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1.
Nature ; 630(8017): 613-618, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38811737

RESUMO

A large qubit capacity and an individual readout capability are two crucial requirements for large-scale quantum computing and simulation1. As one of the leading physical platforms for quantum information processing, the ion trap has achieved a quantum simulation of tens of ions with site-resolved readout in a one-dimensional Paul trap2-4 and of hundreds of ions with global observables in a two-dimensional (2D) Penning trap5,6. However, integrating these two features into a single system is still very challenging. Here we report the stable trapping of 512 ions in a 2D Wigner crystal and the sideband cooling of their transverse motion. We demonstrate the quantum simulation of long-range quantum Ising models with tunable coupling strengths and patterns, with or without frustration, using 300 ions. Enabled by the site resolution in the single-shot measurement, we observe rich spatial correlation patterns in the quasi-adiabatically prepared ground states, which allows us to verify quantum simulation results by comparing the measured two-spin correlations with the calculated collective phonon modes and with classical simulated annealing. We further probe the quench dynamics of the Ising model in a transverse field to demonstrate quantum sampling tasks. Our work paves the way for simulating classically intractable quantum dynamics and for running noisy intermediate-scale quantum algorithms7,8 using 2D ion trap quantum simulators.

2.
Zhonghua Jie He He Hu Xi Za Zhi ; 46(6): 614-618, 2023 Jun 12.
Artigo em Zh | MEDLINE | ID: mdl-37278179

RESUMO

With the emergence of new tuberculosis patients, the number of patients with tuberculosis sequelae is increasing, which not only increases the medical burden of tuberculosis sequelae year by year, but also affects the health-related quality of life (HRQOL) of patients. The HRQOL of patients with tuberculosis sequelae has gradually received attention, but there are few relevant studies. Studies have shown that HRQOL is related to various factors such as post-tuberculosis lung disease, adverse reaction to anti-tuberculosis drugs, decreased physical activity, psychological barriers, low economic status and marital status. This article reviewed the current situation of HRQOL in patients with sequelae of tuberculosis and its influencing factors, in order to provide a reference for improving the quality of life of patients with sequelae of tuberculosis.


Assuntos
Qualidade de Vida , Tuberculose , Humanos , Qualidade de Vida/psicologia , Tuberculose/tratamento farmacológico , Antituberculosos/efeitos adversos
3.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 41(11): 854-856, 2023 Nov 20.
Artigo em Zh | MEDLINE | ID: mdl-38073216

RESUMO

This paper reported a case of acute severe nitrite poisoning with massive pulmonary thromboembolism (PTE), discussed the pathogenesis and summarized the treatment experience. Common symptoms of nitrite poisoning include headache, abdominal pain, shortness of breath, cyanosis, etc., which can be followed by encephalopathy, neurological dysfunction, hemolysis, etc. However, the cases of PTE are rare in clinical practice and are prone to missed diagnosis. Nitrite and methemoglobin may lead to vascular endothelial damage and promote thrombosis. In the diagnosis and treatment of acute severe nitrite poisoning patients, the targeted preventive measures should be taken.


Assuntos
Nitritos , Embolia Pulmonar , Humanos , Pulmão , Nitritos/intoxicação , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/tratamento farmacológico
4.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(6): 560-566, 2022 Jun 12.
Artigo em Zh | MEDLINE | ID: mdl-35658380

RESUMO

Objective: To evaluate two-drug combination interaction between pyrifazimine(TBI-166) and anti-drug-resistant tuberculosis group A drugs Bedaquiline (BDQ), Moxifloxacin (MFX) and the new anti-tuberculosis drug Delamanid (DLM), SQ109, Q203, and PBTZ169 in vitro and in vivo in mouse, so as to provide basis for TBI-166 combination therapy. Methods: This study was performed from September 2020 to July 2021. The chessboard method was used to evaluate the interaction between TBI-166 and BDQ, MFX, DLM, SQ109, and PBTZ169. The time-killing kinetics method was used to evaluate the anti-tuberculosis activity of the two-drug combination with partial synergy. The BALB/c mouse acute infection model was used to evaluate the anti-tuberculosis activity at 4 and 8 weeks in the two-drug combination group (TBI-166+BDQ, TBI-166+SQ109, TBI-166+PBTZ169, TBI-166+Q203) and monotherapy groups (TBI-166, BDQ, SQ109, PBTZ169, Q203). Data analysis was performed using an independent sample t-test. Results: After TBI-166 combined with anti-tuberculosis drugs, MIC was reduced to 6.25% to 25.00% of TBI-166 monotherapy. After TBI-166 combined with BDQ, SQ109 and PBTZ169, the partial inhibitory concentration index (FICI) values were 0.53, 0.75 and 0.75, respectively; the time sterilization experiment showed that the viable population of Mycobacterium tuberculosis treated with two-drug combination of TBI-166 and BDQ, SQ109, PBTZ169 for 14 days decreased at least 3 log10 CFU/ml. In the mouse experiments, it was found that, the amount of viable bacteria in lung tissue of BDQ, SQ109 and PBTZ169 combined with TBI-166 groups was lower than that of the monotherapy group,respectively. The lung tissue culture of mice in the TBI-166+BDQ group was negative after 4 weeks of treatment, and the number of live bacteria in the lungs of the TBI-166+BDQ group was 1.49 log10CFU lower than that of the BDQ monotherapy group(P<0.01). Conclusion: In vitro and in vivo experiments in mice revealed that TBI-166 had synergistic anti-tuberculosis activity after being combined with BDQ, SQ109 and PBTZ169, respectively.


Assuntos
Mycobacterium tuberculosis , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Animais , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Combinação de Medicamentos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , Tuberculose/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico
5.
Appl Opt ; 60(24): 7400-7405, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34613029

RESUMO

Modal decomposition (MD) has become an indispensable analysis approach for revealing the modal characteristics of optical fibers. A new MD approach based on the convolutional neural network (CNN) is presented to retrieve the exact superposition of eigenmodes of few-mode fibers. Using the near-field beam intensity and phase patterns obtained from digital holography, not only the amplitude of each eigenmode but also the exact phase difference between the higher-order modes and the fundamental mode can be predicted. Numerical simulations validate the reliability and feasibility of the approach. When ten modes in the few-mode fiber are considered, the similarities of the intensity and phase pattern between the reconstructed fields and the given fields can achieve to 97.0% and 85.6%, respectively.

6.
Zhonghua Yu Fang Yi Xue Za Zhi ; 55(9): 1089-1093, 2021 Sep 06.
Artigo em Zh | MEDLINE | ID: mdl-34619926

RESUMO

Objective: Based on the genetic diagnosis and follow-up study on pediatric neurofibromatosis 1 (NF1) patients, interrogating the genotype-phenotype correlations of patients with NF1 mutations. Methods: 32 Patients from age of 2 months to 5 years old (17 male and 15 female) suspected for neurofibromatosis 1 were recruited during September 2016 to January 2018 in Shanghai Children's Medical Center retrospectively. Genetic diagnosis was applied to detect pathogenic variants. Long-term follow-up study were conducted to reveal progress of the disease and genotype-phenotype correlations. Results: 27 patients were detected with pathogenic NF1 variants, among them three were not reported. 3 patients inherited pathogenic variants from their NF1 diagnosed parents, all the other variants were de novo. Progressive development of phenotypes wasn't observed in most patients during the follow-up (14/27). Some patients were diagnosed with short stature, pulmonary artery stenosis and developmental delay during the follow-up(7/27). Short stature and pulmonary artery stenosis may be associated with missense mutation and severe truncation mutation of NF1 gene, respectively. Conclusions: Genetic diagnosis is required in young patients of NF1.Follow-up plan of pediatric patients should be adjusted based on genetic findings. Early follow-up of cardiovascular abnormalities should be noted in patients with missense mutation. Height development in patients with severe truncating variants are needed.


Assuntos
Neurofibromatose 1 , Criança , China , Feminino , Seguimentos , Humanos , Masculino , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Neurofibromina 1 , Estudos Retrospectivos
7.
Opt Lett ; 43(18): 4370-4373, 2018 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-30211866

RESUMO

A novel hyperspectral single pixel system was used to compare different compressive basis patterns for intensity imaging, lifetime imaging, and FRET quantification. Six popular basis patterns were compared experimentally in a phantom containing two fluorescent dyes. The basis patterns that performed best for lifetime quantification were used to measure FRET occurrence in well-plate samples with varying acceptor-donor ratios. The ABS-WP approach using Haar patterns and the compressive sensing approach with Hadamard Ranked patterns displayed the best overall performances at a 50% compression ratio.

8.
Zhonghua Zhong Liu Za Zhi ; 40(2): 110-114, 2018 Feb 23.
Artigo em Zh | MEDLINE | ID: mdl-29502370

RESUMO

Objective: To explore the association between the 21-gene recurrence score (RS) and clinicopathologic characteristics as well as prognosis in patients with axillary lymph node negative, hormone receptor (HR) positive breast cancer. Methods: The clinicopathologic data of 439 early breast cancer patients who underwent 21 gene RS testing was retrospectively analyzed. According to the 21 gene RS, the patients were divided into low risk (295 cases), intermediate risk (111 cases) and high-risk (33 cases) group. The relationship between the 21 gene RS and clinicopathological characteristics, treatment, recurrence and metastasis was analyzed. Univariate and multivariate statistical analyses were used to analyze the risk factors for relapse free survival (RFS). Results: Tumor grade, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 index were significantly different among the 3 risk cohorts (P<0.001 for all). After a median follow-up of 32 months, the recurrence rate in low risk group (3.7%) was significantly lower than that in the intermediate-high risk group (9.0%), the locoregional recurrence (LRR) rate of low, intermediate and high risk group was 2.4%, 6.3% and 9.1%; and the distant metastasis (DM) rate in low risk group was 1.4% and 2.1% in the intermediate-high risk group. Univariate analysis showed RS, ER status and endocrine therapy were prognostic factors for RFS (P<0.05 for all). Multivariate analysis showed that RS was an independent significant predictor for RFS (P=0.04). Conclusions: The 21-gene RS is related to tumor grade, ER, PR and Ki-67 index. RS is an independent risk factor for RFS in patients with hormone receptor positive early-stage breast cancer.


Assuntos
Neoplasias da Mama/genética , Recidiva Local de Neoplasia/genética , Análise de Variância , Neoplasias da Mama/química , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Humanos , Antígeno Ki-67/análise , Prognóstico , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Estudos Retrospectivos , Risco , Fatores de Risco
9.
Zhonghua Yi Xue Za Zhi ; 98(37): 3025-3031, 2018 Oct 09.
Artigo em Zh | MEDLINE | ID: mdl-30392262

RESUMO

Objective: To investigate the effect of lipid factor CTRP9 on myocardial remodeling induced by isoproterenol in mice. Methods: Male C57BL/6J mice were randomly assigned to four groups (n=10 per group), then mice were administered 5 mg/kg ISO q12h for 12 days by daily subcutaneous injection to induce myocardial remodeling model. Mice also received subcutaneous injection of CTRP9 (200 µg·kg(-1)·d(-1)) for 12days. Echocardiography was performed to compare the ventricular wall thickness and cardiac function. Heart weight/body weight (HW/BW), lung weight/body weight (LW/BW), heart weight/tibia length (HW/TL) and cross-sectional area of cardiomyocytes were compared between groups. The cardiac hypertrophic markers and fibrotic markers were also compared by RT-PCR between the two groups. Molecular protein changes were evaluated by Western blot. Results: CTRP9 was down-regulated in model group. The LVEDd (4.00 mm vs 4.67 mm), LVEDs (2.60 mm vs 3.12 mm) in mode group were both higher than control group while the LVEF (73% vs 55%) and FS (39% vs 21%) were reduced in mode group. Compared with the control group, the HW/BW, LW/BW, HW/TL and cross-sectional area of cardiomyocytes were much higher in mode group (P<0.05). The transcription level of hypertrophic markers (ANP, BNP, ß-MHC) were elevated. Left ventricular collagen volume was increased as well as the transcription level of fibrosis markers collagen Ⅰ, collagen Ⅲ and a-SMA. Western blot results indicated that CTRP9 increased nNOS and eNOS derived NO production but not iNOS expression. Conclusion: CTRP9 could protect against ISO induced myocardial remodeling by increasing nNOS and eNOS derived NO production.


Assuntos
Modelos Animais de Doenças , Miocárdio , Adiponectina , Animais , Glicoproteínas , Isoproterenol , Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Remodelação Ventricular
10.
Zhonghua Gan Zang Bing Za Zhi ; 26(4): 305-309, 2018 Apr 20.
Artigo em Zh | MEDLINE | ID: mdl-29996344

RESUMO

Objective: To investigate the possible mechanisms of tumor-associated macrophages (TAMs) in regulating epithelia-mesenchymal transition (EMT) of Hep3B hepatoma cells, since EMT is closely associated with the malignancy of hepatoma cells and tumor microenvironment plays an important role in regulating EMT of hepatoma cells, and to provide new regimens for the clinical studies and treatment of liver cancer. Methods: Human monocytic leukemia THP-1 cells were successfully induced to TAMs. With TAMs as target cells, they were co-cultured with the supernatant of Hep3B hepatoma cells or Hep3B hepatoma cells, and Western blot and RT-PCR were used to measure the change in the expression of Toll-like receptor 4 (TLR4) in TAMs. The expression of TLR4 in TAMs was downregulated by transient plasmid transfection with shRNA. With Hep3B hepatoma cells as target cells, the supernatants of TAMs and TAMs transfected with shRNA TLR4 plasmid were used for intervention, and Western blot was used to measure the protein expression of E-cadherin, N-cadherin, and vimentin. The two-sided t-test was used for comparison of the means of two independent samples. Results: THP-1 cells were successfully induced to TAMs. According to the results of Western blot, compared with the control-CM group, the TAM-CM group had a significant reduction in the protein expression of E-cadherin and significant increases in the protein expression of N-cadherin and vimentin in Hep3B cells. After the expression of TLR4 in TAMs was downregulated, the culture solution of TAMs was used for the intervention of Hep3B cells (shRNA group), and compared with the TAM-CM group, the shRNA group had a significant increase in the expression of E-cadherin and significant reductions in the protein expression of N-cadherin and vimentin in Hep3B cells. Western blot and RT-PCR showed that the expression of TLR4 in TAMs was influenced by Hep3B cells. Conclusion: TAMs can promote EMT of Hep3B hepatoma cells, and downregulation of the expression of TLR4 in TAMs may reduce EMT of Hep3B hepatoma cells, suggesting that TLR4 on the surface of TAMs may be a key molecule involved in the interaction between TAMs and Hep3B hepatoma cells.


Assuntos
Carcinoma Hepatocelular/patologia , Movimento Celular , Transição Epitelial-Mesenquimal , Macrófagos/patologia , Adulto , Caderinas/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Humanos , Macrófagos/metabolismo
11.
Acta Endocrinol (Buchar) ; 14(3): 401-407, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31149290

RESUMO

BACKGROUND: Prevention of complications is widely considered as the main aim of diabetes control. And diabetes education is the cornerstone for type 2 diabetes (T2D) management. However, traditional lecture-based diabetes patient education activities have small and short-lasting efficacy. Therefore, technology-based initiatives for diabetes patient education are urgently required. OBJECTIVE: To evaluate Guessing, a popular game, as tool in increasing complication awareness of patients with newly diagnosed T2D during diabetes care. PATIENTS AND METHODS: In a cohort study, 103 patients were split into Guessing Game group and control group. The opinions of patients and educators in Guessing Game group were surveyed. Patient performance was evaluated by test scores and the attendance to diabetes complication screening clinic. RESULTS: A majority of patients and all educators believed that Guessing Game enhanced complication awareness. Educatees achieved higher total scores and test scores in "Fill in the Gaps" (one of 2 types of test item), more actively attended complication screening clinic, after using Guessing Game as an education tool. CONCLUSION: Guessing Game is an attractive and effective educational intervention to increase complication awareness of T2D patients.

12.
Nanotechnology ; 27(39): 395605, 2016 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-27560484

RESUMO

Metal oxide nanowires (NWs) can be easily grown by the thermal oxidation method, but the low adhesion between the NWs and the substrate restricts their practical applications in functional devices. In this work, the conventional hotplate technique is simply modified by introducing one or two stainless steel plates to supply a more stable oxidation environment, which is found to be beneficial to the growth and adhesion of CuO NWs on the Cu substrate. In detail, the Cu foils were heated on the hotplate directly, on one plate over the hotplate, and between two plates over the hotplate at 400 °C in ambient condition. It is found that the NWs obtained between two plates exhibit large length and diameter with moderate density. The sufficient activated oxygen, stable temperature, and proper temperature gradient configuration caused by the two plates accelerate the formation of CuO NWs, and result in the longest NWs with enhanced adhesion. The grain-boundary diffusion and Kirkendall effect are proposed to explain the mechanism of NWs growth and the formation of cracks. The NWs obtained between two plates also showed the best field emission properties, with lowest turn-on field (5.31 V µm(-1)) and threshold field (9.8 V µm(-1)). Excellent field emission properties and enhanced NW-substrate adhesion indicate that these NW arrays could be potentially used as the cathode of field emission displays.

13.
Qual Life Res ; 25(8): 2031-40, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26869477

RESUMO

PURPOSE: We evaluated the effect of plaque-type psoriasis on health-related quality of life (HRQoL) of patients who received infliximab (IFX) in real-world clinical settings. METHODS: REALITY was a prospective, observational, open-label study of the efficacy and safety of up to 98 weeks of IFX (5 mg/kg infused at weeks 0, 2, 6, and every 8 weeks thereafter) in patients with moderate-to-severe plaque-type psoriasis. Patients with ≥25 % Psoriasis Area Severity Index (PASI) improvement (PASI 25) at week 50 were eligible for the Extended Treatment Phase (treatment to week 98). Inclusion criteria were diagnosis of plaque-type psoriasis, age ≥18 years, decision to start IFX, and patient consent. Key secondary efficacy outcomes included the Dermatologic Life Quality Index (DLQI; mean DLQI scores, attainment of DLQI 0/1), which was analyzed over 98 weeks. Post hoc analyses examined improvement in DLQI and the relationship between PASI and DLQI. RESULTS: In the Treatment Phase, patients (n = 516, 66.0 % men, mean age 46.4 years) had a mean baseline PASI of 18.1. Mean DLQI improved from 12.7 at baseline to 4.7 [mean change (95 % CI); -8.0 (-8.9, -7.1)] at week 50; 64.0 % (229/358) of patients improved by ≥5 DLQI points. At week 50 (n = 362), 37.6 % (95 % CI; 32.7, 42.7) achieved a DLQI of 0. In the Extended Treatment Phase, patients (n = 167, 68.3 % men, mean age 46.6 years) had a mean baseline PASI of 20.4. Mean DLQI improved from 12.3 at baseline to 2.8 at week 98 [mean change (95 % CI); -9.4 (-10.8, -8.0)]; 68.6 % (96/140) of patients improved by ≥5 DLQI points. At week 98 (n = 141), 47.5 % (95 % CI; 39.4, 55.7) achieved a DLQI of 0. CONCLUSIONS: Patients with plaque-type psoriasis who received treatment with IFX for 50 weeks or up to 98 weeks reported substantial HRQoL improvement.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Perfil de Impacto da Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacologia , Feminino , Humanos , Infliximab/administração & dosagem , Infliximab/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
14.
Genet Mol Res ; 14(2): 5527-34, 2015 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-26125750

RESUMO

Numerous studies have evaluated the association between the angiotensinogen (AGT) G-217A gene polymorphism and essential hypertension risk. However, the results have been inconsistent. We examined whether the AGT G-217A gene polymorphism confers essential hypertension risk by conducting a meta-analysis. We conducted a literature search of the Google Scholar, PubMed, and China National Knowledge Infrastructure databases for relevant studies that examined the G-217A polymorphism and risk of essential hypertension. Statistical analyses were carried out using Stata 12.0 to combine all relevant studies. Crude odds ratios (ORs) with 95% confidence intervals (95%CIs) were calculated to estimate the strength of this association. A total of 2017 patients with psoriasis and 1708 controls from 7 comparative studies were included in this meta-analysis. We found a significant association between the AGT G-217A gene polymorphism and the risk of essential hypertension (AA vs GG: OR = 2.52, 95%CI = 1.68-3.78; AA vs GA: OR = 2.26, 95%CI = 1.48-3.45; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.20, 95%CI = 1.03-1.39). Further stratified analyses were conducted by ethnicity and sample size and produced similar results. No evidence of publication bias was found. This meta-analysis confirms that the AGT G-217A gene polymorphism is associated with essential hypertension susceptibility.


Assuntos
Angiotensinogênio/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Hipertensão/genética , Hipertensão Essencial , Humanos , Hipertensão/patologia , Polimorfismo de Nucleotídeo Único , Fatores de Risco
15.
Genet Mol Res ; 14(2): 5785-92, 2015 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-26125777

RESUMO

We examined the effect of E-cadherin expression on epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) molecular targeted therapy sensitivity/resistance. We treated MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells with the EGFR-TKIs PD153035 and gefitinib, and then tested the drug-resistance and sensitivity using the MTT method, calculated IC50 values for each cell line, and compared the results to E-cadherin content. The MTT assay was used to determine the survival rates of MCF-7, MDA-MB-231, T24, SiHa, H460, SK-HEP-1, MHCC97-H, and THP-1 cells upon the action of EGFR-TKI (PD153035, gefitinib). For PD153035, the IC50 in MCF-7, MDA-MB-231, T24, and SiHa cells differed from that of H460, SK-HEP-1, MHCC97-H, and THP-1 (P < 0.05). Following gefitinib treatment, the IC50 values of MCF-7, MDA-MB-231, T24, and SiHa cells differed from those of H460, SK-HEP-1, MHCC97-H, and THP-1 cells (P < 0.01). The survival rate of MCF-7, MDA-MB-231, T24, and SiHa cells clearly decreased with increasing drug concentration, indicating the cells were sensitive to the drugs and that E-cadherin expression was positive; however, H460, SK-HEP-1, MHCC97-H, and THP-1 cells showed no significant decreased with increasing drug concentration, indicating that they were resistant to the drugs and that E-cadherin expression was negative. The survival rate of epithelial tumor cells through the action of EGFR-TKI is related to E-cadherin expression. E-cadherin may play a significant role in the sensitivity regulation of EGFR molecular targeting treatment. E-cadherin may provide important clues for selecting proper EGFR-TKI molecular targeting treatment.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Caderinas/biossíntese , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias da Mama/patologia , Caderinas/genética , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Gefitinibe , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética
16.
Genet Mol Res ; 14(3): 11154-61, 2015 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-26400346

RESUMO

Fibroblast growth factor 5 (FGF5) is a secreted signaling protein that belongs to the FGF family, and was found to be associated with hair growth in humans and other animals. The Inner Mongolia Cashmere goat (Capra hircus) is a goat breed that provides superior cashmere; this breed was formed by spontaneous mutation in China. Here, we report the cloning, molecular characterization, and expression pattern of the Cashmere goat FGF5. The cloned FGF5 cDNA was 813 base pairs (KM596772), including an open reading frame encoding a 270-amino-acid polypeptide. The nucleotide sequence shared 99% homology with Ovis aries FGF5 (NM_001246263.1). Bioinformatic analysis revealed that FGF5 contained a signal peptide, an FGF domain, and a heparin-binding growth factor/FGF family signature. There was 1 cAMP- and cGMP-dependent protein kinase phosphorylation site, 11 protein kinase C phosphorylation sites, 4 casein kinase II phosphorylation sites, 1 amidation site, 1 N-glycosylation site, and 1 tyrosine kinase phosphorylation site in FGF5. Real-time polymerase chain reaction showed that FGF5 mRNA levels were higher in testis than in the pancreas and liver. These data suggest that FGF5 may play a crucial role in Cashmere goat hair growth.


Assuntos
Fator 5 de Crescimento de Fibroblastos/genética , Expressão Gênica , Cabras/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Células Cultivadas , Clonagem Molecular , Fator 5 de Crescimento de Fibroblastos/química , Fator 5 de Crescimento de Fibroblastos/metabolismo , Cabras/genética , Masculino , Modelos Moleculares , Dados de Sequência Molecular , Especificidade de Órgãos , Filogenia , RNA Mensageiro , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Testículo/metabolismo
17.
Genet Mol Res ; 14(3): 9675-82, 2015 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-26345900

RESUMO

FKBP38 (also known as FKBP8) is a unique member of the FK506-binding protein (FKBP) family, and its role is controversial because it acts as an upstream regulator of the mTOR signaling pathway, which controls cell growth, proliferation, and differentiation. This study aimed to explore the role of FKBP38 in the activation of mTOR signaling in Cashmere goat (Capra hircus) fetal fibroblasts. To construct a Cashmere goat FKBP38 siRNA eukaryotic expression vector that targets FKBP38 mRNA, we designed shRNA based on the gene sequence deposited in GenBank (accession No. JF714970) and synthesized a DNA fragment encoding the shRNA. The DNA fragment was inserted into the pRNAT-U6.1/Neo vector to construct an expression vector of shRNA, which was labeled pRNAT-FKBP38-shRNA. The recombinant plasmid was used to transfect Cashmere goat fetal fibroblasts (GFb) using lipofectamine™2000. We found that cells were successfully transfected with pRNAT-U6.1/Neo-FKBP38-shRNA. Green fluorescence could be observed in cells following 48-h transfection. Proteins were then isolated from GFbs transfected with pRNAT-FKBP38-shRNA and from control cells, and protein expression was analyzed by western blot. Expression of FKBP38 decreased and mTOR signaling was activated, which induced the phosphorylation of mTOR, S6, and 4EBP1. Thus, FKBP38 gene-silencing activates mTOR signaling in goat cells.


Assuntos
Fibroblastos/metabolismo , Inativação Gênica , Cabras/genética , Cabras/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Animais , Sequência de Bases , Células Cultivadas , Expressão Gênica , Ordem dos Genes , Vetores Genéticos/genética , Fosforilação , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Interferente Pequeno/química , Proteínas Quinases S6 Ribossômicas/metabolismo , Proteínas de Ligação a Tacrolimo/química , Transfecção
18.
Ann Rheum Dis ; 73(1): 101-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23696633

RESUMO

OBJECTIVES: To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs. METHODS: Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance. RESULTS: A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment. CONCLUSIONS: Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Antirreumáticos/administração & dosagem , Naproxeno/administração & dosagem , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Diagnóstico Precoce , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Naproxeno/efeitos adversos , Placebos , Espondilartrite/diagnóstico , Espondilite Anquilosante/diagnóstico , Resultado do Tratamento , Adulto Jovem
19.
Ann Rheum Dis ; 73(1): 108-13, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23740231

RESUMO

OBJECTIVE: To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. METHOD: Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. RESULTS: At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). CONCLUSIONS: In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Naproxeno/administração & dosagem , Espondilartrite/tratamento farmacológico , Espondilite Anquilosante/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Método Duplo-Cego , Diagnóstico Precoce , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Naproxeno/efeitos adversos , Placebos , Indução de Remissão , Espondilartrite/diagnóstico , Espondilite Anquilosante/diagnóstico , Resultado do Tratamento , Adulto Jovem
20.
Br J Dermatol ; 171(3): 631-41, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24673357

RESUMO

BACKGROUND: Tumour necrosis factor-α inhibitors, including infliximab (IFX), can improve disease control of plaque-type psoriasis. OBJECTIVES: The Real-World Assessment of Long-Term Infliximab Therapy for Psoriasis (REALITY) study evaluated the efficacy and safety of maintenance IFX therapy in typical clinical settings. METHODS: In this prospective, observational, open-label, multicentre study in patients with plaque-type psoriasis, IFX 5 mg kg was infused at weeks 0, 2 and 6, and every 8 weeks thereafter during a 50-week treatment phase. The primary outcome was ≥ 75% Psoriasis Area and Severity Index (PASI) improvement from baseline to week 50. Patients with ≥ 25% PASI improvement from baseline to the end of the treatment phase were potentially eligible to enter a 48-week extended treatment phase. Response maintenance and other efficacy measures were evaluated. Adverse events (AEs) were collected. RESULTS: In total 660 patients enrolled. Of 521 efficacy-evaluable treatment phase patients (66% male, mean age 46·5 years, mean PASI 18·1), 56·8% achieved PASI 75 at the end of the treatment phase. Response was maintained at week 50 by 64·7% (205/317) of patients who achieved PASI 75 at week 14. During extended treatment, 66·3% (112/169) of patients attained PASI 75 at week 98; response was maintained at week 98 by 71·6% (101/141) of those who achieved PASI 75 at week 50. IFX was generally well tolerated. During treatment, 7·6% (50/659) of patients had serious AEs. During extended treatment, 4·1% (eight of 193) of patients had serious AEs. CONCLUSIONS: PASI 75 response was achieved by 56·8% and 66·3% of patients at weeks 50 and 98, respectively. The AE pattern was consistent with previous reports.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Feminino , Humanos , Infliximab , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
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