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A general strategy for qualitative screening and quantitative analysis of 403 pesticides in various fruits and vegetables was developed using ultrahigh-performance liquid chromatography (UHPLC) in conjunction with a Thermo Q Exactive Focus high-resolution mass spectrometer, relying on an executable compound database comprised of the exacted mass of precursor ions, retention times, and fragment ions. Taking advantage of the powerful separation capacity of UHPLC, an Orbitrap analyzer with high sensitivity in full scan mode and elevated mass resolution of product ions in the MS/MS mode, eight pairs of isomers and fifty-seven groups of isobaric compounds were selectively identified. The method was then systematically assessed and validated for eight fruits and vegetables, in terms of screening detection limit (SDL), matrix effects, recovery, and precision over 400 pesticides. The results showed that the SDLs of 68.0-84.4% for the pesticides were less than or equal to 10 µg kg-1 in the representative matrices, recoveries in the range of 60-120% accounting for 48.6-84.4% of all the targets at three lower fortified levels of 5, 20, and 50 µg kg-1 with a precision of less than 20% while the range of overall average recoveries for the majority of the pesticides were from 82.4% to 105.1% in the as-selected matrices with RSDs between 3.9% and 7.7%. Using this method, screening data from a survey of pesticide residues in 68 practical samples across 32 different matrix types provides scientific data for the inspection and supervision of pesticide residue safety of fruits and vegetables.
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The comorbidity of anxiety and depression frequently occurs in patients with neuropathic pain. The ventrolateral orbital cortex (VLO) plays a critical role in mediating neuropathic pain and anxiodepression in rodents. Previous studies suggested that 5-HT6 receptors in the VLO are involved in neuropathic pain. Strong evidence supports a close link between 5-HT6 receptors and affective disorders such as depression and anxiety disorders. However, it remains unclear whether the 5-HT6 receptors in the VLO are involved in neuropathic pain-induced anxiodepression. Using a rat neuropathic pain model of spared nerve injury (SNI), we demonstrated that rats exhibited significant anxiodepression-like behaviors and the expression of VLO 5-HT6 receptors obviously decreased four weeks after SNI surgery. Microinjection of the 5-HT6 receptor agonist EMD-386088 into the VLO or overexpression of VLO 5-HT6 receptors alleviated anxiodepression-like behaviors. These effects were blocked by pre-microinjection of a selective 5-HT6 receptor antagonist (SB-258585) or inhibitors of AC (SQ-22536), PKA (H89), and MEK1/2 (U0126) respectively. Meanwhile, the expression of p-ERK, p-CREB, and BDNF in the VLO decreased four weeks after SNI surgery. Furthermore, administration of EMD-386088 upregulated the expression of BDNF, p-ERK, and p-CREB in the VLO of SNI rats, which were reversed by pre-injection of SB-258585. These findings suggest that activating 5-HT6 receptors in the VLO has anti-anxiodepressive effects in rats with neuropathic pain via activating AC-cAMP-PKA-MERK-CREB-BDNF signaling pathway. Accordingly, 5-HT6 receptor in the VLO could be a potential target for the treatment of the comorbidity of neuropathic pain and anxiodepression.
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Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited. Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant. Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled. Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed. Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported. Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.
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Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Pemetrexede , Intervalo Livre de Progressão , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Método Duplo-Cego , Receptores ErbB/genética , Análise de Intenção de Tratamento , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mutação , Pemetrexede/administração & dosagem , Pemetrexede/efeitos adversos , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversosRESUMO
Vertebral artery dissection is a rare pathology that can cause ischemic stroke in young people. Cervical massage, especially improper pulling manipulation, is a cause of vertebral artery dissection. We present a case of 32-year-old woman who developed acute multiple posterior circulation ischemic cerebral infarctions as a result of left vertebral artery V4 segment dissection after receiving neck massage. She underwent emergency vertebral artery stent implantation at the site of the dissection. Symptoms were relieved the day after treatment. The patient recovered without adverse complications or endovascular restenosis in the following year.
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Infarto Cerebral , Massagem , Stents , Dissecação da Artéria Vertebral , Humanos , Feminino , Dissecação da Artéria Vertebral/diagnóstico por imagem , Dissecação da Artéria Vertebral/etiologia , Dissecação da Artéria Vertebral/cirurgia , Adulto , Stents/efeitos adversos , Massagem/efeitos adversos , Infarto Cerebral/etiologia , Infarto Cerebral/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/cirurgiaRESUMO
Objective: According to the World Alzheimer's Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. Systematic review registration: PROSPERO, identifier: CRD42023483561.
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BACKGROUND: Combination of chidamide and anti-PD-L1 inhibitor produce synergistic anti-tumor effect in advanced NSCLC patients resistant to anti-PD-1 treatment. However, the effect of chidamide plus envafolimab has not been reported. AIMS: This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti-PD-1 treatment. MATERIALS AND METHODS: Eligible advanced NSCLC patients after resistant to anti-PD-1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression-free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD-L1, and blood TMB (bTMB) was also analyzed. RESULTS: After a median follow-up of 8.1 (range: 7.6-9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9-5.5) months. Biomarker analysis revealed that patients with high-level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD-L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low-level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable. DISCUSSION: High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD-L1 and low-level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion. CONCLUSION: Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.
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Aminopiridinas , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos , Benzamidas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Antineoplásicos Imunológicos/uso terapêutico , BiomarcadoresRESUMO
The vortex flowmeter occupies a vital position in flow measurement with its unique advantages. It is essentially a fluid vibration instrument, and its measurement process is susceptible to interference, which seriously affects measurement accuracy. In particular, at low flow rates, it is an urgent problem to extract vortex signals from the complex noise. Among many signal processing methods, Empirical Mode Decomposition (EMD) is a time-frequency analysis method suitable for nonlinear, non-stationary signals. EMD can adaptively decompose noisy signals into noise and useful signal components arranged from high frequency to low frequency. For the above problems, an innovative, improved EMD method is proposed in this paper. The digital filter is designed according to the amplitude-frequency characteristic of vortex signals. After filtering, the vortex signal is adjusted to a fixed value, and high-frequency noise is filtered. According to the consistency of the filtered signal's amplitude, we design a decomposition stop criterion for EMD to process the output signal of the vortex sensor. This method not only maintains the characteristic of adaptive decomposition in EMD but also completes the automatic extraction of the vortex signal under complex noise. It provides a new comprehensive method for realizing high-precision and anti-interference vortex flowmeters.
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Radiation therapy is a common treatment modality for patients with malignant tumors of the head and neck, chest and axilla. However, radiotherapy inevitably causes damage to normal tissues at the irradiated site, among which damage to the brachial plexus nerve(BP) is a serious adverse effect in patients receiving radiation therapy in the scapular or axillary regions, with clinical manifestations including abnormal sensation, neuropathic pain, and dyskinesia, etc. These adverse effects seriously reduce the living quality of patients and pose obstacles to their prognosis. Therefore, it is important to elucidate the mechanism of radiation induced brachial plexus injury (RIBP) which remains unclear. Current studies have shown that the pathways of radiation-induced BP injury can be divided into two categories: direct injury and indirect injury, and the indirect injury is closely related to the inflammatory response, microvascular damage, cytokine production and other factors causing radiation-induced fibrosis. In this review, we summarize the underlying mechanisms of RIBP occurrence and possible effective methods to prevent and treat RIBP.
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Neuropatias do Plexo Braquial , Plexo Braquial , Neuralgia , Lesões por Radiação , Humanos , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/epidemiologia , Plexo Braquial/efeitos da radiação , Prognóstico , Neuralgia/complicações , Lesões por Radiação/terapia , Lesões por Radiação/complicaçõesRESUMO
The occurrence and development of tumors are associated with the cell energy metabolism. Inhibiting energy metabolism of lung cancer cells is an important strategy to overcome drug resistance. Based on the cellular energy metabolism pathway, this study observed the effect of combination of shikonin(SKN) and gefitinib(GFB) on the drug resistance in non-small cell lung cancer and explored the underlying mechanism. The human non-small cell lung cancer line HCC827/GR resistant to gefitinib was used as the cell model in vitro. The CCK-8 assay and flow cytometry were employed to investigate the cell viability and apoptosis, respectively. The high performance liquid chromatography was employed to measure the intracellular accumulation of GFB. A Seahorse XFe96 Analyzer was used to detect the changes of cellular energy metabolism. Western blot was employed to determine the expression of the proteins involved in the drug resistance. The tumor-bearing nude mouse model was used to verify the efficacy of SKN+GFB in overcoming drug resistance in vivo. The results showed that SKN+GFB significantly reduced the IC_(50) of GFB on HCC827/GR cells, with the combination index of 0.628, indicating that the combination of the two drugs had a synergistic effect and promoted cell apoptosis. SKN increased the intracellular accumulation of GFB. SKN+GFB lowered the oxygen consumption rate(OCR) and glycolytic proton efflux rate(GlycoPER) in cell energy metabolism, and down-regulated the overexpression of PKM2, p-EGFR, P-gp, and HIF-1α in drug resistance. The results of reversing drug resistance test in vivo showed that GFB or SKN alone had no significant antitumor effect, while the combination at different doses induced the apoptosis of the tumor tissue and inhibited the expression of PKM2 and P-gp, demonstrating a significant antitumor effect. Moreover, the tumor inhibition rate in the high-dose combination group reached 64.01%. In summary, SKN+GFB may interfere with the energy metabolism to limit the function of HCC827/GR cells, thus reversing the GFB resistance in non-small cell lung cancer.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Naftoquinonas , Animais , Camundongos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Quinazolinas/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proliferação de Células , Linhagem Celular Tumoral , ApoptoseRESUMO
Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones (p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH4+-N were positively correlated with prokaryotic diversity (p < 0.05). Also, organic matter and NO3--N were positively correlated to prokaryotic abundance (p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making.
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Background: Immunotherapy has shown intracranial efficacy in non-small cell lung cancer (NSCLC) patients with brain metastases. However, predictive biomarkers for intracranial response to immunotherapy are lacking. This post-hoc analysis aimed to explore the potential of immunological cytokines in cerebrospinal fluid (CSF) to predict intracranial tumor response to immunotherapy in patients with brain metastases. Methods: Treatment-naive NSCLC patients with brain metastases who received camrelizumab plus chemotherapy were enrolled. Paired plasma and CSF samples were prospectively collected at baseline and the first treatment assessment. All samples were analyzed for 92 immuno-oncology cytokines using Olink's panels. Results: A total of 28 patients were included in this analysis. At baseline, most immunological cytokines were significantly lower in CSF than in plasma, whereas a subset comprising CD83, PTN, TNFRSF21, TWEAK, ICOSLG, DCN, IL-8, and MCP-1, was increased in CSF. Baseline CSF levels of LAMP3 were significantly higher in patients with intracranial tumor response, while the levels of CXCL10, IL-12, CXCL11, IL-18, TIE2, HGF, and PDCD1 were significantly lower. Furthermore, the CXCL10, CXCL11, TIE2, PDCD1, IL-18, HGF, and LAMP3 in CSF were also significantly associated with intracranial progression-free survival for immunotherapy. The identified cytokines in CSF were decreased at the first treatment evaluation in patients with intracranial tumor response. The logistic CSF immuno-cytokine model yielded an AUC of 0.91, as compared to PD-L1 expression (AUC of 0.72). Conclusions: Immunological cytokines in CSF could predict intracranial tumor response to immunotherapy in NSCLC patients with brain metastases, and the findings warrant validation in a larger prospective cohort study. Trial registration: ClinicalTrials.gov identifier: NCT04211090.
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Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Interleucina-18/uso terapêutico , Citocinas , Estudos Prospectivos , Imunoterapia , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/secundárioRESUMO
BACKGROUND: Interleukin-34 (IL-34) is a hematopoietic cytokine and a ligand of colony-stimulating factor 1 receptor (CSF-1R). Numerous studies have demonstrated that IL-34 is involved in several inflammatory diseases. Nevertheless, the role of IL-34 is obscure in community-acquired pneumonia (CAP) patients. This research aimed to assess the associations of serum IL-34 with severity and prognosis in CAP patients through a longitudinal study. METHODS: CAP patients and healthy volunteers were recruited. Peripheral blood samples were collected. Serum IL-34 and inflammatory cytokines were tested by enzyme linked immunosorbent assay (ELISA). Demographic characteristics and clinical information were acquired through electronic medical records. RESULTS: Serum IL-34 was elevated in CAP patients compared with healthy volunteers. The content of serum IL-34 was gradually upregulated with increased CAP severity scores. Mixed logistic and linear regression models suggested that serum IL-34 elevation was associated with increased PSI and SMART-COP scores. Correlative analysis found that serum IL-34 was positively correlated with inflammatory cytokines among CAP patients. A longitudinal study indicated that higher serum IL-34 at admission elevated the risks of mechanical ventilation and death during hospitalization. Serum IL-34 had a higher predictive capacity for death than CAP severity scores. CONCLUSION: There are prominently positive dose-response associations between serum IL-34 at admission with the severity and poor prognosis, suggesting that IL-34 is implicated in the occurrence and development of CAP. Serum IL-34 may serve as a biomarker to forecast disease progression and poor prognosis in CAP patients.
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Infecções Comunitárias Adquiridas , Pneumonia , Humanos , Biomarcadores , Citocinas , Interleucinas , Estudos Longitudinais , Pneumonia/diagnóstico , Prognóstico , Índice de Gravidade de DoençaRESUMO
The ventrolateral orbital cortex (VLO) is identified as an integral component of the endogenous analgesic system comprising a spinal cord - thalamic nucleus submedius - VLO - periaqueductal gray (PAG) - spinal cord loop. The present study investigates the effects of 5-HT5A receptor activation in the VLO on allodynia induced by spared nerve injury and formalin-evoked flinching behavior and spinal c-Fos expression in male SD rats, and further examines whether GABAergic modulation is involved in the effects evoked by VLO 5-HT5A receptor activation. We found an upregulation of 5-HT5A receptor expression in the VLO during neuropathic and inflammatory pain states. Microinjection of the non-selective 5-HT5A receptor agonist 5-CT into the VLO dose dependently alleviated allodynia, and flinching behavior and spinal c-Fos expression, which were blocked by the selective 5-HT5A receptor antagonist SB-699551. Moreover, application of the GABAA receptor antagonist bicuculline in the VLO augmented the analgesic effects induced by 5-CT in neuropathic and inflammatory pain states, whereas the GABAA receptor agonist muscimol attenuated these analgesic effects. Additionally, the 5-HT5A receptors were found to be colocalized with GABAergic neurons in the VLO. These results provide new evidence for the involvement of central 5-HT5A receptors in the VLO in modulation of neuropathic and inflammatory pain and support the hypothesis that activation of 5-HT5A receptors may inhibit the inhibitory effect of GABAergic interneurons on output neurons projecting to the PAG (GABAergic disinhibitory mechanisms), consequently activating the brainstem descending inhibitory system that depresses nociceptive transmission at the spinal cord level.
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Hiperalgesia , Doenças do Sistema Nervoso Periférico , Ratos , Masculino , Animais , Hiperalgesia/metabolismo , Serotonina/metabolismo , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismo , Medição da Dor , Dor/tratamento farmacológico , Dor/metabolismo , Analgésicos/farmacologia , Doenças do Sistema Nervoso Periférico/metabolismo , Córtex Pré-FrontalRESUMO
Objective: This study aimed to explore the application of quantitative parameters of computed tomography (CT) texture combined with the detection of serum manganese superoxide dismutase (MnSOD) in the diagnosis of adrenocortical adenoma (ACA). Methods: The study selected 147 patients with suspected ACA received in Yantaishan Hospital from November 2019 to November 2021 as the research objects. These patients were divided into the study group (SG, n = 71, ACA) and the reference group (RG, n = 76, non-ACA) according to the postoperative pathological results to implement CT examination and subsequent serological examination. The quantitative parameters of CT texture and serum MnSOD levels were compared between the two groups, and the receiver operating characteristic curve was used to evaluate the value of single and combined diagnosis of quantitative parameters of CT texture and detection of serum MnSOD. Results: Compared with the RG, the SG had notably lower CT values in the plain scan, venous and delayed phase (p < 0.001) and had overtly higher entropy (p < 0.001). However, no remarkable difference was observed in terms of kurtosis and skewness between the two groups (p > 0.05). The serum MnSOD levels of the SG and RG were 27.26 (24.56, 30.97) U/mL and 43.45 (41.02, 45.08) U/mL, respectively, and the MnSOD level of the SG was significantly lower than that of the RG (p < 0.001). The combined diagnosis of CT entropy parameter and MnSOD detection had higher area under the curve (0.91), sensitivity (88.70%) and specificity (82.90%) than those of each single diagnosis (p < 0.001) and had higher diagnostic efficiency. Conclusions: The entropy in the quantitative parameters of CT texture and detection of MnSOD can be used for the diagnosis of ACA, and their combined diagnosis effect is good, thus providing a new direction for the clinical identification of the disease (AU)
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Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias do Córtex Suprarrenal/diagnóstico , Adenoma/diagnóstico , Superóxido Dismutase , Manganês , Tomografia Computadorizada por Raios X , Sensibilidade e Especificidade , Curva ROCRESUMO
ABSTRACT A method for analysis of 101 pesticide residues in tea leaves was developed and validated for the first time. Pure acetonitrile was used as extraction solvent rather than acetonitrile after matrix hydration based on the amount of co-extracts and recoveries performance. During clean-up procedure, primary-secondary amine/graphitized carbon black (500 mg) was selected, which exhibited outstanding properties in clean-up capabilities and recoveries of pesticides comparing to primary-secondary amine/graphitized carbon black (250 mg), NH2-Carbon and TPT absorbents. The method was validated employing gas chromatography coupled to tandem mass spectrometry at the spiked concentration levels of 0.050 and 0.100 mg kg−1. For most of the targeted pesticides, the percent recoveries range from 70 to 120%, with relative standard deviations <20%. The linear correlation coefficients (r 2) were higher than 0.99 at concentration levels of 0.025–0.250 mg kg−1. Limits of quantification ranged from 1.1 to 25.3 µg kg−1 for all pesticides. The developed method was successfully applied to the determination of pesticides in tea leaf samples.