Publications by authors named "Kan Liu"

250 Publications

Spatio-temporal hybrid neural networks reduce erroneous human "judgement calls" in the diagnosis of Takotsubo syndrome.

EClinicalMedicine 2021 Oct 4;40:101115. Epub 2021 Sep 4.

Division of Cardiology, Department of Medicine, University of Iowa, Iowa City, IA, United States.

Background: We investigate whether deep learning (DL) neural networks can reduce erroneous human "judgment calls" on bedside echocardiograms and help distinguish Takotsubo syndrome (TTS) from anterior wall ST segment elevation myocardial infarction (STEMI).

Methods: We developed a single-channel (DCNN[2D SCI]), a multi-channel (DCNN[2D MCI]), and a 3-dimensional (DCNN[2D+]) deep convolution neural network, and a recurrent neural network (RNN) based on 17,280 still-frame images and 540 videos from 2-dimensional echocardiograms in 10 years (1 January 2008 to 1 January 2018) retrospective cohort in University of Iowa (UI) and eight other medical centers. Echocardiograms from 450 UI patients were randomly divided into training and testing sets for internal training, testing, and model construction. Echocardiograms of 90 patients from the other medical centers were used for external validation to evaluate the model generalizability. A total of 49 board-certified human readers performed human-side classification on the same echocardiography dataset to compare the diagnostic performance and help data visualization.

Findings: The DCNN (2D SCI), DCNN (2D MCI), DCNN(2D+), and RNN models established based on UI dataset for TTS versus STEMI prediction showed mean diagnostic accuracy 73%, 75%, 80%, and 75% respectively, and mean diagnostic accuracy of 74%, 74%, 77%, and 73%, respectively, on the external validation. DCNN(2D+) (area under the curve [AUC] 0·787 vs. 0·699,  = 0·015) and RNN models (AUC 0·774 vs. 0·699,  = 0·033) outperformed human readers in differentiating TTS and STEMI by reducing human erroneous judgement calls on TTS.

Interpretation: Spatio-temporal hybrid DL neural networks reduce erroneous human "judgement calls" in distinguishing TTS from anterior wall STEMI based on bedside echocardiographic videos.

Funding: University of Iowa Obermann Center for Advanced Studies Interdisciplinary Research Grant, and Institute for Clinical and Translational Science Grant. National Institutes of Health Award (1R01EB025018-01).
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http://dx.doi.org/10.1016/j.eclinm.2021.101115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426197PMC
October 2021

Sex differences in cardiovascular adaptations in recreational marathon runners.

Eur J Appl Physiol 2021 Sep 13. Epub 2021 Sep 13.

Department of Exercise Science, Syracuse University, Syracuse, NY, USA.

Introduction: There are well-established sex differences in central hemodynamic and cardiac adaptations to endurance exercise; however, controversial evidence suggests that excessive endurance exercise may be related to detrimental cardiovascular adaptations in marathoners.

Purpose: To examine left ventricle (LV) structure, LV function, 24-h central hemodynamics and ventricular-vascular coupling in male and female marathoners and recreationally active adults.

Methods: 52 marathoners (41 ± 5 years, n = 28 female, completed 6 ± 1 marathons/3 years) and 49 recreationally active controls (42 ± 5 years, n = 25 female) participated in the study. Three-Dimensional Echocardiography (3DE) was used to measure LV mass index and LV longitudinal (LS) circumferential (CS), area (AS), and radial strain (RS). An ambulatory blood pressure (BP) cuff was used to measure 24-h central hemodynamics (BP, pulse wave velocity, PWV, wave reflection index, RIx). Hemodynamic and 3DE measures were combined to derive the ratio of arterial elastance (Ea) to ventricular elastance (Elv) as a global measure of ventricular-vascular coupling.

Results: There were no sex or group differences in LS, CS, AS, and RS (p > 0.05). Females marathoners had similar aortic BP (116 ± 9 vs. 113 ± 1 mmHg), and PWV (5.9 ± 0.5 vs. 5.9 ± 1.1 m/s) compared to female controls but lower aSBP (116 ± 9 vs. 131 ± 10 mmHg) and PWV (5.9 ± 0.5 vs. 6.2 ± 0.5 m/s) compared to male marathoners (p < 0.05). Female marathoners had lower Ea/Elv than female controls (0.67 ± 0.20 vs. 0.93 ± 0.36) and male marathoners (0.67 ± 0.20 vs. 0.85 ± 0.42, p < 0.05).

Conclusions: Women that have completed multiple marathons do not have reduced LV function or increased aortic stiffness and may have better ventricular-vascular coupling compared to male marathoners and their female untrained counterparts.
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http://dx.doi.org/10.1007/s00421-021-04806-1DOI Listing
September 2021

Precise and convenient size barcode on microfluidic chip for multiplex biomarker detection.

Analyst 2021 Aug 31. Epub 2021 Aug 31.

School of Electronic and Electrical Engineering, Wuhan Textile University, Wuhan 430200, People's Republic of China.

The existing multiplex biomarker detection methods are limited by the high demand for coding material and expensive detection equipment. This paper proposes a convenient and precise coding method based on a wedge-shaped microfluidic chip, which can be further applied in multiplex biomarker detection. The proposed microfluidic chip has a microchannel with continuously varying height, which can naturally separate and code microparticles of different sizes. Our data indicate that this method can be applied to code more than 5 or 7 kinds of microparticles, even when their size discrepancies are smaller than 1 μm. Based on these, multiplex biomarker detection can be implemented by using microparticles of different sizes, hence each kind of microparticle that coats one kind of antibody represents the species of targets. This method is simple and easy to operate, with no clogging or sophisticated coding design, showing its significant potential in the area of point-of-care tests (POCT).
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http://dx.doi.org/10.1039/d1an01265gDOI Listing
August 2021

Detection of mitochondrial coupling factor 6 in placental tissues from preeclamptic pregnancies and its influence on biological behavior of trophoblast cells.

Exp Ther Med 2021 Oct 16;22(4):1185. Epub 2021 Aug 16.

Department of Gynecology and Obstetrics, Henan Provincial People's Hospital, Zhengzhou, Henan 450000, P.R. China.

Increased levels of mitochondrial coupling factor 6 (CF6) are present in the peripheral blood of patients with preeclamptic pregnancies, and are particularly evident in cases of early-onset or severe preeclampsia. The present study examined the location and expression levels of CF6 in the placental tissue and its effect on the biological behavior of trophoblast cells. Placental tissue microarrays, including placental villous cytotrophoblast and extravillous cytotrophoblast microarrays, were used to detect the location and relative expression levels of CF6 in the placenta using immunohistochemistry. It was found that CF6 was expressed in both the normal and preeclamptic placenta, but its levels were higher in the preeclamptic tissues. In addition, the effects of the hypoxic environment on the biological behaviors of trophoblast cells were investigated in the JAR and JEG-3 cell lines. Following induction of hypoxia, the expression levels of CF6 were increased. Moreover, exogenous addition of human recombinant CF6 attenuated cell invasion, but exerted no effect on cell proliferation. At the molecular level, the expression levels of MMP-2 were decreased and were accompanied with a reduction in cell invasion following addition of exogenous CF6. In conclusion, the increased expression levels of CF6 and its effects in reducing the invasive abilities of trophoblast cells may be involved in the pathogenesis of severe preeclampsia.
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http://dx.doi.org/10.3892/etm.2021.10619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406808PMC
October 2021

Serrate-Associated Protein 1, a splicing-related protein, promotes miRNA biogenesis in Arabidopsis.

New Phytol 2021 Aug 27. Epub 2021 Aug 27.

School of Biological Sciences & Center for Plant Science Innovation, University of Nebraska-Lincoln, Lincoln, NE, 68588-0666, USA.

MicroRNAs (miRNAs) are essential regulators of gene expression in metazoans and plants. In plants, most miRNAs are generated from primary miRNA transcripts (pri-miRNAs), which are processed by the Dicer-like 1 (DCL1) complex along with accessory proteins. Serrate-Associated Protein 1 (SEAP1), a conserved splicing-related protein, has been studied in human and yeast. However, the functions of SEAP1 in plants remain elusive. Lack of SEAP1 results in embryo lethality and knockdown of SEAP1 by an artificial miRNA (amiR ) causes pleiotropic developmental defects and reduction in miRNA accumulation. SEAP1 associates with the DCL1 complex, and may promote the interaction of the DCL1 complexes with pri-miRNAs. SEAP1 also enhances pri-miRNA accumulation, but does not affect pri-miRNA transcription, suggesting it may indirectly or directly stabilize pri-miRNAs. In addition, SEAP1 affects the splicing of some pri-miRNAs and intron retention of messenger RNAs at global levels. Our findings uncover both conserved and novel functions of SEAP1 in plants. Besides the role as a splicing factor, SEPA1 may promote miRNA biogenesis by positively modulating pri-miRNA splicing, processing and/or stability.
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http://dx.doi.org/10.1111/nph.17691DOI Listing
August 2021

Detection of hypertrophic cardiomyopathy by an artificial intelligence electrocardiogram in children and adolescents.

Int J Cardiol 2021 Oct 19;340:42-47. Epub 2021 Aug 19.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America; Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN, United States of America; Department of Molecular Pharmacology & Experimental Therapeutics; Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic, Rochester, MN, United States of America. Electronic address:

Background: There is no established screening approach for hypertrophic cardiomyopathy (HCM). We recently developed an artificial intelligence (AI) model for the detection of HCM based on the 12‑lead electrocardiogram (AI-ECG) in adults. Here, we aimed to validate this approach of ECG-based HCM detection in pediatric patients (age ≤ 18 years).

Methods: We identified a cohort of 300 children and adolescents with HCM (mean age 12.5 ± 4.6 years, male 68%) who had an ECG and echocardiogram at our institution. Patients were age- and sex-matched to 18,439 non-HCM controls. Diagnostic performance of the AI-ECG model for the detection of HCM was estimated using the previously identified optimal diagnostic threshold of 11% (the probability output derived by the model above which an ECG is considered to belong to an HCM patient).

Results: Mean AI-ECG probabilities of HCM were 92% and 5% in the case and control groups, respectively. The area under the receiver operating characteristic curve (AUC) of the AI-ECG model for HCM detection was 0.98 (95% CI 0.98-0.99) with corresponding sensitivity 92% and specificity 95%. The positive and negative predictive values were 22% and 99%, respectively. The model performed similarly in males and females and in genotype-positive and genotype-negative HCM patients. Performance tended to be superior with increasing age. In the age subgroup <5 years, the test's AUC was 0.93. In comparison, the AUC was 0.99 in the age subgroup 15-18 years.

Conclusions: A deep-learning, AI model can detect pediatric HCM with high accuracy from the standard 12‑lead ECG.
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http://dx.doi.org/10.1016/j.ijcard.2021.08.026DOI Listing
October 2021

Kinetic Constraints in the Specific Interaction between Phosphorylated Ubiquitin and Proteasomal Shuttle Factors.

Biomolecules 2021 07 10;11(7). Epub 2021 Jul 10.

Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, China.

Ubiquitin (Ub) specifically interacts with the Ub-associating domain () in a proteasomal shuttle factor, while the latter is involved in either proteasomal targeting or self-assembly coacervation. PINK1 at S65 and makes Ub alternate between C-terminally relaxed () and retracted conformations (). Using NMR spectroscopy, we show that but not preferentially interacts with the from two proteasomal shuttle factors Ubqln2 and Rad23A. Yet discriminatorily, Ubqln2- binds to more tightly than Rad23A does and selectively enriches upon complex formation. Further, we determine the solution structure of the complex between Ubqln2- and and uncover the thermodynamic basis for the stronger interaction. NMR kinetics analysis at different timescales further suggests an indued-fit binding mechanism for interaction. Notably, at a relatively low saturation level, the dissociation rate of the complex is comparable with the exchange rate between and . Thus, a kinetic constraint would dictate the interaction between Ub and , thus fine-tuning the functional state of the proteasomal shuttle factors.
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http://dx.doi.org/10.3390/biom11071008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301994PMC
July 2021

Fasting plasma glucose in the first trimester is related to gestational diabetes mellitus and adverse pregnancy outcomes.

Endocrine 2021 Aug 3. Epub 2021 Aug 3.

Department of Obstetrics, Shenzhen Maternity & Child Healthcare Hospital, The First School of Clinical Medicine, Southern Medical University, Hongli Road, Futian District, Shenzhen, Guangdong Province, China.

Purpose: To investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population.

Methods: We used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities.

Results: The mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P < 0.05). The univariate analysis showed that first-trimester FPG was strongly associated with risks of outcomes including GDM, cesarean section, macrosomia, GHD, primary cesarean section, and LGA (all OR > 1, all P < 0.05), furthermore, the risks of GDM, primary cesarean section, and LGA was increasing with first-trimester FPG as early as it was at 4.19-4.63 mmol/L. The multivariable analysis showed that the risks of GDM (ORs for FPG 4.19-4.63, 4.63-5.11 and 5.11-7.0 mmol/L were 1.137, 1.592, and 4.031, respectively, all P < 0.05) increased as early as first-trimester FPG was at 4.19-4.63 mmol/L, and first-trimester FPG which was also associated with the risks of cesarean section, macrosomia and LGA (OR for FPG 5.11-7.0 mmol/L of cesarean section: 1.128; OR for FPG 5.11-7.0 mmol/L of macrosomia: 1.561; OR for FPG 4.63-5.11 and 5.11-7.0 mmol/L of LGA: 1.149 and 1.426, respectively, all P < 0.05) and with its increasing, the risks of LGA increased. Furthermore, the nomogram had a C-indices 0.771(95% CI: 0.763~0.779) and 0.770(95% CI:0.758~0.781) in training and testing validation respectively, which showed an acceptable consistency between the observed, validation and nomogram-predicted probabilities, the DAC curve analysis indicated that the nomogram had important clinical application value for GDM risk prediction.

Conclusions: FPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.
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http://dx.doi.org/10.1007/s12020-021-02831-wDOI Listing
August 2021

SQLE Mediates Metabolic Reprogramming to Promote LN Metastasis in Castration-Resistant Prostate Cancer.

Onco Targets Ther 2021 24;14:4285-4295. Epub 2021 Jul 24.

Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital, Changsha, 410013, Hunan, People's Republic of China.

Background: Almost all metastatic hormone-sensitive prostate cancers (mHSPC) will develop into metastatic castration-resistant prostate cancer (mCRPC) after androgen deprivation therapy (ADT). The expression level of squalene monooxygenase (SQLE) is increased in CRPC cells and regulates cholesterol metabolism. This study verified the biological function and mechanisms of SQLE in CRPC.

Methods: The expression of SQLE in human prostate cancer cells was overexpressed or silenced and its efficacy on cell survival was determined by the MTS test. Energy metabolism phenotype test was evaluated by XF real-time ATP rate assay, XF cell mitochondrial stress test, XF glycolysis stress test and XF mito fuel flex test. Cell migration and invasion were evaluated by colony formation assays and transwell assays; the expression of mRNA and protein was assessed by RT-qPCR and Western blot, respectively. Moreover, BALB/c nude mice model was performed to evaluate the lymph node metastasis.

Results: In our study, we found that the expression level of SQLE was significantly increased in bicalutamide-resistant-C4-2B cells compared to LNCaP cells. SQLE knockdown partly restored the sensitivity of drug-resistant cells to bicalutamide and reduced lymph node metastasis by inhibiting fatty acid oxidation in mitochondria. We also found that terbinafine, the specific inhibitor of SQLE, can enhance the sensitivity of prostate cancer cells to bicalutamide.

Conclusion: Our study revealed that SQLE is involved in the progression of castration resistance in CRPC through mediating metabolic reprogramming, presenting SQLE as a new target for the treatment of mCRPC.
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http://dx.doi.org/10.2147/OTT.S315813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318010PMC
July 2021

Impact of Atrial Fibrillation on Outcome in Takotsubo Syndrome: Data From the International Takotsubo Registry.

J Am Heart Assoc 2021 Aug 28;10(15):e014059. Epub 2021 Jul 28.

Department of Cardiology Intensive Care Medicine and Angiology Vincentius-Diakonissen-Hospital Karlsruhe Germany.

Background Atrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS. Methods and Results Patients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher (<0.001), and there were fewer women (=0.046) in the AF than in the non-AF group. Left ventricular ejection fraction was significantly lower (=0.001), and cardiogenic shock was more often observed (<0.001) in the AF group. Both in-hospital (<0.001) and long-term mortality (<0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long-term mortality (hazard ratio, 2.31; 95% CI, 1.50-3.55; <0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in-hospital and long-term outcomes compared with those with a history of AF. Conclusions In patients presenting with TTS, AF on admission is significantly associated with increased in-hospital and long-term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01947621.
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http://dx.doi.org/10.1161/JAHA.119.014059DOI Listing
August 2021

Genomic Landscape of Chinese Clear Cell Renal Cell Carcinoma Patients With Venous Tumor Thrombus Identifies Chromosome 9 and 14 Deletions and Related Immunosuppressive Microenvironment.

Front Oncol 2021 23;11:646338. Epub 2021 Jun 23.

Department of Urology, The Third Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing, China.

Background: Clear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is associated with a poor clinical outcome. Although several studies have examined the genomic features of ccRCC, the genetic profile of VTT along with its matched primary tumor has not been fully elucidated.

Materials And Methods: Samples of VTT tissues and matched primary tumor tissues from ccRCC patients (n = 25), as well as primary tumor tissues from patients without VTT (n = 25) were collected and analyzed using whole-exome sequencing. Four additional ccRCC patients who were unfit for surgery were treated with an anti-programmed death receptor-1 (PD-1) monoclonal antibody (Toripalimab, 240 mg, Q3W, IV).

Results: By comparing the primary kidney tumors from ccRCC patients with or without VTT, a relatively higher prevalence of alterations were found in ccRCC patients with VTT, and these alterations were associated with worse overall survival in the kidney renal clear cell carcinoma (KIRC) database. Based on subclone analysis, VTT was predicted to primarily originate directly from the primary renal mass. A significantly higher prevalence of and alterations were identified in the VTTs compared with the matched primary tumors. An increased prevalence of DNA damage repair genes, especially those involved in homologous recombination repair and non-homologous end joining, was found in ccRCC patients with VTT. Notably, VTT was characterized by the increase incidence of copy number loss in the whole exome ( < 0.05), particularly in the chromosome 9 and 14 regions. Deletion of chromosome 9 and 14 was associated with worse survival, unfavorable clinical features, and the presence of an immunosuppressive microenvironment, which was characterized by higher infiltration of regulatory T cells, follicular helper T cells, and resting mast cells, but lower counts of resting CD4 memory T cells and CD8 positive T cells. A significantly lower count of CD4+ and CD8+ tumor-infiltrated lymphocytes was identified in the VTT samples comparing with matched primary tumor. Of note, three out of the four ccRCC patients with VTT in our cohort who were treated with the anti-PD-1 therapy exhibited remarkable remission in the renal mass but no notable shrinkage in the VTT mass.

Conclusion: Our study revealed the genetic profile of Chinese ccRCC patients with VTT, and identified multiple features associated with known poor outcomes, including gene alterations and copy number loss. The deletions in chromosomes 9 and 14, and the associated immunosuppressive microenvironment may indicate limited sensitivity to anti-PD-1/PD-L1 monotherapy in VTT.
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http://dx.doi.org/10.3389/fonc.2021.646338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260842PMC
June 2021

Androgen Receptor, Although Not a Specific Marker For, Is a Novel Target to Suppress Glioma Stem Cells as a Therapeutic Strategy for Glioblastoma.

Front Oncol 2021 21;11:616625. Epub 2021 May 21.

Department of Radiation Oncology, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, United States.

Targeting androgen receptor (AR) has been shown to be promising in treating glioblastoma (GBM) in cell culture and flank implant models but the mechanisms remain unclear. AR antagonists including enzalutamide are available for treating prostate cancer patients in clinic and can pass the blood-brain barrier, thus are potentially good candidates for GBM treatment but have not been tested in GBM orthotopically. Our current studies confirmed that in patients, a majority of GBM tumors overexpress AR in both genders. Enzalutamide inhibited the proliferation of GBM cells both and . Although confocal microscopy demonstrated that AR is expressed but not specifically in glioma cancer stem cells (CSCs) (CD133+), enzalutamide treatment significantly decreased CSC population in cultured monolayer cells and spheroids, suppressed tumor sphere-forming capacity of GBM cells, and downregulated CSC gene expression at mRNA and protein levels in a dose- and time-dependent manner. We have, for the first time, demonstrated that enzalutamide treatment decreased the density of CSCs and improved survival in an orthotopic GBM mouse model. We conclude that AR antagonists potently target glioma CSCs in addition to suppressing the overall proliferation of GBM cells as a mechanism supporting their repurposing for clinical applications treating GBM.
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http://dx.doi.org/10.3389/fonc.2021.616625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175980PMC
May 2021

Gastric cancer with repeated metastasis in the colonic lumen: a case report and multi-surgical experience.

J Int Med Res 2021 May;49(5):3000605211018420

Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Poorly differentiated gastric adenocarcinoma is commonly associated with lymph node metastasis, peritoneal spread, and liver metastasis but rarely with intraintestinal metastasis. Most patients with metastatic gastric carcinoma are unable to undergo surgical treatment and have a poor prognosis. A 42-year-old man with hunger-related abdominal pain was diagnosed as having gastric cancer. After the first surgery (distal partial gastrectomy) and the second surgery (gastric stump carcinoma (GSC) resection), the patient suffered repeated multiple intracolonic metastases and underwent three additional resection operations. The patient survived for 154 months after the first operation. In patients with gastric carcinoma that metastasizes to the colonic lumen, radical resection, if possible, can extend survival. Once patients develop extensive extraintestinal metastasis, radical resection cannot be performed, and patients often exhibit a poor prognosis.
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http://dx.doi.org/10.1177/03000605211018420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168037PMC
May 2021

A Risk Signature with Autophagy-Related Long Noncoding RNAs for Predicting the Prognosis of Clear Cell Renal Cell Carcinoma: Based on the TCGA Database and Bioinformatics.

Dis Markers 2021 7;2021:8849977. Epub 2021 May 7.

Department of Urology, The Third Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Beijing 100853, China.

Background: Disorders of autophagic processes have been reported to affect the survival outcome of clear cell renal cell carcinoma (ccRCC) patients. The purpose of our study was to identify and validate the candidate prognostic long noncoding RNA signature of autophagy.

Methods: Transcriptome profiles were obtained from The Cancer Genome Atlas. The autophagy gene list was obtained from the Human Autophagy Database. Based on coexpression analysis, we obtained a list of autophagy-related lncRNAs (ARlncRNAs). GO enrichment analysis and KEGG pathway analysis were conducted to explore the functional annotation of these ARlncRNAs. Univariate and multivariate Cox regression analyses were conducted to elucidate the correlation between overall survival and the expression level of each ARlncRNAs. We then established a prognostic signature that was a linear combination of the regression coefficients from the multivariate Cox regression model () multiplied by the expression levels of the respective ARlncRNAs in the training cohort. The predictive performance was tested in the validation cohort. Additionally, the independence of the risk signature was assessed, and the relationship between the risk signature and conventional clinicopathological features was explored.

Results: Seven autophagy-related lncRNAs with prognostic value (SNHG3, SNHG17, MELTF-AS1, HOTAIRM1, EPB41L4A-DT, AP003352.1, and AC145423.2) were identified and integrated into a risk signature, dividing patients into low-risk and high-risk groups. The risk signature was independent of conventional clinical characteristics as a prognostic indicator of ccRCC (HR, 1.074, 95% confidence interval: 1.036-1.113, < 0.001) and was valuable in the prediction of ccRCC progression.

Conclusion: Our risk signature has potential prognostic value in ccRCC, and these ARlncRNAs may play a significant role in ccRCC tumor biology.
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http://dx.doi.org/10.1155/2021/8849977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121606PMC
May 2021

Endoplasmic reticulum stress pathway mediates the early heat stress response of developing rice seeds.

Plant Cell Environ 2021 Aug 6;44(8):2604-2624. Epub 2021 Jun 6.

Department of Agronomy and Horticulture, University of Nebraska-Lincoln, Lincoln, Nebraska, USA.

A transient heat stress occurring during early seed development in rice (Oryza sativa) reduces seed size by altering endosperm development. However, the relationship between the timing of the stress and specific developmental stage on heat sensitivity is not well-understood. To address this, we imposed a series of non-overlapping heat stress treatments and found that young seeds are most sensitive during the first two days after flowering. Temporal transcriptome analysis of developing, heat stressed (35°C) seeds during this window shows that Inositol-requiring enzyme 1 (IRE1)-mediated endoplasmic reticulum (ER) stress response and jasmonic acid (JA) pathways are the early (1-3 h) drivers of heat stress response. We propose that increased JA levels under heat stress may precede ER stress response as JA application promotes the spliced form of OsbZIP50, an ER response marker gene linked to IRE1-specific pathway. This study presents temporal and mechanistic insights into the role of JA and ER stress signalling during early heat stress response of rice seeds that impact both grain size and quality. Modulating the heat sensitivity of the early sensing pathways and downstream endosperm development genes can enhance rice resilience to transient heat stress events.
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http://dx.doi.org/10.1111/pce.14103DOI Listing
August 2021

Endoplasmic reticulum stress promotes epithelial‑mesenchymal transition via the PERK signaling pathway in paraquat‑induced pulmonary fibrosis.

Mol Med Rep 2021 07 26;24(1). Epub 2021 May 26.

Department of Critical Care Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 201620, P.R. China.

Pulmonary fibrosis is the primary reason for mortality in patients with paraquat (PQ) poisoning. Our previous study demonstrated that epithelial‑mesenchymal transition (EMT) had a role in PQ‑induced pulmonary fibrosis. However, the role of endoplasmic reticulum (ER) stress in PQ‑induced EMT remains clear. The present study aimed to determine the role of ER stress in EMT in PQ‑induced pulmonary fibrosis. A549 and RLE‑6TN cells were incubated with LY294002 (a PI3K inhibitor) or transfected with protein kinase RNA‑like ER kinase (PERK) small interfering RNA (si) for 24 h prior to being exposed to PQ. Next, the expression levels of ER stress‑related proteins, PI3K/AKT/GSK‑3β signaling pathway‑related proteins and EMT‑related markers were analyzed by performing western blotting, reverse transcription‑quantitative PCR and immunofluorescence assays. The results of the present study revealed that the protein expression levels of PERK, phosphorylated (p)‑PERK, p‑eukaryotic initiation factor 2 (eIF2)α were significantly upregulated in the PQ group, whereas p‑PI3K, p‑AKT and p‑GSK‑3β were significantly upregulated in the sicontrol + PQ group compared with the sicontrol group. , following transfection with siPERK or treatment with the PI3K inhibitor, the protein expression levels of E‑cadherin (an epithelial marker) were upregulated, whereas the protein expression levels of α‑SMA (a mesenchymal marker) were downregulated. Immunofluorescence analysis revealed that the levels of E‑cadherin were markedly upregulated, whereas the levels of α‑SMA were notably downregulated following transfection with siPERK compared with the sicontrol group. The results of wound healing assay demonstrated that cell migration in the siPERK + PQ group was markedly decreased compared with the sicontrol + PQ group. These indicated that PQ‑induced EMT was suppressed after silencing PERK. The expression levels of p‑GSK‑3β, p‑AKT and p‑PI3K were also markedly downregulated in the siPERK + PQ group compared with the sicontrol + PQ group. In conclusion, the findings of the present study suggested that ER stress may promote EMT through the PERK signaling pathway in PQ‑induced pulmonary fibrosis. Thus, ER stress may represent a potential therapeutic target for PQ‑induced pulmonary fibrosis.
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http://dx.doi.org/10.3892/mmr.2021.12164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170262PMC
July 2021

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry.

Clin Res Cardiol 2021 May 19. Epub 2021 May 19.

Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.

Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes.

Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients.

Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients.

Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.

Trial Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621.
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http://dx.doi.org/10.1007/s00392-021-01857-4DOI Listing
May 2021

Activation of GCN2 in macrophages promotes white adipose tissue browning and lipolysis under leucine deprivation.

FASEB J 2021 06;35(6):e21652

CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Innovation Center for Intervention of Chronic Disease and Promotion of Health, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

We have previously shown that leucine deprivation stimulates browning and lipolysis in white adipose tissue (WAT), which helps to treat obesity. Adipose tissue macrophages (ATMs) significantly influence WAT browning and lipolysis. However, it is unclear whether ATMs are involved in leucine deprivation-induced browning and lipolysis in WAT; the associated signals remain to be elucidated. Here, we investigated the role of ATMs and the possible mechanisms involved in WAT browning and lipolysis under leucine-deprivation conditions. In this study, macrophages were depleted in mice by injecting clodronate-liposomes (CLOD) into subcutaneous white adipose tissues. Then, mice lacking general control nonderepressible 2 kinase (GCN2), which is a sensor of amino acid starvation, specifically in Lyz2-expressing cells, were generated to investigate the changes in leucine deprivation-induced WAT browning and lipolysis. We found leucine deprivation decreased the accumulation and changed the polarization of ATMs. Ablation of macrophages by CLOD impaired WAT browning and lipolysis under leucine-deprivation conditions. Mechanistically, leucine deprivation activated GCN2 signals in macrophages. Myeloid-specific abrogation of GCN2 in mice blocked leucine deprivation-induced browning and lipolysis in WAT. Further analyses revealed that GCN2 activation in macrophages reduced the expression of monoamine oxidase A (MAOA), resulting in increased norepinephrine (NE) secretion from macrophages to adipocytes, and this resulted in enhanced WAT browning and lipolysis. Moreover, the injection of CL316,243, a β3-adrenergic receptor agonist, and inhibition of MAOA effectively increased the level of NE, leading to the enhancement of browning and lipolysis of WAT in myeloid GCN2 knockout mice under leucine deprivation. Collectively, our results demonstrate a novel function of GCN2 signals in macrophages, that is, regulating WAT browning and lipolysis under leucine deprivation. Our study provides important hints for possible treatment for obesity.
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http://dx.doi.org/10.1096/fj.202100061RRDOI Listing
June 2021

Excess fibronectin 1 participates in pathogenesis of pre-eclampsia by promoting apoptosis and autophagy in vascular endothelial cells.

Mol Hum Reprod 2021 05;27(6)

Department of Obstetrical, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Plasma fibronectin 1 (FN1) levels are elevated in individuals with pre-eclampsia (PE), which may be applied as a possible b marker for vascular endothelial injury during PE. In the present study, the possible role of FN1 in the pathogenesis of PE and regulation of apoptosis and autophagy in vascular endothelial cells was explored. Plasma FN1 levels in 80 patients with PE and 40 healthy pregnant individuals were measured using ELISA to verify its relationship with the severity of PE. pcDNA3.1-FN1 or FN1-small interfering (si) RNA was used to manipulate the expression of FN1 in human umbilical vein endothelial cells (HUVECs) to assess the effects of FN1 on cell apoptosis, autophagy, and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway. It was found that upregulation of FN1 promoted apoptosis and autophagy, in addition to significantly inhibiting the activation of AKT and mTOR in HUVECs. By contrast, downregulation of FN1 expression inhibited cell apoptosis and autophagy, but increased AKT and mTOR phosphorylation in HUVECs that were cultured in serum samples obtained from patients with PE. Rescue experiments found that the PI3K/AKT inhibitor LY294002 reversed the effects of FN1-siRNA on apoptosis and autophagy in HUVECs cultured in serum from patients with PE. Therefore, data from the present study suggest that FN1 participates in the pathogenesis of PE by promoting apoptosis and autophagy in vascular endothelial cells, which is associated with the PI3K/AKT/mTOR signaling pathway.
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http://dx.doi.org/10.1093/molehr/gaab030DOI Listing
May 2021

Anlotinib in the treatment of advanced hepatocellular carcinoma: an open-label phase II study (ALTER-0802 study).

Hepatol Int 2021 Jun 7;15(3):621-629. Epub 2021 Apr 7.

Department of Medical Imaging, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People's Republic of China.

Purpose: This study aimed to assess efficacy and safety of anlotinib as a first- or second-line treatment for advanced or metastatic hepatocellular carcinoma (aHCC) and to identify the predictive plasma cytokines on efficacy of anlotinib.

Methods: It was a phase II clinical study. Patients with aHCC were recruited from October 2016 to April 2019 and divided into two cohorts according to previous tyrosine kinase inhibitors (TKIs) therapy. Those without or with prior TKIs were in Cohort 1 or 2, respectively. All patients took anlotinib (12 mg/day, Day1-14, 3 weeks per cycle). The primary endpoint was 12-week progression-free survival (PFS) rate. Relationship between the series plasma cytokine level and the efficacy of anlotinib was analyzed.

Results: Enrolled 26 patients in Cohort 1 and 24 in Cohort 2. In Cohort 1, the 12-week PFS rate was 80.8% [95% confidence interval (CI); 59.8%-91.5%] and median time to progression (TTP) was 5.9 months (95% CI 4.8-6.9). In Cohort 2, the 12-week PFS rate and median TTP was 72.5% (95% CI 48.7%-86.6%) and 4.6 months (95% CI 2.7-10.0), respectively. The median TTP on patients with a baseline plasma level of CXCL1 (C-X-C motif chemokine ligand 1) less than 7.6 ng/μl was significantly longer in both cohorts. The most common grade 3-5 adverse events were hypertension (8%), diarrhea (8%) and hand-foot syndrome (6%).

Conclusion: Anlotinib showed promising efficacy and safety as a first- or second-line treatment with a continuous TKIs treatment strategy in aHCC. The plasma CXCL1 might be a predictor for the efficacy of anlotinib.
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http://dx.doi.org/10.1007/s12072-021-10171-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286948PMC
June 2021

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

ESC Heart Fail 2021 06 13;8(3):1924-1932. Epub 2021 Mar 13.

Department of Cardiology, Charité, Campus Rudolf Virchow, Berlin, Germany.

Aims: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes.

Methods And Results: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002).

Conclusions: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.
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http://dx.doi.org/10.1002/ehf2.13165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120351PMC
June 2021

Effect of Emergency Department Care Bundle on Elderly Patients With Acute Heart Failure.

Authors:
Kan Liu

JAMA 2021 03;325(10):1007

Division of Cardiology and Heart and Vascular Center, University of Iowa, Iowa City.

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http://dx.doi.org/10.1001/jama.2020.27291DOI Listing
March 2021

Giotto: a toolbox for integrative analysis and visualization of spatial expression data.

Genome Biol 2021 03 8;22(1):78. Epub 2021 Mar 8.

Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA.

Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing tissue composition, spatial expression patterns, and cellular interactions. Furthermore, single-cell RNAseq data can be integrated for spatial cell-type enrichment analysis. The visualization module allows users to interactively visualize analysis outputs and imaging features. To demonstrate its general applicability, we apply Giotto to a wide range of datasets encompassing diverse technologies and platforms.
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http://dx.doi.org/10.1186/s13059-021-02286-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938609PMC
March 2021

Prognostic role of bland thrombus in patients treated with resection of renal cell carcinoma with inferior vena cava tumor thrombus.

Urol Oncol 2021 05 5;39(5):302.e1-302.e7. Epub 2021 Mar 5.

Medical School of Chinese PLA, Beijing 100853, China.; Department of Urology/State Key Laboratory of Kidney Diseases, the First Medical Center, Chinese PLA General Hospital, Beijing 100853. Electronic address:

Objectives: To assess the impact of the presence of bland thrombus (BT) on prognosis of patients treated with resection of renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVCTT).

Materials And Methods: The medical records of a total of 145 consecutive postsurgical RCC patients with level I-IV IVCTT were reviewed from January 2008 to August 2018. Associations of BT with clinicopathological variables were estimated by chi-square test or Student's t-test. Kaplan-Meier method and multivariate Cox proportional hazard model were used. The eighth TNM staging system, "Spiess PE" model, University of California at Los Angeles Integrated Staging System and Stage, Size, Grade, and Necrosis (SSIGN) score were selected to assess whether BT could improve their predictive abilities.

Results: BT was observed in 34 (23.4%) patients and was significantly associated with increased levels of IVCTT (P = 0.004) and invasion of IVC wall (P = 0.030). Multivariable Cox analyses revealed that tumor grade, T stage, M stage, tumor thrombus consistency and BT were independent risk factors for both progression-free survival and overall survival. The concordance indexes ranged from a low of 0.652 in TNM to a high of 0.731 in SSIGN, and integrating BT into each base model led to an increased predictive accuracies of 6.2% for TNM (P = 0.025), 4.0% for "Spiess PE" model (P = 0.069), 2.1% for University of California at Los Angeles Integrated Staging System (P = 0.149) and 1.2% for SSIGN (P = 0.290), respectively.

Conclusions: Presence of BT was independently associated with survival in postsurgical patients with RCC-IVCTT. Routine consideration of BT as an adjunct to TNM staging system may be suggested.
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http://dx.doi.org/10.1016/j.urolonc.2021.02.005DOI Listing
May 2021

Systematic evaluation of CdSe/ZnS quantum dots toxicity on the reproduction and offspring health in male BALB/c mice.

Ecotoxicol Environ Saf 2021 Mar 25;211:111946. Epub 2021 Jan 25.

School of Public Health, Shenzhen University Health Sciences Center, Shenzhen 518060, China; Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Shenzhen Key Lab of Synthetic Biology, Department of Physiology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China. Electronic address:

Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111946DOI Listing
March 2021

Sarcomatoid variant urothelial carcinoma of the bladder: a systematic review and meta-analysis of the clinicopathological features and survival outcomes.

Cancer Cell Int 2020 Nov 14;20(1):550. Epub 2020 Nov 14.

Department of Urology, the Third Medical Centre, Chinese PLA General Hospital, Beijing, China.

Background: A systematic review and meta-analysis was performed to compare the clinicopathological features and survival outcomes between sarcomatoid variant (SV)-urothelial carcinoma of the bladder (UCB) and conventional UCB (C-UCB).

Methods: A comprehensive search of PubMed, Embase, and Cochrane Library was performed. Endpoints included clinicopathological features and survival outcomes (overall survival [OS], cancer-specific survival [CSS], and progression-free survival [PFS]). The survival benefits of neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy (AC) for SV-UCB also have been studied.

Results: A total of 8 observational studies were included. Patients with SV-UCB had a higher rate of ≥ stage pT3 (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.64-2.59; p < 0.001) and a lower rate of concomitant carcinoma in situ (OR, 0.25; 95% CI, 0.09-0.72; p = 0.010). The other clinicopathological variables were similar between SV-UCB and C-UCB. With unadjusted data, patients with SV-UCB had a significant inferior OS (HR, 1.24; 95% CI, 1.07-1.44; p = 0.004) and CSS (HR, 2.08; 95% CI, 1.63-2.66; p < 0.001). However, after adjusted, SV-UCB had worse OS (HR, 1.41; 95% CI, 0.95-2.08; p = 0.090) and CSS (HR, 1.54; 95% CI, 0.95-2.52; p = 0.080) approaching the borderline of significance. For SV-UCB, NAC (HR, 0.73; 95% CI, 0.51-1.05; p = 0.090) and AC (HR, 0.88; 95% CI, 0.66-1.17; p = 0.370) seemed to have no benefit on OS.

Conclusions: Compared to C-UCB, SV-UCB was associated with more advanced disease and more inferior OS and CSS. NAC and AC had no survival benefit for SV-UCB.
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http://dx.doi.org/10.1186/s12935-020-01626-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666462PMC
November 2020

A 55-Year-Old Immunocompetent Man With Chest Discomfort and Night Sweats.

Chest 2020 12;158(6):e323-e326

Department of Internal Medicine, University of Iowa, Iowa City, IA. Electronic address:

Case Presentation: A 55-year-old Chinese man without significant medical history presented with progressive chest discomfort and night sweats for the past 2 months. He experienced nonexertional chest tightness and palpitation at night, not associated with dyspnea. These symptoms usually lasted for a few minutes and resolved spontaneously. He also reported night sweats but denied fever, chills, or weight change. He had never smoked and denied recent contact with anyone known to be ill.
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http://dx.doi.org/10.1016/j.chest.2020.07.045DOI Listing
December 2020

An automated detection of influenza virus based on 3-D magnetophoretic separation and magnetic label.

Analyst 2021 Feb 26;146(3):930-936. Epub 2020 Nov 26.

School of Electronic and Electrical Engineering, Wuhan Textile University, Wuhan 430200, People's Republic of China.

Automated detection of the influenza virus is important for the prevention of infectious viruses. Herein, assisted by three-dimensional (3-D) magnetophoretic separation and magnetic label, an automated detection device was constructed for H7N9 influenza virus hemagglutinin. Multi-layer glass slides were used to generate a 3-D microchannel network with two-level channels, realizing 3-D magnetophoretic separation with a magnetic field in the vertical direction to microchannels for the sample treatment. After the immunomagnetic separation, a magnetic-tagged complex was captured in an antibody-modified glass capillary, where magnetic beads further as a label could cause the voltage change of the miniature tube liquid sensor to obtain the detection signal. Moreover, the whole detection process and detection results were controlled and read through a liquid crystal display (LCD) screen to improve the automation. Finally, the detection limit was calculated to be 8.4 ng mL for H7N9 hemagglutinin and had good specificity and reproducibility. These results indicate that this detection device proposes promising automated avenues for the early detection of infectious diseases.
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http://dx.doi.org/10.1039/d0an01854fDOI Listing
February 2021

Acute cardiac injury in adult hospitalized COVID-19 patients in Zhuhai, China.

Cardiovasc Diagn Ther 2020 Oct;10(5):1303-1312

Department of Cardiovascular Medicine, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.

Background: Coronavirus disease 2019 (COVID-19) has already became a public health emergency of international concern. COVID-19 related cardiac injury remains largely unclear.

Methods: We retrospectively analyzed demographic, clinical, laboratory and cardiovascular imaging data of all consecutively admitted adult COVID-19 patients in Zhuhai, China from January 17th, 2020 to February 18th, 2020.

Results: A total of 93 patients were included in the study. Acute cardiac injury was found in 9 (9.7%) COVID-19 patients with median level of hypersensitive cardiac troponin I (hs-cTnI) to be 0.085 µg/L (IQR 0.027-0.560 µg/L). Compared with patients without cardiac injury, the median age of patients with cardiac injury was significantly older (65.0 44.0, P<0.05), hypertension was significantly more common (44.4% 14.3%, P<0.05), and the proportion of severe-critical cases were greater (77.8% 17.9%, P<0.05). Patients with cardiac injury were more likely have elevation of N-terminal proBNP (NT-proBNP) in comparison (66.7% 10.0%, P<0.05). There was no significant difference in echocardiographic parameters between patients with and without cardiac injury. Multivariable logistic regression analysis indicated that older age (OR: 1.093, 95% CI: 1.011-1.182) and increased NT-proBNP (OR: 10.979, 95% CI: 2.024-59.555) were independent risk factors for cardiac injury. Cardiac magnetic resonance (CMR) imaging performed on three patients at around one month after they underwent significant hs-cTnI elevation showed that they had underlying cardiovascular comorbidities.

Conclusions: Acute cardiac injury was seen in the minority of hospitalized COVID-19 patients in Zhuhai, China. Older age and increased NT-proBNP were associated with acute cardiac injury.

Registration Number: ChiCTR2000030952.
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http://dx.doi.org/10.21037/cdt-20-607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666934PMC
October 2020

Machine Learning in Electrocardiography and Echocardiography: Technological Advances in Clinical Cardiology.

Curr Cardiol Rep 2020 10 10;22(12):161. Epub 2020 Oct 10.

Division of Cardiology, Carver College of Medicine, University of Iowa, 4216 RCP UIHC 200 Hawkins Dr., Iowa City, IA, 52754, USA.

Purpose Of Review: Electrocardiography (ECG) and echocardiography are the most widely used diagnostic tools in clinical cardiology. This review focuses on recent advancements in applying machine learning (ML) in ECG and echocardiography and potential synergistic ML integration of ECG and echocardiography.

Recent Findings: ML algorithms have been used in ECG for technical quality assurance, arrhythmia identification, and prognostic predictions, and in echocardiography to recognize image views, quantify measurements, and identify pathologic patterns. Synergistic application of ML in ECG and echocardiograph has demonstrated the potential to optimize therapeutic response, improve risk stratification, and generate new disease classification. There is mounting evidence that ML potentially outperforms in disease diagnoses and outcome prediction with ECG and echocardiography when compared with trained healthcare professionals. The applications of ML in ECG and echocardiography are playing increasingly greater roles in medical research and clinical practice, particularly for their contributions to developing novel diagnostic/prognostic prediction models. The automation in data acquisition, processing, and interpretation help streamline the workflows of ECG and echocardiography in contemporary cardiology practice.
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http://dx.doi.org/10.1007/s11886-020-01416-9DOI Listing
October 2020
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