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Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2-member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11-MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat-Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11-MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11-MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half-lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide-3-kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11-MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11-MIF mRNA is regulated by CCCTC-binding factor and stabilized through RNA N4-acetylcytidine modification facilitated by N-acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11-MIF-PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.
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BACKGROUND: Surgical risk assessment is intriguing for clinical decision-making of brainstem cavernous malformation (BSCM) treatment. While the BSCM grading scale, encompassing size, developmental venous anomaly, crossing axial midpoint, age, and timing of intervention, is increasingly utilized, the clinical relevance of neurological fluctuation and recurrent hemorrhage has not been incorporated. This study aimed to propose a supplementary grading scale with enhanced predictive efficacy. METHODS: Using a retrospective nationwide registry of consecutive patients with BSCMs undergoing surgery in China from March 2011 to May 2023, a new supplementary BSCM grading scale was developed from a derivative cohort of 260 patients and validated in an independent concurrent cohort of 67 patients. The primary outcome was unfavorable neurological function (modified Rankin Scale score >2) at the latest follow-up. The performance of the supplementary grading system was evaluated for discrimination, calibration, and clinical utility and further compared with its original counterpart. RESULTS: Over a follow-up of at least 6 months after surgery, the unfavorable outcomes were 31% in the overall cohort (101/327 patients). A preoperative motor deficit (odds ratio, 3.13; P=0.001), recurrent hemorrhage (odds ratio, 3.05; P<0.001), timing of intervention (odds ratio, 7.08; P<0.001), and crossing the axial midpoint (odds ratio, 2.57; P=0.006) were associated with the unfavorable outcomes and composed the initial Huashan grading variables. A supplementary BSCM grading system was subsequently developed by incorporating the Huashan grading variables into the original BSCM grading scale. The predictive capability of the supplementary scale was consistently superior to the original counterpart in either the derivative cohort (area under the receiver operating characteristic curve, 0.74 [95% CI, 0.68-0.80] for the supplementary versus 0.68 [95% CI, 0.61-0.74] for the original) or the validation cohort (0.75 [95% CI, 0.62-0.87] versus 0.64 [95% CI, 0.48-0.81]). CONCLUSIONS: This study highlights the neurological relevance of BSCM hemorrhage in surgical risk assessment. Via compositing preoperative motor function and recurrent hemorrhages, a supplementary grading scale may improve a dynamic risk assessment for clinical decisions in the management of BSCMs.
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Hemangioma Cavernoso del Sistema Nervioso Central , Humanos , Masculino , Femenino , Adulto , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Estudios Retrospectivos , Persona de Mediana Edad , Tronco Encefálico/cirugía , Sistema de Registros , Resultado del Tratamiento , Adolescente , Adulto Joven , Medición de Riesgo , ChinaRESUMEN
INTRODUCTION: Ovarian cancer (OC) is known for its high mortality rate. Although sodium citrate has anti-tumor effects in various cancers, its effect and mechanism in OC remain unclear. OBJECTIVES: To analyze the inhibitory effect of sodium citrate on ovarian cancer cells and the underlying mechanism. METHODS: Cell apoptosis was examined by TUNEL staining, flow cytometry, and ferroptosis was examined intracellular Fe2+, MDA, LPO assays, respectively. Cell metabolism was examined by OCR and ECAR measurements. Immunoblotting and immunoprecipitation were used to elucidate the mechanism. RESULTS: This study suggested that sodium citrate not only promoted ovarian cancer cell apoptosis but also triggeredferroptosis, manifested as elevated levels of Fe2+, LPO, MDA andlipid ROS production. On one hand, sodium citrate treatment led to a decrease of Ca2+ content in the cytosol by chelatingCa2+, which further inhibited the Ca2+/CAMKK2/AKT/mTOR signaling, thereby suppressing HIF1α-dependent glycolysis pathway and inducing cell apoptosis. On the other hand, the chelation of Ca2+ by sodium citrate resulted in inactivation of CAMKK2 and AMPK, leading to increase of NCOA4-mediated ferritinophagy, causing increased intracellular Fe2+ levels. More importantly, the inhibition of Ca2+/CAMKK2/AMPK signaling pathway reduced the activity of the MCU and Ca2+ concentration within the mitochondria, resulting in an increase in mitochondrial ROS. Additionally, metabolomic analysis indicated that sodium citrate treatment significantly increased de novo lipid synthesis. Altogether, these factors contributed to ferroptosis. As expected, Ca2+ supplementation successfully reversed the cell death and decreased tumor growth induced by sodium citrate. Inspiringly, it was found that coadministration of sodium citrate increased the sensitivity of OC cells to chemo-drugs. CONCLUSION: These results revealed that the sodium citrate exerted its anti-cancer activity by inhibiting Ca2+/CAMKK2-dependent cell apoptosis and ferroptosis. Sodium citrate will hopefully serve as a prospective compound for OC treatment and for improvingthe efficacy of chemo-drugs.
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BACKGROUND: Brainstem cavernous malformations (BSCMs) often present with haemorrhage, but the optimal timing for microsurgical intervention remains unclear. This study aims to explore how intervention timing relates to neurological outcomes in haemorrhagic BSCM patients undergoing microsurgery, offering insights for clinical decisions. METHODS: A total of 293 consecutive patients diagnosed with BSCMs, who underwent microsurgery were identified between March 2011 and January 2023 at two comprehensive centres in China, with a postoperative follow-up duration exceeding 6 months. Utilizing logistic regression models with restricted cubic splines, distinct time groups were identified. Subsequently, matching weight analysis compared these groups in terms of outcomes, new haemorrhage rates, cranial nerve deficits, and perioperative complications. The primary outcome was an unfavourable outcome, which was defined as a mRS score greater than 2 at the latest follow-up. RESULTS: Among the 293 patients, 48.5% were female, median age was (39.9±14.3) years, and median haemorrhage-to-treatment time was 42 days. Patients were categorized into acute (≤21 days), subacute (22-42 days), and delay (>42 days) intervention groups. After matching, 186 patients were analyzed. Adjusted analysis showed lower unfavourable outcome rates for acute [adjusted odds ratio (OR), 0.73; 95% CI, 0.65-0.82; P<0.001] and subacute (adjusted OR, 0.83; 95% CI, 0.72-0.95; P=0.007) groups compared to the delay group. Subacute intervention led to fewer cranial nerve deficits (adjusted OR, 0.76; 95% CI, 0.66-0.88, P<0.001). New haemorrhage incidence didn't significantly differ among groups. CONCLUSIONS: For haemorrhagic BSCMs patients, delayed microsurgical intervention that exceeded 42 days after a prior haemorrhage were associated with an increased risk of unfavourable neurological outcomes.
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Hemangioma Cavernoso del Sistema Nervioso Central , Microcirugia , Tiempo de Tratamiento , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , Hemangioma Cavernoso del Sistema Nervioso Central/cirugía , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Tiempo de Tratamiento/estadística & datos numéricos , China/epidemiología , Estudios de Cohortes , Resultado del Tratamiento , Tronco Encefálico/cirugía , Estudios RetrospectivosRESUMEN
PURPOSE: Early hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. METHODS: We prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3-6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. RESULTS: At baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84-7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01-12.50). CONCLUSION: In this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.
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Circulación Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Femenino , Masculino , Persona de Mediana Edad , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/fisiopatología , Estudios Prospectivos , Tomografía Computarizada por Rayos X/métodos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/etiología , Valor Predictivo de las Pruebas , Angiografía por Tomografía Computarizada/métodosRESUMEN
BACKGROUND: Symptomatic brainstem cavernous malformations (BSCMs) pose a high risk of morbidity and mortality due to recurrent hemorrhage, warranting aggressive management. However, few studies have compared the effectiveness of different treatment modalities for BSCMs. We aimed to assess the association of treatment modalities with recurrent hemorrhage and neurological outcomes in patients with BSCM. METHODS: We conducted a retrospective cohort study using an observational registry database covering population of southwest and southeast China. Adult patients with BSCM were included and followed up between March 1, 2011, to March 31, 2023. We compared outcomes between microsurgery and stereotactic radiosurgery (SRS) in propensity score-matched case pairs, incorporating demographic, medical history, and lesion characteristics. The outcomes studied included recurrent hemorrhage and poor prognosis (defined as a Glasgow Outcome Scale score, <4). Absolute rate differences and hazard ratios (HRs) with 95% CIs were calculated using Cox models. RESULTS: Among 736 diagnosed patients with BSCM, 96 (48 matched pairs) were included after exclusions and propensity score matching (mean age, 43.1 [SD, 12.1] years; 50% women). During the median 5-year follow-up, no significant differences in recurrent hemorrhage (4.2% [microsurgery] versus 14.6% [SRS], HR, 3.90 [95% CI, 0.46-32.65]; P=0.21) and poor prognosis (12.5% [microsurgery] versus 8.3% [SRS], HR, 0.29 [95% CI, 0.08-1.08]; P=0.07) were observed between microsurgery and SRS recipients. Furthermore, either microsurgery or SRS correlated with fewer recurrent hemorrhage (HR, 0.09 [95% CI, 0.02-0.39]; P=0.001; HR, 0.21 [95% CI, 0.07-0.69]; P=0.01) compared with conservative treatment. CONCLUSIONS: In this study, both microsurgery and SRS were safe and effective for BSCM, demonstrated comparable outcomes in recurrent hemorrhage and poor prognosis. However, interpretation should be cautious due to the potential for residual confounding. REGISTRATION: URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2300070907.
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The dynamic defect tolerance under light soaking is a crucial aspect of halide perovskites. However, the underlying physics of light soaking remains elusive and is subject to debate, exhibiting both positive and negative effects. In this investigation, we demonstrated that surface defects in perovskite films significantly impact the performance and stability of perovskite solar cells, closely correlated with light soaking behaviors. Removing the top surface layer through adhesive tape, the surface defect density noticeably decreases, leading to enhanced photoluminescence (PL) efficiency, prolonged carrier lifetime, and higher conductivity. Consequently, the power conversion efficiency (PCE) of solar cells improves from 17.70% to 20.5%. Furthermore, we confirmed a positive correlation between surface defects and the light soaking effect. Perovskite films with low surface defects surprisingly exhibit a 3-fold increase in PL intensity and an 85% increase in carrier lifetime under 500 s of continuous illumination at an intensity of 100 mW/cm2. Beyond the conventional strategy of suppressing defect trapping, we propose increasing the capability of dynamic defect tolerance as an effective strategy to enhance the optoelectronic properties and performance of perovskite solar cells.
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Metal-halide perovskite (MHP) single crystals are emerging as potential competitors to their polycrystalline thin-film counterparts. These materials have shown the specific feature of extended absorbance towards the near-infrared (NIR) region, which promises further extension of their applications in the field of photovoltaics and photodetectors. This notable expansion of absorbance has been explained by the narrower effective optical bandgap of MHP single crystals promoted by their large thickness over several micrometres to millimetres. Herein, the attributes of the material's thickness and the measurement technique used to estimate these characteristics are discussed to elucidate the actual origins of the extended absorbance of MHP single crystals. Contrary to the general belief of the narrower bandgap of the MHP single crystals, we demonstrate that the extended NIR absorption in the MHP single crystals mainly originates from the combination of unique below-bandgap absorption of MHPs, the thickness of single crystals, and the technical limitation of the spectrophotometer, with the key attributes of (i) significantly large thickness of the MHP single crystals by suppressing the transmitted light and (ii) the detector's limited dynamic range. Combining the theoretical and experimental characterizations, we clarify the significant role of the large thickness together with the limited sensitivity of the detector in promoting the well-known red shift of the absorption onset of the MHP single crystals. The observations evidently show that in some special circumstances, the acquired absorption spectrum cannot reliably represent the optical bandgap of MHP materials. This highlights some misinterpretations in the estimation of the narrower optical bandgap of the MHP single crystals from conventional optical methods, while the optical bandgap is an inherent property independent of the thickness. The proposed broad applications of the MHP single crystals are dictated by their fascinating properties, and therefore, a deep insight into these features should be considered besides device applications, because much of their property-function relationships are still ambiguous and a subject of debate.
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BACKGROUND: Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding, relieves symptoms and improve the quality of life for patients. This study aimed to assess the safety and efficacy of Pipeline Embolization Device (PED, Covidien/Medtronic, Irvine, CA) treatment for intracranial aneurysms presenting with mass effect in real-world settings. METHODS: We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation. The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up (3-36 months). We conducted multivariate analysis to identify factors associated with mass effect relief. Subgroup analyses by aneurysm location, size and form were also performed. RESULTS: This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0% (162/218). The postoperative mass effect deterioration rate was 9.6% (21/218). During a median follow-up period of 8.4 months, the mass effect relief rate was 71.6% (156/218). Notably, immediate aneurysm occlusion following treatment was significantly associated with mass effect relief (OR 0.392, 95% CI, 0.170 to 0.907, p=0.029). Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms, while dense embolism impeded symptom relief in aneurysms<10 mm and saccular aneurysms. CONCLUSIONS: Our data confirmed the efficacy of PED in relieving mass effect. The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms. TRIAL REGISTRATION NUMBER: NCT03831672.
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Embolización Terapéutica , Aneurisma Intracraneal , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Aneurisma Intracraneal/terapia , Aneurisma Intracraneal/cirugía , Estudios de Seguimiento , Resultado del Tratamiento , Calidad de Vida , Embolización Terapéutica/efectos adversosRESUMEN
Cisplatin-based chemotherapy is considered the primary treatment option for patients with advanced bladder cancer (BCa). However, the objective response rate to chemotherapy is often unsatisfactory, leading to a poor 5-year survival rate. Furthermore, current strategies for evaluating chemotherapy response and prognosis are limited and inefficient. In this study, we aimed to address these challenges by establishing a chemotherapy response type gene (CRTG) signature consisting of 9 genes and verified the prognostic value of this signature using TCGA and GEO BCa cohorts. The risk scores based on the CRTG signature were found to be associated with advanced clinicopathological status and demonstrated favorable predictive power for chemotherapy response in the TCGA cohort. Meanwhile, tumors with high risk scores exhibited a tendency toward a "cold tumor" phenotype. These tumors showed a low abundance of T cells, CD8+ T cells and cytotoxic lymphocytes, along with a high abundance of cancer-associated fibroblasts. Moreover, they displayed higher mRNA levels of these immune checkpoints: CD200, CD276, CD44, NRP1, PDCD1LG2 (PD-L2), and TNFSF9. Furthermore, we developed a nomogram that integrated the CRTG signature with clinicopathologic risk factors. This nomogram proved to be a more effective tool for predicting the prognosis of BCa patients. Additionally, we identified Rac family small GTPase 3 (RAC3) as a biomarker in our model. RAC3 was found to be overexpressed in chemoresistant BCa tissues and enhance the chemotherapeutic resistance of BCa cells in vitro and in vivo by regulating the PAK1-ERK1/2 pathway. In conclusion, our study presents a novel CRTG model for predicting chemotherapy response and prognosis in BCa. We also highlight the potential of combining chemotherapy with immunotherapy as a promising strategy for chemoresistant BCa and that RAC3 might be a latent target for therapeutic intervention.
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Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Cisplatino , Factores de Transcripción , Proteínas de Unión al GTP rac , Antígenos B7RESUMEN
Inorganic lead-free halide perovskites, devoid of toxic or rare elements, have garnered considerable attention as photocatalysts for pollution control, CO2 reduction and hydrogen production. In the extensive perovskite design space, factors like substitution or doping level profoundly impact their performance. To address this complexity, a synergistic combination of machine learning models and theoretical calculations were used to efficiently screen substitution elements that enhanced the photoactivity of substituted Cs2 AgBiBr6 perovskites. Machine learning models determined the importance of d10 orbitals, highlighting how substituent electron configuration affects electronic structure of Cs2 AgBiBr6 . Conspicuously, d10 -configured Zn2+ boosted the photoactivity of Cs2 AgBiBr6 . Experimental verification validated these model results, revealing a 13-fold increase in photocatalytic toluene conversion compared to the unsubstituted counterpart. This enhancement resulted from the small charge carrier effective mass, as well as the creation of shallow trap states, shifting the conduction band minimum, introducing electron-deficient Br, and altering the distance between the B-site cations d band centre and the halide anions p band centre, a parameter tuneable through d10 configuration substituents. This study exemplifies the application of computational modelling in photocatalyst design and elucidating structure-property relationships. It underscores the potential of synergistic integration of calculations, modelling, and experimental analysis across various applications.
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OBJECTIVE: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post-operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. RESULTS: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591-0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5-12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu1 cohort onward, receding post the Hu4 cohort. CONCLUSION: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH.
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Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Corteza InsularRESUMEN
Pyroptosis is a type of programmed cell death and plays a dual role in distinct cancers. It is elusive to evaluate the activation level of pyroptosis and to appraise the involvement of pyroptosis in the occurrence and development of diverse tumors. Accordingly, we herein established an indicator to evaluate pyroptosis related gene transcription levels based on the expression level of genes involved in pyroptosis and tried to elaborated on the association between pyroptosis and tumors across diverse tumor types. We found that pyroptosis related gene transcription levels could predict the prognosis of patients, which could act as either a favorable or a dreadful factor in diverse cancers. According to signaling pathway analyses we observed that pyroptosis played a significant role in immune regulation and tumorigenesis and had strong links with other forms of cell death. We also performed analysis on the crosstalk between pyroptosis and immune status and further investigated the predictive potential of pyroptosis level for the efficacy of immunotherapy. Lastly, we manifested that pyroptosis status could serve as a biomarker to the efficacy of chemotherapy across various cancers. In summary, this study established a quantitative indicator to evaluate pyroptosis related gene transcription levels, systematically explored the role of pyroptosis in pan-cancer. These results could provide potential research directions targeting pyroptosis, and highlighted that pyroptosis may be used to develop a novel strategy for the treatment of cancer.
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Neoplasias , Piroptosis , Humanos , Piroptosis/genética , Neoplasias/genética , Carcinogénesis , Muerte Celular , Transcripción Genética , Microambiente TumoralRESUMEN
BACKGROUND: This study aimed to compare the risk and benefit profile of microsurgery (MS) and stereotactic radiosurgery (SRS) as the first-line treatment for unruptured and ruptured arteriovenous malformations (AVMs). MATERIALS AND METHODS: The authors included AVMs underwent MS or SRS as the first-line treatment from a nationwide prospective multicenter registry in mainland China. The authors used propensity score-matched methods to balance baseline characteristics between the MS and SRS groups. The primary outcomes were long-term hemorrhagic stroke or death, and the secondary outcomes were long-term obliteration and neurological outcomes. Subgroup analyses and sensitivity analyses with different study designs were performed to confirm the stability of our findings. RESULTS: Of the 4286 consecutive AVMs in the registry from August 2011 to December 2021; 1604 patients were eligible. After matching, 244 unruptured and 442 ruptured AVMs remained for the final analysis. The mean follow-up duration was 7.0 years in the unruptured group and 6.1 years in the ruptured group. In the comparison of primary outcomes, SRS was associated with a higher risk of hemorrhagic stroke or death both in the unruptured and ruptured AVMs (unruptured: hazard ratio 4.06, 95% CI: 1.15-14.41; ruptured: hazard ratio 4.19, 95% CI: 1.58-11.15). In terms of the secondary outcomes, SRS was also observed to have a significant disadvantage in long-term obliteration [unruptured: odds ratio (OR) 0.01, 95% CI: 0.00-0.04; ruptured: OR 0.09, 95% CI: 0.05-0.15]. However, it should be noted that SRS may have advantages in preventing neurofunctional decline (unruptured: OR 0.56, 95% CI: 0.27-1.14; ruptured: OR 0.41, 95% CI: 0.23-0.76). The results of subgroup analyses and sensitivity analyses were consistent in trend but with slightly varied powers. CONCLUSIONS: This clinical practice-based real-world study comprehensively compared MS and SRS for AVMs with long-term outcomes. MS is more effective in preventing future hemorrhage or death and achieving obliteration, while the risk of neurofunctional decline should not be ignored.
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Accidente Cerebrovascular Hemorrágico , Malformaciones Arteriovenosas Intracraneales , Radiocirugia , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Malformaciones Arteriovenosas Intracraneales/cirugía , Malformaciones Arteriovenosas Intracraneales/complicaciones , Microcirugia/efectos adversos , Radiocirugia/efectos adversos , Radiocirugia/métodos , Accidente Cerebrovascular Hemorrágico/complicaciones , Accidente Cerebrovascular Hemorrágico/cirugía , Puntaje de Propensión , Datos de Salud Recolectados Rutinariamente , Estudios de SeguimientoRESUMEN
Purpose: Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients. Patients and Methods: We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis. Results: A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568-0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148-1.615]; P<0.001), pneumonia (OR [95% CI] 1.427 [1.227-1.659]; P<0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124-1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT. Conclusion: In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.
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Brain arteriovenous malformations (AVMs) with a diffuse nidus structure present a therapeutic challenge due to their complexity and elevated risk of hemorrhagic events. This study examines the long-term effectiveness of interventional therapy versus conservative management in reducing hemorrhagic stroke or death in patients with ruptured diffuse AVMs. The analysis was conducted based on a multi-institutional database in China. Patients were divided into two groups: conservative management and interventional therapy. Using propensity score matching, patients were compared for the primary outcome of hemorrhagic stroke or death and the secondary outcomes of disability and neurofunctional decline. Out of 4286 consecutive AVMs in the registry, 901 patients were eligible. After matching, 70 pairs of patients remained with a median follow-up of 4.0 years. The conservative management group showed a trend toward higher rates of the primary outcome compared to the interventional group (4.15 vs. 1.87 per 100 patient-years, P = 0.090). While not statistically significant, intervention reduced the risk of hemorrhagic stroke or death by 55% (HR, 0.45 [95% CI 0.18-1.14], P = 0.094). No significant differences were observed in secondary outcomes of disability (OR, 0.89 [95% CI 0.35-2.26], P = 0.813) and neurofunctional decline (OR, 0.65 [95% CI 0.26 -1.63], P = 0.355). Subgroup analysis revealed particular benefits in interventional therapy for AVMs with a supplemented S-M grade of II-VI (HR, 0.10 [95% CI 0.01-0.79], P = 0.029). This study suggests a trend toward lower long-term hemorrhagic risks with intervention when compared to conservative management in ruptured diffuse AVMs, especially within supplemented S-M grade II-VI subgroups. No evidence indicated that interventional approaches worsen neurofunctional outcomes.
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Lead mixed-halide perovskites offer tunable bandgaps for optoelectronic applications, but illumination-induced phase segregation can quickly lead to changes in their crystal structure, bandgaps, and optoelectronic properties, especially for the Br-I mixed system because CsPbI3 tends to form a non-perovskite phase under ambient conditions. These behaviors can impact their performance in practical applications. By embedding such mixed-halide perovskites in a glassy metal-organic framework, a family of stable nanocomposites with tunable emission is created. Combining cathodoluminescence with elemental mapping under a transmission electron microscope, this research identifies a direct relationship between the halide composition and emission energy at the nanoscale. The composite effectively inhibits halide ion migration, and consequently, phase segregation even under high-energy illumination. The detailed mechanism, studied using a combination of spectroscopic characterizations and theoretical modeling, shows that the interfacial binding, instead of the nanoconfinement effect, is the main contributor to the inhibition of phase segregation. These findings pave the way to suppress the phase segregation in mixed-halide perovskites toward stable and high-performance optoelectronics.
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BACKGROUND: The aim of this study was to construct a clinically practical model to precisely predict lymph node (LN) metastasis in bladder cancer patients. METHODS: Four independent cohorts were included. The least absolute shrinkage and selection operator regression with multivariate logistic regression were applied. The diagnostic efficacy of LN score and CT/MRI was compared by accuracy, sensitivity, specificity, and area under curve (AUC). RESULTS: A total of 606 patients were included to develop a basic prediction model. After multistep gene selection, the LN metastasis prediction model was constructed with 5 genes. The model can accurately predict LN metastasis with an AUC of 0.781. For clinically practical use, we transformed the model into a Fast LN Scoring System using the SYSMH cohort (n = 105). High LN score patients exhibited a 72.2% LN metastasis rate, while low LN score patients showed a 3.4% LN metastasis rate. The LN score achieved a superior accuracy than CT/MRI (0.882 vs. 0.727). Application of LN score can correct the diagnosis of 88% (22/25) patients who were misdiagnosed by CT/MRI. DISCUSSION: The clinically practical LN score can precisely, rapidly, and conveniently predict LN status, which will assist preoperative diagnosis for LN metastasis and guide precise therapy.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Metástasis Linfática , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Modelos Logísticos , Ganglios Linfáticos/patologíaRESUMEN
Vertical gradient band-gap heterostructures of two-dimensional (2D) layered perovskites have attracted considerable research interest due to their superior optoelectronic properties and demonstrated potential for use in optical devices. However, its fabrication has been challenging. In this investigation, 2D Ruddlesden-Popper mixed halide perovskite single crystals with a vertical gradient band gap were synthesized by using a solid-state halide diffusion process. X-ray diffraction (XRD) and scanning electron microscopy (SEM) measurements after diffusion confirm that the crystalline and morphology remain intact. The transmittance and photoluminescence (PL) spectra show the formation of a vertical gradient band gap that is ascribed to gradient halide distribution through halide intermixing. The mixed halide crystal exhibits high stability with completely suppressed phase segregation in the time-dependent PL measurement. The time-resolved photoluminescence (TRPL) spectra prove that the mixed halide sample has an enhanced carrier transport due to the Förster resonance energy transfer (FRET) effect. Besides, the halide diffusion behavior is found to be different from the previously proposed "layer-by-layer" diffusion model in exfoliated crystals. The gradient band-gap structure is critical for various applications in which vertical carrier transport is demanded.