RESUMO
Objective: To evaluate the variation of arterial partial pressure of carbon dioxide (PaCO2) in patients with high-risk pulmonary embolism under mechanical ventilation. Methods: We retrospectively analyzed the cases of high-risk pulmonary embolism who underwent intravenous thrombolysis in Peking Union Medical College Hospital from January 1, 2012, to May 1, 2022. The enrolled patients were divided into a mechanical-ventilated group and an active-breathing group according to whether they received invasive mechanical ventilation or not. The level of PaCO2 under active breathing between the two groups, the changes in PaCO2 before intubation, after intubation and after thrombolysis in the mechanical-ventilated group were compared. The 14-day all-cause mortality of the two groups was calculated and compared. Results: A total of 49 patients with high-risk pulmonary embolism were enrolled, including 22 patients in the mechanical-ventilated group and 27 patients in the active-breathing group. Before intubation, PaCO2 in both groups was lower than normal without statistically significant difference between the two groups. After effective thrombolysis therapy, PaCO2 in both groups recovered to the normal range. In the mechanical-ventilated group, PaCO2 significantly increased 11-147 min after intubation and returned to the normal range after thrombolysis therapy. The 14-day mortality in the mechanical-ventilated group was 54.5%, while all patients in the active-breathing group survived. Conclusions: Under mechanical controlled ventilation, patients with high-risk pulmonary embolism could represent hypercapnia which resolved after effective thrombolytic therapy. In mechanical ventilated patients with sudden-onset hypoxemia and hypercapnia, the possibility of high-risk pulmonary embolism should be considered.
Assuntos
Embolia Pulmonar , Respiração Artificial , Humanos , Hipercapnia , Estudos Retrospectivos , Dióxido de Carbono , Doença Aguda , Embolia Pulmonar/terapiaRESUMO
Objective: Based on a cohort and intervention study of the Eastern Chinese Student Surveillance, Cohort and Intervention Study (ES-SCI), this research aims to explore the correlation between monitor of the school environment and longitudinal data on myopia and provide evidence for the government myopia intervention strategy. Methods: This survey adopts the stratified cluster sampling method with the school as the unit. Students from grade 1 to grade 3 were selected according to the whole class to monitor the school environment in the classroom. Students will use the full-automatic computer optometer (TOPCON RM800) to conduct optometry from 2019 to 2021 under the condition of mydriasis to perform refractive eye examinations. Meantime eye axis length monitoring was also conducted. Cox proportional risk regression model was used to explore the relationship between school environmental monitoring and the occurrence and development of students' myopia. Results: From 2019 to 2021, 2 670 students from 77 classrooms participated in the observation study. The students' diopter after right/left eye mydriasis decreased in varying degrees (P<0.001), and the axial length of the right/left eye increased in various degrees (P<0.001). The weighted qualified rate of per capita area of primary school classrooms increased from 18.0% in 2019 to 26.0% in 2021, the weighted average illuminance pass rate of blackboard surface increased from 23.8% in 2019 to 26.4% in 2021, and the weighted average illuminance pass rate of classroom table decreased from 86.7% in 2019 to 77.5% in 2021. The trend chi-square test was significant (P<0.05). Cox proportional risk regression showed that after correcting for the grade, gender, parental myopia, diet, sleep, near work (sitting posture, working time, electronic mobile equipment, eye exercises), and outdoor activities, the per capita area of 1.36- m2 was the protective factor of eye axis length (HR=0.778, 95%CI: 0.659-0.918, P=0.003); The average reflection ratio of blackboard 0.15-0.19 was the protective factor of eye axis length (HR=0.685, 95%CI: 0.592-0.793, P<0.001); The average illumination of the blackboard 150-, 300-, 500- lx was the protective factor of the eye axis length (HR=0.456, 95%CI: 0.534-0.761, P<0.001; HR=0.794, 95%CI: 0.705-0.895, P<0.001; HR=0.690, 95%CI: 0.619-0.768, P<0.001). The blackboard evenness 0.40-0.59 was the risk factor of eye axis length (HR=1.528, 95%CI: 1.018-2.293, P=0.041), and the blackboard evenness 0.80- was the protection factor of eye axis length (HR=0.542, 95%CI: 0.404-0.726, P<0.001). The evenness of the desktop 0.40-0.59 was the protective factor of eye axis length (HR=0.820, 95%CI: 0.698-0.965, P=0.017). The average illuminance of 150-, 300-, 500- lx was the protective factor of a diopter (HR=0.638, 95%CI: 0.534-0.761, P<0.001; HR=0.911, 95%CI: 0.848-0.978, P=0.011; HR=0.750, 95%CI: 0.702-0.801, P<0.001). The average illumination of desktop 500- lx was a protective factor of a diopter (HR=0.855, 95%CI: 0.763-0.958, P=0.007). Conclusion: School environmental monitoring indicators, such as meeting per capita area standards, passing blackboard, and desk top-related indicators, all play protective effects on myopia development in students.
Assuntos
Midríase , Miopia , Humanos , Miopia/epidemiologia , Miopia/prevenção & controle , Refração Ocular , Estudantes , Inquéritos e Questionários , Instituições AcadêmicasRESUMO
This study aimed to investigate the effect of irisin on LPS-induced inflammation in RAW 264.7 macrophages through inhibition of the mitogen-activated protein kinase (MAPK) pathway. A network pharmacology-based approach, combined with molecular docking and in vitro validation were performed to identify the biological activity, key targets, and potential pharmacological mechanisms of irisin against LPS-induced inflammation. By matching 100 potential genes of irisin with 1893 ulcerative colitis (UC) related genes, 51 common genes were obtained. Using protein-protein interaction networks (PPI) and component-target network analysis,10 core genes of irisin on UC were further identified. The results of gene ontology (GO) enrichment analysis showed that the molecular mechanisms of irisin on UC were mainly related to major enrichment in the categories of response to xenobiotic stimulus, response to the drug, and negative regulation of gene expression. Molecular docking results showed good binding activity for almost all core component targets. More importantly, MTT assay and flow cytometry results showed that LPS-induced cytotoxicity was reversed by irisin, after coincubation with irisin, the level of IL-12 and IL-23 decreased in LPS-stimulated RAW264.7 macrophages. Irisin pretreatment significantly inhibited the phosphorylation of ERK and AKT and increased the expression of PPAR alpha and PPAR gamma. LPS-induced enhancement of phagocytosis and cell clearance were reversed by irisin pretreatment. Irisin ameliorated LPS-induced inflammation by inhibiting cytotoxicity and apoptosis, and this protective effect may be mediated through the MAPK pathway. These findings confirmed our prediction that irisin plays an anti-inflammatory role in LPS-induced inflammation via the MAPK pathway.
Assuntos
Colite Ulcerativa , Fibronectinas , Proteínas Quinases Ativadas por Mitógeno , Fibronectinas/farmacologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Macrófagos , Simulação de Acoplamento Molecular , Animais , Camundongos , Células RAW 264.7RESUMO
Electrocyclic reactions are characterized by the concerted formation and cleavage of both σ and π bonds through a cyclic structure. This structure is known as a pericyclic transition state for thermal reactions and a pericyclic minimum in the excited state for photochemical reactions. However, the structure of the pericyclic geometry has yet to be observed experimentally. We use a combination of ultrafast electron diffraction and excited state wavepacket simulations to image structural dynamics through the pericyclic minimum of a photochemical electrocyclic ring-opening reaction in the molecule α-terpinene. The structural motion into the pericyclic minimum is dominated by rehybridization of two carbon atoms, which is required for the transformation from two to three conjugated π bonds. The σ bond dissociation largely happens after internal conversion from the pericyclic minimum to the electronic ground state. These findings may be transferrable to electrocyclic reactions in general.
RESUMO
OBJECTIVE: This study aimed to explore the early diagnostic value of lymphocyte count in the early diagnosis of surgical site infection (SSI) following posterior lumbar fusion. PATIENTS AND METHODS: In this study, we retrospectively analyzed the data from a total of 37 patients with lumbar SSI from Guizhou Province Orthopaedic Hospital and Nanyang Central Hospital, 2008.1-2018.11, and 104 patients without SSI. We analyzed the C-reactive protein (CRP) level, white blood cell count (WBC) and differential count before instrumented lumbar fusion at 3 and 7 days postoperatively. The significance of the differences was evaluated by one-way ANOVA, followed by Fisher's test. The parameters mentioned above were analyzed on postoperative days 3 and 7 using the receiver operating characteristic curve and the area under the curve (AUC). Furthermore, the analyses were conducted by SPSS 22.0 software. RESULTS: The lymphocyte count in the SSI group on postoperative day 3 was significantly lower than that in the no-SSI group after surgery (p=0.000). According to the ROC curve analysis of related parameters on postoperative day 3, the AUC value of lymphocytes (0.840) was significantly larger than the AUC value of C-reactive protein (0.749). CONCLUSIONS: The lymphocyte count and C-reactive protein level on postoperative day 3 are reliable predictors of infection.
Assuntos
Proteína C-Reativa , Infecção da Ferida Cirúrgica , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Proteína C-Reativa/análise , Estudos Retrospectivos , Contagem de Linfócitos , Contagem de Leucócitos , Diagnóstico Precoce , Curva ROCRESUMO
A high-speed infrared small-angle infrared thermography system (SATS) has been developed and installed on the Experimental Advanced Superconducting Tokamak (EAST) for measuring the surface temperature of the divertor target to calculate the high heat flux induced by Edge Localized Modes (ELMs) and providing observation means for the further physical study of some key parameters, such as power decay length λq and the characteristic time of different types of ELMs. An endoscopic optical system is applied to realize the SATS for clear imaging of the divertor plate area and protection from the harm of impurity deposition and latent tungsten ablation during discharge. The field of view (FOV) of the endoscopic optical system is designed to be 13° in the horizontal direction and 9° in the vertical direction. As a consequence, â¼35° of coverage of the lower-outer divertor and a small part of the lower-inner divertor in toroidal are covered by the FOV with a spatial resolution of around 2 mm/pixel. This paper presents a detailed description of the new SATS and the preliminary experimental diagnostic results. The radial distribution of heat flux induced by an ELM crash was demonstrated.
RESUMO
Objective: To understand HIV self-testing and related factors in men who have sex with men (MSM) in Shijiazhuang. Methods: From August to September 2020, convenient sampling was used to recruit MSM in Shijiazhuang. Online questionnaires were used to collect information about their demographic characteristics, sexual behaviors and HIV self-testing. logistic regression model was used to analyze the related factors associated with HIV self-testing. Results: In the 304 MSM respondents, 52.3% (159/304) had HIV self-testing in the past 6 months, and 95.0% (151/159) used fingertip blood HIV detection reagent. Self-purchase was the main way to obtain HIV testing reagents (45.9%, 73/159), followed by supply from MSM social organization (44.7%, 71/159). The reasons for having HIV self-testing were non-specific testing time (67.9%, 108/159) and privacy protection (62.9%,100/159), the reasons for having no HIV self-testing included inability of using (32.4%, 47/145), being unaware of HIV self-testing reagent (24.1%, 35/145), and worry about inaccurate self-testing results (19.3%, 28/145). Multivariate logistic regression analysis showed that being 18-29 years old (aOR=2.68, 95%CI: 1.20-5.94), obtaining free HIV self-testing kits in recent 6 months (aOR=8.61, 95%CI: 4.09-18.11) and making friends through Internet and social software (aOR=2.68, 95%CI: 1.48-4.88) were positive factors for having HIV self-testing. Conclusion: HIV self-testing is a more flexible and convenient way to detect HIV in MSM, and the promotion of HIV self-testing in MSM should be strengthened to further increase the HIV detection rate in this population.
Assuntos
Homossexualidade Masculina , Minorias Sexuais e de Gênero , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Autoteste , Teste de HIV , Comportamento SexualRESUMO
Agriculture produces food, fiber and biofuels for the world's growing population, however, agriculture can be a major contributor of nitrogen (N) losses including emissions of ammonia (NH3), nitrous oxide (N2O) and nitrate (NO3-) leaching and runoff. A Canadian Agricultural Nitrogen Budget for Reactive N (CANBNr) model was developed to estimate the soil N balance in 3487 soil landscape of Canada polygons from 1981 to 2016. The CANBNr model integrates NH3 emission from fertilizers, manure from housing, storage and field, as well as direct/indirect N2O emissions from fertilizers, manures, crop residues and soil organic matter. The NO3- leaching is estimated based on the residual soil N (RSN) at harvest and drainage derived with the DeNitrification-DeComposition (DNDC) model. From 1981 to 2016, the N input from fertilizer and N fixation increased at a greater rate than N removal in harvested crops in all provinces of Canada, resulting in an increase in the RSN and N losses. In 2016, the Prairie provinces had lower N losses (11.7 kg N ha-1) from N2O, NH3 and NO3- compared with 43.2 kg N ha-1 in central Canada, and 76.5 kg N ha-1 in Atlantic Canada. However, the Prairie provinces had 84.3% of the total Canadian farmland (74.3% of the total Canadian N input), while central Canada had 12.9% of Canadian farmland (21.7% of the total Canadian N input). In the Prairie provinces, the total N2O loss from fertilizer N ranged 4.4-8.6 Gg N whereas NH3 loss ranged from 17.1 to 44.6 Gg N and these values were influenced by both emission intensity and total land area. Total N2O losses from manure were highest in Alberta, Ontario and Quebec resulting in 4.8, 4.4, and 3.4 Gg N and NH3 losses from manure were also highest in these 3 provinces at 61.1, 45.2 and 40.4 Gg N, respectively. Nitrate leaching was impacted by drainage volumes, soil type and N inputs. In the non-growing season, NO3- leaching losses (36-yr average) were 63.3 Gg in Ontario and 57.5 Gg N in Quebec compared with 20.8 Gg N for Ontario and 35.5 Gg N for Quebec in the growing season. In contrast, the Prairie provinces showed higher NO3- leaching in the growing season (23.1-37.4 Gg N) than in the non-growing season (10.4-13.7 Gg N). In summary, total fertilizer N increased the most over the 36 years in the Prairies which resulted in increased RSN and N leaching losses that will require further intervention.
RESUMO
The concentration of ice nucleating particles (INPs) in the atmosphere is critical for understanding cloud microphysics and predicting the climate system. In this study, we collected surface snow samples along a traverse route from the coastal to the inland of East Antarctica to analyze INP concentrations and identify their spatial variations using a droplet freezing device. The overall concentration of INPs was found to be considerably low along the route, averaging at 0.8 ± 0.8 × 105 L-1 in water and 4.2 ± 4.8 × 10-3 L-1 in air at -20 °C. Although coastal areas had higher levels of sea salt species compared to inland regions, the concentration of INPs remained consistent along the route suggesting less important origination of INPs from the around ocean. Additionally, the heating experiment revealed the important contribution of proteinaceous INPs indicating the presence of biological INPs (bio-INPs). The fraction of bio-INPs was 0.52 on average at -20 °C and ranged from 0.1 to 0.7 from -30 °C to -15 °C. Finally, we parameterize the atmospheric INP concentrations as a function of freezing temperature which can be useful for modeling INP concentrations in this region.
RESUMO
Using a novel method of isochronous mass spectrometry, the masses of ^{62}Ge, ^{64}As, ^{66}Se, and ^{70}Kr are measured for the first time, and the masses of ^{58}Zn, ^{61}Ga, ^{63}Ge, ^{65}As, ^{67}Se, ^{71}Kr, and ^{75}Sr are redetermined with improved accuracy. The new masses allow us to derive residual proton-neutron interactions (δV_{pn}) in the N=Z nuclei, which are found to decrease (increase) with increasing mass A for even-even (odd-odd) nuclei beyond Z=28. This bifurcation of δV_{pn} cannot be reproduced by the available mass models, nor is it consistent with expectations of a pseudo-SU(4) symmetry restoration in the fp shell. We performed ab initio calculations with a chiral three-nucleon force (3NF) included, which indicate the enhancement of the T=1 pn pairing over the T=0 pn pairing in this mass region, leading to the opposite evolving trends of δV_{pn} in even-even and odd-odd nuclei.
RESUMO
Objective: To conduct a meta-analysis on the influencing factors of mild cognitive impairment (MCI) in the Chinese elderly. Methods: The literature related to the influencing factors of MCI in Chinese elderly population was retrieved through CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases up to March 13, 2022. Stata17.0 software was used to calculate the combined risk ratio (RR) with the 95% confidence interval (CI), test the heterogeneity, and assess the publication bias. Results: A total of 2 450 articles were retrieved, and 49 articles met the inclusion criteria, including 5 cohort studies and 44 case-control studies. Meta-analysis results showed that male (RR=0.778, 95%CI: 0.696-0.870, I2=73.1), education>6years (RR=0.428, 95%CI: 0.374-0.490, I2=86.9) and regular exercise (RR=0.496, 95%CI: 0.421-0.585, I2=81.5) were protective factors for MCI, while age≥70 years (RR=2.431, 95%CI: 2.086-2.833, I2=79.3), family history of dementia (RR=3.228, 95%CI: 2.140-4.867, I2=0.0), smoking (RR=1.214, 95%CI: 1.098-1.342, I2=78.8), alcohol consumption (RR=1.165, 95%CI: 1.047-1.297, I2=68.2), solitary living (RR=2.816, 95%CI: 2.123-3.736, I2=42.0), insomnia (RR=1.402, 95%CI: 1.093-1.799, I2=41.3), overweight/obesity (RR=1.431, 95%CI: 1.207-1.696, I2=75.9), hypertension (RR=1.731, 95%CI: 1.589-1.886, I2=67.1), hyperlipidemia (RR=1.722, 95%CI: 1.541-1.924, I2=63.9), diabetes mellitus (RR=1.495, 95%CI: 1.341-1.666, I2=71.6), cardiovascular diseases (RR=1.671, 95%CI: 1.446-1.932, I2=74.6) and cerebrovascular diseases (RR=2.309, 95%CI: 2.040-2.613, I2=76.3) were risk factors of MCI. Conclusion: The present study indicates that male, junior high school education or above and regular exercise are protective factors of MCI, while age≥70 years, family history of dementia, smoking, alcohol consumption, living alone, insomnia, overweight/obesity, hypertension, hyperlipidemia, diabetes, cardiovascular diseases and cerebrovascular diseases are risk factors of MCI.
Assuntos
Doenças Cardiovasculares , Disfunção Cognitiva , Demência , Diabetes Mellitus , Hipertensão , Distúrbios do Início e da Manutenção do Sono , Humanos , Masculino , Idoso , Sobrepeso , População do Leste Asiático , Disfunção Cognitiva/epidemiologia , Fatores de Risco , Obesidade , Demência/psicologiaRESUMO
A 75-year-old male patient presented to the hospital with metamorphopsia of the left eye for 1 month. The corrected visual acuity of left eye was 0.5. Fundus examination showed leopard fundus, small patches of pigmentation were present in the macular area, depigmentation around the macula,choroidal macrovessel emerged from the macular area in a horizontal, temporal, serpentine pattern, optical coherence tomography showed an abnormally enlarged hypo-reflective cavity occupying the full thickness of the choroid in the subfovea as well as in the temporal side of the macula. Early fundus indocyanine green angiography showed rapid filling fluorescence tracks distributed from macula to the temporal side. The patient was diagnosed with macular choroidal macrovessel based on medical history, ocular multimodal examination and general examination. The patient was not given special treatment, and was instructed to control blood pressure in the department of internal medicine and to follow up regularly in the outpatient clinic of fundus disease.
Assuntos
Corioide , Tomografia de Coerência Óptica , Masculino , Humanos , Idoso , Angiofluoresceinografia/métodos , Fundo de Olho , Tomografia de Coerência Óptica/métodos , Transtornos da VisãoRESUMO
Objective: To study the diagnostic value of different detection markers in histological categories of endocervical adenocarcinoma (ECA), and their assessment of patient prognosis. Methods: A retrospective study of 54 patients with ECA in the Cancer Hospital, Chinese Academy of Medical Sciences from 2005-2010 were performed. The cases of ECA were classified into two categories, namely human papillomavirus-associated adenocarcinoma (HPVA) and non-human papillomavirus-associated adenocarcinoma (NHPVA), based on the 2018 international endocervical adenocarcinoma criteria and classification (IECC). To detect HR-HPV DNA and HR-HPV E6/E7 mRNA in all patients, we used whole tissue section PCR (WTS-PCR) and HPV E6/E7 mRNA in situ hybridization (ISH) techniques, respectively. Additionally, we performed Laser microdissection PCR (LCM-PCR) on 15 randomly selected HR-HPV DNA-positive cases to confirm the accuracy of the above two assays in identifying ECA lesions. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of markers to identify HPVA and NHPVA. Univariate and multifactorial Cox proportional risk model regression analyses were performed for factors influencing ECA patients' prognoses. Results: Of the 54 patients with ECA, 30 were HPVA and 24 were NHPVA. A total of 96.7% (29/30) of HPVA patients were positive for HR-HPV DNA and 63.3% (19/30) for HR-HPV E6/E7 mRNA, and 33.3% (8/24) of NHPVA patients were positive for HR-HPV DNA and HR-HPV E6/E7 mRNA was not detected (0/24), and the differences were statistically significant (P<0.001). LCM-PCR showed that five patients were positive for HR-HPV DNA in the area of glandular epithelial lesions and others were negative, which was in good agreement with the E6/E7 mRNA ISH assay (Kappa=0.842, P=0.001). Analysis of the ROC results showed that the AUC of HR-HPV DNA, HR-HPV E6/E7 mRNA, and p16 to identify HPVA and NHPVA were 0.817, 0.817, and 0.692, respectively, with sensitivities of 96.7%, 63.3%, and 80.0% and specificities of 66.7%, 100.0%, and 58.3%, respectively. HR-HPV DNA identified HPVA and NHPVA with higher AUC than p16 (P=0.044). The difference in survival rates between HR-HPV DNA (WTS-PCR assay) positive and negative patients was not statistically significant (P=0.156), while the difference in survival rates between HR-HPV E6/E7 mRNA positive and negative patients, and p16 positive and negative patients were statistically significant (both P<0.05). Multifactorial Cox regression analysis showed that International Federation of Obstetrics and Gynecology (FIGO) staging (HR=19.875, 95% CI: 1.526-258.833) and parametrial involvement (HR=14.032, 95% CI: 1.281-153.761) were independent factors influencing the prognosis of patients with ECA. Conclusions: HR-HPV E6/E7 mRNA is more reflective of HPV infection in ECA tissue. The efficacy of HR-HPV E6/E7 mRNA and HR-HPV DNA (WTS-PCR assay) in identifying HPVA and NHPVA is similar, with higher sensitivity of HR-HPV DNA and higher specificity of HR-HPV E6/E7 mRNA. HR-HPV DNA is more effective than p16 in identifying HPVA and NHPVA. HPV E6/E7 mRNA and p16 positive ECA patients have better survival rates than negative.
Assuntos
Adenocarcinoma , Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Infecções por Papillomavirus/diagnóstico , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Prognóstico , Proteínas Oncogênicas Virais/genética , Papillomavirus Humano , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/patologia , RNA Mensageiro/genética , Papillomaviridae/genética , RNA Viral/análise , RNA Viral/genéticaRESUMO
Immune checkpoint molecule PD-1, expressed on the cell surface, impairs antigen-driven activation of T cells and thus plays a critical role in tumorigenesis, progression, and the poor prognosis of oral squamous cell carcinoma (OSCC). In addition, increasing evidence indicates that PD-1 carried on small extracellular vesicles (sEVs) also mediates tumor immunity, although their contributions to OSCC are yet unclear. Here, we investigated the biological functions of sEV PD-1 in patients with OSCC. The cell cycle, proliferation, apoptosis, migration, and invasion of CAL27 cell lines treated with or without sEV PD-1 were examined in vitro. We performed mass spectrometry to investigate the underlying biological process, combined with an immunohistochemical study of SCC7-bearing mice models and OSCC patient samples. In vitro data demonstrated that sEV PD-1 induced senescence and subsequent epithelial-mesenchymal transition (EMT) in CAL27 cells by ligating with tumor cell surface PD-L1 and activating the p38 mitogen-activated protein kinase (MAPK) pathway. Comprehensive immunohistochemical analysis of the xenograft mice models and OSCC patient samples revealed a very close correlation between the level of circulating sEV PD-1 and lymph node metastasis. These results demonstrate that circulating sEV PD-1 triggers senescence-initiated EMT in a PD-L1-p38 MAPK-dependent manner, contributing to tumor metastasis. It also suggests that the inhibition of sEV PD-1 may be a promising therapeutic target for the treatment of OSCC.
RESUMO
OBJECTIVE: This study aimed to investigate the effect of quercetin on cellular immunity (via IL15 expression) against cancer and to elucidate its regulatory mechanism. MATERIALS AND METHODS: HeLa cells and A549 cells were cultured in vitro and were divided into control (DMSO treated) and experimental groups (treated with different concentrations of quercetin). Transcript levels of IL15 and DNA methyltransferase (DNMTS) were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Genomic DNA was extracted, treated with bisulfite, and the promoter region of IL15 was cloned. Finally, Sanger sequencing was used to detect the degree of promoter methylation. RESULTS: Following quercetin treatment, the expression of IL15 was significantly downregulated in HeLa and A549 cells. The methylation level of IL15 promoter in HeLa cells was about twice that of the control group, and the methylation level of IL15 promoter in A549 cells was about three times that of the control group. CONCLUSIONS: Quercetin inhibits cancer cell proliferation while downregulating IL15 expression, and this regulation is achieved by increasing the methylation of the IL15 promoter.
Assuntos
Metilação de DNA , Neoplasias , Humanos , Células HeLa , Quercetina/farmacologia , Interleucina-15/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Neoplasias/genéticaRESUMO
This study aimed to investigate whether the developmental changes in glucose metabolism were associated with insulin signaling in the middle and later stages of goose embryos. Serum and liver were sampled on embryonic day 19, 22, 25, 28, and day of hatchment, with 30 eggs at each sampling time point, and 6 replicates of 5 embryos. The embryonic growth traits, serum glucose, hormone levels, and the hepatic mRNA expressions of target genes related to glucose metabolism and insulin signaling were measured at each time point. Relative body weight, relative liver weight, and relative body length decreased linearly and quadratically from embryonic day 19 to day of hatchment, while relative yolk weight decreased linearly from embryonic day 19 to day of hatchment. Serum glucose, insulin, and free triiodothyronine levels increased linearly with increasing incubation time, while no differences were observed in serum glucagon and free thyroxine levels. The hepatic mRNA expression related to glucose catabolism (hexokinase, phosphofructokinase, and pyruvate kinase) and insulin signaling (insulin receptor, insulin receptor substrate protein, Src homology collagen protein, extracellular signal-regulated kinase, and ribosomal protein S6 kinase, 70 ku) increased quadratically from embryonic day 19 to day of hatchment. The expression of citrate synthase and isocitrate dehydrogenase mRNA decreased linearly and quadratically respectively from embryonic day 19 to day of hatchment. Serum glucose levels were positively related to serum insulin (r = 1.00) and free triiodothyronine (r = 0.90) levels, as well as the hepatic mRNA expression of insulin receptor (r = 1.00), insulin receptor substrate protein (r = 0.64), extracellular signal-regulated kinase (r = 0.81), and ribosomal protein S6 kinase, 70 ku (r = 0.81) related to insulin signaling. In conclusion, glucose catabolism was enhanced and had positive correlations with the insulin signaling in the middle and later stages of geese embryogenesis.
Assuntos
Gansos , Insulina , Animais , Insulina/metabolismo , Gansos/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Tri-Iodotironina , Proteínas Substratos do Receptor de Insulina/metabolismo , Galinhas/genética , Óvulo/metabolismo , Fígado/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Glucose/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , RNA Mensageiro/genéticaRESUMO
BACKGROUND AND PURPOSE: Endovascular treatment is a reference treatment for acute basilar artery occlusion (ABAO). However, no established and specific methods are available for the preoperative screening of patients with ABAO suitable for endovascular treatment. This study explores the potential value of DWI-based radiomics in predicting the functional outcomes of endovascular treatment in ABAO. MATERIALS AND METHODS: Patients with ABAO treated with endovascular treatment from the BASILAR registry (91 patients in the training cohort) and the hospitals in the Northwest of China (31 patients for the external testing cohort) were included in this study. The Mann-Whitney U test, random forests algorithm, and least absolute shrinkage and selection operator were used to reduce the feature dimension. A machine learning model was developed on the basis of the training cohort to predict the prognosis of endovascular treatment. The performance of the model was evaluated on the independent external testing cohort. RESULTS: A subset of radiomics features (n = 6) was used to predict the functional outcomes in patients with ABAO. The areas under the receiver operating characteristic curve of the radiomics model were 0.870 and 0.781 in the training cohort and testing cohort, respectively. The accuracy of the radiomics model was 77.4%, with a sensitivity of 78.9%, specificity of 75%, positive predictive value of 83.3%, and negative predictive value of 69.2% in the testing cohort. CONCLUSIONS: DWI-based radiomics can predict the prognosis of endovascular treatment in patients with ABAO, hence allowing a potentially better selection of patients who are most likely to benefit from this treatment.
Assuntos
Artéria Basilar , Humanos , Artéria Basilar/diagnóstico por imagem , Artéria Basilar/cirurgia , Estudos Retrospectivos , Prognóstico , Valor Preditivo dos Testes , Curva ROCRESUMO
Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.