Publications by authors named "Lili Pan"

111 Publications

Characteristics and risk factors of severe coronary artery disease in systemic lupus erythematosus: A multicenter, Chinese Rheumatism Date Center database study.

Int J Rheum Dis 2022 Jul 26. Epub 2022 Jul 26.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Aim: Systemic lupus erythematosus (SLE) with severe coronary artery disease (CAD) is associated with increased mortality. This study aimed to assess the characteristics and risk factors of severe CAD in SLE.

Method: This multicenter, cross-sectional study enrolled consecutive patients with SLE included in the Chinese Rheumatism Date Center registry. Patients with severe CAD including angiography-confirmed stenosis ≥50% in the left main, ≥70% in other major coronary arteries, or myocardial infarction were classified into the CAD group. Patients without CAD were classified into the control group. Subgroups were stratified according to age (set as above and below 45 and 50 for men and women, respectively) and gender. Binary logistic regression analysis was performed to determine independent risk factors of severe CAD in SLE.

Results: Forty-three patients had severe CAD from a total of 3744 patients with SLE, 30 of whom were female; 35 belonged to the older age group and 8 belonged to the younger age group. In older patients, independent risk factors included age, 5 major CAD risk factors, SLE Disease Activity Index 2000 (SLEDAI-2K), hyperuricemia, and corticosteroid exposure. In younger patients, the risk factors were 5 major CAD risk factors and positive antiphospholipid antibody (APL). Male risk factors were age and 5 major CAD risk factors, whereas female risk factors were age, 5 major CAD risk factors, SLEDAI-2K, and positive APL. Three-vessel disease was most prevalent in patients with severe CAD.

Conclusion: We recommend screening for severe CAD in patients with SLE with age- and gender-stratified risk factors.
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http://dx.doi.org/10.1111/1756-185X.14402DOI Listing
July 2022

Erratum.

Ann Clin Lab Sci 2022 05;52(3):510

Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, China.

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May 2022

Prognostic Significance and Immunological Role of FBXO5 in Human Cancers: A Systematic Pan-Cancer Analysis.

Front Immunol 2022 3;13:901784. Epub 2022 Jun 3.

Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.

F-box protein 5 (FBXO5), an essential subunit of the ubiquitin protein ligase complex, is increasingly recognized to exhibit important biological effects in regulating tumor occurrence and progression. The present research was intended to systematically investigate the latent roles of FBXO5 in prognosis and immunological function across cancers. Pan-cancer analyses of FBXO5 were performed based upon publicly available online databases, mainly including the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UCSC Xena, cBioPortal, and ImmuCellAI, revealing the possible relationships between FBXO5 and prognosis, DNA methylation, tumor microenvironment (TME), infiltration of immune cells, immune-related genes, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI). The results suggested that FBXO5 was expressed at a high level in numerous tumor cell lines with significant upregulation in most cancers as opposed to normal tissues. Of note, elevated expression of FBXO5 was significantly related to an unfavorable prognosis in many cancer types. Furthermore, DNA methylation and TME were confirmed to display evident correlation with the expression of FBXO5 in several malignancies. Moreover, FBXO5 expression was remarkably positively correlated with the levels of infiltrating Treg cells and Tcm cells in most tumors, but negatively correlated with tumor-infiltrating CD8 T cells, NK/NKT cells, and Th2 cells. Meanwhile, FBXO5 was demonstrated to be co-expressed with the genes encoding immune activating and suppressive factors, chemokines, chemokine receptors, and major histocompatibility complex (MHC). Immune checkpoints, TMB, and MSI were also overtly associated with FBXO5 dysregulation among diverse kinds of cancers. Additionally, the enrichment analyses showed close relationships between FBXO5 expression and the processes related to cell cycle and immune inflammatory response. These findings provided a detailed comprehension of the oncogenic function of FBXO5. Because of its crucial roles in cancer immunity and tumorigenesis, FBXO5 may serve as a novel prognostic indicator and immunotherapeutic target for various malignancies.
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http://dx.doi.org/10.3389/fimmu.2022.901784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203914PMC
June 2022

Risk factors and surgical prognosis in patients with aortic valve involvement caused by Takayasu arteritis.

Arthritis Res Ther 2022 05 7;24(1):102. Epub 2022 May 7.

Department of Rheumatology and Immunology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, China.

Objective: Aortic valve involvement is not uncommon in patients with Takayasu arteritis (TAK) and leading to poor prognosis. The aim of our study was to explore the risk factors of aortic valve involvement and to evaluate the prognosis in TAK patients with aortic valve involvement.

Method: In this retrospective study, 172 TAK patients were divided into groups with or without aortic valve involvement to identify the risk factors. Patients who underwent aortic valve surgical treatment were followed up to assess cumulative incidence of postoperative adverse events.

Results: A total of 92 TAK patients (53.49%) had aortic valvular lesion. The infiltration of inflammatory cells was found in surgical specimens of aortic valve. Numano type IIb, elevated high-sensitivity C-reactive protein (hs-CRP) level, and dilation of ascending aorta and aortic root were statistically associated with aortic valvular lesion in TAK patients (OR [95%CI] 6.853 [1.685-27.875], p=0.007; 4.896 [1.646-14.561], p=0.004; 4.509 [1.517-13.403], p=0.007; 9.340 [2.188-39.875], p=0.003). The 1-, 5-, and 7-year cumulative incidence of postoperative adverse events were 14.7%, 14.7%, and 31.8%, respectively. Surgical methods (p=0.024, hazard ratio (HR) 0.082) and postoperatively anti-inflammatory therapy (p=0.036, HR 0.144) were identified as potential predictors of postoperative adverse events.

Conclusions: Regularly echocardiogram screening is suggested in patients with Numano type IIb and aggressive treatment should be performed early in TAK patients. As for TAK patients with aortic valve surgery, aortic root replacement seems to be the preferred option and regular anti-inflammatory therapy may reduce the occurrence of adverse events of them.
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http://dx.doi.org/10.1186/s13075-022-02788-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077813PMC
May 2022

Prediction of Hearing Prognosis of Large Vestibular Aqueduct Syndrome Based on the PyTorch Deep Learning Model.

J Healthc Eng 2022 13;2022:4814577. Epub 2022 Apr 13.

Department of Radiology, Children's Hospital of Fudan University, Shanghai 201102, China.

In order to compare magnetic resonance imaging (MRI) findings of patients with large vestibular aqueduct syndrome (LVAS) in the stable hearing loss (HL) group and the fluctuating HL group, this paper provides reference for clinicians' early intervention. From January 2001 to January 2016, patients with hearing impairment diagnosed as LVAS in infancy in the Department of Otorhinolaryngology, Head and Neck Surgery, Children's Hospital of Fudan University were collected and divided into the stable HL group ( = 29) and the fluctuating HL group ( = 30). MRI images at initial diagnosis were collected, and various deep learning neural network training models were established based on PyTorch to classify and predict the two series. Vgg16_bn, vgg19_bn, and ResNet18, convolutional neural networks (CNNs) with fewer layers, had favorable effects for model building, with accs of 0.9, 0.8, and 0.85, respectively. ResNet50, a CNN with multiple layers and an acc of 0.54, had relatively poor effects. The GoogLeNet-trained model performed best, with an acc of 0.98. We conclude that deep learning-based radiomics can assist doctors in accurately predicting LVAS patients to classify them into either fluctuating or stable HL types and adopt differentiated treatment methods.
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http://dx.doi.org/10.1155/2022/4814577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020928PMC
April 2022

Clinical features and risk factors of intracranial artery disease in patients with Takayasu arteritis.

Clin Rheumatol 2022 Aug 19;41(8):2475-2481. Epub 2022 Apr 19.

Department of Rheumatology, Beijing Anzhen Hospital Affiliated to Capital Medical University, 2 Anzhen Road, Chaoyang District, Beijing, China.

Objectives: It has been known that aorta, subclavian, and extracranial arteries are commonly involved in Takayasu arteritis (TA). However, the involvement of intracranial artery in TA has not been well explored. The purpose of this study was to describe the clinical characteristics of intracranial artery lesions in TA patients and identify associated risk factors.

Methods: A total of 160 patients diagnosed with TA at Beijing Anzhen Hospital from November 2012 to November 2019 were retrospectively enrolled in this study and assigned to different groups according to the presence or absence of intracranial artery lesions.

Results: Our data showed that 20% of the enrolled 160 patients developed intracranial artery lesions and the right internal carotid artery (ICA) was the most common involved artery (53%). The average age of patients with intracranial artery lesions was significantly older compared to that of patients without intracranial artery involvement (43.56 ± 11.40 vs 36.41 ± 12.22, p = 0.003). In addition, more patients in the intracranial artery group had concomitant disease histories of stroke and/or hypertension (p = 0.010, 0.033). Chest tightness, chest pain, palpitation, coronary artery lesions, and extracranial segment lesions of ICA were more commonly observed in patients with intracranial artery lesions (p < 0.001, 0.017, 0.015, < 0.001, 0.003). Furthermore, we discovered that patients with coronary artery involvement, extracranial segment lesions of ICA, and higher Vasculitis Damage Index (VDI) score had an increased risk of developing intracranial artery lesions (p = 0.013, 0.019, 0.019).

Conclusion: Our study showed that the intracranial artery disease was common in TA and was associated with coronary artery lesions, extracranial segment lesions of ICA, and higher VDI score. Key Points • Intracranial artery disease in TA patients had advanced age and higher triglyceride level. • Besides coronary artery lesions, intracranial artery disease in TA patients was associated with the extracranial segment lesions of ICA and higher VDI score.
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http://dx.doi.org/10.1007/s10067-022-06168-1DOI Listing
August 2022

Comparison of Different Thoracic Aortic Wall Characteristics for Assessment of Disease Activity in Takayasu Arteritis: A Quantitative Study with 3.0 T Magnetic Resonance Imaging.

Rev Cardiovasc Med 2022 Mar;23(3):92

Department of Radiology, Beijing Friendship Hospital, Capital Medical University, 100050 Beijing, China.

Background: Determination of disease activity in Takayasu arteritis (TAK) is crucial for clinical management but challenging. The value of different magnetic resonance imaging (MRI) characteristics for the assessment of disease activity remains unclear. This study investigated the imaging findings of the thoracic aortic wall and elasticity by using a comprehensive 3.0 T MRI protocol.

Methods: We prospectively enrolled 52 consecutive TAK patients. TAK activity was recorded according to the ITAS2010. All the patients underwent thoracic aortic MRI. The luminal morphology of the thoracic aorta and its main branches were quantitatively evaluated using a contrast-enhanced magnetic resonance angiography (MRA) sequence. The maximum wall thickness of the thoracic aorta, postcontrast enhancement ratio, and aortic wall edema were analyzed in each patient through pre- and post-enhanced T1-weighted and T2-weighted imaging. Pulse-wave velocity (PWV) of the thoracic aorta was calculated using a four-dimensional flow technique.

Results: The majority of the 52 patients had type V disease (34.62%, 18/52). Among all the MRI indicators of the thoracic aorta, the area under the curve was the largest for the maximal wall thickness (0.804, 95% confidence interval [CI] = 0.667-0.941). The maximal wall thickness (93.33%, 95% CI = 68.1%-99.8%) exhibited the highest sensitivity with a cutoff value of 3.12 mm. Wall edema (84.00%, 95% CI = 63.9%-95.5%) presented the highest specificity. A positive correlation was noted between PWV and patients' age (r = 0.54, < 0.001), disease duration (r = 0.52, < 0.001), and the maximum wall thickness (r = 0.45, = 0.001).

Conclusions: MRI enabled the comprehensive assessment of aortic wall morphology and functional markers for TAK disease activity. Aortic maximal wall thickness was the most accurate indicator of TAK activity. The early phase was superior to the delay phase for aortic wall enhancement analysis for assessing TAK activity.
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http://dx.doi.org/10.31083/j.rcm2303092DOI Listing
March 2022

A putative cap binding protein and the methyl phosphate capping enzyme Bin3/MePCE function in telomerase biogenesis.

Nat Commun 2022 02 25;13(1):1067. Epub 2022 Feb 25.

Faculty of Biology, Johannes Gutenberg University, 55099, Mainz, Germany.

Telomerase reverse transcriptase (TERT) and the noncoding telomerase RNA (TR) subunit constitute the core of telomerase. Additional subunits are required for ribonucleoprotein complex assembly and in some cases remain stably associated with the active holoenzyme. Pof8, a member of the LARP7 protein family is such a constitutive component of telomerase in fission yeast. Using affinity purification of Pof8, we have identified two previously uncharacterized proteins that form a complex with Pof8 and participate in telomerase biogenesis. Both proteins participate in ribonucleoprotein complex assembly and are required for wildtype telomerase activity and telomere length maintenance. One factor we named Thc1 (Telomerase Holoenzyme Component 1) shares structural similarity with the nuclear cap binding complex and the poly-adenosine ribonuclease (PARN), the other is the ortholog of the methyl phosphate capping enzyme (Bin3/MePCE) in metazoans and was named Bmc1 (Bin3/MePCE 1) to reflect its evolutionary roots. Thc1 and Bmc1 function together with Pof8 in recognizing correctly folded telomerase RNA and promoting the recruitment of the Lsm2-8 complex and the catalytic subunit to assemble functional telomerase.
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http://dx.doi.org/10.1038/s41467-022-28545-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8881624PMC
February 2022

RNA helicase DHX15 decreases cell apoptosis by NF-κB signaling pathway in Burkitt lymphoma.

Cancer Cell Int 2022 Feb 22;22(1):92. Epub 2022 Feb 22.

Department of Hematology, Fujian Institute of Hematology, Fujian Medical University Union Hospital, Xinquan Road, No.29, Fuzhou, Fujian, China.

Background: DHX15 is one of the RNA helicase family members involving in several biological processes. Studies have reported that overexpression of DHX15 is related to cancer progression. However, the role of DHX15 in Burkitt lymphoma (BL) and latent Epstein-Barr virus (EBV) infection remains to be elucidated.

Methods: Expression of DHX15 was measured in BL patient by immunohistochemical staining. In vitro study, a CCK-8 assay was used to analyze cell proliferation and flow cytometry was performed to assess cell cycle, apoptosis and mitochondria membrane potential. Members of NF-κB signaling pathway and apoptotic-related proteins expression were measured by western-blot. EBV latent infection products and RNA polymerase III transcripts expression were determined by quantitative real-time PCR and western-blot. In vivo study, HE, IHC, TUNEL and ISH assays were used to analyze the effect of DHX15 on subcutaneous tumor nodes formation.

Results: DHX15 was overexpressed in Burkitt lymphoma patients and tends to be associated with poor progression-free survival and poor overall survival. Knockdown of DHX15 significantly inhibited BL tumor growth, reduced cell proliferation, induced cell cycle arrest and increased cell apoptosis. Further analysis showed that canonical NF-κB signaling and its downstream targets, mitochondria and Caspase were involved in the increased cell apoptosis after DHX15 gene knockdown. Furthermore, knockdown of DHX15 reduced EBV latent infection products expression and inhibited RNA polymerase III activity.

Conclusion: DHX15 may be an oncogene in the development of BL and a potential therapeutic target for the treatment of BL and latent EBV infection.
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http://dx.doi.org/10.1186/s12935-021-02426-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8862312PMC
February 2022

VSNL1 Promotes Cell Proliferation, Migration, and Invasion in Colorectal Cancer by Binding with COL10A1.

Ann Clin Lab Sci 2022 Jan;52(1):60-72

Abdominal Surgery, Medical College of Nanchang University, Cancer Hospital of Jiangxi Province, Nanchang, Jiangxi, China

Objective: The study aimed to explore the role of VSNL1/COL10A1 axis in colorectal cancer.

Methods: The differential-expressed mRNA in colorectal cancer tissues and adjacent tissues were analyzed through GEO database and GEPIA database. The target genes of mRNA were predicted through the Starbase database, and the targeting relationship of mRNA was verified by co-IP assay. The expressions of VSNL1 and COL10A1 were detected by RT-PCR and immunohistochemistry. Cell viability and proliferation were detected by CCK8 assay and EdU assay, respectively. Cell migration and invasion were detected by transwell assay. The expression of related proteins was detected by western blot.

Results: VSNL1 was significantly overexpressed in colorectal cancer tissues compared with adjacent tissues. In addition, downregulation of VSNL1 could inhibit the proliferation, migration, and invasion of colorectal cancer cells. The co-IP experiment indicated that VSNL1 could bind with COL10A1. Further studies demonstrated that upregulation of COL10A1 could promote colorectal cells proliferation, migration, invasion, and reverse the effect of sh-VSNL1 on colorectal cancer cells.

Conclusion: VSNL1 could promote the proliferation, migration, and invasion of colorectal cancer by targeting COL10A1. VSNL1 might be a potential target for colorectal cancer treatment.
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January 2022

Strategic Design of Amyloid-β Species Fluorescent Probes for Alzheimer's Disease.

ACS Chem Neurosci 2022 03 8;13(5):540-551. Epub 2022 Feb 8.

Department of Respiratory and Critical Care Medicine, Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610093, P. R. China.

Alzheimer's disease (AD) is a high mortality and high disability rates neurodegenerative disease characterized by irreversible progression and poses a significant social and economic burden throughout the world. However, currently approved AD therapeutic agents only alleviate symptoms and there is still a lack of practical therapeutic regimens to stop or slow the progression of this disease. Thus, there is urgently needed novel diagnosis tools and drugs for early diagnosis and treatment of AD. Among several AD pathological hallmarks, amyloid-β (Aβ) peptide deposition is considered a critical initiating factor in AD. In recent years, with the advantages of excellent sensitivity and high resolution, near-infrared fluorescence (NIRF) imaging has attracted the attention of many researchers to develop Aβ plaque probes. This review mainly focused on different NIRF probe design strategies for imaging Aβ species to pave the way for the future design of novel NIRF probes for early diagnosis AD.
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http://dx.doi.org/10.1021/acschemneuro.1c00810DOI Listing
March 2022

Synthesis, radiolabeling, and evaluation of a potent β-site APP cleaving enzyme (BACE1) inhibitor for PET imaging of BACE1 in vivo.

Bioorg Med Chem Lett 2022 03 12;59:128543. Epub 2022 Jan 12.

Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China. Electronic address:

The β-site APP-cleaving enzyme 1 (BACE1) plays important roles in the proteolytic processing of amyloid precursor protein, and can be regarded as an important target for the diagnosis and treatment of AD. This study aimed to report the synthesis and evaluation of an F-labeled 2-amino-3,4-dihydroquinazoline analog as a potential BACE1 radioligand. A fluoropropyl side chain was introduced to the phenyl of this 3,4-dihydroquinazoline scaffold to generate the radioligand. Our preliminary data indicated that although the 2-amino-3,4-dihydroquinazoline scaffold possessed favorable in-vitro properties as a PET ligand, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand.
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http://dx.doi.org/10.1016/j.bmcl.2022.128543DOI Listing
March 2022

In vitro and in vivo evaluation of At-labeled fibroblast activation protein inhibitor for glioma treatment.

Bioorg Med Chem 2022 Jan 5;55:116600. Epub 2022 Jan 5.

Key Laboratory of Radiation Physics and Technology of the Ministry of Education; Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, PR China. Electronic address:

Glioma is the most common primary intracranial tumor without effective treatment. Positron emission tomography tracers labeled with Ga targeting fibroblast activation protein (FAP) have shown favorable characteristics in the diagnosis of glioma. However, to the best of our knowledge, FAP-targeted endoradiotherapy has never been explored in glioma. Hence, in this study, we investigated the therapeutic effect of At-labeled fibroblast activation protein inhibitor (FAPI) for glioma in vitro and in vivo. By astatodestannylation reaction, we prepared At-FAPI-04 with a radiochemical yield of 45 ± 6.7% and radiochemical purity of 98%. With good stability in vitro, At-FAPI-04 showed fast and specific binding to FAP-positive U87MG cells, and could significantly reduce the cell viability, arrested cell cycle at G2/M phase and suppressed cell proliferative efficacy. Biodistribution studies revealed that 6-fold higher accumulation in tumor sites was achieved by intratumoral injection in comparison with intravenous injection. In U87MG xenografts, At-FAPI-04 obviously suppressed the tumor growth and prolonged the median survival in a dose-dependent manner without obvious toxicity to normal organs. In addition, reduced proliferation and increased apoptosis were also observed after At-FAPI-04 treatment. All these results suggest that targeted alpha-particle therapy (TAT) mediated by At-FAPI-04 can provide an effective and promising strategy for the treatment of glioma.
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http://dx.doi.org/10.1016/j.bmc.2021.116600DOI Listing
January 2022

A Global Multiregional Proteomic Map of the Human Cerebral Cortex.

Genomics Proteomics Bioinformatics 2021 Nov 8. Epub 2021 Nov 8.

Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. Electronic address:

The Brodmann area (BA)-based map is one of the most widely used cortical maps for studies of human brain functions and in clinical practice; however, the molecular architecture of BAs remains unknown. The present study provided a global multiregional proteomic map of the human cerebral cortex by analyzing 29 BAs. These 29 BAs were grouped into 6 clusters based on similarities in proteomic patterns: the motor and sensory cluster, vision cluster, auditory cluster and Broca's area, Wernicke's area cluster, cingulate cortex cluster, and heterogeneous function cluster. We identified 474 cluster-specific and 134 BA-specific signature proteins whose functions are closely associated with specialized functions and disease vulnerability of the corresponding cluster or BA. The findings of the present study could provide explanations for the functional connections between the anterior cingulate cortex and sensorimotor cortex and for anxiety-related function in the sensorimotor cortex. The brain transcriptomic and proteomic comparison indicated that they both could reflect the function of cerebral cortex, but showed different characteristics. These proteomic data are publicly available at the Human Brain Proteome Atlas (www.brain-omics.com). Our results may enhance our understanding of the molecular basis of brain functions and provide an important resource to support human brain research.
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http://dx.doi.org/10.1016/j.gpb.2021.08.008DOI Listing
November 2021

C Deletion at the re74650330 Locus of the Gene (rs74650330) Increases the Risk of Coronary Artery Disease in Individuals with Low-Density Lipoprotein Cholesterol Levels.

Genet Test Mol Biomarkers 2021 Oct;25(10):660-667

Clinical Medical Research Center, Changzhou Key Laboratory of Individualized Diagnosis and Treatment Associated with High Technology Research, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Genetic variants of the gene are associated with several cardiovascular disease risk factors, including body mass index, systolic blood pressure (SBP), diastolic blood pressure (DBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-density lipoprotein cholesterol (HDL-C) levels. The present study aimed to investigate the association between the SNPs rs13107325 and rs74650330 and CAD in the Han population in Jiangsu (China). Genotyping of these SNPs was performed in 258 patients with CAD and 170 healthy controls using the base-quenched probe technique. The association between the alleles of the rs74650330 locus and blood lipid and glucose profiles was investigated. Receiver operating characteristic (ROC) curve analysis was used to quantify the optimal thresholds for lipid and FBG levels and the risk factors for CAD were estimated by logistic regression analysis. The rs13107325 polymorphism was not found in the 428 Chinese individuals enrolled in the current study. For rs74650330, individuals harboring the C allele had significantly higher HDL levels than those without this allele in the control group ( = 0.039), while the opposite was true for low-density lipoprotein cholesterol (LDL-C) levels ( = 0.046). Further analysis indicated that when LDL-C levels were lower than 2.365 mmol/L, subjects with C/del and del/del had a 7.293-fold increased risk of CAD compared with that of controls without the mutation (odds ratio: 7.293; 95% confidence interval: 0.953-55.79). The susceptibility of polymorphisms to CAD were studied and revealed a possible role for the deletion variant of rs74650330 in increasing the risk of CAD among the Chinese Han population.
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http://dx.doi.org/10.1089/gtmb.2021.0083DOI Listing
October 2021

MicroRNA-425-5p Is Involved in the Development of Diabetic Retinopathy and Regulates the Proliferation and Migration of Retinal Microvascular Endothelial Cells.

Ophthalmic Res 2022 27;65(1):60-67. Epub 2021 Sep 27.

Department of Ophthalmology, Affiliated Hospital of Weifang Medical University, Weifang, China.

Introduction: The objective of this article was to detect the expression pattern and clinical value of miR-425-5p in diabetic retinopathy (DR) patients and investigate its effect on the proliferation and migration of human retinal microvascular endothelial cells (HRMECs) in a high glucose (HG) state.

Methods: The serum miR-425-5p level of the subjects was determined using quantitative real-time PCR. The diagnostic value of serum miR-425-5p was validated using the receiver operating characteristic curve. Pearson analysis detected the correlation between clinical indicators and microRNA. The influence of miR-425-5p on cell proliferation and migration under HG conditions was calculated by using Cell Counting Kit-8 and Transwell assay.

Results: Serum miR-425-5p levels showed a gradual increasing trend in the healthy control group, the diabetic mellitus patients without DR, and DR patients. Moreover, the levels of miR-425-5p in proliferative DR (PDR) patients were elevated than that of non-PDR (NPDR) patients. Furthermore, upregulated miR-425-5p had a high diagnostic value for DR patients and can distinguish PDR patients from NPDR patients. The expression of miR-425-5p was significantly positively correlated with the fasting plasma glucose, glycosylated hemoglobin (HbA1C), homeostasis model assessment of insulin resistance, and disease course of the patients. Under HG conditions, overexpression of miR-425-5p promoted HRMEC proliferation and migration, while inhibition of miR-425-5p led to opposite results.

Conclusion: Present research confirmed that serum miR-425-5p levels in DR are marked by elevation. High expression of miR-425-5p can be used as a feasible diagnostic biomarker for DR patients and can predict the development and severity of DR. Moreover, inhibiting the expression of miR-425-5p levels under the condition of hyperglycemia may be used as a valuable therapeutic strategy for preventing the pathogenesis of DR.
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http://dx.doi.org/10.1159/000516906DOI Listing
March 2022

The role of CD8 Granzyme B T cells in the pathogenesis of Takayasu's arteritis.

Clin Rheumatol 2022 Jan 7;41(1):167-176. Epub 2021 Sep 7.

Department of Rheumatology, Capital Medical University Affiliated Anzhen Hospital, Beijing, China.

Objective: T cell-mediated immune response plays a key role in Takayasu arteritis (TAK). Although previous studies have showed the roles of CD4T cell and its subsets in TAK, the change of CD8 T cell subsets remains unclear. This study investigated the role of CD8 T cell subsets in TAK.

Methods: The study consisted of 56 TA patients and 51 healthy controls. The percentages of CD8T cells, CD8GranzymeB T cells, CD8Perforin T cells, and CD8IFN-γ T cells in blood samples were analyzed by flow cytometry.

Results: We found that the percentages of CD8GranzymeB T cells (P = 0.030), CD8Perforin T cells (P = 0.000), and CD8IFN-γ T cells (P = 0.002) in CD8T cells were higher in TAK patients compared to control group. After 6 months of treatment, the proportion of CD8T cells in lymphocytes were significantly lower in TAK patients than the baseline assessment (P = 0.033). A lower ratio of CD8GranzymeB T cells/CD8 T cells were showed in TAK patents after treatment compared with TAK patients before treatments (P = 0.011). The change of CD8GranzymeB T cells/CD8 T cells ratio was positively correlated with the change of ITAS (r = 0.721, P = 0.002) and ITAS-A (r = 0.637, P = 0.008). Finally, the immunofluorescence staining showed the infiltration of CD8 Granzyme B cells in the aortic tissue of TAK patients.

Conclusion: Our results disclose that the CD8 T lymphocytes may play a role in TAK pathogenesis. Targeting CD8GranzymeB T lymphocytes or Granzyme B inhibitors could be a potential therapeutic approach for the treatment of TAK. Key Points • Our study investigated role the of CD8 T cell subsets in TAK. • We found the percentages of CD8GranzymeB T cells, CD8Perforin T cells, and CD8IFN-γ T cells in CD3CD8T cells were higher in TAK patients. • The proportion of CD8T cells in lymphocytes and the ratio of CD8GranzymeB T cells/CD8 T cells were significantly lower in TAK patients after treatment.
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http://dx.doi.org/10.1007/s10067-021-05903-4DOI Listing
January 2022

Malignant Extrarenal Rhabdoid Tumor of the Vagina on FDG PET/CT.

Clin Nucl Med 2021 Dec;46(12):1020-1021

From the Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China.

Abstract: Malignant rhabdoid tumor is an aggressive neoplasm commonly arising from the kidney during infancy and childhood. Extrarenal forms of this tumor are relatively rare and have been reported in several extrarenal sites including central nervous system, liver, bladder, vulva, and head and neck. Hereby, we present FDG PET/CT findings of malignant extrarenal rhabdoid tumor originating from the vagina in an 8-year-old girl.
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http://dx.doi.org/10.1097/RLU.0000000000003751DOI Listing
December 2021

Relative transmissibility of shigellosis among different age groups: A modeling study in Hubei Province, China.

PLoS Negl Trop Dis 2021 06 10;15(6):e0009501. Epub 2021 Jun 10.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen City, Fujian Province, People's Republic of China.

Shigellosis is a heavy disease burden in China especially in children aged under 5 years. However, the age-related factors involved in transmission of shigellosis are unclear. An age-specific Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model was applied to shigellosis surveillance data maintained by Hubei Province Centers for Disease Control and Prevention from 2005 to 2017. The individuals were divided into four age groups (≤ 5 years, 6-24 years, 25-59 years, and ≥ 60 years). The effective reproduction number (Reff), including infectivity (RI) and susceptibility (RS) was calculated to assess the transmissibility of different age groups. From 2005 to 2017, 130,768 shigellosis cases were reported in Hubei Province. The SEIAR model fitted well with the reported data (P < 0.001). The highest transmissibility (Reff) was from ≤ 5 years to the 25-59 years (mean: 0.76, 95% confidence interval [CI]: 0.34-1.17), followed by from the 6-24 years to the 25-59 years (mean: 0.69, 95% CI: 0.35-1.02), from the ≥ 60 years to the 25-59 years (mean: 0.58, 95% CI: 0.29-0.86), and from the 25-59 years to 25-59 years (mean: 0.50, 95% CI: 0.21-0.78). The highest infectivity was in ≤ 5 years (RI = 1.71), and was most commonly transmitted to the 25-59 years (45.11%). The highest susceptibility was in the 25-59 years (RS = 2.51), and their most common source was the ≤ 5 years (30.15%). Furthermore, "knock out" simulation predicted the greatest reduction in the number of cases occurred by when cutting off transmission routes among ≤ 5 years and from 25-59 years to ≤ 5 years. Transmission in ≤ 5 years occurred mainly within the group, but infections were most commonly introduced by individuals in the 25-59 years. Infectivity was highest in the ≤ 5 years and susceptibility was highest in the 25-59 years. Interventions to stop transmission should be directed at these age groups.
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http://dx.doi.org/10.1371/journal.pntd.0009501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219151PMC
June 2021

Dhx15 regulates zebrafish definitive hematopoiesis through the unfolded protein response pathway.

Cancer Sci 2021 Sep 11;112(9):3884-3894. Epub 2021 Jul 11.

Union Clinical Medical Colleges, Fujian Medical University, Fuzhou, China.

Gene alterations are recognized as important events in acute myeloid leukemia (AML) progression. Studies on hematopoiesis of altered genes contribute to a better understanding on their roles in AML progression. Our previous work reported a DEAH box helicase 15 (DHX15) R222G mutation in AML patients, and we showed DHX15 overexpression is associated with poor prognosis in AML patients. In this work, we further study the role of dhx15 in zebrafish developmental hematopoiesis by generating dhx15 zebrafish using transcription activator-like effector nuclease technology. Whole-mount in situ hybridization (WISH) analysis showed hematopoietic stem/progenitor cells were dramatically perturbed when dhx15 was deleted. Immunofluorescence staining indicated inhibited hematopoietic stem/progenitor cell (HSPC) proliferation instead of accelerated apoptosis were detected in dhx15 zebrafish. Furthermore, our data showed that HSPC defect is mediated through the unfolded protein response (UPR) pathway. DHX15 R222G mutation, a recurrent mutation identified in AML patients, displayed a compromised function in restoring HSPC failure in dhx15 ; Tg (hsp: DHX15 R222G) zebrafish. Collectively, this work revealed a vital role of dhx15 in the maintenance of definitive hematopoiesis in zebrafish through the unfolded protein respone pathway. The study of DHX15 and DHX15 R222G mutation could hold clinical significance for evaluating prognosis of AML patients with aberrant DHX15 expression.
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http://dx.doi.org/10.1111/cas.15002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409414PMC
September 2021

Axillary Glomus Tumor Revealed by FDG PET/CT.

Clin Nucl Med 2021 Oct;46(10):837-839

From the Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China.

Abstract: Glomus tumors are vascular neoplasms arising from glomus bodies. They are typically found in tissues where glomus bodies are concentrated, including the subungual layer of the fingers or the deep dermis of the palm, wrist, forearm, and foot but rarely occur in the axillary region. Herein, we reported the MRI and FDG PET/CT findings of a glomus tumor presenting as an axillary mass in a 25-year-old woman.
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http://dx.doi.org/10.1097/RLU.0000000000003694DOI Listing
October 2021

Dual self-paced multi-view clustering.

Neural Netw 2021 Aug 6;140:184-192. Epub 2021 Mar 6.

School of Software, Shandong University, Jinan 250101, China.

By utilizing the complementary information from multiple views, multi-view clustering (MVC) algorithms typically achieve much better clustering performance than conventional single-view methods. Although in this field, great progresses have been made in past few years, most existing multi-view clustering methods still suffer the following shortcomings: (1) most MVC methods are non-convex and thus are easily stuck into suboptimal local minima; (2) the effectiveness of these methods is sensitive to the existence of noises or outliers; and (3) the qualities of different features and views are usually ignored, which can also influence the clustering result. To address these issues, we propose dual self-paced multi-view clustering (DSMVC) in this paper. Specifically, DSMVC takes advantage of self-paced learning to tackle the non-convex issue. By applying a soft-weighting scheme of self-paced learning for instances, the negative impact caused by noises and outliers can be significantly reduced. Moreover, to alleviate the feature and view quality issues, we develop a novel feature selection approach in a self-paced manner and a weighting term for views. Experimental results on real-world data sets demonstrate the effectiveness of the proposed method.
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http://dx.doi.org/10.1016/j.neunet.2021.02.022DOI Listing
August 2021

FDA Approval Summary: Selumetinib for Plexiform Neurofibroma.

Clin Cancer Res 2021 08 12;27(15):4142-4146. Epub 2021 Mar 12.

Office of Oncologic Diseases, FDA, Silver Spring, Maryland.

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma-related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51-79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit-risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-5032DOI Listing
August 2021

Primary Ewing Sarcoma of Seminal Vesicle on PET/CT.

Clin Nucl Med 2021 May;46(5):422-423

From the Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine.

Abstract: Ewing sarcoma is an aggressive malignancy that most often presents as an undifferentiated primary bone tumor; less commonly, it arises in extraosseous soft tissues of mesenchymal cell origin. Primary extraosseous involvement of seminal vesicle is rarely reported. Herein, we describe FDG PET/CT and MRI findings of a 55-year-old man who presented with a pelvic mass, which was confirmed to be primary Ewing sarcoma/primitive neuroectodermal tumor arising from seminal vesicle by histopathologic findings.
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http://dx.doi.org/10.1097/RLU.0000000000003539DOI Listing
May 2021

PON2 subverts metabolic gatekeeper functions in B cells to promote leukemogenesis.

Proc Natl Acad Sci U S A 2021 02;118(7)

Center of Molecular and Cellular Oncology, Yale Cancer Center, Yale School of Medicine, New Haven, CT 06511;

Unlike other cell types, developing B cells undergo multiple rounds of somatic recombination and hypermutation to evolve high-affinity antibodies. Reflecting the high frequency of DNA double-strand breaks, adaptive immune protection by B cells comes with an increased risk of malignant transformation. B lymphoid transcription factors (e.g., IKZF1 and PAX5) serve as metabolic gatekeepers by limiting glucose to levels insufficient to fuel transformation. We here identified aberrant expression of the lactonase PON2 in B cell acute lymphoblastic leukemia (B-ALL) as a mechanism to bypass metabolic gatekeeper functions. Compared to normal pre-B cells, PON2 expression was elevated in patient-derived B-ALL samples and correlated with poor clinical outcomes in pediatric and adult cohorts. Genetic deletion of had no measurable impact on normal B cell development. However, in mouse models for BCR-ABL1 and NRAS-driven B-ALL, deletion of compromised proliferation, colony formation, and leukemia initiation in transplant recipient mice. Compromised leukemogenesis resulted from defective glucose uptake and adenosine triphosphate (ATP) production in -deficient murine and human B-ALL cells. Mechanistically, PON2 enabled glucose uptake by releasing the glucose-transporter GLUT1 from its inhibitor stomatin (STOM) and genetic deletion of largely rescued deficiency. While not required for glucose transport, the PON2 lactonase moiety hydrolyzes the lactone-prodrug 3OC12 to form a cytotoxic intermediate. Mirroring PON2 expression levels in B-ALL, 3OC12 selectively killed patient-derived B-ALL cells but was well tolerated in transplant recipient mice. Hence, while B-ALL cells critically depend on aberrant expression to evade metabolic gatekeeper functions, PON2 lactonase activity can be leveraged as synthetic lethality to overcome drug resistance in refractory B-ALL.
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http://dx.doi.org/10.1073/pnas.2016553118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896313PMC
February 2021

A Brief Introduction to Porphyrin Compounds used in Tumor Imaging and Therapies.

Mini Rev Med Chem 2021 ;21(11):1303-1313

Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.

As a group of heterocyclic macrocycle organic natural compounds occurring universally in animal tissues and plants, porphyrins are composed of four modified pyrrole subunits. Porphyrin analogues/ derivatives possess multiple biochemical properties because of their unique structures and have been extensively investigated in cancer treatment. Studies have shown that porphyrins and their derivatives have the ability to locate tumor cells in a variety of human cancers, and these compounds not only exhibit potent therapeutic effects as photodynamic agents but also show promising properties in medicinal imaging, such as MRI, photoacoustic imaging, fluorescence imaging, and PET/SPECT imaging. This paper reviews the recent reports of porphyrin derivatives as therapeutic agents used in tumor therapies, such as sonodynamic therapy, photodynamic therapy and radiotherapy, as well as the imaging agents for multimodality tumor imaging. The limitations of porphyrin-based compounds in tumor treatments and future prospects are also summarized.
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http://dx.doi.org/10.2174/1389557520999201209212745DOI Listing
August 2021

The Therapeutic Potential of Purinergic Receptors in Alzheimer's Disease and Promising Therapeutic Modulators.

Mini Rev Med Chem 2021 ;21(11):1288-1302

Department of Nuclear Medicine, Laboratory of Clinical Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Recent studies have proven that the purinergic signaling pathway plays a key role in neurotransmission and neuromodulation, and is involved in various neurodegenerative diseases and psychiatric disorders. With the characterization of the subtypes of receptors in purinergic signaling, i.e. the P1 (adenosine), P2X (ion channel) and P2Y (G protein-coupled), more attention has been paid to the pathophysiology and therapeutic potential of purinergic signaling in the central nervous system disorders. Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. However, as drug development aimed to prevent or control AD has series of failures in recent years, more researchers have focused on the neuroprotection-related mechanisms such as purinergic signaling in AD patients to find a potential cure. This article reviews the recent discoveries of purinergic signaling in AD, and summarizes the potential agents as modulators for the receptors of purinergic signaling in AD-related research and treatments. Thus, our paper provides an insight into purinergic signaling in the development of anti- AD therapies.
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http://dx.doi.org/10.2174/1389557520999201209211610DOI Listing
August 2021

The long noncoding RNA DLGAP1-AS2 facilitates cholangiocarcinoma progression via miR-505 and GALNT10.

FEBS Open Bio 2021 02 31;11(2):413-422. Epub 2020 Dec 31.

Department of Nuclear Medicine, Central Hospital of Shan County, Heze, China.

Cholangiocarcinoma (CCA) is a highly invasive malignant tumor with high mortality. Most cases of CCA are already advanced when they are detected, resulting in poor prognosis. As such, there is an ongoing need for the identification of effective biomarkers for CCA. The long noncoding RNA DLGAP1-AS2 has been reported to have prognostic value in glioma and Wilms' tumor. Here, we investigated the function of DLGAP1-AS2 in CCA. The differential expression of DLGAP1-AS2 in CCA tissues and normal tissues was first examined using data from the The Cancer Genome Atlas database and then in CCA cell lines by quantitative RT-PCR (qRT-PCR). The target gene was predicted by bioinformatics analysis, and the binding sites were confirmed using luciferase assay. DLGAP1-AS2 is up-regulated in CCA, and high DLGAP1-AS2 expression promotes cell viability and is associated with poor prognosis. Notably, DLGAP1-AS2 acts as a sponge to suppress miR-505 expression, and miR-505 reduces the expression of N-acetylgalactosaminyltransferase 10 (GALNT10) in CCA cells. Biofunctional experiments revealed that a miR-505 inhibitor almost completely removed the inhibitory effect of si-DLGAP1-AS2 on CCA cell malignant progression, whereas the malignant phenotype of cells cotransfected with si-DLGAP1-AS2 and si-GALNT10 was significantly reduced as compared with the control. In summary, the DLGAP1-AS2/miR-505/GALNT10 axis may contribute to regulating the malignant progression of CCA and may have potential as a novel target for CCA therapy.
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http://dx.doi.org/10.1002/2211-5463.13061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876506PMC
February 2021

Latent Dirichlet allocation based generative adversarial networks.

Neural Netw 2020 Dec 21;132:461-476. Epub 2020 Sep 21.

School of Computer Science and Technology, Harbin Institute of Technology, Shenzhen, Shenzhen, 510085, China; Center for Artificial Intelligence, Peng Cheng Lab, Shenzhen, 510085, China; SMILE Lab, School of Computer Science and Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China. Electronic address:

Generative adversarial networks have been extensively studied in recent years and powered a wide range of applications, ranging from image generation, image-to-image translation, to text-to-image generation, and visual recognition. These methods typically model the mapping from latent space to image with single or multiple generators. However, they have obvious drawbacks: (i) ignoring the multi-modal structure of images, and (ii) lacking model interpretability. Importantly, the existing methods mostly assume one or more generators can cover all image modes even if we do not know the structure of data. Thus, mode dropping and collapse often take place along with GANs training. Despite the importance of exploring the data structure in generation, it has been almost unexplored. In this work, aiming at generating multi-modal images and interpreting model explicitly, we explore the theory on how to integrate GANs with data structure prior, and propose latent Dirichlet allocation based generative adversarial networks (LDAGAN). This framework is extended to combine with a variety of state-of-the-art single-generator GANs and achieves improved performance. Extensive experiments on synthetic and real datasets demonstrate the efficacy of LDAGAN for multi-modal image generation. An implementation of LDAGAN is available at https://github.com/Sumching/LDAGAN.
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http://dx.doi.org/10.1016/j.neunet.2020.08.012DOI Listing
December 2020

Authors' Response to the Letter to the Editor: Increased Circulating Angiopoietin-Like Protein 8 Levels Are Associated with Thoracic Aortic Dissection and Higher Inflammatory Conditions.

Cardiovasc Drugs Ther 2020 12 3;34(6):881. Epub 2020 Oct 3.

Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing, 100029, China.

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http://dx.doi.org/10.1007/s10557-020-07025-6DOI Listing
December 2020
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