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1.
Food Chem ; 449: 139198, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38574526

RESUMO

The preparation of high specificity and affinity antibodies is challenging due to limited information on characteristic groups of haptens in traditional design strategy. In this study, we first predicted characteristic groups of flurogestone acetate (FGA) using quantitative analysis of molecular surface combined with atomic charge distribution. Subsequently, FGA haptens were rationally designed to expose these identified characteristic groups fully. As a result, seven monoclonal antibodies were obtained with satisfactory performance, exhibiting IC50 values from 0.17 to 0.45 µg/L and negligible cross-reactivities below 1% to other 18 hormones. The antibody recognition mechanism further confirmed hydrogen bonds and hydrophobic interactions involving predicted FGA characteristic groups and specific amino acids in the antibodies contributed to their high specificity and affinity. Finally, one selective and sensitive ic-ELISA was developed for FGA determination with a detection limit as low as 0.12 µg/L, providing an efficient tool for timely monitoring of FGA in goat milk samples.

2.
J Cancer Res Clin Oncol ; 150(3): 109, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427078

RESUMO

BACKGROUND: Neuroblastoma (NB), a prevalent pediatric solid tumor, presents formidable challenges due to its high malignancy and intricate pathogenesis. The role of disulfidptosis, a novel form of programmed cell death, remains poorly understood in the context of NB. METHODS: Gaussian mixture model (GMM)-identified disulfidptosis-related molecular subtypes in NB, differential gene analysis, survival analysis, and gene set variation analysis were conducted subsequently. Weighted gene co-expression network analysis (WGCNA) selected modular genes most relevant to the disulfidptosis core pathways. Integration of machine learning approaches revealed the combination of the Least absolute shrinkage and selection operator (LASSO) and Random Survival Forest (RSF) provided optimal dimensionality reduction of the modular genes. The resulting model was validated, and a nomogram assessed disulfidptosis characteristics in NB. Core genes were filtered and subjected to tumor phenotype and disulfidptosis-related experiments. RESULTS: GMM clustering revealed three distinct subtypes with diverse prognoses, showing significant variations in glucose metabolism, cytoskeletal structure, and tumor-related pathways. WGCNA highlighted the red module of genes highly correlated with disulfide isomerase activity, cytoskeleton formation, and glucose metabolism. The LASSO and RSF combination yielded the most accurate and stable prognostic model, with a significantly worse prognosis for high-scoring patients. Cytological experiments targeting core genes (CYFIP1, EMILIN1) revealed decreased cell proliferation, migration, invasion abilities, and evident cytoskeletal deformation upon core gene knockdown. CONCLUSIONS: This study showcases the utility of disulfidptosis-related gene scores for predicting prognosis and molecular subtypes of NB. The identified core genes, CYFIP1 and EMILIN1, hold promise as potential therapeutic targets and diagnostic markers for NB.


Assuntos
Neuroblastoma , Criança , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Apoptose , Proliferação de Células/genética , Glucose , Aprendizado de Máquina , Neuroblastoma/genética , Prognóstico
3.
Pediatr Surg Int ; 40(1): 63, 2024 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-38431920

RESUMO

PURPOSE: Necrotizing enterocolitis (NEC) is a significant contributor to neonatal mortality. This study aimed to investigate the role of high levels of miR-375-3p in breast milk in the development of NEC and elucidate its mechanism. METHODS: Differential expression of miR-375-3p in the intestines of breast-fed and formula-fed mice was confirmed using real-time polymerase chain reaction (RT-PCR). NEC mice models were established, and intestinal injury was assessed using HE staining. RT-PCR and Western blot were conducted to examine the expression of miR-375-3p, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein ß (YWHAB), as well as the inflammatory in IEC-6 cells, and intestinal tissues obtained from NEC mice and patients. Flow cytometry and cell counting kit-8 (CCK-8) were employed to elucidate the impact of miR-375-3p and YWHAB on cell apoptosis and proliferation. RESULTS: Breastfeeding increases miR-375-3p expression in the intestines. The expression of miR-375-3p in NEC intestinal tissues exhibited a significant decrease compared to the healthy group. Additionally, the expression of interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was higher in the NEC group compared to the control group. Down-regulation of miR-375-3p inhibited IEC-6 cell proliferation, increased apoptosis, and elevated secretion of inflammatory factors. Bioinformatics revealed that YWHAB may be a target of miR-375-3p. RT-PCR and Western blot indicated a down-regulation of YWHAB expression in intestines of NEC patients and mice. Furthermore, YWHAB was found to be positively connected with miR-375-3p. Knockdown miR-375-3p down-regulated YWHAB expression in cells. Inhibition of YWHAB exhibited similar effects to miR-375-3p in IEC-6 cells. YWHAB plasmid partially reverse cellular functional impairment induced by miR-375-3p knockdown. CONCLUSIONS: Breastfeeding elevated miR-375-3p expression in intestines in neonatal mice. MiR-375-3p leads to a decrease in apoptosis of intestinal epithelial cells, an increase in cell proliferation, and a concomitant reduction in the expression of inflammatory factors partly through targeting YWHAB.


Assuntos
Proteínas 14-3-3 , Enterocolite Necrosante , Doenças do Recém-Nascido , MicroRNAs , Animais , Feminino , Humanos , Recém-Nascido , Camundongos , Proteínas 14-3-3/metabolismo , Traumatismos Abdominais , Enterocolite Necrosante/metabolismo , Doenças Fetais , MicroRNAs/genética
4.
Front Plant Sci ; 15: 1341826, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332768

RESUMO

Introduction: Alfalfa (Medicago sativa L.) is the favored premium feed ingredient in animal husbandry production which is in serious jeopardy due to soil moisture shortages. It is largely unknown how different root types of alfalfa respond to arid-induced stress in terms of metabolites and phytohormones. Methods: Therefore, rhizomatous rooted M. sativa 'Qingshui' (or QS), tap-rooted M. sativa 'Longdong' (or LD), and creeping rooted M. varia 'Gannong No. 4' (or GN) were investigated to identify metabolites and phytohormones responses to drought conditions. Results: We found 164, 270, and 68 significantly upregulated differential metabolites were categorized into 35, 38, and 34 metabolic pathways in QS, LD, and GN within aridity stress, respectively. Amino acids, organic acids, sugars, and alkaloids were the four categories of primary differential metabolites detected, which include 6-gingerol, salicylic acid (SA), indole-3-acetic acid (IAA), gibberellin A4 (GA4), abscisic acid (ABA), trans-cinnamic acid, sucrose, L-phenylalanine, L-tyrosine, succinic acid, and nicotinic acid and so on, turns out these metabolites are essential for the resistance of three root-type alfalfa to aridity coercing. Discussion: The plant hormone signal transduction (PST) pathway was dramatically enriched after drought stress. IAA and ABA were significantly accumulated in the metabolites, indicating that they play vital roles in the response of three root types of alfalfa to water stress, and QS and LD exhibit stronger tolerance than GN under drought stress.

5.
Biochem Biophys Rep ; 37: 101638, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38288280

RESUMO

Objectives: Rebleeding after hypertensive intracerebral hemorrhage is a common and serious postoperative complication in neurosurgery, with high mortality and mental disability rates. The aim of this study was to establish a nomogram to analyze the role of thromboelastography in predicting rebleeding after hypertensive intracerebral hemorrhage. Basic methods: We selected 375 patients with hypertensive intracerebral hemorrhage who underwent surgical treatment in Yuebei People's Hospital of Shaoguan City, Guangdong Province from May 2018 to August 2022, and retrospectively analyzed the relevant data of hypertensive intracerebral hemorrhage patients (including general data and clinical thromboelastography data), and analyzed the factors and thromboelastography parameters that affect rebleeding after surgery (45 cases, defined as re-examination of head CT within 72 h after surgery showed that the hematoma in the surgical area exceeded 20 ml). Main results: Time from symptom onset to surgery, taking antiplatelet drugs, taking anticoagulant drugs, diabetes mellitus, difficulty in hemostasis during surgery, R value and EPL value in thromboelastography were risk factors for rebleeding after hypertensive intracerebral hemorrhage (P < 0.05). Logistic regression was used to determine the independent risk factors, and based on these risk factors, a nomogram was established and internally validated using a bootstrap method. ROC curve analysis showed that the nomogram model had high diagnostic value for rebleeding after hypertensive intracerebral hemorrhage, with AUC of 0.7314. The calibration curve of the nomogram showed good consistency between the predicted probabilities and the observed values. The decision curve analysis and clinical impact curve also revealed the potential clinical usefulness of the nomogram. Conclusions: The nomogram based on clinical characteristics and thromboelastography markers may be useful for predicting rebleeding after hypertensive intracerebral hemorrhage.

6.
Acta Pharmaceutica Sinica ; (12): 17-24, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005449

RESUMO

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

7.
Pediatr Surg Int ; 40(1): 25, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38127107

RESUMO

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital disorder resulting from abnormal development of the enteric nervous system (ENS). Given the complexity of its pathogenesis, it is important to investigate the role of epigenetic inheritance in its development. As Circ-MTCL1 is abundant in brain tissue and colon tissue, whether it has a significant part in the development of ENS is worth exploring. This study clarifies its role in HSCR and identifies the specific molecular mechanisms involved. METHODS: Diseased and dilated segment colon tissues diagnosed as HSCR were collected for the assessment of gene expression levels using RT-PCR. EdU and CCK-8 assays were adopted to evaluate cell proliferation, and Transwell assay was adopted to assess cell migration. The interaction between Circ-MTCL1, miR-145-5p and SMAD3 was confirmed by dual luciferase reporter gene analysis, RT-PCR and Western blotting. RESULTS: Circ-MTCL1 was down-regulated in the aganglionic colon tissues. The decreased expression of Circ-MTCL1 associated with a reduction in cell migration and proliferation. Bioinformatics analysis and cellular experiments confirmed its role might have been associated with the inhibition of miR-145-5p. MiR-145-5p was up-regulated in HSCR diseased segment colon tissues, exhibiting a negative correlation with Circ-MTCL1. Overexpression of miR-145-5p reversed the inhibition of cell migration and proliferation associated with Circ-MTCL1 down-regulation. The expression of SMAD3 was inhibited by miR-145-5p. The overexpression of SMAD3 eliminated the miR-145-5p-associated inhibition of cell migration and proliferation. Overexpression of miR-145-5p reversed the inhibitory effects of Circ-MTCL1 down-regulation-associated inhibition of cell migration and proliferation, while suppressing SMAD3 expression. Conversely, overexpression of SMAD3 counteracted the miR-145-5p-associated inhibition of cell migration and proliferation. CONCLUSIONS: Circ-MTCL1 may function as a miR-145-5p sponge, regulating the expression of SMAD3 and influencing cell migration and proliferation, thus participating in the development of HSCR.


Assuntos
Doença de Hirschsprung , MicroRNAs , Humanos , Doença de Hirschsprung/genética , RNA Circular/genética , Proliferação de Células/genética , Movimento Celular/genética , MicroRNAs/genética , Proteína Smad3/genética , Proteínas Associadas aos Microtúbulos
8.
Eur Arch Otorhinolaryngol ; 280(9): 4177-4183, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37395760

RESUMO

BACKGROUND: To investigate the impact of preoperative embolization (p-TAE) on CBT surgical resection and explore the optimal tumor volume for p-TAE of CBT resection. METHODS: This retrospective study reviewed 139 surgically excised CBTs. According to Shamblin classification, tumor volumes, and whether to carry out the p-TAE, the patients were classified into different groups. The demographic, clinical features, and the intraoperative and post-operative information about the patients were retrieved and analyzed from the patient records. RESULTS: A total of 139 CBTs was excised in 130 patients. According to the results of subgroup analysis, there were no significant differences in surgical time, blood loss, adverse events (AEs), and the revascularization when compared with non-embolization group (NEG) for type I, II, III, respectively (all p > 0.05) except for the surgical time in type I (p < 0.05). Then the X-tile program was employed and determine the cutoff point (tumor volume = 6670 mm3) for tumor volumes and blood loss. The average tumor volume was (29,782.37 vs. 31,345.10 mm3, p = 0.65) for embolization group (EG) and NEG. The mean surgical time (208.86 vs. 264.67 min, p > 0.05) and intraoperative blood loss (252.78 vs. 430.00 mL, p < 0.05) were less, and the incidence of revascularization required (35.56 vs. 52.38%, p > 0.05) and total complications (27.78 vs. 57.14%, p < 0.05) were lower in EG when compared with NEG (tumor volume ≥ 6670 mm3). However, the results were not statistically significant when the tumor size was less than 6670 mm3. No surgery-related mortality was observed during the follow-up. CONCLUSIONS: Preoperative selective embolization of CBT is an effective and safe adjunct for surgical resection, especially for Shamblin class II and III tumors (≥ 6670 mm3).


Assuntos
Tumor do Corpo Carotídeo , Embolização Terapêutica , Humanos , Tumor do Corpo Carotídeo/diagnóstico por imagem , Tumor do Corpo Carotídeo/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Embolização Terapêutica/métodos , Procedimentos Cirúrgicos Vasculares/efeitos adversos
9.
Phytomedicine ; 117: 154917, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37301184

RESUMO

OBJECTIVE: Multiple sclerosis (MS) is an immune disease in the central nervous system (CNS) associated with Th17 cells. Moreover, STAT3 initiates Th17 cell differentiation and IL-17A expression through facilitating RORγt in MS. Here, we reported that magnolol, isolated from Magnolia officinalis Rehd. Et Wils, was regarded as a candidate for MS treatment verified by both in vitro and in vivo studies. METHODS: In vivo, experimental autoimmune encephalomyelitis (EAE) model in mice was employed to evaluate the alleviation of magnolol on myeloencephalitis. In vitro, FACS assay was employed to evaluate the effect of magnolol on Th17 and Treg cell differentiation and IL-17A expression; network pharmacology-based study was applied to probe the involved mechanisms; western blotting, immunocytochemistry, and luciferase reporter assay was used to further confirm the regulation of magnolol on JAK/STATs signaling pathway; surface plasmon resonance (SPR) assay and molecular docking were applied to manifest affinity with STAT3 and binding sites; overexpression of STAT3 was employed to verify whether magnolol attenuates IL-17A through STAT3 signaling pathway. RESULTS: In vivo, magnolol alleviated loss of body weight and severity of EAE mice; magnolol improved lesions in spinal cords and attenuated CD45 infiltration, and serum cytokines levels; correspondingly, magnolol focused on inhibiting Th17 differentiation and IL-17A expression in splenocyte of EAE mice; moreover, magnolol selectively inhibited p-STAT3(Y705) and p-STAT4(Y693) of both CD4+ and CD8+ T cells in splenocyte of EAE mice. In vitro, magnolol selectively inhibited Th17 differentiation and IL-17A expression without impact on Treg cells; network pharmacology-based study revealed that magnolol perhaps diminished Th17 cell differentiation through regulating STAT family members; western blotting further confirmed that magnolol inhibited p-JAK2(Y1007) and selectively antagonized p-STAT3(Y705) and slightly decreased p-STAT4(Y693); magnolol antagonized both STAT3 nucleus location and transcription activity; magnolol had a high affinity with STAT3 and the specific binding site perhaps to be at SH2 domain; overexpression of STAT3 resulted in failed inhibition of magnolol on IL-17A. CONCLUSION: Magnolol selectively inhibited Th17 differentiation and cytokine expression through selectively blocking of STAT3 resulting in decreased the ratio of Th17/Treg cells for treating MS, suggesting that the potential of magnolol for treating MS as novel STAT3 inhibitor.


Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Camundongos , Animais , Esclerose Múltipla/tratamento farmacológico , Células Th17 , Interleucina-17/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Simulação de Acoplamento Molecular , Encefalomielite Autoimune Experimental/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Células Th1
10.
Gen Hosp Psychiatry ; 83: 86-92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37148598

RESUMO

OBJECTIVE: Multiple studies have indicated that electroconvulsive therapy (ECT) could increase brain-derived neurotrophic factor (BDNF) concentrations in patients with different mental disorders. The aim of this synthesis was to evaluate post-ECT BDNF concentrations in patients with various mental disorders. METHODS: The Embase, PubMed and Web of Science databases were systematically searched for studies in English comparing BDNF concentrations before and after ECT through 11/2022. We extracted the pertinent information from the included studies and evaluated their quality. The standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated to quantify BDNF concentration differences. RESULTS: In total, 35 studies assessed BDNF concentrations in 868 and 859 patients pre and post-ECT treatment, respectively. Post-ECT-treatment BDNF concentrations were significantly higher than the pretreatment concentrations (Hedges'g = -0.50, 95% CI (-0.70, -0.30), heterogeneity I2 = 74%, p < 0.001). The analysis that combined both ECT responders and non-responders demonstrated a marked increase in total BDNF levels subsequent to ECT treatment (Hedges'g = -0.27, 95% CI (-0.42, -0.11), heterogeneity I2 = 40%, p = 0.0007). CONCLUSION: Irrespective of the effectiveness of ECT, Our study shows that peripheral BDNF concentrations increase significantly after the entire course of ECT, which may enhance our comprehension of the interplay between ECT treatment and BDNF levels. However, BDNF concentrations were not associated with the effectiveness of ECT, and abnormal concentrations of BDNF may be linked to the pathophysiological process of mental illness, necessitating more future research.


Assuntos
Eletroconvulsoterapia , Transtornos Mentais , Humanos , Fator Neurotrófico Derivado do Encéfalo , Transtornos Mentais/terapia
11.
J Hazard Mater ; 445: 130615, 2023 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-37056019

RESUMO

Antibody is the key biomolecule that governing the sensitivity and specificity of an immunoassay for chemical compound, also named hapten molecule. Obviously, predication of hapten effectiveness before chemical synthesis is beneficial to boost success, save cost and improve controllability. Here, we proposed and evaluated an epitopephore based rational hapten design (ERHD) to assist antibody production to chemical compound, combining theoretical evidence and then experimental validation by using dinitrocarbanilide (DNC) as a model analyte. Briefly, epitopephores of DNC were firstly generated by HipHop algorithm after features mapping. A homemade drug database also containing reported fragment haptens (HFR) and new designed full hapten (HFU) were constructed, and then was virtually screened by using generated epitopephore followed by structural analysis and visual inspection. The DNC haptens based on the selected hits were further identified by Density Functional Theory before total synthesis. To prove and clarify the usability of the ERHD, two retrieved HFU haptens, one non-retrieved HFU hapten and three non-retrieved HFR haptens were all selected to produce monoclonal antibodies (mAbs) for comparison purpose. A maximal 6000-fold increased affinity of mAb from retrieved HFU than HFR was observed, while, non-retrieved HFU failed to produce antibody to DNC. More importantly, mAbs from HFU haptens provided highly specificity to DNC, while, mAbs from HFR haptens could recognize 15 others analogues. We then constructed antibody structure and investigated molecular recognition of the mAbs to DNC, well supporting the rationality of the ERHD. Lastly, an icELISA was developed for DNC with an IC50 value as low as 0.19 ng mL-1 with high specificity, which has never achieved before.


Assuntos
Anticorpos Monoclonais , Haptenos , Haptenos/análise , Imunoensaio , Sensibilidade e Especificidade , Ensaio de Imunoadsorção Enzimática
12.
J Ophthalmol ; 2023: 1097704, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36660316

RESUMO

We aim to investigate the effect of overexposure to blue light on the rat ocular surface and explore the potential mechanisms. 450 nm light-emitting diode (LED) derived light at 1000 lux was used to irradiate SD rats, 12 hours a day, for consecutive 28 days. Rats in the control group were exposed to 400 lux white light at the same time (in an indoor environment). Tear film breakup time (TBUT), tear volume, and corneal fluorescein staining scores were used to measure the changes to the ocular surface. Expressions of nuclear factor-κB (NF-κB), inhibitor-κB (I-κB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were measured by real-time PCR, and the activation of the NF-κB pathway was detected by Western blotting, respectively. Cornea ultrastructure was examined by TEM and optical microscope on day 28. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB signaling pathway, was used to measure the inhibition of blue light injury. The above indexes were detected again when compared with the solvent-treated group. On day 28, compared with day 0, the TBUT of the blue light group was significantly shorter, and the score was significantly higher. The amount of tear secretion changed slightly with time. HE and PAS staining revealed significantly decreased corneal epithelial cell layers and increased goblet cells after 28-day irradiation of blue light. Disarranged stromal cells, vacuoles in the basal nuclei, and decreased desmosomes were also found in the blue light group. Significantly increased levels of NF-κB, IL-6, TNF-α, and the ratio of phosphorylated NF-κB p65 (pNF-κB p65) to total NF-κB p65 implied blue light-induced damage and pathway activation. In addition, PDTC significantly reduced the phosphorylation of NF-κB activated in blue light-treated corneas and alleviated the ocular surface changes caused by blue light. Finally, our results demonstrated that long-term blue light exposure in rats could cause ocular surface changes and manifest as dry eye. Inflammation and activation of the NF-κB pathway may play a role in the pathogenesis.

13.
Anticancer Agents Med Chem ; 23(7): 786-793, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36082862

RESUMO

PURPOSE: The study aims to investigate the suppressing tumor-promoting effects via multi-anti-angiogenesis activity of the copper chelator (ammonium tetrathiomolybdate, TM) combined with lenvatinib for hepatocellular carcinoma. METHODS: A total of 55 C57 mice were injected subcutaneously with Hepa1-6 hepatoma cell suspensions into the right posterior thigh. After 7 days, the subcutaneous tumors were formed, and the mice were randomly divided into five groups: TM (G1), Lenvatinib (G2), TM+Lenvatinib (G3), Control (G4), and Copper (II) Gluconate (G5). The copper concentrations in serum and tumors were measured at the predetermined time points. After 14 days of treatments, tumor weight and volumes were analyzed, histology was observed, and the expressions of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in tumor tissues were measured by immunohistochemistry. RESULTS: The median concentration of copper in serum was 401.70, 469.40, and 665.35 µg/L in normal mice, in mice 7 days after implantation, and in the control group, respectively. The intratumoral copper concentrations were higher in G4 mice than in mice 7 days after implantation (P < 0.05). The serum concentration of copper was higher in G5 than all the other groups (P < 0.05; (G1, G2, and G3) vs. G4, P < 0.05; G1 vs. G2, P = 0.013; G2 vs. G3, P = 0.018; G1 vs. G3, P = 0.903. The intratumoral copper concentrations were 608.40, 980.00, 539.31, and 2938.90 µg/L in G1, G2, G3, and G5, respectively. The average tumor weight was 0.55, 0.44, 0.08, 1.37, and 3.11 in G1, G2, G3, G4, and G5, respectively. G5 vs. other groups, P < 0.05; (G1, G2, and G3) vs. G4, P < 0.05; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05; G1 vs. G2, P > 0.05. Furthermore, the expression levels of VEGF were significantly lower in G1, G2, and G3 than in G4 and G5 (P < 0.05). A similar trend was observed for MVD in the five groups, but no significant difference was detected in G1 and G2. CONCLUSION: The study showed a significant positive correlation between tumor load and copper. Copper promotes tumor progression, but copper chelating suppresses tumor growth. The combination of TM with lenvatinib reduces tumor angiogenesis and improves the effect of antitumor treatment. These findings underlie the clinical application of combination therapy.


Assuntos
Neoplasias Hepáticas , Fator A de Crescimento do Endotélio Vascular , Camundongos , Animais , Cobre , Neoplasias Hepáticas/tratamento farmacológico
14.
Chinese Journal of Cardiology ; (12): 504-512, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-984682

RESUMO

Objective: To investigate current use of oral anticoagulant (OAC) therapy and influencing factors among coronary artery disease (CAD) patients with nonvalvular atrial fibrillation (NVAF) in China. Methods: Results of this study derived from "China Atrial Fibrillation Registry Study", the study prospectively enrolled atrial fibrillation (AF) patients from 31 hospitals, and patients with valvular AF or treated with catheter ablation were excluded. Baseline data such as age, sex and type of atrial fibrillation were collected, and drug history, history of concomitant diseases, laboratory results and echocardiography results were recorded. CHA2DS2-VASc score and HAS-BLED score were calculated. The patients were followed up at the 3rd and 6th months after enrollment and every 6 months thereafter. Patients were divided according to whether they had coronary artery disease and whether they took OAC. Results: 11 067 NVAF patients fulfilling guideline criteria for OAC treatment were included in this study, including 1 837 patients with CAD. 95.4% of NVAF patients with CAD had CHA2DS2-VASc score≥2, and 59.7% of patients had HAS-BLED≥3, which was significantly higher than NVAF patients without CAD (P<0.001). Only 34.6% of NVAF patients with CAD were treated with OAC at enrollment. The proportion of HAS-BLED≥3 in the OAC group was significantly lower than in the no-OAC group (36.7% vs. 71.8%, P<0.001). After adjustment with multivariable logistic regression analysis, thromboembolism(OR=2.48,95%CI 1.50-4.10,P<0.001), left atrial diameter≥40 mm(OR=1.89,95%CI 1.23-2.91,P=0.004), stain use (OR=1.83,95%CI 1.01-3.03, P=0.020) and β blocker use (OR=1.74,95%CI 1.13-2.68,P=0.012)were influence factors of OAC treatment. However, the influence factors of no-OAC use were female(OR=0.54,95%CI 0.34-0.86,P=0.001), HAS-BLED≥3 (OR=0.33,95%CI 0.19-0.57,P<0.001), and antiplatelet drug(OR=0.04,95%CI 0.03-0.07,P<0.001). Conclusion: The rate of OAC treatment in NVAF patients with CAD is still low and needs to be further improved. The training and assessment of medical personnel should be strengthened to improve the utilization rate of OAC in these patients.


Assuntos
Humanos , Feminino , Masculino , Fibrilação Atrial/tratamento farmacológico , Doença da Artéria Coronariana/complicações , Anticoagulantes/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , China , Administração Oral , Acidente Vascular Cerebral
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-991742

RESUMO

Objective:To investigate the optimal cut-off values for the prediction of lumbar spinal stenosis using lumbar pedicle thickness.Methods:The clinical data of 64 patients with lumbar spinal stenosis (patient group) admitted to Binzhou Center Hospital from November 2019 to April 2021 and 48 healthy volunteers (healthy control group) who concurrently received routine physical examination involving lumbar spine MRI examination in the same hospital were retrospectively analyzed. Lumbar pedicle thickness was measured on T 2 weighted images of the L 5 vertebral body in the axial projection. Lumbar pedicle thickness was compared between groups using the independent sample t-test. The relationship between lumbar pedicle thickness and age change was analyzed using a one-way analysis of variance. The efficacy of lumbar pedicle thickness in the diagnosis of lumbar spinal stenosis was evaluated using the receiver operating characteristic (ROC) curve, optimal cut-off values, sensitivity, specificity, and the area under the ROC curve. Results:There was no significant correlation between lumbar pedicle thickness and age change ( P > 0.05). Lumbar pedicle thickness of patients with lumbar spinal stenosis was significantly higher than that of healthy controls [(13.25 ± 1.73) mm vs. (8.54 ± 1.88) mm, t = 13.75, P < 0.05]. ROC curve results showed that the optimal cut-off value was 10.50 mm, with a sensitivity of 95.3% and a specificity of 85.4. The area under the ROC curve was 0.963 (95% CI 0.928-0.998). Conclusion:The increase in lumbar pedicle thickness is related to the increase in the incidence of lumbar spinal stenosis. Lumbar pedicle thickness is an accurate, objective, and clear morphological parameter for the prediction of lumbar spinal stenosis. Application of lumbar pedicle thickness to predict lumbar spinal stenosis is innovative and scientific.

16.
Journal of Modern Urology ; (12): 24-28, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005459

RESUMO

【Objective】 To investigate the clinical efficacy and safety of transurethral blue laser vaporescetion of the prostate in the treatment of benign prostatic hyperplasia (BPH). 【Methods】 The clinical data of 100 BPH patients undergoing the surgery in our hospital during May and Sep.2022 were retrospectively analyzed. The observations included operation time, bladder irrigation duration, postoperative catheter indwelling time, hospital stay, complications, as well as changes in hemoglobin, International Prostate Symptom Score (IPSS), Quality of Life Scale (QoL) score, maximum urinary flow rate (Qmax), bladder residual urine volume (PVR), and other related indicators before and 3 months after surgery. 【Results】 All 100 procedures were successfully completed without turning to transurethral resection of the prostate and/or open surgery. No blood transfusion was needed. The operation time was (37.8±19.6) min, bladder irrigation time (1.3±0.5) d, catheter indwelling time (12.7±0.4) d, hospital stay (3.4±0.7) d, hemoglobin drop (4.1±7.1) g/L. The postoperative IPSS and QoL score were significantly lower than those before surgery (P<0.05); postoperative Qmax was higher than that before surgery (P<0.05); postoperative PVR was smaller than that before surgery (P<0.05). Urinary retention occurred in 4 cases (4%) after removal of the catheter; carnal hematuria and bladder clot formation occurred in 3 cases (3%); mixed urinary incontinence occurred in 2 cases (2%); stenosis of the external urethra occurred in 2 cases (2%). All complications were cured after symptomatic treatment. There were no serious perioperative complications, no intraoperative complications such as ureteral orifice injury or bladder perforation, and no serious postoperative complications such as transurethral resection syndrome (TURS), permanent urinary incontinence or bladder neck contracture. 【Conclusion】 The blue laser surgical system had satisfactory effects of vaporization and hemostasia. Transurethral blue laser vaporesection of the prostate is safe and effective in the treatment of BPH.

17.
Sichuan Mental Health ; (6): 497-502, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005283

RESUMO

BackgroundElderly cataract patients with depressive symptoms have heavier self-perceived burden, and worse vision-related quality of life compared to patients without depressive symptoms, resulting in the increase of family burden. Most previous studies showed that family relationship and vision were the main factors leading to depression in elderly cataract patients, and ignored the effects of self-feeling and complicated diseases on the psychological state of elderly cataract patients. ObjectiveTo explore the relationship between depressive symptoms, self-perceived burden and postoperative vision-related quality of life in elderly cataract patients, and to analyze the risk factors of depressive symptoms. So as to provide references for targeted psychological intervention in this population. MethodsA total of 104 elderly cataract patients admitted to Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University) from July 1, 2020 to December 31, 2022 were included. General information, self-perceived burden and postoperative vision-related quality of life were investigated by self-designed questionnaire, Patients' Health Questionnaire depressive Scale-9 item (PHQ-9), Self-Perceived Burden Scale (SPBS) and National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Pearson correlation analysis was performed to analyze the correlation among PHQ-9, SPBS and NEI-VFQ-25 scores. Logistic regression analysis was used to analyze the influencing factors of depressive symptoms in eldery cataract patients. ResultsA total of 100 elderly cataract patients completed an effective questionnaire survey. Among the participants, 31 cases (31.00%) were found to have depressive symptoms. The depressive group exhibited significantly higher SPBS score (t=11.062, P<0.01) and significantly lower NEI-VFQ-25 score (t=-5.235, P<0.01) than those of the non-depressive group. Pearson correlation analysis showed a positive correlation between PHQ-9 and SPBS score (r=0.485, P<0.01), and a negative correlation between PHQ-9 and NEI-VFQ-25 score (r=-0.440, P<0.01). Complicated with diabetes (OR=1.441, P<0.01), osteoarthritis (OR=1.324, P<0.05) and high SPBS score (OR=1.340, P<0.05) were risk factors of depressive sympptoms in elderly cataract patients. ConclusionThe detection rate of depressive symptoms in elderly cataract patients is higher, and postoperative vision-related quality of life in elderly cataract patients complicated with depressive symptoms is poor. Risk factors include diabetes, osteoarthritis and high self-perceived burden. [Funded by 2022 Jiangsu Province Elderly Health Scientific Research Project (number, LKM2022019)]

18.
Acta Pharmaceutica Sinica ; (12): 3090-3098, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999053

RESUMO

Sophorae Flavescentis Radix is the dried root of Sophora flavescens Ait. and Sophorae Tonkinensis Radix et Rhizoma is the dried root and rhizome of Sophora tonkinensis Gagnep. The two drugs are both from the same genus Sophora, having similar and different compositions and efficacies, however, their differences are not fully demonstrated in current standard. In this study, the high-performance thin-layer chromatography with multi-dimensional and multi-level features combined with electric spray mass spectrometry (HPTLC-ESI-MS) was used to discover and identify the characteristic zones in extracts of Sophorae Flavescentis Radix and Sophorae Tonkinensis Radix et Rhizoma, after optimizing the preparation method of the test solution and chromatographic parameters. As a result, 17 main characteristic zones were found on HPTLC chromatograms of Sophorae Flavescentis Radix and Sophorae Tonkinensis Radix et Rhizoma, among them, besides 3 known chemicals, another 12 unknown components were identified by HPTLC-ESI-MS, they are 1 alkaloid and 11 flavonoids. The identification results were verified by the reference standards partially and nuclear magnetic resonance spectra after guided-isolation. Finally, a unified HPTLC specific identification method with different markers was established to identify Sophorae Flavescentis Radix and Sophorae Tonkinensis Radix et Rhizoma simultaneously. Thanks to abundant chemical information provided when using diverse polarity mobile phases and derivatization reagents, the HPTLC technology offers a convenient strategy for discovery, quality evaluation, and identification of target chemicals when connecting with mass spectrometry.

19.
Acta Pharmaceutica Sinica ; (12): 2882-2889, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999041

RESUMO

To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates, an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn) method and BitterX database prediction. The chromatographic operating conditions were as follows, chromatographic column: Acquity UPLC BEH C18 (100 mm × 2.1 mm, 1.7 μm), mobile phase: 0.1% formic acid-water solution (A)-acetonitrile (B) with gradient elution. The data were collected in positive and negative ion modes, respectively. The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry. The compounds were identified by combining retention time, reference substances, reports, and other relevant data, and a total of 57 constituents including flavonoids, alkaloids, and phenylpropanoids were finally identified. Further, the BitterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes, finally 33 potential bitter compounds, including kukoamine A and linarin, were predicted. This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates, it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

20.
Acta Pharmaceutica Sinica ; (12): 2890-2899, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-999036

RESUMO

Aiming at the hysteresis and destructiveness of off-line static detection of critical quality attribute of the moisture content of the raw material unit of the traditional Chinese medicine manufacturing process, honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis were used as the research carriers, and the drying method was used to measure the moisture content as a reference value. The moving stage was used to simulate the movement process of samples on the conveyor belt in the actual on-site production process, and near-infrared (NIR) spectra were collected, combined with machine learning, to establish NIR on-site dynamic detection model of moisture content in multi-variety honey-processed Chinese herbal slice. The results show that the second derivative method is used to preprocess the spectrum. The number of decision trees (ntree), the number of random features (max feature), and the minimum number of samples for generating leaf nodes (node size) are selected: 46, 76, and 8, respectively. The quantitative analysis model of moisture content has the best effect. The prediction coefficient of determination (the prediction coefficient of determination, R2pre) and the root mean square error of prediction (root mean square error of prediction, RMSEP) of the model were 0.903 2 and 0.330 2, respectively. The NIR quantitative model for the moisture content of multi-variety honey-processed Chinese herbal slice established in this study has good predictive performance, and can achieve rapid, accurate and non-destructive quantitative analysis of the moisture content of honey-processed Tussilago farfara, honey-processed Astragalus and honey-processed Glycyrrhiza uralensis at the same time, and provides a method for determining the moisture content of honey-processed Chinese herbal slice of the raw material unit of the traditional Chinese medicine manufacturing process.

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