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1.
J Clin Neurophysiol ; 41(5): 415-422, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38935655

RESUMO

PURPOSE: Stereotactic EEG (SEEG) is gaining increasing popularity in the United States. Patients undergoing SEEG have unique challenges, and their needs are different compared with noninvasive cases. We aim to describe the medical, nursing, and other institutional practices of SEEG evaluations among tertiary referral (level IV) epilepsy centers accredited by the National Association of Epilepsy Centers. METHODS: We analyzed data obtained from a Research Electronic Data Capture (REDCap) survey we formulated and distributed to directors of all level IV epilepsy centers listed by the National Association of Epilepsy Center. Most questions were addressed to the adult and pediatric SEEG programs separately. RESULTS: Among 199 epilepsy center directors invited to complete the survey, 90 (45%) responded. Eighty-three centers (92%) reported they perform SEEG evaluations. Of the 83 respondents, 56 perform SEEG in adult and 47 in pediatric patients. Twenty-two centers evaluate both pediatric and adult subjects. The highest concordance of SEEG workflow was in (1) epilepsy monitoring unit stay duration (1-2 weeks, 79% adult and 85% pediatric programs), (2) use of sleep deprivation (94% both adult and pediatric) and photic stimulation (79% adult and 70% pediatric) for seizure activation, (3) performing electrical cortical stimulation at the end of SEEG evaluation after spontaneous seizures are captured (84% adult and 88% pediatric), and (4) daily head-wrap inspection (76% adult and 80% pediatric). Significant intercenter variabilities were noted in the other aspects of SEEG workflow. CONCLUSIONS: Results showed significant variability in SEEG workflow across polled centers. Prospective, multicenter protocols will help the future development and harmonization of optimal practice patterns.


Assuntos
Eletroencefalografia , Epilepsia , Técnicas Estereotáxicas , Humanos , Epilepsia/cirurgia , Epilepsia/fisiopatologia , Epilepsia/diagnóstico , Epilepsia/terapia , Adulto , Criança , Masculino
3.
Physiol Plant ; 176(2): e14246, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38467573

RESUMO

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) within plant cells due to unfavourable conditions leads to ER stress. This activates interconnected pathways involving reactive oxygen species (ROS) and unfolded protein response (UPR), which play vital roles in regulating ER stress. The aim of this study is to investigate the underlying mechanisms of tunicamycin (TM) induced ER stress and explore the potential therapeutic applications of tauroursodeoxycholic acid (TUDCA) in mitigating cellular responses to ER stress in Pak choi (Brassica campestris subsp. chinensis). The study revealed that ER stress in Pak choi leads to detrimental effects on plant morphology, ROS levels, cellular membrane integrity, and the antioxidant defence system. However, treatment with TUDCA in TM-induced ER stressed Pak choi improved morphological indices, pigment contents, ROS accumulation, cellular membrane integrity, and antioxidant defence system restoration. Additionally, TUDCA also modulates the transcription levels of ER stress sensors genes, ER chaperone genes, and ER-associated degradation (ERAD) genes during ER stress in Pak choi. Furthermore, TUDCA has demonstrated its ability to alleviate ER stress, stabilize the UPR, reduce oxidative stress, prevent apoptosis, and positively influence plant growth and development. These results collectively comprehend TUDCA as a promising agent for mitigating ER stress-induced damage in Pak choi plants and provide valuable insights for further research and potential applications in crop protection and stress management.


Assuntos
Antioxidantes , Ácido Tauroquenodesoxicólico , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Ácido Tauroquenodesoxicólico/farmacologia , Estresse do Retículo Endoplasmático , Tunicamicina/farmacologia
4.
J Tradit Chin Med ; 44(1): 70-77, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213241

RESUMO

OBJECTIVE: To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester (CADPE) molecule, which can prevent colorectal cancer (CRC) in the 1,2-Dimethylhydrazine (DMH)/dextran sodium sulphate (DSS)-induced mouse model. METHODS: Institute of cancer research (ICR) male mice were injected with 20 mg/kg DMH for a week. After that, 2% DSS was administered in the drinking water for another 7 d. The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice. Histopathological examination was used for observing the CRC development at colonic mucosa. Immunohistochemistry (IHC), blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC. The reversing targets searching method was applied with artificial intelligence (AI), computer-aided drug designing (CADD) and Ingenuity Pathway Analysis (IPA) techniques for predicting the potential targets and mechanism of CADPE highly related to CRC. RESULTS: The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment. CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development. Finally, our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK) and mammalian target of rapamycin (mTOR) in two major cancer development pathways. CONCLUSIONS: CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR, ERK and mTOR activities in two highly related CRC developing pathways.


Assuntos
Ácidos Cafeicos , Neoplasias Colorretais , Dextranos , Sulfatos , Camundongos , Masculino , Animais , 1,2-Dimetilidrazina/farmacologia , Dextranos/farmacologia , Inteligência Artificial , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/tratamento farmacológico , Transdução de Sinais , Inflamação , Receptores ErbB/genética , Serina-Treonina Quinases TOR/genética , Mamíferos
5.
Acta Pharmaceutica Sinica ; (12): 764-774, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016607

RESUMO

italic>Cynanchum wallichii and Cynanchum otophyllum belong to the genus Cynanchum in the family Apocynaceae, and are important medicinal plants. In this study, we sequenced and assembled the chloroplast genomes of C. wallichii and C. otophyllum, and performed a phylogenetic analysis of the structural characteristics of their chloroplast genomes and their phylogenetic positions. The results showed that the chloroplast genomes of both C. wallichii and C. otophyllum had a typical tetrad structure, with 133 genes annotated, and the total GC contents of both were similar. Codon preference analysis showed that the relative synonymous codon usage in the chloroplast genomes of C. wallichii and C. otophyllum differed slightly, but the differences were not significant, and there was a strong A or U preference at the third codon position. In both chloroplast genomes, 91 and 103 simple sequence repeats were detected respectively, and the largest proportion of A/T type repeats. Nucleotide polymorphism analysis showed that the nucleotide diversity of the intergenic sequences in the chloroplast genome of genus Cynanchum were generally higher than those of the common gene sequences. A pair of primers was designed based on the high variation region of the chloroplast genome to identify C. wallichii and C. otophyllum. The phylogenetic analysis showed that the C. wallichii and Cynanchum thesioides were the closest relatives, while the C. otophyllum, Cynanchum bungei and Cynanchum wilfordii formed a stable monophyletic clade within the genus Cynanchum, and the three species were closely related. The comparative analysis of the chloroplast genomic characteristics and phylogeny of C. wallichii and C. otophyllum will provide a theoretical basis for the species identification of the two plants and for the study of genetic diversity and phylogeny of the genus Cynanchum.

6.
Chinese Medical Ethics ; (6): 636-642, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1012954

RESUMO

Vaccine cooperation is an important means to deal with global infectious diseases. However, the cooperation cannot be achieved overnight. Ethical dilemma is one of the obstacles that hinders vaccine cooperation. Reviewing the history, the most successful vaccine collaboration to date has been the global smallpox eradication program. In the process of eradicating smallpox, there were also many ethical dilemmas, including the international pattern of the US-Soviet hegemony, which impacted the mutual help between countries, the ethical disputes of the vaccine itself hindering solidarity and cooperation among actors, and the vaccine coercion adopted to overcome vaccine hesitancy undermining the principle of proportionality among the freedom, equality and efficacy. The ethical dilemmas of vaccine cooperation were resolved by shaping professional and scientific consensus among medical professional groups, reaching consensus on cooperation between leading countries and developing countries, and integrating local culture to improve vaccination methods. Finally, in 1980, the world successfully eradicated smallpox. The case of smallpox eradication provides us lessons for vaccine cooperation against COVID-19 and the construction of a community of common health for mankind today.

7.
Biomed Chromatogr ; 37(12): e5738, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37724003

RESUMO

We developed and validated sensitive MS/MS methods for the determination of venetoclax, an oral selective B-cell lymphoma-2 inhibitor, in human plasma and cerebrospinal fluid (CSF). Acetonitrile was used as protein precipitant. The mobile phase was 10 mM ammonium formate consisting of 0.1% formic acid and acetonitrile (40:60, v/v). The analytes were separated on an ACQUITY UPLC HSS T3 column (2.1 × 50 mm, 1.8 µm) in 5 min. An API 4000 mass spectrometer was selected to quantify venetoclax and internal standard using m/z 868.3 → 636.3 and 876.3 → 644.3 under multiple response monitoring mode. In plasma, the calibration curve exhibited good linearity ranging from 20.0 to 5000 ng/mL, whereas in the CSF, the linear range was 0.500-100 ng/mL. The matrix effect of venetoclax and internal standard (venetoclax-d8) was not obvious in both plasma and CSF. The inter- and intra-run accuracy was within ±11.9%, and the inter- and intra-run precision was below 13.6%. Both methods had no carryover, and the recovery was close to 100%. The validated methods were employed to quantify the concentrations of venetoclax in the plasma and CSF of patients diagnosed with chronic lymphocytic leukemia or acute myelogenous leukemia.


Assuntos
Sulfonamidas , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Acetonitrilas , Cromatografia Líquida de Alta Pressão/métodos
8.
J Glob Antimicrob Resist ; 35: 347-353, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37573945

RESUMO

OBJECTIVES: Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients. METHODS: For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability. RESULTS: Prediction-based diagnostics found that the prediction error within ±30% (F30) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance. CONCLUSION: The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.


Assuntos
Transplante de Rim , Modelos Biológicos , Humanos , Adulto , Linezolida/uso terapêutico , Teorema de Bayes , Simulação por Computador , Transplante de Rim/efeitos adversos
9.
BMC Genomics ; 24(1): 340, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340366

RESUMO

BACKGROUND: Oriental river prawn (Macrobrachium nipponense) is one of the most dominant species in shrimp farming in China, which is a rich source of protein and contributes to a significant impact on the quality of human life. Thus, more complete and accurate annotation of gene models are important for the breeding research of oriental river prawn. RESULTS: A full-length transcriptome of oriental river prawn muscle was obtained using the PacBio Sequel platform. Then, 37.99 Gb of subreads were sequenced, including 584,498 circular consensus sequences, among which 512,216 were full length non-chimeric sequences. After Illumina-based correction of long PacBio reads, 6,599 error-corrected isoforms were identified. Transcriptome structural analysis revealed 2,263 and 2,555 alternative splicing (AS) events and alternative polyadenylation (APA) sites, respectively. In total, 620 novel genes (NGs), 197 putative transcription factors (TFs), and 291 novel long non-coding RNAs (lncRNAs) were identified. CONCLUSIONS: In summary, this study offers novel insights into the transcriptome complexity and diversity of this prawn species, and provides valuable information for understanding the genomic structure and improving the draft genome annotation of oriental river prawn.


Assuntos
Palaemonidae , Animais , Humanos , Palaemonidae/genética , Perfilação da Expressão Gênica , Transcriptoma , Processamento Alternativo , Isoformas de Proteínas/genética
10.
Molecules ; 28(3)2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36770870

RESUMO

Ibrutinib, orelabrutinib, and zanubrutinib are all Bruton's tyrosine kinase inhibitors, which have greatly improved the treatment of B-cell malignancies. In this study, an LC-MS/MS method was developed and validated for the determination of orelabrutinib, zanubrutinib, ibrutinib, and its active metabolite dihydrodiol ibrutinib in human plasma. The Ibrutinib-d5 was used as the internal standard. Pretreatment was performed using a simple protein precipitation step using acetonitrile. The ACQUITY UPLC HSS T3 column (2.1×50 mm, 1.8 µm) was used to separate the analytes, and the run time was 6.5 min. The mobile phase consisted of acetonitrile and 10 mM of ammonium formate, which contained 0.1% formic acid. The multiple reactions' monitoring transitions were selected at m/z 428.1→411.2, 472.2→455.2, 441.1→304.2, 475.2→304.2 and 446.2→309.2 respectively for orelabrutinib, zanubrutinib, ibrutinib, dihydrodiol ibrutinib and ibrutinib-d5 using positive ion electrospray ionization. The standard curves were linear, from 0.400 to 200 ng/mL for ibrutinib and dihydrodiol ibrutinib, 1.00-500 ng/mL for orelabrutinib, and 2.00-1000 ng/mL for zanubrutinib. Selectivity, the lower limit of quantitation, precision, accuracy, matrix effect, recovery, stability, and dilution integrity all met the acceptance criteria of FDA guidance. This method was used to quantify the plasma levels of orelabrutinib, zanubrutinib, ibrutinib, and dihydrodiol ibrutinib in clinical patients.


Assuntos
Inibidores de Proteínas Quinases , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Inibidores de Proteínas Quinases/farmacologia , Acetonitrilas
11.
Epilepsy Behav Rep ; 21: 100582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36654732

RESUMO

Background: GNAO1-related neurodevelopmental disorder is a heterogeneous condition characterized by hypotonia, developmental delay, epilepsy, and movement disorder. This study aims to better understand the spectrum of epilepsy associated with GNAO1 variants and experience with anti-seizure medications, and to review published epilepsy phenotypes in GNAO1. Methods: An online survey was distributed to caregivers of individuals diagnosed with GNAO1 pathogenic variants, and a literature review was conducted. Results: Fifteen respondents completed the survey with the median age of 39 months, including a novel variant p.Q52P. Nine had epilepsy - six had onset in the first week of life, three in the first year of life - but two reported no ongoing seizures. Seizure types varied. Individuals were taking a median of 3 seizure medications without a single best treatment. Our cohort was compared to a literature review of epilepsy in GNAO1. In 86 cases, 38 discrete variants were described; epilepsy is reported in 53 % cases, and a developmental and epileptic encephalopathy in 36 %. Conclusions: While GNAO1-related epilepsy is most often early-onset and severe, seizures may not always be drug resistant or lifelong. Experience with anti-seizure medications is varied. Certain variant "hotspots" may correlate with epilepsy phenotype though genotype-phenotype correlation is poorly understood.

12.
Br J Clin Pharmacol ; 89(2): 526-535, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35285970

RESUMO

AIMS: The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). METHODS: Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. RESULTS: The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004). CONCLUSION: Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.


Assuntos
Injúria Renal Aguda , Vancomicina , Humanos , Vancomicina/efeitos adversos , Antibacterianos/efeitos adversos , Farmacêuticos , Estudos Retrospectivos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/prevenção & controle , Creatinina
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 288: 122191, 2023 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-36463623

RESUMO

In this work, a novel triphenylamine-benzofuran derived fluorescent probe, TBF-SS, was developed for detecting hydrogen polysulfide in tea samples and intracellular imaging. TBF-SS showed the practical advantages including high sensitivity (LOD = 0.01 µM), high selectivity, rapid response (within 15 min), and steadiness in various environmental conditions. The detecting system was steady within pH range of 6.0-11.0 and temperature range of 20-55 °C. The probe TBF-SS could guarantee the stable detection of H2Sn for 7 d in storage of either solid or solution. In particular, in the application of various tea samples with different brewing times and testing temperatures, the recovery percentages varied in the range of 95.22 % to 105.0 %. Therefore accurate monitoring of H2Sn could be achieved by using the probe TBF-SS. In addition, TBF-SS could monitor the exogenous level, the ß-lapachone-induced generation and the tea-sample-treated introduction of H2Sn in living MCF-7 cells. This work might inspire the improvement of the serviceability of fluorescent implements.


Assuntos
Benzofuranos , Corantes Fluorescentes , Hidrogênio/análise , Chá
14.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-996421

RESUMO

Objective To analyze the clinical characteristics and meteorological factors of patients with chronic heart failure (CHF) in Qinghai Plateau area, and to provide a theoretical basis for the diagnosis and treatment of patients with chronic heart failure. Methods A total of 356 patients with CHF admitted to our hospital in Qinghai Plateau area from 2019 to 2020 were selected, and the number of cases, age, gender, comorbidity, NYHA cardiac function classification of CHF patients in Qinghai Plateau area from 2019 to 2020 were counted. To compare NYHA cardiac function classification and underlying diseases in CHF patients at different ages and altitudes in Qinghai Plateau area. The daily average temperature (℃), daily temperature and daily range (℃), daily average wind speed (m/s), daily average air pressure (kPa) and daily average relative humidity (%) in Qinghai Plateau from 2019 to 2020 were collected. According to the general clinical data of patients, the changes of the monthly incidence of CHF patients were analyzed. Pearson correlation analysis was used to compare the correlation between the monthly incidence of CHF patients and meteorological factors, and to explore the influence of meteorological factors on the incidence of CHD in Qinghai Plateau. Results Among the 356 CHF patients, there were 181 males and 175 females, with an average age of (72.47 ±6.49) years old. The NYHA classification of cardiac function was grade II in 103 cases, grade ⅲ in 198 cases, and grade ⅳ in 55 cases. NYHA cardiac function classification increased with age, and there was significant difference in NYHA cardiac function classification among CHF patients of different ages (P<0.05). Among 356 CHF patients, 91 cases (25.56%) were complicated with hypertension, 63 cases (17.70%) were complicated with coronary heart disease, 57 cases (16.01%) were complicated with diabetes, and 40 cases (11.24%) were complicated with hypergenic heart disease. 25 cases (7.02%) were complicated with heart valve disease. Hypertension, coronary heart disease, diabetes mellitus, hypergenic heart disease and valvular heart disease increased with age, and there were statistically significant differences between CHF patients with different ages and underlying diseases (P<0.05). CHF patients in Qinghai Plateau region were mainly concentrated in January-March and October-December. Taking the number of CHD admissions as the dependent variable and each meteorological factor as the independent variable, the correlation between each factor was compared. The results showed that the number of CHF cases was positively correlated with the daily temperature range and daily mean air pressure, and negatively correlated with the average daily temperature (P<0.05). Daily temperature range (OR=2.61) and daily mean air pressure (OR=1.89) were independent risk factors for CHF in Qinghai Plateau area (P<0.05). Conclusion CHF is more prevalent in elderly people in high altitude areas in Qinghai Plateau. For months with high temperature changes, wind speed, we should pay attention to weather changes and take preventive measures in advance.

15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-992217

RESUMO

OBJECTIVE Alzheimer disease(AD)is a neurodegenerative disease with clinical hallmarks of pro-gressive cognitive impairment.Synergistic effects of Aβ-tau cascade reaction are tightly implicated in AD patholo-gy,and microglial NLRP3 inflammasome activation drives neuronal tauopathy through microglia and neurons cross-talk.However,the underlying mechanism of how Aβ medi-ates NLRP3 inflammasome remains unclear.Shab related potassium channel member 1(Kv2.1)as a voltage gated po-tassium channel widely distributed in the central nervous system and plays an important role in regulating the out-ward potassium flow in neurons and glial cells.In current work,we aimed to explore the underlying mechanism of Kv2.1 in regulating Aβ/NLRP3 inflammasome/tau axis by using a determined Kv2.1 inhibitor drofenine(Dfe).METHODS Cell-based assays including Western blot-ting and immunofluorescence staining against primary microglia or neurons were carried out to expound the role of Kv2.1 channel in NLRP3 inflammasome activa-tion and subsequent neuronal tau hyperphosphorylation.For animal studies,new object recognition,Y-maze and Morris water maze were performed to evaluate the ame-lioration of Kv2.1 inhibition through either Kv2.1 inhibitor Dfe treatment or adeno-associated virus AAV-ePHP-si-Kv2.1injectionon5×FADADmodel mice.Assays of histol-ogy and immunostaining of tissue sections and Western blotting of brain tissues were performed to verify the con-clusion of cellular assays.RESULTS We reported that oligomeric Aβ(o-Aβ)bound to microglial Kv2.1 and pro-moted Kv2.1-dependent potassium leakage to activate NLRP3 inflammasome through JNK/NF-κB pathway sub-sequently resulting in neuronal tauopathy.Treatment of either Kv2.1 inhibitor Dfe or AAV-ePHP-si-Kv2.1 for brain-specific Kv2.1 knockdown deprived o-A β of its capability in inducing microglial NLRP3 inflammasome activation and neuronal tau hyperphosphorylation,while improved the cognitive impairment of 5×FAD AD model mice.CONCLUSION Our results have highly addressed that Kv2.1 channel is required for o-Aβ driving NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Kv2.1 inhibition is a prom-ising therapeutical strategy for AD and Dfe as a Kv2.1 inhibitor shows potential in the treatment of this disease.

16.
Frontiers of Medicine ; (4): 939-956, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010802

RESUMO

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.


Assuntos
Animais , Camundongos , Diploide , Coração , Miócitos Cardíacos/metabolismo , Comunicação Celular , Perfilação da Expressão Gênica , Mitocôndrias , Regeneração , Mamíferos/genética
17.
Chinese Medical Ethics ; (6): 377-383, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005717

RESUMO

The concept of "virus sovereignty" proposed by Indonesia in 2007 challenges the international tradition of virus sharing. In the context of the global outbreak of coronavirus disease 2019, the issue of virus sharing has become an important topic in the reform of the global health governance mechanisms. Virus sharing is an important guarantee of dealing with major global infectious diseases. However, the emergence of the concept of "virus sovereignty" shows that there are defects in the operation of virus sharing mechanism in the international community. The "virus sovereignty" problem is an ethical issue essentially, involving asymmetric interests hindering unity and cooperation, intellectual property rights expansion challenging the principle of solidarity, and excessive self-defense amplifying utility risks. "Community of common health for mankind" provides a constructive and feasible option to solve the dilemma of "virus sovereignty".

18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1005136

RESUMO

【Objective】 To analyze the demographic characteristics of apheresis platelet donors who participated in the Partnership Plan Competition(PPC) of Beijing Red Cross Blood Center, and to analyze the effect of publicity and recruitment of apheresis platelet donors, so as to provide reference for formulating recruitment strategy of apheresis platelet donation. 【Methods】 Apheresis blood donors who participated in PPC from March 18, 2021 to May 18, 2021 were selected as research subjects, and their demographic data in terms of gender, age, occupation and education, and relevant blood donation data within 12 months such as the number of blood donations, whether they were regular blood donors were collected. The demographic characteristics of PPC donors and promising groups were analyzed. 【Results】 There were 58 recruiters participating in the PPC, and a total of 170 people were recruited; 53.53%(91/170) successfully participated in the donation of apheresis platelets, and 35.16%(32/91) became regular blood donors. Those 18-30 years old college male students were promising group in the PPC, and were more willing to participate in the recruitment and donation of apheresis platelets. 【Conclusion】 The PPC has significant effect on the promotion and recruitment of apheresis platelets donation. Measures such as setting the types of souvenirs according to the preferences of promising groups, strengthening publicity of PPC, encouraging non-blood donors to participate and expanding targeted recruitment can be taken in the future to increase the success rate of blood donation of the recruitment.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1004823

RESUMO

【Objective】 To analyze the relevant factors affecting the positive psychological capital and communication ability of phlebotomist in blood stations based on the theory of positive psychology and communication behavior, so as to provide reference for the development of professional nursing work in blood stations. 【Methods】 According to the Extensive Positive Psychological Capital Questionnaire and Zeng Kai′s Blood Donor Nurses Communication Ability Evaluation Scale, an online survey was conducted by WJX (a platform providing functions equivalent to Amazon Mechanical Turk) and statistical analysis was performed using SPSS25.0. 【Results】 The average score of positive psychological capital among phlebotomists was 4.78±0.75, with four dimensions (from high to low) as optimism 5.23±1.09, hope 4.9±0.92, self-efficacy 4.57±0.88 and resilience 4.52±0.69 (P0.05). There was a positive correlation between positive psychological capital and communication ability of phlebotomists(P<0.01). The academic qualifications, professional titles, training frequency and knowledge of self-perception are the factors affecting the positive psychological capital and communication ability of phlebotomists.. 【Conclusion】 Managers in blood collection and supply institutions should encourge phlebotomists to study, think and practice initiatively, and conduct education and training on psychological and professional quality of phlebotomists continuously.

20.
China Pharmacy ; (12): 3000-3005, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1003536

RESUMO

OBJECTIVE To study the effects of Dayuanyin decoction (DYY) on lung injury and gut microbiota in mice with RSV-Hanshi yufei syndrome. METHODS Thirty-six BALB/c mice were divided into the normal group (NC group), model group (MC group), positive control group (LBM group, 57.59 mg/kg ribavirin), DYY low-dose, medium-dose and high-dose groups (LDYY,MDYY,HDYY groups,1.67,3.34,6.68 g/kg,calculated by crude drug), with 6 mice in each group. Except for NC group, RSV-Hanshi yufei syndrome model was induced by “Hanshi modeling+RSV infection”; after the second cold and wet stimulation, RSV solution was dripped into the nasal cavity at 50% tissue culture infectious dose, once a day, for 3 consecutive days; each administration group was given corresponding solution intragastrically 4 hours after each nasal drip, once a day, for 5 consecutive days. The levels of motilin (MTL) and gastrin (GAS) in serum, the levels of IL-6 and IL-1β in supernatant of lung tissue, and the percentage of peripheral blood lymphocytes were all determined. The pathological changes of lungs were observed, and the changes of gut microbiota were analyzed. RESULTS Compared with MC group, the levels of MTL in serum (except for HDYY group), and the levels of IL-6 and IL-1β in supernatant of lung tissue were all decreased significantly in DYY groups, while the level of GAS (except for HDYY group) in serum was increased significantly (P<0.05 or P<0.01). The pathology of lung tissue was improved, the percentage of T lymphocytes in LDYY group and the percentages of T lymphocyte and B lymphocyte in MDYY group were all increased significantly (P<0.05 or P<0.01). Compared with the NC group, Bacteroidetes, Actinobacteria, Bacteroides, Alistipes, Bacteroidota, Bacteroides acidfaciens and Alloprevotella were expressed in high abundance, while Firmicutes, Proteobacteria, Lachnospiraceae NK4A136 group, Kineothrix and Clostridiales unclassified were expressed in low abundance. After the intervention of medium-dose DYY, the relative abundance of each microbiota tended to be adjusted back, with different species including Lachnospiraceae_UCG-Ruminococcus, etc. CONCLUSIONS Dayuanyin decoctioncan reduce the lung injury caused by RSV, the mechanism of which may be associated with relieving inflammation, regulating gastrointestinal hormone levels, the percentage of lymphocytes and the abundance of beneficial and harmful bacteria in the intestinal tract.

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