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Background Rheumatoid arthritis (RA) and systemic lupus erythematous (SLE) are autoimmune rheumatic diseases that share a complex genetic background and common clinical features. This study’s purpose was to construct machine learning (ML) models for the genomic prediction of RA and SLE. Methods A total of 2,094 patients with RA and 2,190 patients with SLE were enrolled from the Taichung Veterans General Hospital cohort of the Taiwan Precision Medicine Initiative. Genome-wide single nucleotide polymorphism (SNP) data were obtained using Taiwan Biobank version 2 array. The ML methods used were logistic regression (LR), random forest (RF), support vector machine (SVM), gradient tree boosting (GTB), and extreme gradient boosting (XGB). SHapley Additive exPlanation (SHAP) values were calculated to clarify the contribution of each SNPs. Human leukocyte antigen (HLA) imputation was performed using the HLA Genotype Imputation with Attribute Bagging package. Results Compared with LR (area under the curve [AUC] = 0.8247), the RF approach (AUC = 0.9844), SVM (AUC = 0.9828), GTB (AUC = 0.9932), and XGB (AUC = 0.9919) exhibited significantly better prediction performance. The top 20 genes by feature importance and SHAP values included HLA class II alleles. We found that imputed HLA-DQA1*05:01, DQB1*0201 and DRB1*0301 were associated with SLE; HLA-DQA1*03:03, DQB1*0401, DRB1*0405 were more frequently observed in patients with RA. Conclusions We established ML methods for genomic prediction of RA and SLE. Genetic variations at HLA-DQA1, HLA-DQB1, and HLA-DRB1 were crucial for differentiating RA from SLE. Future studies are required to verify our results and explore their mechanistic explanation.

Background Centromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown. Methods Abnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and AKT. Results CENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high 18F-FDG uptake in cancer nests and poor patient prognosis. Transcriptome sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and apoptosis of NPC cells in vitro and in vivo through the AKT pathway. CENP-N formed a complex with AKT in NPC cells. Both an AKT inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance. Conclusions The IRF2/CENP-N/AKT axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/AKT signaling axis is expected to be a new target for NPC therapy.

Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC. Supplementary Information The online version contains supplementary material available at 10.1186/s12943-021-01443-2.

Kidney cancer is a common urological tumour. Owing to its high prevalence and mortality rate, it is the third most malignant tumour of the urinary system, followed by prostate and bladder cancers. It exerts a high degree of malignancy, and most of the distant metastasis occurs at an early stage; it is insensitive to chemoradiotherapy and easily develops drug resistance. The current treatment for kidney cancer mainly includes surgery, interventional embolization and targeted therapy; however, the treatment efficacy is poor. In recent years, the role of exosomes as mediators of intercellular communication and information exchange in the tumour microenvironment in tumour pathogenesis has attracted much attention. Exosomes are rich in bioactive substances such as nucleic acids, proteins and lipids and are involved in angiogenesis, immune regulation, drug resistance, formation of pre-metastatic niche, invasion and metastasis. This article reviews the ongoing research and applications of exosomes for the diagnosis and treatment of kidney cancer.

Introduction Real-world data regarding the impact of hepatic fibrosis on the effectiveness of sofosbuvir/velpatasvir (SOF/VEL) treatment is limited in the Asian population. Methods We analyzed data for all 823 patients with hepatitis C virus treated with SOF/VEL from June 2019 to September 2020 at Chang Gung Memorial Hospital in Chiayi, Taiwan. The degree of fibrosis was determined using the fibrosis-4 (FIB-4) index, with advanced fibrosis or cirrhosis defined as a FIB-4 score of > 3.25. The primary treatment outcome was the rate of sustained virologic response 12 weeks after treatment cessation (SVR). Adverse events (AEs) were also evaluated. Results SVR rates did not significantly differ (p > 0.05) between patients with FIB-4 scores of ≤ 3.25 and those with scores of > 3.25. In the per protocol analysis, 99.2% (593/598) of the FIB-4 ≤ 3.25 group and 100% (172/172) of the FIB-4 > 3.25 group achieved SVR; in the evaluable population analysis, 93.4% (593/635) of the FIB-4 ≤ 3.25 group and 91.5% (172/188) of the FIB-4 > 3.25 group achieved SVR. Five patients with FIB-4 scores of ≤ 3.25 did not attain SVR: two relapsed and three had no response. The most common AEs were comparable (p > 0.05) for the FIB-4 ≤ 3.25 group and the FIB-4 > 3.25 group and included abdominal discomfort (4.4% vs. 5.9%), fatigue (4.1% vs. 5.9%), and skin itching (3.6% vs. 3.2%). Laboratory abnormalities were more common in the FIB-4 > 3.25 group (p 3.25 had total bilirubin elevation > 3 × the upper normal limit (UNL). Alanine transaminase elevation > 5 × the UNL was observed in two patients with FIB-4 scores of ≤ 3.25 and one patient with a FIB-4 score of > 3.25. No AEs resulted in treatment discontinuation. Conclusions SOF/VEL treatment is well tolerated and achieves high SVR rates for patients of Taiwanese ethnicity with HCV, regardless of cirrhosis status.

Background Surfactant therapy is a standard of care for preterm infants with respiratory distress and reduces the incidence of death and bronchopulmonary dysplasia in these patients. Our previous study found that mesenchymal stem cells (MSCs) attenuated hyperoxia-induced lung injury and the combination therapy of surfactant and human umbilical cord-derived MSCs (hUC-MSCs) did not have additive effects on hyperoxia-induced lung injury in neonatal rats. The aim is to evaluate the effects of 2 consecutive days of intratracheal administration of surfactant and hUC-MSCs on hyperoxia-induced lung injury. Methods Neonatal Sprague Dawley rats were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 14. On postnatal day 4, the rats received intratracheal injections of either 20 μL of normal saline (NS) or 20 μL of surfactant. On postnatal day 5, the rats reared in RA received intratracheal NS, and the rats reared in O2 received intratracheal NS or hUC-MSCs (3 × 104 or 3 × 105 cells). Six study groups were examined: RA + NS + NS, RA + surfactant + NS, O2 + NS + NS, O2 + surfactant + NS, O2 + surfactant + hUC-MSCs (3 × 104 cells), and O2 + surfactant + hUC-MSCs (3 × 105 cells). The lungs were excised for histological, western blot, and cytokine analyses. Results The rats reared in hyperoxia and treated with NS yielded significantly higher mean linear intercepts (MLIs) and interleukin (IL)-1β and IL-6 levels and significantly lower vascular endothelial growth factors (VEGFs), platelet-derived growth factor protein expression, and vascular density than did those reared in RA and treated with NS or surfactant. The lowered MLIs and cytokines and the increased VEGF expression and vascular density indicated that the surfactant and surfactant + hUC-MSCs (3 × 104 cells) treatment attenuated hyperoxia-induced lung injury. The surfactant + hUC-MSCs (3 × 105 cells) group exhibited a significantly lower MLI and significantly higher VEGF expression and vascular density than the surfactant + hUC-MSCs (3 × 104 cells) group did. Conclusions Consecutive daily administration of intratracheal surfactant and hUC-MSCs can be an effective regimen for treating hyperoxia-induced lung injury in neonates.

Background Elderly patients with femoral neck fractures are at a higher risk of dislocation after hip arthroplasty procedures. In comparison with total hip arthroplasty (THA), bipolar hemiarthroplasty (HA) and dual-mobility total hip arthroplasty (DM-THA) can be an effective alternative treatment which increases the effective head size and overall stability of the prosthesis. We aim to review the current evidence on the outcome after DM-THA and HA for femoral neck fractures in the elderly. Methods We performed a comprehensive review of literatures on PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials and comparative interventional studies. Of the 936 studies identified, 8 met the inclusion criteria (541 DM-THA and 603 HA procedures). Two reviewers independently reviewed and graded each study and recorded relevant data including dislocation rate, implant failure rate, reoperation rate, 1-year mortality rate, Harris hip score (HHS), operation time, and intraoperative blood loss. Results DM-THA was associated with a lower dislocation rate (OR 3.599; 95% CI 1.954 to 6.630), a lower reoperation rate (OR 2.056; 95% CI 1.211 to 3.490), an increased operation time (SMD − 0.561; 95% CI − 0.795 to − 0.326) and more intraoperative blood loss (SMD − 0.778; 95% CI − 1.238 to − 0.319), compared with the HA group. Moreover, the multivariate regression analysis revealed that age, female sex, posterolateral surgical approach, and choice of DM-THA or HA were not associated with dislocation or reoperation. Conclusions Based on the current evidence, the advantages reported for DM-THA over HA with regard to dislocation and reoperation rate in elderly patients with FNF remain inconclusive. High-quality studies on the high-risk patients with cognitive disorder or dementia are necessary to validate the value of DM-THA.

Background The folding of proteins is challenging in the highly crowded and sticky environment of a cell. Regulation of translation elongation may play a crucial role in ensuring the correct folding of proteins. Much of our knowledge regarding translation elongation comes from the sequencing of mRNA fragments protected by single ribosomes by ribo-seq. However, larger protected mRNA fragments have been observed, suggesting the existence of an alternative and previously hidden layer of regulation. Results In this study, we performed disome-seq to sequence mRNA fragments protected by two stacked ribosomes, a product of translational pauses during which the 5′-elongating ribosome collides with the 3′-paused one. We detected widespread ribosome collisions that are related to slow ribosome release when stop codons are at the A-site, slow peptide bond formation from proline, glycine, asparagine, and cysteine when they are at the P-site, and slow leaving of polylysine from the exit tunnel of ribosomes. The structure of disomes obtained by cryo-electron microscopy suggests a different conformation from the substrate of the ribosome-associated protein quality control pathway. Collisions occurred more frequently in the gap regions between α-helices, where a translational pause can prevent the folding interference from the downstream peptides. Paused or collided ribosomes are associated with specific chaperones, which can aid in the cotranslational folding of the nascent peptides. Conclusions Therefore, cells use regulated ribosome collisions to ensure protein homeostasis.

Background Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. Results This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. Conclusions These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans.

Extracellular adenosine triphosphate (eATP) and its main metabolite adenosine (ADO) constitute an intrinsic part of immunological network in tumor immunity. The concentrations of eATP and ADO in tumor microenvironment (TME) are controlled by ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes expressed on immune cells, endothelial cells and cancer cells. Once accumulated in TME, eATP boosts antitumor immune responses, while ADO attenuates immunity against tumors. eATP and ADO, like yin and yang, represent two opposite aspects from immune-activating to immune-suppressive signals. Here we reviewed the functions of eATP and ADO in tumor immunity and attempt to block eATP hydrolysis, ADO formation and their contradictory effects in tumor models, allowing the induction of effective anti-tumor immune responses in TME. These attempts documented that therapeutic approaches targeting eATP/ADO metabolism and function may be effective methods in cancer therapy.

Background We investigated the risk factors of radiation-induced thyroid dysfunction, then combined the clinical factors and optimum thyroid dosimetric parameters to predict the incidence rate of hypothyroidism (HT) and to guide individualized treatment. Methods A total of 206 patients with histologically proven nasopharyngeal carcinoma (NPC) treated at the Cancer Hospital of the University of Chinese Academy of Sciences between January 2015 and August 2018 were included. Dose–volume histogram (DVH) data, including mean dose, absolute volume, V20, V25, V30, V35, V40, V45, V50, V55, and V60 were extracted and used as dosimetric parameters. A logistic regression analysis model was built to identify predictors related to HT occurring within 2 years. Results Sex, N stage, thyroid volume, mean thyroid dose, and thyroid V20 and V50 were significantly different between patients with and without HT. Logistic regression analysis showed that N stage, thyroid volume, and thyroid V50 were independent predictors of HT. The radiosensitivity of the thyroid decreased as the thyroid volume increased. Patients with N stage > 1 had significantly higher HT incidence (37.38%) than patients with N stage ≤1 (13.11%). The incidence of HT was 54.55% in patients with thyroid V50 > 24% and was 34.15% in patients with thyroid V50 ≤ 24%. Conclusions The incidence of HT is significantly associated with N stage, thyroid volume, and thyroid V50. More attention should be paid to patients with NPC with thyroid volume ≤ 12.82 cm3 and advanced N stage disease.

Background The optimal treatment for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains inconclusive. Previous studies have shown that stereotactic body radiotherapy (SBRT) provides encouraging local control though higher incidence of toxicity in elderly than younger populations. The objective of this study was to compare the outcomes of SBRT and surgical treatment in elderly patients with clinical stage I-II NSCLC. Methods This retrospective analysis included 205 patients aged ≥70 years with clinical stage I NSCLC who underwent SBRT or surgery at Zhejiang Cancer Hospital (Hangzhou, China) from January 2012 to December 2017. A propensity score matching analysis was performed between the two groups. In addition, we compared outcomes and related toxicity in both study arms. Results Each group included 35 patients who met the inclusion criteria. Median follow-up was 50.1 (0.8–74.4) months for surgery and 35.5 (11.5–71.4) months for SBRT. The rate of cancer-specific survival was similar between the two treatment arms (p = 0.958). In patients who underwent surgery, the corresponding 3- and 5-year cancer-specific survival rates were 85.3 and 81.7%, respectively. In those who received radiotherapy, these rates were 91.3 and 74.9%, respectively. Moreover, the 3- and 5-year locoregional control in patients who underwent surgery were 90.0 and 80.0%, respectively. In those who received radiotherapy, these rates were 91.1 and 84.1%, respectively. Notably, the observed differences in progression-free survival were not statistically significant (p = 0.934). In the surgery group, grade 1–2 complications were observed in eleven patients (31%). One patient died due to perioperative infection within 30 days following surgery. There was no grade 3–5 toxicity observed in the SBRT group. Conclusions The outcomes of surgery and SBRT in elderly patients with early-stage NSCLC were similar.

Background Prostate cancer development involves various mechanisms, which are poorly understood but pointing to epithelial mesenchymal transition (EMT) as the key mechanism in progression to metastatic disease. ABI1, a member of WAVE complex and actin cytoskeleton regulator and adaptor protein, acts as tumor suppressor in prostate cancer but the role of ABI1 in EMT is not clear. Methods To investigate the molecular mechanism by which loss of ABI1 contributes to tumor progression, we disrupted the ABI1 gene in the benign prostate epithelial RWPE-1 cell line and determined its phenotype. Levels of ABI1 expression in prostate organoid tumor cell lines was evaluated by Western blotting and RNA sequencing. ABI1 expression and its association with prostate tumor grade was evaluated in a TMA cohort of 505 patients and metastatic cell lines. Results Low ABI1 expression is associated with biochemical recurrence, metastasis and death (p = 0.038). Moreover, ABI1 expression was significantly decreased in Gleason pattern 5 vs. pattern 4 (p = 0.0025) and 3 (p = 0.0012), indicating an association between low ABI1 expression and highly invasive prostate tumors. Disruption of ABI1 gene in RWPE-1 cell line resulted in gain of an invasive phenotype, which was characterized by a loss of cell-cell adhesion markers and increased migratory ability of RWPE-1 spheroids. Through RNA sequencing and protein expression analysis, we discovered that ABI1 loss leads to activation of non-canonical WNT signaling and EMT pathways, which are rescued by re-expression of ABI1. Furthermore, an increase in STAT3 phosphorylation upon ABI1 inactivation and the evidence of a high-affinity interaction between the FYN SH2 domain and ABI1 pY421 support a model in which ABI1 acts as a gatekeeper of non-canonical WNT-EMT pathway activation downstream of the FZD2 receptor. Conclusions ABI1 controls prostate tumor progression and epithelial plasticity through regulation of EMT-WNT pathway. Here we discovered that ABI1 inhibits EMT through suppressing FYN-STAT3 activation downstream from non-canonical WNT signaling thus providing a novel mechanism of prostate tumor suppression.

Background Coronary artery aneurysm (CAA) is a rare disease, and there are limited data on prescribing patterns for CAA. The aim of our study was to investigate prescribing patterns for CAA in Taiwan via the National Health Insurance Research Database (NHIRD). Methods We included all CAA patients in Taiwan from 2005 to 2011. Data from 1 year before and after the CAA diagnosis were used to analyze examinations, comorbidities and prescribing patterns. Results A total of 1397 patients diagnosed with CAA were enrolled in our study. Most pediatric patients with CAA were diagnosed with Kawasaki disease (95.7%). In pediatric CAA patients, the utilization rates of aspirin and gamma globulins were 82.9 and 53.6%, respectively, after CAA diagnosis. Among the antithrombotic agents, aspirin was used most commonly, followed by dipyridamole (16.9%), heparin (5.8%) and warfarin (4.6%). In adult CAA patients, common comorbidities included hypertension (63.4%), hyperlipidemia (39.6%), and diabetes mellitus (26.1%). Coronary atherosclerosis was identified in 72.5% of adult patients after CAA diagnosis. Antithrombotic agents, particularly aspirin, clopidogrel and heparin, were prescribed more frequently after CAA diagnosis. Among the prescribed medications, aspirin (75.8%), β-blockers (48.3%), statins (47.6%), metformin (14.4%), sulfonylureas (14.4%) and isosorbide mononitrate (32.9%) were frequently observed in each category. Conclusions Kawasaki disease was the main cause of CAA in pediatric patients, and coronary artery disease was the most common comorbidity in adult CAA patients. The most commonly used antithrombic agent after CAA diagnosis was aspirin in both adult and pediatric patients.

Background The present meta-analysis was to explore the surgical and oncological outcomes of bursectomy for advanced gastric cancer (AGC). Methods Relevant studies that evaluated the role of bursectomy for AGC were comprehensively examined to perform a meta-analysis. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were the number of harvested lymph nodes (LNs), operation time, operative bleeding, hospital stay, postoperative complication and mortality. Results A total of seven studies comprising 2633 cases (1176 cases in the bursectomy group and 1457 cases in the non-bursectomy group) were finally included. There was no significant difference in OS (HR 0.95, P = 0.647) and DFS (HR 0.99, P = 0.936) between the two groups. Even for patients with serosa-penetrating tumours, OS was comparable between the two groups (HR 0.87, P = 0.356). The operation time of the bursectomy group was longer (weighted mean difference, WMD 32.76 min, P = 0.002). No significant difference was found between the two groups in terms of the number of dissected LNs (WMD 5.86, P = 0.157), operative bleeding (WMD 66.99 ml, P = 0.192) and hospital stay (WMD − 0.15 days, P = 0.766). The overall postoperative complication (relative risk, RR 1.08, P = 0.421) and mortality (RR 0.44, P = 0.195) were similar between two groups. Conclusions This meta-analysis indicated that bursectomy is time-consuming without increasing the number of harvested LNs. Although bursectomy can be safely performed without increasing complications and mortality, it does not prolong the OS and DFS of AGC patients, including patients with serosa-penetrating tumours. Therefore, bursectomy should not be recommended as a standard procedure for AGC. Electronic supplementary material The online version of this article (10.1186/s12957-018-1354-1) contains supplementary material, which is available to authorized users.

Background B-box (BBX) proteins play important roles in plant growth regulation and development including photomorphogenesis, photoperiodic regulation of flowering, and responses to biotic and abiotic stresses. Results In the present study we retrieved total 131 BBX members from five Poaceae species including 36 from maize, 30 from rice, 24 from sorghum, 22 from stiff brome, and 19 from Millet. All the BBX genes were grouped into five subfamilies on the basis of their phylogenetic relationships and structural features. The expression profiles of 12 OsBBX genes in different tissues were evaluated through qRT-PCR, and we found that most rice BBX members showed high expression level in the heading stage compared to seedling and booting stages. The expression of OsBBX1, OsBBX2, OsBBX8, OsBBX19, and OsBBX24 was strongly induced by abiotic stresses such as drought, cold and salt stresses. Furthermore, the expression of OsBBX2, OsBBX7, OsBBX17, OsBBX19, and OsBBX24 genes was up-regulated under GA, SA and MeJA hormones at different time points. Similarly, the transcripts level of OsBBX1, OsBBX7, OsBBX8, OsBBX17, and OsBBX19 genes were significantly affected by heavy metals such as Fe, Ni, Cr and Cd. Conclusion Change in the expression pattern of BBX members in response to abiotic, hormone and heavy metal stresses signifies their potential roles in plant growth and development and in response to multivariate stresses. The findings suggest that BBX genes could be used as potential genetic markers for the plants, particularly in functional analysis and determining their roles under multivariate stresses. Electronic supplementary material The online version of this article (10.1186/s12864-018-5336-z) contains supplementary material, which is available to authorized users.

Background Increasing evidence indicates a pathogenic role of deregulated autophagy in rheumatoid arthritis (RA). We examined the relationship between autophagy and inflammatory parameters in patients with RA receiving biologic therapy. Methods In 72 patients with RA and 20 healthy control subjects (HC), autophagosome levels were determined by the mean fluorescence intensity (MFI) of autophagosomotropic dye incorporated into circulating immune cells, and p62 expression levels in immune cells were measured by flow cytometry. We used immunoblotting to examine protein expression of LC3-II and p62 in peripheral blood mononuclear cells. Results Patients with RA had significantly higher levels of autophagosome reflected by MFI of Cyto-ID in circulating lymphocytes, monocytes, and granulocytes (median values, 3.6, 11.6, and 64.8, respectively) compared with HC (1.9, 6.0, and 35.8; respectively) (all p

Background Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. The disease recurrent rate is relatively high resulted in poor 5-year survival in advanced HCC. Cancer stem cells (CSCs) have been considered to be one of the main mechanisms for chemoresistance, metastasis, and recurrent disease. Interferon-induced protein 44-like (IFI44L) gene is a type I interferon-stimulated gene (ISG) and belongs to the IFI44 family. Previous reports indicated antiviral activity against HCV in IFI44L, however, its precise role and function in HCC has not been unveiled. Methods To explore the characteristics of hepatic CSCs, we successfully enriched hepatic cancer stem-like cells from three established liver cancer cell lines (Hep3B, HepG2, and PLC lines). Parental Hep3B and HepG2 cells and their sphere cells were treated with doxorubicin for 48 h and cell viability was measured by MTT assay. HCC tissue blocks from 217 patients were sampled for tissue microarray (TMA). Follow-up information and histopathological and clinical data including age, gender, tumor grade, advanced stages, HBV, HCV, tumor number, tumor size, relapse-free survival, and overall survival were obtained from the cancer registry and medical charts. The liver TMA was evaluated for IFI44L expression using immunohistochemical staining and scores. Results These hepatic cancer stem-like cells possess important cancer stemness characteristics including sphere-forming abilities, expressing important HCC cancer stem cell markers, and more chemoresistant. Interestingly, we found that overexpression of IFI44L decreased chemoresistance towards doxorubicin and knockdown of IFI44L restored chemoresistance as well as promoted sphere formation. Furthermore, we found that depletion of IFI44L enhanced migration, invasion, and pulmonary metastasis through activating Met/Src signaling pathway. Clinically, the expression level of IFI44L significantly reduced in HCC tumor tissues. Low expression of IFI44L levels also correlated with larger tumor size, disease relapse, advanced stages, and poor clinical survival in HCC patients. Conclusion Taken together, we first demonstrated that IFI44L is a novel tumor suppressor to affect cancer stemness, metastasis, and drug resistance via regulating Met/Src signaling pathway in HCC and can be serve as an important prognostic marker. Electronic supplementary material The online version of this article (10.1186/s12885-018-4529-9) contains supplementary material, which is available to authorized users.

Background Previous studies reported that patients with preexisting radiological interstitial lung abnormalities (ILAs) were more susceptible to developing radiation pneumonitis (RP) after thoracic radiation therapy (TRT). The present study aimed to evaluate the incidence and predictors of RP after TRT in patients with small-cell lung cancer (SCLC) with or without preexisting radiological ILAs. Methods A total of 95 consecutive patients with SCLC between January 2015 and December 2015, who were treated with thoracic intensity-modulated radiation therapy at Shanghai Pulmonary Hospital,Tongji University School of Medicine, were analyzed. The diagnosis of ILAs was reviewed by two experienced thoracic radiologists based on the pretreatment high-resolution computed tomography imaging, such as honeycombing, subpleural reticular opacities, ground-glass opacity, and traction bronchiectasis. Univariate and multivariate analyses were used to assess the correlation of clinical factors, preexisting radiological ILAs, and dose-volume histogram-based dosimetric parameters with RP. Results Fifteen (15.8%) patients had preexisting radiological ILAs. The incidence of ≥ grade 2 and 3 RP at 1 year was 27.1% and 12.7% in the entire cohort, respectively. Preexisting radiological ILAs were associated with an increased risk of ≥grade 2 RP (50.0% in ILAs + vs 23.3% in ILAs−, P = 0.017) and ≥ grade 3 RP (35.8% in ILAs + vs 8.9% in ILAs−, P = 0.005) at 1 year. Preexisting radiological ILAs and smoking history (≥40 pack-years of smoking) were significant predictors of ≥grade 3 RP in multivariate analysis (P = 0.023 and 0.012, respectively). Conclusions Preexisting radiological ILAs and smoking history (≥40 pack-years of smoking) are associated with an increased risk of ≥grade 3 RP after TRT in patients with SCLC.

Background Currently, the role of human papillomavirus (HPV)-58 in southwestern China has been unexplored. Although there is some controversy, it is proposed that the viral load of HPV correlates with the severity of intraepithelial lesions. Methods We identified 7747 patients from south Sichuan and adjacent regions who were diagnosed with HPV between 2013 and 2017. The HR-HPV subtype distribution was analyzed and the patient’s viral loads were quantified using real-time RT-PCR. Results Among all 7747 patients screened for HPV genotypes, 1728 patients (22.31%) were identified as having HR-HPV subtypes. In patients without intraepithelial lesions (12.41%), HPV-52, HPV-16, and HPV-58 were the three most prevalent HR-HPV subtypes. Moreover, HPV-16, HPV-58, and HPV-33 were the most prevalent subtypes in patients with cervical intraepithelial neoplasia grade II (CINII) (42.86%) and grade III (CINIII) (59.81%), and accounted for the majority of invasive cervical cancer (ICC) (69.34%). Thus, viral loads of HPV-58, HPV-16, and HPV-33 positively correlated with the severity of cervical lesions (P

Background Macrophage heterogeneity is the main feature of the tumour microenvironment. Breast cancer is one of the most life-threatening cancers. However, macrophage polarization patterns in different tumour stages and the importance of its relationship to human epidermal growth factor receptor 2 (HER2) in breast cancer remains highly unclear. The present study investigated the patterns of monocyte differentiation and macrophage polarization in breast cancer. Methods Patients with breast cancer (n = 48) and healthy controls (n = 39) were prospectively recruited. The percentages and subsets of circulating macrophage-like cells were analysed by flow cytometry, and the polarization patterns of these cells in the peripheral blood of patients with breast cancer were compared with those of healthy controls. In addition, macrophage polarization patterns in different stages and HER2 status in breast cancer were investigated. Results The percentages of circulating macrophages, which are defined as PM-2 K+ cells in the peripheral blood, were significantly higher in patients with breast cancer than in healthy controls. The percentages of M1-like macrophages were significantly lower, but those of M2-like macrophages were significantly higher in patients with breast cancer than in healthy controls. The percentage of M2c-like macrophages was significantly higher in advanced (stages II and III) breast cancer. However, the patterns of macrophage polarization were not associated with HER2 status in breast cancer. Conclusions Aberrant macrophage polarization was observed in breast cancer and was correlated with breast cancer stage. These quantitative data may provide new molecular biomarkers and potential therapeutic targets in breast cancer. Electronic supplementary material The online version of this article (10.1186/s12885-018-4284-y) contains supplementary material, which is available to authorized users.

Background Normal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Radiation-induced lung fibrosis (RILF) is considered a critical determinant for late normal tissue complications. While RILF mouse models are frequently approached e.g., as a single high dose thoracic irradiation to investigate lung fibrosis and candidate modulators, a systematic radiobiological characterization of RILF mouse model is urgently needed to compare relative biological effectiveness (RBE) of particle irradiation with protons, helium-, carbon and oxygen ions now available at HIT. We aimed to study the dose-response relationship and fractionation effect of photon irradiation in development of pulmonary fibrosis in C57BL/6 mouse. Methods Lung fibrosis was evaluated 24 weeks after single and fractionated whole thoracic irradiation by quantitative assessment of lung alterations using CT. The fibrosis index (FI) was determined based on 3D-segmentation of the lungs considering the two key fibrosis parameters affected by ionizing radiation i.e., a dose/fractionation dependent reduction of the total lung volume and increase of the mean lung density. Results The effective dose required to induce 50% of the maximal possible fibrosis (ED 50) was 14.55 ± 0.34Gy and 27.7 ± 1.22Gy, for single and five- fractions irradiation, respectively. Applying a deterministic model an α/β = 4.49 ± 0.38 Gy for the late lung radiosensitivity was determined. Intriguingly, we found that a linear-quadratic model could be applied to in-vivo log transformed fibrosis (FI) vs. irradiation doses. The LQ model revealed an α/β for lung radiosensitivity of 4.4879 Gy for single fraction and 3.9474 for 5-fractions. Our FI based data were in good agreement with a meta-analysis of previous lung radiosensitivity data derived from different clinical endpoints and various mouse strains. The effect of fractionation on RILF development was further estimated by the biologically effective dose (BED) model with threshold BED (BED Tr) = 30.33 Gy and BED ED50 = 61.63 Gy, respectively. Conclusion The systematic radiobiological characterization of RILF in the C57BL/6 mouse reported in this study marks an important step towards precise estimation of dose-response for development of lung fibrosis. These radiobiological parameters combined with a large repertoire of genetically engineered C57BL/6 mouse models, build a solid foundation for further biologically individualized risk assessment of RILF and functional RBE prediction on novel of particle qualities. Electronic supplementary material The online version of this article (10.1186/s13014-017-0912-y) contains supplementary material, which is available to authorized users.

Background Aging is associated with decreased balance, which increases falling risk. The objective of the current study was to determine the feasibility and effects of whole-body vibration (WBV) training on knee extensor muscle power, limits of stability, and sit-to-stand performance among community-dwelling middle-aged and older adults in the United States. Methods A randomized pilot study with participant blinding was conducted. Feasibility outcomes included recruitment and compliance rate. Twenty-nine community-dwelling older adults were randomly assigned to perform body-weight exercises with either an individualized vibration frequency and amplitude, a fixed vibration frequency and amplitude, or no vibration. Isokinetic knee extensor power, limits of stability, and sit-to-stand tests were conducted before beginning the exercises (baseline) and after 8 weeks of training. Results With a favorable recruitment rate (58%) and compliance rates (attrition 9%; adherence 85%), the intervention was deemed feasible. The limits of stability endpoint excursion score for the individualized frequency–amplitude group was increased by 8.8 (12.9%; P = 0.025) after training, and that group’s maximum excursion score was increased by 9.2 (11.5%; P = 0.006) after training. The average weight transfer time score was significantly decreased by 0.2 s in the fixed group. The participants in the individualized group demonstrated a significant increase (3.2%) in weight rising index score after 8 weeks of WBV training. Conclusions WBV training is feasible for use with elderly people, and this study achieved good recruitment and compliance. The present paper suggests that 8 weeks of WBV training improves limits of stability and sit-to-stand performance. Future studies must determine whether WBV training improves other factors that affect posture control. Trial registration This study was registered at the Texas Woman’s University Institutional Review Board [ TWU IRB 17632 ] on the 3rd of November 2014.

Background CD133 (prominin-1) is widely believed to be a cancer stem cell marker in various solid tumor types, and CD133 has been correlated with tumor-initiating capacity. Recently, the nuclear location of CD133 expression in tumors has been discussed, but hepatocellular carcinoma (HCC) has not been included in these discussions. The goal of this study was to investigate the location of CD133 expression in HCC and this location’s potential value as a prognostic indicator of survival in patients with HCC. Methods We enrolled 119 cancerous tissues and pair-matched adjacent normal liver tissue from HCC patients. These tissues were obtained immediately after operation, and tissue microarrays were subsequently constructed. The expression of CD133 was measured by immunohistochemistry (IHC), and the correlations between this expression and clinical characteristics and prognosis was estimated using statistical analysis. Results The results showed that the CD133 protein expression levels of HCC in both the cytoplasm and nucleus were significantly higher than adjacent normal liver tissue. Kaplan–Meier survival and Cox regression analyses revealed that high CD133 expression in the cytoplasm was an independent predictor of poor prognosis for the overall survival (OS) and relapse-free survival (RFS) rates of HCC patients (P = 0.028 and P = 0.046, respectively). Surprisingly, high nuclear CD133 expression of HCC was an independent predictor of the good prognosis of the OS and RFS rates of HCC patients (P = 0.023 and P = 0.012, respectively). Conclusions The clinical evidence that revealed cytoplasmic CD133 expression was correlated with poor prognosis, while nuclear CD133 expression was significantly correlated with favorable prognosis. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3460-9) contains supplementary material, which is available to authorized users.

Background The current study sought to perform a meta-analysis to compare the preoperative staging of endoscopic ultrasonography (EUS) and multidetector computed tomography (MDCT) in gastric carcinoma. Methods Articles published between January 1, 2000, and April 1, 2016, that compared EUS with MDCT were included, and data were presented as 2 × 2 tables. The sensitivities, specificities and summary receiver operating characteristic (ROC) curves for T and N staging were calculated using a bivariate mixed effects model. Data were weighted by generic variance and then pooled by random-effects modeling. Results Eight studies comprising 1736 patients were included in this meta-analysis. For T1 staging, the sensitivity value for EUS (82%) was significantly higher than that for MDCT (41%) (relative risk (RR): 2.06, 95% confidence interval (CI) 1.07–3.94; P = 0.030). For lymph node involvement, the sensitivity value for EUS (91%) was also significantly higher than that for MDCT (77%) (RR 1.14, 95% CI 1.05–1.23; P = 0.001). However, the specificity values of both EUS and MDCT were quite low, at 49 and 63%, respectively. No significant differences in T2–4 staging between EUS and MDCT were noted. Conclusion This meta-analysis indicates that EUS may be superior to MDCT in preoperative T1 and N staging. Additionally, the low specificity values of EUS and MDCT for N staging merits attention.

Background The purpose of this study was to test effects of negative pressure on tendon–bone healing after reconstruction of anterior cruciate ligament (ACL) in rabbits. Methods Hind legs of 24 New Zealand White rabbits were randomly selected as negative pressure group and the contralateral hind legs as control. Reconstruction of the ACL was done. Joints of the negative pressure side were placed with drainage tubes connecting the micro-negative pressure aspirator. Control side was placed with ordinary drainage tubes. Drainage tubes on both sides were removed at the same time 5 days after operation. After 6 weeks, joint fluid was drawn to detect the expression levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); at the same time, femur–ligament–tibia complex was obtained to determine tendon graft tension and to observe the histomorphology, blood vessels of the tendon–bone interface, and expression of vascular endothelial growth factor (VEGF). Results The maximum load breakage of tendon graft was significantly greater in the negative pressure group than in the control group (P

Von Willebrand disease (VWD) is not uncommon in Taiwan. In type 2 or type 3 VWD hemorrhagic symptoms are severer and laboratory data relatively more distinctive. De novo mutation and somatic mosaicism of type 2 VWD gene were rarely reported. Therefore clinical, laboratory and genetic studies of only type 2A, 2B and 2M VWD will be presented and issues of de novo mutation and somatic mosaicism will be explored. Fifty-four patients belonging to 23 unrelated families from all around the country in whom type 2 VWD exclusive of type 2N has been diagnosed not only by clinical and routine laboratory studies but also by genetic confirmation during 1990–2015 were investigated. A novel technique named amplification refractory mutation system-quantitative polymerase chain reaction (ARMS-qPCR) was used to confirm the presence of somatic mosaicism. Informed consent was obtained for study. De novo mutation was identified in 4 families among 15 families (26.7 %) in whom family members including parents were available for examination. All their parents were free from bleeding symptoms and had no similar mutation as their respective affected daughter. An interesting example of somatic mosaicism of VWF gene mutation was found in a large family with type 2A VWD. The father carrying a mutated VWF gene, p.Arg1597Trp, transmitted this mutation to his 3 daughters, 1 son, 3 granddaughters and 2 grandsons. However, the father had normal laboratory findings and experienced no abnormal bleeding, while his offspring who inherited the mutation showed abnormal laboratory findings compatible with type 2A VWD and had history of abnormal bleedings. ARMS-qPCR revealed that the father had only 25.5 % mutant in his blood cells and 31.1 % mutant in his oral mucosal cells, while all his offspring had about 49 % mutant in their blood cells. De novo mutation of type 2 VWD gene was identified in 4 out of 15 families (26.7 %) examined. Since only one child was affected in each family, germline mosaicism was not likely. A somatic mosaicism of type 2A VWD gene was documented in a big family by a newly in-house developed technique ARMS-qPCR.

Background Autophagy is a cellular degradation process that is highly evolutionarily-conserved in yeast, plants, and animals. In plants, autophagy plays important roles in regulating intracellular degradation and recycling of amino acids in response to nutrient starvation, senescence, and other environmental stresses. Foxtail millet (Setaria italica) has strong resistance to stresses and has been proposed as an ideal material for use in the study of the physiological mechanisms of abiotic stress tolerance in plants. Although the genome sequence of foxtail millet (Setaria italica) is available, the characteristics and functions of abiotic stress-related genes remain largely unknown for this species. Results A total of 37 putative ATG (autophagy-associated genes) genes in the foxtail millet genome were identified. Gene duplication analysis revealed that both segmental and tandem duplication events have played significant roles in the expansion of the ATG gene family in foxtail millet. Comparative synteny mapping between the genomes of foxtail millet and rice suggested that the ATG genes in both species have common ancestors, as their ATG genes were primarily located in similar syntenic regions. Gene expression analysis revealed the induced expression of 31 SiATG genes by one or more phytohormone treatments, 26 SiATG genes by drought, salt and cold, 24 SiATG genes by darkness and 25 SiATG genes by nitrogen starvation. Results of qRT-PCR showing that among 37 SiATG genes, the expression level of SiATG8a was the highest after nitrogen starvation treatment 24 h, suggesting its potential role in tolerance to nutrient starvation. Moreover, the heterologous expression of SiATG8a in rice improved nitrogen starvation tolerance. Compared to wild type rice, the transgenic rice performed better and had higher aboveground total nitrogen content when the plants were grown under nitrogen starvation conditions. Conclusions Our results deepen understanding about the characteristics and functions of ATG genes in foxtail millet and also identify promising new genetic resources that should be of use in future efforts to develop varieties of foxtail millet and other crop species that have resistance to nitrogen deficiency stress. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3113-4) contains supplementary material, which is available to authorized users.

Background The objective of this study was to evaluate the risk of benign peripheral persistent vertigo (BPPV) among patients with anxiety disorders by using the Taiwan National Health Insurance Research Database (NHIRD). Methods We conducted a retrospective study of 15,470 participants (7735 anxiety disorder patients and 7735 control patients) selected from the NHIRD. Patients were observed for a maximum of 9 years to determine the rates of newly diagnosed BPPV. A Cox regression model was used to evaluate the risk of BPPV among the patients with anxiety disorders. Results During the 9-year follow-up period, 178 (2.05 per 1000 person-years) anxiety disorder patients and 71 (0.81 per 1000 person-years) control patients were diagnosed with BPPV. The incidence risk ratio of BPPV between anxiety disorder patients and control patients was 2.52 (95 % confidence interval [CI], 1.90–3.37, P

Background Pulmonary edema is an important cause of complications and death in severe drowning. Continuous veno-venous hemofiltration (CVVH) may reduce pulmonary edema and thus may be a treatment modality for severe sea water drowning resuscitation. Methos 20 dogs were anesthetized and tracheally intubated. 10 ml/kg of sea water was infused into trachea in a minute. All animals developed signs of respiratory distress and severe hypoxia (PaO2

Background Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. Methods We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss®) or the Control group (treatment with GTR and Bio-oss® without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. Results A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p p > 0.05). Conclusions This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size. Trial Registration NCT01357785 Date registered: 18 May 2011.

Objectives To establish a three-dimensional (3D) finite element (FE) model of a maxillary first premolar and to evaluate the stress generated on the tooth (dentine) and on the indirect composite resin restorations by occlusal forces. Methods An embedded intact maxillary first premolar tooth was sliced serially and scanned digitally parallel to the occlusal surface. The 64 images were assembled in a 3D FE mesh and exported to generate a 3D solid tooth model. Simulated, adhesively cemented indirect mesial-occlusal-distal (MOD) inlays of 2 mm (I1), 3 mm (I2) and 4 mm (I3) in width, and MOD onlays with occlusal cusp coverage of 2 mm (O1) and 3 mm (O2) in depth were created. The peak von Mises stress values in the five tooth models resulting from static vertical and oblique occlusal forces (300 N) were evaluated using Patran FE software. Results The peak stress values generated by vertical occlusal force generated in dentine of I1, I2, I3, O1 and O2 restoration were 67, 32, 29, 38 and 27 MPa, respectively, and those generated by oblique occlusal force were 52, 114, 168, 54 and 55 MPa, respectively. The peak von Mises stress values in I1, I2, I3, O1 and O2 restoration subjected to oblique occlusal loading were 79, 120, 1740, 1400 and 1170 MPa, respectively. Conclusion A 3D FE model of a maxillary first premolar was established. Simulated cemented composite resin onlay markedly reduces occlusal stress in the underlying dentine of large MOD preparation. Oblique occlusal force imparts substantially higher stress to large composite resin inlay than to the adjacent dentine.

Background High tibial osteotomy (HTO) with a medially opening wedge has been used to treat osteoarthritic knees. However, the osteotomized tibia becomes a highly unstable structure and necessitates the use of plate and screws to stabilize the medial opening and enhance bone healing. A T-shaped plate (e.g. TomoFix) with locking screws has been extensively used as a stabilizer of the HTO wedge. From the biomechanical viewpoint, however, the different plate sites and support bases of the HTO plate should affect the load-transferring path and wedge-stabilizing ability of the HTO construct. This study uses biomechanical tests and finite-element analyses to evaluate the placement- and base-induced effects of the HTO plates on construct performance. Methods Test-grade synthetic tibiae are chosen as the standard specimens of the static tests. A medial wedge is created for each specimen and stabilized by three plate variations: hybrid use of T- and I-shaped plates (TIP), anteriorly placed TomoFix (APT), and medially placed TomoFix (MPT). There are five tests for each variation. The failure loads of the three constructs are measured and used as the load references of the fatigue finite-element analysis. The residual life after two hundred thousand cycles is predicted for all variations. Results The testing results show no occurrence of implant back-out and breakage under all variations. However, the wedge fracture consistently occurs at the opening tip for the APT and MPT and the medially resected plateau for the TIP, respectively. The testing results reveal that both failure load and wedge stiffness of the TIP are the highest, followed by the MPT, while those of the APT are the least (P

Background MicroRNA-124 (miR-124) has been reported to be downregulated in breast cancer. However, its clinical significance and prognostic value in breast cancer have not been extensively studied. Methods The tissue expression levels of miR-124 were measured using quantitative real-time PCR in 133 breast cancer patients. The correlation between the miR-124 levels and the clinicopathological factors of the patients was also analyzed. Survival and Cox proportional-hazards regression analyses were performed to determine the correlation between miR-124 expression levels and prognosis in the patients. Results Quantitative real-time PCR analysis showed that miR-124 had lower expression in breast cancer specimens than that in matched adjacent normal breast tissues (0.39 ± 0.16 vs. 1.00 ± 0.39; P

Background Predication of gene regularity network (GRN) from expression data is a challenging task. There are many methods that have been developed to address this challenge ranging from supervised to unsupervised methods. Most promising methods are based on support vector machine (SVM). There is a need for comprehensive analysis on prediction accuracy of supervised method SVM using different kernels on different biological experimental conditions and network size. Results We developed a tool (CompareSVM) based on SVM to compare different kernel methods for inference of GRN. Using CompareSVM, we investigated and evaluated different SVM kernel methods on simulated datasets of microarray of different sizes in detail. The results obtained from CompareSVM showed that accuracy of inference method depends upon the nature of experimental condition and size of the network. Conclusions For network with nodes (