Publications by authors named "Ning Zhou"

388 Publications

Search for Light Dark Matter-Electron Scattering in the PandaX-II Experiment.

Phys Rev Lett 2021 May;126(21):211803

Research Center for Particle Science and Technology, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao 266237, Shandong, China.

We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9  tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30  MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38}  cm^{2}.
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http://dx.doi.org/10.1103/PhysRevLett.126.211803DOI Listing
May 2021

Investigating the basis for the antidepressant effects of using an integrated metabolomic strategy.

Iran J Basic Med Sci 2021 Apr;24(4):524-530

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, China.

Objectives: (GS) is a natural antidepressant but its mechanisms of action remain unclear. In the present study, taxifolin (Tax) was selected to determine the role of flavonoids in the antidepressant effects of GS.

Materials And Methods: Urine samples from C57BL/6 mice were analyzed based on ultra performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS). Then, we investigated the therapeutic effects of GS and Tax in depression models An integrated metabolomic approach was used to examine the metabolic profiles of GS/Tax groups and corticosterone model groups (Cor). Metabolic networks in response to GS/Tax treatment were established for the comparison of antidepressant activities.

Results: Corticosterone exposure significantly increased serum levels of corticosterone but decreased serum levels of 5-hydroxytryptamine and sucrose consumption (<0.01). Treatment with GS and Tax improved all measured variables compared to those of the corticosterone-exposed group (< 0.01). The antidepressant effects of GS and Tax involved the regulation of pentose and glucuronate interconversions, arginine and proline metabolism, phenylalanine metabolism, taurine and hypotaurine metabolism, and the citrate cycle.

Conclusion: These findings indicate that flavonoids form the pharmacodynamic basis of the antidepressant effects of GS. Moreover, our findings highlight that integrated metabolomics provides a powerful tool to study the mechanisms and material basis of Chinese herbs.
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http://dx.doi.org/10.22038/ijbms.2021.51975.11781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143708PMC
April 2021

Apatinib strengthens the anti-tumor effect of cisplatin in thyroid carcinoma through downregulating VEGFR2.

J BUON 2021 Mar-Apr;26(2):613-619

Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Purpose: The purpose of this study was to elucidate the influence of Apatinib combined with cisplatin on changing the phenotypes of TPC-1 cells.

Methods: VEGFR2 levels in thyroid carcinoma tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Then, the viability of TPC-1 cells induced with different doses of Apatinib and cisplatin was determined by cell counting kit-8 (CCK-8). Migratory and invasive abilities and apoptosis of TPC-1 cells induced with Apatinib combined with cisplatin were assessed. The protein levels of p-VEGFR2, VEGFR2, p-Akt, Akt, p-mTOR and mTOR in TPC-1 cells influenced by the treatment of Apatinib combined with cisplatin were examined by Western blot.

Results: VEGFR2 was upregulated in thyroid carcinoma tissues. Cisplatin treatment markedly suppressed viability, migratory and invasive abilities, and stimulated apoptosis of TPC-1 cells, which were further strengthened by combination treatment of Apatinib. Apatinib treatment strengthened the anti-tumor influence of cisplatin on TPC-1 cells through downregulating p-VEGFR2, p-Akt and p-mTOR.

Conclusions: Apatinib strengthens the anti-tumor influence of cisplatin in thyroid carcinoma through VEGFR2-Akt-mTOR pathway.
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June 2021

Prognostic value of ferroptosis-related genes in patients with lung adenocarcinoma.

Thorac Cancer 2021 Jun 12;12(12):1890-1899. Epub 2021 May 12.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Background: The prevalence of lung adenocarcinomas (LUADs) has dramatically increased in recent decades. Ferroptosis is a process of iron-dependent regulatory cell death. It is still unclear whether the expression of ferroptosis-related genes (FRGs) is involved in the pathogenesis and survival of patients with LUAD.

Methods: We retrieved LUAD data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and used LASSO Cox regression analysis to select the gene signature suitable for modeling. The risk score was calculated according to the model, and the patients were divided into high- and low-risk groups according to the median risk score. Functional enrichment analysis was carried out by this group, and a model for predicting clinical prognosis was established by combining this group with clinical factors.

Results: Gene set enrichment analysis (GSEA) and single-sample gene set enrichment analysis (ssGSEA) analysis showed that there were several immune-related pathways and immune infiltration differences between high- and low-risk groups. A prognostic model integrating 10 ferroptosis-related genes (FR-DEGs), and clinical factors were constructed and validated in an external cohort.

Conclusions: The FR-DEGs signature was related to immune infiltration, and a model based on FR-DEGs and clinical factors was established to predict the prognosis of patients with LUAD.
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http://dx.doi.org/10.1111/1759-7714.13998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201541PMC
June 2021

Mobile Media Promotes Orientation of 2D/3D Hybrid Lead Halide Perovskite for Efficient Solar Cells.

ACS Nano 2021 May 10;15(5):8350-8362. Epub 2021 May 10.

Beijing Key Laboratory for Theory and Technology of Advanced Battery Materials, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, BIC-ESAT, School of Materials Science and Engineering, Peking University, Beijing 100871, P.R. China.

2D/3D hybrid perovskites have shown great environmental stability for use as solar cells. Yet insulating organic cation spacers affect the formation of vertically oriented crystalline grains to hamper carrier transport. To date, the selection of cation spacers is limited because crystal growth kinetics should be strictly obeyed. Here, we adopted a mobile-media-assisted method to fabricate highly oriented 2D/3D hybrid perovskite films, wherein bulky molecules of (C(CH)NH, TBA) are used as cation spacers. We found the compositional volatile salt promote the orientation of perovskite polycrystalline films with various compositions universally. And we obtained efficient solar cells with a photoelectric conversion efficiency (PCE) of 17.38% and a certified PCE of 19.30% based on 2D/3D hybrid perovskites an overall stoichiometry matching = 10 and 20, respectively, which are one of the highest efficiencies among all 2D/3D hybrid perovskite based solar cells so far. These findings largely broaden the selection category of bulky cations and promote further exploration of more functional organic cations.
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http://dx.doi.org/10.1021/acsnano.0c09822DOI Listing
May 2021

Construction of PD1/CD28 chimeric-switch receptor enhances anti-tumor ability of c-Met CAR-T in gastric cancer.

Oncoimmunology 2021 Mar 31;10(1):1901434. Epub 2021 Mar 31.

Lanzhou University Second Hospital, the Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, China.

Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In , we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells. We detected the secretion levels of different cytokines and the killing ability of CAR-Ts. In , we established a xenograft GC model and observed the anti-tumor effect and off-target toxicity of different CAR-Ts. We find that the expression of c-Met was increased in GC. CD3CD8 T cells and CD62LCCR7 central memory T cells (T) were increased in two CAR-Ts. The stimulation of target cells could promote the expression of PD-1 in c-Met CAR-T. Compared with Mock T, the secretion of cytokines as IFN-γ, TNF-α, IL-6, IL-10 secreted by two CAR-Ts was increased, and the killing ability to c-Met positive GC cells was enhanced. The PD1/CD28 CSR could further enhance the killing ability, especially the long-term anti-tumor effect of c-Met CAR-T, and reduce the release level of IL-6. CAR-Ts target c-Met had no obvious off-target toxicity to normal organs. Thus, the PD1/CD28 CSR could further enhance the anti-tumor ability of c-Met CAR-T, and provides a promising design strategy to improve the efficacy of CAR-T in GC.
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http://dx.doi.org/10.1080/2162402X.2021.1901434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018404PMC
March 2021

Maxillomandibular advancement versus multilevel surgery for treatment of obstructive sleep apnea: A systematic review and meta-analysis.

Sleep Med Rev 2021 Jun 17;57:101471. Epub 2021 Mar 17.

Department of Oral and Maxillofacial Surgery, Amsterdam UMC Location AMC and Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam, Amsterdam, the Netherlands.

Multilevel surgery (MLS) and maxillomandibular advancement surgery (MMA) are two established options in surgical management of obstructive sleep apnea (OSA), which target different levels of airway obstruction. The objective of this review was to comparatively evaluate the clinical efficacy and safety of MMA and MLS in the treatment of OSA. MEDLINE and Embase databases were searched for studies on MMA and/or MLS in OSA patients. Twenty MMA studies and 39 MLS studies were identified. OSA patients who underwent MMA showed significant improvements in AHI, LSAT, ODI, and ESS by -46.2/h, 13.5%, -30.3/h, and -8.5, respectively. The pooled rates of surgical success and cure for MMA were 85.0% and 46.3%, respectively. Patients who underwent MLS showed significant improvements in AHI, LSAT, ODI, and ESS by -24.7/h, 8.7%, -19.1/h, and -5.8, respectively. The pooled surgical success and cure rates for MLS were 65.1% and 28.1%, respectively. The rates of major complication of MMA and MLS were 3.2% and 1.1%, respectively, and the rate of minor complication of MMA was higher than that of MLS. We conclude that both MMA and MLS are effective treatment options for OSA. Compared to MLS, MMA may be more effective in improving OSA. However, the complication rate of MMA is higher.
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http://dx.doi.org/10.1016/j.smrv.2021.101471DOI Listing
June 2021

Batch Fabrication of High-Quality Infrared Chalcogenide Microsphere Resonators.

Small 2021 Apr 2:e2100140. Epub 2021 Apr 2.

State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, Zhejiang University, Hangzhou, 310027, China.

Optical microsphere resonators working in the near- and mid-infrared regions are highly required for a variety of applications, such as optical sensors, filters, modulators, and microlasers. Here, a simple and low-cost approach is reported for batch fabrication of high-quality chalcogenide glass (ChG) microsphere resonators by melting high-purity ChG powders in an oil environment. Q factors as high as 1.2 × 10 (7.4 × 10 ) are observed in As S (As Se ) microspheres (≈30 µm in diameter) around 1550-nm wavelength. Smaller microspheres with sizes around 10 µm also show excellent resonant responses (Q ≈ 2.5 × 10 ). Based on the mode splitting of an azimuthal mode in a microsphere resonator, eccentricities as low as ≈0.13% (≈0.17%) for As S (As Se ) microspheres are measured. Moreover, by coupling ChG microspheres with a biconical As S fiber taper, Q factors of ≈1.7 × 10 (≈1.6 × 10 ) are obtained in As S (As Se ) microspheres in the mid-infrared region (around 4.5 µm). The high-quality ChG microspheres demonstrated here are highly attractive for near- and mid-infrared optics, including optical sensing, optical nonlinearity, cavity quantum electrodynamics, microlasers, nanofocusing, and microscopic imaging.
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http://dx.doi.org/10.1002/smll.202100140DOI Listing
April 2021

Mutations Associated with No Durable Clinical Benefit to Immune Checkpoint Blockade in Non-S-Cell Lung Cancer.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300050, China.

(1) Background: The immune checkpoint blockade (ICB) has shown promising efficacy in non-small-cell lung cancer (NSCLC) patients with significant clinical benefits and durable responses, but the overall response rate to ICBs is only 20%. The lack of responsiveness to ICBs is currently a central problem in cancer immunotherapy. (2) Methods: Four public cohorts comprising 2986 patients with NSCLC were included in the study. We screened 158 patients with NSCLC with no durable clinical benefit (NDB) to ICBs in the Rizvi cohort and identified NDB-related gene mutations in these patients using univariate and multivariate Cox regression analyses. Programmed death-ligand 1 (PD-L1) expression, tumor mutation burden (TMB), neoantigen load, tumor-infiltrating lymphocytes, and immune-related gene expression were analyzed for identifying gene mutations. A comprehensive predictive classifier model was also built to evaluate the efficacy of ICB therapy. (3) Results: Mutations in FAT1 and KEAP1 were found to correlate with NDB in patients with NSCLC to ICBs; however, the analysis suggested that only mutation in FAT1 was valuable in predicting the efficacy of ICB therapy, and that mutation in KEAP1 acted as a prognostic but not a predictive biomarker for NSCLC. Mutations in FAT1 were associated with a higher TMB and lower multiple lymphocyte infiltration, including CD8 (T-Cell Surface Glycoprotein CD8)+ T cells. We established a prognostic model according to PD-L1 expression, TMB, smoking status, treatment regimen, treatment type, and FAT1 mutation, which indicated good accuracy by receiver operating characteristic (ROC) analysis (area under the curve (AUC) for 6-months survival: 0.763; AUC for 12-months survival: 0.871). (4) Conclusions: Mutation in FAT1 may be a predictive biomarker in patients with NSCLC who exhibit NDB to ICBs. We proposed an FAT1 mutation-based model for screening more suitable NSCLC patients to receive ICBs that may contribute to individualized immunotherapy.
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http://dx.doi.org/10.3390/cancers13061397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003499PMC
March 2021

Optimizing Management to Reduce the Mortality of COVID-19: Experience From a Designated Hospital for Severely and Critically Ill Patients in China.

Front Med (Lausanne) 2021 10;8:582764. Epub 2021 Mar 10.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The coronavirus disease 2019 (COVID-19) has swept through the world at a tremendous speed, and there is still limited data available on the treatment for COVID-19. The mortality of severely and critically ill COVID-19 patients in the Optical Valley Branch of Tongji Hospital was low. We aimed to analyze the available treatment strategies to reduce mortality. In this retrospective, single-center study, we included 1,106 COVID-19 patients admitted to the Optical Valley Branch of Tongji Hospital from February 9 to March 9, 2020. Cases were analyzed for demographic and clinical features, laboratory data, and treatment methods. Outcomes were followed up until March 29, 2020. Inflammation-related indices (hs-CRP, ESR, serum ferritin, and procalcitonin) were significantly higher in severe and critically ill patients than those in moderate patients. The levels of cytokines, including IL-6, IL2R, IL-8, and TNF-α, were also higher in the critical patients. Incidence of acute respiratory distress syndrome (ARDS) in the severely and critically ill group was 23.0% (99/431). Sixty-one patients underwent invasive mechanical ventilation. The correlation between SpO/FiO and PaO/FiO was confirmed, and the cut-off value of SpO/FiO related to survival was 134.43. The mortality of patients with low SpO/FiO (<134.43) at intubation was higher than that of patients with high SpO/FiO (>134.43) (72.7 vs. 33.3%). Among critical patients, the application rates of glucocorticoid therapy, continuous renal replacement therapy (CRRT), and anticoagulation treatment reached 55.2% (238/431), 7.2% (31/431), and 37.1% (160/431), respectively. Among the intubated patients, the application rates of glucocorticoid therapy, CRRT, and anticoagulation treatment were respectively 77.0% (47/61), 54.1% (33/61), and 98.4% (60/61). No vaccines or specific antiviral drugs for COVID-19 have been shown to be sufficiently safe and effective to date. Comprehensive treatment including ventilatory support, multiple organ function preservation, glucocorticoid use, renal replacement therapy, anticoagulation, and restrictive fluid management was the main treatment strategy. Early recognition and intervention, multidisciplinary collaboration, multi-organ function support, and personalized treatment might be the key for reducing mortality.
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http://dx.doi.org/10.3389/fmed.2021.582764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987780PMC
March 2021

Diurnal Effect of Sub-GeV Dark Matter Boosted by Cosmic Rays.

Phys Rev Lett 2021 Mar;126(9):091804

School of Physics and Astronomy, Shanghai Jiao Tong University, Key Laboratory for Particle Astrophysics and Cosmology (MOE) and Shanghai Key Laboratory for Particle Physics and Cosmology, Shanghai 200240, China.

We point out a new type of diurnal effect for the cosmic ray boosted dark matter (DM). The DM-nucleon interactions not only allow the direct detection of DM with nuclear recoils but also allow cosmic rays to scatter with and boost the nonrelativistic DM to higher energies. If the DM-nuclei scattering cross sections are sufficiently large, the DM flux is attenuated as it propagates through the Earth, leading to a strong diurnal modulation. This diurnal modulation provides another prominent signature for the direct detection of boosted sub-GeV DM, in addition to signals with higher recoil energy.
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http://dx.doi.org/10.1103/PhysRevLett.126.091804DOI Listing
March 2021

Fixed-Time Cooperative Behavioral Control for Networked Autonomous Agents With Second-Order Nonlinear Dynamics.

IEEE Trans Cybern 2021 Mar 12;PP. Epub 2021 Mar 12.

In this article, we investigate the fixed-time behavioral control problem for a team of second-order nonlinear agents, aiming to achieve a desired formation with collision/obstacle avoidance. In the proposed approach, the two behaviors(tasks) for each agent are prioritized and integrated via the framework of the null-space-based behavioral projection, leading to a desired merged velocity that guarantees the fixed-time convergence of task errors. To track this desired velocity, we design a fixed-time sliding-mode controller for each agent with state-independent adaptive gains, which provides a fixed-time convergence of the tracking error. The control scheme is implemented in a distributed manner, where each agent only acquires information from its neighbors in the network. Moreover, we adopt an online learning algorithm to improve the robustness of the closed system with respect to uncertainties/disturbances. Finally, simulation results are provided to show the effectiveness of the proposed approach.
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http://dx.doi.org/10.1109/TCYB.2021.3057219DOI Listing
March 2021

PTEN/AKT upregulation of TMSB10 contributes to lung cancer cell growth and predicts poor survival of the patients.

Biosci Biotechnol Biochem 2021 Mar;85(4):805-813

Department of Oncology, Fourth Hospital of Hebei Medical University, Hebei, P. R. China.

PTEN/AKT signaling cascade is frequently activated in various cancers, including lung cancer. The downstream effector of this signaling cascade is poorly understood. β-Thymosin 10 (TMSB10) functions as an oncogene or tumor suppressors in cancers, whereas its significance in lung cancer remains unknown. In this study, we showed that the activation of PTEN/AKT signaling promoted the expression of TMSB10. Based on the TCGA database, TMSB10 was upregulated in lung cancer tissues and its overexpression was correlated with poor prognosis of lung cancer patients. Functional experiments demonstrated that TMSB10 knockdown suppressed, while its overexpression promoted the proliferation, growth, and migration of lung cancer cells. Apoptosis and epithelial-mesenchymal transition were also regulated by TMSB10. We therefore suggest that TMSB10 is a novel oncogene for lung cancer. Targeting TMSB10 may benefit lung cancer patients with activated PTEN/AKT signaling.
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http://dx.doi.org/10.1093/bbb/zbaa113DOI Listing
March 2021

Construction of Circular RNA-MicroRNA-Messenger RNA Regulatory Network of Recurrent Implantation Failure to Explore Its Potential Pathogenesis.

Front Genet 2020 16;11:627459. Epub 2021 Feb 16.

Department of Reproductive Medicine, The First Affiliated Hospital of Dali University, Dali, China.

Many studies on circular RNAs (circRNAs) have recently been published. However, the function of circRNAs in recurrent implantation failure (RIF) is unknown and remains to be explored. This study aims to determine the regulatory mechanisms of circRNAs in RIF. Microarray data of RIF circRNA (GSE147442), microRNA (miRNA; GSE71332), and messenger RNA (mRNA; GSE103465) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed circRNA, miRNA, and mRNA. The circRNA-miRNA-mRNA network was constructed by Cytoscape 3.8.0 software, then the protein-protein interaction (PPI) network was constructed by STRING database, and the hub genes were identified by cytoHubba plug-in. The circRNA-miRNA-hub gene regulatory subnetwork was formed to understand the regulatory axis of hub genes in RIF. Finally, the Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the hub genes were performed by clusterProfiler package of Rstudio software, and Reactome Functional Interaction (FI) plug-in was used for reactome analysis to comprehensively analyze the mechanism of hub genes in RIF. A total of eight upregulated differentially expressed circRNAs (DECs), five downregulated DECs, 56 downregulated differentially expressed miRNAs (DEmiRs), 104 upregulated DEmiRs, 429 upregulated differentially expressed genes (DEGs), and 1,067 downregulated DEGs were identified regarding RIF. The miRNA response elements of 13 DECs were then predicted. Seven overlapping miRNAs were obtained by intersecting the predicted miRNA and DEmiRs. Then, 56 overlapping mRNAs were obtained by intersecting the predicted target mRNAs of seven miRNAs with 1,496 DEGs. The circRNA-miRNA-mRNA network and PPI network were constructed through six circRNAs, seven miRNAs, and 56 mRNAs; and four hub genes (YWHAZ, JAK2, MYH9, and RAP2C) were identified. The circRNA-miRNA-hub gene regulatory subnetwork with nine regulatory axes was formed in RIF. Functional enrichment analysis and reactome analysis showed that these four hub genes were closely related to the biological functions and pathways of RIF. The results of this study provide further understanding of the potential pathogenesis from the perspective of circRNA-related competitive endogenous RNA network in RIF.
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http://dx.doi.org/10.3389/fgene.2020.627459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924221PMC
February 2021

Trimetazidine in Heart Failure.

Front Pharmacol 2020 12;11:569132. Epub 2021 Jan 12.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Heart failure is a systemic syndrome caused by multiple pathological factors. Current treatments do not have satisfactory outcomes. Several basic studies have revealed the protective effect of trimetazidine on the heart, not only by metabolism modulation but also by relieving myocardial apoptosis, fibrosis, autophagy, and inflammation. Clinical studies have consistently indicated that trimetazidine acts as an adjunct to conventional treatments and improves the symptoms of heart failure. This review summarizes the basic pathological changes in the myocardium, with an emphasis on the alteration of cardiac metabolism in the development of heart failure. The clinical application of trimetazidine in heart failure and the mechanism of its protective effects on the myocardium are carefully discussed, as well as its main adverse effects. The intention of this review is to highlight this treatment as an effective alternative against heart failure and provide additional perspectives for future studies.
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http://dx.doi.org/10.3389/fphar.2020.569132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883591PMC
January 2021

Conditioned medium-preconditioned EPCs enhanced the ability in oligovascular repair in cerebral ischemia neonatal rats.

Stem Cell Res Ther 2021 Feb 12;12(1):118. Epub 2021 Feb 12.

Department of Cell Biology and Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, 221009, China.

Background: Oligovascular niche mediates interactions between cerebral endothelial cells and oligodendrocyte precursor cells (OPCs). Disruption of OPC-endothelium trophic coupling may aggravate the progress of cerebral white matter injury (WMI) because endothelial cells could not provide sufficient support under diseased conditions. Endothelial progenitor cells (EPCs) have been reported to ameliorate WMI in the adult brain by boosting oligovascular remodeling. It is necessary to clarify the role of the conditioned medium from hypoxic endothelial cells preconditioned EPCs (EC-pEPCs) in WMI since EPCs usually were recruited and play important roles under blood-brain barrier disruption. Here, we investigated the effects of EC-pEPCs on oligovascular remodeling in a neonatal rat model of WMI.

Methods: In vitro, OPC apoptosis induced by the conditioned medium from oxygen-glucose deprivation-injured brain microvascular endothelial cells (OGD-EC-CM) was analyzed by TUNEL and FACS. The effects of EPCs on EC damage and the expression of cytomokine C-X-C motif ligand 12 (CXCL12) were examined by western blot and FACS. The effect of the CM from EC-pEPCs against OPC apoptosis was also verified by western blot and silencing RNA. In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia and treated with EPCs or EC-pEPCs at P7, and then angiogenesis and myelination together with cognitive outcome were evaluated at the 6th week.

Results: In vitro, EPCs enhanced endothelial function and decreased OPC apoptosis. Meanwhile, it was confirmed that OGD-EC-CM induced an increase of CXCL12 in EPCs, and CXCL12-CXCR4 axis is a key signaling since CXCR4 knockdown alleviated the anti-apoptosis effect of EPCs on OPCs. In vivo, the number of EPCs and CXCL12 protein level markedly increased in the WMI rats. Compared to the EPCs, EC-pEPCs significantly decreased OPC apoptosis, increased vascular density and myelination in the corpus callosum, and improved learning and memory deficits in the neonatal rat WMI model.

Conclusions: EC-pEPCs more effectively promote oligovascular remodeling and myelination via CXCL12-CXCR4 axis in the neonatal rat WMI model.
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http://dx.doi.org/10.1186/s13287-021-02157-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881622PMC
February 2021

Sensitivity to Pulse Phase Duration as a Marker of Neural Health Across Cochlear Implant Recipients and Electrodes.

J Assoc Res Otolaryngol 2021 Apr 8;22(2):177-192. Epub 2021 Feb 8.

House Ear Institute, 2100 W. Third St., Suite 101, Los Angeles, CA, 90057, USA.

In cochlear implants, loudness has been shown to grow more slowly with increasing pulse phase duration (PPD) than with pulse amplitude (PA), possibly due to "leaky" charge integration. This leakiness has been recently quantified in terms of "charge integration efficiency," defined as the log difference between the PPD dynamic range and PA dynamic range (both expressed in charge units), relative to a common threshold anchor. Such leakiness may differ across electrodes and/or test ears, and may reflect underlying neural health. In this study, we examined the across-site variation of charge integration in recipients of Cochlear© devices. PPD and PA dynamic ranges were measured relative to two threshold anchors with either a 25- or 50-microsecond PPD. Strength-duration functions, previously shown to relate to survival of spiral ganglion cells and peripheral processes, were compared to charge integration efficiency on selected electrodes. Results showed no significant or systematic relationship between the across-site variation in charge integration efficiency and electrode position or threshold levels. Charge integration efficiency was poorer with the 50-μs threshold anchor, suggesting that greater leakiness was associated with larger PPD dynamic ranges. Poorer and more variable charge integration efficiency across electrodes was associated with longer duration of any hearing loss, consistent with the idea that poor integration is related to neural degeneration. More variable integration efficiency was also associated with poorer speech recognition performance across test ears. The slopes of the strength-duration functions at maximum acceptable loudness were significantly correlated with charge integration efficiency. However, the strength-duration slopes were not predictive of duration of any hearing loss or speech recognition performance in our participants. As such, charge integration efficiency may be a better candidate to measure leakiness in neural populations across the electrode array, as well as the general health of the auditory nerve in human cochlear implant recipients.
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http://dx.doi.org/10.1007/s10162-021-00784-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943680PMC
April 2021

Comparison of antiangina therapies in patients with coronary heart disease in China: study protocol for a multicentre, retrospective, hospital system-based study.

BMJ Open 2021 02 5;11(2):e036954. Epub 2021 Feb 5.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

Introduction: China has the largest number of patients with coronary heart disease (CHD) in the world. Numerous pharmacological strategies are available for CHD in routine clinical practice. CHD-induced angina pectoris affects patients' quality of life and is a key predictor of prognosis. This study will compare the effectiveness of different antiangina treatments, particularly ATP-sensitive potassium channel (K) activators, in the Central China District. This proposal underpins the first comparison of antiangina therapies in patients with CHD in China using a multicentre, retrospective, hospital system-based assessment.

Methods And Analysis: This retrospective real-world study will assess the largest hospital databases in Wuhan City in Central China to evaluate outcomes including mortality, revascularisation, myocardial infarction (MI), stroke and other cardio-cerebrovascular events in patients with CHD. Data will be consecutively collected between 1 April 2009 and 31 August 2019 through the hospital information system, laboratory information system and hospital imaging system. All data will be standardised by at least three independent technicians and statisticians using International Classification of Diseases Tenth Version, ISO15189 and Specification for Drafting of Basic Dataset of Electronic Medical Record (WS445). The data will include patient demographics, physical and laboratory examinations, imaging examinations, medical history, diagnosis, treatment options and payment information. We will compare K activators with other antiangina drugs using propensity score matching. The primary outcome will be major adverse cardiovascular events, defined as a composite of death, MI, stroke and rehospitalisation due to angina.

Ethics And Dissemination: The current study is designed to translate research into improved care for patients. The institutional review board of Wuhan Tongji Hospital (Liao Jiazhi, Du Aiye, Chen Zhishui, Fang Feng, Yu Shiying, Liu Dong and Li Yaping) approved the study protocol (version 1.0, July 2019, approval number TJ-IRB201909112). Here we reported a protocol related to a pre-results. Data will be presented in peer-reviewed journals, social media and relevant conferences.

Trial Registration Number: ChiCTR1900027812; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-036954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925860PMC
February 2021

Safety and Efficacy of Early Carotid Endarterectomy in Patients with Symptomatic Carotid Artery Stenosis: A Meta-Analysis.

Biomed Res Int 2021 8;2021:6623426. Epub 2021 Jan 8.

Shandong Taian City Central Hospital Branch, Taian City, Shandong Province, China.

Design: A systematic document retrieval of studies published in the past 10 years reporting periprocedural stroke/mortality/MI after carotid endarterectomy (CEA) related to the time between CEA and qualifying neurological symptoms. The application database has "PubMed, EMbase and Cochrane databases." RevMan5.3 software provided by the Cochrane collaboration was used for meta-analysis.

Results: A systematic literature search was conducted in databases. A total of 10 articles were included in this study. They were divided into early CEA and delayed CEA with operation within 48 h, 1 w, or 2 w after onset of neurological symptoms. Incidence of the postoperative stroke in patients undergoing delayed CEA (≥48 h) was significantly higher than patients with delayed CEA (<48 h) (OR = 2.14, 95% CI: 1.43-3.21, = 0.0002). The postoperative mortality of patients after delayed CEA (≥48 h) was significantly higher than patients after early CEA (<48 h) (OR = 1.35, 95% CI: 1.06-1.71, = 0.02). The risk of postoperative mortality of patients treated with delayed CEA (≥7 d) was significantly higher than patients after the early CEA group (<7 d) (OR = 1.69, 95% CI: 1.21-2.32, = 0.001).

Conclusion: Early CEA is safe and effective for a part of patients with symptomatic carotid stenosis, but a comprehensive preoperative evaluation of patients with carotid stenosis must be performed.
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http://dx.doi.org/10.1155/2021/6623426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811422PMC
May 2021

Preparation of pH-sensitive food packaging film based on konjac glucomannan and hydroxypropyl methyl cellulose incorporated with mulberry extract.

Int J Biol Macromol 2021 Mar 19;172:515-523. Epub 2021 Jan 19.

College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China; Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou, Fujian 350002, China.; State Key Laboratory of Food Safety Technology for Meat Products, Xiamen, Fujian 361100, China; Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou, Fujian 350002, China. Electronic address:

A pH-sensitive food packaging film was prepared based on konjac glucomannan (KGM) and hydroxypropyl methyl cellulose (HPMC) incorporated with mulberry extracts (MBE). FT-IR and XRD analysis revealed that there are good molecular interactions among the three components. The incorporation of MBE into KGM and HPMC (KH) films can significantly improve the mechanical properties and UV resistance. Notably, the KH-MBE-20% film almost completely blocked UV light in the range of 200-600 nm. The best antioxidant and antibacterial properties were obtained when the addition of MBE in the composite film was 20%. In addition, KH-MBE film has good responsiveness to buffers with pH range from 2 to 12. In visual monitoring experiments using the film on fresh fish, the color of the KH-MBE film changed from purple to gray to yellow as the freshness of the fish decreased, and the KH-MBE-20% film had the best color stability. Therefore, intelligent packaging of KH-MBE film has potential applications in real-time monitoring of fish freshness.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.01.047DOI Listing
March 2021

Imaging of Actively Proliferating Bacterial Infections by Targeting the Bacterial Metabolic Footprint with d-[5-C]-Glutamine.

ACS Infect Dis 2021 02 21;7(2):347-361. Epub 2021 Jan 21.

Since most d-amino acids (DAAs) are utilized by bacterial cells but not by mammalian eukaryotic hosts, recently DAA-based molecular imaging strategies have been extensively explored for noninvasively differentiating bacterial infections from the host's inflammatory responses. Given glutamine's pivotal role in bacterial survival, cell growth, biofilm formation, and even virulence, here we report a new positron emission tomography (PET) imaging approach using d-5-[C]glutamine (d-[5-C]-Gln) for potential clinical assessment of bacterial infection through a comparative study with its l-isomer counterpart, l-[5-C]-Gln. In both control and infected mice, l-[5-C]-Gln had substantially higher uptake levels than d-[5-C]-Gln in most organs except the kidneys, showing the expected higher use of l-[5-C]-Gln by mammalian tissues and more efficient renal excretion of d-[5-C]-Gln. Importantly, our work demonstrates that PET imaging with d-[5-C]-Gln is capable of detecting infections induced by both () and methicillin-resistant (MRSA) in a dual-infection murine myositis model with significantly higher infection-to-background contrast than with l-[5-C]-Gln (in , 1.64; in MRSA, 2.62, = 0.0004). This can be attributed to the fact that d-[5-C]-Gln is utilized by bacteria while being more efficiently cleared from the host tissues. We confirmed the bacterial infection imaging specificity of d-[5-C]-Gln by comparing its uptake in active bacterial infections versus sterile inflammation and with 2-deoxy-2-[F]fluoroglucose ([F]FDG). These results together demonstrate the translational potential of PET imaging with d-[5-C]-Gln for the noninvasive detection of bacterial infectious diseases in humans.
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http://dx.doi.org/10.1021/acsinfecdis.0c00617DOI Listing
February 2021

Emerging role of VCP/p97 in cardiovascular diseases: novel insights and therapeutic opportunities.

Biochem Soc Trans 2021 Feb;49(1):485-494

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.

Valosin-containing protein (VCP/p97) is a member of the conserved type II AAA+ (ATPases associated with diverse cellular activities) family of proteins with multiple biological functions, especially in protein homeostasis. Mutations in VCP/p97 are reportedly related to unique autosomal dominant diseases, which may worsen cardiac function. Although the structure of VCP/p97 has been clearly characterized, with reports of high abundance in the heart, research focusing on the molecular mechanisms underpinning the roles of VCP/p97 in the cardiovascular system has been recently undertaken over the past decades. Recent studies have shown that VCP/p97 deficiency affects myocardial fibers and induces heart failure, while overexpression of VCP/p97 eliminates ischemia/reperfusion injury and relieves pathological cardiac hypertrophy caused by cardiac pressure overload, which is related to changes in the mitochondria and calcium overload. However, certain studies have drawn opposing conclusions, including the mitigation of ischemia/reperfusion injury via inhibition of VCP/p97 ATPase activity. Nevertheless, these emerging studies shed light on the role of VCP/p97 and its therapeutic potential in cardiovascular diseases. In other words, VCP/p97 may be involved in the development of cardiovascular disease, and is anticipated to be a new therapeutic target. This review summarizes current findings regarding VCP/p97 in the cardiovascular system for the first time, and discusses the role of VCP/p97 in cardiovascular disease.
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http://dx.doi.org/10.1042/BST20200981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925001PMC
February 2021

Correlation analysis between extracts and endogenous metabolites to characterise the influence of salt-processing on compatibility mechanism of 'Psoraleae Fructus & Foeniculi Fructus'.

J Ethnopharmacol 2021 Apr 6;270:113782. Epub 2021 Jan 6.

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, PR China; The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, PR China. Electronic address:

Ethnopharmacological Relevance: 'Salt-processed Psoraleae Fructus & salt-processed Foeniculi Fructus' (sPF&sFF) is a common Chinese medicinal combination for treating diarrhoea. However, it is not clear how sPF and sFF work together, and why salt-processing is necessary.

Aim Of The Study: To investigate the compatibility mechanism of sPF&sFF and the influence of salt-processing on it.

Materials And Methods: Firstly, the metabolomics approach was appliedto screen the differential components between four (s)PF&(s)FF extracts, i.e., sPF&sFF, sPF&FF, PF&sFF, and PF&FF extracts. Then, an in vivo metabolomics study was carried out to filter critical metabolites reflecting the curative effects of (s)PF&(s)FF, and construct a metabolic network. Finally, a correlation analysis between chemical components in extracts and critical metabolites in vivo was performed to find out the synergistic and/or antagonistic effects between herbs as well as the influence of salt-processing.

Results: Salt-processing had a direct influence on the contents of chemical components in sPF and sFF extracts, and there existed positive/negative correlations between the content change of chemical components and the effects of critical metabolites. Therefore, salt-processing indirectly affected on these correlations and was (i) conducive to the positive effects of sPF and sFF on bile acids, making sFF play a synergistic role, thereby, sPF&sFF could perform better than sPF and other three combinations and effectively relieve the symptoms of fatty diarrhoea, osmotic diuresis, malnutrition, and weight loss; (ii) conducive to the positive effects of sPF on triacylglycerol, 12(S)-hydroxyeicosatetraenoic acid, cholesterol, and arachidonic acid, and adverse to that of sFF, making sFF play an antagonistic role, thereby, sPF&sFF could prevent a series of side effects caused by over-regulation and suitably relieve the symptoms of osmotic diuresis, polyuria, malnutrition, and weight loss; and (iii) adverse to the positive effects of sPF and sFF on thromboxane A2, sphinganine and sphingosine, making sFF play a synergistic role, thereby, sPF&sFF could prevent a series of side effects and moderately relieve the symptoms of metabolic diarrhoea and polyuria.

Conclusions: Salt-processing indirectly affected on the correlations between chemical components in extracts and critical metabolites in vivo, and exhibited both conducive and adverse effects on the efficacy, making sPF and sFF cooperate with each other to moderately repair the metabolic disorders. Thereby, sPF&sFF could suitably relieve the diarrhoea and polyuria symptoms in the model and exert the most appropriate efficacy. Moreover, this novel strategy provided a feasible approach for further studying the compatibility mechanism of herbs.
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http://dx.doi.org/10.1016/j.jep.2021.113782DOI Listing
April 2021

Identification of Circ_001569 as a Potential Biomarker in the Diagnosis and Prognosis of Pancreatic Cancer.

Technol Cancer Res Treat 2021 Jan-Dec;20:1533033820983302

The Intractable Diseases Diagnosis and Treatment Center for Liver, Gallbladder, Pancreas & Intestine, Department of Hepatopancreatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan Province, People's Republic of China.

Emerging evidence has shown that circular RNAs (circRNAs) serve as a promising biomarker in different malignancies. Specifically, circ_001569 has been found to be upregulated in some types of human gastrointestinal cancer. In this study, we aimed to investigate clinical significances, diagnostic and prognostic values of circ_001569 in pancreatic cancer (PC), and identify its effects on the malignant behaviors of PC cells. The expression of circ_001569 was determined in 26 tissues samples and 97 plasma samples from PC patients by qRT-PCR. Relationship between circ_001569 expression and clinicopathological parameters was analyzed by Chi-square test. Diagnostic and prognostic values of circ_001569 were evaluated by ROC curves, Kaplan-Meier curves, and Cox regression analysis. The effects of circ_001569 on the proliferation, migration, invasion, and apoptosis of PC cells were assessed by MTT, wound healing, Transwell invasion assays, and flow cytometric analysis, respectively. Results showed that the expression of circ_001569 was upregulated in tissues and plasma of PC patients. High circ_001569 level was positively correlated with lymphatic metastasis, clinical stage, and venous invasion. Circ_001569 level was an independent prognostic indicator for overall survival rates of PC patients, and patients with high circ_001569 level had a poor prognosis. The AUC of circ_001569 was 0.716 (95% CI: 0.642-0.790) with a sensitivity and specificity of 62.76% and 74.29%, respectively. , circ_001569 silencing decreased cell proliferation, migration, and invasion, but promoted cell apoptosis of PC cells. Our data demonstrate that high circ_001569 level associates with tumor malignant behaviors, and may serve as a potential biomarker in the diagnosis and prognosis of PC.
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http://dx.doi.org/10.1177/1533033820983302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797582PMC
January 2021

The Association of Low Molecular Weight Heparin Use and In-hospital Mortality Among Patients Hospitalized with COVID-19.

Cardiovasc Drugs Ther 2021 Jan 4. Epub 2021 Jan 4.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, China.

Purpose: To determine the association between low molecular weight heparin (LMWH) use and mortality in hospitalized COVID-19 patients.

Methods: We conducted a retrospective study of patients consecutively enrolled from two major academic hospitals exclusively for COVID-19 in Wuhan, China, from January 26, 2020, to March 26, 2020. The primary outcome was adjusted in-hospital mortality in the LMWH group compared with the non-LMWH group using the propensity score.

Results: Overall, 525 patients with COVID-19 enrolled with a median age of 64 years (IQR 19), and 49.33% men. Among these, 120 (22.86%) were treated with LMWH. Compared with the non-LMWH group, the LMWH group was more likely to be older and male; had a history of hypertension, diabetes, coronary heart disease (CHD), or stroke; and had more severe COVID-19 parameters such as higher inflammatory cytokines or D-dimer. Compared with non-LMWH group, LMWH group had a higher unadjusted in-hospital mortality rate (21.70% vs. 11.10%; p = 0.004), but a lower adjusted mortality risk (adjusted odds ratio [OR], 0.20; 95% CI, 0.09-0.46). A propensity score-weighting analysis demonstrated similar findings (adjusted OR, 0.18; 95% CI, 0.10-0.30). Subgroup analysis showed a significant survival benefit among those who were severely (adjusted OR, 0.07; 95% CI, 0.02-0.23) and critically ill (adjusted OR, 0.32; 95% CI, 0.15-0.65), as well as among the elderly patients' age > 65, IL-6 > 10 times upper limit level, and D-dimer > 5 times upper limit level.

Conclusions: Among hospitalized COVID-19 patients, LMWH use was associated with lower all-cause in-hospital mortality than non-LMWH users. The survival benefit was particularly significant among more severely ill patients.
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http://dx.doi.org/10.1007/s10557-020-07133-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779648PMC
January 2021

miR‑576‑5p promotes epithelial‑to‑mesenchymal transition in colorectal cancer by targeting the Wnt5a‑mediated Wnt/β‑catenin signaling pathway.

Mol Med Rep 2021 02 10;23(2). Epub 2020 Dec 10.

Institute of Cancer and Basic Medicine of Chinese Academy of Sciences; Department of Radiation Oncology, Cancer Hospital of The University of Chinese Academy of Sciences; Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.

Colorectal cancer (CRC) is one of the most common types of malignancy and the third most commonly diagnosed form of cancer worldwide, ranking as the fourth leading cause of cancer‑associated mortality. MicroRNA (miR)‑576‑5p has been reported to be highly expressed in patients with CRC; however, its biological role remains unclear. The present study aimed therefore to investigate the biological role and underlying mechanism of miR‑576‑5p in CRC cell line SW480. The viability of SW480 cells following transfection with miR‑576‑5p mimic or inhibitor was analyzed using MTT assay. Wound healing and Transwell assays were performed to determine the cell migratory and invasive abilities, respectively. A dual luciferase reporter assay was used to verify the predicted binding site between miR‑576‑5p and Wnt5a. Reverse transcription‑quantitative PCR and western blotting were used to analyze the expression levels of miR‑576‑5p, E‑cadherin, N‑cadherin, vimentin, Snail1, Wnt5a, β‑catenin, c‑myc, cyclin D1 and p/t‑c‑Jun. Using bioinformatics analysis, high expression of miR‑576‑5p was found not only in tumor tissues, compared with the normal tissue, but also in CRC cells, compared with NCM460 cells. Furthermore, the inhibition of miR‑576‑5p expression significantly decreased the cell viability and the migratory and invasive abilities of SW480 cells, and suppressed the epithelial‑to‑mesenchymal transition (EMT). In addition, miR‑576‑5p could interact with Wnt5a and regulate the expression level of Wnt5a in order to influence the activity of Wnt/β‑catenin signaling. The results from rescue experiments further demonstrated that the effect of miR‑576‑5p overexpression on cell metastasis and EMT was reversed by Wnt5a overexpression or treatment with XAV‑939, which is an inhibitor of the Wnt/β‑catenin signaling pathway. In conclusion, the findings from the present study suggested that inhibition of miR‑576‑5p may suppress SW480 cell metastasis and EMT by targeting Wnt5a and regulating the Wnt5a‑mediated Wnt/β‑catenin signaling pathway, providing a potential therapeutic target for the treatment of CRC.
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http://dx.doi.org/10.3892/mmr.2020.11733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723166PMC
February 2021

Clinical Outcomes and Safety of Different Treatment Modes for Local Recurrence of Rectal Cancer.

Cancer Manag Res 2020 30;12:12277-12286. Epub 2020 Nov 30.

Department of Abdominal Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences & Zhejiang Cancer Hospital, Hangzhou, People's Republic of China.

Objective: Optimal approaches to patients with local recurrence of rectal cancer are unclear in China. This study aimed to evaluaty -30te the clinical outcomes and toxicity associated with different treatment regimens for patients with local recurrence of rectal cancer.

Methods: A retrospective chart review of patients with local recurrence of rectal cancer and previous radical surgical treatment between March 2010 and December 2017 with curative intent was performed. Disease-related endpoints included treatment progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. Toxicities were assessed using Common Terminology Criteria for Adverse Events, version 5.0, and complications were scored according to the Clavien-Dindo classification.

Results: A total of 71 patients met the inclusion criteria in this study. The recurrence sites were mainly local recurrence in the pelvic cavity and regional lymph node metastasis. Twenty patients received chemoradiotherapy combined with surgery, 10 underwent surgery alone, and others received chemoradiotherapy-alone (n = 27) and chemotherapy-alone (n = 14) treatment. A clear difference was found in PFS between surgery/chemoradiotherapy with surgery and chemoradiotherapy/chemotherapy groups (26.6 months vs 14.1 months, = 0.033). The PFS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 65.2 months, 20.2 months, and 14.2 months, respectively ( = 0.042). The multivariate analysis of PFS demonstrated that surgery was an independent factor. The proportion of patients with distant metastases after chemoradiotherapy/chemotherapy was higher than that of patients undergoing surgery (36.6% vs 21.4%, = 0.179). The OS of patients in the surgery combined with chemoradiotherapy, surgery alone, and chemotherapy/chemoradiotherapy groups was 89.4 months, 66.0 months, and 62.8 months, respectively ( = 0.189). Radiation treatment and surgery did not increase extra severe toxicities.

Conclusion: Surgery combined with chemoradiotherapy was a beneficial treatment mode for managing patients with locally recurrent, nonmetastatic rectal cancer. It was associated with better local disease control, no increase in toxicity, and prolonged survival among patients with locally recurrent rectal cancer.
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http://dx.doi.org/10.2147/CMAR.S278427DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721123PMC
November 2020

Reply to "Novaferon, treatment in COVID-19 patients".

Int J Infect Dis 2021 02 25;103:336-337. Epub 2020 Nov 25.

Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijid.2020.11.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687364PMC
February 2021

The role of CD36 in cardiovascular disease.

Cardiovasc Res 2020 Nov 3. Epub 2020 Nov 3.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.

CD36, also known as the scavenger receptor B2, is a multifunctional receptor widely expressed in various organs. CD36 plays a crucial role in the uptake of long-chain fatty acids, the main metabolic substrate in myocardial tissue. The maturation and transportation of CD36 is regulated by post-translational modifications, including phosphorylation, ubiquitination, glycosylation, and palmitoylation. CD36 is decreased in pathological cardiac hypertrophy caused by ischaemia-reperfusion and pressure overload, and increased in diabetic cardiomyopathy and atherosclerosis. Deficiency of CD36 alleviates diabetic cardiomyopathy and atherosclerosis, while overexpression of CD36 eliminates ischaemia-reperfusion damage, together suggesting that CD36 is closely associated with the progression of cardiovascular diseases and may be a new therapeutic target. This review summarizes the regulation and post-translational modifications of CD36 and evaluates its role in cardiovascular diseases and its potential as a therapeutic target.
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http://dx.doi.org/10.1093/cvr/cvaa319DOI Listing
November 2020