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1.
Brief Bioinform ; 23(3)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35262669

RESUMEN

Drug resistance is a major threat to the global health and a significant concern throughout the clinical treatment of diseases and drug development. The mutation in proteins that is related to drug binding is a common cause for adaptive drug resistance. Therefore, quantitative estimations of how mutations would affect the interaction between a drug and the target protein would be of vital significance for the drug development and the clinical practice. Computational methods that rely on molecular dynamics simulations, Rosetta protocols, as well as machine learning methods have been proven to be capable of predicting ligand affinity changes upon protein mutation. However, the severely limited sample size and heavy noise induced overfitting and generalization issues have impeded wide adoption of machine learning for studying drug resistance. In this paper, we propose a robust machine learning method, termed SPLDExtraTrees, which can accurately predict ligand binding affinity changes upon protein mutation and identify resistance-causing mutations. Especially, the proposed method ranks training data following a specific scheme that starts with easy-to-learn samples and gradually incorporates harder and diverse samples into the training, and then iterates between sample weight recalculations and model updates. In addition, we calculate additional physics-based structural features to provide the machine learning model with the valuable domain knowledge on proteins for these data-limited predictive tasks. The experiments substantiate the capability of the proposed method for predicting kinase inhibitor resistance under three scenarios and achieve predictive accuracy comparable with that of molecular dynamics and Rosetta methods with much less computational costs.


Asunto(s)
Aprendizaje Automático , Proteínas , Ligandos , Simulación de Dinámica Molecular , Mutación , Proteínas/química
2.
Eur Radiol ; 33(12): 8936-8947, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37368104

RESUMEN

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/irrigación sanguínea , Nomogramas , Estudios Retrospectivos
3.
J Surg Res ; 285: 158-167, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36680876

RESUMEN

INTRODUCTION: To establish a blast- and fragment-induced pelvic injury animal model in rabbits, observe its injury characteristics, and explore the effects of hemostatic resuscitation combined with damage control surgery (DCS) with respect to this injury model. METHODS: Forty-eight rabbits were randomly allocated to four groups: group A rabbits were subjected to pelvic injury, group B rabbits to pelvic injury + DCS, group C rabbits to pelvic injury + DCS + resuscitation with Hextend, and group D rabbits to pelvic injury + DCS + Hextend + hemostatic resuscitation with tranexamic acid, fibrinogen concentrate, and prothrombin complex concentrate. Simulated blast and fragment-induced pelvic injury was produced by a custom-made machine. We implemented CT scanning and necropsy to assess the injury state and calculated the coefficient of variation (CV) of the cumulative abbreviated injury scale (AIS) to assess the reproducibility of the animal model. Immediately after instrumentation (0 h), and 1 h, 2 h, 4 h, and 8 h after injury, blood samples were taken for laboratory tests. RESULTS: We found that severe pelvic injury was produced with an AIS CV value of 10.32%, and the rabbits demonstrated severe physiologic impairment and coagulo-fibrinolytic derangements with high mortality. In rabbits of group D, however, physiologic and coagulo-fibrinolytic parameters were significantly enhanced with improved organ function and lowered mortality when compared with the other three groups. CONCLUSIONS: We herein established in rabbits a blast- and fragment-induced pelvic injury animal model that exhibited high reproducibility, and we demonstrated that hemostatic resuscitation plus DCS was effective in improving the outcome.


Asunto(s)
Traumatismos por Explosión , Hemostáticos , Animales , Conejos , Fibrinógeno , Hemostasis , Derivados de Hidroxietil Almidón , Reproducibilidad de los Resultados , Resucitación/métodos
4.
Prehosp Emerg Care ; 27(5): 592-599, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36125429

RESUMEN

Objective: Hemostatic gauze application is an effective way to control major bleeding, which is the most common cause of death in trauma in both civilian and military settings. Coagulation derangement after acute exposure to high altitude might alter the effects of hemostatic gauzes. The present study aimed to observe the hemostatic effects of bio-zeolite gauze (BZG) and QuikClot Combat Gauze® (QCG) on major bleeding in rabbits acutely exposed to high altitude.Methods: Sixty rabbits were randomly and evenly divided into six groups. Animal models of simulated blast- and fragment-induced inguinal major bleeding were prepared in lower altitude and high-altitude areas, and BZG, QCG, and ordinary gauze without hemostatic material were used to control bleeding. The primary outcomes included immediate hemostasis rate, blood loss, and survival rate, while the secondary outcomes included hemodynamic parameters, laboratory examinations, and coagulation-relevant markers.Results: The overall effects of BZG and QCG were better than those of ordinary gauze, with a higher immediate hemostatic rate, less blood loss, and higher survival rate at 90 min after gauze application and higher red blood cell and platelet counts and lower creatinine level at 30 min after gauze application in lower altitude. The concentrations of coagulation factor XII and factor X in rabbits acutely exposed to high altitude were significantly lower than those in lower altitude. At high altitude, the hemostatic effects of BZG did not decrease significantly compared to those in the lower altitude, whereas those of ordinary gauze and QCG decreased significantly at high altitude compared to those in the lower altitude.Conclusions: Coagulation derangement after acute exposure to high altitude has negative effects on ordinary gauze and QCG but has no significant negative hemostatic effects on BZG.


Asunto(s)
Servicios Médicos de Urgencia , Hemostáticos , Zeolitas , Animales , Conejos , Altitud , Hemorragia/tratamiento farmacológico , Hemostasis , Técnicas Hemostáticas , Hemostáticos/farmacología
5.
BMC Med Imaging ; 23(1): 138, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37737166

RESUMEN

BACKGROUND: This study aimed to develop a computed tomography (CT) model to predict Ki-67 expression in hepatocellular carcinoma (HCC) and to examine the added value of radiomics to clinico-radiological features. METHODS: A total of 208 patients (training set, n = 120; internal test set, n = 51; external validation set, n = 37) with pathologically confirmed HCC who underwent contrast-enhanced CT (CE-CT) within 1 month before surgery were retrospectively included from January 2014 to September 2021. Radiomics features were extracted and selected from three phases of CE-CT images, least absolute shrinkage and selection operator regression (LASSO) was used to select features, and the rad-score was calculated. CE-CT imaging and clinical features were selected using univariate and multivariate analyses, respectively. Three prediction models, including clinic-radiologic (CR) model, rad-score (R) model, and clinic-radiologic-radiomic (CRR) model, were developed and validated using logistic regression analysis. The performance of different models for predicting Ki-67 expression was evaluated using the area under the receiver operating characteristic curve (AUROC) and decision curve analysis (DCA). RESULTS: HCCs with high Ki-67 expression were more likely to have high serum α-fetoprotein levels (P = 0.041, odds ratio [OR] 2.54, 95% confidence interval [CI]: 1.04-6.21), non-rim arterial phase hyperenhancement (P = 0.001, OR 15.13, 95% CI 2.87-79.76), portal vein tumor thrombus (P = 0.035, OR 3.19, 95% CI: 1.08-9.37), and two-trait predictor of venous invasion (P = 0.026, OR 14.04, 95% CI: 1.39-144.32). The CR model achieved relatively good and stable performance compared with the R model (AUC, 0.805 [95% CI: 0.683-0.926] vs. 0.678 [95% CI: 0.536-0.839], P = 0.211; and 0.805 [95% CI: 0.657-0.953] vs. 0.667 [95% CI: 0.495-0.839], P = 0.135) in the internal and external validation sets. After combining the CR model with the R model, the AUC of the CRR model increased to 0.903 (95% CI: 0.849-0.956) in the training set, which was significantly higher than that of the CR model (P = 0.0148). However, no significant differences were found between the CRR and CR models in the internal and external validation sets (P = 0.264 and P = 0.084, respectively). CONCLUSIONS: Preoperative models based on clinical and CE-CT imaging features can be used to predict HCC with high Ki-67 expression accurately. However, radiomics cannot provide added value.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Antígeno Ki-67 , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X
6.
Pediatr Surg Int ; 40(1): 10, 2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38006461

RESUMEN

BACKGROUND: To determine the utility of contrast-enhanced voiding urography (CeVUS) in the treatment of vesicoureteral reflux (VUR) through ureterovesical reimplantation in children. METHODS: A total of 159 children with recurrent urinary tract infections were selected for CeVUS and voiding cystourethrography (VCUG) from December 2018 to December 2020, among whom 78 patients were eventually diagnosed with VUR. Overall, 60 pyelo-ureteric units (PUUs) were operated according to surgical indications. Accordingly, we determined the general clinical characteristics of all children, obtained two-dimensional ultrasound images, assessed the reflux status of children using the contrast-enhanced technique, and compared the obtained results via CeVUS and VCUG. Both imaging modalities were reperformed at 6, 12, and 18 months after surgery to evaluate postoperative outcomes. In particular, we assessed the consistency of the evaluation and calculated the diagnostic efficacy of CeVUS for different levels of reflux at different time points. RESULTS: CeVUS showed considerable efficacy in the diagnosis of children with VUR. Notably, the diagnostic results of both CeVUS and VCUG achieved high agreement, with a kappa value of 0.966 (P < 0.001). The results of our follow-up at different stages and evaluation of postoperative efficacy revealed that CeVUS possessed substantial diagnostic efficacy and good consistency with VCUG. CONCLUSION: CeVUS is an accurate and safe examination, with considerable clinical significance for diagnosing VUR in children, determining the treatment approach, conducting follow-up during treatment, and evaluating subsequent treatment outcomes.


Asunto(s)
Uréter , Reflujo Vesicoureteral , Niño , Humanos , Lactante , Reflujo Vesicoureteral/diagnóstico por imagen , Reflujo Vesicoureteral/cirugía , Medios de Contraste , Ultrasonografía/métodos , Urografía/métodos , Micción
7.
Chin J Traumatol ; 26(1): 41-47, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36008213

RESUMEN

PURPOSE: To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries. METHODS: With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches. RESULTS: Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury. CONCLUSIONS: Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.


Asunto(s)
Traumatismos Torácicos , Heridas Penetrantes , Animales , Porcinos , Reproducibilidad de los Resultados , Heridas Penetrantes/cirugía , Toracotomía , Traumatismos Torácicos/cirugía , Hemorragia , Modelos Animales
8.
Langmuir ; 38(23): 7114-7120, 2022 06 14.
Artículo en Inglés | MEDLINE | ID: mdl-35623058

RESUMEN

The development of antithrombotic peptides targeting collagen was proven effective, and an effective antithrombotic peptide LEKNSTY was obtained in part I. However, the plasma stability of LEKNSTY was found to be not good enough. In this part, the LEKNSTY was further optimized for improvement in plasma stability by substitution using d-amino acid residues. Two novel antithrombotic peptides LekNStY and lEKnsTy were designed, where lowercase letters represent d-amino acid residues. Improvements in plasma stability of both LekNStY and lEKnsTy were experimentally confirmed. Moreover, good binding of these antithrombotic peptides on the collagen surface was confirmed by molecular dynamics simulation and experimental validation. For example, a Kd of only 0.75 ± 0.10 µM was observed for lEKnsTy. Moreover, LekNStY and lEKnsTy were found to inhibit platelet adhesion on the collagen surface more effectively than LEKNSTY, and the IC50 of lEKnsTy was only 2/5 of that of LEKNSTY. These results confirmed the successful design of LekNStY and lEKnsTy that had good plasma stability and could effectively inhibit arterial thrombosis, which would be helpful for the research into interfaces involved in thrombus formation and the development of antithrombotic nanomedicine.


Asunto(s)
Fibrinolíticos , Trombosis , Aminoácidos , Colágeno/metabolismo , Fibrinolíticos/química , Fibrinolíticos/farmacología , Humanos , Péptidos/farmacología , Adhesividad Plaquetaria , Trombosis/tratamiento farmacológico , Trombosis/prevención & control
9.
Eur Radiol ; 32(6): 4186-4197, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35048134

RESUMEN

OBJECTIVES: This study aimed to establish a reliable diagnostic scoring model for the preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and biochemical indicators. METHODS: This retrospective study included 129 patients with HCC at our hospital from 2014 to 2020. Based on the intratumoral and peritumoral features on Gd-EOB-DTPA MRI and biochemical indicators, a scoring model was developed for preoperative prediction of MVI, and examined for diagnostic efficacy according to postoperative pathological results. The scoring model was further externally validated in an independent cohort of 63 HCC patients. RESULTS: Logistic regression analysis was performed to identify five parameters related to MVI, including maximum tumor diameter, peritumoral low intensity in the hepatobiliary phase, incomplete capsule, apparent diffusion coefficient (ADC), and [alkaline phosphatase (ALP) (U/L) + gamma-glutamyl transpeptidase (GGT) (U/L)] / lymphocyte count (× 109/L) ratio (AGLR). Based on these five parameters, a scoring model was developed, and the accuracy, sensitivity, specificity, PPV, and NPV in predicting MVI were 93.6%, 94.7%, 93.2%, 85.7%, and 97.6%, respectively, with a score > 8 set as the threshold. CONCLUSION: The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators provides a reliable tool for preoperative prediction of MVI in HCC patients. KEY POINTS: • The scoring model based on Gd-EOB-DTPA MRI and biochemical indicators is practical for preoperative prediction of MVI in HCC patients. • AGLR is an independent risk factor for MVI. • The scoring model could help implement more appropriate interventions, potentially leading to precise and individualized treatments based on the biological characteristics of the tumor.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/patología , Medios de Contraste , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos
10.
Eur Radiol ; 32(12): 8726-8736, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35639145

RESUMEN

OBJECTIVES: To date, there are no data on the noninvasive surrogate of intratumoural immune status that could be prognostic of survival outcomes in non-small cell lung cancer (NSCLC). We aimed to develop and validate the immune ecosystem diversity index (iEDI), an imaging biomarker, to indicate the intratumoural immune status in NSCLC. We further investigated the clinical relevance of the biomarker for survival prediction. METHODS: In this retrospective study, two independent NSCLC cohorts (Resec1, n = 149; Resec2, n = 97) were included to develop and validate the iEDI to classify the intratumoural immune status. Paraffin-embedded resected specimens in Resec1 and Resec2 were stained by immunohistochemistry, and the density percentiles of CD3+, CD4+, and CD8+ T cells to all cells were quantified to estimate intratumoural immune status. Then, EDI features were extracted using preoperative computed tomography to develop an imaging biomarker, called iEDI, to determine the immune status. The prognostic value of iEDI was investigated on NSCLC patients receiving surgical resection (Resec1; Resec2; internal cohort Resec3, n = 419; external cohort Resec4, n = 96; and TCIA cohort Resec5, n = 55). RESULTS: iEDI successfully classified immune status in Resec1 (AUC 0.771, 95% confidence interval [CI] 0.759-0.783; and 0.770 through internal validation) and Resec2 (0.669, 0.647-0.691). Patients with higher iEDI-score had longer overall survival (OS) in Resec3 (unadjusted hazard ratio 0.335, 95%CI 0.206-0.546, p < 0.001), Resec4 (0.199, 0.040-1.000, p < 0.001), and TCIA (0.303, 0.098-0.944, p = 0.001). CONCLUSIONS: iEDI is a non-invasive surrogate of intratumoural immune status and prognostic of OS for NSCLC patients receiving surgical resection. KEY POINTS: • Decoding tumour immune microenvironment enables advanced biomarkers identification. • Immune ecosystem diversity index characterises intratumoural immune status noninvasively. • Immune ecosystem diversity index is prognostic for NSCLC patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Linfocitos T CD8-positivos/patología , Estudios Retrospectivos , Ecosistema , Estadificación de Neoplasias , Pronóstico , Tomografía Computarizada por Rayos X , Biomarcadores , Microambiente Tumoral
11.
Chin J Traumatol ; 25(4): 193-200, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35331606

RESUMEN

PURPOSE: It is challenging to prepare military surgeons with the skills of combat damage control surgery (CDCS). The current study aimed to establish a damage control surgery (DCS) training platform for explosive combined thoraco-abdominal injuries. METHODS: The training platform established in this study consisted of 3 main components: (1) A 50 m × 50 m square yard was constructed as the explosion site. Safety was assessed through cameras. (2) Sixteen pigs were injured by an explosion of trinitrotoluene attached with steel balls and were randomly divided into the DCS group (accepted DCS) and the control group (have not accepted DCS). The mortality rate was observed. (3) The literature was reviewed to identify the key factors for assessing CDCS, and testing standards for CDCS were then established. Expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Then, a 5-day training course with incorporated tests was used to test the efficacy of the established platform. In total, 30 teams attended the first training course. The scores that the trainees received before and after the training were compared. SPSS 11.0 was employed to analyze the results. RESULTS: The high-speed video playback confirmed the safety of the explosion site as no explosion fragments projected beyond the wall. No pig died within 24 h when DCS was performed, while 7 pigs died in the control group. After a literature review, assessment criteria for CDCS were established that had a total score of 100 points and had 4 major parts: leadership and team cooperation, resuscitation, surgical procedure, and final outcome. Expert questionnaire results showed that the scientific score was 8.6 ± 1.25, and the feasibility score was 8.74 ± 1.19. When compared with the basic level, the trainees' score improved significantly after training. CONCLUSION: The platform established in this study was useful for CDCS training.


Asunto(s)
Traumatismos Abdominales , Sustancias Explosivas , Traumatismos Abdominales/cirugía , Animales , Competencia Clínica , Humanos , Resucitación , Porcinos
12.
Langmuir ; 37(22): 6792-6799, 2021 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-34047558

RESUMEN

Exposed collagen surface on diseased blood vessel wall is a trigger of platelet adhesion and subsequent thrombus formation, which is associated with many serious diseases such as myocardial infarction and stroke. Various antithrombotic agents have been developed, but are usually targeted on blood components such as platelet, which suffered from the risk of bleeding due to interference with hemostasis. In contrast, blocking the exposed collagen surface would prevent thrombus formation without the risk of bleeding. In the present study, an antithrombotic nanoconjugate (LWWNSYY-poly glutamic acid, L7-PGA) targeting collagen surface was designed by immobilizing heptapeptide LWWNSYY, a biomimetic inhibitor designed in our previous work, on poly(l-glutamic acid). Successful binding of L7-PGA on the collagen surface was confirmed by a negative ΔG of -5.99 ± 0.26 kcal/mol. L7-PGA was found to effectively inhibit platelet adhesion on the collagen surface, with a reduced IC50 of only 1/5 of that of free LWWNSYY. The inhibition of thrombus formation by L7-PGA was also validated in vivo by a reduction of 31.2% in the weight of thrombus. These results highlight L7-PGA as an effective inhibitor of arterial thrombus formation via blocking exposed collagen surface, which would be helpful for the development of novel antithrombotic nanomedicine.


Asunto(s)
Nanoconjugados , Trombosis , Plaquetas , Colágeno , Ácido Glutámico , Humanos , Adhesividad Plaquetaria , Trombosis/inducido químicamente , Trombosis/tratamiento farmacológico , Trombosis/prevención & control
13.
Am J Hum Genet ; 100(5): 817-823, 2017 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-28413019

RESUMEN

Pituitary adenoma (PA) is one of the most common intracranial neoplasms. Several genetic predisposing factors for PA have been identified, but they account for a small portion of cases. In this study, we sought to identify the PA genetic risk factors by focusing on causative mutations for PAs. Among the 4 affected and 17 asymptomatic members from one family with familial PA, whole-exome sequencing identified cosegregation of the PA phenotype with the heterozygous missense mutation c.4136G>T (p.Arg1379Leu) in cadherin-related 23 (CDH23). This mutation causes an amino acid substitution in the calcium-binding motif of the extracellular cadherin (EC) domains of CDH23 and is predicted to impair cell-cell adhesion. Genomic screening in a total of 12 families with familial PA (20 individuals), 125 individuals with sporadic PA, and 260 control individuals showed that 33% of the families with familial PA (4/12) and 12% of individuals with sporadic PA (15/125) harbored functional CDH23 variants. In contrast, 0.8% of the healthy control individuals (2/260) carried functional CDH23 variants. Gene-based analysis also revealed a significant association between CDH23 genotype and PA (p = 5.54 × 10-7). Moreover, PA individuals who did not harbor functional CDH23 variants displayed tumors that were larger in size (p = 0.005) and more invasive (p < 0.001). Therefore, mutations in CDH23 are linked with familial and sporadic PA and could play important roles in the pathogenesis of PA.


Asunto(s)
Cadherinas/genética , Mutación de Línea Germinal , Neoplasias Hipofisarias/genética , Secuencia de Aminoácidos , Proteínas Relacionadas con las Cadherinas , Estudios de Casos y Controles , Adhesión Celular , Genómica , Heterocigoto , Humanos , Linaje , Fenotipo , Conformación Proteica , Factores de Riesgo
14.
Ann Rheum Dis ; 79(11): 1460-1467, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32737104

RESUMEN

OBJECTIVES AND METHODS: With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them. RESULTS: Lower eBMD were observed in patients with PsA than in controls in both model0 (ß-coefficient=-0.014, p=0.0006) and model1 (ß-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (ß-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture. CONCLUSIONS: The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.


Asunto(s)
Antirreumáticos/uso terapéutico , Densidad Ósea/efectos de los fármacos , Osteoporosis/epidemiología , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Humanos , Análisis de la Aleatorización Mendeliana
15.
J Nerv Ment Dis ; 208(2): 101-107, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31868776

RESUMEN

Mindfulness and self-compassion are reported to have a preventive effects on depression and anxiety disorders. In the present study, we aimed to assess the effect of mindful self-compassion intervention on preventing postpartum depression in a group of symptomatic pregnant women. Participants were screened and assigned to the intervention and control groups randomly. A 6-week Internet-based Mindful Self-Compassion Program was used to train the participants. Multiple scales were used to assess depressive and anxiety symptoms, mindfulness, self-compassion, and mother and infant well-being. All assessments were performed at three time points: baseline, 3 months, and 1 year postpartum. Compared with the control group, the intervention group showed significant improvement in depressive and anxiety behaviors. In addition, the intervention group became more mindful and self-compassionate at 3 months and 1 year postpartum. More importantly, both mothers and infants experienced substantial improvement in well-being. Our findings indicate that mindful self-compassion intervention is effective in preventing postpartum depression and promoting mother and infant well-being.


Asunto(s)
Depresión Posparto/prevención & control , Empatía , Atención Plena , Adulto , Ansiedad/prevención & control , Ansiedad/psicología , Depresión/prevención & control , Depresión/psicología , Depresión Posparto/psicología , Femenino , Humanos , Atención Plena/métodos , Escalas de Valoración Psiquiátrica
16.
Hepatobiliary Pancreat Dis Int ; 19(6): 524-531, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33071179

RESUMEN

BACKGROUND: Hepatic artery occlusion (HAO) after liver transplantation (LT) is typically comprised of hepatic artery thrombosis (HAT) and stenosis (HAS), both of which are severe complications that coexist and interdependent. This study aimed to evaluate an integrated endovascular treatment (EVT) strategy for the resolution of early HAO and identify the risk factors associated with early HAO as well as the procedural challenge encountered in the treatment strategy. METHODS: Consecutive orthotopic LT recipients (n = 366) who underwent transplantation between June 2017 and December 2018 were retrospectively investigated. EVT was performed using an integrated strategy that involved thrombolytic therapy, shunt artery embolization plus vasodilator therapy, percutaneous transluminal angioplasty, and/or stent placement. Simple EVT was defined as the clinical resolution of HAO by one round of EVT with thrombolytic therapy and/or shunt artery embolization plus vasodilator therapy. Otherwise, it was defined as complex EVT. RESULTS: Twenty-six patients (median age 52 years) underwent EVT for early HAO that occurred within 30 days post-LT. The median interval from LT to EVT was 7 (6-16) days. Revascularization time (OR = 1.027; 95% CI: 1.005-1.050; P = 0.018) and the need for conduit (OR = 3.558; 95% CI: 1.241-10.203, P = 0.018) were independent predictors for early HAO. HAT was diagnosed in eight patients, and four out of those presented with concomitant HAS. We achieved 100% technical success and recanalization by performing simple EVT in 19 patients (3 HAT+/HAS- and 16 HAT-/HAS+) and by performing complex EVT in seven patients (1 HAT+/HAS-, 4 HAT+/HAS+, and 2 HAT-/HAS+), without major complications. The primary assisted patency rates at 1, 6, and 12 months were all 100%. The cumulative overall survival rates at 1, 6, and 12 months were 88.5%, 88.5%, and 80.8%, respectively. Autologous transfusion < 600 mL (94.74% vs. 42.86%, P = 0.010) and interrupted suture for hepatic artery anastomosis (78.95% vs. 14.29%, P = 0.005) were more prevalent in simple EVT. CONCLUSIONS: The integrated EVT strategy was a feasible approach providing effective resolution with excellent safety for early HAO after LT. Appropriate autologous transfusion and interrupted suture technique helped simplify EVT.


Asunto(s)
Angioplastia , Arteriopatías Oclusivas/terapia , Embolización Terapéutica , Arteria Hepática , Trasplante de Hígado/efectos adversos , Terapia Trombolítica , Trombosis/terapia , Adulto , Angioplastia/efectos adversos , Angioplastia/instrumentación , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/etiología , Arteriopatías Oclusivas/fisiopatología , Constricción Patológica , Bases de Datos Factuales , Embolización Terapéutica/efectos adversos , Femenino , Arteria Hepática/diagnóstico por imagen , Arteria Hepática/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Stents , Terapia Trombolítica/efectos adversos , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Grado de Desobstrucción Vascular , Vasodilatadores/uso terapéutico
18.
Cell Mol Life Sci ; 79(6): 299, 2022 05 19.
Artículo en Inglés | MEDLINE | ID: mdl-35585304
19.
J Nanosci Nanotechnol ; 18(7): 5113-5118, 2018 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29442702

RESUMEN

One-dimensional (1D) semiconductor ZnO nanowires have been successfully synthesized by a novel soft-chemical hydrothermal method with allylpolyethoxy amino carboxylate (AA-APEA) at low temperature. Their structure and properties have been characterized by a series of techniques, including X-ray diffraction (XRD), energy dispersive X-ray analysis (EDX) and transmission electron microscopy (TEM). It was found that ZnO nanowires with diameters around 50 nm and lengths up to about several micrometers are well-distributed. The photocatalytic activity toward degradation of methylene blue (MB) aqueous solution under ultraviolet (UV) was investigated and the results showed that the ZnO nanowires exhibit a markedly higher photoactivity compared to the ZnO nanoparticles which were obtained without AA-APEA polymer assistant, and it can be ascribed to the special 1D morphology of the ZnO nanowires. In particular, the rate of degradation of the ZnO nanowires was 11 times faster than that of ZnO nanoparticles. In addition, the ZnO nanowires could be easily recycled in UV photocatalytic activity. These observations could promote new applications of photocatalyst for wastewater treatment utilizing oxide semiconductor nanostructures.

20.
Int Orthop ; 42(1): 203-213, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-28988294

RESUMEN

PURPOSE: The purpose of this study was to provide the surgeons with effective and reliable guidelines for surgical decision-making by establishing a scoring system for giant cell tumour (GCTSS) based on evidence and expert opinion. METHODS: The modified Delphi technique and analytic hierarchy process were used to establish the GCTSS. The GCTSS was defined and classified based on different surgical methods using data from 207 patients collected retrospectively between October 2003 and December 2014. Finally, prospective data of 40 patients between December 2014 and October 2015 were used to analyze concordance between score categorization and experts' consensus on surgical procedure. RESULTS: A novel GCTSS included pathological fracture, cortical bone destruction, tumour size, and articular surface involved. The total scores ranged from 1 to 12 points. The strategy for each patient was decided: a total score of 1-4 suggested intralesional curettage alone for excellent post-operative function; 5-9 points indicated intralesional curettage with internal fixation for less surgery-related complications; and 10-12 points indicated prosthesis replacement for long-term local control. The κ-statistic for the predictive validity of total score was 0.611. The κ coefficient of each group represented moderate or substantial agreement, which was acceptable. The intraclass correlation coefficient for inter- and intra-observer reliability of total score was 0.831 and 0.740, respectively. CONCLUSIONS: The novel GCTSS is a comprehensive scoring system with content validity that can aid surgeons in assessing the aggressiveness or severity of giant cell tumour and might become a prognostic tool for surgical decision-making.


Asunto(s)
Neoplasias Óseas/patología , Tumor Óseo de Células Gigantes/patología , Articulación de la Rodilla/patología , Adulto , Neoplasias Óseas/cirugía , China , Consenso , Legrado/métodos , Toma de Decisiones , Técnica Delphi , Femenino , Fijación Interna de Fracturas/métodos , Tumor Óseo de Células Gigantes/cirugía , Humanos , Articulación de la Rodilla/cirugía , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos
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