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1.  Mechanisms of Gefitinib-mediated reversal of tamoxifen resistance in MCF-7 breast cancer cells by inducing ERα re-expression 
Scientific Reports  2015;5:7835.
Estrogen receptor (ER)-positive breast cancer patients may turn ER-negative and develop acquired drug resistance, which compromises the efficacy of endocrine therapy. By investigating the phenomenon that gefitinib can re-sensitise tamoxifen (TAM)-resistant MCF-7 breast cancer cells (MCF-7/TAM) to TAM, the present study verified that gefitinib could reverse the acquired drug resistance in endocrine therapy and further explored the underlying mechanism.ERα-negative MCF-7/TAM cells were established. Upon treating the cells with gefitinib, the mRNA and protein levels of ERα and ERβ, as well as the expression of molecules involved in the MAPK pathway, were examined using the RT-PCR and immunocytochemistry. The RT-PCR results showed that the mRNA levels of ERα and ERβ in MCF-7/TAM cells were up-regulated following gefitinib treatment; specifically, ERα was re-expressed, and ERβ expression was up-regulated. The expression of molecules involved in the MAPK pathway, including RAS, MEK1/2, and p-ERK1/2, in MCF-7/TAM cells was significantly up-regulated, compared with MCF-7 cells. After the gefitinib treatment, the expression levels of MEK1/2 and p-ERK1/2 were significantly down-regulated. ERα loss is the primary cause for TAM resistance. Gefitinib reverses TAM resistance primarily by up-regulating the ERα mRNA level and inducing the re-expression of ERα. The MAPK pathway plays a key role in ERα re-expression.
doi:10.1038/srep07835
PMCID: PMC4314651  PMID: 25644501
2.  Benzoate Metabolism Intermediate Benzoyl Coenzyme A Affects Gentisate Pathway Regulation in Comamonas testosteroni 
Applied and Environmental Microbiology  2014;80(13):4051-4062.
A previous study showed that benzoate was catabolized via a coenzyme A (CoA)-dependent epoxide pathway in Azoarcus evansii (R. Niemetz, U. Altenschmidt, S. Brucker, and G. Fuchs, Eur. J. Biochem. 227:161-168, 1995), but gentisate 1,2-dioxygenase was induced. Similarly, we found that the Comamonas testosteroni strain CNB-1 degraded benzoate via a CoA-dependent epoxide pathway and that gentisate 1,2-dioxygenase (GenA) was also induced when benzoate or 3-hydroxybenzoate served as a carbon source for growth. Genes encoding the CoA-dependent epoxide (box genes) and gentisate (gen genes) pathways were identified. Genetic disruption revealed that the gen genes were not involved in benzoate and 3-hydroxybenzoate degradation. Hence, we investigated gen gene regulation in the CNB-1 strain. The PgenA promoter, a MarR-type regulator (GenR), and the GenR binding site were identified. We found that GenR took gentisate, 3-hydroxybenzoate, and benzoyl-CoA as effectors and that binding of GenR to its target DNA sequence was prohibited when these effectors were present. In vivo studies showed that the CNB-1 mutant that lost benzoyl-CoA synthesis was not able to activate PgenA promoter, while transcription of genA was upregulated in another CNB-1 mutant that lost the ability to degrade benzoyl-CoA. The finding that benzoyl-CoA (a metabolic intermediate of benzoate degradation) and 3-hydroxybenzoate function as GenR effectors explains why GenA was induced when CNB-1 grew on benzoate or 3-hydroxybenzoate. Regulation of gentisate pathways by MarR-, LysR-, and IclR-type regulators in diverse bacterial groups is discussed in detail.
doi:10.1128/AEM.01146-14
PMCID: PMC4054210  PMID: 24771026
3.  Deviation analysis of C2 translaminar screw placement assisted by a novel rapid prototyping drill template: a cadaveric study 
European Spine Journal  2013;22(12):2770-2776.
Purpose
The goal of this study is to evaluate the accuracy of patient-specific CT-based rapid prototype drill templates for C2 translaminar screw insertion.
Methods
Volumetric CT scanning was performed in 32 cadaveric cervical spines. Using computer software, the authors constructed drill templates that fit onto the posterior surface of the C2 vertebrae with drill guides to match the slope of the patient’s lamina. Thirty-two physical templates were created from the computer models using a rapid prototyping machine. The drill templates were used to guide drilling of the lamina and post-operative CT images were obtained. The entry point and direction of the planned and inserted screws were measured and compared.
Results
Sixty-four C2 translaminar screws were placed without violating the cortical bone of a single lamina. The bilateral average transverse angle of intended and actual screw for C2TLS was 56.60 ± 2.22°, 56.38 ± 2.51°, 56.65 ± 2.24°, 56.39 ± 2.45°. The bilateral mean coronal angle of the planned and actual screw for C2TLS was 0°, 0°, −0.07 ± 0.32°, 0.12 ± 0.57°. The average displacement of the entry point of the superior and inferior C2TLS in the x, y, z axis was 0.27 ± 0.85, 0.49 ± 1.46, −0.28 ± 0.69, 0.43 ± 0.88, 0.38 ± 1.51, 0.23 ± 0.64 mm.
Conclusion
The small deviations seen are likely due to human error in the form of small variations in the surgical technique and use of software to design the prototype. This technology improves the safety profile of this fixation technique and should be further studied in clinical applications.
doi:10.1007/s00586-013-2993-0
PMCID: PMC3843787  PMID: 24005997
Rapid prototyping; Post–pre registration; Personalized drill template; Computer-assisted; C2 translaminar screws
4.  Antitumor effects and molecular mechanisms of figitumumab, a humanized monoclonal antibody to IGF-1 receptor, in esophageal carcinoma 
Scientific Reports  2014;4:6855.
The insulin-like growth factor type 1 receptor (IGF-1R) plays an essential role in the development of numerous cancers. Figitumumab (CP) is not only a monocloncal antibody, it also has agonist activity on IGF-1R. The antitumor activity of CP in esophageal squamous cell carcinoma (ESCC) is still unclear. In our study, we identified IGF-1R as an independent prognostic factor in ESCC patients, and investigated the antitumor effects of CP in ESCC cell lines. CP suppressed tumor growth and sensitized cells to chemotherapeutic drugs. In addition, CP inhibited cell proliferation, migration, colony forming activity and anti-apoptosis induced by IGF-1. Our results showed that CP not only inhibited IGF-1 induced receptor autophosphorylation and downstream signaling, but also triggered β-arrestin1 and G protein-coupled receptor kinases (GRKs) mediated ERK1/2 activation, indicating CP as a biased agonist for IGF-1R. Inhibition of ERK1/2 enhanced the antitumor activity of CP. Furthermore, CP was a more powerful agonist for IGF-1R down-regulation than IGF-1, and dysregulation of β-arrestin1 and GRKs affected this down-regulation. Thus, we demonstrated antitumor activities of CP on ESCC, and as a biased agonist, CP induced ERK1/2 activation and receptor down-regulation required β-arrestin1 and GRKs, suggesting a promising role for targeting IGF-1R in ESCC.
doi:10.1038/srep06855
PMCID: PMC4215295  PMID: 25358597
5.  Minimally invasive surgery treatment for the patients with spontaneous supratentorial intracerebral hemorrhage (MISTICH): protocol of a multi-center randomized controlled trial 
BMC Neurology  2014;14(1):206.
Background
The choice of surgical or conservative treatment for patients with spontaneous intracerebral hemorrhage is controversial. Some minimally invasive treatments have been applied to hematoma evacuation and could improve prognosis to some extent. Up to now, studies on minimally invasive surgery for patients with spontaneous intracerebral hemorrhage are still insufficient.
Design
The MISTICH is a multi-center, prospective, randomized, assessor-blinded, parallel group, controlled clinical trial. 2448 eligible patients will be assigned to neuroendoscopy group, stereotactic aspiration group and craniotomy group randomly. Patients will receive the corresponding surgery based on the result of randomization. Surgeries will be performed by well-trained surgeons and standard medical treatment will be given to all patients. Patients will be followed up at 7 days, 30 days, and 6 months. The primary outcome of this study is unfavorable outcome at 6 months. Secondary outcomes include: mortality at 30 days and 6 months after surgery; neurological functional status of 6 months after surgery; complications including rebleeding, ischemic stroke and intracranial infection; days of hospitalization.
Discussion
The MISTICH trial is a randomized controlled trial designed to determine whether minimally invasive surgeries could improve the prognosis for patients with spontaneous intracerebral hemorrhage compared with craniotomy. (ChiCTR-TRC-12002026. Registered 23 March 2012).
doi:10.1186/s12883-014-0206-z
PMCID: PMC4194378  PMID: 25300611
Intracerebral hemorrhage; Minimally invasive surgical treatment; Craniotomy; Neuroendoscope; Stereotactic aspiration
6.  Morphological and karyotypic differences within and among populations of Radopholus similis 
ZooKeys  2014;69-93.
Twenty populations of Radopholus similis from three countries and different hosts (19 populations from ornamental plants and one population from ginger) were compared using morphological characters, morphometrics and karyotype between progeny from both single females and 30 females of each population. Morphological diversity existed in and among the populations, even within the progeny nematodes from single nematodes compared to that of 30 females. The labial disc shape, the number of head annuli, the terminated position of lateral lips, the number of genital papillae before cloacal apertures and female and male tail terminal shape showed variation. In addition, genital papillae arranged in a double row before cloacal apertures was first found in two ornamental populations. The karyotype of all the 20 populations was n = 5. Combining our results and previous studies, we support that Radopholus citrophilus is a synonym of Radopholus similis, and that it is not possible to distinguish physiological races or pathotypes of Radopholus similis according to morphological characters or karyotype.
doi:10.3897/zookeys.444.8186
PMCID: PMC4205733  PMID: 25349501
Burrowing nematode; optical and SEM microscopy; morphological comparison; karyotype
7.  Low-magnitude high-frequency loading, by whole-body vibration, accelerates early implant osseointegration in ovariectomized rats 
Molecular Medicine Reports  2014;10(6):2835-2842.
Osteoporosis deteriorates jaw bone quality and may compromise early implant osseointegration and early implant loading. The influence of low-magnitude, high-frequency (LMHF) vibration on peri-implant bone healing and implant integration in osteoporotic bones remains poorly understood. LMHF loading via whole-body vibration (WBV) for 8 weeks has previously been demonstrated to significantly enhance bone-to-implant contact, peri-implant bone fraction and implant mechanical properties in osteoporotic rats. In the present study, LMHF loading by WBV was performed in osteoporotic rats, with a loading duration of 4 weeks during the early stages of bone healing. The results indicated that 4-week LMHF loading by WBV partly reversed the negative effects of osteoporosis and accelerated early peri-implant osseointegration in ovariectomized rats.
doi:10.3892/mmr.2014.2597
PMCID: PMC4227418  PMID: 25270245
low-magnitude high-frequency loading; whole-body vibration; osteoporosis; dental implants; osseointegration; rat
8.  XPD Asp312Asn polymorphism and esophageal cancer risk: an update meta-analysis based on 3928 cases and 6012 controls 
Background: Although xeroderma pigmentosum group D (XPD) was reported to be related with esophageal cancer (EC) risk, the results remained inconsistent. The aim of this meta-analysis was to make a more precise estimation of the relationship between XPD Asp312Asn polymorphism and EC risk. Methods: We searched PubMed, Web of Science, Embase, Medline, CNKI and Chinese Biomedical database, covering all publications (up to May, 2014). Statistical analyses were performed with Stata software (version 12.0, USA) and RevMan 5.1 (Copenhagen, 2008). The calculation of odds ratios (ORs) with 95% confidence intervals (CI) was calculated to assess the strength of the association. Results: A total of 15 case-control studies from 13 literatures including 3928 cases and 6012 controls described Asp312Asn genotypes and EC risk. A significant association between XPD Asp312Asn polymorphism and EC risk was found when all the eligible studies were pooled into this meta-analysis. It’s also the same result in subgroup analysis of smokers in dominant model (OR=1.63, 95% CI: 1.06-2.50, P=0.03). However, in the stratified analysis by ethnicity and source of population controls, no association between them was discovered. Conclusion: The XPD Asp312Asn polymorphism was proved to contribute to the risk of EC in this meta-analysis. Data showed that tobacco consumption may increase the susceptibility of EC.
PMCID: PMC4211746  PMID: 25356096
XPD polymorphisms; esophageal cancers; ESCC; EADC; meta-analysis
9.  Synergistic effect of puerarin and 5-fluorouracil on hepatocellular carcinoma 
Oncology Letters  2014;8(6):2436-2442.
Hepatocellular carcinoma (HCC) is one of the most common types of human malignancy worldwide, which is becoming increasingly resistant to traditional drug treatments. Puerarin combined with 5-fluorouracil (5-FU) may be a useful treatment for liver cancer. The primary aim of the present study was to determine whether combined treatment with 5-FU and puerarin is more effective against the hepatocellular carcinoma (HCC) cell line, SMMC7721, than treatment with 5-FU or puerarin alone. The growth inhibition of SMMC7721 cells by puerarin or 5-FU alone or in combination was determined by the Cell Counting Kit-8 assay, in vitro. Apoptotic morphological features and the percentage of apoptotic cells were detected using Hoechst 33258 staining and an Annexin V/PI apoptosis kit, respectively. In addition, a tumor xenograft model was established in nude mice using SMMC7721 cells. Puerarin and 5-FU alone or in combination were injected into the mice, and the inhibition of tumor growth was evaluated by monitoring tumor volume and weight. Treatment with 6,400 or 640 μM 5-FU resulted in growth inhibition of 95.56±0.81 and 75.91±3.54%, respectively. The combination index values were <1 when the fraction of affected cells was between 0.2555 and 0.7420. Furthermore, the percentage of apoptotic cells was markedly increased in the combined treatment group when compared with that of the individual treatment groups, in vitro and in vivo. Individual treatment with puerarin resulted in a tumor volume inhibition rate (IR) of 70.58% and a tumor weight IR of 46.20%. Treatment with 5-FU was found to decrease the tumor volume by 76.26% and tumor weight by 49.86%. In the combined treatment group, the tumor volume and weight IRs were 93.11 and 75.21%, respectively. A marked increase in the inhibition of tumor growth and the number of apoptotic cells in response to combined treatment with puerarin and 5-FU was identified with no observed liver or renal toxicity. These results suggest that puerarin and 5-FU exhibit a synergistic treatment effect on the HCC SMMC7721 cell line.
doi:10.3892/ol.2014.2534
PMCID: PMC4214471  PMID: 25364405
chemotherapy; 5-fluorouracil; hepatocellular carcinoma; puerarin
10.  Elevated Levels of miR-155 in Blood and Urine from Patients with Nephrolithiasis 
BioMed Research International  2014;2014:295651.
Background. Both circulating and urinary miRNAs may represent a potential noninvasive molecular biomarker capable of predicting chronic kidney disease, and, in the present study, we will investigate the serum and urinary levels of miR-155 in patients with nephrolithiasis. Methods. Serum and urinary levels of miR-155 are quantified in 60 patients with nephrolithiasis; the result was compared to 50 healthy volunteers. Estimated glomerular filtration (eGFR) was calculated and, by simple regression analysis, the correlations of miR-155/eGFR and miR-155/CRP (C-reactive protein) levels were analyzed as well. Results. The median levels of serum and urinary levels of miR-155 are significantly higher in nephrolithiasis patients than in controls. eGFR inversely correlates with urinary level of miR-155; CRP positively correlates with urinary miR-155. Urinary level of miR-155 inversely correlates with urinary expression of interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α and positively correlates with urinary expression of regulated upon activation, normal T-cell expressed, and secreted (RANTES). Conclusion. Serum and urinary levels of miR-155 were significantly elevated in patients with nephrolithiasis, and the upregulation of miR-155 was correlated with decline of eGFR and elevation of CRP. Our results suggested that miR-155 might play important roles in the pathophysiology of nephrolithiasis via regulating inflammatory cytokines expression. Further study on the molecular pathogenic mechanism and larger scale of clinical trial are required.
doi:10.1155/2014/295651
PMCID: PMC4150454  PMID: 25197634
11.  Clinical outcome of small hepatocellular carcinoma after different treatments: A meta-analysis 
World Journal of Gastroenterology : WJG  2014;20(29):10174-10182.
AIM: To compare clinical outcomes between surgical resection (RES) and nonsurgical-RES (nRES) ablation therapies for small hepatocellular carcinoma (HCC).
METHODS: MEDLINE, Embase and Cochrane Library databases were systematically searched for studies of RES and nRES treatments for small HCC between January 2003 and October 2013. The clinical outcome measures evaluated included overall survival rate, disease-free survival rate, adverse events, and local recurrence rate. Odds ratios (ORs) with 95%CIs were calculated using either the fixed effects model or random effects model. The χ2 and I2 tests were calculated to assess the heterogeneity of the data. Funnel plots were used to assess the risk of publication bias.
RESULTS: Our analysis included 12 studies that consisted of a total of 1952 patients (RES vs nRES), five studies that consisted of 701 patients [radiofrequency ablation (RFA) vs percutaneous ethanol injection (PEI)], and five additional studies [RFA vs RFA + transcatheter arterial chemoembolization (TACE)] that all addressed the treatment of small HCC. For cases of RES vs nRES, there was no significant difference in the 1-year (OR = 0.99, 95%CI: 0.87-1.12, P = 0.85) or 3-year (OR = 0.97, 95%CI: 0.84-1.11, P = 0.98) overall survival rate; however, there was a significant increase in the RES group in the 5-year overall survival rate (OR = 0.81, 95%CI: 0.68-0.95, P = 0.01). The 1-year (OR = 0.94, 95%CI: 0.82-1.08, P = 0.37) and 5-year (OR = 0.99, 95%CI: 0.85-1.14, P = 0.85) disease-free survival rates showed no significant differences between the two groups. The 3-year disease-free survival rate (OR = 0.81, 95%CI: 0.69-0.96; P = 0.02) was higher in the RES group. For cases of RFA vs PEI, our data analysis indicated that RFA treatment was associated with significantly higher 2-year (OR = 0.76, 95%CI: 0.58-0.99, P = 0.043) and 3-year (OR = 0.73, 95%CI: 0.54-0.98, P = 0.039) overall survival rates; however, there were no significant differences in the 1-year (OR = 0.92, 95%CI: 0.72-1.17, P = 0.0502) overall survival rate or incidence of adverse events (OR = 1.84, 95%CI: 0.76-4.45, P = 0.173). For cases of RFA vs RFA+TACE, there were no significant differences in the 1-year (OR = 1.17, 95%CI: 0.88-1.56, P = 0.27) or 3-year (OR = 1.25, 95%CI: 0.90-1.73, P = 0.183) overall survival rate; however, the 5-year overall survival rate (OR = 3.19, 95%CI: 1.51-6.74, P = 0.002) in patients treated by RFA+TACE was higher than that treated by RFA alone.
CONCLUSION: Surgical resection is superior to nonsurgical ablation for the treatment of small HCC. Among the studies analyzed, RFA is the most efficacious single nonsurgical ablation treatment.
doi:10.3748/wjg.v20.i29.10174
PMCID: PMC4123348  PMID: 25110446
Hepatocellular carcinoma; Meta-analysis; Surgical resection; Nonsurgical ablation; Radiofrequency ablation; Percutaneous ethanol injection; Recurrence; Survival
12.  D14-SCFD3-dependent degradation of D53 regulates strigolactone signaling 
Nature  2013;504(7480):406-410.
Strigolactones (SLs) are a new class of carotenoid-derived phytohormones essential for developmental processes shaping plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signaling mechanisms of SL remain poorly understood. Here we show that DWARF53 (D53) acts as a repressor of SL signaling and SLs induce its degradation. We found that the rice d53 mutant, which produces an exaggerated number of tillers compared to wild type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the α/β hydrolase protein DWARF14 (D14) and the F-box protein DWARF3 (D3), two previously identified signaling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signaling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.
doi:10.1038/nature12878
PMCID: PMC4096652  PMID: 24336215
13.  Sound transmission along the ossicular chain in common wild-type laboratory mice 
Hearing research  2012;301:27-34.
The use of genetically modified mice can accelerate progress in auditory research. However, the fundamental profile of mouse hearing has not been thoroughly documented. In the current study, we explored mouse middle ear transmission by measuring sound-evoked vibrations at several key points along the ossicular chain using a laser-Doppler vibrometer. Observations were made through an opening in pars flaccida. Simultaneously, the pressure at the tympanic membrane close to the umbo was monitored using a micro-pressure-sensor. Measurements were performed in C57BL mice, which are widely used in hearing research. Our results show that the ossicular local transfer function, defined as the ratio of velocity to the pressure at the tympanic membrane, was like a high-pass filter, almost flat at frequencies above ~15 kHz, decreasing rapidly at lower frequencies. There was little phase accumulation along the ossicles. Our results suggested that the mouse ossicles moved almost as a rigid body. Based on these 1-dimensional measurements, the malleus–incus-complex primarily rotated around the anatomical axis passing through the gonial termination of the anterior malleus and the short process of the incus, but secondary motions were also present.
doi:10.1016/j.heares.2012.11.015
PMCID: PMC3669248  PMID: 23183032
14.  Antidiabetic and Antioxidative Effect of Jiang Tang Xiao Ke Granule in High-Fat Diet and Low-Dose Streptozotocin Induced Diabetic Rats 
Diabetes mellitus (DM), a kind of metabolic disease, is increasing over the last four decades in the world. The purpose of this study was to investigate the effect of Jiang Tang Xiao Ke (JTXK) granule, a naturally occurring ingredient from Chinese herbal medicines, on serum glucose, lipids, and oxidative stress in DM rats induced by high-fat diet and streptozotocin. JTXK granule 9 g/kg (based on crude herb equivalent) and pioglitazone 1.5 mg/kg (as a positive control for comparison) were orally administrated to DM rats for 4 weeks. Results showed that administration of JTXK granule reduced serum glucose, total cholesterol, triglyceride, and low density lipoprotein levels (by 12%, 33%, 57%, and 44%, resp.) but increased high-density lipoprotein level by 69%, compared with the drug-untreated DM rats. Serum malondialdehyde and nitric oxide levels were lowered (by 34% and 52%, resp.) associated with the elevation in serum superoxide dismutase levels (by 60%) after JTXK granule treatment. In addition, JTXK granule suppressed serum alanine aminotransferase activity (up to 50%) and alleviated pathological changes of pancreas and liver tissues in DM rats. The beneficial changes of pioglitazone on biomarkers were also found in DM rats. These findings suggested that JTXK granule may be an alternative medicine for the management of DM.
doi:10.1155/2014/475192
PMCID: PMC4095829  PMID: 25089145
15.  Clinical significance of serum soluble death receptor 5 concentration in locally advanced non-small cell lung cancer patients 
Oncology Letters  2014;8(3):1333-1339.
There is an urgent requirement for the identification of suitable biomarkers for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). The present study aimed to measure the levels of serum soluble death receptor 5 (sDR5) in patients with locally advanced stage III NSCLC, and to evaluate its diagnostic and prognostic significance in these patients. The sDR5 concentrations were evaluated by the enzyme-linked immunosorbent assay method in 50 healthy controls and 122 patients with locally advanced stage III NSCLC [including 57 adenocarcinoma (ADC) and 65 squamous cell carcinoma (SCC) patients], before and after concurrent chemoradiotherapy. It was found that the pretreatment sDR5 levels in patients with NSCLC were higher than the sDR5 levels of healthy controls (P<0.001). However, no significant difference in the sDR5 levels was observed between the ADC and SCC subgroups (P=0.874). According to multiple clinical classifications, a significant increase in the pretreatment serum sDR5 levels could be observed in IIIB-stage patients compared with IIIA-stage patients (P=0.009). Patients with a tumor burden >3 cm had higher pretreatment sDR5 concentration than those with a tumor burden ≤3 cm (P=0.026). Additionally, T4-stage patients had significantly higher pretreatment sDR5 levels compared with those of T1-stage patients (P<0.001). There were no significant differences between pre- and post-treatment sDR5 concentrations in the total NSCLC patient group (P=0.462), ADC subgroup (P=0.066) and SCC subgroup (P=0.052). Furthermore, when patients were divided according to therapeutic response, the pretreatment sDR5 levels in the responder patients were significantly lower compared with those of the non-responders (P<0.001). Further survival analysis showed that the patients whose pretreatment sDR5 levels were ≤14 pg/ml (cutoff value, 14 pg/ml) had a longer progression-free survival (PFS) time than patients with sDR5 levels >14 pg/ml. However, no correlation was observed between the post-treatment sDR5 levels and therapeutic response or PFS time. To the best of our knowledge, the present study results provide the first evidence that the pretreatment serum levels of sDR5 may be a useful biomarker for the diagnosis, prediction and prognosis of patients with locally advanced stage III NSCLC.
doi:10.3892/ol.2014.2237
PMCID: PMC4114649  PMID: 25120719
soluble death receptor 5; non-small cell lung cancer; chemoradiotherapy
16.  Effects of yoga training in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis 
Journal of Thoracic Disease  2014;6(6):795-802.
Introduction
Currently, several studies have assessed the effect of yoga training on the management of chronic obstructive pulmonary disease (COPD), but these studies involved a wide variation of sample and convey inconclusive results. Hence, the present study was performed a systematic review and meta-analysis to investigate the efficacy of yoga training in COPD patients.
Methods
PubMed, EMBASE, the Cochrane Library, Google Scholar, and ClinicalTrials.gov databases were searched for relevant studies. The primary outcomes were forced expiratory volume in one second (FEV1), FEV1% predicted (% pred). Secondary outcomes included 6-min walking distance (6 MWD), arterial oxygen tension (PaO2), and arterial carbon dioxide tension (PaCO2). Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I2 test.
Results
Five randomized controlled trials (RCTs) involving 233 patients fulfilled the inclusion criteria. Yoga training significantly improved FEV1 (WMD: 123.57 mL, 95% CI: 4.12-243, P=0.04), FEV1% pred (WMD: 3.90%, 95% CI: 2.27-5.54, P<0.00001), and 6 MWD (WMD: 38.84 m, 95% CI: 15.52-62.16, P=0.001). However, yoga training had no significant effects on PaO2 (WMD: 1.29 mmHg, 95% CI: –1.21-3.78, P=0.31) and PaCO2 (WMD: –0.76 mmHg, 95% CI: –2.06-0.53, P=0.25).
Conclusions
The current limited evidence suggested that yoga training has a positive effect on improving lung function and exercise capacity and could be used as an adjunct pulmonary rehabilitation program in COPD patients. However, further studies are needed to substantiate our preliminary findings and to investigate the long-term effects of yoga training.
doi:10.3978/j.issn.2072-1439.2014.06.05
PMCID: PMC4073384  PMID: 24977005
Chronic obstructive pulmonary disease (COPD); yoga; pulmonary function; meta-analysis
17.  Prognostic value of high-sensitivity cardiac troponin T in patients with endomyocardial-biopsy proven cardiac amyloidosis 
Objective
To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients.
Methods
We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients.
Results
The patients with poor prognosis showed older age (56 ± 12 years vs. 50 ± 15 years, P = 0.022), higher incidences of heart failure (36.92% vs. 16.22%, P = 0.041), pericardial effusion (60.00% vs. 35.14%, P = 0.023), greater thickness of interventricular septum (IVS) (15 ± 4 mm vs. 13 ± 4 mm, P = 0.034), higher level of hs-cTnT (0.186 ± 0.249 ng/mL vs. 0.044 ± 0.055 ng/mL, P = 0.001) and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P = 0.006). At multivariate Cox regression analysis, heart failure (HR: 1.78, 95%CI: 1.09–2.92, P = 0.021), greater wall thickness of IVS (HR: 1.44, 95%CI: 1.04–3.01, P = 0.0375) and higher hs-cTnT level (HR: 6.16, 95%CI: 2.20–17.24, P = 0.001) at enrollment emerged as independent predictors of all-cause mortality.
Conclusions
We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.
doi:10.3969/j.issn.1671-5411.2014.02.011
PMCID: PMC4076454  PMID: 25009564
Cardiac amyloidosis; Long-term survival; Troponin T
18.  Mesoporous magnesium silicate-incorporated poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) bioactive composite beneficial to osteoblast behaviors 
Mesoporous magnesium silicate (m-MS) and poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) composite (m-MPC) was synthesized by solvent casting method. The results suggest that the mechanical properties of compressive strength and elastic modulus, as well as hydrophilicity, of the m-MPC increased with increase of m-MS content in the composites. In addition, the weight loss of the m-MPC improved significantly with the increase of m-MS content during composite soaking in phosphate-buffered saline for 10 weeks, indicating that incorporation of m-MS into PCL-PEG-PCL could enhance the degradability of the m-MPC. Moreover, the m-MPC with 40 w% m-MS could induce a dense and continuous apatite layer on its surface after soaking in simulated body fluid for 5 days, which was better than m-MPC 20 w% m-MS, exhibiting excellent in vitro bioactivity. In cell cultural experiments, the results showed that the attachment and viability ratio of MG63 cells on m-MPC increased significantly with the increase of m-MS content, showing that the addition of m-MS into PCL-PEG-PCL could promote cell attachment and proliferation. The results suggest that the incorporation of m-MS into PCL-PEG-PCL could produce bioactive composites with improved hydrophilicity, degradability, bioactivity, and cytocompatibility.
doi:10.2147/IJN.S59040
PMCID: PMC4043715  PMID: 24920903
PCL-PEG-PCL; degradation; cytocompatibility; cell attachment; cell proliferation
19.  Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma 
Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC.
PMCID: PMC4097282  PMID: 25031716
Colorectal carcinoma; metastasis; prognosis; aldehyde dehydrogenase 1A1; β-catenin
20.  High prevalence of HIV and syphilis and associated factors among low-fee female sex workers in mainland China: a cross-sectional study 
BMC Infectious Diseases  2014;14:225.
Background
The prevalence of HIV and syphilis among middle and high-fee female sex workers (FSWs) has been widely reported but little is known among low-fee FSWs. This study aims to determine the prevalence and associated factors of HIV and syphilis among low-fee FSWs in China.
Methods
A cross-sectional study design was used. A convenience sample of low-fee FSWs was recruited from venues by outreach workers in 12 cities. Structured questionnaire interviews and blood sampling for HIV and syphilis were carried out. Univariate and multivariate logistic regression were used for assessing potential associated factors.
Results
This study enrolled 781 low-fee FSWs. There were 37 (4.7%) HIV positive participants and 117 (15.0%) participants were infected with syphilis. Final multivariate analysis identified five factors associated with HIV infection: older age (OR:2.6, 95% CI:1.1-6.1), local household registration (OR:3.3, 95% CI:1.5-6.9), employed in Yunnan province (OR:2.7, 95% CI:1.1-6.7), soliciting in self-rented rooms and “market day” buildings (OR:3.9, 95% CI:1.5-10.0), injection drug use in the past 6 months (OR:13.5, 95% CI:4.5-40.1); and four factors associated with syphilis infection: older age (OR:1.8, 95% CI:1.2-2.9), employed in Yunnan province (OR:2.1, 95% CI:1.2-3.6), soliciting in self-rented rooms and “market day” buildings (OR:2.3, 95% CI:1.4-3.7) , and no consistent condom use with clients in the past 30 days (OR:1.6, 95% CI:1.0-2.6).
Conclusions
A high prevalence of HIV and syphilis were found among low-fee FSWs. Those soliciting in self-rented rooms and “market day” buildings with the lowest income, and injection drug users (IDUs) in this population should take priority in further intervention strategies.
doi:10.1186/1471-2334-14-225
PMCID: PMC4026051  PMID: 24767104
HIV; Syphilis; Sexually transmitted infections; Low-fee sex workers; China
21.  Expression of Stanniocalcin-1 and Stanniocalcin-2 in Laryngeal Squamous Cell Carcinoma and Correlations with Clinical and Pathological Parameters 
PLoS ONE  2014;9(4):e95466.
Background
Stanniocalcin-1 (STC1) and stanniocalcin-2 (STC2) are secreted glycoprotein hormones involved in various types of human malignancies. The roles of STC1 and STC2 in laryngeal squamous cell carcinoma (LSCC) remain unknown. We investigated correlations between STC1 and STC2 expression and clinicopathological or prognostic factors in LSCC.
Methods
Pre-surgical peripheral blood samples were collected between 2012 and 2013 from 62 patients with LSCC. Quantitative RT-PCR analysis was performed to examine mRNA levels of STC1 and STC2. Immunohistochemistry was performed to retrospectively analyze 90 paraffin-embedded LSCC tissue samples, which were obtained from patients who received surgery between 2006 and 2009. These patients did not have histories of treatment or malignancies. Univariate analysis of patient survival was performed by the Kaplan–Meier method. Multivariate analyses were performed with the Cox proportional hazards model.
Results
The relative mRNA levels of STC1 and STC2 in peripheral blood were significantly greater in LSCC patients than those of healthy volunteers (both P<0.05). STC2 protein expression in tumor tissues was associated with invasion into the thyroid cartilage, T-Stage, lymphatic metastasis, clinical stage, and pathological differentiation (all P<0.05). In addition, STC2 protein expression was an independent prognostic factor for overall survival in patients with LSCC (P = 0.025). In contrast, STC1 expression only correlated with clinical stage (P = 0.026) and was not an independent or significant prognostic factor.
Conclusions
Circulating STC1 and STC2 mRNA are potentially useful blood markers for LSCC. Our results strongly suggest that the STC2 protein, but not STC1, may be a valuable biomarker for LSCC malignancies and a prognostic marker for poor outcome following surgery. Future studies should examine STC2 as a novel molecular target for the treatment of LSCC.
doi:10.1371/journal.pone.0095466
PMCID: PMC3990672  PMID: 24743310
22.  Does Adolescents’ Disclosure to their Parents Matter for their Academic Adjustment? 
Child development  2012;84(2):693-710.
The role of adolescents’ disclosure to their parents in their academic adjustment was examined in a study of 825 American and Chinese adolescents (mean age = 12.73 years). Four times over the seventh and eighth grades, adolescents reported on their spontaneous disclosure of everyday activities to their parents, the quality of their relationships with their parents, and their parents’ autonomy support and control. Information about multiple dimensions of adolescents’ academic adjustment (e.g., learning strategies, autonomous vs. controlled motivation, and grades) was also obtained. Both American and Chinese adolescents’ disclosure predicted their enhanced academic adjustment over time. However, when American adolescents disclosed in a negative context (e.g., a poor parent-child relationship or controlling parenting), their autonomous (vs. controlled) motivation was undermined.
doi:10.1111/j.1467-8624.2012.01853.x
PMCID: PMC3530655  PMID: 23006004
Achievement; disclosure; motivation; parent-child relationships; parenting
23.  Unstable Jefferson fractures: Results of transoral osteosynthesis 
Indian Journal of Orthopaedics  2014;48(2):145-151.
Background:
Majority of C1 fractures can be effectively treated conservatively by immobilization or traction unless there is an injury to the transverse ligament. Conservative treatment usually involves a long period of immobilization in a halo-vest. Surgical intervention generally involves fusion, eliminating the motion of the upper cervical spine. We describe the treatment of unstable Jefferson fractures designed to avoid these problems of both conservative and invasive methods.
Materials and Methods:
A retrospective review of 12 patients with unstable Jefferson fractures treated with transoral osteosynthesis of C1 between July 2008 and December 2011 was performed. A steel plate and C1 lateral mass screw fixation were used to repair the unstable Jefferson fractures. Our study group included eight males and four females with an average age of 33 years (range 23-62 years).
Results:
Patients were followed up for an average of 16 months after surgery. Range of motion of the cervical spine was by and large physiologic: Average flexion 35° (range 28-40°), average extension 42° (range 30-48°). Lateral bending to the right and left averaged 30° and 28° respectively (range 12-36° and 14-32° respectively). The average postoperative rotation of the atlantoaxial joint, evaluated by functional computed tomography scan was 60° (range 35-72°). Total average lateral displacement of the lateral masses was 7.0 mm before surgery (range 5-12 mm), which improved to 3.5 mm after surgery (range 1-6.5 mm). The total average difference of the atlanto-dens interval in flexion and extension after surgery was 1.0 mm (range 1-3 mm).
Conclusions:
Transoral osteosynthesis of the anterior ring using C1 lateral mass screws is a viable option for treating unstable Jefferson fractures, which allows maintenance of rotation at the C1-C2 joint and restoration of congruency of the atlanto-occipital and atlantoaxial joints.
doi:10.4103/0019-5413.128750
PMCID: PMC3977369  PMID: 24741135
Jefferson fractures; osteosynthesis; transoral approach
24.  A genetic fuzzy system for unstable angina risk assessment 
Background
Unstable Angina (UA) is widely accepted as a critical phase of coronary heart disease with patients exhibiting widely varying risks. Early risk assessment of UA is at the center of the management program, which allows physicians to categorize patients according to the clinical characteristics and stratification of risk and different prognosis. Although many prognostic models have been widely used for UA risk assessment in clinical practice, a number of studies have highlighted possible shortcomings. One serious drawback is that existing models lack the ability to deal with the intrinsic uncertainty about the variables utilized.
Methods
In order to help physicians refine knowledge for the stratification of UA risk with respect to vagueness in information, this paper develops an intelligent system combining genetic algorithm and fuzzy association rule mining. In detail, it models the input information’s vagueness through fuzzy sets, and then applies a genetic fuzzy system on the acquired fuzzy sets to extract the fuzzy rule set for the problem of UA risk assessment.
Results
The proposed system is evaluated using a real data-set collected from the cardiology department of a Chinese hospital, which consists of 54 patient cases. 9 numerical patient features and 17 categorical patient features that appear in the data-set are selected in the experiments. The proposed system made the same decisions as the physician in 46 (out of a total of 54) tested cases (85.2%).
Conclusions
By comparing the results that are obtained through the proposed system with those resulting from the physician’s decision, it has been found that the developed model is highly reflective of reality. The proposed system could be used for educational purposes, and with further improvements, could assist and guide young physicians in their daily work.
doi:10.1186/1472-6947-14-12
PMCID: PMC3984752  PMID: 24548742
Unstable angina risk assessment; Fuzzy association rule mining; Genetic algorithm
25.  Potential Effects of Mina53 on Tumor Growth in Human Pancreatic Cancer 
Cell Biochemistry and Biophysics  2014;69(3):619-625.
Myc-induced nuclear antigen (Mina53) is a protein with a molecular weight of 53 kDa expression of which is induced by c-Myc. Increased expression of Mina53 is documented in some human carcinomas. In this study, we found markedly increased Mina53 expression in pancreatic cancer tissue specimens. This expression did not correlate with clinicopathological characteristics, such as sex, age, and presence of distant metastasis. However, there was a statistically significant association with histological differentiation, TNM stage, and lymph node metastases. To study functional role of Mina53, we silenced its expression by siRNA in PANC-1 cells. These cells were arrested in the G2/M phase, and apoptosis rates were increased. In conclusion, increased expression of Mina53 may play an important role in the development of human pancreatic cancer. Mina53 can be used as a marker for pancreatic cancer and may potentially be exploited as a target for treatment of pancreatic cancer.
doi:10.1007/s12013-014-9841-7
PMCID: PMC4057634  PMID: 24522517
Mina53; Pancreatic cancer; RNA interference; Quantum dots; Tumor growth

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