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The reaction force of a large-aperture piezoelectric fast steering mirror (PFSM) has adverse coupling interference for the stability and pointing accuracy of laser beams, and the dynamic characteristics of the reaction force are coupled with the inner components of the PFSM. In order to compensate for and eliminate the reaction force, it is essential to accurately analyze the dynamic characteristics. In this paper, a simplified piezoelectric-coupling model of PFSM is established. The coupling mathematical equations for investigating the characteristics of the reaction force are deducted based on the piezoelectric constitutive equation and Hamiltonian's principle. Then the coupling characteristics of the reaction force are probed by a finite element (FE) piezoelectric-coupling method. The simulations for three large apertures' (250, 320, and 400 mm) FE models show that the reaction force has a linear positive correlation with the actuating voltage, and coupled with the materials of the central flexure hinge, the relationship between the reaction force and driving frequency is not completely quadratic. Experiments with the 320 mm aperture are completed, and the testing results are consistent with the mathematical model and the FE piezoelectric-coupling simulation. The dynamic characteristics of the reaction force demonstrated in this paper are significance for the accurate estimation of the reaction force, the design of compensation structure, and the optimization of algorithm for beam jitter controlling.
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Extensive use of neonicotinoids insecticides (NNIs) rapidly garnered widespread attention in the toxicology, since they have been found in human samples, including urine, blood, breast milk and hair. However, the precise mechanism is not completely clear regarding the NNIs-induced hepatotoxicity. In this study, we exposed male mice to three neonicotinoids (dinotefuran (DIN), nitenpyram (NIT) and acetamiprid (ACET) for 30 days. Our results showed that NNIs remarkably induced morphological damage in the liver. Simultaneously, we found that three neonicotinoids could activate the store operated Ca2+ entry (SOCE) in the liver. Further results confirmed that reactive oxide species (ROS) scavenger n-acetylcysteine (NAC) attenuated DIN-induced calcium ion (Ca2+) overload and S-phase arrest via restoring protein expression of SOCE and S phase related genes in L02 hepatocytes. Moreover, we found that NAC obviously combated mitochondrial dysfunction caused by DIN via restoring mitochondrial membrane potential. Meanwhile, DIN treatment significantly increased pyruvate content, impaired the activities of tricarboxylic acid (TCA) cycle rate-limiting enzymes and inhibited adenosine triphosphate (ATP) generation, but these effects were reversed by Serca specific activator CDN1163. Collectively, perturbation of redox states can be recognized as the center of S-phase arrest and Ca2+ overload after NNIs exposure. In this regard, Ca2+ homeostasis dysregulation is a causative event of mitochondrial bioenergetic dysfunction in the liver. These data provides a new perspective for understanding NNI-induced hepatotoxicity mechanisms.
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Environmental mercury is a concern for coastal ecosystem health, and exerts adverse effects on human health. Despite the growing body of evidence showing the hepatoprotective roles of curcumin on mercury, the knowledge between the macroscopic descriptions and the actual mechanism(s) underlying these processes is getting larger remains elusive. Herein, mice received single injection of mercuric chloride (HgCl2) (5 mg/kg body weight) and/or curcumin (50 mg/kg, body weight, p.o.). Firstly, the results showed curcumin could decline HgCl2-induced up-regulated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, we also found that curcumin could suppress inflammatory damage, unbalance of trace elements (including sodium, magnesium, kalium, calcium overload), oxidative burst induced by HgCl2, which could be associated with cytochrome P450 (CYP450) signaling. Secondly, we found that curcumin could prevent HgCl2-induced cell death both in vivo and in vitro. Furthermore, curcumin significantly increased the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and consequently upregulated the expression of heme oxygenase 1 (HO-1) under HgCl2 treatment. Meanwhile, inhibition of HO-1 by zinc protoporphyria could abolish the cytoprotective effects of curcumin in HgCl2-treated L02 hepatocytes. In conclusion, our data identify that curcumin could enhance Nrf2-mediated HO-1 to upregulate antioxidant ability, which might be associate with CYP450 signaling to suppress liver damage induced by HgCl2. The present study further enriches and perfects the mechanism theory of HgCl2 toxicity and suggest that the CYP450 signaling and Nrf2/HO-1 pathway is important in shedding light on curcumin's hepatoprotective effects in HgCl2 toxicity.
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Curcumina/farmacología , Sistema Enzimático del Citocromo P-450/metabolismo , Sustancias Peligrosas/toxicidad , Cloruro de Mercurio/toxicidad , Sustancias Protectoras/farmacología , Alanina Transaminasa/metabolismo , Animales , Antioxidantes/metabolismo , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Ecosistema , Hemo-Oxigenasa 1/genética , Hepatocitos/efectos de los fármacos , Humanos , Ratones , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacosRESUMEN
The reaction force of a fast steering mirror (FSM) directly transmits to the FSM's base, leading to dynamic coupling interference to the optical platform and degradation of laser beam quality in an adaptive optics system. In this paper a $\Phi {320}\;{\rm mm}$Φ320mm aperture symmetrically arranged reactionless FSM actuated by piezoelectric actuators was proposed. The corresponding dynamic equation about reaction force was established by rotational equation of Newton's second law, and the equilibrium condition of reaction force compensation was deduced. Then, the finite element (FE) piezoelectric-coupling method was used to simulate dynamic characteristics, which shows that the elimination ratios of the reaction force are 99% at low frequency (at 50 Hz) and 94.1% at high frequency (at 120 Hz). The experimental results show that the first resonance frequency of the FSM is 159.82 Hz, the tilting angle is $\pm {1.3}^\prime$±1.3', the reaction force at high frequency (at 120 Hz) is 112.95 N, and the elimination ratio of reaction force is 90.14%. The simulation and corresponding test results indicate that the developed reactionless FSM significantly eliminates reaction force and therefore improve the FSM's stability and pointing accuracy.
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Mercury (Hg) pollution poses global human health and environmental risks. However, still knowledge gaps exist on both exposures and health effects. Here, we combined transcriptome sequencing technique to further investigate the specific mechanisms of inorganic Hg toxicity in the kidney. Strikingly, transcriptomic analysis revealed that 4174 unigenes (including 2646 upregulated and 1528 downregulated unigenes) were differentially expressed under acute HgCl2 (5 mg/kg) exposure in the kidney. Additionally, we observed that HgCl2 selectively induced tumor necrosis factor superfamily (TNFSF) to participate in renal damage, which was consistent with the high-throughput sequencing data. The phenomenon is accompanied by NLRP3 inflammasome and NF-κB signal activation in the kidney. Simultaneously, ELISA results shown that TNF-α, IL-1ß and IL-6 concentrations in the kidney were significant increased. KEGG enrichment analysis showed that peroxisome proliferators-activated receptors (PPAR) signaling pathway might be vital toxic mechanism of Hg in the kidney. Then, our data showed that PPARγ agonist (GW 1929) attenuated HgCl2 (15 µg/ml)-induced apoptosis and NLRP3 inflammasome activation via decreasing translocation of NF-κB and increasing Bcl2 levels in vitro. Along with this, we demonstrated that PPARγ antagonists (GW9662) effectively aggravated HgCl2-induced nephrotoxicity. Overall, our results suggested that PPARγ signaling pathway is considered to be a protective mechanism to combat against HgCl2-triggered NLRP3 inflammasome activation and apoptosis.
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Contaminantes Ambientales/toxicidad , Inflamasomas/metabolismo , Riñón/efectos de los fármacos , Cloruro de Mercurio/toxicidad , FN-kappa B/metabolismo , PPAR gamma/agonistas , Transcriptoma/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Benzofenonas/farmacología , Regulación hacia Abajo , Humanos , Riñón/metabolismo , Riñón/patología , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transporte de Proteínas , Transducción de Señal , Tirosina/análogos & derivados , Tirosina/farmacología , Regulación hacia ArribaRESUMEN
OBJECTIVE: The purpose of this study is to evaluate the effectiveness and safety of percutaneous radiofrequency thermocoagulation (PRT) via the foramen rotundum (FR) for the treatment of isolated maxillary (V2) idiopathic trigeminal neuralgia (ITN) and assess the appropriate puncture angle through the anterior coronoid process to reach the FR. METHODS: Between January 2011 and October 2016, 87 patients with V2 ITN refractory to conservative treatment were treated by computed tomography (CT)-guided PRT via the FR at our institution. The outcome of pain relief was assessed by the visual analog scale (VAS) and Barrow Neurological Institute (BNI) pain grade and grouped as complete pain relief (BNI grades I-III) or unsuccessful pain relief (BNI grades IV-V). Recurrence and complications were also monitored and recorded. The puncture angle for this novel approach was assessed based on intraoperative CT images. RESULTS: Of the 87 treated patients, 85 (97.7%) achieved complete pain relief, and two patients (2.3%) experienced unsuccessful pain relief immediately after operation. During the mean follow-up period of 44.3 months, 15 patients (17.2%) experienced recurring pain. No severe complications occurred, except for hypoesthesia restricted to the V2 distribution in all patients (100%) and facial hematoma in 10 patients (11.5%). The mean puncture angle to reach the FR was 33.6° ± 5.7° toward the sagittal plane. DISCUSSION: CT-guided PRT via the FR for refractory isolated V2 ITN is effective and safe and could be a rational therapy for patients with V2 ITN.
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Ablación por Catéter/métodos , Nervio Maxilar/cirugía , Neuralgia del Trigémino/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor/métodos , Radiografía Intervencional , Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: We present a case involving an extensive epidural abscess that was successfully treated with computed tomography (CT)-guided percutaneous needle drainage and systemic antibiotic therapy. METHODS: A 44-year-old woman with a history of spine injection procedures complained of severe backache and progressive radiating pain in her right lower extremity followed by sensory deficits in her right lower limb. A laboratory examination revealed leukocytosis and hyperglycemia. Magnetic resonance imaging of the lumbar region revealed an extremely large posterior spinal epidural abscess (SEA) extending from L2 to S2. Because the patient did not respond to intravenous antibiotics alone, she underwent CT-guided percutaneous needle drainage and irrigation. RESULTS: Staphylococcus aureus was detected in the purulent material from this abscess. Her clinical symptoms were dramatically and immediately relieved after this procedure. She achieved complete neurological recovery after 2 months of antibiotic therapy. CONCLUSION: CT-guided percutaneous needle drainage and irrigation may be a rational treatment choice for patients with SEA with the exception of patients with a chronic abscess, an anterior abscess or discitis.
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Drenaje/métodos , Absceso Epidural/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto , Antibacterianos/uso terapéutico , Absceso Epidural/diagnóstico , Femenino , Humanos , Inyecciones Espinales/efectos adversos , Imagen por Resonancia Magnética , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/cirugía , Staphylococcus aureus/aislamiento & purificación , Irrigación Terapéutica/métodosRESUMEN
A meta-analysis was performed to investigate the outcomes between absorbable screw (AS) and metallic screw (MS) fixation for distal tibiofibular syndesmosis injuries (DTSIs). Randomized controlled trials comparing AS versus MS fixation in DTSIs were searched systematically, and the outcomes were analyzed using Review Manager Software, version 5.2. The risk ratio (RR) or mean difference with the 95% confidence interval (CI) was calculated using the fixed effects or random effects model. A total of 16 studies were included in the meta-analysis. No statistically significant difference was found between AS and MS fixation in excellent and good functional recovery rate (RR 1.11, 95% CI 1.00 to 1.23, I(2) = 60%, p = .06), infection (RR 1.66, 95% CI 0.73 to 3.79, I(2) = 0%, p = .23), incidence of pain (RR 0.68, 95% CI 0.24 to 1.92, I(2) = 12%, p = .47), screw broken (RR 0.31, 95% CI 0.03 to 2.93, I(2) = %, p = .31), heterotopic ossification (RR 1.93, 95% CI 0.21 to 17.62, I(2) = 51%, p = .56; 472 cases in 4 studies), fracture healing time (mean difference -1.88, 95% CI -3.51 to -0.26, I(2) = 93%, p = .02,), duration of operation time (mean difference 7.64, 95% CI -3.80 to 19.09, I(2) = 98%, p = .19). The incidence of foreign body reaction was higher with AS fixation (RR 6.07, 95% CI 2.54 to 14.50, I(2) = 0%, p < .001). The reoperation rate was higher with MS fixation (RR 0.08, 95% CI 0.03 to 0.18, I(2) = 77%, p < .01). The functional outcomes of AS were as good as those with MS for DTSIs. Other than the foreign body reaction, the complications occurring after AS fixation were not as serious as those with MS fixation. AS fixation might be a preferable alternative for reconstruction of DTSIs.
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Implantes Absorbibles , Fracturas de Tobillo/cirugía , Tornillos Óseos , Fijación Interna de Fracturas/instrumentación , Metales , Reacción a Cuerpo Extraño/etiología , Humanos , Complicaciones PosoperatoriasRESUMEN
OBJECTIVE: To systematically evaluate the effectiveness and safety of transforaminal lumbar interbody fusion (TLIF) versus posterior lumbar interbody fusion (PLIF) for lumbar degenerative diseases (LDD). METHODS: Databases including Th e Cochrane Library, PubMed, EMbase,MEDLINE, SCI, CNKI, CBM, WanFang Data were searched to collect the randomized controlled trails (RCTs) and non-RCTs regarding TLIF versus PLIF for LDD. The retrieval time was from early available time to February 2014. The search was followed the inclusion and exclusion criteria. The data were collected and evaluated by 2 reviewers independently. The Meta analysis was conducted by using RevMan 5.2 software. RESULTS: A total of 7 RCTs and 8 non-RCTs involving 1 127 patients were included. The results of Meta-analysis showed that there were significant difference in visual analog score (VAS) [MD=-0.54, 95% CI (-0.79, -0.29), P<0.001], Oswestry disability index (ODI) [MD=-4.20, 95%CI (-6.16, -2.25), P<0.001], intraoperative blood [MD=-170.98, 95% CI (-225.10, -116.85), P< 0.001], duration of operation [MD=3.18, 95% CI (-8.21, 14.56), P=0.58] and Hospital stays [MD=-3.08, 95% CI (-3.03, -1.57), P=0.0003] between the PLIF and Wiltse- TLIF groups. CONCLUSION: Wiltse-TLIF is superior to PLIF in treating LDD, with less operative blood loss, shorter hospital stays and lower postoperative complications. Thus, Wiltse-TLIF is safe and feasible for treating LDD as the indications are under strict control.
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Enfermedades Óseas/cirugía , Vértebras Lumbares/cirugía , Región Lumbosacra/cirugía , Fusión Vertebral/métodos , Pérdida de Sangre Quirúrgica , Humanos , Vértebras Lumbares/patología , Complicaciones Posoperatorias , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in hematogenous dissemination of tumor cells. Abundant platelets were detected in the tumor microenvironment outside of the blood vessel, thus, platelet -tumor cell interaction outside of the bloodstream may play a role in regulating primary tumor growth and metastasis initiation. However, it is unclear that platelet depletion affects tumor vessel structure and dynamics. METHODS: Using thrombocytopenia induction in two different tumor-bearing mouse models, tumor tissues were performed by Westernblotting and immunohistochemical staining. Vascular permeability was evaluated by determination of intratumoral Evans blue and Miles vascular permeability assay. Furthermore, microdialysis was used to examining the intratumoral extracellular angiogenic growth factors (VEGF, TGF-ß) by ELISA. RESULTS: Platelet depletion showed no change in tumor growth and reduced lung metastasis. Platelet depletion led to reduced tumor hypoxia and Met receptor activation and was associated with a decreased release of MMP-2, 9, PAI-1, VEGF, and TGF-ß. Tumor vessels in platelet-depleted mice showed impaired vessel density and maturation. CONCLUSIONS: Our findings demonstrate that platelets within the primary tumor microenvironment play a critical role in the induction of vascular permeability and initiation of tumor metastasis.
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Plaquetas/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Neovascularización Patológica , Inductores de la Angiogénesis/metabolismo , Animales , Plaquetas/patología , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patología , Permeabilidad Capilar , Modelos Animales de Enfermedad , Hipoxia , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares/secundario , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Melanoma Experimental , Ratones , Metástasis de la Neoplasia , Inhibidor 1 de Activador Plasminogénico/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Carga TumoralRESUMEN
Drugs are an effective way to treat various diseases. Some diseases are so complicated that the effect of a single drug for such diseases is limited, which has led to the emergence of combination drug therapy. The use multiple drugs to treat these diseases can improve the drug efficacy, but it can also bring adverse effects. Thus, it is essential to determine drug-drug interactions (DDIs). Recently, deep learning algorithms have become popular to design DDI prediction models. However, most deep learning-based models need several types of drug properties, inducing the application problems for drugs without these properties. In this study, a new deep learning-based model was designed to predict DDIs. For wide applications, drugs were first represented by commonly used properties, referred to as fingerprint features. Then, these features were perfectly fused with the drug interaction network by a type of graph convolutional network method, GraphSAGE, yielding high-level drug features. The inner product was adopted to score the strength of drug pairs. The model was evaluated by 10-fold cross-validation, resulting in an AUROC of 0.9704 and AUPR of 0.9727. Such performance was better than the previous model which directly used drug fingerprint features and was competitive compared with some other previous models that used more drug properties. Furthermore, the ablation tests indicated the importance of the main parts of the model, and we analyzed the strengths and limitations of a model for drugs with different degrees in the network. This model identified some novel DDIs that may bring expected benefits, such as the combination of PEA and cannabinol that may produce better effects. DDIs that may cause unexpected side effects have also been discovered, such as the combined use of WIN 55,212-2 and cannabinol. These DDIs can provide novel insights for treating complex diseases or avoiding adverse drug events.
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Algoritmos , Cannabinol , Interacciones Farmacológicas , MorfolinasRESUMEN
FGFR1 is a receptor tyrosine kinase deregulated in certain breast cancers (BCs) with a poor prognosis. Although FGFR1-activated phosphorylation cascades have been mapped, the key genes regulated by FGFR1 in BC are largely unclear. FOXQ1 is an oncogenic transcription factor. Although we found that activation of FGFR1 robustly upregulated FOXQ1 mRNA, how FGFR1 regulates FOXQ1 gene expression and whether FOXQ1 is essential for FGFR1-stimulated cell proliferation are unknown. Herein, we confirmed that activation of FGFR1 robustly upregulated FOXQ1 mRNA and protein in BC cells. Knockdown of FOXQ1 blocked the FGFR1 signaling-stimulated BC cell proliferation, colony formation, and xenograft tumor growth. Inhibition of MEK or ERK1/2 activities, or knockout of ERK2 but not ERK1 suppressed the FGFR1 signaling-promoted FOXQ1 gene expression. Inhibition of ERK2 in ERK1 knockout cells blocked, while ectopic expression of FOXQ1 in ERK2 knockout cells rescued the FGFR1-signaling-promoted cell growth. Mechanistically, c-FOS, an early response transcription factor upregulated by the FGFR1-MEK-ERK2 pathway, bound to the FOXQ1 promoter to mediate the FGFR1 signaling-promoted FOXQ1 expression. These results indicate that the FGFR1-ERK2-c-FOS-FOXQ1 regulatory axis plays an essential role in the FGFR1 signaling-promoted BC growth. Targeting ERK2 and FOXQ1 should block BC growth caused by a deregulated FGFR1 signaling.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Transducción de Señal/genética , Mama/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Línea Celular Tumoral , Factores de Transcripción Forkhead/metabolismo , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismoRESUMEN
Health policies are regarded as a governance mechanism crucial for reducing health inequity and improving overall health outcomes. Policies that address chronic conditions or health inequity suggest a governance shift toward active health over past decades. However, the current literature in health policy largely focused on some specific health policy changes and their tangible outcomes, or on specific inequality of health policies in gender, age, racial, or economic status, short of comprehensively responding to and addressing the shift. This is exacerbated further by a common confusion that equates health policy with health care policy, which has been burdened by increased population ageing, growing inequalities, rising expenditures, and growing social expectations. This study conducted a narrative literature review to comprehensively and critically analyze the most current knowledge on health policy in order to help us establish a theoretical framework on active health governance. The comprehensive framework proposed in this paper identifies the main elements of a well-defined active health governance and the interactions between these elements. The proposed framework is composed of four elements (governance for health, social determinants of health, lifestyle determinants of health, and health system) and three approaches (whole-of-government approach, whole-of-society approach, and lifespan/life-course approach) that are dynamically interacted to achieve two active health outcomes (health equity and health improvement). The framework provides a conceptual solution to the issues of current literature on health policy and practically serves as a new guide for health policymaking.
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Equidad en Salud , Formulación de Políticas , Gobierno , Política de Salud , Factores SocioeconómicosRESUMEN
Combination drug therapy is an efficient way to treat complicated diseases. Drug-drug interaction (DDI) is an important research topic in this therapy as patient safety is a problem when two or more drugs are taken at the same time. Traditionally, in vitro experiments and clinical trials are common ways to determine DDIs. However, these methods cannot meet the requirements of large-scale tests. It is an alternative way to develop computational methods for predicting DDIs. Although several previous methods have been proposed, they always need several types of drug information, limiting their applications. In this study, we proposed a simple computational method to predict DDIs. In this method, drugs were represented by their fingerprint features, which are most widely used in investigating drug-related problems. These features were refined by three models, including addition, subtraction, and Hadamard models, to generate the representation of DDIs. The powerful classification algorithm, random forest, was picked up to build the classifier. The results of two types of tenfold cross-validation on the classifier indicated good performance for discovering novel DDIs among known drugs and acceptable performance for identifying DDIs between known drugs and unknown drugs or among unknown drugs. Although the classifier adopted a sample scheme to represent DDIs, it was still superior to other methods, which adopted features generated by some advanced computer algorithms. Furthermore, a user-friendly web-server, named DDIPF (http://106.14.164.77:5004/DDIPF/), was developed to implement the classifier.
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Algoritmos , Proyectos de Investigación , Interacciones Farmacológicas , Quimioterapia Combinada , HumanosRESUMEN
OBJECTIVE: To examine the clinical outcomes of a percutaneous lumbar transforaminal endoscopic discectomy (PTED) with intraoperative computed tomography (iCT) navigation for the treatment of L5-S1 far-lateral lumbar disc herniation (LDH). METHODS: A total of 30 patients with L5-S1 far-lateral LDH who underwent PTED with iCT navigation from September 2016 to October 2020 were enrolled in this study. Outcomes were assessed using the visual analog scale pain score, the Oswestry Disability Index, the Japanese Orthopedic Association score, the EQ-5D-5 L and the modified Macnab criteria. Preoperative and postoperative complications were recorded. RESULTS: The mean visual analog scale score for leg pain improved from 8.1 at baseline to 2.3, 0.9, 0.7 and 0.9 at 1 day, 1 week, 6 months, and 12 months postoperatively, respectively (P < 0.01). The mean Oswestry Disability Index improved from 78.1% at baseline to 45.5%, 21.9%, 12.6%, and 11.7% at 1 week, 1 month, 6 months, and 12 months postoperatively, respectively (P < 0.01); and the mean Japanese Orthopedic Association score improved from 8.6 at baseline to 14.2, 20.2, 24.4, and 25.6 at 1 day, 1 week, 6 months, and 12 months postoperatively, respectively (P < 0.01). At 12 months postoperatively, the EQ-5D-5 L value significantly increased, from -0.061 ± 0.138 to 0.903 ± 0.064. The rate of a good or excellent modified Macnab result was 93% (26/28) at 12 months postoperatively. In the present study, combined L5-S1 foraminal stenosis tended to lead poor outcomes, which required more postsurgical treatments. CONCLUSIONS: With iCT navigation, PTED is a feasible and effective minimally invasive surgery for L5-S1 far-lateral LDH.
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Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Discectomía/métodos , Discectomía Percutánea/métodos , Endoscopía/métodos , Humanos , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Dolor/cirugía , Estudios Retrospectivos , Tomografía , Resultado del TratamientoRESUMEN
The repair of spinal cord injury (SCI) is still a tough clinical challenge and needs innovative therapies. Mitochondrial function is significantly compromised after SCI and has emerged as an important factor causing neuronal apoptosis and hindering functional recovery. In this study, umbilical cord mesenchymal stem cells (UCMSC), which are promising seed cells for nerve regeneration, and basic fibroblast growth factor (bFGF) that have been demonstrated to have a variety of effects on neural regeneration were jointly immobilized in extracellular matrix (ECM) and heparin-poloxamer (HP) to create a polymer bioactive system that brings more hope and possibility for the treatment of SCI. Our results in vitro and in vivo showed that the UCMSC-bFGF-ECM-HP thermosensitive hydrogel has good therapeutic effects, mainly in reducing apoptosis and improving the mitochondrial function. It showed promising utility for the functional recovery of impaired mitochondrial function by promoting mitochondrial fusion, reducing pathological mitochondrial fragmentation, increasing mitochondrial energy supply, and improving the metabolism of MDA, LDH, and ROS. In addition, we uncovered a distinct molecular mechanism underlying the protective effects associated with activating p21-activated kinase 1 (PAK1) and mitochondrial sirtuin 4 (SIRT4) by the UCMSC-bFGF-ECM-HP hydrogel. The expansion of new insights into the molecular relationships between PAK1 and SIRT4, which links the mitochondrial function in SCI, can lay the foundation for future applications and help to provide promising interventions of stem-cell-based biological scaffold therapies and potential therapeutic targets for the clinical formulation of SCI treatment strategies.
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Traumatismos de la Médula Espinal , Regeneración de la Medula Espinal , Animales , Heparina/uso terapéutico , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Mitocondrias/metabolismo , Poloxámero/uso terapéutico , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: As a type of breast cancer that has relatively strong invasiveness, triple negative breast cancer (TNBC) seriously affects the survival of patients. microRNAs (miRNAs) have been shown to exert a prominent regulatory effect on the disease, among which miR-133b is reported to be involved in the pathological mechanism of breast cancer, but its role in TNBC remains unclear. METHODS: In this study, real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were performed for detecting the expressions of miR-133b, fibroblast growth factor receptor 1 (FGFR1), and Wingless/Integrated (Wnt)-ß-catenin pathway markers (Wnt1, ß-catenin, nuclear-ß-catenin, p-GSK-3ß, GSK-3ß, cyclinD1, and FOXQ1). With TNBC cells and DDP-resistant TNBC cells (TNBC/DDP cells) used as research objects, their proliferation and apoptosis were measured by Cell Counting Kit-8 (CCK-8) assays and Flow cytometry, respectively. Then, the targeted relationship between miR-133b and FGFR1 was verified by Dual luciferase reporter gene assay (DLRGA). RESULTS: In our study, miR-133b was down-regulated while FGFR1 up-regulated in TNBC. The ectopic expression of miR-133b remarkably inhibited the proliferation and colony formation but induced apoptosis of TNBC cells, and inactivated the Wnt-ß-catenin pathway. The knockdown of FGFR1 had similar effects. Additionally, miR-133b targeted and negatively regulated FGFR1. Up-regulating miR-133b or down-regulating FGFR1 could enhance the proliferation and DDP sensitivity of TNBC cells or TNBC/DDP cells. Up-regulating FGFR1 could offset the anti-TNBC cell survival and DDP sensitization shown by ectopic expression of miR-133b. CONCLUSION: To sum up, miR-133b can inhibit the growth and DDP resistance of TNBC cells by targeting FGFR1 and inactivating the Wnt-ß-catenin pathway.
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BACKGROUND: Percutaneous full-endoscopic surgery was recently developed for the treatment of cervical foraminal stenosis and posterolateral disc herniation. However, there are no studies involving endoscopic surgery to treat cervical spondylotic myelopathy (CSM). OBJECTIVES: To observe the safety, feasibility, and efficacy of posterolateral full-endoscopic ventral decompression (PLEVD) via computed tomography (CT)-guided surgery in patients with single-level CSM. STUDY DESIGN: A prospective cohort study. SETTING: The First Affiliated Hospital of Gannan Medical College. METHODS: From May 2018 to August 2019, 21 patients with single-level CSM underwent CT-guided PLEVD. The posterolateral angle was measured during surgery. The neurologic condition was evaluated via the Japanese Orthopaedic Association (JOA) score and recovery rate, and a Visual Analog Scale (VAS) was used to measure pain relief. The maximum spinal canal diameter (MSCD) was measured on pre- and postoperative CT images. RESULTS: The mean length of follow-up was 11.3 ± 5.3 months. The average posterolateral angle was 36.0° ± 5.6°. The mean VAS score of limbs significantly decreased after surgery. The mean JOA score improved during the follow-up period. Nineteen of the 21 patients achieved good or excellent outcomes, and 2 patients had fair outcomes according to the JOA score 6 months after surgery. The average MSCD was enlarged from 0.55 ± 0.15 cm preoperatively to 1.02 ± 0.18 cm postoperatively. LIMITATIONS: This study was nonrandomized and provides only preliminary clinical results for single-level CSM. CONCLUSION: Under appropriate indications, PLEVD under CT guidance is an available and safe technique for treating single-level CSM.
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Vértebras Cervicales/cirugía , Descompresión Quirúrgica/métodos , Enfermedades de la Médula Espinal/cirugía , Adulto , Anciano , Vértebras Cervicales/diagnóstico por imagen , Endoscopía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Enfermedades de la Médula Espinal/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Escala Visual AnalógicaRESUMEN
BACKGROUND: More evidence is required to support that computerized tomography navigation percutaneous spinal endoscopy in the treatment of highly migrated lumbar disc herniation is a more minimally invasive surgery than open discectomy . OBJECTIVE: To quantitatively evaluate the efficacy and minimal invasiveness of computerized tomography navigation percutaneous spinal endoscopy and open discectomy in highly migrated lumbar disc herniation. STUDY DESIGN: A prospective randomized study. SETTING: First Affiliated Hospital of Gannan Medical College. METHODS: From August 2016 to February 2020, 68 patients with highly migrated lumbar disc herniation had undergone discectomy. Thirty-five of them randomly received computerized tomography (CT) navigation percutaneous spinal endoscopy at the pain department (CT navigation percutaneous spinal endoscopy group), and 33 patients received open discectomy at the orthopedics department (open discectomy group). The Visual Analog Scale (VAS) score, Japanese Orthopaedic Association (JOA) score, and modified MacNab criteria were applied to evaluate the clinical situations pre- and post-operation. The serum concentrations of IL-6, TNF-alpha, creatine phosphokina (CPK), and C-reactive protein (CRP) in the 2 groups were quantitatively measured. RESULTS: The postoperative VAS scores of the back and lower extremity were lower than those pre-operation in both groups, while the VAS score of back pain in the open discectomy group was significantly higher than that in the CT navigation percutaneous spinal endoscopy group at one week post-operation (P < 0.01). The postoperative JOA scores were significantly higher than those pre-operation in both groups. The serum concentrations of IL-6, TNF-alpha, CPK, and CRP in the open discectomy group were higher than those in the computerized tomography navigation percutaneous spinal endoscopy group postoperatively (P < 0.01). LIMITATIONS: This is a single-center randomized study and with the limitation of the sample size. CONCLUSION: CT navigation percutaneous spinal endoscopy is a more minimally invasive surgery than open discectomy.Certificate number for the medical institution conducting the clinical trials for humans in China: 934.
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Discectomía Percutánea , Dolor de Espalda , Humanos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estudios Prospectivos , Tomografía Computarizada por Rayos XRESUMEN
INSTRUCTION: Despite the continuous advancement of liver cancer diagnosis technology and level, there are still nearly two-thirds of patients with primary liver cancer that are already advanced at the time of diagnosis. Ultrasound-guided microwave ablation, as a palliative treatment for intermediate and advanced liver cancer, is currently recognized internationally Standard treatment for patients with unresectable hepatocellular carcinoma. However, recently, some scholars hold that ultrasound-guided microwave ablation does not guarantee complete inactivation of tumor lesions. METHODS/DESIGN: This study will evaluate the safety and effectiveness of ultrasound-guided microwave ablation in patients with advanced hepatocellular carcinoma through retrospective analysis. This study will follow a clinical research method with consecutive enrollment. The overall survival rate, objective tumor remission rate, serum indices and incidence of adverse effects after treatment will be counted for patients. DISCUSSION: At present, there are no good treatment options for intermediate and advanced hepatocellular carcinoma. Therefore, there is a strong demand to explore the individualized multidisciplinary combined treatment model based on ultrasound-guided microwave ablation. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2100052107, Registered on 17 October 2021.