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OBJECTIVE: To investigate the outcome of the rapid lowering of elevated blood pressure in patients with intracerebral hemorrhage and to understand its association with clinical outcome. MATERIALS AND METHODS: Between July 2014 and June 2018, a total of 1,500 patients diagnosed with cerebral hemorrhage were randomized and assessed for their neurological symptoms and diagnosed with CT scan. 1,500 (42%) patients received intensive treatment, while 1,645 (58%) patients were assigned the guideline-recommended therapy. The systolic blood pressure of these patients was measured every half hour during the first day of admission. The intensive-treatment group was further categorized into five different subgroups in 10-mmHg intervals. On the other hand, the clinical outcome, as represented by the volume of hematoma, adverse events, modified Rankin scale etc., was measured and analyzed. RESULTS: The volume of hematoma varied with a p-value of 0.014 among the investigated groups. There was no direct correlation among the five groups based on the systolic blood pressure groups and modified Rankin scale 4 - 6. The 140 - 150 mmHg group observed an elevated risk compared to the 120 - 130 mmHg group in the modified Rankin scale ((OR = 1.59; 95% CI (0.98 - 2.61)). The hematoma enlargement increased significantly with a p-value of 0.012. There was no direct association or statistical significance between the occurrence of the clinical outcome and the multivariate relationship between the five groups based on the multivariates (p = 0.513). CONCLUSION: Systolic blood pressure ranging between 120 and 130 mmHg serves as an optimal goal for acute intracerebral hemorrhage by reducing the hematoma enlargement. It is also evident that the lowering of high mean systolic blood pressure after blood pressure-lowering therapy usually leads to cardiorenal injury.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Hemorragia Cerebral/terapia , Hipertensão/tratamento farmacológico , Idoso , Feminino , Hematoma/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Sístole , Resultado do TratamentoRESUMO
BACKGROUND: Scopoletin (SPT) is known to exert neuroprotective autophagy effect. However, the efficacy of SPT in the treatment of spinal cord injury (SCI) has yet not been explored. The investigation was intended to elucidate whether SPT can exert neuroprotective effect by triggering neuronal autophagy after SCI. The study was also directed to investigate the role of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway in the autophagy facilitated by SPT. MATERIALS AND METHODS: The SCI was developed in female Sprague-Dawley rats by damaging the T10 spinal level using an impounder impact. Three animals groups were investigated - Sham group, SCI group, and SCI + SPT group. The SCI + SPT group was administered with SPT (100 mg/kg) intraperitoneally. Basso, Beattie, and Bresnahan scores and angle of incline test revealed that SPT administration improved the movement of hind limbs after SCI induction. RESULTS: Results indicated that SPT imparted neuronal protection, alleviated neuronal apoptosis, and improved neuronal autophagy. SPT-induced autophagy was identified by increased Beclin-1 expression and LC3B-positive neuronal cells. Further investigations revealed that SPT triggers the pathway involving AMPK/mTOR signaling, thereby stimulating autophagy in SCI-induced rat model. CONCLUSION: The findings of the present investigation strongly advocate the beneficial effects of SPT in the treatment of the SCI. SPT ameliorates the AMPK/mTOR signaling-induced autophagy and thereby improves functional recovery in SCI-induced rats.
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Proteínas Quinases Ativadas por AMP/metabolismo , Fármacos Neuroprotetores/farmacologia , Escopoletina/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Feminino , Locomoção/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Escopoletina/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
BACKGROUND: Astragalus membranaceus (AM) is a commonly used herb in traditional Chinese medicine (TCM), which has been used as an essential tonic to treat various diseases for more than 2000 years. In this study, we aimed to investigate the biological effects of extract from AM on breast cancer cell and its mechanism. METHODS: To prepare the extract, dried AM were ground and extracted with water extraction-ethanol supernatant method. Then the main isoflavones in the extract was detect by HPLC analysis. Furthermore, the anti-proliferative activity of AM extract was examined by MTT assay and morphological observation. Cell apoptosis was evaluated with flow cytometric analysis. The expressions of total and phosphorylated PI3K, GS3Kß, Akt and mTOR were determined by western blot analysis. RESULTS: HPLC analysis demonstrated that AM extract contained with four kinds of isoflavones, campanulin, ononin, calycosin and formononetin. The MTT test and morphological observation indicated that cells proliferation of MCF-7, SK-BR-3 and MDA-MB-231were inhibited by AM extract in a dose dependent manner. Furthermore, flow cytometric analysis displayed that after treated with 25 µg/ml and 50 µg/ml AM extract, apoptosis of breast cancer cells was significantly increased as compared with DMSO and blank control group (all p < 0.05). Western blot analysis found that the level of p-PI3K, p-GS3Kß, p-Akt, and p-mTOR were significantly decreased, but the level of total-mTOR was observably increased as compared with DMSO control group. CONCLUSIONS: Taken together, the inhibited cell proliferation and induced cell apoptosis effect of AM extract via PI3K/AKT/mTOR pathway confirmed the anti-tumor potential of AM. Therefore, our findings provide a new insight into anti-cancer effect of AM extract as a promising agent in breast cancer treatment.
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Astragalus propinquus/química , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Feminino , Humanos , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/genéticaRESUMO
BACKGROUND: Asthma is a chronic disease involving an immune response, which is characterized by non-specific inflammation and airway remodeling. Glucocorticoids are clinically beneficial in controlling asthma, but further options are needed. In our study, fastigial nucleus electrostimulation (FNS) was applied in a rat asthma model for the first time to investigate the effects of pre-intervention. OBJECTIVE: To observe the effects of FNS on airway inflammation and remodeling in asthmatic rats. METHODS: Forty rats were assigned randomly to the normal control (CON), model (MDL), FNS, or budesonide (BUD) groups. Asthma was induced with chicken egg (OVA). The animals in the CON and MDL groups were treated with normal saline. The animals in the other two groups received FNS or budesonide, respectively. RESULTS: The results indicated that IgE in the serum and airway fiber areas were higher in the MDL group than in other groups. After treatment for 3 weeks, collagen fibers in the bronchial wall in the FNS group were significantly lower compared with the MDL group. CONCLUSION: FNS significantly reduced IL-4, IL-13, TNF-α, OVA-IgE and TGF-ß1 in serum and BALF, and increased IFN-γ. Our results suggest that FNS may ameliorate asthma symptoms and induce changes of cytokines in the serum and lung milieu.
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Remodelação das Vias Aéreas/fisiologia , Asma/imunologia , Asma/patologia , Núcleos Cerebelares/fisiologia , Terapia por Estimulação Elétrica/métodos , Animais , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Lake wetlands are extremely important and special ecosystems, which are important for regional water resource storage, environmental protection, and biodiversity maintenance. Sediment bacteria are an important component of lake ecosystems and are a major driver of biogeochemical cycling in lakes. In order to investigate the community structure of bacteria in typical lake sediments in Yinchuan City and their influencing factors, three typical lakes in Yinchuan City (Yuehai Lake, Mingcui Lake, and Xiniu Lake) were selected for the study and surface sediments were collected in January, April, July, and October 2021. The composition of the sediment bacterial community was examined using 16S rDNA high-throughput sequencing technology, and the response relationships between them and heavy metals were explored. The results showed that the ecological hazard coefficient for heavy metals in the sediments of three typical lakes in Yinchuan City was far less than 40, and the ecological hazard index was far less than 150, all of which indicated a minor ecological hazard. There were no significant differences in bacterial community diversity among the three lakes, but there were significant variations in diversity among the lakes in different seasons and significant differences in community composition. The dominant phyla (top three in terms of relative abundance) in Yuehai Lake, Mingcui Lake, and Xiniu Lake were Proteobacteria, Bacteroidetes, and Chloroflexi. The dominant lower orders were Gammaproteobacteria, Alphaproteobacteria, and Deltaproteobacteria. The main divergent species that occurred at the phylum level in typical lakes in Yinchuan were Proteobacteria, Bacteroidetes, Euryarchaeota, Firmicutes, Actinobacteria, and Acidobacteria. The sediment bacterial community structure of Yuehai Lake was significantly correlated with Cu, Fe, Mn, Zn, As, and Pb; the sediment bacterial community structure of Lake Mingcui was significantly correlated with Fe, Pb, and Cr; and the sediment bacterial community structure of Xiniu Lake was not significantly correlated with heavy metals. The types and contents of sediment heavy metals had a significant effect on the bacterial community structure of sediments in Yinchuan Yuehai Lake and Mingcui Lake and were important environmental factors that caused changes in the bacterial community structure of lake sediments.
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Metais Pesados , Poluentes Químicos da Água , Lagos/química , Ecossistema , Chumbo , Metais Pesados/análise , Bactérias/genética , Proteobactérias/genética , Sedimentos Geológicos/química , China , Poluentes Químicos da Água/análise , Medição de Risco , Monitoramento AmbientalRESUMO
OBJECTIVE: To study the association of free immunoglobulin light chain (FLC) with clinical manifestations and lung inflammation in smokers with normal lung function and chronic obstructive pulmonary disease (COPD) patients. METHODS: Thirty-two patients with peripheral lung cancer undergoing surgical resection were enrolled from the Department of Thoracic Surgery,Affiliated Hospital of Xuzhou Medical College. They were divided into non-smoking with normal lung function group (non-smoking group, 10 cases), smoking with normal lung function group (smoking group, 12 cases) and smoking with stable COPD group (COPD group, 10 cases). Their preoperative fasting serum and lung tissues away from cancer were used in the study.Enzyme-linked immunesorbent assays (ELISA) were used to detect the levels of FLC-λ and FLC-κ in serum and lung tissue homogenates. The expression of FLC-λ and FLC-κ in the airway epithelium, alveolar wall and blood vessel wall was detected by immunohistochemistry. The correlation between FLC levels and pulmonary functions were analyzed. RESULTS: The serum levels of FLC-λ and FLC-κ in COPD group and smoking group were (35 ± 11),(38 ± 12) and (26 ± 9),(26 ± 8) mg/L, respectively. They were all significantly increased compared with the non-smoking group [(16 ± 7),(16 ± 5) mg/L]. The differences were all statistically significant (q = 3.590-7.482, P < 0.01), and those of the COPD group were significantly higher than those of the smoking group (q = 3.209-4.198, P < 0.05 and P < 0.01). The concentrations of FLC-λ and FLC-κ in lung tissue homogenates of the COPD group and the smoking group were (1.29 ± 0.31),(1.32 ± 0.30) and (0.86 ± 0.42),(0.85 ± 0.37) µg/mg, respectively. They were all significantly increased compared with those of the non-smoking group [(0.45 ± 0.18),(0.42 ± 0.13) µg/mg],(q = 4.178- 9.795, P < 0.05 and P < 0.01). The levels of FLC-λ and FLC-κ in the lung tissue homogenates from the COPD group were significantly higher than those from the smoking group (q = 4.269-4.349, all P < 0.05). The expression of FLC-λ and FLC-κ was detected in airway epithelium, alveolar wall and blood vessel wall. The levels of FLC-λ and FLC-κ in serum and lung tissue homogenates showed a negative correlation with FEV1 percentage of predicted value (r = -0.476 to -0.591, all P < 0.01). CONCLUSIONS: Expressions of FLC were increased in the serum and the lung tissues of COPD patients and smokers with normal lung function, and closely correlated with airflow limitation. The results suggest that FLC plays a proinflammatory role in the pathogenesis of COPD.
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Cadeias kappa de Imunoglobulina/sangue , Cadeias lambda de Imunoglobulina/sangue , Pulmão/metabolismo , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Volume Expiratório Forçado , Humanos , Cadeias kappa de Imunoglobulina/metabolismo , Cadeias lambda de Imunoglobulina/metabolismo , Imuno-Histoquímica , Inflamação , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/sangue , Testes de Função Respiratória , Fumar/efeitos adversos , Fumar/metabolismoRESUMO
Background: As the worldwide population ages, the population receiving open wedge high tibial osteotomy (OWHTO) is growing, and surgical site infection (SSI) is a rare but fatal surgical complication. This study aimed to identify risk factors independently associated with SSI following OWHTO and develop a predictive nomogram. Methods: Clinical data of patients who received OWHTO and followed up for more than 12 months in our hospital were retrospectively reviewed. Multivariable logistic regression was performed to determine independent risk factors for SSI and to construct predictive nomograms. The study further illustrated the predictive performance of the model by using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: A total of 1294 eligible patients were included in the study. Multivariate analysis revealed tobacco consumption (OR=3.44, p=0.010), osteotomy size ≥12 mm (OR=3.3, p=0.015), the use of allogeneic bone or artificial bone graft substitutes (allogeneic bone vs none, OR=4.08, p=0.037; artificial bone vs none, OR=5.16, p=0.047), Kellgren-Lawrence (K-L) grade IV (OR=2.5, p=0.046), systemic immune-inflammation index (SII) >423.62 (OR=6.2, p<0.001), high-sensitivity C-reactive protein (HCRP) >2.6 mg/L (OR=2.42, p=0.044), and a higher level of fasting blood glucose (FBG) (OR=1.32, p=0.022) were the independent predictors of SSI. The cutoff score of the model was 148, with a sensitivity of 76.0% and specificity of 81.0%. The concordance index (C-index) and Brier score of the nomogram were 0.856 and 0.017, and the corrected values after 1000 bootstrapping validations were 0.820 and 0.018, respectively. Furthermore, the ROC curve, calibration curve, and DCA exhibited excellent predictive accuracy and clinical applicability of the model. Conclusion: This study developed a dynamic nomogram based on seven predictors, which allowed surgeons to individualize risk stratification of patients and intervene promptly to reduce SSI rates.
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Osteoartrite do Joelho , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/complicações , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/complicações , Estudos Retrospectivos , Nomogramas , Osteotomia/efeitos adversos , Fatores de Risco , Tíbia/cirurgiaRESUMO
Background: Heart failure with preserved ejection fraction (HFpEF) is a large subtype of heart failure (HF) characterized by exercise intolerance and reduced quality of life. Studies have shown that traditional Chinese medicine (TCM) combined with conventional Western medicine has a good effect on improving exercise tolerance and quality of life in patients with HFpEF, but the overall quality of evidence is low. This study aimed to determine the safety and efficacy of Yangyin Shuxin (YYSX) decoction in the treatment of HFpEF. Methods: A prospective, single-blind, single-center, randomized controlled clinical study was conducted. 64 patients with HFpEF were randomly assigned to receive oral YYSX decoction (150 ml, twice a day) combined with conventional Western treatment or conventional Western treatment alone at a ratio of 1 : 1. The course of treatment was 2 weeks, and the follow-up was 3 months. The primary outcome was peak oxygen uptake (peak VO2) measured by the cardiopulmonary exercise test (CPET). Furthermore, the safety of YYSX decoction was assessed. Results: 63 patients (31 in the YYSX group and 32 in the control group) were included in the full analysis set. The peak VO2 of the YYSX group was significantly higher than that of the control group (12.04 ± 3.41 vs. 11.02 ± 3.33, P = 0.013) after 2 weeks. The maximum voluntary ventilation (MVV) was significantly higher in the YYSX group compared with the control group (P < 0.05). The YYSX group had a higher EQ-visual analogue scale (EQ-VAS) score (71.13 ± 13.95 vs. 70.94 ± 13.70, P < 0.05) and a lower TCM Four-Dimensional Diagnostic Information Scale (TCMFDIS) score (49.74 ± 24.73 vs. 64.16 ± 27.15, P < 0.05) than the control group. There was no statistical difference between two groups (P = 0.160), although 51.61% of patients in the YYSX group showed a decrease in brain natriuretic peptide (BNP) levels of at least 30%, compared with 37.50% of patients in the control group. No serious adverse events were reported in either group, but systolic and diastolic blood pressure decreased and serum sodium levels increased slightly in the control group. Conclusion: The YYSX decoction combined with conventional Western treatment was superior to the conventional Western treatment alone in improving exercise tolerance, quality of life, and cardiopulmonary function of patients with HFpEF. YYSX decoction is safe and may prevent a drop in blood pressure and sodium retention. Trial Registration. Chinese Clinical Trial Registry (www.chictr.org/cn/, No. ChiCTR-IOR-17014206).
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OBJECTIVE: To investigate the effects of Astragalus polysaccharide (APS) on proliferation of basal-like breast cancer cell line MDA-MB-468 cells and Akt phosphorylation in MDA-MB-468 cells. METHODS: APS at different concentrations was used to culture MDA-MB-468 cells for different time periods, and then proliferation of MDA-MB-468 cells was assayed using methyl thiazolyl tetrazolium (MTT) assay to determine the time- and dose-dependent effects of APS. For observing the effects of APS on phosphor-Akt (p-Akt), in-cell Western blot method was used after 1, 2, 4 and 7 d of culture in APS to detect protein expressions of p-Akt (Thr308) and p-Akt (Ser473). Protein levels of the key targets in p53/murine double minute 2 (MDM2) signaling pathway, such as p53, MDM2 and phosphatase and tensin homolog deleted on chromosome ten (PTEN) were also detected. After PTEN gene was silenced by small interfering RNA (siRNA) in MDA-MB-468 cells, expressions of p-Akt (Thr308 and Ser473) were assayed by the in-cell Western blot method after 2 d of APS treatment. RESULTS: APS at 1 and 0.5 mg/mL concentrations effectively inhibited the proliferation of MDA-MB-468 cells and was used in subsequent tests. Compared with the control group, APS decreased the protein expression of p-Akt (Thr308) in MDA-MB-468 cells after 1-, 2-, 4- and 7-day culture, and also decreased the protein expression of p-Akt (Ser473) and up-regulated the protein expression of MDM2 in MDA-MB-468 cells after 1- and 2-day culture. Expressions of p53 and PTEN were up-regulated after 7 d of APS culture. After silencing PTEN gene by siRNA, APS could not mediate Akt phosphorylation. CONCLUSION: APS can inhibit proliferation of basal-like breast cancer cell line MDA-MB-468, and down-regulate the expression of Akt phosphorylation. The antiproliferation mechanisms may be related to its effects of up-regulating the expressions of p53 and PTEN by regulating p53/MDM2 positive and negative feedback loops.
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Astragalus propinquus/química , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Polissacarídeos/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Humanos , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Proteína Supressora de Tumor p53/metabolismoRESUMO
The aim of the present study was to compare the efficacy of vacuum sealing drainage (VSD) and precise ultrasound-guided debridement in the treatment of non-lactational mastitis and to determine the optimal surgical treatment. A set of 60 cases diagnosed with non-lactational mastitis who had received surgical treatment at the Department of Thoracic and Breast Surgery of Xiamen Hospital of Traditional Chinese Medicine (Xiamen, China) between July 2017 and June 2019 were included. According to the surgical method, 30 patients were assigned to the VSD group and 30 patients were assigned to the precise ultrasound-guided debridement group. The clinicopathological data of the two groups were compared. The overall rates of recurrence and new incidence were 6.8 and 8.5%, respectively. The mean total disease course was 5.3 months and all of the patients were cured after treatment. Except for the hospitalization time and postoperative pain scores, the clinicopathological data between the two groups were similar. The hospitalization time in the VSD group was significantly longer than that in the precise ultrasound-guided debridement group. Pain scores on the first and third days after the operation in the precise ultrasound-guided debridement group were significantly higher than those in the VSD group (P=0.008 and 0.001, respectively). In conclusion, the efficacies of VSD and precise ultrasound-guided debridement for the treatment of non-lactational mastitis were generally both satisfactory without significant differences. Of note, the former is suitable for patients with inverted nipples and obvious skin ulcerations, while the latter is mainly suitable for patients with abscesses, small surgical incisions and those who require short hospital stays.
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BACKGROUND: The incidence of heart failure with normal ejection fraction (HFNEF) is increasing yearly, accounting for approximately half of all heart failure cases. Even after standardized treatment, the patient's prognosis is not good. Therefore, it is necessary to explore new treatment methods for HFNEF. Yangyin Shuxin Decoction, a traditional Chinese medicine prescription from our clinical experience in the treatment of HFNEF, has a potential cardioprotective effect. Preliminary clinical trials have shown that this prescription can improve the quality of life of HFNEF. This prompted us to use more objective indicators to further evaluate whether Yangyin Shuxin Decoction can improve the exercise capacity in HENEF patients. METHODS: This is a single-center parallel randomized controlled trial. The 64 patients who met the inclusion criteria were from the Cardiovascular Clinic. They will be randomly assigned to the treatment group (Yangying Shuxin Decoction combined with standard treatment) or the control group (standard treatment) according to the ratio of 1:1. The course of treatment will be 2 weeks. Both groups were interviewed at the following time points: of at enrollment (V1), and week 2 (V2), week 4 (V3), week 8 (V4), and week 12 (V5) after enrollment. The primary indicator is the peak oxygen consumption (Peak VO2) of the cardiopulmonary exercise test (CPET). Secondary indicators include CPET indicators such as anaerobic threshold oxygen consumption, carbon dioxide ventilation equivalent slope, echocardiographic indicators such as the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity(E/e'), left atrial volume index (LAVI), left ventricular mass index (LVMI), the peak velocity of tricuspid regurgitation (TR), B-type natriuretic peptide (BNP), New York Heart Association (NYHA) cardiac function grading, and so on. These indicators will be used to evaluate the effect of Yangyin Shuxin Decoction on exercise capacity in patients with HFNEF. DISCUSSION: At present, it is unclear whether the exercise capacity can be maintained after long-term use of Yangyin Shuxin Decoction. In this study, we will evaluate whether Yangyin Shuxin Decoction can improve the exercise capacity and quality of life of patients with HFNEF. This will provide an objective basis for the therapeutic effect of traditional Chinese medicine on HFNEF. TRIAL REGISTRATION: This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IOR-17014206, http://www.chictr.org.cn/showproj.aspx?proj=24304) on December 28, 2017.
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Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico/fisiologia , Adulto , Idoso , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome , Resultado do TratamentoRESUMO
OBJECTIVE: This trial aims to evaluate the efficacy and safety of the Baduanjin exercise in patients with acute myocardial infarction (AMI). METHODS: A single-center, open, randomized controlled clinical trial will be conducted to evaluate the effectiveness of the Baduanjin exercise on the rehabilitation of AMI patients. It plans to enroll 64 patients. Patients will be divided evenly into 2 groups using a random number table method. There will be 32 cases in each group. Patients in the experimental group will be treated with standardized drug therapy combined with Baduanjin exercise, while patients in the control group will be treated with standardized drug therapy combined with routine exercise. The primary outcome is the peak oxygen consumption (Peak VO2) during cardiopulmonary exercise test (CPET). The secondary outcomes include CPET, echocardiography, Seattle angina pectoris scale, hospital depression and anxiety scale, Pittsburgh Sleep Quality Index scale, scores of 4 examinations, and diagnostic methods of traditional Chinese medicine and composite endpoint events, etc. DISCUSSION:: This study will be the first to evaluate the effect of the Baduanjin exercise on the Peak VO2 in patients with AMI. STUDY REGISTRATION: This study has been registered on the Chinese Clinical Trial Registry (No: ChiCTR1800016209, protocol version 1.2).
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Reabilitação Cardíaca/métodos , Terapia por Exercício , Infarto do Miocárdio/reabilitação , Terapia Combinada , Humanos , Medicina Tradicional Chinesa , Infarto do Miocárdio/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Integration of several types of therapeutic agents into one nanoplatform to enhance treatment efficacy is being more widely used for cancer therapy. METHODS: Herein, a biocompatible polydopamine (PDA)-coated MoSe2-wrapped doxorubicin (DOX)-loaded hollow mesoporous silica nanoparticles (HMSNs) nanoplatform (PM@HMSNs-DOX) was fabricated for dual-sensitive drug release and chemo-photothermal therapy for enhancing the therapeutic effects on breast cancer. The HMSNs were obtained by a "structural difference-based selective etching" strategy and served as the drug carrier, exhibiting a high DOX loading capacity of 427 mg/g HMSNs-NH2, and then wrapped with PDA-coated MoSe2 layer to form PM@HMSNs-DOX. Various techniques proved the successful fabrication of the nanocomposites. RESULTS: The formed PM@HMSNs-DOX nanocomposites exhibited good biocompatibility, good stability, and super-additive photothermal conversion efficiency due to the cooperation of MoSe2 and PDA. Simultaneously, the pH/near-infrared-responsive drug release profile was observed, which could enhance the synergistic therapeutic anticancer effect. The antitumor effects of PM@HMSNs-DOX were evaluated both in vitro and in vivo, demonstrating that the synergistic therapeutic efficacy was significantly superior to any monotherapy. Also, in vivo pharmacokinetics studies showed that PM@HMSNs-DOX had a much longer circulation time than free DOX. In addition, in vitro and in vivo toxicity studies certified that PM@HMSNs are suitable as biocompatible agents. CONCLUSION: Our nanoplatform loaded with DOX displays pH/near-infrared-induced chemotherapy and excellent photothermal therapy, which hold great potential for cancer treatment.
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Liberação Controlada de Fármacos , Hipertermia Induzida , Indóis/química , Molibdênio/química , Nanopartículas/química , Fototerapia , Polímeros/química , Dióxido de Silício/química , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Morte Celular , Linhagem Celular Tumoral , Preparações de Ação Retardada/uso terapêutico , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Feminino , Humanos , Hidrodinâmica , Concentração de Íons de Hidrogênio , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/ultraestrutura , Ratos Sprague-Dawley , Distribuição TecidualRESUMO
Yiqi formula (YF), a traditional herbal prescription, has long been used to treat triple-negative breast cancer (TNBC) patients. The present study aims to investigate the effects and the related mechanism of YF for treatment of TNBC xenografts. MDA-MB-231 (human TNBC) cells were subcutaneously injected into the second mammary fat pad of 40 female nude mice, which were divided into four groups: control, erlotinib (an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor), YF, and combination (YF plus erlotinib). All treatments were administered orally for 30 days. Inhibition rate of tumor weight by erlotinib, YF, and the combination was 26.47%, 17.24%, and 39.15%, respectively. Western blotting showed that YF, erlotinib, and the combination downregulated p-EGFR (P < 0.01) and p-Akt1 (pT308) (P < 0.05) and upregulated PTEN compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). Similar results were detected by immunohistochemistry. Real-time quantitative PCR showed that YF, erlotinib, and the combination increased PTEN mRNA (P < 0.05, P < 0.01) compared with control, and the combination was more efficacious than erlotinib alone (P < 0.05). In conclusion, YF can regulate the main components of the PI3K/Akt pathway in TNBC xenografts. When YF was used in combination with erlotinib, it enhanced the antitumor effects of erlotinib on TNBC xenografts. These findings suggest that YF is suitable to use for the treatment of TNBC patients.
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OBJECTIVE: To observe the expression of leptin (LP) and its influence on pulmonary fibrosis in experimental rats with silicosis and the correlation between the expressions of leptin and HIF-1α. METHODS: A total of 120 male Sprague-Dawley rats were randomly divided into normal control group, silicosis model group, LP intervention groups (consisting of LP5, LP10 and LP20 groups according to the concentration of LP). The rats in the normal control group were intratracheally administered 1 mL normal sodium, and the ones in the other groups were intratracheally given 1 mL SiO2(40 mg/mL) suspension. The rats in LP intervention groups were intraperitoneally injected with leptin 5, 10, 20 ng/kg.d respectively from the first day. Six rats in each group were sacrificed on the 7th, 14th, 21th and 28th day. The expression of LP on the 7th, 14th, 21th and 28th day and the hydroxyproline content on the 28th day in rat lung tissues were measured by ELISA, and the expressions of HIF-1α and LP proteins in the lung tissues of the silicosis model group were measured by Western blotting. RESULTS: There were significant differences in the expression of LP in the lung tissues at each time point (7th, 14th, 21th and 28th day) among the five groups (F=669.18, 948.67, 1 172.00, 521.55, P<0.05). The LP content in the silicosis model group was significantly higher than that in the normal control group (P<0.05) and the expression of LP in the LP intervention groups were significantly elevated at each time point (P<0.05) as compared with the silicosis model group. Hydroxyproline content on 28th day was (0.89 ± 0.16), (3.14 ± 0.40), (3.78 ± 0.27), (4.35 ± 0.13), (4.87 ± 0.16) mg/g in normal control group, silicosis model group, LP5, LP10 and LP20 intervention groups, respectively. Compared with the normal control group, hydroxyproline content in the silicosis model group significantly increased (P<0.05), and compared with the silicosis model group, hydroxyproline content in LP intervention groups were significantly raised (P<0.05). The significant positive correlations were noted between the expressions of HIF-1α and LP (r=0.876, 0.796, 0.859 and 0.854 at each time, P<0.05). CONCLUSION: The expression of LP goes up significantly in the lung tissues of rats with silicosis. Addition of exogenous leptin can increase the collagen deposition in the lung tissues; meanwhile leptin has a positive correlation with HIF-1α.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leptina/metabolismo , Fibrose Pulmonar/metabolismo , Silicose/metabolismo , Animais , Western Blotting , Colágeno/metabolismo , Ensaio de Imunoadsorção Enzimática , Hidroxiprolina/metabolismo , Injeções Intraperitoneais , Leptina/administração & dosagem , Leptina/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Fibrose Pulmonar/prevenção & controle , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Silicose/prevenção & controle , Fatores de TempoRESUMO
OBJECTIVE: To study the expression of hypoxia-inducible factor (HIF)-1α in lung tissues and sera from chronic obstructive pulmonary disease (COPD) patients and smokers with normal lung function and explore its clinical significance. METHODS: Lung tissue samples were obtained from 32 patients undergoing surgery for peripheral lung tumors. Lung function test was performed before lung cancer surgery. Based on lung function and smoking status, 32 patients were devided into three groups: smokers with stable COPD (COPD group, n=10), smokers with normal lung function (S group, n=10) and nonsmokers with nomal lung function (NS group, n=10). The preoperative fasting sera and lung tissues as far as possible away from the tumor site from all patients were collected. HIF-1α levels in sera and lung tissue homogenates were evaluated by ELISA. The expression of HIF-1α in airway epithelium, alveolar wall and blood vessel wall were detected by immunohistochemistry. Furthermore, the correlation between HIF-1α expression levels and pulmonary function was analyzed. RESULTS: Serum HIF-1α levels were significantly elevated in COPD group [(73.25 ± 6.12) pg/mL] and S group [(60.30 ± 8.00) pg/mL] as compared with NS group [(47.03 ± 8.43) pg/mL, P<0.01], and COPD group was significantly higher than S group (P<0.01). The concentrations of HIF-1α in lung tissue homogenates significantly increased in COPD group [(2.04 ± 0.24) pg/µg] and S group [(1.67 ± 0.34) pg/µg] as compared with NS group [(1.12 ± 0.33) pg/µg, P<0.01], and COPD group was also significantly higher than S group (P<0.01). HIF-1α expression was located in inflammatory cells and macrophages of airway epithelium, alveolar wall and small pulmonary artery wall. HIF-1α levels in sera and lung tissue homogenates showed negative correlations with FEV1/FVC and FEV1% predicted. CONCLUSION: HIF-1α levels are raised in sera and lung tissues of COPD patients and smokers with normal lung function, and they were positively correlated with the severity of airflow limitation.