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Hematopoietic stem/progenitor cells (HSPCs) originate from endothelial cells (ECs) localized on the ventral side of the dorsal aorta (DA), and hemodynamic parameters may suffer sharp changes in DA at HSPCs development stage for intersegmental vessel formation. However, the temporal-spatial shear stress parameters and biomechanics mechanisms of HSPC budding remain unknown. Here, we found that the hematopoietic endothelium (HE) in the aorta-gonad-mesonephros was heterogeneous; that is, HEs were mainly distributed at the ventral side of the vascular bifurcation in zebrafish embryos, which was found to show low shear stress (LSS) through numerical simulation analysis. Furthermore, HSPCs localized in the posterior somite of aorta-gonad-mesonephros with slow velocity. On the temporal scale, there was a slow velocity and LSS during HE budding from 36 h post-fertilization and decreased shear stress with drug expanded HSPC numbers. Mechanistically, matrix metalloproteinase (MMP) expression and macrophage chemotaxis were significantly increased in HEs by RNA-seq. After treatment with an MMP13 inhibitor, HSPCs were significantly reduced in both the aorta-gonad-mesonephros and caudal hematopoietic tissue in embryos. Our results show that HSPC budding is heterogeneous, and the mechanism is that physiological LSS controls the emergence of HSPCs by promoting the accumulation of macrophages and subsequent MMP expression.
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Células Endoteliais , Peixe-Zebra , Animais , Células Endoteliais/metabolismo , Hematopoese , Células-Tronco Hematopoéticas/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Effects of hypertrophic challenge on small-conductance, Ca2+-activated K+(SK2) channel expression were explored in intact murine hearts, isolated ventricular myocytes and neonatal rat cardiomyocytes (NRCMs). An established experimental platform applied angiotensin II (Ang II) challenge in the presence and absence of reduced p21-activated kinase (PAK1) (PAK1cko vs. PAK1f/f, or shRNA-PAK1 interference) expression. SK2 current contributions were detected through their sensitivity to apamin block. Ang II treatment increased such SK2 contributions to optically mapped action potential durations (APD80) and their heterogeneity, and to patch-clamp currents. Such changes were accentuated in PAK1cko compared to PAK1f/f, intact hearts and isolated cardiomyocytes. They paralleled increased histological and echocardiographic hypertrophic indices, reduced cardiac contractility, and increased SK2 protein expression, changes similarly greater with PAK1cko than PAK1f/f. In NRCMs, Ang II challenge replicated such increases in apamin-sensitive SK patch clamp currents as well as in real-time PCR and western blot measures of SK2 mRNA and protein expression and cell hypertrophy. Furthermore, the latter were enhanced by shRNA-PAK1 interference and mitigated by the PAK1 agonist FTY720. Increased CaMKII and CREB phosphorylation accompanied these effects. These were rescued by both FTY720 as well as the CaMKII inhibitor KN93, but not its inactive analogue KN92. Such CREB then specifically bound to the KCNN2 promoter sequence in luciferase assays. These findings associate Ang II induced hypertrophy with increased SK2 expression brought about by a CaMKII/CREB signaling convergent with the PAK1 pathway thence upregulating the KCNN2 promoter activity. SK2 may then influence cardiac electrophysiology under conditions of cardiac hypertrophy and failure.
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Angiotensina II , Quinases Ativadas por p21 , Angiotensina II/metabolismo , Angiotensina II/farmacologia , Animais , Apamina/metabolismo , Apamina/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiomegalia/metabolismo , Cloridrato de Fingolimode/metabolismo , Cloridrato de Fingolimode/farmacologia , Camundongos , Miócitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinases , RNA Interferente Pequeno/metabolismo , Ratos , Regulação para Cima , Quinases Ativadas por p21/genética , Quinases Ativadas por p21/metabolismo , Quinases Ativadas por p21/farmacologiaRESUMO
PURPOSE: To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. MATERIALS AND METHODS: This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. RESULTS: A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. CONCLUSIONS: ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.
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Bilirrubina/sangue , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Técnicas de Apoio para a Decisão , Neoplasias Hepáticas/terapia , Redes Neurais de Computação , Nomogramas , Albumina Sérica Humana/metabolismo , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , China , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To develop a modified assessment for retreatment with transarterial chemoembolization (mART) score that may be more suitable for Chinese patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Chinese patients with HCC who were treated with transarterial chemoembolization in four hospitals were included. A univariate analysis and a multivariate forward Cox regression analysis were used to identify significant prognostic factors of overall survival (OS). A point scoring model was subsequently developed from the training cohort, and the validation process was performed in the validation cohort. RESULTS: The study included 259 patients (124 patients in the training cohort and 135 patients in the validation cohort). Increase in Child-Pugh scores relative to the baseline (P < .001), Barcelona Clinic Liver Cancer (BCLC) stage B before first transarterial chemoembolization (P = .001), and absence of radiologic tumor response (P < .001) were identified as negative prognostic factors for OS and were used to create the mART scores. BCLC staging was substituted for aspartate aminotransferase increase in the mART scores. The mART scores differentiated two groups with distinct prognosis by a cutoff score of 2.5 points (22.9 mo [95% confidence interval (CI), 17.4-28.4] vs 8.9 mo [95% CI, 7.5-10.3] in median survival; P < .001). In the validation cohort, the C index in assessment for retreatment with transarterial chemoembolization (ART) criteria was 0.64, whereas it was 0.82 in mART criteria. CONCLUSIONS: In Chinese patients with HCC, mART score of > 2.5 before second transarterial chemoembolization was associated with poor prognosis. The mART score was probably better validated compared with the ART score.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/terapia , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/mortalidade , Distribuição de Qui-Quadrado , China , Técnicas de Apoio para a Decisão , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Seleção de Pacientes , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The combination of stent insertion and single high-dose brachytherapy is a feasible and safe palliative treatment regimen in patients with unresectable oesophageal cancer. We aimed to further assess the efficacy of this treatment strategy compared to a conventional covered stent in patients with dysphagia caused by unresectable oesophageal cancer. METHODS: In this multicentre, single-blind, randomised, phase 3 trial, we enrolled patients with unresectable oesophageal cancer from 16 hospitals in China. We included adult patients (aged ≥ 20 years) with progressive dysphagia, unresectable tumours due to extensive lesions, metastases, or poor medical condition, and with clear consciousness, cooperation, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-3. Eligible patients were randomly assigned (in 1:1 ratio, no stratification) to receive either a stent loaded with (125)iodine radioactive seeds (irradiation group) or a conventional oesophageal stent (control group). The primary endpoint was overall survival. Survival analyses were done in a modified intention-to-treat group. This study is registered with ClinicalTrials.gov, number NCT01054274. FINDINGS: Between Nov 1, 2009, and Oct 31, 2012, 160 patients were randomly assigned to receive treatment with either an irradiation stent (n=80) or a conventional stent (n=80). During a median follow-up of 138 days (IQR 72-207), 148 stents (73 in the irradiation group and 75 in the control group) were successfully placed into the diseased oesophagus in 148 participants. Median overall survival was 177 days (95% CI 153-201) in the irradiation group versus 147 days (124-170) in the control group (p=0.0046). Major complications and side-effects of the treatment were severe chest pain (17 [23%] of 73 patients in the irradiation group vs 15 [20%] of 75 patents in the control group), fistula formation (six [8%] vs five [7%]), aspiration pneumonia (11 [15%] vs 14 [19%]), haemorrhage (five [7%] vs five [7%]), and recurrent dysphagia (21 [28%] vs 20 [27%]). INTERPRETATION: In patients with unresectable oesophageal cancer, the insertion of an oesophageal stent loaded with (125)iodine seeds prolonged survival when compared with the insertion of a conventional covered self-expandable metallic stent.
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Adenocarcinoma/radioterapia , Braquiterapia/métodos , Carcinoma de Células Escamosas/radioterapia , Neoplasias Esofágicas/radioterapia , Stents , Adenocarcinoma/mortalidade , Idoso , Braquiterapia/instrumentação , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Método Simples-CegoRESUMO
OBJECTIVE: To evaluate the clinical efficacy and radiological changes in patients with painful osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). METHODS: Retrospective analysis was conducted on 195 vertebrae in 142 patients with painful OVCFs treated with vertebroplasty in our hospital from May 2007 to June 2012. The scores of visual analogue scale (VAS) were recorded and the heights of vertebral bodies and Cobb angles were measured in the mid-sagittal plane of the reformatted images at 64-detector row CT during the period of follow-up. Polymethylmethacrylate (PMMA) distribution in vertebrae and whether leakage was observed on CT within 3 days after PVP. The changes in VAS, heights of vertebral bodies and Cobb angles were compared between the cases with and without leakages. RESULTS: The successful rate of technique of PVP was 100%. The mean volume of PMMA injected in each vertebra was (4.5 ± 1.1) ml and (6.0 ± 1.2) ml respectively in thoracic and lumbar. The mean follow-up was (17 ± 6) months. Asymptomatic leakages of PMMA were demonstrated by CT in 38 patients with 43 vertebrae (22.1%). The average decrease in VAS was 5.25 and 1.12 respectively in 24 hours and a month after PVP. The changes in VAS respectively at 1 month, 3 months, 6 months and more than 1 year after procedure were not significantly different.In postoperative 3 days, the average increase in height of vertebral body was 1.55 mm anteriorly and 1.38 mm centrally, the average reduction in Cobb angle were 2.37°. The heights and Cobb angles of vertebral bodies between in 3 days and in more than 1 year after PVP were not significantly different. The scores of VAS and the changes in vertebral body heights and Cobb angles between the patients with or without cement leakages were not significantly different during the period of follow-up. CONCLUSION: PVP is an effective treatment for patients with painful OVCFs that provides immediate and sustained pain relief, increases in the heights of vertebral bodies injected in cement and keeps stable radiological progression within at least 1 year after PVP. Asymptomatic cement leakages around vertebrae have no influence on pain relief and vertebral stability in this group of patients.
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Fraturas por Compressão/cirurgia , Fraturas por Osteoporose/cirurgia , Fraturas da Coluna Vertebral/cirurgia , Cimentos Ósseos , Humanos , Dor , Medição da Dor , Polimetil Metacrilato , Estudos Retrospectivos , Resultado do Tratamento , VertebroplastiaRESUMO
The stent implantation may alter the post-operative patient's blood pressure, and bioresorbable vascular stents (BVS) as a candidate to treat vascular diseases, its degradation is affected by mechanical stress, thus, the altered pressure representing varying stress level will result in different degradation behaviors of the BVS. This paper first proposed a novel stress-regulated PLA degradation model that included swelling factor, and then the degradation evolutions of a PLA BVS within 180 days under normal and high blood pressures were simulated by finite element method, and more four degradation indexes were defined to study the effects of the two blood pressures on the degradation of the PLA BVS. The results showed that the high pressure weakly accelerated the degradation of the PLA BVS with respect to the normal pressure by examining the four indexes, e.g., the residual stent volume v r ( t ) decreased to 0.72 and 0.69, respectively for the normal and high pressures at day 180. The current finding provided a theoretical understanding of the PLA BVS degradation, and hinted that the PLA BVS may not need to be elaborately selected in clinical practices for treating hypertensive patients.
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Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Pressão Sanguínea , Implantes Absorvíveis , Resultado do Tratamento , Stents , Poliésteres , Desenho de Prótese , Intervenção Coronária Percutânea/métodosRESUMO
Biodegradable vascular stents (BVS) are deemed as great potential alternatives for overcoming the inherent limitations of permanent metallic stents in the treatment of coronary artery diseases. The current study aimed to comprehensively compare the mechanical behaviors of four poly(lactic acid) (PLA) BVS designs with varying geometries via numerical methods and to clarify the optimal BVS selection. Four PLA BVS (i.e., Absorb, DESolve, Igaki-Tamai, and Fantom) were first constructed. A degradation model was refined by simply including the fatigue effect induced by pulsatile blood pressures, and an explicit solver was employed to simulate the crimping and degradation behaviors of the four PLA BVS. The degradation dynamics here were characterized by four indices. The results indicated that the stent designs affected crimping and degradation behaviors. Compared to the other three stents, the DESolve stent had the greatest radial stiffness in the crimping simulation and the best diameter maintenance ability despite its faster degradation; moreover, the stent was considered to perform better according to a pilot scoring system. The current work provides a theoretical method for studying and understanding the degradation dynamics of the PLA BVS, and it could be helpful for the design of next-generation BVS.
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Litter decomposition is a vital process for maintaining ecosystem carbon cycling. It is affected by soil fauna which are predators and decomposers of litter. However, how the interactions of soil fauna communities affect litter decomposition remains unclear under warming. Here, we conducted a five-year in-situ manipulative warming experiment by Open-Top Chamber (OTC) in an alpine meadow on the Tibetan Plateau to reveal how warming affects litter decomposition. The results demonstrated that warming decreased the litter decomposition rate by 29 %, the soil collembola abundance by 25 %, and the nematode abundance by 27 %. Nematode ecological indices remain stable but a shift in the decomposition of litter to the fungivores pathway under warming. The piecewise structural equation modelling result revealed that the combined reduction in soil collembola and nematodes synergistically leads to a massive decline in litter decomposition rate under warming. Our results highlight that the interactions of soil fauna can regulate litter decomposition under warming, and collembola abundance as the "speed-limiter" of litter decomposition. Therefore, the response of changes in soil fauna relationships to warming should be completely considered in future climate change modelling of the grassland carbon cycle.
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African swine fever (ASF) caused by the African swine fever virus (ASFV) is a fatal and highly contagious disease of domestic pigs characterized by rapid disease progression and death within 2 weeks. How the immune cells respond to acute ASFV infection and contribute to the immunopathogenesis of ASFV has not been completely understood. In this study, we examined the activation, apoptosis, and functional changes of distinct immune cells in domestic pigs following acute infection with the ASFV CADC_HN09 strain using multicolor flow cytometry. We found that ASFV infection induced broad apoptosis of DCs, monocytes, neutrophils, and lymphocytes in the peripheral blood of pigs over time. The expression of MHC class II molecule (SLA-DR/DQ) on monocytes and conventional DCs as well as CD21 expression on B cells were downregulated after ASFV infection, implying a potential impairment of antigen presentation and humoral response. Further examination of CD69 and ex vivo expression of IFN-γ on immune cells showed that T cells were transiently activated and expressed IFN-γ as early as 5 days post-infection. However, the capability of T cells to produce cytokines was significantly impaired in the infected pigs when stimulated with mitogen. These results suggest that the adaptive cellular immunity to ASFV might be initiated but later overridden by ASFV-induced immunosuppression. Our study clarified the cell types that were affected by ASFV infection and contributed to lymphopenia, improving our understanding of the immunopathogenesis of ASFV.
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OBJECTIVE: To explore the changes of magnetic resonance imaging (MRI) and computed tomography (CT) after transplantation of VX2 carcinoma into lumbar vertebrae of rabbits under CT guidance and examine its relationship with the onset of paralysis. METHODS: A total of 52 rabbits were randomly divided into 4 groups. Under CT guidance, pieces of VX2 carcinoma were transplanted into the first or second lumbar vertebra in Groups A, B and C (n = 14 each) while sham operation was performed in Group D (n = 10). The anticipated endpoints of group A was natural death or Day 50 post-operation, group B Day 3 after onset of paralysis, group C Day 14 post-transplantation and group D natural death or Day 50 post-operation. CT and MR scans were performed at an interval of 7 days and hind limb functions monitored daily post-operation until endpoints. Pathohistological examinations of vertebrae were performed at endpoints. RESULTS: All lumbar vertebrae were successfully transplanted under CT guidance. Thirty-two rabbits with spinal tumor and 9 surviving rabbits in the control group were monitored until endpoints. Abnormal signals on target vertebrae appeared on MRI in all 41 rabbits at Day 7 post-operation while positive CT findings were absent. No abnormal MRI/CT findings were found in 9 control rabbits from Day 14 post-operation to the end of study. Significant differences (P < 0.001) existed between the rates of tumor visualization with 65.6% (21/32) on MR and 3.1% (1/32) on CT at Day 14, 100% (21/21) on MR and 42.9% (9/21) on CT at Day 21. The rates of tumor visualization were 100% on both MR and CT from Day 28 to endpoints. The average survival time of Group A was significantly shorter than Group D (40 ± 4 vs 50 days, P < 0.01). The onset time of paralysis time in Group A (22 ± 5 days) had no significant difference with Group B (22 ± 5 days) (P = 0.952). CONCLUSION: A rabbit model of spinal metastasis is established with high rates of success and reproducibility. Vertebral tumor may be located earlier on MR than CT after transplantation of VX2 carcinoma. The examinations of MRI and CT after Day 7 post-operation are controversial. The survival time of rabbits with paralysis caused by spinal tumor is significantly shortened.
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Biópsia por Agulha/métodos , Neoplasias Experimentais , Neoplasias da Coluna Vertebral/patologia , Animais , Coelhos , Tomografia Computadorizada por Raios XRESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) is a significant threat to the pig industry in China. However, the epidemiological characteristics of PRRSV after the outbreak of African swine fever in China were not thoroughly investigated. In the present study, the serological and epidemiological investigations of PRRSV in pigs from the Hunan and Hebei provinces of China were assessed. The results showed that 73.12% (95% CI 71.74-74.49) of pigs were positive for PRRSV-special antibody by enzyme-linked immunosorbent assay. Out of 5799 samples, 482 (8.31%, 95% CI 7.60-9.02) samples were positive for PRRSV nucleic acids. The positive rates of PRRSV in healthy pigs from farms and slaughterhouses were 2.27% (47/2072) and 7.70% (217/2818), which were lower than that in diseased pigs (23.98%, 218/909). Furthermore, the full-length OFR5 gene sequences of 43 PRRSV strains were sequenced and analysed. Phylogenetic analysis revealed that 43 isolates were classified into three lineages, namely lineage 1 (n = 24), lineage 8 (n = 15), and lineage 3 (n = 4). Lineage 1 could be further divided into sublineage 1.5 (n = 2) and sublineage 1.8 (n = 22), and lineage 8 was classified into sublineage 8.1 (n = 3) and sublineage 8.7 (n = 12). Collectively, our findings revealed the severe prevalence of PRRSV in the Hunan and Hebei provinces, where sublineage 1.8 and sublineage 8.7 predominated. The present study provides the update information of the epidemiological and genetic characteristics of PRRSV in the investigated regions, which will be beneficial for PRRS control.
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Climatic warming can alter grassland nitrous oxide (N2O) emissions due to soil property alterations. However, how the reclamation affect grassland N2O flux under warming conditions remains unclear in alpine meadow ecosystems. We conducted a long-term manipulative warming experiment in a natural alpine meadow and a cultivated grassland on the Qinghai-Tibetan Plateau to explore the separate and interactive effects of warming and reclamation on the soil N2O emission flux. N2O fluxes were measured under four treatments including control (CK), warming (W), reclamation (R) and warming under reclamation (WR) from August 2018 to July 2019. We measured the content of soil C, N nutrients and 5 enzymatic activities in 2018 and 2019. Correlation analysis and structural equation modeling were used to clarify how soil N availability and soil enzyme activities affect N2O emission. Our results indicated that compared to the ambient conditions for the growing and non-growing seasons, soil N2O flux was significantly increased 59.1% and 152.0% by warming and 28.4% and 142.4% by reclamation, respectively. Compared with W, WR significantly increased N2O flux by 18.9% and 81.1% during the growing and non-growing seasons, respectively. Soil moisture was negatively correlated to enzymatic activity and N2O flux. Both warming and reclamation promoted soil nitrification by increasing related enzymatic activities that acted to increase the N2O flux. Reclamation resulted in a greater sensitivity of the activity of ammonia monooxygenase and hydroxylamine oxidoreductase to warming, thus enhancing the effects of warming on increasing the N2O flux. Our research indicated that reclamation can additionally increase the effects of warming on N2O emissions for alpine meadows. Therefore, excessive expansion of arable land should be avoided, and new reclamation sites should be planned scientifically, as warming is expected to intensify in the future.
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Atherosclerotic cardiovascular disease is a typical age-related disease accompanied by stiffening arteries. We aimed to elucidate the influence of aged arteries on in-stent restenosis (ISR) after the implantation of bioresorbable scaffolds (BRS). Histology and optical coherence tomography showed increased lumen loss and ISR in the aged abdominal aorta of Sprague-Dawley rats, with apparent scaffold degradation and deformation, which induce lower wall shear stress (WSS). This was also the case at the distal end of BRS, where the scaffolds degraded faster, and significant lumen loss was followed by a lower WSS. In addition, early thrombosis, inflammation, and delayed re-endothelialization were presented in the aged arteries. Degradation of BRS causes more senescent cells in the aged vasculature, increasing endothelial cell dysfunction and the risk of ISR. Thus, profoundly understanding the mechanism between BRS and senescent cells may give a meaningful guide for the age-related scaffold design. STATEMENT OF SIGNIFICANCE: The degradation of bioresorbable scaffolds aggravates senescent endothelial cells and a much lower wall shear stress areas in the aged vasculature, lead to intimal dysfunction and increasing in-stent restenosis risk. Early thrombosis and inflammation, as well as delayed re-endothelialization, are presented in the aged vasculature after bioresorbable scaffolds implantation. Age stratification during the clinical evaluation and senolytics in the design of new bioresorbable scaffolds should be considered, especially for old patients.
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Reestenose Coronária , Intervenção Coronária Percutânea , Animais , Ratos , Implantes Absorvíveis , Reestenose Coronária/etiologia , Desenho de Prótese , Células Endoteliais , Angiografia Coronária/efeitos adversos , Ratos Sprague-Dawley , Constrição Patológica , Inflamação , Tomografia de Coerência Óptica/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Vasos CoronáriosRESUMO
Biodegradable polymer as traditional material has been widely used in the medical and tissue engineering fields, but there is a great limitation as to its inferior mechanical performance for repairing load-bearing tissues. Thus, it is highly desirable to develop a novel technology to fabricate high-performance biodegradable polymers. Herein, inspired by the bone's superstructure, a versatile disorder-to-order technology (VDOT) is proposed to manufacture a high-strength and high-elastic modulus stereo-composite self-reinforced polymer fiber. The mean tensile strength (336.1 MPa) and elastic modulus (4.1 GPa) of the self-reinforced polylactic acid (PLA) fiber are 5.2 and 2.1 times their counterparts of the traditional PLA fiber prepared by the existing spinning method. Moreover, the polymer fibers have the best ability of strength retention during degradation. Interestingly, the fiber tensile strength is even higher than those of bone (200 MPa) and some medical metals (e.g., Al and Mg). Based on all-polymeric raw materials, the VDOT endows bioinspired polymers with improved strength, elastic modulus, and degradation-controlled mechanical maintenance, making it a versatile update technology for the massive industrial production of high-performance biomedical polymers.
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Materiais Biomiméticos , Polímeros , Polímeros/química , Teste de Materiais , Poliésteres , Resistência à TraçãoRESUMO
BACKGROUND & AIMS: Stenting is a palliative therapy method for relieving malignant biliary obstruction. The aim of this study was to evaluate the safety and effectiveness of an irradiation stent compared to a conventional biliary stent in patients with biliary obstruction caused by both primary and metastatic adenocarcinomas. METHODS: Participants were randomly assigned to receive treatment with a biliary irradiation stent (irradiation stent group) or a conventional biliary stent (control group). After stent implantation, the outcomes were measured in terms of relief of obstructive jaundice, survival time, complications related to the procedure. A p value of less than 0.05 indicated a significant difference. RESULTS: The stents were successfully placed in all the 23 patients. The obstructive jaundice was relieved in all patients except three in the control group. The median and mean overall survivals in the irradiation stent group were higher than those in the control group (7.40 months versus 2.50 months, 8.03 months versus 3.36 months, p=0.006). The patients with stent patent at 3, 6, and 12 months in the irradiation stent group were 11 (91.7%), 7 (58.3%), and 1 (8.3%), respectively. While in the control group, 4 (36.4%), 1 (9.1%), and 0 (0%), respectively. There were no significant differences in the complications related to stent insertion between the two groups. CONCLUSIONS: This interim analysis shows that treatment with the biliary intraluminal irradiation stent in patients with biliary obstruction caused by adenocarcinomas appears safe and technically feasible, has benefits in relieving jaundice, and seems to extend survival when compared to a conventional biliary stent.
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Adenocarcinoma/radioterapia , Neoplasias do Sistema Biliar/radioterapia , Colestase/terapia , Radioisótopos do Iodo/uso terapêutico , Radioterapia/métodos , Stents , Adenocarcinoma/complicações , Adenocarcinoma/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/complicações , Neoplasias do Sistema Biliar/mortalidade , Colestase/etiologia , Terapia Combinada , Feminino , Humanos , Radioisótopos do Iodo/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Método Simples-Cego , Stents/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: To determine the risk factors for new vertebral compression fractures (VCFs) following percutaneous vertebroplasty (PV) in patients with osteoporosis. MATERIALS AND METHODS: This prospective study included 132 consecutive patients with osteoporosis treated with PV in a single institution over 46 months from March 2005 to December 2008. Multivariable logistic regression and univariate analysis were employed to identify risk factors for new VCFs after PV, including patient demographic data, parameters of the initial and new fractured vertebrae, procedure-related information, and follow-up data. RESULTS: During the follow-up period (22.4 months ± 12.1), 80 new vertebral fractures occurred in 36 (27.3%) patients. Multivariate analysis showed that number of VCFs per time frame, computed tomography (CT) value of nonfractured vertebrae (T11-L2), activity level after discharge, duration of follow-up, and cement distribution in the inferior part of the vertebral body or close to the endplate were statistically correlated with new fractures (odds ratios, 2.63, 0.96, 3.59, 1.00, 0.30, and 0.05; P = .006, P = .001, P = .007, P = .004, P = .021 and P = .029). Univariate analysis showed preexisting old VCFs were correlated with new VCFs (P = .045). Subsequent compression fractures in adjacent vertebrae (45 of 80) occurred more frequently and sooner than nonadjacent vertebral fractures (both P < .05). CONCLUSIONS: The incidence of new VCFs after PV is relatively high and affected by several risk factors that are related to both the PV procedure and the natural course of osteoporosis.
Assuntos
Fraturas por Compressão/cirurgia , Osteoporose/complicações , Fraturas da Coluna Vertebral/cirurgia , Vertebroplastia/efeitos adversos , Idoso , China , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/etiologia , Humanos , Incidência , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Estudos Prospectivos , Recidiva , Medição de Risco , Fatores de Risco , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Vertebroplastia/métodosRESUMO
OBJECTIVE: To evaluate the influencing factors of cement leakage in vertebroplasty for the treatment of osteoporosis vertebral compression fracture (OVCF) and vertebral metastases (VM). METHODS: Retrospective analysis was conducted for 653 vertebrae in 356 patients undergoing vertebroplasty at our hospital from May 2007 to January 2011. 251 cases had 438 vertebrae with painful OVCF while 105 cases had 215 vertebrae with VM. Pre-operative computed tomography (CT) was performed to determine the presence of cortical defects or osteolysis and within 3 days after PVP to observe the distribution of polymethylmethacrylate (PMMA) in vertebrae and whether leakage occurred. Volume of PMMA injected into each vertebral body and types of cement leakage were compared between the OVCF and VM groups by Z test or χ². The correlation between cortical defects and cement leakages around vertebrae was assessed with Pearson correlation coefficient. RESULTS: The successful rate of PVP was 100%. The mean volume of PMMA injected into each vertebra was (5.0 ± 2.0) ml and (4.0 ± 1.7) ml in the OVCF and VM groups respectively (P < 0.05). Asymptomatic PMMA leakage was demonstrated by CT in 93 vertebrae (21.2%) in the OVCF group and in 53 vertebrae (28.8%) in the VM group respectively (P < 0.05). Cement leakages into disk were found in 58 vertebrae in the OVCF group and 16 vertebrae in the VM group respectively (P = 0.025). Cement leakages into paravertebral vein were found in 12 vertebrae in the OVCF group and 26 vertebrae in the VM group respectively (P < 0.0001). Correlation was found between cortical defects and cement leakage into paravertebral soft tissues in the OVCF group (r = 0.14) or in the VM group (r = 0.27), between end-plate defects and cement leakage into disk in the OVCF group (r = 0.29) or in the VM group (r = 0.31). CONCLUSION: As a common occurrence in vertebroplasty, cement extravasation is well-tolerated in most patients. It occurs more frequently in the patients with VM than those with OVCF, especially in cases of leakage into paravertebral vein. Cement leakage into disc or paravertebral soft tissue is predisposed in vertebrae with end plate, cortical defects or osteolysis.
Assuntos
Cimentos Ósseos/efeitos adversos , Extravasamento de Materiais Terapêuticos e Diagnósticos/diagnóstico por imagem , Vertebroplastia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the feasibility and safety of catheterization in rat hepatic artery and interventional therapy through carotid artery. METHODS: A total of 30 Sprague-Dawley rats were randomly divided into 2 groups. All were punctured through left common carotid artery (LCCA) under intraperitoneal injection anesthesia. Microcatheter was inserted through a puncturing outer cannula into celiac artery and angiography performed to investigated the anatomical structure. Then a microcatheter was inserted into proper hepatic artery. One group was perfused with epirubicin 5 mg while another embolized with lipidol and polyvinyl (PVA). The status of vascular patency was re-examined by celiac angiography after perfusion and embolization. The 2-week survival rate (SR) and related complications were observed. RESULTS: Except for one failed case, all other cases were successfully inserted and celiac-gastroduodenal arteriography was completed with a success rate of 97% (29/30). The anastomosis between gastroduodenal artery (GDA) and superior mesenteric artery (SMA) was demonstrated in 28 cases (28/29, 96.6%). In 14 cases with perfusion therapy, arteriography demonstrated all branches of celiac artery had no occlusion while 10 embolized cases (10/15, 67%) had the main branch occlusion of gastroduodenal artery and 5 (5/15, 33%) stayed open. No postoperative abnormality was found in the limb motor function. Five had the drooping of left upper eyelid during 12 - 24 h after intervention and subsided after a week. And 10 embolized via main branch of gastroduodenal artery showed a poor appetite within 3 days postoperation and recovered gradually after 3 days. After intervention, 27 rats survived in 2 weeks. The survival rate was 93% (27/29). One died of incision infection and another neck hematoma. CONCLUSION: Catheterization in hepatic artery and interventional therapy through carotid artery is both feasible and safe. It may have a high application value.
Assuntos
Artérias Carótidas , Embolização Terapêutica/métodos , Artéria Hepática , Animais , Feminino , Intubação , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To evaluate the predictive value of serum beta 2-microglobulin level for recurrent stenosis or occlusion in patient undergoing percutaneous transluminal angioplasty (PTA) for lower limb ischemia. METHODS: Between March 2009 and October 2010, 81 patients were admitted with a diagnosis of lower limb ischemia. Among them, 54 patients had a mean age of 64 ± 12 years. The baseline characteristics, stenting and post-procedure events were collected. And the serum level of beta 2-microglobulin was measured by dynamic timing nephelometry assay. Recurrent stenosis or occlusions were confirmed with color Doppler ultrasonography or CTA imaging. Cox regression univariate analysis was performed with variables with P value < 0.20 to investigate the independent predictors of recurrent stenosis or occlusions. Receiver-operating characteristics curves (ROC) were constructed to evaluate the sensitivity and specificity of this model. RESULTS: The baseline characteristics were evenly distributed in two groups. Twenty-three patients (42.5%) were found to have recurrent stenosis or occlusions. The cumulative primary patency was 85%, 69% and 34%at Month 6, 12 and 24 respectively. The serum levels of beta 2-microglobulin decreased during a follow-up period of 3 months and then increased gradually in patients with recurrent stenosis or occlusion. Cox regression analysis identified the serum level of beta 2-microglobulin as an independent predictor of recurrent stenosis or occlusion (Odds Ratio = 1.459, 95%CI 1.199 - 1.777, P = 0.000). The area under the curve (AUC) of the serum level of beta 2-microglobulin was 0.952 for recurrent stenosis or occlusion. And the sensitivity was 95.7% and the specificity 77.4% on a cut-off value 3.2 mg/L. CONCLUSION: With a cut-off value 3.2 mg/L, the serum level of beta 2-microglobulin may be useful for the prediction of recurrent stenosis or occlusion in patients after lower limb PTA.