RESUMO
OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) has been used extensively in the management of thoracic aortic diseases. Numerous efforts have been made to enhance clinical outcomes through the use of stent grafts. This study aimed to investigate the effectiveness and safety of physician-manufactured partial micropore stent grafts (PSMGs) in TEVAR. METHODS: Between December 2017 and June 2022, data were collected from 56 patients who underwent TEVAR using physician-manufactured PSMGs. The evaluation encompassed technical success, perioperative and follow-up morbidity and mortality, stroke incidence, and branch artery patency. RESULTS: In this investigation, 56 patients received treatment with physician-manufactured PSMGs. Of these patients, 46 were male, with a mean age of 62.1 ± 11.2 years. Aortic pathologies comprised aortic dissection (n = 31 [55.4%]), aortic aneurysms (n = 10 [17.9%]), penetrating aortic ulcer (n = 8 [14.3%]), and intramural hematoma (n = 7 [12.5%]). During a median follow-up of 18 months (interquartile range, 13-25 months), the stroke rate, supra-aortic branch patency rate, and endoleak rate were 0%, 100%, and 7.1%, respectively. There were no occurrences of all-cause mortality, stroke, or the necessity for open conversion. CONCLUSIONS: TEVAR with physician-manufactured PSMGs is a viable alternative for addressing aortic arch pathologies in proficient medical centers. The approach demonstrates favorable branch patency, a low complication rate, and minimal postoperative mortality.
Assuntos
Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Prótese Vascular , Correção Endovascular de Aneurisma , Implante de Prótese Vascular/efeitos adversos , Stents/efeitos adversos , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/etiologia , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Desenho de Prótese , Fatores de Tempo , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: The aim of this study was to explore the genetic effects of hormones modulated through the pituitary-thyroid/adrenal/gonadal axis on the risk of developing venous thromboembolism (VTE) and to investigate the potentially causal relationships between them. METHODS: A two-sample Mendelian randomization (MR) design was used. The single-nucleotide polymorphisms (SNPs) used as instrumental variables for various hormones and hormone-mediated diseases were derived from published genome-wide association studies (GWASs). Summary statistics for the risk of developing VTE (including deep venous thrombosis [DVT] and pulmonary embolism [PE]) were obtained from the UK Biobank and the FinnGen consortium. Inverse-variance weighting (IVW) was applied as the primary method to analyse causal associations. Other MR methods were used for supplementary estimates and sensitivity analysis. RESULTS: A genetic predisposition to greater free thyroxine (FT4) concentrations was associated with a greater risk of developing DVT (OR = 1.0007, 95%CI [1.0001-1.0013], p = 0.0174) and VTE (OR = 1.0008, 95%CI [1.0002-1.0013], p = 0.0123). Genetically predicted hyperthyroidism was significantly associated with an increased risk of developing DVT (OR = 1.0685, 95%CI [1.0139-1.1261], p = 0.0134) and VTE (OR = 1.0740, 95%CI [1.0165-1.1348], p = 0.0110). According to the initial MR analysis, testosterone concentrations were positively associated with the risk of developing VTE (OR = 1.0038, 95%CI [1.004-1.0072], p = 0.0285). After sex stratification, estradiol concentrations were positively associated with the risk of developing DVT (OR = 1.0143, 95%CI [1.0020-1.0267], p = 0.0226) and VTE (OR = 1.0156, 95%CI [1.0029-1.0285], p = 0.0158) in females, while the significant relationship between testosterone and VTE did not persist. SHBG rs858518 was identified as the only SNP that was associated with an increased risk of developing VTE, mediated by estradiol, in females. CONCLUSIONS: Genetically predicted hyperthyroidism and increased FT4 concentrations were positively associated with the risk of developing VTE. The effects of genetically predicted sex hormones on the risk of developing VTE differed between males and females. Greater genetically predicted estradiol concentrations were associated with an increased risk of developing VTE in females, while the SHBG rs858518 variant may become a potential prevention and treatment target for female VTE.
Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/genética , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/sangue , Fatores de Risco , Medição de Risco , Feminino , Masculino , Tiroxina/sangue , Fenótipo , Biomarcadores/sangue , Trombose Venosa/genética , Trombose Venosa/epidemiologia , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Fatores Sexuais , Testosterona/sangue , Embolia Pulmonar/genética , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/sangue , Embolia Pulmonar/diagnósticoRESUMO
OBJECTIVE: The evaluation of limb status with the Wound, Ischaemia, and foot Infection (WIfI) classification and the assessment of patient risks combined with systemic factors, are recommended in patients with chronic limb threatening ischaemia (CLTI). However, there is little evidence of the application of the WIfI classification in the Chinese population. This study aimed to verify the use of the WIfI classification in a Chinese patient population, and to further identify local and systemic independent predictors of adverse CLTI outcomes. METHODS: A total of 474 patients who underwent endovascular therapy (EVT) for CLTI in a tertiary hospital between July 2017 and September 2020 were included in this retrospective study. The outcomes included one year major adverse limb events (MALEs), one year all cause mortality, and one year amputation free survival (AFS). Cox regression was used to analyse the association between risk factors and adverse outcomes. RESULTS: In total, 104 (21.9%) all cause deaths were recorded. The rate of MALEs was 17.5%, while the AFS was 71.9%. Multivariable analysis revealed that a body mass index (BMI) < 18.5 kg/m2 (p = .002), a left ventricular ejection fraction (LVEF) < 50% (p < .001), and WIfI wound grade (p < .001) were independent risk factors for MALEs, while age ≥ 77 years (p = .031), BMI < 18.5 kg/m2 (p < .001), coronary heart disease (p = .040), and WIfI clinical stages (p = .021) were independent risk factors for death in patients with CLTI. Age ≥ 77 years (p = .003), BMI < 18.5 kg/m2 (p < .001), coronary heart disease (p = .012), LVEF < 50% (p < .001), WIfI wound grade (p = .004), and WIfI clinical stages (p = .044) were independently associated with a decreased AFS rate. CONCLUSIONS: This study has confirmed the predictive ability of the WIfI classification for Chinese patients with CLTI who underwent EVT. Wound grade was the most sensitive and important risk factor of the three components of WIfI. In addition, systemic factors should be considered to ensure a more accurate prognosis prediction and appropriate clinical decision making in patients with CLTI.
Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Infecção dos Ferimentos , Masculino , Humanos , Idoso , Isquemia Crônica Crítica de Membro , Medição de Risco , Resultado do Tratamento , Estudos Retrospectivos , Volume Sistólico , Salvamento de Membro , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Infecção dos Ferimentos/terapia , Extremidade Inferior/irrigação sanguínea , Função Ventricular Esquerda , Fatores de Risco , Isquemia/diagnóstico , Isquemia/cirurgia , Procedimentos Endovasculares/efeitos adversosRESUMO
Microbial extracellular electron transfer (EET) is the basis for many microbial processes involved in element geochemical recycling, bioenergy harvesting, and bioremediation, including the technique for remediating U(VI)-contaminated environments. However, the low EET rate hinders its full potential from being fulfilled. The main challenge for engineering microbial EET is the difficulty in optimizing cell resource allocation for EET investment and basic metabolism and the optimal coordination of the different EET pathways. Here, we report a novel combinatorial optimization strategy with a physiologically adapted regulatory platform. Through exploring the physiologically adapted regulatory elements, a 271.97-fold strength range, autonomous, and dynamic regulatory platform was established for Shewanella oneidensis, a prominent electrochemically active bacterium. Both direct and mediated EET pathways are modularly reconfigured and tuned at various intensities with the regulatory platform, which were further assembled combinatorically. The optimal combinations exhibit up to 16.12-, 4.51-, and 8.40-fold improvements over the control in the maximum current density (1009.2 mA/m2) of microbial electrolysis cells and the voltage output (413.8 mV) and power density (229.1 mW/m2) of microbial fuel cells. In addition, the optimal strains exhibited up to 6.53-fold improvement in the radionuclide U(VI) removal efficiency. This work provides an effective and feasible approach to boost microbial EET performance for environmental applications.
Assuntos
Fontes de Energia Bioelétrica , Shewanella , Elétrons , Transporte de Elétrons , Biodegradação Ambiental , Shewanella/metabolismoRESUMO
BACKGROUND AND AIMS: Percutaneous mechanical thrombectomy (PMT) along with postoperative thrombolysis (POT) has been the standard treatment for acute iliofemoral deep venous thrombosis (IFDVT). However, commonly used catheter directed thrombolysis (CDT) approaches for POT carry certain disadvantages, including the need for a sheath, inferior comfortability, and catheter-related complications. Therefore, we propose a new simplified method of POT using a central venous catheter (CVC). METHODS: The retrospective study analyzed patients with IFDVT who underwent POT using CVC from January 2020 to August 2021. The treatment modalities included filter placement, thrombus removal, iliac vein obstruction release, postoperative CVC thrombolysis, filter retrieval, and adequate full course anticoagulation. RESULTS: A total of 39 patients were included in this retrospective study. All patients underwent PMT surgery with a procedure success rate of 100%. In the post-PMT CVC thrombolysis, the puncture sites were located in the below-knee vein, including 58.97% in the peroneal vein. The mean duration of CVC-directed thrombolysis was 3.69 ± 1.08 days, and the total urokinase dose was 2.27 ± 0.71 MIU. A total of 37 patients (94.87%) had successful thrombolysis with a length of hospital stay of 5.82 ± 2.21 days. During CVC-directed thrombolysis, only four minor bleeding complications occurred, two of which were indwelling catheter-related. During the 12-month follow-up period, the patency rate and post-thrombotic syndrome incidences were 97.44% and 2.56%, respectively. CONCLUSION: Thrombolysis through a CVC is a feasible, safe, and effective POT method, and could be an alternative to the conventional CDT approach for patients with IFDVT.
Assuntos
Cateteres Venosos Centrais , Trombose Venosa , Humanos , Terapia Trombolítica/métodos , Cateteres Venosos Centrais/efeitos adversos , Estudos Retrospectivos , Veia Femoral/cirurgia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Resultado do Tratamento , Fibrinolíticos/uso terapêuticoRESUMO
The unique extracellular electron transfer (EET) ability has positioned electroactive bacteria (EAB) as a major class of cellular chassis for genetic engineering aimed at favorable environmental, energy, and geoscience applications. However, previous efforts to genetically enhance EET ability have often impaired the basal metabolism and cellular growth due to the competition for the limited cellular resource. Here, we design a quorum sensing-based population-state decision (PSD) system for intelligently reprogramming the EET regulation system, which allows the rebalanced allocation of the cellular resource upon the bacterial growth state. We demonstrate that the electron output from Shewanella oneidensis MR-1 could be greatly enhanced by the PSD system via shifting the dominant metabolic flux from initial bacterial growth to subsequent EET enhancement (i.e., after reaching a certain population-state threshold). The strain engineered with this system achieved up to 4.8-fold EET enhancement and exhibited a substantially improved pollutant reduction ability, increasing the reduction efficiencies of methyl orange and hexavalent chromium by 18.8- and 5.5-fold, respectively. Moreover, the PSD system outcompeted the constant expression system in managing EET enhancement, resulting in considerably enhanced electron output and pollutant bioreduction capability. The PSD system provides a powerful tool for intelligently managing extracellular electron transfer and may inspire the development of new-generation smart bioelectrical devices for various applications.
Assuntos
Transporte de Elétrons/fisiologia , Shewanella/fisiologia , Respiração Celular/fisiologia , Cromo/metabolismo , Elétrons , Percepção de Quorum/fisiologia , Shewanella/metabolismoRESUMO
Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.
Assuntos
Gentamicinas , Fator 2 Relacionado a NF-E2 , Ratos , Animais , Gentamicinas/efeitos adversos , Fator 2 Relacionado a NF-E2/metabolismo , Apoptose , Rim , Malondialdeído/metabolismo , Glutationa/metabolismoRESUMO
The advances in synthetic biology bring exciting new opportunities to reprogram microorganisms with novel functionalities for environmental applications. For real-world applications, a genetic tool that enables genetic engineering in a stably genomic inherited manner is greatly desired. In this work, we design a novel genetic device for rapid and efficient genome engineering based on the intron-encoded homing-endonuclease empowered genome editing (iEditing). The iEditing device enables rapid and efficient genome engineering in Shewanella oneidensis MR-1, the representative strain of the electroactive bacteria group. Moreover, combining with the Red or RecET recombination system, the genome-editing efficiency was greatly improved, up to approximately 100%. Significantly, the iEditing device itself is eliminated simultaneously when genome editing occurs, thereby requiring no follow-up to remove the encoding system. Then, we develop a new extracellular electron transfer (EET) engineering strategy by programming the parallel EET systems to enhance versatile EET. The engineered strains exhibit sufficiently enhanced electron output and pollutant reduction ability. Furthermore, this device has demonstrated its great potential to be extended for genome editing in other important microbes. This work provides a useful and efficient tool for the rapid generation of synthetic microorganisms for various environmental applications.
Assuntos
Fontes de Energia Bioelétrica/microbiologia , Elétrons , Engenharia Genética/métodos , Genoma Bacteriano/genética , Biodegradação Ambiental , Transporte de Elétrons/genética , Poluentes Ambientais/metabolismo , Edição de Genes/instrumentação , Engenharia Genética/instrumentação , Recombinação Genética , Shewanella/genética , Shewanella/metabolismoRESUMO
OBJECTIVE: The effectiveness of endovascular treatment for popliteal arterial injury has not been well-documented. This study was aimed to investigate the midterm outcomes of endovascular repair of traumatic isolated popliteal arterial injury. METHODS: Medical records of the patients who underwent endovascular repair for traumatic popliteal arterial injuries from January 2012 to February 2020 were reviewed retrospectively. Clinical data including patient demographics, Injury Severity Score, type of injury, classification of acute limb ischemia, concomitant extremity fracture, runoff vessel status, complications, time of endovascular procedure, time interval from injury to blood flow restoration, length of hospital stay, reintervention, and follow-up were collected and analyzed. RESULTS: Endovascular repair was performed in 46 patients with traumatic popliteal arterial injuries. The mean Injury Severity Score was 15.8 ± 6.2. The overall limb salvage rate was 89.1%. There were 10 penetrating and 36 blunt injuries (78.3%). The initial angiographic findings revealed occlusion in 34 patients (73.9%), pseudoaneurysm in 2 (4.4%), active extravasation in 9 (19.5%), and arteriovenous fistulas in 1 (2.2%). Technical success was achieved in all 46 patients, via antegrade access in 24 patients (52.2%) and concurrent retrograde access in 22 (47.8%). The mean time interval from popliteal artery injury to blood flow restoration was 10.6 ± 4.9 hours and mean operative time was of 54.9 ± 10.0 minutes. The mean follow-up was 36.1 ± 14.5 months. The primary patency rate was 75.3% at 12 months, 61.9% at 24 months, and 55.7% at 48 months. The secondary patency rate was 92.2% at 12 and 24 months and 85.2% at 48 months. A Cox multivariate analysis revealed that single vessel runoff was an independent risk factor for primary patency loss. CONCLUSIONS: Endovascular repair of an isolated popliteal artery injury may be a safe and effective alternative treatment in select patients, with acceptable midterm outcomes. Single vessel runoff was an independent risk factor for primary patency loss.
Assuntos
Procedimentos Endovasculares , Artéria Poplítea/lesões , Lesões do Sistema Vascular/terapia , Adulto , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Artéria Poplítea/diagnóstico por imagem , Artéria Poplítea/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/fisiopatologiaRESUMO
Dissimilatory metal-reducing bacteria (DMRB) with extracellular electron transfer (EET) capability show great potential in bioremediating the subsurface environments contaminated by uranium through bioreduction and precipitation of hexavalent uranium [U(VI)]. However, the low EET efficiency of DMRB remains a bottleneck for their applications. Herein, we develop an engineered CRISPR platform to drive the extracellular electron pumping of Shewanella oneidensis, a representative DMRB species widely present in aquatic environments. The CRISPR platform allows for highly efficient and multiplex genome editing and rapid platform elimination post-editing in S. oneidensis. Enabled by such a platform, a genomic promoter engineering strategy (GPS) for genome-widely engineering the EET-encoding gene network was established. The production of electron conductive Mtr complex, synthesis of electron shuttle flavin, and generation of NADH as intracellular electron carrier are globally optimized and promoted, leading to a significantly enhanced EET ability. Applied to U(VI) bioreduction, the edited strains achieve up to 3.62-fold higher reduction capacity over the control. Our work endows DMRB with an enhanced ability to remediate the radionuclides-contaminated environments and provides a gene editing approach to handle the growing environmental challenges of radionuclide contaminations.
Assuntos
Shewanella , Urânio , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Transporte de Elétrons , Elétrons , Shewanella/genéticaRESUMO
Cinnamaldehyde (CA) is one of the major active pharmaceutical ingredient of cinnamon bark. Hydrodistillation (HD) is usually used in CA extraction, however, the extraction yield is lower. The cell wall is a key factor limiting the extraction of essential oils. In-situ reactive heat breaking cell wall (RHB) could destroy the cell wall, which was conducive to the diffusion of CA. The aim of this work was to examine the effect of RHB pretreatment to HD extraction. Response surface methodology (RSM) was used to optimize RHB pretreatment parameters, and Box-Behnken Design (BBD) method was performed to evaluate the effects of different operating parameters. The maximum yield was increased to 3.31 ± 0.11% (w/w) from 2.08 ± 0.042% (w/w) after RSM optimization. Scanning electron microscopic (SEM) analysis showed that RHB destroyed and disrupted the cell wall of cinnamon bark. The GC analysis demonstrated that the purity of cinnamaldehyde was improved and no new components were presented in the extraction product from the cinnamon via RHB pretreatment. In conclusion, RHB is an effective pretreatment method for the CA extraction, and also may be used in the other herbal medicine extraction.
Assuntos
Parede Celular/química , Cinnamomum zeylanicum/química , Temperatura Alta , Óxidos de Enxofre/química , Acroleína/análogos & derivados , Acroleína/química , Acroleína/isolamento & purificaçãoRESUMO
OBJECTIVE: This study explored the clinical efficacy and hemodynamic effects of the micropore stent graft (MSG) that could promote aortic remodeling and preserve important organ branches. METHODS: We conducted a retrospective analysis of 26 patients who underwent endovascular repair using an MSG for DeBakey types I and III TAD at our center between December 2014 and December 2017. The main efficacy parameters were rupture of the false lumen or dissection-related death, conversion to open repair, secondary reintervention, branch vessel patency, and the hemodynamic effects of TAD at 12 months. RESULTS: Dissection rupture, dissection-related mortality, conversion to open repair, and secondary reintervention rates at 12 months were 0, 3.9, 0, and 0%, respectively. In the 24 patients with more than 6 months of follow-up, micropore stents were implanted to cover 39 openings in aortic arch branches, 91.7% (22/24) presented with complete thrombosis in the false lumen, 8.3% (2/24) presented with partial thrombosis in the false lumen, 35.2% (6/17) presented with a thrombus in the false lumen that was completely absorbed, and all 39 branches were patent. After surgery, pressure peak value and fluctuation along with the degree and range of unstable blood flow in the aortic lumen decreased. CONCLUSIONS: For type I and type III thoracic artic dissection, endovascular treatment with an MSG may be a safe and effective treatment option with a good midterm outcome.
Assuntos
Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Adulto , Idoso , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/mortalidade , Dissecção Aórtica/fisiopatologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/fisiopatologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Porosidade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Desenho de Prótese , Estudos Retrospectivos , Fatores de Risco , Propriedades de Superfície , Fatores de Tempo , Resultado do Tratamento , Remodelação VascularRESUMO
Pursuing efficient approaches to promote the extracellular electron transfer (EET) of extracellular respiratory bacteria is essential to their application in environmental remediation and waste treatment. Here, we report a new strategy of tuning electron flux by clustered regularly interspaced short palindromic repeat (CRISPR)-ddAsCpf1-based rediverting (namely STAR) to enhance the EET capacity of Shewanella oneidensis MR-1, a model extracellular respiratory bacterium widely present in the environment. The developed CRISPR-ddAsCpf1 system enabled approximately 100% gene repression with the green fluorescent protein (GFP) as a reporter. Using a WO3 probe, 10 representative genes encoding for putative competitive electron transfer proteins were screened, among which 7 genes were identified as valid targets for EET enhancement. Repressing the valid genes not only increased the transcription level of the l-lactate metabolism genes but also affected the genes involved in direct and indirect EET. Increased riboflavin production was also observed. The feasibility of this strategy to enhance the bioreduction of methyl orange, an organic pollutant, and chromium, a typical heavy metal, was demonstrated. This work implies a great potential of the STAR strategy with the CIRPSR-ddAsCpf1 system for enhancing bacterial EET to favor more efficient environmental remediation applications.
Assuntos
Poluentes Ambientais , Shewanella , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Transporte de Elétrons , ElétronsRESUMO
OBJECTIVE: To evaluate the efficacy, safety and long-term outcome of TIPP for the adjunct therapy of superficial venous reflux-related VLUs. METHODS: A total of 93 consecutive patients (104 legs) with superficial venous insufficiency-related VLUs who underwent TIPP (53 legs) or conventional phlebectomy (51 legs) between January 2010 and December 2013 were retrospectively studied. RESULTS: Compared to patients in the conventional phlebectomy group, TIPP patients had larger ulcer areas before surgery (P < 0.005). However, TIPP group required a significantly shorter operation time (P < 0.005), fewer incisions (P < 0.005) but less ulcer healing time (1.25 month vs 2.5 months, P < 0.05). No significant difference in in-hospital and follow-up complications was found between the two groups. For long-term outcome, TIPP group leaded a lower ulcer recurrence rate at 36 months (13.2% vs 29.4%, P < 0.05). CONCLUSION: TIPP may be an adjunct surgical method contributes to healing of VLUs, especially for large ulcer areas.
Assuntos
Tomografia Computadorizada por Raios X , Úlcera Varicosa/diagnóstico por imagem , Úlcera Varicosa/cirurgia , Procedimentos Cirúrgicos Vasculares , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Úlcera Varicosa/fisiopatologiaAssuntos
Veias , Trombose Venosa , Humanos , Veia Ilíaca , Resultado do Tratamento , Stents , Estudos RetrospectivosRESUMO
BACKGROUND/AIMS: Skeletal muscle ischemia/reperfusion (I/R) injury is a common and severe disease. Sonic hedgehog (Shh) plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. METHODS: The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh) to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. RESULTS: We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. CONCLUSION: Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury.
Assuntos
Proteínas Hedgehog/metabolismo , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Traumatismo por Reperfusão/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Imunofluorescência , Proteínas Hedgehog/antagonistas & inibidores , Proteínas Hedgehog/genética , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Alcaloides de Veratrum/uso terapêuticoRESUMO
Platelet-derived growth factor (PDGF) is known to induce phenotypic switching of vascular smooth muscle cells (VSMCs) from contractile to a pathological synthetic state, which played an essential role in proliferation of VSMCs. Sonic hedgehog (Shh) contributes to the proliferation of VSMCs when induced by PDGF. Here, we investigated the probable role of Shh in PDGF-induced VSMC dedifferentiation and its underlying mechanisms. We found that PDGF stimulated Shh expression in VSMCs, which was mediated by activation of PDGFRß/ERK1/2 cell signaling pathway. Further, we found PDGF-induced VSMC phenotypic modulation was accompanied by up-regulation of Shh/Gli family zinc finger 2 (Gli2) signaling and Krüppel-like factor 4 (KLF4). When inhibited Shh in the presence of PDGF, the expressions of KLF4 and VSMC dedifferentiation markers were down-regulated and the effect of PDGF in inducing VSMC dedifferentiation was blocked. In the absence of PDGF, Shh signaling activation increased the expression of KLF4 and promoted VSMC dedifferentiation. The results indicate Shh participated in the regulation of PDGF-induced VSMC dedifferentiation. Finally, we found that KLF4 was closely involved in this process. On inhibition of KLF4, PDGF induced VSMC dedifferentiation was abrogated, even in the presence of Shh. Taken together, the results provide critical insights into the newly discovered role of Shh in phenotypic modulation of VSMCs which depends on KLF4.
Assuntos
Proteínas Hedgehog/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Contração Muscular/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fator de Crescimento Derivado de Plaquetas/farmacologia , Animais , Desdiferenciação Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Fator 4 Semelhante a Kruppel , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fenótipo , Ratos WistarRESUMO
Purpose: This retrospective study aims to evaluate the safety, practicality, and efficacy of the independent retrograde popliteal approach for recanalization superficial femoral artery (SFA) occlusions when the bilateral common femoral artery approach is unavailable, such as after endovascular aneurysm repair or common iliac artery stenting. Methods: This treatment was considered for patients with contralateral iliac artery occlusion, severe iliac tortuosity, or those who had previously undergone endovascular aneurysm repair or common iliac stenting. Patients with SFA lesions extending into the P1-P2 segment of the popliteal artery or with calcification in the P3 segment were excluded. Angioplasty and stenting were conducted via the popliteal artery approach, with hemostasis at the puncture site achieved using an EXOSEAL vascular closure device. Patients were routinely followed up at 3, 6, and 12 months, and annually thereafter. Results: Forty-eight consecutive patients with SFA occlusion who underwent endovascular treatment via the retrograde popliteal artery approach were included in this study. Retrograde puncture of the popliteal artery was successful in all cases. Six-French sheaths were utilized in all procedures. The EXOSEAL vascular closure device was successfully applied in all 48 cases. No instances of pseudoaneurysms, arteriovenous fistulas, major bleeding, or embolic complications were observed. The technical success rate for SFA recanalization was 100 %. All patients experienced clinical improvement. The ankle-brachial index significantly increased from an initial 0.33 ± 0.11 at admission to 0.81 ± 0.19 at discharge (P < 0.001). The mean follow-up period was 25.1 ± 11.7 months. Kaplan-Meier analysis revealed primary patency rates of 82.5 % at 12 months and 71.8 % at 24 months. No patients required major amputation during the follow-up period. Conclusion: The endovascular treatment of SFA occlusions via the independent retrograde popliteal approach is a viable alternative, demonstrating a low incidence of puncture-related complications and a high success rate of recanalization.
RESUMO
BACKGROUND: The modification of N6-methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation of messenger RNA. The YTH domain protein family, acting as "readers" of m6A modifications, affects RNA splicing, stability, and immunogenicity, thereby playing essential roles in immune regulation and antitumor immunity. Despite their significance, the impact of the YTH domain protein family on tumor initiation and progression, as well as their involvement in tumor immune regulation and therapy, remains underexplored and lacks comprehensive review. CONCLUSION: This review introduces the molecular characteristics of the YTH domain protein family and their physiological and pathological roles in biological behavior, emphasizing their mechanisms in regulating immune responses and antitumor immunity. Additionally, the review discusses the roles of the YTH domain protein family in immune-related diseases and tumor resistance, highlighting that abnormal expression or dysfunction of YTH proteins is closely linked to tumor resistance. KEY POINTS: This review provides an in-depth understanding of the YTH domain protein family in immune regulation and antitumor immunity, suggesting new strategies and directions for immunotherapy of related diseases. These insights not only deepen our comprehension of m6A modifications and YTH protein functions but also pave the way for future research and clinical applications.