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1.  Effects of transcutaneous electrical nerve stimulation on pain in patients with spinal cord injury: a randomized controlled trial 
[Purpose] To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on pain in patients with spinal cord injury. [Subjects and Methods] Fifty-two spinal cord injury patients with central pain were randomly allocated into two groups TENS and control with 26 subjects per group. The patients in TENS and control groups were treated with TENS and sham TENS for 20 min (three times a week) for 12 consecutive weeks, respectively. The two group’s pain was assessed using visual analog scale (VAS) and the McGill Pain Questionnaire (including pain rating index-total, pain rating index-affective, pain rating index-sensory, present pain intensity, and number of words chosen) before and after the treatment. [Results] After the intervention, we found significant differences in VAS, pain rating index-total, pain rating index-affective, pain rating index-sensory, present pain intensity, and number of words chosen between the TENS group and the control group. [Conclusion] Our results suggest that TENS effectively decreases pain in patients with spinal cord injury.
doi:10.1589/jpts.27.23
PMCID: PMC4305569  PMID: 25642029
Transcutaneous electrical nerve stimulation; Pain; Spinal cord injury
2.  Seizure Control of Current Shunt on Rats with Temporal Lobe Epilepsy and Neocortical Epilepsy 
PLoS ONE  2014;9(1):e86477.
Purpose
To examine the effects of current shunt on rats with temporal lobe epilepsy and neocortex epilepsy.
Experimental Design
A kainic acid (KA)-induced model of temporal lobe seizure and a penicillin-induced model of neocortical partial seizure were used in this study. Rats of each model were randomly allocated into two groups: control and model groups. The model group was further divided into the KA or penicillin group, sham conduction group and conduction group. The current shunt was realized through the implantation of a customized conduction electrode. After surgery, electroencephalogram (EEG) was recorded for two hours for each rat under anesthesia. Subsequently, the rats were video monitored for 72 h to detect the occurrence of behavioral seizures upon awakening. The average number and duration of seizures on EEG and the number of behavioral seizures were measured.
Results
In KA model, the number of total EEG seizures in conduction group (9.57±2.46) was significantly less than that in sham conduction group (15.13±3.45) (p<0.01). The duration of EEG seizures in conduction group (26.13±7.81 s) was significantly shorter than that in sham conduction group (34.17±7.25 s) (p = 0.001). A significant reduction of behavioral seizures was observed in the conduction group compared with KA (p = 0.000) and sham conduction groups (p = 0.000). In penicillin model, there was a 61% reduction in total EEG seizures in conduction group compared with sham conduction group (p<0.01), and the duration of EEG seizures in conduction group (6.29±2.64 s) was significantly shorter than that in the sham conduction group (12.07±3.81 s) (p = 0.002). A significant reduction of behavioral seizures was observed in conduction group compared with penicillin (p<0.01) and sham conduction groups (p<0.01).
Conclusion
Current shunt effectively reduces the onset and severity of seizures. Current shunt therapy could be an effective alternative minimally invasive approach for temporal lobe epilepsy and neocortex epilepsy.
doi:10.1371/journal.pone.0086477
PMCID: PMC3907408  PMID: 24497949
3.  In-Situ Formation of Cobalt-Phosphate Oxygen-Evolving Complex-Anchored Reduced Graphene Oxide Nanosheets for Oxygen Reduction Reaction 
Scientific Reports  2013;3:2263.
Oxygen conversion process between O2 and H2O by means of electrochemistry or photochemistry has lately received a great deal of attention. Cobalt-phosphate (Co-Pi) catalyst is a new type of cost-effective artificial oxygen-evolving complex (OEC) with amorphous features during photosynthesis. However, can such Co-Pi OEC also act as oxygen reduction reaction (ORR) catalyst in electrochemical processes? The question remains unanswered. Here for the first time we demonstrate that Co-Pi OEC does be rather active for the ORR. Particularly, Co-Pi OEC anchoring on reduced graphite oxide (rGO) nanosheet is shown to possess dramatically improved electrocatalytic activities. Differing from the generally accepted role of rGO as an “electron reservoir”, we suggest that rGO serves as “peroxide cleaner” in enhancing the electrocatalytic behaviors. The present study may bridge the gap between photochemistry and electrochemistry towards oxygen conversion.
doi:10.1038/srep02263
PMCID: PMC3719074  PMID: 23877331
4.  HPV genotypes in paraffin sections of non-cervical squamous cell carcinoma in Qingdao of China 
Oncology Letters  2013;5(4):1219-1222.
Human papillomaviruses (HPVs) are the cause of cervical cancer and possibly a subset of squamous cell carcinomas (SCCs) in other sites. However, the prevalence and distribution of HPV subtypes remain unclear. In the present study, we collected and analyzed 511 paraffin sections of non-cervical SCC from patients in Qingdao, China, for the presence of HPV using polymerase chain reaction (PCR). We identified that 55.77% (285/511) of the samples were positive for HPV infection. There was a significant association between HPV type and the different sites of SCC. An association between HPV-positive cases and tobacco, alcohol, age and tumor differentiation was demonstrated. The information provided by this study may be important for further investigation into the association between HPV and SCC. High-risk HPV subtypes were associated with the malignant degree of SCC. This study provided a theoretical basis for the preventative treatment of non-cervical SCC using HPV vaccines.
doi:10.3892/ol.2013.1181
PMCID: PMC3629125  PMID: 23599766
squamous cell carcinomas; human papillomavirus genotype; polymerase chain reaction
5.  Association between paraoxonase gene and stroke in the Han Chinese population 
BMC Medical Genetics  2013;14:16.
Background
The human paraoxonase (PON) gene family has three isoforms: PON1, PON2 and PON3. These genes are implicated as potential risk factors of cerebrovascular disease and can prevent oxidative modification of low-density lipoproteins and atherosclerosis. This study evaluated the association between the genetic variants of all three PON genes and the risks of total stroke, ischemic stroke and hemorrhagic stroke in the Han Chinese population.
Methods
A total of 1016 subjects were recruited, including 508 healthy controls and 498 patients (328 with ischemic stroke and 170 with hemorrhagic stroke). A total of 11 single nucleotide polymorphisms (SNPs) covering the PON genes were genotyped for statistical analysis. Two of the 11 SNPs (rs662 and rs854560) were contextualized in a meta-analysis of ischemic stroke.
Results
The presence of rs705381 (−162) in the promoter region of PON1 was significantly associated with total stroke (Padjusted = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (Padjusted = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke. There was also a nominal association between rs854571 (−824) and total stroke. Meta-analysis demonstrated a significant nominal association between rs662 and ischemic stroke, but there was no evidence of an association between rs662 and ischemic stroke risk in a single site association study.
Conclusions
These findings indicate that polymorphisms of PON1 gene may be a risk factor of stroke.
doi:10.1186/1471-2350-14-16
PMCID: PMC3562169  PMID: 23356507
Polymorphisms; Paraoxanase gene; Hemorrhagic stroke; Ischemic stroke; Association
6.  Comparative genomic study of gastric epithelial cells co-cultured with Helicobacter pylori 
AIM: To identify genes potentially involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis.
METHODS: GES-1 cells were co-cultured with H. pylori strains isolated from patients with gastric carcinoma (GC, n = 10) or chronic gastritis (CG, n = 10) for in vitro proliferation and apoptosis assays to identify the most and least virulent strains. These two strains were cagA-genotyped and used for further in vivo carcinogenic virulence assays by infecting Mongolian gerbils for 52 wk, respectively; a broth free of H. pylori was lavaged as control. Genomic profiles of GES-1 cells co-cultured with the most and least virulent strains were determined by microarray analysis. The most differentially expressed genes were further verified using quantitative real-time polymerase chain reaction in GES-1 cells infected with the most and least virulent strains, and by immunohistochemistry in H. pylori positive CG, precancerous diseases, and GC biopsy specimens in an independent experiment.
RESULTS: GC-derived H. pylori strains induced a potent proliferative effect in GES-1 cells in co-culture, whereas CG-derived strains did not. The most (from a GC patient) and least (from a CG patient) virulent strains were cagA-positive and negative, respectively. At week 52, CG, atrophy, metaplasia, dysplasia, and GC were observed in 90.0%, 80.0%, 80.0%, 90%, and 60.0%, respectively, of the animals lavaged with the most virulent strain. However, only mild CG was observed in 90% of the animals lavaged with the least virulent strain. On microarray analysis, 800 differentially expressed genes (49 up- and 751 down-regulated), involving those associated with cell cycle regulation, cell apoptosis, cytoskeleton, immune response, and substance and energy metabolisms, were identified in cells co-cultured with the most virulent strain as compared with those co-cultured with the least virulent strain. The six most differentially expressed genes (with a betweenness centrality of 0.1-0.2) were identified among the significant differential gene profile network, including JUN, KRAS, BRCA1, SMAD2, TRAF1, and HDAC6. Quantitative real-time polymerase chain reaction analyses verified that HDAC6 and TRFA1 mRNA expressions were significantly more up-regulated in GES-1 cells co-cultured with the most virulent strain than in those co-cultured with the least virulent strain. Immunohistochemistry of gastric mucosal specimens from H. pylori-positive patients with CG, intestinal metaplasia (IM), dysplasia, and GC showed that moderately positive and strongly positive HDAC6 expression was detected in 21.7% of CG patients, 30.0% of IM patients, 54.5% of dysplasia patients, and 77.8% of GC patients (P < 0.001). The up-regulation of TRAF1 expressions was detected in 34.8%, 53.3%, 72.7%, and 88.9% specimens of CG, IM, dysplasia, and GC, respectively (P < 0.001).
CONCLUSION: The overexpression of HDAC6 and TRAF1 in GES-1 cells co-cultured with the GC-derived strain and in H. pylori-positive dysplasia and GC suggests that HDAC6 and TRAF1 may be involved in H. pylori-induced gastric carcinogenesis.
doi:10.3748/wjg.v18.i48.7212
PMCID: PMC3544023  PMID: 23326126
Helicobacter pylori; Gastric carcinoma; Proliferation; Genomic profiles
7.  Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma 
Oncology Letters  2012;4(6):1321-1324.
Low-grade glioma is predisposed to progress to anaplastic astrocytoma and eventually secondary glioblastoma. The malignant transformation may involve the accumulation of multiple genetic alterations. The purpose of this study was to explore the role of miR-544 in glioma progression and discuss whether it may be a novel biomarker of malignant transformation. The expression of miR-544 was measured in a series of 198 glioma samples (63 low-grade glioma, 44 anaplastic astrocytoma and 91 glioblastoma tumors) using microarrays. Quantitative real-time reverse transcription PCR (qRT-PCR) was used to validate the expression levels of miR-544 in tissue and serum samples in an independent validated cohort (25 low-grade glioma, 21 anaplastic astrocytoma and 20 glioblastoma tumors). A Pearson correlation analysis was performed to examine the correlation between miR-544 levels of tissue and serum samples. Microarrays revealed that the expression levels of miR-544 decreased significantly in anaplastic gliomas (P<0.01) or glioblastoma (P<0.01) compared with low-grade gliomas. In an independent cohort of glioma patients, miR-544 exhibited a progression-associated downregulation in glioma tumors. The levels of miR-544 in serum samples tended to be lower in anaplastic and glioblastoma patients compared with low-grade gliomas, but with no significant difference. The Pearson correlation analysis revealed a weakly positive correlation between tissue and serum levels of miR-544. These data support a significant role for miR-544 aberration in the malignant transformation of glioma. The downregulation of miR-544 in tissue may be used as a novel biomarker.
doi:10.3892/ol.2012.918
PMCID: PMC3506745  PMID: 23205130
miR-544; glioma; malignant transformation
8.  Upregulation of miR-196b Confers a Poor Prognosis in Glioblastoma Patients via Inducing a Proliferative Phenotype 
PLoS ONE  2012;7(6):e38096.
Purpose
To explore the expression pattern, prognostic value and functional role of miR-196b in glioblastoma (GBM) patients using large cohorts.
Experimental Design
MiR-196b expression was measured using the Human v2.0 miRNA Expression BeadChip (Illumina) in 198 frozen glioma tissues. The expression levels of miR-196b were also validated in an independent cohort containing 128 formalin-fixed paraffin-embedded (FFPE) glioma samples using qRT-PCR. The presence of other molecular prognostic indicators was assessed centrally in the glioma samples. Whole genome gene profiling was performed to investigate the underlying biological behavior. MiR-196b functional analyses were performed in U87 and U251 cell lines.
Results
The expression levels of miR-196b were inversely correlated with overall survival in GBM patients. Gene set enrichment analysis (GSEA) showed that the gene sets relating to cell cycle were significantly enriched in the cases with miR-196b overexpression. Functional analyses in U87 and U251 cells revealed that miR-196b was involved in cell proliferation.
Conclusions
MiR-196b is overexpressed and confers a poor prognosis via promoting cellular proliferation in GBM patients.
doi:10.1371/journal.pone.0038096
PMCID: PMC3378534  PMID: 22723849
9.  Serum amyloid A: A new potential serum marker correlated with the stage of breast cancer 
Oncology Letters  2012;3(4):940-944.
Previous studies reported that serum amyloid A (SAA) is elevated in patients with tumors, including breast cancer, compared to healthy controls. In addition, the levels of SAA increase gradually with tumor progression. In this study, we investigated the blood SAA level of breast cancer patients, and evaluated its potential as a serum biomarker for the early diagnosis of breast cancer and as a staging estimate. SAA protein was determined by enzyme-linked immunosorbent assay in serum samples from 30 healthy women, 21 women with benign diseases and 118 breast cancer patients who were subdivided into 4 groups based on their clinical characteristics. SAA levels were not statistically different in stage I breast cancer patients compared with the healthy controls and benign breast disease patients. SAA concentrations had medians of 0.63 µg/ml in normal healthy women, 0.76 µg/ml in patients with benign disease (p>0.05) and 0.82 µg/ml in stage I breast cancer patients (p>0.05). By contrast, SAA values in stage Ⅱ, Ⅲ and Ⅳ patients had a significantly higher median compared to those of the healthy, benign breast diseases and stage I groups (p<0.05). Breast cancer patients with lymph node (LN) metastasis or distant metastasis were found to have significantly higher SAA concentrations than those without metastases. SAA is not a suitable marker for early breast cancer diagnosis, but its level is correlated with the stage of breast cancer. Thus, it may be a good candidate marker for the staging and prognosis of breast cancer.
doi:10.3892/ol.2012.584
PMCID: PMC3362442  PMID: 22741023
serum amyloid A; breast cancer; staging; diagnosis
10.  Elevated expression of c-fos in central nervous system correlates with visceral hypersensitivity in irritable bowel syndrome (IBS): a new target for IBS treatment 
Background and aims
Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its molecular mechanisms are still poorly understood. c-fos is a well-established marker of cell activation. Accumulating evidence demonstrates that norepinephrine (NE) system is dysregulated in IBS; however, very little is known on its mechanism. It is our hypothesis that elevated expression of c-fos in central nervous system (CNS) correlates with visceral hypersensitivity in rat model of IBS. Furthermore, we explored the changes of NE system in IBS patients.
Methods
The rat model of IBS was induced by heterotypic chronic and acute stress. Tissues obtained from rat model were analyzed for c-fos levels in CNS (frontal lobe, hippocampus, cornu dorsale) and colon by immunohistochemistry. Real-time reverse transcription polymerase chain reaction was used to detect tyrosine hydroxylase (TH) in the colonic tissues obtained from IBS patients.
Results
The rat model of IBS was associated with increased expression of c-fos in different parts of CNS (P = 0.001, P = 0.002, and P = 0.002, respectively), but normal in colon (P = 0.207). The clinical parameters (colonic motility and sensation) of rat model were significantly correlated with elevated c-fos in CNS (P < 0.05). Enterochromaffin cells and serotonin in colon were related to the elevated c-fos in CNS (P < 0.05). The TH messenger ribonucleic acid (mRNA level of IBS-D patients was almost four times as much as that of controls.
Conclusions
Elevated expression of c-fos in CNS might be one of key mechanisms in etiology of IBS. Therefore, regulation of CNS activation could be a major targeting effect when treating IBS patients.
doi:10.1007/s00384-011-1153-4
PMCID: PMC3140936  PMID: 21340718
Irritable bowel syndrome; c-fos; Norepinephrine; Tyrosine hydroxylase
11.  Genetic Polymorphism of GSTP1: Prediction of Clinical Outcome to Oxaliplatin/5-FU-based Chemotherapy in Advanced Gastric Cancer 
Journal of Korean Medical Science  2010;25(6):846-852.
The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile105Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile105Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were 105Ile/105Ile 52%, 105Ile/105Val 41% and 105Val/105Val 7%. For patients with 105Ile/105Ile and those with at least one 105Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two 105Ile alleles (P=0.005). In conclusion, patients with at least one 105Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.
doi:10.3346/jkms.2010.25.6.846
PMCID: PMC2877230  PMID: 20514304
Polymorphism; Glutathione S-Transferase pi; Oxaliplatin; Stomach Neoplasms
12.  Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes 
BMC Proceedings  2007;1(Suppl 1):S45.
Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges.
PMCID: PMC2359868  PMID: 18466544
13.  The Genomes of Oryza sativa: A History of Duplications 
Yu, Jun | Wang, Jun | Lin, Wei | Li, Songgang | Li, Heng | Zhou, Jun | Ni, Peixiang | Dong, Wei | Hu, Songnian | Zeng, Changqing | Zhang, Jianguo | Zhang, Yong | Li, Ruiqiang | Xu, Zuyuan | Li, Shengting | Li, Xianran | Zheng, Hongkun | Cong, Lijuan | Lin, Liang | Yin, Jianning | Geng, Jianing | Li, Guangyuan | Shi, Jianping | Liu, Juan | Lv, Hong | Li, Jun | Wang, Jing | Deng, Yajun | Ran, Longhua | Shi, Xiaoli | Wang, Xiyin | Wu, Qingfa | Li, Changfeng | Ren, Xiaoyu | Wang, Jingqiang | Wang, Xiaoling | Li, Dawei | Liu, Dongyuan | Zhang, Xiaowei | Ji, Zhendong | Zhao, Wenming | Sun, Yongqiao | Zhang, Zhenpeng | Bao, Jingyue | Han, Yujun | Dong, Lingli | Ji, Jia | Chen, Peng | Wu, Shuming | Liu, Jinsong | Xiao, Ying | Bu, Dongbo | Tan, Jianlong | Yang, Li | Ye, Chen | Zhang, Jingfen | Xu, Jingyi | Zhou, Yan | Yu, Yingpu | Zhang, Bing | Zhuang, Shulin | Wei, Haibin | Liu, Bin | Lei, Meng | Yu, Hong | Li, Yuanzhe | Xu, Hao | Wei, Shulin | He, Ximiao | Fang, Lijun | Zhang, Zengjin | Zhang, Yunze | Huang, Xiangang | Su, Zhixi | Tong, Wei | Li, Jinhong | Tong, Zongzhong | Li, Shuangli | Ye, Jia | Wang, Lishun | Fang, Lin | Lei, Tingting | Chen, Chen | Chen, Huan | Xu, Zhao | Li, Haihong | Huang, Haiyan | Zhang, Feng | Xu, Huayong | Li, Na | Zhao, Caifeng | Li, Shuting | Dong, Lijun | Huang, Yanqing | Li, Long | Xi, Yan | Qi, Qiuhui | Li, Wenjie | Zhang, Bo | Hu, Wei | Zhang, Yanling | Tian, Xiangjun | Jiao, Yongzhi | Liang, Xiaohu | Jin, Jiao | Gao, Lei | Zheng, Weimou | Hao, Bailin | Liu, Siqi | Wang, Wen | Yuan, Longping | Cao, Mengliang | McDermott, Jason | Samudrala, Ram | Wang, Jian | Wong, Gane Ka-Shu | Yang, Huanming
PLoS Biology  2005;3(2):e38.
We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000–40,000. Only 2%–3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
Comparative genome sequencing of indica and japonica rice reveals that duplication of genes and genomic regions has played a major part in the evolution of grass genomes
doi:10.1371/journal.pbio.0030038
PMCID: PMC546038  PMID: 15685292

Results 1-13 (13)