ABSTRACT
Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.
Subject(s)
Apoptosis , Cell Movement , Melanoma , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Quercetin , Signal Transduction , Quercetin/analogs & derivatives , Quercetin/pharmacology , Quercetin/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Melanoma/drug therapy , Melanoma/metabolism , Humans , Apoptosis/drug effects , Animals , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Mice , Cell Proliferation/drug effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Epithelial-Mesenchymal Transition/drug effects , Biological Products/pharmacology , Biological Products/therapeutic use , Xenograft Model Antitumor Assays , Mice, NudeABSTRACT
PURPOSE: Pancreatic cancer (PC) is a highly malignant tumor that poses a severe threat to human health. Brain glycogen phosphorylase (PYGB) breaks down glycogen and provides an energy source for tumor cells. Although PYGB has been reported in several tumors, its role in PC remains unclear. METHODS: We constructed a risk diagnostic model of PC-related genes by WGCNA and LASSO regression and found PYGB, an essential gene in PC. Then, we explored the pro-carcinogenic role of PYGB in PC by in vivo and in vitro experiments. RESULTS: We found that PYGB, SCL2A1, and SLC16A3 had a significant effect on the diagnosis and prognosis of PC, but PYGB had the most significant effect on the prognosis. Pan-cancer analysis showed that PYGB was highly expressed in most of the tumors but had the highest correlation with PC. In TCGA and GEO databases, we found that PYGB was highly expressed in PC tissues and correlated with PC's prognostic and pathological features. Through in vivo and in vitro experiments, we found that high expression of PYGB promoted the proliferation, invasion, and metastasis of PC cells. Through enrichment analysis, we found that PYGB is associated with several key cell biological processes and signaling pathways. In experiments, we validated that the MAPK/ERK pathway is involved in the pro-tumorigenic mechanism of PYGB in PC. CONCLUSION: Our results suggest that PYGB promotes PC cell proliferation, invasion, and metastasis, leading to poor patient prognosis. PYGB gene may be a novel diagnostic biomarker and gene therapy target for PC.
Subject(s)
Pancreatic Neoplasms , Humans , Biomarkers , Glycogen Phosphorylase, Brain Form/genetics , Glycogen Phosphorylase, Brain Form/metabolism , MAP Kinase Signaling System/genetics , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/therapy , Prognosis , Signal Transduction/geneticsABSTRACT
Pancreatic adenocarcinoma (PAAD) is a frequent malignant tumor in the pancreas. The incomplete understanding of cancer etiology and pathogenesis, as well as the limitations in early detection and diagnostic methods, have created an urgent need for the discovery of new therapeutic targets and drugs to control this disease. As a result, the current therapeutic options are limited. In this study, the weighted gene co-expression network analysis (WGCNA) method was employed to identify key genes associated with the progression and prognosis of pancreatic adenocarcinoma (PAAD) patients in the Gene Expression Profiling Interactive Analysis (GEPIA) database. To identify small molecule drugs with potential in the treatment of pancreatic adenocarcinoma (PAAD), we compared key genes to the reference dataset in the CMAP database. First, we analyzed the antitumor properties of small molecule drugs using cell counting kit-8 (CCK-8), AO/EB and Transwell assays. Subsequently, we integrated network pharmacology with molecular docking to explore the potential mechanisms of the identified molecules' anti-tumor effects. Our findings indicated that the progression and prognosis of PAAD patients in pancreatic cancer were associated with 11 genes, namely, DKK1, S100A2, CDA, KRT6A, ITGA3, GPR87, IL20RB, ZBED2, PMEPA1, CST6, and MUC16. These genes were filtered based on their therapeutic potential through comparing them with the reference dataset in the CMAP database. Taxifolin, a natural small molecule drug with the potential for treating PAAD, was screened by comparing it with the reference dataset in the CMAP database. Cell-based experiments have validated the potential of Taxifolin to facilitate apoptosis in pancreatic cancer cells while restraining their invasion and metastasis. This outcome is believed to be achieved via the HIF-1 signaling pathway. In conclusion, this study provided a theoretical basis for screening genes related to the progression of pancreatic cancer and discovered potentially active small molecule drugs. The experimental results confirm that Taxifolin has the ability to promote apoptosis in pancreatic cancer cells.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Quercetin/analogs & derivatives , Humans , Early Detection of Cancer , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Molecular Docking Simulation , Pancreas , Gene Expression Profiling , Apoptosis/genetics , Prognosis , Gene Expression Regulation, Neoplastic , Membrane Proteins , Receptors, Lysophosphatidic AcidABSTRACT
BACKGROUND: CLDN5 protein is essential for the formation of tight junctions in epithelial cells, and has been associated with epithelial-mesenchymal transition. Research has indicated that CLDN5 is associated with tumor metastasis, the tumor microenvironment, and immunotherapy in multiple types of cancer. Also, no comprehensive evaluation of the expression of CLDN5 and immunotherapy signatures through a pan-cancer analysis or immunoassay has been performed. METHODS: We explored CLDN5's differential expression, survival analysis and clinicopathological staging through the TCGA database, and then corroborated the expression of CLDN5 by utilizing the GEO (Gene expression omnibus) database. To analyze CLDN5 KEGG, GO, and Hallmark mutations, as well as TIMER for immune infiltration, GSEA was utilized with ROC curve, mutation, and other factors such as survival, pathological stage, TME, MSI, TMB, immune cell infiltration, and DNA methylation. Immunohistochemistry was used to assess CLDN5 staining in gastric cancer tissues and paracancerous tissues. Visualization was done with R version 4.2.0 (http://www.rproject.org/). RESULTS: According to TCGA database, CLDN5 expression levels differed significantly between cancer and normal tissues, and the GEO database (GSE49051 and GSE 64951) and tissue microarrays confirmed this result. Infiltrating cluster of differentiation 8+ (CD8+) T cells, CD4+ cells, neutrophils, dendritic cells, and macrophages revealed a correlation with CLDN5 expression. DNA methylation, TMB, and MSI are related to CLDN5 expression. Based on the ROC curve analysis, CLDN5 demonstrates outstanding diagnostic effectiveness for gastric cancer and is comparable to CA-199. CONCLUSIONS: The findings suggest that CLDN5 is implicated in the oncogenesis of diverse cancer types, underscoring its potential significance in cancer biology. Notably, CLDN5 could have implications in immune filtration and immune checkpoint inhibitor therapies, however, further research is needed to confirm this.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Biomarkers , Carcinogenesis , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Tumor Microenvironment/genetics , Claudin-5ABSTRACT
Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases in swine, the most common of which are postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). To investigate the prevalence and genetic diversity of PCV2 in Hebei Province, Northern China, from 2016 to 2019, a total of 448 suspected cases of PCV2 infection were studied, and 179 samples were positive for PCV2. A pathological and histopathological examination suggested PCV2 to be cause of the observed lesions. Phylogenetic analysis showed that four genotypes were prevalent in Hebei Province: PCV2a, 2b, 2d, and 2e. Analysis of PCV2 strains using RDP4 and SimPlot showed that there were genetic recombination events among PCV2 strains in Hebei Province. A total of 3284 serum samples were screened by ELISA, and the positive rate of PCV2 antibodies was 73.9% (2428/3284). This study provides a scientific reference for the prevention and treatment of PCV2 in Hebei Province.
Subject(s)
Antibodies, Viral/blood , Circoviridae Infections/veterinary , Circovirus/classification , Porcine Postweaning Multisystemic Wasting Syndrome/epidemiology , Animals , China/epidemiology , Circoviridae Infections/blood , Circovirus/genetics , Circovirus/isolation & purification , Genetic Variation , Phylogeny , Porcine Postweaning Multisystemic Wasting Syndrome/virology , Prevalence , Retrospective Studies , Sequence Analysis, DNA , SwineABSTRACT
Porcine deltacoronavirus (PDCoV) is a recently identified coronavirus that causes intestinal diseases in neonatal piglets with diarrhea, vomiting, dehydration, and post-infection mortality of 50-100%. Currently, there are no effective treatments or vaccines available to control PDCoV. To study the potential of RNA interference (RNAi) as a strategy against PDCoV infection, two short hairpin RNA (shRNA)-expressing plasmids (pGenesil-M and pGenesil-N) that targeted the M and N genes of PDCoV were constructed and transfected separately into swine testicular (ST) cells, which were then infected with PDCoV strain HB-BD. The potential of the plasmids to inhibit PDCoV replication was evaluated by cytopathic effect, virus titers, and real-time quantitative RT-PCR assay. The cytopathogenicity assays demonstrated that pGenesil-M and pGenesil-N protected ST cells against pathological changes with high specificity and efficacy. The 50% tissue culture infective dose showed that the PDCoV titers in ST cells treated with pGenesil-M and pGenesil-N were reduced 13.2- and 32.4-fold, respectively. Real-time quantitative RT-PCR also confirmed that the amount of viral RNA in cell cultures pre-transfected with pGenesil-M and pGenesil-N was reduced by 45.8 and 56.1%, respectively. This is believed to be the first report to show that shRNAs targeting the M and N genes of PDCoV exert antiviral effects in vitro, which suggests that RNAi is a promising new strategy against PDCoV infection.
Subject(s)
Coronavirus Infections/genetics , Coronavirus/genetics , Viral Proteins/genetics , Virus Replication/genetics , Animals , Coronavirus/pathogenicity , Coronavirus Infections/pathology , Coronavirus Infections/virology , Diarrhea/genetics , Diarrhea/pathology , Diarrhea/veterinary , Diarrhea/virology , Male , Plasmids/genetics , RNA Interference , RNA, Small Interfering/genetics , RNA, Viral/genetics , Swine/virology , Swine Diseases/genetics , Swine Diseases/virology , Testis/growth & development , Testis/virologyABSTRACT
Porcine bocavirus (PBoV), which belongs the genus Bocaparvovirus, has been identified throughout the world. However, serological methods for detecting anti-PBoV antibodies are presently limited. In the present study, an indirect enzyme-linked immunosorbent assay (PBoV-rNP1 ELISA) based on a recombinant form of nucleoprotein 1 (NP1) of PBoV was established for investigating the seroprevalence of PBoV in 2025 serum specimens collected in north-central China from 2016 to 2018, and 42.3% of the samples tested positive for anti-PBoV IgG antibodies, indicating that the seroprevalence of PBoV is high in pig populations in China.
Subject(s)
Antibodies, Viral/blood , Bocavirus/isolation & purification , Nucleoproteins/immunology , Parvoviridae Infections/veterinary , Swine Diseases/virology , Animals , Antibodies, Viral/immunology , Bocavirus/classification , Bocavirus/genetics , China/epidemiology , Enzyme-Linked Immunosorbent Assay , Nucleoproteins/genetics , Parvoviridae Infections/blood , Parvoviridae Infections/epidemiology , Parvoviridae Infections/virology , Phylogeny , Seroepidemiologic Studies , Swine , Swine Diseases/blood , Swine Diseases/diagnosis , Swine Diseases/epidemiologyABSTRACT
Tumor-associated macrophages (TAMs) are abundant population of inflammatory cells which play an essential role in remodeling tumor microenvironment and tumor progression. Previously, we found the high density of TAMs was correlated with lymph node metastasis and poor prognosis in pancreatic ductal adenocarcinoma (PDAC). Therefore, this study was designed to investigate the mechanisms of interaction between TAMs and PDAC. THP-1 monocytes were the exposure to conditioned media (CM) produced by PDAC cells; then, monocyte recruitment and macrophage differentiation were assessed. CM from PDAC attracted and polarized THP-1 monocytes to tumor-driven like macrophages. mRNA expression cytokine profiling and ELISA identified the IL-8 secretion was increasing in tumor-driven like macrophages, and STAT3 pathway was involved. Addition of exogenous recombinant human IL-8 promoted PDAC cells motility in vitro and metastasis in vivo via upregulating Twist expression, which mediated epithelial-mesenchymal transition in cancer cells. What is more, IL-8 expression level in tumor stroma by immunohistochemical analysis was related to lymph node metastasis, the number of tumor CD68 but not CD163 positive macrophages and patient outcome. Taken together, these findings shed light on the important interplay between cancer cells and TAMs in tumor microenvironment and suggested that IL-8 signaling might be a potential therapeutic target for PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Interleukin-8/genetics , Interleukin-8/metabolism , Macrophages/metabolism , Monocytes/cytology , Pancreatic Neoplasms/pathology , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Cell Differentiation/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Culture Media, Conditioned/pharmacology , Epithelial-Mesenchymal Transition , Gene Expression Regulation, Neoplastic , Humans , Macrophages/pathology , Mice , Monocytes/drug effects , Monocytes/metabolism , Neoplasm Metastasis , Neoplasm Transplantation , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , THP-1 Cells , Tumor Microenvironment , Up-Regulation , Pancreatic NeoplasmsABSTRACT
It is critical to understand the pathogenesis of preinvasive stages of pancreatic duct adenocarcinoma (PDAC) for developing novel potential diagnostic and therapeutic targets. The polycomb group family member B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi1) is overexpressed and involved in cancer progression in PDAC; however, its role in the multistep malignant transformation of human pancreatic duct cells has not been directly demonstrated. In this study, we stably expressed Bmi1 in a model of telomerase-immortalized human pancreatic duct-derived cells (HPNE) and showed that Bmi1 promoted HPNE cell proliferation, migration, and invasion but not malignant transformation. We then used mutant KRASG12D as a second oncogene to transform HPNE cells and showed that it further enhanced Bmi1-induced malignant potential. More importantly, coexpression of KRASG12D and Bmi1 caused anchorage-independent growth transformation in vitro but still failed to produce tumors in nude mice. Finally, we found that mutant KRASG12D induced HPNE-Bmi1 cells to undergo partial epithelial-mesenchymal transition (EMT) likely via upregulation of snail. Knockdown of KRASG12D significantly reduced the expression of snail and vimentin at both the messenger RNA (mRNA) and protein level and further impaired the anchorage-independent growth capability of invasive cells. In summary, our findings demonstrate that coexpression of Bmi1 and KRASG12D could lead to transformation of HPNE cells in vitro and suggest potential new targets for diagnosis and treatment of PDAC.
Subject(s)
Carcinoma, Pancreatic Ductal/pathology , Cell Transformation, Neoplastic/genetics , Pancreatic Neoplasms/pathology , Polycomb Repressive Complex 1/genetics , Polycomb Repressive Complex 1/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Animals , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Cell Line, Tumor , Cell Transformation, Neoplastic/metabolism , Cell Transformation, Neoplastic/pathology , Female , Heterografts , Humans , Mice , Mice, Nude , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
BACKGROUND AND OBJECTIVE: Phosphodiesterase type-5 inhibitors (PDE-5 inhibitors) have been suggested as a first-line drug for treating pulmonary arterial hypertension (PAH). The aim of present meta-analysis was to fully evaluate the efficacy and safety of treating PAH with PDE-5 inhibitors, focusing on the improvement of 6-min walk distance (6MWD). METHODS: Studies were identified from The Cochrane Library, EMBASE, and PUBMED databases. We calculated odds ratios (OR) for dichotomous data and weighted mean differences with 95% confidence intervals (CI) for continuous data. RESULTS: Six studies with a total of 1056 patients (729 patients in PDE-5 inhibitors treatment group and 327 patients in placebo group) were included. All-cause mortality rate in the control group and PDE-5 inhibitors group was 2.6% and 0.7%, respectively. In an average of 12.3-week follow-up, PDE-5 inhibitors treatment was associated with a 71% reduction in mortality (OR 0.29; 95 %CI 0.07-1.15; P = 0.08), and increased 6MWD by 40.17 m, improved NYHA functional class and hemodynamic parameters. As for monotherapy and combination therapy patients, 6MWD has improved by 48.94 m and 21.75 m, respectively. CONCLUSIONS: The results of present meta-analysis suggest that treatment with PDE-5 inhibitors improves the 6MWD, clinical symptoms, hemodynamic parameters, and a tendency of survival benefits. In patients treated with PDE-5 inhibitor monotherapy, the 6MWD significantly increased when compared to combination therapies.
Subject(s)
Antihypertensive Agents/therapeutic use , Hypertension, Pulmonary/drug therapy , Phosphodiesterase 5 Inhibitors/therapeutic use , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Drug Therapy, Combination , Exercise Test/methods , Humans , Hypertension, Pulmonary/mortality , Phosphodiesterase 5 Inhibitors/administration & dosage , Phosphodiesterase 5 Inhibitors/adverse effects , Randomized Controlled Trials as Topic , Walking/physiologySubject(s)
Denervation/methods , Kidney/innervation , Tachycardia, Ventricular/surgery , Adult , Humans , MaleABSTRACT
OBJECTIVE: To analyze the efficacy and safety of intra-aortic balloon pump (IABP) therapy in patients with acute myocardial infarction(AMI) based on the meta-analysis. METHODS: Eligible published randomized controlled clinical research (RCT) were retrieved in the Pubmed, EMBase, Cochrane, China biological medical literature, Wanfang, VIP and CNKI database from 1980 to April 2, 2012. The analysis was performed with the software of RevMan 5.1. RESULTS: Thirteen RCTs with 1958 patients (AMI with IABP therapy, n = 970,without IABP therapy, n = 988) were included. The 30-day mortality between the two groups was similar (RR = 0.77, 95%CI 0.58-1.03, P = 0.08), but the 30-day mortality in the cardiac shock subgroup was significantly lower in IABP group than in without IABP group (RR = 0.65, 95%CI 0.44-0.97, P = 0.04). The 6-month mortality was significantly lower in IABP group than in without IABP group (RR = 0.72, 95%CI 0.55-0.94, P = 0.02). The incidence of major bleeding was significantly higher in IABP group than in without IABP group (RR = 1.43, 95%CI 1.16-1.75, P < 0.01). CONCLUSION: IABP therapy is effective to reduce earlier mortality post AMI, particularly for patients with cardiac shock.
Subject(s)
Intra-Aortic Balloon Pumping , Myocardial Infarction/therapy , Humans , Randomized Controlled Trials as Topic , Treatment OutcomeABSTRACT
The present paper aimed at the question that the beam cross-section changes according to the rotation of concave grating during the measuring process, and the appropriate supplement to the principle of the program was done. The appropriate supplement to the principle lay the foundation for the derivation of the beam cross-section k(theta), and the whole analytical expression of changes factor of the beam cross-section k (theta) for concave grating was derived. Because of the relationship between the theoretical values and the factors which affect the diffraction efficiency measuring accuracy was nonlinear, the quadratic nonlinear regression analysis was introduced and the compensating formula was established. The results show further correction to diffraction efficiency measurements for concave grating, the range of differences between the compensated values and the theoretical values was reduced from +/- 2.5% to less than +/- 0.3%, compared with the linear regression analysis, and the quadratic nonlinear regression analysis significantly reduces the variation between the compensated values and the theoretical values, which further ensures the accurate measurement of the diffraction efficiency for concave gratings. The compensating process is embedded in the measurement program; this method is strongly real-time, which can satisfy the requirements of simple operation, testing speediness and preciseness.
ABSTRACT
Echelle spectrograph is a new type of high-resolution, high-precise spectrograph, and its resolution can be up to tens of thousands to hundreds of thousands. In this case, a little error of the structure will affect the resolution and precision greatly, so an accurate adjustment is of importance for the echelle spectrograph. According to the design features, the present paper discusses the adjustment method for echelle spectrograph. This is an uncomplicated, quick method, and adapts to mini, airproof structure of echelle spectrograph. Using this method, the actual state is consistent with the design result. The result of wavelength calibration is given out, and the error is less than 0.002 nm, which satisfies the requirement of the system.
ABSTRACT
BACKGROUND: Births between 37 0/7 and 38 6/7 weeks of gestation are newly defined as early term infants (ETIs), and are increasingly considered to be at higher risk of adverse outcomes than infants born at 39-41 weeks' gestation. To date, the long-term development of ETIs has not been systematically reviewed. OBJECTIVE: To assess the effect of being born early term on long-term developmental outcomes. METHODS: The literature of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, and abstracts from the Society of Pediatric Research were searched. If two or more studies regarding the same outcome were retrieved, a meta-analysis was conducted by RevMan 5. A sensitivity analysis was performed to assess the heterogeneity. RESULTS: Eleven studies involving 4 categories of long-term development were included. Compared with infants born at 39-41 weeks' gestation, ETIs had poorer outcomes in school performance, neurodevelopment, behavior and emotional status and long-term social outcomes. Meta-analyses showed that being born early term significantly increased the risk of cerebral palsy [relative risk, RR, 1.75 (95% confidence interval, CI, 1.32, 2.31)] and mathematical difficulties [RR 1.13 (95% CI 1.04, 1.21)]. The statistical test of heterogeneity for cerebral palsy was significant. Sensitivity analysis demonstrated that variations in follow-up periods were associated with heterogeneity. CONCLUSION: Emerging evidence suggests that ETIs are at risk of adverse long-term outcomes. Due to paucity and heterogeneity of the existing data, future research is needed to clarify the long-term risk of being born early term.
Subject(s)
Child Development/physiology , Infant, Premature/growth & development , Brain/growth & development , Brain/physiology , Gestational Age , Humans , Infant, Low Birth Weight/growth & development , Infant, Low Birth Weight/physiology , Infant, Newborn , Infant, Premature/physiology , Learning Disabilities/epidemiology , Learning Disabilities/etiology , Schools , Time FactorsABSTRACT
BACKGROUND: The Child-Pugh score, the model for end-stage liver disease (MELD) score, and the occurrence of cirrhosis-related complications are independent prognostic predictors used in the assessment of chronic liver diseases. OBJECTIVES: The objectives of this study were to determine the best prognostic scoring system, and to create a combined method to predict the prognosis of liver cirrhosis more accurately. METHODS: We retrospectively reviewed 435 cirrhotic patients from January 2009 to June 2010 and evaluated their short- and medium-term survival. Child-Pugh, MELD and its advanced scoring systems were computed for each patient. The sensitivity and specificity of these scoring systems were analyzed and their validity was assessed using concordance (c)-statistics in predicting the prognosis of cirrhotic patients. RESULTS: Overall, 107 patients died within 6 months and 150 patients died within 1 year. The clinical and biochemical characteristics, cirrhosis-related complications, and the scores were significantly different among the survivors and patients who died. The largest area under the receiver operating characteristic curve was 0.741 for the integrated MELD (iMELD) at 6 months and 0.713 for iMELD at 12 months, indicating that iMELD was the best scoring system tested. Given this result, we created a new scoring system that combined iMELD and an index of cirrhosis-related complications, called iMELD-C. This novel system had c indexes of 0.758 for the 6-month survival and 0.746 for the 1-year survival. CONCLUSIONS: The iMELD-C score is a better predictor of both short- and medium-term survival in patients with cirrhosis.
Subject(s)
End Stage Liver Disease/complications , Liver Cirrhosis/complications , Models, Theoretical , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Young AdultABSTRACT
It is important for the echelle spectrograph to acquire the exact positions of the spots in the two-dimension spectra image, which directly influence the precision of spectral analysis. With the target of high resolution, which is 15 000 in the echelle spectrograph being discussed, the acquired positional error must be less than 0.03 mm-which equals 2 pixels. According to the characters of the two-dimensional spectra, a position-acquiring method for the signal spots based on the centroid computing algorithm was put forward. Applying this method, the signal spots were distinguished from the noise spots and their positions can be acquired accurately and swiftly, with the positional error less than 2 pixels and wavelength error 0.02 nm, which satisfy the requirements of the echelle spectrograph.
ABSTRACT
OBJECTIVE: The efficacy of rate and rhythm control strategies for treating atrial fibrillation (AF) patients was analyzed in this meta-analysis. METHODS: Eligible trials were searched in MEDLINE, the Cochrane Library, the Clinical Trials, the Chinese VIP database up to May 31, 2010. Ten prospective randomized control trials with 7876 patients (rate control n = 3932, rhythm control n = 3944) were included for final analysis. RESULTS: All cause mortality (5.3% vs. 5.0%; OR: 1.03; 95%CI: 0.84 - 1.26; I(2) < 25%) and incidence of worsening heart failure (3.81% vs. 3.61%; OR: 1.04; 95%CI: 0.80 - 1.36; I(2) < 50%) were similar between the two groups. Subgroup analysis showed that all cause mortality (3.6% vs.1.9%; OR: 1.89; 95%CI: 1.01 - 3.53; I(2) < 25%) and rate of worsening heart failure (2.3% vs. 0.3%; OR: 5.6; 95%CI: 1.44 - 21.69; I(2) < 25%) were significantly higher in rate control group than in rhythm control group in patients with age < 65 years. Thromboembolic events (1.49% vs. 1.46%; OR: 1.02, 95%CI: 0.71 - 1.48) and bleeding events (1.78% vs. 1.73%; OR: 1.02, 95%CI: 0.70 - 1.49) were similar between rhythm control and rate control groups while rehospitalization rate was significantly lower in rate control group than in rhythm control group (17.56% vs. 22.98%; OR: 0.37, 95%CI: 0.19 - 0.71). CONCLUSION: This meta-analysis shows that rhythm control strategy is superior to rate control strategy for AF patients with age < 65 years in terms of reducing all cause mortality and incidence of worsening heart failure.
Subject(s)
Arrhythmias, Cardiac/prevention & control , Atrial Fibrillation/prevention & control , Atrial Fibrillation/physiopathology , Heart Rate , Humans , Prospective Studies , Randomized Controlled Trials as TopicABSTRACT
The present paper analyzed the influence of the pinhole diameter, grating parameters, CCD pixel size, prism parameters, system aberrations and found that the first three are the main factors, and then deduced the mutual restraint relationship among them. On this basis, a portable high-resolution echelle spectrograph was designed. Applying this design, aberration was fully corrected and spectral resolution achieved the demand. With the Hg lamp calibrated and restored, the actual resolution gets up to 0.038 nm which is significantly better than target (0.05@200 nm), while the ordinary grating spectrometers need 500 mm focal length to achieve this resolution. From this result, the advantages of the portable echelle spectrograph are fully demonstrated.
ABSTRACT
OBJECTIVE: To investigate the feasibility of transferring p21 gene into lung tissue with recombinant adenovirus with full-length cDNA of p21 inserted in the Wistar rat model of pulmonary hypertension (PAH) induced by left-to-right shunt, study the expression of the desired gene in vivo, find if overexpression of desired gene can inhibit pulmonary hypertension. METHODS: With full-length cDNA of p21 transfected HEK293 cells with clonfectin, and was packed, amplified in order to obtain the high-titer recombinant adenovirus (AdCMV-p21). The infection titer was determined by TCID50 method and was diluted into 1.67 x 10(8) pfu/L. Wistar rats were randomly allocated to control group (n = 10), model group (n = 15), test group (n = 10) and test control group (n = 10). In model group and test group left-to-right shunt pulmonary hypertension was developed by using cuff technique. AdCMV-p21 was transfected into test group and test control group using tracheal inhalation. The mPAP, mRVP and RVHI were measured and compared between every two groups. The left lung was immunohistochemically stained to observe the result of transfection. The right lung was HE stained to observe morphological changes in arteria pulmonalis and calculate WT%. RESULTS: The mRVP, mPAP and WT% in model group and test group were significantly higher than those in control (P < 0.05), which suggested that the rat model of PAH was established successfully. Brown spots in the nucleus of VSMCs of pulmonary artery were seen in test group and test control group, which indicated that AdCMV-p21 was transfected successfully. The rate of transfected cells in test group was (42.8 +/- 11.6)%, which was equal to that of test control group (P > 0.05). In test group, the mPAP was (20.06 +/- 3.40) mm Hg (1 mm Hg = 0.133 kPa), mRVP was (22.53 +/- 2.53) mm Hg, WT% was (30.8 +/- 3.5)%, which were significantly lower than those in model group (P < 0.05), but higher than those in control group and test control group (P < 0.05). CONCLUSION: The recombinant adenovirus could successfully carry p21 and transfect the lung tissue of PAH rat model, and full expression of p21. p21 gene could inhibit the development of PAH.