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Abstract Objectives: This study aimed to compare progression-free survival, overall survival, clinical benefits, and adverse effects in postmenopausal women with hormone receptor-positive and HER2-negative breast cancer who received buparlisib plus fulvestrant against those of women who received dalpiciclib plus fulvestrant, considering ribociclib plus letrozole treatment as the reference standard. Methods: Women received buparlisib plus fulvestrant (BF cohort, n = 108), dalpiciclib plus fulvestrant (DF cohort, n = 132), or ribociclib plus letrozole (RL cohort, n = 150) until unacceptable toxicity was observed. Results: A total of 117 (89 %), 80 (74 %), and 84 (56 %) women in the BF, DF, and RL cohorts, respectively, had clinical benefits. After treatment, the clinical benefits for women and after 42 months of follow-up progression-free survival and overall survival were higher in the DF cohort than in the BF and RL cohorts (p < 0.05 for all). Neutropenia, vomiting, constipation, nausea, diarrhea, and anorexia were reported higher in women of the DF and BF cohorts than in women of the RL cohort. Leukopenia and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the RL cohort than in women in the DF and BF cohorts. Depression, anxiety, and increased levels of alanine aminotransferase and aspartate aminotransferase were reported to be higher in women in the BF cohort than in women in the DF and RL cohorts. Conclusions: Dalpiciclib plus fulvestrant is effective and comparatively safe in postmenopausal women with hormone receptor-positive and HER2-negative breast cancers. Dalpiciclib, buparlisib, fulvestrant, and ribociclib cause neutropenia, severe depression, adverse gastroenterological effects, and adverse hepatological effects, respectively.

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With the gradual transfer of an enormous young and middle age labor force from agricultural field to non-agricultural sectors, the negative role of land fragmentation (LF), which is related to food security, is increasingly reflecting in the process of agricultural modernization. Meanwhile, the positive roles of farmers' combined-tillage in production are gradually emerging. Based on the above background, this study explained the relationship among farmers' combined-tillage, LF and agricultural production efficiency (APE). The study used survey date and the SFA-QR model to empirically investigate the effects of LF and farmers' combined-tillage on APE. Furthermore, this article analyzed the moderating effect of farmers' combined-tillage on the relationship between LF and APE. The results demonstrated that: (1) Farmers combined-tillage improves the APE significantly, especially on low and medium efficiency households; (2) LF has a negative impact on APE, especially on low and medium efficiency households; (3) Combined-tillage could alleviate the adverse effects of LF on APE. In this regard, the paper also proposed some suggestions to face the adverse effects of LF and promote farmers' combined-tillage in production.

Com a transferência gradual de enorme força de trabalho jovem e de meia idade do campo agrícola para os setores não agrícolas, o papel negativo da fragmentação da terra (LF), relacionada à segurança alimentar, está cada vez mais refletido no processo de modernização agrícola. Enquanto isso, os papéis positivos da lavoura combinada dos agricultores na produção estão surgindo gradualmente. Com base no histórico acima, o objetivo deste estudo é explicar a relação entre o plantio direto dos agricultores, LF e eficiência da produção agrícola (APE). O estudo usou dados do levantamento e o modelo SFA-QR para investigar empiricamente os efeitos da FL e do plantio direto dos agricultores sobre o APE. Além disso, este artigo analisou o efeito moderador do plantio combinado dos agricultores na relação entre LF e APE. Os resultados demonstram que: (1) A lavoura combinada dos agricultores melhora significativamente o APE, especialmente em domicílios de baixa e média eficiência; (2) LF tem um impacto negativo na APE, especialmente em domicílios de baixa e média eficiência; (3) A lavoura combinada pode aliviar os efeitos adversos do LF no APE. Nesse sentido, o trabalho também propõe algumas sugestões para enfrentar os efeitos adversos da FL e promover o plantio combinado dos agricultores na produção.

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ABSTRACT: With the gradual transfer of an enormous young and middle age labor force from agricultural field to non-agricultural sectors, the negative role of land fragmentation (LF), which is related to food security, is increasingly reflecting in the process of agricultural modernization. Meanwhile, the positive roles of farmers' combined-tillage in production are gradually emerging. Based on the above background, this study explained the relationship among farmers' combined-tillage, LF and agricultural production efficiency (APE). The study used survey date and the SFA-QR model to empirically investigate the effects of LF and farmers' combined-tillage on APE. Furthermore, this article analyzed the moderating effect of farmers' combined-tillage on the relationship between LF and APE. The results demonstrated that: (1) Farmers combined-tillage improves the APE significantly, especially on low and medium efficiency households; (2) LF has a negative impact on APE, especially on low and medium efficiency households; (3) Combined-tillage could alleviate the adverse effects of LF on APE. In this regard, the paper also proposed some suggestions to face the adverse effects of LF and promote farmers' combined-tillage in production.

RESUMO: Com a transferência gradual de enorme força de trabalho jovem e de meia idade do campo agrícola para os setores não agrícolas, o papel negativo da fragmentação da terra (LF), relacionada à segurança alimentar, está cada vez mais refletido no processo de modernização agrícola. Enquanto isso, os papéis positivos da lavoura combinada dos agricultores na produção estão surgindo gradualmente. Com base no histórico acima, o objetivo deste estudo é explicar a relação entre o plantio direto dos agricultores, LF e eficiência da produção agrícola (APE). O estudo usou dados do levantamento e o modelo SFA-QR para investigar empiricamente os efeitos da FL e do plantio direto dos agricultores sobre o APE. Além disso, este artigo analisou o efeito moderador do plantio combinado dos agricultores na relação entre LF e APE. Os resultados demonstram que: (1) A lavoura combinada dos agricultores melhora significativamente o APE, especialmente em domicílios de baixa e média eficiência; (2) LF tem um impacto negativo na APE, especialmente em domicílios de baixa e média eficiência; (3) A lavoura combinada pode aliviar os efeitos adversos do LF no APE. Nesse sentido, o trabalho também propõe algumas sugestões para enfrentar os efeitos adversos da FL e promover o plantio combinado dos agricultores na produção.

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SUMMARY: Intracranial artery stenosis (ICAS) was one of the main causes of ischemic stroke onset and recurrence. About 30 % of strokes were caused by intracranial artery stenosis. Intracranial artery stenosis had a high incidence in China and faced a high risk of recurrence for a long time. It affected patient safety and quality of life seriously. At the same time, it caused a heavy financial burden for the patient´s family. Therefore, early detection and accuracy of intracranial artery stenosis evaluation were extremely important. High-resolution magnetic resonance imaging (HR-MRI) had been widely used in clinical examinations, making up for the shortcomings of traditional vascular imaging methods that could only show the degree of luminal stenosis, making it possible to perform lumens, tube wall and plaque features of atherosclerotic intracranial arteries at the same time. There were still some controversies about the credibility of this technique in assessing the intracranial artery lumen stenosis. This article reviewed the application efficacy of HR-MRI technology in evaluating the degree of intracranial atherosclerotic stenosis.

RESUMEN: La estenosis de arterias intracraneales (ICAS) es una de las principales causas del ictus isquémico, como así también de su recurrencia. Alrededor del 30 % de los ataques cerebrovasculares son causados por estenosis de la arteria intracraneal. La estenosis de arterias intracraneales tiene una alta incidencia en China y enfrenta un alto riesgo de recurrencia, afectando gravemente la seguridad y la calidad de vida de los pacientes. Al mismo tiempo, supone una importante carga financiera para la familia de los pacientes. Por lo tanto, la detección temprana y la precisión de la evaluación de la estenosis de arterias intracraneales es extremadamente importante. La resonancia magnética de alta resolución (HR-MRI, por sus siglas en inglés) es utilizada ampliamente en los exámenes clínicos, compensando las deficiencias de los métodos tradicionales de imágenes vasculares que solo pueden mostrar el grado de estenosis luminal, haciendo posible el estudio de las características del lumen, pared vascular y la placa ateroesclerótica, de las arterias intracraneales afectadas, al mismo tiempo. Aún existen algunas controversias sobre la credibilidad de esta técnica en la evaluación de la estenosis del lumen de arterias intracraneales. En este artículo se revisó la eficacia de la aplicación de la tecnología HR-MRI para evaluar el grado de estenosis aterosclerótica intracraneal.

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The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/ß-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.

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The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/β-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.

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OBJECTIVES: This study investigated whether tissue Doppler imaging parameters, especially the peak systolic velocity of the left ventricular lead-implanted segment (Ss), affect cardiac resynchronization therapy response. METHODS: In this case-control study, 110 enrolled patients were divided into cases (responder group, n=65) and controls (nonresponder group, n=45) based on whether their left ventricular end-systolic volume was reduced by ≥15% at 6 months after surgery. Preoperative clinical and echocardiographic data were collected. Multivariate logistic regression models were used to analyze the factors affecting the response to cardiac resynchronization therapy, and receiver operating characteristic curves were plotted to evaluate their diagnostic values. RESULTS: The proportion of patients with left bundle branch block in the case group was higher than that in the control group. The control group showed a higher left atrial volume index, E/A ratio and E/Em ratio but lower Ss than that of the case group. A multivariate regression analysis showed that left bundle branch block, Ss, and an E/Em ratio>14 were independent risk factors affecting the response to cardiac resynchronization therapy. Ss=4.1 cm/s was the best diagnostic threshold according to the receiver operating characteristic curve. CONCLUSIONS: Ss is an important factor affecting the response to cardiac resynchronization therapy. Patients with heart failure associated with Ss<4.1 cm/s have a higher risk of nonresponse.

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OBJECTIVES: This study investigated whether tissue Doppler imaging parameters, especially the peak systolic velocity of the left ventricular lead-implanted segment (Ss), affect cardiac resynchronization therapy response. METHODS: In this case-control study, 110 enrolled patients were divided into cases (responder group, n=65) and controls (nonresponder group, n=45) based on whether their left ventricular end-systolic volume was reduced by ≥15% at 6 months after surgery. Preoperative clinical and echocardiographic data were collected. Multivariate logistic regression models were used to analyze the factors affecting the response to cardiac resynchronization therapy, and receiver operating characteristic curves were plotted to evaluate their diagnostic values. RESULTS: The proportion of patients with left bundle branch block in the case group was higher than that in the control group. The control group showed a higher left atrial volume index, E/A ratio and E/Em ratio but lower Ss than that of the case group. A multivariate regression analysis showed that left bundle branch block, Ss, and an E/Em ratio>14 were independent risk factors affecting the response to cardiac resynchronization therapy. Ss=4.1 cm/s was the best diagnostic threshold according to the receiver operating characteristic curve. CONCLUSIONS: Ss is an important factor affecting the response to cardiac resynchronization therapy. Patients with heart failure associated with Ss<4.1 cm/s have a higher risk of nonresponse.

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OBJECTIVES:: To investigate the association between diastolic function and the different beneficial effects of cardiac resynchronization therapy in patients with heart failure due to different causes. METHODS:: The 104 enrolled patients were divided into an ischemic cardiomyopathy group (n=27) and a non-ischemic cardiomyopathy group (n=77) according to the cause of heart failure. Before implantation, left ventricular diastolic function was evaluated in all patients using echocardiography. After six months of follow-up, the beneficial effects of cardiac resynchronization therapy were evaluated using a combination of clinical symptoms and echocardiography parameters. RESULTS:: The ischemic cardiomyopathy group included significantly more patients with restrictive filling than the non-ischemic cardiomyopathy group. The response rate after the implantation procedure was significantly higher in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Degrees of improvement in echocardiography parameters were significantly greater in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Multivariate regression analysis showed that a restrictive filling pattern was an independent factor that influenced responses to cardiac resynchronization therapy. CONCLUSIONS:: This study again confirmed that the etiology of heart failure affects the beneficial effects of cardiac resynchronization therapy and a lower degree of improvement in ventricular systolic function and remodelling was observed in ischemic cardiomyopathy patients than in non-ischemic cardiomyopathy patients. In addition, systolic heart failure patients with severe diastolic dysfunction had poor responses to cardiac resynchronization therapy. Ischemic cardiomyopathy patients exhibited more severe diastolic dysfunction than non-ischemic cardiomyopathy patients, which may be a reason for the reduced beneficial effect of cardiac resynchronization therapy.

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OBJECTIVES: To investigate the association between diastolic function and the different beneficial effects of cardiac resynchronization therapy in patients with heart failure due to different causes. METHODS: The 104 enrolled patients were divided into an ischemic cardiomyopathy group (n=27) and a non-ischemic cardiomyopathy group (n=77) according to the cause of heart failure. Before implantation, left ventricular diastolic function was evaluated in all patients using echocardiography. After six months of follow-up, the beneficial effects of cardiac resynchronization therapy were evaluated using a combination of clinical symptoms and echocardiography parameters. RESULTS: The ischemic cardiomyopathy group included significantly more patients with restrictive filling than the non-ischemic cardiomyopathy group. The response rate after the implantation procedure was significantly higher in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Degrees of improvement in echocardiography parameters were significantly greater in the non-ischemic cardiomyopathy group than in the ischemic cardiomyopathy group. Multivariate regression analysis showed that a restrictive filling pattern was an independent factor that influenced responses to cardiac resynchronization therapy. CONCLUSIONS: This study again confirmed that the etiology of heart failure affects the beneficial effects of cardiac resynchronization therapy and a lower degree of improvement in ventricular systolic function and remodelling was observed in ischemic cardiomyopathy patients than in non-ischemic cardiomyopathy patients. In addition, systolic heart failure patients with severe diastolic dysfunction had poor responses to cardiac resynchronization therapy. Ischemic cardiomyopathy patients exhibited more severe diastolic dysfunction than non-ischemic cardiomyopathy patients, which may be a reason for the reduced beneficial effect of cardiac resynchronization therapy.

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