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Background: The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods.Methods: Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed.Results: The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD < 1.0 cm group (26.82%). The critical values of MAD and SCC-Ag in determining lymph node metastasis were 1.0 cm and 5.2 ng/mL, respectively. The accuracy, specificity, and Youden index of MAD ≥1.0 cm combined with SCC-Ag ≥ 5.2 ng/mL for evaluating lymph node metastasis were 75.71%, 100%, and 0.59, respectively, and were significantly different from the values for the MAD ≥1.0 cm (72.09%, 80.56%, and 0.47, respectively) and SCC-Ag ≥ 5.2 ng/mL (71.43%, 68.97%, and 0.42, respectively) groups. Correlation analysis showed that non-squamous cell carcinoma, pelvic lymph node (PLN) MAD ≥1.0 cm plus number ≥ 2, and 1 PLN MAD ≥1.0 cm with CILN and/or PALN MAD 0.5-1.0 cm were risk factors for CILN and/or PALN metastasis.Conclusion: Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD < 1.0 cm and SCC-Ag < 5.2 ng/mL may be treated with chemoradiotherapy directly based on imaging, given the low lymph node metastasis rate. [ABSTRACT FROM AUTHOR]

Background: This study investigated UGP2 (uridine diphosphate-glucose pyrophosphorylase-2) and CFL1 (cofilin-1) expression in pancreatic ductal carcinoma (PDC), paracancerous tissue (PT), benign lesions (BL), and normal tissue (NT) and their clinicopathological significance. Methods: Surgical specimens, which were collected from 106 cases of pancreatic ductal carcinoma, 35 cases of paracancerous tissues, 55 cases of benign lesions and 13 cases of normal pancreatic tissues, were fixed with 4% formaldehyde to prepare conventional paraffin-embedded sections. EnVision immunohistochemical was used to stain for UGP2 and CFL1. Kaplan-Meier survival analysis was performed to assess the correlation of expression pattern with survival. Results: We found that positive UGP2 and CFL1 expression in PDC were significantly higher than those in PT, BL, and NT. In PT and BL with positive UGP2 and CFL1 expression, mild to severe atypical hyperplasia or intraepithelial neoplasia of grades II-III was observed in ductal epithelium. Positive UGP2 and CFL1 expression in cases with high differentiation, no lymph node metastasis, no surrounding invasion, and TNM (tumor-node-metastasis) staging I or/and II were significantly lower than those in cases with poor differentiation, lymph node metastasis, surrounding invasion, and TNM stage III and/or IV. Positive UGP2 expression in male patients was significantly lower than that in female patients. UGP2 and CFL1 expression in PDC were positively correlated. Kaplan-Meier survival analysis showed the degree of differentiation, tumor maximal diameter, TNM stage, lymph node metastasis, and surrounding invasion, and UGP2 and CFL1 expression were closely related to the average survival time of patients with PDC. The survival time of patients with positive UGP2 and CFL1 expression was significantly shorter than that of patients with negative expression. Cox multivariate analysis showed that poor differentiation, tumor maximal diameter = 3 cm, TNM stage III or IV, lymph node metastasis, surrounding invasion, and positive UGP2 and CFL1 expression was negatively correlated with the postoperative survival rate and positively correlated with the mortality of patients with PDC. Conclusion: Positive expression of UGP2 and CFL1 can serve a valuable prognostic factor in pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Loss of neural function is a critical but unsolved issue after cerebral ischemia insult. Neuronal plasticity and remodeling are crucial for recovery of neural functions after brain injury. Buyang Huanwu decoction, which is a classic formula in traditional Chinese medicine, can positively alter synaptic plasticity. This study assessed the effects of Buyang Huanwu decoction in combination with physical exercise on neuronal plasticity in cerebral ischemic rats. Methods: Cerebral ischemic rats were administered Buyang Huanwu decoction and participated in physical exercise after the induction of a permanent middle cerebral artery occlusion. The neurobehavioral functions and infarct volumes were evaluated. The presynaptic (SYN), postsynaptic (GAP-43) and cytoskeletal (MAP-2) proteins in the coronal brain samples were evaluated by immunohistochemistry and western blot analyses. The ultrastructure of the neuronal synaptic junctions in the same region were analyzed using transmission electron microscopy. Results: Combination treatment of Buyang Huanwu decoction and physical exercise ameliorated the neurobehavioral deficits (p < 0.05), significantly enhanced the expression levels of SYN, GAP-43 and MAP-2 (p < 0.05), and maintained the synaptic ultrastructure. Conclusions: Buyang Huanwu decoction facilitated neurorehabilitation following a cerebral ischemia insult through an improvement in synaptic plasticity. [ABSTRACT FROM AUTHOR]

Background: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7), inducers of G1 cell cycle arrest, are two recently discovered good biomarkers for early diagnosis of acute kidney injury (AKI). To obtain a more robust performance measurement, the present meta-analysis was performed, pooling existing studies.Methods: Literature in the MEDLINE (via PubMed), Ovid, Embase, and Cochrane Library databases was systematically searched from inception to 12 October 2016. Studies that met the set inclusion and exclusion criteria were identified by two independent investigators. The diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was evaluated by pooled sensitivity, specificity, likelihood ratio (LR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curve analyses. The causes of heterogeneity were explored by sensitivity and subgroup analyses.Results: A total of nine published and eligible studies assessing 1886 cases were included in this meta-analysis. Early diagnostic value of urinary [TIMP-2] × [IGFBP7] for AKI was assessed using a random-effects model. Pooled sensitivity and specificity with corresponding 95% CIs were 0.83 (95% CI 0.79-0.87, heterogeneity I 2  = 68.8%) and 0.55 (95% CI 0.52-0.57, I 2  = 92.9%), respectively. Pooled positive LR, negative LR, and DOR were 2.37 (95% CI 1.87-2.99, I 2  = 82.6%), 0.30 (95% CI 0.21-0.41, I 2  = 43.4%), and 9.92 (95% CI 6.09-16.18, I 2  = 38.5%), respectively. The AUC estimated by SROC was 0.846 (SE 0.027) with a Q* value of 0.777 (SE 0.026). Sensitivity analysis indicated that one study significantly affected the stability of pooled results. Subgroup analysis showed that population setting and AKI threshold were the key factors causing heterogeneity in pooled sensitivity and specificity.Conclusions: On the basis of recent evidence, urinary [TIMP-2] × [IGFBP7] is an effective predictive factor of AKI.Trial Registration: PROSPERO registration number: CRD42016051186 . Registered on 10 November 2016. [ABSTRACT FROM AUTHOR]

Background: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.Methods: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included.Results: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036).Conclusions: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Susceptible barcode recognition plays an important role in the diagnosis and treatment of complex diseases. Numerous approaches have been proposed to identify risky barcodes involved in the progress of complex diseases. However, some methods only consider differences in barcode frequencies between the control and disease groups; as such, these methods may be partial or even wrong. For example, some barcodes with a high risk ratio yield a low frequency on cases or exhibit a high frequency on controls, which may unreasonable from a statistical point. Results: In our study, a stricter criteria, maximum discrepancy and maximum constituency, is designed to evaluate each barcode and ant colony algorithm is used to search combination space of epistasis. For complex diseases with multi-subtypes, our method can list several potential barcodes contributing to different subtypes of complex diseases. Another contribution of this work is to introduce a method for determining the length of barcodes and excluding noisy barcodes whose frequencies are abnormal. In addition, common pathogenic genes shared by different risky barcodes are also recognized, which may provide key clue for further study, such as gene function analysis. Conclusions: Experimental results reveal that our method can find multiple risky barcodes whose risk ratio and odds ratio are >1. These barcodes could be related to different subtypes of complex diseases. [ABSTRACT FROM AUTHOR]

Background: Cervical spondylosis is a very common disorder and cervical spondylotic radiculopathy (CSR) is the most common form of spinal degenerative disease. Its clinical manifestations focus on pain and numbness of the neck and arm as well as restricted movement of the neck, which greatly affect the patient's life and work. The orthopedic of traditional Chinese medicine (TCM) theory holds that the basic pathologic change in spinal degenerative diseases is the imbalance between the dynamic system and the static system of the cervical spine. Based on this theory, some Chinese physicians have developed a balance chiropractic therapy (BCT) to treat CSR, which has been clinically examined for more than 50 years to effectively cure CSR. The purpose of this study is to evaluate the therapeutic effect and safety of BCT on CSR and to investigate the mechanism by which the efficacy is achieved. Methods/design: We propose a multicenter, parallel-group, randomized controlled trial to evaluate the efficacy and safety of BCT for CSR. Participants aged 18 to 65 years, who are in conformity with the diagnostic criteria of CSR and whose pain score on a Visual Analog Scale (VAS) is more than 4 points and less than 8 points, will be included and randomly allocated into two groups: a treatment group and a control group. Participants in the treatment group will be treated with BCT, while the control group will receive traction therapy (TT). The primary outcome is pain severity (measured with a VAS). Secondary outcomes will include cervical curvature (measured by the Borden Index), a composite of functional status (measured by the Neck Disability Index, NDI), patient health status (evaluated by the SF-36 health survey) and adverse events (AEs) as reported in the trial. Discussion: If BCT can relieve neck pain without adverse effects, it may be a novel strategy for the treatment of CSR. Furthermore, the mechanism of BCT for CSR will be partially elucidated. Trial registration: Clinical Trials.gov Identifier: NCT02705131. Registered on 9 March 2016. [ABSTRACT FROM AUTHOR]

Background: This paper seeks to assess the function of malaria control consultation and service posts (MCCSPs) that are located on the border areas of Yunnan province, P.R. China, as a strategy for eliminating malaria among the mobile and migrant population in these areas. Methods: A retrospective descriptive analytical study was conducted. Blood smear examinations conducted at all MCCSPs in Yunnan from 2008 to 2014 were analysed. A cross-sectional survey was conducted in 2014 to understand how the MCCSPs function and to elucidate the quality of the blood smear examinations that they conduct. Results: Out of the surveyed MCCSPs, 66 % (39/59), 22 % (13/59), and 12 % (7/59) were attached to local township hospitals, village health clinics, and the county centre for disease control and prevention or private clinics, respectively. More than 64 % (38/59) of the posts' staff were part-time workers from township hospitals and village health facilities. Less than 31 % (18/59) of the posts' staff were full-time workers. A total of 35 positive malaria cases were reported from seven MCCSPs in 2014. Four MCCSPs were unable to perform their functions due to under staffing in 2014. There was a small fluctuation in blood smear examinations from January 2008 to June 2009, with two peaks during the period from July 2009 to October 2010. The number of blood smear examinations has been increasing since 2011. The yearly mean number of blood smear examinations in each post increased from 44 per month in 2011 to 109 per month in 2014, and the number of positive malaria cases detected by blood smear examinations has declined (χ2 = 90.67, P = 0.000). The percentage of people from Yingjiang county getting blood smear examinations increased between 2008 and 2014, while percentages of the mobile population including Myanmar people, people from other provinces, and people from other Yunnan counties getting blood smear examinations decreased. Conclusion: MCCSPs face challenges in the phase of malaria elimination in Yunnan, China. New case detection strategies should be designed for MCCSPs taking into account the current trends of migration. [ABSTRACT FROM AUTHOR]

Background: The responses of immunological factors to different subtypes of Kawasaki disease (KD) remain poorly understood.Methods: We recruited 388 patients with KD, 160 patients with infectious febrile disease and 85 normal children who served as control subjects. Both the levels and percentages of T lymphocyte subsets, natural killer cells (NK cells) and B cells were analyzed via flow cytometry. The levels of serum IgG, IgM, IgA and C3, C4 were assessed via velocity scatter turbidimetry.Results: The most significant differences noted between the patients with infectious febrile disease and the normal children were the elevated levels of B cells, C3 and the ratio of CD4/CD8, and the decreased levels of CD8+ T cells and NK cells, as well as the moderate increase in the absolute value of the CD3+ cells. The decreased T cell levels and the elevated B cell levels were helpful in distinguishing typical KD from atypical KD; the elevated T cell levels, the elevated NK cell and B cell levels and the decreased B cell levels were helpful in predicting the effectiveness of IVIG; low C3 and C4 levels were linked with prodromal infections.Conclusions: Lymphocytes subsets and complement markers may be useful in differentiating among the different subtypes of KD and in helping clinicians understand the pathophysiology of KD. [ABSTRACT FROM AUTHOR]

Background: Porcine reproductive and respiratory syndrome (PRRS) is characterized by severe reproductive failure and severe pneumonia in neonatal pigs and is caused by PRRS virus (PRRSV). Glycoprotein 5 (GP5) from PRRSV is a key inducer of neutralizing antibodies. Flagellin, a toll-like receptor 5 (TLR-5) agonist, is an effective inducer of innate immune responses. This study presents a novel PRRSV vaccine candidate based on the adjuvant effect of Salmonella Typhimurium FljB fused with PRRSV GP5. Results: A truncated rGP5 gene lacking the signal peptide and transmembrane sequences was amplified and inserted into prokaryotic expression vectors, pColdI or pGEX-6p-1. Salmonella Typhimurium flagellin fljB was amplified and inserted into the plasmid pCold-rGP5, generating recombinant plasmid pCold-rGP5-fljB. Histidine (His)-tagged rGP5 and fusion protein rGP5-FljB were induced with isopropyl-β-d-thiogalactoside, verified by SDS-PAGE and western blotting, and purified via Ni-NTA affinity columns. The TLR-5-specific bioactivity of fusion protein rGP5-FljB was determined by detecting the expression levels of the cytokine IL-8 in HEK293-mTLR5 cells by sandwich ELISA. The purified endotoxin-free proteins were administered intraperitoneally in a C3H/HeJ mouse model. The results show that immunization with the fusion protein rGP5-FljB induced a significantly enhanced GP5-specific and PRRSV-specific IgG response that persisted for almost 5 weeks. Co-administration of the rGP5 with R848 or Alum also yielded a higher IgG response than administration of rGP5 alone. The IgG1/IgG2a ratio in the rGP5-FljB immunization group was significantly higher (9-fold) than that in the rGP5 alone group and was equivalent to the response in the rGP5 + Alum immunization group, suggesting a strong Th2 immune response was induced by the fusion protein. Conclusions: Purified fusion protein rGP5-FljB is capable of activating the innate immune response, as demonstrated by the results of our TLR-5-specific bioactivity assay, and FljB has adjuvant activity, as shown by the results from our administration of rGP5-FljB in a mouse model. Our findings confirm that FljB could serve as an excellent adjuvant for the production of GP5-specific and PRRSV-specific IgG antibodies as part of an induction of a robust humoral immune response. [ABSTRACT FROM AUTHOR]

Background: The mouse is an organism that is widely used as a mammalian model for studying human physiology or disease, and the development of immunodeficient mice has provided a valuable tool for basic and applied human disease research. Following the development of large-scale mouse knockout programs and genome-editing tools, it has become increasingly efficient to generate genetically modified mouse strains with immunodeficiency. However, due to the lack of a standardized system for evaluating the immuno-capacity that prevents tumor progression in mice, an objective choice of the appropriate immunodeficient mouse strains to be used for tumor engrafting experiments is difficult. Methods: In this study, we developed a tumor engraftment index (TEI) to quantify the immunodeficiency response to hematologic malignant cells and solid tumor cells of six immunodeficient mouse strains and C57BL/6 wild-type mouse (WT). Results: Mice with a more severely impaired immune system attained a higher TEI score. We then validated that the NOD-scid-IL2Rg-/-(NSI) mice, which had the highest TEI score, were more suitable for xenograft and allograft experiments using multiple functional assays. Conclusions: The TEI score was effectively able to reflect the immunodeficiency of a mouse strain. [ABSTRACT FROM AUTHOR]

Background: Genitourinary embryonal rhabdomyosarcoma is rarely reported in China. This retrospective analysis aimed to characterize the clinicopathologic features and treatment outcomes of genitourinary embryonal rhabdomyosarcoma in a sample of Chinese patients. Methods: Basic demographic and clinical data of 29 patients, who were diagnosed with genitourinary embryonal rhabdomyosarcoma between January 2000 and December 2011, were retrieved and analyzed. Results: In these patients, 25 were males and 4 were females with a median age of 12 years. Paratesticule was the most common lesion site, followed by the prostate, bladder, and vagina. The median tumor size was 5.80 cm. Six patients had clinically positive regional nodes. At the initial diagnosis, patients had a metastatic disease. According to the TNM staging classification for the IRS-IV, phase I lesions were detected in ten cases, phase II lesions in six cases, phase III lesions in four cases, and phase IV lesions in nine cases. The median survival of all patients was 63 (range from 6 to 118) months. The 1-, 3-, and 5-year survival rates for these patients were 93%, 83%, and 52%, respectively. Multivariate analyses demonstrated that staging and anemia were significant predictors of prognosis. Conclusions: Our findings suggest that metastasis predicts a poor prognosis. Chemotherapy played an important role in comprehensive treatment. Palliative and neo-adjuvant chemotherapy could increase median survival time. [ABSTRACT FROM AUTHOR]

Background: A large number of single nucleotide polymorphisms (SNPs) associated with cervical cancer have been identified through candidate gene association studies and genome-wide association studies (GWAs). However, some studies have yielded different results for the same SNP. To obtain a more comprehensive understanding, we performed a meta-analysis on previously published case–control studies involving the SNPs associated with cervical cancer. Methods: Electronic searches of PubMed and Embase were conducted for all publications about the association between gene polymorphisms and cervical cancer. One-hundred and sixty-seven association studies were included in our research. For each SNP, three models (the allele, dominant and recessive effect models) were adopted in the meta-analysis. For each model, the effect summary odds ratio (OR) and 95% CI were calculated. Heterogeneity between studies was evaluated by Cochran’s Q test. If the p value of Q test was less than 0.01, a random effect model was used; otherwise, a fixed effect model was used. Results: The results of our meta-analysis showed that: (1) There were 8, 2 and 8 SNPs that were significantly associated with cervical cancer (P < 0.01) in the allele, dominant and recessive effect models, respectively. (2) rs1048943 (CYP1A1 A4889G) showed the strongest association with cervical cancer in the allele effect model (1.83[1.57, 2.13]); in addition, rs1048943 (CYP1A1 A4889G) had a very strong association in the dominant and recessive effect model. (3) 15, 11 and 10 SNPs had high heterogeneity (P < 0.01) in the three models, respectively. (4) There was no published bias for most of the SNPs according to Egger’s test (P < 0.01) and Funnel plot analysis. For some SNPs, their association with cervical cancer was only tested in a few studies and, therefore, might have been subjected to published bias. More studies on these loci are required. Conclusion: Our meta-analysis provides a comprehensive evaluation of cervical cancer association studies. [ABSTRACT FROM AUTHOR]

Background: Bushen-Qiangdu-Zhilv Decoction (BQZ) is one of famous traditional Chinese medical formula for treating ankylosing spondylitis (AS). However, the mechanisms underlying effects of BQZ remains unknown. Pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1, play an important role in AS. We therefore evaluated if BQZ could affect the expression of these cytokines. Methods: Crude extracts were prepared and fractioned with petroleum ether (PE), ethyl acetate (EA), n-butanol (BU) and finally water (ACE). The stability of the extracts was confirmed by high-pressure liquid chromatography (HPLC) analysis. M1-polarized RAW264.7 was induced and subsequently treated with BQZ extracts. Quantitative real-time PCR experiments were performed to measure mRNA expression of TNF-α and IL-1. Results: It was found that TNF-α could be significantly suppressed by ACE extracts, whereas IL-1 was dramatically inhibited by BU extracts, which was further confirmed by dose-dependent experiments. Importantly, MTS assays showed that both ACE and BU extracts had a low cytotoxicity. Conclusion: Altogether, our study indicates that BQZ decoction exerts anti-AS effects via its anti-inflammatory activity and may have a low side-effect. Further analysis of the extracts of BQZ decoction could lead to a discovery of some novel drugs adding to therapeutic strategy for AS patients. [ABSTRACT FROM AUTHOR]

Background: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) in patients with residual nasopharyngeal carcinoma (NPC). Methods: From January 2000 to December 2009, 136 NPC patients with residual lesions after primary radiotherapy (RT) were treated by FSRT. The total dose of primary RT was 68.0-78.0 Gy (median, 70.0 Gy). The median time from the primary RT to FSRT was 24.5 days. Tumor volumes for FSRT ranged from 0.60 to 77.13 cm3 (median, 13.45 cm3). The total FSRT doses were 8.0-32.0Gy (median, 19.5 Gy) with 2.0-10.0 Gy per fraction. Results: Five-year local failure-free survival (LFFS), freedom from distant metastasis (FFDM), overall survival (OS), and disease free survival (DFS) rates for all patients were 92.5%, 77.0%, 76.2%, and 73.6%, respectively. No statistical significant differences were found in LFFS, DFS and OS in patients with stage I/II versus stage III/ IV diseases. Nineteen patients exhibited late toxicity. T stage at diagnosis was a significant prognostic factor for OS and DFS. Age was a prognostic factor for OS. Conclusion: FSRT after external beam radiotherapy provides excellent local control for patients with residual NPC. The incidence of severe late toxicity is low and acceptable. Further investigation of optimal fractionation regimens will facilitate reduction of long-term complications. [ABSTRACT FROM AUTHOR]

Currently, Saphenous vein (SV) and internal thoracic artery (ITA) are still the most common graft materials in Coronary Artery Bypass Grafting (CABG) whereas SV graft have a lower long-term patency than ITA. Vascular smooth muscle cells (VSMCs) phenotype conversion, proliferation and migration may play a key role in mechanism of vein graft restenosis. To explore differential gene expression profile in VSMCs from SV and ITA will help to further elucidate the mechanism of VSMCs in vein graft restenosis after CABG and to provide new thread of gene therapy. Methods: VSMCs from paired SV and ITA were cultured for experiments of Affymetrix microarrays and verification using FQ RT-PCR, while the database for annotation, visualization and integrated discovery bioinformatics resources (DAVID 2.0) was utilized for bioinformatics analysis of differential gene expression profile between SV VSMCs and ITA VSMCs. RNA of tunica media from SV and ITA segments were extracted for FQ RT-PCR to display differential expression of PLAT Results: 54,613 probe sets were examined by gene microarray experiments. In SV VSMCs, 1,075 genes were up-regulated and 406 of them were higher than two-fold; 1,399 genes were down-regulated and 424 of them were lower than two-fold as compare with ITA VSMCs.14 ECM-related genes differentially expressed were verificated and listed as following: COL4A4, COL11A1, FN1, TNC, THBS, FBLN, MMP3, MMP9, TIMP3, WNT5A, SGCD were higher whereas COL14A1, ELN, PLAT lower in SV VSMCs than ITA VSMCs. In addition, PLAT was lower in tunica media from SV segments than ITA. Conclusion: VSMCs from SV and ITA have distinct phenotypes characteristics. Both promoting and inhibiting migration ECM-related genes were higher in VSMCs from SV as compared with ITA, suggesting that VSMCs from SV have more potential migrating capability whereas less PLAT both in SV VSMCs and vascular tissue,implying that SV may prone to be restenosis after CABG. [ABSTRACT FROM AUTHOR]

Background: A key challenge in the post genome era is to identify genome-wide transcriptional regulatory networks, which specify the interactions between transcription factors and their target genes. Numerous methods have been developed for reconstructing gene regulatory networks from expression data. However, most of them are based on coarse grained qualitative models, and cannot provide a quantitative view of regulatory systems. Results: A binding affinity based regulatory model is proposed to quantify the transcriptional regulatory network. Multiple quantities, including binding affinity and the activity level of transcription factor (TF) are incorporated into a general learning model. The sequence features of the promoter and the possible occupancy of nucleosomes are exploited to estimate the binding probability of regulators. Comparing with the previous models that only employ microarray data, the proposed model can bridge the gap between the relative background frequency of the observed nucleotide and the gene's transcription rate. Conclusions: We testify the proposed approach on two real-world microarray datasets. Experimental results show that the proposed model can effectively identify the parameters and the activity level of TF. Moreover, the kinetic parameters introduced in the proposed model can reveal more biological sense than previous models can do. [ABSTRACT FROM AUTHOR]

Background: The Janus kinase (JAK) family of tyrosine kinases includes JAK1, JAK2, JAK3 and TYK2, and is required for signaling through Type I and Type II cytokine receptors. CP-690,550 is a potent and selective JAK inhibitor currently in clinical trials for rheumatoid arthritis (RA) and other autoimmune disease indications. In RA trials, dosedependent decreases in neutrophil counts (PBNC) were observed with CP-690,550 treatment. These studies were undertaken to better understand the relationship between JAK selectivity and PBNC decreases observed with CP-690,550 treatment. Methods: Potency and selectivity of CP-690,550 for mouse, rat and human JAKs was evaluated in a panel of in vitro assays. The effect of CP-690,550 on granulopoiesis from progenitor cells was also assessed in vitro using colony forming assays. In vivo the potency of orally administered CP-690,550 on arthritis (paw edema), plasma cytokines, PBNC and bone marrow differentials were evaluated in the rat adjuvant-induced arthritis (AIA) model. Results: CP-690,550 potently inhibited signaling through JAK1 and JAK3 with 5-100 fold selectivity over JAK2 in cellular assays, despite inhibiting all four JAK isoforms with nM potency in in vitro enzyme assays. Dose-dependent inhibition of paw edema was observed in vivo with CP-690,550 treatment. Plasma cytokines (IL-6 and IL-17), PBNC, and bone marrow myeloid progenitor cells were elevated in the context of AIA disease. At efficacious exposures, CP-690,550 returned all of these parameters to pre-disease levels. The plasma concentration of CP-690,550 at efficacious doses was above the in vitro whole blood IC50 of JAK1 and JAK3 inhibition, but not that of JAK2. Conclusion: Results from this investigation suggest that CP-690,550 is a potent inhibitor of JAK1 and JAK3 with potentially reduced cellular potency for JAK2. In rat AIA, as in the case of human RA, PBNC were decreased at efficacious exposures of CP-690,550. Inflammatory end points were similarly reduced, as judged by attenuation of paw edema and cytokines IL-6 and IL-17. Plasma concentration at these exposures was consistent with inhibition of JAK1 and JAK3 but not JAK2. Decreases in PBNC following CP-690,550 treatment may thus be related to attenuation of inflammation and are likely not due to suppression of granulopoiesis through JAK2 inhibition. [ABSTRACT FROM AUTHOR]

Key message: The vertical transport of dissolved organic carbon (DOC) is an important determinant of carbon distribution across a soil profile. The transport of DOC down a soil profile can be largely influenced by incoming DOC and soil organic carbon (SOC) levels, which insulate DOC from adsorption processes regulated by soil texture and Fe/Al mineralogy.Context: Uncertainties about how soil properties affect DOC transport through the soil profile require study because soils can differ strongly with respect to texture or Fe/Al mineralogy and yet retain similar quantities of DOC.Aims: This study aimed to assess the role of incoming DOC and native SOC in regulating DOC migration in soils and investigate the contribution of DOC movement to SOC allocation.Methods: We leached a standard DOC solution extracted from Castanopsis carlesii litter through two distinct soil types, using two leaching strategies: single leaching and sequential leaching. The two soil types under a natural Castanopsis carlesii (Hemsl.) Hayata forest and a natural Castanopsis fargesii Franch. forest, respectively, differ strongly with respect to soil texture, Fe/Al oxide abundances, and SOC nature.Results: With single leaching, where each of six soil layers making up an entire 0-100-cm soil depth profile received single doses of standard DOC solution, deeper soil layers retained more DOC than upper soil layers, with native SOC largely masking the effects of soil texture and Fe/Al mineralogy on DOC migration. Following sequential leaching, where a sixfold larger amount of standard DOC solution sequentially percolated through the six soil layers, the upper soil layers generally retained more DOC than deeper layers. Nevertheless, in sequential leaching, desorption-induced transfer of carbon from upper soil layers to deeper soil layers resulted in greater total carbon retention than in single leaching.Conclusion: Forest subsoils (40-100 cm) are well below C saturation, but DOC vertical movement from top soils only transfers limited organic carbon to them. However, DOC vertical movement may greatly alter SOC allocation along the top soil profile (0-40 cm), with part of outer sphere native SOC displaced by incoming DOC and migrating downwards, which is a natural way to preserve SOC. [ABSTRACT FROM AUTHOR]

Background: Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments.Results: PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group.Conclusion: We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia. [ABSTRACT FROM AUTHOR]

Background: The purpose of this case series is to investigate the relationship between splenic thickness (ST) and postoperative outcomes after hepatic resection in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients., Methods: The clinical data of 320 patients with HBV-associated HCC who had undergone liver resection were retrospectively analyzed. The value of ST in predicting postoperative outcomes was evaluated., Results: A total of 320 patients were enrolled in the study. An increase in ST was significantly associated with an increase in portal vein diameter (PVD), indocyanine green retention rate 15 min (ICG R15), and total bilirubin (TBIL); however, it was negatively correlated with platelet count (PLT). Post-hepatectomy liver failure (PHLF) occurred in 35 (10.9%) patients. Multivariate logistic regression analysis showed that ST was an independent predictor of morbidity and mortality after hepatectomy. Meanwhile, ST was associated with an almost sixfold increased risk for developing perioperative complications (OR 5.678; 95% CI 2.873 to 11.224; P < 0.001) and almost 13-fold increased risk for mortality after hepatectomy (OR 13.007; 95% CI 1.238 to 136.627; P = 0.033).The area under the receiver operating characteristic (ROC) curve (AUC) of ST for predicting the incidence of PHLF was 0.754 (95% confidence interval (CI) 0.667 to 0.841; P < 0.001), with a sensitivity of 57.1% and a specificity of 82.5%, which were significantly greater than those of the ICG R15 level (AUC 0.670; 95% CI 0.560 to 0.779; P < 0.001). The critical value of ST was 43.5 mm., Conclusions: ST, which is an easy, inexpensive, and routinely available perioperative marker, showed a favorable predictive value for postoperative outcomes in HBV-associated HCC patients.

The outsourcing of genomic data into public cloud computing settings raises concerns over privacy and security. Significant advancements in secure computation methods have emerged over the past several years, but such techniques need to be rigorously evaluated for their ability to support the analysis of human genomic data in an efficient and cost-effective manner. With respect to public cloud environments, there are concerns about the inadvertent exposure of human genomic data to unauthorized users. In analyses involving multiple institutions, there is additional concern about data being used beyond agreed research scope and being prcoessed in untrused computational environments, which may not satisfy institutional policies. To systematically investigate these issues, the NIH-funded National Center for Biomedical Computing iDASH (integrating Data for Analysis, 'anonymization' and SHaring) hosted the second Critical Assessment of Data Privacy and Protection competition to assess the capacity of cryptographic technologies for protecting computation over human genomes in the cloud and promoting cross-institutional collaboration. Data scientists were challenged to design and engineer practical algorithms for secure outsourcing of genome computation tasks in working software, whereby analyses are performed only on encrypted data. They were also challenged to develop approaches to enable secure collaboration on data from genomic studies generated by multiple organizations (e.g., medical centers) to jointly compute aggregate statistics without sharing individual-level records. The results of the competition indicated that secure computation techniques can enable comparative analysis of human genomes, but greater efficiency (in terms of compute time and memory utilization) are needed before they are sufficiently practical for real world environments.

Background: Pancreatic cancer ranks as the fourth leading cause of cancer-related mortality in the USA. And gemcitabine has been the standard of care for advanced pancreatic cancer. However, a combined use of gemcitabine plus cisplatin (GemCis) has shown promising efficacies in pancreatic cancer patients. Here, system review and meta-analysis were performed to compare the efficacy and safety of GemCis versus gemcitabine (Gem) alone in the treatment of pancreatic cancer., Methods: The databases of MEDLINE (PubMed), EMBASE, and Cochrane Library were systematically searched for retrieving the relevant publications prior to 31 September 2014. The primary end point was overall survival (OS) and secondary end points included 6-month survival, 1 year survival, overall response rate (ORR), clinical benefit rate (CBR), time to progression/progression-free survival (TTP/PFS), and toxicities., Results: A total of nine randomized controlled trials involving 1354 patients were included for systematic evaluations. Overall, as compared with Gem alone, GemCis significantly improved the 6-month survival rate (relative risk (RR) = 1.303, 95% confidence interval (CI) 1.090-1.558, P = 0.004), ORR (RR = 1.482, 95% CI 1.148-1.913, P = 0.003), PFS/TTP (hazard ratio (HR) = 0.87; 95% CI 0.78-0.93, P = 0.022), and the overall toxicities (RR = 2.164, 95% CI 1.837-2.549, P = 0.000). However, no significance difference existed in overall survival (HR = 0.90, 95% CI 0.80-1.42, P = 1.02), 1-year survival rate (RR = 0.956, 95% CI 0.770-1.187, P = 0.684), and CBR (RR = 0.854, 95% CI 0.681-1.072, P = 0.175). As for grade III/IV toxicity, seven kinds of toxicities were higher in the GemCis group. However, no significant inter-group statistical differences existed in the incidence of leukopenia, thrombocytopenia, or diarrhea., Conclusions: Despite a higher incidence of three-fourths toxicity, GemCis offers better outcomes of ORR, PFS/TTP, and 6-month survival, which indicates GemCis may be a promising therapy for pancreatic cancer.

Background: Penicillium digitatum is one of the most destructive postharvest pathogen of citrus fruits, causing fruit decay and economic loss. The emergence of fungicide-resistant strains made the control of P. digitatum more difficult. While the genome of P. digitatum is available, there has been few reports about its resistant mechanism from the transcriptome perspective and there has been no large-scale functional annotation of the genome using expressed genes derived from transcriptomes., Methods: Total RNA of P. digitatum strain HS-F6 (prochloraz-resistant strain) and HS-E3 (prochloraz-susceptible strain) before and after prochloraz-treatment were extracted and sequenced on an Illumina Hiseq 2000 platform. The transcriptome data of four samples were compared and analyzed using differential expression analysis, novel transcripts prediction and alternative splicing analysis, SNP analysis and quantitative real-time PCR., Results: We present a large scale analysis about the transcriptome data of P. digitatum. The whole RNA was extracted from a prochloraz-resistant strain (HS-F6) and a prochloraz-susceptible strain (HS-E3) before and after prochloraz-treatment and sequenced by Illumina technology. A total of more than 100 million reads were generated and de novo assembled into 9760 transcripts that contained annotated genes after quality control and sequence assembling. 6625 single nucleotide variations (SNVs) were identified from the sequences aligned against the reference genome. Gene expression profiling analysis was performed upon prochloraz treatment in HS-F6 and HS-E3, and differential expression analysis was used to identify genes related to prochloraz-response and drug-resistance: there are 224 differentially expressed genes in HS-E3 and 1100 differentially expressed genes in HS-F6 after prochloraz-treatment. Moreover, gene expression profile in prochloraz-resistant strain HS-F6 is quite different from that in HS-E3 before prochloraz-treatment, 1520 differential expression genes were identified between the two strains. Gene ontology (GO) term enrichment and KEGG enrichment were then performed to classify the differential expression genes. Among these genes, there are a lot of transporter encoding genes including 14 MFS (Major Facilitator Superfamily) transporters, 8 ABC (ATP-binding cassette transporter) and 3 MATE (multidrug and toxic compound extrusion family) transporters. Meanwhile, the roles of typical MFS, ABC and MATE proteins in prochloraz resistance were investigated using real-time quantitative PCR., Conclusions: The sequencing-based transcriptome data of P. digitatum demonstrate differences between prochloraz-resistant and prochloraz-susceptible strains with prochloraz-treatment. The differences existed in expressed transcripts, splice isoforms and GO categories, which would contribute to our knowledge on the molecular mechanisms involved in drug resistance of P. digitatum.

Background: The responses of immunological factors to different subtypes of Kawasaki disease (KD) remain poorly understood., Methods: We recruited 388 patients with KD, 160 patients with infectious febrile disease and 85 normal children who served as control subjects. Both the levels and percentages of T lymphocyte subsets, natural killer cells (NK cells) and B cells were analyzed via flow cytometry. The levels of serum IgG, IgM, IgA and C3, C4 were assessed via velocity scatter turbidimetry., Results: The most significant differences noted between the patients with infectious febrile disease and the normal children were the elevated levels of B cells, C3 and the ratio of CD4/CD8, and the decreased levels of CD8+ T cells and NK cells, as well as the moderate increase in the absolute value of the CD3+ cells. The decreased T cell levels and the elevated B cell levels were helpful in distinguishing typical KD from atypical KD; the elevated T cell levels, the elevated NK cell and B cell levels and the decreased B cell levels were helpful in predicting the effectiveness of IVIG; low C3 and C4 levels were linked with prodromal infections., Conclusions: Lymphocytes subsets and complement markers may be useful in differentiating among the different subtypes of KD and in helping clinicians understand the pathophysiology of KD.

Background: Aberrant hypermethylation of gene promoter regions is a primary mechanism by which tumor suppressor genes become inactivated in breast cancer. Epigenetic inactivation of the protein tyrosine phosphatase receptor-type O gene (PTPRO) has been described in several types of cancer., Results: We screened primary breast cancer tissues for PTPRO promoter hypermethylation and assessed potential associations with pathological features and patient outcome. We also evaluated its potential as a breast cancer biomarker. PTPRO methylation was observed in 53 of 98 (54%) breast cancer tissues but not in adjacent normal tissue. Among matched peripheral blood samples from breast cancer patients, 33 of 98 (34%) exhibited methylated PTPRO in plasma. In contrast, no methylated PTPRO was observed in normal peripheral blood from 30 healthy individuals. PTPRO methylation was positively associated with lymph node involvement (P = 0.014), poorly differentiated histology (P = 0.037), depth of invasion (P = 0.004), and HER2 amplification (P = 0.001). Multivariate analysis indicated that aberrant PTPRO methylation could serve as an independent predictor for overall survival hazard ratio (HR): 2.7; 95% CI: 1.1-6.2; P = 0.023), especially for patients with HER2-positive (hazard ratio (HR): 7.5; 95% CI: 1.8-31.3; P = 0.006), but not in ER + and PR + subpopulation. In addition, demethylation induced by 5-azacytidine led to gene reactivation in PTPRO-methylated and -silenced breast cancer cell lines., Conclusions: Here, we report that tumor PTPRO methylation is a strong prognostic factor in breast cancer. Methylation of PTPRO silences its expression and plays an important role in breast carcinogenesis. The data we present here may provide insight into the development of novel therapies for breast cancer treatment. Additionally, detection of PTPRO methylation in peripheral blood of breast cancer patients may provide a noninvasive means to diagnose and monitor the disease.

Background: Privacy protecting is an important issue in medical informatics and differential privacy is a state-of-the-art framework for data privacy research. Differential privacy offers provable privacy against attackers who have auxiliary information, and can be applied to data mining models (for example, logistic regression). However, differentially private methods sometimes introduce too much noise and make outputs less useful. Given available public data in medical research (e.g. from patients who sign open-consent agreements), we can design algorithms that use both public and private data sets to decrease the amount of noise that is introduced., Methodology: In this paper, we modify the update step in Newton-Raphson method to propose a differentially private distributed logistic regression model based on both public and private data., Experiments and Results: We try our algorithm on three different data sets, and show its advantage over: (1) a logistic regression model based solely on public data, and (2) a differentially private distributed logistic regression model based on private data under various scenarios., Conclusion: Logistic regression models built with our new algorithm based on both private and public datasets demonstrate better utility than models that trained on private or public datasets alone without sacrificing the rigorous privacy guarantee.

Background: Neurotrophic factors such as brain derived neurotrophic factor (BDNF) are synthesized in a variety of neural and non-neuronal cell types and regulate survival, proliferation and apoptosis. In addition, bone morphogenetic proteins (BMPs) inhibit the proliferation of pulmonary large carcinoma cells bone morphogenetic protein receptor, type IA (BMPR1A). Little is known about the expression of BDNF or BMPR1A in malignant gall bladder lesions. This study was to evaluate BDNF and BMPR1A expression and evaluate the clinicopathological significance in benign and malignant lesions of the gallbladder., Methods: The BDNF and BMPR1A expression of gallbladder adenocarcinoma, peritumoral tissues, adenoma, polyp and chronic cholecystitis were Immunohistochemically determined., Results: BDNF expression was significantly higher in gallbladder adenocarcinoma than in peritumoral tissues, adenoma, polyps and chronic cholecystitis samples. However, BMPR1A expression was significantly lower in gallbladder adenocarcinoma than in peritumoral tissues, adenomas, polyps and chronic cholecystitis tissues. The specimens with increased expression of BDNF in the benign lesions exhibited moderate- or severe-dysplasia of gallbladder epithelium. BDNF expression was significantly lower in well-differentiated adenocarcinomas with maximum tumor diameter <2 cm, no metastasis to lymph nodes, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder adenocarcinoma. BMPR1A expression were significantly higher in the well-differentiated adenocarcinoma with maximal tumor diameter <2 cm, no metastasis of lymph node, and no invasion of regional tissues compared to poorly-differentiated adenocarcinomas with maximal tumor diameter >2 cm, metastasis of lymph node, and invasiveness of regional tissues in gallbladder. Univariate Kaplan-Meier analysis indicated increased expression of BDNF or decreased expression of BMPR1A was associated with decreased disease specific survival (DSS) rates. Similarly, multivariate Cox regression analysis showed increased expression of BDNF or decreased expression of BMPR1A are independent predictors of poor DSS rates in gallbladder adenocarcinoma., Conclusions: In gallbladder malignancies, the increased expression of BDNF and decreased expression of BMPR1A were associated with increased risk of metastasis, regional invasion and mortality. They might serve as novel indicators of gallbladder adenocarcinoma outcomes, which may prove valuable for the development of personalized therapeutic paradigms.

Background: Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option., Results: A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 μg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops., Conclusions: Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies.