Development of quantum dot‐based fluorescence lateral flow immunoassay strip for rapid and quantitative detection of serum interleukin‐6

BackgroundInterleukin‐6 (IL‐6) is an inflammatory factor that increases rapidly in response to infectious diseases including sepsis. The aim of this study is to develop a quantum dot (QD)‐based fluorescence lateral flow immunoassay (LFIA) strip that can rapidly and accurately detect IL‐6 levels.MethodsQD‐based LFIA strips were fabricated by conjugating CdSe/ZnS QDs to the IL‐6 antibody. Performance verification and clinical sample analysis were carried out to evaluate the newly developed strip.ResultsQD‐based LFIA strips were successfully fabricated. The test strip''s linear range was 10–4000 pg/ml, with a linear correlation coefficient of R ² ≥ .959. The sensitivity of the test strip was 1.995 pg/ml. The recovery rate was 95.72%–102.63%, indicating satisfying accuracy. The coefficient of variation (CV) of the intra‐assay was 2.148%–3.903%, while the inter‐assay was 2.412%–5.293%, verifying the strip''s high precision. The cross‐reaction rates with various interleukins (IL‐1α, IL‐1β, IL‐2, IL‐4, and IL‐8) and interferon‐γ (IFN‐γ) were all <0.1%. When the strip was placed in a 50°C oven for 1, 2, 3, and 4 weeks, the test results were not significantly altered compared to storage at room temperature. Furthermore, 200 clinical serum samples were analyzed to compare the strip with the Beckman chemiluminescence immunoassay (CLIA) kit, which revealed a high correlation (n = 200, R ² = .9971) for the detection of IL‐6.ConclusionsThe QD‐based test strip can rapidly and quantitatively detect IL‐6 levels, thus meeting the requirement of point‐of‐care test (POCT) and showing excellent clinical prospects.     

USP21 promotes cell proliferation by maintaining the EZH2 level in diffuse large B‐cell lymphoma

BackgroundDiffuse large B‐cell lymphoma (DLBCL) is the most common category of non‐Hodgkin lymphoma (NHL). However, the underlying molecular mechanism of DLBCL remains unclear.MethodsReal‐time PCR and Western blot analysis were performed to assess the expression of ubiquitin‐specific peptidase 21 (USP21) or enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2). CCK8 assay and cell death staining were carried out to examine the role of USP21 in cell proliferation and cell death, respectively.ResultsWe found that the deubiquitinase USP21 was highly expressed in the DLBCL lymphoid tissue. The expression of USP21 promoted DLBCL cell proliferation, while it had no obvious effect on cell death. In addition, we found that USP21 regulated cell proliferation via cysteine 221, the catalytic site of USP21. Furthermore, we identified that USP21 could stabilize EZH2, a protein required for germinal center formation and lymphoma formation.ConclusionThe deubiquitinase USP21 promotes cell proliferation by maintaining the EZH2 protein level in DLBCL.     

Tp‐e and (Tp‐e)/QT ratio as a non‐invasive risk factors for malignant ventricular arrhythmia in patients with idiopathic ventricular premature complexes

BackgroundTo evaluate the role of Tp‐e and (Tp‐e)/QT ratio in differentiating benign ventricular premature complex (VPC) and malignant polymorphic ventricular tachycardia (PVT).MethodsFrom January 2017 to December 2017, patients with documented polymorphic ventricular tachycardia (PVT) or ventricular fibrillation (VF) were consecutive included and classified as PVT/VF group. Sixty age‐ and sex‐matched healthy individuals were recruited as comparative control and subdivided into non‐VPC and VPC group. Clinical characteristics and Tp‐e and Tp‐e/QT ratio between the three groups were compared.ResultsTp‐e and (Tp‐e)/QT ratio were significantly higher in patients of PVT/VF group compared with the other two groups (P < .001). Episodes of syncope were more frequent in patients with PVT/VF (P < .05). The sensitivity and specificity of a Tp‐e interval ≥86 ms for malignant arrhythmias triggered by VPCs were 88% and 66%, respectively, while the sensitivity and specificity of the Tp‐e/QT ratio ≥0.24 were 82% and 70%, respectively. Five patients complained recurrence of syncope in the PVT/VF group and 1 patient died with mean follow‐up of 18 months.ConclusionTp‐e interval and the Tp‐Te/QT ratio is significantly increased in patients with PVT/VF and may be used as a novel non‐invasive marker of differentiating malignant and benign VPC.     

自动体外除颤仪的配置现状及实施研究进展

自动体外除颤仪(automated external defibrillator,AED)是一种便携式的医疗设备,用于院外心脏骤停(out-of-hospital cardiac arrest,OHCA)患者的早期除颤。欧美等发达国家自上世纪90年代实施推广AED以来取得一定成效,但国内居民对其认知水平和普及程度较低。本文通过综述国内外AED的研究现状及存在问题,为我国今后的研究及相关政策制定提供参考。     

Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma

BACKGROUNDPatients with p16⁺ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16⁺ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16⁺ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning–based metric, the multinucleation index (MuNI), for prognostication in p16⁺ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16⁺ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis–free survival (DMFS) in p16⁺ OPSCC, with HRs of 1.78 (95% CI: 1.37–2.30), 1.94 (1.44–2.60), and 1.88 (1.43–2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain–based digital biomarker test for counseling, treatment, and surveillance of patients with p16⁺ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.     

Association of Implementation of a Comprehensive Preconception-to-Pregnancy Management Plan With Pregnancy Outcomes Among Chinese Pregnant Women With Type 1 Diabetes: The CARNATION Study

OBJECTIVETo investigate the effect on pregnancy outcome of integrating a comprehensive management plan for patients with type 1 diabetes (T1D) into the World Health Organization universal maternal care infrastructure.RESEARCH DESIGN AND METHODSA comprehensive preconception-to-pregnancy management plan for women with T1D was implemented in 11 centers from 8 Chinese cities from 2015 to 2017. Sequential eligible pregnant women (n = 133 out of 137 initially enrolled) with T1D and singleton pregnancies attending these management centers formed the prospective cohort. The main outcome was severe adverse pregnancy outcome comprising maternal mortality, neonatal death, congenital malformations, miscarriage in the second trimester, and stillbirth. We compared pregnancy outcomes in this prospective cohort with two control groups with the same inclusion and exclusion criteria: a retrospective cohort (n = 153) of all eligible pregnant women with T1D attending the same management centers from 2012 to 2014 and a comparison cohort (n = 116) of all eligible pregnant women with T1D receiving routine care from 2015 to 2017 in 11 different centers from 7 cities.RESULTSThe rate of severe adverse pregnancy outcome was lower in the prospective cohort (6.02%) than in either the retrospective cohort (18.30%; adjusted odds ratio [aOR] 0.31 [95% CI 0.13–0.74]) or the contemporaneous comparison cohort (25.00%; aOR 0.22 [95% CI 0.09–0.52]).CONCLUSIONSThe substantial improvements in the prospective cohort are evidence of a potentially clinically important effect of the comprehensive management plan on pregnancy outcomes among Chinese pregnant women with pregestational T1D. This supports the development of similar approaches in other countries.