RESUMO
PURPOSE: The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from a Chinese societal perspective. METHODS: A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study. RESULTS: Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY. CONCLUSIONS: The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias Colorretais/economia , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Capecitabina/administração & dosagem , China , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Metástase Neoplásica , PrognósticoRESUMO
In this study, we assessed the association between the EFEMP1 rs3791679 polymorphism and glioma risk in a Chinese Han population. A total of 94 glioma patients and 206 healthy controls who conformed to the inclusion and exclusion criteria were recruited from Baogang Hospital between March 2012 and October 2014. The EFEMP1 rs3791679 gene polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism assay and the results were statistically analyzed using SPSS Statistics 17.0. The results of unconditional logistic regression analysis revealed that the GG genotype of EFEMP1 rs3791679 was positively correlated with increased susceptibility to glioma (adjusted OR = 2.09, 95%CI = 1.21-7.81). Moreover, the GG genotype of EFEMP1 rs3791679 was correlated with higher risk of glioma compared to the AA+GA genotype (OR = 2.60, 95%CI = 1.08-6.28) in the regressive model. In conclusion, we report that the EFEMP1 rs3791679 polymorphism influences glioma susceptibility in the Chinese Han population.
Assuntos
Neoplasias Encefálicas/genética , Proteínas da Matriz Extracelular/genética , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/etnologia , Neoplasias Encefálicas/patologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Glioma/diagnóstico , Glioma/etnologia , Glioma/patologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Fatores de RiscoRESUMO
Activity of methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, is influenced by mutations in the corresponding gene, contributing to a decrease in 5,10-MTHF. Due to such polymorphisms, individuals differ in MTHFR enzyme activity and plasma folate levels. We investigated the relationship between two common MTHFR polymorphisms (C677T and A1298C) and breast cancer (BC) chemotherapy response. From February 2013 to January 2016, 148 advanced BC patients at the Center Hospital of Cangzhou were enrolled and treated with six different chemotherapy regimens. Subjects were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Forty-one (27.7%), 70 (47.3%), and 37 (25.0%) patients carried the C/C, C/T, and T/T C677T genotypes, respectively; 101 (68.2%), 42 (28.4%), and 5 (3.4%) had the A/A, A/C, and C/C genotypes of A1298C, respectively. Total chemotherapy efficacy was 66.9% (99/148), with 7 (4.7%), 92 (62.2%), 36 (24.3%), and 13 (8.8%) cases showing complete response, partial response, no change, and progressive disease, respectively. Chemotherapy regimens did not differ in effectiveness (P > 0.05). Efficacy rates associated with C677T C/C, C/T, and T/T genotypes were 58.5, 58.6, and 91.9%, respectively, with T/T carriers exhibiting significantly better responses than the C/C (P < 0.05) and C/T groups (P < 0.05). Effectiveness among A1298C A/A, A/C, and C/C carriers was 70.6, 64.3, and 0.0%, respectively, but no difference was established between these genotypes in this regard (P > 0.05). The MTHFR C677T genotype may be associated with BC chemotherapy response, and could be of great value in guiding individualized treatment for this disease.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Predisposição Genética para Doença , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Adulto , Idoso , Neoplasias da Mama/enzimologia , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae), is an economically important pest that causes major losses in some main crop-producing areas of China. To control this pest effectively, it is necessary to investigate its population genetic diversity and genetic structure around the Bohai Gulf area of China. In this study, we used two mitochondrial genes, COI (578 bp) and Cytb (724 bp), to investigate its genetic diversity. We obtained 622 COI sequences and 462 Cytb sequences from 23 populations, and 28 and 73 haplotypes, respectively, were identified. Low to moderate levels of genetic diversity (COI: Hd = 0.267 ± 0.023, Pi = 0.00082 ± 0.00010; Cytb: Hd = 0.689 ± 0.018, Pi = 0.00255 ± 0.00029) for the total populations were observed. Phylogenetic and median-joining network analyses indicated no distinct geographical distribution pattern among the haplotypes. Overall, this study revealed that there was significant differentiation among the populations (COI: FST = 0.158, P < 0.001; Cytb: FST = 0.148, P < 0.001). FST values for Shenyang, Baoding, and Funing were significantly different to those for most of the other populations. Finally, unimodal mismatch distribution analysis, combined with negative neutrality test results, showed a recent population expansion of the beet armyworm around the Bohai Gulf area of China.
Assuntos
Spodoptera/genética , Animais , China , DNA Mitocondrial/genética , Perfilação da Expressão Gênica , Genes Mitocondriais , Variação Genética , Genética Populacional , Haplótipos , Mitocôndrias/genética , Filogeografia/métodos , Análise de Sequência de DNARESUMO
As a proven tool, DNA barcoding can identify species rapidly and unambiguously. In this study, we used mtDNA cyt b, COI, and 16s rRNA sequences of six species of Pseudohynobius, Protohynobius puxiongensis, Liua shihi, Ranodon sibiricus, and Pachyhynobius shangchengensis, to reconstruct the phylogenetic relationships using Bayesian inference and maximum likelihood methods. Approximate lineage divergence times were also estimated, the divergence between them was calculated to have taken place mainly in Miocene. Our results showed that: 1) Ps. guizhouensis is an independent and valid species that is a sister species to Ps. kuankuoshuiensis; 2) five Pseudohynobius species formed a monophyletic group; 3) Ps. tsinpaensis is different from L. shihi, and should be classified as belonging to the Liua genus; and 4) Pr. puxiongensis is the sister lineage to all Pseudohynobius species, and should therefore be named Pseudohynobius puxiongensis.
Assuntos
Urodelos/genética , Animais , Teorema de Bayes , Citocromos b/genética , Código de Barras de DNA Taxonômico/métodos , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
Chromosomal abnormality is the most common genetic cause of male infertility, particularly in cases of azoospermia, oligozoospermia, and recurrent spontaneous abortion. Chromosomal rearrangement may interrupt an important gene or exert position effects. The functionality of genes at specific breakpoints, perhaps with a specific role in spermatogenesis, may be altered by such rearrangements. Structural chromosome abnormalities are furthermore known to increase the risk of pregnancy loss. In this study, we aimed to assess chromosomal defects in infertile men from Jilin Province, China, by genetic screening and to evaluate the relationship between structural chromosome abnormalities and male infertility. The prevalence of chromosomal abnormalities among the study participants (receiving genetic counseling in Jilin Province, China) was 10.55%. The most common chromosome abnormality was Klinefelter syndrome, and the study findings suggested that azoospermia and oligospermia may result from structural chromosomal abnormalities. Chromosome 1 was shown to be most commonly involved in male infertility and balanced chromosomal translocation was identified as one of the causes of recurrent spontaneous abortion. Chromosomes 4, 7, and 10 were the most commonly involved chromosomes in male partners of women experiencing repeated abortion.
Assuntos
Aberrações Cromossômicas , Testes Genéticos , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Adolescente , Adulto , Azoospermia/diagnóstico , Azoospermia/epidemiologia , Azoospermia/genética , China/epidemiologia , Aconselhamento Genético , Testes Genéticos/métodos , Humanos , Infertilidade Masculina/epidemiologia , Cariótipo , Cariotipagem , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Oligospermia/diagnóstico , Oligospermia/epidemiologia , Oligospermia/genética , Análise do Sêmen , Adulto JovemRESUMO
The aim of this study was to explore the correlation between the expression levels of Gli1 and p53 in pancreatic ductal adenocarcinoma (PDAC) and its pathological significance. Immunohistochemistry (IHC) was employed to measure the expression level of Gli1 and p53 in 85 sets of paraffin-embedded PDAC and corresponding para-carcinoma tissue specimens. The relationship between these results and the respective patients' clinicopathologic parameters was analyzed. IHC staining revealed that the expression levels of Gli1 and p53 in cancer tissues were evidently higher than that of para-carcinoma tissues (P < 0.05); while Gli1 expression levels correlated with the corresponding TNM stage and tumor infiltration depth, p53 expression level correlated with the respective TNM stage (P < 0.05). Taken together, this study demonstrates increased expression of Gli1 and p53 in PDAC, and proves that Gli1 could be apotential biomarker for prognostic judgment.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fatores de Transcrição/genética , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/genética , Feminino , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Pâncreas/metabolismo , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Prognóstico , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína GLI1 em Dedos de Zinco , Neoplasias PancreáticasRESUMO
In this study, the relationship between CYP19 gene polymorphisms and breast cancer in Xinjiang Uigur women was investigated. A case-control study was designed to compare 112 Uigur breast cancer patients with 139 Uigur healthy controls. Individuals were genotyped for the CYP19 rs10046 polymorphism using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Accordingly, the relationship between the rs10046 polymorphism and the susceptibility of Xinjiang Uigur women to breast cancer was analyzed. Given that the allele at the rs10046 site varies between C and T within the CYP19 gene, the frequency distribution of the C and T allele in breast cancer subjects were 48.2 and 51.8% respectively, and 47.5 and 52.5% in control cases. Moreover, the frequency distribution of the TC, CC, and TT genotype were 26.8, 42.9, and 30.4% in breast cancer cases, but 18.0, 59.0, and 23.0% in control cases (P < 0.05). Risk factors within the Uigur population for breast cancer included an age ≥ 50 years old, a BMI ≥ 25 kg/m(2), and a parity ≥ 2. Conversely, an abortion and the CYP19 rs10046 TC genotype were protective factors. Menopause was another independent risk factor for breast cancer in Uigur women after the correction for age, BMI, age at first parity, pregnancy, and breastfeeding. In conclusion, breast cancer in Xinjiang Uigur women is closely connected with the age, BMI, parity, abortion, and CYP19 rs10046 polymorphisms. The TC genotype and an abortion can reduce the risk of the breast cancer disease in Uigur women.
Assuntos
Aromatase/genética , Neoplasias da Mama/genética , Adulto , Idoso , Povo Asiático/genética , Neoplasias da Mama/enzimologia , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto JovemRESUMO
Preliminary studies have suggested that a characteristic element of the matrix attachment region (MAR) in human interferon-ß mediates the adhesion of vectors to Chinese hamster ovary (CHO) cells. In this study, we investigated if vector adhesion increased nerve growth factor (NGF) expression in CHO cells. The MAR characteristic element sequence of human interferon-ß was inserted into the multiple-cloning site of the pEGFP-C1 vector. The target NGF gene was inserted upstream of the MAR characteristic element sequence to construct the MAR/NGF expression vector. The recombinant plasmid was transfected into CHO cells and stable monoclonal cells were selected using G418. NGF mRNA and protein expression was detected by reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Plasmid reduction experiments were used to determine the state of transfected plasmid in mammalian cells. The insertion of MAR into the vector increased NGF expression levels in CHO cells (1.93- fold) compared to the control. The recombinant plasmid expressing the MAR sequence was digested into a linear space vector. The inserted MAR and NGF sequences were consistent with those inserted into the plasmid before recombination. Therefore, we concluded that the MAR characteristic element mediates vector adhesion to CHO cells and enhances the stability and efficiency of the target gene expression.
Assuntos
Regulação da Expressão Gênica , Vetores Genéticos/genética , Regiões de Interação com a Matriz , Fator de Crescimento Neural/genética , Animais , Células CHO , Cricetulus , Ordem dos Genes , Plasmídeos/genéticaRESUMO
This study evaluated the feasibility and effectiveness of using the bispectral index (BIS) to monitor anesthetic depth in patients with severe burns receiving intravenous target-controlled infusion (TCI) of remifentanil and propofol. We randomly assigned 80 patients undergoing elective escharectomy (<1 week) to BIS (A) and control (B) groups. All patients received remifentanil and propofol as intravenous TCI anesthesia. Clinical data were recorded at different time points. The time from drug withdrawal to eye opening upon the patient hearing his/her name called and upon reaching an Aldrete score of 9 points was also recorded. During anesthesia maintenance, the target concentrations of remifentanil and propofol in group A were significantly lower than that in group B (2.12 ± 0.35 vs 2.50 ± 0.21 ng/mL and 2.54 ± 0.22 vs 2.86 ± 0.31 µg/mL, respectively; P < 0.01). The time from drug withdrawal to eye opening upon the patient hearing his/her name called and reaching an Aldrete score of 9 points in group A was considerably shorter than that in group B (7.90 ± 0.58 vs 8.35 ± 0.66 min and 9.15 ± 0.69 vs 11.13 ± 0.96 min, respectively; P < 0.01). In both groups, mean arterial pressure and heart rate values at each time point after loss of consciousness were significantly lower than the baseline values (P < 0.05), with the exception of 2 min after intubation. The use of BIS to monitor anesthetic depth in patients with severe burns receiving TCI of remifentanil and propofol during the perioperative period reduces propofol consumption and shortens the consciousness recovery time in patients.