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1.
Background  Smoking is the leading cause of death in the world. This study focused on the difference of the serum proteomic profiling between healthy smokers and nonsmokers in order to find smoking-specific serum biomarkers.
Methods  Pattern-based proteomic profiling of 100 serum samples (from 50 Chinese male smokers and 50 matched nonsmokers) was performed through magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and resulting data were statistically analyzed by Ciphergen ProteinChip software 3.0.2.
Results  We found 72 serum peaks were significantly different between smokers and nonsmokers (P <0.05). Marker peaks of mass-to-charge ratio (m/z) 3159.13, 7561.03 and 9407.32 were smoking-specific.
Conclusion  The preliminary data suggested that smoking-specific serum biomarkers could be detected in humans.
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2.
Background  Osteoclast-associated receptor (OSCAR) is a member of the newly identified leukocyte receptor complex, and has recently been described as a key molecule in osteoclastogenesis. In this study, we measured the levels of soluble osteoclast-associated receptor (sOSCAR) in the serum of rheumatoid arthritis (RA) patients and healthy controls to examine whether sOSCAR may play a role in the process of inflammatory arthritis.
Methods  Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of sOSCAR in the serum of 40 healthy controls and 40 RA patients.
Results  The serum levels of sOSCAR were significantly lower in RA patients than in healthy controls, and were inversely associated with inflammatory activity.
Conclusion  sOSCAR is decreased in patients with RA and reduced levels of the protein are associated with increased inflammatory response.
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3.
Background  Liver cirrhosis is the fatal consequence of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a broad population with alcoholism or hepatitis B virus (HBV) infection remains difficult. In this study, we used a metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis.
Methods  Serum specimens were collected prospectively from normal control subjects (n=22) and patients with alcoholic cirrhosis (n=18) or HBV-induced cirrhosis (n=19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA).
Results  Significant differences in the metabonomics among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) were decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide were increased in the serum of patients with hepatic cirrhosis. These metabolites are considered “common” biomarkers for hepatic cirrhosis. Oleamide and myristamide were increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis.
Conclusions  There are significant metabonomic differences between alcohol- and HBV-induced liver cirrhosis. Metabonomics is a top-down systems biology tool for conducting research on clinical problems.
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4.
Background  Fourier transform infrared spectroscopy (FT-IR) combined with chemometrics discriminant analysis technology could improve diagnosis. The present study aimed to evaluate the effects of FT-IR on malignant colon tissue samples in diagnosis of colon cancer.
Methods  Principal component analysis (PCA) and support vector machine classification were used to discriminate FT-IR spectra from malignant and normal tissue. Colon tissues samples from 85 patients were used to demonstrate the procedure.
Results  For this set of colon spectral data, the  sensitivity and specificity of the support vector machine (SVM) classification were found both higher than 90%.
Conclusions  FT-IR provided important information about cancerous tissue, which could be used to discriminate malignant from normal tissues. The combination of PCA and SVM classification indicated that FT-IR has a potential clinical application in diagnosis of colon cancer.
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5.
6.
Background  Gastric cancer (GC) is one of the most common types of cancer in the world. A change in the metabolism of lipids in tumor cells could lead to the pathogenesis of cancer. In this study, we investigated fatty acid and fatty acid amide metabolic perturbations associated with GC morbidity.
Methods  Gas chromatography/mass spectrometry (GC/MS) was utilized to analyze fatty acids (FAs) and fatty acid amides (FAAs) of GC tissues and matched normal mucosae from 30 GC patients. Acquired lipid data was analyzed using non parametric Wilcoxon rank sum test to find the differential biomarkers for GC and diagnostic models for GC were established by using orthogonal partial least squares discriminant analysis (OPLS-DA).
Results  A total of 13 FAs and 4 FAAs were detected using GC/MS and 5 differential FAs as well as oleamide were identified with significant difference (P <0.05). The OPLS-DA model generated from lipid profile showed adequate discrimination of GC tissues from normal mucosae while the OPLS-DA model failed to separate GC specimens of different TNM stages. A total of 8 variables were obtained for their most contribution in the discriminating model (Variable importance in the projection (VIP) value >1.0), five of which were detected with significant difference (P <0.05).
Conclusions  FA and FAA metabolic profiles have great potential in detecting GC and helping understand perturbations of lipid metabolism associated with GC morbidity.
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7.
 
Background  Varieties of restorative materials are widely used in dentistry. The aim of this study is to explore the influence of different dental restorative materials on bond interface reliability.
Methods  A two-dimensional finite element analysis method was adopted to simulate the shear-bond efficacy test. The influence of elastic modulus and Poisson’s ratio were investigated separately. Several dental restorative materials including resins, metals, and ceramics were analyzed in this study.
Results  The deformation and peak equivalent stress level of the dentin-adhesive interface rose sharply following a decrease in the elasticity of restorative materials, especially those with a low elastic modulus range. The influence of the Poisson’s coefficient was not significant. Ceramics and gold alloy were preferred to resin composite in restorations bearing extensive shear load during service.
Conclusions  Restorative materials with an elastic modulus similar to that of teeth are not always the best clinical choice. This research provides a helpful guide for the application of different restorative materials in clinical practice.
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8.
Objective  To review the senescent remodeling of the immune system with aging and its relevance to the increased susceptibility of the elderly to infectious diseases, along with an outlook on emerging immunological biomarkers.
Data sources  The data selected were from PubMed with relevant published articles in English or French from 1995 to the present. Searches were made using the terms “immunosenescence” and “aging” paired with the following: “innate immunity”, “T-cell”, “B-cell”, “adaptive immunity” and “biomarkers”. Articles were reviewed for additional citations and some information was gathered from web searches.
Study selection  Articles on aging of both the innate and adaptive immunity were reviewed, with special attention to the remodeling effect on the ability of the immune system to fight infectious diseases. Articles related to biomarkers of immunosenescence were selected with the goal of identifying immunological biomarkers predisposing the elderly to infections.
Results  Innate immunity is generally thought to be relatively well preserved or enhanced during aging compared with adaptive immunity which manifests more profound alterations. However, evidence, particularly in the last decade, reveals that both limbs of the immune system undergo profound remodeling with aging. Reported data on adaptive immunity is consistent and changes are well established but conflicting results about innate immunity were reported between in vivo and in vitro studies, as well as between murine and human studies. Epidemiological data suggests increased predisposition of the elderly to infections, but no compelling scientific evidence has directly linked senescent immune remodeling to this increased susceptibility. Recently, growing interest in identifying immunological biomarkers and defining “immune risk phenotypes/profiles” (IRP) has been expressed. Identification of biomarkers is in its early days and few potential biomarkers have been identified, with the Swedish having defined one IRP based on the adaptive immune response.

Conclusions  Aging does not necessarily lead to an unavoidable decline in immune functions. Instead, a complex remodeling occurs. Despite the lack of compelling scientific evidence, senescent immune remodeling surely is a significant contributing factor to the increased risk and severity of infections in the elderly. Although, no immunological biomarker has been formally linked to the increased risk of infections in the elderly, biomarkers remain a promising tool to predict the likelihood of healthy aging, the level of immune competence, and mortality risk in the elderly. Hence, more research is required to define healthy aging and identify immunological biomarkers.

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9.
10.
《中华医学杂志(英文版)》2012,125(19):3548-3555
Objective  To review the updated research progress about the application of echocardiography in resynchronization treatment of chronic heart failure patients.
Data sources  The data used in this review were from PubMed, published in English and using the key terms “heart failure”, “echocardiography” and “cardiac resynchronization therapy”.
Study selection  Relevant articles were reviewed and selected to address the stated purpose.
Results Increasing numbers of studies have suggested the importance of echocardiography in resynchronization treatment of chronic heart failure patients. Echocardiography can evaluate atrioventricular, inter- and intra-ventricular mechanical dyssynchrony before cardiac resynchronization therapy (CRT), as a guidance to assess the optimal left ventricular (LV) pacing location, optimize the atrioventricular and interventricular delays and predict response to CRT.
Conclusions  Echocardiography is both non invasive and easily repeatable, and plays a crucial role in appraisal of heart synchronism, instruction of actuator placement, optimization of the device procedure, and prediction of the response to CRT.
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11.
Background  Neuroblastoma (NB) is one of the most common malignant solid tumors of childhood. It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c (Cyt c) in the serum of the cancer patients. The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.
Methods  We subcutaneously inoculated human NB cells (KP-N-NS) into nude mice and collected the sera of tumor-bearing mice (n=14) and control mice (n=25) 4 weeks later in order to screen for and identify differentially expressed proteins in the serum. Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-flight (SELDI-TOF) mass spectrometry.
Results  The relative intensity of a protein having a mass-to-charge ratio (m/z) of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group, indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group. Serum proteins were separated and purified by high-performance liquid chromatography (HPLC). Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to produce peptide mass fingerprints (PMFs). Spectrum analysis and a database search revealed that the highly expressed protein (m/z=11 605.4) from the serum of tumor-bearing mice was the mouse Cyt c.
Conclusions  Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.
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12.
Background  Over-expression of P-glycoprotein (P-gp), encoded by the MDR1 gene, confers multidrug resistance (MDR) in renal cell carcinoma (RCC) and is a major reason for unsuccessful chemotherapy. This study aimed to determine the effct of RNA interference (RNAi) on the reversal of MDR in human RCC.
Methods  We designed and selected one short hairpin RNA (shRNA) targeting MDR1 gene, which is stably expressed from integrated plasmid and transfected by lentivirus fluid in human RCC A498 cell.
Results  The MDR1-targeted RNAi resulted in decreased MDR1 gene mRNA level (P <0.001), almost abolished P-gp expression and reversed MDR to different chemotherapy drugs in the RCC A498 cell line.

Conclusion  MDR could be reversed by RNAi in human RCC A498 cell line, which may be used for clinical application in future.

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13.
Objective  To summarize the development of gene delivery vectors in peritoneal fibrosis research and discuss the feasibility and superiority of lentiviral vectors.
Data sources  The data in this article were collected from PubMed database with relevant English articles published from 1995 to 2011.
Study selection  Articles regarding the gene therapy in peritoneal fibrosis research using non-viral vectors, adenoviral vectors, retroviral vectors, and lentiviral vectors were selected. Data were mainly extracted from 60 articles, which are listed in the reference section of this review.
Results  Non-viral vector-mediated gene delivery (including naked DNA for ex vivo, oligonucleotides, ultrasound- contrast agent mediated naked gene delivery, etc.) and viral vector-mediated gene delivery (including adenovirus, helper-dependant adenovirus, and retrovirus vectors) have been successfully applied both in the mechanistic investigation and the potential prevention and treatment of peritoneal fibrosis.
Conclusions  Peritoneal fibrosis is a major complication of peritoneal dialysis (PD). Recently, the wide use of the gene delivery technique made it possible to access and further research peritoneal fibrosis. The use of lentiviral vector is expected to be widely used in PD research in the future due to its advantages in gene delivery.
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14.
Background  Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time.
Methods  Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells (BMSCs) expressing recombinant human bone morphogenetic protein-2 (rhBMP-2) and green fluorescent protein (GFP). Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed.
Results  The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae.
Conclusion  Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.
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15.
Background  Phenotypic and genotypic heterogeneity is a known feature of many cancers. Whether serum tumor marker kinds vary and change following chemotherapy is still unclear. The aim of this study was to investigate whether there is a change in the expression of serum tumor markers following chemotherapy, and the potential clinical significance in patients with epithelial ovarian carcinoma (EOC) or primary serous peritoneal carcinoma (PSPC).
Methods  Samples were collected before surgery, during chemotherapy and during follow-up for enzyme-linked immunosorbent assay (ELISA)-based evaluation of serum CA-125, CA19-9 and CP2 levels in patients with EOC or PSPC who had received primary debulking surgery followed by adjuvant chemotherapy. In total, 72 patients were examined, including 37 patients with recurrent lesions and 35 patients receiving first-line chemotherapy.
Results  In 35 de novo patients, 20% (7/35) demonstrated a significant changed serum tumor marker kinds among whom the patients with mucinous carcinoma (57.1%, 4/7) showed resistance to chemotherapy. In the 37 recurrent patients, 51.4% (19/37) had changed serum tumor markers, of whom 57.9% (11/19) presented with serous carcinoma. There was no significant difference in median progression-free survival or overall survival in patients with drug-sensitive or drug-resistant recurrence in patients with changed tumor marker kinds relative to those with unchanged markers. However, for patients with changed serum tumor markers there was a trend towards prolonged survival compared with the unchanged serum tumor marker group. In the 17 patients with secondary recurrence, 37.5% (6/17) had changed tumor marker levels. The ratios of CA-125/CP2 and CA-125/CA19-9 were significantly different after either chemotherapy or recurrence.
Conclusions  Serum tumor marker expression in patients with EOC or PSPC may change after chemotherapy or recurrence, indicating that in addition to the markers that are abnormal before surgery, those markers that are normal should also be monitored during chemotherapy and follow-up.
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16.
Background  Pulmonary capillary hemangiomatosis (PCH) is a rare disease and no Chinese case has been reported yet. The disease is often misdiagnosed and its clinical characteristics are incompletely described. The aim of this study was to describe two Chinese cases and to clarify the clinical and radiographic parameters of patients with PCH.
Methods  Two PCH cases were presented and other cases were searched from the English literature. All available clinical and radiographic data were collected from 62 literature reported PCH cases. A pooled analysis of total 64 cases was made.
Results  Dyspnea and hemoptysis were the most common clinical symptoms of PCH. Pulmonary hypertension (PH) was found in 78% of the reported cases. PCH typically showed characteristic diffuse or patchy ground-glass opacities (GGOs) and/or multiple ill-defined centrilobular nodules in the computed tomography.
Conclusions  The diagnosis of PCH requires a high clinical suspicion. However, both clinical presentations and radiographic studies often provide clues to the diagnosis, which may prompt early lung biopsy for a definite diagnosis.
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17.
《中华医学杂志(英文版)》2012,125(24):4460-4465
Background  The research of cancer in patients on hemodialysis (HD) in China has not been reported. The aim of this study was to investigate the clinical and histological features and outcomes of cancer in Chinese HD patients.
Methods  The study subjects were 49 cancer patients (1.4%) out of 3448 end stage renal disease (ESRD) patients maintained on HD at China-Japan Friendship Hospital from October 1997 to July 2011.
Results  Urinary tract cancer (74%) was the most common followed by gastrointestinal tract cancer (12%), breast cancer (6%), lung cancer (4%), thyroid cancer (2%), and hematologic cancer (2%). Thirty-three patients (67%) had urinary tract transitional cell carcinoma (TCC) and 29 of them had aristolochic acid nephropathy (AAN) as underlying disease. Death occurred in eight patients out of 49, and the survival rate of HD patients with cancer was similar to those without cancer (P=0.120).
Conclusion  The urinary tract TCC is the most common cancer in HD patients with AAN in one of the centers of northern China.
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18.
Background  The correlation between the plasma D-dimer level and deep vein thrombosis has not been conclusive in various studies. The aim of this research was to study the relationship between plasma D-dimer levels and the severity of orthopedic trauma by retrospective examination of orthopedic trauma cases.
Methods  Clinically acute trauma and non-acute trauma patients were selected and their plasma D-dimer levels were measured. Plasma D-dimer levels in patients of these two groups were compared. The relationship between the plasma D-dimer level and the severity of the trauma was also studied.
Results  There were 548 cases in the acute trauma group and 501 cases in the non-acute trauma group. The levels of plasma D-dimer were significantly higher in the acute trauma group than in the non-acute trauma group (P <0.01). In the acute trauma group, the correlation between the D-dimer level and the number of fractures was a positive linear correlation (r=0.9532).
Conclusions  Elevated plasma D-dimer is common in trauma patients. The D-dimer level and the number of fractures in the trauma patients are closely correlated. D-dimer is not only an indicator for the diagnosis of deep vein thrombosis and pulmonary embolus, but also an indicator of the severity of trauma in acute trauma patients.
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19.
《中华医学杂志(英文版)》2012,125(22):4031-4036
Background  Repair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly(lactic-co-glycolic acid) (PLGA) to promote new bone formation within rabbit ulnar segmental bone defects.
Methods  Rabbit bone marrow-derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental bone defects, each 15 mm in length, were created in the rabbit ulna, from which periosteum was obtained. Bone defects were treated with either PLGA alone (group A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum-wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were detected by gross observation, radiological examination (X-ray and micro-CT) and histological analyses.
Results  Group D, comprising both periosteum and MSCs, showed better bone quality, higher X-ray scores and a greater amount of bone volume compared with the other three groups at each time point (P <0.05). No significant differences in radiological scores and amount of bone volume were found between groups B and C (P >0.05), both of which were significantly higher than group A (P <0.05). 
Conclusions  Implanted MSCs combined with periosteum have a synergistic effect on segmental bone regeneration and that periosteum plays a critical role in the process. Fabrication of angiogenic and osteogenic cellular constructs or tissue-engineered periosteum will have broad applications in bone tissue engineering.
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