Publications by authors named "Xuhui Yang"

27 Publications

  • Page 1 of 1

Comprehensive analysis of tumor microenvironment and identification of an immune signature to predict the prognosis and immunotherapeutic response in lung squamous cell carcinoma.

Ann Transl Med 2021 Apr;9(7):569

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: Tumor mutation burden (TMB) and immune microenvironment are important determinants of prognosis and immunotherapeutic efficacy for cancer patients. The aim of the present study was to develop an immune signature to effectively predict prognosis and immunotherapeutic response in patients with lung squamous cell carcinoma (LUSC).

Methods: TMB and immune microenvironment characteristics were comprehensively analyzed by multi-omics data in LUSC. The immune signature was further constructed and validated in multiple independent datasets by LASSO Cox regression analysis. Next, the value of immune signature in predicting the response of immunotherapy was evaluated. Finally, the possible mechanism of immune signature was also investigated.

Results: A novel immune signature based on 5 genes was constructed and validated to predict the prognosis of LUSC patients. These genes were filamin-C, Rho family GTPase 1, interleukin 4-induced gene-1, transglutaminase 2, and prostaglandin I2 synthase. High-risk patients had significantly poorer survival than low-risk patients. A nomogram was also developed based on the immune signature and tumor stage, which showed good application. Furthermore, we found that the immune signature had a significant correlation with immune checkpoint, microsatellite instability, tumor infiltrating lymphocytes, cytotoxic activity scores, and T-cell-inflamed score, suggesting low-risk patients are more likely to benefit from immunotherapy. Finally, functional enrichment and pathway analyses revealed several significantly enriched immune-related biological processes and metabolic pathways.

Conclusions: In the present study, we developed a novel immune signature that could predict prognosis and immunotherapeutic response in LUSC patients. The results not only help identify LUSC patients with poor survival, but also increase our understanding of the immune microenvironment and immunotherapy in LUSC.
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http://dx.doi.org/10.21037/atm-21-463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105790PMC
April 2021

The long intergenic noncoding RNA GAS5 reduces cisplatin-resistance in non-small cell lung cancer through the miR-217/LHPP axis.

Aging (Albany NY) 2021 01 8;13(2):2864-2884. Epub 2021 Jan 8.

Department of Thoracic Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.

Long noncoding RNAs (lncRNAs) are known to exert their effects to tumor progression. In this study, the role of the lncRNA GAS5 (growth arrest specific 5) was confirmed in reducing non-small cell lung cancer (NSCLC) cisplatin (DDP) resistance. In NSCLC tissue samples, GAS5 expression decreased significantly. Low GAS5 levels were positively correlated with NSCLC characteristics including TNM, tumor size and lymphatic metastasis. Functionally, GAS5 significantly reduced NSCLC/DDP cell migration, invasion and epithelial-mesenchymal transition (EMT) progression . , GAS5 upregulation inhibited remarkably NSCLC/DDP cell tumor growth. Mechanism analysis suggested that GAS5 was a molecular sponge of miR-217, inhibiting the expression of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). In conclusion, this study reveals that the GAS5/miR-217/LHPP pathway reduces NSCLC cisplatin resistance and that LHPP may serve as a potential therapeutic target for NSCLC cisplatin resistance.
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http://dx.doi.org/10.18632/aging.202352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880381PMC
January 2021

Reverse "L" surgical approach for the management of giant tumors of the cervicothoracic junction.

J Thorac Dis 2020 Aug;12(8):3995-4001

Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: An isolated cervical or thoracic surgical approach provides insufficient exposure for achieving complete resection of tumors of the cervicothoracic junction. This study examines reverse "L" thoracotomy as a surgical approach to these tumors. Additionally, the feasibility, safety, and effectiveness of reverse "L" surgical incision for tumor resection was also analyzed.

Methods: Patients with cervicothoracic tumors were identified from an internal database. Subjects were selected on the basis of undergoing reverse "L" thoracotomy from August 2014 to August 2018. The tumor characteristics, surgical technique, completeness of resection, morbidity, and patient outcome were reviewed.

Results: All patients successfully underwent resection through reverse "L" surgical approach. No patients needed to undergo full sternotomy. There were 6 neurogenic tumors, 4 thyroid adenocarcinomas, 4 bronchogenic tumors, and 7 other cases in the study. The median operative time was 191.0 min (range, 113.0-348.0 min) and postoperative in-hospital stay ranged from 3 to 7 days. Horner syndrome was observed in 1 case. Hoarseness and lymphatic leakage were evident in 3 and 1 case(s), respectively. Hemidiaphragm paralysis was observed in 1 case. Three cases were unsuccessful in achieving R0 resection. The duration of follow-up ranged from 6 to 42 months. Eleven of 13 patients who underwent resection had no evidence of tumor recurrence. Two patients with metastatic disease died of distant progression within 15 months.

Conclusions: Applying reverse "L" surgical approach is safe, feasible, and effective for the resection of giant tumors of the cervicothoracic junction.
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http://dx.doi.org/10.21037/jtd-20-288BDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475594PMC
August 2020

High hsa_circ_0020123 expression indicates poor progression to non-small cell lung cancer by regulating the miR-495/HOXC9 axis.

Aging (Albany NY) 2020 Sep 14;12(17):17343-17352. Epub 2020 Sep 14.

Department of Cardiothoracic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.

Circular RNAs (circRNAs) belong to non-protein-coding RNAs that regulate different pathophysiological procedures. Upregulation of hsa_circ_0020123 is found in non-small cell lung cancer (NSCLC); however, its activity and functions are not clear. In this study, the results showed that hsa_circ_0020123 expression increased in both tumor tissues and NSCLC cells. A higher hsa_circ_0020123 expression also led to poor prognoses among NSCLC patients assayed via FISH. The data of FISH also confirmed that hsa_circ_0020123 primarily had a cytoplasmic location. Hsa_circ_0020123 knockdown caused a significant decrease in nude mouse xenograft growth. Bioinformatics analyses and dual luciferase reporter assays confirmed that hsa_circ_0020123 was an miR-495 sponge and that the gene was a miR-495 target. The miR-495 downregulation reversed cell migration and proliferation inhibition induced by hsa_circ_0020123 silencing . HOXC9 overexpression reversed miR-495-induced inhibition of cell migration and proliferation. The dual luciferase reporter assay demonstrated that hsa_circ_0020123 interacted with miR-495 by binding to the HOXC9 3'-UTR to suppresses post-transcriptional HOXC9 expression. Taken together, our study found that hsa_circ_0020123 functioned like a tumor promoter via a novel hsa_circ_0020123/miR-495/HOXC9 axis, highlighting its possibility as a new NSCLC therapeutic target.
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http://dx.doi.org/10.18632/aging.103722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521531PMC
September 2020

Identifying Cancer-Related lncRNAs Based on a Convolutional Neural Network.

Front Cell Dev Biol 2020 11;8:637. Epub 2020 Aug 11.

Department of Oncology, Medical School of Chinese PLA, Chinese PLA General Hospital, Beijing, China.

Millions of people are suffering from cancers, but accurate early diagnosis and effective treatment are still tough for all doctors. In recent years, long non-coding RNAs (lncRNAs) have been proven to play an important role in diseases, especially cancers. These lncRNAs execute their functions by regulating gene expression. Therefore, identifying lncRNAs which are related to cancers could help researchers gain a deeper understanding of cancer mechanisms and help them find treatment options. A large number of relationships between lncRNAs and cancers have been verified by biological experiments, which give us a chance to use computational methods to identify cancer-related lncRNAs. In this paper, we applied the convolutional neural network (CNN) to identify cancer-related lncRNAs by lncRNA's target genes and their tissue expression specificity. Since lncRNA regulates target gene expression and it has been reported to have tissue expression specificity, their target genes and expression in different tissues were used as features of lncRNAs. Then, the deep belief network (DBN) was used to unsupervised encode features of lncRNAs. Finally, CNN was used to predict cancer-related lncRNAs based on known relationships between lncRNAs and cancers. For each type of cancer, we built a CNN model to predict its related lncRNAs. We identified more related lncRNAs for 41 kinds of cancers. Ten-cross validation has been used to prove the performance of our method. The results showed that our method is better than several previous methods with area under the curve (AUC) 0.81 and area under the precision-recall curve (AUPR) 0.79. To verify the accuracy of our results, case studies have been done.
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http://dx.doi.org/10.3389/fcell.2020.00637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432192PMC
August 2020

Polylactide pins can effectively fix severely comminuted and unsalvageable radial head fracture: A retrospective study of 40 patients.

Injury 2020 Oct 19;51(10):2253-2258. Epub 2020 Jul 19.

Department of orthopedic, the University-town Hospital of Chongqing Medical University, China.

Background: The treatment of comminuted unsalvageable radial head fracture remains controversial. Open reduction and internal fixation with metallic plates and screws are hard to achieve. Conventional techniques include radial head resection and arthroplasty. Both methods have inevitable complications. The purpose of this retrospective study is to prove the feasibility of treating unsalvageable radial head fractures with absorbable polylactide pins.

Methods: A total of 17 patients with severely comminuted Mason type III radial head fractures were treated with open reduction and internal fixation using polylactide pins and 23 with metallic plates and screws. Patients receiving both modalities were followed-up for a mean of 24 months (standard deviation SD: 2.6). Radiographic analysis was conducted 2, 30, 60, and 120 days after surgery. Measurements of range of motion (ROM), disability of arm shoulder and hands, Mayo elbow performance score, and Broberg and Morrey elbow score were recorded, with treatments compared using a Mann-Whitney U test.

Result: By the time of last follow up, All fractures in both groups healed successfully. The duration (134 min SD:21 min to 131 min SD:19 min) and blood loss (121 ml SD: 25 ml to 124 ml SD: 27 ml) during surgery of polylactide pin and metallic implant group have no statistical differences. The MEPI score (91 SD:7 to 94 SD:9), the Broberg and Morrey score (93 SD:3 to 93 SD:5), the DASH outcome measures (4.5 SD: 3.0 to 3.7 SD: 3.5), the range of motion also shows no statistical differences. Complications were infrequent and did not cause disability in both groups. All patients were satisfied with the surgical outcomes.

Conclusion: Polylactide pins can feasibly treat severely comminuted radial head fractures, which usually are considered unreducible. This technique provides an optional treatment plan in addition to resection or arthroplasty, especially for young patients that refuse that form of treatment.
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http://dx.doi.org/10.1016/j.injury.2020.07.041DOI Listing
October 2020

miR-489-3p/SIX1 Axis Regulates Melanoma Proliferation and Glycolytic Potential.

Mol Ther Oncolytics 2020 Mar 27;16:30-40. Epub 2019 Nov 27.

Department of Medical Molecular Biology, Beijing Institute of Biotechnology, No. 27 Taiping Road, Beijing 100850, China.

Sine oculis homeobox 1 (SIX1), a key transcription factor for regulating aerobic glycolysis, participates in the occurrence of various cancer types. However, the role of SIX1 in melanoma and the upstream regulating mechanisms of SIX1 remain to be further investigated. MicroRNAs (miRNAs) have emerged as key regulators in tumorigenesis and progression. Here, we show that miR-489-3p suppresses SIX1 expression by directly targeting its 3' untranslated region (3' UTR) in melanoma cells. miR-489-3p suppressed melanoma cell proliferation, migration, and invasion through inhibition of SIX1. Mechanistically, by targeting SIX1, miR-489-3p dampens glycolysis, with decreased glucose uptake, lactate production, ATP generation, and extracellular acidification rate (ECAR), as well as an increased oxygen consumption rate (OCR). Importantly, glycolysis regulated by the miR-489-3p/SIX1 axis is critical for its regulation of melanoma growth and metastasis both and . In melanoma patients, miR-489-3p expression is negatively correlated with SIX1 expression. In addition, patients who had increased glucose uptake in tumors and with metastasis assessed by positron emission tomography (PET) scans showed decreased miR-489-3p expression and increased expression of SIX1. Collectively, our study demonstrates the importance of the miR-489-3p/SIX1 axis in melanoma, which can be a potential and a promising therapeutic target in melanoma.
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http://dx.doi.org/10.1016/j.omto.2019.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109510PMC
March 2020

Image Denoising via Sequential Ensemble Learning.

IEEE Trans Image Process 2020 Mar 11. Epub 2020 Mar 11.

Image denoising is about removing measurement noise from input image for better signal-to-noise ratio. In recent years, there has been great progress on the development of data-driven approaches for image denoising, which introduce various techniques and paradigms from machine learning in the design of image denoisers. This paper aims at investigating the application of ensemble learning in image denoising, which combines a set of simple base denoisers to form a more effective image denoiser. Based on different types of image priors, two types of base denoisers in the form of transform-shrinkage are proposed for constructing the ensemble. Then, with an effective re-sampling scheme, several ensemble-learning-based image denoisers are constructed using different sequential combinations of multiple proposed base denoisers. The experiments showed that sequential ensemble learning can effectively boost the performance of image denoising.
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http://dx.doi.org/10.1109/TIP.2020.2978645DOI Listing
March 2020

Activation of TGF-β1 Pathway by SCUBE3 Regulates TWIST1 Expression and Promotes Breast Cancer Progression.

Cancer Biother Radiopharm 2020 Mar 19;35(2):120-128. Epub 2019 Nov 19.

Department of General Surgery, Liyuan Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.

Recently, signal peptide-CUB-EGF-like domain containing protein 3 (SCUBE3) has been found to be associated with the development of several cancers. However, the biological role of SCUBE3 in breast cancer progression has not been reported. Western blotting and quantitative real-time polymerase chain reaction were used to measure the expressions of SCUBE3, TGF-β (transforming growth factor-β) signaling pathway markers, and epithelial-mesenchymal transition markers. The influence of SCUBE3 on the breast cancer cell proliferation, invasion, and migration was detected using methyl thiazolyl tetrazolium, wound healing, colony formation, and transwell assay. The role of SCUBE3 was confirmed using tumor xenograft experiment. SCUBE3 expression was markedly increased in breast cancer cells and tissues. Knockdown of SCUBE3 suppressed cell growth, invasion, and migration, while SCUBE3 overexpression promoted cell growth, invasion, and migration in breast cancer cells. In addition, TGF-β1 and its downstream proteins were positively regulated by SCUBE3, and the promotion effect on TWIST1 expression induced by pcDNA3.1-SCUBE3 can be reversed by TGF-β1 inhibitor in breast cancer cell lines. Moreover, silencing of SCUBE3 suppressed breast cancer cell growth and tumorigenesis through reducing TGF-β1 . Knockdown of SCUBE3 downregulated TGF-β1 and TWIST1 expression, thereby inhibiting breast cancer cell growth and tumorigenesis.
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http://dx.doi.org/10.1089/cbr.2019.2990DOI Listing
March 2020

Elastic Anisotropy and Optic Isotropy in Black Phosphorene/Transition-Metal Trisulfide van der Waals Heterostructures.

ACS Omega 2019 Feb 22;4(2):4101-4108. Epub 2019 Feb 22.

Key Laboratory of Eco-materials Advanced Technology, College of Materials Science and Engineering, Fuzhou University, Fuzhou 350108, P. R. China.

Anisotropic two-dimensional materials with direction-dependent mechanical and optical properties have attracted significant attention in recent years. In this work, based on density functional theory calculations, unexpected elastic anisotropy and optical isotropy in van der Waals (vdW) heterostructures have been theoretically proposed by assembling the well-known anisotropic black phosphorene (BP) and transition-metal trisulfides MS (M = Ti, Hf) together. It is interesting to see that the BP/MS vdW heterostructures show anisotropic flexibility in different directions according to the elastic constants, Young's modulus, and Poisson's ratio. We have further unraveled their physical origin of the type-II band structure nature with their conduction band minimum and valence band maximum separated in different layers. In particular, our results on the optical response functions including the excitonic effects of the BP/MS vdW heterostructures suggest their unexpected optical isotropies together with the enhancements of the solar energy conversion efficiency.
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http://dx.doi.org/10.1021/acsomega.9b00011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6648407PMC
February 2019

MiR-150-5p regulates melanoma proliferation, invasion and metastasis via SIX1-mediated Warburg Effect.

Biochem Biophys Res Commun 2019 07 23;515(1):85-91. Epub 2019 May 23.

Department of Oncology, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing, 100853, China; Department of Oncology, Fourth Medical Center of Chinese PLA General Hospital, Beijing, 100037, China. Electronic address:

Aerobic glycolysis is a hallmark of cancer. Sine oculis homeobox 1 (SIX1), a key transcription factor in terms of regulating aerobic glycolysis (the Warburg Effect), plays a critical role in tumorigenesis of various cancer types, including breast cancer, liver cancer, and lung cancer. However, the upstream regulating mechanisms of SIX1 in melanoma remain to be determined. MicroRNAs (miRNAs) have emerged as key regulators in tumorigenesis and progression. Here, we initially showed that microRNA-150-5p (miR-150-5p) inhibits SIX1 expression by directly targeting its 3'-UTR in melanoma cells. miR-150-5p suppressed melanoma cell proliferation, migration, and invasion through inhibition of SIX1. Mechanistically, miR-150-5p dampens glycolysis by decreasing the glucose uptake, lactate production, ATP generation, and extracellular acidification rate (ECAR), and increasing oxygen consumption rate (OCR) by targeting SIX1. Importantly, glycolysis regulated by miR-150-5p/SIX1 axis is critical for its regulation of melanoma growth and metastasis both in vitro and in vivo. Collectively, our study demonstrates the importance of miR-150-5p/SIX1 axis in melanoma, which could be a promising therapeutic target in melanoma.
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http://dx.doi.org/10.1016/j.bbrc.2019.05.111DOI Listing
July 2019

Mitochondrial NDUFA4L2 protein promotes the vitality of lung cancer cells by repressing oxidative stress.

Thorac Cancer 2019 04 2;10(4):676-685. Epub 2019 Feb 2.

Department of Cardiothoracic Surgery, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Non-small cell lung cancer (NSCLC) accounts for a significant proportion of cancer-related deaths and lacks an effective treatment strategy. NSCLC tissues are generally found in a low oxygen environment. The NDUFA4L2 protein, located in the mitochondria, is encoded by the nucleus genome and is considered a crucial mediator that regulates cell survival. A better understanding of the mechanism of NDUFA4L2 in NSCLC survival in hypoxic environments is essential to design new therapeutic methods.

Methods: Twenty NSCLC and corresponding paired non-tumorous lung tissue samples were collected. NSCLC cell lines were cultured in hypoxic conditions to investigate the mechanism of NDUFA4L2 in NSCLC. The role of NDUFA4L2 was confirmed by using Western blotting, reactive oxygen species measurement, flow cytometry, immunofluorescence analysis, and wound healing and colony formation assays.

Results: The expression of HIF-1α and mitochondrial NDUFA4L2 increased in NSCLC cell lines cultured in hypoxic conditions (1% O ). NDUFA4L2 was drastically overexpressed in human NSCLC tissues and cell lines cultured in hypoxic conditions. HIF-1α regulated the expression of NDUFA4L2. Knockdown of NDUFA4L2 notably increased mitochondrial reactive oxygen species production, which suppressed the viability of NSCLC.

Conclusion: In conclusion, overexpression of NDUFA4L2 is a key factor for maintaining NSCLC growth, suggesting that mitochondrial NDUFA4L2 may be a potential target for the treatment of lung cancer.
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http://dx.doi.org/10.1111/1759-7714.12984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449242PMC
April 2019

Ubiquitin‑specific protease 7 promotes osteosarcoma cell metastasis by inducing epithelial‑mesenchymal transition.

Oncol Rep 2019 Jan 31;41(1):543-551. Epub 2018 Oct 31.

Department of Orthopaedics, University‑Town Hospital of Chongqing Medical University, Chongqing, Sichuan 401331, P.R. China.

Osteosarcoma (OS) is the most common primary malignant bone tumour among adolescents and young adults; however, its molecular pathogenesis has not been completely elucidated. Ubiquitin‑specific protease 7 (USP7), a member of the deubiquitinating enzyme family, plays a role in the malignancy process of various cancer types by targeting the key oncoprotein; however, its biological function and mechanism in OS have not been elucidated. The present study demonstrated that USP7 expression in OS tumour tissues was markedly higher than that in the paired surrounding tissues, and high USP7 expression was positively correlated with the TNM stage and metastasis in patients with OS. Next, biological function assays demonstrated that USP7 knockdown markedly inhibited OS cell migration and invasion, whereas USP7 overexpression enhanced it. Notably, USP7 can directly bind with β‑catenin to activate the Wnt/β‑catenin signalling pathway and induce epithelial‑mesenchymal transition (EMT) of OS cells. Overall, USP7 overexpression could promote OS cell metastasis by activating the Wnt/β‑catenin signalling pathway by inducing EMT, suggesting that USP7 is a potential therapeutic target for OS.
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http://dx.doi.org/10.3892/or.2018.6835DOI Listing
January 2019

Comparison of the electrochemical performance of iron hexacyanoferrate with high and low quality as cathode materials for aqueous sodium-ion batteries.

Chem Commun (Camb) 2017 Jun;53(50):6780-6783

College of Materials Science and Engineering, Fuzhou University, Fuzhou 350108, P. R. China.

In this work, high quality iron hexacyanoferrate nanocubes (HQ-PB NCs) were synthesized through a simple hydrothermal method and then investigated as cathode electrode materials for aqueous sodium-ion batteries (SIBs), which displayed a much enhanced electrochemical performance compared with the PB nanoparticles with low quality (LQ-PB NPs). The HQ-PB NCs could be promising cathode materials for aqueous SIBs.
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http://dx.doi.org/10.1039/c7cc02516eDOI Listing
June 2017

Human respiratory syncytial virus in children with lower respiratory tract infections or influenza-like illness and its co-infection characteristics with viruses and atypical bacteria in Hangzhou, China.

J Clin Virol 2015 Aug 21;69:1-6. Epub 2015 May 21.

Microbiology Laboratory, Hangzhou Center for Disease Control and Prevention, Hangzhou, China.

Background: Human respiratory syncytial virus (RSV) is the most important viral pathogen in children. However, its epidemic patterns and co-infection characteristics are not fully understood.

Objectives: We attempted to determine the level of genetic variation of RSV, and describe the prevalence and co-infection characteristics of RSV in Hangzhou during two epidemic seasons.

Study Design: Single respiratory samples from 1820 pediatric patients were screened for RSV and genotyped by RT-PCR and sequencing. In all RSV positive specimens, we screened for viruses and atypical bacteria. Demographic and clinical information was recorded and analyzed.

Results: A total of 34.5% and 3.8% of samples from acute lower respiratory tract infections (ALRI) and influenza-like illness (ILI) were positive for RSV, respectively. Phylogenetic analysis revealed that 61.1% of the selected 167 RSV strains were NA1, 31.1% were BA, 3.6% were ON1, 2.4% were CB1, and 1.8% were NA3. A new genotype, BA11 was identified, which comprised 98.1% of BA strains in this study, while the rest were BA10. A total of 36.4% and 9.1% of RSV-positive children with ALRI and ILI respectively were found to be co-infected. Rhinovirus was the most common additional respiratory virus, followed by human metapneumovirus. Except for fever, no significant differences in other clinical presentation between the RSV mono-infection and co-infection groups were observed.

Conclusions: The circulating RSV strains had high genetic variability with RSV-B showing a more local pattern. In ALRI cases, co-infection of RSV with other viruses or atypical bacteria has no significant effect on the clinical presentation except fever.
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http://dx.doi.org/10.1016/j.jcv.2015.05.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185398PMC
August 2015

The diversity of avian influenza virus subtypes in live poultry markets before and during the second wave of A(H7N9) infections in Hangzhou, China.

Emerg Microbes Infect 2015 Feb 25;4(2):e14. Epub 2015 Feb 25.

Microbiology Laboratory, Hangzhou Center for Disease Control and Prevention , Hangzhou 310021, Zhejiang province, China.

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http://dx.doi.org/10.1038/emi.2015.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345288PMC
February 2015

Outbreak of coinfection with human metapneumovirus and measles virus resulting in the death of a child at a hospital in China.

Am J Infect Control 2015 Apr 14;43(4):365-7. Epub 2015 Feb 14.

Microbiology Laboratory, Hangzhou Center for Disease Control and Prevention, Hangzhou, China. Electronic address:

Two children with different digestive diseases were admitted to the gastroenterology department of a children's hospital in Hangzhou, Zhejiang Province, China, in May 2010. They manifested successively acute lower respiratory tract infection symptoms during their stay in the hospital. The epidemiologic and experimental evidence supports that one child acquired nosocomial coinfection with measles virus and human metapneumovirus from another child while they shared the same ward.
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http://dx.doi.org/10.1016/j.ajic.2015.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115315PMC
April 2015

[Molecular epidemiology of human metapneumovirus in children with respiratory tract infection in Hangzhou].

Zhonghua Liu Xing Bing Xue Za Zhi 2014 Dec;35(12):1384-8

Microbiology Laboratory, Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, China.

Objective: To understand the molecular epidemiologic features of human metapnenmovirus (hMPV) in children with respiratory tract infection in Hangzhou.

Methods: 2 593 throat swabs were collected from patients with respiratory tract infections who visited the hospitals with sentinel surveillance programs from January 2011 to December 2013, including 1 676 outpatients and 917 inpatients. Total nucleic acid was extracted from the specimens and the fusion (F) protein gene of hMPV was amplified by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR), with positive samples picked to compare with the sequence of hMPV in GenBank, after the sequence of amplification products were determined. Other two types of common respiratory virus were tested using RT-PCR.

Results: The overall positive rate in this study was 6.51% (169/2 593), with 6.62% (111/1 676) in outpatients and 6.32% (58/917) in inpatients, but no statistically significant difference was found (χ(2) = 0.086, P = 0.769). The rates was 7.01% in males and 5.72% in females, with no statistically significant difference in different sex (χ(2) = 1.676, P = 0.195). The positive rate was 14.14% (28/198)in the 2-year-olds, 14.01% (22/158)in 3-year olds. The rate in 2-year olds was higher than in other groups, with statistically significant differences between the groups (χ(2) = 38.654, P = 0.000). Of the 169 positive cases, 153 (90.53%) in the younger than 5 years olds. The rates of infection with hMPV in winter and spring were statistically higher than in summer and autumn (χ(2) = 67.032, P = 0.000). The rate of co-infection was 19.52% (33/169). 88 amplified productions were selected for gene sequence analysis, and the F gene homology were 81.6%-100.0% with reference strains in GenBank. Data showed that all the 4 viral subtypes: A2 (52.27% , 46/88), B1 (37.51%, 33/88), B2 (9.09%, 8/88) and A1 (1.13%, 1/88) co-circulated during the study. However, different subtypes appeared predominant in different years:hMPV subtype B1 was in 2011 and 2012, subtype A2 in the end of 2012 and in 2013. Of the 88 specimens, gene sequences were determinate, with A genotype accounted for 67.56% (25/37), B genotype for 32.43% (12/37)in children younger than 1-year olds, and A genotype accounted for 43.13% (22/51), B genotype for 56.86% (29/51)in children above 1-year olds. Significant differences between the two groups (χ(2) = 5.143, P = 0.023) were noticed.

Conclusion: It was confirmed that hMPV was one of the substantial pathogens causing the respiratory tract infections. Data from our study suggested that the peak time of hMPV infection predominated during winter and spring in Hangzhou. Both hMPV subtype B1 and subtype A2 were found popular in this study, with hMPV genotype A dominating in children younger than 1-year olds.
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December 2014

A family cluster of three confirmed cases infected with avian influenza A (H7N9) virus in Zhejiang Province of China.

BMC Infect Dis 2014 Dec 31;14:698. Epub 2014 Dec 31.

Division of Infectious Disease, Key Laboratory of Surveillance and Early-warning on Infectious Disease, Chinese Center for Disease Control and Prevention, No. 155 Changbai Road, Changping District, Beijing, China.

Background: A total of 453 laboratory-confirmed cases infected with avian influenza A (H7N9) virus (including 175 deaths) have been reported till October 2,2014, of which 30.68% (139/453) of the cases were identified from Zhejiang Province. We describe the largest reported cluster of virologically confirmed H7N9 cases, comprised by a fatal Index case and two mild secondary cases.

Methods: A retrospective investigation was conducted in January of 2014. Three confirmed cases, their close contacts, and relevant environments samples were tested by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), viral culture, and sequencing. Serum samples were tested by haemagglutination inhibition (HI) assay.

Results: The Index case, a 49-year-old farmer with type II diabetes, who lived with his daughter (Case 2, aged 24) and wife (Case 3, aged 43) and his son-in-law (H7N9 negative). The Index case and Case 3 worked daily in a live bird market. Onset of illness in Index case occurred in January 13, 2014 and subsequently, he died of multi-organ failure on January 20. Case 2 presented with mild symptoms on January 20 following frequent unprotected bed-side care of the Index case between January 14 to 19, and exposed to live bird market on January 17. Case 3 became unwell on January 23 after providing bedside care to the Index case on January 17 to 18, and following the contact with Case 2 during January 21 to 22 at the funeral of the Index case. The two secondary cases were discharged on February 2 and 5 separately after early treatment with antiviral medication. Four virus strains were isolated and genome analyses showed 99.6 ~100% genetic homology, with two amino mutations (V192I in NS and V280A in NP). 42% (11/26) of environmental samples collected in January were H7N9 positive. Twenty-five close contacts remained well and were negative for H7N9 infection by RT-PCR and HI assay.

Conclusions: In the present study, the Index case was infected from a live bird market while the two secondary cases were infected by the Index case during unprotected exposure. This family cluster is, therefore, compatible with non-sustained person-to-person transmission of avian influenza A/H7N9.
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http://dx.doi.org/10.1186/s12879-014-0698-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304124PMC
December 2014

[Analysis of epidemiologic and etiology of hepatitis E in Hangzhou, 2004-2011].

Zhonghua Yu Fang Yi Xue Za Zhi 2014 Sep;48(9):766-70

Institute for Communicable Disease Control and Prevention, Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, China.

Objective: To comprehend the epidemiologic of hepatitis E and genetic characteristics of hepatitis E virus (HEV) in Hangzhou from 2004 to 2011.

Methods: Using China information system for disease control and prevention, the incidence of hepatitis E from 2004 to 2011 in Hangzhou city, and the basic information of patients were collected. In 2011, 65 hepatitis E laboratory confirmed cases were selected by random number table sampling method from the hospitals designated infectious diseases in Hangzhou city, and acquisition of the 60 blood specimens and stool specimens of 18 copies. One city and two surrounding counties were selected by cluster random sampling method in the context of Hangzhou city, and the pig slaughters and farmers were selected as the sampling point, and acquisition of pig gallbladder specimens of 52 copies, and 30 stool samples of scatter-feed pigs, 15 stool specimens of scatter-feed rabbits. HEV was tested in samples, gene extraction and analysis of gene sequence were conducted which were compared with gene bank HEV gene sequence, and a phylogenetic tree was formed. The epidemic characteristics of hepatitis E of Hangzhou city from 2004 to 2011 were described. The difference of incidence of hepatitis E was analyzed between years and sexes in Hangzhou city.

Results: There were reported a total of 3 490 cases of hepatitis E in Hangzhou from 2004 to 2011, and 3 cases of death; The average annual incidence rate was 5.79/100 000 (3 490/60 276 338). There was the overall upward trend in incidence between different years (χ² = 52.38, P < 0.01) , which the highest was 8.10/100 000 (705/8 700 373) in 2011, and the lowest incidence rate was 4.19/100 000 in 2005. The incidence of males (8.12/100 000 (2 474/30 450 990) ) was significantly higher than that of the females (3.46/100 000 (1 016/29 384 491) ) (χ² = 558.45, P < 0.05). 78 specimens of blood and stool were collected, including 16 positive samples, with positive rate 21%. There were a total of 97 specimens of pig gallbladder, pig manure and rabbit stool, including 2 positive rabbit stool samples, with positive rate of 2%. HEV genes isolated from Hangzhou were mainly type IV, with homology of 91.8% to 100%; compared with human type IV strains, the homology of nucleotide was 84.6%-96.7%; compared with type IV strain of pig genome sequence alignment, homology was 82.6%-95.2%.

Conclusion: Hepatitis E's incidence showed an increasing trend year by year in Hangzhou. HEV of type IV was dominant, and HEV strains in the human and swine were highly homologous.
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September 2014

Generation of a human bone marrow-derived mesenchymal stem cell line expressing and secreting high levels of bioactive α-melanocyte-stimulating hormone.

J Biochem 2013 Apr 22;153(4):371-9. Epub 2013 Jan 22.

Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China.

α-Melanocyte-stimulating hormone (α-MSH) functions as a mediator of inflammation and immunity; however, the short half-life and high dose needed limit the comprehensive clinical application of α-MSH. The aim of this study was to generate human bone marrow-derived mesenchymal stem cells (MSCs) that express and secrete high levels of bioactive α-MSH. MSCs were obtained from a normal donor and assessed for proliferation, surface markers, and adipogenic and osteogenic differentiation. A lentivirus-encoding α-MSH was constructed. MSCs were infected with this lentivirus-encoding α-MSH and assessed for stability and the expression and secretion of bioactive α-MSH. The cumulative MSC expansion rates pre- and post-lentivirus infection were not significantly different (P > 0.05). The MSCs remained stable after infection with the lentivirus-encoding α-MSH. The concentration of α-MSH in the supernatants of MSCs infected with the lentivirus-encoding α-MSH was 17.55 ng/ml (P < 0.001), and a melanin assay indicated that bioactive α-MSH was secreted from MSCs infected with the lentivirus-encoding α-MSH, with an optical absorbance at OD(405) of 0.886 (P < 0.001). These results suggested that MSCs were promising cell carriers for the expression and secretion of high levels of bioactive α-MSH.
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http://dx.doi.org/10.1093/jb/mvt003DOI Listing
April 2013

[Mouse melanoma cell line B16F10-derived conditioned medium inhibits sodium L-ascorbate-induced B16F10 cell apoptosis].

Nan Fang Yi Ke Da Xue Xue Bao 2012 Feb;32(2):146-50

Guangdong Women and Children's Hospital, Guangzhou, China.

Objective: To investigate the effect of mouse melanoma cell line B16F10-derived conditioned medium on the apoptosis of B16F10 cells.

Methods: B16F10 cells were cultured in high-glucose DMEM in the presence of 10% fetal bovine serum, and upon cell confluence, the growth medium was replaced with serum-free high-glucose DMEM. After 8 h, the medium was collected and infiltrated to serve as the conditioned medium. B16F10 cells cultured in normal growth medium or the conditioned medium were exposed to 10 mmol/L sodium L-ascorbate, and the cell apoptosis was analyzed. The ingredients in the conditioned medium with relative molecular mass less or more than 5 000 were extracted to assess their effect on sodium L-ascorbate-induced cell apoptosis.

Results: The conditioned medium for B16F10 cells significantly inhibited cell apoptosis induced by sodium L-ascorbate, and the effective ingredients in the medium showed a relative molecular mass below 5,000.

Conclusion: Mouse melanoma cell line B16F10-derived conditioned medium can suppress sodium L-ascorbate- induced apoptosis of B16F10 cells, and the ingredients with relative molecular mass less than 5 000 are responsible for this effect.
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February 2012

[Effect of lentivirus-mediated nestin gene silencing on metastatic potential of human melanoma cell line UACC903 in vitro].

Nan Fang Yi Ke Da Xue Xue Bao 2012 Jan;32(1):7-13

Guangdong Women and Children's Hospital, Guangzhou, China.

Objective: To study the effect of lentivirus-mediated RNA interference (RNAi) of nestin on the metastatic potential of human melanoma cell line UACC903.

Methods: A lentiviral vector for RNAi targeting the coding region of human nestin mRNA (nestin-RNAi-LV) and another control vector containing a nonsense sequence were constructed. The vectors were transfected into UACC903 cells, and nestin expression in the cells was detected by RT-PCR, immunofluorence assay and Western blotting. The invasive ability and migration of the transfected UACC903 cells was evaluated using Transwell and scrape assay, respectively. Fluorescence assay was used to examine the expressions of E-cadherin, N-cadherin and β-catenin in the cells.

Results: The lentiviral vector nestin-RNAi-LV was constructed successfully. Compared with the control vector, nestin-RNAi-LV resulted in obviously reduced expression of nestin mRNA and protein, lowered migration ability of UACC903 cells, and reduced cell adhesion and invasiveness (P<0.05).

Conclusion: Lentivirus-mediated nestin RNAi can specifically inhibit nestin expression to cause decreased cell migration and invasiveness of human melanoma cell line UACC903.
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January 2012

A novel biomimetic composite scaffold hybridized with mesenchymal stem cells in repair of rat bone defects models.

J Biomed Mater Res A 2010 Nov;95(2):495-503

Center for Stem Cell Biology and Tissue Engineering, SunYat-sen University, The Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Guangzhou, Guangdong 510080, People's Republic of China.

In this study, the in vivo bone-regenerative potential of a novel bioactive glass-collagen-hyaluronic acid-Phosphatidylserine (BG-COL-HYA-PS) composite scaffold hybridized with mesenchymal stem cells (MSCs) was investigated in a rat bone defect model. HrGFP-labeled MSCs were cultured for 2 weeks on the BG-COL-HYA-PS scaffold before implantation into the defect. A cell-free scaffold and an untreated defect were used as controls. The regeneration process was evaluated by histology, X-ray, and mechanical rigidity experiments at different time points post-implantation. The results revealed that BG-COL-HYA-PS scaffold exhibited a low inflammatory response and foreign body response within 3 weeks. At week 6, those responses disappeared following the resorption of scaffolds and the formation of new bone. Compared with the pure scaffold or empty group, the introduction of MSCs into the porous scaffold dramatically enhanced the efficiency of the new bone formation and biomechanical property of the femur. In addition, the transplanted MSCs could survive for up to 3 weeks or longer. The results demonstrated that the BG-COL-HYA-PS scaffold was biocompatible and osteoconductive and the transplanted MSCs with the scaffold enhanced the healing of the bone defect.
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http://dx.doi.org/10.1002/jbm.a.32877DOI Listing
November 2010

Expression of nestin in lymph node metastasis and lymphangiogenesis in non-small cell lung cancer patients.

Hum Pathol 2010 May 4;41(5):737-44. Epub 2010 Feb 4.

Department of Thoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China.

Stem cell marker nestin has been reported to be activated in various neoplasms, and its expression is correlated with poor prognosis. However, nestin expression in non-small cell lung cancer still remains unclear. The present study aimed to investigate nestin expression in 52 tissue samples of non-small cell lung cancer by immunohistochemical staining and explore its correlation with some clinicopathologic characteristics. The associations of nestin with lymphatic vessel density, microvessel density, vascular endothelial growth factor, vascular endothelial growth factor-C, and cyclooxygenase-2 (COX-2) were further observed to determine the linkage between nestin and lymphangiogenesis. The results showed that nestin expressed in tumor cells of 45 samples. High nestin expression correlated significantly with poor differentiation (P = .007), adenocarcinoma (P = .000), N2 lymph node metastasis (P = .006), high microvessel density (P = .033), and lymphatic vessel density (P = .020). Multivariate analysis of N1 and N2 lymph node metastasis revealed a 1.086-fold increase in hazard ratio of N2 lymph node involvement (P = .011) in patients with high nestin expression in primary tumor. More important, multivariate analysis showed a significant correlation of lymphatic vessel density with nestin and vascular endothelial growth factor-C expression (P = .039 and P = .045), independent of vascular endothelial growth factor, COX-2, and other clinicopathologic characteristics. The results demonstrated that nestin expressed in most tumor cells of non-small cell lung cancer tissue and had a direct linkage to lymph node metastasis and tumor-induced lymphangiogenesis, independent of COX-2 signal pathway.
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http://dx.doi.org/10.1016/j.humpath.2009.10.018DOI Listing
May 2010

Hedgehog-mediated paracrine interaction between hepatic stellate cells and marrow-derived mesenchymal stem cells.

Biochem Biophys Res Commun 2008 Jul 16;372(1):260-5. Epub 2008 May 16.

Division of Hepatology, The Third Hospital of Sun Yat-Sen University, Tianhe Road 600, Guangzhou City 510630, Guangdong Province, China.

During liver injury, bone marrow-derived mesenchymal stem cells (MSCs) can migrate and differentiate into hepatocytes. Hepatic stellate cell (SC) activation is a pivotal event in the development of liver fibrosis. Therefore, we hypothesized that SCs may play an important role in regulating MSC proliferation and differentiation through the paracrine signaling pathway. We demonstrate that MSCs and SCs both express hedgehog (Hh) pathway components, including its ligands, receptors, and target genes. Transwell co-cultures of SCs and MSCs showed that the SCs produced sonic hedgehog (Shh), which enhanced the proliferation and differentiation of MSCs. These findings demonstrate that SCs indirectly modulate the activity of MSCs in vitro via the Hh pathway, and provide a plausible explanation for the mechanisms of transplanted MSCs in the treatment of liver fibrosis.
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http://dx.doi.org/10.1016/j.bbrc.2008.05.029DOI Listing
July 2008

Evaluation of human mesenchymal stem cells response to biomimetic bioglass-collagen-hyaluronic acid-phosphatidylserine composite scaffolds for bone tissue engineering.

J Biomed Mater Res A 2009 Jan;88(1):264-73

Center for Stem Cell Biology and Tissue Engineering, SunYat-sen University, Guangzhou, Guangdong, China.

The aim of this study was to examine in vitro the response of human mesenchymal stem cells (hMSCs) on the novel biomimetic bioglass-collagen-hyaluronic acid-phosphatidylserine (BG-COL-HYA-PS) composite scaffold for potential use in bone tissue engineering. The initial attachment, the proliferation, migration and differentiation behavior of the cells on the BG-COL-HYA-PS composites were assessed in comparison with those on pure 58sBG, BG-COL, and BG-COL-HYA composites in either growth medium (L-DMEM supplemented with 10% fetal bovine serum) or osteogenic medium (growth medium supplemented with 0.1 microM dexamethasone, 10 mM beta-glycerophosphate, and 50 microM ascorbic acid). HMSCs attached, and subsequently proliferated and migrated on the BG-COL-HYA-PS composites to a significantly higher degree. The alkaline phosphatase (ALP) staining, ALP activity and the expression of the bone associated gene ALP, osteocalcin (OC), and osteopontin (OPN) was also significantly higher in the hMSCs on the BG-COL-HYA-PS scaffolds than those on the BG-COL, BG-COL-HYA composites and the pure 58sBG. These findings suggest that the BG-COL-HYA-PS composite porous scaffolds have high potential for use as scaffolds in bone tissue engineering and repair.
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http://dx.doi.org/10.1002/jbm.a.31931DOI Listing
January 2009