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1.
Front Plant Sci ; 13: 856826, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557736

RESUMO

The dispersal stage of pathogens is crucial for the successful spread and infection of their hosts. Some plant-parasitic nematodes (PPNs) have evolved specialized dispersal stages to reach healthy hosts by being carried out by insect vectors. Because gene gain and loss is a major factor contributing to the evolution of novel characteristics, it is essential to clarify the gene family characteristics among nematodes with different dispersal modes to disentangle the evolution of insect-mediated dispersal. Here, the size of the C-type lectin (CTL) family genes of insect-vectored nematodes was found to be drastically reduced compared with those of self-dispersing nematodes, whereas the diversity of their functional domains was significantly higher. The gene family sizes of vector-dispersed nematodes were only a twentieth of the size of that of a self-dispersing (i.e., without a biotic vector) nematode model Caenorhabditis elegans, and these genes were inactive during the dispersal stage. Phylogenetic analysis showed that some CTL genes of vector-borne PPNs shared higher homology to the animal parasitic nematodes compared with other PPNs. Moreover, homology modeling predicted that the CTLs of insect-vectored nematodes bear remarkable structural similarity to the lectin genes of their vector's immune system. Because CTL genes are important sugar-binding proteins for the innate immune response of C. elegans, the loss of some CTL genes of vector-transmitted PPNs might be responsible for their parallel adaptations to a mutualistic relationship with their vector. These results expand our understanding of the evolutionary benefits of vector-mediated transmission for the nematode and vector-nematode co-evolution.

2.
Front Genet ; 13: 865052, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559024

RESUMO

Background: Increasing evidence has revealed that epithelial-mesenchymal transition (EMT) and immunity play key roles in idiopathic pulmonary fibrosis (IPF). However, correlation between EMT and immune response and the prognostic significance of EMT in IPF remains unclear. Methods: Two microarray expression profiling datasets (GSE70866 and GSE28221) were downloaded from the Gene Expression Omnibus (GEO) database. EMT- and immune-related genes were identified by gene set variation analysis (GSVA) and the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate the functions of these EMT- and immune-related genes. Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were used to screen prognostic genes and establish a gene signature. Gene Set Enrichment Analysis (GSEA) and Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) were used to investigate the function of the EMT- and immune-related signatures and correlation between the EMT- and immune-related signatures and immune cell infiltration. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to investigate the mRNA expression of genes in the EMT- and immune-related signatures. Results: Functional enrichment analysis suggested that these genes were mainly involved in immune response. Moreover, the EMT- and immune-related signatures were constructed based on three EMT- and immune-related genes (IL1R2, S100A12, and CCL8), and the K-M and ROC curves presented that the signature could affect the prognosis of IPF patients and could predict the 1-, 2-, and 3-year survival well. Furthermore, a nomogram was developed based on the expression of IL1R2, S100A12, and CCL8, and the calibration curve showed that the nomogram could visually and accurately predict the 1-, 2-, 3-year survival of IPF patients. Finally, we further found that immune-related pathways were activated in the high-risk group of patients, and the EMT- and immune-related signatures were associated with NK cells activated, macrophages M0, dendritic cells resting, mast cells resting, and mast cells activated. qRT-PCR suggested that the mRNA expression of IL1R2, S100A12, and CCL8 was upregulated in whole blood of IPF patients compared with normal samples. Conclusion: IL1R2, S100A12, and CCL8 might play key roles in IPF by regulating immune response and could be used as prognostic biomarkers of IPF.

3.
J Clin Lab Anal ; : e24466, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35561264

RESUMO

BACKGROUND: Community-acquired Pseudomonas aeruginosa pneumonia in immunocompetent children is a rare occurrence. METHODS: A retrospective analysis of the clinical manifestations, imaging characteristics, laboratory examinations, and treatment of a child with community-acquired Pseudomonas aeruginosa pneumonia presented with bloody pleural effusion. RESULTS: The 1-year-old previously healthy patient, who developed community-acquired pneumonia caused by Pseudomonas aeruginosa and influenza virus. The patient manifested bloody pleural effusion although his condition improved after anti-infective therapy and closed thoracic drainage. After 10 days of hospitalization, his symptoms worsened, accompanied by hemoptysis, and the pathogen developed resistance to carbapenems. The antibiotic strategy was adjusted to combined antipseudomonal regimen. He developed low-grade fever and was extubated, although these manifestations and imaging were eventually alleviated. CONCLUSIONS: Community-acquired Pseudomonas aeruginosa pneumonia in children may be non-septic, with bloody pleural effusion as presentation, and the disease may progress after 10 days of treatment due to drug resistance in Pseudomonas aeruginosa. Early extubation should be considered after adequate drainage.

4.
Emerg Microbes Infect ; 11(1): 1356-1370, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35538876

RESUMO

Chronic hepatitis B virus (HBV) infection due to perinatal mother-to-infant transmission (MTIT) remains a serious global public health problem. It has been shown that intrauterine exposure to HBV antigens might account for the MTIT-related chronic infection. However, whether hepatitis B surface antigen (HBsAg) intrauterine exposure affected the offspring's immune response against HBV and MTIT of HBV has not been fully clarified. In this study, we investigated the effects and the potential mechanisms of the HBsAg intrauterine exposure on the persistence of HBV replication using a solely HBsAg intrauterine exposure mice model. Our results revealed that solely HBsAg intrauterine exposure significantly accelerated the clearance of HBV when these mice were hydrodynamically injected with pBB4.5-HBV1.2 plasmids after birth, which may be due to the increased number of HBs-specific CD8+ T cells and interferon-gamma secretion in the liver of mice. Mechanismly, HBsAg intrauterine exposure activated antigen-presenting dendritic cells, which led to the generation of antigen-specific cellular immunological memory. Our data provide an important experimental evidence for the activation of neonatal immune response by HBsAg intrauterine exposure.

5.
Leuk Lymphoma ; : 1-10, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442137

RESUMO

We conducted a phase Ib/II multi-arm, parallel cohort study to simultaneously evaluate various immunotherapeutic agents and combinations in relapsed/refractory acute myeloid leukemia (AML). Overall, 50 patients were enrolled into one of 6 arms: (A) single agent PF-04518600 (OX40 agonist monoclonal antibody), (B) azacitidine + venetoclax + gemtuzumab ozogamicin (GO), (C) azacitidine + avelumab (anti-PD-L1 monoclonal antibody) + GO, (D) azacitidine + venetoclax + avelumab, (E) azacitidine + avelumab + PF-04518600, and (F) glasdegib + GO. Among all regimens evaluated, azacitidine + venetoclax + GO appeared most promising. In this arm, the CR/CRi rates among venetoclax-naïve and prior venetoclax-exposed patients were 50% and 22%, respectively, and the 1-year OS rate was 31%. This study shows the feasibility of a conducting a multi-arm trial to efficiently and simultaneously evaluate novel therapies in AML, a needed strategy in light of the plethora of emerging therapies. This trial was registered at www.clinicaltrials.gov as NCT03390296.

6.
J Diabetes Res ; 2022: 5064264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392484

RESUMO

Objectives: Peripheral artery disease (PAD) in diabetic populations is a vital chronic disease all over the world due to its high morbidity and mortality. It is important to find early simple screening biomarkers and find residual risk factors that may provide a new target for prevention and treatment of PAD in diabetic patients besides traditional cardiometabolic risk factors. Methods: We performed a cross-sectional retrospective study, and a total of 1671 T2DM participants were recruited. Receiver operating characteristic analysis, stepwise logistic regression analysis, points score system, and decision curve analysis were performed to assess the risk factors for PAD. Results: The prevalence of PAD in the study was 7.18% (n = 120). Compared to the participants with the lowest quartile of cystatin C (CysC), the risk of developing PAD in participants with the highest quartile of CysC increased 6.339-fold. The CysC was the superior indicators to distinguish participants with PAD from those without PAD, with an AUC of 0.716. Stepwise logistic regression analysis showed that CysC was independent risk factor for PAD besides traditional risk factors. Combined exposure to these traditional risk factors and CysC was associated with a stepwise increase in the risk of developing PAD and even increased 11.976-fold in participants with the highest quintiles of combined exposure score (CES) based on traditional risk factors and CysC compared to the participants with the lowest quintiles of CES. Conclusions: CysC was associated with PAD independent of potential risk factors in diabetic populations. The CysC was a reliable marker for the early screening of PAD in diabetic patients besides traditional cardiometabolic risk factors.


Assuntos
Diabetes Mellitus Tipo 2 , Doença Arterial Periférica , Biomarcadores , China/epidemiologia , Estudos Transversais , Cistatina C , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Estudos Retrospectivos , Fatores de Risco
7.
J Genet Genomics ; 49(5): 427-436, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35231639

RESUMO

African cultivated rice, Oryza glaberrima, is characterized by its glabrous glumes. During domestication, the pubescent glumes of its wild ancestor, Oryza barthii, lost their trichomes, and in this study, we show that glabrous glume 5 (GLAG5), a WUSCHEL-like homeobox transcription factor gene on chromosome 5, is required for trichome development. DNA methylation associated with an hAT transposable element inserted in the promoter region of GLAG5 is found to reduce its expression, leading to the formation of glabrous glumes and leaves in African cultivated rice. Among 82 African cultivated rice varieties investigated in this study, 59 (approximately 71%) lines exhibit glabrous glumes and harbor the hAT transposon; however, the other 23 varieties (approximately 29%), which exhibit pubescent glumes, lack the hAT transposon, indicating that glag5 had undergone strong artificial selection. The πw/πc ratios also show the hAT transposon insertions influence the genetic diversity of an approximately 150-kb interval encompassing the GLAG5 locus. The identification of the GLAG5 gene provides new insights into the domestication of cultivated rice in Africa. We speculate that the selection of varieties with mutations in their promoter regions is an important aspect of crop domestication.


Assuntos
Domesticação , Oryza , África , Variação Genética , Mutação , Oryza/genética
8.
J Alzheimers Dis ; 87(1): 211-222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35275534

RESUMO

BACKGROUND: Recent studies had explored that gut microbiota was associated with neurodegenerative diseases (including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS)) through the gut-brain axis, among which metabolic pathways played an important role. However, the underlying causality remained unclear. OBJECTIVE: Our study aimed to evaluate potential causal relationships between gut microbiota, metabolites, and neurodegenerative diseases through Mendelian randomization (MR) approach. METHODS: We selected genetic variants associated with gut microbiota traits (N = 18,340) and gut microbiota-derived metabolites (N = 7,824) from genome-wide association studies. Summary statistics of neurodegenerative diseases were obtained from IGAP (AD, 17,008 cases; 37,154 controls), IPDGC (PD, 37,688 cases; 141,779 controls), and IALSC (ALS, 20,806 cases; 59,804 controls) respectively. RESULTS: Greater abundance of Ruminococcus (OR, 1.245; 95% CI, 1.103-1.405; p = 0.0004) was found significantly related to higher risk of ALS. Besides, our study found suggestive associations of Actinobacteria, Lactobacillaceae, Faecalibacterium, Ruminiclostridium, and Lachnoclostridium with AD, of Lentisphaerae, Lentisphaeria, Oxalobacteraceae, Victivallales, Bacillales, Eubacteriumhalliigroup, Anaerostipes, and Clostridiumsensustricto1 with PD, and of Lachnospira, Fusicatenibacter, Catenibacterium, and Ruminococcusgnavusgroup with ALS. Our study also revealed suggestive associations between 12 gut microbiome-dependent metabolites and neurodegenerative diseases. Glutamine was related to lower risk of AD. For the serotonin pathway, serotonin was found as a protective factor of PD, while kynurenine as a risk factor for ALS. CONCLUSION: Our study firstly applied a two-sample MR approach to detect causal relationships among gut microbiota, gut metabolites, and neurodegenerative diseases. Our findings may provide new targets for treatments and may offer valuable insights for further studies on the underlying mechanisms.


Assuntos
Doença de Alzheimer , Esclerose Amiotrófica Lateral , Microbioma Gastrointestinal , Doenças Neurodegenerativas , Doença de Parkinson , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Esclerose Amiotrófica Lateral/complicações , Esclerose Amiotrófica Lateral/genética , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Doenças Neurodegenerativas/genética , Doença de Parkinson/complicações , Doença de Parkinson/genética , Fatores de Risco , Serotonina
9.
Front Pharmacol ; 13: 856784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35295338

RESUMO

CYP3A4-mediated Phase I biotransformation is the rate-limiting step of elimination for many commonly used clinically agents. The modulatory effects of herbal medicines on CYP3A4 activity are one of the risk factors affecting the safe use of drug and herbal medicine. In the present study, the inhibitory effects of nearly hundred kinds of herbal medicines against CYP3A4 were evaluated based on a visual high-throughput screening method. Furthermore, biflavone components including bilobetin (7-demethylginkgetin, DGK), ginkgetin (GK), isoginkgetin (IGK), and amentoflavone (AMF) were identified as the main inhibitory components of Ginkgo biloba L. (GB) and Selaginella tamariscina (P. Beauv.) Spring (ST), which displayed very strong inhibitory effects toward CYP3A4. The inhibitory effects of these biflavones on clinical drugs that mainly undergo CYP3A4-dependent metabolism were evaluated. The IC 50 of GK toward tamoxifen, gefitinib and ticagrelor were found to be of 0.478 ± 0.003, 0.869 ± 0.001, and 1.61 ± 0.039 µM, respectively. These results suggest the potential pharmacokinetic interactions between the identified biflavones and clinical drugs undergoing CYP3A4-mediated biotransformation. The obtained information is important for guiding the rational use of herbal medicine in combination with synthetic pharmaceuticals.

10.
Hepatology ; 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35229329

RESUMO

BACKGROUND AND AIMS: Etiological risk factors for cirrhosis have changed in the last decade. It remains unclear to what extent these trends in cirrhosis risk factors have changed HCC risk. APPROACH AND RESULTS: We used data from two contemporary, prospective multiethnic cohorts of patients with cirrhosis: the Texas Hepatocellular Carcinoma Consortium Cohort and the Houston Veterans Administration Cirrhosis Surveillance Cohort. Patients with cirrhosis were enrolled from seven US centers and followed until HCC diagnosis, transplant, death, or June 30, 2021. We calculated the annual incidence rates for HCC and examined the effects of etiology, demographic, clinical, and lifestyle factors on the risk of HCC. We included 2733 patients with cirrhosis (mean age 60.1 years, 31.3% women). At enrollment, 19.0% had active HCV, 23.3% had cured HCV, 16.1% had alcoholic liver disease, and 30.1% had NAFLD. During 7406 person-years of follow-up, 135 patients developed HCC at an annual incidence rate of 1.82% (95% CI, 1.51-2.13). The annual HCC incidence rate was 1.71% in patients with cured HCV, 1.32% in patients with alcoholic liver disease, and 1.24% in patients with NAFLD cirrhosis. Compared to patients with NAFLD, the risk of progression to HCC was 2-fold higher in patients with cured HCV (HR, 2.04; 95% CI, 1.24-3.35). Current smoking (HR, 1.63; 95% CI, 1.01-2.63) and overweight/obesity (HR, 1.79; 95% CI, 1.08-2.95) were also associated with HCC risk. CONCLUSIONS: HCC incidence among patients with cirrhosis was lower than previously reported. HCC risk was variable across etiologies, with higher risk in patients with HCV cirrhosis and lower risk in those with NAFLD cirrhosis. Current smoking and overweight/obesity increased HCC risk across etiologies.

11.
Mar Pollut Bull ; 176: 113416, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35228034

RESUMO

The construction of world-class Bay makes the marine ecology in Guangdong-Hong Kong-Macao Great Bay Area in risk. Based on the DPSIR index framework, Lotka-Volterra symbiosis model is applied to calculate symbiosis degree between coastal socio-economic system and marine ecosystem in 9 coastal cities. It is found that the marine ecological pressure in this area have not been reversed in recent 20 years. Most cities are in the stage that socio-economic development and marine ecological damage coexist. In Shenzhen, Guangzhou, Dongguan and Zhongshan, the damaged marine ecology has begun to restrain the further expansion of economy and society. The massive population agglomeration in Hong Kong, Macao and other places has caused serious marine ecological stress. It is urgent to improve the marine ecological security by cultivating ecological industrial system and industrial clusters, establishing a land-sea ecological restoration, promoting joint-protection and co-governance across different administrative regions.


Assuntos
Ecossistema , Biologia Marinha , China , Cidades , Conservação dos Recursos Naturais , Hong Kong , Macau
12.
Front Pediatr ; 10: 813614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35281240

RESUMO

Background: In children, refractory Mycoplasma pneumoniae pneumonia (RMPP) may result in severe complications and high medical costs. There is research on a simple and easy-to-use nomogram for early prediction and timely treatment of RMPP. Methods: From December 2018 to June 2021, we retrospectively reviewed medical records of 299 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in Tianjin Children's Hospital. According to their clinical manifestations, patients were divided into the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group. The clinical manifestations, laboratory indicators, and radiological data of the two groups were obtained. Stepwise regression was employed for variable selection of RMPP. The predictive factors selected were used to construct a prediction model which presented with a nomogram. The performance of the prediction model was evaluated by C statistics, calibration curve, and receiver operating characteristic (ROC) curve. Results: The RMPP group significantly showed a higher proportion of females, longer fever duration, and longer hospital stay than the GMPP group (P < 0.05). Additionally, the RMPP group revealed severe clinical characteristics, including higher incidences of extrapulmonary complications, decreased breath sounds, unilateral pulmonary consolidation >2/3, and plastic bronchitis than the GMPP group (P < 0.05). The RMPP group had higher neutrophil ratio (N%), C-reactive protein (CRP), interleukin-6 (IL-6), lactic dehydrogenase (LDH), and D-dimer than the GMPP group (P < 0.05). Stepwise regression demonstrated that CRP [OR = 1.075 (95% CI: 1.020-1.133), P < 0.001], LDH [OR = 1.015 (95% CI: 1.010-1.020), P < 0.001], and D-dimer [OR = 70.94 (95% CI: 23.861-210.904), P < 0.001] were predictive factors for RMPP, and developed a prediction model of RMPP, which can be visualized and accurately quantified using a nomogram. The nomogram showed good discrimination and calibration. The area under the ROC curve of the nomogram was 0.881, 95% CI (0.843, 0.918) in training cohorts and 0.777, 95% CI (0.661, 0.893) in validation cohorts, respectively. Conclusion: C-reactive protein, LDH, and D-dimer were predictive factors for RMPP. The simple and easy-to-use nomogram assisted us in quantifying the risk for predicting RMPP, and more accurately and conveniently guiding clinicians to recognize RMPP, and contribute to a rational therapeutic choice.

13.
Curr Biol ; 32(6): 1211-1231.e7, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35139360

RESUMO

Many animals detect other individuals effortlessly. In Drosophila, previous studies have examined sensory processing during social interactions using simple blobs as visual stimulation; however, whether and how flies extract higher-order features from conspecifics to guide behavior remains elusive. Arguing that this should be reflected in sensorimotor relations, we developed unbiased machine learning tools for natural behavior quantification and applied these tools, which may prove broadly useful, to study interacting pairs. By transforming motor patterns with female-centered reference frames, we established circling, where heading and traveling directions intersect, as a unique pattern of social interaction during courtship. We found circling to be highly visual, with males exhibiting view-tuned motor patterns. Interestingly, males select specific wing and leg actions based on the positions and motions of the females' heads and tails. Using system identification, we derived visuomotor transformation functions indicating history-dependent action selection, with distance predicting action initiation and angular position predicting wing choices and locomotion directions. Integration of vision with somatosensation further boosts these sensorimotor relations. Essentially comprised of orchestrated wing and leg maneuvers that are more variable in the light, circling induces mutually synchronized conspecific responses stronger than wing extension alone. Finally, we found that actions depend on integrating spatiotemporally structured features with goals. Altogether, we identified a series of sensorimotor relations during circling, implying that during courtship, flies detect complex spatiotemporally structured features of conspecifics, laying the foundation for a mechanistic understanding of conspecific recognition in Drosophila.


Assuntos
Corte , Drosophila , Animais , Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Feminino , Masculino , Comportamento Sexual Animal/fisiologia , Visão Ocular , Asas de Animais
14.
Radiat Prot Dosimetry ; 198(3): 147-157, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35137238

RESUMO

In case of a nuclear or radiological emergency, there may be a very large population of individuals being affected by radiation exposure. Rapid and on-site examinations of possible internal radioactive contaminations are required for early dose assessment and large-scale screening. With the appropriate methodology, early dose information of internal exposure can be instantly obtained by a handheld spectrometer only. In this study, we extended the use of a handheld LaBr3 spectrometer to rough internal dose assessment. A family of real source BOMAB phantoms was applied for efficiency calibration of different detecting geometries. Detecting limits of several nuclides of major concern was also investigated. The result of this study can be used for initial dose assessment and medical triage during the first response of nuclear and radiological emergencies.


Assuntos
Exposição à Radiação , Monitoramento de Radiação , Liberação Nociva de Radioativos , Radioatividade , Humanos , Imagens de Fantasmas , Exposição à Radiação/análise , Monitoramento de Radiação/métodos , Liberação Nociva de Radioativos/prevenção & controle
15.
J Med Chem ; 65(5): 4018-4029, 2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35094507

RESUMO

Identifying the alert groups of mechanism-based inactivators of human cytochrome P450s (hCYPs) is very helpful for early prediction of drug toxicity and for rational drug design to avoid idiosyncratic toxicity. Here, we report that a natural compound bufalin (BF) could time-dependently inactivate hCYP3A via complex CYP-catalyzed cascade oxidative metabolism. Metabolite profiling and time-dependent inhibition assays showed that 3-keto-bufalin (3-KBF), a unique nonpolar oxidative metabolite of BF, was the key substance responsible for hCYP3A inactivation. Further investigations demonstrated that 3-KBF was further metabolized by hCYPs to generate two mono-hydroxylated metabolites, which could be readily dehydrated and then covalently bound on glutathione or hCYP3A4. Collectively, this study uncovers unique CYP-catalyzed cascade oxidative pathways of BF in which two reactive intermediates bearing a Michael acceptor are finally formed as hCYP3A inactivators. These findings expand the current knowledge of CYP inactivators and suggest that some steroids bearing the 3-keto group may trigger time-dependent CYP3A inactivation.


Assuntos
Bufanolídeos , Citocromo P-450 CYP3A , Bufanolídeos/metabolismo , Bufanolídeos/farmacologia , Citocromo P-450 CYP3A/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Microssomos Hepáticos/metabolismo , Estresse Oxidativo
16.
Lifetime Data Anal ; 28(2): 219-240, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35061146

RESUMO

Accurate risk prediction has been the central goal in many studies of survival outcomes. In the presence of multiple risk factors, a censored regression model can be employed to estimate a risk prediction rule. Before the prediction tool can be popularized for practical use, it is crucial to rigorously assess its prediction performance. In our motivating example, researchers are interested in developing and validating a risk prediction tool to identify future lung cancer cases by integrating demographic information, disease characteristics and smoking-related data. Considering the long latency period of cancer, it is desirable for a prediction tool to achieve discriminative performance that does not weaken over time. We propose estimation and inferential procedures to comprehensively assess both the overall predictive discrimination and the temporal pattern of an estimated prediction rule. The proposed methods readily accommodate commonly used censored regression models, including the Cox proportional hazards model and the accelerated failure time model. The estimators are consistent and asymptotically normal, and reliable variance estimators are also developed. The proposed methods offer an informative tool for inferring time-dependent predictive discrimination, as well as for comparing the discrimination performance between candidate models. Applications of the proposed methods demonstrate enduring performance of the risk prediction tool in the PLCO study and detected decaying performance in a study of liver disease.


Assuntos
Modelos de Riscos Proporcionais , Humanos , Prognóstico
17.
Health Policy Plan ; 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35032390

RESUMO

Long-term care insurance (LTCI) is one of the important institutional responses to the growing care needs of the ageing population. Although previous studies have evaluated the impacts of LTCI on health care utilization and expenditure in developed countries, whether such impacts exist in developing countries is unknown. The Chinese government has initiated policy experimentation on LTCI to cope with the growing and unmet need for aged care. Employing a quasi-experiment design, this study aims to examine the policy treatment effect of LTCI on health care utilization and out-of-pocket health expenditure in China. The Propensity Score Matching with Difference-in-difference approach was used to analyse the data obtained from four waves of China Health and Retirement Longitudinal Study (CHARLS). Our findings indicated that, in the aspect of health care utilization, the introduction of LTCI significantly reduced the number of outpatient visits by 0.322 times (p<0.05), the number of hospitalizations by 0.158 times (p<0.01), and the length of inpatient stay during last year by 1.441 days (p<0.01). In the aspect of out-of-pocket health expenditure, we found that LTCI significantly reduced the inpatient out-of-pocket health expenditure during last year by 533.47 yuan (p<0.01), but it did not exhibit an impact on the outpatient out-of-pocket health expenditure during last year. LTCI also had a significantly negative impact on the total out-of-pocket health expenditure by 512.56 yuan. These results are stable in the robustness tests. Considering the evident policy treatment effect of LTCI on health care utilization and out-of-pocket health expenditure, the expansion of LTCI could help reduce the needs for health care services and contain the increases in out-of-pocket health care expenditure in China.

19.
Medicine (Baltimore) ; 101(2): e28491, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029199

RESUMO

ABSTRACT: There is a scarcity of research into the impact of medication beliefs on adherence in patients with non-dialysis chronic kidney disease (CKD). This study is to determine the psychometric properties of the Chinese version of the Beliefs about Medicines Questionnaire (BMQ)-Specific among patients with non-dialysis CKD stages 3-5, and to assess the beliefs of CKD patients and their association with medication adherence.A cross-sectional study was conducted in CKD patients who recruited at the nephrology clinics of Xi'an Central Hospital, Xi'an, Shaanxi, China. The original BMQ-Specific was translated into Chinese. The internal consistency and test-retest reliability of the Chinese version of the BMQ-Specific scale were assessed, while exploratory and confirmatory factor analyses were also applied to determine its reliability and validity. The Kruskal-Wallis test and multiple ordered logistic regression were performed to identify the relationship between beliefs about and adherence to medication among CKD patients.This study recruited 248 patients. Cronbach's α values of the BMQ-Specific necessity and concern subscales were 0.826 and 0.820, respectively, with intraclass correlation coefficients of 0.784 and 0.732. Factor analysis showed that BMQ-Specific provided a good fit to the two-factor model. The adherence of patients was positively correlated with perceived necessity (r = 0.264, P < .001) and negatively correlated with concern (r = -0.294, P < .001). Medication adherence was significantly higher for the accepting group (high necessity and low concern scores) than for the ambivalent group (high necessity and concern scores; ß = -0.880, 95% confidence interval [CI] = -1.475 to -0.285), skeptical group (low necessity and high concern scores; ß = -2.620, 95% CI = -4.209 to -1.031) and indifferent group (low necessity and concern scores; ß = -0.918, 95% CI = -1.724 to -0.112).The Chinese version of BMQ-Specific exhibited satisfactory reliability and validity for use in patients with non-dialysis CKD stages 3-5 and has been demonstrated to be a reliable screening tool for clinicians to use to predict and identify the non-adherence behaviors of patients.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Adesão à Medicação , Insuficiência Renal Crônica , China , Estudos Transversais , Humanos , Psicometria , Insuficiência Renal Crônica/tratamento farmacológico , Reprodutibilidade dos Testes , Inquéritos e Questionários
20.
Nucl Med Commun ; 43(2): 186-192, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34783717

RESUMO

OBJECTIVE: T cell lymphomas are associated with an aggressive worse prognosis. This study is designed to assess T cell lymphomas using 18F-FDG PET/CT. METHODS: Sixty-four patients with newly diagnosed T cell lymphomas underwent PET/computed tomography (PET/CT) scans, 47 cases who were fully followed up were retrospectively reviewed and analyzed. Overall survival (OS) and progression-free survival (PFS) were recorded for prognosis. We measured the maximum standardized uptake value (SUVmax) in all cases, analyzed the correlation between SUVmax and survival and other clinicopathologic parameters. Kaplan-Meier log-rank tests were then used to compare the survival of high and low PET/CT parameter groups, and multivariate Cox proportional hazards regression analysis was carried out to identify predictors of OS and PFS. RESULTS: With a median follow-up of 26.5 (range 0.7-117.5) months, the 1-, 2- and 3-year OS were 75.6, 61.7 and 49.2%, and PFS were 49.3, 39.9 and 29.9%, respectively in 47 patients. Among them, 33 cases progressed with a median time of 9.5 (0.7-115.0) months, and 26 patients died with a median survival time of 26.5 (0.7-117.5) months. Multivariate analysis showed the following independent prognostic factors for OS: age >60 years (P = 0.002), SUVmax >9.7 (P = 0.009) and extranodal involvement of more than one site (P = 0.018). In addition, lactate dehydrogenase level (P = 0.003) and B symptoms (P = 0.018) were independent risk factors for PFS. CONCLUSION: Pretherapy SUVmax may serve as an independent predictor of outcome in patients with newly diagnosed T cell lymphomas.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
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