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RNA splicing is a dynamic molecular process in response to environmental stimuli and is strictly regulated by the spliceosome. Sm proteins, constituents of the spliceosome, are key components that mediate splicing reactions; however, their potential role in hepatocellular carcinoma (HCC) is poorly understood. In the study, SNRPD2 (PD2) is found to be the most highly upregulated Sm protein in HCC and to act as an oncogene. PD2 modulates DDX39A intron retention together with HNRNPL to sustain the DDX39A short variant (39A_S) expression. Mechanistically, 39A_S can mediate MYC mRNA nuclear export to maintain high MYC protein expression, while MYC in turn potentiates PD2 transcription. Importantly, digitoxin can directly interact with PD2 and has a notable cancer-suppressive effect on HCC. The study reveals a novel mechanism by which DDX39A senses oncogenic MYC signaling and undergoes splicing via PD2 to form a positive feedback loop in HCC, which can be targeted by digitoxin.
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Fast-decaying scintillators show subnanoseconds or nanoseconds lifetime and high time resolution, making them important in nuclear physics, medical diagnostics, scientific research, and other fields. Metal halide perovskites (MHPs) show great potential for scintillator applications owing to their easy synthesis procedure and attractive optical properties. However, MHPs scintillators still need further improvement in decay lifetime. To optimize the decay lifetime, great progress has been achieved recently. In this Perspective, we first summarize the structural characteristics of MHPs in various dimensions, which brings different exciton behaviors. Then, recent advances in designing fast-decaying MHPs according to different exciton behaviors have been concluded, focusing on the photophysical mechanisms to achieve fast-decaying lifetimes. These advancements in decay lifetimes could facilitate the MHPs scintillators in advanced applications, such as time-of-flight positron emission tomography (TOF-PET), photon-counting computed tomography (PCCT), etc. Finally, the challenges and future opportunities are discussed to provide a roadmap for designing novel fast-decaying MHPs scintillators.
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BACKGROUND: Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. METHODS: In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. RESULTS: Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. CONCLUSIONS: The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. TRIAL REGISTRATION: All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).
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Imagen por Resonancia Magnética , Accidente Cerebrovascular , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Driven by iron-dependent lipid peroxidation, ferroptosis is regulated by p53 and solute carrier family 7 member 11 (SLC7A11)/glutathione/glutathione peroxidase 4 (GPX4) axis in colorectal cancer (CRC). This study aimed to investigate the influence of curcumin (CUR) on ferroptosis in CRC. The efficacies of CUR on the malignant phenotype of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide, wound healing, and clonogenic assays. The effects of CUR on ferroptosis of CRC cells were evaluated by transmission electron microscopy, lactate dehydrogenase release assay, Fe2+ staining, and analyses of reactive oxygen species, lipid peroxide, malondialdehyde, and glutathione levels. CUR's targets in ferroptosis were predicted by network pharmacological study and molecular docking. With SW620 xenograft tumors, the efficacy of CUR on CRC was investigated, and the effects of CUR on ferroptosis were assessed by detection of Fe2+, malondialdehyde, and glutathione levels. The effects of CUR on expressions of p53, SLC7A11, and GPX4 in CRC cells and tumors were analyzed by quantitative reverse transcription-polymerase chain reaction, western blotting, and immunohistochemistry. CUR suppressed the proliferation, migration, and clonogenesis of CRC cells and xenograft tumor growth by causing ferroptosis, with enhanced lactate dehydrogenase release and Fe2+, reactive oxygen species, lipid peroxide, and malondialdehyde levels, but attenuated glutathione level in CRC. In silico study indicated that CUR may bind p53, SLC7A11, and GPX4, consolidated by that CUR heightened p53 but attenuated SLC7A11 and GPX4 mRNA and protein levels in CRC. CUR may exert an inhibitory effect on CRC by inducing ferroptosis via regulation of p53 and SLC7A11/glutathione/GPX4 axis.
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Sistema de Transporte de Aminoácidos y+ , Neoplasias Colorrectales , Curcumina , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Proteína p53 Supresora de Tumor , Ferroptosis/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Sistema de Transporte de Aminoácidos y+/metabolismo , Curcumina/farmacología , Animales , Ratones , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Glutatión/metabolismo , Ratones Desnudos , Ratones Endogámicos BALB C , Ensayos Antitumor por Modelo de Xenoinjerto , Peroxidación de Lípido/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Masculino , Simulación del Acoplamiento Molecular , Proliferación Celular/efectos de los fármacosRESUMEN
Alternating electric fields (AEFs) at intermediate frequencies (100-300 kHz) and low intensities (1-3 V/cm) have shown promise as an effective approach for inhibiting cancer cell proliferation. However, a noticeable research gap exists in comparing the biophysical properties of invasive and non-invasive AEFs methods, and AEFs delivery strategies require further improvement. In this study, we constructed a realistic head model to simulate the effects of non-invasive and invasive AEFs on malignant gliomas. Additionally, a novel method was proposed involving the placement of a return electrode under the scalp. We simulated the electric field and temperature distributions in the brain tissue for each method. Our results underscore the advantages of invasive AEFs, showcasing their superior tumor-targeting abilities and reduced energy requirements. The analysis of brain tissue temperature changes reveals that non-invasive AEFs primarily generate heat at the scalp level, whereas invasive methods localize heat production within the tumor itself, thereby preserving surrounding healthy brain tissue. Our proposed invasive AEFs method also shows potential for selective electric field intervention. In conclusion, invasive AEFs demonstrate potential for precise and effective tumor treatment. Its enhanced targeting capabilities and limited impact on healthy tissue make it a promising avenue for further research in the realm of cancer treatment.
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Using noninvasive biomarkers to identify high-risk individuals prior to endoscopic examination is crucial for optimization of screening strategies for esophageal squamous cell carcinoma (ESCC). We conducted a nested case-control study based on two community-based screening cohorts to evaluate the warning value of serum metabolites for esophageal malignancy. The serum samples were collected at enrollment when the cases had not been diagnosed. We identified 74 differential metabolites and two prominent perturbed metabolic pathways, and constructed Metabolic Risk Score (MRS) based on 22 selected metabolic predictors. The MRS generated an area under the receiver operating characteristics curve (AUC) of 0.815. The model performed well for the within-1-year interval (AUC: 0.868) and 1-to-5-year interval (AUC: 0.845) from blood draw to diagnosis, but showed limited ability in predicting long-term cases (>5 years). In summary, the MRS could serve as a potential early warning and risk stratification tool for establishing a precision strategy of ESCC screening.
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OBJECTIVE: Liver cancer is the world's sixth most prevalent cancer and the third most frequent cause of cancer-related mortality. Glucose metabolic disorders, indicated by a high fasting plasma glucose (HFPG) concentration, is a contributor to the etiology of liver cancer. With the rising prevalence of glucose metabolic disorders, an assessment of the global burden of liver cancer attributable to HFPG is warranted to inform global liver cancer prevention and control strategies. METHODS AND ANALYSIS: We evaluated the global death and disability-adjusted life years (DALYs) of liver cancer and its subtypes attributable to HFPG at global, regional, and country level. The temporal trend and disparity across geographic regions, social development level, age groups and sex were assessed. RESULTS: In 2019, HFPG-attributable liver cancer was estimated to have caused 4,729.49 deaths and to be responsible for 99,302.25 DALYs. The age-standardized mortality and DALY rate were 0.06 and 1.20 per 100,000 population, and displayed a significantly increasing temporal trend from 1990 to 2019. The age-standardized mortality rate of patients with liver cancer that was attributable to HFPG was higher in men than women. Sex-based disparity narrowed after the women reached menopause, but increased between 1990 and 2019. CONCLUSION: The burden of liver cancer that are attributable to HFPG has been influenced by longitudinal changes in lifestyle, the etiology of liver disease, age demographics, and hormonal status in women. These findings suggest that comprehensive strategies could be implemented, especially for patients with NASH and hyperglycemia, to prevent liver cancer.
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Glucemia , Ayuno , Carga Global de Enfermedades , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/etiología , Masculino , Femenino , Glucemia/análisis , Glucemia/metabolismo , Persona de Mediana Edad , Anciano , Ayuno/sangre , Salud Global/estadística & datos numéricos , Años de Vida Ajustados por Discapacidad , Adulto , Anciano de 80 o más Años , PrevalenciaRESUMEN
The regulation of seed development is critical for determining crop yield. Auxins are vital phytohormones that play roles in various aspects of plant growth and development. However, its role in amino acid biosynthesis and metabolism in seeds is not fully understood. In this study, we identified a mutant with small seeds through forward genetic screening in Medicago truncatula. The mutated gene encodes MtPIN4, an ortholog of PIN1. Using molecular approaches and integrative omics analyses, we discovered that auxin and amino acid content significantly decreased in mtpin4 seeds, highlighting the role of MtPIN4-mediated auxin distribution in amino acid biosynthesis and metabolism. Furthermore, genetic analysis revealed that the three orthologs of PIN1 have specific and overlapping functions in various developmental processes in M. truncatula. Our findings emphasize the significance of MtPIN4 in seed development and offer insights into the molecular mechanisms governing the regulation of seed size in crops. This knowledge could be applied to enhance crop quality by targeted manipulation of seed protein regulatory pathways.
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PURPOSE: Ovarian cancer can be categorized into distinct histologic subtypes with varying identifiable risk factors, molecular composition, clinical features, and treatment. The global incidence of ovarian cancer subtypes remains limited, especially in low- and middle-income countries (LMICs) without high-quality cancer registry systems. MATERIALS AND METHODS: We used data from population-based cancer registries of the Cancer Incidence in Five Continents project to calculate the proportions of serous, mucinous, endometrioid, clear cell, and other histologic subtypes of ovarian cancer. Proportions were applied to the estimated numbers of patients with ovarian cancer from Global Cancer Observatory 2020. Age-standardized incidence rates were calculated. RESULTS: Globally, an estimated 133,818 new patients of serous cancer, 35,712 new patients of mucinous cancer, 29,319 new patients of endometrioid cancer, and 17,894 new patients of clear cell cancer were identified in 2020. The distribution of ovarian cancer histologic subtypes exhibited regional variation. Eastern Europe had the highest rate of serous and mucinous carcinomas, whereas Northern Africa and Eastern Asia had the highest burden of endometrioid and clear cell carcinomas, respectively. CONCLUSION: This study provides a global incidence landscape of histologic subtypes of ovarian cancer, particularly in LMICs lacking comprehensive registry systems. Our analysis offers valuable insights into disease burden and guidance for tailored strategies for prevention of ovarian cancer.
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Neoplasias Ováricas , Sistema de Registros , Humanos , Femenino , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/patología , Sistema de Registros/estadística & datos numéricos , Incidencia , Persona de Mediana Edad , Salud Global/estadística & datos numéricos , Adulto , Anciano , Adenocarcinoma Mucinoso/epidemiología , Adenocarcinoma Mucinoso/patología , Carcinoma Endometrioide/epidemiología , Carcinoma Endometrioide/patología , Adenocarcinoma de Células Claras/epidemiología , Adenocarcinoma de Células Claras/patologíaRESUMEN
The oldest-old population, those aged ≥ 80 years, is the fastest-growing group in the United States (US), grappling with an increasingly heavy burden of dementia. We aimed to dissect the trends in dementia prevalence, mortality, and risk factors, and predict future levels among this demographic. Leveraging data from the Global Burden of Disease Study 2019, we examined the trends in dementia prevalence, mortality, and risk factors (with a particular focus on body mass index, BMI) for US oldest-old adults. Through decomposition analysis, we identified key population-level contributors to these trends. Predictive modeling was employed to estimate future prevalence and mortality levels over the next decade. Between 1990 and 2019, the number of dementia cases and deaths among the oldest-old in the US increased by approximately 1.37 million and 60,000 respectively. The population growth and aging were highlighted as the primary drivers of this increase. High BMI emerged as a growing risk factor. Females showed a disproportionately higher dementia burden, characterized by a unique risk factor profile, including BMI. Predictions for 2030 anticipate nearly 4 million dementia cases and 160,000 related deaths, with a marked increase in prevalence and mortality anticipated among those aged 80-89. The past 30 years have witnessed a notable rise in both the prevalence and mortality of dementia among the oldest-old in the US, accompanied by a significant shift in risk factors, with obesity taking a forefront position. Targeted age and sex-specific public health strategies that address obesity control are needed to mitigate the dementia burden effectively.
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Background: Stroke is a common and frequently occurring disease among middle-aged and elderly people, with approximately 55%-75% of patients remaining with upper limb dysfunction. How to promote the recovery of motor function at an early stage is crucial to the life of the patient. Objectives: This study aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) of the primary motor cortex (M1) functional area in poststroke patients in the subacute phase is more effective in improving upper limb function than conventional tDCS. Methods: This randomized, sham-controlled clinical trial included 69 patients with subcortical stroke. They were randomly divided into the HD-tDCS, anodal tDCS (a-tDCS), and sham groups. Each group received 20 sessions of stimulation. The patients were assessed using the Action Research Arm Test, Fugl-Meyer score for upper extremities, Motor Function Assessment Scale, and modified Barthel index (MBI) pretreatment and posttreatment. Results: The intragroup comparison scores improved after 4 weeks of treatment. The HD-tDCS group showed a slightly greater, but nonsignificant improvement as compared to a-tDCS group in terms of mean change observed in function of trained items. The MBI score of the HD-tDCS group was maintained up to 8 weeks of follow-up and was higher than that in the a-tDCS group. Conclusion: Both HD-tDCS and a-tDCS can improve upper limb motor function and daily activities of poststroke patients in the subacute stage. This trial is registered with ChiCTR2000031314.
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Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Estimulación Transcraneal de Corriente Directa , Anciano , Persona de Mediana Edad , Humanos , Recuperación de la Función , Accidente Cerebrovascular/terapia , Extremidad Superior , Resultado del TratamientoRESUMEN
Importance: The lack of evidence-based implementation strategies is a major contributor to increasing mortality due to out-of-hospital cardiac arrest (OHCA) in developing countries with limited resources. Objective: To evaluate whether the implementation of legislation is associated with increased bystander cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use and improved clinical outcomes for patients experiencing OHCA and to provide policy implications for low-income and middle-income settings. Design, Setting, and Participants: This observational cohort study analyzed a prospective city registry of patients with bystander-witnessed OHCA between January 1, 2010, and December 31, 2022. The Emergency Medical Aid Act was implemented in Shenzhen, China, on October 1, 2018. An interrupted time-series analysis was used to assess changes in outcomes before and after the law. Data analysis was performed from May to October 2023. Exposure: The Emergency Medical Aid Act stipulated the use of AEDs and CPR training for the public and provided clear legal guidance for OHCA rescuing. Main Outcomes and Measures: The primary outcomes were rates of bystander-initiated CPR and use of AEDs. Secondary outcomes were rates of prehospital return of spontaneous circulation (ROSC), survival to arrival at the hospital, and survival at discharge. Results: A total of 13â¯751 patients with OHCA (median [IQR] age, 59 [43-76] years; 10â¯011 men [72.83%]) were included, with 7858 OHCAs occurring during the prelegislation period (January 1, 2010, to September 30, 2018) and 5893 OHCAs occurring during the postlegislation period (October 1, 2018, to December 31, 2022). The rates of bystander-initiated CPR (320 patients [4.10%] vs 1103 patients [18.73%]) and AED use (214 patients [4.12%] vs 182 patients [5.29%]) increased significantly after legislation implementation vs rates before the legislation. Rates of prehospital ROSC (72 patients [0.92%] vs 425 patients [7.21%]), survival to arrival at the hospital (68 patients [0.87%] vs 321 patients [5.45%]), and survival at discharge (44 patients [0.56%] vs 165 patients [2.80%]) were significantly increased during the postlegislation period. Interrupted time-series models demonstrated a significant slope change in the rates of all outcomes. Conclusions and Relevance: These findings suggest that implementation of the Emergency Medical Aid Act in China was associated with increased rates of CPR and public AED use and improved survival of patients with OHCA. The use of a systemwide approach to enact resuscitation initiatives and provide legal support may reduce the burden of OHCA in low-income and middle-income settings.
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Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidad , Humanos , Reanimación Cardiopulmonar/estadística & datos numéricos , Reanimación Cardiopulmonar/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , China/epidemiología , Sistema de Registros/estadística & datos numéricos , Desfibriladores/estadística & datos numéricos , Servicios Médicos de Urgencia/legislación & jurisprudencia , Servicios Médicos de Urgencia/estadística & datos numéricos , Estudios Prospectivos , AdultoRESUMEN
This study investigated the mediating effect of Triethanolamine on Fe@C-Rhodobacter sphaeroides hybrid photosynthetic system to achieve efficient biohydrogen production. The biocompatible Fe@C generates excited electrons upon exposure to light, releasing ferrum for nitrogenase synthesis, and regulating the pH of the fermentation environment. Triethanolamine was introduced to optimize the electron transfer chain, thereby improving system stability, prolonging electron lifespan, and facilitating ferrum corrosion. This, in turn, stimulated the lactic acid synthetic metabolic pathway of Rhodobacter sphaeroides, resulting in increased reducing power in the biohybrid system. The ternary coupling system was analyzed through the regulation of concentration, initial pH, and light intensity. The system achieved the highest total H2 production of 5410.9 mL/L, 1.29 times higher than the control (2360.5 mL/L). This research provides a valuable strategy for constructing ferrum-carbon-based composite-cellular biohybrid systems for photo-fermentation H2 production.
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Etanolaminas , Hidrógeno , Luz , Rhodobacter sphaeroides , Rhodobacter sphaeroides/metabolismo , Hidrógeno/metabolismo , Etanolaminas/metabolismo , Etanolaminas/química , Hierro/química , Catálisis , Concentración de Iones de Hidrógeno , Carbono , Fermentación , FotosíntesisRESUMEN
Tumor-treating fields (TTFields) is a novel treatment modality for malignant solid tumors, often employing electric field simulations to analyze the distribution of electric fields on the tumor under different parameters of TTFields. Due to the present difficulties and high costs associated with reproducing or implementing the simulation model construction techniques, this study used readily available open-source software tools to construct a highly accurate, easily implementable finite element simulation model for TTFields. The accuracy of the model is at a level of 1 mm 3. Using this simulation model, the study carried out analyses of different factors, such as tissue electrical parameters and electrode configurations. The results show that factors influncing the distribution of the internal electric field of the tumor include changes in scalp and skull conductivity (with a maximum variation of 21.0% in the treatment field of the tumor), changes in tumor conductivity (with a maximum variation of 157.8% in the treatment field of the tumor), and different electrode positions and combinations (with a maximum variation of 74.2% in the treatment field of the tumor). In summary, the results of this study validate the feasibility and effectiveness of the proposed modeling method, which can provide an important reference for future simulation analyses of TTFields and clinical applications.
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Simulación por Computador , Análisis de Elementos Finitos , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/radioterapia , Electrodos , Conductividad Eléctrica , Programas Informáticos , Cuero Cabelludo , CráneoRESUMEN
Cell plate formation during cytokinesis entails multiple stages occurring concurrently and requiring orchestrated vesicle delivery, membrane remodelling, and timely deposition of polysaccharides, such as callose. Understanding such a dynamic process requires dissection in time and space; this has been a major hurdle in studying cytokinesis. Using lattice light sheet microscopy (LLSM), we studied cell plate development in four dimensions, through the behavior of yellow fluorescent protein (YFP)-tagged cytokinesis-specific GTPase RABA2a vesicles. We monitored the entire duration of cell plate development, from its first emergence, with the aid of YFP-RABA2a, in both the presence and absence of cytokinetic callose. By developing a robust cytokinetic vesicle volume analysis pipeline, we identified distinct behavioral patterns, allowing the identification of three easily trackable cell plate developmental phases. Notably, the phase transition between phase I and phase II is striking, indicating a switch from membrane accumulation to the recycling of excess membrane material. We interrogated the role of callose using pharmacological inhibition with LLSM and electron microscopy. Loss of callose inhibited the phase transitions, establishing the critical role and timing of the polysaccharide deposition in cell plate expansion and maturation. This study exemplifies the power of combining LLSM with quantitative analysis to decode and untangle such a complex process.
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Arabidopsis , Citocinesis , Glucanos , Arabidopsis/crecimiento & desarrollo , Arabidopsis/metabolismo , Glucanos/metabolismo , MicroscopíaRESUMEN
PURPOSE: Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients. METHODS: Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4 weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05). RESULTS: After 4, 12, and 24 weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5 g/L, 104 g/L, and 106.5 g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91 g/L, 94.5 g/L, and 94.5 g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels. CONCLUSION: In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels.
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Anemia , Eritropoyetina , Isoquinolinas , Puntaje de Propensión , Insuficiencia Renal Crónica , Humanos , Masculino , Femenino , Persona de Mediana Edad , Eritropoyetina/uso terapéutico , Insuficiencia Renal Crónica/complicaciones , Anemia/tratamiento farmacológico , Anemia/etiología , Anciano , Isoquinolinas/uso terapéutico , Glicina/análogos & derivados , Glicina/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Resultado del Tratamiento , Hemoglobinas/análisis , Hemoglobinas/metabolismo , Estudios Retrospectivos , Diabetes Mellitus/tratamiento farmacológicoRESUMEN
Chimeric antigen receptor (CAR-T) cell therapy is a newly developed immunotherapy strategy and has achieved satisfactory outcomes in the treatment of hematological malignancies. However, some adverse effects related to CAR-T cell therapy have to be resolved before it is widely used in clinics as a cancer treatment. Furthermore, the application of CAR-T cell therapy in the treatment of solid tumors has been hampered by numerous limitations. Therefore, it is essential to explore novel strategies to improve the therapeutic effect of CAR-T cell therapy. In this review, we summarized the recently developed strategies aimed at optimizing the generation of CAR-T cells and improving the anti-tumor efficiency of CAR-T cell therapy. Furthermore, the discovery of new targets for CAR-T cell therapy and the combined treatment strategies of CAR-T cell therapy with chemotherapy, radiotherapy, cancer vaccines and nanomaterials are highlighted.
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Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , Humanos , Inmunoterapia Adoptiva/métodos , Neoplasias/terapia , Neoplasias/inmunología , Receptores Quiméricos de Antígenos/inmunología , Animales , Inmunoterapia/métodos , Linfocitos T/inmunología , Terapia Combinada/métodos , Vacunas contra el Cáncer/uso terapéutico , Vacunas contra el Cáncer/inmunologíaRESUMEN
Armeniacae semen amarum-seeds of Prunus armeniaca L. (Rosaceae) (ASA), also known as Kuxingren in Chinese, is a traditional Chinese herbal drug commonly used for lung disease and intestinal disorders. It has long been used to treat coughs and asthma, as well as to lubricate the colon and reduce constipation. ASA refers to the dried ripe seed of diverse species of Rosaceae and contains a variety of phytochemical components, including glycosides, organic acids, amino acids, flavonoids, terpenes, phytosterols, phenylpropanoids, and other components. Extensive data shows that ASA exhibits various pharmacological activities, such as anticancer activity, anti-oxidation, antimicrobial activity, anti-inflammation, protection of cardiovascular, neural, respiratory and digestive systems, antidiabetic effects, and protection of the liver and kidney, and other activities. In clinical practice, ASA can be used as a single drug or in combination with other traditional Chinese medicines, forming ASA-containing formulas, to treat various afflictions. However, it is important to consider the potential adverse reactions and pharmacokinetic properties of ASA during its clinical use. Overall, with various bioactive components, diversified pharmacological actions and potent efficacies, ASA is a promising drug that merits in-depth study on its functional mechanisms to facilitate its clinical application.
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BACKGROUND: Significant differences in clinical manifestations between first-episode and recurrent major depression disorder (FE-MDD/R-MDD) have been demonstrated in previous studies, including the degree of suicide attempt. However, the potential brain mechanism underlying the effect of depressive episode frequency on suicidal ideation (SI) remains unclear. METHODS: In this study, 102 patients with FE-MDD (SI/non-SI: N = 70/32) and 71 matched normal controls (NCs), as well as 75 patients with R-MDD (SI/non-SI: N = 37/38) and 49 matched NCs were screened from the Chinese REST-meta-MDD consortium. T1-weighted and resting-state fMRI images were used to calculate gray matter volume (GMV) and fractional amplitude of low-frequency fluctuations (fALFF), respectively. RESULTS: Group comparisons revealed that FE-MDD showed changes only in GMV, while R-MDD showed changes in both GMV and fALFF compared to NCs. SI-specific GMV decreases were observed in the right cerebellum, superior marginal gyrus, and left middle temporal gyrus in FE-MDD patients, while SI-specific fALFF decreases in bilateral superior frontal gyrus and increases in bilateral cerebellum and left parahippocampal gyrus were obserevd in R-MDD patients. Moreover, a negative correlation was found between GMV value in right cerebellum and HAMD score. CONCLUSIONS: These findings suggest that first-episode and recurrent MDD show different effects on brain structure and function in patients with SI, providing a potential explanation for the distinct clinical manifestations of MDD patients from a brain mechanisms perspective.