Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y12 receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches to reduce complications.(Targeting Platelet-Leukocyte Aggregates in Pneumonia With Ticagrelor [XANTHIPPE]; NCT01883869)
Abstract Background Germline mutations represent a high risk of hereditary cancers in population. The landscape and characteristics of germline mutations in genitourinary cancer are largely unknown, and their correlation with patient prognosis has not been defined. Methods Variant data and relevant clinical data of 10,389 cancer patients in The Cancer Genome Atlas (TCGA) database was downloaded. The subset of data of 206 genitourinary cancer patients containing bladder urothelial carcinoma (BLCA), kidney chromophobe carcinoma (KICH), kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP) and prostate adenocarcinoma (PRAD) cancer with germline mutation information was filtered for further analysis. Variants were classified into pathogenic, likely pathogenic and non-pathogenic categories based on American College of Medical Genetics and Genomics (ACMG) guidelines. Genome Aggregation Database (gnomAD) database was used to assist risk analysis. Results There were 48, 7, 44, 45 and 62 patients with germline mutations identified in BLCA, KICH, KIRC, KIRP and PRAD, respectively. Pathogenic germline mutations from 26 genes and likely pathogenic mutations from 33 genes were revealed. GJB2 , MET , MUTYH and VHL mutations ranked top in kidney cancers, and ATM and CHEK2 mutations ranked top for bladder cancer, while ATM and BRCA1 mutations ranked top for prostate cancer. Frameshift, stop gained and missense mutations were the predominant mutation types. BLCA exhibited the highest ratio of stop gained mutations (22/48 = 45.8%). No difference in patient age was found among pathogenic, likely pathogenic and non-pathogenic groups for all cancer types. The number of male patients far overweight female patients whether PRAD was included ( P = 0) or excluded ( P < 0.001). Patients with pathogenic or likely pathogenic germline mutations exhibited significantly worse overall survival rate than the non-pathogenic group for all genitourinary cancers. More important, analyses assisted by gnomAD database revealed that pathogenic or likely pathogenic germline mutations significantly increased the risk for genitourinary cancer in population, with the odds ratio at 14.88 (95%CI 11.80–18.77) and 33.18 (95%CI 24.90–44.20), respectively. Conclusions The germline mutational status for genitourinary cancers has been comprehensively characterized. Pathogenic and likely pathogenic germline mutations increased the risk and indicated poor prognosis of genitourinary cancers.
Background: There are many articles related to child injuries during the coronavirus disease of 2019 in other countries, but only few studies in this field in China.This study analyzes the clinical characteristics of unintentional childhood injury during the pandemic, to provide reference for the prevention of unintentional childhood injury in the context of pandemic.Methods: A comparative study was performed on the medical data of 2,497 children with unintentional injury who were hospitalized at Chengdu Women's and Children's Central Hospital between 1 January, 2018 and 31 May, 2021.The study period was divided into 2 periods, before the pandemic (1 January, 2018 to 31 May, 2019), during the pandemic (1 January, 2020 to 31 May, 2021).The number of unintentional childhood injuries and age distribution before and during the pandemic were compared.Group differences were examined using Mann-Whitney U for continuous variables and Chi-squared or Kruskal-Wallis tests for categorical variables.Results: There were significant differences in age, accident location, hospitalization days, and medical expenses before and during the pandemic (P<0.05).During the pandemic, the number of children's unintentional injuries increased by 34.24% (1,066 vs. 1,431, P=0.000), and the significantly increased types of unintentional injuries included foreign bodies, falls, crush injuries, and sharp injuries.During the pandemic, the highest proportion of unintentional injury to children was foreign bodies, whereas the proportion of falls was the highest before the pandemic.During the pandemic, the number of foreign body injuries in toddler was significantly higher than before the pandemic (P=0.001),but the number of falls, crush injuries, and sharp injuries in preschooler was significantly higher (P<0.05). Conclusions:In the circumstance of the COVID-19, the number of foreign bodies, falls, crush injuries, and sharp injuries, in children increased significantly.It is necessary to strengthen the prevention of foreign bodies in toddler, and falls, crush injuries, and sharp injuries in preschooler.
Objective
To explore the application value of noninvasive cardiac output monitoring (NICOM) in children with sepsis.
Methods
A total of 51 children with sepsis admitted to pediatric intensive care unit in Chengdu Women and Children′s Center Hospital were enrolled.They were divided into three groups: sepsis without cardiovascular functional disorder group( sepsis group, n=16), septic shock compensation group (n=22), septic shock decompensation group (n=13). The cardiac function of the children was detected by NICOM and echocardiography at the time of admission 0 hours and 1 hours after admission respectively.Cardiac index (CI), stroke volume(SV) measured by NICOM and ejection fraction (EF), SV measured by echocardiography were recorded.The correlation between CI and EF at 0 hours and 1 hours after admission was analyzed, and the SV measured by the two methods were compared.
Results
(1) In the sepsis group, the CI measured by NICOM was(3.54±0.36) L/(min·m2) and EF measured by echocardiography was (66.9±4.4)%.There was a significant positive correlation between CI and EF(r=0.941, P 0.05). (3) In the septic shock decompensation group, CI was (1.26±0.28) L/(min·m2) and EF was (41.23±4.73)% at 0 hours after admission, and there was no positive correlation between CI and EF(r=0.515, P=0.121). CI was(1.61±0.32)L/(min·m2)and EF was(47.77±6.19)% at 1 hours after admission, and there was no positive correlation between CI and EF(r=0.531, P=0.085). There was significant difference between the value of SV measured by NICOM and that measured by echocardiography at 0 hours and 1 hours after admission (P<0.05).
Conclusion
NICOM can accurately evaluate cardiac output when the hemodynamics is stable, but the results are not accurate when the hemodynamics is unstable.NICOM has certain application value in pediatric critical care.
Key words:
Noninvasive cardiac output monitoring; Cardiac function; Septic shock; Correlation analysis,
Peganum harmala is the representative species of Peganum mainly growing in saline soils in temperate deserts and Mediterranean regions. Here, we report the complete chloroplast genome sequence of P. harmala. The genome was 160,068 bp in length with the GC content of 37.5%. The genome encoded 127 genes including 82 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenomic analysis suggested that P. harmala forms a monophyletic group with Nitraria, which supported to divide Peganum and Nitraria from Zygophyllaceae as Nitrariaceae.
To investigate the anti metastatic potential of retinoic acid as an important determinant of metastatic behavior in thyroid carcinoma and understand the role of invasion associated proteins.Differentiated thyroid carcinoma cell lines FTC-133 and XTC.UC1, anaplastic thyroid cancer cell lines C643 and HTH74 were studied. All cell lines were cultured with all-trans-RA (ATRA) or solvent ethanol. The in vitro invasion and adhesion potency were studied by transwell experiment and short-term adhesion assay. The functions of invasion associated proteins, urokinase type plasminogen activator (uPA), uPA receptor (uPAR), MMP2 and E-cadherin were investigated by semi-quantitative RT-PCR and Western blot.In vitro invasion assay revealed that ATRA treatment could reduce the invasive potency in all the thyroid cancer cell lines. On Day 5 of ATRA treatment, the numbers of cells that migrated through extracellular matrix were as follows, in contrast to control group, FTC-133: 91±9 vs 118±10, C643: 92±17 vs 164±21, HTH74: 87±18 vs 169±15, and XTC.UC1: 95±23 vs 136±15, respectively (all P<0.05). Short term adhesion assay suggested that ATRA increases cancer cell adhesion to extracellular matrix (ECM) in C643, HTH74 and XTC.UC1. RT-PCR and Western blot both revealed diminished expression of uPAR in all four carcinoma cell lines. In C643 and HTH74 cell lines, the expression of uPA was reduced and the expression of E-Cadherin was increased; whereas the MMP2 expression was not significantly down-regulated in ATRA treated group. In ATRA treated FTC-133 and XTC.UC1 cell lines, MMP2 expression was decreased, but no significant changes in uPA and E-Cadherin expression were observed.The present study demonstrates the influence of ATRA on two important determinants of metastatic behavior ("de adhesion" and proteolysis) in thyroid carcinoma cell lines.
To study the effects of erythropoietin (EPO) on serum levels of neuron-specific enolase (NSE) and S-100B in neonates with hypoxic-ischemic encephalopathy (HIE) and the underlying mechanism.Forty neonates with HIE were randomly divided into conventional treatment (n=20) and EPO treatment groups (n=20). Twenty healthy full-term neonates born during the same period were randomly selected as the normal control group. The conventional treatment group received conventional treatment, while the EPO treatment group received conventional treatment as well as EPO [200 IU/(kg.d)] which was given by intravenous infusion from the second day after birth. The course of treatment was 7 days. Blood samples of the three groups were collected on the first day after birth (before treatment) and the ninth day after birth (after treatment). Serum levels of NSE and S-100B were measured by double-antibody sandwich ABC-ELISA.Before treatment, the two treatment groups had significantly higher serum NSE and S-100B levels than the normal control group (P<0.01), whereas no significant differences in the levels of NSE and S-100B were observed between the conventional treatment and EPO treatment groups (P>0.05). The serum NSE and S-100B levels on the ninth day after birth were significantly lower than those on the first day after birth in the three groups (P<0.01). After treatment, the serum NSE and S-100B levels were significantly lower in the EPO treatment group than in the conventional treatment group (P<0.05).Dynamic monitoring of serum NSE and S-100B levels may be helpful for the early diagnosis of HIE and the assessment of brain injury repair in newborns with HIE. EPO may be helpful for the repair of neurons and glial cells.
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