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Objectives: Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered optional consolidation therapy especially for relapsed/refractory extranodal NK/T-cell lymphoma (ENKL), but its applications to newly diagnosed advanced-stage ENKL is currently limited. Methods: We collected 51 cases of newly diagnosed advanced-stage ENKL patients, including 26 with auto-HSCT and 25 with chemotherapy rather than HSCT, from our hospital between 2014/01 and 2023/12. We summarized the patients' characteristics, conducted survival analysis of the 51 cases, and analyzed the potential benefits of auto-HSCT to ENKL patients. Results: It shows that after a median follow-up time of 39 months, the estimated 5-year overall survival (OS) of the 51 newly diagnosed advanced-stage ENKL patients is 73.4%, and their estimated 5-year progression-free survival (PFS) is 73.4%. For patients receiving auto-HSCT, the 5-year OS (91.7%) and PFS (91.0%) are significantly different from those of patients receiving chemotherapy without HSCT (OS 53.3%, PFS 54.5%) (p < 0.05). Univariate and multivariate analysis results suggest that only the l-asparaginase usage in chemotherapy showed significant impact on the OS, and none of concerned factors showed significant impact on the PFS. Conclusions: Auto-HSCT is indeed an option to newly diagnosed advanced-stage ENKL, but further studies are still required for more strict disease management.
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OBJECTIVE: Obesity-associated insulin resistance (IR) is responsible for considerable morbidity and mortality globally. Despite vast genomic data, many areas, from pathogenesis to management, still have significant knowledge gaps. We aimed to characterize visceral adipose tissue (VAT) in obesity and IR through a multi-omics approach. METHODS: We procured data on VAT samples from the Gene Expression Omnibus (GEO) for the following two groups: 1) populations with obesity (n = 34) versus those without (n = 26); and 2) populations with obesity and IR (n = 15) versus those with obesity but without IR (n = 15). Gene set enrichment, protein-protein interaction network construction, hub gene identification, and drug-gene interactions were performed, followed by regulatory network prediction involving transcription factors (TFs) and microRNAs (miRNAs). RESULTS: Interleukin signaling pathways, cellular differentiation, and regulation of immune response revealed a significant cross talk between VAT and the immune system. Other findings include cancer pathways, neurotrophin signaling, and aging. A total of 10 hub genes, i.e., STAT1, KLF4, DUSP1, EGR1, FOS, JUN, IL2, IL6, MMP9, and FGF9, 24 TFs, and approved hub gene-targeting drugs were obtained. A total of 10 targeting miRNAs (e.g., hsa-miR-155-5p, hsa-miR-34a-5p) were associated with obesity and IR-related pathways. CONCLUSIONS: Our multi-omics integration method revealed hub genes, TFs, and miRNAs that can be potential targets for investigation in VAT-related inflammatory processes and IR, therapeutic management, and risk stratifications.
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Vascular covered stents play a significant therapeutic role in cardiovascular diseases. However, the poor compliance and biological inertness of commercial materials cause post-implantation complications. Silk fibroin (SF), as a biomaterial, possesses satisfactory hemocompatibility and tissue compatibility. In this study, we developed a silk film for use in covered stents by employing a layer-by-layer self-assembly strategy with regenerated SF on silk braiding fabric. We investigated the effects on the mechanical properties of the silk films in detail, which were closely correlated with fabric parameters and layer-by-layer self-assembly. The results showed that there was a significant relationship between these factors and both the compliance and mechanical strength. The 1 × 2/90°/100/SF6 film exhibited excellent mechanical properties. Notably, compliance reached 2.6%/100 mmHg, matching that of the human saphenous vein. Thus, this strategy shows promise in developing a novel covered stent, with biocompatible and comprehensive mechanical properties, and significant potential for clinical applications.
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Fibroínas , Teste de Materiais , Engenharia Tecidual , Engenharia Tecidual/métodos , Humanos , Fibroínas/química , Stents , Seda/química , Materiais Biocompatíveis/química , Animais , Células Endoteliais da Veia Umbilical Humana , Materiais Revestidos Biocompatíveis/química , Bombyx , Prótese VascularRESUMO
The dorsomedial prefrontal cortex (dmPFC) plays a crucial role in social cognitive functions, including perspective-taking. Although perspective-taking has been linked to self-control, the mechanism by which the dmPFC might facilitate self-control remains unclear. Using the multimodal neuroimaging dataset from the Human Connectome Project (Study 1, N =978 adults), we established a reliable association between the dmPFC and self-control, as measured by discounting rate-the tendency to prefer smaller, immediate rewards over larger, delayed ones. Experiments (Study 2, N = 36 adults) involving high-definition transcranial direct current stimulation showed that anodal stimulation of the dmPFC reduces the discounting of delayed rewards and decreases the congruency effect in egocentric but not allocentric perspective in the visual perspective-taking tasks. These findings suggest that the dmPFC promotes self-control by inhibiting the egocentric perspective, offering new insights into the neural underpinnings of self-control and perspective-taking, and opening new avenues for interventions targeting disorders characterized by impaired self-regulation.
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Conectoma , Córtex Pré-Frontal , Autocontrole , Estimulação Transcraniana por Corrente Contínua , Humanos , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Masculino , Feminino , Adulto , Adulto Jovem , Imageamento por Ressonância Magnética , Recompensa , Desvalorização pelo Atraso/fisiologiaRESUMO
Renal fibrosis, inflammation, and gut dysbiosis are all linked to chronic kidney disease (CKD). Here we show that Bacteroides ovatus protects against renal fibrosis. Mechanistically, B. ovatus enhances intestinal hyodeoxycholic acid (HDCA) levels by upregulating a strain of intestinal bacteria, Clostridium scindens, that has the capacity for direct HDCA production in mice. HDCA significantly promoted GLP-1 secretion by upregulating the expression of TGR5 and downregulating the expression of farnesoid X receptor (FXR) in the gut. Activation of renal GLP-1R attenuates renal fibrosis while delaying the subsequent development of CKD. In addition, HDCA can also protect against renal fibrosis by directly upregulating renal TGR5. The natural product neohesperidin (NHP) was found to exert its anti-renal fibrotic effects by promoting the growth of B. ovatus. Our findings provide mechanistic insights into the therapeutic potential of B. ovatus, C. scindens, and HDCA in treating CKD.
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Bacteroides , Fibrose , Camundongos Endogâmicos C57BL , Regulação para Cima , Animais , Camundongos , Regulação para Cima/efeitos dos fármacos , Bacteroides/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Rim/efeitos dos fármacos , Clostridium/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/microbiologia , Insuficiência Renal Crônica/metabolismo , Humanos , Peptídeo 1 Semelhante ao Glucagon/metabolismoRESUMO
In esophageal squamous cell carcinoma (ESCC), lymph node (LN) metastasis is associated with poor survival. Emerging evidence has demonstrated elevated CD8+ T-cell levels in metastatic LNs following immunotherapy and increased chemoresistance. However, the underlying regulatory mechanisms of CD8+ T cells in chemoresistant/metastatic patients have not been elucidated. Given that metastasis is linked to aberrant splicing patterns, transcripts with alternative splicing forms also play a critical role. With spatial transcriptomics (ST), spatial isoform transcriptomics (SiT), single-cell RNA sequencing (scRNA-seq), and T-cell receptor (TCR) sequencing, the spatial isoforms are analyzed quantitatively in human solid tumors and LNs. These isoforms are classified according to expression and spatial distribution patterns and proposed that the temporal heterogeneity in isoforms is attributed to isoform biogenesis dynamics. C1QC+ tumor-associated macrophages (TAMs) contribute to the formation of metastases in the context of both immunotherapy and chemotherapy. Additionally, CD74 isoforms can be targeted by mRNA drugs, such as antisense oligonucleotides (ASOs) and RNA interference (RNAi), to prevent chemoresistance and metastasis. Overall, this work suggests that C1QC+ TAMs interact with CD8+ CXCL13+ Tex cells via enrichment with the CD74 isoform in the ESCC 's metastatic lymph node.
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Iron deficiency is a common nutritional issue that seriously affects male reproductive health. Lotus root polysaccharide iron (LRPF), a novel nutritional supplement, may ameliorate the damage caused by iron deficiency, however, the mechanism is unclear. In this study, we comprehensively determined the benefits of LRPF on reproduction in iron-deficient mice by integrating transcriptomics, microbiomics and serum metabolomics. Microbiomics showed that LRPF could restore changes to the intestinal microbiota caused by iron deficiency. Metabolomics results showed that LRPF stabilised steroid hormone and fatty acid metabolism in iron-deficient mice, reduced the content of ethyl chrysanthemumate (EC) and ameliorated the reproductive impairment. The transcriptomic analysis showed that LRPF regulated steroid hormone synthesis and the peroxisome proliferator-activated receptor (PPAR) signalling pathway in iron-deficient mice. In vitro experiments showed that LRPF could promote steroid hormone synthesis in Leydig cells by activating PPARγ. In conclusion, this study highlights the advantage of LRPF to improve testicular development.
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A major bottleneck in the development of wearable ion-selective sensors is the inherent conditioning and calibration procedures at the user's end due to the signal's instability and non-uniformity. To address this challenge, we developed a strategy that integrates three interdependent materials and device engineering approaches to realize a Ready-to-use Wearable ElectroAnalytical Reporting system (r-WEAR) for reliable electrolytes monitoring. The strategy collectively utilized (1) finely-configured diffusion-limiting polymers to stabilize the electromotive force in the electrodes, (2) a uniform electrical induction in electrochemical cells to normalize the open-circuit potential (OCP), and (3) an electrical shunt to maintain the OCP across the entire sensor in the r-WEAR. The approaches jointly enable fabrication of homogeneously stable and uniform ion-selective sensors, eliminating common conditioning and calibration practices. As a result, the r-WEAR demonstrated a signal's variation down to ±1.99 mV with a signal drift of 0.5 % per hour (0.12 mV h-1) during a 12-h continuous measurement of 10 sensors and a signal drift as low as 13.3 µV h-1 during storage. On-body evaluations of the r-WEAR for four days without conditioning and re-/calibration further validated the sensor's performance in realistic settings, indicating its remarkable potential for practical usage in a user operation-free manner in wearable healthcare applications.
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This study investigated the effect of heat treatments on the pungency and aroma profiles of a spice oleoresin blend, and the emulsion stability with different surfactants, encapsulating agents, and homogenization mechanisms. Total pungency increased with heat until 120 °C and drastically reduced at 150 °C. Thermal processing induced aroma release, and 46 compounds were identified at 90 °C, predominantly comprising sesquiterpenes. Tween 80 dispersed the highest oleoresin mass (6.21 ± 0.31 mg/mL) and reported the maximum emulsion stability index. The oleoresin percentage significantly influenced the emulsion stability, with 1% oleoresin producing the most stable emulsion. High-pressure homogenization applied on gum Arabic resulted in a greater encapsulation efficiency, exceeding 86%, and the lowest creaming index (4.70 ± 0.06%), while Hi-Cap 100 produced the best flow properties. The findings provide insights into incorporating lipophilic spice oleoresin blends in aqueous food systems and understanding the release of flavor compounds during thermal food processing.
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Emulsões , Aromatizantes , Temperatura Alta , Extratos Vegetais , Especiarias , Emulsões/química , Aromatizantes/química , Extratos Vegetais/química , Especiarias/análise , Manipulação de Alimentos , PaladarRESUMO
Infertility is a global health problem affecting millions of people of reproductive age worldwide, with approximately half caused by males. Chitosan oligosaccharide (COS) has strong antioxidant capacity, but its impact on the male reproductive system has not been effectively evaluated. To address this, we integrated RNA-seq, serum metabolomics and intestinal 16â¯S rDNA analysis to conduct a comprehensive investigation on the male reproductive system. The results showed that COS has potential targets for the treatment of oligospermia, which can promote the expression of meiotic proteins DDX4, DAZL and SYCP1, benefit germ cell proliferation and testicular development, enhance antioxidant capacity, and increase the expression of testicular steroid proteins STAR and CYP11A1. At the same time, COS can activate PI3K-Akt signaling pathway in testis and TM3 cells. Microbiome and metabolomics analysis suggested that COS alters gut microbial community composition and cooperates with serum metabolites to regulate spermatogenesis. Therefore, COS promotes male reproduction by regulating intestinal microorganisms and serum metabolism, activating PI3K-Akt signaling pathway, improving testicular antioxidant capacity and steroid regulation.
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Quitosana , Oligossacarídeos , Testículo , Masculino , Animais , Testículo/efeitos dos fármacos , Quitosana/farmacologia , Oligossacarídeos/farmacologia , Camundongos , Metabolômica , Oligospermia , Microbioma Gastrointestinal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Since wearable technologies for telemedicine have emerged to tackle global health concerns, the demand for well-attested wearable healthcare devices with high user comfort also arises. Skin-wearables for health monitoring require mechanical flexibility and stretchability for not only high compatibility with the skin's dynamic nature but also a robust collection of fine health signals from within. Stretchable electrical interconnects, which determine the device's overall integrity, are one of the fundamental units being understated in wearable bioelectronics. In this review, a broad class of materials and engineering methodologies recently researched and developed are presented, and their respective attributes, limitations, and opportunities in designing stretchable interconnects for wearable bioelectronics are offered. Specifically, the electrical and mechanical characteristics of various materials (metals, polymers, carbons, and their composites) are highlighted, along with their compatibility with diverse geometric configurations. Detailed insights into fabrication techniques that are compatible with soft substrates are also provided. Importantly, successful examples of establishing reliable interfacial connections between soft and rigid elements using novel interconnects are reviewed. Lastly, some perspectives and prospects of remaining research challenges and potential pathways for practical utilization of interconnects in wearables are laid out.
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As the core of a hypersonic propulsion system, the effective mixing efficiency of fuel and air in a supersonic combustor is crucial for its performance. This study focuses on a cold supersonic flow and employs computational fluid dynamics (CFD) techniques combined with Euler-Lagrange method's discrete-phase model (DPM) for multiphase flows, K-H and R-T (Kelvin-Helmholtz and Rayleigh-Taylor) mixing and atomization models, turbulence models, and surface evaporation models to investigate the injection, atomization, and mixing characteristics of kerosene in supersonic airflow. In order to enhance the mixing efficiency between kerosene and air while reducing flow losses, this study examines a staggered dual-jet injection scheme, with the dual jets arranged at the center of the cavity and having a dual-jet spacing of 10 and 20 mm, respectively. Starting from the interaction mechanism between jets, the impact of different staggered dual-jet spacings on the kerosene jet penetration height, span expansion area, angle of the shock wave, and Sauter mean diameter distribution was analyzed. The results show that a short dual-jet spacing (10 mm) leads to greater penetration height, wider span expansion, and a larger angle of the shock wave. When the dual-jet spacing is shorter, the interaction between the fuel jet and the cavity shear layer is stronger, resulting in an improved fuel mixing efficiency. The achievements of this study are consistent with previous experimental measurements and the literature, demonstrating a strong theoretical foundation for optimizing the design of hypersonic engines by deepening the understanding of the fundamental atomization mechanisms of kerosene jets in cold-state supersonic flows. Moreover, these results hold practical significance in improving the efficiency of kerosene combustion and enhancing the performance of flame stabilization devices.
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Medicinal mushrooms, such as Taiwanofungus camphoratus, Inonotus obliquus, and Tropicoporus linteus, have been used in traditional medicine for therapeutic purposes and promotion of overall health in China and many East Asian countries for centuries. Modern pharmacological studies have demonstrated the large amounts of bioactive constituents (such as polysaccharides, triterpenoids, and phenolic compounds) available in these medicinal mushrooms and their potential therapeutic properties. Due to the rising demand for the health-promoting medicinal mushrooms, various cultivation methods have been explored to combat over-harvesting of the fungi. Evidence of the robust pharmacological properties, including their anticancer, hypoglycemic, hypolipidemic, antioxidant, and antiviral activities, have been provided in various studies, where the health-benefiting properties of the medicinal fungi have been further proven through numerous clinical trials. In this review, the cultivation methods, available bioactive constituents, therapeutic properties, and potential uses of T. camphoratus, I. obliquus and T. linteus are explored.
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Acupuncture can reduce blood pressure, heart rate (HR), and ameliorate cardiac damage by modulating the excitability of the sympathetic nervous system, but the exact mechanism of this effect remains unclear. This study investigated the potential mechanisms of acupuncture in the treatment of cardiac damage in hypertension. Spontaneously hypertensive rats (SHR) were used as the hypertension model with Wistar-Kyoto rats as the control. Manual acupuncture, electroacupuncture, and metoprolol were used as interventions. Systolic and diastolic blood pressure (SBP, DBP) plus HR were monitored with cardiac structure determined using Masson staining. Angiotensin II (Ang II) and norepinephrine in myocardium were detected with ELISA as was Ang(1-7) and gamma aminobutyric acid (GABA) in the rostral ventrolateral medulla (RVLM). Expression of mRNA for collagen type I (Col-I), Col-III, actin α1 (ACTA1), and thrombospondin 4 (THBS4) in myocardium was detected using real-time PCR. Expression of angiotensin converting enzyme (ACE), Ang II, angiotensin II type 1 receptor (AT1R), ACE2, and Mas receptor (MasR) proteins in RVLM was monitored using western blot. After manual acupuncture and electroacupuncture treatment, SHRs showed decreased SBP, DBP and HR, reduced myocardial damage. There was decreased expression of the ACE/Ang II/AT1R axis, and increased expression of the ACE2/Ang(1-7)/MasR axis within the RVLM. GABA levels were increased within the RVLM and norepinephrine levels were decreased in myocardial tissue. Metoprolol was more effective than either manual acupuncture or electroacupuncture. Acupuncture directed against hypertensive cardiac damage may be associated with regulation of ACE/Ang II/AT1R and the ACE2/Ang(1-7)/MasR pathway within the RLVM to reduce cardiac sympathetic excitability.
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Terapia por Acupuntura , Angiotensina II , Angiotensina I , Enzima de Conversão de Angiotensina 2 , Hipertensão , Bulbo , Fragmentos de Peptídeos , Peptidil Dipeptidase A , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina , Animais , Angiotensina I/metabolismo , Hipertensão/metabolismo , Hipertensão/terapia , Fragmentos de Peptídeos/metabolismo , Enzima de Conversão de Angiotensina 2/metabolismo , Masculino , Receptor Tipo 1 de Angiotensina/metabolismo , Receptor Tipo 1 de Angiotensina/genética , Bulbo/metabolismo , Angiotensina II/metabolismo , Terapia por Acupuntura/métodos , Peptidil Dipeptidase A/metabolismo , Peptidil Dipeptidase A/genética , Proto-Oncogene Mas , Sistema Nervoso Simpático/metabolismo , Ratos , Proteínas Proto-Oncogênicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Pressão Sanguínea/fisiologia , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients. METHODS: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed. RESULTS: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689). CONCLUSION: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon.
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Aquaporina 4 , Autoanticorpos , Esclerose Múltipla , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Humanos , Feminino , Masculino , Aquaporina 4/imunologia , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/diagnóstico , Adulto , Estudos Retrospectivos , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/diagnóstico , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Autoanticorpos/sangue , Transtornos Mentais/epidemiologia , Transtornos Mentais/diagnóstico , Comorbidade , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/diagnóstico , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/sangueRESUMO
BACKGROUND: ICU nurses provide critical care and meticulously document electronic medical records (EMRs), tracking vital signs, interventions, and medication hourly. Despite China's ICUs effectively integrating real-time monitor and ventilator data into EMRs, challenges persist. Patient movements can introduce inaccuracies, and the demands of critical care may lead nurses to miss assessments like pain and nutrition. Traditional manual EMR verification is inefficient and error-prone, highlighting the urgent need for standardized, technology-aided EMR practices in ICU nursing. OBJECTIVE: This study aimed to describe the development and evaluation of an electronic medical records quality control system implemented in a Chinese tertiary care ICU setting, where current practices impact the accuracy of electronic medical records. METHODS: A prospective controlled trial was conducted with 600 ICU patients in Zhejiang Province from January to December 2023. An automated EMR quality control system was implemented in July 2023, facilitating real-time data collection and quality control for vital signs, medication management, and nursing evaluations. RESULTS: After implementing the ICU nursing electronic medical record quality control system, the prevalence of false data on vital signs decreased from 9 to 1.33%. Additionally, the incidence of incomplete medication administration dropped from 3.33 to 1.67%, and the rate of missing evaluations of assessment items in EMRs was reduced from 8 to 1.33%. Besides, the average time spent on quality control of the electronic medical records was 62 (48,76) seconds per record, which was significantly lower than the 264 (195.5,337.5) seconds using the traditional method. The nurses' satisfaction with the nursing electronic medical record quality control was (105.73 ± 9.31). CONCLUSIONS: The ICU nursing electronic medical record quality control system has led to substantial improvements in the quality and reliability of EMRs. The reduction in false data on vital signs, instances of incomplete medication administration, and missing evaluations of assessment items demonstrates the system's positive impact on nursing documentation practices. These improvements not only enhance the accuracy of patient records but also contribute to better patient care and safety within the ICU setting.
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While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of Leea indica, a local medicinal plant, in CML. Using high-performance liquid chromatography-electrospray ionization-mass spectrometry, a chemical constituent from L. indica extract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid from L. indica inhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34+ cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK/MAPK, FLT3 and JAK/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficient ρ0 cells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential of L. indica in CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.
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Apoptose , Proliferação de Células , Proteínas de Fusão bcr-abl , Ácido Gálico , Leucemia Mielogênica Crônica BCR-ABL Positiva , Mitocôndrias , Inibidores de Proteínas Quinases , Transdução de Sinais , Ácido Gálico/farmacologia , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular TumoralRESUMO
The formation of phytoene by condensing two geranylgeranyl diphosphate molecules catalyzed by phytoene synthase (PSY) is the first committed and rate-limiting step in carotenoid biosynthesis, which has been extensively investigated in bacteria, land plants and microalgae. However, this step in macroalgae remains unknown. In the present study, a gene encoding putative phytoene synthase was cloned from the economic red alga Pyropia yezoensis-a species that has long been used in food and pharmaceuticals. The conservative motifs/domains and the tertiary structure predicted using bioinformatic tools suggested that the cloned PyPSY should encode a phytoene synthase; this was empirically confirmed by pigment complementation in E. coli. This phytoene synthase was encoded by a single copy gene, whose expression was presumably regulated by many factors. The phylogenetic relationship of PSYs from different organisms suggested that red algae are probably the progeny of primary endosymbiosis and plastid donors of secondary endosymbiosis.
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Geranil-Geranildifosfato Geranil-Geraniltransferase , Filogenia , Rodófitas , Rodófitas/genética , Rodófitas/enzimologia , Geranil-Geranildifosfato Geranil-Geraniltransferase/genética , Geranil-Geranildifosfato Geranil-Geraniltransferase/metabolismo , Carotenoides/metabolismo , Escherichia coli/genética , Clonagem Molecular , Algas Comestíveis , PorphyraRESUMO
Chrononutrition, an emerging body of evidence on the relationship between biological rhythms and metabolism, has been established to be associated with glycemic responses. However, the available evidence is inconsistent, due to protocol variations. Therefore, this review aims to summarize the findings on chrononutrition characteristics and their association with glycemic responses among adults. Systematic searches were conducted across six databases (PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science) to identify all relevant studies published from January 2012. Two reviewers independently screened the abstracts and full-text articles based on the inclusion and exclusion criteria. Details about population characteristics, study methods and key findings were extracted following the PRISMA-ScR guideline. The quality of selected studies was evaluated using the mixed methods appraisal tool. The searchers identified 49 studies eligible for analysis. The results showed that meal timing, particularly night-time eating and snacking were associated with glycemic responses. Regarding meal regularity, skipping breakfast may affect glycemic responses, but no clear conclusion was drawn about its effect on insulin. The association between meal frequency and glycemic responses was inconclusive. Night fasting duration and restricted eating window are potentially associated with glycemic responses. The current review extensively investigates the association between chrononutrition factors and glycemic responses in adults. However, more prospective cohort and interventional studies are needed to better understand this causal-effect relationship.