fold dilution neutralization test compared to the 2-fold dilution neutralization test with 8% (95% CI: 1%-12%) and 9% (95% CI: 1%-17%), respectively. Conclusion:The 2-dilution and 4-dilution neutralization tests yielded comparable results when estimating the population′s GMT; however, the difference between the two is not negligible when assessing the seroincidence.

Objective:To evaluate consistency between 2-fold serial and 4-fold serial diluted neutralization tests against Enterovirus A71 (EV-A71) in estimating titer, Geometric mean titer (GMT), seroprevalence, and seroincidence.Methods:Based on a prospective cohort of 1-9 years old children, mothers and infants established in Anhua County, Hunan Province, during 2013-2018, from which 92 participants with a total of 386 blood specimens were sampled and tested with a 2-fold serial dilution and a 4-fold serial dilution neutralization tests against EV-A71 at the same time. Agreement was estimated using the Bland-Altman method. Stratified analysis was conducted to estimate effect dilution approach on GMT, seroprevalence and seroincidence.Results:The mean difference (0.04, 95% CI:-0.02-0.10) between the two dilution approaches was not significant. However, the limits of agreement (LOA) (-1.12-1.21), with the 95% confidence interval of upper LOA (1.10-1.31) and of lower LOA (-1.22--1.02), significantly exceeded the Clinic accept interval (-1, 1) indicating insufficient agreement between the two approaches in practice. While the dilution approaches did not affect estimates of GMT of the total population and the positive population, and seroincidence with seroconversion only, the differences were 2, 6 and 2%, respectively ( P>0.05). Estimates of seroincidence with at least 4-fold increase and seroconversion/4-fold increase were significantly higher using a 4-fold dilution neutralization test compared to the 2-fold dilution neutralization test with 8% (95% CI: 1%-12%) and 9% (95% CI: 1%-17%), respectively. Conclusion:The 2-dilution and 4-dilution neutralization tests yielded comparable results when estimating the population′s GMT; however, the difference between the two is not negligible when assessing the seroincidence.

BACKGROUNDAlcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology.

METHODSA genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans.

RESULTSSeveral genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51 × 10(-8)). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption.

CONCLUSIONThe evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.

Adult ; Aged ; Alcohol Drinking ; genetics ; Blood Proteins ; Cytokines ; Female ; Genome-Wide Association Study ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Proteins ; genetics ; Receptors, Cytokine ; genetics

Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest-a phenomenon known as mitotic catastrophe, which is followed by immediate cell death apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.

Adult ; Aged ; China ; epidemiology ; Female ; Hospital Mortality ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; Risk Factors ; Trauma Centers ; Trauma Severity Indices ; Wounds and Injuries ; epidemiology ; mortality

Animals ; Monkeypox/drug therapy* ; Antiviral Agents/therapeutic use* ; Phosphoric Monoester Hydrolases/therapeutic use* ; Macaca fascicularis

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.