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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 122-130, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554808

RESUMO

OBJECTIVE: To investigate the effect of neutrophil/lymphocyte ratio (NLR) and monocyte/lymphocyte ratio (MLR) in the valuation prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 82 patients with initially diagnosed MM admitted to Gansu Provincial People's Hospital was analyzed retrospectively. NLR and MLR were calculated based on blood routine results respectively. The optimal cut-off point of NLR and MLR was determined according to the ROC curve, and the patients were divided into the high NLR/MLR group and the low NLR/MLR group. The general data, biochemical indicators and prognosis of the patients in each groups were compared respectively. The prognostic significance of the high NLR/MLR group and the low NLR/MLR group in patients between different treatment regimens and different clinical characteristics were analyzed. Risk stratification was designed based on NLR and high MLR as two risk factors, and the effect of risk factors, on the prognosis of MM patients were compared. RESULTS: ROC curve analysis determined that the optimal cut-off point of NLR was 3.1 (sensitivity 75%, specificity 70.7%) and the optimal cut-off point of MLR was 0.34 (sensitivity 83.3%, specificity 53.4%). The lactate dehydrogenase (LDH) and mean platelet volume (MPV) were correlated to NLR and MLR (P<0.05). There were no significant difference in age, sex, serum calcium (Ca), ß 2-microglobulin (ß 2-MG), albumin (Alb), hemoglobin (Hb), platelet (PLT), serum creatinine (Cr), bone marrow plasma cell ratio and ISS stage between the two groups (P>0.05). The OS rate of patients with higher NLR and MLR was lower than those with low NLR and MLR and showed poor prognosis; Further analysis showed that there were statistically significant differences in OS time among patients with different MLR and NLR in the new drug treatment group and the traditional chemotherapy group, as well as patients in different age stratification groups, different ß 2-MG stratification groups and different serum creatinine stratification groups. Patients with 2 risk factors showed a poorer prognosis than those with 0-1 risk factor. CONCLUSION: Elevated NLR and MLR are associated with poor prognosis in MM patients and may serve as the cost-effective and readily available prognostic biomarkers.


Assuntos
Mieloma Múltiplo , Neutrófilos , Plaquetas , Humanos , Linfócitos , Monócitos , Prognóstico , Estudos Retrospectivos
2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 152-157, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554812

RESUMO

OBJECTIVE: To analyze the risk factors, distribution of pathogenic strains and tolerance of pulmonary infection in patients with multiple myeloma(MM) during bortezomib chemotherapy. METHODS: The clinical data of 85 patients with multiple myeloma treated by bortezomib in our hospital from January 2015 to January 2019 was analyzed. The patients were divided into infection group and control group according to whether they were infected. The tolerance, pathogen distribution, and related risk factors were retrospectively analyzed. RESULTS: Pulmonary infection rate was 55.29% in 85 MM patients. The proportions of the patients with anemia, neutropenia, and ECOG score ≥2 points in the infection group were significantly higher than those in the control group (P<0.05). In this study, 30 strains of pathogenic bacteria were detected, with gram-negative bacteria accounting for 60%, gram-positive bacteria for 33.33%, fungi for 3.3% and tuberculosis bacteria for 3.3%. Pseudomonas aeruginosa, klebsiella pneumoniae, streptococcus pneumoniae, staphylococcus aureus accounted showed the highest proportion. Most of MM patients with pulmonary infection showed a heterprognosis after two weeks antibiotic treatment, while 3 patients died. About 30 percent of early deaths were due to pulmonary infections. CONCLUSION: Anemia, neutropenia, ECOG score ≥2 points are the major clinical characteristics of the multiple myeloma patients with pulmonary infections. Pulmonary infection is an important cause of early death in patients with multiple myeloma. Pathogenic bacteria are mainly composed of gram-negative bacteria. Beta-lacta/ beta-lactamase inhibitor combinations or Carbapenems are effective empiric treatment for controlling the progression of pulmonary infection.


Assuntos
Mieloma Múltiplo , Bortezomib , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
3.
Health Commun ; : 1-10, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33601990

RESUMO

Misinformation on social media pertaining to COVID-19 poses a great threat to public health. The active correction of misinformation by social media users and an understanding of the drivers of such behavior can help solve this ongoing issue. Drawing on the influence of presumed influence model and cognitive appraisal theory, an online experiment (N = 400) was conducted to examine how exposure to corrective messages with regard to COVID-19 misinformation induced individuals' threat appraisals of the influence of the misinformation on others and how these threat appraisals and the corresponding emotional responses motivated individuals to take corrective actions. The results suggested that people's perceptions of the severity of the influence of misinformation on others engendered anticipated guilt, which, in turn, strengthened their intentions to correct misinformation related to COVID-19. The study offers guidance on how to effectively craft a corrective message to encourage audiences to counter misinformation together.

4.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1885-1891, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283715

RESUMO

OBJECTIVE: To investigated the anti-tumor in vivo effect and mechanism of the acid RNA protein complex (FA-2-b-ß) of Agaricus blazei Murrill extract. METHODS: CCK-8 method was used to detected the inhibitory effect of FA-2-b-ß on proliferation of primary CML cells from newly diagnosed CML patients, the CML mouse model was established by trail-venous injection of primary CML cells, and the survival time, blood cell count and body weight were observed, the immunoflouresence and immunehistochemistry analysis, RT-qPCR, Western bolt were used to detemine the expression of caspase-3 signal pathway-related apoptosis genes and proteins. RESULTS: The experiments in vitro showed that the proliferative inhibitory rate in drug-treated group increased with concentration- and time-dependent manner (r24=0.9092, r48=0.9442, r72=0.9546), the inter group comparison showed the statistical difference of results. The experiments in vitro showed that the survival time prolonged, blood cell count increased and body weight recovered in FA-2-b-ß-treated group and imatinib-treated group, despite the WBC count is still high. The RT-qPCR and Western blot showed that the expression of BAX and caspase-3 gene and protein were up-regulated, the expression of BCL-2, cytochroime C, caspase-8, caspase-9 and BCL-ABL gene and protein were down-regulated. CONCLUSION: The FA-2-b-ß can induce apoptosis of primary CML cells and prolong the survival time of CML model mouse, which may be related with the caspase-3 signal pathway related genes and proteins.

5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(6): 1972-1976, 2020 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-33283728

RESUMO

OBJECTIVE: To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib. METHODS: Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed. RESULTS: Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P<0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P<0.05). CONCLUSION: The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.

6.
Macromol Biosci ; : e2000336, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33346401

RESUMO

Bone defects remains a challenge for surgeons. Bone graft scaffold can fill the defect and enhance the bone regeneration. Demineralized bone matrix (DBM) is an allogeneic bone graft substitute, which can only be used as a filling material rather than a structural bone graft. Coating of the scaffolds with nanoscale DBM may enhance the osteoinductivity or osteoconductivity. Herein the lyophilization method is presented to coat the nano-DBM on surface of the porous polycaprolactone (PCL)/ß-tricalcium phosphate (ß-TCP) scaffolds fabricated by 3D printing technology. The morphology, elastic modulus, in vitro cell biocompatibility, and in vivo performance are investigated. Scanning electron microscope (SEM) shows DBM particle clusters with size of 200-500 nm are observed on scaffolds fibers after coating. MC3T3-E1 cells on nano-DBM coated PCL/ß-TCP scaffold show better activity than on PCL/ß-TCP scaffold. In vivo tests show better infiltration of new bone tissue in nano-DBM coated PCL/ß-TCP scaffold than PCL/ß-TCP scaffold via the interface. These results show the presence of nano-DBM coating on PCL/ß-TCP scaffold could enhance the attachment, proliferation, and viability of cells and benefit for the new bone formation surrounding and deep inside the scaffolds. Nano-DBM could potentially be used as a new kind of biomaterial for bone defect treatment.

7.
Int J Biol Macromol ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33166558

RESUMO

Bacillus licheniformis 2709 is the major alkaline protease producer, which has great potential value of industrial application, but how the high-producer can be regulated rationally is still not completely understood. It's meaningful to understand the metabolic processes during alkaline protease production in industrial fermentation medium. Here, we collected the transcription database at various enzyme-producing stages (preliminary stage, stable phase and decline phase) to specifically research the synthesized and regulatory mechanism of alkaline protease in B. licheniformis. The RNA-sequencing analysis showed differential expression of numerous genes related to several processes, among which genes correlated with regulators were concerned, especially the major differential gene abrB on enzyme (AprE) synthesis was investigated. It was further verified that AbrB is a repressor of AprE by plasmid-mediated over-expression due to the severely descending enzyme activity (11,300 U/mL to 2695 U/mL), but interestingly it is indispensable for alkaline protease production because the enzyme activity of the null abrB mutant was just about 2279 U/mL. Thus, we investigated the aprE transcription by eliminating the theoretical binding site (TGGAA) of AbrB protein predicated by computational strategy, which significantly improved the enzyme activity by 1.21-fold and gene transcription level by 1.77-fold in the mid-log phase at a cultivation time of 18 h. Taken together, it is of great significance to improve the production strategy, control the metabolic process and oriented engineering by rational molecular modification of regulatory network based on the high throughput sequencing and computational prediction.

8.
J R Stat Soc Ser C Appl Stat ; 69(4): 791-814, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33191955

RESUMO

Deployment of the recently licensed CYD-TDV dengue vaccine requires understanding of how the risk of dengue disease in vaccine recipients depends jointly on a host biomarker measured after vaccination (neutralization titer - NAb) and on a "mark" feature of the dengue disease failure event (the amino acid sequence distance of the dengue virus to the dengue sequence represented in the vaccine). The CYD14 phase 3 trial of CYD-TDV measured NAb via case-cohort sampling and the mark in dengue disease failure events, with about a third missing marks. We addressed the question of interest by developing inferential procedures for the stratified mark-specific proportional hazards model with missing covariates and missing marks. Two hybrid approaches are investigated that leverage both augmented inverse probability weighting and nearest neighborhood hot deck multiple imputation. The two approaches differ in how the imputed marks are pooled in estimation. Our investigation shows that NNHD imputation can lead to biased estimation without properly selected neighborhood. Simulations show that the developed hybrid methods perform well with unbiased NNHD imputations from proper neighborhood selection. The new methods applied to CYD14 show that NAb is strongly inversely associated with risk of dengue disease in vaccine recipients, more strongly against dengue viruses with shorter distances.

9.
Health Commun ; : 1-10, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33095088

RESUMO

This study proposes a theory-driven model to concurrently examine the cognitive and emotional factors that motivate vaccine supporters to combat erroneous online anti-vaccination information. The model was tested using data from a web survey of 599 vaccination supporters in the United States. The vaccine supporters reported greater support for government regulation of misinformation when they perceived greater susceptibility among the general public to the influence of misinformation. Surprisingly, the perceived severity of the influence was inversely related to respondents' intention to correct misinformation. In addition, perceived susceptibility to the influence of anti-vaccine misinformation and perceived severity of its influence on others induced negative emotions that included anticipated guilt and anger. The negative emotions in turn motivate vaccine supporters to attitudinally support government's media restriction or behaviorally correct the online misinformation.

10.
Oncol Lett ; 20(5): 270, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32989404

RESUMO

Agaricus blazei Murill (AbM) is a mushroom belonging to the Basidiomycetes family, which is believed to have antitumor and antioxidative activities. Proteoglycans and ergosterol are considered the key compounds of AbM for antitumor properties and so are used in complementary and alternative medicine as an anticancer drug. AbM is used to avoid serious side effects that would inevitably affect patients. Currently, the efficacy of AbM against chronic myeloid leukemia (CML) has not been established. The present study aimed to investigate the antitumor activities of the acidic RNA protein complex, FA-2-b-ß, extracted from wild edible AbM. The CML K562 cells or primary CML bone marrow (BM) cells were treated with FA-2-b-ß at different concentrations and time points. CML cell line proliferation and apoptosis were determined using the CCK-8 assay or Annexin V/propidium iodide (PI) labeling, RT-qPCR and western blotting was performed to determine the involvement of the Wnt/ß-catenin-associated apoptotic pathway. The results of the present study demonstrated that FA-2-b-ß has a high anti-proliferative potency and strong pro-apoptotic effects. Thus, daily intake of mushrooms containing FA-2-b-ß may be an adequate source as an alternative medicine in the management of CML, and may provide useful information for the development of a novel therapeutic target in this area.

11.
Lifetime Data Anal ; 26(4): 731-760, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32274677

RESUMO

This paper studies the Cox model with time-varying coefficients for cause-specific hazard functions when the causes of failure are subject to missingness. Inverse probability weighted and augmented inverse probability weighted estimators are investigated. The latter is considered as a two-stage estimator by directly utilizing the inverse probability weighted estimator and through modeling available auxiliary variables to improve efficiency. The asymptotic properties of the two estimators are investigated. Hypothesis testing procedures are developed to test the null hypotheses that the covariate effects are zero and that the covariate effects are constant. We conduct simulation studies to examine the finite sample properties of the proposed estimation and hypothesis testing procedures under various settings of the auxiliary variables and the percentages of the failure causes that are missing. These simulation results demonstrate that the augmented inverse probability weighted estimators are more efficient than the inverse probability weighted estimators and that the proposed testing procedures have the expected satisfactory results in sizes and powers. The proposed methods are illustrated using the Mashi clinical trial data for investigating the effect of randomization to formula-feeding versus breastfeeding plus extended infant zidovudine prophylaxis on death due to mother-to-child HIV transmission in Botswana.

12.
Can J Stat ; 47(3): 352-373, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31827312

RESUMO

The generalized semiparametric mixed varying-coefficient effects model for longitudinal data can accommodate a variety of link functions and flexibly model different types of covariate effects, including time-constant, time-varying, and covariate-varying effects. The time-varying effects are unspecified functions of time and the covariate-varying effects are nonparametric functions of a possibly time-dependent exposure variable. A semiparametric estimation procedure is developed that uses local linear smoothing and profile weighted least squares, which requires smoothing in the two different and yet connected domains of time and the time-dependent exposure variable. The asymptotic properties of the estimators of both nonparametric and parametric effects are investigated. In addition, hypothesis testing procedures are developed to examine the covariate effects. The finite-sample properties of the proposed estimators and testing procedures are examined through simulations, indicating satisfactory performances. The proposed methods are applied to analyze the ACTG 244 clinical trial to investigate the effects of antiretroviral treatment switching in HIV-infected patients before and after developing the T215Y antiretroviral drug resistance mutation.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(6): 1761-1766, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31839035

RESUMO

OBJECTIVE: To investigate the apoptosis of CD34+CD38--KG1a leukemia stem cells induced by Qinba selenium-mushroom extract(FA-2-b-ß), and its related mechanism. METHODS: CD34+CD38---KG1a cells were isolated from KG1a cell line by magnetic activated cell sorting. The proliferation ability of KG1a stem cells treatd by various concentration of FA-2-b-ß(1.2-2.4 mg/ml) in vitro for 24 and 48 hours were tested by cell counting Kit-8(CCK8). Flow cytometry was used to detect the apoptosis rate of KG1a stem cells in each group after treated by FA-2-b-ß in vitro. Expression of BAX,BCL-2,Casepase-3 and Cyclin D1 protein were detected by Western blot. RESULTS: The proportion of CD34+CD38---KG1a stem cells was (95.35±2.63)% after immunomagnetic isolation. The proliferation of KG1a stem cells was inhibited significantly by FA-2-b-ß, which shows a time- and dose-dependent manner (24 h,r=0.943; 48 h,r=0.976). Flow cytometry shows that with the increasing of drug concentration, the apoptosis was also increased, when KG1a stem cells was treated by FA-2-b-ß for 24 h. Western blot indicated that the expression of apoptosis-related protein BAX and Casepase-3 were up-regulated, the expression of BCL-2 and Cyclin D1 were down-regulated. CONCLUSION: FA-2-b-ß can regulate proliferation and apoptosis KG1a stem cells, the involved mechanism may be related with the activation of mitochondrial-mediated apoptotic pathway.


Assuntos
Células-Tronco Neoplásicas , ADP-Ribosil Ciclase 1 , Antígenos CD34 , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Glicoproteínas de Membrana , Selênio
14.
Toxicology ; 427: 152301, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31568845

RESUMO

Benzo[a]pyrene (BaP) stimulates male reproductive toxicity. In this study, we want to examine the ameliorative potential of Lycopene (LYC) on BaP-induced testicular toxicity. Adult male Wistar rats were segregated into 5 groups: Control, LYC, BaP, BaP + LYC and BaP + PQ7. Sperm parameters, testosterone level, oxidant and antioxidant parameters were determined. MRNA and protein abundances of key genes were analyzed. Cell death and apoptosis were assessed by trypan blue exclusion and Annexin V-FITC staining assay, respectively. LYC inhibited BaP-caused decrease in sperm motility and epididymal sperm concentration, and increase in head, tail and total abnormal sperm rate. LYC inhibited BaP-caused decrease in testosterone level in serum and intratesticular fluids. LYC protected germ cells from BaP-caused oxidative stress. LYC also prevented BaP-caused germ cell death and apoptosis by inhibiting apoptotic pathway. Besides, LYC ameliorated BaP-mediated gap-junction dysfunction of sertoli cells, as shown by the inhibited sertoli cell death and apoptosis, the upregulation of Bcl2 and Cx43, the downregulation of Cleaved Caspase 3, Bax and CaM, and the decrease in Ca2+ level. LYC ameliorated BaP-caused testicular damage via inhibiting oxidative stress and apoptosis, and relieving the gap-junction dysfunction of sertoli cells.


Assuntos
Benzo(a)pireno/toxicidade , Licopeno/farmacologia , Substâncias Protetoras/farmacologia , Testículo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Contagem de Espermatozoides , Testículo/metabolismo , Testosterona/sangue , Testosterona/metabolismo
15.
Ann Inst Stat Math ; 71(2): 365-387, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31530958

RESUMO

This paper presents simple weighted and fully augmented weighted estimators for the additive hazards model with missing covariates when they are missing at random. The additive hazards model estimates the difference in hazards and has an intuitive biological interpretation. The proposed weighted estimators for the additive hazards model use incomplete data nonparametrically and have close-form expressions. We show that they are consistent and asymptotically normal, and are more efficient than the simple weighted estimator which only uses the complete data. We illustrate their finite-sample performance through simulation studies and an application to study the progression from mild cognitive impairment to dementia using data from the Alzheimer's Disease Neuroimaging Initiative as well as an application to the mouse leukemia study.

16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(2): 489-493, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-30998159

RESUMO

OBJECTIVE: To study the value of neutrophil/lymphocyte ratio (NLR) in the evaluation of prognosis of patients with multiple myeloma (MM). METHODS: NLR was calculated on the basis of the blood routine examination results of 65 patients with primary MM (MM group) and 83 persons receiving physical examination as control group, and the difference in 2 group was compared; moreover according to the median as threshold, the patients were divided into low NLR group (NLR<2.34) and high NLR group (NLR≥2.34); the differences of age, sex, serum calcium ß2 (Ca), microglobulin (ß2-MG), albumin (Alb), serum creatinine (Cr), hemoglobin (Hb), red blood cell distribution width (RDW) and lactate dehydrogenase (LDH) in 2 group were analyzed, and the survival rate was compared between the high and low-NLR group. RESULTS: the NLR of MM patients was statistically significantly higher than that of the control group (z=-2.415, P<0.05). Compared with the low NLR group, the ß2-MG and Cr levels of patients in the high NLR group seemed higher, but the difference was not statistically significant. The single-factor analysis showed that NLR, ß2-MG and Alb levels were risk factors for the prognosis of MM patients, and the multi-factor analysis showed that NLR and Alb level were independent risk factors influencing the prognosis of MM patients. CONCLUSION: NLR elevation in patients with primary diagnosis of MM indicates a poor prognosis, which is an independent risk factor affecting the prognosis.


Assuntos
Linfócitos , Mieloma Múltiplo , Neutrófilos , Humanos , Contagem de Leucócitos , Prognóstico , Estudos Retrospectivos
17.
Econom Stat ; 9: 140-155, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30740554

RESUMO

A semiparametric varying-coefficient mixed regressive spatial autoregressive model is used to study covariate effects on spatially dependent responses, where the effects of some covariates are allowed to vary with other variables. A semiparametric series-based least squares estimating procedure is proposed with the introduction of instrumental variables and series approximations of the conditional expectations. The estimators for both the nonparametric and parametric components of the model are shown to be consistent and their asymptotic distributions are derived. The proposed estimators perform well in simulations. The proposed method is applied to analyze a data set on teen pregnancy to investigate effects of neighborhood as well as other social and economic factors on the teen pregnancy rate.

18.
Stat Med ; 37(27): 3959-3974, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-29992591

RESUMO

This paper investigates the semiparametric statistical methods for recurrent events. The mean number of the recurrent events are modeled with the generalized semiparametric varying-coefficient model that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects. We assume that the time-varying effects are unspecified functions of time and the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. Different link functions can be selected to provide a rich family of models for recurrent events data. The profile estimation methods are developed for the parametric and nonparametric components. The asymptotic properties are established. We also develop some hypothesis testing procedures to test validity of the parametric forms of covariate-varying effects. The simulation study shows that both estimation and hypothesis testing procedures perform well. The proposed method is applied to analyze a data set from an acyclovir study and investigate whether acyclovir treatment reduces the mean relapse recurrences.


Assuntos
Interpretação Estatística de Dados , Substituição de Medicamentos/métodos , Modelos Estatísticos , Análise de Regressão , Aciclovir/uso terapêutico , Humanos , Esclerose Múltipla/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Recidiva , Projetos de Pesquisa , Estatística como Assunto , Fatores de Tempo , Resultado do Tratamento
19.
Am J Transl Res ; 10(5): 1457-1468, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29887959

RESUMO

Osteoporosis is a common disease associated with age and menopausal status. Postmenopausal osteoporosis is the most common type of primary osteoporosis and is accompanied by increased risk of osteoporotic fracture. Natural and herbal compounds have long been used to prevent and treat many human diseases. Here, we demonstrated that tanshinone IIA prevented ovariectomy-induced bone loss in an in vivo mouse model that closely mimics osteoporosis. In addition, we found that tanshinone IIA inhibited the receptor activator of nuclear factor NF-κB ligand (RANKL)-induced osteoclast differentiation and osteoclastogenesis in vitro. Tanshinone IIA treatment also abrogated RANKL-induced activation of the NF-κB pathway, PI3-kinase/Akt signaling, and the mitogen-activated protein kinase (MAPK) pathways, including nuclear translocation of NF-κB p65 and phosphorylation of IκB, extracellular signal-regulated kinase (ERK), p38, and Akt. Inactivation of these pathways resulted in deceased expression of osteoclastogenesis-related markers. These results suggest that tanshinone IIA, a natural drug, has the potential to treat and prevent bone loss diseases, including postmenopausal osteoporosis.

20.
Comput Stat Data Anal ; 122: 59-79, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29892140

RESUMO

The cumulative incidence function quantifies the probability of failure over time due to a specific cause for competing risks data. The generalized semiparametric regression models for the cumulative incidence functions with missing covariates are investigated. The effects of some covariates are modeled as non-parametric functions of time while others are modeled as parametric functions of time. Different link functions can be selected to add flexibility in modeling the cumulative incidence functions. The estimation procedures based on the direct binomial regression and the inverse probability weighting of complete cases are developed. This approach modifies the full data weighted least squares equations by weighting the contributions of observed members through the inverses of estimated sampling probabilities which depend on the censoring status and the event types among other subject characteristics. The asymptotic properties of the proposed estimators are established. The finite-sample performances of the proposed estimators and their relative efficiencies under different two-phase sampling designs are examined in simulations. The methods are applied to analyze data from the RV144 vaccine efficacy trial to investigate the associations of immune response biomarkers with the cumulative incidence of HIV-1 infection.

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