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1.  Does hydroxyapatite coating have no advantage over porous coating in primary total hip arthroplasty? A meta-analysis 
There are some arguments between the use of hydroxyapatite and porous coating. Some studies have shown that there is no difference between these two coatings in total hip arthroplasty (THA), while several other studies have shown that hydroxyapatite has advantages over the porous one. We have collected the studies in Pubmed, MEDLINE, EMBASE, and the Cochrane library from the earliest possible years to present, with the search strategy of “(HA OR hydroxyapatite) AND ((total hip arthroplasty) OR (total hip replacement)) AND (RCT* OR randomiz* OR control* OR compar* OR trial*)”. The randomized controlled trials and comparative observation trials that evaluated the clinical and radiographic effects between hydroxyapatite coating and porous coating were included. Our main outcome measurements were Harris hip score (HHS) and survival, while the secondary outcome measurements were osteolysis, radiolucent lines, and polyethylene wear. Twelve RCTs and 9 comparative observation trials were included. Hydroxyapatite coating could improve the HHS (p < 0.01), reduce the incidence of thigh pain (p = 0.01), and reduce the incidence of femoral osteolysis (p = 0.01), but hydroxyapatite coating had no advantages on survival (p = 0.32), polyethylene wear (p = 0.08), and radiolucent lines (p = 0.78). Hydroxyapatite coating has shown to have an advantage over porous coating. The HHS and survival was duration-dependent—if given the sufficient duration of follow-up, hydroxyapatite coating would be better than porous coating for the survival. The properties of hydroxyapatite and the implant design had influence on thigh pain incidence, femoral osteolysis, and polyethylene wear. Thickness of 50 to 80 μm and purity larger than 90% increased the thigh pain incidence. Anatomic design had less polyethylene wear.
doi:10.1186/s13018-015-0161-4
PMCID: PMC4314743  PMID: 25626520
Hydroxyapatite; Porous; Harris hip score; Survival; Total hip arthroplasty
2.  In Vitro and In Vivo Evaluation of Vancomycin-Loaded PMMA Cement in Combination with Ultrasound and Microbubbles-Mediated Ultrasound 
BioMed Research International  2015;2015:309739.
Ultrasound (US) has been used to increase elution of antibiotic from an antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC). We aimed to further investigate whether microbubbles-mediated US (US + MB) facilitate elution of vancomycin (VAN) from cylindrical specimens and enhance the activity of the eluted antibiotic against Staphylococcus aureus (S. aureus) in vitro. The study groups comprised cylindrical bone cement fabricated with VAN (VAN), ALBC using US (VAN + US), and ALBC using MB-mediated US (VAN + US + MB). We also carried out an in vivo study involving the activity of VAN from cylindrical cement implanted in tibiae of New Zealand white rabbits inoculated with S. aureus. We found that (1) in vitro, elution from VAN + US + MB cylinders was significantly higher than from either the VAN or VAN + US specimens; (2) the activity of the eluted VAN from the VAN + US + MB cylinders against planktonic S. aureus was significantly higher than from either the control or VAN or VAN + US specimens; and (3) in the rabbits, the activity of the eluted VAN from the VAN + US + MB cylinders against S. aureus was significantly higher than from either the control or VAN or VAN + US specimens. The present results suggest that VAN-loaded PMMA cement irradiated with MB-mediated US may have a role in controlling prosthetic joint infection.
doi:10.1155/2015/309739
PMCID: PMC4302969  PMID: 25632389
3.  Cartilage Oligomeric Matrix Protein Gene Multilayers Inhibit Osteogenic Differentiation and Promote Chondrogenic Differentiation of Mesenchymal Stem Cells 
There are still many challenges to acquire the optimal integration of biomedical materials with the surrounding tissues. Gene coatings on the surface of biomaterials may offer an effective approach to solve the problem. In order to investigate the gene multilayers mediated differentiation of mesenchymal stem cells (MSCs), gene functionalized films of hyaluronic acid (HA) and lipid-DNA complex (LDc) encoding cartilage oligomeric matrix protein (COMP) were constructed in this study via the layer-by-layer self-assembly technique. Characterizations of the HA/DNA multilayered films indicated the successful build-up process. Cells could be directly transfected by gene films and a higher expression could be obtained with the increasing bilayer number. The multilayered films were stable for a long period and DNA could be easily released in an enzymatic condition. Real-time polymerase chain reaction (RT-PCR) assay presented significantly higher (p < 0.01) COMP expression of MSCs cultured with HA/COMP multilayered films. Compared with control groups, the osteogenic gene expression levels of MSCs with HA/COMP multilayered films were down-regulated while the chondrogenic gene expression levels were up-regulated. Similarly, the alkaline phosphatase (ALP) staining and Alizarin red S staining of MSCs with HA/COMP films were weakened while the alcian blue staining was enhanced. These results demonstrated that HA/COMP multilayered films could inhibit osteogenic differentiation and promote chondrogenic differentiation of MSCs, which might provide new insight for physiological ligament-bone healing.
doi:10.3390/ijms151120117
PMCID: PMC4264159  PMID: 25380520
cartilage oligomeric matrix protein; layer-by-layer self-assembly; gene delivery; mesenchymal stem cells; cell differentiation
4.  Features and Risk Factors of Nonfatal Injury among the Rural Children: A Survey of Seven Schools in a Mountain Area in Southwest China 
PLoS ONE  2014;9(7):e102099.
Objective
We aimed to investigate the patterns and risk factors of nonfatal injuries among rural mountain-area children in southwest China.
Methods
A stratified sampling method was used to recruit rural children aged 8 to 17 years (mainly 9–14 years) from 7 schools. Self-reported injuries during the past 12 months and relevant concerns were collected from June to December 2012 by using a structured questionnaire in a class interview.
Results
The mean age of the 2,854 children was 12.2±1.5 years. The probability of annual injury was 16.7% (95% confidence interval [95% CI] 15.3–18.1%), with slightly higher injury risk for boys than girls (17.7% vs. 16.0%; P>0.05). The top 3 causes of injuries were falls (37.3%), animal-related incidents (20.6%), and burns (14.9%). The main injury risk factors included being involved in a violent episode (odds ratio [OR] 1.34, 95% CI 1.08–1.66, P = 0.007), maltreatment by parents or guardians (1.42, 1.17–1.72, P<0.001), and being from a single-child family (1.30, 1.10–1.66, P = 0.039). Older age was a protective factor (0.81, 0.76–0.87, P<0.001).
Conclusions
The incidence of nonfatal injury among rural children was high, and falls were the leading cause. Younger children and boys from poor-care and poor-living environments were at increased risk of injury, which requires urgent attention. Injury prevention programs targeting these issues are needed in this mountain area and similar rural regions of China.
doi:10.1371/journal.pone.0102099
PMCID: PMC4092098  PMID: 25010712
5.  Melatonin Promotes Superovulation in Sika Deer (Cervus nippon) 
In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.
doi:10.3390/ijms150712107
PMCID: PMC4139832  PMID: 25007067
melatonin; superovulation; FSH; LH; PRL; sika deer
6.  Piperlongumine Induces Apoptosis and Synergizes with Cisplatin or Paclitaxel in Human Ovarian Cancer Cells 
Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.
doi:10.1155/2014/906804
PMCID: PMC4034765  PMID: 24895529
7.  Dissecting the Characteristics and Dynamics of Human Protein Complexes at Transcriptome Cascade Using RNA-Seq Data 
PLoS ONE  2013;8(6):e66521.
Human protein complexes play crucial roles in various biological processes as the functional module. However, the expression features of human protein complexes at the transcriptome cascade are poorly understood. Here, we used the RNA-Seq data from 16 disparate tissues and four types of human cancers to explore the characteristics and dynamics of human protein complexes. We observed that many individual components of human protein complexes can be generated by multiple distinct transcripts. Similar with yeast, the human protein complex constituents are inclined to co-express in diverse tissues. The dominant isoform of the genes involved in protein complexes tend to encode the complex constituents in each tissue. Our results indicate that the protein complex dynamics not only correlate with the presence or absence of complexes, but may also be related to the major isoform switching for complex subunits. Between any two cancers of breast, colon, lung and prostate, we found that only a few of the differentially expressed transcripts associated with complexes were identical, but 5–10 times more protein complexes involved in differentially expressed transcripts were common. Collectively, our study reveals novel properties and dynamics of human protein complexes at the transcriptome cascade in diverse normal tissues and different cancers.
doi:10.1371/journal.pone.0066521
PMCID: PMC3688907  PMID: 23824284
8.  CD33+/p-STAT1+ double-positive cell as a prognostic factor for stage IIIa gastric cancer 
Tumor-infiltrating immune cells are associated with tumor prognosis, although the type of immune cells responsible for local immune escape is still unknown. This study examined the relationship between gastric cancer survival and the density of immune cells, including CD8+ T cells, CD20+ B cells, and CD33+/p-STAT1+ cells, which represent myeloid-derived suppressor cells, to evaluate the role of immune cells in the progression of gastric cancer. One hundred pathologically confirmed specimens were obtained from stage IIIa gastric cancers between 2003 and 2006 at Sun Yat-sen University Cancer Center, China. The density of tumor-infiltrating immune cells in tumor tissue was examined using immunohistochemical analysis. Clinicopathologic parameters and the survival rate were analyzed in relation to the density of immune cells. A high density of CD8+ T cells and CD20+ B cells was associated with a good clinical outcome, but a high density of CD33+/p-STAT1+ cells was associated with a poor clinical outcome. Most importantly, the density of CD33+/p-STAT1+ cells was an independent prognostic factor and inversely related to the infiltration of CD8+ T cells. Although the infiltration of CD8+ T cells and CD20+ B cells is involved in the progression of gastric cancer, these data suggest that CD33+/p-STAT1+ cells play a central role in the regulation of the local immune response, suggesting that CD33+/p-STAT1+ cells might be therapeutic targets in gastric cancer.
doi:10.1007/s12032-012-0442-2
PMCID: PMC3586391  PMID: 23307253
Gastric cancer; CD33; STAT1; T cell; B cell; Regulation
9.  Successful treatment of a patient with an extraordinarily large deep burn 
Summary
Background
Treatment of extraordinarily large deep burns remains a huge clinical challenge.
Case Report
This article is a summary of our experience with the treatment of a patient with an extraordinarily large deep burn (99.5% TBSA and 23% fourth degree burn) by using the “microskin autografting and alloskin repeated grafting” method to close the deep burn wound because of scarcity of skin sources of the patient.
Conclusions
The patient has been observed for 2 years, and is able to face the reality of life peacefully with the support of his family.
doi:10.12659/MSM.881704
PMCID: PMC3539531  PMID: 21455113
deep burn wound; burn operation; Quality of Life
10.  Consistency of predictive signature genes and classifiers generated using different microarray platforms 
The Pharmacogenomics Journal  2010;10(4):247-257.
Microarray-based classifiers and associated signature genes generated from various platforms are abundantly reported in the literature; however, the utility of the classifiers and signature genes in cross-platform prediction applications remains largely uncertain. As part of the MicroArray Quality Control Phase II (MAQC-II) project, we show in this study 80–90% cross-platform prediction consistency using a large toxicogenomics data set by illustrating that: (1) the signature genes of a classifier generated from one platform can be directly applied to another platform to develop a predictive classifier; (2) a classifier developed using data generated from one platform can accurately predict samples that were profiled using a different platform. The results suggest the potential utility of using published signature genes in cross-platform applications and the possible adoption of the published classifiers for a variety of applications. The study reveals an opportunity for possible translation of biomarkers identified using microarrays to clinically validated non-array gene expression assays.
doi:10.1038/tpj.2010.34
PMCID: PMC2920073  PMID: 20676064
microarray; cross-platform; gene signature; classifier; MAQC; hepatotoxicity
11.  Mesenchymal Stem Cells Derived from Human Gingiva Are Capable of Immunomodulatory Functions and Ameliorate Inflammation-Related Tissue Destruction in Experimental Colitis1 
Aside from the well-established self-renewal and multipotent differentiation properties, mesenchymal stem cells exhibit both immunomodulatory and anti-inflammatory roles in several experimental autoimmune and inflammatory diseases. In this study, we isolated a new population of stem cells from human gingiva, a tissue source easily accessible from the oral cavity, namely, gingiva-derived mesenchymal stem cells (GMSCs), which exhibited clonogenicity, self-renewal, and multipotent differentiation capacities. Most importantly, GMSCs were capable of immunomodulatory functions, specifically suppressed peripheral blood lymphocyte proliferation, induced expression of a wide panel of immunosuppressive factors including IL-10, IDO, inducible NO synthase (iNOS), and cyclooxygenase 2 (COX-2) in response to the inflammatory cytokine, IFN-γ. Cell-based therapy using systemic infusion of GMSCs in experimental colitis significantly ameliorated both clinical and histopathological severity of the colonic inflammation, restored the injured gastrointestinal mucosal tissues, reversed diarrhea and weight loss, and suppressed the overall disease activity in mice. The therapeutic effect of GMSCs was mediated, in part, by the suppression of inflammatory infiltrates and inflammatory cytokines/mediators and the increased infiltration of regulatory T cells and the expression of anti-inflammatory cytokine IL-10 at the colonic sites. Taken together, GMSCs can function as an immunomodulatory and anti-inflammatory component of the immune system in vivo and is a promising cell source for cell-based treatment in experimental inflammatory diseases.
doi:10.4049/jimmunol.0902318
PMCID: PMC2881945  PMID: 19923445
12.  Significance of hepatitis B virus surface antigen, hepatitis C virus expression in hepatocellular carcinoma and pericarcinomatous tissues 
AIM: To investigate the correlation between hepatitis B virus surface antigen (HBsAg), hepatitis C virus (HCV) expression in hepatocellular carcinoma (HCC), the HAI score of the noncancerous region of the liver and the serum Alpha fetoprotein (AFP) level.
METHODS: The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embedded sections with immuno-histochemistry, the histological status was determined by one pathologist and one surgeon simultaneously using the hepatitis activity index (HAI) score, and AFP was detected by radioimmunity. The study included 100 consecutive patients who underwent curative resection for HCC. Based on HBsAg and HCV expression, the patients were classified into 4 groups: patients positive for HBsAg (HBsAg group), patients positive for HCV (HCV group), patients negative for both HCV and HBsAg (NBNC group) and patients positive for both HBsAg and HCV (BC group).
RESULTS: The BC group had significantly higher HAI scores than the other three groups. (BC > HCV > HBsAg > NBNC). HBV and HCV virus infection was positively correlated with HAI (rs = 0.39, P = 0.0001). The positive rate of AFP (85.7%) and the value of AFP (541.2 ng/mL) in the group with HBV and HCV co-infection were the highest among the four groups. The positive rate (53.3%) of AFP and the value of AFP ( 53.3 ng/mL) in the group with none-infection of HBV and HCV were the lowest. HBV and HCV virus infection was positively correlated with AFP(rs = 0.38, P = 0.0001).
CONCLUSION: The AFP increase in patients with liver cancer was positively correlated with the infection of HBV and HCV. The serum AFP elevation by the infection of HBV and HCV is one of mechanisms which lead to hepatocarcinogenesis, and the antivirus intervening treatment of hepatitis is significant for the prognosis of liver cancer. From our Spearman’s rank correlation analysis, we can conclude that the severity of virally induced inflammation is correlated with HBsAg and HCV expression in HCC tissues and noncancerous tissues. Prior co-infection of HBV in HCV patients may be an adverse risk factor for intrahepatic inflammation.
doi:10.3748/wjg.v13.i12.1870
PMCID: PMC4149970  PMID: 17465484
Hepatitis B virus surface antigen; Hepatitis C virus antigen; Histological activity index; Immunohisto-chemistry; Hepatocellular carcinoma; Alpha-fetoprotein.
13.  A comparison of batch effect removal methods for enhancement of prediction performance using MAQC-II microarray gene expression data 
The Pharmacogenomics Journal  2010;10(4):278-291.
Batch effects are the systematic non-biological differences between batches (groups) of samples in microarray experiments due to various causes such as differences in sample preparation and hybridization protocols. Previous work focused mainly on the development of methods for effective batch effects removal. However, their impact on cross-batch prediction performance, which is one of the most important goals in microarray-based applications, has not been addressed. This paper uses a broad selection of data sets from the Microarray Quality Control Phase II (MAQC-II) effort, generated on three microarray platforms with different causes of batch effects to assess the efficacy of their removal. Two data sets from cross-tissue and cross-platform experiments are also included. Of the 120 cases studied using Support vector machines (SVM) and K nearest neighbors (KNN) as classifiers and Matthews correlation coefficient (MCC) as performance metric, we find that Ratio-G, Ratio-A, EJLR, mean-centering and standardization methods perform better or equivalent to no batch effect removal in 89, 85, 83, 79 and 75% of the cases, respectively, suggesting that the application of these methods is generally advisable and ratio-based methods are preferred.
doi:10.1038/tpj.2010.57
PMCID: PMC2920074  PMID: 20676067
batch effect; batch effect removal; cross-batch prediction; microarray; gene expression; MAQC-II
14.  Functional analysis of multiple genomic signatures demonstrates that classification algorithms choose phenotype-related genes 
The Pharmacogenomics Journal  2010;10(4):310-323.
Gene expression signatures of toxicity and clinical response benefit both safety assessment and clinical practice; however, difficulties in connecting signature genes with the predicted end points have limited their application. The Microarray Quality Control Consortium II (MAQCII) project generated 262 signatures for ten clinical and three toxicological end points from six gene expression data sets, an unprecedented collection of diverse signatures that has permitted a wide-ranging analysis on the nature of such predictive models. A comprehensive analysis of the genes of these signatures and their nonredundant unions using ontology enrichment, biological network building and interactome connectivity analyses demonstrated the link between gene signatures and the biological basis of their predictive power. Different signatures for a given end point were more similar at the level of biological properties and transcriptional control than at the gene level. Signatures tended to be enriched in function and pathway in an end point and model-specific manner, and showed a topological bias for incoming interactions. Importantly, the level of biological similarity between different signatures for a given end point correlated positively with the accuracy of the signature predictions. These findings will aid the understanding, and application of predictive genomic signatures, and support their broader application in predictive medicine.
doi:10.1038/tpj.2010.35
PMCID: PMC2920075  PMID: 20676069
genomic signatures; enrichment analysis; network reconstruction; biological pathways; interactome; MAQCII
15.  Ataxia and hypogonadism caused by the loss of ubiquitin ligase activity of the U box protein CHIP 
Human Molecular Genetics  2013;23(4):1013-1024.
Gordon Holmes syndrome (GHS) is a rare Mendelian neurodegenerative disorder characterized by ataxia and hypogonadism. Recently, it was suggested that disordered ubiquitination underlies GHS though the discovery of exome mutations in the E3 ligase RNF216 and deubiquitinase OTUD4. We performed exome sequencing in a family with two of three siblings afflicted with ataxia and hypogonadism and identified a homozygous mutation in STUB1 (NM_005861) c.737C→T, p.Thr246Met, a gene that encodes the protein CHIP (C-terminus of HSC70-interacting protein). CHIP plays a central role in regulating protein quality control, in part through its ability to function as an E3 ligase. Loss of CHIP function has long been associated with protein misfolding and aggregation in several genetic mouse models of neurodegenerative disorders; however, a role for CHIP in human neurological disease has yet to be identified. Introduction of the Thr246Met mutation into CHIP results in a loss of ubiquitin ligase activity measured directly using recombinant proteins as well as in cell culture models. Loss of CHIP function in mice resulted in behavioral and reproductive impairments that mimic human ataxia and hypogonadism. We conclude that GHS can be caused by a loss-of-function mutation in CHIP. Our findings further highlight the role of disordered ubiquitination and protein quality control in the pathogenesis of neurodegenerative disease and demonstrate the utility of combining whole-exome sequencing with molecular analyses and animal models to define causal disease polymorphisms.
doi:10.1093/hmg/ddt497
PMCID: PMC3900109  PMID: 24113144
16.  Hierarchical ZnO Nanostructures with Blooming Flowers Driven by Screw Dislocations 
Scientific Reports  2015;5:8226.
Hierarchical ZnO nanostructures with a large yield were fabricated by a simple thermal evaporation method. For the first time, novel ZnO flowers were observed blooming at certain sites of a variety of spines, identified as Zn-terminated polar (0001) planes or tips. The spines for as-synthesized hierarchical structures can be nanowires, nanobelts, nanodendrites, nanobrushes, etc. This growth phenomenon determines the key role of polar sites in the fabrication of hierarchical structures. The spiral feature of ZnO flowers indicates an unusual screw dislocation driven growth mechanism, which is attributed to a high concentration of Zn vapor.
doi:10.1038/srep08226
PMCID: PMC4316161  PMID: 25648112
17.  Effects of Entecavir on Hepatitis B Virus Covalently Closed Circular DNA in Hepatitis B e Antigen-Positive Patients with Hepatitis B 
PLoS ONE  2015;10(2):e0117741.
The aim of this study was to assess the effect of 48-week entecavir therapy on serum and intrahepatic hepatitis B virus, covalently closed circular DNA (HBV cccDNA) levels in hepatitis B e antigen (HBeAg)-positive patients. A total of 120 patients with HBeAg-positive chronic hepatitis were treated with entecavir for 48 weeks. Serum HBV markers, total HBV DNA, and HBV cccDNA levels were measured at baseline and week 48. Biopsies from 20 patients were available for both intrahepatic total HBV DNA and cccDNA testing at these timepoints. HBV cccDNA levels were decreased from a median level of 5.1×106 copies/mL at baseline to a median level of 2.4×103 copies/mL at week 48. Reduction magnitudes of HBV cccDNA in patients with normalized alanine aminotransferase levels and those undergoing HBeAg seroconversion were significantly greater than those in alanine aminotransferase-abnormal and HBeAg positive patients. Intrahepatic HBV cccDNA was decreased significantly after 48 weeks of treatment, but could not be eradicated. In conclusion, treatment of HBeAg-positive hepatitis B patients with entecavir for 48 weeks decreased serum and intrahepatic HBV cccDNA significantly, and the magnitude of HBV cccDNA reduction was related to total HBV DNA decrease, alanine aminotransferase normalization, and HBeAg seroconversion.
doi:10.1371/journal.pone.0117741
PMCID: PMC4315599  PMID: 25647607
18.  A comprehensive database of Duchenne and Becker muscular dystrophy patients (0–18 years old) in East China 
Background
Currently, there is no cure for Duchenne and Becker muscular dystrophies (DMD/BMD). However, clinical trials with new therapeutic strategies are being conducted or considered. A comprehensive database is critical for patient recruitment and efficacy evaluation. China has the largest population, yet, no comprehensive database for DMD/BMD is available. Our study registered the data of the DMD/BMD patients in East China.
Methods
A modified registry form of Remudy (http://www.remudy.jp/) was applied to Chinese DMD/BMD patients through the outpatient clinic at Children’s Hospital of Fudan University, Shanghai during the period of August 2011 to December 2013. The data included geographic distribution of patients, age at diagnosis, clinical manifestation, genetic analysis and treatment status.
Results
194 DMD and 35 BMD patients were registered. Most patients lived in East China, namely Jiangsu province, Anhui province, Zhejiang province, Jiangxi province, Shanghai, Fujian province and Shandong province. All individuals aged less than 18 years (age limit to a children’s hospital). Diagnosis was made for a majority of patients during the age of 3–4 (16.6%) and 7–8 (14.8%) years old. Exon deletion was the most frequent genetic mutations (65.5% and 74.3%) followed by point mutations (14.4% and 11.4%), duplications (9.8% and 8.6%) and small insertion/deletion (9.3% and 2.9%) for DMD and BMD, respectively. 82.5% of DMD registrants were ambulatory, and all the BMD registrants were able to walk. 26.3% of DMD registrants have been treated with steroids. Cardiac functions were examined for 46.4% DMD boys and 45.7% BMD boys and respiratory functions were examined for 18.6% DMD boys and 14.3% BMD boys. Four boys with abnormal cardiac function were prescribed for treatment with cardiac medicine. 33.2% of DMD patients are eligible for exon skipping therapy, and among them 9.2% and 4.3% patients are eligible for skipping exon 51 and 53, respectively.
Conclusions
The database is the first linking accurate genetic diagnosis with clinical manifestation and treatment status of dystrophinopathy patients in East China. It provides comprehensive information essential for further patient management, especially for promotion of international cooperation in developing experimental therapies such as exon skipping and read-through of nonsense mutations targeting a subgroup of DMD patient population.
doi:10.1186/s13023-014-0220-7
PMCID: PMC4323212  PMID: 25612904
Duchenne and Becker muscular dystrophy; The CHFU database; Patient management
19.  Pretreatment 18 F-FDG uptake heterogeneity can predict survival in patients with locally advanced nasopharyngeal carcinoma——a retrospective study 
Background
Intratumoural heterogeneity has been demonstrated to be a strong indicator of malignant transformation. Our study was to investigate pretreatment 18 F-FDG parameters, including 18 F-FDG based heterogeneity for predicting survival in patients with locally advanced nasopharyngeal carcinoma (NPC).
Methods
Forty newly diagnosed, biopsy-proven locally advanced NPC patients who underwent 18 F-FDG PET/CT were retrospectively included. The following PET parameters were assessed: maximum and mean standardised uptake value (SUVmax and SUVmean), metabolic tumour volume (MTV), total lesion glycolysis (TLG) and intratumoral heterogeneity index (HI). The previous parameters were recorded both for the primary tumor (-T) and neck lymph nodes (-N). The following endpoints were evaluated: local control (LC), progression-free survival (PFS) and overall survival (OS). The survival analyses were performed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test.
Results
Patients with a lower HI-T, SUVmax-T, SUVmean-T and TLG-T had significantly better 2-year LC. In predicting PFS, we found that both lower HI-T and HI-N had significantly better prognosis. However, the OS was only statistically associated with HI-T.
Conclusion
18 F-FDG based heterogeneity appears to be an potential predicator of patient survival after treatment.
doi:10.1186/s13014-014-0268-5
PMCID: PMC4311496  PMID: 25566697
Nasopharyngeal carcinoma; 18 F-FDG PET/CT; Prognosis; Heterogeneity
20.  MEK/ERK signaling pathway is required for enterovirus 71 replication in immature dendritic cells 
Virology Journal  2014;11(1):227.
Background
The mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) signaling pathway is involved in viral life cycle. However, the effect of MEK/ERK pathway in enterovirus 71(EV71)-infected immature dendritic cells (iDCs) is still unclear.
Methods
Human peripheral blood mononuclear cells (PBMCs) were isolated and induced to generate iDCs. Unifected iDCs and EV71-infected iDCs with a multiplicity of infection (MOI = 5) were analyzed by flow cytometry. Differential gene expressions of MEK/ERK signaling pathway molecules in EV71-infected iDCs were performed by PCR arrays. The phosphorylation of MEK/ERK pathway molecules in EV71-infected iDCs preincubated without or with U0126 (20 μM) at indicated times was detected by Western blot. The concentrations of IL-1α, IL-2, IL-6, IL-12, TNF-α, IFN-α1, IFN-β and IFN-γ in culture supernatant were analyzed by the luminex fluorescent technique.
Results
When iDCs were infected with EV71 for 24 h, the percentage of CD80, CD83, CD86 and HLA-DR expressed on iDCs significantly increased. PCR arrays showed that gene expressions of molecules in MEK/ERK signaling pathway were remarkably upregulated in EV71-infected iDCs. EV71 infection activated both MEK1/2 and ERK1/2, which phosphorylated their downstream transcription factor c-Fos, c-Jun, c-myc and Elk1. Importantly, the treatment of U0126 significantly inhibited MEK/ERK signaling pathway molecules and severely impaired virus replication., Additionally, EV71 infection promoted the expression of son of sevenless (SOS1) and increased the secretion of IL-1α, IL-2, IL-6, IL-12, TNF-α,IFN-β and IFN-γ. Furthermore,the release of IL-1α, IL-2,IL-6 and TNF-α could be effectively suppressed by inhibitor U0126.
Conclusions
Our data suggest that the MEK/ERK signaling pathway plays an important role in EV71-infected iDCs and these molecules may be potential targets for the development of new anti-EV71 drugs.
doi:10.1186/s12985-014-0227-7
PMCID: PMC4304142  PMID: 25548009
Enterovirus 71; Virus replication; MEK/ERK; SOS1; Immature dendritic cells
21.  Multidisciplinary treatment based on surgery leading to long-term survival of a patient with multiple asynchronous rare primary malignant neoplasms: A case report and literature review 
Oncology Letters  2014;9(3):1135-1141.
Patients that present with multiple primary malignant neoplasms are increasingly encountered, but the treatment of such patients presents specific challenges and long-term survival is rare. The present study reports the case of a 45-year-old female diagnosed with three rare, distinct primary malignant neoplasms, including epithelioid hemangioendothelioma (EHE) of the brain, Ewing’s sarcoma of the lumbar 2 vertebra and a malignant solitary fibrous tumour (SFT) of the liver, at different time points. The patient underwent multidisciplinary treatment according to the diagnoses, including radial resection of all primary lesions, chemotherapy (consisting of vincristine, dactinomycin, cyclophosphamide and adriamycin) and radiotherapy, to treat Ewing’s sarcoma and metastases of EHE and malignant SFT. Following these treatments, the patient survived for >14 years. Multidisciplinary treatment regimens based on surgery can lead to long-term survival of patients with multiple asynchronous rare primary malignant neoplasms. The present study reported that multidisciplinary treatment regimens based on surgery can lead to the long-term survival of patients with multiple asynchronous rare primary malignant neoplasms.
doi:10.3892/ol.2014.2833
PMCID: PMC4315099  PMID: 25663869
multiple primary malignant neoplasms; epithelioid hemangioendothelioma; Ewing’s sarcoma; malignant solitary fibrous tumour; multidisciplinary treatment
22.  Identification of Genomic Alterations in Pancreatic Cancer Using Array-Based Comparative Genomic Hybridization 
PLoS ONE  2014;9(12):e114616.
Background
Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer.
Materials and Methods
We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry.
Results
Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3–q22.1 and 19q13.2 and homozygous deletions at 1p33–p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer.
Conclusion
These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.
doi:10.1371/journal.pone.0114616
PMCID: PMC4263743  PMID: 25502777
23.  Fine scale Spatial-temporal cluster analysis for the infection risk of Schistosomiasis japonica using space-time scan statistics 
Parasites & Vectors  2014;7(1):578.
Background
Marching towards the elimination of schistosomiasis in China, both the incidence and prevalence have witnessed profound decline over the past decades, with the strategy shifting from morbidity control to transmission control. The current challenge is to find out hotspots of transmission risk for precise targeted control in low-prevalence areas. This study assessed the risk at the village level, using the spatial and temporal characteristics of Schistosomiasis japonica in Anhui province from 2006 to 2012.
Method
The comprehensive database was generated from annual surveillance data at village level in Anhui province between 2006 and 2012, comprising schistosomiasis prevalence among humans and cattle, occurrence rate of infected environments and incidence rate of acute schistosomiasis. The database parameters were matched with geographic data of the study area and fine scale spatial-temporal cluster analysis based on retrospective space-time scan statistics was used to assess the clustering pattern of schistosomiasis. The analysis was conducted by using SaTScan 9.1.1 and ArcGIS 10.0. A spatial statistical modelling was carried out to determine the spatial dependency of prevalence of human infection by using Geoda 1.4.3.
Result
A pronounced decline was found in the prevalence of human infection, cattle infection, occurrence rate of environment with infected vector snails and incidence rate of acute schistosomiasis from 2006 to 2012 by 48.6%, 71.5%, 91.9% and 96.4%, respectively. Meanwhile, all 4 indicators showed a statistically significant clustering pattern both in time and space, with a total of 16, 6, 8 and 4 corresponding clustering foci found respectively. However, the number of clustering foci declined with time, and none was found after year 2010. All clustering foci were mainly distributed along the Yangtze River and its connecting branches. The result shows that there is a direct spatial relationship between prevalence of human infection and the other indicators.
Conclusion
A decreasing trend in space-time clustering of schistosomiasis endemic status was observed between 2006 and 2012 in Anhui province. Nevertheless, giving the complexity in schistosomiasis control, areas within the upper-stream of Yangtze River in Anhui section and its connecting branches should be targeted for effective implementation of control strategies in the future.
doi:10.1186/s13071-014-0578-3
PMCID: PMC4273478  PMID: 25491192
Fine scale spatial-temporal scan statistics; Schistosomiasis japonica; Infection risk analysis; Anhui province
24.  Resistant mutants induced by adefovir dipivoxil in hepatitis B virus isolates 
World Journal of Gastroenterology : WJG  2014;20(45):17100-17106.
AIM: To investigate the loci of adefovir dipivoxil (ADV)-induced resistance in hepatitis B virus (HBV) isolates and optimize the management of ADV-treated patients.
METHODS: Between June 2008 and August 2010, a cross-sectional control study was conducted comprising 79 patients with chronic HBV infection-related liver disease who had been administered ADV monotherapy. Patients underwent liver imaging. Serum DNA extracts were analyzed for HBV DNA levels, genotypes, and serology markers, and deep sequencing of the HBV P gene was performed.
RESULTS: ADV-resistant patients were found either with a single mutated locus, or with coexisting mutated loci. The most prevalent mutations were rtA181T, rtV214A, and rtN236T. Twenty-six patients had more than two mutated loci. The mutants were distributed among the patients without any significant affinity for gender, age, end-stage of liver disease, complications of non-alcoholic fatty liver disease, or HBV DNA levels. Patients with the rtA181T mutant were primarily infected with genotype C and e-antigen negative HBV, while patients with the rtN236T mutant were primarily infected by genotype B HBV (χ2 = 6.004, 7.159; P = 0.023, 0.007). The duration of treatment with ADV was shorter in the single mutant group compared with the multi-mutant group (t = 2.426, P = 0.018).
CONCLUSION: Drug-resistant HBV mutants are complex and diverse. Patients should receive the standard and first-line antiviral treatment, strictly comply with medication dosage, and avoid short-term withdrawal.
doi:10.3748/wjg.v20.i45.17100
PMCID: PMC4258578  PMID: 25493022
Hepatitis B virus; Adefovir dipivoxil; Drug-resistant mutant; Gene sequencing
25.  Use of Electrical Impedance Tomography to Monitor Regional Cerebral Edema during Clinical Dehydration Treatment 
PLoS ONE  2014;9(12):e113202.
Objective
Variations of conductive fluid content in brain tissue (e.g. cerebral edema) change tissue impedance and can potentially be measured by Electrical Impedance Tomography (EIT), an emerging medical imaging technique. The objective of this work is to establish the feasibility of using EIT as an imaging tool for monitoring brain fluid content.
Design
a prospective study.
Setting
In this study EIT was used, for the first time, to monitor variations in cerebral fluid content in a clinical model with patients undergoing clinical dehydration treatment. The EIT system was developed in house and its imaging sensitivity and spatial resolution were evaluated on a saline-filled tank.
Patients
23 patients with brain edema.
Interventions
The patients were continuously imaged by EIT for two hours after initiation of dehydration treatment using 0.5 g/kg intravenous infusion of mannitol for 20 minutes.
Measurement and Main Results
Overall impedance across the brain increased significantly before and after mannitol dehydration treatment (p = 0.0027). Of the all 23 patients, 14 showed high-level impedance increase and maintained this around 4 hours after the dehydration treatment whereas the other 9 also showed great impedance gain during the treatment but it gradually decreased after the treatment. Further analysis of the regions of interest in the EIT images revealed that diseased regions, identified on corresponding CT images, showed significantly less impedance changes than normal regions during the monitoring period, indicating variations in different patients' responses to such treatment.
Conclusions
EIT shows potential promise as an imaging tool for real-time and non-invasive monitoring of brain edema patients.
doi:10.1371/journal.pone.0113202
PMCID: PMC4256286  PMID: 25474474

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