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Endometrial cancer (EC) is a common gynaecological malignant tumour with unclear pathogenesis. Small nucleolar RNA (snoRNA) is involved in many biological processes, including those of cancers. Using the Cancer Genome Atlas (TCGA) database, the expression pattern of a snoRNA, SNORA73B, was analysed. The biological functions of SNORA73B were assessed by in vitro proliferation, apoptosis, migration, and invasion assays and in vivo by the xenograft model. RNA sequencing (RNA-seq) and RNA immunoprecipitation assays were performed to determine the relationship between SNORA73B and its target genes. High-performance liquid chromatography (HPLC) was performed to detect the pseudouridine content of the mindbomb E3 ubiquitin protein ligase 1 gene (MIB1). The stability of MIB1 mRNA was evaluated using a transcription inhibitor, actinomycin D. By performing co-immunoprecipitation assays, the change in the ubiquitin levels of the Jagged canonical Notch ligand 1 (Jag 1), caused by SNORA73B and MIB1, was identified. RNA-seq and qRT-PCR were performed to detect the alternative splicing of the regulator of the chromosome condensation 1 gene (RCC1). The TCGA database analysis showed that SNORA73B was highly expressed in EC. SNORA73B promoted cell proliferation, migration, and invasion and inhibited apoptosis. SNORA73B modified the pseudouridine content in MIB1 and increased the stability of MIB1 mRNA and protein; thus, it affected Jag 1 ubiquitination and further activated the Notch pathway. SNORA73B also affected the alternative splicing of RCC1, increasing the number of transcripts, RCC1-T2 and RCC1-T3, which promoted cell proliferation, migration, and invasion. SNORA73B can be a potential target for EC.
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Neoplasias do Endométrio , Ubiquitina-Proteína Ligases , Feminino , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Processamento Alternativo/genética , Pseudouridina/metabolismo , RNA Nucleolar Pequeno/genética , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , RNA Mensageiro/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/genética , Proteínas de Ciclo Celular/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genéticaRESUMO
Social interaction deficit is core symptom of children with autism, owing to interaction of genetic predisposition and environmental toxins. Sevoflurane could induce neurotoxicity in developing brain in rodent models. This study aims to investigate whether sevoflurane anesthesia in neonatal period could impair social behaviors in male and female mice. Twenty-eight male and thirty-one female mice were randomly assigned to receive 3.0% sevoflurane or 60% oxygen on postnatal day 6. They were tested for social interaction behaviors at one- and two-month-old. In addition, the cortex and hippocampus of neonatal mice undergoing sevoflurane anesthesia were harvested for immunoblotting analysis. As a result, both male and female mice undergoing sevoflurane anesthesia showed strong sociability and weak preference for social novelty at juvenile age. In addition, the male mice developed normal preference for social novelty at early-adulthood; However, the female mice remained weak preference for social novelty. Furthurmore, sevoflurane anesthesia could decrease the levels of PSD95 but not Neuroligin-1 in the hippocampus but not cortex of neonatal mice. In conclusion, sevoflurane anesthesia in neonatal period could disturb development of social memory and impair preference for social novelty in female mice at early-adulthood, with the potential mechanism of decreasing PSD95 expression in the hippocampus of C57BL/6 mice.
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Comportamento Animal/efeitos dos fármacos , Córtex Cerebral/patologia , Hipocampo/patologia , Efeitos Tardios da Exposição Pré-Natal/patologia , Sevoflurano/toxicidade , Comportamento Social , Animais , Animais Recém-Nascidos , Córtex Cerebral/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Inibidores da Agregação Plaquetária/toxicidade , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamenteRESUMO
Environmental sanitation of maternal contact during pregnancy is extremely important for the development of different fetal tissues and organs. In particular, during early pregnancy, any adverse exposure may cause abnormal fetal growth or inhibit the development of embryogenic organs. The potential risks of phthalate exposure, which affects the development of humans and animals, are becoming a serious concern worldwide. However, the specific molecular mechanism of di-(2-ethylhexyl) phthalate (DEHP)-induced cardiotoxicity in fetal mice remains unclear. In this study, animal models of DEHP gavage at concentrations of 250, 500, and 1000 mg/kg/day within 8.5-18.5 days of pregnancy were established. The cell proliferation, survival, and apoptosis rates were evaluated using CCK8, EdU, TUNEL and flow cytometry. The molecular mechanism was assessed via transcriptome sequencing, immunohistochemistry, immunofluorescence, reverse transcription-quantitative polymerase chain reaction, and Western blot analysis. In vivo, DEHP increased apoptosis, decreased Ki67 and CD31 expression, reduced heart weight and area, slowed down myocardial sarcomere development, and caused cardiac septal defect in fetal mice heart. Transcriptome sequencing showed that DEHP decreased NRG1 expression and downregulated the ErbB2/ErbB4-PI3K/AKT signaling pathway-related target genes. In vitro, primary cardiomyocytes were cultured with DEHP at a concentration of 150 µg/mL combined with ErbB inhibitor (AG1478, 10 µmol/L) and/or NRG1 protein (100 ng/mL) for 72 h. After DEHP intervention, the expression of NRG1 and the phosphorylation level of ErbB2, ErbB4, PI3K, and AKT decreased, and the apoptosis-related protein levels increased. Moreover, the apoptosis rate increased. After adding exogenous NRG1, the phosphorylation level of the NRG1/ERbB2/ERbB4-PI3K/AKT pathway increased, and the apoptosis-related protein levels decreased. Further, the apoptosis rate reduced. Interestingly, after exposure to DEHP and AG1478 + NRG1, the anti-apoptotic effect of NRG1 and cardiomyocyte proliferation decreased by inhibiting the NRG1/ERbB2/ERbB4-PI3K/AKT pathway. Hence, the NRG1-dependent regulation of the ERbB2/ERbB4-PI3K/AKT signaling pathway may be a key mechanism of DEHP-induced myocardial cytotoxicity.
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Dietilexilftalato , Proteínas Proto-Oncogênicas c-akt , Animais , Dietilexilftalato/toxicidade , Feminino , Feto , Humanos , Camundongos , Neuregulina-1/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Ácidos Ftálicos , Gravidez , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor ErbB-2 , Receptor ErbB-4/genética , Receptor ErbB-4/metabolismo , Receptor ErbB-4/farmacologia , Transdução de SinaisRESUMO
Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.
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Autofagia , Células Espumosas , Inflamação , Lipoproteínas LDL/metabolismo , Macrófagos , Rutina/farmacologia , Animais , Sobrevivência Celular , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Células Espumosas/metabolismo , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fosfatidilinositol 3-Quinase/metabolismo , Células RAW 264.7 , Transdução de SinaisRESUMO
OBJECTIVES: The optimal core temperature for hypothermic circulatory arrest during aortic arch surgery remains contentious. This study aims to evaluate patient outcomes under various temperatures within a large single-center cohort. METHODS: Between 2010 and 2018, patients diagnosed with type A aortic dissection underwent total arch replacement at Fuwai Hospital were enrolled. They were categorized into four groups: deep hypothermia group, low-moderate hypothermia group, high-moderate hypothermia group, and mild hypothermia group. Clinical data were analyzed to ascertain differences between the groups. RESULTS: A total of 1310 patients were included in this cohort. Operative mortality stood at 6.9% (90/1310), with a higher incidence observed in the deep hypothermia group [29 (12.9%); 35 (6.9%); 21 (4.8%); 5 (3.4%); all adjusted P < 0.05]. Overall 10-year survival was 80.3%. Long-term outcomes did not significantly differ among the groups. Multivariable logistic analysis revealed a protective effect of higher core temperature on operative mortality (odds ratio 0.848, 95% confidence interval 0.766-0.939; P = 0.001). High-moderate hypothermia emerged as an independent protective factor for operative mortality (odds ratio 0.303, 95% confidence interval 0.126-0.727; P = 0.007). Multivariable Cox analysis did not detect an effect of hypothermic circulatory arrest on long-term survival (all P > 0.05). CONCLUSIONS: High-moderate hypothermia (24.1-28 °C) offers the most effective protection against surgical mortality and is therefore recommended. Different hypothermic circulatory arrest temperatures do not influence long-term survival or quality of life.
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BACKGROUND: Ibrutinib could increase the risk of atrial fibrillation (AF) in chronic lymphocytic leukemia (CLL) patients. However, the precise mechanism underlying ibrutinib-induced AF remains incompletely elucidated. METHODS: We investigated the proportion of ibrutinib-treated CLL patients with new-onset AF. Optical mapping was conducted to reveal the proarrhythmic effect of ibrutinib on HL-1 cells. Fluorescence staining and western blot were used to compare connexins 43 and 40 expression in ibrutinib-treated and control groups. To identify autophagy phenotypes, we used western blot to detect autophagy-related proteins, transmission electron microscopy to picture autophagosomes, and transfected mCherry-GFP-LC3 virus to label autophagosomes and lysosomes. Hydroxychloroquine as an autophagy inhibitor was administered to rescue ibrutinib-induced Cx43 and Cx40 degradation. RESULTS: About 2.67% of patients developed atrial arrhythmias after ibrutinib administration. HL-1 cells treated with ibrutinib exhibited diminished conduction velocity and a higher incidence of reentry-like arrhythmias compared to controls. Cx43 and Cx40 expression reduced along with autophagy markers increased in HL-1 cells treated with ibrutinib. Inhibiting autophagy upregulated Cx43 and Cx40. CONCLUSIONS: The off-target effect of ibrutinib on the PI3K-AKT-mTOR signaling pathway caused connexin degradation and atrial arrhythmia via promoting autophagy. CLINICAL TRIAL REGISTRATION: ChiCTR2100046062, https://clin.larvol.com/trial-detail/ChiCTR2100046062.
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Adenina , Fibrilação Atrial , Autofagia , Conexina 43 , Conexinas , Fosfatidilinositol 3-Quinases , Piperidinas , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Adenina/análogos & derivados , Adenina/farmacologia , Adenina/efeitos adversos , Serina-Treonina Quinases TOR/metabolismo , Autofagia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piperidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Conexina 43/metabolismo , Conexina 43/genética , Feminino , Fibrilação Atrial/metabolismo , Fibrilação Atrial/induzido quimicamente , Conexinas/metabolismo , Conexinas/genética , Masculino , Idoso , Pessoa de Meia-Idade , Proteína alfa-5 de Junções Comunicantes , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/induzido quimicamenteRESUMO
BACKGROUND: Most of the endometrial cancer (EC) patients are diagnosis in early stage with a good prognosis while the patients with locally advanced recurrent or metastatic result in a poor prognosis. Adjuvant therapy could benefit the prognosis of patients with high-risk factors. Unfortunately, the molecular classification of great prognostic value has not yet reached an agreement and need to be further refined. The present study aims to identify new targets that have prognostic value in EC based on the method of EC patient-derived organ-like organs (PDOs), and further investigate their efficacy and mechanism. METHODS: The Cancer Genome Atlas (TCGA) database was used to determine SNORD14E expression. The effects of SNORD14E were investigated using CCK8, Transwell, wound-healing assays, and a xenograft model experiment; apoptosis was measured by flow cytometry. Antisense oligonucleotide (ASO) targeting SNORD14E was designed and patient-derived organoids (PDO) models in EC patients was established. A xenograft mouse and PDO model were employed to evaluate the effects of ASO targeting SNORD14E. RNA-seq, Nm-seq, and RNA immunoprecipitation (RIP) experiments were employed to confirm the alternative splicing (AS) and modification induced by SNORD14E. A minigene reporter gene assay was conducted to confirm AS and splicing factors on a variable exon. Actinomycin-d (Act-D) and Reverse Transcription at Low deoxy-ribonucleoside triphosphate concentrations followed by PCR (RTL-P) were utilized to confirm the effects of 2'-O methylation modification on FOXM1. RESULTS: We found that SNORD14E was overexpressed in EC tissues and patients with high expressed SNORD14E were distributed in the TCGA biomolecular classification subgroups without difference. Further, SNORD14E could reduce disease-free survival (DFS) and recurrence free survival (RFS) of EC patients. SNORD14E promoted proliferation, migration, and invasion and inhibited the apoptosis of EC cells in vitro. ASOs targeting SNORD14E inhibited cell proliferation, migration, invasion while promoted cell apoptosis. ASOs targeting SNORD14E inhibited tumor growth in the xenograft mouse model. TCGA-UCEC database showed that the proportion of patients with high expression of SNORD14E in middle-high risk and high-risk patients recommended by EMSO-ESGO-ESTRO guidelines for adjuvant therapy is more than 50%. Next, we enrolled 8 cases of high-risk and high-risk EC patients according to EMSO-ESGO-ESTRO guidelines and successfully constructed EC-PDOs. ASOs targeting SNORD14E inhibited the EC-PDO growth. Mechanistically, SNORD14E could recognize the mRNA of FOXM1 and recruit SRSF1 to promote the shearing of the variable exon VIIa of FOXM1, resulting in the overexpression of the FOXM1 malignant subtypes FOXM1b and FOXM1c. In addition, SNORD14E modified FOXM1 mRNA with 2`-O-methylation, which prolonged the half-life of FOXM1 mRNA. The nucleus accumulation of ß-catenin caused by aberrant FOXM1 expression led to EC progression. CONCLUSIONS: ASO targeting SNORD14E can be an effective treatment for EC.
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Neoplasias do Endométrio , Oligonucleotídeos Antissenso , Humanos , Animais , Camundongos , Feminino , beta Catenina , Oligonucleotídeos , Neoplasias do Endométrio/genética , Éxons , Proteína Forkhead Box M1/genética , Fatores de Processamento de Serina-ArgininaRESUMO
Acute lung injury (ALI) is a life-threatening complication of cardiac surgery that has a high rate of morbidity and mortality. Epithelial ferroptosis is believed to be involved in the pathogenesis of ALI. MOTS-c has been reported to play a role in regulating inflammation and sepsis-associated ALI. The purpose of this study is to observe the effect of MOTS-c on myocardial ischemia reperfusion (MIR)-induced ALI and ferroptosis. In humans, we used ELISA kits to investigate MOTS-c and malondialdehyde (MDA) levels in patients undergoing off-pump coronary artery bypass grafting (CABG). In vivo, we pretreated Sprague-Dawley rats with MOTS-c, Ferrostatin-1 and Fe-citrate(⠢). We conducted Hematoxylin and Eosin (H&E) staining and detection of ferroptosis-related genes in MIR-induced ALI rats. In vitro, we evaluated the effect of MOTS-c on hypoxia regeneration (HR)-induced mouse lung epithelial-12 (MLE-12) ferroptosis and analyzed the expression of PPARγ through western blotting. We found that circulating MOTS-c levels were decreased in postoperative ALI patients after off-pump CABG, and that ferroptosis contributed to ALI induced by MIR in rats. MOTS-c suppressed ferroptosis and alleviated ALI induced by MIR, and the protective effect of MOTS-c- was dependent on PPARγ signaling pathway. Additionally, HR promoted ferroptosis in MLE-12 cells, and MOTS-c inhibited ferroptosis against HR through the PPARγ signaling pathway. These findings highlight the therapeutic potential of MOTS-c for improving postoperative ALI induced by cardiac surgery.
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Lesão Pulmonar Aguda , Doença da Artéria Coronariana , Ferroptose , Traumatismo por Reperfusão Miocárdica , Traumatismo por Reperfusão , Humanos , Camundongos , Ratos , Animais , PPAR gama/metabolismo , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Doença da Artéria Coronariana/complicações , Fatores de Transcrição , Isquemia/complicações , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/induzido quimicamente , Peptídeos/farmacologia , Traumatismo por Reperfusão/complicaçõesRESUMO
There is an ongoing debate concerning the optimal surgical option of myocardial revascularization for octogenarians. The current meta-analysis aimed to compare clinical outcomes following off-pump coronary artery bypass grafting (OPCABG) or conventional coronary artery bypass grafting (CCABG) in octogenarians. PubMed, Cochrane, Web of Science, and EMBASE databases were searched to identify eligible studies from inception to March 2021. The analysis was performed using STATA 15.1. A literature search yielded 18 retrospective studies involving 146 372 patients (OPCABG = 44 522 vs. CCABG = 101 850). Pooled analysis showed a strong trend toward reducing mortality risk in the OPCABG group (odds ratio: 0.75, 95% confidence interval: 0.56-1.00, p = .05). However, it did not reach statistical significance. The sensitive analysis demonstrated that OPCABG was less likely to cause death than CCABG. There were comparable data in myocardial infarction, renal failure, deep sternal wound infection, and hospital stays between the two groups, although the incidence of stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding was significantly lower in the OPCAGB group. OPCABG may be an effective surgical strategy for myocardial revascularization, especially in reducing the incidence of postoperative stroke, atrial fibrillation, prolonged ventilation, and reoperation for bleeding.
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Fibrilação Atrial , Acidente Vascular Cerebral , Idoso de 80 Anos ou mais , Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/efeitos adversos , Humanos , Octogenários , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
A distinctive feature of ferroptosis is intracellular iron accumulation and the impairment of antioxidant capacity, resulting in a lethal accumulation of lipid peroxides leading to cell death. This study was conducted to determine whether inhibiting isocitrate dehydrogenase 1 (IDH1) may help to prevent foam cell formation by reducing oxidized low-density lipoprotein (ox-LDL)-induced ferroptosis in macrophages and activating nuclear factor erythroid 2-related factor 2 (NRF2). Gene expression profiling (GSE70126 and GSE70619) revealed 21 significantly different genes, and subsequent bioinformatics research revealed that ferroptosis and IDH1 play essential roles in foam cell production. We also confirmed that ox-LDL elevates macrophage ferroptosis and IDH1 protein levels considerably as compared with controls. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, reduced ox-LDL-induced elevated Fe2+ levels, lipid peroxidation (LPO) buildup, lactate dehydrogenase (LDH) buildup, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4), ferritin heavy polypeptide 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) protein downregulation. More crucially, inhibiting IDH1 reduced Fe2+ overload, lipid peroxidation, LDH, and glutathione depletion, and elevated GPX4, FTH1, and SLC7A11 protein expression, resulting in a reduction in ox-LDL-induced macrophage ferroptosis. IDH1 inhibition suppressed ox-LDL-induced macrophage damage and apoptosis while raising NRF2 protein levels. We have demonstrated that inhibiting IDH1 reduces ox-LDL-induced ferroptosis and foam cell formation in macrophages, implying that IDH1 may be an important molecule regulating foam cell formation and may be a promising molecular target for the treatment of atherosclerosis.
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To investigate the relationship of preoperative high-sensitivity cardiac troponin T (hs-cTnT) with early postoperative hypoxemia (EPH) following off-pump coronary artery bypass grafting (OPCAB). Records of patients undergoing OPCAB between 2018 and 2022 were reviewed. Baseline characteristics and postoperative arterial blood gas analysis were derived from the cardiovascular surgery electronic medical records. Preoperative hs-cTnT levels were measured routinely in all patients. Logistic regression analyses were performed to test the association of preoperative hs-cTnT with EPH. A total of 318 OPCAB patients were included, who had a preoperative hs-cTnT test available for review. Before surgery, 198 patients (62%) had a rise in hs-cTnT level (≥14 ng/L) and 127 patients (40%) had a more severe hs-cTnT level (≥25 ng/L). The preoperative hs-cTnT level was associated with EPH (odds ratio per ng/L, 1.86; 95% confidence interval 1.30−2.68; p < 0.001), prolonged intensive care unit stay (odds ratio, 1.58; 95% confidence interval 1.08−2.32; p = 0.019), and delayed extubating time (odds ratio, 1.63; 95% confidence interval 1.15−2.34; p = 0.007). On multivariable analysis, adjusted for BMI, hypertension, smoking status, serum creatinine, and cardiac function, preoperative hs-cTnT remained an independent factor associated with EPH. Elevation of hs-cTnT concentrations are significantly associated with EPH after OPCAB. Review of presurgical hs-cTnT concentration may help identify patients who would benefit from OPCAB to improve surgical risk assessment.
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A great number of pediatric patients undergoing varied procedures make neonatal surgery plus anesthesia become a matter of great concern owing to underlying neurotoxicity in developing brain. The authors set out to assess long-term effects of surgery plus anesthesia in mouse model. Six-day-old C57BL/6 mice were randomized to receive either anesthesia with 3% sevoflurane, abdominal surgery under the same anesthesia, or the control condition. These mice were examined of learning and memory at juvenile age in Morris water maze test. The brain tissues of mice were harvested for Western blot analysis, including purinergic receptors P2X family, CaMKII and NF-κB. Another battery of mice were administered with inhibitors of P2RX2/3 (e.g., A317491) into hippocampal dentate gyrus before behavioral testing. We found that neonatal surgery plus anesthesia, but not sevoflurane anesthesia alone, impaired the learning and memory of juvenile mice, as evidenced by delayed escape latency and reduced platform-crossing times. Immunoblotting analysis showed that behavioral abnormalities were associated with increased levels of P2RX2, phosphorylated-CaMKIIß and activated NF-κB in mouse hippocampus. Injection of A317491 ameliorated the impaired learning and memory of juvenile mice undergoing neonatal surgery plus anesthesia, and it also mitigated the neonatal surgery-induced signaling enhancement of P2RX2/CaMKII/NF-κB. Together, these results indicate that neonatal surgery plus anesthesia may cause long-term cognitive dysfunction, with potential mechanism of increasing P2RX2 and downstream signaling of phosphorylated-CaMKII and NF-κB. Our findings will promote more studies to assess detrimental effects of surgery and accompanying inflammation, diverse anesthetics and even sleeping deprivation on mouse neurodevelopment and neurobehavioral performance.
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Anestesia , Hipocampo , Aprendizagem em Labirinto , Transtornos da Memória , Anestesia/efeitos adversos , Animais , Animais Recém-Nascidos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Hipocampo/efeitos dos fármacos , Hipocampo/fisiopatologia , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/epidemiologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Receptores Purinérgicos P2X2 , Sevoflurano/farmacologiaRESUMO
BACKGROUND: Hypertension is a lifestyle-induced chronic disease that threatens the lives of patients. Control of hypertension requires patients to follow self-management regimes; unfortunately, however, patient compliance with hypertension self-management is low, especially in developing countries. Improvement of patient compliance is premised on meeting patient needs. Mobile health apps are becoming increasingly popular for self-management of chronic diseases. However, few mobile apps have been designed to meet patient needs for hypertension self-management. OBJECTIVE: The goal of this study was to develop a mobile health app to improve patient compliance with hypertension self-management and evaluate the effectiveness of the app in terms of patient compliance. METHODS: The goal-directed design method was applied to guide study design. We divided the study into 4 stages. Stages 1 to 3 comprised the development process. To improve the applicability of the goal-directed design method to chronic disease management, we extracted elements of user models concerned with patient compliance and defined a concrete process for user modeling. In stage 1, personas of hypertensive patients were built using qualitative and quantitative methods. Clustering methods based on questionnaire responses were used to group patients. Qualitative interviews were conducted to identify the needs of different groups. In stage 2, several functional modules were designed to meet the needs of different groups based on the results from stage 1. In stage 3, prototypes of functional modules were designed and implemented as a real app. Stage 4 was the deployment process, in which we conducted a pilot study to investigate patient compliance after using the app. Patient compliance was calculated through the frequency with which they took blood pressure measurements. In addition, qualitative interviews were conducted to learn the underlying reasons for the compliance results. RESULTS: In stage 1, patients were divided into 3 groups based on 82 valid questionnaire responses. Eighteen patients from the different groups (7, 5, and 6 patients) were interviewed, and the needs of the groups were summarized as follows: improve self-management ability, enhance self-management motivation, and receive self-management support. In stages 2 and 3, 6 functional modules were designed and implemented based on specified needs, and the usability of the app was improved through usability tests. In stage 4, 143 patients were recruited to use different versions of the app for 2 months. Results show that patient compliance improved as functional modules were added (P<.001) and was maintained at a high level (rate of 0.73). Interview results from 32 patients show that the design of the app met different needs; thus, patients were more compliant with it. CONCLUSIONS: This study developed a mobile health app for hypertension self-management using the goal-directed design method. The app proved to be effective for improving patient compliance with hypertension self-management.
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Hipertensão , Aplicativos Móveis , Cooperação do Paciente , Telemedicina , Feminino , Objetivos , Humanos , Hipertensão/terapia , Masculino , Pessoa de Meia-Idade , Motivação , Projetos PilotoRESUMO
[This corrects the article DOI: 10.2196/14466.].
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BACKGROUND: Chronic disease patients often face multiple challenges from difficult comorbidities. Smartphone health technology can be used to help them manage their conditions only if they accept and use the technology. OBJECTIVE: The aim of this study was to develop and test a theoretical model to predict and explain the factors influencing patients' acceptance of smartphone health technology for chronic disease management. METHODS: Multiple theories and factors that may influence patients' acceptance of smartphone health technology have been reviewed. A hybrid theoretical model was built based on the technology acceptance model, dual-factor model, health belief model, and the factors identified from interviews that might influence patients' acceptance of smartphone health technology for chronic disease management. Data were collected from patient questionnaire surveys and computer log records about 157 hypertensive patients' actual use of a smartphone health app. The partial least square method was used to test the theoretical model. RESULTS: The model accounted for .412 of the variance in patients' intention to adopt the smartphone health technology. Intention to use accounted for .111 of the variance in actual use and had a significant weak relationship with the latter. Perceived ease of use was affected by patients' smartphone usage experience, relationship with doctor, and self-efficacy. Although without a significant effect on intention to use, perceived ease of use had a significant positive influence on perceived usefulness. Relationship with doctor and perceived health threat had significant positive effects on perceived usefulness, countering the negative influence of resistance to change. Perceived usefulness, perceived health threat, and resistance to change significantly predicted patients' intentions to use the technology. Age and gender had no significant influence on patients' acceptance of smartphone technology. The study also confirmed the positive relationship between intention to use and actual use of smartphone health apps for chronic disease management. CONCLUSIONS: This study developed a theoretical model to predict patients' acceptance of smartphone health technology for chronic disease management. Although resistance to change is a significant barrier to technology acceptance, careful management of doctor-patient relationship, and raising patients' awareness of the negative effect of chronic disease can negate the effect of resistance and encourage acceptance and use of smartphone health technology to support chronic disease management for patients in the community.
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Ionic liquids with intermediate nonpolar cationic side-chain lengths are known to have nanoscale spatial heterogeneities with nonpolar tail domains separated by a continuous polar network. In this work, we use coarse-grained molecular dynamics simulations to show that, when the nonpolar cationic side chain is sufficiently long, due to the stronger van der Waals interactions between the side chains, the structure of ionic liquids goes through a transition from spatially heterogeneous to liquid crystalline-like. For XMIm(+)/NO(3)(-) ionic liquids, change occurs when the number of carbon groups on the cationic side chain varies from 14 to 16. In the liquid crystal-like phase, the cationic side chains tend to be parallel to each other, while the cationic head groups and anions, although being mostly layered perpendicularly to the direction along the side chains, still form a continuous polar network.