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1.
Nutr Clin Pract ; 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33978988

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) is spreading globally and has caused many deaths. This study investigated, for the first time, COVID-19 patients' nutrition status and its effects on their inflammatory and immune responses. METHODS: Forty-seven COVID-19 patients were recruited for this prospective study. According to the subjective global assessment at admission, patients were divided into the normal nutrition (NN), risk of malnutrition (RMN), or MN group. Serum cytokines and whole blood T-cell subpopulations were measured to assess the inflammatory and immune responses in COVID-19 patients. Analysis of covariance and χ2 tests were used. RESULTS: On admission, the incidences of MN and the RMN in COVID-19 patients were 17.0% and 38.3%, respectively. The MN group had a higher proportion with severe/critical COVID-19 and a longer hospitalization duration than the NN group. Serum interleukin (IL) 6 concentrations were elevated in 97.9% of the patients and were the highest in malnourished patients. The IL-4 and IL-10 levels were elevated in 46.8% and 48.9% of the patients, respectively. The proportion of CD8+ T cells was significantly lower in the MN group than in the NN group. CONCLUSION: A high proportion of COVID-19 patients are malnourished or at risk of malnuourishment, especially those with severe disease. MN is associated with hyperinflammation and immunosuppression in COVID-19 patients, and it may contribute to disease progression.

2.
Adv Sci (Weinh) ; 8(9): 2002017, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33977041

RESUMO

Grasping and manipulation are fundamental ways for many creatures to interact with their environments. Different morphologies and grasping methods of "grippers" are highly evolved to adapt to harsh survival conditions. For example, human hands and bird feet are composed of rigid frames and soft joints. Compared with human hands, some plants like Drosera do not have rigid frames, so they can bend at arbitrary points of the body to capture their prey. Furthermore, many muscular hydrostat animals and plant tendrils can implement more complex twisting motions in 3D space. Recently, inspired by the flexible grasping methods present in nature, increasingly more bio-inspired soft grippers have been fabricated with compliant and soft materials. Based on this, the present review focuses on the recent research progress of bio-inspired soft grippers based on impactive gripping. According to their types of movement and a classification model inspired by biological "grippers", soft grippers are classified into three types, namely, non-continuum bending-type grippers, continuum bending-type grippers, and continuum twisting-type grippers. An exhaustive and updated analysis of each type of gripper is provided. Moreover, this review offers an overview of the different stiffness-controllable strategies developed in recent years.

3.
PLoS Biol ; 19(5): e3001209, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33961621

RESUMO

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.

4.
J Hazard Mater ; 413: 125379, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33930952

RESUMO

Multifunctional filtration membranes (MFMs), which can both effectively separate oil and selectively remove dyes from polluted aquatic system with robust anti-viscous-oil-fouling capacity, strong chemical/physical resistance, and long cycled stability, are highly required but still a challenge to be realized. Herein, a simple route has been demonstrated to address this challenge aforementioned by decorating both halloysite nanotubes (HNTs) and zwitterionic poly (sulfobetaine methyl methacrylate) (PSBMA) on the microporous polyvinylidene fluoride (PVDF) membrane surface via modified polydopamine (PDA) coating route. The as-prepared membrane exhibits super-hydrophilic/underwater super-oleophobic performance and high water permeation flux (32529 ± 278 L m-2 h-1 at 0.85 bar) to purify the diverse viscous oil-in-water emulsions from oily wastewater accompanying with good cycled stability (the recovery rate of permeate flux is close to 100% after 5 cycles). Moreover, the as-prepared MFM possesses not only strong chemical resistance under wide range of pH value (from 1 to 12) and high saline (NaCl: 10 wt%) environment, but also physical resistance against ultrasound bath for 30 min. Given the presence of HNTs, PDA, and PSBMA, our MFM shows enough active sites to adsorb the soluble dyes and metallic ions in wastewater. These excellent properties endow our MFM with great potential for the remediation of complex wastewater.

5.
BMJ Open ; 11(4): e042679, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795295

RESUMO

OBJECTIVES: To enhance the understanding of non-communicable disease (NCD) multimorbidity in children who are inpatients by delineating the characteristics of and identifying patterns among paediatric inpatients with multimorbidity in China. DESIGN: Cross-sectional study. SETTING: Paediatric wards (n=17) in Pudong New Area, Shanghai, China. PARTICIPANTS: A total of 193 432 paediatric inpatients in the electronic health record systems of 17 hospitals from 2011 to 2016 participated in the study, and 91 004 children with NCDs were extracted and classified based on International Classification of Diseases, 10th version codes. MAIN OUTCOME MEASURES: Number of the NCDs and multimorbidity patterns of the paediatric inpatients. RESULTS: In total, 47.05% (95% CI 46.83 to 47.27) of the paediatric inpatients had one or more chronic diseases, and 16.30% (95% CI 16.14 to 16.46) had multimorbidity. Congenital anomalies accounted for 19.43% (95% CI 19.25 to 19.61) of the principal diagnoses among the paediatric inpatients. Five common multimorbidity patterns were identified: a neurological-respiratory cluster, a neurological-respiratory-ear cluster, a cardiovascular-circulatory cluster, a genitourinary cluster (boy group) and a musculoskeletal-connective cluster (10-18 years age group). CONCLUSIONS: Multimorbidity in paediatric inpatients suggests that decisions about reasonable allocation of paediatric inpatient resources should be fully considered. Multimorbidity patterns in paediatric inpatients revealed that prevention, including innovative treatments targeting children, should be further studied.

6.
Artigo em Chinês | MEDLINE | ID: mdl-33794628

RESUMO

Objective:The aim of this study was to evaluate the predicting role of tumor volume as evaluated by postoperative pathologic examination on overall survival(OS) and disease free survival(DFS) in patients with local advanced glottic carcinoma. Methods:In this study, the records of 406 consecutive patients with local advanced glottic carcinoma(T3-T4 stages) who underwent surgery ± chemoradiotherapy from January 2005 to December 2010 were retrospectively reviewed and followed up. The demographic characteristics, disease staging, and pathologic tumor volume were analyzed. The optimal cutoff values of tumor volume for OS and DFS were obtained by using receiver operating characteristic(ROC) curves. The association of tumor volume with T stages were assessed by using Logistic regression model, and the relationship between tumor volume and OS and DFS rates were evaluated by using Cox regression models. Results:The 5-and 10-year OS rates were 62.9% and 55.4%, respectively. The 5-and 10-year DFS rates were 55.5% and 50.8%, respectively. The mean tumor volume was(5.1±6.7) cm³, T4 stage patients had higher tumor volume than those of patients with T3 stage(P<0.001). The factor of tumor volume was correlated with T stages by using Logistic regression analyses(OR=13.81, 95%CI: 6.03-31.59, P<0.001). The optimal cutoff values of tumor volume that were both at 3 cm³ for OS and DFS rates were obtained by using ROC curve plots. The OS and DFS rates of glottic carcinoma patients with tumor volume ≤ 3 cm³ were better when compared with those of patients with tumor volume>3 cm³ï¼ˆP<0.001). Upon multivariate analyses, tumor volume was strongly correlated with poorer OS and DFS rates and remained independent prognostic factors for both the OS and DFS of patients with glottic carcinoma(OS: HR=1.59, 95%CI: 1.09-2.32, P=0.017; DFS: HR=1.54, 95%CI: 1.08-2.20, P=0.016). Conclusion:This study demonstrates that tumor volume is correlated with T stages, and this factor is an independent predictive factor of survival outcomes in patients with local advanced glottic carcinoma.


Assuntos
Carcinoma , Neoplasias Laríngeas , Intervalo Livre de Doença , Glote/patologia , Humanos , Neoplasias Laríngeas/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Carga Tumoral
7.
Molecules ; 26(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33805241

RESUMO

The efficiency roll-off and operational lifetime of organic light-emitting diodes (OLEDs) with a tetradentate Pt(II) emitter is improved by engaging an n-doped electron-transporting layer (ETL). Compared to those devices with non-doped ETL, the driving voltage is lowered, the charged carrier is balanced, and the exciton density in the emissive layer (EML) is decreased in the device with n-doped ETL with 8-hydroxyquinolinolatolithium (Liq). High luminance of almost 70,000 cd m-2 and high current efficiency of 40.5 cd A-1 at high luminance of 10,000 cd m-2 is achieved in the device with 50 wt%-Liq-doped ETL. More importantly, the extended operational lifetime of 1945 h is recorded at the initial luminance of 1000 cd m-2 in the 50 wt%-Liq-doped device, which is longer than that of the device with non-doped ETL by almost 10 times. This result manifests the potential application of tetradentate Pt(II) complexes in the OLED industry.

8.
Comput Biol Chem ; 92: 107481, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33838390

RESUMO

In this study, firstly, the pharmacophore model was established based on LAR inhibitors. ZINC database and drug-like database were screened by Hypo-1-LAR model, and the embryonic compound ZINC71414996 was obtained. Based on this compound, we designed 9 compounds. Secondly, the synthetic route of the compound was determined by consulting Reaxys and Scifinder databases, and 9 compounds (1a-1i) were synthesized by nucleophilic substitution, Suzuki reaction and so on. Meanwhile, their structures were confirmed by 1H NMR and 13C NMR. Thirdly, the Enzymatic assays was carried out, the biological evaluation of compounds 1a-1i led to the identification of a novel PTP-LAR inhibitor 1c, which displayed an IC50 value of 4.8 µM. At last, molecular dynamics simulation showed that compounds could interact strongly with the key amino acids LYS1350, LYS1352, ARG1354, TYR1355, LYS1433, ASP1435, TRP1488, ASP1490, VAL1493, SER1523, ARG1528, ARG1561, GLN1570, LYS1681, thereby inhibiting the protein activity. This study constructed the pharmacophore model of LAR protein, designed small-molecule inhibitors, conducted compound synthesis and enzyme activity screening, so as to provide a basis for searching for drug-capable lead compounds.

9.
Biomed Res Int ; 2021: 6692328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33860052

RESUMO

To investigate the effects of ficin on biofilm formation of conditionally cariogenic Streptococcus mutans (S. mutans). Biomass and metabolic activity of biofilm were assessed using crystal violet assay, colony-forming unit (CFU) counting, and MTT assay. Extracellular polysaccharide (EPS) synthesis was displayed by SEM imaging, bacteria/EPS staining, and anthrone method while acid production was revealed by lactic acid assay. Growth curve and live/dead bacterial staining were conducted to monitor bacterial growth state in both planktonic and biofilm form. Total protein and extracellular proteins of S. mutans biofilm were analyzed by protein/bacterial staining and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), severally. qRT-PCR was conducted to detect acid production, acid tolerance, and biofilm formation associated genes. Crystal violet assay, CFU counting, and MTT assay showed that the suppression effect of ficin on S. mutans biofilm formation was concentration dependent. 4 mg/mL ficin had significant inhibitory effect on S. mutans biofilm formation including biomass, metabolic activity, EPS synthesis, and lactic acid production (p < 0.05). The growth curves from 0 mg/mL to 4 mg/mL ficin were aligned with each other. There was no significant difference among different ficin groups in terms of live/dead bacterial staining result (p > 0.05). Protein/bacterial staining outcome indicated that ficin inhibit both total protein and biofilm formation during the biofilm development. There were more relatively small molecular weight protein bands in extracellular proteins of 4 mg/mL ficin group when compared with the control. Generally, ficin could inhibit biofilm formation and reduce cariogenic virulence of S. mutans effectively in vitro; thus, it could be a potential anticaries agent.

10.
J Palliat Med ; 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835877

RESUMO

Background: Fatigue is a frequent debilitating symptom among patients with lung cancer. The effect of exercise on fatigue remains to be quantified. Objective: This review aimed to examine the effect of exercise on fatigue by synthesizing findings from randomized controlled trials (RCTs). Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted in five electronic databases from inception to March 2020. Only RCT was included. The primary outcome was fatigue and the secondary outcomes included depression, anxiety, quality of life, and functional capacity. Pooled weighted or standardized mean difference (WMD or SMD) with 95% confidence interval (CI) was calculated. Results: Eight RCTs were included. The exercise intervention was delivered in the supervised environment (n = 6) or free-living settings (n = 2). Exercise reduced the level of fatigue (SMD = -0.33; 95% CI = -0.54 to -0.13). Exercise also decreased depressive symptom (WMD = -1.57; 95% CI = -2.69 to -0.44) and anxiety (WMD = -1.39; 95% CI = -2.60 to -0.18). Exercise showed a moderate effect on the quality of life, with an SMD of 0.33 (95% CI = 0.08 to 0.58). Exercise intervention increased functional capacity as measured by the six-minute walk test by 20 meters (95% CI = 14.2 to 55.0), but the effect was not significant (p = 0.247). Conclusion: Exercise demonstrated a moderate effect on fatigue in patients with lung cancer. Exercise also improved depressive symptoms, anxiety, and quality of life; however, its impact on functional capacity was not significant. More clinical trials are warranted to explore the mechanisms underlying the impact of exercise on fatigue. Strategies improving adherence to exercise prescription should be developed to help these patients overcome potential challenges.

11.
Biosensors (Basel) ; 11(4)2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33924324

RESUMO

According to the WTO, there were 1.13 billion hypertension patients worldwide in 2015. The WTO encouraged people to check the blood pressure regularly because a large amount of patients do not have any symptoms. However, traditional cuff measurement results are not enough to represent the patient's blood pressure status over a period of time. Therefore, there is an urgent need for portable, easy to operate, continuous measurement, and low-cost blood pressure measuring devices. In this paper, we adopted the convolutional neural network (CNN), based on the Hilbert-Huang Transform (HHT) method, to predict blood pressure (BP) risk level using photoplethysmography (PPG). Considering that the PPG's first and second derivative signals are related to atherosclerosis and vascular elasticity, we created a dataset called PPG+; the images of PPG+ carry information on PPG and its derivatives. We built three classification experiments by collecting 582 data records (the length of each record is 10 s) from the Medical Information Mart for Intensive Care (MIMIC) database: NT (normotension) vs. HT (hypertension), NT vs. PHT (prehypertension), and (NT + PHT) vs. HT; the F1 scores of the PPG + experiments using AlexNet were 98.90%, 85.80%, and 93.54%, respectively. We found that, first, the dataset established by the HHT method performed well in the BP grade prediction experiment. Second, because the Hilbert spectra of the PPG are simple and periodic, AlexNet, which has only 8 layers, got better results. More layers instead increased the cost and difficulty of training.

12.
Technol Cancer Res Treat ; 20: 1533033821997834, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33858283

RESUMO

Renal cell carcinoma (RCC) is a type of urinary tumor with a high incidence and is often associated with tumor metastasis. Long non-coding RNA (lncRNA) regulates tumorigenesis, progression, and metastasis. However, the role and the predictive value of lncRNA in RCC progression and metastasis have not been elucidated. The purpose of this study was to evaluate the effect of a newly discovered lncRNA LOC648987 on RCC proliferation and metastasis. LOC648987 was identified by RT-PCR for high expression in human RCC tissues as well as in metastatic RCC tissues. In the cell experiments, we infected the RCC cell lines ACHN and 786-O cells with LOC648987-shRNA and its negative control (shNC). The results showed that the knockdown of LOC648987 inhibited the proliferation of ACHN and 786-O cells and colony formation. The cell cycle and the apoptosis progression of ACHN and 786-O cells were assessed using flow cytometry. The knockdown of LOC648987 significantly inhibited the progression of ACHN and 786-O cells from G0/G1 to S phase and promoted cell apoptosis. The metastasis promoting effects of LOC648987 on ACHN and 786-O cells were verified by transwell migration assays, which depended on vimentin and MMP-9 to regulate the epithelial-mesenchymal transition. Finally, the promotion of LOC648987 on RCC tumorigenesis was evaluated in BALb/c nude mice. These data confirmed that lncRNA LOC648987 promoted RCC cell proliferation and tumor metastasis and regulated the expression of EMT-related proteins in RCC cells.

13.
Biomed Res Int ; 2021: 2342784, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33791361

RESUMO

Objectives: Recently, immunotherapy and microRNA have shown much more promises in oncology research, inspiring new hope for a cure for various malignancies. Specifically, the function and mechanisms of action of pembrolizumab have been investigated in many cancers, but not in laryngeal squamous cell carcinoma. The present study thus focused on the effect of hsa-miR-128a on pembrolizumab in laryngeal cancer cells as well as tried to elucidate the mechanisms that may mediate this effect. Methods: Hep2 and AMC-HN8 cell lines were utilized to create stable cell lines that overexpressing hsa-miR-128a. Using the immunotherapy assay, the contribution of hsa-miR-128a to pembrolizumab sensitivity was evaluated. By performing the dual luciferase assay and quantitative real-time polymerase chain reaction, the possible mechanisms of hsa-miR-128a were identified. Results: Hsa-miR-128a was overexpressed in laryngeal cancer cell lines successfully. The immunotherapy assay revealed that upregulating hsa-miR-128a augmented the effect of pembrolizumab. Moreover, hsa-miR-128a targeted BMI-1 and might played a role in the p53 pathway. Conclusion: Hsa-miR-128a boosted the effect of pembrolizumab on laryngeal cancer cells, perhaps via the p53 pathway. Therefore, hsa-miR-128a might be a novel target in laryngeal cancer treatment.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33792281

RESUMO

TiO2 has been intensively investigated as an anode material for lithium-ion batteries (LIBs) in 1.0-3.0 V (vs Li+/Li). However, it is a challenge to realize its theoretical capacity (336 mAh g-1) in this limited potential range. Extending the potential range below 1.0 V would increase its capacity but usually at the expense of its cyclic stability owing to the sluggish ionic diffusion and unsatisfactory structural stability. Here, three-dimensional (3D) macroporous TiO2 microspheres with interconnected pores and nanocrystalline thin walls have been constructed through a scalable template-assisted spray drying method to overcome these obstacles. When applied to LIBs, high and stable discharge capacity (300 mAh g-1 at 0.1 A g-1) as well as superior cyclic stability (242 mAh g-1 after 1000 cycles at 1.0 A g-1) can be achieved under deep discharging/charging conditions (0.01-3.0 V vs Li+/Li). Furthermore, the 3D macroporous structure is well preserved under deep discharging/charging and the in situ X-ray diffraction (XRD) patterns and Raman spectra reveal the dominant pseudocapacitive contribution at low potentials (0.01-1.0 V). This work not only develops a facile method to synthesize macroporous metal oxides but also provides insight into the lithium storage mechanism of TiO2 under deep discharging/charging conditions.

15.
Biol Trace Elem Res ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792858

RESUMO

Wild-caught seafood contains significant amounts of mercury. Investigating the mercury accumulation levels in wild-caught seafood and analyzing its migration and transformation are of great value for assessing the health risks of mercury intake and for the tracking of mercury sources. We determined the concentrations and stable mercury isotopic compositions (δ202Hg, Δ199Hg, Δ200Hg, and Δ201Hg) of 104 muscle samples collected from 38 species of seafood typically harvested from the Taiwan Shallow Fishing Ground (TSFG), Southern Taiwan Strait. Overall, the concentrations of total mercury (THg) and methylmercury (MeHg) ranged from 11 to 479 ng/g (dry weight, dw) and 10 to 363 ng/g (dw), respectively, and were below the threshold value established by the USEPA and the Chinese government. Demersal and near-benthic species accumulated more mercury than pelagic or mesopelagic species. The characteristics of mercury isotopes in wild-caught marine species differed in terms of vertical and horizontal distribution. Considering the known peripheral land sources of mercury (Δ199Hg ≈ 0), the mercury in seafood from the TSFG (Δ199Hg > 0) did not originate from anthropogenic emissions. The ratio of Δ199Hg and Δ201Hg (1.18 ± 0.03) suggested that the photoreduction of Hg (II) and the photo-degradation of MeHg equally contributed to mass-independent fractionation. Based on the values of Δ199Hg/δ202Hg (1.18 ± 0.03), about 67% of the mercury in seawater had undergone microbial demethylation prior to methylation and entering the seafood. Additionally, the vertical distribution of Δ200Hg in seafood from different water depths implies that mercury input was in part caused by atmospheric deposition. Our results provide detailed information on the sources of mercury and its transfer in the food web in offshore fishing grounds.

16.
CNS Neurosci Ther ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764684

RESUMO

AIMS: The basal forebrain (BF) plays an essential role in wakefulness and cognition. Two subtypes of BF gamma-aminobutyric acid (GABA) neurons, including somatostatin-expressing (GABASOM ) and parvalbumin-positive (GABAParv ) neurons, function differently in mediating the natural sleep-wake cycle. Since the loss of consciousness induced by general anesthesia and the natural sleep-wake cycle probably share similar mechanisms, it is important to clarify the accurate roles of these neurons in general anesthesia procedure. METHODS: Based on two transgenic mouse lines expressing SOM-IRES-Cre and PV-IRES-Cre, we used a combination of genetic activation, inactivation, and chronic ablation approaches to further explore the behavioral and electroencephalography (EEG) roles of BFSOM and BFParv neurons in general anesthesia. After a single intravenous injection of propofol and the induction and recovery times of isoflurane anesthesia, the anesthesia time was compared. The changes in cortical EEG under different conditions were also compared. RESULTS: Activation of BF GABASOM neurons facilitates both the propofol and isoflurane anesthesia, manifesting as a longer anesthesia duration time with propofol anesthesia and a fast induction time and longer recovery time with isoflurane anesthesia. Moreover, BF GABASOM -activated mice displayed a greater suppression of cortical electrical activity during anesthesia, showing an increase in δ power bands or a simultaneous decrease in high-frequency power bands. However, only a limited and nuanced effect on propofol and isoflurane anesthesia was observed with the manipulated BF GABAParv neurons. CONCLUSIONS: Our results suggested that BF GABASOM neurons play a critical role in propofol and isoflurane general anesthesia, while BF GABAParv neurons appeared to have little effect.

17.
J Am Heart Assoc ; 10(6): e019184, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33682435

RESUMO

Background Long-term antithrombotic strategies for patients with chronic coronary syndrome with high-risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta-analysis to evaluate the efficacy and safety of long-term antithrombotic strategies in patients with chronic coronary syndrome. Methods and Results Four randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS-TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti-platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta-analysis showed that, compared with aspirin monotherapy, the ORs for trial-defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80-0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78-1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64-0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,-0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial-defined major bleeding were 2.15 (95% CI, 1.78-2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23-1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37-2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65-0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66-0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69-0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41-0.82) regimens. Conclusions All antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all-cause mortality, rivaroxaban plus aspirin appears to be the preferred long-term antithrombotic regimen for patients with chronic coronary syndrome and high-risk factors.

18.
Aust N Z J Psychiatry ; : 4867421998804, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726535

RESUMO

OBJECTIVES: Physical diseases are well-established risk factor for suicide, particularly among older adults. However, little is known about the underlying mechanism of the association. This study aimed to describe the prevalence of physical diseases and their influences on the elderly in rural China and to examine the underlying mechanisms of the relationship between physical diseases and suicide. METHODS: This matched case-control psychological autopsy study was conducted from June 2014 to September 2015. Consecutive suicide cases (242) among people aged 60 years or above were identified in three Chinese provinces. The suicide cases were 1:1 matched with living comparisons based on age, gender and residential area. Two informants for each participant were interviewed to collect data on their demographic characteristics, the severity index of physical diseases, depressive symptoms, feelings of hopelessness, mental disorders and social support. RESULTS: A significant difference was found between suicide cases and living comparisons regarding the prevalence of physical diseases (83.5% vs 66.5%, p < 0.001) and their severity (11.3 ± 6.2 vs 6.7 ± 5.3, p < 0.001). Independent risks of suicide included the following: not currently married (OR = 2.81, 95% CI = [1.04, 7.62]), mental disorders (OR = 7.18, 95% CI = [1.83, 28.13]), depressive symptoms (OR = 1.15, 95% CI = [1.05, 1.26]) and feelings of hopelessness (OR = 1.51, 95% CI = [1.20, 1.90]). The structural equation model indicated that the relationship between the severity index of physical diseases and suicide was mediated by depressive symptoms, feelings of hopelessness and mental disorders. CONCLUSION: The severity and number of physical diseases were found to be correlated with suicide among the elderly in rural China, after controlling for demographic characteristics. Physical diseases elevate one's suicide risk by increasing depressive symptoms, feelings of hopelessness and mental disorders. Efforts for suicide prevention should be integrated with strategies to treat physical diseases along with psychological interventions.

19.
Life Sci ; 275: 119288, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33667514

RESUMO

AIMS: Hepatocellular carcinoma (HCC) is a malignant cancer that threatened human life seriously. Long non-coding RNA (lncRNA) BACE1-AS has been reported as a key regulator in tumorigenesis. Yet the specific correlation between BACE1-AS and HCC still needs further investigation. The primary purpose of our study is to reveal the exact correlation between BACE1-AS and HCC. MAIN METHODS: Bioinformatics via TCGA database revealed BACE1-AS closely related with HCC. qRT-PCR confirmed the abnormal BACE1-AS level in HCC tissues and cells. Databases prediction suggested that miR-377-3p might be a modulatory target of BACE1-AS and luciferase assay confirmed this hypothesis. Further study discovered that CELF1 also partook in the regulatory axis of BACE1-AS/miR-377-3p. Wound healing assays and transwell assays were utilized to investigate the impact of BACE1-AS, miR-377-3p and CELF1 in vitro. In vivo metastasis was examined by pulmonary metastasis model. KEY FINDINGS: This study found that BACE1-AS was overexpressed in HCC tissues and cell lines. Knockdown of BACE1-AS could restrain HCC progression in vitro, and inhibit pulmonary metastasis in vivo. MiR-377-3p was negatively modulated by BACE1-AS in HCC tumor tissues and cells. MiR-377-3p up-regulation inhibited HCC cells migration and invasion via inactivating EMT process. Moreover, CELF1 was identified as a downstream regulator of miR-377-3p and served as an oncogene in HCC cells. SIGNIFICANCE: Our findings supported that lncRNA BACE1-AS was up-regulated in HCC, promoting invasion and metastasis of hepatocellular carcinoma cells by modulating miR-377-3p/CELF1 axis via contributing to EMT pathway. BACE1-AS could be a potential biomarker in HCC for future treatment.


Assuntos
Proteínas CELF1/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Western Blotting , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Invasividade Neoplásica , Transplante de Neoplasias , RNA Longo não Codificante/fisiologia , Reação em Cadeia da Polimerase em Tempo Real
20.
Clin Transl Sci ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33650258

RESUMO

Epilepsy is a common disorder with complex inheritance, and its treatment is very unsatisfactory. An association between the GABRG2 C588T polymorphism and genetic generalized epilepsy has been studied by several genetic association studies. However, these results were inconsistent, and the role of GABRG2 in epilepsy treatment remains unknown. To evaluate the role of GABRG2 in epilepsy, we performed meta-analysis, expression quantitative trait loci analysis, protein-protein interaction analysis, and drug-gene interaction analysis. The combined results indicated that the GABRG2 C588T polymorphism was associated with genetic generalized epilepsy risk under dominant and allelic models (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.02-1.54, p = 0.03, I2  = 0% and OR = 1.21, 95% CI = 1.03-1.42, p = 0.02, I2  = 20%, respectively). In the Asian population, we also found similar results under dominant and allelic models (OR = 1.93, 95% CI = 1.18-3.16, p = 0.009, I2  = 0% and OR = 1.69, 95% CI = 1.20-2.37, p = 0.003, I2  = 11%, respectively). We first found that the GABRG2 C588T polymorphism regulates GABRG2 expression in human brain tissues and that the protein encoded by GABRG2 interacts with targets of approved antiepileptic drugs (AEDs). Interestingly, we also found that GABRG2 itself interacts with approved AEDs. Taken together, the results indicate that the C588T polymorphism might alter the GABAA receptor by modulating GABRG2 gene expression, resulting in increased risk for epilepsy, and that GABRG2 may be a potential therapeutic target for epilepsy.

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