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BACKGROUND: We aimed to develop and validate a nomogram for predicting the risk of intraoperatively acquired pressure injuries (IAPIs) in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This study retrospectively included 208 children aged 21 days to 8 years who underwent cardiac surgery with CPB in a tertiary hospital in China between January 2020 and October 2023. All patients' data were collected from the hospital's medical record system and randomly divided into the training (n = 146) and validation (n = 62) cohorts by a ratio of 7:3. Logistic regression analysis was conducted in the training cohort to identify independent risk factors and establish the nomogram. Finally, calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA) were performed in both cohorts to validate the predictive ability of the nomogram. RESULTS: 43 (14.7%) children developed IAPIs. Multivariate analysis showed that low Braden Q scores, use of steroids, skin abnormalities, and low intraoperative SpO2 were independent risk factors for IAPIs. A nomogram integrating the 4 factors was established. The areas under the curve (AUCs) of the nomogram were 0.836 and 0.903 in the training and validation cohorts, respectively. Furthermore, calibration curves and DCA demonstrated good calibration and clinical applicability of the nomogram. CONCLUSION: We constructed a reliable nomogram based on specific risk factors for children undergoing cardiac surgery with CPB, which could be used as an effective and convenient tool for prevention of IAPIs.
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Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Complicações Intraoperatórias , Nomogramas , Úlcera por Pressão , Humanos , Estudos Retrospectivos , Ponte Cardiopulmonar/efeitos adversos , Lactente , Pré-Escolar , Masculino , Feminino , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Úlcera por Pressão/etiologia , Úlcera por Pressão/prevenção & controle , Fatores de Risco , Recém-Nascido , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/etiologia , China , Curva ROC , Medição de Risco/métodosRESUMO
The mitogen-activated protein kinase (MAPK) pathway is a key driver in many histiocytic disorders, including Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD). This has led to successful and promising treatment with targeted therapies, including BRAF inhibitors and MEK inhibitors. Additional novel inhibitors have also demonstrated encouraging results. Nevertheless, there are several problems concerning targeted therapy that need to be addressed. These include, among others, incomplete responsiveness and the emergence of resistance to BRAF inhibition as observed in other BRAF-mutant malignancies. Drug resistance and relapse after treatment interruption remain problems with current targeted therapies. Targeted therapy does not seem to eradicate the mutated clone, leading to inevitable relapes, which is a huge challenge for the future. More fundamental research and clinical trials are needed to address these issues and to develop improved targeted therapies that can overcome resistance and achieve long-lasting remissions.
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Background: Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. Methods: This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023 at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25 mg days 1-21 plus dexamethasone 40 mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p < 0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). Findings: The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n = 9) and 70% (n = 16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n = 7) complete remission, 57% (n = 13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p = 0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p = 0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n = 12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n = 2, 9%), glucose intolerance (n = 2, 9%), edema (n = 2, 9%), insomnia (n = 1, 4%), and tremor (n = 1, 4%). Interpretation: Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. Funding: National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.
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BACKGROUND AND AIMS: Liver involvement portends poor prognosis in adults. We aimed to characterize the clinical features, liver function tests, radiologic findings, molecular profiles, therapeutic approaches and outcomes of adults patients with Langerhans cell histiocytosis (LCH) with liver involvement. METHODS: We conducted a retrospective analysis of all adults with LCH (≥â 18 years) seen at Peking Union Medical College Hospital (Beijing, China) between January 2001 and December 2022. RESULTS: Among the 445 newly diagnosed adults with LCH, 90 patients had liver involvement at diagnosis and 22 patients at relapse. The median age was 32 years (range, 18-66 years). Of 112 evaluable patients, 108 had full liver function testing, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), and total bilirubin and albumin. Elevated ALP was seen in 63.0% and GGT in 86.1%; 14.8% had elevated bilirubin. Next-generation sequencing of 54 patients revealed frequent BRAFN486_P490 (29.6%), BRAFV600E (18.5%), and MAP2K1 (14.8%). OUTCOMES: After a median 40 months' follow-up (range 1-168 months), 3-year progression-free survival (PFS) and overall survival were 49.7% and 86.6% respectively. In multivariable analyses, ≥3 abnormal liver function tests (HR 3.384, 95% CI 1.550-7.388, Pâ =â .002) associated with inferior PFS; immunomodulatory drug therapy (HR 0.073, 95% CI, 0.010-0.541, Pâ =â .010) correlated with superior PFS versus chemotherapy. CONCLUSIONS: In summary, elevated GGT and ALP were common in adults with LCH liver involvement. Greater than equal to 3 abnormal liver function tests predicted poor outcomes. Immunomodulatory drug therapy was associated with favorable progression-free survival compared to chemotherapy.
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Mixed potential ammonia (NH3) sensors with the Fe- and Mo-codoped BiVO4 sensing electrode and Ag reference electrode based on the yttria-stabilized zirconia solid electrolyte were developed. Fe- and Mo-doped BiVO4 sensing materials were prepared using solution combustion synthesis and then characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and X-ray photoelectron spectroscopy (XPS). It was observed that Fe doping could greatly improve the response rate, while Mo doping could enhance the response signal (ΔU) and sensitivity. Based on the optimal doping ratio of Fe and Mo each, the synergistic enhancement of the performance by Fe and Mo codoping was investigated. The sensor coated by BiV0.75Fe0.2Mo0.05Oδ materials exhibited a prominent sensing performance to a low concentration of 10-50 ppm of NH3 at 525 °C with the outstanding sensitivity of -148.988 mV/decade. Fe and Mo doping also improved the selectivity of the sensor to NH3, with the relative deviations less than ±8% of other typical gases' interference including NO, NO2, CO, CO2, and CH4. Besides, the sensor showed good resistance to fluctuations in the oxygen concentration and favorable stability against changes in the water vapor concentration. In addition, the sensor also exhibited good long-term stability. The mixed potential response mechanism was further discussed and analyzed through polarization curves as well as through gas chromatography and infrared absorption spectroscopy.
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BACKGROUND: To study the age-adjusted Charlson comorbidity index (ACCI) scale, which is a comprehensive quantification of multimorbidity coexistence, for the assessment of the risk of acute myocardial infarction death in elderly people. METHODS AND RESULTS: A total of 502 older patients with acute myocardial infarction were studied at Qilu Hospital from September 2017 to March 2022. They were categorized on the basis of ACCI into low (≤5), intermediate (6, 7), and high (≥8) risk groups. Hospitalization duration was observed, with death as the end point. least absolute shrinkage and selection operator regression was used to screen variables, 10-fold cross-validation was performed to validate the screened variables, a Cox regression nomogram predicting the risk of patient death was prepared, hazard ratio with 95% CI was calculated, a nomogram calibration curve was constructed, and a receiver operating characteristic curve, decision curve analysis, and a clinical impact curve were established. From 62 potential factors in a least absolute shrinkage and selection operator regression, 12 were selected via 10-fold cross-validation. Retain variables with significant statistical differences in the Cox regression. A nomogram of the risk of death from acute infarction was constructed, and risk factors included ventricular tachycardia/fibrillation, atrial fibrillation, nicorandil, angiotensin-converting enzyme inhibitors/angiotensin-converting enzyme inhibitors, ß blockers, and ACCI score, carbon dioxide combining power, and blood calcium concentration. CONCLUSIONS: The ACCI score effectively assesses multimorbidity in the older patients. As ACCI rises, the death risk from acute myocardial infarction grows. The study's nomogram is valid and clinically applicable.
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Mortalidade Hospitalar , Infarto do Miocárdio , Nomogramas , Humanos , Masculino , Idoso , Feminino , Medição de Risco/métodos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/diagnóstico , Idoso de 80 Anos ou mais , Fatores de Risco , Fatores Etários , Estudos Retrospectivos , Comorbidade , Prognóstico , China/epidemiologia , Valor Preditivo dos TestesRESUMO
BACKGROUND: Carotenoids are a group of tetraterpenoid lipophilic pigments linked to depression, but studies on individual carotenoid components are lacking. We aimed to assess the association between each serum carotenoids and depressive symptoms in adults. METHODS: This cross-sectional study included 7264 adults from the National Health and Nutrition Examination Survey (NHANES). Serum carotenoid levels (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) were measured using high-performance liquid chromatography. Participants with a Patient Health Questionnaire score ≥ 10 were considered to have depressive symptoms. The association between each carotenoid and depressive symptoms was investigated using multivariable-adjusted logistic regression, restricted cubic spline, and weighted quantile sum regression models. RESULTS: The participants' average age was 46.0 (interquartile range: 34.0-60.0) years (50.9 % females), and 545 participants (7.5 %) were diagnosed with depressive symptoms. The logistic regression model demonstrated that high serum α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin levels were associated with a lower likelihood of depressive symptoms. The restricted cubic spline model revealed that the significantly inverse relationships between serum carotenoid levels and the risk of depressive symptoms were nonlinear for α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin and were linear for lycopene. The threshold effect analysis further identified the inflection points were 12.1, 35.7, 5.9, and 7.7 µg/dL for α-carotene, ß-carotene, ß-cryptoxanthin, and lutein/zeaxanthin, respectively. The weighted quantile sum regression model revealed that ß-cryptoxanthin (35.2 %) and α-carotene (34.5 %) were the top-weighted carotenoids correlated with depressive symptoms. CONCLUSIONS: The present results suggested an association between higher levels of each serum carotenoids and a decreased risk of depressive symptoms in adults.
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beta-Criptoxantina , Carotenoides , Depressão , Inquéritos Nutricionais , Zeaxantinas , Humanos , Feminino , Carotenoides/sangue , Masculino , Adulto , Pessoa de Meia-Idade , Depressão/sangue , Depressão/epidemiologia , Estudos Transversais , Zeaxantinas/sangue , beta-Criptoxantina/sangue , Luteína/sangue , beta Caroteno/sangue , Licopeno/sangue , Modelos LogísticosRESUMO
This study explores the enhancement of aqueous zinc-ion batteries (AZIBs) using ammonium-enhanced vanadium oxide cathodes. Density Functional Theory (DFT) calculations reveal that NH4+ incorporation into V6O16 lattices significantly facilitates Zn2+ ion diffusion by reducing electrostatic interactions, acting as a structural lubricant. Subsequent experimental validation using (NH4)2V6O16 cathodes synthesized via a hydrothermal method corroborates the DFT findings, demonstrating remarkable electrochemical stability with a capacity retention of 90% after 2000 cycles at 5 A g-1. These results underscore the potential of NH4+ in improving the performance and longevity of AZIBs, providing a pathway for sustainable energy storage solutions.
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Objective: Systemic lupus erythematosus (SLE) is a disease characterised by immune inflammation and damage to multiple organs. Recent investigations have linked competing endogenous RNAs (ceRNAs) to lupus. However, the exact mechanism through which the ceRNAs network affects SLE is still unclear. This study aims to investigate the regulatory functions of the ceRNAs network, which are important pathways that control the pathophysiological processes of SLE. Methods: CircRNA microarray for our tested assays were derived from bone marrow samples from three healthy individuals and three SLE patients in our hospital. The other sequencing data of circRNA, miRNA and mRNA were obtained from Gene Expression Omnibus (GEO) datasets. Using the limma package of R program, the differential expression of mRNA and miRNA in the GEO database was discovered. Then predicted miRNA-mRNA and circRNA-miRNA were established using miRMap, miRanda, miRDB, TargetScan, and miTarBase. CircRNA-miRNA-mRNA ceRNA network was constructed using Cytoscape, and hub genes were screened using a protein-protein interaction network. Immune infiltration analysis of the hub gene was also performed by CIBERSORT and GSEA. Results: 230 overlapped circRNAs, 86 DEmiRNAs and 2083 DEmRNAs were identified in SLE patients as compared to healthy controls. We constructed a circRNA-miRNA-mRNA ceRNAs network contained 11 overlapped circRNAs, 9 miRNAs and 51 mRNAs. ESR1 and SIRT1 were the most frequently associated protein-protein interactions in the PPI network. KEGG analysis showed that DEGs was enriched in FoxO signaling pathway as well as lipids and atherosclerosis. We constructed a novel circRNA-miRNA-mRNA ceRNA network (HSA circ 0000345- HSA miR-22-3-P-ESR1/SIRT1) that may have a major impact on SLE. Conclusion: Through this bioinformatics and integrated analysis, we suggest a regulatory role for ceRNA network in the pathogenesis and treatment of SLE.
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OBJECTIVE: To evaluate the heart response of Erdheim-Chester disease (ECD) through continuous follow-up within our large cohort, for which there is a lack of understanding. METHODS: We conducted a retrospective analysis of clinical data from patients with ECD with cardiac involvement diagnosed at our centre between January 2010 and August 2023. We assessed the heart response by integrating pericardial effusion and metabolic responses. RESULTS: A total of 40 patients were included, with a median age of 51.5 years (range: 29-66) and a BRAFV600E mutation rate of 56%. The most common imaging manifestations observed were pericardial effusion (73%), right atrium (70%) and right atrioventricular sulcus infiltration (58%). Among 21 evaluable patients, 18 (86%) achieved a heart response including 5 (24%) complete response (CR) and 13 (62%) partial response (PR). The CR rate of pericardial effusion response was 33%, while the PR rate was 56%. Regarding the cardiac mass response, 33% of patients showed PR. For cardiac metabolic response, 32% and 53% of patients achieved complete and partial metabolic response, respectively. There was a correlation between pericardial effusion response and cardiac metabolic response (r=0.73 (95% CI 0.12 to 0.83), p<0.001). The median follow-up was 50.2 months (range: 1.0-102.8 months). The estimated 5-year overall survival was 78.9%. The median progression-free survival was 59.4 months (95% CI 26.2 to 92.7 months). Patients who received BRAF inhibitors achieved better heart response (p=0.037) regardless of treatment lines. CONCLUSION: We pioneered the evaluation of heart response of ECD considering both pericardial effusion and cardiac metabolic response within our cohort, revealing a correlation between these two indicators. BRAF inhibitors may improve heart response, regardless of the treatment lines.
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Doença de Erdheim-Chester , Derrame Pericárdico , Humanos , Doença de Erdheim-Chester/complicações , Doença de Erdheim-Chester/tratamento farmacológico , Doença de Erdheim-Chester/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Derrame Pericárdico/etiologia , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Resultado do Tratamento , MutaçãoRESUMO
Recently, due to high price, resource shortage and unstable supply of cobalt, the development of low-cost cobalt-free Ni-rich cathodes has attracted extensive attention with the ever-increasing lithium-ion batteries (LIBs) industry. Selecting cost-effective elements to replace cobalt in Ni-rich cathodes is urgent. However, the principle of structural design of Ni-rich cathode remains unclear, hampering the selection of alternative elements. Herein, the cobalt-free cathodes of LiNi0.95Mg0.05O2 (NiMg) and LiNi0.95Mn0.05O2 (NiMn) are designed as alternatives to LiNi0.96Co0.04O2 (NiCo). NiMg has comparable cycle stability with NiCo, while NiMn has inferior cycle performance. Reverse Monte Carlo modelling was used to generate structural model and uncover local structure by fitting pair distribution function. It reveals Mn causes more severe Jahn-Teller distortions and disordered lattice host framework (Ni0.95M0.05O2, M = Co/Mn/Mg) than Co and Mg due to the strong size effect and coulomb interactions of Mn in Ni0.95Mn0.05O2 layer. The outstanding cycle stability of NiMg and NiCo originates from the ordered lattice host frameworks, which relieve stress and inhibit particle breakage during cycle. Meanwhile, the ordered lattice host framework induced guest Li+ disordering reduces Li+ diffusion energy barrier, improving the rate capability. This study provides a new perspective for the structural design of cobalt-free Ni-rich cathodes.
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Derived from hazelnuts, hazel leaf has been utilized in traditional folk medicine for centuries in countries such as Portugal, Sweden, and Iran. In our previous investigations, we conducted a preliminary assessment of the hazel leaf polyphenol extract (referred to as ZP) and identified nine compounds, such as kaempferol and chlorogenic acid, in its composition. ZP has shown promising properties as an antioxidant and anti-inflammatory agent. Our research has revealed that ZP has protective effects against cisplatin-induced acute kidney injury (AKI). We conducted a comprehensive examination of both the pathological and ultrastructural aspects and found that ZP effectively ameliorated renal tissue lesions and mitigated mitochondrial damage. Moreover, ZP significantly suppressed malondialdehyde levels while increasing glutathione and catalase concentrations in the kidneys of AKI-induced mice. ZP decreased the number of apoptotic cells and decreased pro-apoptotic protein expression in the kidneys of mice and human renal tubular epithelial cells (HK-2). Furthermore, treatment with ZP increased the levels of proteins marking anti-ferroptosis, such as GPX4, FTH1, and FSP1, in experiments both in vivo and in vitro. We elucidated the underlying mechanisms of ZP's actions, revealing its inhibitory effect on Yap phosphorylation and its regulation of Lats expression, which exert a protective influence on the kidneys. Furthermore, we found that inhibiting the Hippo pathway compromised ZP's nephroprotective effects in both in vitro and in vivo studies. In summary, this research shows that ZP exhibits renoprotective properties, effectively reducing oxidative damage, apoptosis, and ferroptosis in the kidneys by targeting the Hippo pathway.
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Injúria Renal Aguda , Cisplatino , Ferroptose , Via de Sinalização Hippo , Extratos Vegetais , Folhas de Planta , Polifenóis , Transdução de Sinais , Animais , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/induzido quimicamente , Ferroptose/efeitos dos fármacos , Cisplatino/efeitos adversos , Polifenóis/farmacologia , Polifenóis/química , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Humanos , Transdução de Sinais/efeitos dos fármacos , Folhas de Planta/química , Proteínas Serina-Treonina Quinases/metabolismo , Masculino , Linhagem Celular , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
Ovarian cancer is a prevalent malignancy in the female reproductive system, representing a significantly fatal and incurable tumor. Chelerythrine (CHE), a natural benzopyridine alkaloid, has demonstrated a broad spectrum of anticancer activities. Nevertheless, the ovarian cancer inhibitory impact of CHE remains unclear. In this study, we investigated the cytotoxic mechanism and potential targets of CHE on in vitro cultures of A2780 and SKOV3 cells derived from ovarian cancer. Additionally, in vivo experiments were conducted to confirm the suppressive impact of CHE on tumor growth in nude mice. The findings revealed that CHE impeded the growth of A2780 and SKOV3 cells in a concentration-time-dependent manner and significantly suppressed the development of tumors in nude mice. CHE elevated the level of oxidative stress in tumor cells, prompted cell cycle halt in the S phase, and increased their mitochondrial membrane potential. Western blotting results demonstrated that CHE could modulate the expression of proteins associated with apoptotic and ferroptosis processes in A2780 and SKOV3 cells. Nrf2 was verified to be an upstream key target mediating the inhibitory impact of CHE on ovarian cancer cells. In summary, CHE exerts its anti-cancer effects on ovarian cancer by modulating Nrf2, inhibiting cellular proliferation, and promoting apoptosis and ferroptosis.
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Apoptose , Benzofenantridinas , Proliferação de Células , Ferroptose , Camundongos Nus , Fator 2 Relacionado a NF-E2 , Neoplasias Ovarianas , Feminino , Benzofenantridinas/farmacologia , Humanos , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Linhagem Celular Tumoral , Ferroptose/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18-66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456-9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126-7.874) as poor prognostic factors for EFS. The most common grade 3-4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.
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Citarabina , Histiocitose de Células de Langerhans , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/diagnóstico , Intervalo Livre de Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
We propose a two-dimensional carbon allotrope (named KT-graphene) by incorporating kagome and tetragonal lattices consisting of trigonal, quadrilateral, octagonal, and dodecagonal rings. The introduction of non-hexagonal rings can give rise to the localized electronic states that improve the chemical reactivity toward potassium, making KT-graphene a high-performance anode material for potassium-ion batteries. It shows a high theoretical capacity (892 mAh g-1), a low diffusion barrier (0.33 eV), and a low average open-circuit voltage (0.51 V). The presence of electrolyte solvents is propitious to boost the K-ion adsorption and diffusion capabilities. Moreover, one-dimensional nanotubes (KT-CNTs), rolled up by the KT-graphene sheet, are metallic regardless of the tube diameter. As the curvature increases, KT-CNTs exhibit significantly increased surface activity, which can promote the electron-donating ability of K. Furthermore, the curvature effect greatly enhances the efficiency of K diffusion on the inner surface compared to that on the outer surface.
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Circular RNAs (circRNAs) are a widespread, cell-, tissue-, and disease-specific class of largely non-coding RNA transcripts. These single-stranded, covalently-closed transcripts arise through non-canonical splicing of pre-mRNA, a process called back-splicing. Back-splicing results in circRNAs which are distinguishable from their cognate mRNA as they possess a unique sequence of nucleic acids called the backsplice junction (BSJ). CircRNAs have been shown to play key functional roles in various cellular contexts and achieve this through their interaction with other macromolecules, particularly other RNA molecules and proteins. To elucidate the molecular mechanisms underlying circRNA function, it is necessary to identify these interacting partners. Herein, we present an optimized strategy for the simultaneous purification of the circRNA interactome within eukaryotic cells, allowing the identification of both circRNA-RNA and circRNA-protein interactions.
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Ginsenosides are a class of natural products with hormone-like activity of triterpenoid saponins and have a variety of pharmacological activities such as anti-aging, immune regulation and cognitive improvement. With the great research interest in alternative medicine and natural products, they are gradually becoming research hotspots. Ginsenosides have a four-ring rigid steroid backbone similar to steroid hormones, and a series of experimental studies have shown that they can exhibit hormone-like activity by binding to nuclear receptors or affecting hormone levels, thereby affecting a wide range of inflammatory conditions, cancers, and menopause-related diseases. This review summarizes the mechanisms and potential health effects of ginsenosides exhibiting estrogen-like, glucocorticoid-like and androgen-like activities, providing an important reference for the exploration of safe phytohormone replacement therapy.
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Produtos Biológicos , Ginsenosídeos , Panax , Ginsenosídeos/farmacologia , Ginsenosídeos/uso terapêutico , Estrogênios , Receptores Citoplasmáticos e Nucleares , EsteroidesRESUMO
Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.
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Corylus , Hiperuricemia , Animais , Polifenóis/farmacologia , Ácido Clorogênico/farmacologia , Simulação de Acoplamento Molecular , Peixe-Zebra , Farmacologia em Rede , Quempferóis , Hiperuricemia/tratamento farmacológico , Xantina Oxidase , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.