RESUMO
S100 calcium binding protein A9 (S100A9) is involved in a variety of biological processes such as inflammation and tumor cell migration and invasion regulation. The purpose of this study was to construct S100A9 gene-edited mice by using CRISPR/Cas9 technology, thereby providing an animal model for exploring the biological functions of this gene. According to the S100A9 gene sequence, the single-stranded small guide RNA (sgRNA) targeting exons 2 and 3 was transcribed in vitro, and a mixture of Cas9 mRNA and candidate sgRNA was injected into mouse fertilized eggs by microinjection. Early embryos were obtained and transferred to surrogate mice, and F0 mice were obtained and identified by PCR identification and gene sequencing. F0 mice were further mated with wild-type C57BL/6 mice to obtain F1 heterozygous mice, and then homozygous offspring were obtained through F1 mice self-crossing. Real-time PCR, Western blot and immunohistochemistry (IHC) were used to verify the expression and distribution of S100A9. In order to observe the pathological changes of mouse lung tissue using HE staining, an allergic asthma model was induced by ovalbumin from chicken egg white (OVA). The results showed that the 2 492 bp of exons 2, 3 of the S100A9 gene was successfully knocked out, and S100A9-/- mice with stable inheritance were obtained. Furthermore, it was found that S100A9 gene was highly expressed in the lung and spleen of wild-type mice. The expression of S100A9 mRNA and protein was not detected in the lung and spleen of S100A9-/- mice. However, compared with wild-type mice, the lungs of S100A9-/- mice showed a significantly worse inflammatory phenotype, and the proportion of eosinophils in bronchoalveolar lavage fluid (BALF) was significantly increased in response to the treatment of OVA. These results suggest we have successfully constructed a new strain of S100A9-/- mice, and preliminarily confirmed that the lack of S100A9 function can aggravate airway inflammation in asthmatic mice, providing a new mouse model for further study of S100A9 gene function.
Assuntos
Marcação de Genes , Animais , Líquido da Lavagem Broncoalveolar , Sistemas CRISPR-Cas/genética , Calgranulina B , Modelos Animais de Doenças , Técnicas de Inativação de Genes , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina , FenótipoRESUMO
We investigated the relationship among red cell distribution width (RDW), to total serum calcium (TSC) ratio (RCR), and in-hospital mortality in patients with acute ischemic stroke (AIS). This study was a retrospective analysis. The data of 2700 AIS patients was retrospectively analyzed from the Medical Information Mart for Intensive Care database (version IV). The main outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether RCR was independently associated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves for RCR. Subgroup analyses were performed to measure the mortality across various subgroups. The area under curve (AUC) of receiver operating characteristic curve (ROC) was calculated to ascertain the quality of RCR as a predictor of in-hospital mortality in patients with AIS. In the multivariate analysis, statistically significant differences were identified in age, ethnicity, length of ICU stay, mechanical ventilation, sequential organ failure assessment (SOFA) score, RDW, hemoglobin, RCR, whether taking anticoagulants, hyperlipidemia, and atrial fibrillation (Pâ <â .05). A threshold inflection point value of 1.83 was obtained through a two-piecewise regression model. There was a non-linear relationship between RCR and hospital mortality in patients with AIS. The hazard ratio (HR) and the 95% confidence intervals (CI) on the right and left of the inflection point were 0.93 (0.57-1.51; Pâ =â .7660) and 2.96 (1.37-6.42; Pâ =â .0060), respectively. The Kaplan-Meier curve indicated that survival rates were higher when RCR wasâ ≤â 1.83 and lower when RDW wasâ >â 1.83 after adjustment for age, gender, BMI, ethnicity. The area under curve (AUC) of RCR was 0.715. A higher RCR was associated with an increased risk of in-hospital mortality in patients with AIS.
Assuntos
Cálcio , Índices de Eritrócitos , Mortalidade Hospitalar , AVC Isquêmico , Humanos , Feminino , Masculino , Estudos Retrospectivos , Idoso , AVC Isquêmico/sangue , AVC Isquêmico/mortalidade , Pessoa de Meia-Idade , Cálcio/sangue , Curva ROC , Idoso de 80 Anos ou mais , Modelos de Riscos Proporcionais , Fatores de Risco , Estimativa de Kaplan-MeierRESUMO
Objective: Given the immense stress faced by medical staff during the COVID-19 pandemic, this study aimed to evaluate the relationship between mindful attention awareness, fatigue, and perceived symptoms among frontline nurses who performed nucleic acid sample collection during the COVID-19 pandemic, to reduce their fatigue and help them cope with perceived uncomfortable symptoms. Methods: A convenience sampling method was used to survey nurses who travelled to Hainan for nucleic acid sampling in August 2022 using an online (WeChat) questionnaire. A total of 514 frontline nurses who performed nucleic acid tests completed the questionnaire. The questionnaire covered basic demographic information, Mindful Attention Awareness Scale (MAAS) ratings, and Fatigue Severity Scale (FSS) ratings. Spearman correlation analysis was used to separate the relationship between MASS and FSS, and univariate and multivariate factor analyses were used to explore the relevant influences contributing to the occurrence of fatigue. Results: A total of 514 individuals completed the survey,93.97% (n=483) were female, mean age was 31.15 ± 5.7, MASS score was 69.01 ± 13.53, and 296 (57.59%) nurses experienced symptoms of fatigue during the auxiliary period. Spearman correlation analysis showed that FSS was associated with MASS. Multifactorial analysis showed that sex, age, marital status, fertility status, years of work, adaptation to dietary habits, hidrorrhea, and MAAS scores affected the presence of fatigue symptoms among the medical staff in Hainan (P<0.05). Conclusion: The psychological status of frontline nurses undergoing nucleic acid testing during the pandemic was poor, and the appearance of fatigue symptoms could be effectively reduced by increasing levels of positive thinking among medical staff to help them cope with public health emergencies.
RESUMO
OBJECTIVES: We aimed to investigate the association between red cell distribution width-to-platelet ratio (RPR), and in-hospital mortality in critically ill patients with acute myocardial infarction (AMI). DESIGN: A retrospective cohort study. SETTING: Data were collected from the Medical Information Mart for Intensive Care database (MIMIC-IV) consisting of critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Centre in Boston. PARTICIPANTS: A total of 5067 patients with AMI were enrolled from the MIMIC-IV database. PRIMARY AND SECONDARY OUTCOME: In-hospital mortality. RESULTS: A total of 4034 patients survived, while 1033 died. In a multiple regression analysis adjusted for age, weight and ethnicity, RPR also showed a positive correlation with in-hospital mortality (HR 1.91, 95% CI 1.42 to 2.56, p<0.0001). Moreover, after adjusting for additional confounding factors, obvious changes were observed (HR 1.63, 95% CI 1.03 to 2.57, p=0.0357). In model 2, the high ratio quartile remained positively associated with hospital mortality compared with the low ratio quartile (HR 1.20, 95% CI 1.01 to 1. 43), with a p-value trend of 0.0177. Subgroup analyses showed no significant effect modifications on the association between RPR and in-hospital mortality in the different AMI groups (p>0.05). CONCLUSION: RPR is an independent predictor of in-hospital mortality in critically ill patients with AMI.
Assuntos
Índices de Eritrócitos , Infarto do Miocárdio , Humanos , Mortalidade Hospitalar , Estudos Retrospectivos , Estado TerminalRESUMO
Geldanamycin (GA) is a specific inhibitor of the 90 kDs heat shock protein (Hsp90) in the cytoplasm of mammalian cells, which binds directly to Hsp90 and promotes proteolytic degradation of its client proteins. As an antitumor drug, GA antagonizes the protecting effects of Hsp90 on cell survival, while its mechanisms remain unclear. Here, we show that GA induces apoptosis in a human neuroblastoma cell line, SH-SY5Y. Treatment of the cells with all trans retinoic acid (RA) generates a neuron-like, morphological change of differentiation, and results in the activation of ERK and Akt pathways, an inhibition of the nuclear translocation of p53 induced by GA, and induces higher resistance to the GA-induced apoptosis. These results provide the first evidence for the requirement of p53 nucleation in SH-SY5Y cells to counteract GA in neuron survival.
Assuntos
Apoptose/efeitos dos fármacos , Benzoquinonas/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lactamas Macrocíclicas/farmacologia , Neuroblastoma/tratamento farmacológico , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/fisiologia , Antibióticos Antineoplásicos/farmacologia , Apoptose/fisiologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/fisiopatologia , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Gânglios Simpáticos/efeitos dos fármacos , Gânglios Simpáticos/metabolismo , Gânglios Simpáticos/fisiopatologia , Humanos , Neuroblastoma/metabolismo , Neuroblastoma/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Tretinoína/farmacologia , Proteína Supressora de Tumor p53/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismoRESUMO
AIM: To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD). METHODS: Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0. RESULTS: This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001) but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001). CONCLUSION: The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.
Assuntos
Antibacterianos/uso terapêutico , Dispepsia/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Distribuição de Qui-Quadrado , Quimioterapia Combinada , Dispepsia/diagnóstico , Dispepsia/microbiologia , Feminino , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/patogenicidade , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Indução de Remissão , Fatores de Risco , Resultado do TratamentoRESUMO
Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle.
Assuntos
Antirreumáticos/farmacologia , Cloroquina/farmacologia , Canais Iônicos/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Acetilcolina/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Cálcio/metabolismo , Canais de Cálcio Tipo L/metabolismo , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Contração Muscular/efeitos dos fármacos , Músculo Liso/citologia , Nifedipino/farmacologia , Técnicas de Patch-Clamp , Canais de Potássio/metabolismo , Pirazóis/farmacologia , Canais de Cátion TRPC/antagonistas & inibidores , Canais de Cátion TRPC/metabolismoRESUMO
OBJECTIVE: To assess the potential impact of warming climate in winter to the scale and severity of schistosomiasis epidemics in China. METHODS: Based on the data of mean temperature and monthly minimum temperature in January from 126 (out of 733) weather observation stations in China, the trend and oscillation amplitude was analyzed. The impact of warming climate in winter to the scale of schistosomiasis spreading was assessed, using the indices of 0 degrees C mean temperature and -4 degrees C mean monthly minimum temperature in January. Correlation between these two indices was analyzed. RESULTS: Evidences showed the warming climate in winter was seen all over China with the mean monthly minimum temperature and the mean temperature in January had increased 1.3 degrees C and 0.9 degrees C since 1986. The contours of mean monthly minimum temperature -4 degrees C and mean temperature 0 degrees C in January moved 1 - 2 latitudes northward. CONCLUSION: The warming climate phenomenon seen in winter was considered favorable to the living of snails in winter, resulting in the possible increase of northward spreading of snails.Thus, monitoring of snails should be paid special attention.