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1.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1537-1546, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787152

RESUMO

To systematically evaluate the clinical efficacy and safety of Ginkgo Leaf Tablets(GLT) in the treatment of acute cerebral infarction(ACI). Seven databases both at home and abroad were systematically retrieved from their establishment to March 2020. The data of the included studies were extracted after review and screening. The quality of the included studies was assessed with the Cochrane risk bias assessment tool, and then the included studies were put into Meta-analysis by RevMan 5.3 to evaluate the total cli-nical efficiency, neurological function score, blood lipids and incidence of adverse reactions in treatment of ACI by GLT. Finally, the GRADE system was adopted to evaluate the evidence quality of each outcome indicator and form recommendations. Ten studies involving 886 participants were included, all of which were of low quality. Meta-analysis results showed that,(1)in terms of the total clinical efficiency, GLT+Western medicine was superior to Western medicine alone(RR_(NDS)=1.20, 95%CI[1.06, 1.36], P=0.005; RR_(NIHSS)=1.35, 95%CI[1.09, 1.69], P=0.007), and there was no statistical difference between GLT+Xuesaitong Injection+Wes-tern medicine and Xuesaitong Injection+Western medicine(RR=1.16, 95%CI[1.00, 1.35], P=0.05).(2)In terms of improving neurological function score, GLT+Western medicine was superior to Western medicine alone(MD_(NIHSS[moderate(severe)])=-1.55, 95%CI[-2.22,-0.88], P<0.000 01; MD_(NIHSS(severe))=-7.51, 95%CI[-8.00,-7.02], P<0.000 01; MD_(NDS)=-1.36, 95%CI[-2.39,-0.33], P=0.01), and GLT+Danshen Injection+Western medicine was superior to Danshen Injection+Western medicine(MD_(NDS)=-3.09, 95%CI[-3.84,-2.34], P<0.000 01).(3)In terms of regulating blood lipids, GLT+Western medicine was superior to Wes-tern medicine alone(MD_(TC)=-1.40, 95%CI[-2.13,-0.66], P=0.000 2; MD_(TG)=-1.29, 95%CI[-1.86,-0.73], P<0.000 01; MD_(LDL-C)=-1.48, 95%CI[-2.91,-0.04], P=0.04; MD_(HDL-C)=0.07, 95%CI[0.02, 0.12], P=0.009).(4)In terms of incidence of adverse reactions, there was no statistical difference between GLT+Western medicine and Western medicine alone(RR=0.63, 95%CI[0.30, 1.32], P=0.22). The results of the evaluation showed that the evidence level of each outcome indicator was low, and the recommendation was at weak level. In conclusion, GLT+Western medicine could improve the total clinical efficiency, neurological function score, and blood lipid status, with a low incidence of adverse reactions. However, due to the small amount of included stu-dies, low study quality and low level of evidence, it is expected to carry out clinical studies with standardized design and large sample size in the future to further investigate the clinical efficacy and safety of GLT in the treatment of ACI.


Assuntos
Infarto Cerebral , Ginkgo biloba , Infarto Cerebral/tratamento farmacológico , Humanos , Folhas de Planta , Comprimidos , Resultado do Tratamento
2.
Eur J Prev Cardiol ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33778872

RESUMO

AIMS: Type 2 diabetes mellitus (T2DM) is an independent risk factor for cardiovascular disease. However, the association between T2DM and coronary artery disease (CAD) in patients with heterozygous familial hypercholesterolaemia (HeFH) has not been thoroughly evaluated. Our study aimed to assess the effect of T2DM on CAD severity and hard cardiovascular endpoints in a HeFH cohort. METHODS AND RESULTS: A total of 432 patients with HeFH with a molecular and/or clinical Dutch Lipid Clinic Network score ≥6 (definite and probable) were enrolled. Patients were divided into a T2DM group (n = 99) and a non-T2DM group (n = 333). The severity of coronary stenosis was assessed by the number of diseased vessels and Gensini, SYNTAX, and Jeopardy scores. Hard endpoints included a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiac death. Cox regression and Kaplan-Meier analyses were used to evaluate the effect of T2DM on hard cardiovascular endpoints. The prevalence of CAD was higher in patients with T2DM compared with those without (96.0% vs. 77.5%, respectively; P < 0.001). Patients with T2DM demonstrated a greater number of diseased vessels (P = 0.029) and more severe coronary lesions with high Gensini, SYNTAX, and Jeopardy score tertiles (P = 0.031, P = 0.001, and P = 0.024, respectively). During a median of 3.75 years up to a maximum of 9 years of follow-up, hard endpoints occurred in 13 of 99 patients with T2DM and 16 of 333 without T2DM at baseline. Compared with patients without T2DM, patients with T2DM were at a significantly greater risk of hard endpoints [multivariate adjusted hazard ratio (HR) 2.32, 95% confidence interval (CI) 1.02-4.84; P = 0.025]. Additionally, patients with T2DM and good glucose control (HbA1c < 7.0%) were at a lower risk of hard endpoints compared with those with poor glucose control (HbA1c ≥ 7.0%, HR 0.08, 95% CI 0.01-0.56; P = 0.011). CONCLUSION: We conclude that T2DM is an independent predictor of CAD severity when assessed by number of diseased vessels, Gensini, SYNTAX, Jeopardy scores, and hard cardiovascular endpoints, suggesting that T2DM could be further used for risk stratification of patients with HeFH.

3.
Hepatol Int ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740211

RESUMO

BACKGROUND: Although non-invasive liver fibrosis scores (LFSs) have already been considered as effective tools for estimating cardiovascular risk, their roles in predicting disease severity and cardiovascular event (CVEs) in patients with stable coronary artery disease (CAD) are not comprehensively evaluated. The aim of the present study was to investigate whether non-alcoholic fatty liver disease fibrosis score (NAFLD-FS) and fibrosis-4 (FIB-4) are associated with CVEs in a large cohort with long-term follow-up. METHODS: A cohort of 5143 patients with angiography-proven stable CAD were consecutively enrolled and followed up for CVEs. The degree of coronary severity was assessed using the number of diseased vessels, Gensini, Syntax, and Jeopardy scores. The predictive values of NAFLD-FS and FIB-4 scores to coronary severity, coronary calcification (CAC), and CVEs were assessed, respectively. RESULTS: During a median follow-up of 7 years, 435 CVEs were recorded. Both NAFLD-FS and FIB-4 were predictors for the presence of CAC. The degree of coronary stenosis was significantly higher in high NAFLD-FS categories while FIB-4 was only positively associated with the number of diseased vessels and Gensini score. In Kaplan-Meier analysis, the patients with intermediate and high NAFLD-FS and FIB-4 had higher risk of CVEs and cardiovascular mortality. In multivariate Cox regression analysis, NAFLD-FS and FIB-4 were independently associated with CVEs [hazard ratio (95% confidence interval): 1.150 (1.063-1.244), p < 0.001 and 1.128 (1.026-1.240), p = 0.012]. CONCLUSION: The current data first indicated that both NAFLD-FS and FIB-4 scores were not only significantly related to coronary severity but also associated with CAC and CVEs. CLINICAL TRIALS REGISTRATION: None.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33744147

RESUMO

BACKGROUND: Longitudinal strain of the right ventricular (RV) free wall (RVFWLS) assessed by 2-dimensional (2D) speckle-tracking echocardiography (STE) has been recently demonstrated to correlate with the extent of RV myocardial fibrosis (MF). However, the value of 3-dimensional (3D) STE-derived strain parameters in predicting RV MF has not been investigated in patients with end-stage heart failure (HF). OBJECTIVES: This study aimed to determine which RV strain parameter assessed by 2D-STE and 3D-STE was the most reliable parameter for predicting RV MF in patients with end-stage HF against histological confirmation of MF. METHODS: A total of 105 consecutive patients with end-stage HF undergoing heart transplantation were enrolled in our study. The conventional RV function parameters, 2D-RVFWLS, and 3D-RVFWLS were obtained in these patients. The degree of MF was quantified by Masson trichrome staining in RV myocardial samples. The study population was divided into 3 groups according to the degree of MF on histology. RESULTS: Patients with severe MF had lower 3D-RVFWLS, 2D-RVFWLS, and conventional parameters of RV function compared with those with mild and moderate MF. RV MF strongly correlated with 3D-RVFWLS (r = -0.72; p < 0.001), modestly with 2D-RVFWLS (r = -0.53; p < 0.001), and weakly with conventional RV function parameters (r = -0.21 to -0.49; p < 0.01). 3D-RVFWLS correlated best with the degree of MF (r = -0.72 vs. -0.21 to -0.53; p < 0.05) compared with 2D-RVFWLS and conventional RV function parameters. 3D-RVFWLS had the highest accuracy for detecting severe MF (area under the receiver-operating characteristic curve: 0.90 vs. 0.24-0.80; p < 0.05) compared with 2D-RVFWLS and conventional RV parameters. The model with 3D-RVFWLS (R2 = 0.63; p < 0.001) was better in predicting the degree of RV MF than that with 2D-RVFWLS (R2 = 0.54; p < 0.001). CONCLUSIONS: 3D-RVFWLS may be the most robust echocardiographic measure for predicting the extent of RV MF in patients with end-stage HF.

5.
Cell Death Dis ; 12(3): 247, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33664254

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is prevalent in the world, accounting for a huge part of non-melanoma skin cancer. Most cSCCs are associated with a distinct pre-cancerous lesion, the actinic keratosis (AK). However, the progression trajectory from normal skin to AK and cSCC has not been fully demonstrated yet. To identify genes involved in this progression trajectory and possible therapeutic targets for cSCC, here we constructed a UV-induced cSCC mouse model covering the progression from normal skin to AK to cSCC, which mimicked the solar UV radiation perfectly using the solar-like ratio of UVA and UVB, firstly. Then, transcriptome analysis and a series of bioinformatics analyses and cell experiments proved that Rorα is a key transcript factor during cSCC progression. Rorα could downregulate the expressions of S100a9 and Sprr2f in cSCC cells, which can inhibit the proliferation and migration in cSCC cells, but not the normal keratinocyte. Finally, further animal experiments confirmed the inhibitory effect of cSCC growth by Rorα in vivo. Our findings showed that Rorα would serve as a potential novel target for cSCC, which will facilitate the treatment of cSCC in the future.

6.
IEEE Trans Cybern ; PP2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33661749

RESUMO

An event-triggered adaptive dynamic programming (ADP) algorithm is developed in this article to solve the tracking control problem for partially unknown constrained uncertain systems. First, an augmented system is constructed, and the solution of the optimal tracking control problem of the uncertain system is transformed into an optimal regulation of the nominal augmented system with a discounted value function. The integral reinforcement learning is employed to avoid the requirement of augmented drift dynamics. Second, the event-triggered ADP is adopted for its implementation, where the learning of neural network weights not only relaxes the initial admissible control but also executes only when the predefined execution rule is violated. Third, the tracking error and the weight estimation error prove to be uniformly ultimately bounded, and the existence of a lower bound for the interexecution times is analyzed. Finally, simulation results demonstrate the effectiveness of the present event-triggered ADP method.

7.
Fertil Steril ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33714537

RESUMO

OBJECTIVE: To identify targets and discover drugs for ovarian endometriosis (OE) DESIGN: A basic study based on a data-driven hypothesis and experimental validation SETTING: Center for Reproductive Medicine PATIENT(S)/ANIMAL(S): Fourteen patients with OE and 7 healthy donors were recruited, and 15 female C57/BL6 mice were involved. INTERVENTION(S): Samples of OE lesions and normal endometrium were obtained. The ITPR1-knockdowned ectopic human endometrial stromal cells (HESCs) were subjected to ribonucleic acid (RNA) sequencing, cell-counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, and flow cytometry. Camptothecin was administered to HESCs and in an OE mouse model. MAIN OUTCOME MEASURE(S): ITPR1 expression in OE lesions and normal endometrium, cell proliferation and apoptosis of HESCs with ITPR1 knockdown or camptothecin treatment, and autograft volume in the OE mouse model RESULT(S): Two significant OE-relevant gene modules were identified and involved the PI3K/Akt and aging-relevant pathways. Fifteen hub genes were identified and confirmed, among which the most significant gene, ITPR1, was robustly elevated in OE lesions. RNA sequencing revealed that ITPR1 was highly relevant to cell proliferation and apoptosis, which was further confirmed by CCK-8 assay, EdU staining, and flow cytometry analysis. ITPR1 knockdown inhibited cell proliferation and induced HESC apoptosis. The candidate drugs targeting these modules were screened, among which camptothecin and irinotecan were identified as promising drugs. Both compounds suppressed HESC proliferation and induced apoptosis; ITPR1 expression was suppressed by camptothecin. The therapeutic effect of camptothecin was also validated in the OE mouse model. CONCLUSION(S): This study identified the therapeutic targets and promising drugs for OE and shed light on the use of camptothecin in OE treatment.

8.
Inorg Chem ; 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33641331

RESUMO

Mechanochromic luminescent (MCL) materials are promising in pressure sensors, security papers, photoelectric devices and optical data recording. Although some kinds of MCL-active iridium(III) complexes with various soft substituent functional ligands (e.g., dendritic carbazole, flexible chains, and Schiff base ligands) were reported, the MCL mechanism is still not clear and mainly ascribes to the physical phase transformations from crystalline state to amorphous state in response to force stimulus at present stage, and deserves further study in order to obtain more intelligent MCL materials. Herein, two new iridium(III) complex isomers are tactfully constructed and show distinctly opposite MCL properties in spite of the same physical phase transformations happening on them. The absolutely out of the ordinary MCL mechanism has been presented on account of molecular level for the first time via the comparative study of photophysical properties based on isomers 1 and 2 with the help of crystal structure analysis, room/low temperature emission spectra, NMR, PXRD, and TD-DFT calculations. All of these results suggest that the emitting state dominated by the triplet charge transfer excited state (3CT) plays a key role in achieving mechanochromic luminescence in iridium(III) complex systems.

9.
Inorg Chem ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645962

RESUMO

Metal-organic frameworks (MOFs) are important photocatalytic materials for H2 production. To clarify the structure-function relationship and improve the photocatalytic activity, herein we explored a series of porphyrin-based zirconium MOFs (PCN-H2/Ptx:y, where x:y = 4:1, 3:2, 2:3, and 0:1) containing different ratios of H2TCPP and PtIITCPP [TCPP = tetrakis(4-carboxyphenyl)porphyrinate] as isostructural ligands and Zr6 clusters as nodes. Under visible-light irradiation, PCN-H2/Pt0:1 shows the highest average H2 evolution reaction rate (351.08 µmol h-1 g-1), which decreases along with lowering of the ratio of PtIITCPP in the PCN-H2/Ptx:y series. The differences in photocatalytic activity are attributed to more uniformly dispersed Pt2+ ions in PCN-H2/Pt0:1, which promotes charge transfer from porphyrins (photosensitizers) to PtII ions (catalytic centers), leading to efficient charge separation in the MOF materials. The bifunctional MOFs with photosensitizers and catalytic centers provide new insight for the design and application of porphyrin-based photocatalytic systems for visible-light-driven H2 production.

10.
Viral Immunol ; 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33646067

RESUMO

CD100 is an important immune semaphorin that is a secreted and membrane bound protein involved in infectious diseases. However, CD100 expression profile and the regulation to innate immune system in hepatitis B virus (HBV)-associated acute-on-chronic liver failure (ACLF) was not previously reported. The aim of this study was to investigate CD100 level and modulatory function of CD100 to CD14+ monocytes in HBV-ACLF patients. Plasma-soluble CD100 (sCD100) level and membrane-bound CD100 (mCD100) expression on peripheral CD14+ monocytes was analyzed in HBV-ACLF patients. CD14+ monocytes-induced cytotoxicity and CD14+ monocytes-mediated T cell activation in response to CD100 stimulation was also assessed in direct and indirect contact coculture culture systems. HBV-ACLF patients had lower plasma sCD100 and higher mCD100 level on CD14+ monocytes compared with asymptomatic HBV carriers, chronic hepatitis B patients, and controls. CD14+ monocytes from HBV-ACLF patients induced limited target Huh7.5 cell death and secreted less interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and granzyme B in both direct and indirect contact coculture systems compared with controls. Recombinant sCD100 not only enhanced CD14+ monocytes-mediated Huh7.5 cell death and granzyme B secretion, but it also elevated CD14+ monocytes-induced IFN-γ/interleukin-17 production by CD4+ T cells as well as IFN-γ/TNF-α secretion by CD8+ T cells in HBV-ACLF patients. The current data indicated that severe inflammation induced sCD100/mCD100 imbalance to inactivate CD14+ monocytes response, which might be beneficial for the survival of HBV-ACLF patients.

11.
Clin Transplant ; : e14275, 2021 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-33682171

RESUMO

Post-operative delirium after lung transplantation is common. Its associations with health-related quality of life (HRQL), depression, and mortality remains unknown. In 236 lung transplant recipients, HRQL and depressive symptoms were assessed as part of a structured survey battery before and after transplantation. Surveys included the Geriatric Depressive Scale (GDS) and Short Form 12 (SF12). Delirium was assessed throughout the post-operative intensive care unit (ICU) stay with Confusion Assessment Method for ICU. Delirium and mortality data were extracted from electronic medical records. We examined associations between delirium and changes in depressive symptoms and HRQL using linear mixed effects models and association between delirium and mortality with Cox-proportional hazard models. Post-operative delirium occurred in 34 participants (14%). Delirium was associated with attenuated improvements in SF12-PCS (difference ₋4.0; 95%CI: -7.4, -0.7) but not SF12-MCS (difference 2.2; 95%CI: -0.7,5.7) or GDS (difference ₋0.4; 95%CI: -1.5,0.7). Thirty-two participants died during the study period. Delirium was associated with increased adjusted hazard risk of mortality (HR 17.9, 95%CI: 4.4,72.5). Delirium after lung transplantation identifies a group at increased risk for poorer HRQL and death within the first post-operative year. Further studies should investigate potential causal links between delirium, and poorer HRQL and mortality risk after lung transplantation.

12.
Chemistry ; 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33786898

RESUMO

Quantum mechanics and molecular dynamics simulations were carried out on a series of anthracene- o -carborane derivatives ( ANT-H , ANT-Ph , ANT-Me and ANT-TMS ) with rare red-light emission in solid state. The simulation on the heating process of the crystals and further comparison of the molecular structures and excited-state properties before and after heating help us to disclose the thermochromic behavior, i.e., the red-shift emission is caused by the elongation of the C1-C2 bond in the carborane moiety after heating. Thus we believe that the molecular structure in crystal is severely affected by the heating. Molecular conformation transformation appears in ANT-H crystal with the increase of temperature. More specifically, the anthracene moiety changes from nearly parallel to the C1-C2 bond to nearly perpendicular, leading to the disappearance of the short-wavelength emission after heating. As for the aggregation-induced emission phenomenon, the structures and photophysical properties were comparatively investigated in both isolated state and crystal state, which suggests that the energy dissipation in crystal surroundings was greatly reduced through hindering structure relaxation from excited state to ground state. We expect that the discussion of the thermochromic behavior provides a new analysis perspective for the molecular design of o -carborane derivatives.

13.
Arch Oral Biol ; 125: 105090, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33676362

RESUMO

OBJECTIVES: The aim of the present study was to explore the functional role of miR-524 in oral squamous cell carcinoma (OSCC) and determine its underlying mechanism. MATERIALS AND METHODS: Tumor tissues and adjacent tissues were obtained from 55 patients with OSCC (20 females and 35 males) with a mean age of 54 years (range from 24 to 72 years). Additionally, OSCC cell lines culture was used and Reverse transcription­quantitative PCR (RT-qPCR) was applied to measure the expression of miR-524 in OSCC tissues and cells. The protein density of Metadherin (MTDH) in OSCC tissues was detected by Immunohistochemistry (IHC) assay. MiR-524 mimic was employed to investigate the impact of miR-524 on proliferation, migration, and invasion using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and transwell assays. The dual luciferase reporter assay was utilized to investigate the interaction between MTDH and miR-524 expression. Cells transfected with miR-524 mimic and pcDNA-MTDH were subjected to western blot to investigate the role of NF-κB signaling in miR-524/MTDH axis mediated cell proliferation, migration, and invasion. RESULTS: MiR-524 expression was decreased significantly in OSCC tissues compared to adjacent tissues, and closely related to clinical stage, tumor size, and lymph node metastasis. Over-expression of miR-524 suppressed the proliferation, migration, and invasion of OSCC cells. Luciferase reporter assay results demonstrated that MTDH was the target gene of miR-524. Over-expression of miR-524 reduced MTDH expression and inhibited NF-κB signaling pathway. Rescue experiments revealed that over-expression of MTDH partially reversed the efficacy of miR-524 mimic on OSCC cells. CONCLUSIONS: These results indicated that miR-524 inhibits the activation of NF-κB signaling pathway via inhibiting MTDH, resulting in the suppression of cell proliferation, migration, and invasion.

14.
Biosci Rep ; 41(4)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33749777

RESUMO

OBJECTIVES: The present study aimed to develop a random forest (RF) based prediction model for hyperuricemia (HUA) and compare its performance with the conventional logistic regression (LR) model. METHODS: This cross-sectional study recruited 91,690 participants (14,032 with HUA, 77,658 without HUA). We constructed a RF-based prediction model in the training sets and evaluated it in the validation sets. Performance of the RF model was compared with the LR model by receiver operating characteristic (ROC) curve analysis. RESULTS: The sensitivity and specificity of the RF models were 0.702 and 0.650 in males, 0.767 and 0.721 in females. The positive predictive value (PPV) and negative predictive value (NPV) were 0.372 and 0.881 in males, 0.159 and 0.978 in females. AUC of the RF models was 0.739 (0.728-0.750) in males and 0.818 (0.799-0.837) in females. AUC of the LR models were 0.730 (0.718-0.741) for males and 0.815 (0.795-0.835) for females. The predictive power of RF was slightly higher than that of LR, but was not statistically significant in females (Delong tests, P=0.0015 for males, P=0.5415 for females). CONCLUSION: Compared with LR, the good performance in HUA status prediction and the tolerance of features associations or interactions showed great potential of RF in further application. A prospective cohort is necessary for HUA developing prediction. People with high risk factors should be encouraged to actively control to reduce the probability of developing HUA.

15.
Medicine (Baltimore) ; 100(12): e25264, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761726

RESUMO

RATIONALE: Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor. PATIENTS CONCERNS: A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month. DIAGNOSIS: The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected. INTERVENTIONS: The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times. OUTCOMES: Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction. LESSONS: Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.


Assuntos
Cisplatino/administração & dosagem , Procedimentos Cirúrgicos de Citorredução/métodos , Docetaxel/administração & dosagem , Pemetrexede/administração & dosagem , Neoplasias Peritoneais , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Idoso , Antineoplásicos/administração & dosagem , Embolização Terapêutica/métodos , Humanos , Imuno-Histoquímica , Masculino , /patologia , /terapia , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/fisiopatologia , Neoplasias Peritoneais/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Sequenciamento Completo do Exoma/métodos
16.
Neuroimage Clin ; 30: 102597, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33684729

RESUMO

Aphasia, one of the most common cognitive impairments after stroke, is commonly considered to be a cortical deficit. However, many studies have reported cases of post subcortical stroke aphasia (PSSA). The pathology and recovery mechanism of PSSA remain unclear. This study aimed to investigate PSSA mechanism through a multimodal magnetic resonance imaging (MRI) approach and a two-session study design (baseline and one month after treatment). Thirty-six PSSA patients and twenty-four matched healthy controls (HC) were included. All patients had subcortical infarctions involving left subcortical white matter for 1 to 6 months. The patients underwent MRI scan and Western Aphasia Battery (WAB) examination before and after one month's comprehensive treatment. Region-wise lesion-symptom mapping (RLSM), tractography, fractional anisotropy (FA), and amplitude of low-frequency fluctuations (ALFF) analysis were conducted. After MRI preprocessing and exclusion, FA analysis included 35 patients pre-treatment and 16 patients post-treatment. ALFF analysis included 30 patients pre-treatment and 14 patients post-treatment. We found: 1) the amount of damage in the left uncinate fasciculus (UF) was associated with WAB aphasia quotient (AQ); 2) the left UF FA and left temporal pole (TP) ALFF were decreased and positively correlated with WAB-AQ, spontaneous speech, and naming in PSSA patients; and 3) PSSA patients showed increased left TP ALFF when their language ability recovered after treatment. The left TP ALFF change was positively correlated with AQ change. Our results demonstrate the importance of left UF and left TP (one of the cortical terminals of the left UF) in PSSA pathology and recovery. These results may further provide support for the disconnection theory in the mechanism of PSSA.

17.
Nutrition ; 86: 111143, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33601118

RESUMO

OBJECTIVES: Dietary ω-3 polyunsaturated fatty acids (ω-3 PUFAs) may affect infants' executive function (EF), although it remains unclear whether this may be the effect of total ω-3 PUFAs or any specific ω-3 PUFA. We assessed the associations between ω-3 PUFAs in breast milk and EF in infants at 8 mo of age. METHODS: Milk samples from the mothers of 120 breast-fed infants were collected at 42 d and 8 mo postpartum in Beijing, China. Infant's EF was evaluated by planning tasks and A-not-B tasks, including working memory, distractibility, and inhibition of prepotent response at age 8 mo. RESULTS: Eicosapentaenoic acid (EPA) concentrations in breast milk were significantly higher at 42 d than 8 mo postpartum. Breast milk EPA levels at both 42 d (P = 0.037) and 8 mo (P = 0.005) postpartum were negatively associated with infant distractibility when EPA levels were low (< 0.05%). No significant association was observed for other ω-3 PUFAs with infant EF scores. CONCLUSIONS: Our results suggest a beneficial effect of higher EPA in breast milk (improving infant's attention) when its levels are below a certain threshold.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33624914

RESUMO

The tracking of cellular senescence usually depends on the detection of senescence-associated ß-galactosidase (SA-ß-gal). Previous probes for SA-ß-gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous ß-gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de-acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA-ß-gal from cancer-associated ß-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli ß-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.

19.
Mol Oncol ; 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33641229

RESUMO

Ovarian cancer (OC) is highly prevalent and is associated with high mortality rates due to metastasis and relapse. In this study, we assessed the role of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in OC to gain further insight into mechanisms that contribute to its aggressiveness. We analyzed the correlation between SNHG1, miR-454 and zinc finger E-box-binding homeobox 1 (ZEB1) using a dual-luciferase reporter assay. Alterations in cell metastasis and invasiveness were observed using wound-healing and Transwell invasion assays, respectively. Tumor xenografts allowed us to monitor liver metastasis of mice injected with A2780 cells. We found that SNHG1 is overexpressed in OC. Downregulation of SNHG1 promoted miR-454 expression and reduced ZEB1 levels. In addition, knockdown of SNHG1, also reduced the aggressiveness of A2780 and SK-OV3 cells. Furthermore, SNHG1 downregulation by siRNA hindered cell migration and invasion; however, this effect was reversed by co-transfection of miR-454 into A2780 and SK-OV3 cells. Moreover, SNHG1 increased ZEB1 expression by downregulating miR-454 and activated Akt signaling, thereby promoting epithelial-mesenchymal transition and enhancing the invasiveness of OC cells. Tumor xenograft analyses confirmed that SNHG1 affects OC proliferation and metastasis in vivo. In summary, our data demonstrate that SNHG1 plays crucial roles in tumor progression and may be a useful maker for OC prognosis.

20.
Ann Am Thorac Soc ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565917

RESUMO

RATIONALE: Sarcopenia is associated with disability and death. The optimal definition and clinical relevance of sarcopenia in lung transplantation remain unknown. OBJECTIVE: To assess the construct and predictive validity of sarcopenia definitions in lung transplant candidates. METHODS: In a multicenter prospective cohort of 424 lung transplant candidates, we evaluated limited (muscle mass only) and expanded (muscle mass and quality) sarcopenia definitions from the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), Foundation for the National Institutes of Health (FNIH), and a cohort-specific distribution-based lowest quartile definition. We assessed construct validity using associations with conceptually related factors. We evaluated the relationship between sarcopenia and frailty using generalized additive models. We also evaluated associations between sarcopenia definitions and key pre-transplant outcomes including disability (quantified by the Lung Transplant Valued Life Activities scale [range 0-3, higher scores = worse disability; minimally important difference: 0.3]) and waitlist delisting/death by multivariate linear and Cox regression, respectively. RESULTS: Sarcopenia prevalence ranged from 6-13% by definition used. The limited EWGSOP2 definition demonstrated the highest construct validity, followed by the expanded EWGSOP2 and both limited and expanded FNIH and lowest quartile definitions. Sarcopenia exhibited a linear association with the risk of frailty. The EWGSOP2 and expanded lowest quartile definitions were associated with disability, ranging from 0.20 to 0.25 higher LT-VLA scores. Sarcopenia was associated with increased risk of waitlist delisting or death by the limited and expanded lowest quartile definitions (HR: 3.8; 95%CI: 1.4, 9.9 and HR: 3.5; 95%CI: 1.1, 11.0, respectively) and the EWGSOP2 limited definition (HR 2.8; 95%CI: 0.9, 8.6) but not with the three other candidate definitions. CONCLUSIONS: The prevalence and validity of sarcopenia vary by definition; the EWGSOP2 limited definition exhibited the broadest validity in lung transplant candidates. The linear relationship between low muscle mass and frailty highlights sarcopenia's contribution to frailty and also questions the clinical utility of a sarcopenia cut-point in advanced lung disease. The associations between sarcopenia and important pre-transplant outcomes support further investigation into using body composition for candidate risk stratification.

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