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BACKGROUND: Acute Kidney Injury (AKI), a prevalent complication of Liver Transplantation (LT) that occurs during the perioperative period has been established to profoundly impact the prognosis of transplant recipients. This study aimed to investigate the mechanism of the hepatic IRI-induced AKI and to identify potential therapeutic targets for treating this condition and improving the prognosis of LT patients. METHODS: An integrated transcriptomics and proteomics approach was employed to investigate transcriptional and proteomic alterations in hepatic IRI-induced AKI and the hypoxia-reoxygenation (H/R) model using TCMK-1 cells and the hepatic IRI-induced AKI mouse model using male C57BL/6 J mice were employed to elucidate the underlying mechanisms. Hematoxylin-eosin staining, reverse transcription quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and Western blot were used to assess the effect of Rosiglitazone (RGZ) on hepatic IRI-induced AKI in vitro and in vivo. RESULTS: According to the results, 322 genes and 128 proteins were differentially expressed between the sham and AKI groups. Furthermore, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomics (KEGG) pathway analyses revealed significant enrichment in pathways related to amino acid and lipid metabolism. Additionally, the Protein-Protein Interaction (PPI) network analysis of the kidney tissues obtained from a hepatic IRI-induced AKI mouse model highlighted arachidonic acid metabolism as the most prominent pathway. Animal and cellular analyses further revealed that RGZ, a PPAR-γ agonist, could inhibit the expression of the PPAR-γ/NF-κB signaling pathway-associated proteins in in vitro and in vivo. CONCLUSIONS: These findings collectively suggest that RGZ ameliorates hepatic IRI-induced AKI via PPAR-γ/NF-κB signaling pathway modulation, highlighting PPAR-γ as a crucial therapeutic target for AKI prevention post-LT.
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Acute rejection is an important factor affecting the survival of recipients after liver transplantation. Salidroside has various properties, including anti-inflammatory, antioxidant, and hepatoprotective properties. This study aims to investigate whether salidroside can prevent acute rejection after liver transplantation and to examine the underlying mechanisms involved. An in vivo acute rejection model is established in rats that are pretreated with tacrolimus (1â mg/kg/d) or salidroside (10 or 20â mg/kg/d) for seven days after liver transplantation. In addition, an in vitro experiment is performed using neutrophils incubated with salidroside (1, 10, 50 or 100â µM). Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, immunosorbent assays, immunofluorescence analysis, Evans blue staining, and western blot analysis are performed to examine the impact of salidroside on NET formation and acute rejection in vitro and in vivo. We find that Salidroside treatment reduces pathological liver damage, serum aminotransferase level, and serum levels of IL-1ß, IL-6, and TNF-α in vivo. The expressions of proteins associated with the HMGB1/TLR-4/MAPK signaling pathway (HMGB1, TLR-4, p-ERK1/2, p-JNK, p-P38, cleaved caspase-3, cleaved caspase-9, Bcl-2, Bax, IL-1ß, TNF-α, and IL-6) are also decreased after salidroside treatment. In vitro experiments show that the release of HMGB1/TLR-4/MAPK signaling pathway-associated proteins from neutrophils treated with lipopolysaccharide is decreased by salidroside. Moreover, salidroside inhibits NETosis and protects against acute rejection by regulating the HMGB1/TLR-4/MAPK signaling pathway. Furthermore, salidroside combined with tacrolimus has a better effect than either of the other treatments alone. In summary, salidroside can prevent acute liver rejection after liver transplantation by reducing neutrophil extracellular trap development through the HMGB1/TLR-4/MAPK signaling pathway.
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Trampas Extracelulares , Glucósidos , Rechazo de Injerto , Proteína HMGB1 , Trasplante de Hígado , Neutrófilos , Fenoles , Receptor Toll-Like 4 , Animales , Fenoles/farmacología , Glucósidos/farmacología , Trampas Extracelulares/efectos de los fármacos , Trampas Extracelulares/metabolismo , Rechazo de Injerto/prevención & control , Rechazo de Injerto/patología , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/metabolismo , Proteína HMGB1/metabolismo , Receptor Toll-Like 4/metabolismo , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Ratas , Ratas Sprague-Dawley , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Apoptosis/efectos de los fármacosRESUMEN
BACKGROUND: Impaired fasting glucose (IFG) is a prediabetic condition. Considering that the clinical symptoms of IFG are inconspicuous, these tend to be easily ignored by individuals, leading to conversion to diabetes mellitus (DM). In this study, we established a prediction model for the onset risk of IFG in the Chongqing health check-up population to provide a reference for prevention in a health check-up cohort. METHODS: We conducted a retrospective longitudinal cohort study in Chongqing, China from January 2009 to December 2019. The qualified subjects were more than 20 years old and had more than two health check-ups. After following the inclusion and exclusion criteria, the cohort population was randomly divided into a training set and a test set at a ratio of 7:3. We first selected the predictor variables through the univariate generalized estimation equation (GEE), and then the training set was used to establish the IFG risk model based on multivariate GEE. Finally, the sensitivity, specificity, and receiver operating characteristic curves were used to verify the performance of the model. RESULTS: A total of 4,926 subjects were included in this study, with an average of 3.87 check-up records, including 2,634 males and 2,292 females. There were 442 IFG cases during the follow-up period, including 286 men and 156 women. The incidence density was 26.88/1000 person-years for men and 18.53/1000 person-years for women (P<0.001). The predictor variables of our prediction model include male (relative risk (RR) =1.422, 95 % confidence interval (CI): 0.923-2.193, P=0.3849), age (RR=1.030, 95 %CI: 1.016-1.044, P<0.0001), waist circumference (RR=1.005, 95 %CI: 0.999-1.012, P=0.0975), systolic blood pressure (RR=1.004, 95 %CI: 0.993-1.016, P=0.4712), diastolic blood pressure (RR=1.023, 95 %CI: 1.005-1.041, P=0.0106), obesity (RR=1.797, 95 %CI: 1.126-2.867, P=0.0140), triglycerides (RR=1.107, 95 %CI: 0.943-1.299, P=0.2127), high-density lipoprotein cholesterol (RR=0.992, 95 %CI: 0.476-2.063, P=0.9818), low-density lipoprotein cholesterol (RR=1.793, 95 %CI: 1.085-2.963, P=0.0228), blood urea (RR=1.142, 95 %CI: 1.022-1.276, P=0.0192), serum uric acid (RR=1.004, 95 %CI: 1.002-1.005, P=0.0003), total cholesterol (RR=0.674, 95 %CI: 0.403-1.128, P=0.1331), and serum creatinine levels (RR=0.960, 95 %CI: 0.945-0.976, P<0.0001). The area under the receiver operating characteristic curve (AUC) in the training set was 0.740 (95 %CI: 0.712-0.768), and the AUC in the test set was 0.751 (95 %CI: 0.714-0.817). CONCLUSIONS: The prediction model for the onset risk of IFG had good predictive ability in the health check-up cohort.
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Intolerancia a la Glucosa , Modelos Estadísticos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Osteoporosis is a gradually recognized health problem with risks related to disease history and living habits. This study aims to establish the optimal prediction model by comparing the performance of four prediction models that incorporated disease history and living habits in predicting the risk of Osteoporosis in Chongqing adults. METHODS: We conduct a cross-sectional survey with convenience sampling in this study. We use a questionnaire From January 2019 to December 2019 to collect data on disease history and adults' living habits who got dual-energy X-ray absorptiometry. We established the prediction models of osteoporosis in three steps. Firstly, we performed feature selection to identify risk factors related to osteoporosis. Secondly, the qualified participants were randomly divided into a training set and a test set in the ratio of 7:3. Then the prediction models of osteoporosis were established based on Artificial Neural Network (ANN), Deep Belief Network (DBN), Support Vector Machine (SVM) and combinatorial heuristic method (Genetic Algorithm - Decision Tree (GA-DT)). Finally, we compared the prediction models' performance through accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) to select the optimal prediction model. RESULTS: The univariate logistic model found that taking calcium tablet (odds ratio [OR] = 0.431), SBP (OR = 1.010), fracture (OR = 1.796), coronary heart disease (OR = 4.299), drinking alcohol (OR = 1.835), physical exercise (OR = 0.747) and other factors were related to the risk of osteoporosis. The AUCs of the training set and test set of the prediction models based on ANN, DBN, SVM and GA-DT were 0.901, 0.762; 0.622, 0.618; 0.698, 0.627; 0.744, 0.724, respectively. After evaluating four prediction models' performance, we selected a three-layer back propagation neural network (BPNN) with 18, 4, and 1 neuron in the input layer, hidden and output layers respectively, as the optimal prediction model. When the probability was greater than 0.330, osteoporosis would occur. CONCLUSIONS: Compared with DBN, SVM and GA-DT, the established ANN model had the best prediction ability and can be used to predict the risk of osteoporosis in physical examination of the Chongqing population. The model needs to be further improved through large sample research.
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Redes Neurales de la Computación , Osteoporosis , Adulto , China/epidemiología , Estudios Transversales , Hábitos , Humanos , Osteoporosis/epidemiología , Examen FísicoRESUMEN
Tumor cells with damaged mitochondria undergo metabolic reprogramming, but gene therapy targeting mitochondria has not been comprehensively reported. In this study, plasmids targeting the normal hepatocyte cell line (L-O2) and hepatocellular carcinoma cell line were generated using three genes SIRT3, SIRT4, and SIRT5. These deacetylases play a variety of regulatory roles in cancer and are related to mitochondrial function. Compared with L-O2, SIRT3 and SIRT4 significantly ameliorated mitochondrial damage in HCCLM3, Hep3B and HepG2 cell lines and regulated mitochondrial biogenesis and mitophagy, respectively. We constructed double-gene plasmid for co-express SIRT3 and SIRT4 using the internal ribosome entry site (IRES). The results indicated that the double-gene plasmid effectively expressed SIRT3 and SIRT4, significantly improved mitochondrial quality and function, and reduced mtDNA level and oxidative stress in HCC cells. MitoTracker analysis revealed that the mitochondrial network was restored. The proliferation, migration capabilities of HCC cells were reduced, whereas their differentiation abilities were enhanced. This study demonstrated that the use of IRES-linked SIRT3 and SIRT4 double-gene vectors induced the differentiation of HCC cells and inhibited their development by ameliorating mitochondrial dysfunction. This intervention helped reverse metabolic reprogramming, and may provide a groundbreaking new framework for HCC treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Sirtuina 3 , Sirtuinas , Humanos , Sirtuina 3/genética , Sirtuina 3/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Sirtuinas/genética , Sirtuinas/metabolismo , Sirtuinas/farmacología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mitocondrias/metabolismo , Línea Celular , Fenotipo , Proteínas Mitocondriales/metabolismoRESUMEN
BACKGROUND: The polymorphisms of VKORC1 and CYP2C9 play increasingly important roles in the inter-individual variability in warfarin dose. This study aimed to evaluate the feasibility of clinical application of pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement in a randomized and controlled trial. METHODS: One hundred and one consecutive patients of Han nationality with rheumatic heart disease undergoing valve surgery were enrolled and randomly assigned to an experimental group (n=50, based on CYP2C9 and VKORC1 genotypes, pharmacogenetic-based "predicted warfarin dose" for 3 days and then was adjusted to INR until stable warfarin maintenance dose) or a control group (n=51, 2.5mg/d for 3 days and then was adjusted to INR until stable warfarin maintenance dose). All included patients were followed for 50 days after initiation of warfarin therapy. The primary end-point was the time to reach a stable warfarin maintenance dose. RESULTS: During the follow-up, 84.0% patients in the experimental group and 58.8% patients in the control group received warfarin maintenance dose. Compared with control group, patients in the experimental group had shorter mean time elapse from initiation of warfarin therapy until warfarin maintenance dose (27.5±1.8 d versus 34.7±1.8 d, p<0.001). Cox regression revealed that group (HR for experimental versus control group: 1.568, 95%CI 1.103-3.284) and age were two significant variables related to the time elapse from initiation of warfarin therapy until warfarin maintenance dose. The predicted warfarin maintenance dose was prominently correlated with the actual warfarin maintenance dose (r=0.684, p<0.001). CONCLUSION: Based on CYP2C9 and VKORC1 genotypes, the pharmacogenetic-based warfarin-dosing algorithm may shorten the time elapse from initiation of warfarin therapy until warfarin maintenance dose. It is feasible for the clinical application of the pharmacogenetic-based warfarin-dosing algorithm in patients of Han nationality with rheumatic heart disease after valve replacement.
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Algoritmos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Farmacogenética/métodos , Enfermedades Reumáticas/cirugía , Warfarina/administración & dosificación , Warfarina/uso terapéutico , Adulto , Pueblo Asiatico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Studies have explored the relation between serum uric acid (SUA) and carotid intima-media thickness (CIMT), but the relation remains controversial. The purpose of this study was to examine SUA concentration and its correlation with carotid artery atherosclerosis according to age group and gender. Subjects who underwent physical examinations at the First Affiliated Hospital of Chongqing Medical University from 2016 to 2020 were selected. Using traditional atherosclerosis risk factors as adjustment variables, the association between blood uric acid level and atherosclerosis was assessed by logistic regression analysis. A total of 15,843 subjects (73.90% men) were included, with an average age of 52 ± 12 years. The prevalence of increased CIMT was 9.51%, and the prevalence of plaque was 28.59%. Univariate analysis results showed that there were significant differences in the occurrence of increased CIMT and plaque among different SUA-level groups in both men and women (p <0.0001). After adjustment for conventional cardiovascular risk factors, increased SUA level was significantly associated with an increased risk of carotid intima-media thickening. Correlation analysis in each age subgroup showed that CIMT was significantly associated with SUA in men ≥60 years old and women 45 to 60 years old or ≥60 years old (p <0.0001). In conclusion, in both men and women, increased SUA levels are closely associated with increased CIMT. The age at which this association was observed was lower in women than in men; whether the lower age in women is due to changes in hormone levels between before and after menopause remains to be prospectively studied.
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Aterosclerosis , Enfermedades de las Arterias Carótidas , Adulto , Aterosclerosis/epidemiología , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores Sexuales , Ácido ÚricoRESUMEN
The 15-minute community life circle (15min-CLC) strategy is one of Shanghai's important methods for building a global city and facing a society with a more diverse population structure in the future. In the existing research, the balance between the construction of the life circle and the needs of the people in the life circle still needs to be further fulfilled. This paper is based on the city's multi-source large data set including 2018 AutoNavi POI (Point of Interests), OSM (OpenStreetMap) road network data and LandScan population data set, and evaluates the current status of Shanghai's 15min-CLC through the fusion of kernel density estimation, service area analysis and other statistical models and proposes relevant optimization suggestions. The results show that there are the following shortcomings: (1) From the perspective of different types of infrastructure service facilities, the spatial construction of Shanghai's overall life service facilities and shopping service facilities needs to be optimized. (2) From the perspective of comprehensive evaluation, the comprehensive service convenience of infrastructure service facilities in the downtown area is relatively high, while the comprehensive service convenience of urban infrastructure service facilities in the suburbs and outer suburbs is relatively low; The diversity of basic service facilities in the 15min-CLC in the downtown area is more consistent with the population distribution; However, in the peripheral areas of the urban area, too many infrastructure service facilities have been constructed. Based on the above shortcomings and the perspective of supply and demand matching, relevant optimization strategies are proposed in different regions and different types of infrastructure service facilities: (1) focus on the construction of basic service facilities in the urban fringe and urban-rural areas, improve the full coverage of the basic service facilities, and appropriately reduce the number of basic service facilities in the downtown area. (2) The development of community business models can be used to promote the development of new life service facilities and shopping service facilities. (3) Improve community medical institutions through facility function conversion, merger and reconstruction, etc. (4) Optimize the hierarchical basic service facility system and improve the population supporting facilities of basic service facilities in the 15min-CLC. This paper incorporates people's needs and concerns on the living environment into the 15min-CLC evaluation model, and uses Shanghai as an example to conduct research, summarizes the existing shortcomings, and proposes corresponding optimization strategies based on the matching of supply and demand. This article attempts to explore a replicable 15min-CLC planning model, so that it can be extended to the Yangtze River Delta urban agglomeration, to provide reference for further research on the 15min-CLC, and to promote urban construction under the concept of sustainable development.
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Entorno Construido , Planificación de Ciudades/métodos , Características de la Residencia , Remodelación Urbana/métodos , Actividades Cotidianas , China , Ciudades , Demografía , Humanos , Modelos Estadísticos , Población UrbanaRESUMEN
OBJECTIVE: Recently, increasing epidemiological evidence has shown that there is a correlation between serum uric acid level (SUA) and carotid intima-media thickness (CIMT). This paper explored the relationship between them through meta-analysis. METHODS: PubMed, Cochrane Library, EMBASE, Web of Science and Google Scholar were searched to obtain literature. The keywords used to retrieve the literature were carotid intima thickness, intima-media thickness, carotid atherosclerosis, carotid stenosis, carotid artery, uric acid, blood uric acid, and hyperuricaemia. The retrieval time was from the establishment of the database through July 2020. Stata15.0 and RevMan5.3 software were used for statistical analysis. The standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated by a random effect model to estimate the correlation. Publication bias was assessed using the Begg and Egger tests. The stability of these results was evaluated using sensitivity analyses. RESULTS: Fifteen studies were included with a total sample size of 11382, including 7597 participants in the high uric acid group and 3785 in the control group, on the basis of the inclusion and exclusion criteria. According to the evaluation of the JBI scale, the literature was of high quality. The average age ranged from 42 to 74. Meta-analysis showed that CIMT in the high uric acid group was significantly higher than that in the control group (SMD = 0.53, 95% CI: [0.38, 0.68]), and the difference was significant (z = 6.98, P < 0.00001). The heterogeneity among the 15 articles was obvious (I2 = 89%, P < 0.00001). Subgroup analysis by disease status illustrated a positive relationship between SUA and CIMT in healthy people and people with diseases. SUA was shown to be positively correlated with CIMT in people aged 45-60 years and ≥60 years by subgroup analysis by age. SUA was also found to be positively correlated with CIMT in a population with BMI>24 kg/m2 by subgroup analysis by BMI. In addition, subgroup analysis of other risk factors for CIMT, including TC, SBP, DBP, triglycerides, and LDL-C, all showed a positive correlation between SUA and CIMT. CONCLUSIONS: There is a significant correlation between serum uric acid level and carotid intima-media thickness, and a high concentration of serum uric acid is related to carotid artery intima-media thickness.
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Arterias Carótidas/patología , Grosor Intima-Media Carotídeo , Ácido Úrico/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/patología , Estenosis Carotídea/sangre , Estenosis Carotídea/patología , Humanos , Hiperuricemia/sangre , Hiperuricemia/patologíaRESUMEN
COVID-19 (Corona Virus Disease 2019) is globally spreading and the international cooperation is urgently required in joint prevention and control of the epidemic. Using the Maximum-Hasting (MH) parameter estimation method and the modified Susceptible Exposed Infectious Recovered (SEIR) model, the spread of the epidemic under three intervention scenarios (suppression, mitigation, mildness) is simulated and predicted in South Africa, Egypt, and Algeria, where the epidemic situations are severe. The studies are also conducted in Nigeria, Senegal and Kenya, where the epidemic situations are growing rapidly and the socio-economic are relatively under-developed, resulting in more difficulties in preventing the epidemic. Results indicated that the epidemic can be basically controlled in late April with strict control of scenario one, manifested by the circumstance in the South Africa and Senegal. Under moderate control of scenario two, the number of infected people will increase by 1.43-1.55 times of that in scenario one, the date of the epidemic being controlled will be delayed by about 10 days, and Algeria, Nigeria, and Kenya are in accordance with this situation. In the third scenario of weak control, the epidemic will be controlled by late May, the total number of infected cases will double that in scenario two, and Egypt is in line with this prediction. In the end, a series of epidemic controlling methods are proposed, including patient quarantine, close contact tracing, population movement control, government intervention, city and county epidemic risk level classification, and medical cooperation and the Chinese assistance.
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Betacoronavirus , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , África , COVID-19 , Humanos , SARS-CoV-2RESUMEN
We introduce a multiscale dataset obtained from Heihe Watershed Allied Telemetry Experimental Research (HiWATER) in an oasis-desert area in 2012. Upscaling of eco-hydrological processes on a heterogeneous surface is a grand challenge. Progress in this field is hindered by the poor availability of multiscale observations. HiWATER is an experiment designed to address this challenge through instrumentation on hierarchically nested scales to obtain multiscale and multidisciplinary data. The HiWATER observation system consists of a flux observation matrix of eddy covariance towers, large aperture scintillometers, and automatic meteorological stations; an eco-hydrological sensor network of soil moisture and leaf area index; hyper-resolution airborne remote sensing using LiDAR, imaging spectrometer, multi-angle thermal imager, and L-band microwave radiometer; and synchronical ground measurements of vegetation dynamics, and photosynthesis processes. All observational data were carefully quality controlled throughout sensor calibration, data collection, data processing, and datasets generation. The data are freely available at figshare and the Cold and Arid Regions Science Data Centre. The data should be useful for elucidating multiscale eco-hydrological processes and developing upscaling methods.
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OBJECTIVE: To analyze the characters of incidence, pathological and immunological phenotype of malignant lymphoma(ML), and to study the significance of IgH and TCR T cell receptor gene rearrangement for NHL typing. METHODS: Immunological phenotyping was conducted by SABC, and IgH (FR2A, FR3A) & TCR (beta,gamma) gene rearrangement detected by PCR of some pathological wax and bone marrow samples. RESULTS: (1) In ML, the percentage of non-Hodgkin lymphoma, (NHL) was 88.6% and Hodgkin lymphoma (HL) was 11.4%. The incidence increased with the patient's age. The percentage of patients over 60 years was 38.6%, and the median survival time of those older than 60 years was significantly shorter than that of the younger. (2) The percentage of B-NHL was 68.6%, and that of T-NHL was 28.6%; 3 years' survival time rate of B-NHL was higher than that of T-NHL. (3) The percentage of low grade NHL was 42%, and that of middle and high grade NHL was 58%; and the overall survival time was not significantly different between the two groups. But the overall survival time was longer in patients in stages I-II than in stages III-IV. (4) The results of detection on wax and bone marrow samples showed that B-NHL FR2A were 66.7% and 56.2% positive, FR3A 90.4% and 81.2% positive; in T-NHL patients, TCR-beta and TCR-gamma gene rearrangements were 91.7% and 75.0% positive; T and B classification were the same as the immunological phenotype. CONCLUSION: Age, T and B classifications and staging are the important factors, which affect the prognosis of NHL. Molecular biological methods can help T/B classification when we couldn't get it by phenotyping.
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Linfoma no Hodgkin/diagnóstico , Análisis Factorial , Reordenamiento Génico , Humanos , Inmunofenotipificación , Linfoma no Hodgkin/patología , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
PURPOSE: The study aims to find candidate probes of fluorescence in situ hybridization (FISH) for detection of lung cancer with bronchial brushings and to evaluate whether the accuracy of diagnosing lung cancer by cytological deviant and genetic abnormalities is greater than that of cytology alone. METHODS: Centromeric enumeration probes (CEPs) for chromosomes 2, 3, 6, 7, 8, 9, 11, 12, and 17 were analyzed using FISH in 74 surgical resection tissues, 32 operative margin tissues without tumor involvement of lung cancer, and 174 bronchial brushings. RESULTS: The aneuploidy rates of the tested probes were 61.7, 89.1, 80.0, 92.7, 65.0, 70.4, 66.7, 71.8, 68.9 % in tumor tissues, and 29.3, 58.9, 33.3, 69.6, 67.0, 40.3, 38.0, 49.3, 35.1 % in bronchial brushings. The combination of cytology and FISH using the three-probe set for chromosomes 3+7+8 significantly improved the sensitivity of bronchial brushing examination for lung cancer detection (P = 0.00003), especially squamous cell carcinoma (SCC), which increased from 78.0 to 98.2 %. The specificity of the 3+7+8 probe set was 94.6 %. Moreover, a high aneuploidy rate of the probe set in bronchial brushings was detected more often in SCCs (P = 0.029) and late-stage non-small-cell lung cancer (NSCLC) (P = 0.044). Kaplan-Meier curves indicated that adenocarcinoma (ADC) patients with high aneuploidy rate of CEP3 in tissue samples exhibited poorer overall survival (P = 0.016). CONCLUSIONS: FISH performed on cytology preparations is useful for confirmation of cancer diagnosis. The three-probe set, 3+7+8, has potential value for the detection of SCCs in bronchial brushings.
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Sondas de ADN/genética , Hibridación Fluorescente in Situ/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Bronquios/metabolismo , Bronquios/patología , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Centrómero/genética , Cromosomas Humanos Par 3/genética , Cromosomas Humanos Par 7/genética , Cromosomas Humanos Par 8/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Myocyte apoptosis is considered to be the major causative factor of left ventricular (LV) remodeling following myocardial infarction (MI). We previously reported that 3', 4'-dihydroxyflavonol (DiOHF), was able to suppress oxidative stress and preserve the expression of endothelial nitric oxide synthase during myocardial reperfusion injury, which may benefit the reduction of myocyte apoptosis. We therefore aimed to evaluate the potential actions of DiOHF against myocyte apoptosis and post-infarction LV remodeling in this study. METHODS: Following experimental MI, surgical instrumented goats were randomly assigned into vehicle and DiOHF (2 mg/kg; i.v., daily) groups to receive 4 weeks of reperfusion with corresponding treatments. LV pressure recordings and echocardiogram were performed at baseline, 2 and 4 weeks of reperfusion. Myocardial tissues were collected in the end to determine infarct size and apoptosis related assays. RESULTS: LV end-diastolic volume and diameter were significantly increased 4 weeks after MI in the vehicle group, accompanied by reduced posterior wall thickness, septal thickness and LV mass, whereas those changes were markedly prevented by DiOHF treatment. Similarly, significantly reduced infarct size was found in DiOHF group as compared to vehicle group, and DiOHF dramatically inhibited the increase in LV end-diastolic pressure and the reductions in ejection fraction, fraction shortening and dP/dt(max). Moreover, DiOHF treatment significantly reduced the extent of myocyte apoptosis detected by TUNEL assay, enhanced the protein expression of caspase-3, Fas, Bax and cytochrome c in the non-infarcted myocardium in comparison to vehicle. CONCLUSIONS: Daily DiOHF treatment during the reperfusion period after MI in the ovine hearts markedly reduced the magnitude of post-infarction LV remodeling through the inhibition of myocyte apoptosis in the remote non-infarcted myocardium.
Asunto(s)
Apoptosis/efectos de los fármacos , Flavonoles/farmacología , Infarto del Miocardio/fisiopatología , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Caspasa 3/metabolismo , Citocromos c/metabolismo , Ecocardiografía , Femenino , Cabras , Etiquetado Corte-Fin in Situ , Masculino , Infarto del Miocardio/metabolismo , Distribución Aleatoria , Proteína X Asociada a bcl-2/metabolismo , Receptor fas/metabolismoRESUMEN
OBJECTIVE: To investigate the clinical value of glycosylated G-CSF combined with middle-high dose cyclophosphamide (Cy) or conventional chemotherapy with increased dose of Cy for mobilizing peripheral blood progenitor cells in patients with tumor. METHODS: Thirty patients from four hospitals in Beijing region were enrolled in this clinical study. Diagnoses of the patients were non-Hodgkin' lymphoma (n = 21), Hodgkin disease (n = 1), breast cancer (n = 7) and ovary cancer (n = 1). Autologous peripheral blood progenitor cells (APBPC) were mobilized by middle-high dose Cy or conventional chemotherapy with increased dose of Cy combined with G-CSF. G-CSF was given subcutaneously from the nadir of the white blood cell (WBC) count to the end of PBPC collection. The dosage of G-CSF was 250 microg/d in 29 patients and 500 microg/d in 1 patient. When WBC count was > 5 x 10(9)/L, APBPC were harvested with CS 3000 plus/COBE Spectra. RESULTS: The average dosage of Cy was 3.95 g (2.3 g/m(2)). The doses of G-CSF were 3.1 approximately 6.4 microg x kg(-1) x d(-1). Thirteen patients (43%) were collected twice, 14 patients (47%) three times and 3 patients (10%) four times. All of the patients could tolerate the treatment regimens. Seven patients had bone pain after G-CSF injection and one was severe, one patient had headache and one had nausea and vomiting. CONCLUSION: 250 microg glycosylated G-CSF combined with middle-high Cy or conventional chemotherapy with increased dose of Cy combined G-CSF is an optimal method for APBPC mobilization in tumor patients.