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Simultaneous localization and mapping (SLAM) algorithms are widely applied in fields such as autonomous driving and target tracking. However, the effect of moving objects on localization and mapping remains a challenge in natural dynamic scenarios. To overcome this challenge, this paper proposes an algorithm for dynamic point cloud detection that fuses laser and visual identification data, the multi-stage moving object identification algorithm (MoTI). The MoTI algorithm consists of two stages: rough processing and precise processing. In the rough processing stage, a statistical method is employed to preliminarily detect dynamic points based on the range image error of the point cloud. In the precise processing stage, the radius search strategy is used to statistically test the nearest neighbor points. Next, visual identification information and point cloud registration results are fused using a method of statistics and information weighting to construct a probability model for identifying whether a point cloud cluster originates from a moving object. The algorithm is integrated into the front-end of the LOAM system, which significantly improves the localization accuracy. The MoTI algorithm is evaluated on an actual indoor dynamic environment and several KITTI datasets, and the results demonstrate its ability to accurately detect dynamic targets in the background and improve the localization accuracy of the robot.
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This paper is concerned with the problem of state estimation for nonlinear multi-sensor systems with cross-correlated noise and packet loss compensation. In this case, the cross-correlated noise is modeled by the synchronous correlation of the observation noise of each sensor, and the observation noise of each sensor is correlated with the process noise at the previous moment. Meanwhile, in the process of state estimation, since the measurement data may be transmitted in an unreliable network, data packet dropout will inevitably occur, leading to a reduction in estimation accuracy. To address this undesirable situation, this paper proposes a state estimation method for nonlinear multi-sensor systems with cross-correlated noise and packet dropout compensation based on a sequential fusion framework. Firstly, a prediction compensation mechanism and a strategy based on observation noise estimation are used to update the measurement data while avoiding the noise decorrelation step. Secondly, a design step for a sequential fusion state estimation filter is derived based on an innovation analysis method. Then, a numerical implementation of the sequential fusion state estimator is given based on the third-degree spherical-radial cubature rule. Finally, the univariate nonstationary growth model (UNGM) is combined with simulation to verify the effectiveness and feasibility of the proposed algorithm.
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OBJECTIVE: To construct an auxiliary scoring model for myelosuppression in patients with lung cancer undergoing chemotherapy based on a random forest algorithm, and to evaluate the predictive performance of the model. METHODS: Patients with lung cancer who received chemotherapy in Shanxi Province Cancer Hospital from January 2019 to January 2022 were retrospectively selected as research subjects, and their general demographic information, disease-related indicators, and laboratory test results before chemotherapy were collected. Patients were divided into a training set (136 cases) and a validation set (68 cases) in a ratio of 2:1. R software was used to establish a scoring model of myelosuppression in lung cancer patients in the training set, and the receiver operating characteristic curve, accuracy, sensitivity, and balanced F-score were used in the two data sets to evaluate the predictive performance of the model. RESULTS: Among the 204 lung cancer patients enrolled, 75 patients developed myelosuppression during the follow-up period after chemotherapy, with an incidence of 36.76%. The factors in the constructed random forest model were ranked in order of age (23.233), bone metastasis (21.704), chemotherapy course (19.259), Alb (13.833), and gender (11.471) according to the mean decrease accuracy. The areas under the curve of the model in the training and validation sets were 0.878 and 0.885, respectively (all P < 0.05). The predictive accuracy of the validated model was 82.35%, the sensitivity and specificity were 84.00% and 81.40%, respectively, and the balanced F-score was 77.78% (all P < 0.05). CONCLUSION: The risk assessment model for the occurrence of myelosuppression in patients with lung cancer chemotherapy based on a random forest algorithm can provide a reference for the accurate identification of high-risk patients.
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INTRODUCTION: Major depressive disorder (MDD) has been found to be nearly twice as prevalent in females as in males. One hypothesis proposed that abused females were particularly prone to MDD. We aim to examine the sex-specific associations between various types of childhood trauma and MDD. METHODS: In this study, 290 outpatients diagnosed with MDD were recruited from Beijing Anding Hospital, and 290 healthy volunteers were recruited from neighborhoods nearby the hospital, with sex, age, and family history matched. Childhood Trauma Questionnaire-Short Form (CTQ-SF) developed by Bernstein et al. was used to assess the severity of five different types of childhood abuse and neglect. McNemar's test and conditional logistic regression models with potential confounders (i.e., marital status, educational level, and body mass index) controlled were used to explore the sex-specific associations between different types of childhood maltreatment and MDD. RESULTS: In the full sample, patients with MDD showed a significant higher rate of any childhood maltreatment (i.e., emotional abuse, sexual abuse, physical abuse, emotional neglect, and physical neglect). Among females, all types of childhood abuse were statistically significant. For males, significant differences were only found in emotional abuse and in emotional neglect. CONCLUSION: It would appear that MDD in the outpatients is associated with any type of childhood trauma in women and emotional abuse or neglect in men.
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Maltrato a los Niños , Trastorno Depresivo Mayor , Masculino , Humanos , Niño , Femenino , Trastorno Depresivo Mayor/epidemiología , Estudios de Casos y Controles , Maltrato a los Niños/psicología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Clinically, Charcot-Marie-Tooth disease (CMT)-associated muscle atrophy still lacks effective treatment. Deletion and mutation of L-periaxin can be involved in CMT type 4F (CMT4F) by destroying the myelin sheath form, which may be related to the inhibitory role of Ezrin in the self-association of L-periaxin. However, it is still unknown whether L-periaxin and Ezrin are independently or interactively involved in the process of muscle atrophy by affecting the function of muscle satellite cells. METHOD: A gastrocnemius muscle atrophy model was prepared to mimic CMT4F and its associated muscle atrophy by mechanical clamping of the peroneal nerve. Differentiating C2C12 myoblast cells were treated with adenovirus-mediated overexpression or knockdown of Ezrin. Then, overexpression of L-periaxin and NFATc1/c2 or knockdown of L-periaxin and NFATc3/c4 mediated by adenovirus vectors were used to confirm their role in Ezrin-mediated myoblast differentiation, myotube formation and gastrocnemius muscle repair in a peroneal nerve injury model. RNA-seq, real-time PCR, immunofluorescence staining and Western blot were used in the above observation. RESULTS: For the first time, instantaneous L-periaxin expression was highest on the 6th day, while Ezrin expression peaked on the 4th day during myoblast differentiation/fusion in vitro. In vivo transduction of adenovirus vectors carrying Ezrin, but not Periaxin, into the gastrocnemius muscle in a peroneal nerve injury model increased the numbers of muscle myosin heavy chain (MyHC) I and II type myofibers, reducing muscle atrophy and fibrosis. Local muscle injection of overexpressed Ezrin combined with incubation of knockdown L-periaxin within the injured peroneal nerve or injection of knockdown L-periaxin into peroneal nerve-injured gastrocnemius muscle not only increased the number of muscle fibers but also recovered their size to a relatively normal level in vivo. Overexpression of Ezrin promoted myoblast differentiation/fusion, inducing increased MyHC-I+ and MyHC-II + muscle fiber specialization, and the specific effects could be enhanced by the addition of adenovirus vectors for knockdown of L-periaxin by shRNA. Overexpression of L-periaxin did not alter the inhibitory effects on myoblast differentiation and fusion mediated by knockdown of Ezrin by shRNA in vitro but decreased myotube length and size. Mechanistically, overexpressing Ezrin did not alter protein kinase A gamma catalytic subunit (PKA-γ cat), protein kinase A I alpha regulatory subunit (PKA reg Iα) or PKA reg Iß levels but increased PKA-α cat and PKA reg II α levels, leading to a decreased ratio of PKA reg I/II. The PKA inhibitor H-89 remarkably abolished the effects of overexpressing-Ezrin on increased myoblast differentiation/fusion. In contrast, knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by an increased PKA reg I/II ratio, and the inhibitory effects could be eliminated by the PKA reg activator N6-Bz-cAMP. Meanwhile, overexpressing Ezrin enhanced type I muscle fiber specialization, accompanied by an increase in NFATc2/c3 levels and a decrease in NFATc1 levels. Furthermore, overexpressing NFATc2 or knocking down NFATc3 reversed the inhibitory effects of Ezrin knockdown on myoblast differentiation/fusion. CONCLUSIONS: The spatiotemporal pattern of Ezrin/Periaxin expression was involved in the control of myoblast differentiation/fusion, myotube length and size, and myofiber specialization, which was related to the activated PKA-NFAT-MEF2C signaling pathway, providing a novel L-Periaxin/Ezrin joint strategy for the treatment of muscle atrophy induced by nerve injury, especially in CMT4F.
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Enfermedad de Charcot-Marie-Tooth , Neuropatía Hereditaria Motora y Sensorial , Humanos , Atrofia Muscular , Diferenciación Celular , Fibras Musculares EsqueléticasRESUMEN
We aimed to explore whether superfluous sympathetic activity affects myoblast differentiation, fusion, and myofiber types using a continuous single-dose isoprenaline exposure model in vitro and to further confirm the role of distinct NFATs in ISO-mediated effects. Compared with delivery of single and interval single, continuous single-dose ISO most obviously diminished myotube size while postponing myoblast differentiation/fusion in a time- and dose-dependent pattern, accompanied by an apparent decrease in nuclear NFATc1/c2 levels and a slight increase in nuclear NFATc3/c4 levels. Overexpression of NFATc1 or NFATc2, particularly NFATc1, markedly abolished the inhibitory effects of ISO on myoblast differentiation/fusion, myotube size and Myh7 expression, which was attributed to a remarkable increase in the nuclear NFATc1/c2 levels and a reduction in the nuclear NFATc4 levels and the associated increase in the numbers of MyoG and MEF2C positive nuclei within more than 3 nuclei myotubes, especially in MEF2C. Moreover, knockdown of NFATc3 by shRNA did not alter the inhibitory effect of ISO on myoblast differentiation/fusion or myotube size but partially recovered the expression of Myh7, which was related to the slightly increased nuclear levels of NFATc1/c2, MyoG and MEF2C. Knockdown of NFATc4 by shRNA prominently increased the number of MyHC +, MyoG or MEF2C + myoblast cells with 1 ~ 2 nuclei, causing fewer numbers and smaller myotube sizes. However, NFATc4 knockdown further deteriorated the effects of ISO on myoblast fusion and myotube size, with more than 5 nuclei and Myh1/2/4 expression, which was associated with a decrease in nuclear NFATc2/c3 levels. Therefore, ISO inhibited myoblast differentiation/fusion and myotube size through the NFAT-MyoG-MEF2C signaling pathway.
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Fibras Musculares Esqueléticas , Transducción de Señal , Isoproterenol/farmacología , Isoproterenol/metabolismo , Diferenciación Celular , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , ARN Interferente Pequeño/metabolismoRESUMEN
Objective: Determine the predictive value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) combined with echocardiography in the diagnosis of anthracyclines-induced chronic cardiotoxicity. Methods: A total of 80 female breast cancer patients from January 2019 to October 2021 were included in our hospital. Twenty-six patients with cardiotoxicity were divided into the cardiac impairment group, and the 54 patients without cardiotoxicity were classified into the normal control group. NT-proBNP levels and cardiac echocardiography were measured before the start of the chemotherapy cycle, in cycle 3 of the chemotherapy, and after the chemotherapy cycle in all patients. Results: After three cycles of chemotherapy and chemotherapy, the levels of NT-proBNP in patients of the two groups were significantly higher than those before chemotherapy (P < 0.05). The levels of NT-proBNP in the cardiac injury group after three cycles of chemotherapy and chemotherapy were higher than those in the normal control group at the same time point (P < 0.05). The LVEF of patients in the cardiac impairment group after chemotherapy was lower than that before chemotherapy, and the LVEF after chemotherapy was lower than that in the normal control group (P < 0.05). NT-proBNP had a negative correlation with LVEF (r = -0.549, P < 0.001). The AUC of NT-proBNP in combination with LVEF for predicting cardiotoxicity in our patient was 0.898(95%CI:0.829-0.966). Conclusion: NT-proBNP combined with echocardiography has clinical significance in the detection of anthracyclines-induced cardiotoxicity, and it can detect early myocardial injury induced by anthracyclines, with early prediction value. It is important to protect heart function and judge prognosis.
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The aim of this study was to evaluate the outcomes of surgical treatment of intra-articular calcaneal fractures by using the sinus tarsi approach combined with percutaneous medial reduction by leverage technique and percutaneous screw fixation. We assessed the outcomes of 29 patients treated using sinus tarsi approach with percutaneous screw fixation. All patients were evaluated both clinically and radiologically. The Böhler and Gissane angle were evaluated postoperatively using radiographs. During the median follow-up period of 27.0 ± 10.3 months, no cases with failure to reduce or displace hardware were detected. All cases achieved the restoration of a normal Böhler and Gissane angle. The median preoperative Böhler angle was 12.3° ± 2.5° while postoperatively it was 30.5° ± 5.7° (p < .01). The median preoperative Gissane angle was 98.1° ± 7.5°, which was 125.9° ± 3.6° postoperatively (p < .01). At the last follow-up, the median American Orthopedic Foot and Ankle Society hindfoot score was 87.7 ± 5.9, and the median Maryland foot score was 88.6 ± 5.9. Our technique for intra-articular calcaneal fractures can effectively correct calcaneal tuberosity outward displacement, medial wall overlapping, and the hindfoot varus deformity with less soft tissue damage. This technique is a good alternative for the treatment of calcaneal fractures, resulting in minimal soft tissue damage, few wound complications, and excellent radiological and clinical outcomes.
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Traumatismos del Tobillo , Calcáneo , Traumatismos de los Pies , Fracturas Óseas , Fracturas Intraarticulares , Traumatismos de la Rodilla , Traumatismos del Tobillo/etiología , Placas Óseas , Tornillos Óseos , Calcáneo/diagnóstico por imagen , Calcáneo/cirugía , Traumatismos de los Pies/etiología , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/etiología , Fracturas Óseas/cirugía , Talón/cirugía , Humanos , Fracturas Intraarticulares/diagnóstico por imagen , Fracturas Intraarticulares/cirugía , Resultado del TratamientoRESUMEN
OBJECTIVES: To observe and analyse the efficacy of retrograde sural neurofasciocutaneous flap repair combined with Jingulian capsules to treat foot and ankle soft tissue defects. METHODS: One hundred and eighty patients with foot and ankle soft tissue defects were enrolled in the study from January 2016 to June 2019 in The Second Department of General Surgery,Baoding First Central Hospital. They were divided into a study group and a reference group with the same case number. The former group was provided combination treatment, i.e. retrograde sural neurofasciocutaneous flap repair combined with Jingulian capsules; the latter group was given vacuum sealing drainage. Then, the treatment outcomes of the two groups were compared. RESULTS: The study group needed fewer dressing changes, less preoperative preparation time and antibiotic use than the reference group, p<0.05. The study group had a significantly lower incidence of wound infections and flap necrosis than the reference group, p<0.05. The study group was significantly superior to the reference group regarding ankle function scores and the pain visual analogue scores (VAS) p<0.05. CONCLUSIONS: Retrograde sural neurofasciocutaneous flap repair combined with Jingulian capsules is a protocol that improves efficacy for soft tissue defects in the foot and ankle, which are worthy of promotion and practice.
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AIMS: The aim of this study was to identify the molecular mechanism for hyperglycaemia-induced metabolic memory in endothelial cells (ECs), and to show its critical importance to development of cardiovascular dysfunction in diabetes. METHODS AND RESULTS: Hyperglycaemia induces increased nuclear factor-κB (NF-κB) signalling, up-regulation of miR-27a-3p, down-regulation of nuclear factor erythroid-2 related factor 2 (NRF2) expression, increased transforming growth factor-ß (TGF-ß) signalling, down-regulation of miR-29, and induction of endothelial-to-mesenchymal transition (EndMT), all of which are memorized by ECs and not erased when switched to a low glucose condition, thereby causing perivascular fibrosis and cardiac dysfunction. Similar metabolic memory effects are found for production of nitric oxide (NO), generation of reactive oxygen species (ROS), and the mitochondrial oxygen consumption rate in two different types of ECs. The observed metabolic memory effects in ECs are blocked by NRF2 activator tert-butylhydroquinone and a miR-27a-3p inhibitor. In vivo, the NRF2 activator and miR-27a-3p inhibitor block cardiac perivascular fibrosis and restore cardiovascular function by decreasing NF-κB signalling, down-regulating miR-27a-3p, up-regulating NRF2 expression, reducing TGF-ß signalling, and inhibiting EndMT during insulin treatment of diabetes in streptozotocin-induced diabetic mice, whereas insulin alone does not improve cardiac function. CONCLUSIONS: Our data indicate that disruption of hyperglycaemia-induced EC metabolic memory is required for restoring cardiac function during treatment of diabetes, and identify a novel molecular signalling pathway of NF-κB/miR-27a-3p/NRF2/ROS/TGF-ß/EndMT involved in metabolic memory.
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Glucemia/metabolismo , Cardiomiopatías Diabéticas/metabolismo , Células Endoteliales/metabolismo , Metabolismo Energético , Transición Epitelial-Mesenquimal , Animales , Células Cultivadas , Cardiomiopatías Diabéticas/tratamiento farmacológico , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Células Endoteliales/patología , Metabolismo Energético/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis , Humanos , Hidroquinonas/farmacología , Masculino , Ratones Endogámicos BALB C , MicroARNs/genética , MicroARNs/metabolismo , Factor 2 Relacionado con NF-E2/agonistas , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Cyanidin-3-glucoside (C3G) is a well-known natural anthocyanin with antioxidant and anti-inflammatory properties. In this study, we explored the role and action mechanism of C3G in high glucose (HG)-induced damage of human nucleus pulposus cells (HNPCs). Cell viability was assessed by CCK-8 assay. TUNEL assay was performed for detecting apoptotic rate. Western blot was performed to determine the expression levels of cl-caspase-3, caspase-3, Bax, Bim, collagen II, aggrecan, MMP-3, MMP-13, and ADAMTS5. Reactive oxygen species (ROS) generation was analyzed using DCFH-DA staining. The Nrf2 was knocked down or overexpressed in HNPCs through transfection with si-Nrf2 or pcDNA3.0-Nrf2. C3G treatment (12.5, 25, and 50 µM) improved cell viability of HNPCs under HG condition. HG-induced cell apoptosis of HNPCs was attenuated by C3G with decreased apoptotic rate and relative levels of cl-caspase-3/caspase-3, Bax, and Bim. C3G treatment caused significant increase in expression levels of collagen II and aggrecan and decrease in the relative levels of MMP-3, MMP-13, and ADAMTS5. After treatment with C3G, ROS generation in HNPCs was markedly reduced. Treatment with N-acetylcysteine (NAC) reversed HG-induced cell apoptosis and extracellular matrix (ECM) degradation. C3G treatment induced the expression of Nrf2 and HO-1 in HG-induced HNPCs. Moreover, knockdown of Nrf2 reversed the inhibitory effect of C3G on ROS production. Summarily, C3G exerted a protective effect on ROS-mediated cellular damage in HNPCs under HG condition, which was attributed to the induction of the Nrf2/HO-1 signaling pathway.
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Antocianinas , Núcleo Pulposo , Agrecanos/metabolismo , Agrecanos/farmacología , Antocianinas/metabolismo , Antocianinas/farmacología , Apoptosis , Caspasa 3/metabolismo , Glucosa/metabolismo , Glucosa/toxicidad , Humanos , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/farmacología , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/farmacología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Núcleo Pulposo/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Adjusting the local coordination environment of lanthanide luminescent ions is a useful method to manipulate the relevant photoluminescence (PL) property. K3Lu(PO4)2 is a phase-change material, and according to the stable temperature range from low to high, the related polymorphs are phase I [P21/m, coordination number (CN) of Lu3+ = 7], phase II (P21/m, CN = 6), and phase III (P3Ì , CN = 6), respectively. Based on the temperature-dependent PL analysis of K3Lu(PO4)2:Pr3+, we find that Pr3+ ions occupy the noninversion sites (Cs) in the two low-temperature phases but preferentially enter into the inversion ones (C3i) in phase III. Compared to Pr3+-doped phase I (78 K), Pr3+ ions in phase III (300 K) manifest a weaker fluorescence intensity (170-fold lower). To enhance the room-temperature PL property of K3Lu(PO4)2:Pr3+, a polymorphous adjustment strategy was proposed by the use of the ion-doping method. By introducing the Gd3+ ions into the lattice, Pr3+-doped phase I is successfully stabilized to room temperature, manifesting a 27-fold fluorescence increase in comparison to K3Lu(PO4)2:Pr3+ (0.1 at. %). The finding discussed in this study highlights the significance of site engineering for luminescent ions and also presents the application value of phase-change hosts in the development of high-performance luminescent materials.
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OBJECTIVE: This meta-analysis was performed to investigate whether percutaneous endoscopic lumbar discectomy (PELD) had a superior effect than other surgeries in the treatment of patients with lumbar disc herniation (LDH). METHOD: We searched PubMed, Embase, and Web of Science through February 2018 to identify eligible studies that compared the effects and complications between PELD and other surgical interventions in LDH. The outcomes included success rate, recurrence rate, complication rate, operation time, hospital stay, blood loss, visual analog scale (VAS) score for back pain and leg pain, 12-item Short Form Health Survey (SF12) physical component score, mental component score, Japanese Orthopaedic Association Score, Oswestry Disability Index. A random-effects or fixed-effects model was used to pool the estimate, according to the heterogeneity among the included studies. RESULTS: Fourteen studies (involving 2,528 patients) were included in this meta-analysis. Compared with other surgeries, PELD had favorable clinical outcomes for LDH, including shorter operation time (weight mean difference, WMD=-18.14 minutes, 95%CI: -25.24, -11.05; Pâ<â.001) and hospital stay (WMDâ=â-2.59âdays, 95%CI: -3.87, -1.31; Pâ<â.001), less blood loss (WMDâ=â-30.14âml, 95%CI: -43.16, -17.13; Pâ<â.001), and improved SF12- mental component score (WMDâ=â2.28, 95%CI: 0.50, 4.06; Pâ=â.012)) and SF12- physical component score (WMDâ=â1.04, 95%CI: 0.37, 1.71; Pâ=â.02). However, it also was associated with a significantly higher rate of recurrent disc herniation (relative risk [RR]â=â1.65, 95%CI: 1.08, 2.52; Pâ=â.021). There were no significant differences between the PELD group and other surgical group in terms of success rate (RRâ=â1.01, 95%CI: 0.97, 1.04; Pâ=â.733), complication rate (RRâ=â0.86, 95%CI: 0.63, 1.18; Pâ=â.361), Japanese Orthopaedic Association Score score (WMDâ=â0.19, 95%CI: -1.90, 2.27; Pâ=â.861), visual analog scale score for back pain (WMDâ=â-0.17, 95%CI: -0.55, 0.21; Pâ=â.384) and leg pain (WMDâ=â0.00, 95%CI: -0.10, 0.10; Pâ=â.991), and Oswestry Disability Index score (WMDâ=â-0.29, 95%CI: -1.00, 0.43; Pâ=â.434). CONCLUSION: PELD was associated with better effects and similar complications with other surgeries in LDH. However, it also resulted in a higher recurrence rate. Considering the potential limitations in the present study, further large-scale, well-performed randomized trials are needed to verify our findings.
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Descompresión Quirúrgica/estadística & datos numéricos , Discectomía Percutánea/estadística & datos numéricos , Endoscopía/estadística & datos numéricos , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dolor de Espalda/etiología , Dolor de Espalda/cirugía , Estudios de Casos y Controles , Estudios de Cohortes , Descompresión Quirúrgica/métodos , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dimensión del Dolor , Dolor Postoperatorio/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto JovenRESUMEN
Improving angiogenic capacity under hypoxic conditions is essential for improving the survival of skin grafts, as they often lack the necessary blood supply. The stable expression levels of hypoxiainducible factor1α (HIF1α) in the nucleus directly affect the downstream vascular endothelial growth factor (VEGF) signaling pathway and regulate angiogenesis in a hypoxic environment. Astragaloside IV (ASIV), an active component isolated from Astragalus membranaceus, has multiple biological effects including antioxidant and antidiabetic effects, and the ability to provide protection from cardiovascular damage. However, the mechanisms underlying these effects have not previously been elucidated. The present study investigated whether ASIV promotes angiogenesis via affecting the balance between ubiquitination and small ubiquitinrelated modifier (SUMO) modification of HIF1α. The results demonstrated that persistent hypoxia induces changes in expression levels of HIF1α protein and significantly increases the proportion of dysplastic blood vessels. Further western blotting experiments showed that rapid attenuation and delayed compensation of SUMO1 activity is one of the reasons for the initial increase then decrease in HIF1α levels. SUMO1 overexpression stabilized the presence of HIF1α in the nucleus and decreased the extent of abnormal blood vessel morphology observed following hypoxia. ASIV induces vascular endothelial cells to continuously produce SUMO1, stabilizes the HIF1α/VEGF pathway and improves angiogenesis in hypoxic conditions. In summary, the present study confirmed that ASIV stimulates vascular endothelial cells to continuously resupply SUMO1, stabilizes the presence of HIF1α protein and improves angiogenesis in adverse hypoxic conditions, which may improve the success rate of flap graft surgery following trauma or burn.
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Células Endoteliales de la Vena Umbilical Humana/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/biosíntesis , Neovascularización Fisiológica/efectos de los fármacos , Saponinas/farmacología , Sumoilación/efectos de los fármacos , Triterpenos/farmacología , Hipoxia de la Célula/efectos de los fármacos , HumanosRESUMEN
BACKGROUND: LY03004, a novel investigational risperidone long-acting injection (LAI) microsphere formulation, can release risperidone more quickly after injection than Risperdal Consta®. This study aimed to investigate the effects of genetic polymorphisms on the pharmacokinetics of LY03004 compared with those on Risperdal Consta®. METHODS: A total of 100 Chinese patients with stable schizophrenia were randomly assigned to the LY03004 or Risperdal Consta® treatment group. Each patient received five biweekly intramuscular injections of 25 mg risperidone long-acting injection microspheres. A total of 34 blood samples before and after injections from Day 1 to Day 113 were collected from each patient, and polymorphic alleles of cytochrome P450 enzymes CYP2D6 (*4, *10, *14), CYP3A5 (*3), and ABCB1 (C1236 > T, G2677T/A, and C3435T) were analyzed using Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The risperidone Cmax,ss, Cmin,ss, AUC0-tau,ss, and the ratio of risperidone to 9-hydroxyrisperidone (9-OH-R) in CYP2D6 intermediate metabolizers (IMs) were significantly different compared with those in normal metabolizers (NMs) in both the LY03004 and Risperdal Consta® groups (P < 0.05). However, 9-OH-R was not significantly different between IMs and NMs (P > 0.05). The AUC0-tau,ss of the active moiety (risperidone plus 9-OH-R) was 6.51 ± 3.34 in NMs and 7.00 ± 1.81 in IMs (P = 0.071) in the LY03004 group and 6.07 ± 2.31 and 7.95 ± 3.42 (P = 0.053) in NMs and IMs, respectively, in the Risperdal Consta® group. In the LY03004 group, the Cmax,ss of risperidone in carriers of the ABCB1-C3435T TT variant was significantly lower than that in CC and CT carriers (TT 7.76 ± 4.23 ng/mL, CT 11.6 ± 8.27 ng/mL, CC 14.3 ± 7.66 ng/ml; P = 0.045), but no significant differences were found in the active moiety. In the Risperdal Consta® group, C3435T TT carriers had significantly lower Cmin,ss of the active moiety (TT 5.09 ± 4.38 ng/mL, CT 11.4 ± 8.42 ng/mL, CC 14.3 ± 6.43 ng/mL; P = 0.007). Furthermore, Cmin,ss of the active moiety was significantly different among all ABCB1-G2677T/A genotypes (P < 0.05). CONCLUSION: The pharmacokinetics of risperidone and the ratio of risperidone to 9-OH-R were highly dependent on CYP2D6 activity. However, there was no significant effect in 9-OH-R. A future study involving a larger sample is required to verify whether CYP2D6 IMs have lower risperidone active moiety clearance than CYP2D6 NMs for LAI formulations. In addition, the risperidone active moiety was eliminated faster in ABCB1-G2677T/A and C3435T TT carriers receiving Risperdal Consta®.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Antipsicóticos/farmacocinética , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP3A/genética , Risperidona/farmacocinética , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/uso terapéutico , Femenino , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Farmacogenética , Polimorfismo de Nucleótido Simple , Risperidona/uso terapéutico , Esquizofrenia/genéticaRESUMEN
Pore structure and fractal dimensions can characterize the adsorption, desorption and seepage characteristics of shale gas reservoirs. In this study, pore structure, fractal characteristics and influencing factors were studied of the Longmaxi formation shale gas reservoir in southeastern Chongqing, China. Scanning electron microscopy was used to describe the characteristics of various reservoirs. High pressure mercury intrusion and low temperature liquid N2 and CO2 adsorption experiments were used to obtain pore structure parameters. V-S model, FHH model and Menger sponge model were selected to calculate the micropore, mesopore and macropore fractal dimensions, respectively. The results show that organic matter pores, inter-granular pores, intra-granular pores and micro-fractures are developed within the shale, and the pore morphology is mostly ink pores and parallel plate pores with aperture essentially in the 1-2 nm and 2-50 nm ranges. Moreover, macropores are the most complex in these samples, with mesopores being less complex than macropores, and the micropores being the simplest. D1 (micropore fractal dimension) ranges from 2.31 to 2.50, D2 (mesopore fractal dimension) ranges from 2.74 to 2.83, D3 (macropore fractal dimension) ranges from 2.87 to 2.95, and Dt (comprehensive fractal dimension) ranges from 2.69 to 2.83 of fractal characteristics. D1 and D2 are mainly controlled by TOC content, while D3 and Dt are mainly controlled by brittle and clay mineral content. These results may be helpful for exploration and the development of shale gas in southeastern Chongqing, China.
RESUMEN
BACKGROUND: Total hip arthroplasty (THA) is a safe and mature surgical method for the treatment of post-traumatic arthritis and end-stage degenerative osteoarthritis. The cohort study regarding the outcomes of THA following acetabulum fracture is sparse. Therefore, we carried out this present retrospective paired cohort study to study the long-term outcomes of patients receiving THA after the acetabular fracture versus patients receiving THA for the primary osteoarthritis. METHODS: Patients with posttraumatic arthritis who received the initial THA after open reduction and internal fixation of acetabular fractures or patients with end-stage degenerative osteoarthritis were included in our study. A retrospective review of patients who receiving the primary total hip arthroplasty in the same institution from 2008 to 2015 was conducted. This present retrospective cohort research was authorized via our hospital institutional review committee. The patients in cohort group were matched 2:1 with the patients in study group according to following criteria: body mass index (±3 points), and age at THA time (±3 years), sex, as well as the score of American Society of Anesthesiologists (±1 point). The measure of primary outcome was the improved Harris Hip Score. Secondary outcomes included surgery time, hip range of motion, revision, complications (infection, loosening, polyethylene wear, dislocation, wound complications, deep vein thrombosis, or pulmonary embolism). RESULTS: It was assumed that there is a remarkable difference in postoperative outcomes between the 2 groups. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5921).
Asunto(s)
Acetábulo/lesiones , Artroplastia de Reemplazo de Cadera , Fracturas Óseas , Osteoartritis de la Cadera/cirugía , Humanos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The molecular composition of organic matter formed during pyrolysis is complex. Fourier transform infrared spectroscopy (FTIR) is a good technique to investigate the coal chemical structural evolution. However, reports on the effects of chemical structure on the n-alkane yields and their relative functional groups are scarce in the literature. In our case, the chemical structural evolution process of bituminous coal obtained by pyrolysis at two different heating rates has been analyzed by pyrolysis-gas chromatography (Py-GC) and FTIR. Furthermore, some of the small molecular compounds (e.g., n-alkanes 24 can generate n-alkanes 20 or low-weight compounds) generated by gold-tube pyrolysis were identified using other GC techniques. Biomarkers were analyzed and compared to generated n-alkanes from the gold-tube pyrolysis experiments. We present the results of the relationship between the FTIR parameters and the molecular compositions that were analyzed. A good linear relationship can be seen between the FTIR parameters (C=O, C=C, and C-factor values), the carbon preference index (CPI), and the ratio of the pristane content and n-C17 alkane content (Pr/n-C17). Furthermore, the n-alkane fraction of the pyrolysates, in particular pristane, phytane, n-C17 alkane, and n-C18 alkane, changed upon maturation. Our conclusions indicate that FTIR is applicable as a structural and chemical change probe to explore the pyrolysis process.
RESUMEN
AIMS: Cardiac fibrosis is a major cause of heart failure (HF), and mediated by the differentiation of cardiac fibroblasts into myofibroblasts. However, limited tools are available to block cardiac fibrosis. ADAMTS16 is a member of the ADAMTS superfamily of extracellular protease enzymes involved in extracellular matrix (ECM) degradation and remodelling. In this study, we aimed to establish ADAMTS16 as a key regulator of cardiac fibrosis. METHODS AND RESULTS: Western blot and qRT-PCR analyses demonstrated that ADAMTS16 was significantly up-regulated in mice with transverse aortic constriction (TAC) associated with left ventricular hypertrophy and HF, which was correlated with increased expression of Mmp2, Mmp9, Col1a1, and Col3a1. Overexpression of ADAMTS16 accelerated the AngII-induced activation of cardiac fibroblasts into myofibroblasts. Protein structural analysis and co-immunoprecipitation revealed that ADAMTS16 interacted with the latency-associated peptide (LAP)-transforming growth factor (TGF)-ß via a RRFR motif. Overexpression of ADAMTS16 induced the activation of TGF-ß in cardiac fibroblasts; however, the effects were blocked by a mutation of the RRFR motif to IIFI, knockdown of Adamts16 expression, or a TGF-ß-neutralizing antibody (ΝAb). The RRFR tetrapeptide, but not control IIFI peptide, blocked the interaction between ADAMTS16 and LAP-TGF-ß, and accelerated the activation of TGF-ß in cardiac fibroblasts. In TAC mice, the RRFR tetrapeptide aggravated cardiac fibrosis and hypertrophy by up-regulation of ECM proteins, activation of TGF-ß, and increased SMAD2/SMAD3 signalling, however, the effects were blocked by TGF-ß-NAb. CONCLUSION: ADAMTS16 promotes cardiac fibrosis, cardiac hypertrophy, and HF by facilitating cardiac fibroblasts activation via interacting with and activating LAP-TGF-ß signalling. The RRFR motif of ADAMTS16 disrupts the interaction between ADAMTS16 and LAP-TGF-ß, activates TGF-ß, and aggravated cardiac fibrosis and hypertrophy. This study identifies a novel regulator of TGF-ß signalling and cardiac fibrosis, and provides a new target for the development of therapeutic treatment of cardiac fibrosis and HF.