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Front Immunol ; 12: 723609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621270


Radiotherapy is an effective local treatment modality of NSCLC. Its capabilities of eliminating tumor cells by inducing double strand DNA (dsDNA) damage and modulating anti-tumor immune response in irradiated and nonirradiated sites have been elucidated. The novel ICIs therapy has brought hope to patients resistant to traditional treatment methods, including radiotherapy. The integration of radiotherapy with immunotherapy has shown improved efficacy to control tumor progression and prolong survival in NSCLC. In this context, biomarkers that help choose the most effective treatment modality for individuals and avoid unnecessary toxicities caused by ineffective treatment are urgently needed. This article summarized the effects of radiation in the tumor immune microenvironment and the mechanisms involved. Outcomes of multiple clinical trials investigating immuno-radiotherapy were also discussed here. Furthermore, we outlined the emerging biomarkers for the efficacy of PD-1/PD-L1 blockades and radiation therapy and discussed their predictive value in NSCLC.

Glob Heart ; 16(1): 17, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33833941


Background: Patient education is the first step in implementing a cardiac rehabilitation (CR) program and a powerful tool for promoting behavioral changes in cardiac patients. In China, the clinical workload is so heavy that a short and reliable tool for assessing disease-related knowledge is needed for targeted patient education. Objective: The aim of this study was to translate, adapt and validate the Chinese version of the Coronary Artery Disease Education Questionnaire - Short Version (CADE-Q SV). Methods: The CADE-Q SV was translated to simplified Chinese and culturally adapted to the Chinese context. The translated version was reviewed by a committee of seven experts in cardiovascular disease, and the content validity of the questionnaire was established. The psychometric properties of the questionnaire were analyzed considering the responses of 240 CR patients. The Kuder-Richardson-20 (KR-20) coefficient and Cronbach's alpha were used to assess internal consistency. The intraclass correlation coefficient (ICC) was used to assess test-retest reliability. The criterion-related validity was evaluated by determining whether there were differences in the total scores of patients with different educational levels. Confirmatory factor analysis (CFA) was used to assess the factor structure. Results: Three items from the original version were adapted to reflect Chinese culture. The content validity index was 0.94. The KR-20 score was 0.856. All ICC values were > 0.70. The knowledge scores of patients with different educational levels were significantly different, indicating that the criterion-related validity of the Chinese CADE-Q-SV was acceptable. CFA validated the five-factor structure of the Chinese CADE-Q-SV. Conclusion: The Chinese CADE-Q SV questionnaire has good reliability and validity. This short, efficient tool can be completed quickly, assess disease-related knowledge in cardiovascular patients and serve as a reference for individualized patient education in China. It can also be used to evaluate the effectiveness of CR-related patient education interventions.

Reabilitação Cardíaca , Doença da Artéria Coronariana , China , Doença da Artéria Coronariana/diagnóstico , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários
Front Oncol ; 10: 595466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194761


Radiation resistance is linked to immune escaping and radiation sensitivity. In this study, we found that the PD-L1 expressions of non-killed tumor cells in NSCLC were enhanced after radiotherapy, and dihydroartemisinin (DHA) could synergistically enhance the antitumor effect of radiotherapy in NSCLC. A total of 48 NSCLC patients with sufficient tumor tissues for further analyses were enrolled. The PD-L1 expressions of NSCLC were evaluated by immunohistochemistry. Cell apoptosis was measured by flow cytometry, and the relationship between the PD-L1 expression and radiation resistance was investigated in patient specimens, xenograft model, and cell lines. First, the results indicate that the PD-L1 expression of NSCLC was positively related with the radiation resistance. Second, we found that DHA could eliminate the radiation resistance and synergistically enhance the antitumor effect of radiotherapy in the NSCLC cells lines and xenograft model. Finally, mechanistically, DHA could inhibit the PD-L1 expression to avoid immune escaping by inhibiting TGF-ß, PI3K/Akt, and STAT3 signaling pathways. In addition, DHA could activate TRIM21 and regulate the EMT-related proteins by inhibiting the PD-L1 so as to enhance the radiation sensitivity and eliminate radiation resistance to NSCLC. Collectively, this study established a basis for the rational design of integrated radiotherapy and DHA for the treatment of NSCLC.

Kardiol Pol ; 77(2): 207-216, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30740643


BACKGROUND: Due to the myopathic adverse events of statins, safer alternatives are being studied. Bempedoic acid (ETC-1002) is a novel low-density lipoprotein cholesterol (LDL-C)-lowering agent, currently under trial in hypercholesterolaemic patients. AIM: To investigate the tolerability and efficacy of ETC-1002 in hypercholesterolaemic patients through a systematic review of published randomised controlled trials (RCTs). METHODS: Five databases were searched for RCTs that investigated the safety and efficacy of ETC-1002 in hypercholesterol-aemic patients. The retrieved search results were screened, and then data were extracted and analysed (as mean difference [MD] or odds ratio [OR]) using the RevMan software. RESULTS: Five RCTs (625 hypercholesterolaemic patients) were identified. ETC-1002 was superior to placebo in terms of percent-age changes from baseline in serum levels of LDL-C (MD -26.58, 95% confidence interval [CI] -35.50 to -17.66, p < 0.0001), non-high-density lipoprotein cholesterol (MD -21.54, 95% CI -28.48 to -14.6, p < 0.00001), and apolipoprotein-B (MD -15.97, 95% CI -19.36 to -12.57, p < 0.0001). When compared to ezetimibe, ETC-1002 was superior in reducing LDL-C (-30.1 ± 1.3 vs. -21.1 ± 1.3). Regarding safety, ETC-1002 did not increase the risk of all adverse events (OR 0.58, 95% CI 0.37-0.91, p = 0.02) and arthralgia (OR 0.32, 95% CI 0.13-0.81, p = 0.02) compared to placebo. All other adverse events including myalgia, headache, and urinary tract infections were similar between ETC-1002 and placebo groups. The evidence certainty in the assessed outcomes was moderate to high except for lipoprotein(a), free fatty acids, and very low-density lipoprotein particle number (very low certainty). CONCLUSIONS: ETC-1002 is a safe and effective lipid-lowering agent and may be a suitable alternative in statin-intolerant pa-tients. Well-designed studies are needed to explore the long-term safety and efficacy of ETC-1002 in these patients.

Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Idoso , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Ezetimiba/efeitos adversos , Ezetimiba/uso terapêutico , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hipercolesterolemia/sangue , Hipolipemiantes/efeitos adversos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
Int J Clin Exp Pathol ; 8(9): 10555-64, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26617765


UNLABELLED: This study was initiated to investigate the efficacy of myocardial fibrosis intervention via signal transducer and activators of transcription (STAT) signaling using bone marrow (BM) mesenchymal stromal cells (MSC) in which being over-expressed with the aid of bispecific antibody (BiAb) and ultrasound-mediated microbubbles (MB). BiAb was prepared and combined with isolated MSC with CD47 overexpression from male mice and trans-fused into female mice with isoproterenol-induced myocardial fibrosis via the tail vein, followed by MB. This study included five groups. Five weeks after treatment, expression levels of the sex-determining region of Y-chromosome (SRY), matrix metalloproteinases (MMP)-9, tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth factor (VEGF) in myocardium were detected by fluorescent quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of signal transducer and activators of transcription (STAT) 1 and STAT 3 was detected by Western blot. RESULTS: The highest homing number of MSC was in the CD47 + MSC + BiAb + MB group, second highest in the CD47 + MSC + BiAb group, and lowest in MSC alone. Compared with the Control group, CD47 + MSC + BiAb + MB, CD47 + MSC + BiAb, CD47 + MSC and MSC groups had decreased levels of MMP-9, TIMP-1, STAT 1 and collagen deposition, and increased levels of STAT 3. Up regulated STAT 3 and down regulated TIMP-1 were significantly different in CD47 + MSC + BiAb + MB compared with CD47 + MSC or CD47 + MSC + BiAb. CONCLUSION: CD47 can enhance the homing rate and repairing efficacy of MSC. MSC can improve MMP-TIMP expression in injured myocardium and interfere with myocardial fibrosis after homing, a mechanism that may be related to the STAT-mediated signaling pathway.

Antígeno CD47/metabolismo , Cardiomiopatias/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Miocárdio/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Anticorpos Biespecíficos/imunologia , Antígeno CD47/genética , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/genética , Cardiomiopatias/imunologia , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Feminino , Fibrose , Regulação da Expressão Gênica , Isoproterenol , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/imunologia , Miocárdio/imunologia , Miocárdio/patologia , Fenótipo , Ratos Sprague-Dawley , Proteína da Região Y Determinante do Sexo/genética , Proteína da Região Y Determinante do Sexo/metabolismo , Transdução de Sinais , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Transfecção , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
Zhong Yao Cai ; 38(3): 556-61, 2015 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-26495659


OBJECTIVE: To evaluate the absorption feature and mechanism of tenuifolin(TF) and polygalaxanthone III (PT) in different intestinal parts of rats and the impact of MRP2 and P-glycoprotein (P-gp) on it. METHODS: In situ unidirectional perfusion was used to detect the concentration of TF and PT through HPLC-DAD with gravimetric method. Furthermore, impact of different parts, cosolvents and inhibitors to TF and PT was also explored with data of Ka and Papp. RESULTS: Tween as cosolvent, Ka and Papp of TF was significantly higher in colon than in other intestinal parts(P <0. 05 or P <0. 01). Whereas, Ka of PT was in sequence of colon, duodenum, jejunum, ileum,but with no significant difference among them(P >0. 05). SDS as cosolvent, Papp of TF was higher in colon than in duodenum(P <0. 05). K. of TF was significantly higher compared with control when added with VH, an inhibitor of P-gp(P <0. 05). In addition, Papp of PT in different concentration of VH increased(P <0. 05, P <0. 01). Papp of TF significantly increased with IT at the concentration of 0. 02 and 0. 04 mmol/L, an inhibitor of MRP2(P <0. 05, P <0. 01). Meanwhile, Ka of PT,with IT at the concentration of 0. 04 and 0. 08 mmol/L, was significantly higher(P <0. 05, P <0. 01). CONCLUSION: TF is mainly absorbed in colon, whereas PT is in duodenum. P-gp but not MRP2 influences the intestinal absorption of TF, indicating TF as substrate of P-gp. However, both of P-gp and MRP2 impact the absorption of PT, illustrating PT as substrate of P-gp and MRP2. It also indicates that inhibitors of P-gp and/or MRP2 in combined application may improve the absorption of PT and TF.

Diterpenos do Tipo Caurano/farmacocinética , Glicosídeos/farmacocinética , Absorção Intestinal , Polygala/química , Xantonas/farmacocinética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Colo/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Íleo/metabolismo , Jejuno/metabolismo , Ratos