Publications by authors named "Siyang Chen"

25 Publications

  • Page 1 of 1

The Relationship Between Unexplained Chest Pain in Children and Head-Up Tilt Test.

Front Pediatr 2022 2;10:901919. Epub 2022 Jun 2.

Department of Pediatric Cardiovasology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: To explore the relationship between unexplained chest pain in children and head-up tilt test (HUTT).

Materials And Methods: A total of 825 children with the main symptom of unexplained chest pain were admitted to the Specialist Outpatient Clinic of Children's Cardiovascular Disease from October 2000 to November 2021 at The Second Xiangya Hospital, Central South University. Among them, 473 were male and 352 were female, with a mean age of 10.61 ± 2.21 years. The control group included 58 cases, comprising 35 males and 23 females, with a mean age of 10.26 ± 2.66 years. The detailed history, physical examinations, conventional 12-lead electrocardiogram, chest X-ray, echocardiography, myocardial enzymes, electroencephalogram, and blood series were all examined. Disorders of the chest wall, lung, heart, mediastinum, and esophageal reflux, as well as drug effects, were ruled out. All the children underwent HUTT. Demographic description, univariate analysis, and multivariate logistic regression analysis were used to explore the possible linear or non-linear relationships between the children's unexplained chest pain and HUTT.

Results: Among the 825 chest pain cases, 301 (36.48%) were HUTT positive and 524 (63.52%) were HUTT negative. HUTT-positive patients were older than HUTT-negative patients (11.04 ± 2.03 vs. 10.34 ± 2.31 years, < 0.001). The logistic regression results showed that each year of age increased the probability of being HUTT positive by 17.90% ( < 0.000), and females were 91.30% more likely to be HUTT positive than males ( < 0.000).

Conclusion: Clinically unexplained chest pain in children is mainly caused by unbalanced autonomic nervous function. HUTT can help clear the cause of unexplained chest pain.
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http://dx.doi.org/10.3389/fped.2022.901919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9203148PMC
June 2022

Feature Extraction of the Brain's Dynamic Complex Network Based on EEG and a Framework for Discrimination of Pediatric Epilepsy.

Sensors (Basel) 2022 Mar 26;22(7). Epub 2022 Mar 26.

Department of Medical Statistics, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.

Most of the current complex network studies about epilepsy used the electroencephalogram (EEG) to directly construct the static complex network for analysis and discarded the dynamic characteristics. This study constructed the dynamic complex network on EEG from pediatric epilepsy and pediatric control when they were asleep by the sliding window method. Dynamic features were extracted and incorporated into various machine learning classifiers to explore their classification performances. We compared these performances between the static and dynamic complex network. In the univariate analysis, the initially insignificant topological characteristics in the static complex network can be transformed to be significant in the dynamic complex network. Under most connectivity calculation methods between leads, the accuracy of using dynamic complex network features for discrimination was higher than that of static complex network features. Particularly in the imaginary part of the coherency function (iCOH) method under the full-frequency band, the discrimination accuracies of most machine learning classifiers were higher than 95%, and the discrimination accuracies in the higher-frequency band (beta-frequency band) and the full-frequency band were higher than that of the lower-frequency bands. Our proposed method and framework could efficiently summarize more time-varying features in the EEG and improve the accuracies of the discrimination of the machine learning classifiers more than using static complex network features.
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http://dx.doi.org/10.3390/s22072553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9003013PMC
March 2022

Trends in Incidence and Mortality of Stroke in China From 1990 to 2019.

Front Neurol 2021 22;12:759221. Epub 2021 Nov 22.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Stroke is a leading cause of mortality and morbidity globally. This study aimed to analyze the burden and 30-year trends of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in China. Data that include incidence and mortality of stroke in China from January 1, 1990 to December 31, 2019 were derived from the Global Burden of Disease (GBD) study 2019. The absolute numbers of incident cases and deaths over the time, and age-standardized rates per 100,000, such as age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR), were analyzed. In 2019, there were 3.9 (95% uncertainty intervals () 3.4-4.5) million incident cases and 2.1 (3.4-4.5) million deaths related to stroke in China. The ASIR and ASMR of stroke in China was 200 (176-230) and 127 (110-144). From 1990 to 2019, the ASIR of ischemic stroke had increased by 35.0% (29.0-40.0) while the ASIR of ICH and SAH had decreased by -53.0% (-56.0 to -50.0) and by -39.0% (-44.0 to -35.0), respectively. The ASMR of ischemic stroke had increased by 3.0% (-26.0 to 16.0) while the ASMR of ICH and SAH had decreased by -48.0% (-59.0 to -38.0) and by -84.0% (-89.0 to -69.0), respectively. Although the incidence and mortality rates of stroke in China were decreased from 1990 to 2019, the number of incident cases and deaths nearly doubled. A sharp increase in the incidence rate of ischemic stroke was observed. A higher incidence rate of ischemic stroke in the women was also observed.
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http://dx.doi.org/10.3389/fneur.2021.759221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645546PMC
November 2021

Association of Preoperative Cerebrospinal Fluids Parameters With Early Shunt Obstruction in Patients With Post-hemorrhagic Hydrocephalus Treated by Lumboperitoneal Shunt.

Front Neurol 2021 30;12:693554. Epub 2021 Aug 30.

Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, China.

Early shunt obstruction (SO) remains the most common cause of lumboperitoneal shunt (LPS) failure. Although there is anecdotal evidence that the level of cerebrospinal fluid (CSF) parameters might affect shunt performance, its association with early LPS obstruction in adults with post-hemorrhagic hydrocephalus (PHH) is unclear. The retrospective study was performed by reviewing the adults with PHH treated by LPS from years 2014 to 2018. We included patients with CSF samples analyzed within 1 week prior to shunt insertion or at the time of shunt insertion. Baseline characteristics of each patient were collected. The primary outcomes were the incidence rate and associated factors of SO occurring within 3 months of shunt placement. The secondary outcomes included scores on the National Institute of Health Stroke Scale (NIHSS) and Evans Index at discharge. A total of 76 eligible patients were analyzed, of whom 61 were obstruction-free and 15 were early SO. The overall rate of early SO was 15.6%. The RBCs count and nucleated cells count in preoperative CSF were actually higher in patients with early SO, compared to patients in the control group. Multivariate analysis identified RBC elevation (>0 × 10/L; OR: 10.629, 95% CI: 1.238-91.224, = 0.031) as a dependent risk factor for early SO. NIHSS dramatically decreased at discharge while the alteration of ventricular size was not observed. This study suggested that the presence of RBCs in preoperative CSF was associated with early SO in patients with PHH treated by LPS.
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http://dx.doi.org/10.3389/fneur.2021.693554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435900PMC
August 2021

LZerD webserver for pairwise and multiple protein-protein docking.

Nucleic Acids Res 2021 07;49(W1):W359-W365

Department of Computer Science, Purdue University, West Lafayette, IN 47907, USA.

Protein complexes are involved in many important processes in living cells. To understand the mechanisms of these processes, it is necessary to solve the 3D structures of the protein complexes. When protein complex structures have not yet been determined by experiment, protein-protein docking tools can be used to computationally model the structures of these complexes. Here, we present a webserver which provides access to LZerD and Multi-LZerD protein docking tools. The protocol provided by the server have performed consistently among the top in the CAPRI blind evaluation. LZerD docks pairs of structures, while Multi-LZerD can dock three or more structures simultaneously. LZerD uses a soft protein surface representation with 3D Zernike descriptors and explores the binding pose space using geometric hashing. Multi-LZerD performs multi-chain docking by combining pairwise solutions by LZerD. Both methods output full-atom docked models of the input proteins. Users can also input distance constraints between interacting or non-interacting residues as well as residues that locate at the interface or far from the interface. The webserver is equipped with a user-friendly panel that visualizes the distribution and structures of binding poses of top scoring models. The LZerD webserver is available at https://lzerd.kiharalab.org.
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http://dx.doi.org/10.1093/nar/gkab336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262708PMC
July 2021

VESPER: global and local cryo-EM map alignment using local density vectors.

Nat Commun 2021 04 7;12(1):2090. Epub 2021 Apr 7.

Department of Biological Sciences, Purdue University, West Lafayette, IN, USA.

An increasing number of density maps of biological macromolecules have been determined by cryo-electron microscopy (cryo-EM) and stored in the public database, EMDB. To interpret the structural information contained in EM density maps, alignment of maps is an essential step for structure modeling, comparison of maps, and for database search. Here, we developed VESPER, which captures the similarity of underlying molecular structures embedded in density maps by taking local gradient directions into consideration. Compared to existing methods, VESPER achieved substantially more accurate global and local alignment of maps as well as database retrieval.
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http://dx.doi.org/10.1038/s41467-021-22401-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027200PMC
April 2021

Effects of SARS-CoV-2 and its functional receptor ACE2 on the cardiovascular system.

Herz 2020 Nov 6;45(7):659-662. Epub 2020 Oct 6.

Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Medical College, Wuhan University of Science and Technology, 430065, Wuhan, China.

The clinical manifestations of COVID-19 are mainly respiratory symptoms, but some patients present with cardiovascular system disease such as palpitations and shortness of breath as the first or secondary symptoms. In this paper, we describe the characteristics of SARS-CoV‑2 and its functional receptor angiotensin-converting enzyme 2 (ACE2). Furthermore, we explore the impact of virus-induced myocardial damage, decreased ACE2 activity, immune imbalance, hypoxemia, and heart damage caused by antiviral drugs.
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http://dx.doi.org/10.1007/s00059-020-04989-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7537586PMC
November 2020

Automatic Changes Detection between Outdated Building Maps and New VHR Images Based on Pre-Trained Fully Convolutional Feature Maps.

Sensors (Basel) 2020 Sep 27;20(19). Epub 2020 Sep 27.

School of Geoscience and Info-Physics, Central South University, Changsha 410083, China.

Detecting changes between the existing building basemaps and newly acquired high spatial resolution remotely sensed (HRS) images is a time-consuming task. This is mainly because of the data labeling and poor performance of hand-crafted features. In this paper, for efficient feature extraction, we propose a fully convolutional feature extractor that is reconstructed from the deep convolutional neural network (DCNN) and pre-trained on the Pascal VOC dataset. Our proposed method extract pixel-wise features, and choose salient features based on a random forest (RF) algorithm using the existing basemaps. A data cleaning method through cross-validation and label-uncertainty estimation is also proposed to select potential correct labels and use them for training an RF classifier to extract the building from new HRS images. The pixel-wise initial classification results are refined based on a superpixel-based graph cuts algorithm and compared to the existing building basemaps to obtain the change map. Experiments with two simulated and three real datasets confirm the effectiveness of our proposed method and indicate high accuracy and low false alarm rate.
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http://dx.doi.org/10.3390/s20195538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582738PMC
September 2020

Comment on "Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus -2 (SARS-CoV-2)".

J Med Virol 2020 09 9;92(9):1399-1400. Epub 2020 Jun 9.

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California.

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http://dx.doi.org/10.1002/jmv.25991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7267376PMC
September 2020

Identification of human peripheral blood monocyte gene markers for early screening of solid tumors.

PLoS One 2020 30;15(3):e0230905. Epub 2020 Mar 30.

Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, Jiangxi, P.R. China.

As cancer mortality is high in most regions of the world, early screening of cancer has become increasingly important. Minimally invasive screening programs that use peripheral blood mononuclear cells (PBMCs) are a new and reliable strategy that can achieve early detection of tumors by identifying marker genes. From 797 datasets, four (GSE12771, GSE24536, GSE27562, and GSE42834) including 428 samples, 236 solid tumor cases, and 192 healthy controls were chosen according to the inclusion criteria. A total of 285 genes from among 440 reported genes were selected by meta-analysis. Among them, 4 of the top significantly differentially expressed genes (ANXA1, IFI44, IFI44L, and OAS1) were identified as marker genes of PBMCs. Pathway enrichment analysis identified, two significant pathways, the 'primary immunodeficiency' pathway and the 'cytokine-cytokine receptor interaction' pathway. Protein- protein interaction (PPI) network analysis revealed the top 27 hubs with a degree centrality greater than 23 to be hub genes. We also identified 3 modules in Molecular Complex Detection (MCODE) analysis: Cluster 1 (related to ANXA1), Cluster 2 (related to IFI44 and IFI44L) and Cluster 3 (related to OAS1). Among the 4 marker genes, IFI44, IFI44L, and OAS1 are potential diagnostic biomarkers, even though their results were not as remarkable as those for ANXA1 in our study. ANXA1 is involved in the immunosuppressive mechanism in tumor-bearing hosts and may be used in a new strategy involving the use of the host's own immunity to achieve tumor suppression.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230905PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105127PMC
June 2020

Surfactant protein A expression and distribution in human lung samples from smokers with or without chronic obstructive pulmonary disease in China.

Medicine (Baltimore) 2020 Feb;99(7):e19118

Department of Respiratory Medicine, Yiwu Fuyuan Hospital.

Cigarette smoking is considered the main risk factor for chronic obstructive pulmonary disease (COPD), although the mechanism remains unknown. surfactant protein A (SP-A) is thought to protect the lung from smoking-induced damage, but related studies performed in China are scarce. The aim of the study is to assess alterations of SP-A expression and distribution in lung samples from Chinese smokers with or without COPD.This cross-sectional study assessed 45 men in Wuhan Tongji Hospital after lobectomy for lung cancer in June 2010 to September 2010. Peripheral lung specimens were collected from control nonsmokers without airflow obstruction (nonsmoking group, n = 15), smokers without airflow obstruction (smoking group, n = 15), and patients with COPD (COPD group, n = 15). SP-A expression levels in lung tissue samples and its distribution in lung cells, type II pneumocytes (PNII), and alveolar macrophages (MACR) were determined by immunoblotting and immunohistochemistry.SP-A levels were significantly decreased in the COPD group (1.00 ± 0.25) compared with the smoking (2.31 ± 0.64) and nonsmoking (8.03 ± 2.80) groups; the smoking group also showed significantly reduced levels compared with the nonsmoking group (P < .05). PNII expressing SP-A were less abundant in the COPD group (39.3% ± 7.1%) compared with the smoking group (76.2% ± 29.8%), whereas SP-A MACR were more abundant (92.4% ± 7.1% vs 68.5% ± 20.2%) (all P < .05). Among the 30 smokers, forced expiratory volume in one second (% predicted) was positively correlated with SP-A levels (r = 0.739) and the rate of SP-A+ PNII (r = 0.811), and negatively correlated with the rate of SP-A+ MACR (r = -0.758) (all P < .05).Changes in SP-A expression and distribution in lung tissues may be involved in COPD pathogenesis in smokers.
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http://dx.doi.org/10.1097/MD.0000000000019118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035059PMC
February 2020

α-GalCer and iNKT Cell-Based Cancer Immunotherapy: Realizing the Therapeutic Potentials.

Front Immunol 2019 6;10:1126. Epub 2019 Jun 6.

Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.

NKT cells are CD1d-restricted innate-like T cells expressing both T cell receptor and NK cell markers. The major group of NKT cells in both human and mice is the invariant NKT (iNKT) cells and the best-known function of iNKT cells is their potent anti-tumor function in mice. Since its discovery 25 years ago, the prototype ligand of iNKT cells, α-galactosylceramide (α-GalCer) has been used in over 30 anti-tumor clinical trials with mostly suboptimal outcomes. To realize its therapeutic potential, numerous preclinical models have been developed to optimize the scheme and strategies for α-GalCer-based cancer immunotherapies. Nevertheless, since there is no standard protocol for α-GalCer delivery, we reviewed the preclinical studies with a focus on B16 melanoma model in the goal of identifying the best treatment schemes for α-GalCer treatment. We then reviewed the current progress in developing more clinically relevant mouse models for these preclinical studies, most notably the generation of new mouse models with a humanized CD1d/iNKT cell system. With ever-emerging novel iNKT cell ligands, invention of novel α-GalCer delivery strategies and significantly improved preclinical models for optimizing these new strategies, one can be hopeful that the full potential of anti-tumor potential for α-GalCer will be realized in the not too distant future.
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http://dx.doi.org/10.3389/fimmu.2019.01126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6562299PMC
October 2020

A global map of the protein shape universe.

PLoS Comput Biol 2019 04 12;15(4):e1006969. Epub 2019 Apr 12.

Department of Biological Sciences, Purdue University, West Lafayette, Indiana, United States of America.

Proteins are involved in almost all functions in a living cell, and functions of proteins are realized by their tertiary structures. Obtaining a global perspective of the variety and distribution of protein structures lays a foundation for our understanding of the building principle of protein structures. In light of the rapid accumulation of low-resolution structure data from electron tomography and cryo-electron microscopy, here we map and classify three-dimensional (3D) surface shapes of proteins into a similarity space. Surface shapes of proteins were represented with 3D Zernike descriptors, mathematical moment-based invariants, which have previously been demonstrated effective for biomolecular structure similarity search. In addition to single chains of proteins, we have also analyzed the shape space occupied by protein complexes. From the mapping, we have obtained various new insights into the relationship between shapes, main-chain folds, and complex formation. The unique view obtained from shape mapping opens up new ways to understand design principles, functions, and evolution of proteins.
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http://dx.doi.org/10.1371/journal.pcbi.1006969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481876PMC
April 2019

Increasing the Difference in Decision Making for Oneself and for Others by Stimulating the Right Temporoparietal Junction.

Front Psychol 2019 6;10:185. Epub 2019 Feb 6.

Department of Psychology, Renmin University of China, Beijing, China.

The right temporoparietal junction (rTPJ) has been thought to be associated with the difference in self-other decision making. In the present study, using noninvasive transcranial direct current stimulation (tDCS), we examined whether stimulating the rTPJ could modulate the self-other decision-making difference. We found that after receiving anodal stimulation of the rTPJ, participants were more likely to choose a high-value item for others than for themselves in the situations where the win probability of the high-value item was equal to or greater than that of a low-value item, indicating that elevating the cortical excitability of the rTPJ might increase the self-other decision-making difference in certain decision contexts. Our results suggest that decision making for others depends on neural activity in the rTPJ and regulation of the excitability of the rTPJ can influence the self-other decision-making difference.
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http://dx.doi.org/10.3389/fpsyg.2019.00185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372537PMC
February 2019

Review: Acute superior mesenteric artery embolism: A vascular emergency cannot be ignored by physicians.

Medicine (Baltimore) 2019 Feb;98(6):e14446

Department of Gastroenterology.

Background: Acute mesenteric ischemia (AMI) is a life-threatening medical condition that occurs when a sudden decreased perfusion to the intestines which leads to bowel infarction, and acute superior mesenteric artery embolism (ASMAE) is the main cause of AMI. Unfortunately, with the improvement of diagnosis and treatment technology, the mortality remains high due to less frequent clinical suspicion resulted from the unclear clinical manifestation and non-specific laboratory findings.

Methods: Relevant studies published were identified by searching the PubMed, Embase and Cochrane Library databases. This review presented the literatures to introduce the research progress of ASMAE in recent years.

Results: Patients with the history of atrial fibrillation, heart valve disease and atherosclerosis should be considered as ASMAE. Laboratory findings are insensitive and unspecific, however, angiography and Computed tomography angiography (CTA) can provide a clear diagnosis sensitively and specifically. Endovascular approaches have been increasingly reported in multiple case series. The key to successful treatment of AMI involves early clinical recognition and early intervention to move the embolus, which can reduce the rate of misdiagnosis and save the precious time and lives of patients.

Conclusions: Loss of time eventually leads to progression of ischemia to transmural bowel necrosis with peritonitis and septicemia, which may further worsen patients' outcomes. It is important for physicians to make a timely and accurate diagnosis, which can save precious time and reduce the mortality.
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http://dx.doi.org/10.1097/MD.0000000000014446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380707PMC
February 2019

Gene expression profile-based drug screen identifies SAHA as a novel treatment for NAFLD.

Mol Omics 2019 02;15(1):50-58

Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi Province 330031, P. R. China.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Being part of the metabolic syndrome, NAFLD is characterized by the deposition of triglycerides (TGs) as lipid droplets in the cytoplasm of hepatic cells. Recently, the rapid development of high-throughput genome analysis technologies provided opportunities to screen for new drugs for NAFLD. In this study, we screened for potential drugs based on the gene expression profiles of 73 compounds and identified histone deacetylase (HDAC) inhibitors as a novel treatment for the accumulation of lipids in hepatocytes. In the subsequent analysis and experiments, we discovered that SAHA inhibited the fatty acid and lipid metabolism pathways in hepatic cells and induced a significant deficiency of lipid accumulation in HepG2 and SMMC-7721 cells. Furthermore, SAHA inhibited lipid synthesis in hepatic cells by directly suppressing the expression of DGAT2. Hence, our study provides a novel method to screen for effective drugs for liver diseases and identifies SAHA as a potent treatment for NAFLD.
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http://dx.doi.org/10.1039/c8mo00214bDOI Listing
February 2019

Identification of core genes in ovarian cancer by an integrative meta-analysis.

J Ovarian Res 2018 Nov 19;11(1):94. Epub 2018 Nov 19.

The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330031, People's Republic of China.

Background: Epithelial ovarian cancer is one of the most severe public health threats in women. Since it is still challenging to screen in early stages, identification of core genes that play an essential role in epithelial ovarian cancer initiation and progression is of vital importance.

Results: Seven gene expression datasets (GSE6008, GSE18520, GSE26712, GSE27651, GSE29450, GSE36668, and GSE52037) containing 396 ovarian cancer samples and 54 healthy control samples were analyzed to identify the significant differentially expressed genes (DEGs). We identified 563 DEGs, including 245 upregulated and 318 downregulated genes. Enrichment analysis based on the gene ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that the upregulated genes were significantly enriched in cell division, cell cycle, tight junction, and oocyte meiosis, while the downregulated genes were associated with response to endogenous stimuli, complement and coagulation cascades, the cGMP-PKG signaling pathway, and serotonergic synapse. Two significant modules were identified from a protein-protein interaction network by using the Molecular Complex Detection (MCODE) software. Moreover, 12 hub genes with degree centrality more than 29 were selected from the protein-protein interaction network, and module analysis illustrated that these 12 hub genes belong to module 1. Furthermore, Kaplan-Meier analysis for overall survival indicated that 9 of these hub genes was correlated with poor prognosis of epithelial ovarian cancer patients.

Conclusion: The present study systematically validates the results of previous studies and fills the gap regarding a large-scale meta-analysis in the field of epithelial ovarian cancer. Furthermore, hub genes that could be used as a novel biomarkers to facilitate early diagnosis and therapeutic approaches are evaluated, providing compelling evidence for future genomic-based individualized treatment of epithelial ovarian cancer.
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http://dx.doi.org/10.1186/s13048-018-0467-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240943PMC
November 2018

Herpes Simplex Virus 1 Specifically Targets Human CD1d Antigen Presentation To Enhance Its Pathogenicity.

J Virol 2018 11 29;92(22). Epub 2018 Oct 29.

Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

Herpes simplex virus 1 (HSV-1) is one of the most prevalent herpesviruses in humans and represents a constant health threat to aged and immunocompromised populations. How HSV-1 interacts with the host immune system to efficiently establish infection and latency is only partially known. CD1d-restricted NKT cells are a critical arm of the host innate immune system and play potent roles in anti-infection and antitumor immune responses. We discovered previously that upon infection, HSV-1 rapidly and efficiently downregulates CD1d expression on the cell surface and suppresses the function of NKT cells. Furthermore, we identified the viral serine/threonine protein kinase US3 as a major viral factor downregulating CD1d during infection. Interestingly, neither HSV-1 nor its US3 protein efficiently inhibits mouse CD1d expression, suggesting that HSV-1 has coevolved with the human immune system to specifically suppress human CD1d (hCD1d) and NKT cell function for its pathogenesis. This is consistent with the fact that wild-type mice are mostly resistant to HSV-1 infection. On the other hand, infection of CD1d-humanized mice (hCD1d knock-in mice) showed that HSV-1 can indeed evade hCD1d function and establish infection in these mice. We also report here that US3-deficient viruses cannot efficiently infect hCD1d knock-in mice but infect mice lacking all NKT cells at a higher efficiency. Together, these studies supported HSV-1 evasion of human CD1d and NKT cell function as an important pathogenic factor for the virus. Our results also validated the potent roles of NKT cells in antiherpesvirus immune responses and pointed to the potential of NKT cell ligands as adjuvants for future vaccine development. Herpes simplex virus 1 (HSV-1) is among the most common human pathogens. Little is known regarding the exact mechanism by which this virus evades the human immune system, particularly the innate immune system. We reported previously that HSV-1 employs its protein kinase US3 to modulate the expression of the key antigen-presenting molecule, CD1d, so as to evade the antiviral function of NKT cells. Here we demonstrated that the virus has coevolved with the human CD1d and NKT cell system and that NKT cells indeed play potent roles in anti-HSV immune responses. These studies point to the great potential of exploring NKT cell ligands as adjuvants for HSV vaccines.
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http://dx.doi.org/10.1128/JVI.01490-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206489PMC
November 2018

TGF-β1 and connexin-43 expression in neurogenic bladder from rats with sacral spinal cord injury.

Neurourol Urodyn 2018 11 2;37(8):2502-2509. Epub 2018 Aug 2.

Department of Urology, Beijing Youan Hospital, Capital Medical University, Beijing, China.

Aims: Sacral spinal cord injury (SCI) could induce underactive bladder (UAB). Malfunction of connexin 43 (CX43) regulated by TGF-β1 might involve in urinary bladder dysfunction. We studied the changes of CX43 and TGF-β1/Smad3 signaling in detrusor of neurogenic bladder (NB) in sacral SCI rats.

Methods: Sacral SCI was produced by hemisection (SSCH) or transection (SSCT) of spinal cord between L4 and L5 in female Wistar rats. BBB scores, residual urine volume and bladder weight as well as characteristic cystometric parameters at 6th week were used to confirm the successful establishment of NB. Western blotting and qRT-PCR were used to exam the protein and mRNA expression levels of CX43, CX45, TGF-β1, and Smad3 in detrusor.

Results: BBB scores were significantly decreased, with the lowest in SSCT rats (P < 0.01). The residual urine volume, mean bladder weight, and cystometric parameters were increased, with the highest in SSCT rats. CX43 and phospho-CX43 protein levels were significantly decreased, but those of TGF-β1, Smad3, and phospho-Smad3 were significantly increased. It was the protein and mRNA levels of CX43 but not those of CX45 which were decreased in negative accordance with those of TGF-β1 and Smad3. Those changes were more significant in SSCT than in SSCH rats.

Conclusions: This study indicates that voiding dysfunction is related to the decreased CX43 function in detrusor from NB. TGF-β1/Smad3 signaling might be involved in the down-regulation of CX43 in SCI rats. Early regulation of CX43 might be beneficial to patients with voiding dysfunction.
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http://dx.doi.org/10.1002/nau.23767DOI Listing
November 2018

Wuzhi Tablet ( Extract) is a Promising Tacrolimus-Sparing Agent for Renal Transplant Recipients Who are CYP3A5 Expressers: a Two-Phase Prospective Study.

Drug Metab Dispos 2017 11 1;45(11):1114-1119. Epub 2017 Sep 1.

Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (J.L., X.Q., H.B., Y.Z., X.W., M.H.); Kidney Transplant Department, Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (S.C., Q.F., L.L., C.W.); Guangdong Food and Drug Vocational College, Guangzhou, China (X.Q.); and School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China (Y.Z.)

Tacrolimus is a potent but expensive first-line immunosuppressant, thus solutions to reduce tacrolimus consumption while maintain therapeutic level are in urgent need. A two-phase prospective study was conducted to assess the efficacy of an ethanolic extraction preparation of (Wuzhi tablet) as a tacrolimus-sparing agent in renal transplant recipients who were high-dose tacrolimus consumers ( allele carriers, CYP3A5 expressers). A total of 12 patients were included in the Part I study. After co-administration of Wuzhi tablet, the average individual increment (%) in dose-adjusted C, C and AUC of tacrolimus were 198.8% (95% CI 149.2, 248.3), 111.0% (95% CI 63.4, 158.6) and 126.1% (95% CI 89.4, 162.8), respectively ( < 0.01), while the average individual reduction (%) in tacrolimus daily dose was 40.9% (95% CI 25.2, 56.6) ( < 0.01). Subsequently, 32 patients were enrolled in a prospective, randomized, controlled study and randomly assigned to receive tacrolimus by genotype plus Wuzhi tablet co-administration guided dosing (study group) or standard dosing (control group). Besides less tacrolimus dose requirement ( < 0.01), a more accurate tacrolimus initial dose characterized by lower incidence of out-of-range C after initial dose ( < 0.01) and fewer dose changes ( < 0.01) was found in the study group. Moreover, no significant differences in acute rejection rate and serum creatinine levels were observed between two groups. Our results show that genotype plus Wuzhi tablet co-administration guided tacrolimus dosing is a promising therapy for CYP3A5 expressers in the early post-transplant stage, while further study with a larger sample size is required to prove these findings.
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http://dx.doi.org/10.1124/dmd.117.076737DOI Listing
November 2017

[Conjunctival Fas-FasL expression in chronic Stevens-Johnson syndrome].

Zhonghua Yan Ke Za Zhi 2014 Sep;50(9):691-4

Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences,Beijing 100730, China. Email:

Objective: To investigate the expression level of Fas-FasL in conjunctiva tissue of chronic Stevens-Johnson syndrome (SJS) patients and to analyze the role of Fas-FasL pathway in the mechanism of ocular damage related to SJS.

Methods: Conjunctiva tissue was obtained during symblepharon release operation and cryostat sectioned at 5 µm. The tissue morphology was observed by electron microscopy. The expression of Fas-FasL (CD95/CD178) in conjunctiva was detected by immunohistochemistry (direct immunofluorescence). The conjunctiva tissue of normal people was also observed and tested as contrast group.

Results: The pathogenic changes included incrassation of epithelium and cavity of mucous glands in the sub-epithelium. The expression of Fas in SJS patients focusing in the basal layer of epithelium appeared a lower level compared to that in normal human conjunctiva, which distributed equally in all layers of epithelium. The expressions of FasL in SJS patients and normal people were both weak.

Conclusions: The low level expression of Fas-FasL in conjunctiva of SJS patients has certain effect on the chronic ocular damage.
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September 2014

Dryland soil hydrological processes and their impacts on the nitrogen balance in a soil-maize system of a freeze-thawing agricultural area.

PLoS One 2014 7;9(7):e101282. Epub 2014 Jul 7.

School of Environment, State Key Laboratory of Water Environment Simulation, Beijing Normal University, Beijing, China.

Understanding the fates of soil hydrological processes and nitrogen (N) is essential for optimizing the water and N in a dryland crop system with the goal of obtaining a maximum yield. Few investigations have addressed the dynamics of dryland N and its association with the soil hydrological process in a freeze-thawing agricultural area. With the daily monitoring of soil water content and acquisition rates at 15, 30, 60 and 90 cm depths, the soil hydrological process with the influence of rainfall was identified. The temporal-vertical soil water storage analysis indicated the local albic soil texture provided a stable soil water condition for maize growth with the rainfall as the only water source. Soil storage water averages at 0-20, 20-40 and 40-60 cm were observed to be 490.2, 593.8, and 358 m3 ha-1, respectively, during the growing season. The evapo-transpiration (ET), rainfall, and water loss analysis demonstrated that these factors increased in same temporal pattern and provided necessary water conditions for maize growth in a short period. The dry weight and N concentration of maize organs (root, leaf, stem, tassel, and grain) demonstrated the N accumulation increased to a peak in the maturity period and that grain had the most N. The maximum N accumulative rate reached about 500 mg m-2d-1 in leaves and grain. Over the entire growing season, the soil nitrate N decreased by amounts ranging from 48.9 kg N ha-1 to 65.3 kg N ha-1 over the 90 cm profile and the loss of ammonia-N ranged from 9.79 to 12.69 kg N ha-1. With soil water loss and N balance calculation, the N usage efficiency (NUE) over the 0-90 cm soil profile was 43%. The soil hydrological process due to special soil texture and the temporal features of rainfall determined the maize growth in the freeze-thawing agricultural area.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0101282PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085067PMC
February 2015

Clinical significance of myeloid-derived suppressor cells in human renal transplantation with acute T cell-mediated rejection.

Inflammation 2014 Oct;37(5):1799-805

Department of Organ Transplant, The Third Affiliated Hospital of Guangzhou Medical University, 63 Duobao Road, Guangzhou, China.

Myeloid-derived suppressor cells (MDSCs) are negative regulators of the immune response and are in part responsible for the inhibition of the T cell-mediated immune response. A recent paper indicated that MDSCs were involved in prolonged allograft survival in animal models of transplantation, but the significance of MDSCs in human renal transplantation is still unknown. In our study, 50 patients with biopsy-proven acute T cell-mediated rejection (ATCMR) were included. The ratio of MDSCs in peripheral blood mononuclear cell (PBMC) was evaluated with FACS, and the patients were divided into the MDSCs high group (MDSCs, >10 %) or the MDSCs low group (MDSCs, <10 %). We compared the allograft function, severity of tissue injury, and long-time survival between the two groups. In the MDSCs high group, allograft function was significantly increased compared with the MDSCs low group. Furthermore, we found that isolated MDSCs from transplant recipients are capable of expanding regulatory T cell (Treg), meanwhile, inhibiting production of IL-17 in vitro. We also found that the ratio between Foxp3(+) and IL-17-producing CD4(+) T cells positively correlated with MDSCs frequency in PBMC. In conclusion, we demonstrated a potential role for MDSCs in prolonging allograft survival after ATCMR, and this was associated with higher CD4(+)Foxp3(+)/CD4(+)IL-17(+) ratio in PBMC.
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http://dx.doi.org/10.1007/s10753-014-9910-5DOI Listing
October 2014

Combined impacts of freeze-thaw processes on paddy land and dry land in Northeast China.

Sci Total Environ 2013 Jul 10;456-457:24-33. Epub 2013 Apr 10.

School of Environment, State Key Laboratory of Water Environment Simulation, Beijing Normal University, Beijing 100875, China.

The quantity of spring snowmelt infiltration and runoff, which affects the hydrology of the freeze zone, depends on the antecedent soil water content (SWC) conditions at the time of the soil's freezing. An understanding of the characteristics of frozen soil is essential for spring sowing in the agricultural freeze zones. The main goal of this study was to evaluate the differences in the freeze-thaw process and the freeze-thaw-induced water redistribution between the paddy and dry lands in a freeze zone. For this purpose, a field study was conducted in the winter of 2011-2012 for two types of farmlands in Northeast China. To illustrate the soil's frost dynamics over time, the measured SWCs at different depths (15, 30, 60, and 90 cm) were transformed into different expressions including the SWC dynamic, the frozen soil's profile, and the freezing and thawing front trace. The freezing characteristics in the paddy land, in contrast to that in the dry land, had a higher freezing point temperature, a larger amount of water movement to the upper layer, and a 2.76 mm larger accumulation of water in the upper layer. However, the increase of SWC (which is equivalent to thawing) was evidently faster than the decrease of SWC (which is equivalent to freezing). The water in the frozen soil's profile was most likely redistributed towards the freezing front before soil temperature (ST) falls below the freezing point. The findings may partially explain the soil's freeze-thaw characteristics for the different stages as well as the combined impact of these characteristics with farmland use types on soil hydrology; the findings may also provide a foundation for forecasting the hydrologic response of the freeze-thaw process and provide guidance for management strategies dealing with seasonally frozen agricultural soils.
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http://dx.doi.org/10.1016/j.scitotenv.2013.03.059DOI Listing
July 2013

Suppression of alloimmunity in mice by regulatory T cells converted with conditioned media.

J Surg Res 2011 Dec 15;171(2):797-806. Epub 2010 Apr 15.

Department of Organ Transplantation, First Affiliated Hospital, Sun Yat-sen University, Guangzhou City, China.

Background: Compared with rare CD4+CD25+ regulatory T cells (Tregs), CD4+CD25- T cells are abundant in peripheral blood. Studies have demonstrated that tumors can convert naive CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs; however, the potential application of the converted Tregs in transplant medicine has not well demonstrated.

Materials And Methods: CD4+CD25- T cells isolated cultured for 5 d in various combinations of cell culture medium and conditioned medium from RenCa cells. Foxp3 levels were determined by flow cytometry and real-time polymerase chain reaction. BALB/c mouse mononuclear cells (responder) combined with different ratios of the converted CD4+CD25+ Tregs were co-cultured with inactivated C57BL/6 mononuclear cells (stimulator) in one-way mixed lymphocyte reaction (MLR). In addition, the converted Tregs were transferred into a mouse skin transplant model, and graft histology, survival time, and delayed-type hypersensitivity were assessed.

Results: CD4+CD25- T cells cultured in media supplemented with increasing concentrations of RenCa conditioned medium were partially converted into CD4+CD25+ Tregs; conversion increased as the percentage of conditioned medium increased. Moreover, the converted CD4+CD25+ Tregs possessed characteristics similar to those of naturally occurring Tregs, including Foxp3 expression and the ability to suppress T cell proliferation in one-way MLR in a concentration-dependent manner. Immunosuppressive effects of the converted CD4+CD25+ Tregs were also similar to those of naturally occurring Tregs in vivo, suppressing allograft rejection and prolonging survival time of allogeneic skin grafts following adoptive transfer in mice (P<0.05).

Conclusion: Our findings indicate that CD4+CD25- T cells cultured with conditioned media from tumor cells may be useful for obtaining sufficient numbers of Tregs, which may help suppress acute rejection and prolong graft survival.
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http://dx.doi.org/10.1016/j.jss.2010.03.044DOI Listing
December 2011
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