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1.
Food Chem ; 336: 127714, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32828014

RESUMO

Five new flavonoids (1-5), along with 25 known compounds, were isolated from the rhizomes of Potentilla anserina L. and their structures were identified using spectroscopic and chemical evidence. The extract, all fractions, and all isolated compounds were evaluated for their antioxidant, α-glucosidase, and tyrosinase inhibitory activities, and their structure-activity relationship was interpreted. The biflavanols and quercetin-3-O-α-l-rhamnopyranoside-2″-gallate (14) exhibited significant antioxidant and α-glucosidase inhibition activities. In this study, anti-tyrosinase activity and its mechanism of active compounds (potenserin C (4), potenserin D (5), and quercetin-3-O-α-l-rhamnopyranoside-2″-gallate (14)) were explored by a combination of computational simulations and kinetic studies. Kinetic studies indicated that potenserin C (4) and quercetin-3-O-α-l-rhamnopyranoside-2″-gallate (14) inhibited tyrosinase in a competitive manner, whereas potenserin D (5) acted in a reversible noncompetitive manner. The molecular docking result indicated that the substitution of the glucose moiety with galloyl and the presence of 3', 4', 5'-OH in flavonoid aglycones played a crucial role for the tyrosinase inhibiting effect. Moreover, the presence of biflavanols increased the activity against tyrosinase because of strong hydrogen binding, π-alkyl binding, and electrostatic interaction. Thus, the presented experiments developed several new lead compounds that could act as antioxidants and α-glucosidase inhibitors. Furthermore, biflavanols and quercetin-3-O-α-l-rhamnopyranoside-2″-gallate played important roles in the anti-browning activity during food processing.

2.
J Mater Chem B ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057550

RESUMO

IR780 as a commercially available dye with near-infrared emission has been extensively applied in fluorescent probes and bioimaging. In this work, to further intensify the optical behavior, a tetrahydropyridine ring was used to replace the cyclohexene ring at the center of IR780, forming a cyanine dye Cy-NH with near-infrared emission. Photophysical properties demonstrated that Cy-NH exhibits good optical performance. In particular, Cy-NH contains two functional reaction sites (e.g. Cl and NH sites on the tetrahydropyridine ring) and can be used to construct functional cyanine dyes. Investigation on imaging showed that these cyanines can be used as near-infrared fluorescent imaging agents in living cells and in vivo.

3.
J Environ Sci (China) ; 98: 179-185, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33097150

RESUMO

Bioaugmentation of denitrifying bacteria can serve as a promising technique to improve nutrient removal during wastewater treatment. While denitrification inhibition by bacterial quorum sensing (QS) in Pseudomonas aeruginosa has been indicated, the application of bacterial QS disruption to improve nitrate removal from wastewater has not been investigated. In this study, the effect of bioaugmentation of P. aeruginosa SD-1 on nitrate removal in sequencing batch reactors that treat nitrate rich wastewater was assessed. Additionally, the potential of a quorum sensing inhibitor (QSI) to improve denitrification following bacterial bioaugmentation was evaluated. Curcumin, a natural plant extract, was used as a QSI. The chemical oxygen demand (COD) and initial nitrate concentration of the influent were 700±20 mg/L and 200±10 mg/L respectively, and their respective concentrations in the effluent were 56.9±3.2 mg/L and 9.0±3.2 mg/L. Thus, the results revealed that bioaugmentation of P. aeruginosa SD-1 resulted in an increased nitrate removal to 82%±1%. Further, nitrate was almost completely removed following the addition of the QSI, and activities of nitrate reductase and nitrite reductase increased by 88%±2% and 74%±2% respectively. The nitrogen mass balance indicated that aerobic denitrification was employed as the main pathway for nitrogen removal in the reactors. The results imply that bioaugmentation and modulation of QS in denitrifying bacteria, through the use of a QSI, can enhance nitrate removal during wastewater treatment.

4.
Rev Cardiovasc Med ; 21(3): 419-432, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070546

RESUMO

Several observational studies have shown a survival benefit for patients with atrial fibrillation (AF) who are treated with catheter ablation (CA) rather than medical management (MM). However, data from randomized controlled trials (RCTs) are uncertain. Therefore, we performed a meta-analysis of RCTs that compared the benefits of CA and MM in treatment of AF. We searched the Cochrane Library, PubMed, and EMBASE databases for RCTs that compared AF ablation with MM from the time of database establishment up to January 2020. The risk ratio (RR) with a 95% confidence interval (CI) was used as a measure treatment effect. Twenty-six RCTs that enrolled a total of 5788 patients were included in the meta-analysis. In this meta-analysis, the effect of AF ablation depended on the baseline level of left ventricular ejection fraction (LVEF) in the heart failure (HF) patients. AF ablation appears to be of benefit to patients with a lesser degree of advanced HF and better LVEF by reducing mortality. Meanwhile, this mortality advantage was manifested in long-term follow-up. CA increased the risk for hospitalization when it was used as first-line therapy and decreased the risk when used as second-line therapy. CA reduced recurrence of atrial arrhythmia for different types of AF (paroxysmal or persistent AF) and CA-related complications were non-negligible. There was no convincing evidence for a reduction in long-term stroke risk after AF ablation, and additional high quality RCTs are needed to address that issue.

5.
Plant Cell Environ ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33073369

RESUMO

Crassulacean acid metabolism (CAM) crops are important agricultural commodities in water-limited environments across the globe, yet modeling of CAM productivity lacks the sophistication of widely used C3 and C4 crop models, in part due to the complex responses of the CAM cycle to environmental conditions. This work builds on recent advances in CAM modeling to provide a framework for estimating CAM biomass yield and water use efficiency from basic principles. These advances, which integrate the CAM circadian rhythm with established models of carbon fixation, stomatal conductance, and the soil-plant-atmosphere continuum, are coupled to models of light attenuation, plant respiration, and biomass partitioning. Resulting biomass yield and transpiration for Opuntia ficus-indica and Agave tequilana are validated against field data and compared with predictions of CAM productivity obtained using the empirically-based Environmental Productivity Index (EPI). By representing regulation of the circadian state as a nonlinear oscillator, the modeling approach captures the diurnal dynamics of CAM stomatal conductance, allowing the prediction of CAM transpiration and water use efficiency for the first time at the plot scale. This approach may improve estimates of CAM productivity under light-limiting conditions when compared with previous methods. This article is protected by copyright. All rights reserved.

6.
BMC Cancer ; 20(1): 832, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873270

RESUMO

BACKGROUND: Phase 3 studies suggest that induction chemotherapy (ICT) of cisplatin and 5-fluorouracil plus docetaxel (TPF) is effective but toxic for patients with squamous-cell carcinoma of the head and neck (SCCHN). Dose-dense chemotherapy may yield favorable outcomes compared with standard-dose chemotherapy, yet the optimal induction regimen remains undefined. We assessed the efficacy and tolerability of biweekly dose-dense TPF ICT in patients with SCCHN. METHODS: In this prospective phase II study, We enrolled patients with stage III/IV (AJCC 7th edition) unresectable squamous cell carcinoma of head and neck cancer. Patients received dose-dense TPF (ddTPF) with cisplatin and docetaxel 50 mg/m2 on day 1, leucovorin 250 mg/m2 on day1, followed by 48-h continuous infusion of 2500 mg/m2 of 5-fluorouracil on day 1 and 2, every 2 weeks for 6 cycles followed by radiotherapy. The primary endpoint was the response rate (RR) after ICT. RESULTS: Fifty-eight patients were enrolled from June 2014 to September 2015. Overall RR after ICT was 89.6% [complete response (CR), 31%; partial response (PR), 58.6%]. Grade 3/4 neutropenia, mucositis, and diarrhea incidences were 25.9, 1.7, and 1.7%, respectively. 94.8% of patients completed all treatment courses of ICT without dose reduction. The 3-year overall survival (OS) was 54.3% (95%CI: 39.7 to 66.8%) and progression-free survival (PFS) was 34.3% (95%CI: 22.0 to 46.9%). Multivariate analysis showed that CR after ICT is an independent prognostic factor for OS and PFS. CONCLUSIONS: Six cycles of ddTPF is an active, well-tolerated induction regimen for patients with SCCHN. The presence of CR after ICT predicted long-term survival. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04397341 , May 21, 2020, retrospectively registered.

7.
Carbohydr Polym ; 249: 116813, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933661

RESUMO

Arabinoxylan (BIF-60) was isolated from barley water-insoluble fiber (BIF) by ethanol precipitation at 60 % (v/v). BIF-60 was composed of xylose (48.5 %) and arabinose (30.3 %). Its average molecular weight was 1360 kDa. Methylation and 1D/2D NMR analysis showed that BIF-60 possessed ß-(l→4)-xylan as backbone, comprised of un-substituted (1,4-linked ß-Xylp, 56.9 %), mono-substituted (1,2,4-linked and 1,3,4-linked ß-Xylp, 22.1 %) and di-substituted (1,2,3,4-lin4ked ß-Xylp, 18.4 %) xylose units, as well as other residues (T-Araf-(1→, T-Xylp-(1→, →5)-Araf-(1→, →2)-Araf-(1→, →3)-Araf-(1→ and →4)-Glcp-(1→). BIF-60 exhibited shear-thinning behaviour, low gel stability and weak gelling ability at high concentrations. This work provides a theoretical and experimental basis for molecular structure and properties of the alkali-extracted arabinoxylan from barley kernel, which could guide further functional research and application of barley-derived arabinoxylan.

8.
Carbohydr Polym ; 249: 116886, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933699

RESUMO

Arabinoxylan (AX), an important dietary fiber from cereal grains, is mainly metabolised in the large intestine by gut bacteria, especially bifidobacteria. This study investigated the uptake and metabolism of wheat AX by a Bifidobacterium longum strain that could grow well with AX as the sole carbon source. The bacterial growth rate showed a significant correlation to the molecular weight (MW) of AX and its acid hydrolysates. Assessment of the key AX degrading enzymes suggested that the uptake and consumption of AX involved extracellular cleavage of xylan backbone and intracellular degradation of both the backbone and the arabinose substitution. The preference for native or partially hydrolysed AX with single substitutions and a sufficiently high MW suggested the structure-dependant uptake by the bacterial cells. Genetic analysis of B. longum showed the lack of ß-xylosidase, suggesting the existence of unknown enzymes or dual/multiple-specific enzymes for hydrolysis of the non-reducing end of xylan backbone.

9.
J Exp Med ; 217(12)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-32941599

RESUMO

Variations in many genes linked to sporadic Alzheimer's disease (AD) show abundant expression in microglia, but relationships among these genes remain largely elusive. Here, we establish isogenic human ESC-derived microglia-like cell lines (hMGLs) harboring AD variants in CD33, INPP5D, SORL1, and TREM2 loci and curate a comprehensive atlas comprising ATAC-seq, ChIP-seq, RNA-seq, and proteomics datasets. AD-like expression signatures are observed in AD mutant SORL1 and TREM2 hMGLs, while integrative multi-omic analysis of combined epigenetic and expression datasets indicates up-regulation of APOE as a convergent pathogenic node. We also observe cross-regulatory relationships between SORL1 and TREM2, in which SORL1R744X hMGLs induce TREM2 expression to enhance APOE expression. AD-associated SORL1 and TREM2 mutations also impaired hMGL Aß uptake in an APOE-dependent manner in vitro and attenuated Aß uptake/clearance in mouse AD brain xenotransplants. Using this modeling and analysis platform for human microglia, we provide new insight into epistatic interactions in AD genes and demonstrate convergence of microglial AD genes at the APOE locus.

10.
Clin Neurol Neurosurg ; 197: 106169, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32905977

RESUMO

OBJECTIVES: The treatment safety and efficiency as well as the life quality of patients are still main concerns in gamma knife radiosurgery. In this study, the feasibility of applying diffusion tensor imaging (DTI) in gamma knife radiosurgery for the treatment of brain tumor in motor function areas was investigated, which aims to provide protection on the pyramidal tract and preserve the motor function in patients. PATIENTS AND METHODS: Total 74 patients with solid brain tumor were enrolled and divided into DTI group and control group. The tumor control rate was assessed at 3 months after surgery. The muscle strength of affected limb, KPS scores, ZEW scores and complications were evaluated at 3 and 6 months after gamma knife radiosurgery. RESULTS: Our results indicated that the tumor control rate, complication rate, the muscle strength of affected limb and KPS scores were not significantly different between the two groups at 3 months after surgery. At 6 months after gamma knife radiosurgery, the complication rate (0% vs 50 %, P = 0.044), KPS scores (64.9 % vs 37.8 %, P = 0.036) and ZEW scores (78.4 % vs 54.1 %, P = 0.044) of DTI group were better than the control group. Furthermore, the stability of muscle strength in patients with limb dysfunction was significantly improved in DTI group (86.4 % vs 50 %, P = 0.028). CONCLUSION: In summary, the application of DTI in gamma knife radiosurgery for the treatment of brain tumors in motor function areas can precisely define the tumor edge from pyramidal tract, which will support on designing individual treatment plan, reducing the incidence of complications, and improving long-term life quality in patients.

11.
J Zhejiang Univ Sci B ; 21(9): 740-744, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32893530

RESUMO

Acute lymphocytic leukemia (ALL) is one of the most common malignancies, especially in young people. Combination chemotherapy for ALL typically includes corticosteroids (Kantarjian et al., 2000). Hyperglycemia is a well-recognized complication of corticosteroids, and chemotherapy-induced diabetes (CID) is not uncommon (27.5%-37.0%) during the treatment of ALL (Hsu et al., 2002; Weiser et al., 2004; Alves et al., 2007). Besides the effect of corticosteroids, potential factors triggering hyperglycemia in ALL also include direct infiltration of the pancreas by leukemia cells and ß cell dysfunction induced by chemotherapeutic agents such as L-asparagine (Mohn et al., 2004).

12.
Nat Commun ; 11(1): 4781, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32963258

RESUMO

As photovoltaic power is expanding rapidly worldwide, it is imperative to assess its promise under future climate scenarios. While a great deal of research has been devoted to trends in mean solar radiation, less attention has been paid to its intermittent character, a key challenge when compounded with uncertainties related to climate variability. Using both satellite data and climate model outputs, we characterize solar radiation intermittency to assess future photovoltaic reliability. We find that the relation between the future power supply and long-term mean solar radiation trends is spatially heterogeneous, showing power reliability is more sensitive to the fluctuations of mean solar radiation in hot arid regions. Our results highlight how reliability analysis must account simultaneously for the mean and intermittency of solar inputs when assessing the impacts of climate change on photovoltaics.

13.
J Biopharm Stat ; : 1-20, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32966167

RESUMO

The rise of targeted therapy and immunotherapy has challenged the conventional more-is-better phase I trial design paradigm that focuses on finding the MTD. In this article, we propose a novel model-assisted phase I/II design, called checkerboard design, that considers both toxicity and efficacy. As an extension of the keyboard design, the checkerboard design models the joint distribution of toxicity and efficacy, and divides toxicity and efficacy domain into a series of equal-width intervals or keys. In light of interim data, the checkerboard design continuously updates the posterior distribution of toxicity and efficacy, and adaptively determine the optimal dose for treating the next cohort of patients based on the posterior probability of toxicity and efficacy keys. As a model-assisted design, one important advantage of the checkerboard design is that its decision rule can be pretabulated, greatly simplifying its implementation. We also extend the checkerboard design to handle continuous efficacy endpoint. Simulations study shows that the checkerboard design yields competitive performance comparable to existing model-based phase I/II designs, but is simpler and easier to implement in real applications.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32969687

RESUMO

How do we distribute attention to interactive biological motion (BM)? There are 2 main hypotheses: (a) distribution-by-individual hypothesis, suggesting that interactive BM will not be taken as one unit in attention distribution, and an individual BM is independently selected; and (b) distribution-by-group hypothesis, indicating that interactions between BM can integrate them as one attention unit. We examined these hypotheses using a modified cueing paradigm. Participants observed 4 upright BM interacting in pairs (paired condition) or not interacting (unpaired condition), and after a cue for 1 agent, they determined whether the probe was the letters T or L (Experiment 1, sample size = 20). The results demonstrated better performance for probes presented on BM in the same interaction compared to BM equidistant but in different interactions. These differences were not present in the unpaired condition or for inverted BM (Experiment 2, sample size = 20), excluding a possible influence of low-level features. The findings indicate that interactive BM can serve as the elementary unit of attention in accordance with the distribution-by-group hypothesis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

15.
J Neurosci ; 40(41): 7837-7854, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-32958568

RESUMO

As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.

16.
Food Chem ; 340: 127845, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32889218

RESUMO

Astringency is an important quality attribute of green tea infusion, and (-)-Epigallocatechin gallate (EGCG) is the main contributor to astringency. Turbidity was used to predict the intensity of astringency for EGCG. The interactions between the selected proteins and EGCG, and the impacts of temperature, pH, protein structure, and EGCG concentration were studied. Mucin was selected as the protein in study for the prediction of EGCG astringency intensity. A predictive model (R2 = 0.994) was developed based on the relationship between the astringency of EGCG and the turbidity of EGCG/mucin mixtures at pH 5.0 and 37 °C. The fluorescence quenching analyses showed the interactions between EGCG and the selected proteins, which induced the reversible protein molecule conformational changes. The interactions were considered as the main reason that causes the astringency of tea infusions. The results provided a biochemical approach to explore the sensory qualities of green tea.

17.
FASEB J ; 34(11): 15492-15503, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981181

RESUMO

Kv1.3 potassium channel is considered as a target for the treatment of autoimmune diseases such as multiple sclerosis (MS), since Kv1.3 blockade suppresses memory T cell activation including cytotoxic CD8+ T cells. However, the underlying signaling pathway related to autoimmune CD8+ T cell inhibition by Kv1.3 channel in neuroinflammatory diseases remains unclear. We found that ImK, a selective Kv1.3 blocker, reduced auto-reactive CD8+ T cell infiltration in the spinal cords of experimental autoimmune encephalomyelitis (EAE) rats, an animal model of MS. ImK suppressed transcriptional factor Blimp-1 expression and reduced the cytotoxicity of CD8+ T cells on neuronal cells. Furthermore, ImK upregulated co-inhibitory molecule PD-1 to inhibit B lymphocyte-induced maturation protein (Blimp-1) in an IL-2 independent way. In addition, PD-1 inhibitor impaired the suppression of ImK on CD8+ T cells and accelerated EAE progression. Our study demonstrated a novel regulatory mechanism of Kv1.3 blockade on modulating CD8+ T cell differentiation through PD-1/Blimp-1 signaling. This work expands the understanding of Kv1.3 channel for modulating neuroinflammation.

18.
Nature ; 584(7820): 210-214, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32788736

RESUMO

Of the two stable forms of graphite, hexagonal and rhombohedral, the former is more common and has been studied extensively. The latter is less stable, which has so far precluded its detailed investigation, despite many theoretical predictions about the abundance of exotic interaction-induced physics1-6. Advances in van der Waals heterostructure technology7 have now allowed us to make high-quality rhombohedral graphite films up to 50 graphene layers thick and study their transport properties. Here we show that the bulk electronic states in such rhombohedral graphite are gapped8 and, at low temperatures, electron transport is dominated by surface states. Because of their proposed topological nature, the surface states are of sufficiently high quality to observe the quantum Hall effect, whereby rhombohedral graphite exhibits phase transitions between a gapless semimetallic phase and a gapped quantum spin Hall phase with giant Berry curvature. We find that an energy gap can also be opened in the surface states by breaking their inversion symmetry by applying a perpendicular electric field. Moreover, in rhombohedral graphite thinner than four nanometres, a gap is present even without an external electric field. This spontaneous gap opening shows pronounced hysteresis and other signatures characteristic of electronic phase separation, which we attribute to emergence of strongly correlated electronic surface states.

19.
Zhongguo Fei Ai Za Zhi ; 23(8): 655-661, 2020 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-32838488

RESUMO

BACKGROUND: Anaplastic lymphoma kinase (ALK) rearrangement is a common driver gene of non-small cell lung cancer (NSCLC). Ceritinib is a second-generation ALK inhibitor, which can bring survival benefits to ALK-positive metastatic NSCLC. However, few studies focus on the safety and efficacy of ceritinib in China. Therefore, this study intends to investigate the safety and preliminary efficacy of ceritinib 450 mg with meals in Chinese patients with ALK-positive NSCLC through a real world study. METHODS: From October 2018 to December 2019, patients with ALK-positive NSCLC from 8 medical centers in Sichuan province were recruited in this study. All of these participants received ceritinib 450 mg/d with food. The basic characteristics, adverse effects (AEs) and responses were collected and analyzed in order to evaluate the safety and efficacy of ceritinib. RESULTS: A total of 109 patients were included in this study. Data cutoff was January 23, 2020. The median duration of treatment exposure was 5.87 mon (range: 0.4 mon-15.7 mon). Total AEs were reported in 98 (89.9%) of 109 patients and grade 3 or 4 AEs were reported in 22.9% of patients. Most common AEs (mainly grade 1 or 2) were diarrhea (60.6%), elevated alanine aminotransferase (ALT)(38.5%) and aspartate aminotransferase (AST)(37.6%). As of data cutoff, 45 patients discontinued ceritinib. The overall response rate (ORR) was 37.6% (95%CI: 28.5%-47.4%) and disease control rate (DCR) was 86.2% (95%CI: 78.3%-92.1%). CONCLUSIONS: The treatment of ceritinib 450 mg with food for Chinese ALK-positive NSCLC patients had a good safety profile and favorable DCR in real-world setting. However, this conclusion needs to be further verified by large sample, prospective trials.

20.
J Clin Invest ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32841213

RESUMO

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we showed that lesions of the dmPFC induced an algesic and anxious state. By using multiple tracing methods including rabies-based transsynaptic tracing method, an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG) was outlined. Specific activation of the dmPFC-vlPAG neural pathway by an optogenetic manipulation, produced analgesic and anxiolytic effects in a chronic pain mice model. Inhibitory neurons in the dmPFC were specifically activated by using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of GABAAR or mGluR1 were applied to the dmPFC, which produced analgesic and anxiolytic effects. In summary, the present results suggest that the dmPFC-vlPAG neural pathway might participate in the maintenance of pain thresholds and anxiolytic behaviors under normal conditions, while silencing or suppressing the dmPFC-vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

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