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1.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1021197

RESUMEN

BACKGROUND:Studies have shown that atorvastatin can up-regulate the expression of heme oxygenase-1 and enhance the anti-inflammation and anti-oxidative damage ability of cells.However,whether atorvastatin can regulate macrophage polarization,inhibit inflammation and reduce cholesterol accumulation by inducing heme oxygenase-1 expression remains unclear. OBJECTIVE:To investigate the effect of atorvastatin on polarization,inflammation and cholesterol content of oxidized low-density lipoprotein stimulated RAW264.7 macrophages by inducing heme oxygenase-1 expression and its related mechanism. METHODS:Firstly,RAW264.7 cells were randomly divided into six groups and incubated with different concentrations of atorvastatin for 24 hours.The expression of heme oxygenase-1 protein and cell activity were detected to explore the optimal dose of atorvastatin for subsequent studies.RAW264.7 cells were randomly divided into control group,atorvastatin group and heme oxygenase-1 inhibition group.Cells were preincubated with pure medium,atorvastatin 20 μmol/L and atorvastatin 20 μmol/L + zinc protoporphyrin IX 10 μmol/L for 24 hours,and then oxidized low-density lipoprotein 50 mg/L was added for 48 hours.The polarization of macrophages was detected by flow cytometry.The secretion of inflammatory factors such as transforming growth factor β,interleukin 10,interleukin 1β,and tumor necrosis factor α was detected by ELISA.The expression levels of heme oxygenase-1,LC3II,LC3I,P62,PPARγ and ABCA1 were detected by western blot assay.The intracellular cholesterol content was measured with the oxidose method and the accumulation degree of intracellular lipid droplets was evaluated by oil red O staining. RESULTS AND CONCLUSION:(1)Atorvastatin could induce the expression of heme oxygenase-1 protein in macrophages in a dose-dependent manner.(2)Oxidized low-density lipoprotein could induce macrophages to polarize towards M1,secrete proinflammatory factors,and increase the accumulation of intracellular cholesterol.(3)Compared with the control group,the heme oxygenase-1 protein expression of macrophages was increased after atorvastatin intervention,and the cells turned to M2-type polarization and mainly secreted anti-inflammatory factors such as transforming growth factor-β and interleukin-10.PPARγ,ABCA1,LC3II/I and other signal molecules reflecting cholesterol efflux and autophagy increased,and the contents of intracellular cholesterol and lipid droplets decreased significantly(P<0.05).(4)The heme oxygenase-1 inhibition group treated with zinc protoporphyrin IX significantly reversed the above changes in the atorvastatin group.(5)The results have shown that atorvastatin may promote the polarization of macrophages stimulated by oxidized low-density lipoprotein to M2 type and inhibit inflammation by up-regulating the expression of heme oxygenase-1 and by up-regulating PPARγ/ABCA1 signaling pathway and enhancing autophagy.Atorvastatin can increase the outflow of intracellular cholesterol and reduce the accumulation of intracellular lipids.

2.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-1039025

RESUMEN

ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.

3.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-990343

RESUMEN

Objective:To summarize the best evidence of thirst management in ICU patients and provide evidence-based basis for dinical practice.Method:According to the "6S" evidence pyramid model, the literature on thirst management of ICU patients was systematically retrieved from relevant guidelines websites, evidence-based databases, association websites and original literature databases at home and abroad. The retrieval time was from the establishment of the database to June 31, 2022. Two researchers with evidence-based nursing training independently completed literature quality evaluation. To extract and summarize the evidence of the literature that meets the quality standard.Results:A total of 17 articles were included, including 8 randomized controlled trials, 5 quasi-experimental studies and 4 cross-sectional studies. The 18 pieces of best evidence were formed, including 5 aspects: basic requirements of thirst management, intervention evaluation, intervention methods, matters needing attention and health education.Conclusions:This study summarized the best evidence of thirst management in ICU patients. Nurses should translate and apply the best evidence in combination with the clinical situation and specific policies of the department to relieve the thirst symptoms of ICU patients.

4.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-996122

RESUMEN

Objective: To investigate the effects of herbal cake-partitioned moxibustion on the plasma levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and flavin-containing monooxygenase 3 (FMO3) in rabbits with atherosclerosis (AS), as well as to explore the possible mechanism of herbal cake-partitioned moxibustion in treating AS. Methods: After 1-week adaptive feeding, 28 male New Zealand rabbits were divided into a blank group, a model group, an antibiotic group, and a herbal cake-partitioned moxibustion group according to the random number table method, with 7 rabbits in each group. Rabbits were fed with a basic diet in the blank group, while with a basic diet plus 1% choline in the remaining groups to prepare the AS model. Rabbits were given drinking water with broad-spectrum antibiotics in the antibiotic group, and herbal cake-partitioned moxibustion in the herbal cake-partitioned moxibustion group for 12 weeks. The atherosclerotic plaques by hematoxylin-eosin (HE) staining, the blood lipid levels, the plasma TMA and TMAO levels by liquid chromatography-mass spectrometry were detected for rabbits in each group at the end of interventions. Liver FMO3 protein expression was detected by Western blotting. Liver FMO3 mRNA expression was detected by real-time fluorescence quantitative polymerase chain reaction. Results: HE staining showed that the arterial wall was rough, the intima was significantly thickened, and more foam cells and lipid deposits were seen in rabbits of the model group. Arterial wall thickening was not obvious with a few foam cells and lipid deposits in the herbal cake-partitioned moxibustion group. Compared with the blank group, the serum levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were increased (P<0.01), the plasma levels of TMA and TMAO were increased (P<0.05, P<0.01), and the expression levels of liver FMO3 protein and mRNA were all increased (P<0.05, P<0.01); while the serum high-density lipoprotein cholesterol (HDL-C) level was decreased in the model group (P<0.05). Compared with the model group, the LDL-C and TC levels were decreased (P<0.01 or P<0.05), the HDL-C levels were increased (P<0.01), the TMA and TMAO levels were decreased (P<0.05), while the protein and mRNA expression levels of FMO3 were decreased without statistical significance in the herbal cake-partitioned moxibustion group and the antibiotic group. Conclusion: Herbal cake-partitioned moxibustion can slow atherosclerotic plaque formation and regulate lipid levels in AS rabbits, and the mechanism may be related to the down-regulation of TMA and TMAO expression in the plasma.

5.
Acta Pharmaceutica Sinica B ; (6): 2976-2989, 2023.
Artículo en Inglés | WPRIM (Pacífico Occidental) | ID: wpr-982894

RESUMEN

Osteoarthritis (OA) is one of the most common chronic diseases in the world. However, current treatment modalities mainly relieve pain and inhibit cartilage degradation, but do not promote cartilage regeneration. In this study, we show that G protein-coupled receptor class C group 5 member B (GPRC5B), an orphan G-protein-couple receptor, not only inhibits cartilage degradation, but also increases cartilage regeneration and thereby is protective against OA. We observed that Gprc5b deficient chondrocytes had an upregulation of cartilage catabolic gene expression, along with downregulation of anabolic genes in vitro. Furthermore, mice deficient in Gprc5b displayed a more severe OA phenotype in the destabilization of the medial meniscus (DMM) induced OA mouse model, with upregulation of cartilage catabolic factors and downregulation of anabolic factors, consistent with our in vitro findings. Overexpression of Gprc5b by lentiviral vectors alleviated the cartilage degeneration in DMM-induced OA mouse model by inhibiting cartilage degradation and promoting regeneration. We also assessed the molecular mechanisms downstream of Gprc5b that may mediate these observed effects and identify the role of protein kinase B (AKT)-mammalian target of rapamycin (mTOR)-autophagy signaling pathway. Thus, we demonstrate an integral role of GPRC5B in OA pathogenesis, and activation of GPRC5B has the potential in preventing the progression of OA.

6.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-981967

RESUMEN

OBJECTIVES@#To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis.@*METHODS@#The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB.@*RESULTS@#A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%.@*CONCLUSIONS@#The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.


Asunto(s)
Lactante , Niño , Humanos , Broncoscopía/métodos , Constricción Patológica/complicaciones , Enfermedades Bronquiales/terapia , Estudios Retrospectivos , Tuberculosis/diagnóstico , Obstrucción de las Vías Aéreas/terapia
7.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-982004

RESUMEN

OBJECTIVES@#To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB.@*METHODS@#This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed.@*RESULTS@#A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05).@*CONCLUSIONS@#Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.


Asunto(s)
Femenino , Masculino , Niño , Humanos , Preescolar , Insuficiencia Multiorgánica , Estudios Retrospectivos , Bronquitis/etiología , Disnea , Derrame Pleural , Atelectasia Pulmonar , Plásticos , Insuficiencia Respiratoria
8.
Chinese Journal of Pediatrics ; (12): 719-725, 2023.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013161

RESUMEN

Objective: To investigate the risk factors for airway mucus hypersecretion in childhood pneumonia infected by different pathogens. Method: A retrospective cohort included 968 children who were hospitalized for Mycoplasma pneumoniae pneumonia (MPP), respiratory syncytial virus (RSV) pneumonia, adenovirus pneumonia and underwent bronchoscopy in Respiratory Department of Children's Hospital of Chongqing Medical University from January 2019 to December 2021 was conducted. The children were divided into two groups distinguished by airway mucus secretion according to the airway mucus hypersecretion score which were scored according to the mucus secretion under the bronchoscope. The demographic characteristics, clinical characteristics, laboratory tests and disease severity of the two groups were compared. And the risk factors for the development of airway mucus hypersecretion in two groups were analyzed. Chi square test, Mann-Whithey U test and Fisher exact test were used to analyze the differences between the two groups, and multivariate Logistic regression was used to analyze the influencing factors. Result: There were 559 males and 409 females in the 968 children, with an age of 4.0 (1.4, 6.0) years. Among the 642 children with MPP, 185 cases were in the hypersecretion group and 457 cases were in the non-hypersecretion group. There were 41 cases in the hypersecretion group and 160 cases in the non-hypersecretion group of 201 children with RSV pneumonia. In the 125 children with adenovirus pneumonia, there were 39 cases in the hypersecretion group and 86 cases in the non-hypersecretion group. In these children, the age of children in the hypersecretion group was older than that in the non-hypersecretion group (6.0 (4.0, 7.0) vs. 5.0 (3.0, 7.0) years old, 1.5 (0.5, 3.6) vs. 0.8 (0.4, 1.6) years old, 2.0 (1.2, 4.5) vs. 1.3 (0.8, 2.0) years old, U=35 295.00, 2 492.00, 1 101.00, all P<0.05). Through multivariate Logistic regression analysis it found that increased risk of airway mucus hypersecretion was present in childhood MPP with increase in peripheral blood white blood cell count (OR=3.30, 95%CI 1.51-7.93, P=0.004) or increase in neutrophil ratio (OR=2.24, 95%CI 1.16-4.33, P=0.016) or decrease in lymphocyte count (OR=3.22, 95%CI 1.66-6.31, P<0.001) or decrease in serum albumin (OR=2.00, 95%CI 1.01-3.98, P=0.047). The risk of airway mucus hypersecretion was increased in children with RSV pneumonia combined with elevated peripheral blood eosinophils (OR=3.04, 95%CI 1.02-8.93, P=0.043). Meanwhile, airway mucus hypersecretion was associated with severe pneumonia (OR=2.46, 95%CI 1.03-6.15, P=0.047) in children with RSV pneumonia. Older age was associated with increased risk of airway mucus hypersecretion in children with adenovirus pneumonia (OR=1.02, 95%CI 1.00-1.04, P=0.026). In these children with occurrence of pulmonary rales, wheezes or sputum sounds (OR=3.65, 95%CI 1.22-12.64, P=0.028) had an increased risk of airway mucus hypersecretion. Neutrophils in bronchoalveolar lavage fluid (BALF) demonstrated higher ratio in hypersecretion group from children with MPP (0.65 (0.43, 0.81) vs. 0.59 (0.34, 0.76), U=24 507.00, P<0.01), while the proportion of macrophages in BALF was lower (0.10 (0.05, 0.20) vs. 0.12 (0.06, 0.24), U=33 043.00, P<0.05). Nucleated cell count and neutrophil ratio in BALF were higher in hypersecretion group of children with RSV pneumonia (1 210 (442, 2 100)×106 vs. 490 (210, 1 510)×106/L, 0.43 (0.26, 0.62) vs. 0.30 (0.13, 0.52), U=2 043.00, 2 064.00, all P<0.05). Conclusions: The increase in peripheral blood white blood cell count, neutrophil ratio and decrease in lymphocyte count, serum albumin in children with MPP is related to the development of airway mucus hypersecretion. In children with RSV pneumonia, the abnormal increase of eosinophils in peripheral blood has relationship with hypersecretion. The appearance of lung rale, wheezing, and sputum rale are associated with airway mucus hypersecretion in children with adenovirus pneumonia. In addition, local neutrophil infiltration in the respiratory tract is closely related to the occurrence of airway mucus hypersecretion caused by Mycoplasma pneumoniae and RSV infection.


Asunto(s)
Niño , Masculino , Femenino , Humanos , Lactante , Preescolar , Estudios Retrospectivos , Ruidos Respiratorios , Neumonía por Mycoplasma , Pulmón , Infecciones por Virus Sincitial Respiratorio , Moco , Neumonía Viral , Factores de Riesgo
9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-928183

RESUMEN

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.


Asunto(s)
Areca , Arecolina/análisis , Medicamentos Herbarios Chinos/análisis , Cinética , Semillas/química , Agua/análisis
10.
Sichuan Mental Health ; (6): 381-385, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-987402

RESUMEN

This article gives a review on domestic and foreign researches on the non-drug intervention for patients with perimenopausal depression published from 2012 to 2022, so as to provide a reference for clinical treatment and nursing. Currently, pharmacotherapy is the mainstay of treatment for perimenopausal depression, while many existing problems remain to be solved such as the variation in treatment effect and the difficulty in maintaining emotional stability. however,high safety and relatively low cost are the characteristics of non-drug intervention, so this article expounds on the non-drug intervention measures for perimenopausal depression, such as music therapy, dietary therapy, exercise therapy, acupuncture therapy and repetitive transcranial magnetic stimulation (rTMS).

11.
- The COvid-19 Multi-omics Blood ATlas (COMBAT) Consortium; David J Ahern; Zhichao Ai; Mark Ainsworth; Chris Allan; Alice Allcock; Azim Ansari; Carolina V Arancibia-Carcamo; Dominik Aschenbrenner; Moustafa Attar; J. Kenneth Baillie; Eleanor Barnes; Rachael Bashford-Rogers; Archana Bashyal; Sally Beer; Georgina Berridge; Amy Beveridge; Sagida Bibi; Tihana Bicanic; Luke Blackwell; Paul Bowness; Andrew Brent; Andrew Brown; John Broxholme; David Buck; Katie L Burnham; Helen Byrne; Susana Camara; Ivan Candido Ferreira; Philip Charles; Wentao Chen; Yi-Ling Chen; Amanda Chong; Elizabeth Clutterbuck; Mark Coles; Christopher P Conlon; Richard Cornall; Adam P Cribbs; Fabiola Curion; Emma E Davenport; Neil Davidson; Simon Davis; Calliope Dendrou; Julie Dequaire; Lea Dib; James Docker; Christina Dold; Tao Dong; Damien Downes; Alexander Drakesmith; Susanna J Dunachie; David A Duncan; Chris Eijsbouts; Robert Esnouf; Alexis Espinosa; Rachel Etherington; Benjamin Fairfax; Rory Fairhead; Hai Fang; Shayan Fassih; Sally Felle; Maria Fernandez Mendoza; Ricardo Ferreira; Roman Fischer; Thomas Foord; Aden Forrow; John Frater; Anastasia Fries; Veronica Gallardo Sanchez; Lucy Garner; Clementine Geeves; Dominique Georgiou; Leila Godfrey; Tanya Golubchik; Maria Gomez Vazquez; Angie Green; Hong Harper; Heather A Harrington; Raphael Heilig; Svenja Hester; Jennifer Hill; Charles Hinds; Clare Hird; Ling-Pei Ho; Renee Hoekzema; Benjamin Hollis; Jim Hughes; Paula Hutton; Matthew Jackson; Ashwin Jainarayanan; Anna James-Bott; Kathrin Jansen; Katie Jeffery; Elizabeth Jones; Luke Jostins; Georgina Kerr; David Kim; Paul Klenerman; Julian C Knight; Vinod Kumar; Piyush Kumar Sharma; Prathiba Kurupati; Andrew Kwok; Angela Lee; Aline Linder; Teresa Lockett; Lorne Lonie; Maria Lopopolo; Martyna Lukoseviciute; Jian Luo; Spyridoula Marinou; Brian Marsden; Jose Martinez; Philippa Matthews; Michalina Mazurczyk; Simon McGowan; Stuart McKechnie; Adam Mead; Alexander J Mentzer; Yuxin Mi; Claudia Monaco; Ruddy Montadon; Giorgio Napolitani; Isar Nassiri; Alex Novak; Darragh O'Brien; Daniel O'Connor; Denise O'Donnell; Graham Ogg; Lauren Overend; Inhye Park; Ian Pavord; Yanchun Peng; Frank Penkava; Mariana Pereira Pinho; Elena Perez; Andrew J Pollard; Fiona Powrie; Bethan Psaila; T. Phuong Quan; Emmanouela Repapi; Santiago Revale; Laura Silva-Reyes; Jean-Baptiste Richard; Charlotte Rich-Griffin; Thomas Ritter; Christine S Rollier; Matthew Rowland; Fabian Ruehle; Mariolina Salio; Stephen N Sansom; Alberto Santos Delgado; Tatjana Sauka-Spengler; Ron Schwessinger; Giuseppe Scozzafava; Gavin Screaton; Anna Seigal; Malcolm G Semple; Martin Sergeant; Christina Simoglou Karali; David Sims; Donal Skelly; Hubert Slawinski; Alberto Sobrinodiaz; Nikolaos Sousos; Lizzie Stafford; Lisa Stockdale; Marie Strickland; Otto Sumray; Bo Sun; Chelsea Taylor; Stephen Taylor; Adan Taylor; Supat Thongjuea; Hannah Thraves; John A Todd; Adriana Tomic; Orion Tong; Amy Trebes; Dominik Trzupek; Felicia A Tucci; Lance Turtle; Irina Udalova; Holm Uhlig; Erinke van Grinsven; Iolanda Vendrell; Marije Verheul; Alexandru Voda; Guanlin Wang; Lihui Wang; Dapeng Wang; Peter Watkinson; Robert Watson; Michael Weinberger; Justin Whalley; Lorna Witty; Katherine Wray; Luzheng Xue; Hing Yuen Yeung; Zixi Yin; Rebecca K Young; Jonathan Youngs; Ping Zhang; Yasemin-Xiomara Zurke.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21256877

RESUMEN

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

12.
Clin Rheumatol ; 40(3): 1039-1046, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32681364

RESUMEN

INTRODUCTION/OBJECTIVES: Osteoarthritis (OA) ranks the most common joint disorder and the leading cause of disability. Growing evidence has revealed that OA has a strong genetic background, except for aging and obesity. The aim of this study is to determine the associations between potential functional variants of the GLIS3 and GLIS3-AS1 gene and risk of knee OA among a Chinese population. METHODS: In this case-control study with 810 knee OA cases and 900 healthy controls, seven selected functional SNPs of the GLIS3 and GLIS3-AS1 gene were evaluated. RESULTS: We found minor alleles of rs10116772 (OR: 0.80, 95% CI: 0.69-0.92, P = 0.002), rs7045410 (OR: 0.74, 95% CI: 0.61-0.92, P = 0.005), and rs7032713 (OR: 0.76, 95% CI: 0.63-0.93, P = 0.006) were significantly associated with decreased risk of knee OA. Results of the dominant and recessive model, stratified analyses using Kellgren-Lawrence (KL) grading presented that the significant associations were not materially changed. Haplotype analysis indicated that haplotype CGT (OR: 0.66, 95% CI: 0.46-0.96, P = 0.031) and ATT (OR: 0.76, 95% CI: 0.6-0.95, P = 0.017) were significantly associated with decreased risk of knee OA. Further, they were also significantly associated with lower expression level of GLIS3, as well as higher expression level of GLIS3-AS1 in the articular cartilage specimens. Genotype-tissue expression (GTEX) data also validated that minor alleles of rs7045410 and rs7032713 were significantly associated with higher expression level of GLIS3-AS1 in thyroid and pituitary tissues (P < 0.001). CONCLUSIONS: These findings revealed the essential role of genetic variants of the GLIS3 and GLIS3-AS1 gene in the occurrence of knee OA together. Key Point • Functional variants of the GLIS3 and GLIS3-AS1 gene were significantly associated with decreased risk of knee OA.


Asunto(s)
Osteoartritis de la Rodilla , Estudios de Casos y Controles , Proteínas de Unión al ADN , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Osteoartritis de la Rodilla/genética , Polimorfismo de Nucleótido Simple , Proteínas Represoras , Transactivadores
13.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-912875

RESUMEN

Objective: To explore the protective mechanism of acupuncture plus mild hypothermia for cerebral ischemia-reperfusion injury (CIRI) by observing the effects of acupuncture plus mild hypothermia on miRNA-204 and its target gene expressions in CIRI rat brain tissues. Methods: Sixty Sprague-Dawley rats were divided into a blank control group, a sham operation group, a model group, an acupuncture group, a mild hypothermia group and an acupuncture plus mild hypothermia group according to the random number table method (n=10). Except for the blank control group and the sham operation group, rats in the other 4 groups received CIRI modeling. After the model was successfully established, rats in the blank control group were bred routinely for 72 h without any interventions; rats in the sham operation group and the model group were bred routinely for 72 h, and only received binding without other interventions after surgery; rats in the acupuncture group were bred routinely for 72 h, and received acupuncture at Dazhui (GV 14), Baihui (GV 20) and Shuigou (GV 26) after binding; rats in the mild hypothermia group were bred routinely for 72 h, and received mild hypothermia intervention for 72 h after binding; rats in the acupuncture plus mild hypothermia group were bred routinely for 72 h, followed by receiving acupuncture as in the acupuncture group and mild hypothermia therapy as in the mild hypothermia group after binding. The neurological impairment score, cerebral infarction area ratio, the expressions of miRNA-204 and its target genes including Map3k8, Ntrk2 and Ppp3r1 in the ischemic hippocampus of each group were observed after 72 h of intervention. Results: Before intervention, compared with the blank control group and the sham operation group, the neurological impairment scores and the infarction area ratios of the modelled rats were statistically significantly increased (all P<0.01), indicating that the model was successful. After intervention, compared with the model group, the neurological impairment scores of the three intervention groups were significantly reduced (all P<0.01); compared with the acupuncture group and the mild hypothermia group, the infarction area ratio in the acupuncture plus mild hypothermia group was significantly reduced (both P<0.01); compared with the model group, the three intervention groups showed significant inhibition of miRNA-204 expression in brain tissues (all P<0.05), which was most significant in the acupuncture plus mild hypothermia group (P<0.01); compared with the acupuncture group and the mild hypothermia group, the Map3k8 expression in the acupuncture plus mild hypothermia group was significantly increased (both P<0.01), but there were no significant differences in Ntrk2 and Ppp3r1 expressions between groups (all P>0.05). Conclusion: Acupuncture, mild hypothermia, and acupuncture plus mild hypothermia reduced the neurological impairment score and the cerebral infarction area in CIRI rats, while acupuncture plus mild hypothermia showed the most significant effect. In regulating miRNA-204 target gene expressions, acupuncture plus mild hypothermia showed the same effect on Ntrk2 and Ppp3r1 expressions, while better effect on Map3k8 expression compared with either acupuncture or hypothermia.

14.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-879811

RESUMEN

OBJECTIVE@#To study the detection rate, epidemic pattern, and clinical features of respiratory syncytial virus (RSV) in hospitalized children with acute lower respiratory infection (ALRI).@*METHODS@#Nasopharyngeal aspirates were collected from children with ALRI, aged < 2 years, who were hospitalized in Children's Hospital of Chongqing Medical University from June 2013 to May 2018. Multiplex PCR was used to detect 16 common respiratory viruses. The epidemiological characteristics of RSV were analyzed.@*RESULTS@#A total of 2 066 hospitalized children with ALRI were enrolled. Among the children, 1 595 (77.20%) tested positive for virus and 826 (39.98%) tested positive for RSV [410(49.6%) positive for RSV-A, 414 (50.1%) positive for RSV-B, and 2 (0.2%) positive for both RSV-A and RSV-B]. RSV-B was the main subtype detected in 2013-2014 and 2016-2017, while RSV-A was the main subtype in 2014-2015 and 2017-2018, and these two subtypes were prevalent in 2015-2016. The highest detection rate of RSV was noted in winter. RSV + human rhinovirus was the most common combination of viruses and was detected in 123 children. These children were more likely to develop wheezing than those with single RSV detected (@*CONCLUSIONS@#In Chongqing in 2013-2018, RSV-A and RSV-B not only can predominate alternately, but also can co-circulate during a season. RSV is the major viral pathogen of hospitalized children with ALRI and can cause severe lower respiratory tract infection. There are no differences in clinical manifestations between children with RSV-A infection and those with RSV-B infection, but boys are more susceptible to RSV-A infection.


Asunto(s)
Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Niño Hospitalizado , China/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio/epidemiología
15.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-942976

RESUMEN

Objective: To explore whether the cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) can improve the survival rate of colorectal cancer patients with peritoneal metastasis. Methods: The relevant studies were systematically retrieved from PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP database, and the study of French Elias' team on peritoneal metastasis was retrieved manually. Inclusion criteria: (1) The patients were colorectal cancer peritoneal metastasis. (2) There were CRS+HIPEC treatments (treatment group) and other treatments (control group). (3) Survival analysis data of treatment group and control group were available. (4) Types of studies were randomized controlled trials, cohort studies, or case-control studies. (5) The literature was in Chinese or English. Exclusion criteria: (1) studies without full-text; (2) studies without complete data. The literature screening and data extraction were carried out by two people independently, and the third person decided on the literature with differences. The extracted data included authors, year of publication, number of patients, time of enrollment, time of follow-up, studies design, treatment regimen, hazard ratio (HR) and 95% CI of treatment group and control groups. If the HR and 95% CI of the treatment group and control group were not provided in the literature, Engauge Digitizer 11.1 software was used to extract the time of follow-up and the survival rate at the corresponding time point from the survival curves of both groups, and the HR and 95% CI of both groups were calculated by combining the number of both groups. The quality of study was evaluated by Newcastle-Ottawa scale (NOS) or Cochrane collaboration's tool for assessing risk bias. STATA 15.1 software was used for statistical analysis. HR and 95% CI of both groups were pooled and analyzed. Inter-trial heterogeneity was assessed by Q test and I(2) statistics. When there was no significant heterogeneity (Q test: P≥0.10), fixed-effect model was used for pooled analysis. When significant heterogeneity existed (Q test: P<0.10), random effect model was used for pooled analysis, and subgroup analysis was used to find out the source of heterogeneity. Sensitivity analysis was used to evaluate the stability of the pooled results. Publication bias was assessed by Egger's test and Begg's test (P<0.05 indicated publication bias) and it is reflected by the visual symmetry of Begg's funnel plot on the natural logarithm of HR. Results: A total of 10 studies were enrolled in the meta-analysis, including 1 randomized controlled trial and 9 cohort studies. The risk of bias in 1 randomized controlled trial was uncertain, and 9 cohort studies were all higher than 7 points, indicating high quality literatures. There were 781 patients in treatment group receiving CRS+HIPEC and 2452 patients in control group receiving other treatment, including tumor cytoreductive surgery (CRS), palliative chemotherapy (PC) and intraperitoneal chemotherapy (IPC). The results of pooled analysis by random effect model showed that the OS rate in treatment group was significantly higher than that in control group (HR=0.43, 95% CI: 0.34-0.54), but the heterogeneity of the study was high (P=0.024, I(2)=52.9%). The subgroup analysis of different control treatments showed that the OS rate in treatment group was significantly higher than that in CRS control group (HR=0.63, 95% CI: 0.44-0.90), in PC control group (HR=0.37, 95% CI: 0.32-0.43), in CRS+ IPC control group (HR=0.60, 95% CI: 0.37-0.96), and the heterogeneity of each subgroup was low (CRS control group: P=0.255, I(2)=22.9%; PC control group: P=0.222, I(2)=29.9%; CRS+IPC control group: P=0.947, I(2)=0). Due to the low heterogeneity of subgroups, fixed-effect models were used to pool and analysis. The results of sensitivity analysis revealed that there was little difference between the pooled analysis results after each study was deleted, suggesting that the pooled analysis results were more reliable. Publication bias detection of each study showed Begg's test (P=0.088) >0.05 and Egger's test (P=0.138)>0.05. According to the Begg's funnel plot, the scatter point distribution was basically symmetric, indicating that there was no publication bias in the included study. Conclusion: CRS+HIPEC can improve the OS of patients with colorectal cancer peritoneal metastasis.


Asunto(s)
Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/tratamiento farmacológico , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tasa de Supervivencia
16.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-880436

RESUMEN

Effects of heat treatment conditions (including temperature and time) on the shape memory recovery and corrosion resistance of NiTi self-expanding vascular stents were studied based on working mechanism and clinical use. The


Asunto(s)
Aleaciones , Corrosión , Calor , Ensayo de Materiales , Stents , Propiedades de Superficie , Temperatura , Titanio
17.
Acta Pharmaceutica Sinica ; (12): 1301-1313, 2021.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-887067

RESUMEN

In recent years, the phenomenon of glass transition has been gradually applied to the field of pharmaceutics. And it exhibits important influences on multiple operating units of pharmaceutical preparations, and the properties and storage of pharmaceutical intermediates and products. At present, it has been widely used in the process of preparations such as drying, granulation, coating, tableting, holt-melt extrusion, cryogenic comminution, and so on. Meanwhile, it showed guiding significance for the process of preparation intermediates and their products, such as solid dispersion, microcapsule, liposome, particle, tablet, and other preparation intermediates and their products. Therefore, this article conducts a detailed analysis and systematic summary of the application guidance of the phenomenon of glass transition in the preparation process, and its influence on the preparation intermediates and products, so as to provide theoretical guidance for preparation production and product storage.

18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-888071

RESUMEN

This paper explores the statistical distribution characteristics of coating film thickness, so as to present a new method for determining coating endpoint based on 3σ criterion and logic regression. Firstly, the spectrum and thickness of 4 batch samples were collected. Secondly, the spectral range of normal products was obtained by 3σ criterion, with the spectral feature NI as the number of test spectrum in the above range. Then, the model based on 3σ criterion and logic regression was built according to the best condition in K-fold cross-validation and the determined threshold of qualified rate in the coating endpoint. Finally, the qualified rate of test set samples at different time points was calculated by the above model, and the above change trend and the threshold value were combined to determine the coating endpoint. The results of KS analysis showed the distribution of thickness of the qualified products followed the normal distribution(P=0.081>0.05). The accuracy of the coating endpoint determination was as high as 100% by the model based on 3σ criterion and logic regression when the determined threshold of qualified rate was 90%. Therefore, the 3σ criterion was feasible to the research of coating eligibility. This paper reveals certain random phenomena in the coating process, and the method features a high accuracy, quick analysis and a good interpretability, which provides a reference for online detection and qualify evaluation in future.


Asunto(s)
Determinación de Punto Final , Lógica , Proyectos de Investigación , Comprimidos
19.
Zhongguo Zhong Yao Za Zhi ; 45(20): 4882-4888, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33350260

RESUMEN

The changes of active ingredients content, moisture status and texture characteristics during the moistening of Paeoniae Radix Alba were studied by low-field NMR and imaging(LF-NMR/MRI) and texture analyzer, so as to analyze the correlation between LF-NMR parameters, texture characteristics and active ingredient content of Paeoniae Radix Alba during the moistening at diffe-rent times. The results showed that MRI technology could directly, vividly and accurately characterize the degree of moistening and the process of water migration, and the degree of moistening was consistent with the judgment results of traditional experience. The characteristics of moisture migration and moisture phase state in the moistening process of Paeoniae Radix Alba were that the total water content increased and existed in the form of free water, with an increased moisture mobility. In the case of dampening, the total water content did not increase, but the more watery part of the medicinal material was distributed to the less watery part, with a reduced fluidity. Finally, the medicinal materials were moistened, which can be mutually verified with the MRI results. The free water content and the total water content of Paeoniae Radix Alba had extremely negative correlations with hardness, surface toughness, internal toughness, Paeoniflorin and albiflorin contents(P<0.01). It showed that the use of LF-NMR/MRI and texture analyzer could better characterize the moistening process. It provides data characterization for the scientific connotation of "less soaking and more moisturizing, and the drug is completely saturated with water", and the traditional experience of "observing the water head". The feasible and objective evaluation method was helpful to optimize the softening process parameters, scientifically standardize the operating specifications, define the scienti-fic connotation of traditional Chinese medicine softening, and promote the inheritance and innovation of traditional Chinese medicine processing.


Asunto(s)
Medicamentos Herbarios Chinos , Paeonia , Imagen por Resonancia Magnética , Medicina Tradicional China , Agua
20.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4625-4632, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33164426

RESUMEN

To conduct endpoint determination of tablet coating and analyze coating process by near-infrared spectroscopy(NIRS). Firstly, the layered k-fold cross validation was used to discuss the optimal combination of spectral interval and preprocessing method, and the optimal result was used as the modeling condition. Secondly, in above condition, the qualitative model was proposed based on the throught of principal component analysis(PCA) and confidence interval, this model and the conformity test model were established respectively in this study, and the discrimination performance of coating eligibility was calculated. Then, the internal cross validation was used to obtain the coating end-point conforming rate as the threshold for determining the endpoint of tablet coating. Finally, the results of predicted conforming rate and discrimination parameters for the test samples of different batches were calculated with the above models, which were then further used for end-point detection and process analysis. As compared with the conformity test, this method proposed in this study was more accurate and stable in determining the coating conformity, and the coating endpoint can be accurately determined when 95% of the eligibility rate was used as the discriminant threshold. Meanwhile, in the process analysis, the change trend of the process parameters(model discrimination parameters, prediction conforming rate) was basically consistent with that in the conformity test. The results indicate that the method proposed in this study has a good and stable performance, which can be used to determine the endpoint of coating and analyze the process. It is of great significance to reduce the difference between batches and improve the product consistency. Meanwhile, this research method also lays a foundation for the future researches by online near infrared measurements.


Asunto(s)
Espectroscopía Infrarroja Corta , Determinación de Punto Final , Análisis de los Mínimos Cuadrados , Análisis de Componente Principal , Comprimidos
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