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1.
Chembiochem ; : e202400374, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38785030

RESUMO

Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi-targeting strategy to overcome drug resistance. Nonetheless, many in-cell catalysts in development are hindered by deactivation by endogenous nucleophiles. We have synthesised a highly potent, stable Os-based 16-electron half-sandwich ('piano stool') catalyst by introducing a permanent covalent tether between the arene and chelated diamine ligand. This catalyst exhibits antiproliferative activity comparable to the clinical drug cisplatin towards triple-negative breast cancer cells and can overcome tamoxifen resistance. Speciation experiments revealed Os to be almost exclusively albumin-bound in the extracellular medium, while cellular accumulation studies identified an energy-dependent, protein-mediated Os accumulation pathway, consistent with albumin-mediated uptake. Importantly, the tethered Os complex was active for in-cell transfer hydrogenation catalysis, initiated by co-administration of a non-toxic dose of sodium formate as a source of hydride, indicating that the Os catalyst is delivered to the cytosol of cancer cells intact. The mechanism of action involves the generation of reactive oxygen species (ROS), thus exploiting the inherent redox vulnerability of cancer cells, accompanied by selectivity for cancerous cells over non-tumorigenic cells.

2.
Anaesthesia ; 79(4): 399-409, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38093485

RESUMO

While videolaryngoscopy has resulted in better overall success rates of tracheal intubation, airway assessment is still an important prerequisite for safe airway management. This study aimed to create an artificial intelligence model to identify difficult videolaryngoscopy using a neural network. Baseline characteristics, medical history, bedside examination and seven facial images were included as predictor variables. ResNet-18 was introduced to recognise images and extract features. Different machine learning algorithms were utilised to develop predictive models. A videolaryngoscopy view of Cormack-Lehane grade of 1 or 2 was classified as 'non-difficult', while grade 3 or 4 was classified as 'difficult'. A total of 5849 patients were included, of whom 5335 had non-difficult and 514 had difficult videolaryngoscopy. The facial model (only including facial images) using the Light Gradient Boosting Machine algorithm showed the highest area under the curve (95%CI) of 0.779 (0.733-0.825) with a sensitivity (95%CI) of 0.757 (0.650-0.845) and specificity (95%CI) of 0.721 (0.626-0.794) in the test set. Compared with bedside examination and multivariate scores (El-Ganzouri and Wilson), the facial model had significantly higher predictive performance (p < 0.001). Artificial intelligence-based facial analysis is a feasible technique for predicting difficulty during videolaryngoscopy, and the model developed using neural networks has higher predictive performance than traditional methods.


Assuntos
Aprendizado Profundo , Laringoscópios , Humanos , Laringoscopia/métodos , Inteligência Artificial , Estudos de Viabilidade , Intubação Intratraqueal/métodos
3.
Public Health ; 231: 179-186, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703492

RESUMO

OBJECTIVES: We aimed to estimate the effects of temperature and total cloud cover before birth on newborn vitamin D status. STUDY DESIGN: Prospective birth cohort. METHODS: This study included 2055 mother-newborn pairs in Wuhan, Hubei province, China. The data of temperature and total cloud cover from 30 days before birth were collected, and cord blood 25-hydroxyvitamin D [25(OH)D] were determined. Restricted cubic spline regression models, multiple linear regression models, and logistic regression models were applied to estimate the associations. RESULTS: A "J" shaped curve was observed between temperature and vitamin D status, and an inverse "J" shaped curve was observed between total cloud cover and vitamin D status. Compared to the fourth quartile (75-100th percentile, Q4) of average temperature (30 days before birth), the odds ratio (OR) for Q1 (0-25th percentile) associated with the vitamin D deficiency occurrence (<20 ng/mL) was 3.63 (95% CI, 1.54, 8.65). Compared to Q1 of the average total cloud cover (30 days before birth), the OR associated with the occurrence of vitamin D deficiency was 2.38 (95% CI, 1.63, 3.50) for the Q4. CONCLUSIONS: Low temperature and high cloud cover before delivery were significantly associated with an increased probability of vitamin D deficiency in newborns. The findings suggested that pregnancy women lacking sufficient sunlight exposure still need vitamin D supplement to overcome the potential vitamin D deficiency status.


Assuntos
Temperatura , Deficiência de Vitamina D , Vitamina D , Humanos , Feminino , Gravidez , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Recém-Nascido , Vitamina D/sangue , Vitamina D/análogos & derivados , Estudos Prospectivos , China/epidemiologia , Adulto , Sangue Fetal/química , Masculino
4.
Zhonghua Yu Fang Yi Xue Za Zhi ; 58(6): 905-909, 2024 Jun 06.
Artigo em Zh | MEDLINE | ID: mdl-38955740

RESUMO

To investigate the status and epidemiological characteristics of respiratory pathogens infections in children with influenza-like illnesses (ILI) in Beijing Children's Hospital from 2022 to 2023. A dual amplification technique was used to detect nucleic acids of seven common respiratory pathogens, including influenza A virus (Flu A), influenza B virus (Flu B), mycoplasma pneumoniae (MP), respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus (ADV), and Chlamydia pneumoniae (CP), in outpatient and inpatient children (aged 0-18 years) with influenza-like symptoms who sought medical care at Beijing Children's Hospital, from January 2022 to March 2023. A total of 43 663 children were included in the study, of which 27 903 tested positive for respiratory pathogens with a total detection rate of 63.91%. Flu A had the highest detection rate of 69.93% (27 332/39 084), followed by MP about 13.22% (380/2 875). The total detection rate of RSV, PIV and ADV was 7.69% (131/1 704). Flu B had a detection rate of 0.16% (64/39 084). No CP was detected in this study. A total of 7 cases of dual infections were detected, with a detection rate of 0.41% (7/1 704). The Chi-square test was used to analyze the differences in detection rates of pathogens among different genders, age groups, and different seasons. Among the seven pathogens, only Flu A had statistically significant differences in gender (χ2=16.712, P<0.001). The detection rates of Flu A and MP showed an increasing trend with age (both P trend<0.001), while the detection rates of RSV and PIV showed a decreasing trend with age (both P trend<0.001). Flu A had its epidemic peak in winter and spring, with detection rates of 61.30% (3 907/6 374) and 77.47% (23 207/29 958) respectively; MP and PIV had higher detection rates in autumn (25.14% and 7.64% respectively); RSV showed a relatively higher detection rate in winter (8.69%); Flu B and ADV had lower detection rates throughout the study period (0.16% and 1.17% respectively). In conclusion, children with ILI in 2022-2023 were mainly infected with a single respiratory pathogen, and occasionally dual pathogen infections were observed. Among them, the detection rate of Flu A was the highest, and only Flu A showed a gender difference in detection rate. As the age of the children patients increased, the detection rate of Flu A and MP showed an increasing trend, while RSV and PIV showed a decreasing trend. The prevalence of Flu A, Flu B, MP, PIV, and RSV were seasonal.


Assuntos
Influenza Humana , Infecções Respiratórias , Humanos , Criança , Pré-Escolar , Lactente , Adolescente , Influenza Humana/epidemiologia , Masculino , Feminino , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Infecções Respiratórias/microbiologia , Pequim/epidemiologia , Vírus da Influenza B/isolamento & purificação , Vírus da Influenza A/isolamento & purificação , Mycoplasma pneumoniae/isolamento & purificação , Recém-Nascido , Vírus Sinciciais Respiratórios/isolamento & purificação , Hospitais Pediátricos , Chlamydophila pneumoniae/isolamento & purificação , Infecções por Vírus Respiratório Sincicial/epidemiologia , China/epidemiologia , Adenoviridae/isolamento & purificação
5.
Zhonghua Yi Xue Za Zhi ; 103(8): 585-593, 2023 Feb 28.
Artigo em Zh | MEDLINE | ID: mdl-36822870

RESUMO

Objectives: To investigate the associations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) gene polymorphism and plasma soluble TRAIL level (sTRAIL) with Crohn's disease (CD) and to retrospectively analyze the effects of TRAIL gene variants and plasma sTRAIL levels on clinical response to infliximab (IFX). Methods: From January 2012 to January 2021, 312 CD patients [205 males, 107 females, average age (33.9±9.8) years] and 514 age-and gender-matched healthy controls [304 males, 210 females, average age (34.9±9.4) years] were recruited from the Department of Gastroenterology, the Second Affiliated Hospital of Wenzhou Medical University. Among them, 72 patients with active CD who were ineffective or intolerant to traditional drug therapy regularly received IFX (5 mg/kg) treatment. According to the changes in the Harvey-Bradshaw index (HBI) and the Simplified Endoscopic Score for Crohn's Disease (SES-CD) in the 14th week, these patients were classified into response group (a decrease in HBI≥3 or a decrease in SES-CD≥50%) and non-response group. TRAIL (rs1131568) gene polymorphism was analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry technique. The plasma sTRAIL level was examined by enzyme-linked immunosorbent assay (ELISA). Based on the Montreal CD classification criteria, all CD patients were divided into different subgroups. Finally, a comprehensive analysis was performed to investigate the relationship between TRAIL (rs1131568) gene polymorphism, the plasma sTRAIL level and the risk of CD, the clinicopathological characteristics of CD patients, and the clinical response to IFX. Results: The recessive model analysis showed that the homozygous variant genotype (CC) was more prevalent in patients with moderately to severely active CD than in those with mildly active CD (45.34% vs 29.23%, P=0.005). Both variant allele (C) and homozygous variant genotype (CC) in patients with stricturing and penetrating CD were more frequent than those in patients with non-stricturing and non-penetrating CD (65.48% vs 57.53%, P=0.046; 49.21% vs 31.18%, P=0.001). The dominant model analysis showed that variant allele (C) and variant genotype (TC+CC) was higher in CD patients with perianal lesions than in those without perianal lesions (66.83% vs 58.17%, P=0.037; 92.31% vs 78.37%, P=0.002). The average plasma sTRAIL level was higher in CD patients than in healthy controls [(243.04±42.74) ng/L vs (194.16±31.14) ng/L, P<0.001]. Compared with the patients with mildly active CD, the plasma sTRAIL level was increased in those with moderately to severely active CD [263.47(242.09, 281.91) ng/L vs 231.13(211.11, 247.11) ng/L, P<0.001]. The same conclusion was also drawn for the patients with stricturing and penetrating CD in contrast to those with non-stricturing and non-penetrating CD [266.18 (246.68, 289.91) ng/L vs 227.19 (204.57, 249.59) ng/L, P<0.001]. The plasma sTRAIL level was also higher in patients with perianal disease than in those without perianal disease [(261.40±41.51) ng/L vs (233.86±40.41) ng/L, P<0.001]. Multiple linear regression analysis further showed that disease activity (ß=22.640, P<0.001) and homozygous variant genotype (CC) (ß=16.814, P<0.001) may be positively related to the plasma sTRAIL level in CD patients independently. At the 14th week of IFX treatment, the plasma sTRAIL level in the response group was lower than that in the non-response group [205.98(190.72, 214.56) ng/L vs (238.33±29.38) ng/L, P<0.001]. Compared with week 0, the plasma sTRAIL level was decreased in the response group in the 14th week [(205.98 (190.72, 214.56) ng/L vs (239.89±42.43) ng/L, P<0.001]. Non-conditional logistic regression analysis showed that variant allele (C) and variant genotype (TC+CC) were less frequent in the response group than in the non-response group (53.33% vs 70.83%, P=0.037; 70.00% vs 91.67%, P=0.036). Conclusions: The increased plasma sTRAIL level may be a risk factor for CD. TRAIL (rs1131568) gene variation and the increase of plasma sTRAIL level may be associated with the increased disease activity of CD and may be the risk factors for stenosis, penetration, and perianal lesions in CD patients. In addition, TRAIL (rs1131568) gene variation or the increase of plasma sTRAIL level may be related to no response to IFX treatment in CD patients.


Assuntos
Doença de Crohn , Ligante Indutor de Apoptose Relacionado a TNF , Feminino , Humanos , Masculino , Doença de Crohn/genética , Ligantes , Fenótipo , Polimorfismo Genético , Estudos Retrospectivos , Adulto Jovem , Adulto , Ligante Indutor de Apoptose Relacionado a TNF/genética
6.
Zhonghua Yi Xue Za Zhi ; 103(21): 1643-1648, 2023 Jun 06.
Artigo em Zh | MEDLINE | ID: mdl-37248065

RESUMO

Objective: To investigate the endoscopic ultrasonographic (EUS) characteristics of submucosal lesions of upper digestive tract suspected gastrointestinal stromal tumors (GIST) and their correlation with biological behaviors and pathological risk grade of the tumors. Methods: Retrospective cohort study. The EUS findings, follow-up review, surgical treatment and pathological data of patients with suspected GIST at the Gastrointestinal Endoscopy Center of Peking University People's Hospital from January 2013 to April 2021 were collected. All samples were divided into follow-up group and treatment group based on the pathological condition and the patient's treatment intention. According to whether or not the tumor was enlarged in EUS, the follow-up group was divided into non-enlarged group and enlarged group. Paired T-test was used to compare the lesion size before and after follow-up, and logistic regression was used to analyze the risk factors of tumor enlargement. According to the treatment methods, the treatment group was further divided into endoscopic treatment group and surgical treatment group. According to the pathological results and risk grade, the treatment group was further divided into the low-risk group and the medium-risk group. The risk factors of pathological malignant risk were analyzed by logistic regression, and the tumor diameter of patients with moderate or above pathological risk was predicted by receiver operation characteristic (ROC) curve. The relationship between the findings of EUS and the progression and pathological risk of GIST were also explored. Results: Seventy-three cases including 23 males and 50 females, with an age of 58 (30-88) years, were included in the follow-up group, with a mean lesion diameter of (1.21±0.49) cm before follow-up, median follow-up interval of 33.8 months, and a lesion diameter of (1.18±0.49) cm after follow-up. There was no significant difference (all P>0.05) in lesion diameter between before and after follow-up. There was no significant difference (all P>0.05) between tumor enlargement group (18 cases, 24.7%) and non-enlargement group (55 cases, 75.3%). One hundred and thirty-eight cases, including 52 males and 86 females, with an age of 60 (19-84) years, were enrolled in the treatment group, with a mean EUS estimated diameter of (2.55±1.35) cm and pathological diameters of (3.43±2.42) cm. Ninety-five (68.8%) of these cases were pathologically confirmed as GIST while 43 cases were diagnosed as other tumor types, including 37 benign tumors and 6 malignant tumors. In multifactorial logistic regression analysis, only the increase of tumor diameter [OR (95%CI): 1.800 (1.172-2.766), P=0.007] was a risk factor for pathological intermediate or higher risk. The optimal tumor diameter for predicting pathological intermediate or higher risk using ROC curve analysis was 2.75 cm, with a sensitivity 71.4%, specificity 79.0%, Youden index 0.5 and area under ROC curve 0.807 (95%CI: 0.703-0.909). Conclusions: EUS is essential for assessing the risk of progression and malignancy of submucosal lesions of upper digestive tract suspected GIST. For lesions of small diameter, the interval of follow-up shall be relatively extended while the indication of treatment could be partially waived.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Endoscopia , Endossonografia/métodos , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/cirurgia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/cirurgia , Adulto
7.
Bull Exp Biol Med ; 176(1): 19-25, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38087140

RESUMO

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet ß cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic ß cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-ß1, TNFα, and IL-1ß. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Animais , Camundongos , Quinase 5 Dependente de Ciclina/genética , Quinase 5 Dependente de Ciclina/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose/toxicidade , Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Camundongos Endogâmicos C57BL , Peptídeos/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia
8.
Zhonghua Wai Ke Za Zhi ; 61(6): 467-473, 2023 Jun 01.
Artigo em Zh | MEDLINE | ID: mdl-37088478

RESUMO

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignant tumor in the liver after hepatocellular carcinoma. Its incidence and mortality rates have increased worldwide in recent years. Surgical resection is the best treatment modality for ICC;however,the overall prognosis remains poor. Accurate evaluation of post operative prognosis allows personalized treatment and improved long-term outcomes of ICC. The American Joint Commission on Cancer TNM staging manual is the basis for the standardized diagnosis and treatment of ICC;however,the contents of stage T and stage N need to be improved. The nomogram model or scoring system established in the analysis of commonly used clinicopathological parameters can provide individualized prognostic evaluation and improve prediction accuracy;however,more studies are needed to validate the results before clinical use. Meanwhile,imaging features exhibit great potential to establish the post operative prognosis evaluation system for ICC. Molecular-based classification provides an accurate guarantee for prognostic assessment as well as selection of populations that are sensitive to targeted therapy or immunotherapy. Therefore,the establishment of a prognosis evaluation system,based on clinical and pathological characteristics and centered on the combination of multidisciplinary and multi-omics,will be conducive to improving the long-term outcomes of ICC after surgical resection in the context of big medical data.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias Hepáticas , Humanos , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Prognóstico , Neoplasias Hepáticas/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia
9.
Zhonghua Wai Ke Za Zhi ; 61(1): 61-65, 2023 Jan 01.
Artigo em Zh | MEDLINE | ID: mdl-36603886

RESUMO

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.


Assuntos
Neoplasias Encefálicas , Robótica , Masculino , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Imagem de Tensor de Difusão , Estudos Retrospectivos , Biópsia , Software , Técnicas Estereotáxicas
10.
Zhonghua Wai Ke Za Zhi ; 62(1): 58-65, 2023 Dec 01.
Artigo em Zh | MEDLINE | ID: mdl-38044609

RESUMO

Objective: To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer. Methods: This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery,Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher's exact test. Results: A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant (χ2 value were 156.24, 4.08, 36.56, P value were<0.01, 0.043,<0.01). Conclusion: Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

11.
Osteoarthritis Cartilage ; 30(11): 1455-1467, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36041665

RESUMO

OBJECTIVE: Extracellular vesicles released by mesenchymal stem cells (MSC-EVs) can be applied to alleviate intervertebral disc degeneration (IVDD) by curbing apoptosis of nucleus pulposus cells (NPCs). The current study aims to evaluate the effect of MSC-EVs on NPC apoptosis and IVDD and the related regulatory mechanisms involving microRNA (miR)-217. METHOD: Expression of miR-217 was examined in tumor necrosis factor-α (TNF-α)-induced NPCs and MSC-EVs, followed by identification in the relationship between miR-217, enhancer of zeste homolog 2 (EZH2) and forkhead box O-3 (FOXO3). After isolation of EVs from MSCs and subsequent co-culture with NPCs, we assessed effects of miR-217 on NPC viability, autophagy, senescence and apoptosis along with extracellular matrix (ECM) degradation. Further in vivo experiments were conducted in rat models of IVDD to substantiate the effect of miR-217 on IVDD. RESULTS: Poor miR-217 expression was found in TNF-α-induced NPCs, while high miR-217 expression was identified in MSC-EVs (P < 0.05). MSC-EVs transferred miR-217 to NPCs and increased its expression, thus attenuating NPC apoptosis and ECM degradation (elevated collagen II and aggrecan but reduced MMP13 and ADAMTS5) (P < 0.05). miR-217 targeted EZH2, and EZH2 bound to the FOXO3 promoter and consequently downregulated its expression. FOXO3 restrained NPC apoptosis and ECM degradation by stimulating cell autophagy (P < 0.05). Furthermore, in vivo experimental results confirmed the suppressive role of miR-217 shuttled by MSC-EVs in IVDD. CONCLUSION: Overall, the delivery of miR-217 may be a novel mechanism underlying the effect of MSC-EVs on NPC apoptosis and ECM degradation following IVDD.


Assuntos
Vesículas Extracelulares , Degeneração do Disco Intervertebral , Células-Tronco Mesenquimais , MicroRNAs , Núcleo Pulposo , Animais , Ratos , Agrecanas/metabolismo , Apoptose , Colágeno/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/prevenção & controle , Metaloproteinase 13 da Matriz/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/metabolismo , Núcleo Pulposo/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Zhonghua Nei Ke Za Zhi ; 61(7): 785-792, 2022 Jul 01.
Artigo em Zh | MEDLINE | ID: mdl-35764562

RESUMO

Objective: To analyze the influence of vitamin D3 supplementation on the clinical efficacy of mesalazine in patients with ulcerative colitis (UC). Methods: From January 2015 to December 2020, patients with mild-to-moderate active UC were retrospectively and continuously enrolled, who accepted mesalazine treatment for at least 12 months at the Second Affiliated Hospital of Wenzhou Medical University. According to simultaneous supplement of vitamin D3 (125 IU/d), the patients were divided into study group and control group. Demographic and disease characteristics, serum 25-hydroxyvitamin D[25(OH)D] levels and other information were collected through retrieving hospital database. Student's t-test, Mann-Whitney U test and Chi-square test were applied for comparison of disease characteristics. The changes of modified Mayo scores[ΔMayo] and 25(OH)D[Δ25(OH)D] were compared before and after treatment by paired t-test, Wilcoxon signed rank test and Chi-square test. Multiple linear regression model was used to analyze the independent factors affecting ΔMayo and Δ25(OH)D, and variables with P-values less than 0.20 in the univariate analysis were allowed for further multivariate analysis. Results: A total of 74 UC patients (44 males, 30 females), with median age (range) 39.5 (20-76) years old, were analyzed and respectively assigned into study group (n=36) and control group (n=38). In study group, the average level of serum 25(OH)D was significantly increased at month 12 compared with that at baseline [(22.87±7.30) µg/L vs. (18.15±7.48) µg/L,P<0.001]. However, no significant elevation of serum 25(OH)D was found in control group [(19.17±8.49) µg/L vs. (19.82±9.47) µg/L,P=0.466]. Furthermore, there was a significant decrease of modified Mayo score [-3(-4.75, -1.25) vs.-2(-3.25, 0), P=0.034] and a higher clinical remission rate (55.6% vs. 28.9%, P=0.020) at month 12 in study group than those in control group. In addition, according to the baseline level of serum 25(OH)D before mesalazine treatment, 74 UC patients were divided into vitamin D deficiency group (n=38, serum 25(OH)D<20 µg/L) and non-deficiency group (n=36, serum 25(OH)D≥20 µg/L). At month 12 in vitamin D deficiency group, patients with vitamin D3 supplementation had a greater decline in modified Mayo score [-4(-5.75, -2) vs.-2(-4, 0), P=0.048] and a higher clinical remission rate (60.0% vs. 22.2%, P=0.019) compared with those without. Conclusions: In patients with mild-to-moderate active UC receiving mesalazine treatment, vitamin D3 supplementation may improve the clinical efficacy, especially in patients with vitamin D deficiency.


Assuntos
Colite Ulcerativa , Deficiência de Vitamina D , Adulto , Colecalciferol/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Feminino , Humanos , Masculino , Mesalamina/uso terapêutico , Estudos Retrospectivos , Vitamina D/uso terapêutico , Deficiência de Vitamina D/tratamento farmacológico
13.
Rev Med Liege ; 77(10): 549-550, 2022 Oct.
Artigo em Francês | MEDLINE | ID: mdl-36226389

RESUMO

Mucinous nevus is an exceptional entity and presents as flesh-colored to brownish papules or plaques, coalescing to form a pigmentary or verrucous lesion with either a blaschkoid, linear, grouped or zosteriform disposition. It usually appears at birth or during early childhood, but late onset has also been described. Mucinous nevus does not require additional work-up as no internal pathologies have been described. Abstention of any therapeutic intervention is usually preferred.


: Le naevus mucineux est une entité exceptionnelle, se présentant par des papules ou des plaques de couleur chair à brunâtre qui confluent sous la forme d'une lésion pigmentaire ou verruqueuse de distribution blaschkoïde, linéaire, groupée ou zostériforme. Il est le plus souvent congénital ou d'apparition précoce, mais des formes tardives ont également été rapportées. Le naevus mucineux n'est jamais associé à une pathologie interne et ne nécessite pas d'exploration complémentaire. Au vu du caractère bénin, l'abstention thérapeutique est généralement la règle.


Assuntos
Nevo , Anormalidades da Pele , Neoplasias Cutâneas , Pré-Escolar , Humanos , Recém-Nascido , Nevo/diagnóstico , Nevo/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
14.
Zhonghua Jie He He Hu Xi Za Zhi ; 45(10): 1015-1021, 2022 Oct 12.
Artigo em Zh | MEDLINE | ID: mdl-36207958

RESUMO

Objective: To investigate the clinical characteristics and outcomes of acute respiratory distress syndrome (ARDS) caused by Chlamydia psittaci pneumonia. Methods: From June 2016 to January 2021, 10 cases were diagnosed as severe Chlamydia psittaci pneumonia induced ARDS in Intensive Care Unit of Respiratory and Critical Care Medicine Department (RICU) of Beijing Chao-Yang Hospital Affiliated to Capital Medical University. We collected the clinical data including clinical features, laboratory tests, imaging and outcomes of the patients. Results: The pathogenic diagnosis was confirmed by metagenomic Next-generation Sequencing (mNGS) in these 10 patients, with a median age of 59 (46, 67) years. In addition to high fever, cough and dyspnea, the patients also had multiple organ involvement. Six patients had elevated peripheral leukocyte count, 10 cases had increased type B natriuretic peptide, 7 cases had increased aspartate aminotransferase/alanine aminotransferase, 9 cases had hyponatremia and 3 cases had elevated creatinine. The imaging findings were bilateral consolidation with air bronchogram and infiltrates, and pleural effusion were found in 5 cases. All cases were combined with respiratory failure. Six patients received invasive mechanical ventilation. Nine patients received moxifloxacin and one patient was administrated with Azithromycin. All the patients were improved and discharged after the treatment, and the mean duration of RICU stay was 13.5 (11, 16.7) days. One month follow-up of nine patients showed significant improvement in lung lesions. Conclusions: Severe Chlamydia psittiaci pneumonia may be complicated with respiratory failure and/or multiple organ involvement. For severe pneumonia with an exposure history of sick birds, the possibility of Chlamydia psittaci infection should be considered. mNGS may help etiological diagnosis. All patients in this study had a good prognosis after targeted treatment.


Assuntos
Chlamydophila psittaci , Pneumonia , Síndrome do Desconforto Respiratório , Insuficiência Respiratória , Idoso , Alanina Transaminase , Aspartato Aminotransferases , Azitromicina , Creatinina , Humanos , Pessoa de Meia-Idade , Moxifloxacina , Peptídeo Natriurético Encefálico , Síndrome do Desconforto Respiratório/terapia
15.
Zhonghua Wai Ke Za Zhi ; 60(2): 148-153, 2022 Feb 01.
Artigo em Zh | MEDLINE | ID: mdl-35012274

RESUMO

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.


Assuntos
Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Colectomia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Masculino , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
16.
Tijdschr Psychiatr ; 64(2): 94-100, 2022.
Artigo em Holandês | MEDLINE | ID: mdl-35420152

RESUMO

BACKGROUND: Leukemia is the most common pediatric malignancy. Acute lymphoblastic leukemia (ALL) is the most commonly observed subtype. AIM: To assess cognitive functioning in children and adolescents with ALL post-treatment: chemotherapy-only (CT-only) or in combination with radiation therapy (CTRT). METHODS We searched in PubMed and PsycINFO (OvidSP). Relevant data were analyzed using statistical program Comprehensive Meta-Analysis (version 2). RESULTS: 44 studies were included in the overall meta-analysis with a total of 5059 patients. A weighted mean IQ of 100.1 (95% CI 99.1-101.0) was found overall after ALL treatment. In subanalyses, we found for CT-only a weighted mean IQ of 100.7 (95% CI: 99.5-101.9) and for CTRT-treatment a weighted mean IQ of 98.2 (95%100.7 (95% CI: 96.3-100.3). There was no significant difference from the normative control (mean: 100.0; SD: 15). CONCLUSION: No significant cognitive sequelae were shown in childhood survivors of leukemia who were exposed to either CT-only or CTRT therapy. Prospective studies are needed with inclusion of pre-and post-treatment IQ measurements, ideally compared to age and socio-economic status matched control groups.


Assuntos
Transtornos Cognitivos , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Cognição , Humanos , Inteligência , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Sobreviventes
17.
Plant J ; 104(5): 1382-1398, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33048402

RESUMO

Plants cannot fix nitrogen directly; they must absorb it from the soil through their roots, or in rare cases, form associations with nitrogen-fixing bacteria. The efficiency of nitrogen use in most domesticated crops is low, and more than half of the available nitrogen in the soil can leach into the environment. Understanding the nitrogen signaling pathways is essential for maximizing the efficiency of nitrogen use in crops. In the present study, we characterized the Myeloblastosis (Myb)-like gene NITROGEN RESPONSE DEFICIENCY 1 (NID1). We observed that the growth performance of nid1 knockout (KO) mutant Arabidopsis plants was better than that of wild-type Col-0 plants under very low-nitrate conditions, leading to improved growth performance in the nid1 KO plants. The results of chromatin immunoprecipitation and electrophoretic mobility shift assays indicated that NID1 binds to the promoter of the NITRATE TRANSPORTER (NRT)1.1 gene. Furthermore, nid1 KO plants exhibited similar growth performance to the nid1 KO/chl1-5 (nrt1.1 KO) double mutant and chl1-5 (nrt1.1 KO) plants in response to low-nitrate conditions. We suggest that NID1 plays a crucial role as a transcription factor in optimizing plant growth by modulating the transcript abundance of the nitrate transceptor CHL1, leading to enhanced ABA accumulation in low-nitrate conditions.


Assuntos
Proteínas de Transporte de Ânions/genética , Arabidopsis/crescimento & desenvolvimento , Nitratos/metabolismo , Proteínas de Plantas/genética , Ácido Abscísico/metabolismo , Proteínas de Transporte de Ânions/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Mutação , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
18.
Phys Rev Lett ; 126(24): 242301, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213947

RESUMO

Using combined data from the Relativistic Heavy Ion and Large Hadron Colliders, we constrain the shear and bulk viscosities of quark-gluon plasma (QGP) at temperatures of ∼150-350 MeV. We use Bayesian inference to translate experimental and theoretical uncertainties into probabilistic constraints for the viscosities. With Bayesian model averaging we propagate an estimate of the model uncertainty generated by the transition from hydrodynamics to hadron transport in the plasma's final evolution stage, providing the most reliable phenomenological constraints to date on the QGP viscosities.

19.
J Dairy Sci ; 104(7): 8177-8187, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33865591

RESUMO

Left displaced abomasum (LDA) leads to substantial changes in the metabolism of dairy cows. Surgical correction of LDA can rapidly improve the health of cows; however, changes in metabolism following surgery are rarely described. To investigate the changes of plasma metabolome in cows with LDA before and after surgical correction, blood samples were collected from 10 healthy postpartum cows and 10 cows with LDA on the day of diagnosis, then again from the LDA cows 14 d after surgery. Serum nonesterified fatty acid, ß-hydroxybutyric acid, cortisol and histamine concentration, and antioxidant enzyme (superoxide dismutase and glutathione peroxidase) activities were evaluated, and the metabolic profile in plasma was analyzed using ultra-high-performance liquid chromatography time-of-flight mass spectrometry. The results demonstrated that cows with LDA experienced severe negative energy balance and oxidative stress, which can be improved by surgical correction. The metabolic profile was analyzed using multidimensional and univariate statistical analyses, and different metabolites were identified. In total, 102 metabolites differed between cows with LDA and healthy cows. After surgical correction, 65 metabolites changed in cows with LDA, compared with these cows during the LDA event. Following surgical correction, AA levels tended to increase, and lipid levels tended to decrease in cows with LDA. Pathway analysis indicated marked changes in linoleic acid metabolism, Arg biosynthesis, and Gly, Ser, and Thr metabolism in cows at the onset of LDA and following surgical correction. Surgical treatment reversed the changes in AA and lipid metabolism in cows with LDA.


Assuntos
Doenças dos Bovinos , Gastropatias , Ácido 3-Hidroxibutírico , Abomaso/cirurgia , Animais , Bovinos , Doenças dos Bovinos/cirurgia , Feminino , Metaboloma , Gastropatias/cirurgia , Gastropatias/veterinária
20.
Public Health ; 199: 34-41, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34534888

RESUMO

OBJECTIVES: Simple reaction time (SRT) and choice reaction time (CRT) have been shown to be good indicators for quantitatively assessing the level of human cognitive impairment, but these parameters have also been linked to the risk of human death. This study aimed to quantitatively assess the independent predictive value of SRT or CRT for all-cause mortality or cardiovascular disease (CVD) mortality by conducting a meta-analysis of prospective studies. STUDY DESIGN: The study design of this study is a prospective cohort study. METHODS: We conducted a meta-analysis by combining hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SRT or CRT with all-cause mortality or CVD mortality in healthy community residents aged 18 and over. Heterogeneity was evaluated by using Q statistics and Cochrane's I2 statistics. RESULTS: A total of seven prospective studies that examined all-cause mortality and CVD mortality were included. The pooled HR of all-cause mortality in SRT was 1.099 (1.065-1.134, I2 = 11.9%), and an increased risk of CVD mortality was associated with lower SRT (HR = 1.186, 95% CI = 1.137-1.236; I2 = 52.4%). Similarly, the pooled HR of all-cause mortality in CRT was 1.140 (95% CI = 1.085-1.197, I2 = 33.7%). However, lower CRT was not statistically associated with an increased risk of CVD mortality. CONCLUSION: SRT may be a predictor of all-cause-mortality and CVD mortality, and CRT is significantly associated with an increased risk of all-cause mortality.


Assuntos
Doenças Cardiovasculares , Adolescente , Adulto , Causas de Morte , Nível de Saúde , Humanos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Tempo de Reação , Fatores de Risco
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