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1.
Abdom Radiol (NY) ; 47(10): 3414-3423, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35896683

RESUMEN

OBJECTIVES: The study aimed to predict surgical risks for patients with symptomatic stricturing Crohn's disease (CD) using computed tomography enterography (CTE) and to assess the association between CTE findings and pathological changes. METHODS: Crohn's disease patients with symptomatic stricture(s) were included. Exclusion criteria were concomitant penetrating disease, intra-abdominal abscess, previous bowel resection, or asymptomatic. Patients from January 2016 to December 2019 were identified as the primary cohort and those from January 2020 to June 2020 were identified as the validation cohort. Two independent experienced radiologists evaluated CTE variables including mucosal enhancement, mural stratification, wall enhancement, comb sign, lymphadenopathy, thick non-enhancing wall, bowel wall thickness, luminal diameter, and upstream lumen. Receiver operating characteristic, logistic regression, and nomogram were performed to identify the independent predictors of surgical-free survival. Histopathological scores of surgical specimens were also evaluated. RESULTS: 198 patients (primary cohort, 123 with surgery and 75 under non-surgical intervention, and 41 patients (validation cohort) were analyzed. Bowel wall thickness < 5.9 mm, luminal stenosis > 3.35 mm, and upstream lumen < 27.5 mm were predictors of surgical-free survival for symptomatic stricturing CD patients. Logistic analysis showed the three CTE variables were the independent predictors of surgical-free survival (p < 0.001). A nomogram was developed with the concordance indexes of 0.905 and 0.892 in the primary and validation cohorts. Histopathological analysis showed bowel wall muscular hyperplasia/hypertrophy significantly correlated with luminal stenosis (r = - 0.655, p = 0.008) and combined CTE variable (r = - 0.683, p = 0.005). CONCLUSIONS: CTE is highly predictive of disease course and surgical-free survival for patients with symptomatic stricturing CD, suggesting the important role of CTE in decision-making of treatment.


Asunto(s)
Enfermedad de Crohn , Enema Opaco , Constricción Patológica/complicaciones , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/cirugía , Enfermedad de Crohn/complicaciones , Enfermedad de Crohn/diagnóstico por imagen , Enfermedad de Crohn/cirugía , Humanos , Intestinos/diagnóstico por imagen , Intestinos/patología , Intestinos/cirugía , Tomografía Computarizada por Rayos X/métodos
2.
Cell Signal ; 95: 110336, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35452821

RESUMEN

The intratumoral androgen synthesis is one of the mechanisms by which androgen receptor (AR) is aberrantly re-activated in castration-resistant prostate cancer (CRPC) after androgen ablation. However, pathways controlling steroidogenic enzyme expression and de novo androgen synthesis in prostate cancer (PCa) cells are largely unknown. In this study, we explored the potential roles of DAB2IP in testosterone synthesis and CRPC tumor growth. Indeed, DAB2IP loss could maintain AR transcriptional activity, PSA re-expression and tumor growth under castrated condition in vitro and in vivo, and reprogram the expression profiles of steroidogenic enzymes, including AKR1C3. Mechanistically, DAB2IP could dramatically inhibit the AKR1C3 promoter activity and the conversion from androgen precursors (i.e., DHEA) to testosterone through PI3K/AKT/mTOR/ETS1 signaling. Consistently, there was a high co-expression of ETS1 and AKR1C3 in PCa tissues and xenografts, and their expression in prostate tissues could also restore AR nuclear staining in castrated DAB2IP-/- mice after DHEA supplement. Together, this study reveals a novel regulation of intratumoral de novo androgen synthesis in CRPC, and provides the DAB2IP/ETS1/AKR1C3 signaling as a potential therapeutic target.


Asunto(s)
Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas , Andrógenos , Neoplasias de la Próstata Resistentes a la Castración , Proteína Proto-Oncogénica c-ets-1 , Testosterona , Proteínas Activadoras de ras GTPasa , Miembro C3 de la Familia 1 de las Aldo-Ceto Reductasas/metabolismo , Andrógenos/metabolismo , Animales , Línea Celular Tumoral , Deshidroepiandrosterona/farmacología , Humanos , Masculino , Ratones , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Proteína Proto-Oncogénica c-ets-1/metabolismo , Receptores Androgénicos/metabolismo , Transducción de Señal , Testosterona/biosíntesis , Testosterona/metabolismo , Proteínas Activadoras de ras GTPasa/metabolismo
3.
Artículo en Chino | MEDLINE | ID: mdl-34304460

RESUMEN

Objective:To observe the characteristics of different negativity negativity (MMN) in patients with unilateral sudden deafness, and compare them with normal MMN, in order to provide theoretical reference for discussing the pathogenesis of unilateral sudden deafness and their relationship with the auditory centers, and to provide theoretical basis for the treatment of sudden deafness in the future. Methods:Twenty-six cases of unilateral total sudden deafness were recruited as experimental group, 25 cases of normal healthy people as control group, the MMN inspections was performed respectively, the two groups using classical mode of oddball, standard and deviation stimulate with 1000 Hz and 2000 Hz short pure tone test MMN respectively, to observe the MMN latency and amplitude characteristics, and compare the latent period and amplitude difference between the two groups. Results:Among the 51 subjects, only 1 patient with unilateral total sudden deafness did not elicit MMN waveform, while the rest were all induced. The average incubation period of MMN in the experimental group was (162.03±38.64) ms, the average amplitude was (2.83±1.14)µV, and the mean age was (48.64±10.27) y. While the average incubation period of MMN in the control group was (197.52±27.43) ms, the average amplitude was (2.58±1.07)µV, and the mean age was (45.00±8.20) y. The MMN latency was significantly different between the two groups (P<0.01). There was no statistical difference in amplitude between the two groups (P>0.05). There was no statistical difference in age between the two groups (P>0.05). Conclusion:The latency period of MMN of unilateral total sudden deafness is shorter than that of the control group. It suggests that the auditory center function of patients with acute sudden deafness has changed, and we speculate that the auditory center of patients with acute sudden deafness may have corresponding emergency changes, so as to make its function have adaptive changes, which will provide further reference for the discussion of the pathophysiological mechanism and treatment of sudden deafness in the future.We speculated that acute unilateral auditory deprivation caused by unilateral total deafness sudden deafness has an impact on cerebral cortical auditory function, which provides further reference for the discussion of pathophysiological mechanism and treatment plan of sudden deafness in the future.


Asunto(s)
Sordera , Pérdida Auditiva Súbita , Estimulación Acústica , Potenciales Evocados Auditivos , Audición , Humanos
4.
Phytomedicine ; 89: 153593, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34182194

RESUMEN

BACKGROUND: Effective therapies are needed to prevent the secondary injury and poor prognosis associated with emergency craniotomy of traumatic brain injury (TBI). HYPOTHESIS/PURPOSE: The wound-healing medicine Yunnan Baiyao (YB) and Xingnaojing (XNJ) adjunct-therapy may improve the outcome of orthodox mono-therapy (OT). STUDY DESIGN: Randomized controlled trial. METHODS: Eighty patients with moderate-to-severe TBI received emergency craniotomy (within 12 h after TBI) at the Chinese PLA General Hospital before being randomly assigned to 4 different treatments (n = 20) for 7 days: 1) OT; 2) OT+XNJ (i.v. 20 ml/daily); 3) OT+low dose-YB (oral, 1,000 mg/day); 4) OT+high dose-YB, 2,000 mg/day). RESULTS: GCS score was improved more quickly and became significantly higher in XNJ, l-YB, h-YB groups than in OT group (p<0.01). Serum S100B peaked higher but declined more slowly in OT group than in other groups (p<0.01). On postoperative Day 7, S100B was 20% below baseline in YB and XNJ groups but remained 19% above baseline in OT group which also lost 38% of superoxide dismutase (SOD) activity on Day 3 and recovered 69% of SOD on Day 7 whereas the YB and XNJ groups lost 16%∼23% of SOD activity on Day 3 and recovered 92%∼99% of SOD on Day 7 (p<0.01). Clinical prognosis (Glasgow Outcome Scale and Karnofsky Performance Scale) were significantly better (25%∼30%) in the XNJ, l-YB and h-YB groups than in OT group 3 months post-surgery and were correlated with serum S100B and SOD. CONCLUSIONS: YB and XNJ adjunct therapies improved postoperative recovery and clinical prognosis in patients with moderate-to-severe TBI partly through divergent regulation of S100B and SOD pathways. (The trial was registered at Chinese Clinical Trial Registry (ChiCTR) trial registration number: ChiCTR2000030280).


Asunto(s)
Lesiones Traumáticas del Encéfalo , Medicamentos Herbarios Chinos/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/cirugía , China , Terapia Combinada , Craneotomía , Humanos , Cuidados Posoperatorios , Pronóstico
5.
BMJ Open ; 9(3): e025944, 2019 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-30904869

RESUMEN

INTRODUCTION: Preoperative radiotherapy followed by total mesorectal excision with adjuvant chemotherapy has been recommended as the preferred treatment method for locally advanced rectal cancer (LARC). Similar rates of local control, survival and toxicity were observed in preoperative long-course chemoradiotherapy (LCRT) (45-50.4 Gy in 25-28 fractions) and in short-course radiotherapy (SCRT) with 25 Gy over five fractions. Both regimens lower the local recurrence rates compared with that of surgery followed by postoperative radiotherapy. With the simplicity and lower cost of SCRT, a growing number of patients have been receiving SCRT as preoperative radiotherapy. However, the currently established SCRT (25 Gy over five fractions) followed immediately by surgery resulted in poor downstaging and sphincter preservation rate. The pathological complete response (pCR) rate is also markedly lower with SCRT than with LCRT (0.7%vs16%). Several studies recommended SCRT with delayed surgery for more than 4 weeks with expectation of improved pathological outcomes and fewer postoperative complications. While a number of clinical trials demonstrated a persistently better overall local control with SCRT than with LCRT, overall survival advantage has not been observed. Since survival is mainly depended on distant metastases, efforts should be made towards more effective pathological response and systemic treatment. Given the apparent advantages of SCRT, we aimed to establish a dose escalation of SCRT and sequential modified FOLFOX6 (mFOLFOX6) as preoperative therapy for LARC with objectives of achieving an optimal balance of safety, cost effectiveness and clinical outcome, and to support further investigation of this regimen in a phase II/III setting. METHODS: In this phase I study, three dose levels (6Gy×5F, 7Gy×5F, 8Gy×5F to gross tumour volume, while keeping the rest of irradiated volume at 5Gy×5) of SCRT followed by four cycles of mFOLFOX6 chemotherapy as neoadjuvant therapy will be tested by using the traditional 3+3 design. The pCR rate, R0 resection rate, sphincter preservation rate and treatment related toxicity will be assessed. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Fujian Medical University Union Hospital (No. 2017YF020-02) and all participants provided written informed consent. Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality. TRIAL REGISTRATION NUMBER: NCT03466424; Pre-results.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ensayos Clínicos Fase I como Asunto/métodos , Neoplasias del Recto/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Terapia Neoadyuvante , Estudios Observacionales como Asunto/métodos , Compuestos Organoplatinos/administración & dosificación , Evaluación del Resultado de la Atención al Paciente , Selección de Paciente , Cuidados Preoperatorios/métodos , Dosificación Radioterapéutica , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/cirugía
6.
Medicine (Baltimore) ; 97(37): e12271, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30212963

RESUMEN

BACKGROUND: Clinical trials examining the therapeutic benefit of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on nonalcoholic fatty liver disease (NAFLD) have reported inconsistent results. We performed a meta-analysis of randomized controlled trials (RCTs) examining the effect of ω-3 PUFA supplementation on NAFLD, and provide substantial evidence on whether ω-3 PUFA supplementation has a favorable effect for treating NAFLD. METHODS: We searched the PubMed, Cochrane Library, Springer Link, China National Knowledge Infrastructure (CNKI), Wanfang, and Chinese Scientific and Technological Journal (VIP) databases for RCTs on oral ω-3 PUFA supplementation in patients with NAFLD. The data were pooled; meta-analyses were conducted using random-effect or fixed-effect models. RESULTS: Eighteen studies involving 1424 patients were included. We found a significant benefit for ω-3 PUFAs vs control for liver fat, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, triglycerides, insulin resistance, and glucose. However, there was significant interstudy heterogeneity. Subgroup and regression analyses showed no significantly clear methodologic discrepancy. Publication bias and serious adverse events were not detected. CONCLUSIONS: Our meta-analysis suggests that ω-3 PUFA supplementation may decrease liver fat and hepatic enzyme parameters. However, more large-scale, well-designed RCTs are needed to confirm the effect of ω-3 PUFA supplementation on these parameters.


Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Glucemia , Pesos y Medidas Corporales , Ácidos Grasos Omega-3/farmacología , Humanos , Resistencia a la Insulina , Pruebas de Función Hepática , Enfermedad del Hígado Graso no Alcohólico/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Triglicéridos/sangre
7.
Phytother Res ; 25(1): 137-41, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20632296

RESUMEN

Ginkgo biloba extracts (GBE) have long been used as a traditional herbal medicine for treating central nervous system diseases and peripheral vascular diseases, but the underlying mechanisms have yet to be elucidated. Furthermore, traditional GBE is in the form of microsomes and only dissolves in organic solvents; its clinical applications have been greatly limited. Therefore, in the present study, nanometer GBE (nGBE) was prepared utilizing supercritical anti-solvent (SAS) upon CO(2) -supercritical fluid extraction (CO(2) -SPF). Using whole-cell patch clamp techniques, the effects of different preparations of GBE on N-methyl-D-aspartate (NMDA)-activated currents (I(NMDA) ) from acutely isolated rat hippocampal neurons were investigated and the difference in protective potency between nGBE and mGBE evaluated. The results showed that the inward current activated by NMDA could be depressed by mGBE and nGBE. The inhibitory rates were 40% ± 17% and 64% ± 15%, and the half-inhibition concentrations (IC(50) ) were 0.0210 ± 0.0055 and 0.0262 ± 0.0038 mg/mL, respectively. In comparison, the modulatory effect of nGBE (dissolved in extracellular solution) on NMDA-activated current was significantly greater than that of mGBE (dissolved in DMSO) (p < 0.05). This indicated that the modulatory effects of GBE on NMDA-activated current may contribute to the neuroprotective effects of GBE and the modulatory effect of nGBE on NMDA-activated current was greater than that of mGBE.


Asunto(s)
Ginkgo biloba/química , Hipocampo/efectos de los fármacos , N-Metilaspartato/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Animales , Neuronas/fisiología , Fármacos Neuroprotectores/aislamiento & purificación , Tamaño de la Partícula , Técnicas de Placa-Clamp , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/fisiología , Solubilidad
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