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Chemotherapy in combination with immunotherapy has gradually shown substantial promise to increase T cell infiltration and antitumor efficacy. However, paclitaxel in combination with immune checkpoint inhibitor targeting PD-1/PD-L1 was only used to treat a small proportion of metastatic triple-negative breast cancer (TNBC), and the clinical outcomes was very limited. In addition, this regimen cannot prevent paclitaxel-induced peripheral neuropathy. Therefore, there was an urgent need for a novel target to enhance the antitumor activity of paclitaxel and alleviate chemotherapy-induced peripheral neuropathy in breast cancer. Here, we found that Dickkopf-1 (DKK1) expression was upregulated in multiply subtypes of human breast cancer specimens after paclitaxel-based chemotherapy. Mechanistic studies revealed that paclitaxel promoted DKK1 expression by inducing EGFR signaling in breast cancer cells, and the upregulation of DKK1 could hinder the therapeutic efficacy of paclitaxel by suppressing the infiltration and activity of CD8+ T cells in tumor microenvironment. Moreover, paclitaxel treatment in tumor-bearing mice also increased DKK1 expression through the activation of EGFR signaling in the primary sensory dorsal root ganglion (DRG) neurons, leading to the development of peripheral neuropathy, which is charactered by myelin damage in the sciatic nerve, neuropathic pain, and loss of cutaneous innervation in hindpaw skin. The addition of an anti-DKK1 antibody not only improved therapeutic efficacy of paclitaxel in two murine subtype models of breast cancer but also alleviated paclitaxel-induced peripheral neuropathy. Taken together, our findings providing a potential chemoimmunotherapy strategy with low neurotoxicity that can benefit multiple subtypes of breast cancer patients.
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Péptidos y Proteínas de Señalización Intercelular , Paclitaxel , Enfermedades del Sistema Nervioso Periférico , Paclitaxel/efectos adversos , Paclitaxel/farmacología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Humanos , Animales , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Femenino , Ratones , Línea Celular Tumoral , Receptores ErbB/metabolismo , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
BACKGROUND: According to traditional Chinese medicine (TCM), drugs supplementing the vital energy, Qi, can eliminate tumors by restoring host immunity. The objective of this study is to investigate the underlying immune mechanisms of anti-tumor activity associated with Qi-supplementing herbs, specifically the paired use of Huangqi and Danggui. METHODS: Analysis of compatibility regularity was conducted to screen the combination of Qi-supplementing TCMs. Using the MTT assay and a transplanted tumor mice model, the anti-tumor effects of combination TCMs were investigated in vitro and in vivo. High content analysis and flow cytometry were then used to evaluate cellular immunity, followed by network pharmacology and molecular docking to dissect the significant active compounds and potential mechanisms. Finally, the anti-tumor activity and the mechanism of the active ingredients were verified by molecular experiments. RESULTS: There is an optimal combination of Huangqi and Danggui that, administered as an aqueous extract, can activate immunity to suppress tumor and is more effective than each drug on its own in vitro and in vivo. Based on network pharmacology analysis, PIK3R1 is the core target for the anti-tumor immunity activity of combined Huangqi and Danggui. Molecular docking analysis shows 6 components of the combined Danggui and Huangqi extract (quercetin, jaranol, isorhamnetin, kaempferol, calycosin, and suchilactone) that bind to PIK3R1. Jaranol is the most important component against breast cancer. The suchilactone/jaranol combination and, especially, the suchilactone/kaempferol combination are key for immunity enhancement and the anti-tumor effects of the extract. CONCLUSIONS: The combination of Huangqi and Danggui can activate immunity to suppress breast cancer and is more effective than the individual drugs alone.
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Neoplasias de la Mama , Medicamentos Herbarios Chinos , Ratones Endogámicos BALB C , Simulación del Acoplamiento Molecular , Medicamentos Herbarios Chinos/farmacología , Animales , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Ratones , Humanos , Astragalus propinquus , Línea Celular Tumoral , Regulación hacia Arriba/efectos de los fármacosRESUMEN
PURPOSE: To understand the current situation and needs of occlusal function exercise in patients with mandibular defects after oral tumor surgery. METHODSï¼ Twenty-seven patients with mandibular defects after oral tumor surgery were interviewed semi-structurally by objective sampling method. The three-level coding system of rooting theory was used for reference, and Nvivo11 qualitative analysis software was used for bottom-up coding analysis. RESULTS: The current situation and needs of occlusal function exercise in patients with mandibular defects can be summarized into five themes, the impact of mandibular defects on patients, lack of knowledge related to occlusal function exercise, demand for content of occlusal function exercise (looking forward to professional health guidance), demand for education methods of occlusal function exercise(expecting diversified education methods and various obstacles to reduce patient compliance). CONCLUSIONS: To establish a unified and standardized program of occlusal function exercise, doctors and nurses should pay attention to various obstacles of patients, adjust the psychological state of patients, and maximize the compliance of patients with occlusal function exercise.
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Mandíbula , Neoplasias de la Boca , Humanos , Programas InformáticosRESUMEN
Lactate acts as an important metabolic substrate and signalling molecule modulating neural activities in the brain, and recent preclinical and clinical studies have revealed its antidepressant effect after acute or chronic peripheral administration. However, the neural mechanism underlying the antidepressant effect of lactate, in particular when lactate is acutely administered remains largely unknown. In the current study, we focused on forced swimming test (FST) to elucidate the neural mechanisms through which acute intracerebroventricular (ICV) infusion of lactate exerts antidepressant-like effect. A total of 238 male Sprague Dawley rats were used as experimental subjects. Results showed lactate produced antidepressant-like effect, as indicated by reduced immobility, in a dose- and time-dependent manner. Moreover, the antidepressant-like effect of lactate was dependent of new protein synthesis but not new gene expression, lactate's metabolic effect or hydroxy-carboxylic acid receptor 1 (HCAR1) activation. Furthermore, lactate rapidly promoted dephosphorylation of eukaryotic elongation factor 2 (eEF2) and increased brain-derived neurotrophic factor (BDNF) protein synthesis in the hippocampus in a cyclic adenosine monophosphate (cAMP)-dependent manner. Finally, inhibition of cAMP production blocked the antidepressant-like effect of lactate. These findings suggest that acute administration of lactate exerts antidepressant-like effect through cAMP-dependent protein synthesis.
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Depresión , Ácido Láctico , Humanos , Ratas , Animales , Masculino , Depresión/tratamiento farmacológico , Ácido Láctico/metabolismo , Ratas Sprague-Dawley , Antidepresivos , Natación , AMP Cíclico/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismoRESUMEN
PURPOSE: To construct a virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients by virtual simulation technology, and to evaluate its application effect. METHODS: Through virtual reality, animation, human-computer interaction and other technologies, a 3D experiment scene based on high simulation virtual human was constructed to reproduce the virtual rescue scenes of craniofacial injury patients, such as emergency reception, first-aid cooperation, massive hemorrhage rescue cooperation, and tracheotomy cooperation in emergency rescue of sudden airway obstruction, and exercise modules and assessment modules were set. In the virtual simulation platform, the students used the holistic nursing theory and the PDCA cycle method to observe, evaluate and care for craniofacial injury patients. Preliminary evaluation of the platform was carried out in the training of 62 dental nurses. RESULTS: The virtual simulation platform could improve students' comprehensive first-aid ability for craniofacial injury patients. The item with the highest satisfaction rate for the virtual simulation platform was the consistency between the content of the virtual simulation platform and the theoretical course (the satisfaction rate was 91.9%), and the lowest satisfaction rate was the convenience of the virtual simulation platform operation and the page setting (the satisfaction rate was 80.6%). The evaluation module of the virtual simulation platform showed that the highest score of the comprehensive evaluation was 97, the lowest score was 56, and the average score was 80.2. CONCLUSIONS: The virtual simulation teaching platform for in-hospital first aid of craniofacial injury patients can create an immersive learning mode, provide an intuitive rescue experience to the students, and improve their comprehensive first-aid ability.
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Enfermería de Urgencia , Humanos , Aprendizaje , Competencia ClínicaRESUMEN
OBJECTIVE: To investigate the clinical efficacy of electrophysiological appropriateness technique (EAT) therapy based on the traditional Chinese medicine (TCM) meridian theory in managing postoperative pain after urethral reconstruction surgery. METHODS: Using the real-world study approach, we enrolled 61 male patients undergoing urethral reconstruction and divided them into a control group (n = 30) and an observation group (n = 31), the former receiving patient-controlled intravenous analgesia (PCIA), while the latter PCIA plus EAT at 4 pairs of acupoints (Hegu, Neiguan, Zusanli and Sanyinjiao bilaterally) and the Ashi point, with 100 mg tramadol hydrochloride given orally as remedial analgesia in both groups in case of postoperative Visual Analogue Scale (VAS) score ≥4. We compared the VAS scores at 4, 12, 24 and 48 hours postoperatively, the dose of cumulative fentanyl used at 48 hours, the number of cases needing remedial analgesia, the time to first flatus and the incidence of adverse reactions between the two groups of patients. RESULTS: The VAS scores were markedly lower in the observation than in the control group at 4, 12, 24 and 48 hours after surgery (P < 0.05), with statistically significant differences in time-dependent effect and interactive effect (P < 0.05). Significant reduction was observed in the doses of cumulative fentanyl (P < 0.05) and remedial tramadol analgesia (P < 0.05), time to first flatus (P < 0.05), and incidence of adverse reactions (P < 0.05) in the observation group in comparison with the controls. CONCLUSION: Electrophysiological therapy based on the TCM meridian theory can safely and effectively alleviate postoperative pain after urethral reconstruction, reduce opioid consumption, and decrease adverse events.
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Meridianos , Tramadol , Humanos , Masculino , Medicina Tradicional China , Flatulencia , Dolor Postoperatorio/tratamiento farmacológico , Analgesia Controlada por el Paciente/métodos , Analgésicos Opioides/uso terapéutico , Tramadol/uso terapéutico , Fentanilo/uso terapéuticoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality in the world. However, the anticancer effects of aucubin against HCC have yet to be reported. Cisplatin often decreased CD8+ tumor-infiltrating lymphocytes in the tumor microenvironment through increasing programmed death-ligand 1 (PD-L1) expression, which seriously affected the prognostic effect of cisplatin in the treatment of patients with HCC. Therefore, it is necessary to identify a novel therapeutic avenue to increase the sensitivity of cisplatin against HCC. PURPOSE: This study aims to evaluate the anti-tumor effect of aucubin on HCC, and also to reveal the synergistic effects and mechanism of aucubin and cisplatin against HCC. STUDY DESIGN AND METHODS: An H22 xenograft mouse model was established for the in vivo experiments. Cancer cell proliferation was detected by MTT assay. RT-qPCR was performed to analyze CD274 mRNA expression in vitro. Western blotting was employed to determine the expression levels of the PD-L1, p-Akt, Akt, p-ß-catenin, and ß-catenin in vitro. Immunofluorescence was carried out to examine ß-catenin nuclear accumulation in HCC cells. Immunohistochemistry was used to detect tumoral PD-L1 and CD8α expression in xenograft mouse model. RESULTS: Aucubin inhibits tumor growth in a xenograft HCC mouse model, but did not affect HCC cell viability in vitro. Aucubin treatment significantly inhibited PD-L1 expression through inactivating Akt/ß-catenin signaling pathway in HCC cells. Overexpression of PD-L1 dramatically reversed aucubin-mediated tumoral CD8+ T cell infiltration and alleviated the antitumor activity of aucubin in xenograft mouse model. Moreover, Cisplatin could induce the expression of PD-L1 through the activation of the Akt/ß-catenin signaling pathway in HCC cells, which can be blocked by aucubin in vitro. In xenograft mouse model, cisplatin treatment induced PD-L1 expression and alleviated the infiltration of CD8+ T lymphocytes in the tumor microenvironment. Aucubin not only abrogated cisplatin-induced PD-L1 expression but also enhanced the antitumor efficacy of cisplatin in a mouse xenograft model of HCC. CONCLUSION: Aucubin exerts antitumor activity against HCC and also enhances the antitumor activity of cisplatin by suppressing the Akt/ß-catenin/PD-L1 axis.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/metabolismo , Cisplatino/farmacología , Cisplatino/uso terapéutico , Antígeno B7-H1/metabolismo , Neoplasias Hepáticas/metabolismo , beta Catenina/metabolismo , Proteínas Proto-Oncogénicas c-akt , Línea Celular Tumoral , Microambiente TumoralRESUMEN
Human dental pulp stem cells (hDPSCs) are considered promising multipotent cell sources for tissue regeneration. Regulation of apoptosis and maintaining the cell homeostasis is a critical point for the application of hDPSCs. Osteomodulin (OMD), a member of the small leucine-rich proteoglycan family, was proved an important regulatory protein of hDPSCs in our previous research. Thus, the role of OMD in the apoptosis of hDPSCs was explored in this study. The expression of OMD following apoptotic induction was investigated and then the hDPSCs stably overexpressing or knocking down OMD were established by lentiviral transfection. The proportion of apoptotic cells and apoptosis-relative genes and proteins were examined with flow cytometry, Hoechst staining, Caspase 3 activity assay, qRT-PCR and western blotting. RNA-Seq analysis was used to explore possible biological function and mechanism. Results showed that the expression of OMD decreased following the apoptotic induction. Overexpression of OMD enhanced the viability of hDPSCs, decreased the activity of Caspase-3 and protected hDPSCs from apoptosis. Knockdown of OMD showed the opposite results. Mechanistically, OMD may act as a negative modulator of apoptosis via activation of the Akt/Glycogen synthase kinase 3ß (GSK-3ß)/ß-Catenin signaling pathway and more functional and mechanistic possibilities were revealed with RNA-Seq analysis. The present study provided evidence of OMD as a negative regulator of apoptosis in hDPSCs. Akt/GSK-3ß/ß-Catenin signaling pathway was involved in this process and more possible mechanism detected needed further exploration. This anti-apoptotic function of OMD provided a promising application prospect for hDPSCs in tissue regeneration.
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Cisplatino , beta Catenina , Humanos , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Pulpa Dental , Apoptosis/genética , Células MadreRESUMEN
BACKGROUND: Insular thyroid carcinoma (ITC) is an uncommon poorly differentiated thyroid malignancy. Due to its rarity, its demographic and clinicopathological features and survival remains unclear. The present study aimed to describe the features and survival of ITC, determine its prognostic factors, and establish a prognostic nomogram. METHODS: Patients with ITC were identified in the Surveillance, Epidemiology, and End Results database from 2004 to 2019. The features and survival of patients with ITC and other thyroid carcinomas were compared after balancing the baseline characteristics using propensity score matching (PSM). Univariate and multivariate Cox analyses were used to identify the prognostic factors for ITC. Moreover, overall survival (OS)- or cancer-specific survival (CSS)-specific nomograms were established to predict ITC prognosis. RESULTS: A total of 206 patients with ITCs were identified. The 1-, 2-, 5-, and 10-year OS rates of 206 patients with ITC were 90.3%, 82.0%, 62.2%, and 42.5%, respectively. The median OS was 93 months (95% CI, 73.0-140.0), while the median CSS was 141 months (95% CI, 93.0-173.0). After PSM analysis, the survival analysis of the matched cohort revealed that ITC had a worse clinical outcome than papillary thyroid cancer and follicular thyroid cancer, and better survival than anaplastic thyroid carcinoma. Multivariate Cox regression analysis demonstrated that age, N stage, M stage, and surgery were independent prognostic factors for both OS and CSS in ITC patients. The C-indices for the OS- and CSS-specific nomograms were 0.778 (95% CI, 0.724-0.832) and 0.808 (95% CI, 0.754-0.862), respectively. The calibration curve and ROC analysis indicated that the nomogram models exhibited a good discriminative ability. Decision curve analysis suggested that the nomogram models had a significant positive net benefit and were better than the traditional TNM staging system at predicting survival. CONCLUSION: ITC has distinct clinicopathological characteristics and survival compared to other thyroid carcinomas, and the established nomogram could predict the survival probability of patients with ITC accurately with a higher net benefit.
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Adenocarcinoma Folicular , Neoplasias de la Tiroides , Humanos , Nomogramas , Pronóstico , Neoplasias de la Tiroides/diagnóstico , Cáncer Papilar Tiroideo , Estadificación de NeoplasiasRESUMEN
NUAK1 is a serine/threonine kinase that has been shown to be associated with poor prognosis in several cancers. Although NUAK1 is frequently overexpressed at the transcript level in hepatocellular carcinoma (HCC), the actual role of NUAK1 and the mechanism of its overexpression in HCC has yet to be reported. In the present study, we found that NUAK1 expression was significantly increased in human HCC tumor tissues. Overexpression of NUAK1 dramatically enhanced HCC cells proliferation and migration in vitro. Stable induction of NUAK1 expression promoted tumor growth and tumor metastases to the lungs in the subcutaneous xenograft models and intravenous metastasis models. At the cellular level, enforced expression of Dickkopf-1 (DKK1) activated the Akt signaling pathway, thereby promoting the mRNA and protein expression of NUAK1 in HCC cells. By contrast, depletion of DKK1 was found to attenuate the mRNA and protein expression of NUAK1. In the subcutaneous xenograft models, stable induction of DKK1 expression not only accelerated tumor growth but also increased p-Akt and NUAK1 expression; whereas knockdown of DKK1 inhibited tumor growth, p-Akt and NUAK1 expression. Furthermore, immunohistochemical analysis of 20 HCC clinical samples showed that the expression level of NUAK1 was positively correlated with DKK1 and p-Akt. Taken together, we provide the first evidence that DKK1 promotes NUAK1 transcriptional expression via the activation Akt in HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Línea Celular Tumoral , ARN Mensajero , Modelos Animales de Enfermedad , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Proteínas Quinasas/metabolismo , Proteínas Represoras/metabolismo , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/metabolismoRESUMEN
PURPOSE: To systematically assess the efficacy of psychological intervention for patients with head and neck cancer (HNC) in easing negative emotion and improving quality of life, so as to provide evidence-based reference for clinical psycho-intervention of HNC patients. METHODS: PubMed, Central, Embase, clinicaltrials.gov, ICTRP, Web of science, CBM, CNKI, VIP, and Wan Fang database were searched from inception to 15th, May for randomized controlled trails conducted to assess psychological intervention for HNC patients. The retrieval, screening, quality evaluation, and data extraction were elaborately proceeded by two reviewers independently. Meta analysis was performed using RevMan 5.4 software. RESULTS: Eighteen RCTs were included with 2 097 participants. Meta analysis showed that compared to control group, psychological intervention group manifested greater decrease in anxiety scores [SMD=-2.33, 95%CIï¼-2.96ï¼-1.70ï¼, Pï¼0.000 01] and depression scores [SMD=-2.26, 95%CIï¼-2.78ï¼-1.74ï¼, Pï¼0.000 01], and better increase in QOL scores [SMD=6.04, 95%CIï¼1.53ï¼10.56ï¼, P=0.009] and SQL-90 scores [MD=29.99, 95%CIï¼-36.22, -23.76ï¼ï¼Pï¼0.000 01]. CONCLUSIONS: The anxiety and depression of HNC patients can be effectively relieved through psychological intervention, so that their quality of life and metal health status can be improved. Due to the limitation of quality of included RCT , the result remains to be further validated by more well-designed and better-qualified study.
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Neoplasias de Cabeza y Cuello , Calidad de Vida , Ansiedad/terapia , Neoplasias de Cabeza y Cuello/terapia , Humanos , Intervención PsicosocialRESUMEN
OBJECTIVE: In the present study, we determined whether the glycogen phosphorylase(GP)inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) ameliorates pentylenetetrazole (PTZ)-induced acute seizure, neuroinflammation and memory impairment in rats. METHODS: In experiment 1, rats were randomly divided into the Vehicle (n=5) and PTZ (n=5) groups, and received intraperitoneal injection of saline or PTZ (70 mg/kg), respectively. Hippocampal tissues were collected 30 min after drug injection. Western blot was used to examine the levels of GP expression. Colorimetric assay was used to determine the levels of lactate. In experiment 2, rats were randomly divided into the Vehicle+Vehicle (n=18), DAB+Vehicle (n=18), Vehicle+PTZ (n=19) and DAB+PTZ (n=18) groups. Rats received intracerebroventricular injection of PBS or DAB (50 µg/2 µl) 15 min before receiving intraperitoneal injection of saline or PTZ (70 mg/kg). Behavioural assays and the Racine scale were used to evaluate seizure severity. Western blot was used to examine the levels of targeted protein of hippocampal tissues. Novel object recognition test was used to assess memory performance. RESULTS: â Compared with the Vehicle group, the levels of GP and lactate in the hippocampal tissues of the PTZ group were increased significantly (both Pï¼0.01). â¡ Compared with the Vehicle+PTZ group, in the DAB+PTZ group, the levels of myoclonic body jerk latency, forelimb clonus latency and tonic-clonic seizure latency were increased significantly (all Pï¼0.01), while the duration of seizure and seizure scores were decreased significantly (both Pï¼0.01). ⢠Compared with the Vehicle+Vehicle group, in the Vehicle +PTZ group, the levels of IL-1ß, IL-6, TNF-α, IBA-1 and GFAP in the hippocampal tissues were increased significantly (all Pï¼0.01), and the discrimination index in the novel object recognition test was decreased significantly (Pï¼0.01). Compared with the Vehicle+PTZ group, in the DAB+PTZ group, the levels of IL-1ß, TNF-α, IBA-1 and GFAP in the hippocampal tissues were decreased significantly (all, Pï¼0.01), while the discrimination index in the novel object recognition test was increased significantly (Pï¼0.01). CONCLUSION: DAB ameliorates PTZ-induced seizure, neuroinflammation and memory impairment in rats, suggesting that DAB may serve as a novel agent for potential clinical treatment of epilepsy.
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Glucógeno Fosforilasa , Enfermedades Neuroinflamatorias , Convulsiones , Animales , Ratas , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéutico , Glucógeno Fosforilasa/antagonistas & inhibidores , Lactatos/efectos adversos , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Pentilenotetrazol/efectos adversos , Convulsiones/inducido químicamente , Convulsiones/complicaciones , Factor de Necrosis Tumoral alfaRESUMEN
PURPOSE: To investigate the current status of oral health cognition behavior and oral health status of children, and to provide countermeasures for the prevention and treatment of oral diseases in children. METHODS: A total of 387 primary school students in the urban area of Shanghai from December 2018 to February 2019 were surveyed using Children's Oral Health Questionnaire and child oral health impact profileï¼COHIPï¼. SPSS 24.0 software package was used to conduct statistical analysis of the results through descriptive, univariate and multivariate analysis. RESULTS: The cognition of oral health of children aged 6-9 years old in Shanghai urban area was generally good, but their oral health behavior was average. The caries rate of 387 children reached 57.4%, and the oral health status was not good. Correlation analysis and regression analysis showed that children's oral health behavior was positively correlated with oral health cognitionï¼r=0.260ï¼P<0.05ï¼, and negatively correlated with positive and negative effects of oral health statusï¼r=-0.333ï¼-0.181ï¼P<0.05ï¼, while children's oral health cognition had no significant effect on their oral health statusï¼P>0.05ï¼. CONCLUSIONS: The better the oral health behavior habits of children, the greater the positive impact on oral health status; the development of oral health education for children requires more attention to the cultivation of oral health behavior patterns.
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Caries Dental , Salud Bucal , Niño , China/epidemiología , Cognición , Caries Dental/epidemiología , Conductas Relacionadas con la Salud , Educación en Salud Dental , HumanosRESUMEN
BACKGROUND Baicalein, one of the major flavonoids in the plant [i]Scutellaria baicalensis[/i], can regulate the invasive ability of cancer cells. The invasion of trophoblasts is similar to the invasion of tumor cells into host tissues. The appropriate invasion of trophoblast cells into the endometrium is an important factor for successful embryo implantation. In this research, we investigated the effect of baicalein on the invasion and migration of trophoblast cells and its possible molecular mechanism. MATERIAL AND METHODS We treated HTR-8/SVneo cells with different concentrations (0, 0.05, 0.1, and 0.5 µM) of baicalein. The invasion and migration abilities of HTR-8/SVneo cells were studied. Protein levels and gene expression related to invasion and migration were analyzed by Western blot analysis and reverse transcription-quantitative polymerase chain reaction, respectively. RESULTS Baicalein enhanced the migration and invasion of HTR-8/SVneo cells. In addition, gene expression and protein levels of MMP-9 in HTR-8/SVneo cells changed in the presence of baicalein. Moreover, the data show that baicalein activated the NF-κB pathway. Baicalein was also able to rescue effects of an NF-κB-specific inhibitor (JSH-23) on the migration and invasion of HTR-8/SVneo cells. CONCLUSIONS In conclusion, our results indicate that baicalein enhances migration and invasion of HTR-8/SVneo cells, which is important for successful pregnancy.
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Movimiento Celular/efectos de los fármacos , Flavanonas/farmacología , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Trofoblastos/citología , Línea Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Supervivencia Celular/efectos de los fármacos , Femenino , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Fenilendiaminas/farmacología , Transporte de Proteínas/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Trofoblastos/efectos de los fármacos , Trofoblastos/enzimologíaRESUMEN
The herbal medicine Yin Huang Mixture (YHHJ; patent no. 200910031240.7) is an aqueous extract composed from various herbs, including Artemisia capillaries Thunb, Hypericum japonicum Thunb, Eucommia ulmoides Oliver, Rheum officinale Baill, Gardenia jasminoides Ellis, Poria cocos Wolf and Dictamnus dasycarpus Turcz. Previous studies have indicated that YHHJ treatment has a beneficial effect on ameliorating itching and reducing serum bile acid levels in patients with intrahepatic cholestasis of pregnancy (ICP). However, the molecular mechanisms of action of YHHJ in ICP have not been fully elucidated. Therefore, the present study investigated an experimental hepatocellular cholestasis model to explore the regulatory role of YHHJ on the expression of the bile acid carriers, multidrug resistance-associated protein 2 (MRP2) and the bile salt export pump (BSEP). Initially, 5 mg/kg/day 17-α ethinylestradiol (EE) was used to induce cholestasis in rats and primary isolated rat hepatocytes. Subsequently, 9 or 36 g/kg/day YHHJ water extract was administrated. Blood samples were collected and serum biochemical parameters of total bile acids (TBA), total bilirubin (TBil), alanine transaminase and aspartate aminotransferase levels were determined. Rat livers and primary isolated rat hepatocytes were obtained and the protein and mRNA expression levels of MRP2 and BSEP were analyzed by western blot analysis and reverse transcription-quantitative polymerase chain reaction, respectively. Results revealed that EE-induced hepatocellular cholestasis was associated with a significant increase in serum TBA and TBil levels, whereas, YHHJ treatment significantly reversed this effect (P<0.01). Further experiments on the molecular mechanism revealed that EE significantly decreased the expression of MRP2 and BSEP compared with the control group, whereas YHHJ treatment significantly upregulated MRP2 and BSEP expression in vivo and in vitro compared with no YHHJ treatment (P<0.01). In addition, to establish whether upregulation of MRP2 and BSEP protein expression levels resulted from increased expression of their respective mRNA, the mRNA expression levels were determined. Results indicated that YHHJ treatment significantly increased MRP2 and BSEP mRNA expression levels in EE-induced hepatocellular cholestasis compared with no YHHJ treatment (P<0.01). In conclusion, the present findings suggest that YHHJ effects EE-induced cholestasis and this process may be mediated through regulating hepatobiliary transporters, MRP2 and BSEP.
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BACKGROUND: Lung cancer is a serious threat to human health and life worldwide. Anxiety is common amongst palliative care patients with lung cancer and adversely affects quality of life. Acupuncture is an effective and safe treatment method used for the treatment of depressive mood status. We aimed to assess the influence of electrical acupuncture stimulation on self-reported anxiety in palliative care among patients with lung cancer. METHODS: This pilot study had an experimental, 3-group, research plan. A total of 188 participants were enrolled from the Shanghai Pulmonary Hospital, Tongji University, Shanghai, China from 2014-2015. This pilot study had an experimental, 3-group, research plan. In TEAS group, participants received standardized palliative care and electrical acupuncture stimulation in Zusanli, Sanyinjiao and Hegu acu-points. Group MS received standardized palliative care and muscle stimulation nearby nonacupoint. Controlled group received standardized palliative care. The patients maintained their assigned acupuncture stimulation for 7 days. Demographic Instrument, Karnofsky Performance Scale Index, SF-16 health questionnaire and Self-Rating Anxiety Scale (SAS) were used. RESULTS: The mean SAS scores in TEAS Group before and after electrical intervention in palliative care intervention were 31.17±7.55,34.58±13.98 and 27.86±6.73, (P=0.00) QoL score showed elevation from 57.13 in 8th day to 60.12 in 28th day, rising further to 5%. Comfort Score showed continuous elevation trend for 28 days. CONCLUSION: Electric acupuncture stimulation could reduce the anxiety of patients, promote rehabilitation and increase the quality of life among patients with lung cancer in palliative care.
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Tolerancia Inmunológica/efectos de los fármacos , Materia Medica/uso terapéutico , Medicina Tradicional China , Complicaciones del Embarazo/tratamiento farmacológico , Pueblo Asiatico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , EmbarazoRESUMEN
Excessive release of high mobility group box-1 (HMGB1) protein from ischemic cardiomyocytes activates inflammatory cascades and enhances myocardial injury after reperfusion. Here we report evidence that electroacupuncture of mice at Neiguan acupoints can inhibit the up-regulation of cardiac HMGB1 following myocardial ischemia and attenuate the associated inflammatory responses and myocardial injury during reperfusion. These benefits of electroacupuncture were partially reversed by administering recombinant HMGB1 to the mice, and further potentiated by administering anti-HMGB1 antibody. Electroacupuncture-induced inhibition of HMGB1 release was markedly reduced by unilateral vagotomy or administration of nicotinic receptor antagonist, but not by chemical sympathectomy. The cholinesterase inhibitor neostigmine mimicked the effects of electroacupuncture on HMGB1 release and myocardial ischemia reperfusion injury. Culture experiments with isolated neonatal cardiomyocytes showed that acetylcholine, but not noradrenaline, inhibited hypoxia-induced release of HMGB1 via a α7nAchR-dependent pathway. These results suggest that electroacupuncture acts via the vagal nerve and its nicotinic receptor-mediated signaling to inhibit HMGB1 release from ischemic cardiomyocytes. This helps attenuate pro-inflammatory responses and myocardial injury during reperfusion.
Asunto(s)
Electroacupuntura , Proteína HMGB1/fisiología , Isquemia Miocárdica/prevención & control , Daño por Reperfusión/prevención & control , Animales , RatonesRESUMEN
BACKGROUND: Lung cancer is a disease with a poor prognosis and psychological impact. Lung cancer causes both physical and psychological burdens on patients, and financial burdens on families and society. The aim of this study was to examine the relationship between depression and influencing factors in non-small-cell lung cancer (NSCLC) patients. METHODS: A quantitative study was applied. Data was obtained from the Shanghai Pulmonary Hospital in China. One hundred and four patients with NSCLC were surveyed. Self-rating depression scale (SDS), social support rating scale (SSRS), and visual analog scale (VAS) were used. RESULTS: Among the 104 patients, 48 (46.1%) were diagnosed with depression. Gender (P = 0.000), disease duration (P = 0.006), self-care ability (P = 0.004), and pain (P = 0.003) were statistically significant predictors of self-reported depression in non-small-cell lung cancer patients. CONCLUSIONS: Self-reported depression is highly prevalent in NSCLC patients. In addition, gender, disease duration, self-care ability, pain and social support may increase self-reported depression.
RESUMEN
BACKGROUND: The goal of total knee arthroplasty (TKA) is to restore knee kinematics. Knee prosthesis design plays a very important role in successful restoration. Here, kinematics models of normal and prosthetic knees were created and validated using previously published data. METHODS: Computed tomography and magnetic resonance imaging scans of a healthy, anticorrosive female cadaver were used to establish a model of the entire lower limbs, including the femur, tibia, patella, fibula, distal femur cartilage, and medial and lateral menisci, as well as the anterior cruciate, posterior cruciate, medial collateral, and lateral collateral ligaments. The data from the three-dimensional models of the normal knee joint and a posterior-stabilized (PS) knee prosthesis were imported into finite element analysis software to create the final kinematic model of the TKA prosthesis, which was then validated by comparison with a previous study. The displacement of the medial/lateral femur and the internal rotation angle of the tibia were analyzed during 0-135° flexion. RESULTS: Both the output data trends and the measured values derived from the normal knee's kinematics model were very close to the results reported in a previous in vivo study, suggesting that this model can be used for further analyses. The PS knee prosthesis underwent an abnormal forward displacement compared with the normal knee and has insufficient, or insufficiently aggressive, "rollback" compared with the lateral femur of the normal knee. In addition, a certain degree of reverse rotation occurs during flexion of the PS knee prosthesis. CONCLUSIONS: There were still several differences between the kinematics of the PS knee prosthesis and a normal knee, suggesting room for improving the design of the PS knee prosthesis. The abnormal kinematics during early flexion shows that the design of the articular surface played a vital role in improving the kinematics of the PS knee prosthesis.