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1.  Effectiveness of neuromuscular electrical stimulation for the rehabilitation of moderate-to-severe COPD: a meta-analysis 
Patients with COPD often experience skeletal muscle dysfunction. For those who are unable or unwilling to undertake physical training, neuromuscular electrical stimulation (NMES) may provide an alternative method of rehabilitation. The purpose of this meta-analysis was to investigate the controversial topic of whether this therapy is effective in patients with moderate-to-severe COPD.
Patients and methods
We pooled data from nine trials published between January 9, 2002 and January 4, 2016 across PubMed, Embase, Cochrane Central Register of Controlled Trials, Google Scholar, and relevant websites for randomized controlled trials. In these trials, patients with moderate-to-severe COPD were randomly allocated to receive NMES. Primary outcomes were quadricep strength and exercise capacity. The secondary outcome was health-related quality of life.
We extracted data from 276 patients. NMES contributed to statistically improved quadricep strength (standardized mean difference 1.12, 95% confidence interval [CI] 0.64–1.59, I2=54%; P<0.00001) and exercise capacity, including longer exercise distance (weighted mean difference 51.53, 95% CI 20.13–82.93, I2=90%; P=0.001), and longer exercise endurance (standardized mean difference 1.11, 95% CI 0.14–2.08, I2=85%; P=0.02). There was no significant difference in St George’s Respiratory Questionnaire scores (weighted mean difference −0.07, 95% CI −2.44 to 2.30, I2=56%; P=0.95).
NMES appears an effectual means of enhancing quadricep strength and exercise capacity in moderate-to-severe COPD patients. Further research is demanded to clarify its effect on other outcomes and determine the optimal parameters for an NMES program.
PMCID: PMC5135061  PMID: 27932876
neuromuscular electrical stimulation; chronic obstructive pulmonary disease; quadriceps muscle strength; exercise capacity
2.  Suberoylanilide hydroxamic acid attenuates paraquat-induced pulmonary fibrosis by preventing Smad7 from deacetylation in rats 
Journal of Thoracic Disease  2016;8(9):2485-2494.
Recent evidence suggests that a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has anti-fibrotic effect. However, the exact mechanism of its anti-fibrotic potential remains is unclear. In this study, we investigated the molecular mechanism of SAHA in attenuating pulmonary fibrosis by regulating stability of Smad7 in paraquat (PQ)-induced lung fibrosis animal model and cultured pulmonary fibroblasts.
Rats with paraquat-induced lung fibrosis were fed with a SAHA solution (15 mg/kg) by gastric gavage. Human pulmonary fibroblasts (HFL1) pre-treated with TGF-β1 (5 ng/mL) were treated with SAHA (5 µM).
SAHA (histone deacetylase inhibitor, HDACi) suppressed PQ-induced lung fibrosis in rats by stabilizing Smad7 level, thus attenuating Smad3 activity, resulting in the inhibition of fibroblast differentiation and collagen expression. In vitro study showed that SAHA suppressed TGF-β1-induced fibroblast differentiation into myofibroblasts. SAHA exerted its antifibrotic effect through preventing Smad7 from deacetylation most maybe by inhibiting TGF-β1-induced HDAC1 activity.
SAHA repressed PQ-induced lung fibrosis via preventing Smad7 from deacetylation.
PMCID: PMC5059239  PMID: 27747000
Pulmonary fibrosis; suberoylanilide hydroxamic acid (SAHA); TGF-β1; histone deacetylase 1 (HDAC1); Smad7 acetylation
3.  Transjugular intrahepatic portosystemic shunt combined with esophagogastric variceal embolization in the treatment of a large gastrorenal shunt 
World Journal of Hepatology  2016;8(20):850-857.
AIM: To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) combined with stomach and esophageal variceal embolization (SEVE) in cirrhotic patients with a large gastrorenal vessel shunt (GRVS).
METHODS: Eighty-one cirrhotic patients with gastric variceal bleeding (GVB) associated with a GRVS were enrolled in the study and accepted TIPS combined with SEVE (TIPS + SEVE), by which portosystemic pressure gradient (PPG), biochemical, TIPS-related complications, shunt dysfunction, rebleeding, and death were evaluated.
RESULTS: The PPGs before TIPS were greater than 12 mmHg in 81 patients. TIPS + SEVE treatment caused a significant decrease in PPG (from 37.97 ± 6.36 mmHg to 28.15 ± 6.52 mmHg, t = 19.22, P < 0.001). The percentage of reduction in PPG was greater than 20% from baseline. There were no significant differences in albumin, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time, or Child-Pugh score before and after operation. In all patients, rebleeding rates were 3%, 6%, 12%, 18%, and 18% at 1, 3, 6, 12, and 18 mo, respectively. Five patients (6.2%) were diagnosed as having hepatic encephalopathy. The rates of shunt dysfunction were 0%, 4%, 9%, 26%, and 26%, at 1, 3, 6, 12, and 18 mo, respectively. The cumulative survival rates in 1, 3, 6, 12, and 18 mo were 100%, 100%, 95%, 90%, and 90%, respectively.
CONCLUSION: Our preliminary results indicated that the efficacy and safety of TIPS + SEVE were satisfactory in cirrhotic patients with GVB associated with a GRVS (GVB + GRVS).
PMCID: PMC4945505  PMID: 27458505
Transjugular intrahepatic portosystemic shunt; Cirrhosis; Gastric varices; Variceal embolization; Gastrorenal shunt
4.  Correlation of primary middle and distal esophageal cancers motion with surrounding tissues using four-dimensional computed tomography 
OncoTargets and therapy  2016;9:3705-3710.
To investigate the correlation of gross tumor volume (GTV) motion with the structure of interest (SOI) motion and volume variation for middle and distal esophageal cancers using four-dimensional computed tomography (4DCT).
Patients and methods
Thirty-three patients with middle or distal esophageal carcinoma underwent 4DCT simulation scan during free breathing. All image sets were registered with 0% phase, and the GTV, apex of diaphragm, lung, and heart were delineated on each phase of the 4DCT data. The position of GTV and SOI was identified in all 4DCT phases, and the volume of lung and heart was also achieved. The phase relationship between the GTV and SOI was estimated through Pearson’s correlation test.
The mean peak-to-peak displacement of all primary tumors in the lateral (LR), anteroposterior (AP), and superoinferior (SI) directions was 0.13 cm, 0.20 cm, and 0.30 cm, respectively. The SI peak-to-peak motion of the GTV was defined as the greatest magnitude of motion. The displacement of GTV correlated well with heart in three dimensions and significantly associated with bilateral lung in LR and SI directions. A significant correlation was found between the GTV and apex of the diaphragm in SI direction (rleft=0.918 and rright=0.928). A significant inverse correlation was found between GTV motion and varying lung volume, but the correlation was not significant with heart (rLR=−0.530, rAP=−0.531, and rSI=−0.588) during respiratory cycle.
For middle and distal esophageal cancers, GTV should expand asymmetric internal margins. The primary tumor motion has quite good correlation with diaphragm, heart, and lung.
PMCID: PMC4922815  PMID: 27382308
esophageal neoplasms; 4D-CT; gross tumor volume; displacement correlation
5.  A comparison of dosimetric variance for external-beam partial breast irradiation using three-dimensional and four-dimensional computed tomography 
OncoTargets and therapy  2016;9:1857-1863.
To investigate the potential dosimetric benefits from four-dimensional computed tomography (4DCT) compared with three-dimensional computed tomography (3DCT) in radiotherapy treatment planning for external-beam partial breast irradiation (EB-PBI).
Patients and methods
3DCT and 4DCT scan sets were acquired for 20 patients who underwent EB-PBI. The volume of the tumor bed (TB) was determined based on seroma or surgical clips on 3DCT images (defined as TB3D) and the end inhalation (EI) and end exhalation (EE) phases of 4DCT images (defined as TBEI and TBEE, respectively). The clinical target volume (CTV) consisted of the TB plus a 1.0 cm margin. The planning target volume (PTV) was the CTV plus 0.5 cm (defined as PTV3D, PTVEI, and PTVEE). For each patient, a conventional 3D conformal plan (3D-CRT) was generated (defined as EB-PBI3D, EB-PBIEI, and EB-PBIEE).
The PTV3D, PTVEI, and PTVEE were similar (P=0.549), but the PTV coverage of EB-PBI3D was significantly less than that of EB-PBIEI or EB-PBIEE (P=0.001 and P=0.025, respectively). There were no significant differences in the homogeneity or conformity indexes between the three treatment plans (P=0.125 and P=0.536, respectively). The EB-PBI3D plan resulted in the largest organs at risk dose.
There was a significant benefit for patients when using 3D-CRT based on 4DCT for EB-PBI with regard to reducing nontarget organ exposure. Respiratory motion did not affect the dosimetric distribution during free breathing, but might result in poor dose coverage when the PTV is determined using 3DCT.
PMCID: PMC4821394  PMID: 27099517
breast cancer; external-beam partial breast irradiation; three-dimensional computed tomography; four-dimensional computed tomography; dosimetric parameters
6.  Oxymatrine Inhibits Renal Tubular EMT Induced by High Glucose via Upregulation of SnoN and Inhibition of TGF-β1/Smad Signaling Pathway 
PLoS ONE  2016;11(3):e0151986.
Transforming growth factor-β1 (TGF-β1) signaling has been shown to play a critical role in the development of diabetic nephropathy (DN). The nuclear transcription co-repressor Ski-related novel protein N (SnoN) is an important negative regulator of TGF-β1/Smad signal transduction, and subsequent biological responses including tubule epithelial-mesenchymal transition (EMT), extracellular matrix accumulation and tubulointerstitial fibrosis. Oxymatrine (OM) is an alkaloid extracted from the Chinese herb Sophora japonica and has been demonstrated to prevent fibrosis. However, the anti-fibrosis effect of OM in DN is still unclear. In this study, we cultured normal rat renal tubular epithelial cells (NRK52Es) in high glucose and high glucose plus OM, and detected the expression of E-cadherin, α-SMA, FN, TGF-β1, SnoN, Arkadia, p-Smad2 and p-Smad3 and poly-ubiquitination of SnoN. The results showed that E-cadherin and SnoN expression in NRK52Es decreased significantly, but poly-ubiquitination of SnoN, TGF-β1, α-SMA, FN, Arkadia, p-Smad2 and p-Smad3 expression significantly increased due to high glucose stimulation, which could be almost completely reversed by OM, suggesting that OM may alleviate EMT induced by high glucose via upregulating SnoN expression and inhibiting TGF-β1/Smad signaling pathway activation. Hence, OM could be a novel therapeutic for DN.
PMCID: PMC4807015  PMID: 27010330
7.  Plasma Metabolic Profiles in Women are Menopause Dependent 
PLoS ONE  2015;10(11):e0141743.
Menopause is an endocrinological transition that greatly affects health and disease susceptibility in middle-aged and elderly women. To gain new insights into the metabolic process of menopause, plasma metabolic profiles in 115 pre- and post-menopausal women were systematically analyzed by ultra-performance liquid chromatography/mass spectrometry in conjunction with univariate and multivariate statistical analysis. Metabolic signatures revealed considerable differences between pre- and post-menopausal women, and clear separations were observed between the groups in partial least-squares discriminant analysis score plots. In total, 28 metabolites were identified as potential metabolite markers for menopause, including up-regulated acylcarnitines, fatty acids, lysophosphatidylcholines, lysophosphatidylethanolamines, and down-regulated pregnanediol-3-glucuronide, dehydroepiandrosterone sulfate, p-hydroxyphenylacetic acid and dihydrolipoic acid. These differences highlight that significant alterations occur in fatty acid β-oxidation, phospholipid metabolism, hormone metabolism and amino acid metabolism in post-menopausal women. In conclusion, our plasma metabolomics study provides novel understanding of the metabolic profiles related to menopause, and will be useful for investigating menopause-related diseases and assessing metabolomic confounding factors.
PMCID: PMC4651324  PMID: 26580805
8.  Dosimetric impact of tumor bed delineation variability based on 4DCT scan for external-beam partial breast irradiation 
This study sought to evaluate the dosimetric impact of tumor bed delineation variability (based on clips, seroma or both clips and seroma) during external-beam partial breast irradiation (EB-PBI) planned utilizing four-dimensional computed tomography (4DCT) scans. 4DCT scans of 20 patients with a seroma clarity score (SCS) 3~5 and ≥5 surgical clips were included in this study. The combined volume of the tumor bed formed using clips, seroma, or both clips and seroma on the 10 phases of 4DCT was defined as the internal gross target volume (termed IGTVC, IGTVS and IGTVC+S, respectively). A 1.5-cm margin was added by defining the planning target volume (termed PTVC, PTVS and PTVC+S, respectively). Three treatment plans were established using the 4DCT images (termed EB-PBIC, EB-PBIS, EB-PBIC+S, respectively). The results showed that the volume of IGTVC+S was significantly larger than that of IGTVCand IGTVS. Similarly, the volume of PTVC+S was markedly larger than that of PTVC and PTVS. However, the PTV coverage for EB-PBIC+S was similar to that of EB-PBIC and EB-PBIS, and there were no significant differences in the homogeneity index or conformity index between the three treatment plans (P=0.878, 0.086). The EB-PBIS plan resulted in the lowest ipsilateral normal breast and ipsilateral lung doses compared with the EB-PBIC and EB-PBIC+S plans. To conclude, the volume variability delineated based on clips, seroma or both clips and seroma resulted in dosimetric variability for organs at risk, but did not show a marked influence on the dosimetric distribution.
PMCID: PMC4723953  PMID: 26885108
Breast cancer; external beam partial breast irradiation; four-dimensional computed tomography; clips; seroma
9.  Decoding brain responses to pixelized images in the primary visual cortex: implications for visual cortical prostheses 
Neural Regeneration Research  2015;10(10):1622-1627.
Visual cortical prostheses have the potential to restore partial vision. Still limited by the low-resolution visual percepts provided by visual cortical prostheses, implant wearers can currently only “see” pixelized images, and how to obtain the specific brain responses to different pixelized images in the primary visual cortex (the implant area) is still unknown. We conducted a functional magnetic resonance imaging experiment on normal human participants to investigate the brain activation patterns in response to 18 different pixelized images. There were 100 voxels in the brain activation pattern that were selected from the primary visual cortex, and voxel size was 4 mm × 4 mm × 4 mm. Multi-voxel pattern analysis was used to test if these 18 different brain activation patterns were specific. We chose a Linear Support Vector Machine (LSVM) as the classifier in this study. The results showed that the classification accuracies of different brain activation patterns were significantly above chance level, which suggests that the classifier can successfully distinguish the brain activation patterns. Our results suggest that the specific brain activation patterns to different pixelized images can be obtained in the primary visual cortex using a 4 mm × 4 mm × 4 mm voxel size and a 100-voxel pattern.
PMCID: PMC4660756  PMID: 26692860
nerve regeneration; primary visual cortex; electrical stimulation; visual cortical prosthesis; low resolution vision; pixelized image; functional magnetic resonance imaging; voxel size; neural regeneration; brain activation pattern
10.  The Antibacterial Activity of Ta-doped ZnO Nanoparticles 
A novel photocatalyst of Ta-doped ZnO nanoparticles was prepared by a modified Pechini-type method. The antimicrobial study of Ta-doped ZnO nanoparticles on several bacteria of Gram-positive Bacillus subtilis (B. subtilis) and Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) were performed using a standard microbial method. The Ta-doping concentration effect on the minimum inhibitory concentration (MIC) of various bacteria under dark ambient has been evaluated. The photocatalytical inactivation of Ta-doped ZnO nanoparticles under visible light irradiation was examined. The MIC results indicate that the incorporation of Ta5+ ions into ZnO significantly improve the bacteriostasis effect of ZnO nanoparticles on E. coli, S. aureus, and B. subtilis in the absence of light. Compared to MIC results without light irradiation, Ta-doped ZnO and pure ZnO nanoparticles show much stronger bactericidal efficacy on P. aeruginosa, E. coli, and S. aureus under visible light illumination. The possible antimicrobial mechanisms in Ta-doped ZnO systems under visible light and dark conditions were also proposed. Ta-doped ZnO nanoparticles exhibit more effective bactericidal efficacy than pure ZnO in dark ambient, which can be attributed to the synergistic effect of enhanced surface bioactivity and increased electrostatic force due to the incorporation of Ta5+ ions into ZnO. Based on the antibacterial tests, 5 % Ta-doped ZnO is a more effective antimicrobial agent than pure ZnO.
PMCID: PMC4546064  PMID: 26293495
Ta-doped ZnO; Photocatalytical inactivation; Minimum inhibitory concentration; Antibacterial activity
11.  Insulin therapy and the risk of colorectal cancer in patients with type 2 diabetes: a meta-analysis of observational studies 
Several epidemiological studies have reported inconsistent associations between insulin therapy and the risk of colorectal cancer (CRC) in patients with type 2 diabetes mellitus. We performed this meta-analysis of observational studies to evaluate the effect of insulin therapy on the risk of CRC.
We carried out a systematic search of PubMed, Embase and the Cochrane Library Central database between January 1966 and August 2013. Fixed-effects and random-effects models were used to estimate the pooled relative risk (RR) and corresponding 95% confidence interval (CI).
A total of 12 epidemiological studies were included in the present meta-analysis, involving a total of 7947 CRC cases and 491 384 participants. There was significant heterogeneity among the studies, but no publication bias. Insulin therapy significantly increased the risk of CRC [RR = 1.69, 95% CI (1.25, 2.27)]. When the various studies were stratified by study design, we found that insulin use was associated with a statistically significant 115% higher risk of CRC among case–control studies [RR = 2.15, 95% CI (1.41, 3.26)], but not among cohort studies [RR = 1.25, 95% CI (0.95, 1.65)]. Furthermore, a significant association was noted among studies conducted in USA [RR = 1.73, 95% CI (1.15, 2.60)] and Asia [RR = 2.55, 95% CI (2.14, 3.04)], but not in Europe [RR = 1.20, 95% CI (0.92, 1.57)].
The present meta-analysis suggests that insulin therapy may increase the risk of CRC. More prospective cohort studies with longer follow-up durations are warranted to confirm this association. Furthermore, future studies should report results stratified by gender and race and should adjust the results by more confounders.
PMCID: PMC4137822  PMID: 25099257
colorectal cancer; epidemiology; insulin; meta-analysis
12.  Thoracic surgery: single-port video-assisted thoracoscopic lobectomy 
Single-port video-assisted thoracoscopic surgery (VATS) has been increasingly applied in clinical settings in the past two years along with the improvements in both endoscopic instruments and surgical skills. Our center began to perform single-port VATS lobectomy in May 2014 and had performed this procedure in 121 patients till January 2015. The surgical incision (3.5-4.5 cm in length) was created in the 4th or 5th intercostal space at the anterior axillary line at the diseased side. The operator standed at the abdominal side of the patient and operated using the endoscopic instruments only. The surgical steps of single-port VATS lobectomy were same as those of the triple-port VATS lobectomy. There was no fixed mode in handling the three major structures of the pulmonary lobes, and the resection sequence can be scheduled based on the development status of pulmonary fissures and on the difficulties in dissecting the relevant structures. We believe the single-port VATS lobectomy is a safe and feasible procedure and warrants further clinical applications after finishing these surgeries.
PMCID: PMC4486919  PMID: 26207236
Single-port; video-assisted thoracoscopic surgery (VATS); lobectomy
13.  Hereditary protein S deficiency leads to ischemic stroke 
Molecular Medicine Reports  2015;12(3):3279-3284.
Hereditary protein S (PS) deficiency is an independent risk factor for venous thromboembolism. However, the correlation between PS and arterial thrombotic disease, such as cerebral thrombosis, is not clear. The present study focused on the molecular mechanisms underlying ischemic stroke caused by a PS gene mutation in one family. The activity of antithrombin, protein C and PS in the plasma of the proband was measured, and the genes encoding PS were amplified and sequenced. The cellular localization and expression of PS were analyzed in HEK-293 cells. The proband was a 50-year-old male. Plasma PS activity of the proband was 38.9%, which was significantly decreased compared with normal levels. Sequencing analysis revealed a PROS1 c.1486_1490delGATTA mutation on exon 12. This frameshift mutation converts Asp496 in the precursor PS into the termination codon. In addition, the PROS1 mutation was correlated with low PS activity in the family. Functional tests revealed that the mutant protein aggregated in the cytoplasm and its secretion and expression decreased. In conclusion, protein S mutation appeared to be the primary cause of thrombosis in the family of the present study. However, the correlation between PS deficiency and ischemic stroke requires further investigation.
PMCID: PMC4526054  PMID: 25997409
protein S; mutation; expression study; arterial thrombotic disease
14.  Nitric oxide donor, NOC7, reveals dose dependently and cGMP pathway independently biphasic effects on contractile force of isolated rat heart after global ischemia 
Purpose: Our purpose was to investigate whether the 3-(2-hydroxy-1-methyl-2-nitroso-hydrazino)-N-methyl-1-propanamine (NOC7), an ideal NO donor was dose dependently and cGMP-independent in restored cardiac function after global ischemia in an isolated rat heart model. Methods: Langendorff preparations of an isolated rat heart model were established. Isolated rat hearts (n = 40) were randomly divided into 5 groups (ischemic control group, NOC7 groups and NOC7+NS2028 groups). All groups were subjected to 35 min global ischemia, followed by 30 min reperfusion with Krebs-Henseleit bicarbonate buffer (KHB), and NOC7, NOC7+NS2028 at 2 and 200 μM, respectively. Left ventricular developed pressure (LVDP), the maximum and the minimal rate of rise in LVP (±dP/dt), and coronary flows were measured continuously. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels were measured in myocardium homogenate, using enzyme immunoassay (EIA). Results: 30 min of global ischemia increased LVDP to 121.9±11.5% at 35 min of reperfusion of 2 μM NOC7 group and 2 μM NOC7 associated with NS2028 group from the ischemic control group (P < 0.05). While in 200 μM NOC7 group and 200 μM NOC7 associated with NS2028 group, the LVDP value only slightly reduced, resulting in a value of only 45.3±10.4% and 35.3±6.0% of baseline (P > 0.05). Conclusion: NOC7 has biphasic effect on isolated rat heart after ischemia and reperfusion myocardial contractility. This biphasic effect shows neither concentration-dependent nor the cGMP-dependent characteristics.
PMCID: PMC4466954  PMID: 26097567
Myocardial contractility; ischemia/reperfusion; post-resuscitation period; soluble guanosine cyclase inhibition; cyclic nucleotides
15.  Interobserver variability in the delineation of the tumour bed using seroma and surgical clips based on 4DCT scan for external-beam partial breast irradiation 
To explore the interobserver variability in the delineation of the tumour bed using seroma and surgical clips based on the four-dimensional computed tomography (4DCT) scan for external-beam partial breast irradiation (EB-PBI) during free breathing.
Patients with a seroma clarity score (SCS) 3 ~ 5 and ≥5 surgical clips in the lumpectomy cavity after breast-conserving surgery who were recruited for EB-PBI underwent 4DCT simulation. Based on the ten sets of 4DCT images acquired, the tumour bed formed using the clips, the seroma, and both the clips and seroma (defined as TBC, TBS and TBC+S, respectively) were delineated by five radiation oncologists using specific guidelines. The following parameters were calculated to analyse interobserver variability: volume of the tumour bed (TBC, TBS, TBC+S), coefficient of variation (COVC, COVS, COVC+S), and matching degree (MDC, MDS, MDC+S).
The interobserver variability for TBC and TBC+S and for COVC and COVC+S were statistically significant (p = 0.021, 0.008, 0.002, 0.015). No significant difference was observed for TBS and COVS (p = 0.867, 0.061). Significant differences in interobserver variability were observed for MDC vs MDS, MDC vs MDC+S, MDS vs MDC+S (p = 0.000, 0.032, 0.008), the interobserver variability of MDS was smaller than that of MDC and MDC+S (MDS > MDC+S > MDC).
When the SCS was 3 ~ 5 points and the number of surgical clips was ≥5, interobserver variability was minimal for the delineation of the tumour bed based on seroma.
PMCID: PMC4363049  PMID: 25889620
Breast cancer; Four-dimensional computed tomography; Interobserver variability; Surgical clips; Seroma
16.  Transcriptome analysis of cattle muscle identifies potential markers for skeletal muscle growth rate and major cell types 
BMC Genomics  2015;16(1):177.
This study aimed to identify markers for muscle growth rate and the different cellular contributors to cattle muscle and to link the muscle growth rate markers to specific cell types.
The expression of two groups of genes in the longissimus muscle (LM) of 48 Brahman steers of similar age, significantly enriched for “cell cycle” and “ECM (extracellular matrix) organization” Gene Ontology (GO) terms was correlated with average daily gain/kg liveweight (ADG/kg) of the animals. However, expression of the same genes was only partly related to growth rate across a time course of postnatal LM development in two cattle genotypes, Piedmontese x Hereford (high muscling) and Wagyu x Hereford (high marbling). The deposition of intramuscular fat (IMF) altered the relationship between the expression of these genes and growth rate. K-means clustering across the development time course with a large set of genes (5,596) with similar expression profiles to the ECM genes was undertaken. The locations in the clusters of published markers of different cell types in muscle were identified and used to link clusters of genes to the cell type most likely to be expressing them. Overall correspondence between published cell type expression of markers and predicted major cell types of expression in cattle LM was high. However, some exceptions were identified: expression of SOX8 previously attributed to muscle satellite cells was correlated with angiogenesis. Analysis of the clusters and cell types suggested that the “cell cycle” and “ECM” signals were from the fibro/adipogenic lineage. Significant contributions to these signals from the muscle satellite cells, angiogenic cells and adipocytes themselves were not as strongly supported. Based on the clusters and cell type markers, sets of five genes predicted to be representative of fibro/adipogenic precursors (FAPs) and endothelial cells, and/or ECM remodelling and angiogenesis were identified.
Gene sets and gene markers for the analysis of many of the major processes/cell populations contributing to muscle composition and growth have been proposed, enabling a consistent interpretation of gene expression datasets from cattle LM. The same gene sets are likely to be applicable in other cattle muscles and in other species.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1403-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4364331  PMID: 25887672
Adipogenesis; ADG; Angiogenesis; Cattle muscle; Development; Extracellular matrix
17.  Preliminary study of a new pathological evolution-based clinical hepatolithiasis classification 
AIM: To investigate clinical features, treatment strategies and outcomes of patients with hepatolithiasis (HL) undergoing surgical treatment, using a new clinical classification.
METHODS: Sixty-eight HL patients were hospitalized and treated surgically from August 2011 to December 2012 and they were classified into four HL types according to pathological evolution of the disease. These four HL types included type I primary type (defined as no previous biliary tract surgery), type II inflammatory type (with previous biliary tract surgery and cholangitis), type III mass-forming type (HL complicated by hepatic mass-forming lesion), and type IV terminal type (with secondary biliary cirrhosis and resultant portal hypertension). The perioperative data including general information, imaging data, postoperative complications, and immediate and final stone clearance rate were obtained and analyzed.
RESULTS: In all 68 patients, the proportion of HL type I-IV was 50% (34/68), 36.8% (25/68), 10.3% (7/68) and 2.8% (2/68), respectively. Abdominal pain was the main clinical manifestation in type I (88.2%), fever was predominant in type II (52.0%), the malignancy rate in type III was high (71.4%), and portal hypertension and spleen enlargement were common in type IV (2/2, 100.0%). Liver resection rate for types I-III was 79.4%, 72.0% and 71.4%, respectively. The overall incidence of postoperative complications was 23.5% (16/68). There were no perioperative deaths. The average length of hospital stay was 12.7 ± 7.3 d. Immediate and final stone clearance rate was 73.5% (50/68) and 89.7% (61/68), respectively. Fifty-nine of 68 patients (86.8%) were followed- up for > 1 year after surgery, and 96.6% of these patients (57/59) had a good quality of life according to a criterion recommended for postoperative evaluation of quality of life.
CONCLUSION: The pathological evolution-based clinical classification of HL has a role in optimizing treatment strategy, and patients can benefit from this classification when it is used properly.
PMCID: PMC4326155  PMID: 25717253
Liver diseases; Hepatolithiasis; Clinical pathology; Disease classification; Surgery
18.  Oncogenic induction of cellular high CpG methylation by Epstein-Barr virus in malignant epithelial cells 
Chinese Journal of Cancer  2014;33(12):604-608.
Epstein-Barr virus (EBV) is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma (NPC) and ∼10% of gastric cancer (GC) worldwide. Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC. However, even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC (EBVaGC), suggesting a predominant role of epigenetic abnormities, especially promoter CpG methylation, in the pathogenesis of NPC and EBVaGC. High frequencies of promoter methylation of tumor suppressor genes (TSGs) have been frequently reported in NPC and EBVaGC, with several EBV-induced methylated TSGs identified. Further characterization of the epigenomes (genome-wide CpG methylation profile—methylome) of NPC and EBVaGC shows that these EBV-associated tumors display a unique high CpG methylation epigenotype with more extensive gene methylation accumulation, indicating that EBV acts as a direct epigenetic driver for these cancers. Mechanistically, oncogenic modulation of cellular CpG methylation machinery, such as DNA methyltransferases (DNMTs), by EBV-encoded viral proteins accounts for the EBV-induced high CpG methylation epigenotype in NPC and EBVaGC. Thus, uncovering the EBV-associated unique epigenotype of NPC and EBVaGC would provide new insight into the molecular pathogenesis of these unique EBV-associated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.
PMCID: PMC4308656  PMID: 25322866
Epstein-Barr virus; CpG methylation; DNA methyltransferase; tumor suppressor gene; naso-pharyngeal carcinoma; gastric cancer
19.  Compound Danshen Dripping Pill Pretreatment to Prevent Contrast-Induced Nephropathy in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention 
Background. Contrast-induced nephropathy (CIN) limits the outcome of percutaneous coronary intervention (PCI). Objective. To investigate whether pretreatment with Compound Danshen Dripping Pills (CDDP) will decrease the incidence of CIN after PCI. Methods. A total of 229 patients with acute coronary syndrome (ACS) undergoing PCI were divided into the control group (n = 114) and the CDDP (containing salvia miltiorrhiza and sanqi) group (n = 115; given 20 CDDP pills, three times daily before PCI). Serum creatinine, creatinine clearance (CrCl), high-sensitivity C-reactive protein (hsCRP), P-selectin, and intercellular adhesion molecule-1 (ICAM-1) were measured at admission and 24 and 48 h after PCI. Results. CrCl decreased after PCI but recovered after 48 h. In the CDDP group, CrCl recovered more rapidly (P < 0.05). The procedure increased the hsCRP, P-selectin, and ICAM-1 levels, but these levels were less in the CDDP group (P < 0.05). Conclusions. Pretreatment with CDDP can decrease the occurrence of CIN in patients undergoing PCI, suggesting that the early use of CDDP is an appropriate adjuvant pharmacological therapy before PCI.
PMCID: PMC4216665  PMID: 25386219
20.  Chemotherapy for transarterial chemoembolization in patients with unresectable hepatocellular carcinoma 
World Journal of Gastroenterology : WJG  2014;20(31):10960-10968.
AIM: To compare the efficacy of different chemotherapeutic agents during conventional transarterial chemoembolization (cTACE) in the treatment of unresectable hepatocellular carcinoma (HCC).
METHODS: A retrospective review was undertaken of patients with unresectable HCC undergoing cTACE from May 2003 to November 2011. A total of 107 patients were treated with at least one cTACE session. Irinotecan (CPT-11) was used as a chemotherapeutic agent in 24 patients, gemcitabine (GEM) in 24 and doxorubicin in 59.
RESULTS: The time to progression and overall survival rates were significantly superior in patients treated with CPT-11 compared with the GEM or doxorubicin treated groups (11.4, 8.2, 9.5 mo, P = 0.02 and 21.7, 12.7, 14.5 mo, P = 0.004, respectively). Subgroup analysis showed that for intermediate-stage HCC, CPT-11 resulted in a significantly longer time to progression and overall survival compared with the GEM or doxorubicin treated groups (P = 0.022; P = 0.003, respectively). There were no significant differences in adverse events among the three groups (P > 0.05).
CONCLUSION: For patients treated with cTACE, the chemotherapeutic agent CPT-11 was significantly associated with improved overall survival and delayed tumor progression compared with GEM or doxorubicin. There were no significant differences in clinical adverse events between the three agents. CPT-11 thus appears to be a promising agent when combined with cTACE for the treatment of HCC.
PMCID: PMC4138477  PMID: 25152600
Irinotecan; Gemcitabine; Transarterial chemoembolization; Hepatocellular carcinoma; Overall survival
21.  Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft 
This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates.
This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system.
Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%).
The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.
PMCID: PMC4101797  PMID: 24957053
Mandibular tumor; Mandible reconstruction; Virtual surgical planning
22.  A gene expression estimator of intramuscular fat percentage for use in both cattle and sheep 
The expression of genes encoding proteins involved in triacyglyceride and fatty acid synthesis and storage in cattle muscle are correlated with intramuscular fat (IMF)%. Are the same genes also correlated with IMF% in sheep muscle, and can the same set of genes be used to estimate IMF% in both species?
The correlation between gene expression (microarray) and IMF% in the longissimus muscle (LM) of twenty sheep was calculated. An integrated analysis of this dataset with an equivalent cattle correlation dataset and a cattle differential expression dataset was undertaken. A total of 30 genes were identified to be strongly correlated with IMF% in both cattle and sheep. The overlap of genes was highly significant, 8 of the 13 genes in the TAG gene set and 8 of the 13 genes in the FA gene set were in the top 100 and 500 genes respectively most correlated with IMF% in sheep, P-value = 0. Of the 30 genes, CIDEA, THRSP, ACSM1, DGAT2 and FABP4 had the highest average rank in both species. Using the data from two small groups of Brahman cattle (control and Hormone growth promotant-treated [known to decrease IMF% in muscle]) and 22 animals in total, the utility of a direct measure and different estimators of IMF% (ultrasound and gene expression) to differentiate between the two groups were examined. Directly measured IMF% and IMF% estimated from ultrasound scanning could not discriminate between the two groups. However, using gene expression to estimate IMF% discriminated between the two groups. Increasing the number of genes used to estimate IMF% from one to five significantly increased the discrimination power; but increasing the number of genes to 15 resulted in little further improvement.
We have demonstrated the utility of a comparative approach to identify robust estimators of IMF% in the LM in cattle and sheep. We have also demonstrated a number of approaches (potentially applicable to much smaller groups of animals than conventional methods) to using gene expression to rank animals for IMF% within a single farm/treatment, or to estimate differences in IMF% between two farms/treatments.
PMCID: PMC4099020  PMID: 25028604
Cattle; Gene expression phenotype; IMF%; Sheep
23.  Isolation and Characterization of the Diatom Phaeodactylum Δ5-Elongase Gene for Transgenic LC-PUFA Production in Pichia pastoris 
Marine Drugs  2014;12(3):1317-1334.
The diatom Phaeodactylum tricornutum can accumulate eicosapentaenoic acid (EPA) up to 30% of the total fatty acids. This species has been targeted for isolating gene encoding desaturases and elongases for long-chain polyunsaturated fatty acid (LC-PUFA) metabolic engineering. Here we first report the cloning and characterization of Δ5-elongase gene in P. tricornutum. A full-length cDNA sequence, designated PhtELO5, was shown to contain a 1110 bp open reading frame encoding a 369 amino acid polypeptide. The putative protein contains seven transmembrane regions and two elongase characteristic motifs of FLHXYHH and MYSYY, the latter being typical for microalgal Δ5-elongases. Phylogenetic analysis indicated that PhtELO5 belongs to the ELO5 group, tightly clustered with the counterpart of Thalassiosira pseudonana. Heterologous expression of PhtELO5 in Pichia pastoris confirmed that it encodes a specific Δ5-elongase capable of elongating arachidonic acid and eicosapentaenoic acid. Co-expression of PhtELO5 and IsFAD4 (a ∆4-desaturase from Isochrysis sphaerica) demonstrated that the high-efficiency biosynthetic pathway of docosahexaenoic acid was assembled in the transgenic yeast. Substrate competition revealed that PhtELO5 exhibited higher activity towards n-3 PUFA than n-6 PUFA. It is hypothesized that Phaeodactylum ELO5 may preferentially participate in biosynthesis of transgenic LC-PUFA via a n-3 pathway in the yeast host.
PMCID: PMC3967212  PMID: 24608969
diatom fatty acids metabolites; Phaeodactylum Δ5-elongase; functional stacking of ELO5 and FAD4
24.  Radiation Dose in the Thyroid and the Thyroid Cancer Risk Attributable to CT Scans for Pediatric Patients in One General Hospital of China 
Objective: To quantify the radiation dose in the thyroid attributable to different CT scans and to estimate the thyroid cancer risk in pediatric patients. Methods: The information about pediatric patients who underwent CT scans was abstracted from the radiology information system in one general hospital between 1 January 2012 and 31 December 2012. The radiation doses were calculated using the ImPACT Patient Dosimetry Calculator and the lifetime attributable risk (LAR) of thyroid cancer incidence was estimated based on the National Academies Biologic Effects of Ionizing Radiation VII model. Results: The subjects comprised 922 children, 68% were males, and received 971 CT scans. The range of typical radiation dose to the thyroid was estimated to be 0.61–0.92 mGy for paranasal sinus CT scans, 1.10–2.45 mGy for head CT scans, and 2.63–5.76 mGy for chest CT scans. The LAR of thyroid cancer were as follows: for head CT, 1.1 per 100,000 for boys and 8.7 per 100,000 for girls; for paranasal sinus CT scans, 0.4 per 100,000 for boys and 2.7 per 100,000 for girls; for chest CT scans, 2.1 per 100,000 for boys and 14.1 per 100,000 for girls. The risk of thyroid cancer was substantially higher for girls than for the boys, and from chest CT scans was higher than that from head or paransal sinus CT scans. Conclusions: Chest CT scans caused higher thyroid dose and the LAR of thyroid cancer incidence, compared with paransal sinus or head CT scans. Therefore, physicians should pay more attention to protect the thyroid when children underwent CT scans, especially chest CT scans.
PMCID: PMC3987004  PMID: 24608902
cancer risk; pediatric CT; radiation dose
25.  DNA Methylation and Regulation of the CD8A after Duck Hepatitis Virus Type 1 Infection 
PLoS ONE  2014;9(2):e88023.
Cluster of differentiation 8 (CD8) is expressed in cytotoxic T cells, where it functions as a co-receptor for the T-cell receptor by binding to major histocompatibility complex class I (MHCI) proteins, which present peptides on the cell surface. CD8A is critical for cell-mediated immune defense and T-cell development. CD8A transcription is controlled by several cis-acting elements and trans-acting elements and is also regulated by DNA methylation. However, the epigenetic regulation of CD8A in the duck and its relationship with virus infection are still unclear.
We investigated the epigenetic transcriptional regulatory mechanisms, such as DNA methylation, for the expression of the CD8A and further evaluated the contribution of such epigenetic regulatory mechanisms to DHV-I infection in the duck. Real-time quantitative polymerase chain reaction (RT-qPCR) revealed the highest level of CD8A expression to be in the thymus, followed by the lungs, spleen, and liver, and the levels of CD8A expression were very low in the kidney, cerebrum, cerebellum, and muscle in the duck. RT-qPCR also demonstrated that the CD8A mRNA was down-regulated significantly in morbid ducklings treated with DHV-1 and up-regulated significantly in non-morbid ducklings in all the tissues tested. In addition, hypermethylation of CD8A was detected in the morbid ducklings, whereas relatively low methylation of CD8A was evident in the non-morbid ducklings. The CD8A mRNA level was negatively associated with the CpG methylation level of CD8A and global methylation status.
We concluded that the mRNA level of the CD8A was negatively associated with the CpG methylation level of CD8A and global methylation status in the duck, suggesting that the hypermethylation of CD8A may be associated with DHV-1 infection. The first two CpG sites of the CD8A promoter region could be considered as epigenetic biomarkers for resistance breeding against duckling hepatitis disease in the duck.
PMCID: PMC3913717  PMID: 24505360

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