Publications by authors named "Yue Cui"

273 Publications

The Frequency of Genetic Mutations Associated With Behavioral Variant Frontotemporal Dementia in Chinese Han Patients.

Front Aging Neurosci 2021 8;13:699836. Epub 2021 Jul 8.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Behavioral variant frontotemporal dementia (bvFTD) is a clinically heterogeneous syndrome with high heredity. However, the frequencies of mutations associated with bvFTD have yet to be determined. The aim of the current study was to investigate the frequency of Chinese Han patients harboring genetic bvFTD variants.

Methods: A total of 49 bvFTD patients selected from our frontotemporal lobar degeneration database, including 14 familial cases belonging to eight families and 35 sporadic cases were consecutively recruited from July 2014 to December 2019 at Xuanwu Hospital (Beijing, China). Whole-exome sequencing (WES) was performed and repeat-primed PCR was used to test samples for the C9orf72 hexanucleotide repeat expansion mutation. The frequency of genetic variants and the pathogenicity of the novel variants were analyzed.

Results: Ten pathogenic or likely pathogenic variants were identified in 17 bvFTD patients, including C9orf72 repeat expansions, six previously reported mutations and three novel mutations (MAPT p. R5C, p. D54N, GRN p. P451L). Genetic mutations accounted for 27.9% (12/43) of total cases, 87.5% (7/8) of patients with familial bvFTD, and 14.3% (5/35) with sporadic bvFTD. Pathogenic variants mostly occurred in MAPT gene (20.9%, 9/43), followed by C9orf72 repeat expansions (2.3%, 1/43), GRN gene (2.3%, 1/43) and FUS gene (2.3%, 1/43).

Conclusion: There was a high prevalence of genetic variants in Chinese bvFTD patients, highlighting the necessity of genetic testing for bvFTD.
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http://dx.doi.org/10.3389/fnagi.2021.699836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297439PMC
July 2021

Long-Term Safety and Efficacy of CT-Guided I Radioactive Seed Implantation as a Salvage Therapy for Recurrent Head and Neck Squamous Carcinoma: A Multicenter Retrospective Study.

Front Oncol 2021 1;11:645077. Epub 2021 Jul 1.

Department of Radiation Oncology, Peking University 3rdHospital, Beijing, China.

Purpose: To investigate the safety and efficacy of CT-guided I radioactive seed implantation (RSI) as a salvage therapy for recurrent head and neck squamous carcinoma (rHNSC) after external beam radiotherapy (EBRT) or surgery.

Materials And Methods: This is a multicenter retrospective study of 113 patients (83 males; median age 57 years) with rHNSC who underwent CT-guided I RSI between February 2003 and December 2017. Of the included patients, 107 patients previously received EBRT and 65 patients received surgery and all were ineligible or rejected for salvage surgery and/or repeat EBRT.

Results: During a median follow-up duration of 20 months (range, 3-152 months), 87 patients died. The 1-, 2-, 3-, and 5-year local control rate were 57.4%, 41.8%, 29.3%, and 15.2%, respectively. The median time to progression was 15 months [95% confidence interval (CI), 6.1-23.9 months]. The median overall survival (OS) was 20 months (95% CI, 12.4-27.6 months). The 1-, 2-, 3-, and 5-year OS rate were 63.6%, 44.6%, 29.9%, and 21.7%, respectively. Univariate and multivariate analyses revealed that KPS score and postoperative D90 were significantly associated with patients' OS. The complications were mainly grade I/II skin and mucosal reactions: 18 cases (15.9%) of grade I/II and eight cases (7.0%) of grade III radiation dermatitis, and 14 cases (12.4%) of grade I/II and three cases (2.7%) grade III mucosal reactions. No grade IV or severer complications were found.

Conclusion: CT-guided I RSI may be safe as a salvage therapy for rHNSC after EBRT/surgery, yielding promising efficacy compared with historical data. KPS score and postoperative D90 may be significantly associated with OS.
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http://dx.doi.org/10.3389/fonc.2021.645077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281320PMC
July 2021

Bibliometric analysis of phosphogypsum research from 1990 to 2020 based on literatures and patents.

Environ Sci Pollut Res Int 2021 Jul 8. Epub 2021 Jul 8.

College of Environmental Science and Engineering, Nankai University, Tianjin, 300350, People's Republic of China.

The demand together with the urgency of phosphogypsum (PG) treatment will pose significant challenges for many countries. This research aims to explore the research progress of PG, including basic status, cooperation situation, research fields, and development trends, based on the Web of Science database through bibliometric analysis of publications (articles and patents) from 1990 to 2020. The results show that academic research on PG originated early, but the number of patents grew quickly. China is a global leader in terms of the number of publications and plays a significant role in international cooperation. The knowledge of PG has remained concentrated in the fields of natural radioactivity, cement paste backfilling, soil, crystal morphology, and synthetic gas. However, academic hotspots focus on the microstructure of chemical processes and various environmental impacts; patents and hot technologies are based on the production of refractory materials, ceramics, surface materials, cement mortar, and composite materials. The academic frontiers of PG will be centered on exploiting the methods of recovering rare earth elements from PG, the conditions of ion solidification/stabilization in PG, the impact of reaction conditions on product quality, and the reaction mechanism at the micro-level. The frontiers of patents need to focus on the improvement of manufacturing equipment, new wall materials, and chemically modified polymer materials. Envisaging the number of articles and patents to be published in the future, architectural research has a large room for improvement. This paper conducts an in-depth analysis of PG and provides information on the technological development prospects and opportunities, which is helpful for researchers engaged in PG management.
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http://dx.doi.org/10.1007/s11356-021-15237-yDOI Listing
July 2021

A feedback circuit comprising EHD1 and 14-3-3ζ sustains β-catenin/c-Myc-mediated aerobic glycolysis and proliferation in non-small cell lung cancer.

Cancer Lett 2021 Jul 2;520:12-25. Epub 2021 Jul 2.

PET/CT-MRI Centre, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150040, China. Electronic address:

Mammalian Eps15 homology domain 1 (EHD1) participates in the development of non-small cell lung cancer (NSCLC). However, its role in mediating aerobic glycolysis remains unclear. Herein, microarray analysis revealed that EHD1 expression was significantly correlated with the glycolysis/gluconeogenesis pathway. Clinically, EHD1 expression was positively correlated with the maximum standard uptake value (SUVmax) in F-FDG PET/CT scans. Additionally, EHD1 knockdown inhibited aerobic glycolysis and proliferation in vitro and in vivo. Furthermore, Wnt/β-catenin signaling was identified as a critical EHD1-regulated pathway. Co-IP, native gel electrophoresis, and immunoblotting showed that EHD1 contributed to 14-3-3 dimerization via 14-3-3ζ and subsequent activation of β-catenin/c-Myc signaling. Analysis of the EHD1 regulatory region via ENCODE revealed the potential for c-Myc recruitment, leading to transcriptional activation of EHD1 and formation of an EHD1/14-3-3ζ/β-catenin/c-Myc positive feedback circuit. Notably, blocking this circuit with a Wnt/β-catenin inhibitor dramatically inhibited tumor growth in vivo. The positive correlations among EHD1, 14-3-3ζ, c-Myc, and LDHA were further confirmed in NSCLC tissues. Collectively, our study demonstrated that EHD1 activates a 14-3-3ζ/β-catenin/c-Myc regulatory circuit that synergistically promotes aerobic glycolysis and may constitute a promising therapeutic target for NSCLC.
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http://dx.doi.org/10.1016/j.canlet.2021.06.023DOI Listing
July 2021

Regulatory Focus, Motivation, and Their Relationship With Creativity Among Adolescents.

Front Psychol 2021 20;12:666071. Epub 2021 May 20.

Beijing Key Laboratory of Learning and Cognition, School of Psychology, Capital Normal University, Beijing, China.

Due to the close relationship among intrinsic/extrinsic motivation, regulatory focus, and creativity revealed by previous literature, intrinsic/extrinsic motivation may play a mediating role between regulatory focus and creativity. Therefore, the present study aimed to investigate the relationship between regulatory focus and creativity by combining intrinsic/extrinsic motivation. In this study, senior high school students ( = 418) completed the Regulatory Focus Questionnaire, the Working Preference Inventory, the Williams Creativity Assessment Packet, and the Kirton Adaption-Innovation Inventory. The correlation analysis showed that both promotion and prevention focus positively correlated with intrinsic motivation; intrinsic motivation and promotion focus positively correlated with creativity personality and innovative-adaptive cognitive style; and extrinsic motivation and prevention focus negatively correlated with innovative-adaptive cognitive style. Furthermore, a path model showed that promotion focus positively predicted creativity through the mediation of intrinsic motivation. In general, our study suggests that intrinsic motivation plays a mediating role between promotion focus and creativity. Our results complement those of previous studies and serve as inspiration for the cultivation of creativity in classroom or enterprise settings.
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http://dx.doi.org/10.3389/fpsyg.2021.666071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172616PMC
May 2021

White Matter Integrity Involvement in the Preclinical Stage of Familial Creutzfeldt-Jakob Disease: A Diffusion Tensor Imaging Study.

Front Aging Neurosci 2021 19;13:655667. Epub 2021 May 19.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Objective: The objective of the study was to explore patterns of white matter (WM) alteration in preclinical stage familial Creutzfeldt-Jakob disease (fCJD) using diffusion tensor imaging (DTI).

Methods: Seven asymptomatic carriers of the G114V mutation and six non-carriers were recruited from the same fCJD kindred and follow-up obtained from all asymptomatic carriers and two non-carriers 2 years later. Overlapping WM patterns were also explored in asymptomatic carriers and symptomatic CJD patients. All participants underwent clinical and neuropsychological assessments and DTI at baseline and follow-up. DTI data were subjected to whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) in WM using tract-based spatial statistics. Three comparisons were conducted: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between patients with symptomatic CJD and healthy controls (CJD patient analysis).

Results: Neither carriers nor non-carriers developed any neurological symptoms during 2 years of follow-up. Baseline analysis showed no differences between the carrier and non-carrier groups in MD and FA. Follow-up analysis showed significantly increased MD in multiple WM tracts, among which increased MD in the bilateral superior longitudinal fasciculus, bilateral anterior thalamic radiation, bilateral cingulate gyrus, and left uncinate fasciculus overlapped the patterns observed in patients with symptomatic CJD.

Conclusion: Changes in integrity within multiple WM tracts can be detected during the preclinical stage of fCJD.
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http://dx.doi.org/10.3389/fnagi.2021.655667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171061PMC
May 2021

Screening of differential components of Gegenqinlian decoction and their comparative pharmacokinetics in normal and pyrexia rats using UHPLC-FT-ICR-MS and UHPLC-MS/MS.

Biomed Chromatogr 2021 Jun 2:e5186. Epub 2021 Jun 2.

Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.

UHPLC combined with Fourier-transform ion cyclotron resonance MS metabonomic approach was employed to screen the differential components between normal rats and yeast-induced pyrexia rats after an oral administration of Gegenqinlian decoction (GQLD). Nine compounds, namely puerarin, daidzein, baicalin, wogonoside, wogonin, berberine, palmatine, jateorhizine, and coptisine, were identified as differential components in the plasma. A rapid, sensitive, selective, and accurate UHPLC-MS method was developed and fully validated for the simultaneous determination of the screened components in rat plasma after an oral administration of GQLD. The values for the limit of quantification ranged from 0.025 to 5.0 ng/mL. The inter- and intra-day precision of all analytes was ≤10.7%, with an accuracy of ≤10.5%. Good extraction recovery and matrix effects were also obtained. The method was successfully applied to a comparative pharmacokinetic study of GQLD in normal and pyrexia rats. The results showed that the pharmacokinetic behavior of the analytes was changed in pyrexia rats compared to normal rats. These results could provide beneficial guidance for clinical applications of GQLD.
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http://dx.doi.org/10.1002/bmc.5186DOI Listing
June 2021

Novel PSEN1 and PSEN2 Mutations Identified in Sporadic Early-onset Alzheimer Disease and Posterior Cortical Atrophy.

Alzheimer Dis Assoc Disord 2021 May 11. Epub 2021 May 11.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background/purpose: Sporadic early-onset Alzheimer disease (sEOAD) and its visual variant, posterior cortical atrophy (PCA), have a disease onset at less than 65 years of age with no familial aggregation. The etiology and genetic basis of these diseases remain poorly understood. Our study aimed to identify additional mutations or variants associated with sEOAD and PCA and to further examine their genetic and phenotypic spectrums.

Methods: We performed whole-exome sequencing and analyzed the clinical and neuroimaging features of mutation carriers with 29 patients having sEOAD and 25 having PCA.

Results: Nine rare damaging variants were identified in 4 patients with sEOAD and 3 with PCA. A novel mutation (p.A136V) in PSEN1 was identified in a patient with sEOAD and a likely pathogenic variant (p.M239T) was identified for PSEN2 in a patient with PCA. In addition, 7 rare damaging variants were detected in other genes related to neurodegenerative diseases. The patient carrying the PSEN1 p.A136V mutation presented with typical clinical and imaging features of sEOAD, and the PCA patient with the PSEN2 p.M239T mutation presented with visuospatial impairment as the initial symptom.

Conclusion: Our study expands the PSEN1 mutation spectrum of sEOAD and highlights the importance of screening PSEN1 and/or PSEN2 mutations in PCA patients.
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http://dx.doi.org/10.1097/WAD.0000000000000438DOI Listing
May 2021

Classification of Prostate Transitional Zone Cancer and Hyperplasia Using Deep Transfer Learning From Disease-Related Images.

Cureus 2021 Mar 25;13(3):e14108. Epub 2021 Mar 25.

Department of Radiology, Fourth Military Medical University, Shaanxi, CHN.

Purpose The diagnosis of prostate transition zone cancer (PTZC) remains a clinical challenge due to their similarity to benign prostatic hyperplasia (BPH) on MRI. The Deep Convolutional Neural Networks (DCNNs) showed high efficacy in diagnosing PTZC on medical imaging but was limited by the small data size. A transfer learning (TL) method was combined with deep learning to overcome this challenge. Materials and methods A retrospective investigation was conducted on 217 patients enrolled from our hospital database (208 patients) and The Cancer Imaging Archive (nine patients). Using T2-weighted images (T2WIs) and apparent diffusion coefficient (ADC) maps, DCNN models were trained and compared between different TL databases (ImageNet vs. disease-related images) and protocols (from scratch, fine-tuning, or transductive transferring). Results PTZC and BPH can be classified through traditional DCNN. The efficacy of TL from natural images was limited but improved by transferring knowledge from the disease-related images. Furthermore, transductive TL from disease-related images had comparable efficacy to the fine-tuning method. Limitations include retrospective design and a relatively small sample size. Conclusion Deep TL from disease-related images is a powerful tool for an automated PTZC diagnostic system. In developing regions where only conventional MR scans are available, the accurate diagnosis of PTZC can be achieved via transductive deep TL from disease-related images.
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http://dx.doi.org/10.7759/cureus.14108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075764PMC
March 2021

Ursodeoxycholic acid in intrahepatic cholestasis of pregnancy: a systematic review and individual participant data meta-analysis.

Lancet Gastroenterol Hepatol 2021 Jul 27;6(7):547-558. Epub 2021 Apr 27.

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.

Background: Ursodeoxycholic acid is commonly used to treat intrahepatic cholestasis of pregnancy, yet its largest trial detected minimal benefit for a composite outcome (stillbirth, preterm birth, and neonatal unit admission). We aimed to examine whether ursodeoxycholic acid affects specific adverse perinatal outcomes.

Methods: In this systematic review and individual participant data meta-analysis, we searched PubMed, Web of Science, Embase, MEDLINE, CINAHL, Global Health, MIDIRS, and Cochrane without language restrictions for relevant articles published between database inception, and Jan 1, 2020, using search terms referencing intrahepatic cholestasis of pregnancy, ursodeoxycholic acid, and perinatal outcomes. Eligible studies had 30 or more study participants and reported on at least one individual with intrahepatic cholestasis of pregnancy and bile acid concentrations of 40 μmol/L or more. We also included two unpublished cohort studies. Individual participant data were collected from the authors of selected studies. The primary outcome was the prevalence of stillbirth, for which we anticipated there would be insufficient data to achieve statistical power. Therefore, we included a composite of stillbirth and preterm birth as a main secondary outcome. A mixed-effects meta-analysis was done using multi-level modelling and adjusting for bile acid concentration, parity, and multifetal pregnancy. Individual participant data analyses were done for all studies and in different subgroups, which were produced by limiting analyses to randomised controlled trials only, singleton pregnancies only, or two-arm studies only. This study is registered with PROSPERO, CRD42019131495.

Findings: The authors of the 85 studies fulfilling our inclusion criteria were contacted. Individual participant data from 6974 women in 34 studies were included in the meta-analysis, of whom 4726 (67·8%) took ursodeoxycholic acid. Stillbirth occurred in 35 (0·7%) of 5097 fetuses among women with intrahepatic cholestasis of pregnancy treated with ursodeoxycholic acid and in 12 (0·6%) of 2038 fetuses among women with intrahepatic cholestasis of pregnancy not treated with ursodeoxycholic acid (adjusted odds ratio [aOR] 1·04, 95% CI 0·35-3·07; p=0·95). Ursodeoxycholic acid treatment also had no effect on the prevalence of stillbirth when considering only randomised controlled trials (aOR 0·29, 95% CI 0·04-2·42; p=0·25). Ursodeoxycholic acid treatment had no effect on the prevalence of the composite outcome in all studies (aOR 1·28, 95% CI 0·86-1·91; p=0·22), but was associated with a reduced composite outcome when considering only randomised controlled trials (0·60, 0·39-0·91; p=0·016).

Interpretation: Ursodeoxycholic acid treatment had no significant effect on the prevalence of stillbirth in women with intrahepatic cholestasis of pregnancy, but our analysis was probably limited by the low overall event rate. However, when considering only randomised controlled trials, ursodeoxycholic acid was associated with a reduction in stillbirth in combination with preterm birth, providing evidence for the clinical benefit of antenatal ursodeoxycholic acid treatment.

Funding: Tommy's, the Wellcome Trust, ICP Support, and the National Institute for Health Research.
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http://dx.doi.org/10.1016/S2468-1253(21)00074-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192305PMC
July 2021

Enhancement of enzyme activities and VFA conversion by adding Fe/C in two-phase high-solid digestion of food waste: Performance and microbial community structure.

Bioresour Technol 2021 Jul 17;331:125004. Epub 2021 Mar 17.

Department of Environmental Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Two-phase high-solid digestion is conducive to the degradation of food waste. In this study, Fe/C was added in high-solid digestion in different acidification and/or methanogenic phase. The experimental results indicated that it significantly increased the cumulative yield of biomethane. When Fe/C was added to the acidification phase only and both the acidification and methanogenic phases, the biomethane yield reached 474.07 ± 7.03 and 475.47 ± 4.68 mL·g VS , respectively, and the biodegradation rate reached 87.30% and 87.58%, respectively, indicating that Fe/C had mainly effect on the performance of acidification phase. In a two-phase anaerobic fermentation system, the activity of dehydrogenases and the concentration of coenzyme F were 2.23-2.95 mg·g·h and 0.0063-0.0294 mol·g volatile solids, respectively. Additionally, the archaeal communities production pathway of methane from using acetic acid to using hydrogen as the reactant.
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http://dx.doi.org/10.1016/j.biortech.2021.125004DOI Listing
July 2021

Predictive values of multiple non-invasive markers for myocardial fibrosis in hypertrophic cardiomyopathy patients with preserved ejection fraction.

Sci Rep 2021 Feb 22;11(1):4297. Epub 2021 Feb 22.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.

Myocardial fibrosis assessed by late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) is associated with cardiovascular outcomes in hypertrophic cardiomyopathy (HCM) patients, but little is known about the utility of non-invasive markers for detecting LGE. This study aims to explore the association between cardiac-specific biomarkers, CMR myocardial strain, left ventricular (LV) hypertrophy and LGE in HCM patients with preserved ejection fraction (EF) and investigate the predictive values of these indexes for LGE. We recruited 33 healthy volunteers and 86 HCM patients with preserved EF to undergo contrast-enhanced CMR examinations. In total, 48 of 86 HCM patients had the presence of LGE. The LGE-positive patients had significant higher serum high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro b-type natriuretic peptide (Nt-proBNP) levels and lower global longitudinal (GLS) and circumferential (GCS) strains than the LGE-negative group. The LGE% was independently associated with the Nt-proBNP levels, GCS, LV end-diastolic maximum wall thickness (MWT) and beta-blocker treatment. In the receiver operating characteristic curve analysis, the combined parameters of Nt-proBNP ≥ 108.00 pg/mL and MWT ≥ 17.30 mm had good diagnostic performance for LGE, with a specificity of 81.25% and sensitivity of 70.00%. These data indicate that serum Nt-proBNP is a potential biomarker associated with LGE% and, combined with MWT, were useful for identifying myocardial fibrosis in HCM patients with preserved EF. Additionally, LV GCS may be a more sensitive indicator for reflecting the presence of myocardial fibrosis than GLS.
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http://dx.doi.org/10.1038/s41598-021-83678-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900233PMC
February 2021

Carbon Nanotube Field-Effect Transistor-Based Chemical and Biological Sensors.

Sensors (Basel) 2021 Feb 2;21(3). Epub 2021 Feb 2.

School of Materials Science and Engineering, Peking University, Beijing 100871, China.

Chemical and biological sensors have attracted great interest due to their importance in applications of healthcare, food quality monitoring, environmental monitoring, etc. Carbon nanotube (CNT)-based field-effect transistors (FETs) are novel sensing device configurations and are very promising for their potential to drive many technological advancements in this field due to the extraordinary electrical properties of CNTs. This review focuses on the implementation of CNT-based FETs (CNTFETs) in chemical and biological sensors. It begins with the introduction of properties, and surface functionalization of CNTs for sensing. Then, configurations and sensing mechanisms for CNT FETs are introduced. Next, recent progresses of CNTFET-based chemical sensors, and biological sensors are summarized. Finally, we end the review with an overview about the current application status and the remaining challenges for the CNTFET-based chemical and biological sensors.
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http://dx.doi.org/10.3390/s21030995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867273PMC
February 2021

CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis.

Open Med (Wars) 2021 4;16(1):104-116. Epub 2021 Jan 4.

Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, No 295 Xichang Road, Kunming 650032, Yunnan, China.

Background: The aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial-mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC.

Methods: The protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay.

Results: We discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis , while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights . We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities.

Conclusion: Circ_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.
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http://dx.doi.org/10.1515/med-2021-0001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801883PMC
January 2021

Metabonomic analysis of plasma biochemical changes in pyrexia rats after treatment with Gegenqinlian decoction, aspirin and itraconazole by UHPLC-FT-ICR-MS.

J Pharm Anal 2020 Dec 27;10(6):581-587. Epub 2019 Nov 27.

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.

A metabonomic approach involving an ultrahigh-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) was used to investigate the changes in the endogenous metabolites in the plasma of rats with yeast-induced pyrexia treated with Gegenqinlian decoction (GQLD), aspirin and itraconazole. The differences in the small molecule profiles of treatment using traditional Chinese medicine, etiological treatment and symptomatic treatment were elucidated. Thirty-six plasma metabolites were identified or putatively identified, and the effects of the three medicines on the thirty-six metabolites were studied. Their metabolic pathways indicated that GQLD, aspirin and itraconazole ameliorated the rats with yeast-induced pyrexia predominantly by regulating the metabolisms of phospholipid, sphingolipid, fatty acid oxidation, fatty acid amides, amino acid and glycerolipid in vivo The pharmacodynamics and metabonomic results showed that the three medicines exhibited the therapeutic effects on pyrexia by regulating the perturbations of multiple metabolisms. The study provided a scientific basis for an in-depth understanding of the therapeutic effects of GQLD, aspirin and itraconazole on rats with yeast-induced pyrexia.
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http://dx.doi.org/10.1016/j.jpha.2019.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775848PMC
December 2020

Case Report: [F]PI2620 as a Tau Imaging Agent in Posterior Cortical Atrophy.

Front Neurol 2020 8;11:566667. Epub 2020 Dec 8.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing, China.

Posterior cortical atrophy (PCA) is widely considered as an atypical variant of Alzheimer disease and is characterized by a progressive decline in visual function. PCA has been investigated from the standpoints of brain structure and metabolism, but tau deposition and its relationship to disease severity still remain unclear. Here, we used a novel tau ligand, [F]PI2620, to visualize tau deposition in a PCA patient. The results showed that high [F]PI2620 uptake in posterior cortical regions was associated with clinical manifestations, morphologic changes in the brain observed by magnetic resonance imaging (MRI), and hypometabolism detected by [F] fluorodeoxyglucose (FDG) positron emission tomography (PET). This is the first report demonstrating a clinical anatomical correspondence between [F]PI2620 PET results, clinical manifestations, MRI, and [F]FDG PET findings in a Chinese patient with PCA. The results also support the utility of [F]PI2620 for visualizing tau aggregation in PCA.
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http://dx.doi.org/10.3389/fneur.2020.566667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753187PMC
December 2020

An inversion model for estimating the negative air ion concentration using MODIS images of the Daxing'anling region.

PLoS One 2020 24;15(11):e0242554. Epub 2020 Nov 24.

Heilongjiang Province Key Laboratory of Geographical Environment Monitoring and Spatial Information Service in Cold Regions, Harbin Normal University, Harbin, China.

The negative air ion (NAI) concentration is an essential indicator of air quality and atmospheric pollution. The NAI concentration can be used to monitor air quality on a regional scale and is commonly determined using field measurements. However, obtaining these measurements is time-consuming. In this paper, the relationship between remotely sensed surface parameters (such as land surface temperature, normalized difference vegetation index (NDVI), and leaf area index) obtained from MODIS data products and the measured NAI concentration using a stepwise regression method was analyzed to estimate the spatial distribution of the NAI concentration and verify the precision. The results indicated that the NAI concentration had a negative correlation with temperature, leaf area index (LAI), and gross primary production while it exhibited a positive correlation with the NDVI. The relationship between land surface temperature and the NAI concentration in the Daxing'anling region is expressed by the regression equation of y = -35.51x1 + 11206.813 (R2 = 0.6123). Additionally, the NAI concentration in northwest regions with high forest coverage was higher than that in southeast regions with low forest coverage, suggesting that forests influence the air quality and reduce the impact of environmental pollution. The proposed inversion model is suitable for evaluating the air quality in Daxing'anling and provides a reference for air quality evaluation in other areas. In the future, we will expand the quantity and distribution range of sampling points, conduct continuous observations of NAI concentrations and environmental parameters in the research areas with different land-use types, and further improve the accuracy of inversion results to analyze the spatiotemporal dynamic changes in NAI concentration and explore the possibility of expanding the application areas of NAI monitoring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242554PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685430PMC
January 2021

X-linked cellular mosaicism underlies age-dependent occurrence of seizure-like events in mouse models of CDKL5 deficiency disorder.

Neurobiol Dis 2021 01 13;148:105176. Epub 2020 Nov 13.

Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address:

CDKL5 deficiency disorder (CDD) is an infantile, epileptic encephalopathy presenting with early-onset seizures, intellectual disability, motor impairment, and autistic features. The disorder has been linked to mutations in the X-linked CDKL5, and mouse models of the disease recapitulate several aspects of CDD symptomology, including learning and memory impairments, motor deficits, and autistic-like features. Although early-onset epilepsy is one of the hallmark features of CDD, evidence of spontaneous seizure activity has only recently been described in Cdkl5-deficient heterozygous female mice, but the etiology, prevalence, and sex-specificity of this phenotype remain unknown. Here, we report the first observation of disturbance-associated seizure-like events in heterozygous female mice across two independent mouse models of CDD: Cdkl5 knockout mice and CDKL5 R59X knock-in mice. We find that both the prevalence and severity of this phenotype increase with aging, with a median onset around 28 weeks of age. Similar seizure-like events are not observed in hemizygous knockout male or homozygous knockout female littermates, suggesting that X-linked cellular mosaicism is a driving factor underlying these seizure-like events. Together, these findings not only contribute to our understanding of the effects of CDKL5 loss on seizure susceptibility, but also document a novel, pre-clinical phenotype for future therapeutic investigation.
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http://dx.doi.org/10.1016/j.nbd.2020.105176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856307PMC
January 2021

[Prenatal diagnosis and pedigree analysis of a case of Nail-patella syndrome].

Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2020 Nov;37(11):1257-1260

Changzhou Children's Hospital, Changzhou, Jiangsu 213003, China.

Objective: To carried out prenatal diagnosis and genetic analysis for a case with Nail-patella syndrome.

Methods: Based on the clinical phenotype and prenatal imaging, genetic testing and prenatal diagnosis were carried out through whole exome sequencing (WES) and Sanger sequencing.

Results: Analysis of amniotic fluid showed that the fetus has carried a heterozygous c.139+1G>T splicing site variant [Chr9(GRCh37): g.129376868G>T] of the LMX1B gene, which was verified by Sanger sequencing. The same heterozygous variant was found in the pregnant woman, her daughter and her mother but not in her husband. Searching of HGMD database showed that the c.139+1G>T was previously unreported.

Conclusion: Nail-patella syndrome is an autosomal dominant genetic disorder with various clinical manifestations. WES is helpful for its genetic and prenatal diagnosis.
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http://dx.doi.org/10.3760/cma.j.cn511374-20191218-00645DOI Listing
November 2020

CUEDC1 inhibits epithelial-mesenchymal transition via the TβRI/Smad signaling pathway and suppresses tumor progression in non-small cell lung cancer.

Aging (Albany NY) 2020 10 25;12(20):20047-20068. Epub 2020 Oct 25.

The Fourth Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.

Lung cancer remains the most lethal cancer worldwide because of its high metastasis potential. Epithelial-mesenchymal transition (EMT) is known as the first step of the metastasis cascade, but the potential regulatory mechanisms of EMT have not been clearly established. In this study, we first found that low CUEDC1 expression correlated with lymph node metastasis in non-small cell lung cancer (NSCLC) patients using immunohistochemistry (IHC). CUEDC1 knockdown promoted the metastasis of NSCLC cells and EMT process and activated TβRI/Smad signaling pathway. Overexpression of CUEDC1 decreased the metastatic potential of lung cancer cells and inhibited the EMT process and inactivated TβRI/Smad signaling pathway. Immunoprecipitation (IP) assays showed that Smurf2 is a novel CUEDC1-interacting protein. Furthermore, CUEDC1 could regulate Smurf2 expression through the degradation of Smurf2. Overexpression of Smurf2 abolished CUEDC1 knockdown induced-EMT and the activation of TβRI/Smad signaling pathway, while siRNA Smurf2 reversed CUEDC1 overexpression-mediated regulation of EMT and TβRI/Smad signaling pathway. Additionally, CUEDC1 inhibited proliferation and promoted apoptosis of NSCLC cells. , CUEDC1-knockdown cells promoted metastasis and tumor growth compared with control cells. In conclusion, our findings indicate that the crucial role of CUEDC1 in NSCLC progression and provide support for its clinical investigation for therapeutic approaches.
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http://dx.doi.org/10.18632/aging.103329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655170PMC
October 2020

Early Life Exposure to Environmental Contaminants (BDE-47, TBBPA, and BPS) Produced Persistent Alterations in Fecal Microbiome in Adult Male Mice.

Toxicol Sci 2021 01;179(1):14-30

Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA.

The gut microbiome is a pivotal player in toxicological responses. We investigated the effects of maternal exposure to 3 human health-relevant toxicants (BDE-47, tetrabromobisphenol [TBBPA], and bisphenol S [BPS]) on the composition and metabolite levels (bile acids [BAs] and short-chain fatty acids [SCFAs]) of the gut microbiome in adult pups. CD-1 mouse dams were orally exposed to vehicle (corn oil, 10 ml/kg), BDE-47 (0.2 mg/kg), TBBPA (0.2 mg/kg), or BPS (0.2 mg/kg) once daily from gestational day 8 to the end of lactation (postnatal day 21). 16S rRNA sequencing and targeted metabolomics were performed in feces of 20-week-old adult male pups (n = 14 - 23/group). Host gene expression and BA levels were quantified in liver. BPS had the most prominent effect on the beta-diversity of the fecal microbiome compared with TBPPA and BDE-47 (QIIME). Seventy-three taxa were persistently altered by at least 1 chemical, and 12 taxa were commonly regulated by all chemicals (most of which were from the Clostridia class and were decreased). The most distinct microbial biomarkers were S24-7 for BDE-47, Rikenellaceae for TBBPA, and Lactobacillus for BPS (LefSe). The community-wide contributions to the shift in microbial pathways were predicted using FishTaco. Consistent with FishTaco predictions, BDE-47 persistently increased fecal and hepatic BAs within the 12α hydroxylation pathway, corresponding to an up-regulation with the hepatic BA-synthetic enzyme Cyp7a1. Fecal BAs were also persistently up-regulated by TBBPA and BPS (liquid chromatography-mass spectrometry). TBBPA increased propionic acid and succinate, whereas BPS decreased acetic acid (gas chromatography-mass spectrometry). There was a general trend in the hepatic down-regulation of proinflammatory cytokines and the oxidative stress sensor target gene (Nqo1), and a decrease in G6Pdx (the deficiency of which leads to dyslipidemia). In conclusion, maternal exposure to these toxicants persistently modified the gut-liver axis, which may produce an immune-suppressive and dyslipidemia-prone signature later in life.
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http://dx.doi.org/10.1093/toxsci/kfaa161DOI Listing
January 2021

Omega-3 fatty acids improve flow-induced vasodilation by enhancing TRPV4 in arteries from diet-induced obese mice.

Cardiovasc Res 2020 Oct 18. Epub 2020 Oct 18.

Wuxi School of Medicine, Jiangnan University, Wuxi, China.

Aims: Previous studies have shown the intake of omega-3 polyunsaturated fatty acids are associated with low rates of obesity and ischemic pathologies. Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation.

Methods And Results: Flow-mediated vasodilation in 2nd-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4-/- mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice.

Conclusion: Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation.

Translational Perspective: Omega-3 improve the endothelial function via enhancing TRPV4 activity and augmenting the endothelial-dependent flow-induced vasodilation in DIO mice resistance arteries. This study provides a strategy of improving vascular function under obesity, namely, by targeting TRPV4 via the usage of omega-3.
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http://dx.doi.org/10.1093/cvr/cvaa296DOI Listing
October 2020

Prognostic value of baseline clinical and HRCT findings in 101 patients with severe COVID-19 in Wuhan, China.

Sci Rep 2020 10 16;10(1):17543. Epub 2020 Oct 16.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

The aim of this study was to assess the prognostic value of baseline clinical and high resolution CT (HRCT) findings in patients with severe COVID-19. In this retrospective, two-center study, we included two groups of inpatients with severe COVID-19 who had been discharged or died in Jin Yin-tan hospital and Wuhan union hospital between January 5, 2020, and February 22, 2020. Cases were confirmed by real-time polymerase chain reaction. Demographic, clinical, and laboratory data, and HRCT imaging were collected and compared between discharged and deceased patients. Univariable and multivariable logistic regression models were used to assess predictors of mortality risk in these patients. 101 patients were included in this study, of whom 66 were discharged and 35 died in the hospital. The mean age was 56.6 ± 15.1 years and 67 (66.3%) were men. Of the 101 patients, hypertension (38, 37.6%), cardiovascular disease (21,20.8%), diabetes (18,17.8%), and chronic pulmonary disease (16,15.8%) were the most common coexisting conditions. The multivariable regression analysis showed older age (OR: 1.142, 95% CI 1.059-1.231, p < 0.001), acute respiratory distress syndrome (ARDS) (OR: 10.142, 95% CI 1.611-63.853, p = 0.014), reduced lymphocyte count (OR: 0.004, 95% CI 0.001-0.306, p = 0.013), and elevated HRCT score (OR: 1.276, 95% CI 1.002-1.625, p = 0.049) to be independent predictors of mortality risk on admission in severe COVID-19 patients. These findings may have important clinical implications for decision-making based on risk stratification of severe COVID-19 patients.
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http://dx.doi.org/10.1038/s41598-020-74497-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567846PMC
October 2020

The nonparametric Behrens-Fisher problem in partially complete clustered data.

Biom J 2021 01 14;63(1):148-167. Epub 2020 Oct 14.

Dr. Bing Zhang Department of Statistics, University of Kentucky, Lexington, KY, USA.

In randomized trials or observational studies involving clustered units, the assumption of independence within clusters is not practical. Existing parametric or semiparametric methods assume specific dependence structures within a cluster. Furthermore, parametric model assumptions may not even be realistic when data are measured in a nonmetric scale as commonly happens, for example, in quality-of-life outcomes. In this paper, nonparametric effect-size measures for clustered data that allow meaningful and interpretable probabilistic comparisons of treatments or intervention programs will be introduced. The dependence among observations within a cluster can be arbitrary. Point estimators along with their asymptotic properties for computing confidence intervals and performing hypothesis test will be discussed. Small sample approximations that retain some of the optimal asymptotic behaviors will be presented. In our setup, some clusters may involve observations coming from both intervention groups (referred to as complete clusters), while others may contain observations from one group only (referred to as incomplete clusters). In deriving the asymptotic theories, we do not impose any relation in the rate of divergence of the numbers of complete and incomplete clusters. Simulations show favorable performance of the methods for arbitrary combinations of complete and incomplete clusters. The developed nonparametric methods are illustrated using data from a randomized trial of indoor wood smoke reduction to improve asthma symptoms and a cluster-randomized trial for smoking cessation.
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http://dx.doi.org/10.1002/bimj.201900310DOI Listing
January 2021

Genome-Wide Identification and Expression Analysis of the Gene Family in L. Under Various Abiotic Stresses.

DNA Cell Biol 2020 Nov 2;39(11):1976-1989. Epub 2020 Oct 2.

State Key Laboratory of Grassland Agro-Ecosystems, Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs, Engineering Research Center of Grassland Industry, Ministry of Education, College of Pastoral Agriculture Science and Technology, Lanzhou University, Lanzhou, China.

The Dof transcription factor is a plant-specific transcriptional regulator that plays important roles in plant development and acts as a mediator in plant external stress responses. However, Dofs have previously been identified in several plants but not in alfalfa ( L.), one of the most widely cultivated forage legumes. In the present study, a total of 40 genes were identified, and the phylogenetic reconstruction, classification, conserved motifs, and expression patterns under abscisic acid (ABA), cold, heat, drought and salt stresses of these genes were comprehensively analyzed. The genes family in alfalfa could be classified into eight classes. Gene ontology (GO) and tissue-specific analysis indicated that most genes may be involved in biological functions during plant growth. Moreover, the expression profiles and quantitative real-time PCR analysis indicated that eight candidate abiotic tolerance genes were induced in response to four abiotic stresses. This study identified the possibility of abiotic tolerance candidate genes playing various roles in stress resistance at the whole genome level, which would provide new information on the Dof family in alfalfa.
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http://dx.doi.org/10.1089/dna.2020.5652DOI Listing
November 2020

Quantification of myocardial strain in patients with isolated left ventricular non-compaction and healthy subjects using deformable registration algorithm: comparison with feature tracking.

BMC Cardiovasc Disord 2020 09 3;20(1):400. Epub 2020 Sep 3.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: Systolic dysfunction of the left ventricle is frequently associated with isolated left ventricular non-compaction (iLVNC). Clinically, the ejection fraction (EF) is the primary index of cardiac function. However, changes of EF usually occur later in the disease course. Feature tracking (FT) and deformable registration algorithm (DRA) have become appealing techniques for myocardial strain assessment.

Methods: Thirty patients with iLVNC (36.7 ± 13.3 years old) and fifty healthy volunteers (42.3 ± 13.6 years old) underwent cardiovascular magnetic resonance (CMR) examination on a 1.5 T MR scanner. Strain values in the radial, circumferential, longitudinal directions were analyzed based on the short-axis and long-axis cine images using FT and DRA methods. The iLVNC patients were further divided based on the ejection fraction, into EF ≥ 50% group (n = 11) and EF < 50% group (n = 19). Receiver-operating-characteristic (ROC) analysis was performed to assess the diagnostic performance of the global strain values. Intraclass correlation coefficient (ICC) analysis was used to evaluate the intra- and inter-observer agreement.

Results: Global radial strain (GRS) was statistically lower in EF ≥ 50% group compared with control group [GRS (DRA)/% vs. controls: 34.6 ± 7.0 vs. 37.6 ± 7.2, P < 0.001; GRS (FT)/% vs. controls: 37.4 ± 13.2 vs. 56.9 ± 16.4, P < 0.01]. ROC analysis of global strain values derived from DRA and FT demonstrated high area under curve (range, 0.743-0.854). DRA showed excellent intra- and inter-observer agreement of global strain in both iLVNC patients (ICC: 0.995-0.999) and normal controls (ICC: 0.934-0.996). While for FT analysis, global radial strain of normal controls showed moderate intra-observer (ICC: 0.509) and poor inter-observer agreement (ICC: 0.394).

Conclusions: In patients with iLVNC, DRA can be used to quantitatively analyze the strain of left ventricle, with global radial strain being an earlier marker of LV systolic dysfunction. DRA has better reproducibility in evaluating both the global and segmental strain.
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http://dx.doi.org/10.1186/s12872-020-01668-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469314PMC
September 2020

Effect of a Previous History of Antiretroviral Treatment on Clinical Picture of Patients with Co-infection of SARS-CoV-2 and HIV: A Preliminary Study.

Int J Infect Dis 2020 Nov 20;100:141-148. Epub 2020 Aug 20.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Rd, Wuhan 430022, Hubei, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei, China. Electronic address:

Objectives: We aimed to explore the effect of antiretroviral treatment (ART) history on clinical characteristics of patients with co-infection of SARS-CoV-2 and HIV.

Methods: We retrospectively reviewed 20 patients with laboratory-confirmed co-infection of SARS-CoV-2 and HIV in a designated hospital. Patients were divided into medicine group (n = 12) and non-medicine group (n = 8) according to previous ART history before SARS-CoV-2 infection.

Results: The median age was 46.5 years and 15 (75%) were female. Ten patients had initial negative RT-PCR on admission, 5 of which had normal CT appearance and 4 were asymptomatic. Lymphocytes were low in 9 patients (45%), CD4 cell count and CD4/CD8 were low in all patients. The predominant CT features in 19 patients were multiple (42%) ground-glass opacities (58%) and consolidations (32%). Erythrocyte sedimentation rate (ESR) in the medicine group was significantly lower than that in the non-medicine group [median (interquartile range, IQR):14.0 (10.0-34.0) vs. 51.0 (35.8-62.0), P = 0.005]. Nineteen patients (95%) were discharged with a median hospital stay of 30 days (IQR, 26-30).

Conclusions: Most patients with SARS-CoV-2 and HIV co-infection exhibited mild to moderate symptoms. The milder extent of inflammatory response to SARS-CoV-2 infection might be associated with a previous history of ART in HIV-infected patients.
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http://dx.doi.org/10.1016/j.ijid.2020.08.045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439831PMC
November 2020

Discovery of a molecular glue promoting CDK12-DDB1 interaction to trigger cyclin K degradation.

Elife 2020 08 17;9. Epub 2020 Aug 17.

National Institute of Biological Sciences, Beijing, China.

Molecular-glue degraders mediate interactions between target proteins and components of the ubiquitin-proteasome system to cause selective protein degradation. Here, we report a new molecular glue HQ461 discovered by high-throughput screening. Using loss-of-function and gain-of-function genetic screening in human cancer cells followed by biochemical reconstitution, we show that HQ461 acts by promoting an interaction between CDK12 and DDB1-CUL4-RBX1 E3 ubiquitin ligase, leading to polyubiquitination and degradation of CDK12-interacting protein Cyclin K (CCNK). Degradation of CCNK mediated by HQ461 compromised CDK12 function, leading to reduced phosphorylation of a CDK12 substrate, downregulation of DNA damage response genes, and cell death. Structure-activity relationship analysis of HQ461 revealed the importance of a 5-methylthiazol-2-amine pharmacophore and resulted in an HQ461 derivate with improved potency. Our studies reveal a new molecular glue that recruits its target protein directly to DDB1 to bypass the requirement of a substrate-specific receptor, presenting a new strategy for targeted protein degradation.
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http://dx.doi.org/10.7554/eLife.59994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462607PMC
August 2020

Evaluation and Comparison of Quantitative Right Ventricular Strain Assessment by Cardiac Magnetic Resonance in Pulmonary Hypertension Using Feature Tracking and Deformable Registration Algorithms.

Acad Radiol 2020 Jul 2. Epub 2020 Jul 2.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China. Electronic address:

Rationale And Objective: Deformable registration algorithms (DRA) has been used to detect left ventricular myocardial changes, however, its clinical utility in right ventricular (RV) function has not been evaluated. In this study, we aim to evaluate and compare quantitative RV strain assessment by cardiac magnetic resonance in pulmonary hypertension (PH) using feature tracking (FT) and DRA.

Materials And Methods: Thirty patients were confirmed to have PH using right heart catheterization, and 16 healthy controls were evaluated with cardiac magnetic resonance. Global and segmental RV strain was measured by DRA and FT methods. Intraclass correlation coefficients (ICCs), coefficient of variation, and Bland-Altman analysis were used to assess and compare the interobserver and intraobserver variability of the DRA and FT methods.

Results: DRA was more sensitive than FT in the detection of RV circumferential and septal dysfunction. The global longitudinal strain (GLS) obtained by the two methods was reduced in mild-moderate PH patients (mean pulmonary artery pressure≤45 mm Hg), and the GLS and global circumferential strain (GCS) were reduced in severe PH patients (mean pulmonary artery pressure >45 mm Hg). DRA and FT methods demonstrate similar observer agreement in global strain using ICC (ICC greater than 0.90), but RV strain derived from DRA had lower variability using COV ([8%-14%] for DRA versus [11%-39%] for FT).For segmental longitudinal strain, DRA showed higher ICC and lower COV compared with that of the FT method. Correlations between RVEF and RV global strain parameters were strong (p < 0.01):GLS-DRA, r = -0.696; GLS-FT, r = -0.832; GCS-DRA, r = -0.745; and GCS-FT, r = -0.817. GLS-DRA was weakly correlated with mPAP (r = 0.385, p < 0.05).In multiple linear regression analysis, RVEF and mPAP were independent predictors of GLS-DRA (R = 0.57, p < 0.01).

Conclusions: The DRA method is more sensitive and robust for RV myocardial strain measurements than FT method.
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http://dx.doi.org/10.1016/j.acra.2020.06.015DOI Listing
July 2020

Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: A retrospective study.

Diabetes Res Clin Pract 2020 Aug 3;166:108299. Epub 2020 Jul 3.

Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, China. Electronic address:

Aims: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes.

Methods: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11 mmol/L (group 1) and >11 mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications.

Results: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.2%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 μg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively.

Conclusions: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11 mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.
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http://dx.doi.org/10.1016/j.diabres.2020.108299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332424PMC
August 2020
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