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1.
Brain Behav Immun ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34728390

RESUMO

BACKGROUND: Post-stroke depression (PSD) is the most common psychological consequence among stroke patients. Increased inflammatory markers resulted from ischemic stroke probably played an important role in pathogenesis of depressive symptomology. We aimed to determine the relationship among stroke severity, systemic low-grade inflammation and depressive symptomology. METHODS: A total of 897 patients were consecutively recruited in this prospective cohort study and followed up for 1 year. The sample consisted of 436 ischemic stroke patients (23.4% female, median age = 57 years) from this cohort. Serum concentrations of inflammatory markers were measured in all 436 ischemic stroke patients, from fasting morning venous blood draws on admission. Stroke severity was evaluated by National Institutes of Health Stroke Scale (NIHSS) on admission and post-stroke depressive symptomology were evaluated by 17-item Hamilton Rating Scale for Depression (HRSD) at 1 year after ischemic stroke. RESULTS: After fully adjusted for covariates, we observed that 1) NIHSS (Model 2: ß=0.200, 95%CI, 0.057∼0.332), fibrinogen (Model 2: ß=0.828, 95%CI, 0.269∼1.435), WBC (Model 2: ß=0.354, 95%CI, 0.122∼0.577) and neutrophil count (Model 2: ß=0.401, 95%CI, 0.126∼0.655) can independently predict the 1-year depressive symptomology after ischemic stroke; 2) fibrinogen (Indirect effect=0.027, 95%CI, 0.007∼0.063, 13.4% mediated), white blood count (WBC, Indirect effect=0.024, 95%CI, 0.005∼0.058, 11.8% mediated) and neutrophil counts (Indirect effect=0.030, 95%CI, 0.006∼0.069, 14.8% mediated) could partially mediated the association between stroke severity (NIHSS) and 1-year depressive symptomology, and 3) stroke severity might cause depressive symptomology partly through the chain mediating role of both fibrinogen and neutrophil count (chain mediated effect=0.003, 95%CI, 0.000∼0.011, p=0.025, 1.6% mediated). CONCLUSIONS: These results suggested that fibrinogen, WBC and neutrophil count in systemic low-grade inflammation might be significant predictors of 1-year post stroke depressive symptomology and partial mediators of the relationship between stroke severity and 1-year depressive symptomology among ischemic stroke patients. In addition, the chain mediating effect of fibrinogen and neutrophil count might play an important role in the occurrence of 1-year post stroke depressive symptomology. However, no inflammatory marker was associated with 1-year depressive symptomology in females.

2.
Chem Commun (Camb) ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807198

RESUMO

The transmetalation as the rate-limiting step was effectively accelerated by newly designed N-heterocyclic carbenes with triazine wingtips (T-NHC). By using a ppm-level precatalyst T-NHC-Pd (8), the highly efficient coupling of aryl iodide, alkyne and carbon monoxide furnished a variety of ynone compounds. T-NHC-Pd (5), which deprotonated 4-methyl-phenylacetylene under mild conditions, converted into alkynyl-coordinated catalytic active species PdCl(T-NHC)(Py)(alkynyl). In the putative Pd/Pd catalytic cycle, both triazine-wingtips and NHCs are key players for establishing the carbonylative cross-couplings with high TON and TOF.

3.
Nature ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795452

RESUMO

Nutrients are emerging regulators of adaptive immunity1. Selective nutrients interplay with immunological signals to activate mechanistic target of rapamycin complex 1 (mTORC1), a key driver of cell metabolism2-4, but how these environmental signals are integrated for immune regulation remains unclear. Here we use genome-wide CRISPR screening combined with protein-protein interaction networks to identify regulatory modules that mediate immune receptor- and nutrient-dependent signalling to mTORC1 in mouse regulatory T (Treg) cells. SEC31A is identified to promote mTORC1 activation by interacting with the GATOR2 component SEC13 to protect it from SKP1-dependent proteasomal degradation. Accordingly, loss of SEC31A impairs T cell priming and Treg suppressive function in mice. In addition, the SWI/SNF complex restricts expression of the amino acid sensor CASTOR1, thereby enhancing mTORC1 activation. Moreover, we reveal that the CCDC101-associated SAGA complex is a potent inhibitor of mTORC1, which limits the expression of glucose and amino acid transporters and maintains T cell quiescence in vivo. Specific deletion of Ccdc101 in mouse Treg cells results in uncontrolled inflammation but improved antitumour immunity. Collectively, our results establish epigenetic and post-translational mechanisms that underpin how nutrient transporters, sensors and transducers interplay with immune signals for three-tiered regulation of mTORC1 activity and identify their pivotal roles in licensing T cell immunity and immune tolerance.

4.
Plant Methods ; 17(1): 116, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772413

RESUMO

BACKGROUND: The estimation of total iron content at the regional scale is of much significance as iron deficiency has become a routine problem for many crops. METHODS: In this study, a novel method for estimating total iron content in soil (TICS) was proposed using harmonic analysis (HA) and back propagation (BP) neural network model. Several data preprocessing methods of first derivative (FD), wavelet packet transform (WPT), and HA were conducted to improve the correlation between the soil spectra and TICS. The principal component analysis (PCA) was exploited to obtained three kinds of characteristic variables (FD, WPT-FD, and WPT-FD-HA) for TICS estimation. Furthermore, the estimated accuracy of three BP models based on these variables was compared. RESULTS: The results showed that the BP models of different soil types based on WPT-FD-HA had better estimation accuracy, with the highest R2 value of 0.95, and the RMSE of 0.68 for the loessial soil. It was proved that the characteristic variable obtained by harmonic decomposition improved the validity of the input variables and the estimation accuracy of the TICS models. Meanwhile, it was identified that the WPT-FD-HA-BP model can not only estimate the total iron content of a single soil type with high accuracy but also demonstrate a good effect on the estimation of TICS of mixed soil. CONCLUSION: The HA method and BP neural network combined with WPT and FD have great potential in TICS estimation under the conditions of single soil and mixed soil. This method can be expected to be applied to the prediction of crop biochemical parameters.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34775558

RESUMO

Financial inclusion (FI) is the backbone for every economy; however, a sustainable environment is also inevitable. Therefore, this study investigates the nexus of FI and environment, i.e., ecological footprint (EF) by controlling energy consumption (EC), economic growth (Y), infrastructure (INF), and corruption (CR) in OECD countries from 2004 to 2017. To validate this nexus, the study builds an index of FI and infrastructure through "Principal Component Analysis" (PCA). Furthermore, to estimate the above-said nexus, the study uses the "augmented mean group (AMG), and common correlated effects mean group (CCE-MG)" techniques to produce reliable results. Findings report the supportive role of INF by indicating the need to promote INF to attain a sustainable environment. However, FI, EC, and CR are found to be prominent reasons for environmental degradation. The study has robust policy implications for OECD economies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34595533

RESUMO

AIMS: Frailty has a great impact on the quality of life of patients with chronic heart failure (CHF), which needs to be judged in time. To develop a diagnostic model based on nutritional indicators to judge the frailty status of patients with chronic heart failure (Frailty-CHF). METHODS AND RESULTS: In the data collection part of this study, questionnaire method and biomedical measurement method were adopted. The trace elements in serum samples were detected by high performance liquid chromatography, chemiluminescence, and inductively coupled plasma mass spectrometry. We used Excel for data consolidation, and then imported the data into R software for modelling. Lasso method was used for variable screening, and Logistics regression fitting model was used after variables were determined. The internal validation of the model was completed by Bootstrap re-sampling. A total of 123 patients were included in this study. After variables' screening, age, nutritional status-heart failure, New York Heart Association Functional Class (NYHA), micronutrients B12, Ca, folic acid, and Se were included in the model, the c statistic and Brier score of the original model were 0.9697 and 0.0685, respectively. After Bootstrap re-sampling adjustment, the c statistic and Brier score were 0.8503 and 0.1690. CONCLUSION: In this study, a diagnostic model of age, nutritional status-heart failure, NYHA, the micronutrients B12, Ca, folic acid, and Se was established. It could help healthcare professionals better identify the frailty status in patients with CHF.

7.
Ann Clin Microbiol Antimicrob ; 20(1): 71, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598679

RESUMO

BACKGROUND: Corynebacterium striatum was confirmed to be an important opportunistic pathogen, which could lead to multiple-site infections and presented high prevalence of multidrug resistance, particularly to quinolone antibiotics. This study aimed to investigate the mechanism underlying resistance to quinolones and the epidemiological features of 410 quinolone-resistant C. striatum clinical strains isolated from three tertiary hospitals in China. METHODS: A total of 410 C. striatum clinical strains were isolated from different clinical samples of patients admitted to three tertiary teaching hospitals in China. Antibiotic susceptibility testing was performed using the microdilution broth method and pulsed-field gel electrophoresis (PFGE) was used for genotyping. Gene sequencing was used to identify possible mutations in the quinolone resistance-determining regions (QRDRs) of gyrA. RESULTS: In total, 410 C. striatum isolates were sensitive to vancomycin, linezolid, and daptomycin but resistant to ciprofloxacin. Depending on the antibiotic susceptibility testing results of 12 antimicrobial agents, the 410 C. striatum strains were classified into 12 resistant biotypes; of these, the three biotypes R1, R2, and R3 were dominant and accounted for 47.3% (194/410), 21.0% (86/410), and 23.2% (95/410) of the resistant biotypes, respectively. Mutations in the QRDRs ofgyrA were detected in all quinolone-resistant C. striatum isolates, and 97.3% of the isolates (399/410) showed double mutations in codons 87 and 91 of the QRDRs of gyrA. Ser-87 to Phe-87 and Asp-91 to Ala-91 double mutation in C. striatum was the most prevalent and accounted for 72.2% (296/410) of all mutations. Four new mutations in gyrA were identified in this study; these included Ser-87 to Tyr-87 and Asp-91 to Ala-91 (double mutation, 101 isolates); Ser-87 to Val-87 and Asp-91 toGly-91 (double mutation, one isolate); Ser-87 to Val-87 and Asp-91 to Ala-91 (double mutation, one isolate); and Ser-87 to Ile-87 (single mutation, one isolate). The minimum inhibitory concentration of ciprofloxacin for isolates with double (96.5%; 385/399) and single (72.7%; 8/11) mutations was high (≥ 32 µg/mL). Based on the PFGE typing results, 101 randomly selected C. striatum strains were classified into 50 genotypes (T01-T50), including the three multidrug-resistant epidemic clones T02, T06, and T28; these accounted for 14.9% (15/101), 5.9% (6/101), and 11.9% (12/101) of all genotypes, respectively. The multidrug-resistant T02 clone was identified in hospitals A and C and persisted from 2016 to 2018. Three outbreaks resulting from the T02, T06, and T28 clones were observed among intensive care unit (ICU) patients in hospital C between April and May 2019. CONCLUSIONS: Quinolone-resistant C. striatum isolates showed a high prevalence of multidrug resistance. Point mutations in the QRDRs of gyrA conferred quinolone resistance to C. striatum, and several mutations in gyrA were newly found in this study. The great clonal diversity, high-level quinolone resistance and increased prevalence among patients susceptible to C. striatum isolates deserve more attention in the future. Moreover, more thorough investigation of the relationship between quinolone exposure and resistance evolution in C. striatum is necessary.

8.
Front Med (Lausanne) ; 8: 720144, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660632

RESUMO

Objective: As of date, Kimura disease (KD) has an unclear etiology, no accepted diagnostic standard, and no definite treatment regimen. In this study, clinical and pathological laboratory characteristics and treatment regimens of patients with KD with different tumor sizes and status of tumor recurrence were analyzed. This was performed to identify the factors, which determine tumor size and recurrence, and to identify effective treatment methods for patients with KD. Methods: A total of 33 hospitalized patients with a definite diagnosis of KD were enrolled in this study. Results: There were 15 patients (45.5%) with a maximum tumor diameter of <3 cm. There were no statistically significant differences in age, gender, clinical symptoms, lesion sites, laboratory indicators, and treatment regimens among patients with a maximum tumor diameter <3 cm or ≥3 cm (P > 0.05). Among the 25 patients who completed the follow-up, there were 18 patients (72%) who had a recurrence of KD. There were no statistically significant differences in age, gender, clinical symptoms, the maximum tumor diameter, lesion sites, laboratory indicators, and initial treatment regimens between patients with or without the recurrence of KD (P > 0.05). There was a statistically significant difference in systolic blood pressure (SBP) between patients with or without the recurrence of KD (P < 0.05). All patients who received only surgical treatment had disease recurrence, 33.3% of patients who received prednisone therapy had no disease recurrence, and 37.5% of patients who received combination therapy showed recurrence. Conclusion: The current study summarized clinical manifestations, pathological features, laboratory indicators, and treatment regimens of patients with KD. There were no significant differences in these aspects among patients with different tumor sizes, and there was no significant difference in these aspects except in the SBP between patients with or without the recurrence of KD, indicating that SBP is a significant clinical factor affecting disease recurrence in patients. Combination therapy with prednisone was found to be superior to surgical treatment.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34678098

RESUMO

Purpose: To compare the clinical effects of postoperative versus perioperative injection of anti-vascular endothelial growth factor (VEGF) drugs before and after pars plana vitrectomy (PPV) in patients with vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Methods: This was a retrospective study of patients who underwent PPV due to vitreous hemorrhage between October 2013 and June 2019 at Ningbo Eye Hospital. The patients who underwent PPV surgery due to PCV-secondary vitreous hemorrhage were included. The primary outcome was the changes in best-corrected visual acuity. The secondary outcome was the central macular thickness. Results: Compared with the postoperative group (n = 20), the perioperative group (n = 18) showed a smaller number of postoperative anti-VEGF injections (5.1 ± 0.8 vs. 8.0 ± 1.5, P < 0.05) and lower frequencies of early hyphema (5.6% vs. 30.0%, P < 0.05), and recurrent vitreous hemorrhage (11.1% vs. 30.0%, P < 0.05). The logarithm of minimal angle resolution (LogMAR) was smaller in the perioperative group compared with the postoperative group at 1 week, 1 month, and 3 months after PPV (P < 0.05), but there were no differences thereafter. Compared with the postoperative group, the perioperative group had thinner fovea at 1 week, 1 month, and 3 months (P < 0.05), but the differences disappeared after 3 months. Conclusion: In patients with PCV and vitreous hemorrhage, compared with postoperative anti-VEGF, perioperative anti-VEGF could reduce the difficulty of surgery and reduce the occurrence of postoperative complications, but there were no differences in long-term vision and macular thickness after surgery.

10.
J Psychosom Res ; 150: 110632, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34624525

RESUMO

OBJECTIVE: Previous studies have shown that excess weight (including obesity and overweight) can increase the risk of cardiovascular, cerebrovascular and other diseases, but there is no study on the incidence of post-stroke depression (PSD) and related factors in patients with excessive weight. The main purpose of this study was to find related factors of PSD at 3 months after stroke in patients with excessive weight and construct artificial neural network (ANN) and decision tree (DT) models. METHODS: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Five hundred and three stroke patients with Body Mass Index(BMI) ≥ 24 were included in this study. The diagnostic criteria of PSD is according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) diagnostic criteria for depression due to other medical conditions and the HAMD-17 scores > 7 at 3 months after stroke was used as the primary endpoint. The χ2 test, Mann-Whitney U test or t-test were used to check for statistical significance. RESULTS: Our study found that sleeping time < 5 h, CHD, physical exercise, BI score, N dimension(EPQ) and subjective support(SSRS) were associated with PSD in patients with excessive weight. Physical exercise(odd ratio [OR] = 0.49, p = 0.001, 95%CI [confidence interval]: 0.32-0.75) and BI score(OR = 0.99, p < 0.001, 95%CI: 0.98-0.99) were protective factors; sleeping time < 5 h(OR = 2.86, p < 0.001, 95%CI: 1.62-5.04), CHD(OR = 2.18, p = 0.018, 95%CI: 1.14-4.15), N dimension(OR = 1.08, p = 0.001, 95%CI: 1.03-1.13) and subjective support(OR = 1.04, p = 0.022, 95%CI: 1.01-1.07) were risk factors. CONCLUSION: This study found several factors related to the occurrence of PSD at 3 months in patients with excessive weight. Meanwhile, ANN and DT models were constructed for clinicians to use.

11.
Chin J Physiol ; 64(5): 251-256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708717

RESUMO

Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.


Assuntos
Neoplasias da Mama , Proteínas de Choque Térmico HSP90/genética , Derrame Papilar , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Feminino , Humanos
12.
Arthritis Res Ther ; 23(1): 257, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641948

RESUMO

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a chronic systemic autoimmune disease which has focal lymphocytic infiltration including a majority of CD4+ T cells. This study was to investigate the correlation of peripheral granzyme B (GranzB)-expressing CD4+ T cells with disease severity and histological lesion in patients with pSS. METHODS: We recruited 116 pSS and 46 health control (HC) using flow cytometry to examine the percentage of CD4+GranzB+CTLs in the peripheral blood, and immunofluorescence to test their expression in the labial gland. RESULTS: The percentage of CD4+GranzB+CTLs was significantly upregulated in pSS than in HC (7.1 ± 4.9% vs 3.1 ± 1.9%, p < 0.0001) and positive correlation with ESSDAI. The frequency of them was markedly higher in pSS with extraglandular manifestations. After excluding the other risk factors associated with pSS, they were still related to ESSDIA and extraglandular manifestations independently (p < 0.05), and they are the risk factor of extraglandular involvement (odds ratio = 1.928). Moreover, they could be observed in the LSGs. ROC curve analysis indicated that the area under the curve (AUC) of CD4+GranzB+CTLs was 0.796 to predict the activity of pSS and 0.851 to presume extraglandular manifestations. The best diagnostic cutoff point was 4.865 for pSS patients. CONCLUSION: In this study, we provide new evidence indicating the involvement of CD4+GranzB+CTLs over activation in the pathophysiology of pSS, which may serve as a new biomarker to evaluate the activity and severity of pSS.


Assuntos
Síndrome de Sjogren , Linfócitos T CD4-Positivos , Granzimas , Humanos , Glândulas Salivares Menores , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico
13.
BMC Geriatr ; 21(1): 608, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34706663

RESUMO

OBJECTIVE: To investigate the association between sleep duration and cognitive frailty among older adults dwelling in western China. METHODS: We used the baseline data from West China Health and Aging Trend (WCHAT) study. Sleep duration was classified as short sleep duration (< 6 h), normal sleep duration (6-8 h) and long sleep duration (≥ 9 h). Fried frailty criteria and Short Portable Mental Status Questionnaire were used to measure cognitive frailty. Multinomial logistic regression was conducted to estimate odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 4093 older adults (age = 67.8 ± 5.9 years, 1708 males and 2385 females) were included in the analysis. The prevalence of cognitive frailty was 11.8% among older adults in western China. Approximately 11.9% participants had short sleep duration (< 6 h); 22.2% had a long sleep duration (≥ 9 h). After adjusting for covariates, only long sleep duration was significantly associated with high risk of cognitive frailty (OR = 2.07, 95%CI = 1.60-2.68, P <  0.001) in western China older adults compared to normal sleep duration. CONCLUSIONS: Long sleep duration was significantly related to cognitive frailty in older adults. Intervention for long sleep duration may be helpful to prevent cognitive frailty. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800018895 .


Assuntos
Fragilidade , Idoso , Envelhecimento , China/epidemiologia , Cognição , Estudos Transversais , Feminino , Idoso Fragilizado , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Avaliação Geriátrica , Humanos , Vida Independente , Masculino , Sono
14.
EMBO Mol Med ; : e14544, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34672091

RESUMO

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs.

15.
BMC Neurol ; 21(1): 383, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607565

RESUMO

BACKGROUND: Fasting C-peptide (FCP) has been shown to play an important role in the pathophysiology of mood disorders including depression and schizophrenia, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between FCP and PSD at 6 months after acute ischemic-stroke onset among Chinese subjects. METHODS: A total of 656 stroke patients were consecutively recruited from three hospitals of Wuhan city, Hubei province. Clinical and laboratory data were collected on admission. PSD status was evaluated by DSM-V criteria and 17-item Hamilton Rating Scale for Depression (HAMD-17) at 6 months after acute ischemic stroke. The χ2-test, Mann-Whitney U-test, and t-test were used to check for statistical significance. Multivariate logistic regression model was used to explore independent predictor of PSD. RESULTS: In the univariate analysis, significant differences were found between the PSD and non-PSD groups in terms of FCP level (p = 0.009). After multivariate adjustments, FCP remained a significant independent predictor of PSD, with an adjusted odds ratio of 1.179 (95%CI: 1.040-1.337, p = 0.010). CONCLUSIONS: Higher FCP levels on admission were found to be associated with PSD at 6 months after acute ischemic-stroke onset. For stroke patients, doctors should pay attention to the baseline FCP for screening high-risk PSD in clinical practice.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Peptídeo C , Depressão/epidemiologia , Depressão/etiologia , Jejum , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/complicações
16.
Clin Rheumatol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34709497

RESUMO

OBJECTIVE: The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. METHODS: We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. RESULTS: HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. CONCLUSION: This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. TRIAL REGISTRATION: http://www.chictr.org.cn/enindex.aspx , ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab.

17.
J Agric Food Chem ; 69(43): 12891-12899, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34694786

RESUMO

Novel acylurea derivatives 7a-7ab were designed and synthesized by linking the active substructures trifluoromethylpyridine and anthranilic diamide via an acylurea bridge. Most of the title compounds exhibited good activity against tobacco mosaic virus (TMV), particularly compound 7x (EC50 of 211.8 µg/mL), which showed much higher curative activity than ningnanmycin (EC50 of 389.8 µg/mL), and compound 7ab, which showed excellent inactivation activity (EC50 of 36.1 µg/mL), similar to ningnanmycin (EC50 of 23.2 µg/mL). The preliminary mechanism of these derivatives was investigated. Autodocking analysis revealed that compounds 7x and 7ab had good affinity for TMV coat protein (TMV CP), with low binding energies (-7.86 and -8.59 kcal/mol) comparable to ningnanmycin (-8.75 kcal/mol). Molecular dynamics simulation showed that compound 7x had a stable system structure with a better binding free energy (-32.94 kcal/mol) than ningnanmycin (-25.62 kcal/mol). Microscale thermophoresis showed that compound 7x bound more strongly to TMV CP (Kd of 19.8 ± 7.3 µM) than ningnanmycin (Kd of 21.2 ± 7.3 µM). Transmission electron microscopy and self-assembly experiments demonstrated that compounds 7x and 7ab significantly obstructed the self-assembly of TMV RNA and TMV CP. This new acylurea derivative has excellent antiviral activity by targeting TMV CP and inhibiting TMV self-assembly and can be considered a candidate for antiviral applications.


Assuntos
Antivirais , Vírus do Mosaico do Tabaco , Antivirais/farmacologia , Desenho de Fármacos , Piridinas , Relação Estrutura-Atividade
18.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575941

RESUMO

Drought is the main environmental factor that limits the yield and quality of apples (Malus × domestica) grown in arid and semi-arid regions. Nuclear factor Ys (NF-Ys) are important transcription factors involved in the regulation of plant growth, development, and various stress responses. However, the function of NF-Y genes is poorly understood in apples. Here, we identified 43 NF-Y genes in the genome of apples and conducted an initial functional characterization of the apple NF-Y. Expression analysis of NF-Y members in M. sieversii revealed that a large number of NF-Ys were highly expressed in the roots compared with the leaves, and a large proportion of NF-Y genes responded to drought treatment. Furthermore, heterologous expression of MsNF-YB21, which was significantly upregulated by drought, led to a longer root length and, thus, conferred improved osmotic and salt tolerance in Arabidopsis. Moreover, the physiological analysis of MsNF-YB21 overexpression revealed enhanced antioxidant systems, including antioxidant enzymes and compatible solutes. In addition, genes encoding catalase (AtCAT2, AtCAT3), superoxide dismutase (AtFSD1, AtFSD3, AtCSD1), and peroxidase (AtPER12, AtPER42, AtPER47, AtPER51) showed upregulated expression in the MsNF-YB21 overexpression lines. These results for the MsNF-Y gene family provide useful information for future studies on NF-Ys in apples, and the functional analysis of MsNF-YB21 supports it as a potential target in the improvement of apple drought tolerance via biotechnological strategies.


Assuntos
Arabidopsis/genética , Malus/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Arabidopsis/crescimento & desenvolvimento , Secas , Regulação da Expressão Gênica de Plantas/genética , Pressão Osmótica , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas/crescimento & desenvolvimento , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética
19.
J Gastrointest Oncol ; 12(4): 1498-1508, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532105

RESUMO

Background: Preoperative chemotherapy has widely been used in colorectal cancer liver metastasis (CRLM). Pathological response to chemotherapy is very important in evaluating tumor biology. However, there is still a lack of a non-invasive and accurate method to evaluate pathological response before surgery. Methods: We retrospectively analyzed the clinicopathologic data of patients with CRLM who underwent liver resection after preoperative chemotherapy between January 2006 and December 2018. Pathological responses were defined as minor when there are ≥50% remnant viable cells and as major when 0-49% remnant viable cells exist. Results: A total of 482 patients were included and randomly divided into training (n=241) and validation (n=241) cohorts. The proportion of major pathologic response was similar between the two groups (51.5% and 48.5%). Multivariate analysis determined the disease-free interval (DFI), tumor size, tumor number, and RAS status as independent predictors of major pathologic response to preoperative chemotherapy. The nomogram incorporating these variables showed good concordance statistics in the training cohort (0.746, 95% CI: 0.685-0.807) and validation cohort (0.764, 95% CI: 0.704-0.823). In addition, the nomogram showed good applicability in patients with different characteristics. Conclusions: The established nomogram model performed well in predicting pathological response in patients with CRLM.

20.
Front Psychiatry ; 12: 704045, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483996

RESUMO

Background: The QTc interval may be significantly prolonged in schizophrenia patients taking antipsychotics. Few studies have addressed QTc prolongation (QTP) in Chinese patients. Objectives: This study was designed to evaluate the prevalence of QTP and its clinical correlates in Chinese hospitalized patients with chronic schizophrenia. Methods: A total of 436 inpatients and 291 normal controls matched with age and sex were included. QTc prolongation was defined as 2 standard deviations (SD) above the mean value of normal controls. Positive and Negative Syndrome Scale (PANSS) and its five-factor model were used to evaluate psychopathological symptoms. Results: QTc interval was significantly longer in patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. More women than men displayed QTP. Compared with patients without QTP, the patients with QTP had significantly higher concrete/disorganized subscore, lower low density lipoprotein (LDL) and lower total protein (TP). Furthermore, binary logistic regression analysis showed that higher number of hospitalizations, higher concrete/disorganized subscore and lower LDL were risk factors for QTP. Correlation analysis indicated significant association between QTc interval and the following variables: sex, age, duration of illness, the number of hospitalizations, PANSS total score, fasting blood glucose (FPG). Finally, a multiple regression analysis showed that older age, antipsychotic polypharmacy, higher PANSS total score, and lower LDL were risk factors for QTP. Among them, LDL seemed to be a protective factor for QTP. Conclusions: QTc interval was longer in schizophrenia patients than in normal controls. The prevalence of QTP is 8.26% in Chinese hospitalized patients with chronic schizophrenia. Some clinical characteristics were risk factors for QTP. And LDL seemed to be a protective factor for QTP.

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