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author:("Zhu, heiming")
1.  Extracellular matrix production in vitro in cartilage tissue engineering 
Cartilage tissue engineering is arising as a technique for the repair of cartilage lesions in clinical applications. However, fibrocartilage formation weakened the mechanical functions of the articular, which compromises the clinical outcomes. Due to the low proliferation ability, dedifferentiation property and low production of cartilage-specific extracellular matrix (ECM) of the chondrocytes, the cartilage synthesis in vitro has been one of the major limitations for obtaining high-quality engineered cartilage constructs. This review discusses cells, biomaterial scaffolds and stimulating factors that can facilitate the cartilage-specific ECM production and accumulation in the in vitro culture system. Special emphasis has been put on the factors that affect the production of ECM macromolecules such as collagen type II and proteoglycans in the review, aiming at providing new strategies to improve the quality of tissue-engineered cartilage.
PMCID: PMC4233628  PMID: 24708713
Cartilage; Tissue engineering; Extracellular matrix; Collagen type II
2.  Application of a computerised navigation technique to assist arthroscopic anterior cruciate ligament reconstruction 
International Orthopaedics  2013;37(2):233-238.
Based on biomechanical cadaver studies, anatomical double-bundle reconstruction of the anterior cruciate ligament (ACL) was introduced to achieve better stability in the knee, particularly in respect of rotatory loads. Previously, the success of ACL reconstruction was believed to be mainly dependent on correct positioning of the graft, irrespective of the number of bundles for which computer-assisted surgery was developed to avoid malpositioning of the tunnel. The aim of this study was to compare rotational and translational stability after computer-navigated standard single-bundle and anatomical double-bundle ACL reconstruction.
The authors investigated 42 consecutive patients who had undergone the single-bundle or double-bundle ACL reconstruction procedure using autogenous hamstring tendon grafts and ENDOBUTTON fixation in patients who had been followed up for a minimum of 24 months. Post-operative anteroposterior and rotational laxity was measured with the KT3000 and compared between groups.
Both surgical procedures significantly improve rotational and translational stability compared to the preoperative ACL-deficient knee (P<0.05). No significant differences were registered between groups with regard to anteroposterior displacement of the tibia. The International Knee Documentation Committee (IKDC) and Lysholm scores were significantly higher in the double-bundle group. However, the results were excellent in both groups.
The use of computer-assisted ACL reconstruction, which is a highly accurate method of graft placement, could be useful for inexperienced surgeons to avoid malposition. Long-term results of at least five years are needed to determine whether double-bundle ACL reconstruction, which was associated with improved rotational laxity and significantly better IKDC and Lysholm scores compared to the standard single-bundle ACL reconstruction procedure, exerts an influence in terms of avoiding osteoarthritis or meniscus degeneration.
PMCID: PMC3560909  PMID: 23314335
4.  NONCODEv4: exploring the world of long non-coding RNA genes 
Nucleic Acids Research  2013;42(Database issue):D98-D103.
NONCODE ( is an integrated knowledge database dedicated to non-coding RNAs (excluding tRNAs and rRNAs). Non-coding RNAs (ncRNAs) have been implied in diseases and identified to play important roles in various biological processes. Since NONCODE version 3.0 was released 2 years ago, discovery of novel ncRNAs has been promoted by high-throughput RNA sequencing (RNA-Seq). In this update of NONCODE, we expand the ncRNA data set by collection of newly identified ncRNAs from literature published in the last 2 years and integration of the latest version of RefSeq and Ensembl. Particularly, the number of long non-coding RNA (lncRNA) has increased sharply from 73 327 to 210 831. Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA genes was put forward to help systematic understanding of lncRNAs. The 56 018 and 46 475 lncRNA genes were generated from 95 135 and 67 628 lncRNAs for human and mouse, respectively. Additionally, we present expression profile of lncRNA genes by graphs based on public RNA-seq data for human and mouse, as well as predict functions of these lncRNA genes. The improvements brought to the database also include an incorporation of an ID conversion tool from RefSeq or Ensembl ID to NONCODE ID and a service of lncRNA identification. NONCODE is also accessible through
PMCID: PMC3965073  PMID: 24285305
5.  PD-L1 Blockade Attenuated Sepsis-Induced Liver Injury in a Mouse Cecal Ligation and Puncture Model 
Mediators of Inflammation  2013;2013:361501.
Liver plays a major role in hypermetabolism and produces acute phase proteins during systemic inflammatory response syndrome and it is of vital importance in host defense and bacteria clearance. Our previous studies indicated that programmed death-1 (PD-1) and its ligand programmed death ligand-1 (PD-L1) are crucial modulators of host immune responses during sepsis. Our current study was designed to investigate the role of PD-L1 in sepsis-induced liver injury by a mouse cecal ligation and puncture (CLP) model. Our results indicated that there was a significant increase of PD-L1 expression in liver after CLP challenge compared to sham-operated controls, in terms of levels of mRNA transcription and immunohistochemistry. Anti-PD-L1 antibody significantly alleviated the morphology of liver injury in CLP mice. Anti-PD-L1 antibody administration decreased ALT and AST release in CLP mice, decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 mRNA in liver after sepsis challenge. Thus, anti-PD-L1 antibody might have a therapeutic potential in attenuating liver injury in sepsis.
PMCID: PMC3844221  PMID: 24324295
6.  Brain natriuretic peptide for prediction of mortality in patients with sepsis: a systematic review and meta-analysis 
Critical Care  2012;16(3):R74.
Early identification of septic patients at high risk of dying remains a challenge. The prognostic role of brain natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) in septic patients remains controversial. The purpose of this systematic review and meta-analysis was to investigate the value of elevated BNP or NT-proBNP in predicting mortality in septic patients.
PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched (up to February 18, 2011). Studies were included if they had prospectively collected data on all-cause mortality in adult septic patients with either plasma BNP or NT-proBNP measurement. Studies that failed to construct a 2 × 2 table of results were excluded. Two authors independently determined the validity of included studies and extracted data.
12 studies with a total of 1,865 patients were included. Elevated natriuretic peptides were significantly associated with increased risk of mortality (odds ratio (OR) 8.65, 95% confidence interval (CI) 4.94 to 15.13, P < 0.00001). The association was consistent for BNP (OR 10.44, 95% CI 4.99 to 21.58, P < 0.00001) and NT-proBNP (OR 6.62, 95% CI 2.68 to 16.34, P < 0.0001). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were 79% (95% CI 75 to 83), 60% (95% CI 57 to 62), 2.27 (95% CI 1.83 to 2.81) and 0.32 (95% CI 0.22 to 0.46), respectively.
Our results suggested that an elevated BNP or NT-proBNP level may prove to be a powerful predictor of mortality in septic patients. Future larger and more adequately powered prospective studies are warranted to clarify the assay standardization, the optimal cut-off, and the prognostic value of BNPs in conjunction with other biomarkers.
PMCID: PMC3580616  PMID: 22559153
7.  Experimental study of nano-HA artificial bone with different pore sizes for repairing the radial defect 
International Orthopaedics  2008;33(2):567-571.
The purpose of this study was to examine the repairing ability of nano-hydroxyapatite (nano-HA) artificial bone with different pore sizes. Animal models of bone defects were created in both radii of 60 New Zealand white rabbits. The bone defects in A, B, and C groups were repaired with nano-HA artificial bone with three different pore sizes while those in group D were left unrepaired. The repairing ability of material was evaluated by gross observation, histopathological study, X-ray examination, scanning electron microscope (SEM), and biomechanical analysis in the fourth, eighth, and 12th weeks. Group B stimulated more bone formation than the other groups. Nano-HA artificial bone is capable of good bone formation and biocompatibility. The ability of bone formation of nano-HA artificial bone may be affected significantly by the pore size. The material with pore size in the range of 100 –250 μm has a greater ability to form bone.
PMCID: PMC2899063  PMID: 18500516
8.  A Humanized Anti-VEGF Rabbit Monoclonal Antibody Inhibits Angiogenesis and Blocks Tumor Growth in Xenograft Models 
PLoS ONE  2010;5(2):e9072.
Rabbit antibodies have been widely used in research and diagnostics due to their high antigen specificity and affinity. Though these properties are also highly desirable for therapeutic applications, rabbit antibodies have remained untapped for human disease therapy. To evaluate the therapeutic potential of rabbit monoclonal antibodies (RabMAbs), we generated a panel of neutralizing RabMAbs against human vascular endothelial growth factor-A (VEGF). These neutralizing RabMAbs are specific to VEGF and do not cross-react to other members of the VEGF protein family. Guided by sequence and lineage analysis of a panel of neutralizing RabMAbs, we humanized the lead candidate by substituting non-critical residues with human residues within both the frameworks and the CDR regions. We showed that the humanized RabMAb retained its parental biological properties and showed potent inhibition of the growth of H460 lung carcinoma and A673 rhabdomyosarcoma xenografts in mice. These studies provide proof of principle for the feasibility of developing humanized RabMAbs as therapeutics.
PMCID: PMC2816707  PMID: 20140208
9.  Priorities for nucleotide trace, sequence and annotation data capture at the Ensembl Trace Archive and the EMBL Nucleotide Sequence Database 
Nucleic Acids Research  2007;36(Database issue):D5-D12.
The Ensembl Trace Archive ( and the EMBL Nucleotide Sequence Database (, known together as the European Nucleotide Archive, continue to see growth in data volume and diversity. Selected major developments of 2007 are presented briefly, along with data submission and retrieval information. In the face of increasing requirements for nucleotide trace, sequence and annotation data archiving, data capture priority decisions have been taken at the European Nucleotide Archive. Priorities are discussed in terms of how reliably information can be captured, the long-term benefits of its capture and the ease with which it can be captured.
PMCID: PMC2238915  PMID: 18039715
10.  EMBL Nucleotide Sequence Database in 2006 
Nucleic Acids Research  2006;35(Database issue):D16-D20.
The EMBL Nucleotide Sequence Database () at the EMBL European Bioinformatics Institute, UK, offers a large and freely accessible collection of nucleotide sequences and accompanying annotation. The database is maintained in collaboration with DDBJ and GenBank. Data are exchanged between the collaborating databases on a daily basis to achieve optimal synchrony. Webin is the preferred tool for individual submissions of nucleotide sequences, including Third Party Annotation, alignments and bulk data. Automated procedures are provided for submissions from large-scale sequencing projects and data from the European Patent Office. In 2006, the volume of data has continued to grow exponentially. Access to the data is provided via SRS, ftp and variety of other methods. Extensive external and internal cross-references enable users to search for related information across other databases and within the database. All available resources can be accessed via the EBI home page at . Changes over the past year include changes to the file format, further development of the EMBLCDS dataset and developments to the XML format.
PMCID: PMC1897316  PMID: 17148479
11.  Mfge8 Is Critical for Mammary Gland Remodeling during Involution 
Molecular Biology of the Cell  2005;16(12):5528-5537.
Apoptosis is a critical process in normal mammary gland development and the rapid clearance of apoptotic cells prevents tissue injury associated with the release of intracellular antigens from dying cells. Milk fat globule-EGF-factor 8 (Mfge8) is a milk glycoprotein that is abundantly expressed in the mammary gland epithelium and has been shown to facilitate the clearance of apoptotic lymphocytes by splenic macrophages. We report that mice with disruption of Mfge8 had normal mammary gland development until involution. However, abnormal mammary gland remodeling was observed postlactation in Mfge8 mutant mice. During early involution, Mfge8 mutant mice had increased numbers of apoptotic cells within the mammary gland associated with a delay in alveolar collapse and fat cell repopulation. As involution progressed, Mfge8 mutants developed inflammation as assessed by CD45 and CD11b staining of mammary gland tissue sections. With additional pregnancies, Mfge8 mutant mice developed progressive dilatation of the mammary gland ductal network. These data demonstrate that Mfge8 regulates the clearance of apoptotic epithelial cells during mammary gland involution and that the absence of Mfge8 leads to inflammation and abnormal mammary gland remodeling.
PMCID: PMC1289399  PMID: 16195353
12.  EMBL Nucleotide Sequence Database: developments in 2005 
Nucleic Acids Research  2005;34(Database issue):D10-D15.
The EMBL Nucleotide Sequence Database () at the EMBL European Bioinformatics Institute, UK, offers a comprehensive set of publicly available nucleotide sequence and annotation, freely accessible to all. Maintained in collaboration with partners DDBJ and GenBank, coverage includes whole genome sequencing project data, directly submitted sequence, sequence recorded in support of patent applications and much more. The database continues to offer submission tools, data retrieval facilities and user support. In 2005, the volume of data offered has continued to grow exponentially. In addition to the newly presented data, the database encompasses a range of new data types generated by novel technologies, offers enhanced presentation and searchability of the data and has greater integration with other data resources offered at the EBI and elsewhere. In stride with these developing data types, the database has continued to develop submission and retrieval tools to maximise the information content of submitted data and to offer the simplest possible submission routes for data producers. New developments, the submission process, data retrieval and access to support are presented in this paper, along with links to sources of further information.
PMCID: PMC1347492  PMID: 16381823
13.  Potent Antiviral Activity of North-Methanocarbathymidine against Kaposi's Sarcoma-Associated Herpesvirus 
Antimicrobial Agents and Chemotherapy  2005;49(12):4965-4973.
Kaposi's sarcoma-associated herpesvirus (KSHV) infection is a prerequisite for the development of Kaposi's sarcoma (KS). Blocking lytic KSHV replication may hinder KS tumorigenesis. Here, we report potent in vitro anti-KSHV activity of 2′-exo-methanocarbathymidine [North-methanocarbathymidine (N-MCT)], a thymidine analog with a pseudosugar ring locked in the northern conformation, which has previously been shown to block the replication of herpes simplex virus types 1 and 2. N-MCT inhibited KSHV virion production in lytically induced KSHV-infected BCBL-1 cells with a substantially lower 50% inhibitory concentration (IC50) than those of cidofovir (CDV) and ganciclovir (GCV) (IC50, mean ± standard deviation: 0.08 ± 0.03, 0.42 ± 0.07, and 0.96 ± 0.49 μM for N-MCT, CDV, and GCV, respectively). The reduction in KSHV virion production was accompanied by a corresponding decrease in KSHV DNA levels in the N-MCT-treated BCBL-1 cells, indicating that the compound blocked lytic KSHV DNA replication. A time- and dose-dependent accumulation of N-MCT-triphosphate (TP) was demonstrated in lytically induced BCBL-1 cells, while uninfected cells showed virtually no accumulation. The levels of N-MCT-TP were significantly decreased in the presence of 5′-ethynylthymidine, a potent inhibitor of herpesvirus thymidine kinase, resulting in the abrogation of anti-KSHV activity of N-MCT. N-MCT-TP more effectively blocked in vitro DNA synthesis by KSHV DNA polymerase with an IC50 of 6.24 ± 0.08 μM (mean ± standard deviation) compared to CDV-diphosphate (14.70 ±2.47 μM) or GCV-TP (24.59 ± 5.60 μM). Taken together, N-MCT is a highly potent and target-specific anti-KSHV agent which inhibits lytic KSHV DNA synthesis through its triphosphate metabolite produced in KSHV-infected cells expressing a virally encoded thymidine kinase.
PMCID: PMC1315933  PMID: 16304159
14.  Discovery of Small-Molecule Human Immunodeficiency Virus Type 1 Entry Inhibitors That Target the gp120-Binding Domain of CD4†  
Journal of Virology  2005;79(10):6122-6133.
The interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and the CD4 receptor is highly specific and involves relatively small contact surfaces on both proteins according to crystal structure analysis. This molecularly conserved interaction presents an excellent opportunity for antiviral targeting. Here we report a group of pentavalent antimony-containing small molecule compounds, NSC 13778 (molecular weight, 319) and its analogs, which exert a potent anti-HIV activity. These compounds block the entry of X4-, R5-, and X4/R5-tropic HIV-1 strains into CD4+ cells but show little or no activity in CD4-negative cells or against vesicular stomatitis virus-G pseudotyped virions. The compounds compete with gp120 for binding to CD4: either immobilized on a solid phase (soluble CD4) or on the T-cell surface (native CD4 receptor) as determined by a competitive gp120 capture enzyme-linked immunosorbent assay or flow cytometry. NSC 13778 binds to an N-terminal two-domain CD4 protein, D1/D2 CD4, immobilized on a surface plasmon resonance sensor chip, and dose dependently reduces the emission intensity of intrinsic tryptophan fluorescence of D1/D2 CD4, which contains two of the three tryptophan residues in the gp120-binding domain. Furthermore, T cells incubated with the compounds alone show decreased reactivity to anti-CD4 monoclonal antibodies known to recognize the gp120-binding site. In contrast to gp120-binders that inhibit gp120-CD4 interaction by binding to gp120, these compounds appear to disrupt gp120-CD4 contact by targeting the specific gp120-binding domain of CD4. NSC 13778 may represent a prototype of a new class of HIV-1 entry inhibitors that can break into the gp120-CD4 interface and mask the gp120-binding site on the CD4 molecules, effectively repelling incoming virions.
PMCID: PMC1091715  PMID: 15857997
15.  The EMBL Nucleotide Sequence Database 
Nucleic Acids Research  2004;32(Database issue):D27-D30.
The EMBL Nucleotide Sequence Database (, maintained at the European Bioinformatics Institute (EBI), incorporates, organizes and distributes nucleotide sequences from public sources. The database is a part of an international collaboration with DDBJ (Japan) and GenBank (USA). Data are exchanged between the collaborating databases on a daily basis to achieve optimal synchrony. The web-based tool, Webin, is the preferred system for individual submission of nucleotide sequences, including Third Party Annotation (TPA) and alignment data. Automatic submission procedures are used for submission of data from large-scale genome sequencing centres and from the European Patent Office. Database releases are produced quarterly. The latest data collection can be accessed via FTP, email and WWW interfaces. The EBI’s Sequence Retrieval System (SRS) integrates and links the main nucleotide and protein databases as well as many other specialist molecular biology databases. For sequence similarity searching, a variety of tools (e.g. FASTA and BLAST) are available that allow external users to compare their own sequences against the data in the EMBL Nucleotide Sequence Database, the complete genomic component subsection of the database, the WGS data sets and other databases. All available resources can be accessed via the EBI home page at
PMCID: PMC308854  PMID: 14681351
16.  Progress in Establishing Common Standards for Exchanging Proteomics Data: The Second Meeting of the HUPO Proteomics Standards Initiative 
The Proteomics Standards Initiative (PSI) aims to define community standards for data representation in proteomics and to facilitate data comparison, exchange and verification. Rapid progress has been made in the development of common standards for data exchange in the fields of both mass spectrometry and protein–protein interactions since the first PSI meeting [1]. Both hardware and software manufacturers have agreed to work to ensure that a proteomics-specific extension is created for the emerging ASTM mass spectrometry standard and the data model for a proteomics experiment has advanced significantly. The Protein–Protein Interactions (PPI) group expects to publish the Level 1 PSI data exchange format for protein–protein interactions by early summer this year, and discussion as to the additional content of Level 2 has been initiated.
PMCID: PMC2447408  PMID: 18629121
17.  Identification of rCop-1, a New Member of the CCN Protein Family, as a Negative Regulator for Cell Transformation 
Molecular and Cellular Biology  1998;18(10):6131-6141.
By using a model system for cell transformation mediated by the cooperation of the activated H-ras oncogene and the inactivated p53 tumor suppressor gene, rCop-1 was identified by mRNA differential display as a gene whose expression became lost after cell transformation. Homology analysis indicates that rCop-1 belongs to an emerging cysteine-rich growth regulator family called CCN, which includes connective-tissue growth factor, CYR61, CEF10 (v-src inducible), and the product of the nov proto-oncogene. Unlike the other members of the CCN gene family, rCop-1 is not an immediate-early gene, it lacks the conserved C-terminal domain which was shown to confer both growth-stimulating and heparin-binding activities, and its expression is lost in cells transformed by a variety of mechanisms. Ectopic expression of rCop-1 by retroviral gene transfers led to cell death in a transformation-specific manner. These results suggest that rCop-1 represents a new class of CCN family proteins that have functions opposing those of the previously identified members.
PMCID: PMC109199  PMID: 9742130

Results 1-17 (17)