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1.
Adv Sci (Weinh) ; : e2401983, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38894574

RESUMO

Physical unclonable function (PUF) is attractive in modern encryption technologies. Addressing the disadvantage of slow data storage/authentication in optical PUF is paramount for practical applications but remains an on-going challenge. Here, a highly efficient PUF strategy based on random structural color domains (SCDs) of cellulose nanocrystal (CNC) is proposed for the first time, combing with hyperspectral imaging system (HIS) for ultrafast storage and authentication. By controlling the growth and fusion behavior of the tactoids of CNC, the SCDs display an irregular and random distribution of colors, shapes, sizes, and reflectance spectra, which grant unique and inherent fingerprint-like characteristics that are non-duplicated. Based on images and spectra, these fingerprint features are used to develop two sets of PUF key generation methods, which can be respectively authenticated at the user-end and the manufacturer-front-end that achieving a high coding capacity of at least 22304. Notably, the use of HIS greatly shortens the time of key reading and generation (≈5 s for recording, 0.5-0.7 s for authentication). This new optical PUF labels can not only solve slow data storage and complicated authentication in optical PUF, but also impulse the development of CNC in industrial applications by reducing color uniformity requirement.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36884009

RESUMO

Currently, there have been widespread investigation conducted into responsive photonic crystal hydrogels (RPCHs) characterized by high selectivity and sensitivity for colorimetric indicators and physical/chemical sensors. In spite of this, it remains challenging to use RPCHs for sensing due to their limited mechanical property and molding capability. In the present study, a double-network structure is proposed to design highly stretchable, sensitive, and reusable ion-detection photonic papers (IDPPs) for assessing the quality of visual and portable comestible liquids (e.g., soy sauce). It is constructed by integrating polyacrylamide and poly-methacryloxyethyl trimethyl ammonium chloride with highly ordered polystyrene microspheres. The double-network structure improves the mechanical properties of IDPPs with their elongation at break increasing from 110 to 1600%. Meanwhile, the optical properties of photonic crystals are retained. The IDPPs achieve a fast ion response by applying control on the swelling behavior of the hydration radius of the counter ions through ion exchange. Given a certain concentration range (0.01-0.10 M), chloride ions can be detected fast (3-30 s) by exchanging ions with a small hydration radius through an IDPP, which is clearly observable. Due to the improvement of mechanical properties and the reversible exchange of ions derived from IDPPs, their reusability is significantly enhanced (>30 times). Characterized by a simple operation, high durability, and excellent sustainability, these IDPPs are promising for practical application in food security and human health assessment.

3.
J Cell Mol Med ; 26(20): 5326-5329, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36102237

RESUMO

A 55-year-old Chinese man with a right lung mass and lymph node metastasis (T4N3M0 IIIB) was diagnosed with lung adenocarcinoma after a CT-guided biopsy. With the wide application of next-generation sequencing (NGS) in tumour detection, we found a rare CCDC85A-ALK fusion. The patient received alectinib, which had marked efficacy. This is the first report of a lung adenocarcinoma patient harbouring a new uncommon anaplastic lymphocyte kinase fusion that showed a remarkable response to alectinib. NGS aids in selecting treatment in non-small cell lung cancer patients.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Carbazóis/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Piperidinas , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
4.
Front Immunol ; 13: 1088683, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703977

RESUMO

Genetic mutations that render mismatch repair defective may result in microsatellite instability, which is common in colorectal carcinomas and gastric cancers as well as Lynch syndrome. Mismatch repair deficiency/high microsatellite instability (dMMR/MSI-H) predicts the tumor response to immune checkpoint inhibitors. However, few studies have evaluated the efficacy of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) patients with dMMR/MSI-H. In this work, we present a patient with advanced squamous lung cancer with dMMR/MSI-H and a high tumor mutational burden (TMB-H) who obtained a long-term benefit from immunotherapy. NSCLC patients with dMMR/MSI-H/TMB-H may thus benefit from immune checkpoint inhibitors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Inibidores de Checkpoint Imunológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNA/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Imunoterapia
5.
Front Oncol ; 11: 731572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540698

RESUMO

The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.

6.
Photodiagnosis Photodyn Ther ; 36: 102521, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34481977

RESUMO

Colorectal cancer is with high incidence worlwide.. Because of the heterogeneity of the tumor, combination therapy is probably of great significance to improve the prognosis of colorectal cancer patients. Herein, the pH-responsive supramolecular hydrogels mPEG-luteolin-BTZ@ICG based on bortezomib (BTZ) and indocyanine green (ICG) were prepared, and the colorectal cancer was treated with mPEG-luteolin-BTZ@ICG through the combination of photothermal/photodynamic and chemotherapy. BTZ performed drug therapy, meanwhile ICG wrapped in supramolecular hydrogels possessed higher light stability than free ICG to perform photothermal/photodynamic therapy. In vitro and in vivo assays showed excellent inhibition of tumor cells due to the combined effect of BTZ and ICG. The mPEG-luteolin-BTZ@ICG combined with laser therapy possessed exceptional biological safety and provided new candidates for advanced colon cancer therapy and important references for other tumor therapies.


Assuntos
Neoplasias Colorretais , Hipertermia Induzida , Nanopartículas , Fotoquimioterapia , Bortezomib , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Humanos , Hidrogéis , Concentração de Íons de Hidrogênio , Verde de Indocianina , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Fototerapia
7.
Polymers (Basel) ; 13(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068082

RESUMO

Despite the rapid development of two-dimensional covalent organic frameworks (2D COFs) in recent years, it remains a great challenge to synthesize highly crystalline COF materials. Here, a CNC-assisted approach was adopted to synthesize high crystallinity COF materials. A series of 2D COF films were synthesized at the air-water interface by using cellulose nanocrystals (CNCs) as the template. The occurrence of Schiff reactions based on the imine bond was demonstrated by Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) exhibited the appearances of 2D COF films were flower-like. When CNCs were added to a certain extent, the size of a single petal in the flowers gradually increased with the amount of CNCs. The film with large petals was characterized by Ultraviolet-Visible diffuse reflectance spectroscopy (UV-Vis DRS), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). In UV-Vis DRS curves, the S-band of COF-366 film was red-shifted by 24 nm compared with that of 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphyrin (TAPP), confirming the existence of extended conjugation in COF-366 film. XPS was used to identify the surface composition of the sample. The N1s signal of the film indicated that each TAPP formed four imine bonds with 2,5-dihydroxyterephthalaldehyde (DHTA) in COF-366 film. TEM images showed that CNCs had an influence on the crystal size. It was observed from SAED that the crystallinity of the film with CNCs was higher than the film without CNCs. This work provided a new template for improving the crystallinity of 2D COF films.

8.
Front Oncol ; 11: 629394, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33912453

RESUMO

BACKGROUND: Cisplatin-based chemotherapy was previously considered as the standard adjuvant therapy for improved overall survival (OS) in patients with non-small cell lung cancer (NSCLC) after surgery. However, the benefit was limited due to high risks of recurrence and adverse events. In the present study, the efficacy of adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for EGFR-mutant patients after surgery was investigated using the latest updated data. METHODS: This meta-analysis included a comprehensive range of relevant studies identified from database searches. Disease-free survival (DFS) and OS with hazard ratios (HRs) were calculated using random-effect or fixed-effect models. Subgroup analysis was also performed. RESULTS: A total of seven randomized clinical trials were included in the meta-analysis and involved 1,283 NSCLC patients harboring EGFR mutations. In resected EGFR-mutant NSCLC patients, adjuvant EGFR-TKIs were significantly better than chemotherapy in terms of DFS (HR: 0.41; 95%CI: 0.24-0.70, P = 0.001), without showing any benefit in OS (HR: 0.72; 95%CI: 0.37-1.41, P = 0.336). No significant difference in DFS was observed between patients with EGFR exon 19 deletion and those with L858R mutation. Resected EGFR-mutant NSCLC patients treated with osimertinib experienced improved DFS and a lower risk of brain recurrence than those treated with gefitinib or erlotinib. Adjuvant EGFR-TKIs reduced the risk of bone and lung relapse, without decreasing the risk of local recurrence and liver relapse. CONCLUSION: This meta-analysis shows that adjuvant EGFR-TKI therapy could significantly prolong DFS in patients with resected EGFR-mutant NSCLC. Treatment with osimertinib showed improved DFS with a lower risk of brain recurrence than treatment with gefitinib or erlotinib for resected disease.

9.
Clin Lung Cancer ; 22(2): 100-109.e3, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33317922

RESUMO

BACKGROUND: Mutations in TP53 are commonly found in patients with epidermal growth factor receptor (EGFR) mutant advanced non-small-cell lung cancer (NSCLC). In this study, we determined the predictive and prognostic potential of different subtypes of TP53 using data from a phase III randomized trial (CTONG 0901). PATIENTS AND METHODS: The trial enrolled 195 patients who had undergone next-generation sequencing of 168 genes before treatment with EGFR tyrosine kinase inhibitors. Mutations in TP53 (exon 4 or 7, other mutations, and wild-type) were analyzed based on the therapeutic response and survival. A Cox proportional hazards model was used to determine the potential of the predictive and prognostic factors. RESULTS: All 195 patients harbored activating EGFR mutations: the most common concomitant mutations were TP53 (134/195, 68.7%), CTNNB1 (20/195, 10.3%), and RB1 (16/195, 8.2%). The genetic profiles between patient subgroups administered first-line (132, 67.7%) or later-line (63, 32.3%) treatments did not significantly differ. The median progression-free survival in patients with mutations in exon 4 or 7 of TP53, other TP53 mutations, and wild-type TP53 were 9.4, 11.0, and 14.5 months (P = .009), respectively. Overall survival times were 15.8, 20.0, and 26.1 months (P = .004), respectively. Mutations in exon 4 or 7 of TP53 served as independent prognostic factors for progression-free (P = .001) and overall survival (P = .004) in patients. CONCLUSION: Mutations in exon 4 and/or 7 in TP53 are promising predictive and prognostic indicators in EGFR-mutated NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteína Supressora de Tumor p53/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Éxons/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de Sobrevida
10.
Front Immunol ; 11: 1933, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072067

RESUMO

Background: Limited treatment strategies are available for squamous-cell lung cancer (SQLC) patients. Few studies have addressed whether immune-related genes (IRGs) or the tumor immune microenvironment can predict the prognosis for SQLC patients. Our study aimed to construct a signature predict prognosis for SQLC patients based on IRGs. Methods: We constructed and validated a signature from SQLC patients in The Cancer Genome Atlas (TCGA) using bioinformatics analysis. The underlying mechanisms of the signature were also explored with immune cells and mutation profiles. Results: A total of 464 eligible SQLC patients from TCGA dataset were enrolled and were randomly divided into the training cohort (n = 232) and the testing cohort (n = 232). Eight differentially expressed IRGs were identified and applied to construct the immune signature in the training cohort. The signature showed a significant difference in overall survival (OS) between low-risk and high-risk cohorts (P < 0.001), with an area under the curve of 0.76. The predictive capability was verified with the testing and total cohorts. Multivariate analysis revealed that the 8-IRG signature served as an independent prognostic factor for OS in SQLC patients. Naive B cells, resting memory CD4 T cells, follicular helper T cells, and M2 macrophages were found to significantly associate with OS. There was no statistical difference in terms of tumor mutational burden between the high-risk and low-risk cohorts. Conclusion: Our study constructed and validated an 8-IRG signature prognostic model that predicts clinical outcomes for SQLC patients. However, this signature model needs further validation with a larger number of patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Transcriptoma , Idoso , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/terapia , Bases de Dados Genéticas , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Microambiente Tumoral
11.
Immunotherapy ; 11(17): 1481-1490, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713453

RESUMO

Aim: We performed a meta-analysis to explore the efficacy of immunotherapy for patients with squamous non-small-cell lung cancer (NSCLC). Materials & methods: Randomized clinical trials comparing immunotherapy with chemotherapy for advanced NSCLC patients were included. Results: A total of 11 trials (3112 patients) were included. PD-1/PD-L1 inhibitors demonstrated significant superiority to chemotherapy in overall survival (OS) (hazard ratio [HR]: 0.74; p < 0.001) and progression-free survival (PFS) (HR: 0.66; p < 0.001) for squamous NSCLC. The OS and PFS benefits of PD-1/PD-L1 inhibitors for squamous NSCLC were similar in subgroup analyses of line settings, PD-L1 expression and different study methodologies. No advantage in OS was found in advanced squamous NSCLC patients treated with atezolizumab (HR: 0.87; p = 0.087). Conclusion: PD-1/PD-L1 inhibitors significantly improved OS and PFS in advanced squamous NSCLC patients when compared with chemotherapy.


Assuntos
Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias de Células Escamosas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias de Células Escamosas/mortalidade
12.
BMC Cancer ; 18(1): 1171, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477470

RESUMO

OBJECTIVE: Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI). The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression. METHODS: Totally, 4622 advanced NSCLC patients from two institutes (3762 patients at the Guangdong Lung Cancer Institute from January 2011 to December 2016 and 860 cases at the Perking Cancer Hospital from January 2015 to December 2016) were screened for ALK rearrangement with any method of IHC, RACE-coupled PCR or FISH. C-Met expression was performed by IHC in ALK-rearranged patients, and more than 50% of cells with high staining were defined as c-Met overexpression. The efficacy of crizotinib was explored in the ALK-rearranged patients with or without c-Met overexpression. RESULTS: Sixteen patients were identified with c-Met overexpression in 160 ALK-rearranged cases, with the incidence of 10.0% (16/160). A total of 116 ALK-rearranged patients received the treatment of crizotinib. Objective response rate (ORR) was 86.7% (13/15) in ALK-rearranged patients with c-Met overexpression and 59.4% (60/101)in those without c-Met overexpression, P = 0.041. Median PFS showed a trend of superiority in c-Met overexpression group (15.2 versus 11.0 months, P = 0.263). Median overall survival (OS) showed a significant difference for ALK-rearranged patients with c-Met overexpression group of 33.5 months with the hazard ratio (HR) of 3.2. CONCLUSIONS: C-Met overexpression co-exists with ALK rearrangement in a small population of advanced NSCLC. There may be a trend of favorable efficacy of crizotinib in such co-altered patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/uso terapêutico , Expressão Gênica , Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Amplificação de Genes , Genes erbB-1 , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Análise de Sobrevida
13.
J Thorac Oncol ; 13(11): 1668-1675, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30056164

RESUMO

INTRODUCTION: This study evaluated whether tumor expression of programmed death ligand 1 (PD-L1) could predict the response of EGFR-mutated NSCLC to EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: We retrospectively evaluated patients who received EGFR-TKIs for advanced NSCLC at the Guangdong Lung Cancer Institute between April 2016 and September 2017 and were not enrolled in clinical studies. The patients' EGFR and PD-L1 statuses were simultaneously evaluated. RESULTS: Among the 101 eligible patients, strong PD-L1 expression significantly decreased objective response rate, compared with weak or negative PD-L1 expression (35.7% versus 63.2% versus 67.3%, p = 0.002), and shortened progression-free survival (3.8 versus 6.0 versus 9.5 months, p < 0.001), regardless of EGFR mutation type (19del or L858R). Furthermore, positive PD-L1 expression was predominantly observed among patients with de novo resistance rather than acquired resistance to EGFR-TKIs (66.7% versus 30.2%, p = 0.009). Notably, we found a high proportion of PD-L1 and cluster of differentiation 8 (CD8) dual-positive cases among patients with de novo resistance (46.7%, 7 of 15). Finally, one patient with de novo resistance to EGFR-TKIs and PD-L1 and CD8 dual positivity experienced a favorable response to anti-programmed death 1 therapy. CONCLUSIONS: This study revealed the adverse effects of PD-L1 expression on EGFR-TKI efficacy, especially in NSCLC patients with de novo resistance. The findings indicate the reshaping of an inflamed immune phenotype characterized by PD-L1 and CD8 dual positivity and suggest potential therapeutic sensitivity to programmed death 1 blockade.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/biossíntese , Inibidores de Proteínas Quinases/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Mutação , Estudos Retrospectivos , Análise de Sobrevida
14.
AAPS PharmSciTech ; 18(1): 224-230, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-26961968

RESUMO

The aim of this study was to prepare APAP crystals by cooling, anti-solvent, and solvent evaporation crystallization to enhance its dissolution rate and to make comparisons of the three methods. Agitating speeds and types were regarded as factors affecting crystallization procedure. Samples were made with different ratios of PEG4000. They were characterized by X-ray diffraction and scanning electron microscopy. Dissolution tests were conducted to assess their dissolution property. The proportions of carriers existing in crystals by cooling and anti-solvent crystallization ranged from 1.3 to 5.1%. Mean dissolution time (MDT) of samples by the two methods was about 3 min, which was 17.2 min for untreated APAP. Addition of too much PEG4000 in solvent evaporation crystallization could decrease dissolution rate of APAP. Samples agitated by a rotor with speed of 100, 500, and 1000 rpm dissolved faster than those by a high shear mixer with speed of 3400 and 5000 rpm or by a glass rod. Agitating speed and type could affect particle size and drug dissolution. Dissolution enhancement of APAP might be attributed to decrease of fine particles and increase of particle wettability.


Assuntos
Acetaminofen/química , Solventes/química , Cristalização/métodos , Microscopia Eletrônica de Varredura/métodos , Polietilenoglicóis/química , Solubilidade , Molhabilidade , Difração de Raios X/métodos
15.
Acta Pharm Sin B ; 6(5): 468-474, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27709016

RESUMO

The previous investigation has proved that their existed pharmacokinetic difference between the different crystal forms of the polymorphic drugs after oral administration. However, no systemic investigations have been made on the change of this pharmacokinetic difference, resulted either from the physiological or from the pathological factors. In this paper, we used polymorphic nimodipine (Nim) as a model drug and investigated the effect of age difference (2- and 9-month old) on the pharmacokinetics after oral delivery in rats. As the results shown, for L-form of Nim (L-Nim), the AUC0-24 h in 2-month-old rats was 343.68±47.15 ng·h/mL, which is 23.36% higher than that in 9-month-old rats. For H-form of Nim (H-Nim), the AUC0-24 h in 2-month-old rats was 140.91±19.47 ng·h/mL, which is 54.64% higher than that in 9-month-old rats. The AUC0-24 h ratio between H-Nim and L-Nim was 2.44 in 2-month-old rats and 3.06 in 9-month-old rats. Since age difference could result in unparallelled change of the absorption and bioavailability of the polymorphic drugs, the results in this experiment are of value for further investigation of crystal form selection in clinical trials and rational clinical application of the polymorphic drugs.

16.
Chin J Integr Med ; 22(3): 168-76, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26818127

RESUMO

OBJECTIVE: To determine the effectiveness and safety of Xinfeng Capsules (XFC) for the treatment of rheumatoid arthritis (RA) patients with decreased pulmonary function. METHODS: This was a randomized controlled clinical trial of 80 RA patients. Participants were assigned to the trial group (40 cases) and the control group (40 cases) by block randomization. The trial group was treated with XFC, three pills each time three times daily for 2 months. The control group was treated with tripterygium glycoside (TPT), two pills each time three times daily for 2 months. Both groups were followed up after 2 months. The clinical effects, changes in joint and pulmonary function, and quality of life before and after treatment were observed; safety indices were also evaluated. RESULTS: Pain, swelling, tenderness, and duration of morning stiffness of joints were obviously decreased after treatment in both the trial and the control groups compared with baseline (P<0.01). Compared with before treatment, hand grip strength increased significantly after treatment in the trial group (P=0.0000); pulmonary function parameters such as forced expiratory volume in the first second of expiration/forced vital capacity (FEV1/FVC), 50% of the expiratory flow of forced vital capacity (FEF50), carbon monoxide diffusing capacity (DLco) were increased (P<0.01 or P<0.05); measures of quality of life such as role-physical, body pain, vitality and mental health were also improved after treatment in the trial group (all P<0.05). Joint swelling in the trial group decreased compared with the control group (P=0.0043), while hand grip strength was increased after treatment (P=0.0000). The increase in FEF50, DLco, and the dimensions of quality of life such as vitality and mental health were all significantly greater in the trial group than the control group (P<0.05 or P<0.01). CONCLUSIONS: XFC not only relieved joint pain in RA patients, but also significantly improved the ventilation and diffusion function of the lungs. Therefore, XFC could improve the whole body function and enhance the quality of life of RA patients.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/patologia , Sedimentação Sanguínea , Proteína C-Reativa , Cápsulas , Feminino , Humanos , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Testes de Função Respiratória , Inquéritos e Questionários , Resultado do Tratamento
17.
J Tradit Chin Med ; 34(5): 532-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25417401

RESUMO

OBJECTIVE: To observe the influence of Xinfengcapsule (XFC) on abarticular pathologic changes (APCs) and other indices of patients with rheumatoid arthritis (RA) and explore the mechanism of action of XFC in improving such changes. METHODS: Three-hundred RA patients were divided randomly into a treatment group (n = 150) and control group (n = 150). A normal control (NC) group (n = 90) was also created. Changes in cardiac function, pulmonary function, anemia indices and platelet parameters of RA patients were measured. Curative effects of the two groups were compared, and comparison carried out with the NC group. RESULTS: In 300 RA patients, late diastolic peak flow velocity (A peak) was much higher (P < 0.01) and early diastolic peak flow velocity (E peak), E/A, and left ventricular fraction shortening much lower(P < 0.01) than those in the NC group. Vital capacity (VC), forced vital capacity in one second, forced vitalcapacity (FVC), maximal voluntary ventilation (MVV), maximal expiratory flow in 50% of VC (FEF50) and FEF75 were lowered remarkably (P < 0.05 or P < 0.01). Platelet count (PLT), plateletcrit (PCT) and mean platelet volume (MPV) increased markedly (P < 0.05 or P < 0.01), and hemoglobin (Hb) level decreased significantly (P < 0.05). After XFC treatment, the A peak and PLT and PCT were much lower (P < 0.05), and E/A and the number of red blood cells as well as Hb level were much higher (P < 0.05), as were FVC, MVV and FEF50 (P < 0.05 or P < 0.01), in the treatment group than those in the NC group. Total score of pain and swelling in joints, uric-acid level and high-sensitivity C-reactive protein level were much lower, and superoxide dismutase level as well as the number of CD4 + CD25+ regulation T cells (Treg) and CD4+ CD25+ CD127- Treg were much higher (P < 0.05 or P < 0.01) in the treatment group than those in the NC group. CONCLUSION: RA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors. XFC can improve the symptoms of RA patients, ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors. XFC lowers the immune inflammatory reaction to improve APCs in RA patients.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Cartilagem Articular/patologia , Medicamentos de Ervas Chinesas/uso terapêutico , Adulto , Idoso , Animais , Artralgia/tratamento farmacológico , Artralgia/imunologia , Artralgia/patologia , Artralgia/fisiopatologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Proteína C-Reativa/imunologia , Cápsulas/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/imunologia , Cartilagem Articular/fisiopatologia , Feminino , Coração/efeitos dos fármacos , Coração/fisiopatologia , Humanos , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(4): 418-25, 2013 07.
Artigo em Chinês | MEDLINE | ID: mdl-24022930

RESUMO

OBJECTIVE: To investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats. METHODS: The rats were randomly divided into five groups: normal control (NC), model control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-ß1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration. RESULTS: Compared to NC group, the levels of E, AI, alveolitis score, TGF-ß1 and Smad3 were significantly increased (P <0.05 or P <0.01); maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF), CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P <0.05 or P < 0.01). Compared to MC group,the expression of E, AI, TGF-ß1 and Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were elevated in XFC group (P <0.05 or P <0.01). Compared to XFC group, the level of body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P <0.05 or P <0.01). CONCLUSION: There are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-ß1 and adjusting TGF-ß1/Smads signal pathway.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Pulmão/efeitos dos fármacos , Pulmão/fisiopatologia , Animais , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Cápsulas , Fatores de Transcrição Forkhead/metabolismo , Pulmão/patologia , Masculino , Ratos , Ratos Wistar , Proteína Smad3/metabolismo , Proteína Smad7/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
19.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 33(12): 1599-602, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24517052

RESUMO

OBJECTIVE: To observe the curative effect of Xinfeng Capsule (XC) in treatment of rheumatoid arthritis (RA). METHODS: Recruited were 80 active RA patients, who were randomly assigned to the normal control group and the treatment group, 40 in each group. All patients received the same routine anti-rheumatic treatment: Methotrexate 10 mg per week; Diclofenac 50 mg when pain was obvious, twice daily. Patients in the treatment group took XC 3 tablets each time, thrice daily. All treatment lasted for 12 consecutive weeks. Serum iron (SI), serum ferritin (SF), transferrin (TRF); and RA disease activity index (DAS-28) were detected in all patients. RESULTS: XC could improve HAQ, DAS-28, hypersensitive C reactive protein (hs-CRP), prostaglandins A (PGA), erythrocyte sedimentation rate (ESR), number of swelling joints, number of tender joints, and morning stiffness time in acute RA patients, showing statistical difference when compared with those of the control group (P < 0.01, P < 0.05). Compared with the control group, SI, SF, DAS-28, and TRF significantly decreased in the treatment group (P < 0.05). CONCLUSION: XC could improve DAS-28, and SI reserve in patients with active RA, and lower DAS-28 related indicators.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Adulto , Antirreumáticos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
20.
J Tradit Chin Med ; 32(3): 430-6, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23297568

RESUMO

OBJECTIVE: To observe the impact of xinfeng xapsule (XFC) on pulmonary function in a rat model of adjuvant arthritis (AA) and to investigate the mechanism of action. METHODS: Forty rats were randomly divided into four groups of ten: normal control (NC); model control (MC); tripterygium glycosides tablet (TPT); and xinfeng capsule (XFC). Except for the NC group, AA was induced in all rats by intracutaneous injection of 0.1 mL Freund's complete adjuvant in the right paw on the 19th day. NC and MC groups were given (0.9%) physiological saline. The TPT and XFC groups were given TPT (10 mg/kg) and XFC (1.2 g/ kg), respectively. Thirty days after administration, changes in paw edema (E), the arthritis index (AI), pulmonary function, levels of regulatory T-cells (Treg), ultrastructure of lung tissue, and expression of Notch receptors and ligands in lung tissue were observed. RESULTS: In the MC group, E and the AI were increased and pulmonary function significantly decreased; the structure of alveolar type-III cells was damaged; ratios ofTreg in peripheral blood were reduced; and expression of Notch receptors such as Notch3 and Notch4 and ligands such as Deltal in lung tissue were significantly increased whereas expression of Notch1, Jagged 1 and Jagged2 were significantly decreased. After intervention with XFC, E and the AI were decreased; pulmonary function was enhanced; the structure of alveolar type-II cells was improved; and expression of Treg, Notch1, Jagged1, Jagged2 was elevated, whereas that of Notch3, Notch4 and Delta1 was reduced. CONCLUSION: XFC can not only inhibit E and the AI and improve joint symptoms, it can also improve pulmonary function and reduce inflammation in lung tissue. These actions could be carried out through increases in the expression of Treg, Notch receptors (Notch1) and ligands (Jagged1, Jagged2), and reductions in the expression of Notch3, Notch4 and Delta1. These phenomena would reduce the deposition of immune complexes and the inflammatory response in lung tissue, thereby improving joint symptoms and pulmonary function.


Assuntos
Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Pulmão/fisiopatologia , Receptores Notch/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Cápsulas/administração & dosagem , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Receptores Notch/genética , Transdução de Sinais/efeitos dos fármacos
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