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Periodontal defects present a significant challenge in dentistry, necessitating innovative solutions for comprehensive regeneration. Traditional restoration methods have inherent limitations in achieving complete and functional periodontal tissue reconstruction. Tissue engineering, a multidisciplinary approach integrating cells, biomaterials, and bioactive factors, holds tremendous promise in addressing this challenge. Central to tissue engineering strategies are scaffolds, pivotal in supporting cell behavior and orchestrating tissue regeneration. Natural and synthetic materials have been extensively explored, each offering unique advantages in terms of biocompatibility and tunable properties. The integration of growth factors and stem cells further amplifies the regenerative potential, contributing to enhanced tissue healing and functional restoration. Despite significant progress, challenges persist. Achieving the seamless integration of regenerated tissues, establishing proper vascularization, and developing biomimetic scaffolds that faithfully replicate the natural periodontal environment are ongoing research endeavors. Collaborative efforts across diverse scientific disciplines are essential to overcoming these hurdles. This comprehensive review underscores the critical need for continued research and development in tissue engineering strategies for periodontal regeneration. By addressing current challenges and fostering interdisciplinary collaborations, we can unlock the full regenerative potential, paving the way for transformative advancements in periodontal care. This research not only enhances our understanding of periodontal tissues but also offers innovative approaches that can revolutionize dental therapies, improving patient outcomes and reshaping the future of periodontal treatments.
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To extend the network life, an ordinal potential game is introduced into network topology control, and a network topology control algorithm based on the Theil entropy measure is designed by improving the revenue function. The revenue function is based on the Theil entropy measure, whose factors are in the residual energy of the nodes and their neighbors. By using a primary payoff function that considers all initial network factors and a secondary one that addresses connectivity in case of reduced residual energy, a segmentation function can calculate the model's payoff. Simulation experiments show that compared to the existing game algorithms of 3DK-RNG, DEBA, and EFPC, the proposed algorithm can effectively eliminate redundant links, reduce node degree and network link length, balance node energy consumption, enhance network load, and extend the network life cycle.â¢A Network Topology Control Algorithm Based on the Fusion of Thiel Entropy and Ordinal Potential Games.â¢A network topology control method for extending the network lifecycle is successfully established.â¢It proposes that the performance of the fusion topology control algorithm is significantly superior to other single algorithms in the paper.
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AIM: To determine whether or not a decoction made from Qigu Zhushui has a suppressive impact on malignant ascites in mice. BACKGROUND: Malignant ascites are one of the common complications of advanced malignant tumors. Patients with malignant ascites typically have a poor prognosis, with only 12 to 20 weeks of survival. Currently, the standard treatments for malignant ascites are systemic chemotherapy, which is ineffective in eradicating the disease and is associated with issues such as safety, short duration of sustained high-level drug concentration in localised regions, and drug resistance. OBJECTIVE: To clarify the effect of Qigu Zhushui decoction on inhibiting malignant ascites in mice and provide the experimental basis for further research. METHODS: The ascites model of liver cancer in mice was established by intraperitoneal injection of the H22-H8D8 cell line of liver cancer. ELISA detected the content of CEA, VEGF and TNF-α in ascites. RESULTS: Qigu Zhushui decoction combined with cisplatin group and Qigu Zhushui decoction highdose group could significantly reduce the weight, abdominal circumference and ascites volume of mice, and their survival days and survival rate were also greatly improved; The levels of CEA and VEGF in the combination group decreased significantly, while the level of TNF-α increased; The level of TNF-a in the high dose group of Qigu Zhushui decoction was significantly increased, while the level of CEA and VEGF in the moderate dose group was decreased. CONCLUSION: Qigu Zhushui decoction can reduce the malignant ascites in mice, and the combination of Qigu Zhushui decoction and cisplatin has a significant anti-malignant ascites effect, which can significantly prolong the survival time and improve the survival rate.
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Ascitis , Neoplasias Hepáticas , Humanos , Animales , Ratones , Ascitis/tratamiento farmacológico , Ascitis/etiología , Ascitis/metabolismo , Cisplatino/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Factor de Necrosis Tumoral alfa , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patologíaRESUMEN
Wearable devices have gradually integrated into people's healthy lives because of their mobility, portability, and other characteristics, and have shown their value and status in sports and health. Wearable devices can be used to capture a large amount of human body activity data, but how to effectively use these data to serve people and help people form a healthy lifestyle is a problem to be considered. In order to further study the feasibility of wearable devices to guide scientific movements and promote health, a new layered motion recognition algorithm is proposed in this study. In this study, a C4.5-based decision tree algorithm is used to identify the state layer, and only the mean and variance features are extracted from the acceleration sensor data. Three corresponding BP neural network classifiers are constructed and classified. Each classifier is responsible for identifying actions in the corresponding states and verifying the method in this study through experiments. The experimental results in this study show that the recognition rate of the mRMR feature selection recognition algorithm is 1.13% higher than the BE algorithm and 2.02% higher than the recognition method without any feature selection algorithm. In addition, the research in this article found that wearable devices can realize the real-time detection of the physiological indicators of the wearer throughout the day to evaluate the efficacy of the drug and apply it to the early detection and treatment of diseases, which may improve patient compliance and promote health to a certain extent.
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Promoción de la Salud , Dispositivos Electrónicos Vestibles , Algoritmos , Estudios de Factibilidad , Humanos , Movimiento/fisiología , Redes Neurales de la ComputaciónRESUMEN
Referring Expression Comprehension (REC) is an important task in the vision-and-language community, since it is an essential step for many cross-modal tasks such as VQA, image retrieval and image caption. To obtain a better trade-off between speed and accuracy, existing researches usually follow a one-stage paradigm, where this task can be considered as a language-conditioned object detection task. Meanwhile, previous one-stage REC frameworks provide many different research perspectives, such as the strategies of fusion, the stage of fusion and the design of detection head. Surprisingly, these works mostly ignore the value of integrating multi-level features and even only apply single-scale features to locate the target. In this paper, we focus on rethinking and improving feature pyramids for one-stage REC. By experimental validations, we first prove that although multi-scale fusion is an effective approach for improving performance, the mature neck structures from object detection (e.g., FPN, BFN and HRFPN) have a limited impact on this task. Further, we visualize the outputs of FPN and find the underlying reason is that these coarse-grained FPN fusion strategies suffer from semantic ambiguity problem. Based on the above insights, we propose a new Language-Guided FPN (LG-FPN) method, which can dynamically allocate and select the fine-grained information by stacking language-gate and union-gate. A large number of contrastive and ablative experiments show that our LG-FPN is an effective and reliable module that can adapt to different visual backbones, fusion strategies and detection heads. Finally, our method achieves state-of-the-art performance on four referring expression datasets.
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NEW FINDINGS: What is the central question of this study? Does danthron alleviate experimental atherosclerosis by inhibiting the formation of foam cells? What are the main findings and their importance? Danthron improved serum lipid profiles and significantly reduced the atherosclerotic plaque areas and lipid accumulation in the aortic root of ApoE-/- mice. Danthron inhibited foam cell formation in oxidized low-density lipoprotein-induced RAW264.7 macrophages. Furthermore, danthron exerted its function in atherosclerosis at least partly through activating the AMP-activated protein kinase-sirtuin 1 signalling pathway. These findings suggest that danthron has the potential to alleviate atherosclerosis. ABSTRACT: Danthron, an ingredient isolated from Rheum palmatum L., has been revealed to reduce lipid accumulation in vitro. This study aimed to discover the effects of danthron on the development of atherosclerosis and to delineate the underlying mechanisms. For in vivo studies, male ApoE-/- mice were fed a high-fat diet and orally treated with danthron (30 or 60 mg/kg/day) for 12 weeks. For in vitro studies, RAW264.7 cells were induced by oxidized low-density lipoprotein (ox-LDL, 50 µg/ml) for 48 h and subsequently administered danthron at appropriate concentrations for 24 h. AMP-activated protein kinase (AMPK) inhibitor compound C was added to ox-LDL-stimulated RAW264.7 cells 2 h before danthron administration to confirm the role of the AMPK signalling pathway in the regulation by danthron of foam cell formation. We found that danthron improved serum lipid profiles, and significantly reduced atherosclerotic plaque areas and lipid accumulation in the aortic root of atherosclerotic mice. Moreover, danthron upregulated the mRNA and protein expression of ATP-binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor α (LXRα), which play a crucial role in lipid metabolism, and activated the AMPK-sirtuin 1 (SIRT1) pathway. In an in vitro study, danthron inhibited foam cell formation in ox-LDL-induced RAW264.7 macrophages with an increase in the expression of ABCA1, ABCG1 and LXRα as well as activation of the AMPK-SIRT1 pathway. Furthermore, compound C abolished the effects of danthron on lipid accumulation and the protein expression of ABCA1/G1 and LXRα in vitro. Our results highlight that danthron possesses potential benefits in alleviating experimental atherosclerosis by targeting foam cell formation by activating the AMPK-SIRT1 signalling pathway.
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Aterosclerosis , Células Espumosas , Animales , Antraquinonas/metabolismo , Antraquinonas/farmacología , Aterosclerosis/tratamiento farmacológico , Células Espumosas/metabolismo , Macrófagos/metabolismo , Masculino , RatonesRESUMEN
BACKGROUND: In 2018, the diagnosis-related groups prospective payment system (DRGs-PPS) was introduced in a trial operation in Beijing according to the requirements of medical and health reform. The implementation of the system requires that more than 300 disease types pay through the DRGs-PPS for medical insurance. Colorectal cancer (CRC), as a common malignant tumor with high prevalence in recent years, was among the 300 disease types. AIM: To investigate the composition and factors related to inpatient medical expenditure in CRC patients based on disease DRGs, and to provide a basis for the rational economic control of hospitalization expenses for the diagnosis and treatment of CRC. METHODS: The basic material and cost data for 1026 CRC inpatients in a Grade-A tertiary hospital in Beijing during 2014-2018 were collected using the medical record system. A variance analysis of the composition of medical expenditure was carried out, and a multivariate linear regression model was used to select influencing factors with the greatest statistical significance. A decision tree model based on the exhaustive χ 2 automatic interaction detector (E-CHAID) algorithm for DRG grouping was built by setting chosen factors as separation nodes, and the payment standard of each diagnostic group and upper limit cost were calculated. The correctness and rationality of the data were re-evaluated and verified by clinical practice. RESULTS: The average hospital stay of the 1026 CRC patients investigated was 18.5 d, and the average hospitalization cost was 57872.4 RMB yuan. Factors including age, gender, length of hospital stay, diagnosis and treatment, as well as clinical operations had significant influence on inpatient expenditure (P < 0.05). By adopting age, diagnosis, treatment, and surgery as the grouping nodes, a decision tree model based on the E-CHAID algorithm was established, and the CRC patients were divided into 12 DRG cost groups. Among these 12 groups, the number of patients aged ≤ 67 years, and underwent surgery and chemotherapy or radiotherapy was largest; while patients aged > 67 years, and underwent surgery and chemotherapy or radiotherapy had the highest medical cost. In addition, the standard cost and upper limit cost in the 12 groups were calculated and re-evaluated. CONCLUSION: It is important to strengthen the control over the use of drugs and management of the hospitalization process, surgery, diagnosis and treatment to reduce the economic burden on patients. Tailored adjustments to medical payment standards should be made according to the characteristics and treatment of disease types to improve the comprehensiveness and practicability of the DRGs-PPS.
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Single-nucleotide polymorphisms (SNPs) is associated with efficacy of specific drugs. Although there are several methods for SNP genotyping in clinical settings, alternative methods with lower cost, higher throughout and less complexity are still needed. In this study, we modified Kompetitive Allele Specific PCR to enable multiplex SNP genotyping by introducing additional fluorescent cassettes that specifically help to differentiate more amplification signals in a single reaction. This new format of assay achieved a limit of detection down to 310 copies/ reactions for simultaneous detection of 2 SNPs with only standard end-point PCR workflow for synthetic controls, and genotyped 117 clinical samples with results that were in 100% agreement with hospital reports. This study presented a simplified, cost-effective high-throughput SNP genotyping alternative for pharmacogenetic variants, and enabled easier access to pharmaceutical guidance when needed.
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Técnicas de Genotipaje/métodos , Reacción en Cadena de la Polimerasa Multiplex/métodos , Farmacogenética/métodos , Polimorfismo de Nucleótido Simple/genética , Alelos , Genotipo , HumanosRESUMEN
OBJECTIVES: The aim of this analysis was to study the impact of marital status on inflammatory breast cancer (IBC) patients, as the prognostic impact is yet to be studied in detail. METHODS: Data of IBC patients from 2004 to 2010 were sorted out from the database of surveillance, epidemiology, and end results (SEER), and overall survival (OS) rates and breast cancer-specific survival (CSS) rates were compared between a group of married and unmarried patients. The comparison was performed by Kaplan-Meier method with log-rank test, and multivariate survival analysis of CSS and OS was performed using the Cox proportional hazard model. RESULTS: Data of 1342 patients were collected from the SEER database, on an average 52% of married patients (n = 698, 52.01%) and 48% of unmarried patients (n = 644, 47.99%) for this analysis. Married patients were more likely to be more younger (aged ≤ 56) (52.44% vs. 43.94%), white ethnicity (83.24% vs. 71.58%), HoR positive (48.28% vs. 41.61%), more patients received surgery (78.51% vs. 64.60%), chemotherapy (90.69% vs. 80.12%) and radiotherapy (53.44% vs. 44.41%) compared to unmarried group, and less likely to be AJCC stage IV (26.22% vs. 35.40%) (All P Ë 0.05). Married patients had better 5-year CSS (74.90% vs. 65.55%, P < 0.0001) and OS rates (45.43% vs. 33.11%, P < 0.0001). The multivariate analysis revealed that marital status is an independent prognostic factor, whereas the data of unmarried patients showed worse CSS (HR 1.188; 95% CI 1.033-1.367; P = 0.016) and OS rates (HR 1.245; 95% CI 1.090-1.421; P = 0.001).The subgroup analysis further revealed that the OS and CSS rates in the married group were better than the unmarried group, regardless of different AJCC stages. CONCLUSION: Marital status was an independent prognostic indicator in IBC patients. As the study reveals, the CSS and OS rates of the married patients were better than those of the unmarried patients.
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Neoplasias Inflamatorias de la Mama/epidemiología , Estado Civil , Adulto , Anciano , Anciano de 80 o más Años , Animales , Bases de Datos Factuales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Neoplasias Inflamatorias de la Mama/diagnóstico , Neoplasias Inflamatorias de la Mama/mortalidad , Neoplasias Inflamatorias de la Mama/terapia , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Vigilancia de la Población , Pronóstico , Modelos de Riesgos Proporcionales , Medición de Riesgo , Factores de Riesgo , Programa de VERF , Adulto JovenRESUMEN
BACKGROUND: The development and application of medical technologies reflect the medical quality and clinical capacity of a hospital. It is also an effective approach in upgrading medical service and core competitiveness among medical institutions. This study aimed to build a quantitative medical technology evaluation system through questionnaire survey within medical institutions to perform an assessment to medical technologies more objectively and accurately, and promote the management of medical quality technologies and ensure the medical safety of various operations among the hospitals. METHODS: A two-leveled quantitative medical technology evaluation system was built through a two-round questionnaire survey of chosen experts. The Delphi method was applied in identifying the structure of evaluation system and indicators. The judgment of the experts on the indicators was adopted in building the matrix so that the weight coefficient and maximum eigenvalue (λ max), consistency index (CI), and random consistency ratio (CR) could be obtained and collected. The results were verified through consistency tests, and the index weight coefficient of each indicator was conducted and calculated through analytical hierarchy process. RESULTS: Twenty-six experts of different medical fields were involved in the questionnaire survey, 25 of whom successfully responded to the two-round research. Altogether, 4 primary indicators (safety, effectiveness, innovativeness, and benefits), as well as 13 secondary indicators, were included in the evaluation system. The matrix is built to conduct the λ max, CI, and CR of each expert in the survey, and the index weight coefficients of primary indicators were 0.33, 0.28, 0.27, and 0.12, respectively, and the index weight coefficients of secondary indicators were conducted and calculated accordingly. CONCLUSIONS: As the two-round questionnaire survey of experts and statistical analysis were performed and credibility of the results was verified through consistency evaluation test, the study established a quantitative medical technology evaluation system model and assessment indicators within medical institutions based on the Delphi method and analytical hierarchy process. Moreover, further verifications, adjustments, and optimizations of the system and indicators will be performed in follow-up studies.
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Tecnología Biomédica/métodos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Cervical cancer shows a growing incidence and medical cost in recent years that has increased severe financial pressure on patients and medical insurance institutions. This study aimed to investigate the medical economic characteristics of cervical cancer patients with different payment modes within a Grade A tertiary hospital to provide evidence and suggestions for inpatient cost control and to verify the application of Gamma model in medical cost analysis. METHODS: The basic and cost information of cervical cancer cases within a Grade A tertiary hospital in the year 2011-2016 were collected. The Gamma model was adopted to analyze the differences in each cost item between medical insured patient and uninsured patients. Meanwhile, the marginal means of different cost items were calculated to estimate the influence of payment modes toward different medical cost items among cervical cancer patients in the study. RESULTS:: A total of 1321 inpatients with cervical cancer between the 2011 and 2016 were collected through the medical records system. Of the 1321 cases, 65.9% accounted for medical insured patients and 34.1% were uninsured patients. The total inpatient medical expenditure of insured patients was RMB 29,509.1 Yuan and uninsured patients was RMB 22,114.3 Yuan, respectively. Payment modes, therapeutic options as well as the recurrence and metastasis of tumor toward the inpatient medical expenditures between the two groups were statistically significant. To the specifics, drug costs accounted for 37.7% and 33.8% of the total, surgery costs accounted for 21.5% and 25.5%, treatment costs accounted for 18.7% and 16.4%, whereas the costs of imaging and laboratory examinations accounted for 16.4% and 15.2% for the insured patient and uninsured patients, respectively. As the effects of covariates were controlled, the total hospitalization costs, drug costs, treatment costs as well as imaging and laboratory examination costs showed statistical significance. The total hospitalization costs, drug costs, treatment costs as well as imaging and laboratory examination costs of insured patient were 1.33, 1.42, 1.52, and 1.44 times of uninsured patients. CONCLUSIONS: The analysis of different payment modes toward the medical economic characteristics based on Gamma model is basically rational. Medical payment modes are having certain influence toward the hospitalization expenses of cervical cancer patients in an extent, as drug costs, treatment costs, and examination costs appear to be the main causes.
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Costos de la Atención en Salud , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Costos y Análisis de Costo , Femenino , Gastos en Salud , Humanos , Persona de Mediana Edad , Centros de Atención TerciariaRESUMEN
BACKGROUND: With the rising incidence as well as the medical expenditure among patients with unstable angina pectoris, the research aimed to investigate the inpatient medical expenditure through the combination of diagnosis-related groups (DRGs) among patients with unstable angina pectoris in a Grade A tertiary hospital to conduct the referential standards of medical costs for the diagnosis. METHODS: Single-factor analysis and multiple linear stepwise regression method were used to investigate 3933 cases between 2014 and 2016 in Beijing Hospital (China) whose main diagnosis was defined as unstable angina pectoris to determine the main factors influencing the inpatient medical expenditure, and decision tree method was adopted to establish the model of DRGs grouping combinations. RESULTS: The major influential factors of inpatient medical expenditure included age, operative method, therapeutic effects as well as comorbidity and complications (CCs) of the disease, and the 3933 cases were divided into ten DRGs by four factors: age, CCs, therapeutic effects, and the type of surgery with corresponding inpatient medical expenditure standards setup. Data of nonparametric test on medical costs among different groups were all significant (P < 0.001, by Kruskal-Wallis test), with R2 = 0.53 and coefficient of variation (CV) = 0.524. CONCLUSIONS: The classification of DRGs by adopting the type of surgery as the main branch node to develop cost control standards in inpatient treatment of unstable angina pectoris is conducive in standardizing the diagnosis and treatment behaviors of the hospital and reducing economic burdens among patients.
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Angina Inestable/economía , Gastos en Salud/estadística & datos numéricos , China , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Pacientes Internos/estadística & datos numéricos , Modelos Lineales , Masculino , Análisis MultivarianteAsunto(s)
Tecnología Biomédica , Política de Salud , China , Atención a la Salud , Manejo de la EnfermedadRESUMEN
BACKGROUND: The study was to explore the causes of high inpatient expenditure through analyzing the distribution characteristics as well as the influence factors of high inpatient expenditure cases during 3 years within a Grade-A tertiary hospital through various aspects and multiple angles, thus identifying the major influence factors for high medical expenditure to develop further research. METHODS: We retrospectively studied 2041 inpatient cases which cost more than RMB 100,000 Yuan per case in a Grade-A tertiary hospital from 2013 to 2015. We analyzed the compositions of the medical cost to evaluate the major factors that cause the high inpatient expenditure. All the data and materials were collected from medical record system, and the statistical methods included t-test, variance of analysis, and multivariate linear regression. RESULTS: The average cost of the 2,041 cases was RMB 152,173 Yuan for medicines and materials of medical costs, which respectively accounted for 33.03% and 32.32% of the total cost; and the average length of hospital stay was 28.39 days/person. Diseases of skeletal and muscular system, circulatory system, and tumor were the top three disease categories of high inpatient expenditure, which accounted for 39.00%, 33.46%, and 18.03%, respectively. Complications, criticality of the disease, gender of the patients, the occurrence of death, and the excessive length of hospital stay all had great impacts on average medical expenditure, while age, hospital infection, and surgery showed no significant impact on average medical cost. CONCLUSIONS: The main factors for high inpatient expenditure included the inadequate use of high-value medicines and materials, lacking cost control measures within the hospital, the excessive length of hospital stay for inpatients, and the unnecessary treatment for the patients.
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Gastos en Salud/estadística & datos numéricos , Hospitalización/economía , China , Femenino , Humanos , Pacientes Internos/estadística & datos numéricos , Tiempo de Internación/economía , Masculino , Análisis Multivariante , Estudios RetrospectivosRESUMEN
We aim to investigate the therapeutic effects of QSYQ on a pig myocardial ischemia (MI) model and to determine its mechanism of action. The MI model was induced by Ameroid constriction of the left anterior descending coronary (LAD) in Ba-Ma miniature pigs. Four groups were created: model group, digoxin group, QSYQ group, and sham-operated group. Heart function, Ang II, CGMP, TXB2, BNP, and cTnT were evaluated before (3 weeks after operation: 0 weeks) and at 2, 4, and 8 weeks after drug administration. After 8 weeks of administration, the pigs were sacrificed for cardiac injury measurements. Pigs with MI showed obvious histological changes, including BNP, cTnT, Ang II, CGRP, TXB2, and ET, deregulated heart function, and increased levels of apoptotic cells in myocardial tissue. Treatment with QSYQ improved cardiac remodeling by counteracting those events. The administration of QSYQ was accompanied by a restoration of heart function and of the levels of Ang II, CGRP, TXB2, ET BNP, and cTnT. In addition, QSYQ attenuated administration, reduced the apoptosis, and decreased the level of TNF- α and active caspase-3. In conclusion, administration of QSYQ could attenuate Ameroid constrictor induced myocardial ischemia, and TNF- α and active caspase-3 seemed to be the critical potential target of QSYQ.
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BACKGROUND: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias and atrial fibrillation. OBJECTIVE: The objective of the present study was to determine the pharmacokinetics (PK) of a pilsicainide hydrochloride injection in healthy Chinese adults. The study was conducted to meet China State Food and Drug Administration requirements for the marketing of the new generic formulation of pilsicainide hydrochloride. METHODS: This Phase I, randomized, parallel-group, open-label, single-dose PK study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of 0.25-, 0.50-, and 0.75-mg/kg pilsicainide hydrochloride with a 10-minute intravenous infusion. Serial blood and urine samples were collected up to 24 hours after dosing; drug concentrations in plasma and urine were then determined by using LC-MS/MS. The PK parameters of pilsicainide were calculated from the plasma concentration-time data according to noncompartmental methods. Safety profile was evaluated by monitoring adverse events, clinical laboratory parameters, and the results of 12-lead ECGs. RESULTS: Thirty healthy volunteers (mean [SD] age, 28.0 [4.95] years; weight, 59.3 [6.51] kg; height, 165.0 [7.25] cm; body mass index, 21.7 [1.94] kg/m(2)) were randomly divided into 3 groups, each consisting of 5 men and 5 women. After single-dose intravenous administration of 0.25, 0.50, and 0.75 mg/kg of pilsicainide hydrochloride, mean Cmax was 0.34 (0.11), 0.54 (0.15), and 1.05 (0.19) µg/mL, respectively; AUC0-24 was 0.76 (0.12), 1.61 (0.37), and 2.61 (0.46) h · µg/mL; and AUC0-∞ was 0.79 (0.13), 1.71 (0.46), and 2.72 (0.50) h · µg/mL. The ranges for t½z, CL, and Vz were 5.19 to 5.98 hours, 4.73 to 5.44 mL/min/kg, and 2.23 to 0.58 L/kg, respectively. The mean urinary recovery rate within 24 hours was 75.0% (12.0%), 65.0% (19.2%), and 66.4% (14.1%). Men and women had significantly different AUC0-24 values in the 0.50-mg/kg dose group (P = 0.044), and Vz showed significant differences between men and women in all 3 dose groups (P = 0.001). According to ECG parameters, PR intervals were significantly prolonged after administration at all 3 doses (P = 0.034, P < 0.001, and P = 0.034); no significant changes were seen in QRS width, QTc interval, or other parameters. CONCLUSIONS: Pilsicainide hydrochloride demonstrated linear PK, and the increase in the exposure of pilsicainide (AUC0-24 and AUC0-∞) was dose proportional after single doses of 0.25, 0.50, and 0.75 mg/kg. All 3 pilsicainide hydrochloride doses were well tolerated in these Chinese volunteers. ChiCTR-ONC-13003546.
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Antiarrítmicos/efectos adversos , Antiarrítmicos/farmacocinética , Medicamentos Genéricos/efectos adversos , Medicamentos Genéricos/farmacocinética , Lidocaína/análogos & derivados , Administración Intravenosa/efectos adversos , Adulto , Antiarrítmicos/administración & dosificación , Química Farmacéutica , China , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Lidocaína/administración & dosificación , Lidocaína/efectos adversos , Lidocaína/farmacocinética , MasculinoRESUMEN
OBJECTIVE: To investigate the dynamic expression of Heat shock protein 70 (Hsp70) in the lungs and plasma of rats with pulmonary fibrosis induced by silicon dioxide (SiO2). METHODS: Forty-eight Wistar rats were randomly divided into the control group exposed to normal solution and group exposed to SiO2 (50 mg/ml) with intratracheal injection. Each group was divided into four subgroups. The animals of SiO2 group and control group were sacrificed and lungs were collected on the 7th, 14th and 28th days after exposure, respectively. The left lung tissues were examined with the histopathologic HE staining. The expression and localization of Hsp70 protein in the lung tissues were examined with western blot assay and immunohistochemistry, respectively. The expression levels of Hsp70 protein in the plasma were measured by ELISA. RESULTS: The expression of Hsp70 in lung tissues of SiO2 group increased on the 7th day and reached the peak value on the 14th day then decreased, but still was significantly higher than that of the control group, the expression of Hsp70 in plasma of SiO2 group still was significantly higher than that of the control group (P < 0.05). The maximum expression level of Hsp70 in plasma of SiO2 group on the 21st day after exposure was 0.216 ± 0.027 µg/ml. CONCLUSION: The expression levels of Hsp70 protein in the lung tissues and plasma of the group exposed to SiO2 significantly increased, which were associated with the process of pulmonary fibrosis. It was suggested that Hsp70 protein may play an important biological role in the pulmonary fibrosis induced by SiO2.