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1.
Acta Pharmacol Sin ; 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38907048

RÉSUMÉ

Adjuvants for vaccines with characteristics of improving adaptive immunity particularly via leverage of antigen presenting cells (APCs) are currently lacking. In a previous work we obtained a new soluble 300 kDa homogeneous ß-glucan named GFPBW1 from the fruit bodies of Granola frondosa. GFPBW1 could activate macrophages by targeting dendritic cell associated C-type lectin 1 (Dectin-1)/Syk/NF-κB signaling to achieve antitumour effects. In this study the adjuvant effects of GFPBW1 were explored with OVA-antigen and B16-OVA tumor model. We showed that GFPBW1 (5, 50, 500 µg/mL) dose-dependently promoted activation and maturation of APCs in vitro by increasing CD80, CD86 and MHC II expression. We immunized female mice with OVA in combination with GFPBW1 (50 or 300 µg) twice with an interval of two weeks. GFPBW1 markedly and dose-dependently increased OVA-specific antibody titers of different subtypes including IgG1, IgG2a, IgG2b and IgG3, suggesting that it could serve as an adjuvant for both Th1 and Th2 type immune responses. Furthermore, GFPBW1 in combination with aluminum significantly increased the titers of OVA-specific IgG2a and IgG2b, but not those of IgG1, suggesting that GFPBW1 could be used as a co-adjuvant of aluminum to compensate for Th1 deficiency. For mice immunized with OVA plus GFPBW1, no obvious pathological injury was observed in either major organs or injection sites, and no abnormalities were noted for any of the hematological parameters. When GFPBW1 served as an adjuvant in the B16-OVA cancer vaccine models, it could accomplish entire tumor suppression with preventive vaccines, and enhance antitumour efficacy with therapeutic vaccines. Differentially expressed genes were found to be enriched in antigen processing process, specifically increased tumor infiltration of DCs, B1 cells and plasma cells in the OVA plus GFPBW1 group, in accordance with its activation and maturation function of APCs. Collectively, this study systematically describes the properties of GFPBW1 as a novel potent and safe adjuvant and highlights its great potential in vaccine development.

2.
Yi Chuan ; 46(5): 373-386, 2024 May 20.
Article de Anglais | MEDLINE | ID: mdl-38763772

RÉSUMÉ

Cardioembolic stroke, characterized by severe illness, poor prognosis, and high recurrence rate, is one of the important causes of ischemic stroke. In the field of genetic research, numerous genes associated with cardioembolic stroke have been identified, and their potential in predicting disease risk and evaluating risk factors has been progressively explored. Here, we provide an overview of the latest advancements in genetics for cardioembolic stroke, including genome-wide association studies, copy number variation studies, whole-genome sequencing studies. Furthermore, we also summarize the application of genetic datasets in polygenic risk score and Mendelian randomization. The aim of this overview is to provide insights and references from multiple perspectives for future investigations on the genetic information for cardioembolic stroke.


Sujet(s)
Variations de nombre de copies de segment d'ADN , Accident vasculaire cérébral embolique , Prédisposition génétique à une maladie , Étude d'association pangénomique , Humains , Accident vasculaire cérébral embolique/génétique , Accident vasculaire cérébral embolique/étiologie , Facteurs de risque
3.
Heliyon ; 10(9): e30378, 2024 May 15.
Article de Anglais | MEDLINE | ID: mdl-38707441

RÉSUMÉ

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

4.
Prostaglandins Other Lipid Mediat ; 172: 106832, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38460759

RÉSUMÉ

Atherosclerosis (AS) represents a prevalent initiating factor for cardiovascular events. Insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) is an oncofetal RNA-binding protein that participates in cardiovascular diseases. This work aimed to elaborate the effects of IGF2BP3 on AS and the probable mechanism by using an oxidized low-density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) model. Results indicated that IGF2BP3 expression was declined in the blood of AS patients and ox-LDL-induced HUVECs. IGF2BP3 elevation alleviated ox-LDL-provoked viability loss, apoptosis, oxidative DNA damage and endothelial dysfunction in HUVECs. Moreover, IGF2BP3 bound SESN1 and stabilized SESN1 mRNA. Furthermore, SESN1 interference reversed the impacts of IGF2BP3 overexpression on the apoptosis, oxidative DNA damage and endothelial dysfunction of ox-LDL-challenged HUVECs. Additionally, the activation of Nrf2 signaling mediated by IGF2BP3 up-regulation in ox-LDL-treated HUVECs was blocked by SESN1 absence. Collectively, SESN1 stabilized by IGF2BP3 might protect against AS by activating Nrf2 signaling.


Sujet(s)
Cellules endothéliales de la veine ombilicale humaine , Lipoprotéines LDL , Facteur-2 apparenté à NF-E2 , Stress oxydatif , ARN messager , Protéines de liaison à l'ARN , Transduction du signal , Humains , Cellules endothéliales de la veine ombilicale humaine/métabolisme , Cellules endothéliales de la veine ombilicale humaine/effets des médicaments et des substances chimiques , Lipoprotéines LDL/pharmacologie , Lipoprotéines LDL/métabolisme , Facteur-2 apparenté à NF-E2/métabolisme , Facteur-2 apparenté à NF-E2/génétique , Protéines de liaison à l'ARN/métabolisme , Protéines de liaison à l'ARN/génétique , Stress oxydatif/effets des médicaments et des substances chimiques , Transduction du signal/effets des médicaments et des substances chimiques , ARN messager/génétique , ARN messager/métabolisme , Protéines nucléaires/métabolisme , Protéines nucléaires/génétique , Apoptose/effets des médicaments et des substances chimiques , Athérosclérose/métabolisme , Athérosclérose/génétique , Athérosclérose/anatomopathologie , Stabilité de l'ARN/effets des médicaments et des substances chimiques , Altération de l'ADN , Sestrines
5.
Eur J Anaesthesiol ; 41(4): 305-313, 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38298060

RÉSUMÉ

BACKGROUND: Tracheal injuries, vocal cord injuries, sore throat and hoarseness are common complications of double-lumen tube (DLT) intubation. OBJECTIVE: This study aimed to evaluate the effects of 'video double-lumen tubes' (VDLTs) on intubation complications in patients undergoing thoracic surgery. DESIGN: A randomised controlled study. SETTINGT: Xuzhou Cancer Hospital, Xuzhou, China, from January 2023 to June 2023. PATIENTS: One hundred eighty-two patients undergoing elective thoracic surgery with one-lung ventilation were randomised into two groups: 90 in the DLT group and 92 in the VDLT group. INTERVENTION: VDLT was selected for intubation in the VDLT group, and DLT was selected for intubation in the DLT group. A fibreoptic bronchoscope (FOB) was used to record tracheal and vocal cord injuries. MAIN OUTCOME MEASURES: The primary outcomes were the incidence of moderate-to-severe tracheal injury and the incidence of vocal cord injury. The secondary outcomes included the incidence and severity of postoperative 24 and 48 h sore throat and hoarseness. RESULTS: The incidence of moderate-to-severe tracheal injury was 32/90 (35.6%) in the DLT group, and 45/92 (48.9%) in the VDLT group ( P  = 0.077; relative risk 1.38, 95% CI, 0.97 to 1.95). The incidence of vocal cord injury was 31/90 (34.4%) and 34/92 (37%) in the DLT and VDLT groups, respectively ( P  = 0.449). The incidence of postoperative 24 h sore throat and hoarseness was significantly higher in the VDLT group than in the DLT group (for sore throat: P  = 0.032, relative risk 1.63, 95% CI, 1.03 to 2.57; for hoarseness: P  = 0.018, relative risk 1.48, 95% CI, 1.06 to 2.06). CONCLUSION: There was no statistically significant difference in the incidence of moderate-to-severe tracheal injury and vocal cord injury between DLTs and VDLTs. While improving the first-attempt success rate, intubation with VDLT increased the incidence of postoperative 24 h sore throat and hoarseness. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier: ChiCTR2300067348.


Sujet(s)
Pharyngite , Chirurgie thoracique , Procédures de chirurgie thoracique , Humains , Enrouement/diagnostic , Enrouement/épidémiologie , Enrouement/étiologie , Procédures de chirurgie thoracique/effets indésirables , Bronchoscopes , Pharyngite/épidémiologie , Pharyngite/étiologie
6.
Sci Rep ; 13(1): 18498, 2023 10 28.
Article de Anglais | MEDLINE | ID: mdl-37898687

RÉSUMÉ

Laryngeal squamous cell carcinoma (LSCC) is a common tumor type. High recurrence rates remain an important factor affecting the survival and quality of life of advanced LSCC patients. We aimed to build a new nomogram and a random survival forest model using machine learning to predict the risk of LSCC progress. The study included 671 patients with AJCC stages III-IV LSCC. To develop a prognostic model, Cox regression analyses were used to assess the relationship between clinic-pathologic factors and disease-free survival (DFS). RSF analysis was also used to predict the DFS of LSCC patients. The ROC curve revealed that the Cox model exhibited good sensitivity and specificity in predicting DFS in the training and validation cohorts (1 year, validation AUC = 0.679, training AUC = 0.693; 3 years, validation AUC = 0.716, training AUC = 0.655; 5 years, validation AUC = 0.717, training AUC = 0.659). Random survival forest analysis showed that N stage, clinical stage, and postoperative chemoradiotherapy were prognostically significant variables associated with survival. The random forest model exhibited better prediction ability than the Cox regression model in the training cohort; however, the two models showed similar prediction ability in the validation cohort.


Sujet(s)
Carcinome épidermoïde , Tumeurs de la tête et du cou , Humains , Carcinome épidermoïde de la tête et du cou , Modèles des risques proportionnels , Carcinome épidermoïde/anatomopathologie , Qualité de vie , Pronostic , Apprentissage machine
7.
Tissue Cell ; 85: 102250, 2023 Dec.
Article de Anglais | MEDLINE | ID: mdl-37866150

RÉSUMÉ

Non-small cell lung cancer (NSCLC) is a malignant tumor with extremely high mortality. Uroplakin1B (UPK1B) promotes the occurrence and development of multiple types of cancer by enhancing the expression of c-myc and Sox4. However, whether UPK1B can modulate the development of NSCLC by regulating c-myc/Sox4 axis is unclear. In this study, UPK1B was overexpressed or knocked down in the non-small cell lung cancer cells (NSCLCs) were. Next, the proliferation and invasion of those cells were detected with the EdU staining and transwell assays. Sphere formation assays was performed to examine the stem cell characteristics of those cells. Then, we overexpressed the Sox4 in UPK1B knockdown cells and determined the proliferation and invasion of those cells. Our results showed that UPK1B promoted the proliferation, invasion and stem cell characteristics of NSCLCs. In addition, UPK1B enhanced the expression of c-myc, Sox4 and stem cell associated proteins in those cells. Overexpression of Sox4 rescued the proliferation and invasion of NSCLCs, which were suppressed by the UPK1B knockdown. In summary, our study suggested that UPK1B enhanced the invasiveness and stem cell characteristics of NSCLCs by activating c-myc/UPK1B axis.


Sujet(s)
Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , microARN , Humains , Carcinome pulmonaire non à petites cellules/génétique , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Lignée cellulaire tumorale , Invasion tumorale/génétique , Prolifération cellulaire/génétique , Mouvement cellulaire/génétique , Facteurs de transcription , Cellules souches/anatomopathologie , Régulation de l'expression des gènes tumoraux , Uroplakine Ib
8.
J Cardiovasc Pharmacol ; 82(6): 496-503, 2023 12 01.
Article de Anglais | MEDLINE | ID: mdl-37548460

RÉSUMÉ

ABSTRACT: This study aims to investigate whether venous injection of sedative agent or regional nerve block in alliance with major anesthesia could decrease the risk of postoperative delirium occurrence in patients receiving cardiothoracic surgery. Electronic academic databases were retrieved for related publications, and statistical software was used for data pooling and analysis. Forest plot was used to show the pooled sensitivity, specificity, and diagnostic odds ratio. Combined receiver operating characteristic curve was used to show the area under the curve of complex data. Seven studies were included for analysis. The risk of occurrence of delirium still showed no difference (risk rate = 0.93, 95% CI, 0.85-1.03) between the intervention group and placebo group. Postoperative pain feeling was more alleviated in patients with prophylactic application of regional nerve block. In addition, prophylactic application of regional nerve block could decrease the risk of postoperative in-hospital stay (risk rate = 0.28, 95% CI, 0.02-0.54). Our study demonstrated that, in elderly patients or pediatric patients undergoing cardiac surgery, prophylactic application of regional nerve block failed to decrease the incidence of postoperative delirium. However, the option of regional nerve block could decrease the duration of in-hospitalization stay and alleviate the acute pain during the postoperative period after open-heart surgery.


Sujet(s)
Délire d'émergence , Bloc nerveux , Humains , Enfant , Sujet âgé , Délire d'émergence/étiologie , Durée du séjour , Douleur postopératoire/diagnostic , Douleur postopératoire/prévention et contrôle , Douleur postopératoire/étiologie , Bloc nerveux/effets indésirables , Anesthésie générale
9.
Chinese Pharmacological Bulletin ; (12): 1731-1739, 2023.
Article de Chinois | WPRIM (Pacifique Occidental) | ID: wpr-1013721

RÉSUMÉ

Aim To investigate the effects of Cichorium glandulosum N-butanol extraction site (C G E) on hepatic fibrosis (H F) in SD rats and to determine the content of the main effective component matricin. Methods HPLC method was used to determine the content of matricin in CGE. The SD rats were randomly divided into control group, model group, CGE low-dose groups, medium-dose and high-dose, and curcumin group. In addition to control group rats' back subcutaneous injection (s c) normal saline, rats in the other groups were treated with body weight sc 40 % CC1

10.
Technol Cancer Res Treat ; 21: 15330338221107710, 2022.
Article de Anglais | MEDLINE | ID: mdl-35815926

RÉSUMÉ

Background: Head and neck squamous cell carcinoma (HNSCC) was the seventh most common cancer worldwide in 2018. Lymphatic metastasis (LM) is closely related to HNSCC prognosis and recurrence. However, the underlying mechanism of LM remains unclear. Therefore, this study aimed to identify the key genes in the LM of HNSCC. Methods: We used The Cancer Genome Atlas (TCGA) to identify differentially expressed genes (DEGs) between LM and non-LM cases. A random forest model, the Search Tool for the Retrieval of Interacting Genes, Cytoscape, and cytoHubba were used to identify hub genes among DEGs, including KRT20 (Cytokeratins 20). We analyzed the survival of KRT20 in TCGA, and we overexpressed KRT20 in HNSCC cell lines to investigate its effects on migration and invasion. We also correlated the expression of KRT20 in HNSCC tissue microarrays with survival and clinicopathological features. Results: We identified 243 DEGs-143 upregulated genes and 100 downregulated genes. Further analysis revealed that KRT20 is a potential key gene associated with LM and overall survival rates among patients with HNSCC. Overexpression of KRT20 increased the migration and invasion ability of HNSCC cell lines Tu686 and FD-LSC-1. Tissue microarray studies demonstrated an overexpression of KRT20 among N1+ patients (including N1-N3 patients). Survival analysis results and the clinicopathological features of HNSCC tissue microarrays were consistent with our analysis of TCGA. Thus, a high KRT20 expression level might suggest an adverse HNSCC prognosis. Our gene set enrichment analysis showed that KRT20 participates in many metabolic pathways, including those related to tumorigenesis and cancer development. Conclusions: We propose that KRT20 may be a key gene in HNSCC with LM.


Sujet(s)
Tumeurs de la tête et du cou , Marqueurs biologiques tumoraux/génétique , Régulation de l'expression des gènes tumoraux , Tumeurs de la tête et du cou/génétique , Humains , Kératine-20/génétique , Métastase lymphatique , Pronostic , Carcinome épidermoïde de la tête et du cou/génétique
11.
Thorac Cardiovasc Surg ; 70(5): 439-444, 2022 08.
Article de Anglais | MEDLINE | ID: mdl-34521135

RÉSUMÉ

OBJECTIVES: Thoracic surgery often causes postoperative delirium (POD) in geriatric patients. This study aimed to explore the effect of ultrasound-guided continuous thoracic paravertebral block (UG-TPVB) on POD in geriatric patients undergoing pulmonary resection. METHODS: Total 128 patients who underwent pulmonary resection were randomly allocated to either the conventional patient-controlled analgesia (PCA) group or the UG-TPVB group (n = 64 per group). The consumption of opioid agents (propofol and remifentanil), postoperative hospital stay, postoperative pulmonary atelectasis, postoperative nausea/vomiting, and postoperative itchiness were recorded. The diagnosis of delirium was dependent on the Nursing Delirium Screening Scale. The postoperative pain was assessed by visual analogue scale (VAS) score. The serum levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α were used to evaluate the postoperative neuroinflammation. RESULTS: The consumption of propofol and remifentanil, postoperative hospital stay, postoperative pulmonary atelectasis, postoperative nausea/vomiting, and postoperative itchiness in the UG-TPVB group were lower than that in the PCA group. Compared with the PCA group, the prevalence of POD was decreased in the UG-TPVB group. In addition, use of UG-TPVB not only reduced postoperative pain (VAS score) but also decreased postoperative neuroinflammation compared with PCA in geriatric patients undergoing pulmonary resection. CONCLUSIONS: This study determined the benefits of UG-TPVB over PCA, providing an effectiveness approach to alleviate POD in geriatric patients undergoing pulmonary resection.


Sujet(s)
Délire avec confusion , Propofol , Atélectasie pulmonaire , Sujet âgé , Délire avec confusion/diagnostic , Délire avec confusion/étiologie , Délire avec confusion/prévention et contrôle , Humains , Nausée , Douleur postopératoire/diagnostic , Douleur postopératoire/étiologie , Douleur postopératoire/prévention et contrôle , Propofol/effets indésirables , Rémifentanil , Résultat thérapeutique , Vomissement
12.
Acta Pharmacol Sin ; 42(12): 2094-2105, 2021 Dec.
Article de Anglais | MEDLINE | ID: mdl-33686245

RÉSUMÉ

Aristolochic acid I (AAI) is a well-known nephrotoxic carcinogen, which is currently reported to be also associated with hepatocellular carcinoma (HCC). Whether AAI is a direct hepatocarcinogen remains controversial. In this study we investigated the association between AAI exposure and HCC in adult rats using a sensitive rat liver bioassay with several cofactors. Formation of glutathione S-transferase placental form-positive (GST-P+) foci was used as the marker for preneoplastic lesions/clonal expansion. We first conducted a medium-term (8 weeks) study to investigate whether AAI had any tumor-initiating or -promoting activity. Then a long-term (52 weeks) study was conducted to determine whether AAI can directly induce HCC. We showed that oral administration of single dose of AAI (20, 50, or 100 mg/kg) in combination with partial hepatectomy (PH) to stimulate liver proliferation did not induce typical GST-P+ foci in liver. In the 8-week study, only high dose of AAI (10 mg · kg-1 · d-1, 5 days a week for 6 weeks) in combination with PH significantly increased the number and area of GST-P+ foci initiated by diethylnitrosamine (DEN) in liver. Similarly, only high dose of AAI (10 mg· kg-1· d-1, 5 days a week for 52 weeks) in combination with PH significantly increased the number and area of hepatic GST-P+ foci in the 52-week study. No any nodules or HCC were observed in liver of any AAI-treated groups. In contrast, long-term administration of AAI (0.1, 1, 10 mg· kg-1· d-1) time- and dose-dependently caused death due to the occurrence of cancers in the forestomach, intestine, and/or kidney. Besides, AAI-DNA adducts accumulated in the forestomach, kidney, and liver in a time- and dose-dependent manner. Taken together, AAI promotes clonal expansion only in the high-dose group but did not induce any nodules or HCC in liver of adult rats till their deaths caused by cancers developed in the forestomach, intestine, and/or kidney. Findings from our animal studies will pave the way for further large-scale epidemiological investigation of the associations between AA and HCC.


Sujet(s)
Acides aristolochiques/toxicité , Cancérogènes/toxicité , Carcinome hépatocellulaire/étiologie , Hépatocytes/métabolisme , Tumeurs du foie/étiologie , Mutagènes/toxicité , Animaux , Carcinogenèse/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Adduits à l'ADN/effets des médicaments et des substances chimiques , Glutathione S-transferase pi/métabolisme , Tumeurs de l'intestin/induit chimiquement , Intestins/anatomopathologie , Rein/anatomopathologie , Tumeurs du rein/induit chimiquement , Foie/métabolisme , Foie/anatomopathologie , Mâle , Rat Sprague-Dawley , Estomac/anatomopathologie , Tumeurs de l'estomac/induit chimiquement
13.
Medicine (Baltimore) ; 99(17): e19896, 2020 Apr.
Article de Anglais | MEDLINE | ID: mdl-32332664

RÉSUMÉ

BACKGROUND: Delirium is a common postoperative complication in older patients undergoing thoracic surgery and presages poor outcomes. Postoperative pain is an important factor in the progression of delirium. The purpose of this study was to test whether continuous thoracic paravertebral block (PVB), a more effective approach for analgesia, could decrease the incidence of delirium in elderly patients undergoing esophagectomy. METHODS: A total of 180 geriatric patients undergoing esophagectomy were randomly divided into 2 groups and treated with PVB or patient-controlled analgesia (PCA). Perioperative plasma CRP, IL-1ß, IL-6, and TNF-α levels were detected in all patients. Pain intensity was measured by a numerical rating scale. Delirium was assessed using the confusion assessment method. RESULTS: The incidence of postoperative delirium was significantly lower in the PVB group than in the PCA group. Patients in the PVB group had lower plasma CRP, IL-1ß, IL-6, and TNF-α levels and less pain when coughing after surgery. CONCLUSIONS: Ultrasound-guided continuous thoracic paravertebral block improved analgesia, reduced the inflammatory reaction and decreased the occurrence of delirium after surgery.


Sujet(s)
Délire avec confusion/prévention et contrôle , Oesophagectomie/normes , Bloc nerveux/méthodes , Échographie/normes , Sujet âgé , Sujet âgé de 80 ans ou plus , Analgésie autocontrôlée/méthodes , Analgésie autocontrôlée/normes , Délire avec confusion/traitement médicamenteux , Oesophagectomie/méthodes , Femelle , Gériatrie/méthodes , Humains , Mâle , Adulte d'âge moyen , Bloc nerveux/normes , Complications postopératoires/traitement médicamenteux , Complications postopératoires/prévention et contrôle , Études prospectives , Échographie/méthodes , Échographie/statistiques et données numériques
14.
Acta Pharmacol Sin ; 41(3): 348-357, 2020 Mar.
Article de Anglais | MEDLINE | ID: mdl-31506573

RÉSUMÉ

Intestinal mucositis is a common side effect of anticancer regimens that exerts a negative impact on chemotherapy. Superoxide dismutase (SOD) is a potential therapy for mucositis but efficient product is not available because the enzyme is degraded following oral administration or induces an immune reaction after intravascular infusion. Multi-modified Stable Anti-Oxidant Enzymes® (MS-AOE®) is a new recombinant SOD with better resistance to pepsin and trypsin. We referred it as MS-SOD to distinguish from other SODs. In this study we investigated its potential to alleviate 5-FU-induced intestinal injury and the mechanisms. An intestinal mucositis model was established in C57/BL6 mice by 5-day administration of 5-FU (50 mg/kg every day, ip). MS-SOD (800 IU/10 g, ig) was given once daily for 9 days. 5-FU caused severe mucositis with intestinal morphological damage, bodyweight loss and diarrhea; MS-SOD significantly decreased the severity. 5-FU markedly increased reactive oxygen species (ROS) and inflammatory cytokines in the intestine which were ameliorated by MS-SOD. Furthermore, MS-SOD modified intestinal microbes, particularly reduced Verrucomicrobia, compared with the 5-FU group. In Caco2 cells, MS-SOD (250-1000 U/mL) dose-dependently decreased tBHP-induced ROS generation. In RAW264.7 cells, MS-SOD (500 U/mL) had no effect on LPS-induced inflammatory cytokines, but inhibited iNOS expression. These results demonstrate that MS-SOD can scavenge ROS at the initial stage of injury, thus play an indirect role in anti-inflammatory and barrier protein protection. In conclusion, MS-SOD attenuates 5-FU-induced intestinal mucositis by suppressing oxidative stress and inflammation, and influencing microbes. MS-SOD may exert beneficial effect in prevention of intestinal mucositis during chemotherapy in clinic.


Sujet(s)
Fluorouracil/effets indésirables , Muqueuse intestinale/métabolisme , Superoxide dismutase/métabolisme , Administration par voie orale , Animaux , Fluorouracil/administration et posologie , Fluorouracil/métabolisme , Injections péritoneales , Muqueuse intestinale/anatomopathologie , Mâle , Souris , Souris de lignée C57BL , Protéines recombinantes/administration et posologie , Protéines recombinantes/métabolisme , Superoxide dismutase/administration et posologie
15.
Front Neurol ; 9: 633, 2018.
Article de Anglais | MEDLINE | ID: mdl-30131758

RÉSUMÉ

Objective: Inflammation plays a key role in the etiology and pathology of postoperative cognitive dysfunction (POCD). Cyclooxygenase (COX)-2 inhibitor celecoxib is used for the treatment of acute pain due to its potent anti-inflammatory and analgesic effects. Herein, we evaluated the effects of celecoxib on POCD in geriatric patients. Methods: A total of 178 geriatric patients undergoing total knee arthroplasty were randomly divided into two groups and treated with celecoxib (group C) or placebo (group P). The levels of perioperative plasma COX-2, IL-1ß, IL-6, TNF-α, neuron-specific enolase, and S100ß were detected in all patients. The pain intensity was measured by numerical rating scale (NRS). A battery of 9 neuropsychological tests was performed pre-operatively and 1 week, and 3 months postoperatively. Patients, whose postoperative performance declined by ≧1 standard deviation as compared to each preoperative test score on ≧2 tests, were classified as POCD. Results: A significant decrease in POCD incidence was found in group C as compared to group P on postoperative day 7 (12.3% vs. 34.1%; p < 0.05). POCD incidence did not differ between the two groups at the 3-month follow-up (8.8 vs. 9.7%). NRS scores at days 3 and 4 post-surgery were significantly lower in group C (p < 0.05). Patients in group C showed lower level of plasma COX-2, IL-1ß, IL-6, TNF-α, and S100ß as compared to group P postoperatively (p < 0.05). Conclusion: These results demonstrated that celecoxib can decrease early POCD incidence after total knee arthroplasty in geriatric patients, which might be mediated by suppressing inflammation and acute postoperative pain caused by surgical trauma. Registration: Chinese Clinical Trial Register, ChiCTR-IOR-16008168.

16.
Acta Pharmacol Sin ; 39(12): 1865-1873, 2018 Dec.
Article de Anglais | MEDLINE | ID: mdl-30061734

RÉSUMÉ

Cholestasis is a common feature of liver injury, which manifests as bile acid excretion and/or enterohepatic circulation disorders. However, very few effective therapies exist for cholestasis. Recently, 18ß-Glycyrrhetinic acid (18b-GA), a major metabolic component of glycyrrhizin, which is the main ingredient of licorice, was reported to protect against alpha-naphthylisothiocyanate (ANIT)-induced cholestasis. However, its protective mechanism remains unclear. We hypothesized that 18b-GA may stimulate the signaling pathway of bile acid (BA) transportation in hepatocytes, resulting its hepatoprotective effect. According to the results, 18b-GA markedly attenuated ANIT-induced liver injury as indicated the hepatic plasma chemistry index and histopathology examination. In addition, the expression levels of nuclear factors, including Sirt1, FXR and Nrf2, and their target efflux transporters in the liver, which mainly mediate bile acid homeostasis in hepatocytes, significantly increased. Furthermore, we first revealed that 18b-GA treatment significantly activated FXR, and which can be significantly reduced by EX-527 (a potent and selective Sirt1 inhibitor), indicating that 18b-GA activates FXR through Sirt1. Taken together, 18b-GA confers hepatoprotection against ANIT-induced cholestasis by activating FXR through Sirt1, which promotes gene expression of the efflux transporter, and consequently attenuates dysregulation of bile acid homeostasis in hepatocyte compartments.


Sujet(s)
Cholestase/prévention et contrôle , Énoxolone/analogues et dérivés , Agents protecteurs/usage thérapeutique , Récepteurs cytoplasmiques et nucléaires/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Sirtuine-1/métabolisme , 1-Naphtyl-isothiocyanate , Animaux , Cholestase/induit chimiquement , Énoxolone/usage thérapeutique , Mâle , Facteur-2 apparenté à NF-E2/métabolisme , Rat Sprague-Dawley
17.
Medicine (Baltimore) ; 95(32): e4440, 2016 Aug.
Article de Anglais | MEDLINE | ID: mdl-27512858

RÉSUMÉ

Anesthesia followed by placement in the prone position takes time and may result in complications. This study aimed to evaluate the feasibility of awake nasotracheal fiberoptic intubation and self-positioning followed by anesthesia induction in prone-positioned patients under general anesthesia.Sixty-two patients (ASA physical status I-II) scheduled for awake nasotracheal fiberoptic intubation and prone self-positioning before surgery under general anesthesia were selected. Patient preparation began with detailed preoperative counseling regarding the procedure. Premedication with sedative and antisialagogue was followed by airway anesthesia with topical lidocaine; then, awake nasotracheal fiberoptic intubation was carried out. The patients then positioned themselves comfortably before induction of general anesthesia. The changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), incidence of coughing or gagging, and rate pressure product (RPP) were assessed. Statistical analysis was performed with repeated-measures one-way analysis of variance.Fifty-eight of the 62 patients completed prone self-positioning smoothly. Compared with values before intubation, SBP, DBP, HR, and RPP were slightly increased after intubation, although the difference was not statistically significant (P > 0.05). One patient had moderate coughing and 1 patient had gagging during prone self-positioning, which were tolerable.These findings indicated that awake nasotracheal fiberoptic intubation and self-positioning followed by induction of anesthesia is safe and feasible alternative to routine prone positioning after induction of general anesthesia.


Sujet(s)
Anesthésie générale/méthodes , Intubation gastro-intestinale/méthodes , Positionnement du patient , Sujet âgé , Pression sanguine , Conscience , Toux/étiologie , Études de faisabilité , Femelle , Réflexe pharyngé , Rythme cardiaque , Humains , Mâle , Fibres optiques , Projets pilotes , Décubitus ventral
18.
Oncotarget ; 5(21): 10571-83, 2014 Nov 15.
Article de Anglais | MEDLINE | ID: mdl-25301735

RÉSUMÉ

SOX10 was identified as a methylated gene in our previous cancer methylome study. Here we further analyzed its epigenetic inactivation, biological functions and related cell signaling in digestive cancers (colorectal, gastric and esophageal cancers) in detail. SOX10 expression was decreased in multiple digestive cancer cell lines as well as primary tumors due to its promoter methylation. Pharmacologic or genetic demethylation reversed SOX10 silencing. Ectopic expression of SOX10 in SOX10-deficient cancer cells inhibits their proliferation, tumorigenicity, and metastatic potentials in vitro and in vivo. SOX10 also suppressed the epithelial to mesenchymal transition (EMT) and stemness properties of digestive tumor cells. Mechanistically, SOX10 competes with TCF4 to bind ß-catenin and transrepresses its downstream target genes via its own DNA-binding property. SOX10 mutations that disrupt the SOX10-ß-catenin interaction partially prevented tumor suppression. SOX10is thus a commonly inactivated tumor suppressor that antagonizes Wnt/ß-catenin signaling in cancer cells from different digestive tissues.


Sujet(s)
Mouvement cellulaire , Prolifération cellulaire , Tumeurs colorectales/prévention et contrôle , Tumeurs du foie/prévention et contrôle , Facteurs de transcription SOX-E/métabolisme , Protéines de type Wingless/métabolisme , bêta-Caténine/métabolisme , Animaux , Apoptose , Technique de Western , Adhérence cellulaire , Tumeurs colorectales/métabolisme , Tumeurs colorectales/anatomopathologie , Transition épithélio-mésenchymateuse , Technique d'immunofluorescence , Régulation de l'expression des gènes tumoraux , Gènes suppresseurs de tumeur , Humains , Techniques immunoenzymatiques , Tumeurs du foie/métabolisme , Tumeurs du foie/secondaire , Mâle , Mélanome/métabolisme , Mélanome/anatomopathologie , Mélanome/prévention et contrôle , Souris , Souris de lignée BALB C , Souris nude , ARN messager/génétique , Réaction de polymérisation en chaine en temps réel , RT-PCR , Facteurs de transcription SOX-E/génétique , Transduction du signal , Analyse sur puce à tissus , Cellules cancéreuses en culture , Protéines de type Wingless/génétique , Tests d'activité antitumorale sur modèle de xénogreffe , bêta-Caténine/génétique
19.
World J Gastroenterol ; 20(29): 10166-73, 2014 Aug 07.
Article de Anglais | MEDLINE | ID: mdl-25110445

RÉSUMÉ

AIM: To assess the clinical significance of pouch size in total gastrectomy for gastric malignancies. METHODS: We manually searched the English-language literature in PubMed, Cochrane Library, Web of Science and BIOSIS Previews up to October 31, 2013. Only randomized control trials comparing small pouch with large pouch in gastric reconstruction after total gastrectomy were eligible for inclusion. Two reviewers independently carried out the literature search, study selection, data extraction and quality assessment of included publications. Standard mean difference (SMD) or relative risk (RR) and corresponding 95%CI were calculated as summary measures of effects. RESULTS: Five RCTs published between 1996 and 2011 comparing small pouch formation with large pouch formation after total gastrectomy were included. Eating capacity per meal in patients with a small pouch was significantly higher than that in patients with a large pouch (SMD = 0.85, 95%CI: 0.25-1.44, I(2) = 0, P = 0.792), and the operative time spent in the small pouch group was significantly longer than that in the large pouch group [SMD = -3.87, 95%CI: -7.68-(-0.09), I (2) = 95.6%, P = 0]. There were no significant differences in body weight at 3 mo (SMD = 1.45, 95%CI: -4.24-7.15, I(2) = 97.7%, P = 0) or 12 mo (SMD = -1.34, 95%CI: -3.67-0.99, I(2) = 94.2%, P = 0) after gastrectomy, and no significant improvement of post-gastrectomy symptoms (heartburn, RR = 0.39, 95%CI: 0.12-1.29, I(2) = 0, P = 0.386; dysphagia, RR = 0.86, 95%CI: 0.58-1.27, I(2) = 0, P = 0.435; and vomiting, RR = 0.5, 95%CI: 0.15-1.62, I(2) = 0, P = 0.981) between the two groups. CONCLUSION: Small pouch can significantly improve the eating capacity per meal after surgery, and may improve the post-gastrectomy symptoms, including heartburn, dysphagia and vomiting.


Sujet(s)
Gastrectomie , , Tumeurs de l'estomac/chirurgie , Reconstructions chirurgicales , Consommation alimentaire , Comportement alimentaire , Gastrectomie/effets indésirables , Humains , Complications postopératoires/étiologie , /effets indésirables , Tumeurs de l'estomac/anatomopathologie , Reconstructions chirurgicales/effets indésirables , Résultat thérapeutique
20.
Article de Chinois | MEDLINE | ID: mdl-23687821

RÉSUMÉ

OBJECTIVE: To explore the sustainable development control strategies on soil-transmitted parasitic diseases appropriate to current epidemic characteristics so as to effectively reduce the epidemic level and harm to people in Shandong Province. METHODS: This project was led by the Shandong Medical Department, governed and instructed by the Shandong Institute of Parasitic Diseases, concretely implemented by the centers for disease control and prevention in counties or cities. All the work was carried out according to the Control Programming of National Key Parasitic Diseases, and with the combination of routine and key control strategies according to the actual situation. RESULTS: The average infection rate of soil-transmitted parasitic diseases in Shandong Province was 18.26% in 2003. During the 2007 to 2009 period, 3,115,194 people from 74 counties in 9 cities received anthelmintic medicine. The numbers receiving health education were 39 866 923 in county, 34,730,663 in city, 3,2000 in province, respectively. The coverage rate of non-hazardous sanitary latrines was 58.05%. In 2009, 6,581 people were surveyed from 7 counties or cities and the infection rate of soil-transmitted parasitic diseases was 7.61%. During three years, 30 provincial training classes were held and 2,130 people attended, 52 municipal classes were held and 3110 people attended, and 403 county classes were held and 12,789 people attended. In the whole province, the infection rate of soil-transmitted parasitic diseases reduced to 7.10% in 2009, with the reduction rate of 61.12%, reaching the national objective. CONCLUSIONS: The comprehensive control model for soil-transmitted parasitic diseases is very successful in Shandong Province.


Sujet(s)
Contrôle des maladies transmissibles/méthodes , Maladies parasitaires/prévention et contrôle , Maladies parasitaires/transmission , Sol/parasitologie , Animaux , Chine/épidémiologie , Contrôle des maladies transmissibles/statistiques et données numériques , Humains , Maladies parasitaires/épidémiologie
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