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1.  Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma 
World Journal of Gastroenterology : WJG  2014;20(47):17883-17893.
AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma.
METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens.
RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, χ2 = 6.28) and EGC (P = 0.008, χ2 = 6.94).
CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.
doi:10.3748/wjg.v20.i47.17883
PMCID: PMC4273138  PMID: 25548486
Gastric early-stage adenocarcinoma; High-and low-grade intraepithelial neoplasia; G0/G1 switch 2; Whole genome expression microarray; Quantitative real-time PCR; Immunohistochemical staining
2.  Impact of Glutathione S-Transferase M1 and T1 on Anti-Tuberculosis Drug–Induced Hepatotoxicity in Chinese Pediatric Patients 
PLoS ONE  2014;9(12):e115410.
Background
Anti-tuberculosis drug induced hepatotoxicity (ATDH) is a major adverse drug reaction associated for anti-tuberculosis therapy. The glutathione S-transferases (GST) plays a crucial role in the detoxification of hepatotoxic metabolites of anti-tuberculosis drugs.An association between GSTM1/GSTT1 null mutations and increased risk of ATDH has been demonstrated in adults. Given the ethnic differences and developmental changes, our study aims to investigate the potential impacts of GSTM1/GSTT1genotypes on the development of ATDH in Han Chinese children treated with anti-tuberculosis therapy.
Methods
Children receiving anti-tuberculosis therapy with or without evidence of ATDH were considered as the cases or controls, respectively. The GSTM1 and GSTT1 genotyping were performed using the polymerase chain reaction.
Results
One hundred sixty-three children (20 cases and 143 controls) with a mean age of 4.7 years (range: 2 months-14.1 years) were included. For the GSTM1, 14 (70.0%) cases and 96 (67.1%) controls had homozygous null mutations. For the GSTT1, 13 (65.0%) cases and 97 (67.8%) controls had homozygous null mutations. Neither the GSTM1, nor the GSTT1 polymorphism was significantly correlated with the occurrence of ATHD.
Conclusion
Ourresults did not support the GSTM1 and GSTT1 polymorphisms as the predictors of ADTH in Chinese Han children treated with anti-tuberculosis drugs. An age-related association between pharmacogenetics and ATHD need to be confirmed in the further study.
doi:10.1371/journal.pone.0115410
PMCID: PMC4272297  PMID: 25525805
3.  A Reconstruction Method Based on AL0FGD for Compressed Sensing in Border Monitoring WSN System 
PLoS ONE  2014;9(12):e112932.
In this paper, to monitor the border in real-time with high efficiency and accuracy, we applied the compressed sensing (CS) technology on the border monitoring wireless sensor network (WSN) system and proposed a reconstruction method based on approximately l0 norm and fast gradient descent (AL0FGD) for CS. In the frontend of the system, the measurement matrix was used to sense the border information in a compressed manner, and then the proposed reconstruction method was applied to recover the border information at the monitoring terminal. To evaluate the performance of the proposed method, the helicopter sound signal was used as an example in the experimental simulation, and three other typical reconstruction algorithms 1)split Bregman algorithm, 2)iterative shrinkage algorithm, and 3)smoothed approximate l0 norm (SL0), were employed for comparison. The experimental results showed that the proposed method has a better performance in recovering the helicopter sound signal in most cases, which could be used as a basis for further study of the border monitoring WSN system.
doi:10.1371/journal.pone.0112932
PMCID: PMC4251983  PMID: 25461759
4.  Osteogenic fate of hypertrophic chondrocytes 
Cell Research  2014;24(10):1266-1269.
doi:10.1038/cr.2014.111
PMCID: PMC4185343  PMID: 25145361
5.  Toll-like receptor-4 pathway is required for the pathogenesis of human chronic endometritis 
Toll-like receptor (TLR) signal transduction is a central component of the primary innate immune response to pathogenic challenge. TLR4, a member of the TLR family, is highly expressed in the endometrial cells of the uterus and could thus be a key link between human chronic endometritis (CE) and the immune system. However, the exact biological function of TLR4 in human CE remains largely unexplored. The present study aimed to examine the role of TLR4 in human CE. A comprehensive expression and activation analysis of TLR4 in the endometrial cells of the uterus from patients with human CE (n=25) and normal endometrial (NE) tissue (n=15) was performed. Western blot analyses demonstrated that compared with NE, the protein expression TLR4 markedly increased in human CE. Endometrial tissue scrapings were also used for total RNA extraction and were transcribed and amplified by reverse transcription quantitative polymerase chain reaction. The results showed that significant upregulation of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and downregulation of IL-10 mRNA was observed in CE compared with the NE group. Furthermore, the protein of the signaling adapter myeloid differentiation factor-88 and the accessory molecules (TNF receptor associated factor 6 and transforming growth factor-β-activated kinase 1) were also detected in all the assayed tissues. Of note, differential expression (CE versus NE) was observed by immunoblotting at each level of the nuclear factor-κB signaling cascade, including inhibitor κBα and P65 (all P<0.05). The altered TLR4 and its corresponding downstream signaling molecules in CE cells may be of relevance for the progression of the human CE. These findings indicate that the evaluation of expression patterns of TLR4 holds promise for the treatment of human CE.
doi:10.3892/etm.2014.1990
PMCID: PMC4217777  PMID: 25371751
Toll-like receptor 4; chronic endometritis; inflammation; signaling pathway
6.  An intensity ratio of interlocking loops determines circadian period length 
Nucleic Acids Research  2014;42(16):10278-10287.
Circadian clocks allow organisms to orchestrate the daily rhythms in physiology and behaviors, and disruption of circadian rhythmicity can profoundly affect fitness. The mammalian circadian oscillator consists of a negative primary feedback loop and is associated with some ‘auxiliary’ loops. This raises the questions of how these interlocking loops coordinate to regulate the period and maintain its robustness. Here, we focused on the REV-ERBα/Cry1 auxiliary loop, consisting of Rev-Erbα/ROR-binding elements (RORE) mediated Cry1 transcription, coordinates with the negative primary feedback loop to modulate the mammalian circadian period. The silicon simulation revealed an unexpected rule: the intensity ratio of the primary loop to the auxiliary loop is inversely related to the period length, even when post-translational feedback is fixed. Then we measured the mRNA levels from two loops in 10-mutant mice and observed the similar monotonic relationship. Additionally, our simulation and the experimental results in human osteosarcoma cells suggest that a coupling effect between the numerator and denominator of this intensity ratio ensures the robustness of circadian period and, therefore, provides an efficient means of correcting circadian disorders. This ratio rule highlights the contribution of the transcriptional architecture to the period dynamics and might be helpful in the construction of synthetic oscillators.
doi:10.1093/nar/gku701
PMCID: PMC4176327  PMID: 25122753
7.  Management of lymph node metastases from an unknown primary site to the head and neck (Review) 
Molecular and Clinical Oncology  2014;2(6):917-922.
Cancer of unknown primary site (CUP) is an intriguing clinical phenomenon found in ~3–9% of all head and neck cancers. It has not yet been determined whether CUP forms a distinct biological entity with specific genetic and phenotypic characteristics, or whether it is the clinical presentation of metastasis in patients with an undetected primary tumor and no visible clinical signs. The treatment of patients with cervical lymph node metastases from CUP remains controversial, due to the lack of randomized clinical trials comparing different treatment options. Consequently, treatment is currently based on non-randomized data and institutional policy. In the present review, the range and limitations of diagnostic procedures are summarized and an optimal diagnostic work-up is recommended. The initial preferred diagnostic procedures include fine-needle aspiration biopsy (FNAB) and imaging. Although neck dissection followed by postoperative radiotherapy is the the most generally accepted approach, other curative options may be used in certain patients, such as neck dissection alone, nodal excision followed by postoperative radiotherapy, or radiotherapy alone. There remains controversy regarding target radiation volumes, ranging from ipsilateral neck irradiation to prophylactic irradiation of all the potential mucosal sites and both sides of the neck. When no primary lesion is identified with imaging and endoscopy in patients without history of smoking and alcohol abuse, molecular profiling of an FNAB sample for human papillomavirus and/or Epstein-Barr virus is required.
doi:10.3892/mco.2014.361
PMCID: PMC4179835  PMID: 25279174
cervical lymph node metastases; unknown primary tumor; squamous cell carcinoma; diagnostics; treatment
8.  Sulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation 
Cell  2013;154(2):416-429.
SUMMARY
Protein translation is an energetically demanding process that must be regulated in response to changes in nutrient availability. Herein, we report that the thiolation status of wobble-uridine (U34) nucleotides present on lysine, glutamine or glutamate tRNAs reflects intracellular methionine and cysteine availability, and regulates cellular translational capacity and metabolic homeostasis. tRNA thiolation is important for growth under nutritionally challenging environments and required for efficient translation of genes enriched in lysine, glutamine, and glutamate codons, which frequently encode proteins important for translation and growth-specific processes. tRNA thiolation is down-regulated during sulfur starvation in order to decrease sulfur consumption and growth, and its absence leads to a compensatory increase in enzymes involved in methionine, cysteine, and lysine biosynthesis. Thus, tRNA thiolation enables cells to modulate translational capacity according to the availability of sulfur amino acids, establishing a functional significance for this conserved tRNA nucleotide modification in cell growth control.
doi:10.1016/j.cell.2013.06.043
PMCID: PMC3757545  PMID: 23870129
9.  Methionine Inhibits Autophagy and Promotes Growth by Inducing the SAM-Responsive Methylation of PP2A 
Cell  2013;154(2):403-415.
Summary
Autophagy is a process of cellular self-digestion induced by various forms of starvation. The mechanisms by which metabolic deficiencies are sensed by a cell to regulate autophagy remain unclear. While nitrogen deficit is a common trigger, yeast cells induce autophagy upon switch from a rich to minimal media without nitrogen starvation. We show that the amino acid methionine is sufficient to inhibit such non-nitrogen starvation (NNS)-induced autophagy. Methionine boosts synthesis of the methyl donor, S-adenosylmethionine (SAM). SAM inhibits autophagy and promotes growth through the action of the methyltransferase Ppm1p, which methylates the catalytic subunit of PP2A in tune with SAM levels. Methylated PP2A promotes dephosphorylation of Npr2p, a component of a conserved complex that regulates NNS-autophagy and other growth-related processes. Thus, methionine and SAM levels represent a critical gauge of amino acid availability that is sensed via this distinctive methylation modification of PP2A to reciprocally regulate cell growth and autophagy.
doi:10.1016/j.cell.2013.06.041
PMCID: PMC3774293  PMID: 23870128
10.  Effects of dimethyl sulfoxide on asymmetric division and cytokinesis in mouse oocytes 
Background
Dimethyl sulfoxide (DMSO) is used extensively as a permeable cryoprotectant and is a common solvent utilized for several water-insoluble substances. DMSO has various biological and pharmacological activities; however, the effect of DMSO on mouse oocyte meiotic maturation remains unknown.
Results
In DMSO-treated oocytes, we observed abnormal MII oocytes that contained large polar bodies, including 2-cell–like MII oocytes, during in vitro maturation. Oocyte polarization did not occur, due to the absence of actin cap formation and spindle migration. These features are among the primary causes of abnormal symmetric division; however, analysis of the mRNA expression levels of genes related to asymmetric division revealed no significant difference in the expression of these factors between the 3% DMSO-treated group and the control group. After each “blastomere” of the 2-cell–like MII stage oocytes was injected by one sperm head respectively, the oocytes still possessed the ability to extrude the second polar body from each “blastomere” and to begin cleavage. However, MII oocytes with large polar bodies developed to the blastocyst stage after intracytoplasmic sperm injection (ICSI). Furthermore, other permeable cryoprotectants, such as ethylene glycol and glycerol, also caused asymmetric division failure.
Conclusion
Permeable cryoprotectants, such as DMSO, ethylene glycol, and glycerol, affect asymmetric division. DMSO disrupts cytokinesis completion by inhibiting cortical reorganization and polarization. Oocytes that undergo symmetric division maintain the ability to begin cleavage after ICSI.
doi:10.1186/1471-213X-14-28
PMCID: PMC4074394  PMID: 24953160
Dimethyl sulfoxide (DMSO); Asymmetric division; Actin cap; Spindle migration; Oocyte maturation
11.  Evaluation and improvement of doctor–patient communication competence for emergency neurosurgeons: a standardized family model 
Disease treatments have been significantly influenced by the communications between patients, their families, and doctors the lack of which may lead to malpractice allegations and complaints. In particular, inadequate communication may delay diagnosis and treatment. Therefore, for doctors communication and interpersonal skills, are as important as clinical skills and medical knowledge. In this study we intended to develop two detailed communication content checklists and a modified interpersonal skills inventory, aiming to evaluate their integrity in the midst of communication skills assessments, to provide feedback for some participants, and to observe their communication competence in both aspects
doi:10.2147/PPA.S45488
PMCID: PMC4074176  PMID: 25018623
standardized patient; communication skill; training; medical education; neurosurgeon
12.  Non-local mean denoising in diffusion tensor space 
The aim of the present study was to present a novel non-local mean (NLM) method to denoise diffusion tensor imaging (DTI) data in the tensor space. Compared with the original NLM method, which uses intensity similarity to weigh the voxel, the proposed method weighs the voxel using tensor similarity measures in the diffusion tensor space. Euclidean distance with rotational invariance, and Riemannian distance and Log-Euclidean distance with affine invariance were implemented to compare the geometric and orientation features of the diffusion tensor comprehensively. The accuracy and efficacy of the proposed novel NLM method using these three similarity measures in DTI space, along with unbiased novel NLM in diffusion-weighted image space, were compared quantitatively and qualitatively in the present study.
doi:10.3892/etm.2014.1764
PMCID: PMC4079421  PMID: 25009599
diffusion tensor imaging; denoising; non-local mean
13.  Effectiveness Study of Moxibustion on Pain Relief in Primary Dysmenorrhea: Study Protocol of a Randomized Controlled Trial 
Dysmenorrhea is a prevalent problem in menstruating women. As a nonpharmacologic and free of relevant side effects intervention, moxibustion is considered as a safe treatment and has long been recommended for dysmenorrhea in China. However, the exact effects of moxibustion in PD have not been fully understood. Therefore we designed this random clinical trial aiming to (1) investigate whether moxibustion is safe and effective for pain relief in primary dysmenorrhea when compared to conventional pain-killers and (2) assess the acceptability and side effects associated with moxibustion. The results of this trial will contribute to a better understanding of the different effects of moxibustion in pain relief in primary dysmenorrhea when compared to conventional pharmacologic pain treatment.
doi:10.1155/2014/434978
PMCID: PMC3996889  PMID: 24803947
14.  ALOX5 Is Associated with Tuberculosis in a Subset of the Pediatric Population of North China 
Background: Genetic factors are involved in the etiology of Mycobacterium tuberculosis infection. Recently, ALOX5 has been identified as a candidate gene for tuberculosis (TB) susceptibility. We investigated whether an association between ALOX5 and TB exists in a Chinese pediatric population from northern China. Methods: We conducted a case–control study comprising 488 individuals aged 2 months to 17 years by genotyping 18 tag-single-nucleotide polymorphisms (SNPs) from the ALOX5 gene. The tag-SNPs were selected from the international HapMap project. An Illumina BeadXpress Scanner was utilized for genotyping, supported by the high-density BeadArray technology in combination with an allele-specific extension, adapter ligation, and amplification assay. Statistical analyses were performed to determine correlations between genetic variation and disease. Results: Our study is the first to show that ALOX5 is associated with susceptibility to pediatric TB in a subset of children in northern China. The rs2115819 T allele of ALOX5 presents a risk factor for childhood TB disease.
doi:10.1089/gtmb.2012.0426
PMCID: PMC3609609  PMID: 23448388
15.  A 3'UTR Polymorphism of IL-6R Is Associated with Chinese Pediatric Tuberculosis 
BioMed Research International  2014;2014:483759.
Background. IL-6 is a proinflammatory cytokine that plays a critical role in host defense against tuberculosis (TB). Genetic polymorphisms of IL-6 and its receptor IL-6R had been discussed in adult TB recently. However, their role in pediatric TB is still unclear. Due to the obvious differences in TB pathophysiology in children, which may also reflect differences in genetic background, further association studies in pediatric populations are needed. Methods. A case-control study was carried out in a Chinese pediatric population including 353 TB patients and 400 healthy controls. Tag-SNPs of IL-6 and IL-6R genes were selected by Haploview software, genotyped using MassArray, and analyzed statistically. Results. One polymorphism, rs2229238, in the 3'UTR region of IL-6R was observed to be associated with increased resistance to TB (adjusted P = 0.03). The rs2229238 T allele contributed to a reduced risk to TB in recessive heritable model (OR, 0.53; 95% CI, 0.35–0.78). Conclusions. By tag-SNP genotyping based case-control study, we identified a genetic polymorphism in the IL-6R 3'UTR that regulates host resistance to pediatric TB in a Chinese population.
doi:10.1155/2014/483759
PMCID: PMC3977562  PMID: 24772425
16.  Efficacy and Safety Profile of Combining Sorafenib with Chemotherapy in Patients with HER2-Negative Advanced Breast Cancer: A Meta-analysis 
Journal of Breast Cancer  2014;17(1):61-68.
Purpose
The aim of the study was to evaluate the efficacy and safety of combining sorafenib with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer.
Methods
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, American Society for Clinical Oncology abstracts, and European Society for Medical Oncology abstracts were searched. Randomized clinical trials that compared the efficacy and safety of sorafenib plus chemotherapy in patients with HER2-negative advanced breast cancer with placebo plus chemotherapy were eligible. The endpoints were progression-free survival (PFS), overall survival (OS), time to progression (TTP), duration of response (DOR), overall response rate (ORR), clinical benefits, and adverse effects. The meta-analysis was performed using Review Manager 5.2.6 (The Nordic Cochrane Centre), and the fixed-effect model weighted by the Mantel-Haenszel method was used. When considerable heterogeneity was found (p<0.1), further analysis (subgroup analysis, sensitivity analysis, or random-effect model) was performed to identify the potential cause. The results are expressed as hazard ratios or risk ratios, with their corresponding 95% confidence intervals.
Results
The final analysis included four trials comprising 844 patients. The results revealed longer PFS and TTP, and higher ORR and clinical benefit rates in patients receiving sorafenib combined with chemotherapy compared to those receiving chemotherapy and placebo. OS and DOR were similar in the two groups. Meanwhile, the incidence of some adverse effects, including hand-foot skin reaction/hand-foot syndrome, diarrhea, rash, and hypertension, were significantly higher in the sorafenib arm.
Conclusion
Sorafenib combined with chemotherapy may prolong PFS and TTP. This treatment was associated with manageable toxicities, but frequent dose interruptions and reductions were required.
doi:10.4048/jbc.2014.17.1.61
PMCID: PMC3988344  PMID: 24744799
Breast neoplasms; Meta-analysis; Sorafenib; Treatment outcome
17.  Genome-wide association study in Han Chinese identifies four new susceptibility loci for coronary artery disease 
Nature genetics  2012;44(8):890-894.
We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases with coronary artery disease and 5,019 controls, followed by de novo replication studies in 15,460 cases and 11,472 controls, all of Chinese Han descent. We successfully identified four new loci for coronary artery disease reaching genome-wide significance (P < 5 × 10−8), which mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (PHACTR1, TCF21, CDKN2A/B and C12orf51). These findings provide new insights into biological pathways for the susceptibility of coronary artery disease in Chinese Han population.
doi:10.1038/ng.2337
PMCID: PMC3927410  PMID: 22751097
18.  Internet-based health education in China: a content analysis of websites 
BMC Medical Education  2014;14:16.
Background
The Internet is increasingly being applied in health education worldwide; however there is little knowledge of its use in Chinese higher education institutions. The present study provides the first review and highlights the deficiencies and required future advances in Chinese Internet-based health education.
Methods
Two authors independently conducted a duplicate Internet search in order to identify information regarding Internet-based health education in China.
Results
The findings showed that Internet-based education began in China in September 1998. Currently, only 16 of 150 (10.7%) health education institutions in China offer fee-based online undergraduate degree courses, awarding associates and/or bachelors degrees. Fifteen of the 16 institutions were located in the middle or on the eastern coast of China, where were more developed than other regions. Nursing was the most popular discipline in Internet-based health education, while some other disciplines, such as preventive medicine, were only offered at one university. Besides degree education, Chinese institutions also offered non-degree online training and free resources. The content was mainly presented in the form of PowerPoint slides or videos for self-learning. Very little online interactive mentoring was offered with any of the courses.
Conclusions
There is considerable potential for the further development of Internet-based health education in China. These developments should include a focus on strengthening cooperation among higher education institutions in order to develop balanced online health curricula, and on enhancing distance education in low- and middle-income regions to meet extensive learning demands.
doi:10.1186/1472-6920-14-16
PMCID: PMC3910239  PMID: 24467710
19.  Age-related bone turnover markers and osteoporotic risk in native Chinese women 
Background
The rate of bone turnover is closely related to osteoporosis risk. We investigated the correlation between bone turnover markers and BMD at various skeletal sites in healthy native Chinese women, and to study the effect of changes in the levels of bone turnover markers on the risk of osteoporosis.
Methods
A cross-section study of 891 healthy Chinese women aged 20–80 years was conducted. The levels of serum osteocalcin (OC), bone-specific alkaline phosphatase (BAP), serum cross-linked N-terminal telopeptides of type I collagen (sNTX), cross-linked C-terminal telopeptides of type I collagen (sCTX), urinary NTX (uNTX), urinary CTX (uCTX) and total urinary deoxypyridinoline (uDPD) were determined. BMD at the posteroanterior spine and the hip was measured using DXA.
Results
Pearson’s correlation coefficient found significant negative correlation between bone turnover marker and BMD T-score at different skeletal sites (r = −0.08 to −0.52, all P = 0.038–0.000). After adjustments for age and body mass index, the partial correlation coefficients between the OC, BAP, sNTX, sCTX and uCTX, and the T-scores at various skeletal sites were still significant. After adjustment of height and weight, the correlation coefficients between most BTMs and PA lumbar spine BMD were also significant. Multiple linear regression analysis showed that bone turnover markers were negative determinants of T-scores. BAP and OC accounted for 33.1% and 7.8% of the variations in the T-scores of the PA spine, respectively. Serum OC, BAP, uDPD, and sNTX accounted for 0.4–21.9% of the variations in the femoral neck and total hip T-scores. The bone turnover marker levels were grouped as per quartile intervals, and the T-scores, osteoporosis prevalence and risk were found to markedly and increase with increase in bone turnover marker levels.
Conclusions
This study clarified the relationship between bone turnover markers and osteoporosis risk in native Chinese women. Bone turnover marker levels were found to be important determinants of BMD T-scores. Furthermore, osteoporotic risk significantly increased with increase in the levels of bone turnover markers.
doi:10.1186/1472-6823-14-8
PMCID: PMC3974151  PMID: 24447701
Bone turnover markers; BMD T-scores; Osteoporosis; Osteoporotic risk; Native Chinese women
20.  InterRett, a model for international data collection in a rare genetic disorder 
Research in autism spectrum disorders  2009;3(3):10.1016/j.rasd.2008.12.004.
Rett syndrome (RTT) is a rare genetic disorder within the autistic spectrum. This study compared socio-demographic, clinical and genetic characteristics of the international database, InterRett, and the population based Australian Rett syndrome database (ARSD). It also explored the strengths and limitations of InterRett in comparison with other studies. A literature review compared InterRett with RTT population-based and case-based studies of thirty or more cases that investigated genotype and/or phenotype relationships. Questionnaire data were used to determine case status and to investigate the comparability of InterRett and ARSD. Twenty four case series, five population based studies and a MECP2 mutation database were identified of which twenty one (70%) collected phenotype and genotype data. Only three studies were representative of their underlying case population and many had low numbers. Of one thousand one hundred and fourteen InterRett subjects, nine hundred and thirty five born after 1976 could be verified as Rett cases and compared with the two hundred and ninety five ARSD subjects. Although more InterRett families had higher education and occupation levels and their children were marginally less severe, the distribution of MECP2 mutation types was similar. The InterRett can be used with confidence to investigate genotype phenotype associations and clinical variation in RTT and provides an exemplary international model for other rare disorders.
doi:10.1016/j.rasd.2008.12.004
PMCID: PMC3858578  PMID: 24348750
Rett syndrome; international database; rare disorder; MECP2; phenotype
21.  DNA aptamers that target human glioblastoma multiforme cells overexpressing epidermal growth factor receptor variant III in vitro 
Acta Pharmacologica Sinica  2013;34(12):1491-1498.
Aim:
Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule in cells, thus may act as effective vehicles for drug or siRNA delivery. In this study we investigated the DNA aptamers that target human glioblastoma multiforme (GBM) cells overexpressing epidermal growth factor receptor variant III (EGFRvIII), which was linked to radiation and chemotherapeutic resistance of this most aggressive brain tumor.
Methods:
A 73-mer ssDNA library containing molecules with 30 nt of random sequence flanked by two primer hybridization sites was chosen as the initial library. Cell systematic evolution of ligands by exponential enrichment (Cell-SELEX) method was used to select the DNA aptamers that target EGFRvIII. The binding affinity of the aptamers was measured using a cell-based biotin-avidin ELISA.
Results:
After 14 rounds of selection, four DNA aptamers (32, 41, 43, and 47) that specifically bound to the EGFRvIII-overexpressing human glioma U87Δ cells with Kd values of less than 100 nmol/L were discovered. These aptamers were able to distinguish the U87Δ cells from the negative control human glioma U87MG cells and HEK293 cells. Aptamer 32 specifically bound to the EGFRvIII protein with an affinity similar to the EGFR antibody (Kd values of aptamer 32 and the EGFR antibody were 0.62±0.04 and 0.32±0.01 nmol/L, respectively), and this aptamer was localized in the cell nucleus.
Conclusion:
The DNA aptamers are promising molecular probes for the diagnosis and treatment of GBM.
doi:10.1038/aps.2013.137
PMCID: PMC4002567  PMID: 24304919
DNA aptamer; drug delivery; brain tumor; glioblastoma multiforme; epidermal growth factor receptor variant III; cell systematic evolution of ligands by exponential enrichment
22.  Microdeletion and Microduplication Analysis of Chinese Conotruncal Defects Patients with Targeted Array Comparative Genomic Hybridization 
PLoS ONE  2013;8(10):e76314.
Objective
The current study aimed to develop a reliable targeted array comparative genomic hybridization (aCGH) to detect microdeletions and microduplications in congenital conotruncal defects (CTDs), especially on 22q11.2 region, and for some other chromosomal aberrations, such as 5p15-5p, 7q11.23 and 4p16.3.
Methods
Twenty-seven patients with CTDs, including 12 pulmonary atresia (PA), 10 double-outlet right ventricle (DORV), 3 transposition of great arteries (TGA), 1 tetralogy of Fallot (TOF) and one ventricular septal defect (VSD), were enrolled in this study and screened for pathogenic copy number variations (CNVs), using Agilent 8 x 15K targeted aCGH. Real-time quantitative polymerase chain reaction (qPCR) was performed to test the molecular results of targeted aCGH.
Results
Four of 27 patients (14.8%) had 22q11.2 CNVs, 1 microdeletion and 3 microduplications. qPCR test confirmed the microdeletion and microduplication detected by the targeted aCGH.
Conclusion
Chromosomal abnormalities were a well-known cause of multiple congenital anomalies (MCA). This aCGH using arrays with high-density coverage in the targeted regions can detect genomic imbalances including 22q11.2 and other 10 kinds CNVs effectively and quickly. This approach has the potential to be applied to detect aneuploidy and common microdeletion/microduplication syndromes on a single microarray.
doi:10.1371/journal.pone.0076314
PMCID: PMC3788710  PMID: 24098474
23.  A Systematically Combined Genotype and Functional Combination Analysis of CYP2E1, CYP2D6, CYP2C9, CYP2C19 in Different Geographic Areas of Mainland China – A Basis for Personalized Therapy 
PLoS ONE  2013;8(10):e71934.
The cytochrome P450 is the major enzyme involved in drug metabolism. Single CYP genotypes and metabolic phenotypes have been widely studied, but no combination analysis has been conducted in the context of specific populations and geographical areas. This study is the first to systematically analyze the combined genotypes and functional combinations of 400 samples of major CYP genes—CYP2E1, CYP2D6, CYP2C9, and CYP2C19 in four geographical areas of mainland China. 167 different genotype combinations were identified, of which 25 had a greater than 1% frequency in the Chinese Han population. In addition, phenotypes of the four genes for each sample were in line with the predictions of previous studies of the four geographical areas. On the basis of the genotype classification, we were able to produce a systemic functional combinations analysis for the population. 25 of the combinations detected had at least two non-wild phenotypes and four showed a frequency above 1%. A bioinformatics analysis of the relationship between particular drugs and multi-genes was conducted. This is the first systematic study to analyze genotype combinations and functional combinations across whole Chinese population and could make a significant contribution in the field of personalized medicine and therapy.
doi:10.1371/journal.pone.0071934
PMCID: PMC3788764  PMID: 24098323
24.  Thermostable Alcohol Dehydrogenase from Thermococcus kodakarensis KOD1 for Enantioselective Bioconversion of Aromatic Secondary Alcohols 
A novel thermostable alcohol dehydrogenase (ADH) showing activity toward aromatic secondary alcohols was identified from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1 (TkADH). The gene, tk0845, which encodes an aldo-keto reductase, was heterologously expressed in Escherichia coli. The enzyme was found to be a monomer with a molecular mass of 31 kDa. It was highly thermostable with an optimal temperature of 90°C and a half-life of 4.5 h at 95°C. The apparent Km values for the cofactors NAD(P)+ and NADPH were similar within a range of 66 to 127 μM. TkADH preferred secondary alcohols and accepted various ketones and aldehydes as substrates. Interestingly, the enzyme could oxidize 1-phenylethanol and its derivatives having substituents at the meta and para positions with high enantioselectivity, yielding the corresponding (R)-alcohols with optical purities of greater than 99.8% enantiomeric excess (ee). TkADH could also reduce 2,2,2-trifluoroacetophenone to (R)-2,2,2-trifluoro-1-phenylethanol with high enantioselectivity (>99.6% ee). Furthermore, the enzyme showed high resistance to organic solvents and was particularly highly active in the presence of H2O–20% 2-propanol and H2O–50% n-hexane or n-octane. This ADH is expected to be a useful tool for the production of aromatic chiral alcohols.
doi:10.1128/AEM.03873-12
PMCID: PMC3623261  PMID: 23354700
25.  Management of traumatic hemipelvectomy: an institutional experience on four consecutive cases 
Background and objective
The incidence of traumatic hemipelvectomy is rare, but it is a devastating injury. Recently, an increasing number of patients with traumatic hemipelvectomy are admitted to trauma centers alive due to improvements of the pre-hospital care. Successful management requires prompt recognition of the nature of this injury and meticulous surgical technique. We present our successful experiences on four cases of traumatic hemipelvectomy in the past nine years.
Patients and methods
Four cases with traumatic hemipelvectomy were admited to our hospital from June 21, 2002 to September 3, 2011. All injuries occurred due to vehicle accident and all patients were in a state of severe hypotension, with two of them having anal lacerations. These four cases were treated immediately with resuscitation, control of hemorrhage, early amputation, repeated debridement and closure of the wounds. An angiographic embolization was given to control hemorrhage in two of the cases preoperatively. One case underwent fecal diversion. Wound infection occurred in all of cases which was successfully controlled by repeated debridements, effective anti-biotic regimen, split-thickness skin grafts.
Results
All four cases were saved successfully with well-healed wounds during follow up from 1 to 7 years. They were able to walk by themself using crutches.
Conclusion
Adhering to the surgery principles of damage control including appropriate resuscitation, hemorrhage control, coagulopathy correction and multiple debridements and closure of the wounds in reasonable period of time can save the life of cases suffering from severe pelvic ring injury.
doi:10.1186/1757-7241-21-64
PMCID: PMC3765128  PMID: 23953033
Trauma; Hemipelvectomy; Damage control

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