RESUMEN
Currently, the planting of 'Qi-Nan' is continuously increasing, yet a substantial amount of 'Qi-Nan' leaves have not been properly exploited. To improve the 'Qi-Nan' tree 's utilization value, 'Qi-Nan' leaves were used as a raw material. An ultrasound-assisted method was performed to obtain the flavonoids from the 'Qi-Nan' leaves, followed by optimization of the extraction factors using a one-way and response surface methodology to enhance the extraction of flavonoids. Subsequently, the composition of the flavonoids, as well as their bioactive abilities, were analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and in vitro activity testing methods. The findings demonstrated that a 1:50 material-to-liquid ratio, 60% ethanol concentration, and ultrasound-assisted extraction time of 30 min were the ideal procedures for extracting flavonoids (flavonoid content: 6.68%). Meanwhile, the 'Qi-Nan' leaves possessed the antioxidant and medicinal potential to prevent diabetes and Alzheimer 's disease, as evidenced by the semi-inhibitory concentrations (IC50 values) of flavonoid extracts for scavenging DPPH⢠free radicals, scavenging ABTSâ¢+ free radicals, inhibiting acetylcholinesterase, and inhibiting α-glucosidase, which were 12.64 µg/mL, 66.58 µg/mL, 102.31 µg/mL, and 38.76 µg/mL, respectively, which indicated that the 'Qi-Nan' leaves possessed the properties of antioxidant and medicinal potential for the prevention of Alzheimer 's disease and diabetes.
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Antioxidantes , Flavonoides , Extractos Vegetales , Hojas de la Planta , Flavonoides/análisis , Flavonoides/química , Flavonoides/aislamiento & purificación , Hojas de la Planta/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Cromatografía Líquida de Alta Presión , Thymelaeaceae/químicaRESUMEN
NEW FINDINGS: What is the central question of this study? What is the relationship of chemokine (C-C motif) ligand 8 (CCL8) to thoracic aortic aneurysm and dissection (TAAD) formation in postnatal mice with vascular smooth muscle cell (VSMC) Tgfbr2 disruption, and is dexamethasone a potential treatment? What is the main finding and its importance? CCL8 was associated with the formation of TAAD in VSMC Tgfbr2-disrupted mice. Dexamethasone reduced TAAD formation and inhibited mitogen-activated protein kinase (p-p38) and nuclear factor-κB (p-p65) signalling pathways. CCL8 might be an important promoter of aortic inflammation. Dexamethasone provided potential therapeutic effects in TAAD treatment. ABSTRACT: Aortic inflammation plays a vital role in initiation and progression of thoracic aortic aneurysm and dissection (TAAD). Disturbance of the transforming growth factor-ß (TGF-ß) signalling pathway is believed to be one of the pathogenic mechanisms of TAAD. Initially, Myh11-CreERT2 .Tgfbr2f/f male mice were used to build a TAAD mouse model, and bioinformatic analyses revealed enriched inflammatory signal pathways and upregulated chemokine (C-C motif) ligand 8 (CCL8). So we hypothesized that vascular smooth muscle cell (VSMC) Tgfbr2 disruption in postnatal mice results in aortic inflammation associated with CCL8 secretion. Real-time quantitative PCR and serum enzyme-linked immunosorbent assay (ELISA) results confirmed that CCL8 expression began to increase after VSMC Tgfbr2 disruption. Next, we cultured mouse thoracic aortas ex vivo, and observed that the protein expression of CCL8 in culture supernatants was increased by ELISA. Subsequently, the co-localization of CCL8 with α-smooth muscle actin or CD68 was found to be significantly increased by immunofluorescence. Then, dexamethasone (DEX) was used to treat TAAD in VSMC Tgfbr2-disrupted mice; the results of histochemical, immunofluorescence and immunohistochemical staining indicated that DEX therapy reduced CCL8 secretion, inflammatory cell recruitment, aortic medial thickening, elastic fibre fragmentation, extracellular matrix degradation and contractile apparatus impairment, and thereby ameliorated TAAD formation. Western blotting showed that mitogen-activated protein kinase and nuclear factor-κB signalling pathways in aorta were overactivated after VSMC Tgfbr2 disruption, but inhibited by DEX therapy. Altogether, CCL8 might be an important promoter in TAAD formation of VSMC Tgfbr2-disrupted mice, and DEX provided potential therapeutic effects in TAAD treatment.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Dexametasona , Músculo Liso Vascular , Disección Aórtica/tratamiento farmacológico , Disección Aórtica/metabolismo , Disección Aórtica/patología , Animales , Aneurisma de la Aorta Torácica/tratamiento farmacológico , Aneurisma de la Aorta Torácica/metabolismo , Aneurisma de la Aorta Torácica/patología , Quimiocina CCL8/metabolismo , Dexametasona/farmacología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/metabolismo , FN-kappa B/metabolismo , Receptor Tipo II de Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening vascular disease with no effective pharmaceutical therapies currently available. Inflammation plays a key role in the progression of aneurysms. Dexamethasone (DEX), a synthetic glucocorticoid, has showed alleviating effects on cells in vitro from TAAD patients. Here we performed a study aiming at investigating the protective role of DEX in a ß-aminopropionitrile monofumarate (BAPN)-induced TAAD mouse model. DEX (dose: 0.04 mg/kg/day) treatment significantly reduced the aortic diameter and inhibited TAAD formation. DEX reduced infiltration of macrophages and neutrophils, apoptosis of vascular smooth muscle cells (VSMCs), expression of metalloproteinase 2/9, and extracellular matrix degradation in BAPN-treated TAAD mice. Furthermore, DEX therapy downregulated the expression of p-p65 in macrophages and VSMCs, which suggested that DEX might ameliorate BAPN-induced TAAD by suppressing NF-κB signaling. Therefore, DEX therapy attenuates the progression of BAPN-induced TAAD murine model and could be used as an effective adjuvant therapy for treating TAAD.
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Aneurisma de la Aorta Torácica/tratamiento farmacológico , Disección Aórtica/tratamiento farmacológico , Dexametasona/farmacología , Miocitos del Músculo Liso/efectos de los fármacos , Aminopropionitrilo/metabolismo , Disección Aórtica/metabolismo , Animales , Aneurisma de la Aorta Torácica/metabolismo , Macrófagos/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Miocitos del Músculo Liso/metabolismoRESUMEN
OBJECTIVES: To compare drug-coated balloon (DCB) and bare metal stent (BMS) for primary lesions in femoropopliteal artery disease in Chinese population and to make subgroup analysis between the groups. METHODS: Patients with primary lesions who underwent BMS or DCB treatment of a single tertiary vascular center were included and followed up for 24 months. Clinical and anatomic status were reported using the criteria recommended by the Society for Vascular Surgery. The primary endpoint included primary patency, clinically target limb revascularization, composite safety endpoint and all-cause death over 24 months assessed by Kaplan-Meier. Secondary endpoints included technical success rate and stent-related complications. RESULTS: A total of 284 patients with 324 limbs were pooled into analysis and most of the baseline characteristics did not show significant difference. A total of 74 in BMS group and 71 in DCB group were claudicants while 83 in BMS group and 56 in DCB group suffered from chronic limb threatening ischemia (CLTI). The mean cumulative lesion length was 18.7 ± 9.8cm in BMS group while 17.2 ± 10.3cm in DCB group. Kaplan-Meier estimates of primary patency were 75.3% and 80.9% for BMS and DCB groups at 12 months while decreased to 63.9% and 70.2% at 24 months (log-rank P = 0.167), respectively. Freedom from clinically driven target limb revascularization was 86.8% and 92.7% for BMS and DCB groups at 12 months while dropped to 82.5% and 85.9% at 24 months (log-rank P = 0.342). Estimates of primary patency between BMS and DCB group did not show significant difference on lesions with poor runoff (58.8% vs. 67.3%, log-rank P = 0.127), severe calcification (64.5% vs. 69.4%, log-rank P = 0.525) and popliteal artery involvement (59.3% vs. 60.3%, log-rank P = 0.695) at 24 months. The overall survival (92.6% for BMS, 90.3% for DCB, log-rank P = 0.391) and freedom from composite safety endpoint (79.3% for BMS, 79.2% for DCB, log-rank P = 0.941) showed no significant difference at 24 months. CONCLUSIONS: Over the 24 month follow-up, BMS and DCB showed equivalent efficacy and safety outcomes for primary femoropopliteal artery disease, which indicated the reduction of permanent metallic implant insertion might be possible.
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Angioplastia de Balón , Enfermedad Arterial Periférica , Aleaciones , Angioplastia de Balón/efectos adversos , Materiales Biocompatibles Revestidos , Arteria Femoral/cirugía , Humanos , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Arteria Poplítea , Stents , Resultado del Tratamiento , Grado de Desobstrucción VascularRESUMEN
Unicentric Castleman disease, a rare lymphoproliferative disorder, is always known as a solitary, well-defined lymph node enlargement. We reported an extraordinary case of retroperitoneal Castleman disease, which invades wall of right iliac vein and inferior vena cava, treated successfully by tumorectomy with vascular repair.
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Enfermedad de Castleman/cirugía , Vena Ilíaca/cirugía , Procedimientos Quirúrgicos Vasculares , Vena Cava Inferior/cirugía , Enfermedad de Castleman/diagnóstico por imagen , Enfermedad de Castleman/patología , Humanos , Vena Ilíaca/diagnóstico por imagen , Vena Ilíaca/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Espacio Retroperitoneal , Resultado del Tratamiento , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/patologíaRESUMEN
OBJECTIVE: Elastin deficiency because of heterozygous loss of an ELN allele in Williams syndrome causes obstructive aortopathy characterized by medial thickening and fibrosis and consequent aortic stiffening. Previous work in Eln-null mice with a severe arterial phenotype showed that inhibition of mTOR (mechanistic target of rapamycin), a key regulator of cell growth, lessened the aortic obstruction but did not prevent early postnatal death. We investigated the effects of mTOR inhibition in Eln-null mice partially rescued by human ELN that manifest a less severe arterial phenotype and survive long term. APPROACH AND RESULTS: Thoracic aortas of neonatal and juvenile mice with graded elastin deficiency exhibited increased signaling through both mTOR complex 1 and 2. Despite lower predicted wall stress, there was increased phosphorylation of focal adhesion kinase, suggestive of greater integrin activation, and increased transforming growth factor-ß-signaling mediators, associated with increased collagen expression. Pharmacological blockade of mTOR by rapalogs did not improve luminal stenosis but reduced mechanosignaling (in delayed fashion after mTOR complex 1 inhibition), medial collagen accumulation, and stiffening of the aorta. Rapalog administration also retarded somatic growth, however, and precipitated neonatal deaths. Complementary, less-toxic strategies to inhibit mTOR via altered growth factor and nutrient responses were not effective. CONCLUSIONS: In addition to previously demonstrated therapeutic benefits of rapalogs decreasing smooth muscle cell proliferation in the absence of elastin, we find that rapalogs also prevent aortic fibrosis and stiffening attributable to partial elastin deficiency. Our findings suggest that mTOR-sensitive perturbation of smooth muscle cell mechanosensing contributes to elastin aortopathy.
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Enfermedades de la Aorta/tratamiento farmacológico , Colágeno/metabolismo , Elastina/deficiencia , Mecanotransducción Celular/efectos de los fármacos , Músculo Liso Vascular/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Rigidez Vascular/efectos de los fármacos , Síndrome de Williams/tratamiento farmacológico , Animales , Aorta Torácica/efectos de los fármacos , Aorta Torácica/enzimología , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Enfermedades de la Aorta/enzimología , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/fisiopatología , Proliferación Celular/efectos de los fármacos , Elastina/genética , Everolimus/farmacología , Quinasa 1 de Adhesión Focal/metabolismo , Predisposición Genética a la Enfermedad , Humanos , Mesilato de Imatinib/farmacología , Diana Mecanicista del Complejo 1 de la Rapamicina , Diana Mecanicista del Complejo 2 de la Rapamicina , Ratones Endogámicos C57BL , Ratones Noqueados , Complejos Multiproteicos/metabolismo , Músculo Liso Vascular/enzimología , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Fenotipo , Fosforilación , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Factores de Tiempo , Síndrome de Williams/enzimología , Síndrome de Williams/patología , Síndrome de Williams/fisiopatologíaRESUMEN
OBJECTIVE: Williams syndrome is characterized by obstructive aortopathy attributable to heterozygous loss of ELN, the gene encoding elastin. Lesions are thought to result primarily from excessive smooth muscle cell (SMC) proliferation and consequent medial expansion, although an initially smaller caliber and increased stiffness of the aorta may contribute to luminal narrowing. The relative contributions of such abnormalities to the obstructive phenotype had not been defined. APPROACH AND RESULTS: We quantified determinants of luminal stenosis in thoracic aortas of Eln-/- mice incompletely rescued by human ELN. Moderate obstruction was largely because of deficient circumferential growth, most prominently of ascending segments, despite increased axial growth. Medial thickening was evident in these smaller diameter elastin-deficient aortas, with medial area similar to that of larger diameter control aortas. There was no difference in cross-sectional SMC number between mutant and wild-type genotypes at multiple stages of postnatal development. Decreased elastin content was associated with medial fibrosis and reduced aortic distensibility because of increased structural stiffness but preserved material stiffness. Elastin-deficient SMCs exhibited greater contractile-to-proliferative phenotypic modulation in vitro than in vivo. We confirmed increased medial collagen without evidence of increased medial area or SMC number in a small ascending aorta with thickened media of a Williams syndrome subject. CONCLUSIONS: Deficient circumferential growth is the predominant mechanism for moderate obstructive aortic disease resulting from partial elastin deficiency. Our findings suggest that diverse aortic manifestations in Williams syndrome result from graded elastin content, and SMC hyperplasia causing medial expansion requires additional elastin loss superimposed on ELN haploinsufficiency.
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Aorta Torácica/crecimiento & desarrollo , Enfermedades de la Aorta/fisiopatología , Elastina/metabolismo , Síndrome de Williams/fisiopatología , Adulto , Animales , Aorta Torácica/metabolismo , Aorta Torácica/patología , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/patología , Proliferación Celular , Células Cultivadas , Colágeno/metabolismo , Constricción Patológica , Modelos Animales de Enfermedad , Elastina/deficiencia , Elastina/genética , Fibrosis , Predisposición Genética a la Enfermedad , Humanos , Hiperplasia , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Músculo Liso Vascular/crecimiento & desarrollo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Fenotipo , Factores de Tiempo , Rigidez Vascular , Vasoconstricción , Síndrome de Williams/genética , Síndrome de Williams/metabolismo , Síndrome de Williams/patologíaRESUMEN
RATIONALE: Transplantation, the most effective therapy for end-stage organ failure, is markedly limited by early-onset cardiovascular disease (CVD) and premature death of the host. The mechanistic basis of this increased CVD is not fully explained by known risk factors. OBJECTIVE: To investigate the role of alloimmune responses in promoting CVD of organ transplant recipients. METHODS AND RESULTS: We established an animal model of graft-exacerbated host CVD by combining murine models of atherosclerosis (apolipoprotein E-deficient recipients on standard diet) and of intra-abdominal graft rejection (heterotopic cardiac transplantation without immunosuppression). CVD was absent in normolipidemic hosts receiving allogeneic grafts and varied in severity among hyperlipidemic grafted hosts according to recipient-donor genetic disparities, most strikingly across an isolated major histocompatibility complex class II antigen barrier. Host disease manifested as increased atherosclerosis of the aorta that also involved the native coronary arteries and new findings of decreased cardiac contractility, ventricular dilatation, and diminished aortic compliance. Exacerbated CVD was accompanied by greater levels of circulating cytokines, especially interferon-γ and other Th1-type cytokines, and showed both systemic and intralesional activation of leukocytes, particularly T-helper cells. Serological neutralization of interferon-γ after allotransplantation prevented graft-related atherosclerosis, cardiomyopathy, and aortic stiffening in the host. CONCLUSIONS: Our study reveals that sustained activation of the immune system because of chronic allorecognition exacerbates the atherogenic diathesis of hyperlipidemia and results in de novo cardiovascular dysfunction in organ transplant recipients.
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Enfermedades Cardiovasculares/etiología , Rechazo de Injerto/complicaciones , Trasplante de Corazón/efectos adversos , Hiperlipidemias/complicaciones , Mediadores de Inflamación/sangre , Interferón gamma/sangre , Aloinjertos , Animales , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/inmunología , Enfermedades de la Aorta/prevención & control , Apolipoproteínas E , Aterosclerosis/sangre , Aterosclerosis/etiología , Aterosclerosis/inmunología , Aterosclerosis/prevención & control , Cardiomiopatías/sangre , Cardiomiopatías/etiología , Cardiomiopatías/inmunología , Cardiomiopatías/prevención & control , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/prevención & control , Modelos Animales de Enfermedad , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Hemodinámica , Antígenos de Histocompatibilidad Clase II/inmunología , Hiperlipidemias/sangre , Hiperlipidemias/genética , Mediadores de Inflamación/inmunología , Interferón gamma/inmunología , Activación de Linfocitos , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal , Células TH1/inmunología , Células TH1/metabolismo , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/inmunología , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular IzquierdaRESUMEN
OBJECTIVE: To evaluate the clinical safety and efficacy of percutaneous transluminal atherectomy for in-stent restenosis (ISR) in patients with low extremity peripheral arterial diseases (PAD). METHODS: PubMed, Elsevier, EBSCO, Spring databases and Cochrane Library were searched for relevant articles. Based on the different mechanisms of atherectomy, the patients were divided into mechanic atherectomy group and laser atherectomy group. The safety end points included the rate of distal embolism and severe arterial wall injuries. And the efficacy end points included primary patency rate and freedom from target vessel revascularization (TVR-free) 6 months and 12 months after surgery. RESULTS: A total of 9 studies and 620 patients (published between 2006 and 2014) were accepted. The rate of distal embolism was 4.2% (95% confidence interval (CI): 1.7%-6.7%), while that of severe arterial wall injuries was 1.9% (95%CI: 0.9%-3.0%), respectively. Laser atherectomy was responsible for more distal embolism (6.8%) compared to mechanic atherectomy (2.0%), which was significantly different (Q=21.66, P=0.010). At 6-month follow-up, primary patency rate and rate of TVR-free were 63.0% (95% CI: 55.5%-70.6%) and 80.4% (95% CI: 70.5%-90.3%), while at 12-month follow-up were 43.5% (95%CI: 32.2%-54.9%) and 58.0% (95% CI: 52.1%-63.9%), respectively. The free-TVR rate at 6 months follow-up in mechanical atherectomy group was 77.9%, and was inferior to that in laser atherectomy group (80.8%, Q=13.49, P=0.009). Published bias was discovered at the analysis of 12-month TVR-free rate by means of Begg Test (P=0.039). Meta analysis concerned about the 3 randomized controlled trials demonstrated that there was no significant improvement using atherectomy for ISR comparing to standard balloon at 6-month TVR-free rate (OR=1.34, 95% CI: 0.86-2.07, P=0.196). CONCLUSIONS: To treat ISR lesion in lower extremities, laser atherectomy has a lower free-TVR rate in the middle term follow-up.A higher rate of distal embolism is noted though. On balance, percutaneous transluminal atherectomy demonstrates no significant improvement compared to plain balloon angioplasty for ISR lesions.
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Constricción Patológica , Enfermedad Arterial Periférica , Stents , Angioplastia de Balón , Angioplastia Coronaria con Balón , Aterectomía , Humanos , Extremidad InferiorRESUMEN
OBJECTIVE: To study the treatment strategy and survival of patients with primary leiomyosarcoma of inferior vena cava (PIVCLMS). METHODS: Clinical data of 12 cases with PIVCLMS admitted in Peking University People's Hospital from January 2006 to September 2014 were reviewed retrospectively. All cases were confirmed by pathology examination. Among them, there were 4 male and 8 female patients with a mean age of (54 ± 9) years old. Tumors arose from the inferior vena cava (IVC) upper segment in 5 patients, from the middle in other 7 patients. Cardiac extension was observed in 4 cases. Tumor resection was undertaken in 8 patients, the other 4 patients were inoperable. The series was analyzed to identify clinical outcome of surgical strategy and protective factors for patient survival. RESULTS: In tumor resection group, 6 patients had radical resection and 2 underwent palliative resection. As for IVC reconstruction, caval wall resection with a direct suture was carried out in 6 patients or with prosthetic patch in 1 patient. The other 1 patient underwent a segment caval resection and prosthetic graft replacement in situ. In 4 cases of suprahepatic PIVCLMS cardiopulmonary bypass or perfusion by right atrial intubation was performed to assist bleeding control and maintain circulation stabilization, among them 1 patient survived for more than 101 months with no tumor recurrence or metastasis. Among the patients submitted to tumor resection 2 early postoperative deaths occurred, and another 2 patients had complications. All 4 patients submitted to non-resective operation (only neoplasm biopsy) died of PIVCLMS within 8 months. Except for 2 cases of early death, mean survival after tumor resection was (54 ± 40) months. Two patients presented local recurrence and hepatic metastasis at follow-up of 16 months and 68 months. CONCLUSIONS: Tumor resection is the only therapy for PIVCLMS with an expectation for long-term survival. The applicant of cardiopulmonary bypass makes some inoperable indicated to tumor resection.
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Leiomiosarcoma/cirugía , Neoplasias Vasculares/cirugía , Vena Cava Inferior/patología , Adulto , Implantación de Prótesis Vascular , Puente Cardiopulmonar , Femenino , Humanos , Leiomiosarcoma/diagnóstico , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Neoplasias Vasculares/diagnósticoRESUMEN
OBJECTIVE: Patients with elastin deficiency attributable to gene mutation (supravalvular aortic stenosis) or chromosomal microdeletion (Williams syndrome) are characterized by obstructive arteriopathy resulting from excessive smooth muscle cell (SMC) proliferation, mural expansion, and inadequate vessel size. We investigated whether rapamycin, an inhibitor of the cell growth regulator mammalian target of rapamycin (mTOR) and effective against other SMC proliferative disorders, is of therapeutic benefit in experimental models of elastin deficiency. APPROACH AND RESULTS: As previously reported, Eln(-/-) mice demonstrated SMC hyperplasia and severe stenosis of the aorta, whereas Eln(+/-) mice exhibited a smaller diameter aorta with more numerous but thinner elastic lamellae. Increased mTOR signaling was detected in elastin-deficient aortas of newborn pups that was inhibited by maternal administration of rapamycin. mTOR inhibition reduced SMC proliferation and aortic obstruction in Eln(-/-) pups and prevented medial hyperlamellation in Eln(+/-) weanlings without compromising aortic size. However, rapamycin did not prolong the survival of Eln(-/-) pups, and it retarded the somatic growth of juvenile Eln(+/-) and Eln(+/+) mice. In cell cultures, rapamycin inhibited prolonged mTOR activation and enhanced proliferation of SMC derived from patients with supravalvular aortic stenosis and with Williams syndrome. CONCLUSIONS: mTOR inhibition may represent a pharmacological strategy to treat diffuse arteriopathy resulting from elastin deficiency.
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Arteriopatías Oclusivas/etiología , Elastina/deficiencia , Músculo Liso Vascular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Adulto , Animales , Estenosis Aórtica Supravalvular/complicaciones , Arteriopatías Oclusivas/prevención & control , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Músculo Liso Vascular/citología , Miocitos del Músculo Liso/fisiología , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/fisiología , Síndrome de Williams/complicacionesRESUMEN
OBJECTIVE: To evaluate the results of the surgical treatment of patients with Budd-Chiari syndrome (BCS). METHODS: The clinic data of 120 BCS patients who underwent various consecutive surgical treatments from July 2001 to October 2010 was analyzed. There were 82 male and 38 female patients, aging from 11 to 72 years with a mean age of (41 ± 13) years. All patients experienced various examinations to identify the pathological type of BCS. There were 5 cases of small hepatic veins type, 28 cases of large hepatic veins (LHV) type, 31 cases of inferior vena cava (IVC) type and 56 cases of combined obstruction of LHV and IVC. Totally, 25 patients experienced interventional treatment, include percutaneous transluminal angioplasty and/or stenting for stenosis of hepatic vein and/or IVC, 77 patients experienced open-thorax operation for BCS radical resection under protection of right atrium by-pass with extracorporeal circulation. RESULTS: Totally 97 cases were followed up from 1 to 120 months after various surgical treatment methods. Perioperative mortality was 6.2% (6/97). Follow-up period mortality was 8.2% (8/97). The restenosis of IVC and/or hepatic vein happened in 3 cases out of 25 cases in intervention treatment group in contrast with 15 cases out of 77 cases in radical resection group. The 5-year patency and survival rate of IVC/hepatic vein were 64.5% and 83.3%. CONCLUSIONS: The surgical treatment of BCS need to get accurate diagnosis and pathological classification firstly, then, to choose appropriate therapeutic strategies based on individual pathological classification. The BCS radical resection can be an alternative method in some particular pathological classifications and the cases who failed in interventional treatment.
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Síndrome de Budd-Chiari/cirugía , Adolescente , Adulto , Anciano , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Thoracic aortic aneurysm and dissection (TAAD) is a high-risk aortic disease. Mouse models are usually used to explore the pathological progression of TAAD. In our studies, we performed bioinformatics analysis on a microarray dataset (GSE36778) and verified experiments to define the integrated hub genes of TAAD in three different mouse models. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analyses, and histological and quantitative reverse transcription-PCR (qRT-PCR) experiments were used in our study. First, differentially expressed genes (DEGs) were identified, and twelve common differentially expressed genes were found. Second, genes related to the cell cycle and inflammation were enriched by using GO and PPI. We focused on filtering and validating eighteen hub genes that were upregulated. Then, expression data from human ascending aortic tissues in the GSE153434 dataset were also used to verify our findings. These results indicated that cell cycle-related genes participate in the pathological mechanism of TAAD and provide new insight into the molecular mechanisms of TAAD.
RESUMEN
OBJECTIVE: To summarize the vascular surgical strategies for chest and abdomen tumors with the invasion of great vessels. METHODS: The clinical data were collected for 67 patients undergoing surgical treatment for tumors with the invasion of thoracic and abdominal great vessels at our hospital from January 2001 to June 2009. Then a retrospective analysis was performed. Among this dataset, there were 31 cases with only vessel wall invasion and 20 cases with only intravascular tumor thrombus. In the meanwhile, both the invasion of vascular walls and the formation of tumor thrombus were located in 16 patients. RESULTS: Among 67 operated patients, various strategies were used, including surgical adhesion lysis (n = 15), vascular resection direct suture (n = 24), artificial blood vessel patch (n = 10), pericardial patch (n = 3), artificial vascular replacement or bypass (n = 15) and cavity thrombectomy (n = 36). Cavity thrombectomy was performed under cardiopulmonary bypass for 8 patents with tumor invasion of right atrium. Among them, 58 patients received radical tumor resection while palliative resection was performed for 9 patients with a rate of complete resection at 86.6%. There was no intraoperative mortality with the perioperative death of 8 cases. A follow-up study was successfully conducted for 52 patients. And 7 patients were lost to follow-up. The overall follow-up rate was 88.1%. By June 2009, the survival period of this group of patients was as follows: 18 cases (> 48 months), 29 cases (> 24 months), 38 cases (> 12 months), 50 cases (> 6 months) and 2 cases (≤ 6 months). Among these patients, the major cause of mortality was tumor metastasis. The patients with kidney cancer showed the most favorable surgical outcomes. CONCLUSION: Managed by a variety of vascular surgical techniques, the patients with tumors involving major blood vessels may achieve an excellent success rate of tumor resection and a better postoperative quality-of-life.
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Venas Braquiocefálicas/patología , Neoplasias Vasculares/patología , Neoplasias Vasculares/cirugía , Vena Cava Inferior/patología , Adolescente , Adulto , Anciano , Aorta/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: To explore the diagnostic features and therapeutic methods of intravenous leiomyomatosis with a potential of heart invasion. METHODS: Eight cases of cardiac involvement with intravenous leiomyomatosis treated at our hospital from November 2002 to August 2011 were analyzed and compared. RESULTS: Either imaging or surgery confirmed that in all 8 patients the pelvic lesions originated from the inferior vena cava and heart involvement without pulmonary embolism. In 3 cases, palpitations and chest tightness were noticed. Four cases showed lower extremity edema and abdominal distension while no obvious clinical symptom was found for 1 case. All 8 cases had a history of uterine fibroids and 6 underwent previous hysterectomy. Among 8 patients, there were 5 cases of cardiopulmonary bypassing right heart, inferior vena cava tumor resection and pelvic involvement vein ligation and 2 cases of routine off-pumping of inferior vena cava with pelvic tumor resection. Palliative therapy was administered in 1 case. Two patients were resection the right heart and inferior vena cava tumor in the cardiopulmonary bypass, 3 months later were resection gynecologic uterine, double-accessories and broad ligament and were not treated with hormone. After operation, another 5 surgery patients received high-dose hormone treatments. 2 cases of recurrence in each group were found by ultrasound follow-ups from 15 - 90 months. CONCLUSION: Invasion of the heart intravenous leiomyomatosis is a rare case, which can be tackled with a good effect by completely surgical resection and a limited effect on hormone therapy to prevent recurrence.
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Neoplasias Cardíacas/patología , Leiomiomatosis/patología , Neoplasias Vasculares/patología , Adulto , Femenino , Humanos , Leiomiomatosis/diagnóstico , Persona de Mediana Edad , Invasividad Neoplásica , Estudios RetrospectivosRESUMEN
BACKGROUND: Although aggressive medical treatment is recommended in patients with type B aortic intramural hematoma (IMH), a variety of aortic events can occur during the later period. For early identification of these patients, the present study was aimed at evaluating the prognostic validity of estimated glomerular filtration rate (eGFR) and the presence of proteinuria in type B aortic IMH. METHODS: Data of 61 patients with type B IMH in Peking University People's Hospital from January 2008 to December 2018 were retrospectively collected. The serum creatinine level and urine protein levels were measured at admission. And eGFR were calculated by the CKD-EPI equation. Adverse aortic-related events were defined as a composite of satisfaction of criteria for surgical conversion (with or without actual surgical intervention) and death from aortic rupture. RESULTS: Initial eGFR was significantly different between patients with adverse aortic-related events and those without (P=0.003). On multivariate analysis, eGFR <90 mL/min/1.73 m2 (OR, 8.726; 95% CI: 1.711-46.144; P=0.009) and ULP (OR, 17.516; 95% CI: 3.322-92.258; P=0.001) were independent predictors of adverse aorta-related events. Furthermore, eGFR <90 mL/min/1.73 m2 and proteinuria (+) (OR, 8.344; P=0.030) had significantly greater rates of aortic-related events. In addition, eGFR <90 mL/min/1.73 m2 and proteinuria (+) had incremental prognostic value (C-statistic, 0.860, P=0.039) compared with ulcer-like projection (C-statistic, 0.815) alone. CONCLUSIONS: Initial eGFR and presence of proteinuria were able to provide incremental prognostic information in addition to ulcer-like projection in patients with type B aortic IMH.
RESUMEN
OBJECTIVE: The anatomic distribution of lower extremity deep venous thrombosis (LEDVT) plays an important role in its prevention and treatment. This study aimed to evaluate the anatomic distribution of hospital-acquired LEDVT (HA-LEDVT) and its probable role in the occurrence of pulmonary embolism (PE). METHODS: We retrospectively analyzed the demographic data, ultrasound results, and PE-related findings of inpatients with HA-LEDVT in 28 clinical departments at Peking University People's Hospital between January 1, 2007, and December 31, 2018. RESULTS: This study included 1431 HA-LEDVT events: 35.8%, 31%, and 33.3% were left, right, and bilateral LEDVT. Isolated distal, proximal, and blended DVT were detected in 83.4%, 7.3%, and 9.3% of the patients, respectively. The distribution of HA-LEDVT in the left and right lower extremities were not significantly different except in patients aged ≥40 years (left: 2.07 vs right: 1.88 per 1000 extremities, P = .04). For anatomic types of HA-LEDVT, isolated distal HA-LEDVT was 5.02 times more prevalent than proximal HA-LEDVT (1.24 vs 0.26 per 1000 extremities, P ï¼ .01). The involvement rates of specific deep veins by HA-LEDVT were highest in the muscular calf vein (87.5%) followed by the popliteal vein (10.1%), superficial femoral vein (9.3%), and common femoral vein (9.2%). HA-LEDVT involving multiple vein segments simultaneously occurred in 338 extremities. HA-LEDVT involving the muscular calf vein and at least one of three connected axial veins of the muscular calf vein occurred most frequently. Eighty-eight patients with HA-LEDVT (6.15%) had PE. The frequency of PE among patients with proximal and distal DVT (7.89% vs 6.23% P = .275) was not significantly different. The incidence of PE was highest in patients with bilateral proximal DVT (15.4%) and lowest in patients with a single right distal DVT (4.5%). PE occurred in 6% of muscular calf vein HA-LEDVT. In isolated muscular calf vein DVT cases, PE were more likely to occur in cases with a ï¼6.05-mm-diameter thrombus than in those with a ï¼6.05-mm-diameter thrombus (10.3% vs 4.2%, P ï¼ .0001). CONCLUSIONS: HA-LEDVT is characterized by a significantly high percentage of DVT in the muscular calf vein. Muscular calf vein thrombosis may be the primary origin of lower extremity deep vein thrombosis. The diameter of the thrombus in the muscular calf vein may be associated with the occurrence of PE. More prospective studies are needed to more fully determine the natural history of HA-LEDVT and develop prevention and treatment guidelines for HA-LEDVT.
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Extremidad Inferior/irrigación sanguínea , Embolia Pulmonar/etiología , Trombosis de la Vena/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Masculino , Estudios Retrospectivos , Adulto JovenRESUMEN
OBJECTIVE: Report the experience of management of graft occlusion in patients with lower extremity bypasses and discuss the appropriate treatment strategy. METHODS: From Oct. 2004 to Oct. 2009, 104 cases of graft occlusion were treated in 53 patients with lower extremity arterial bypasses, including medical therapy for 10 cases and redo operations for 94 cases: graft thrombectomy alone for 26 cases, redo bypass or extension bypass with prosthetic or autologous vein grafts for 23 cases, graft thrombectomy plus balloon angioplasty for 18 cases, major amputation for 14 cases, graft thrombectomy plus femoral or popliteal artery endarterectomy for 10 cases, removal of occluded graft with infection for 2 case, and autologous stem cell transplantation for 1 case. RESULTS: 77 reconstructive procedures were applied and graft failures recurred in 49 cases (63.6%). One patient died of acute renal failure during peri-operative period and 9 patients died during follow-up; 6 patients were lost to follow-up. The remaining 37 patients were followed: major amputation for 12 patients, patent grafts after reconstruction in 18 patients, and medical therapy after graft occlusion for 7 patients with limb salvage. Kaplan-Meier survival analysis revealed 3-year survival of 77.4%, limb salvage of 64.7%, and graft patency of 45.7%. Effect of different procedures on cumulative patency was of no statistical significance. CONCLUSIONS: Graft occlusions after lower extremity bypasses may result in high rate of reocclusion and amputation. Optimal management should be based on a thorough analysis of individual condition.
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Arteriosclerosis Obliterante/terapia , Prótesis Vascular , Oclusión de Injerto Vascular/terapia , Anciano , Anciano de 80 o más Años , Arteriosclerosis Obliterante/etiología , Arteriosclerosis Obliterante/cirugía , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/cirugía , Humanos , Extremidad Inferior/irrigación sanguínea , Masculino , Persona de Mediana Edad , Arteria Poplítea/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: To explore the experience of management of graft occlusion in patients with lower extremity bypass grafting. METHODS: From July 2002 to September 2009, 115 cases of graft occlusion were treated in 64 patients with lower extremity arterial bypass, including medical therapy for 8 cases and redo operations for 107 cases: graft thrombectomy alone for 32 cases, redo bypass operation with prosthetic grafts for 27 cases, graft thrombectomy plus balloon angioplasty for 17 cases, major amputation for 13 cases, graft thrombectomy plus endarterectomy for 10 cases, removal of occluded graft with infection for 4 case, distally bypass grafting with autologous saphenous vein for 3 case, and autologous stem cell transplanting for 1 case. RESULTS: One patient died of acute renal failure during peri-operative period and 3 patients died during follow-up period, 5 patients were lost to follow-up including 2 with medical therapy. The remaining 55 patients were followed up for 4 to 70 months (average 39 months): medical therapy for 8 patients, major amputation for 12 patients (21.8%), and patent grafts after reconstruction in 35 patients (63.6%). CONCLUSION: For graft occlusions after lower extremity bypass grafting, redo bypass operation and graft thrombectomy plus endarterectomy or balloon angioplasty may produce better early results.
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Oclusión de Injerto Vascular/cirugía , Extremidad Inferior/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Angioplastia de Balón , Implantación de Prótesis Vascular , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , TrombectomíaRESUMEN
OBJECTIVE: To summarize the experience in management of prosthetic graft infection (PGI) after lower limb arterial bypasses and investigate optimal measures for prevention and treatment. METHODS: Records of 15 cases of PGI between January 2004 and December 2009 were retrospectively analyzed, including 14 male and 1 female with the average age of 64.8 years (ranged from 40 to 84 years). PGI occurred from 5 d to 59 months (average 6.4 months) after the last reconstructive procedures with symptoms as follow: nonhealing wound with vascular graft exposure in 8 cases, persistent sinus related to vascular graft with purulent secretion in 5 cases and without secretion in 1 case, and ill-incorporated graft with peri-graft fluid in 1 case. Broad-spectrum antibiotics were administrated in all PGI cases. Surgical treatments included local debridement and drainage in 4 cases (one death from postoperative acute myocardial infarction), local debridement and skin flap rotation in one case, complete removal of the occluded infected grafts in 8 cases including major amputation in 3 cases, removal of patent infected graft and extra-anatomic bypass with silver-bonded Dacron vascular graft in 1 case, and partial removal of patent infected graft without reconstruction in 1 case with a re-canalized stent-graft. RESULTS: Limb salvage was achieved in 9 cases, and 4 cases received major amputation. One case was failed to follow-up and one died of postoperative acute myocardial infarction. Initially 13 patients were followed and 2 died during follow-up (because of colon carcinoma and intracranial hemorrhage respectively). Eleven patients were followed for 1 to 70 months (average 22.3 months) including 8 cases with limb salvage and 3 with major amputation. Accumulative mortality rate, amputation rate, and graft occlusion rate were 20% (3/15), 26.7% (4/15), and 53.3% (8/15) respectively. CONCLUSIONS: PGI after lower limb arterial bypasses is a devastating complication with high risk of graft occlusion and amputation. Removal of the infected grafts may be mandatory for most cases, but local management for patent infected grafts may be recommendable for selected cases.