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1.
Inflamm Res ; 73(1): 145-155, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38085279

RESUMEN

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.


Asunto(s)
Citocinas , Sepsis , Humanos , Citocinas/metabolismo , Interleucina-10/metabolismo , Linfocitos T CD8-positivos , Activación de Linfocitos , Linfocitos T Reguladores , Sepsis/metabolismo , Subgrupos de Linfocitos T
2.
Am J Emerg Med ; 75: 198.e1-198.e5, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37925304

RESUMEN

A 54-year-old woman in good health was admitted to our hospital with diquat poisoning. The patient drank an unknown dose of diquat, and acute kidney injury developed early. However, there were no obvious pulmonary abnormalities and no signs of central nervous system toxicity in the early stage. The woman underwent active treatment, which resulted in a significant decrease in blood diquat levels, but her lung condition progressively worsened and neurological symptoms developed. Fortunately, the patient survived after intensive hemoperfusion combined with continuous renal replacement therapy (CRRT), intracranial pressure reduction, and anti-infective treatment. This case report highlights the importance of being aware of the development of delayed pulmonary symptoms and neurologic complications when caring for patients poisoned with diquat, even in those with low diquat blood concentrations. Interestingly, we also detected the concentration of diquat in the cerebrospinal fluid (CSF) of patients with diquat poisoning, and found that the rate of decrease of diquat concentration in the CSF was considerably slower than that in the blood.Notably, a specific correlation was observed between the concentration of diquat in the CSF, rather than in the blood, and both the intracranial pressure (ICP) and the severity of cerebral edema in this patient.


Asunto(s)
Terapia de Reemplazo Renal Continuo , Hemoperfusión , Intoxicación , Humanos , Femenino , Persona de Mediana Edad , Diquat , Sistema Nervioso Central , Pulmón , Intoxicación/terapia
3.
Radiat Oncol ; 18(1): 155, 2023 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-37735389

RESUMEN

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Radioterapia de Intensidad Modulada/efectos adversos , Protones , Estudios Retrospectivos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias de Cabeza y Cuello/radioterapia , Necrosis , Neoplasias Nasofaríngeas/radioterapia
4.
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
5.
World J Emerg Med ; 13(5): 361-366, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36119775

RESUMEN

BACKGROUND: Traumatic aortic dissection (TAD) has a low incidence but extremely high mortality. It always presents atypical clinical manifestations that are easily missed or misdiagnosed. This study mainly aims to describe the imaging characteristics and management of TAD patients. METHODS: A retrospective analysis of 27 blunt TAD patients was performed between 2013 and 2020. Demographic features, imaging characteristics, and management were analyzed. RESULTS: Twenty-seven patients with type B aortic dissection (age 56.04±16.07 years, 20 men) were included. Aortic intimal tears were mostly initiated from the aortic isthmus. The sizes of the proximal intimal tears in the greater curvature were larger than those in the lesser curvature (1.78±0.56 cm vs. 1.24±0.52 cm, P=0.031). Compared with those in the control group, the maximum diameters of the aortic arch, thoracic aorta, and abdominal aorta in the TAD patients were all significantly widened (all P<0.050). Multivariate logistic regression analysis showed that the maximum diameter of the thoracic aorta was an independent risk factor for TAD, with a predictive value with an area under the receiver operating characteristic curve (AUC) of 0.673. Finally, 26 patients successfully underwent delayed thoracic endovascular aortic repair (TEVAR), and the remaining one patient was treated conservatively. No progression of aortic dissection or death occurred during the six-month follow-up period. CONCLUSIONS: In blunt trauma, the aortic isthmus is the most common site of proximal intimal tears. An accurate diagnosis of TAD requires an overall consideration of medical history and imaging characteristics. Delayed TEVAR might be an effective therapeutic option for TAD.

6.
Abdom Radiol (NY) ; 47(10): 3468-3477, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35842888

RESUMEN

PURPOSE: This study aimed to establish a reliable diagnostic score model for the preoperative determination of pathological grade in HCC based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and biochemical indicators. METHODS: In this retrospective study, we analyzed 139 patients with HCC who underwent Gd-EOB-DTPA MRI between 2014 and 2020, including an establishment cohort of 76 patients and a validation cohort of 63 patients. Based on the imaging features demonstrated on Gd-EOB-DTPA MRI images and biochemical indicators of the establishment cohort, a scoring model based on logistic regression was developed, and compared with postoperative pathological findings in terms of effective determination of pathological grade. The validity of the scoring model was assessed by ROC curves and an independent external validation cohort. RESULTS: Three parameters related to pathological grades were identified, including maximum diameter of the tumor, peritumoral hypointensity in the hepatobiliary phase, and [alkaline phosphatase (U/L) + gamma glutamyl transpeptidase (U/L)]/ lymphocyte count (× 109/L) (AGLR) ratios. Based on these three parameters, a scoring model was developed. ROC curve showed that a score of > 5 was set as the threshold for determining pathological grades with accuracy, sensitivity, specificity, PPV, and NPV of 89.5%, 75.0%, 95.1%, 85.7%, and 90.7%, respectively. CONCLUSION: The study provided the groundwork for a promising and easily implementable scoring model for preoperative determination of HCC pathological grades, for which further validation should be pursued.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Medios de Contraste , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos
7.
Hu Li Za Zhi ; 69(3): 31-40, 2022 Jun.
Artículo en Chino | MEDLINE | ID: mdl-35644595

RESUMEN

BACKGROUND: A valid and reliable nursing record audit tool can simplify nursing records and provide a basis for quality auditing. PURPOSE: To ensure the validity and reliability of the Nursing Process Scale to promote accurate monitoring of nursing record quality. METHODS: This study employed structural equation modeling to examine the content validity and reliability of the current Nursing Process Scale. A total of 660 results from a medical center were used to revise the content and then the validity and reliability of the revised scale were analyzed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used in three stages, namely item generation and content validity testing, item analysis and validity testing, and reliability testing. RESULTS: Validity, reliability, and organization based on clinical practice were used to identify and remove scale items with low factor loadings. The remaining items were organized under several factors in the revised Nursing Process Scale, which had good internal consistency with a Cronbach's α of .653 in the EFA, a Kaiser-Meyer-Olkin value of .614, and a significant Bartlett's test of sphericity value. Five factors and 22 questions were extracted from the original 32 questions. The CFA conducted after the model correction reduced the number of questions to 10 and the number of factors to 3, with each index reaching the ideal level. To improve ease-of-use in clinical settings, the important items were reduced from 32 to 22 questions, including the 10 questions suggested by the CFA. CONCLUSIONS: The validity, reliability, and organization based on clinical practice were considered in the removal of items with low factor loadings. Axial conversion was used to generate a component matrix, which allowed item rearrangement across factors and the revision of the Nursing Process Scale. The development of simple valid and reliable audit tools will save auditor time and allow the effective evaluation of nursing record quality and improvement in record integrity. This revised scale was reviewed and approved for implementation in 42 clinical wards.


Asunto(s)
Proceso de Enfermería , Registros de Enfermería , Análisis Factorial , Humanos , Reproducibilidad de los Resultados
8.
J Patient Saf ; 18(6): e1004-e1009, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35532975

RESUMEN

OBJECTIVES: In the medical environment, teamwork among medical care personnel is closely related to patient safety and care quality. This research has developed an Intranet-based call-for-help system to establish an emergency support system. Few studies have explored the effects of the timely call-for-help system on teamwork. This study explored the effects of the timely call-for-help system intervention. METHODS: This study was designed by 2 groups of pretest and posttest. This research was conducted at a medical center in Taiwan. The subjects of the study were nurses in inpatient wards. The newly established call-for-help system was used in the 4 experimental wards, enabling nurses to immediately seek help from each other when faced with challenges and difficulties. This study was blind with the outcome evaluator and data analyst blinded to the group of participants. RESULTS: A total of 165 nurses were included in the study, 84 in the intervention group and 81 in the control group. After the intervention of the call-for-help system, the experimental group had significantly better teamwork, work efficiency, job satisfaction, and lower job stress than the control group ( P < 0.01). The generalized estimating equation showed that the progress scores of the experimental group on the 4 scales were significantly higher than those of the control group ( P < 0.01). CONCLUSIONS: The implementation of timely call-for-help system can enable nursing staff to get immediate support, strengthen teamwork, create a positive nursing practice environment, and improve patient safety and quality of care. These improvements in teamwork and support are very important and worthy of promotion.


Asunto(s)
Personal de Enfermería en Hospital , Estrés Laboral , Redes de Comunicación de Computadores , Humanos , Satisfacción en el Trabajo , Calidad de la Atención de Salud , Encuestas y Cuestionarios , Taiwán
9.
J Clin Psychol Med Settings ; 29(2): 432-445, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35249176

RESUMEN

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD - 3.48, CI - 4.07, - 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD - 0.42, CI - 0.70, - 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD - 0.64, CI - 1.09, - 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages.


Asunto(s)
Atención Plena , Neoplasias , Ansiedad/etiología , Ansiedad/psicología , Ansiedad/terapia , Fatiga/etiología , Fatiga/psicología , Fatiga/terapia , Humanos , Atención Plena/métodos , Neoplasias/complicaciones , Neoplasias/terapia , Dolor , Calidad de Vida
10.
J Med Chem ; 65(7): 5642-5659, 2022 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-35293758

RESUMEN

Class I histone deacetylase (HDAC) enzymes 1, 2, and 3 organize chromatin as the catalytic subunits within seven distinct multiprotein corepressor complexes and are established drug targets. We report optimization studies of benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTACs) and for the first time describe transcriptome perturbations resulting from these degraders. By modifying the linker and VHL ligand, we identified PROTACs 7, 9, and 22 with submicromolar DC50 values for HDAC1 and/or HDAC3 in HCT116 cells. A hook effect was observed for HDAC3 that could be negated by modifying the position of attachment of the VHL ligand to the linker. The more potent HDAC1/2 degraders correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells. We demonstrate that HDAC1/2 degradation by PROTACs correlates with enhanced global gene expression and apoptosis, important for the development of more efficacious HDAC therapeutics with reduced side effects.


Asunto(s)
Histona Desacetilasas , Neoplasias , Apoptosis , Quimera/metabolismo , Histona Desacetilasa 1/metabolismo , Histona Desacetilasas/metabolismo , Humanos , Ligandos , Neoplasias/tratamiento farmacológico , Proteolisis , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo
11.
Hepatobiliary Pancreat Dis Int ; 21(3): 257-266, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35168873

RESUMEN

BACKGROUND: Amanita poisoning as a foodborne disease has raised concerning mortality issues. Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita poisoning patients, while treatment is highly dependent on a confirmed diagnosis. To this end, we developed an early detection-guided intervention strategy by optimizing diagnostic process with performing α-amanitin detection, and further explored whether this strategy influenced the progression of Amanita poisoning. METHODS: This study was a retrospective analysis of 25 Amanita poisoning patients. Thirteen patients in the detection group were diagnosed mainly based on α-amanitin detection, and 12 patients were diagnosed essentially on the basis of mushroom consumption history, typical clinical patterns and mushroom identification (conventional group). Amanita poisoning patients received uniform therapy, in which plasmapheresis was executed once confirming the diagnosis of Amanita poisoning. We compared the demographic baseline, clinical and laboratory data, treatment and outcomes between the two groups, and further explored the predictive value of α-amanitin concentration in serum. RESULTS: Liver injury induced by Amanita appeared worst at the fourth day and alanine aminotransferase (ALT) rose higher than aspartate aminotransferase (AST). The mortality rate was 7.7% (1/13) in the detection group and 50.0% (6/12) in the conventional group (P = 0.030), since patients in the detection group arrived hospital much earlier and received plasmapheresis at the early stage of disease. The early detection-guided intervention helped alleviate liver impairment caused by Amanita and decreased the peak AST as well as ALT. However, the predictive value of α-amanitin concentration in serum was still considered limited. CONCLUSIONS: In the management of mushroom poisoning, consideration should be given to the rapid detection of α-amanitin in suspected Amanita poisoning patients and the immediate initiation of medical treatment upon a positive toxin screening result.


Asunto(s)
Amanita , Intoxicación por Setas , Alfa-Amanitina , Humanos , Hígado , Intoxicación por Setas/complicaciones , Intoxicación por Setas/diagnóstico , Intoxicación por Setas/terapia , Estudios Retrospectivos
12.
Artículo en Inglés | MEDLINE | ID: mdl-34769646

RESUMEN

Ventilator-associated pneumonia is a common hospital-acquired infection. It causes patients to stay longer in the hospital and increases medical costs. This study explores the effect of applying an automatic medical information system to implement five-item prevention care bundles on the prevention of ventilator-related pneumonia. This study was a retrospective cohort study. This study was conducted from October 2017 to February 2018 and collected data from the intensive care unit of a medical center in southern Taiwan from January 2013 to May 2016. The control group (enrolled from January 2013 to June 2014) received oral hygiene. The experimental group (enrolled from July 2014 to December 2015) received five-item ventilator-associated pneumonia prevention care bundles, which consisted of (1) elevation of the head of the bed to 30-45°; (2) daily oral care with 0.12-0.2% chlorhexidine twice daily; (3) daily assessment of readiness to extubate; (4) daily sedative interruption; and (5) emptying water from the respirator tube. Results showed the incidence of ventilator-associated pneumonia in the bundle group was significantly less than the oral hygiene group (p = 0.029). The factors that significantly affected the incidence of ventilator-associated pneumonia were ventilator-associated pneumonia care bundle, ventilator-days, and intensive care unit length of stay. A significant reduction in ventilator-associated pneumonia rate in the bundle group compared to the oral hygiene group (OR = 0.366, 95% CI = 0.159-0.840) was observed, with 63.4% effectiveness. Application of an automatic medical information system to implement bundle care can significantly reduce the incidence of ventilator-associated pneumonia.


Asunto(s)
Paquetes de Atención al Paciente , Neumonía Asociada al Ventilador , Humanos , Sistemas de Información , Unidades de Cuidados Intensivos , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/prevención & control , Estudios Retrospectivos
13.
Medicine (Baltimore) ; 100(30): e26768, 2021 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-34397723

RESUMEN

ABSTRACT: Pain is a common health problem for hospitalized patients. It is necessary to understand the factors that affect patients' pain to provide individual and complete pain management. This study explored the severity and incidence of pain in hospitalized patients on the admission day, during the hospitalization, and the discharge day, and explored the predictive factors that affect the patient's pain on the discharge day.This was a retrospective study that reviewed the medical records of 73,814 hospitalized patients from January 2016 to April 2018. The number of pain assessments was 471,339.The incidence of pain on the discharge day of patients was significantly higher than that on the admission day. The factors that affect and predict the pain of patients on discharge day include the degree of pain on the day of admission, emotional distress on the day of discharge, disease category, gender, age, and length of stay in hospital. It shows that the higher the degree of pain on the day of admission, the higher the degree of emotional distress on the day of discharge, female patients, younger patients, longer hospitalization days, and surgical and gynecological patients have significantly higher pain levels on the day of discharge (P < .05).This study found that the incidence of pain on the discharge day of patients was 46.5%. Previous pain level, disease category, emotional distress, gender, age, and length of hospital stay were important factors affecting patient pain on the discharge day. The influencing factors of patient pain should be fully assessed to provide individual and complete pain management, and improve patient quality of life after discharge.


Asunto(s)
Pacientes Internos/estadística & datos numéricos , Manejo del Dolor/estadística & datos numéricos , Alta del Paciente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
14.
Chin Med J (Engl) ; 134(9): 1052-1054, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33942799
15.
Front Immunol ; 11: 1299, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32719675

RESUMEN

Background: Myeloid derived suppressor cells (MDSCs) have been reported to keep elevating during sepsis. The current study was performed to investigate the immunosuppressive effect of MDSCs and their subsets with the underlying mechanisms. Methods: The immunosuppressive status was manifested by the apoptosis of splenocytes, quantity of T cells and PD-1 expression. The dynamics of quantity and PD-L1 level of MDSCs and the subsets were determined over time. The subset of MDSCs with high PD-L1 level was co-cultured with T cells to observe the suppressive effect. Results: Abdominal abscess was observed after 7 days post-sepsis. Five biomarkers related to organ functions were all significantly higher in the CLP group. The survival rate was consistent with the middle grade severity of sepsis model. Apoptosis of splenocytes increased over time during sepsis; CD4 + T cell decreased from day 1 post-sepsis; CD8+ T cells significantly reduced at day 7. The PD-1 expression in spleen was upregulated from an early stage of sepsis, and negatively related with the quantity of T cells. MDSCs were low at day 1 post-sepsis, but increased to a high level later; the dynamics of PMN-MDSC was similar to MDSCs. PD-L1 on MDSCs was highest at day 1 post-sepsis; PMN-MDSC was the main subset expressing PD-L1. The PMN-MDSC with high PD-L1 expression level extracted on day 1 after surgery from CLP mice significantly inhibited the proliferation of T cells. Conclusions: Sepsis-induced immunosuppression is initiated from a very early stage, a high expression level of PD-L1 on MDSCs and the main subset, PMN-MDSC might play a critical role suppressive role on T cells through PD-L1/PD-1 axis.


Asunto(s)
Antígeno B7-H1/metabolismo , Inmunomodulación , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Sepsis/etiología , Sepsis/metabolismo , Animales , Apoptosis/genética , Apoptosis/inmunología , Biomarcadores , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Inflamación/etiología , Inflamación/metabolismo , Inflamación/patología , Masculino , Ratones , Índice de Severidad de la Enfermedad , Bazo/inmunología , Bazo/metabolismo , Linfocitos T/inmunología , Linfocitos T/metabolismo
16.
Neuroscience ; 438: 145-157, 2020 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-32413397

RESUMEN

Brain derived neurotrophic factor (BDNF) is a member of the neurotrophin family, best characterized for its survival and differentiative effects in the central nervous system. Pro-BDNF, known as the precursor of BDNF, is believed to have opposite functions to mature BDNF (mBDNF). The opposing effects of Pro-BDNF and mBDNF have led researchers to propose a 'yin' (Pro-BDNF) and 'yang' (mBDNF) model of which, the specific mechanism of its opposing functions is unclear and requires further investigation. In order to elucidate pro-BDNF's explicit role, we established a pro-BDNF knockout (KO) mouse model. This BDNF pro-domain KO mouse model showed significant weight loss, impaired righting reflex, abnormal motor behaviours and short lifespan (less than 22 days), mimicking a Huntington's disease (HD)-like phenotype. ELISA results showed BDNF pro-domain KO not only blocked pro-BDNF, but also significantly affected the level of mBDNF. Abnormal morphologic changes were found in the dentate gyrus (DG) of the hippocampus in pro-BDNF KO mice, and western blot confirmed significant cell apoptosis in pro-BDNF KO mice brains. Furthermore, the expression of glutamic acid decarboxylase 65/67 (GAD65/67) was significantly reduced in pro-BDNF KO mice, indicating impaired inhibitory neurotransmission. Heterozygous (Het) mice showed impaired learning and memory capability and depressive-like behaviours, compared with wild type (WT) mice. Overall, these results support that pro-domain of BDNF is an indispensable part of the BDNF gene; without the proper formation of pro-BDNF, mBDNF cannot be produced successfully and function correctly on its own. Our study also supports the BDNF hypothesis in the pathogenesis of HD.


Asunto(s)
Factor Neurotrófico Derivado del Encéfalo , Precursores de Proteínas , Animales , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Hipocampo/metabolismo , Ratones , Ratones Noqueados , Precursores de Proteínas/genética , Precursores de Proteínas/metabolismo
17.
ACS Med Chem Lett ; 11(4): 497-505, 2020 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-32292556

RESUMEN

A combination of focused library and virtual screening, hit expansion, and rational design has resulted in the development of a series of inhibitors of RETV804M kinase, the anticipated drug-resistant mutant of RET kinase. These agents do not inhibit the wild type (wt) isoforms of RET or KDR and therefore offer a potential adjunct to RET inhibitors currently undergoing clinical evaluation.

18.
J Clin Lab Anal ; 34(7): e23281, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32157743

RESUMEN

BACKGROUND: Detection of hepatitis B virus (HBV) is vital for the diagnosis of hepatitis B infection. A novel test loop-mediated isothermal amplification (LAMP) has been successfully applied to detect various pathogens. However, the accuracy of LAMP in diagnosing HBV remains unclear. Therefore, in the present study, the accuracy of LAMP for HBV detection was evaluated systematically. METHODS: Embase, Cochrane Library, and PubMed databases were searched for studies using LAMP to detect HBV. Then, two researchers extracted data and assessed the quality of literature using the QUADAS-2 tool independently. I2 statistic and chi-square test were analyzed to investigate the heterogeneity, and Deek's funnel plot assessed the publication bias. The pooled sensitivity (SEN), specificity (SPE), positive LR (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals were displayed in forest plots. We calculated the area under the curve (AUC) to assess the overall efficiency of LAMP for HBV detection. RESULTS: A total of nine studies with 1298 samples were finally included in this evaluation. The pooled sensitivity and specificity of HBV detection were 0.91 (95% CI: 0.89 ~ 0.92) and 0.97 (95% CI: 0.94 ~ 0.99), respectively. The PLR, NLR, and DOR were 16.93 (95% CI: 6.15 ~ 46.55), 0.08 (95% CI: 0.05 ~ 0.14), and 397.57 (95% CI: 145.41 ~ 1087.07). Besides, the AUC was 0.9872, and Deek's plot suggested that there existed publication bias in the studies. CONCLUSION: Compared with PCR, LAMP is a simple, rapid, and effective assay to diagnose HBV. However, additional evidence is essential to confirm that LAMP can replace other methods in diagnosing HBV infection.


Asunto(s)
Hepatitis B/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificación de Ácido Nucleico/métodos , Hepatitis B/sangre , Humanos , Control de Calidad , Sensibilidad y Especificidad
19.
Worldviews Evid Based Nurs ; 16(6): 433-443, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31621181

RESUMEN

BACKGROUND: Findings from previous studies examining the effectiveness of symptom management on patients with diabetes that were implemented in home settings were inconclusive. Exploring the effects of a diabetes symptom management program on patients with type 2 diabetes mellitus (T2DM) in clinical settings is useful for healthcare providers to improve their diabetes care. AIMS: To examine the effects of a diabetes symptom management program (DSMP) on HbA1c levels, self-care behaviors, quality of life (QoL), and symptom severity in clinics in patients with T2DM. METHODS: This study was a single-blind randomized controlled trial. The control group (n = 30) received usual care. The experimental group (n = 30) received DSMP and usual care. The primary outcome variable was HbA1c levels; the secondary outcome variables were self-care behaviors, QoL, and diabetes symptom severity. Outcome variables were measured at baseline (T0), 3 months (T1) and 6 months after the intervention (T2), and HbA1c levels were further collected at 9 months after the intervention (T3). RESULTS: The decreasing levels of HbA1c from T0 to T2 and from T0 to T3 and for severity of diabetes symptoms from T0 to T2 in the experimental group were significantly better than those in the control group. The increasing levels of self-care behavior and QoL from T0 to T1 and from T0 to T2 in the experimental group were significantly higher than those in the control group. LINKING EVIDENCE TO ACTION: DSMP implemented in the clinic setting has effects on improving HbA1c, self-care behaviors, QoL, and preventing worsening severity of diabetes symptoms for outpatients with T2DM. Healthcare providers could assess diabetes symptoms of patients with high HbA1c levels and provide symptom management care rather than merely providing education on improvement of self-care behaviors.


Asunto(s)
Diabetes Mellitus Tipo 2/terapia , Anciano , Distribución de Chi-Cuadrado , Diabetes Mellitus Tipo 2/enfermería , Manejo de la Enfermedad , Práctica Clínica Basada en la Evidencia/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Automanejo/métodos , Método Simple Ciego , Encuestas y Cuestionarios , Síndrome
20.
Artículo en Inglés | MEDLINE | ID: mdl-31558906

RESUMEN

BACKGROUND: Facial threading is a common tradition in Taiwan, Southeast Asia (called "Bande Abru"), Middle East (called "Khite"), and Egypt (called "Fatlah"). In addition to the ability to remove facial vellus hairs, facial threading can make the skin fairer and shinier. However, there has been a lack of hard evidence regarding the effects of facial threading on the skin. OBJECTIVE: To examine the effects of facial threading on skin physiology as well as visual and touch senses by using scientific instruments. METHODS: A total of 80 participants were allocated to receive facial threading, application of powder only, exfoliation, and shaving. Prior to and following the assigned treatment, a noninvasive skin condition detection device was used to measure skin coarseness, hydration, melanin, and erythema index. Sense assessment and image analysis were also performed. RESULTS: This study showed that facial threading was found to improve the facial skin roughness indices with significant decreases by 30.4%, 35.9%, and 16.7%, respectively, for the participants' forehead, cheek, and mouth corner skin. No significant adverse changes in moisture levels and skin pigment indices were detected. In addition, there was improvement in subjects' touch sense of their skin and feelings about skin color. CONCLUSIONS: Traditional facial threading can remove facial vellus hairs and lower skin roughness levels, thereby improving the skin texture. However, pricking sensation appeared during the facial threading process, which might cause concerns about irritation.

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