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BACKGROUND: Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. METHODS: To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. RESULTS: Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p < 0.0001) and the CRC subcutaneous murine model (35.0 ± 2.6, p < 0.0001). CCR8 was found to be preferentially expressed on these tumor-infiltrating Tregs (CRC patients: 63.6 ± 16.0, p < 0.0001; CRC murine model: 65.3 ± 9.5, p < 0.0001), which correlated with poor survival. We found that majority of the CCR8+ Tregs expressed activation markers and exhibited strong suppressive functions. Treatment with anti-CCR8 antibody hampered the growth of subcutaneous CRC tumor through effectively restoring the anti-tumor immunity of CD4+ conventional T cells (CD4+ Tconvs) and CD8+ T cells, which was confirmed in the ex vivo examinations. CONCLUSIONS: Collectively, these findings illustrate the importance of CCR8+ Tregs for an immunosuppressive microenvironment in CRC tumors by functional inhibition of CD4+ Tconvs and CD8+ T cells, and suggest for the applicable value of CCR8-targeted therapy for CRC.
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Linfócitos T CD8-Positivos , Neoplasias Colorretais , Linfócitos do Interstício Tumoral , Receptores CCR8 , Linfócitos T Reguladores , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Imunidade , Linfócitos do Interstício Tumoral/imunologia , Camundongos Endogâmicos BALB C , Linfócitos T Reguladores/imunologia , IdosoRESUMO
Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy.
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Classe I de Fosfatidilinositol 3-Quinases , Mutação , Neoplasias , Receptores de Antígenos de Linfócitos T , Humanos , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/genética , Imunoterapia/métodos , Antígeno HLA-A11/genética , Antígeno HLA-A11/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/genética , Linhagem Celular TumoralRESUMO
The phase transition of AF2 difluorides strongly depends on pressure, temperature, and cationic radius. Here, we have investigated the phase transition of three difluorides, including MgF2, CaF2, and BaF2, at simultaneously high pressures and temperatures using Raman spectroscopy and X-ray diffraction in externally heated diamond anvil cells up to 55 GPa at 300-700 K. Rutile-type difluoride MgF2 with a small cationic radius undergoes a transition to the CaCl2-type phase at 9.9(1) GPa and 300 K, to the HP-PdF2-type phase at 21.0(2) GPa, and to the cotunnite-type phase at 44.2(2) GPa. The phase transition pressure to the HP-PdF2 and cotunnite structure at 300 K for our single crystal was found to be higher than that in previous studies using polycrystalline samples. Elevating the temperature increases the transition pressure from rutile- to the CaCl2-type phase but has a negative influence on the transition pressure when MgF2 transforms from the HP-PdF2- to cotunnite-type phase. Meanwhile, the transition pressure from the CaCl2- to HP-PdF2-type phase for MgF2 was identified to be independent of the temperature. Raman peaks suspected to belong to the α-PbO2-type phase were observed at 14.6-21.0(1) GPa and 400-700 K. At 300 K, difluorides CaF2 and BaF2 in the fluorite structure with larger cationic radii transform to the cotunnite-type phase at 9.6(3) and 3.0(3) GPa at 300 K, respectively, and BaF2 further undergoes a transition to the Ni2In-type phase at 15.5(4) GPa. For both CaF2 and BaF2, elevating the temperature leads to a lower transition pressure from fluorite- to the cotunnite-type phase but has little influence on the transition to the Ni2In structure. Raman data provide valuable insights for mode Grüneisen parameters. We note that the mode Grüneisen parameters for both difluorides and dioxides vary linearly with the cation radius. Further calculations for the mode Grüneisen parameters at high pressures for MgF2, CaF2, and BaF2 yield a deeper understanding of the thermodynamic properties of the difluorides.
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Machine learning algorithms are frequently used to clinical risk prediction. Our study was designed to predict risk factors of prolonged intra-aortic balloon pump (IABP) use in patients with coronary artery bypass grafting (CABG) through developing machine learning-based models. Patients who received perioperative IABP therapy were divided into two groups based on their length of IABP implantation longer than the 75th percentile for the whole cohort: normal (≤ 10 days) and prolonged (> 10 days) groups. Seven machine learning-based models were created and evaluated, and then the Shapley Additive exPlanations (SHAP) method was employed to further illustrate the influence of the features on model. In our study, a total of 143 patients were included, comprising 56 cases (38.16%) in the prolonged group. The logistic regression model was considered the final prediction model according to its most excellent performance. Furthermore, feature important analysis identified left ventricular end-systolic or diastolic diameter, preoperative IABP use, diabetes, and cardiac troponin T as the top five risk variables for prolonged IABP implantation in patients. The SHAP analysis further explained the features attributed to the model. Machine learning models were successfully developed and used to predict risk variables of prolonged IABP implantation in patients with CABG. This may help early identification for prolonged IABP use and initiate clinical interventions.
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Ponte de Artéria Coronária , Balão Intra-Aórtico , Aprendizado de Máquina , Humanos , Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/métodos , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Medição de Risco/métodos , Doença da Artéria Coronariana/cirurgia , Fatores de TempoRESUMO
China is home to the second largest population of children and adolescents in the world. Yet demographic shifts mean that the government must manage the challenge of fewer children with the needs of an ageing population, while considering the delicate tension between economic growth and environmental sustainability. We mapped the health problems and risks of contemporary school-aged children and adolescents in China against current national health policies. We involved multidisciplinary experts, including young people, with the aim of identifying actionable strategies and specific recommendations to promote child and adolescent health and wellbeing. Notwithstanding major improvements in their health over the past few decades, contemporary Chinese children and adolescents face distinct social challenges, including high academic pressures and youth unemployment, and new health concerns including obesity, mental health issues, and sexually transmitted infections. Inequality by gender, geography, and ethnicity remains a feature of health risks and outcomes. We identified a mismatch between current health determinants, risks and outcomes, and government policies. To promote the health of children and adolescents in China, we recommend a set of strategies that target government-led initiatives across the health, education, and community sectors, which aim to build supportive and responsive families, safe communities, and engaging and respectful learning environments. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Política de Saúde , Adolescente , Criança , Feminino , Humanos , Masculino , Saúde do Adolescente , Saúde da Criança , China , População do Leste Asiático , Necessidades e Demandas de Serviços de SaúdeRESUMO
OBJECTIVES: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. METHODS: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. RESULTS: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. CONCLUSIONS: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients.
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Terapia de Substituição Renal Contínua , Ponte de Artéria Coronária , Aprendizado de Máquina , Humanos , Ponte de Artéria Coronária/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Medição de Risco , Fatores de Risco , Estudos Retrospectivos , Teorema de Bayes , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Injúria Renal Aguda/diagnóstico , Curva ROC , Unidades de Terapia IntensivaRESUMO
BACKGROUND: Medical service prices play a crucial role in cost containment in China. This study aimed to assess the change in medical service price levels at the macro level and the relationship with relevant macroeconomic factors. METHODS: Data from the 2022 China Statistics Yearbook, the 2022 China Health Statistics Yearbook, and the 2020 China National Health Accounts Report were used. Time trends of health price levels, utilization, and health expenditure were examined. A time-series regression model was employed to measure the impact of service utilization and medical service prices on total medical service expenditure growth from 2000 to 2021. The Johansen cointegration test was conducted to test the cointegrating relationship between medical service price levels and total medical service expenditure, average wage of employees and CPI. The Granger causality test was performed to observe the direction of causality. RESULTS: Descriptive analyses showed consistent growth in utilization and medical service price levels from 2000 to 2021. The time-series model indicated that medical service expenditure was influenced by the rise in inpatient admissions and price levels of medical service and medicine. The Johansen cointegration test identified a long-term equilibrium relationship between medical service price levels and total medical service expenditure, average wage and CPI. The change in medical service price levels was the Granger cause of the change in medical service expenditure, but it had no impact on average wage and CPI. However, the change in medical service price levels was influenced by these three macroeconomic factors. CONCLUSIONS: The growth of medical service expenditure in China was driven by inpatient use and price level. There was a long-term equilibrium relationship between medical service price levels and relevant macroeconomic factors. However, medical service price levels only affected medical service expenditure and have no impact on average wage and CPI. It is necessary to improve the value transmission mechanism of medical service prices.
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Gastos em Saúde , Nível de Saúde , Humanos , China , Hospitalização , Pacientes InternadosRESUMO
Asymmetric synthesis based on a metallate shift of tetracoordinate borons is an intriguing and challenging topic. Despite the construction of central chirality from tetracoordinate boron species via a 1,2-metallate shift, catalytic asymmetric synthesis of axially chiral compounds from such boron 'ate' complexes is an ongoing challenge. Axially chiral alkenes have received great attention due to their unique characteristics and intriguing molecular scaffolds. Here we report an enantioselective nickel-catalysed strategy for the construction of axially chiral alkenes via a 1,3-metallate shift of alkynyl tetracoordinate boron species. The chemoselectivity, regioselectivity and atroposelectivity can be regulated and well-controlled from readily accessible starting materials with a cheap transition-metal catalyst. Downstream transformations indicate the powerful conversion ability of such compounds in this protocol, and late-stage elaborations of bioactive compounds can also be achieved. Mechanistic experiments reveal that regioselective syn-addition of an aryl-Ni complex with a carbon-carbon triple bond and subsequent 1,3-phenyl migration are the two key steps for the synthesis of axially chiral alkenes.
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One of the major pathological processes in cataracts has been identified as ferroptosis. However, studies on the iron metabolism mechanism in lens epithelial cells (LECs) and the methods of effectively alleviating ferroptosis in LECs are scarce. Along these lines, we found that in the ultraviolet radiation b (UVB) induced cataract model in vitro and in vivo, the ferritin of LECs is over-degraded by lysosomes, resulting in the occurrence of iron homeostasis disorder. Glycine can affect the ferritin degradation through the proton-coupled amino acid transporter (PAT1) on the lysosome membrane, further upregulating the content of nuclear factor erythrocyte 2 related factor 2 (Nrf2) to reduce the damage of LECs from two aspects of regulating iron homeostasis and alleviating oxidative stress. By co-staining, we further demonstrate that there is a more sensitive poly-(rC)-binding protein 2 (PCBP2) transportation of iron ions in LECs after UVB irradiation. Additionally, this study illustrated the increased expression of nuclear receptor coactivator 4 (NCOA4) in NRF2-KO mice, indicating that Nrf2 may affect ferritin degradation by decreasing the expression of NCOA4. Collectively, glycine can effectively regulate cellular iron homeostasis by synergistically affecting the lysosome-dependent ferritin degradation and PCBP2-mediated ferrous ion transportation, ultimately delaying the development of cataracts.
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Catarata , Ferritinas , Camundongos , Animais , Ferritinas/metabolismo , Glicina/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Raios Ultravioleta , Ferro/metabolismo , Células Epiteliais/metabolismo , Catarata/metabolismo , Homeostase/fisiologia , Lisossomos/metabolismoRESUMO
Background: Non-communicable diseases (NCDs) such as cancer, diabetes, heart disease, mental disorder and chronic lung conditions are the leading cause of death and disability in Indonesia. Adolescence is when risks for NCDs emerge and it is also an important life stage for intervention, yet young people are often at the margins of NCD policy and actions. This study aimed to understand how policies and actions should address NCD risks (tobacco smoking, inadequate physical activity, and diet) for adolescents in Indonesia, and how young people can be meaningfully involved. Methods: Qualitative in-depth interviews over videoconference (n = 21) were conducted in English or Bahasa with stakeholders in Indonesia. Participants included policymakers, implementation partners, and advocates who were focused on adolescent health or NCDs. Interviews were recorded, transcribed, translated, and thematically analysed using NVivo12. Findings were disseminated to participants for validation and feedback. Youth participants (n = 7) attended an additional workshop and considered recommendations and actions arising from this research. Findings: Participants identified that government and non-government organisations are acting on NCDs in Indonesia, but few of the existing initiatives target adolescents, and adolescent services rarely addressed NCD risks. Participants also felt that policies to protect adolescents from NCD risks (i.e., smoke-free areas in public) were not always enforced. For programs or initiatives focused on adolescent health, those that had engaged adolescents as co-creators and leaders were perceived to be more successful. As such, participants recommended more meaningful engagement of young people, including young people's leadership of initiatives. Additional recommendations included the need for intersectoral engagement and a 'whole-of-government' approach to prevention given the complex determinants of NCD risks, and the need for evidence-based actions that are underpinned by quality data to enable monitoring of progress. Interpretation: There is a recognised need to strengthen policies and actions to address NCD risks amongst adolescents in Indonesia. Meaningful youth engagement that allows young people to take the lead, intersectoral actions, and evidence-based data driven responses were key strategies identified. Funding: UNICEF East Asia and Pacific Regional Office.
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BACKGROUND: Price differences of medical services across regions may affect equity in health financing. This study aimed to estimate the spatial price index of medical services to measure price levels across regions in the Yangtze River Delta, China. METHODS: Gini-Éltetö-Köves-Szulc method and minimum spanning tree method based on the purchasing power parities were used in this study. RESULTS: According to the Gini-Éltetö-Köves-Szulc method, Shanghai and Anhui province had price levels that are 127.55% and 103.45% respectively of the price level in Zhejiang province, whereas in Jiangsu medical services were priced at 92.71% of that in Zhejiang province. The spatial price index of medical services in the Yangtze River Delta based on the minimum spanning tree method provided similar results. CONCLUSIONS: Regions in the Yangtze River Delta had significant gaps in medical services price levels. And the price levels tended to not correlate with socioeconomic levels. It is necessary to promote the regional coordination of medical services price and better achieve equity in health.
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Rios , Humanos , China , CidadesRESUMO
A cost-effective approach has been developed to synthesize Cu nanoparticles encapsulated into B and N double-doped carbon nanotubes (Cu@BCNNTs) by one-step pyrolysis. According to the specific binding of Cu-Cl and Cu-glutathione (GSH), we employed Cu@BCNNTs to build an electrochemical sensing platform to detect GSH. The unique space-confined structure can prevent Cu nanoparticles from agglomeration. In addition, B and N co-doped porous hollow tubes can improve the electrochemical conductivity, expand the number of active sites, enhance surface adsorption, and shorten the transport path. These favorable characteristics of Cu@BCNNTs make them have excellent electrocatalytic properties. These results display that the prepared sensor can detect GSH from 0.5 to 120 µM with a detection limit of 0.024 µM. The obtained sensors can be successfully applied in the human serum with recovery of GSH ranging from 100.2 to 103.9%. This work provides a new vision to synthesize nanoparticles confined in a hollow tube for the applications in biosensing and medical diagnostics.
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Técnicas Biossensoriais , Nanopartículas , Nanotubos de Carbono , Humanos , Nanotubos de Carbono/química , Porosidade , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Eletrodos , Nanopartículas/química , Glutationa , NanotecnologiaRESUMO
Total of 172 total suspended particulate (TSP) samples and its chemical compositions were collected and analyzed from January to December 2010 in Pengjia Yu Island, an open region in East China Sea (ECS). Despite the predominance of sea-salt major ions (Na+, Cl-), the presence of non-sea-salt SO42- (nss-SO42-) and NO3- as well as combustion-derived trace metals clearly establishes the impact of anthropogenic sources over ECS. The annual contributions of coal, heavy-fuel oil and traffic to the measured chemical species were 21.0 %, 15.0 % and 15.5 %, respectively. Especially in spring, the contributions of crustal minerals to measured chemical species during dust period (33.6 %) were higher than that (13.2 %) during non-dust period. The calculated annual average dry deposition fluxes for trace metals and total inorganic nitrogen were 246.1 ± 345.8 µg/m2/d and 2950.4 ± 2245.0 µg/m2/d, suggesting that atmospheric deposition is an important source of nutrient elements for the south of ECS.
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Poluentes Atmosféricos , Material Particulado , Material Particulado/análise , Poluentes Atmosféricos/análise , Estações do Ano , Poeira/análise , China , Íons/análise , Minerais , Carvão Mineral/análise , Monitoramento Ambiental , Aerossóis/análiseRESUMO
Although statins are shown to have cardiac pleiotropic effects independent of lowering cholesterol, the underlying mechanism remains unclear. Mitochondrial dysfunction induced by increased fatty acid oxidation (FAO) is the culprit in the development of cardiac hypertrophy and dysfunction. This study was to explore whether the cardiac pleiotropic effects of atorvastatin were associated with FAO regulation, with a specific focus on carnitine palmitoyltransferase 1 (CPT1). High-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated neonatal rat primary cardiomyocytes (NRCMs) were treated with atorvastatin, with or without FAO modulators, signal transducer and activator of transcription 3 (STAT3) agonist, and inhibitor. Atorvastatin (3 mg/kg) did not reduce serum cholesterol levels in HFD-fed mice but ameliorated mitochondrial dysfunction and cardiac hypertrophy. In vitro, atorvastatin and the FAO inhibitor alleviated PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy. However, the FAO enhancer eliminated atorvastatin's protective effects. Furthermore, atorvastatin decreased CPT1 and FAO levels and prevented STAT3 phosphorylation and nuclear translocation. STAT3 inhibitor had the same inhibitory effects as atorvastatin on CPT1, FAO levels, and cardiomyocyte hypertrophy, whereas STAT3 agonist disrupted these effects of atorvastatin. Our results demonstrate that atorvastatin decreases myocardial FAO by inactivating the p-STAT3/CPT1 signaling pathway, which improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy in a cholesterol-independent manner. This is the first study to explore the cardiac pleiotropic effects of atorvastatin with respect to FAO. However, whether atorvastatin regulates FAO in the cardiac hypertrophy model induced by other variables has not been investigated in this work, and this is expected to be performed in the future.
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Carnitina O-Palmitoiltransferase , Fator de Transcrição STAT3 , Ratos , Camundongos , Animais , Carnitina O-Palmitoiltransferase/metabolismo , Fator de Transcrição STAT3/metabolismo , Atorvastatina/farmacologia , Cardiomegalia/metabolismo , Miócitos Cardíacos , Ácido Palmítico/farmacologia , Mitocôndrias , Ácidos Graxos/metabolismoRESUMO
BACKGROUND: Although standard bicaval techniques has become popular in orthotopic heart transplantation, distortion, bleeding, thrombosis and arrhythmia were still causes for concern. This study was designed to compare the standard bicaval techniques and modified bicaval techniques in our institution. MATERIALS AND METHODS: A total of 70 recipients underwent orthotopic heart transplantation at our center from June 2015 to April 2019 (standard group = 24 cases, modified group = 46 cases). The average follow-up period was 46.4 ± 17.4 months. Atrioventricular cavity diameter was measured by ultrasonography and left atrial morphology was evaluated by CT-angiography and three-dimensional reconstruction. RESULTS: Recipients in both groups were similar with pre-operative characteristics. Total ischemic, cardiopulmonary bypass and cross-clamp times were similar. The modified bicaval techniques group has a significantly fewer blood transfusion, lower post-transplant tricuspid regurgitation grade and the incidence of post-operative atrial arrhythmia than standard bicaval techniques group. CT-angiography and three-dimensional reconstruction illustrated ideal and physiologic left atrial morphological structure. Short-term survival differed significantly and the cumulative proportion of survival was significantly higher in the modified bicaval techniques group than that in the standard bicaval techniques group. CONCLUSIONS: This study showed that modified bicaval techniques offers a better early outcome than standard bicaval techniques. The significant reduction of intraoperative blood transfusion and post-transplant tricuspid regurgitation grade in the modified bicaval techniques group may has a major impact on the short-term survival.
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Fibrilação Atrial , Transplante de Coração , Insuficiência da Valva Tricúspide , Humanos , Insuficiência da Valva Tricúspide/etiologia , Tração/efeitos adversos , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Anastomose Cirúrgica/métodos , Técnicas de Sutura/efeitos adversosRESUMO
BACKGROUND: The endothelial-mesenchymal transition (EndMT) is an important mechanism in tissue regeneration and the development of organ fibrosis. Whether EndMT occurs in wound healing and scarring remains unknown. MATERIALS AND METHODS: The isolated cells from the normal dermal tissue and the wound tissue of mouse with full-thickness skin wound, and human scar tissue sections were performed with CD31/factorVII and α-SMA immunohistochemical staining and H and E staining. The ratio of factor VII or CD31/α-SMA double-positive cells in factor VII-positive cells was assessed in the isolated cells and in scar tissues. RESULTS: In this study, we found that approximately 27-60% of ECs coexpressed VII factor and α-SMA in the isolated cells from the wound tissues of mice, which was significantly higher than that of normal dermal tissue cells. Accordingly, the number of CD31/α-SMA double-positive cells in mouse wound tissue sections was also significantly more than that in normal dermal tissue sections. In scar tissues, in addition to high-density microvessels, a large number of proliferative ECs in scar strama and CD31/α-SMA double-positive cells were also found. Approximately 46.82 to 84.11% of ECs and 68.77 to 95.25% of myofibroblasts coexpressed VII factor and α-SMA, and these two values in hypertrophic scars were significantly higher than those in keloids. CONCLUSION: These results confirmed that ECs might contribute to the emergence of myofibroblasts in the wound and scar tissue via the process of EndMT.
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Cicatriz Hipertrófica , Queloide , Humanos , Camundongos , Animais , Miofibroblastos/patologia , Fator VII , Cicatrização , Cicatriz Hipertrófica/patologiaRESUMO
OBJECTIVE: Infection is one of the important and frequent complications following implantable pulse generator and deep brain stimulation (DBS) electrode insertion. The goal of this study was to retrospectively evaluate and identify potential risk factors for DBS infections. METHODS: From January 2015 to January 2021 in Qingdao municipal hospital (training cohort) and The First Affiliated Hospital of the University of Science and Technology of China (validation cohort), the authors enrolled patients with Parkinson disease who had undergone primary DBS placement or implantable pulse generator replacement. The cases were divided into infection or no-infection groups according to the 6-month follow-up. The authors used the logistic regression models to determine the association between the variables and DBS infection. Depending on the results of logistic regression, the authors established a nomogram. The calibration curves, receiver operating characteristic curve analysis, and decision curves were used to evaluate the reliability of the nomogram. RESULTS: There were 191 cases enrolled in the no-infection group and 20 cases in the infection group in the training cohort. The univariate logistic regression showed that BMI, blood glucose, and albumin were all significant predictors of infection after DBS surgery (OR 0.832 [p = 0.009], OR 1.735 [p < 0.001], and OR 0.823 [p = 0.001], respectively). In the crude, adjust I, and adjust II models, the three variables stated above were all considered to be significant predictors of infection after DBS surgery. The calibration curves in both training and validation cohorts showed that the predicted outcome fitted well to the observed outcome (p > 0.05). The decision curves showed that the nomogram had more benefits than the "All or None" scheme. The areas under the curve were 0.93 and 0.83 in the training and validation cohorts, respectively. CONCLUSIONS: The nomogram included BMI, blood glucose, and albumin, which were significant predictors of infection in patients with DBS surgery. The nomogram was reliable for clinical application.
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Estimulação Encefálica Profunda , Nomogramas , Humanos , Glicemia , Estimulação Encefálica Profunda/efeitos adversos , Reprodutibilidade dos Testes , Estudos Retrospectivos , AlbuminasRESUMO
The repetitive applications of vaccine boosters have been brought up in face of continuous emergence of SARS-CoV-2 variants with neutralization escape mutations, but their protective efficacy and potential adverse effects remain largely unknown. Here, we compared the humoral and cellular immune responses of an extended course of recombinant receptor binding domain (RBD) vaccine boosters with those from conventional immunization strategy in a Balb/c mice model. Multiple vaccine boosters after the conventional vaccination course significantly decreased RBD-specific antibody titers and serum neutralizing efficacy against the Delta and Omicron variants, and profoundly impaired CD4+ and CD8+T cell activation and increased PD-1 and LAG-3 expressions in these T cells. Mechanistically, we confirmed that extended vaccination with RBD boosters overturned the protective immune memories by promoting adaptive immune tolerance. Our findings demonstrate potential risks with the continuous use of SARS-CoV-2 vaccine boosters, providing immediate implications for the global COVID-19 vaccination enhancement strategies.
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BMP10 signaling has been implicated in regulation of cardiovascular cell fate determination and diseases, while the underlying molecular mechanism still remains uncertain. Here, the human embryonic stem cell line (H7-BMP10del) with homozygous deletion of BMP10 was generated by CRISPR/Cas9 method. Thus, the crosstalk related to BMP10 signaling could be investigated in cell fate determination and the molecular pathogenesis of cardiovascular disease.
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Sistemas CRISPR-Cas , Células-Tronco Embrionárias Humanas , Humanos , Proteínas Morfogenéticas Ósseas , Sistemas CRISPR-Cas/genética , Homozigoto , Deleção de Sequência , Linhagem CelularRESUMO
Subsequently to the publication of this paper, an interested reader drew to the authors' attention that the same control ßactin bands had apparently been included in the western blots featured in Fig. 5E and F, even though different experiments were presented in these figure parts. The authors have reexamined their data and realized that Fig. 5G was assembled incorrectly. The results from all the originally performed experiments were presented to the Editorial Office for our perusal. The revised version of Fig. 5, containing the correct ßactin data for the western blots in Fig. 5F, is shown on the next page. The authors regret the inadvertent error that was made during the preparation of Fig. 5, and confirm that this error did not seriously affect the conclusions reported in the paper. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish a Corrigendum, and all the authors agree to this Corrigendum. Furthermore, they apologise to the readership for any inconvenience caused.[Oncology Reports 41: 26892702, 2019; DOI: 10.3892/or.2019.7054].