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Objective: To compare the safety and short-term efficacy of robotic-assisted thoracic surgery(RATS) and video-assisted thoracoscopic surgery(VATS) in patients with non-small cell lung cancer (NSCLC). Methods: A retrospective analysis of the clinical data of 2 058 NSCLC patients who underwent RATS and VATS from January 2021 to December 2022 in Xiangya Hospital of Central South University was conducted, including 1 006 males and 1 052 females, with the age of (57.3±9.9) years. According to the surgical approach, the patients were divided into RATS group (n=1 190) and VATS group (n=868). The nearest neighbor matching method was used to perform 1â¶1 propensity score matching (PSM). A comparison was made about the intraoperative conditions and postoperative complication rates between the RATS and VATS groups before and after PSM. Furthermore, after PSM, a stratified analysis was conducted based on surgical approach, separately comparing the intraoperative conditions and postoperative complication rates between the VATS and RATS groups among patients who underwent lobectomy and segmentectomy, respectively. Results: After PSM, a total of 1 692 patients were included, with 846 patients in both the VATS and RATS groups. After stratification based on surgical approach, there were 503 patients in the RATS group and 548 patients in the VATS group for lobectomy, and 338 patients in the RATS group and 298 patients in the VATS group for segmentectomy. Before PSM, statistically significant differences were observed between the RATS and VATS groups in terms of intraoperative conversion to open thoracotomy, number of lymph node dissection/sampling stations, extubation time, total length of hospital stay, and total hospitalization costs (all P<0.001). After PSM, compared with the VATS group, the RATS group had a lower intraoperative conversion rate to open surgery [1.2% (10/846) vs 5.1% (43/846)], less intraoperative blood loss [(73.6±77.4) ml vs (112.6±239.3) ml], a greater number of sampled/dissected lymph node stations [(4.8±2.0) vs (3.7±1.8)], a shorter duration of drainage tube placement [(3.6±2.7) d vs (4.1±2.5) d], and a higher postoperative drainage volume [(273.9±183.0) ml vs (256.5±168.7) ml] (all P<0.001). There was no statistically significant difference in the incidence of postoperative complications between the two groups (P=0.108). The results of the surgical stratification analysis showed statistically significant differences between the two groups in terms of intraoperative blood loss, number of lymph node dissection/sampling stations, extubation time, and total hospitalization costs for both lobectomy and segmentectomy surgeries (all P<0.001). In lobectomy surgeries, the RATS group had a lower rate of intraoperative conversion to open thoracotomy than that of VATS group [1.6% (8/503) vs 7.7% (42/548), P<0.001]. In segmentectomy surgeries, the RATS group had more postoperative drainage volume than that of VATS group [(249.8±151.5) ml vs (218.7±132.9) ml, P=0.023]. There was no statistically significant difference in the incidence of surgical complications between the two groups for both lobectomy and segmentectomy surgeries (both P>0.05). Conclusion: In the surgical management of NSCLC, RATS offers more advantages over VATS in reducing conversion rates to open surgery, minimizing perioperative adverse events, and facilitating faster patient recovery postoperatively.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neumonectomía , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Cirugía Torácica Asistida por Video , Masculino , Neoplasias Pulmonares/cirugía , Humanos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Persona de Mediana Edad , Femenino , Cirugía Torácica Asistida por Video/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Estudios Retrospectivos , Neumonectomía/métodos , Resultado del Tratamiento , Puntaje de PropensiónRESUMEN
Optical coherence tomography (OCT) is a specialized optical imaging technique with a history of more than 30 years, known as'optical biopsy' because of its high resolution and high sensitivity. OCT has been used in the airway for more than 20 years, and researchers have explored and improved the imaging methods of OCT in the airway, focusing mainly on expanding the imaging site and enriching the imaging content. In terms of broadening the imaging site, it covers the airway from generation 0 to 9. In terms of enriching imaging content, additional assessment of airway wall blood vessels, airway smooth muscle, fibrous tissue, and airway compliance can be performed. It plays an important role in the study of various respiratory diseases. Therefore, this paper mainly summarized the exploration of the imaging site and content of airway OCT as follows.
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Músculo Liso , Tomografía de Coherencia Óptica , BiopsiaRESUMEN
OBJECTIVE: In order to solve the problem of image real-time processing and correction for high-speed endoscopic swept-source optical coherence tomography (SS-OCT), we highly optimize a computer-unified device architecture-based platform and use a field-programmable gate array to summarize the application experience. MATERIALS AND METHODS: We use the Half-Sync/Half-Asyn mode to optimize memory in order to build a high-throughput data thread pool for CPU. We use asynchronous streaming architecture to multiplex multiple threads at high speed to accelerate data processing. At the same time, we design a rotary scanning position information encoding feedback module to suppress image drift, which can realize 25ns logic-timing sequence synchronization control through FPGA 40MHz clock. RESULTS: The maximum complete attainable axial-scan-processing rate (including memory transfer and display of B-scan frames) is 3.52 MHz for a 16-bit pixel depth and A-scans/s of 1024 pixels. To our knowledge, this is the fastest processing rate reported to date with a single-chip graphical processing unit for SS-OCT. Finally, the established high-speed SS-OCT is used to image mouse esophagus and human fingers, and the output images are stable. When the image size is 1024 × 1024 pixels, the real-time imaging rate is 200 frames per second. CONCLUSIONS: This paper develops a real-time image processing and reconstruction technology suitable for high-throughput SS-OCT systems, which can have high-density operation and efficient parallelism, while suppressing high-speed image drift. It lays the foundation for the non-destructive, in vivo, non-staining, fast and convenient early tumor diagnosis of high-speed endoscopic SS-OCT.
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Procesamiento de Imagen Asistido por Computador , Tomografía de Coherencia Óptica , Animales , Ratones , Humanos , Tomografía de Coherencia Óptica/métodos , Programas Informáticos , AceleraciónRESUMEN
The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various industrial applications, from actuators and medical devices to high-precision instruments1,2. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys3-including gum metals4,5 and strain glass alloys6,7-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation3. Recently, chemically complex alloys, such as 'high-entropy' alloys8, have attracted tremendous research interest owing to their promising properties9-15. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10-4) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.
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Objective: To evaluate the effectiveness and safety of the robotic assisted bronchoscope system for localizing and removing the spring coils that placed in the peripheral lung of beagle dogs. Methods: The study was conducted from June 18th to June 20th, 2021. Metallic lung coils were placed as the simulated lesions to the periphery of the lungs of two adult male beagle dogs using a bronchoscope under general anesthesia. The navigation path was planned by the navigation function that built in the robotic bronchoscope system. After training, the doctors operated the robotic bronchoscope system to locate and remove the coils from the lung. The navigation success rate, sampling success rate, position of the coil, navigation time, sampling time, and operation time were evaluated. The damage to the airway mucosa during the operation and the vital signs of the beagles during and post-operation were accessed. Chest computerized tomography (CT) was performed post-operation to detect if there were complications such as pneumothorax and bleeding. Results: A total of 12 spring coils were successfully inserted into the two beagles. All the navigation paths of the simulated lesions were successfully planned. The navigation success rate was 12/12. The navigation time was (43.9±19.8) seconds. The distance between the tip of the flexible endoscope arm and the target point measured by the navigation system was (6.93±2.15) mm. The locations of the simulated lesions were distributed in the 6th-8th generation of bronchi. The sampling success rate was 12/12. The sampling time was (42.4±11.3) seconds. There was no pneumothorax or mediastinal emphysema after the placement of the coil. The vital signs of the beagle dogs were stable throughout the operation, and no operation-related or postoperative complications occurred. Conclusions: The robotic bronchoscope system can be used to locate and remove the spring coils from the peripheral lung of beagle dogs, and the procedure is simple and safe. It suggests that the robotic bronchoscopy system has great clinical significance in the sampling and diagnosis of peripheral lung lesions.
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Broncoscopía , Procedimientos Quirúrgicos Robotizados , Animales , Broncoscopios , Perros , Pulmón/diagnóstico por imagen , Pulmón/cirugía , Masculino , Proyectos PilotoRESUMEN
Objective: To identify the factors associated with successful transrectal specimen extraction after laparoscopic rectal cancer resection. Methods: A retrospective case-control study was conducted. Clinical data of rectal cancer patients who did or did not successfully undergo transrectal specimen extraction in Shanghai East Hospital between January 2017 and December 2017 were retrieved through the rectal cancer database of Shanghai East Hospital. Case inclusion criteria: (1) tumor size ≤7 cm by pelvic MRI; (2) body mass index (BMI)≤ 30 kg/m(2); (3) no history of neoadjuvant chemoradiotherapy; (4) no anal stenosis. Clinical data including age, gender, BMI, tumor obstruction, distance from tumor to anal verge, history of abdominal operation, maximal diameter of tumor and width of mesorectum in the anteroposterior dimension measured by pelvic MRI, etc. were collected. The χ(2) test was used to perform univariate analysis. Multivariate logistic regression was used to identify factors affecting transrectal specimen extraction. Results: A total of 208 patients were included in the analysis. Of 208 patients, 132 were men and 76 were women; mean age was (63±11) years old and median tumor size was 3.8 (IQR, 3.0 to 5.0) cm. Sixty-six (31.7%) patients completed transrectal specimen extraction successfully. Univariate analysis showed that patients who completed transrectal specimen extraction were more likely to have a lower BMI (χ(2)=7.420, P=0.006), be free from malignant obstruction (χ(2)=8.972, P=0.003), have a shorter distance from tumor to the anal verge (<5.0 cm) (χ(2)=14.960, P<0.001), a smaller tumor size (≤5.0 cm) (χ(2)=18.495, P<0.001) and a thinner mesorectum in the anteroposterior dimension (≤6.0 cm) (χ(2)=34.612, P<0.001) than those who failed to perform transrectal specimen extraction. Gender, age or history of abdominal operation were not associated with the successful extraction (all P>0.05). Multivariate analysis revealed that BMI ≤25.0 kg/m(2) (OR=2.32, 95% CI: 1.06 to 5.06, P=0.034), free from malignant obstruction (OR=3.01, 95% CI: 1.82 to 6.69, P<0.001), the distance from tumor to the anal verge <5.0 cm (OR=3.73, 95% CI: 1.22 to 11.43, P=0.021), tumor size ≤ 5.0 cm (OR=4.43, 95% CI: 1.39 to 14.09, P=0.012), and the anteroposterior width of mesorectum ≤ 6.0 cm (OR=4.30, 95% CI: 2.02 to 9.18, P<0.001) were independent protective factors for successful transrectal specimen extraction. Conclusion: Preoperative assessment of BMI, malignant obstruction, distance from tumor to the anal verge, tumor size and anteroposterior width of mesorectum is beneficial to choose appropriate patients with rectal cancer to undergo transrectal specimen extraction.
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Cirugía Endoscópica por Orificios Naturales , Proctectomía/métodos , Neoplasias del Recto/cirugía , Recto/cirugía , Anciano , Estudios de Casos y Controles , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proctoscopía , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIM: Perineal wound complications after abdominoperineal resection (APR) have become a major clinical challenge. Myocutaneous flap closure has been proposed in place of primary closure to improve wound healing. We conducted this comprehensive meta-analysis to evaluate the current scientific evidence of primary closure vs myocutaneous flap closure of perineal defects following APR for colorectal disease. METHODS: We systematically searched the MEDLINE, Embase, PubMed, Web of Science and Cochrane Library databases to identify all relevant studies. After data extraction from the included studies, meta-analysis was performed to compare perioperative outcomes of primary closure and myocutaneous flap closure. RESULTS: Eighteen studies with a total of 17 913 patients (16 346 primary closure vs 1567 myocutaneous flap closure) were included. We found that primary closure was significantly associated with higher total perineal wound complications (P = 0.007), major perineal wound complications (P < 0.001) and perineal wound infection (P = 0.001). On the other hand, myocutaneous flap closure takes more operation time (P < 0.001) and increases the risk of perineal wound dehiscence (P = 0.01), deep surgical site infection (P < 0.001), enterocutaneous fistulas (P = 0.03) and return to the operating room (P = 0.0005). There were no significant differences between the two groups for other outcomes. CONCLUSIONS: This is the first systematic review with meta-analysis comparing primary closure with myocutaneous flap closure of perineal defects after APR for colorectal disease. Although taking more operation time and an increased risk of specific complications, the pooled results have validated the use of myocutaneous flaps for reducing total/major perineal wound complications. More investigations are needed to draw definitive conclusions on this dilemma.
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Cirugía Colorrectal/métodos , Colgajo Miocutáneo , Perineo/cirugía , Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/cirugía , Dehiscencia de la Herida Operatoria/cirugía , HumanosRESUMEN
Trace amounts of selenium (Se) are essential for several organisms, and deficiencies therein have adverse effects on growth, development, and reproduction; this is particularly significant in animals raised for milk and livestock production. To study the effect of Se on Guanzhong dairy goats, their diets were supplemented with different sources (inorganic or organic) and Se concentrations (0.2 or 0.4 mg Se/kg). A non-Se-fortified basal diet served as a negative control, and a sixth treatment group received both inorganic and organic Se sources (0.2 mg Se/kg diet each). Dietary Se supplementation increased milk production, with organic Se being more effective than inorganic Se. Selenium supplementation also increased Se concentration and glutathione peroxidase activity in whole blood, with organic Se more effective than inorganic Se at the same Se concentration. With increasing Se in diets, the Se content in milk increased markedly, reaching a plateau value at day 30 in all groups, and organic Se (0.4 mg/kg diet) had the best effect. In addition, dietary Se sources and concentrations markedly affected Se concentrations in different tissues and organs. Thus, organic Se supplementation of a basal diet at 0.4 mg/kg is practically applicable for Se-enriched milk and meat production in Guanzhong dairy goats.
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Lactancia/efectos de los fármacos , Leche/química , Selenio/farmacología , Alimentación Animal , Animales , Suplementos Dietéticos , CabrasRESUMEN
Euphorbia humifusa Willd. (EH), rich in flavonoids, has long been used for the treatment of bacillary dysentery and enteritis in China, and is known to have antioxidant, hypotensive and hypolipidemic properties. However, the vasorelaxant effect of total flavonoids of EH (TFEH) and action mechanisms are not clearly defined yet. The aim of the present study was to investigate the effects of TFEH on the vascular tension and its underlying mechanisms. Experiments were performed in rat thoracic aorta using the organ bath system. TFEH (0.01 - 100 µg/ml) caused a concentration-dependent vasorelaxation, which was dependent on a functional endothelium, and were significantly attenuated by inhibitors of endothelial NO synthase, its upstream signaling pathway, PI3K/Akt, and soluble guanylate cyclase, but not by blockade of KCa channel, KATP channel, cyclooxygenase, muscarinic and ß-adrenergic receptors. Extracellular Ca2+ depletion, and pre-treatment with modulators of the store-operated Ca2+ entry channels, Gd3+ and 2-aminoethyl diphenylborinate, significantly attenuated the TFEH-induced vasorelaxation. Our findings suggest that TFEH elicit vasorelaxation via endothelium-dependent NO-cGMP pathway through activation of PI3K/Akt- and Ca2+-eNOS-NO signaling. Further, it is suggested that TFEH-induced activation of the NO-soluble guanylate cyclase-cGMP-protein kinase G signaling relaxes vascular smooth muscle cells through an inhibition of the L-type Ca2+ channel activity.
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Aorta Torácica/efectos de los fármacos , Euphorbia/química , Flavonoides/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Aorta Torácica/metabolismo , Calcio/metabolismo , Canales de Calcio/metabolismo , GMP Cíclico/metabolismo , Medicamentos Herbarios Chinos/farmacología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/farmacología , Prostaglandina-Endoperóxido Sintasas/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Guanilil Ciclasa Soluble/metabolismoRESUMEN
Proper HOXA10 expression was essential for endometrial receptivity what was crucial for successful embryo implantation in mammalian. This study confirmed that miR-182 regulated the expression levels of HOXA10 by binding to its 3' UTR, selectively downregulated HOXA10 in goat endometrial epithelium cells (gEECs) but not stromal cell (gESCs) in vitro. However, HOXA10 and miR-182 both up-expressed in the goat endometrium at gestational day 15 (D15) compared with gestational day 5 (D5), suggesting that there were some other factors regulated the expression of HOXA10 during the development of goat endometrium in vivo. What's more, HOXA10 gene silencing (HOXA10-siRNA) resulted in gEECs apoptosis in vitro, and it regulated the protein levels of oestrogen receptor a (ERa), progesterone receptor B (PRb), insulin-like growth factor 1 receptor (IGF1R), BCL-2, pleiotrophin (PTN), AKT and p-JNK in gEECs. Furthermore, HOXA10 might regulate the protein levels of endometrial receptivity biomarker genes, including vascular endothelial growth factor (VEGF), osteopontin (OPN), cyclooxygenase-2 (COX-2) and prolactin receptor (PRLR) in gEECs. In conclusion, miR-182 targeted HOXA10 selectively in EECs in vitro, and HOXA10 played an important role in maintaining the function of EECs in dairy goats.
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Endometrio/metabolismo , Cabras/metabolismo , Proteínas de Homeodominio/metabolismo , MicroARNs/fisiología , Regiones no Traducidas 3' , Animales , Apoptosis , Células Cultivadas , Endometrio/citología , Células Epiteliales/fisiología , Femenino , Regulación de la Expresión Génica , Cabras/genética , Péptidos y Proteínas de Señalización Intercelular/genética , ARN Interferente Pequeño , Células del Estroma/fisiologíaRESUMEN
Objective: To evaluate the safety of the procedures of whole lung lavage(WLL) for pulmonary alveolar proteinosis(PAP) in perioperative period. Methods: In this retrospective study, we collected clinical data from 78 WLL procedures of PAP patients from January 2006 to June 2016 in Guangzhou Institute of Respiratory Disease. The causes of perioperative complications were analyzed. Results: Eighteen (23.07%) of the 78 procedures developed complications, including pleural effusion(n=4), pneumonia(n=4), cardiac failure(n=2), cardiac arrhythmia (n=2), pneumothorax(n=2), atelectasis(n=1), lung edema(n=1), laryngeal edema(n=1), pleural effusion and pneumonia(n=1). All complications were mild and easy to treat. Seventy-four procedures had successful extubation, but 4 procedures developed a prolonged time of extubation. Age, DSS, PaCO(2,)FEV(1,)lavage volume, lavage times and underlying diseases were not predictors for any complications(each P>0.05). High fluid recovering rate had a protective effect against the occurring of complications (Wald=7.672, OR<0.01, P<0.05). Conclusions: Whole lung lavage was a safe procedure in the treatment of PAP. Complications could recovery after proper therapy. The perioperative complications showed a correlation with low fluid recover rate. Operation under guideline was the key to avoid complications.
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Lavado Broncoalveolar/métodos , Pulmón/patología , Proteinosis Alveolar Pulmonar/terapia , Lavado Broncoalveolar/estadística & datos numéricos , Líquido del Lavado Bronquioalveolar , Humanos , Pulmón/metabolismo , Neumotórax , Proteinosis Alveolar Pulmonar/epidemiología , Proteinosis Alveolar Pulmonar/metabolismo , Pruebas de Función Respiratoria , Estudios RetrospectivosRESUMEN
Although ketamine shows a rapid and sustained antidepressant effect, the precise mechanisms underlying its effect are unknown. Recent studies indicate a key role of p11 (also known as S100A10) in depression-like behavior in rodents. The present study aimed to investigate the role of p11 in the antidepressant-like action of ketamine in chronic unpredictable mild stress (CUMS) rat model. The open-field test, forced swimming test and sucrose preference test were performed after administration of ketamine (10 mg kg(-1)) or a combination of ketamine and ANA-12 (a tropomyosin-related kinase B (TrkB) antagonist; 0.5 mg kg(-1)). The lentivirus vector for p11 was constructed to knock down the hippocampal expression of p11. In the CUMS rats, ketamine showed a rapid (0.5 h) and sustained (72 h) antidepressant effect, and its effect was significantly blocked by co-administration of ANA-12. Furthermore, ketamine significantly increased the reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of CUMS rats, whereas ketamine did not affect the expression of p11 in CUMS rats 0.5 h after administration. In addition, ketamine significantly increased the reduced ratio of p-TrkB/TrkB in the hippocampus by CUMS rats, and its effect was also blocked by ANA-12. Moreover, the reduced expression of BDNF and p11 in the hippocampus of CUMS rats was significantly recovered to control levels 72 h after ketamine administration. Interestingly, knockdown of hippocampal p11 caused increased immobility time and decreased sucrose preference, which were not improved by ketamine administration. These results suggest that p11 in the hippocampus may have a key role in the sustained antidepressant effect of ketamine in the CUMS model of depression.
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Anexina A2/metabolismo , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Hipocampo/metabolismo , Ketamina/farmacología , Proteínas S100/metabolismo , Estrés Psicológico/complicaciones , Analgésicos/farmacología , Animales , Anexina A2/genética , Enfermedad Crónica , Depresión/etiología , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-Dawley , Proteínas S100/genéticaRESUMEN
OBJECTIVE: The aim of this study was to examine the function of tramadol on cell proliferation, migration and invasion in breast cancer cells in vitro, and to evaluate the effect of tramadol in vivo. Further, we explore the mechanism accounting for the role of tramadol on breast cancer cells. MATERIALS AND METHODS: Cell proliferation was detected by the methyl thiazolyl tetrazolium (MTT) assay. Wound healing assay and transwell assay was applied to quantify the migration and invasion ability of MDA-MB-231 cells. The expression of endogenous α2-adrenoceptor and ERK was measured by Western blotting. RESULTS: Tramadol at a clinical dose of up to 2 µM significantly inhibited the proliferation, migration and invasion in a time-dependent manner from day 0 to 28 in vitro. Moreover, tramadol suppressed the growth of xenotransplant tumor in vivo markedly. Furthermore, the protein levels of α2-adrenoceptor and phosphorylated ERK were decreased by tramadol, whereas the expression of total ERK remained unchanged. In addition, downregulation of α2-adrenoceptor by yohimbine could mimic the effect of tramadol treatment. CONCLUSIONS: Collectively, we demonstrated that tramadol could inhibit proliferation, migration and invasion of breast cancers via inactivating α2-adrenoceptor signaling pathway. Our data provide the experimental fundamental for further investigation of the anti-cancer effect of tramadol in breast cancer cells.
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Analgésicos Opioides/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Receptores Adrenérgicos alfa 2/efectos de los fármacos , Tramadol/farmacología , Animales , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: To verify whether mesenchymal stem cells protected the islet allograft via modulating follicular B helper T cells (Tfh) cells. METHODS: The recipient mice were divided into 5 groups. Group A: the diabetic group (n = 12); Group B: islets alone group (n = 12); Group C: MSCs and islets co-transplanted group (n = 12, MSCs = 0.5 × 10(6)); Group D: MSCs and islets co-transplanted group (n = 12, MSCs = 1 × 10(6)); Group E: MSCs and islets co-transplanted group (n = 12, MSCs = 2 × 10(6)); One control group of normal NOD mice was set as well. ELISA was used to examine the autoantibody level of GAD65 Ab, insulin autoantibodies, and insulin. The Tfh count was determined by fluorescence-activated cell sorting. The insulin expression of islet grafts, the infiltration of lymphocytes, and the Tfh cells were observed via hematoxylin and eosin staining and immunohistochemical staining. RESULTS: There was significant prolonged graft survival and more insulin expression of islet grafts observed in the co-transplant group. A lower level of the Tfh cells and autoantibody GAD65 Ab, insulin autoantibodies were also presented in the co-transplant group (P < .01). The infiltration of lymphocytes in the co-transplant group was notably less than in the islet-alone group (P < .01). CONCLUSIONS: Mesenchymal stem cells were able to protect the islet allograft by regulating the follicular helper T cells.
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Diabetes Mellitus Experimental/cirugía , Supervivencia de Injerto/inmunología , Tolerancia Inmunológica , Trasplante de Islotes Pancreáticos , Células Madre Mesenquimatosas/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Aloinjertos/metabolismo , Animales , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Experimental/metabolismo , Femenino , Citometría de Flujo , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NODRESUMEN
Current available antidepressants exhibit low remission rate with a long response lag time. Growing evidence has demonstrated acute sub-anesthetic dose of ketamine exerts rapid, robust, and lasting antidepressant effects. However, a long term use of ketamine tends to elicit its adverse reactions. The present study aimed to investigate the antidepressant-like effects of intermittent and consecutive administrations of ketamine on chronic unpredictable mild stress (CUMS) rats, and to determine whether ketamine can redeem the time lag for treatment response of classic antidepressants. The behavioral responses were assessed by the sucrose preference test, forced swimming test, and open field test. In the first stage of experiments, all the four treatment regimens of ketamine (10mg/kg ip, once daily for 3 or 7 consecutive days, or once every 7 or 3 days, in a total 21 days) showed robust antidepressant-like effects, with no significant influence on locomotor activity and stereotype behavior in the CUMS rats. The intermittent administration regimens produced longer antidepressant-like effects than the consecutive administration regimens and the administration every 7 days presented similar antidepressant-like effects with less administration times compared with the administration every 3 days. In the second stage of experiments, the combination of ketamine (10 mg/kg ip, once every 7 days) and citalopram (20 mg/kg po, once daily) for 21 days caused more rapid and sustained antidepressant-like effects than citalopram administered alone. In summary, repeated sub-anesthestic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram, suggesting the combination of ketamine and classic antidepressants is a promising regimen for depression with quick onset time and stable and lasting effects.
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Antidepresivos/farmacología , Conducta Animal/efectos de los fármacos , Citalopram/farmacología , Trastorno Depresivo/tratamiento farmacológico , Ketamina/farmacología , Natación , Animales , Antidepresivos/administración & dosificación , Citalopram/administración & dosificación , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Conducta Exploratoria/efectos de los fármacos , Ketamina/administración & dosificación , Ratas , Ratas WistarRESUMEN
Rumex acetosa L. (RA) (Polygonaceae) is an important traditional Chinese medicine (TCM) commonly used in clinic for a long history in China and the aerial parts of RA has a wide variety of pharmacological actions such as diuretic, anti-hypertensive, anti-oxidative, and anti-cancer effects. However, the mechanisms involved are to be defined. The purpose of the present study was to evaluate the vasorelaxant effect and define the mechanism of action of the ethanol extract of Rumex acetosa L. (ERA) in rat aorta. ERA was examined for its vascular relaxant effect in isolated phenylephrine-precontracted rat thoracic aorta and its acute effects on arterial blood pressure. In addition, the roles of the nitric oxide synthase (NOS)-nitric oxide (NO) signaling in the ERA-induced effects were tested in human umbilical vein endothelial cells (HUVECs). The phosphorylation levels of Akt and eNOS were assessed by Western blot analysis in the cultured HUVECs. ERA induced endothelium-dependent vasorelaxation. The ERA-induced vasorelaxation was abolished by L-NAME (an NOS inhibitor) or ODQ (a sGC inhibitor), but not by indomethacin. Inhibition of PI3-kinase/Akt signaling pathway markedly reduced the ERA-induced vasorelaxation. In HUVECs, ERA increased NO formation in a dose-dependent manner, which was inhibited by L-NAME and by removing extracellular Ca(2+). In addition, ERA promoted phosphorylation of Akt and eNOS, which was prevented by wortmannin and LY294002, indicating that ERA induces eNOS phosphorylation through the PI3-kinase/Akt pathway. Further, in anesthetized rats, intravenously administered ERA decreased arterial blood pressure in a dose-dependent manner through an activation of the NOS-NO system. In summary, the ERA- induced vasorelaxation was dependent on endothelial integrity and NO production, and was mediated by activation of both the endothelial PI3-kinase/Akt- and Ca(2+)-eNOS-NO signaling and muscular NO-sGC-cGMP signaling.