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1.  Axon guidance molecule semaphorin3A is a novel tumor suppressor in head and neck squamous cell carcinoma 
Oncotarget  2016;7(5):6048-6062.
Semaphorin3A (SEMA3A), an axon guidance molecule in the nervous system, plays an inhibitory role in oncogenesis. Here, we investigated the expression pattern and biological roles of SEMA3A in head and neck squamous cell carcinoma (HNSCC) by gain-of-function assays using adenovirus transfection and recombinant human SEMA3A protein. In addition, we explored the therapeutic efficacy of SEMA3A against HNSCC in vivo. We found that lower expression of SEMA3A correlated with shorter overall survival and had independent prognostic importance in patients with HNSCC. Both genetic and recombinant SEMA3A protein inhibited cell proliferation and colony formation and induced apoptosis, accompanied by decreased cyclin E, cyclin D, CDK2, CDK4 and CDK6 and increased P21, P27, activated caspase-5 and caspase-7. Moreover, over-expression of SEMA3A suppressed migration, invasion and epithelial-to-mesenchymal transition due in part to the inhibition of NF-κB and SNAI2 in HNSCC cell lines. Furthermore, intratumoral SEMA3A delivery significantly stagnated tumor growth in a xenograft model. Taken together, our results indicate that SEMA3A serves as a tumor suppressor during HNSCC tumorigenesis and a new target for the treatment of HNSCC.
PMCID: PMC4868739  PMID: 26755661
semaphorin3A; HNSCC; apoptosis; NF-kappaB; Snail
3.  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.
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.
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.
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.
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.
PMCID: PMC3990672  PMID: 24743310
4.  Prognostic Role of microRNA-155 in Various Carcinomas: Results from a Meta-Analysis 
Disease markers  2013;34(6):379-386.
BACKGROUND: Recent studies have shown that microRNAs (miRNA) have prognostic values in cancers. This meta-analysis seeks to summarize the global predicting role of miR-155 for survival in patients with a variety of carcinomas.
METHODS: Eligible studies were identified through multiple search strategies. Data were extracted from studies investigating the relationship between miR-155 expression and survival in cancer patients. Combined hazard ratios (HRs) of miR-155 for outcome were analyzed.
RESULTS: A total of 16 studies dealing with various carcinomas were included for this meta-analysis. For overall survival, higher miR-155 expression could significantly predict worse outcome with the pooled HR of 2.057 (95% CI: 1.392–3.039). For relapse or progress-free survival, elevated miR-155 was also a significant predictor, with a combined HR of 1.918 (95% CI: 1.311–2.806,). In addition, subgroup analysis showed that higher expression of miR-155 had the trends to predict worse outcome in lung cancer. However, the HRs did not reach the statistical significance.
CONCLUSION: Our findings suggest that miR-155 detection has a prognostic value in cancer patients. Regularly measuring miR-155 expression may be useful in clinical practice.
PMCID: PMC3810250  PMID: 23481631
miR-155; cancer; prognosis; clinical
5.  Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies 
Abnet, Christian C. | Wang, Zhaoming | Song, Xin | Hu, Nan | Zhou, Fu-You | Freedman, Neal D. | Li, Xue-Min | Yu, Kai | Shu, Xiao-Ou | Yuan, Jian-Min | Zheng, Wei | Dawsey, Sanford M. | Liao, Linda M. | Lee, Maxwell P. | Ding, Ti | Qiao, You-Lin | Gao, Yu-Tang | Koh, Woon-Puay | Xiang, Yong-Bing | Tang, Ze-Zhong | Fan, Jin-Hu | Chung, Charles C. | Wang, Chaoyu | Wheeler, William | Yeager, Meredith | Yuenger, Jeff | Hutchinson, Amy | Jacobs, Kevin B. | Giffen, Carol A. | Burdett, Laurie | Fraumeni, Joseph F. | Tucker, Margaret A. | Chow, Wong-Ho | Zhao, Xue-Ke | Li, Jiang-Man | Li, Ai-Li | Sun, Liang-Dan | Wei, Wu | Li, Ji-Lin | Zhang, Peng | Li, Hong-Lei | Cui, Wen-Yan | Wang, Wei-Peng | Liu, Zhi-Cai | Yang, Xia | Fu, Wen-Jing | Cui, Ji-Li | Lin, Hong-Li | Zhu, Wen-Liang | Liu, Min | Chen, Xi | Chen, Jie | Guo, Li | Han, Jing-Jing | Zhou, Sheng-Li | Huang, Jia | Wu, Yue | Yuan, Chao | Huang, Jing | Ji, Ai-Fang | Kul, Jian-Wei | Fan, Zhong-Min | Wang, Jian-Po | Zhang, Dong-Yun | Zhang, Lian-Qun | Zhang, Wei | Chen, Yuan-Fang | Ren, Jing-Li | Li, Xiu-Min | Dong, Jin-Cheng | Xing, Guo-Lan | Guo, Zhi-Gang | Yang, Jian-Xue | Mao, Yi-Ming | Yuan, Yuan | Guo, Er-Tao | Zhang, Wei | Hou, Zhi-Chao | Liu, Jing | Li, Yan | Tang, Sa | Chang, Jia | Peng, Xiu-Qin | Han, Min | Yin, Wan-Li | Liu, Ya-Li | Hu, Yan-Long | Liu, Yu | Yang, Liu-Qin | Zhu, Fu-Guo | Yang, Xiu-Feng | Feng, Xiao-Shan | Wang, Zhou | Li, Yin | Gao, She-Gan | Liu, Hai-Lin | Yuan, Ling | Jin, Yan | Zhang, Yan-Rui | Sheyhidin, Ilyar | Li, Feng | Chen, Bao-Ping | Ren, Shu-Wei | Liu, Bin | Li, Dan | Zhang, Gao-Fu | Yue, Wen-Bin | Feng, Chang-Wei | Qige, Qirenwang | Zhao, Jian-Ting | Yang, Wen-Jun | Lei, Guang-Yan | Chen, Long-Qi | Li, En-Min | Xu, Li-Yan | Wu, Zhi-Yong | Bao, Zhi-Qin | Chen, Ji-Li | Li, Xian-Chang | Zhuang, Xiang | Zhou, Ying-Fa | Zuo, Xian-Bo | Dong, Zi-Ming | Wang, Lu-Wen | Fan, Xue-Pin | Wang, Jin | Zhou, Qi | Ma, Guo-Shun | Zhang, Qin-Xian | Liu, Hai | Jian, Xin-Ying | Lian, Sin-Yong | Wang, Jin-Sheng | Chang, Fu-Bao | Lu, Chang-Dong | Miao, Jian-Jun | Chen, Zhi-Guo | Wang, Ran | Guo, Ming | Fan, Zeng-Lin | Tao, Ping | Liu, Tai-Jing | Wei, Jin-Chang | Kong, Qing-Peng | Fan, Lei | Wang, Xian-Zeng | Gao, Fu-Sheng | Wang, Tian-Yun | Xie, Dong | Wang, Li | Chen, Shu-Qing | Yang, Wan-Cai | Hong, Jun-Yan | Wang, Liang | Qiu, Song-Liang | Goldstein, Alisa M. | Yuan, Zhi-Qing | Chanock, Stephen J. | Zhang, Xue-Jun | Taylor, Philip R. | Wang, Li-Dong
Human Molecular Genetics  2012;21(9):2132-2141.
Genome-wide association studies have identified susceptibility loci for esophageal squamous cell carcinoma (ESCC). We conducted a meta-analysis of all single-nucleotide polymorphisms (SNPs) that showed nominally significant P-values in two previously published genome-wide scans that included a total of 2961 ESCC cases and 3400 controls. The meta-analysis revealed five SNPs at 2q33 with P< 5 × 10−8, and the strongest signal was rs13016963, with a combined odds ratio (95% confidence interval) of 1.29 (1.19–1.40) and P= 7.63 × 10−10. An imputation analysis of 4304 SNPs at 2q33 suggested a single association signal, and the strongest imputed SNP associations were similar to those from the genotyped SNPs. We conducted an ancestral recombination graph analysis with 53 SNPs to identify one or more haplotypes that harbor the variants directly responsible for the detected association signal. This showed that the five SNPs exist in a single haplotype along with 45 imputed SNPs in strong linkage disequilibrium, and the strongest candidate was rs10201587, one of the genotyped SNPs. Our meta-analysis found genome-wide significant SNPs at 2q33 that map to the CASP8/ALS2CR12/TRAK2 gene region. Variants in CASP8 have been extensively studied across a spectrum of cancers with mixed results. The locus we identified appears to be distinct from the widely studied rs3834129 and rs1045485 SNPs in CASP8. Future studies of esophageal and other cancers should focus on comprehensive sequencing of this 2q33 locus and functional analysis of rs13016963 and rs10201587 and other strongly correlated variants.
PMCID: PMC3315211  PMID: 22323360
6.  The Epithelial–Mesenchymal Transition Promotes Transdifferentiation of Subcutaneously Implanted Hepatic Oval Cells Into Mesenchymal Tumor Tissue 
Stem Cells and Development  2009;18(9):1293-1298.
Hepatic oval cells are thought to represent facultative hepatic epithelial stem cells in liver in which damage inhibits hepatocyte proliferation and liver regeneration. The LE/6 hepatic stem cell line was derived from the liver of male Sprague-Dawley rats fed a choline-deficient diet containing 0.1% ethionine. They are histochemically characterized by their expression of hepatocytic (hepPar1), cholangiocytic cytokeratin (CK19), hepatic progenitor cell (OV-6), and hematopoietic stem cell (c-kit) markers. In this study, we transplanted LE/6 cells by subcutaneous injection into adult female nude mice, and examined their engraftment and differentiation potential in the subcutaneous microenvironment in vivo. Our results demonstrated that following subcutaneous transplantation, differentiation of LE/6 cells into mesenchymal tumor tissue (MTT) was associated with reduced E-cadherin expression, upregulation of E-cadherin repressor molecules (Snail proteins), and increased expression of vimentin and N-cadherin, all of these events are characteristic of the epithelial–mesenchymal transition (EMT).
PMCID: PMC3156617  PMID: 19226223
7.  Major complications after radiofrequency ablation for liver tumors: Analysis of 255 patients 
AIM: To investigate the major complications after radiofrequency ablation (RFA) for the treatment of liver tumors and analyze possible risk factors that precipitate these complications.
METHODS: From March 2001 to April 2008, 255 patients with liver tumors (205 male, 50 female; age range, 18-89 years; mean age, 56.0 years) who received RFA were enrolled in this study. Of these patients, 212 had hepatocellular carcinoma, 39 had metastatic liver tumors and four had cholangiocellular carcinoma. One hundred and forty eight patients had a single tumor, and 107 had multiple tumors. Maximum diameter of the tumors ranged 1.3-20 cm (mean, 5.1 cm). All patients were treated with a cooled-tip perfusion electrode attached to a radiofrequency generator (Radionics, Burlington, MA, USA). RFA was performed via the percutaneous approach (n = 257), laparoscopy (n = 7), or open surgical treatment (n = 86). The major complications related to RFA were recorded. The resultant data were analyzed to determine risk factors associated these complications.
RESULTS: Among the 255 patients, 425 liver tumors were treated and 350 RFA sessions were performed. Thirty-seven (10%) major complications were observed which included 13 cases of liver failure, 10 cases of hydrothorax requiring drainage, three cases of tumor seeding, one case of upper gastrointestinal bleeding, one case of intrahepatic abscess, one case of bile duct injury, one case of cardiac arrest, and five cases of hyperglycemia. Seven patients had more than two complications. Liver failure was the most severe complication and was associated with the highest mortality. Eleven patients died due to worsening liver decompensation. Child-Pugh classification (P = 0.001) and choice of approach (P = 0.045) were related to post-treatment liver failure, whereas patient age, tumor size and number were not significant factors precipitating this complication.
CONCLUSION: RFA can be accepted as a relatively safe procedure for the treatment of liver tumors. However, attention should be paid to possible complications even though the incidences of these complications are rare. Careful patient selection and the best approach choice (percutaneous, laparoscopy, or laparotomy) will help to minimize the incidence and morbidity rate of complications which occur after RFA.
PMCID: PMC2691498  PMID: 19496197
Complication; Hepatocellular carcinoma; Metastatic liver tumor; Radiofrequency ablation; Liver failure
8.  Effect of SLCO1B1 genetic polymorphism on the pharmacokinetics of nateglinide 
Nateglinide is a meglitinide analogue with antidiabetic action. A recent study showed that SLCO1B1 (which codes the OATP1B1 gene, also known as OATP-C, OATP2) is a major determinant which markedly affects the pharmacokinetics of repaglinide. Our objective was to assess the association between single nucleotide polymorphisms (SNPs) of SLCO1B1 and the pharmacokinetics of nateglinide.
Seventeen healthy volunteers with different SLCO1B1 genotypes (11 with 521TT, four with 521TC and two with 521CC) were enrolled in this study. Each was given a single oral dose of 90 mg nateglinide. Plasma concentrations of nateglinide were measured up to 8 h by HPLC.
The Cmax and AUC(0,∞) of nateglinide were 83% (P = 0.002) and 82% (P = 0.001) higher in the SLCO1B 1521TC subjects (n = 4), and 76% (P = 0.016) and 108% (P = 0.001) higher in the SLCO1B1521CC subjects (n = 2) than in the SLCO1B1521TT subjects (n = 11), respectively. The t1/2 of nateglinide in SLCO1B1521CC subjects was 78% longer than that in 521TT subjects (P = 0.036). The difference in tmax values among the three genotypic groups was not statistically significant.
Our results suggest that OATP1B1-mediated hepatic uptake of nateglinide may be the prior step for its metabolism and elimination. SLCO1B1521T > C SNP might play an important role in the pharmacokinetics of nateglinide.
PMCID: PMC1885174  PMID: 16796707
nateglinide; pharmacokinetics; SLCO1B1 polymorphism
9.  Cerebrospinal Fluid IL-10 and IL-10/IL-6 as Accurate Diagnostic Biomarkers for Primary Central Nervous System Large B-cell Lymphoma 
Scientific Reports  2016;6:38671.
Early diagnosis of primary central nervous system lymphoma (PCNSL) represents a challenge, and cerebrospinal fluid (CSF) cytokines may be diagnostic biomarkers for PCNSL. We used an electrochemiluminescence immunoassay to measure interleukin (IL)-10, IL-6, IL-8 and tumor necrosis factor α (TNF-α) in the CSF of 22 B cell PCNSL patients and 80 patients with other CNS diseases. CSF IL-10 was significantly higher in PCNSL patients than in the control group (median 74.7 pg/ml vs < 5.0 pg/ml, P < 0.000). Using a CSF IL-10 cutoff value of 8.2 pg/ml, the diagnostic sensitivity and specificity were 95.5% and 96.1%, respectively (AUC, 0.957; 95% CI, 0.901–1.000). For a CSF IL-10/IL-6 cutoff value of 0.72, the sensitivity was 95.5%, and the specificity was 100.0% (AUC, 0.976; 95% CI, 0.929–1.000). An increased CSF IL-10 level at diagnosis and post-treatment was associated with poor Progression free survival (PFS) for patients with PCNSL (P = 0.0181 and P = 0.0002, respectively). A low diagnostic value for PCNSL was found with CSF IL-8 or TNF-α. In conclusion, increased CSF IL-10 was a reliable diagnostic biomarker for large B cell PCNSL, and an IL-10/IL-6 ratio facilitates differentiation from other conditions, especially a CNS infection.
PMCID: PMC5141427  PMID: 27924864
10.  Molecular Structure and Dynamics of Water on Pristine and Strained Phosphorene: Wetting and Diffusion at Nanoscale 
Scientific Reports  2016;6:38327.
Phosphorene, a newly fabricated two-dimensional (2D) nanomaterial, has emerged as a promising material for biomedical applications with great potential. Nonetheless, understanding the wetting and diffusive properties of bio-fluids on phosphorene which are of fundamental importance to these applications remains elusive. In this work, using molecular dynamics (MD) simulations, we investigated the structural and dynamic properties of water on both pristine and strained phosphorene. Our simulations indicate that the diffusion of water molecules on the phosphorene surface is anisotropic, with strain-enhanced diffusion clearly present, which arises from strain-induced smoothing of the energy landscape. The contact angle of water droplet on phosphorene exhibits a non-monotonic variation with the transverse strain. The structure of water on transverse stretched phosphorene is demonstrated to be different from that on longitudinal stretched phosphorene. Moreover, the contact angle of water on strained phosphorene is proportional to the quotient of the longitudinal and transverse diffusion coefficients of the interfacial water. These findings thereby offer helpful insights into the mechanism of the wetting and transport of water at nanoscale, and provide a better foundation for future biomedical applications of phosphorene.
PMCID: PMC5138611  PMID: 27922072
11.  Application of Ultrasound-Guided Ilioinguinal/Iliohypogastric Nerve Block in Pediatric Same-Day Surgery 
The Indian Journal of Surgery  2015;77(6):512-516.
The aim of this study was to evaluate the safety and efficacy of ultrasound-guided ilioinguinal/iliohypogastric nerve block (IINB) in pediatric patients undergoing same-day inguinal region surgery. Ninety patients aged 4–6 years, ASA levels I–II, were randomly divided into three groups: U, T, or C (n = 30 each). After basic anesthesia, patients in group U underwent ultrasound-guided IINB, those in group T underwent traditional Schulte-Steinberg IINB, and those in group C (controls) received intravenous anesthesia (ketamine-propofol) only. Patients who remained sensitive to intraoperative stimuli received additional intravenous doses of 1 mg/kg ketamine. Heart rate (HR), mean arterial pressure (MAP), and oxygen saturation (SPO2) were recorded upon entering the operating room (T0), at skin incision (T1), while pulling the hernia sac (T2), during skin closing (T3), and upon awakening (T4) at recovery. HR and MAP at T1, T2, and T4 were higher in group C than those in the other two groups, and recovery time in group C was significantly prolonged (P < 0.05). Group U required significantly lower quantities and frequency of ketamine injection, and pain scores in group U during awakening were lower than those in the other two groups (P < 0.05). Ultrasound-guided IINB provided an improved nerve block effect and postoperative analgesia, reduced the amount of local anesthetic required, facilitated more rapid postoperative recovery, and was a safe and effective method of anesthesia.
PMCID: PMC4744206  PMID: 26884660
Ultrasonography; Ilioinguinal/iliohypogastric nerve; Nerve block; Daytime surgery
12.  Predictive Factors for Surgical Intervention in Patients over the Age of 80 with Adhensive Small-Bowel Obstruction 
The Indian Journal of Surgery  2015;77(Suppl 3):1280-1284.
Adhensive small-bowel obstruction (SBO) remains a common cause of admission to surgical wards around the world. Given the growing elderly population, the number of elderly patients with adhensive SBO can be expected to increase substantially. Timely and appropriate treatment would improve morbidity and mortality rates in elderly patients with adhensive SBO. However, accurately determining which patients should undergo surgical treatment during the hospitalization remains difficult. The aim of this study was to identify predictive factors for surgical intervention in patients aged over 80 years presenting with SBO due to postoperative adhesions. A clinical and radiological data for the assessment of patients presenting with adhensive SBO were collected. A logistic regression model was applied to identify risk factors that would predict the need of surgical intervention. A total of 21 patients (13 males, 8 females) were treated during a 3.5-year period. The mean age was 85.5 ± 4.7 years, ranging from 80 to 97 years. There is no significant difference in age (group 1 87.6 ± 5.9 years vs. group 2 84.8 ± 4.3 years, p = 0.262) between two groups. Serious coexisting diseases were noted in 13 (61.9 %, 13/21) patients. Primary hypertension, cardiac diseases, and diabetes mellitus were common coexisting conditions. However, there is no significant difference in comorbidities (40 vs. 68.8 %, p = 0.325) between group 1 and group 2. Adhensive SBO was successfully treated with conservative treatment in 16 patients (76.2 %, 16/21, group 2), whereas conservative treatment failed in 5 patients (23.8 %, 5/21, group 1), who subsequently underwent laparotomy. Postoperative complication rate was 14.3 % (wound infection, 1/5) and mortality was 0 % (0/5) in group 1. One patient death was recorded in group 2 (1/16, 6.3 %). The overall mean hospital stay was 10.0 ± 5.9 days (range 3–27 days). Group 1 had a longer hospital stay than group 2. However, the difference did not reach the significant level (12.8 ± 8.2 vs. 9.1 ± 5.9 days, p = 0.274). On univariate analysis, the need for surgical intervention was significantly associated with granulocyte percentage (2.768, 0.961–7.975, p = 0.059), CT findings of free intraabdominal fluid (28.000, 1.988–394.405, p = 0.014), and level of albumin (0.265, 0.073–0.970, p = 0.045). On multivariate analysis, the predictive factor was free intraabdominal fluid (28.000, 1.988–394.405, p = 0.014). Conservative treatment remains a major consideration in patients over the age of 80. Although major cases of adhensive SBO are successfully treated with conservative methods, some fail to respond, and the independent risk factor for surgical indication is free intraabdominal fluid.
PMCID: PMC4775599  PMID: 27011551
Small-bowel obstruction; Surgery; Risk factors; Adhesion; The elderly
13.  Human Cartilage-Derived Progenitor Cells From Committed Chondrocytes for Efficient Cartilage Repair and Regeneration 
A population of cartilage stem/progenitor cells can be derived from fully differentiated chondrocytes that have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. This novel concept supports the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint repair.
Articular cartilage is not a physiologically self-renewing tissue. Injury of cartilage often progresses from the articular surface to the subchondral bone, leading to pathogenesis of tissue degenerative diseases, such as osteoarthritis. Therapies to treat cartilage defects using autologous chondrocyte-based tissue engineering have been developed and used for more than 20 years; however, the challenge of chondrocyte expansion in vitro remains. A promising cell source, cartilage stem/progenitor cells (CSPCs), has attracted recent attention. Because their origin and identity are still unclear, the application potential of CSPCs is under active investigation. Here we have captured the emergence of a group of stem/progenitor cells derived from adult human chondrocytes, highlighted by dynamic changes in expression of the mature chondrocyte marker, COL2, and mesenchymal stromal/stem cell (MSC) marker, CD146. These cells are termed chondrocyte-derived progenitor cells (CDPCs). The stem cell-like potency and differentiation status of CDPCs were determined by physical and biochemical cues during culture. A low-density, low-glucose 2-dimensional culture condition (2DLL) was critical for the emergence and proliferation enhancement of CDPCs. CDPCs showed similar phenotype as bone marrow mesenchymal stromal/stem cells but exhibited greater chondrogenic potential. Moreover, the 2DLL-cultured CDPCs proved efficient in cartilage formation both in vitro and in vivo and in repairing large knee cartilage defects (6–13 cm2) in 15 patients. These findings suggest a phenotype conversion between chondrocytes and CDPCs and provide conditions that promote the conversion. These insights expand our understanding of cartilage biology and may enhance the success of chondrocyte-based therapies.
Injury of cartilage, a non-self-repairing tissue, often progresses to pathogenesis of degenerative joint diseases, such as osteoarthritis. Although tissue-derived stem cells have been shown to contribute to tissue renewal and homeostasis, the derivation, biological function, and application potential of stem/progenitor cells found in adult human articular cartilage are incompletely understood. This study reports the derivation of a population of cartilage stem/progenitor cells from fully differentiated chondrocytes under specific culture conditions, which have the potential to reassume their chondrocytic phenotype for efficient cartilage regeneration. These findings support the possibility of using in vitro amplified chondrocyte-derived progenitor cells for joint cartilage repair.
PMCID: PMC4878331  PMID: 27130221
Stem and progenitor cells; Chondrocytes; Cartilage repair; Tissue regeneration; Osteoarthritis; Dedifferentiation; Stemness; Stem cell markers; Cell transplantation
15.  Transcriptome analysis reveals the genetic basis underlying the seasonal development of keratinized nuptial spines in Leptobrachium boringii 
BMC Genomics  2016;17:978.
The expression of sexually selected traits often varies with populations’ breeding cycles in many animals. The elucidation of mechanisms underlying the expression of such traits is a research topic in evolutionary biology; however, the genetic basis of the seasonal development of their expression remains unknown. Male Leptobrachium boringii develop keratinized nuptial spines on their upper jaw during the breeding season that fall off when the breeding season ends. To illuminate the genetic basis for the expression of this trait and its seasonal development, we assessed the de novo transcriptome for L. boringii using brain, testis and upper jaw skin and compared gene expression profiles of these tissues between two critical periods of the spine growth cycle.
We identified 94,900 unigenes in our transcriptome. Among them, 2,131 genes were differentially expressed between the breeding period when the spines developed and the post-breeding period when the spines were sloughed. An increased number of differentially expressed genes (DEGs) were identified in the upper jaw skin compared with the testis and brain. In the upper jaw skin, DEGs were mainly enriched in cytosolic part, peptidase inhibitor activity and peptidase regulator activity based on GO enrichment analysis and in glycolysis/gluconeogenesis, ribosome biogenesis in eukaryotes and retinol metabolism based on KEGG enrichment analysis. In the other two tissues, DEGs were primarily involved in the cell cycle, DNA replication and melatonin production. Specifically, insulin/insulin-like growth factor and sex steroid hormone-related DEGs were identified in the upper jaw skin, indicating . The expression variation of IGF2 and estrogen-related genes may be the main factors regulating the seasonal development of the spines.
Our study provides a list of potential genes involved in the regulation of seasonal development of nuptial spines in L. boringii. This is the first transcriptome survey of seasonally developed sexually selected traits for non-model amphibian species, and candidate genes provided here may provide valuable information for further studies of L. boringii.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-016-3295-9) contains supplementary material, which is available to authorized users.
PMCID: PMC5126826  PMID: 27894252
Leptobrachium boringii; Nuptial spine; Transcriptome; Estrogen; Insulin growth factor; Sexually selected traits
16.  Suprapedicular Foraminal Endoscopic Approach to Lumbar Lateral Recess Decompression Surgery to Treat Degenerative Lumbar Spinal Stenosis 
To discuss the strategy of suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression and evaluate the safety and effectiveness of this strategy.
Complete clinical information of 52 cases of lumbar lateral recess decompression with therapy of suprapedicular foraminal endoscopic approach were analyzed during the period from February 2010 to April 2014 in the Third Hospital of Hebei. All patients were followed up for 24 months, and VAS, JOA, ODI, and LRD were compared between preoperative and postoperative therapy and changes of FA. Intraoperative and postoperative complications were recorded and the safety of the surgery was evaluated. The surgical “excellent” and “good” rates were evaluated using MacNab score.
VAS scores for lumbago and leg pain at 3, 6, 12, and 24 months after surgery were significantly lower than before surgery (p<0.05). JOA scores at 12 and 24 months after surgery were significantly higher than before surgery (p<0.05). ODI at 12 and 24 months after surgery were significantly lower than before surgery (p<0.05). LRD after surgery was higher (p<0.05), and FA was lower than before surgery.
Use of the suprapedicular foraminal endoscopic approach to lumbar lateral recess decompression is safe and effective, and this minimally invasive treatment can achieve satisfactory results, especially for elderly patients with complicated underlying diseases.
PMCID: PMC5142585  PMID: 27890911
Lumbar Vertebrae; Spinal Puncture; Spine
17.  Isolation and characterization of adenoviruses infecting endangered golden snub-nosed monkeys (Rhinopithecus roxellana) 
Virology Journal  2016;13:190.
Adenoviruses are important pathogens with the potential for interspecies transmission between humans and non-human primates. Although many adenoviruses have been identified in monkeys, the knowledge of these viruses from the Colobinae members is quite limited.
We conducted a surveillance of viral infection in endangered golden snub-nosed monkeys (Rhinopithecus roxellana) in the subfamily Colobinae in China, and found that 5.1% of sampled individuals were positive for adenovirus. One of the adenoviruses (SAdV-WIV19) was successfully isolated and its full-length genome was sequenced. The full-length genome of WIV19 is 33,562 bp in size, has a G + C content of 56.2%, and encodes 35 putative genes. Sequence analysis revealed that this virus represents a novel species in the genus Mastadenovirus. Diverse cell lines, including those of human origin, were susceptible to WIV19.
We report the first time the isolation and full-length genomic characterization of an adenovirus from the subfamily Colobinae.
Electronic supplementary material
The online version of this article (doi:10.1186/s12985-016-0648-6) contains supplementary material, which is available to authorized users.
PMCID: PMC5123214  PMID: 27884154
Mastadenovirus; Simian adenovirus; Golden snub-nosed monkey
18.  Hydrogen Sulfide and/or Ammonia Reduces Spermatozoa Motility through AMPK/AKT Related Pathways 
Scientific Reports  2016;6:37884.
A number of emerging studies suggest that air pollutants such as hydrogen sulfide (H2S) and ammonia (NH3) may cause a decline in spermatozoa motility. The impact and underlying mechanisms are currently unknown. Boar spermatozoa (in vitro) and peripubertal male mice (in vivo) were exposed to H2S and/or NH3 to evaluate the impact on spermatozoa motility. Na2S and/or NH4Cl reduced the motility of boar spermatozoa in vitro. Na2S and/or NH4Cl disrupted multiple signaling pathways including decreasing Na+/K+ ATPase activity and protein kinase B (AKT) levels, activating Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and phosphatase and tensin homolog deleted on chromosome ten (PTEN), and increasing reactive oxygen species (ROS) to diminish boar spermatozoa motility. The increase in ROS might have activated PTEN, which in turn diminished AKT activation. The ATP deficiency (indicated by reduction in Na+/K+ ATPase activity), transforming growth factor (TGFβ) activated kinase-1 (TAK1) activation, and AKT deactivation stimulated AMPK, which caused a decline in boar spermatozoa motility. Simultaneously, the deactivation of AKT might play some role in the reduction of boar spermatozoa motility. Furthermore, Na2S and/or NH4Cl declined the motility of mouse spermatozoa without affecting mouse body weight gain in vivo. Findings of the present study suggest that H2S and/or NH3 are adversely associated with spermatozoa motility.
PMCID: PMC5121643  PMID: 27883089
19.  Effect of Pregnane X Receptor*1B genetic polymorphisms on postoperative analgesia with fentanyl in Chinese patients undergoing gynecological surgery 
BMC Medical Genetics  2016;17:87.
The purpose of the study was to investigate the effects of the pregnane X receptor (PXR)*1B polymorphisms on CYP3A4 enzyme activity and postoperative fentanyl consumption in Chinese patients undergoing gynecological surgery.
A total of 287 females of Han ethnicity, aged 20 to 50 years old, ASA I or II, scheduled to abdominal total hysterectomy or myomectomy under general anesthesia were enrolled. The analgesic model used was fentanyl consumption via patient-controlled intravenous analgesia (PCIA) in the post-operative period. Additionally, pain was assessed using a visual analog score (VAS). Pain scores, occurrence of adverse reactions and consumption of fentanyl were recorded during the 24 h postoperative period. The enzyme activity of CYP3A4 was evaluated by measuring the plasma ratio of 1′-hydroxymidazolam to midazolam 1 h after intravenous administration of 0.1 mg/kg midazolam. PXR genotyping was performed by direct DNA sequencing and the PXR * 1B haplotype was analyzed via PHASE V.2.1 software.
The polymorphism frequency of PXR11156A > C/11193 T > C and 8055C > T were 49.6 and 49.3%, and the rate of PXR * 1B haplotype was 48.8% in our study. None of the pain scores, consumption of fentanyl 24 h post-operatively or enzyme activity of CYP3A4, showed differences among different genotypes.
PXR11156A > C, PXR11193T > C, PXR8055C > T or the PXR * 1B haplotype do not appear to be important factors contributing to CYP3A4 activity and interindividual variations in postoperative fentanyl consumption in Han female patients undergoing gynecological surgery.
Trial registration
The DNA samples were obtained since 2007 to 2010 year in our hospital, there was no registration at that time. So this section is not applicable to our research.
PMCID: PMC5120516  PMID: 27876007
Fentanyl; CYP3A4; Pregnane X receptor; Polymorphism; Analgesia
20.  Will Gay Sex–Seeking Mobile Phone Applications Facilitate Group Sex? A Cross-Sectional Online Survey among Men Who Have Sex with Men in China 
PLoS ONE  2016;11(11):e0167238.
China is amidst a sexual revolution, with changing sexual practices and behaviors. Sex–seeking mobile phone applications (gay apps) that allow multiple people to meet up quickly may facilitate group sex. This study was therefore undertaken to evaluate group sex among Chinese MSM and to better understand factors associated with group sex.
An online survey was conducted from September-October 2014, collecting data on socio-demographics, sexual behaviors, use of gay apps and occurrence of group sex among Chinese MSM. Univariate and multivariable logistic regressions were used to compare group sex and non-group sex participants.
Of the 1,424 MSM, the majority were under 30 years old (77.5%), unmarried (83.9%), and were gay apps users (57.9%). Overall, 141 (9.9%) participants engaged in group sex in the last 12 months. Multivariate analyses showed that men living with HIV, engaged in condomless anal intercourse with men, and used gay apps were more likely to engage in group sex, with adjusted ORs of 3.74 (95% CI 1.92–7.28), 2.88 (95% CI 2.00–4.16) and 1.46 (95% CI: 1.00–2.13), respectively. Among gay app users, the likelihood of group sex increases with the number of sex partners and the number of sex acts with partners met through a gay app.
Chinese MSM who engage in group sex are also more likely to engage in other risky sexual behaviors, and gay app use may facilitate group sex. Further research is needed among MSM who engage in group sex in order to target interventions and surveillance.
PMCID: PMC5120867  PMID: 27880823
21.  Cloning and characterization of TaVIP2 gene from Triticum aestivum and functional analysis in Nicotiana tabacum 
Scientific Reports  2016;6:37602.
Wheat is recalcitrant to genetic transformation. A potential solution is to manipulate the expression of some host proteins involved in T-DNA integration process. VirE2 interacting protein 2 (VIP2) plays an important role in T-DNA transport and integration. In this study, a TaVIP2 gene was cloned from common wheat. Southern blot and allele-specific polymerase chain reaction (AS-PCR) combined with an online chromosomal location software tool revealed that three TaVIP2 genes were located on wheat chromosomes 1AL, 1BL, and 1DL. These three homoeoallelic TaVIP2 genes all contained 13 exons and 12 introns, and their coding sequences were the same; there were a few single nucleotide polymorphisms (SNPs) among the three genes. The heterologous expression of the TaVIP2 gene in tobacco led to enhancement of the Agrobacterium-mediated transformation efficiency up to 2.5-fold. Transgenic tobacco plants expressing TaVIP2 showed enhanced resistance to powdery mildew. Further quantitative real-time PCR (qRT-PCR) revealed that overexpression of TaVIP2 in transgenic tobacco up-regulated the expression of an endogenous gene, NtPR-1, which likely contributed to powdery mildew resistance in transgenic tobacco. Our study indicates that the TaVIP2 gene may be highly useful in efforts to improve Agrobacterium-mediated transformation efficiency and to enhance powdery mildew resistance in wheat.
PMCID: PMC5114603  PMID: 27857194
22.  Characterization of radiographic features of consecutive lumbar spondylolisthesis 
Medicine  2016;95(46):e5323.
Radiographic features of consecutive lumbar spondylolisthesis were retrospectively analyzed in a total of 17 patients treated for this condition at the Third Hospital of Hebei Medical University from June 2005 to March 2012.
To investigate the radiographic features, pelvic compensatory mechanisms, and possible underlying etiologies of consecutive lumbar spondylolisthesis.
To the best of our knowledge, there is no previous report concerning the characteristics of consecutive lumbar spondylolisthesis.
The Taillard index and the lumbar lordosis (LL), pelvic incidence (PI), sacrum slope (SS), and pelvic tilt (PT) were determined on lateral X-ray images, and the angular displacement was analyzed on flexion–extension X-ray images. Correlation between LL and various pelvic parameters and correlation between Taillard index and angular displacement were assessed by Pearson correlation analysis.
A total of 20 cases of isthmic spondylolisthesis and 14 of degenerative spondylolisthesis were retrospectively studied in 17 patients. The Taillard index and the angular displacement in the lower vertebrae were both larger than those in the upper vertebrae. Statistical analysis revealed that LL was correlated with PI and PT, whereas PI was correlated with PT and SS. However, no correlation was identified between Taillard index and angular displacement.
In consecutive lumbar spondylolisthesis, the degree of vertebral slip and the angular displacement of the lower vertebrae were both greater than those of the upper vertebrae, indicating that the compensatory mechanism of the pelvis plays an important role in maintaining sagittal balance.
PMCID: PMC5120916  PMID: 27861359
angular displacement; consecutive lumbar spondylolisthesis; pelvic sagittal parameters; Taillard index
23.  Early initiation of renal replacement treatment in patients with acute kidney injury 
Medicine  2016;95(46):e5434.
Acute kidney injury (AKI) is associated with a substantially increased risk of mortality for many hospitalized patients. It has been suggested that early initiation of renal replacement treatment has a favorable outcome in critically ill patients complicated with AKI. However, results of studies evaluating the effect of early initiation strategy of renal replacement treatment on AKI have been controversial and contradictory. The aim of this meta-analysis is to examine the effect of early initiation of renal replacement treatment on patients with AKI.
The authors searched relevant studies in PubMed, EMBASE, and the Cochrane Library through August 2016. We searched for all eligible randomized controlled trials with regard to the role of early initiation of renal replacement treatment in mortality among patients with AKI. We extracted the following information from each study: mortality, length of stay in intensive care unit (ICU), and length of stay in hospital. Random and fixed effect models were used for pooling data.
Twelve trials including 1756 patients were included. The results of this meta-analysis showed that there was no significant difference between the mortality of early and delayed strategy for the initiation of renal replacement treatment using the random effect model (odds ratio = 0.78; 95% confidence interval [CI], 0.52–1.19; P = 0.25), with wild heterogeneity (chi2 = 33.50; I2 = 67%). Analyses from subgroup sepsis and postsurgery came to similar results. In addition, compared with delayed initiation strategy, early initiation showed no significant advantage in length of stay in ICU (mean difference = −0.80; 95% CI, −2.59 to 0.99; P = 0.56) and length of stay in hospital (mean difference = −7.69; 95% CI, −16.14 to 0.76; P = 0.07).
According to the results from present meta-analysis, early initiation of renal replacement treatment showed no survival benefits in patients with AKI. To achieve optimal timing of renal replacement treatment, further large multicenter randomized trials, with widely accepted and standardized definition of early initiation, are still needed.
PMCID: PMC5120945  PMID: 27861388
acute kidney injury; renal replacement therapy; time factors
24.  Functional Effect of the Mutations Similar to the Cleavage during Platelet Activation at Integrin β3 Cytoplasmic Tail when Expressed in Mouse Platelets 
PLoS ONE  2016;11(11):e0166136.
Previous studies in Chinese hamster ovary cells showed that truncational mutations of β3 at sites of F754 and Y759 mimicking calpain cleavage regulate integrin signaling. The roles of the sequence from F754 to C-terminus and the conservative N756ITY759 motif in platelet function have yet to be elaborated. Mice expressing β3 with F754 and Y759 truncations, or NITY deletion (β3-ΔTNITYRGT, β3-ΔRGT, or β3-ΔNITY) were established through transplanting the homozygous β3-deficient mouse bone marrow cells infected by the GFP tagged MSCV MigR1 retroviral vector encoding different β3 mutants into lethally radiated wild-type mice. The platelets were harvested for soluble fibrinogen binding and platelet spreading on immobilized fibrinogen. Platelet adhesion on fibrinogen- and collagen-coated surface under flow was also tested to assess the ability of the platelets to resist hydrodynamic drag forces. Data showed a drastic inhibition of the β3-ΔTNITYRGT platelets to bind soluble fibrinogen and spread on immobilized fibrinogen in contrast to a partially impaired fibrinogen binding and an almost unaffected spreading exhibited in the β3-ΔNITY platelets. Behaviors of the β3-ΔRGT platelets were consistent with the previous observations in the β3-ΔRGT knock-in platelets. The adhesion impairment of platelets with the β3 mutants under flow was in different orders of magnitude shown as: β3-ΔTNITYRGT>β3-ΔRGT>β3-ΔNITY to fibrinogen-coated surface, and β3-ΔTNITYRGT>β3-ΔNITY>β3-ΔRGT to collagen-coated surface. To evaluate the interaction of the β3 mutants with signaling molecules, GST pull-down and immunofluorescent assays were performed. Results showed that β3-ΔRGT interacted with kindlin but not c-Src, β3-ΔNITY interacted with c-Src but not kindlin, while β3-ΔTNITYRGT did not interact with both proteins. This study provided evidence in platelets at both static and flow conditions that the calpain cleavage-related sequences of integrin β3, i.e. T755NITYRGT762, R760GT762, and N756ITY759 participate in bidirectional, outside-in, and inside-out signaling, respectively and the association of c-Src or kindlin with β3 integrin may regulate these processes.
PMCID: PMC5112943  PMID: 27851790
25.  Profiling ribonucleotide and deoxyribonucleotide pools perturbed by gemcitabine in human non-small cell lung cancer cells 
Scientific Reports  2016;6:37250.
In this study, we investigated the dosage effect of gemcitabine, an inhibitor of ribonucleotide reductase (RR), on cellular levels of ribonucleotides and deoxyribonucleotides using high performance liquid chromatography-electrospray ionization tandem mass spectrometric method. As anticipated, after 4-h incubation of non-small cell lung cancer (A549) cells with gemcitabine at 0.5 and 2 μM, there were consistent reductions in levels of deoxyribonucleoside diphosphates (dNDP) and their corresponding deoxyribonucleoside triphosphates (dNTP). However, after 24-h exposure to 0.5 μM gemcitabine, the amounts of dNTP were increased by about 3 fold, whereas cells after 24-h 2 μM gemcitabine treatment exhibited deoxycytidine diphosphate (dCDP), deoxyadenosine diphosphate (dADP) and deoxyguanosine diphosphate (dGDP) levels less than 50% of control values, with deoxycytidine triphosphate (dCTP) and deoxyguanosine triphosphate (dGTP) returning to the control level. Using cell cycle analysis, we found that 24-h incubation at 0.5 μM gemcitabine resulted in a significant increase in S phase arrest, while 2 μM treatment increased G0/G1 population. Our data demonstrated the correlation between the level of RR and the increased levels of dNTPs in the group of 0.5 μM treatment for 24-h with a markedly reduced level of dFdCTP. Accordingly, we proposed that the dosage of dFdC could determine the arrested phase of cell cycle, in turn affecting the recovery of dNTPs pools.
PMCID: PMC5109029  PMID: 27845436

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