RESUMEN
Neural network (NN)-based equalizers have been widely applied for dealing with nonlinear impairments in intensity-modulated direct detection (IM/DD) systems due to their excellent performance. However, the computational complexity (CC) is a major concern that limits the real-time application of NN-based receivers. In this Letter, we propose, to our knowledge, a novel weight-adaptive joint mixed-precision quantization and pruning approach to reduce the CC of NN-based equalizers, where only integer arithmetic is taken into account instead of floating-point operations. The NN connections are either directly cutoff or represented by a proper number of quantization bits by weight partitioning, leading to a hybrid compressed sparse network that computes much faster and consumes less hardware resources. The proposed approach is verified in a 50-Gb/s 25-km pulse amplitude modulation (PAM)-4 IM/DD link using a directly modulated laser (DML) in the C-band. Compared with the traditional fully connected NN-based equalizer operated with standard floating-point arithmetic, about 80% memory can be saved at a minimum network size without degrading the system performance. Quantization is also shown to be more suitable to over-parameterized NN-based equalizers compared with NNs selected at a minimum size.
RESUMEN
OBJECTIVE: To investigate the external validation and scalability of four predictive models regarding new vertebral fractures following percutaneous vertebroplasty. METHODS: Utilizing retrospective data acquired from two centers, compute the area under the curve (AUC), calibration curve, and Kaplan-Meier plot to assess the model's discrimination and calibration. RESULTS: In the external validation of Zhong et al.'s 2015 predictive model for the probability of new fractures post-vertebroplasty, the AUC for re-fracture at 1, 2, and 3 years postoperatively was 0.570, 0.617, and 0.664, respectively. The AUC for Zhong et al.'s 2016 predictive model for the probability of new fractures in neighboring vertebrae was 0.738. Kaplan-Meier plot results for both models indicated a significantly lower incidence of re-fracture in low-risk patients compared to high-risk patients. Li et al.'s 2021 model had an AUC of 0.518, and its calibration curve suggested an overestimation of the probability of new fractures. Li et al.'s 2022 model had an AUC of 0.556, and its calibration curve suggested an underestimation of the probability of new fractures. CONCLUSION: The external validation of four models demonstrated that the predictive model proposed by Zhong et al. in 2016 exhibited superior external generalization capabilities.
RESUMEN
Histone deacetylases (HDACs) contribute significantly to the initiation, progression, and prognosis of colorectal adenocarcinoma (COAD). Additionally, HDACs regulate the tumor microenvironment, immune escape, and tumor stem cells, and are closely linked to COAD prognosis. We developed a prognostic model for COAD that incorporates HDACs to evaluate their specific roles. The COAD dataset containing clinical and mutation data was collected using the TCGA and GEO databases to obtain genes associated with HDAC. LASSO analysis and univariate and multivariate Cox regression analysis were used to determine the presence of prognostic genes. Multivariate Cox analysis was also used to determine risk scores for HDAC-related features. Furthermore, genomic alterations, immune infiltration, and drug response were compared between high- and low-risk groups. Cellular experiments validated the potential regulatory role of BRD3 on COAD proliferation, migration, and apoptosis. The median risk scores, calculated based on the characteristics, demonstrated a more significant prognostic improvement in patients in the low-risk group. Furthermore, HDAC-related features were identified as important independent prognostic factors for patients with COAD. Additionally, genomic mutation status, immune infiltration, and function, as well as response to immunotherapy and chemotherapy, were found to be associated with risk scores. Subgroup analyses indicate that anti-PD-1 therapy may be beneficial for patients in the low-risk group. Additionally, a decrease in risk score was associated with a decrease in immune infiltration. Finally, HCT116 and HT29 cells exhibited inhibition of BRD3 gene proliferation and migration, as well as promotion of apoptosis. In patients with COAD, HDAC-related characteristics may be useful in predicting survival and selecting treatment.
Asunto(s)
Adenocarcinoma , Neoplasias del Colon , Neoplasias Colorrectales , Humanos , Pronóstico , Neoplasias del Colon/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Genes Reguladores , Histona Desacetilasas/genética , Microambiente Tumoral/genéticaRESUMEN
Background: Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. Methods: The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. Results: A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Conclusion: Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop risk-adapted therapy for RPLS patients.
RESUMEN
Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.
Asunto(s)
Hemangiosarcoma , Sarcoma , Neoplasias de los Tejidos Blandos , Humanos , Proteómica , Sarcoma/metabolismo , Biomarcadores , Análisis por Conglomerados , Neoplasias de los Tejidos Blandos/genética , Neoplasias de los Tejidos Blandos/patología , Microambiente TumoralRESUMEN
In this Letter, the impact of non-Gaussian noise caused by a nonlinear equalizer on low-density parity-check code (LDPC) performance is investigated in a 25-km 50-Gb/s pulse amplitude modulation4 (PAM4) direct detection system. The lookup table (LUT)-based log-likelihood ratio (LLR) calculation method is proposed to enhance the LDPC performance for the non-Gaussian noise case. Compared to the conventional LLR calculation method based on Gaussian distribution, the proposed method can improve 0.6-dB sensitivity in artificial neural network (ANN) equalizer systems. In addition, the conventional generalized mutual information (GMI) is proven to be an imperfect predictor of LDPC performance after nonlinear equalizers, such as decision feedback equalization (DFE) and ANN equalizer.
RESUMEN
The phase noise-induced interference (PNII) in coherently detected OTDR systems is investigated. A close-form relationship between signal to (interference) noise ratio (SNR) and laser linewidth is derived for the first time, to the best of our knowledge, and numerical simulations are conducted to verify the theoretical results. Additionally, the proportion of noise composition of PNII is studied. It is shown that the amplitude noise accounts for one-third of the total interference. This analytical form of PNII will assist in understanding the COTDR system that utilizes the full field of information (rather than intensity alone) at the receiver and, more importantly, provides a crucial guideline for designing high-performance and cost-effective COTDR systems in various applications.
RESUMEN
BACKGROUND: To assess the correlation between clinical outcomes and diagnostic accuracy of evaluations carried out by a preoperative multidisciplinary team versus standard surgical care for patients with retroperitoneal liposarcoma undergoing surgery. METHODS: This comparative study was conducted retrospectively at a specialist assessment center within Zhongshan Hospital, Fudan University, China, between April 2011 and March 2021. Patients were assigned to a multidisciplinary team or nonmultidisciplinary team cohort based on referral to the multidisciplinary team. The primary outcome measured was long-term clinical prognosis, with other outcomes including diagnostic accuracy, 30-day reoperation, duration of stay, perioperative mortality, and medical complications. To mitigate selection bias, we conducted propensity-score matching. Uni- and multivariable Cox proportional hazard models were then used to evaluate the effect of multidisciplinary teams on postoperative survival. The previously specified questionnaire was used to measure the enhancement of awareness and treatment adherence facilitated by multidisciplinary team management. Data analysis was carried out between January 2023 and August 2023. RESULTS: Of the 521 records that were screened, 139 patients were deemed eligible for inclusion and defined as the multidisciplinary team cohort. At the same time, 382 patients without multidisciplinary team management were also included during that period and defined as the nonmultidisciplinary team cohort. The multidisciplinary team cohort exhibited lower numbers of primary retroperitoneal liposarcoma but a higher tumor grade and a greater proportion of R2 resection. After propensity-score matching, the 1-, 3-, and 5-year overall survival rates were 89.5%, 70.5%, and 62.9%, respectively, in the multidisciplinary team cohort, and 77.1%, 49.8%, and 45.1% in the nonmultidisciplinary team cohort. The diagnostic consistency of the multidisciplinary team group was significantly superior to that of the nonmultidisciplinary cohort (92.5% vs 83.6%, P = .042). Although no significant links were shown with duration of stay (P = .232) and 30-day reoperation (P = .447), the multidisciplinary team participation was linked to a substantial decrease in perioperative mortality (P = .036) and postoperative complications (P = .002). Additionally, the multidisciplinary team group indicated stronger illness awareness and postoperative adherence among individuals with retroperitoneal liposarcoma. CONCLUSION: The study's findings indicate that multidisciplinary team management could result in improved clinical outcomes, higher diagnostic accuracy, and reduced duration of postoperative stays, complications, and perioperative mortality. The intervention may also enhance disease awareness and postoperative compliance in retroperitoneal liposarcoma patients who undergo surgery. However, evidence quality was deemed low, and prospective studies with robust designs are required. Nonetheless, these results are worth considering.
Asunto(s)
Liposarcoma , Neoplasias Retroperitoneales , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Liposarcoma/diagnóstico , Liposarcoma/cirugía , Neoplasias Retroperitoneales/cirugíaRESUMEN
Typical sources of nitrate pollution in the fragile ecological environment of karst areas, such as agricultural production activities and domestic sewage, have long attracted serious concern. However, coal development can play an equally significant role in releasing the nitrogen fixed in coal into surface watersheds in the form of nitrate, nitrite, or ammonia, consequently threatening the water quality of surface water systems in mining areas. In this study, a typical karst surface watershed system affected by coal mining activities was selected for an in-depth investigation with the aim of realistically assessing the potential contribution of coal mining to nitrogen pollution. The results reveal increasingly concerning nitrate pollution from August 2020 to November 2021 in the Huatan River watershed under the influence of anthropogenic activities, especially mining development and agricultural production. Given that the nitrogen and oxygen isotope compositions of nitrate do not support the presence of denitrification, the variation in the NO3-/Cl- ratio and the relatively stable Cl- concentration may be a reflection of nitrification. Although the leaching of atmospheric precipitation on the strata in the basin promoted the release of nitrogen associated with coal mining, the higher rate of nitrogen cycling in the oligotrophic mine water environment limited the contribution of coal mining to nitrogen pollution in the surface watershed. Specifically, the contribution of coal mining activities to nitrogen pollution in surface karst river is mainly NH4+-N, which contributes 10% or less to the nitrate input to the waters of the Huatan River. The findings thus highlight the necessity of further uncovering the geochemical cycling process of nitrogen during the transport of mine water in the coal mining environment.
Asunto(s)
Minas de Carbón , Agua Subterránea , Contaminantes Químicos del Agua , Nitratos/análisis , Monitoreo del Ambiente/métodos , Ríos/química , Nitrógeno/análisis , Carbón Mineral , China , Contaminantes Químicos del Agua/análisis , Isótopos de Nitrógeno/análisis , Agua Subterránea/químicaRESUMEN
Shelling with chalcogenides on the surface of lead halide perovskite (LHP) nanocrystals (NCs) is believed to be an effective approach to increase their stability under high-moisture/aqueous conditions, which is important for LHP NC-based optoelectronic devices. However, it is still a challenge to prepare high-quality LHP/chalcogenide core/shell NCs with moisture/aqueous stability. In this work, a surface-defect-induced strategy is carried out to facilitate the adsorption of Br- ions and subsequently Zn2+ ions to preform a bipolar surface, which reduces the energy barrier at the CsPbBr3/ZnS interface and promotes the epitaxial growth of the ZnS shell layer. The aqueous stability of the as-received NCs shows an increase of over 12 times compared to that of the original one. Likewise, Mn2+ ions are introduced to further reduce the geometric symmetry mismatch and defect density at the CsPbBr3/ZnS interface. Interestingly, aqueous stability characterizations illustrate negligible degradation even after 230 min of ultrasonication, suggesting their outstanding stability. This work proposes an effective approach to prepare high-quality LHP/chalcogenide core/shell NCs, which possess great potential in the fabrication of stable optoelectronic devices.
RESUMEN
BACKGROUND: Primary retroperitoneal sarcoma (RPS) comprises over 70 histologic subtypes, yet there are limited studies that have developed prognostic nomograms for RPS patients to predict overall survival (OS) and cancer-specific survival (CSS). The objective of this study was to construct prognostic nomograms for predicting OS and CSS in RPS patients. METHODS: We identified a total of 1166 RPS patients from the Surveillance, Epidemiology and End Results (SEER) database, and an additional 261 cases were collected from a tertiary cancer center. The study incorporated various clinicopathological and epidemiologic features as variables, and prediction windows for overall survival (OS) and cancer-specific survival (CSS) were set at 3, 5, and 7 years. Multivariable Cox models were utilized to develop the nomograms, and variable selection was performed using a backward procedure based on the Akaike Information Criterion. To evaluate the performance of the nomograms in terms of calibration and discrimination, we used calibration plots, coherence index, and area under the curve. FINDINGS: The study included 818 patients in the development cohort, 348 patients in the internal validation cohort, and 261 patients in the external validation cohort. The backward procedure selected the following variables: age, French Federation of Cancer Centers Sarcoma Group (FNCLCC) grade, pre-/postoperative chemotherapy, tumor size, primary site surgery, and tumor multifocality. The validation results demonstrated that the nomograms had good calibration and discrimination, with C-indices of 0.76 for OS and 0.81 for CSS. Calibration plots also showed good consistency between the predicted and actual survival rates. Furthermore, the areas under the time-dependent receiver operating characteristic curves for the 3-, 5-, and 7-year OS (0.84, 0.82, and 0.78, respectively) and CSS (0.88, 0.88, and 0.85, respectively) confirmed the accuracy of the nomograms. INTERPRETATION: Our study developed accurate nomograms to predict OS and CSS in patients with RPS. These nomograms have important clinical implications and can assist healthcare providers in making informed decisions regarding patient care and treatment options. They may also aid in patient counseling and stratification in clinical trials.
RESUMEN
INTRODUCTION: Magnolol is beneficial against inflammation-mediated damage. However, the underlying mechanisms by which m+agnolol exerts anti-inflammatory effects on macrophages remain unclear. OBJECTIVE: In this study, network pharmacology and experimental validation were used to assess the effect of magnolol on inflammation caused by lipopolysaccharide (LPS) in RAW264.7 cells. MATERIALS AND METHODS: Genes related to magnolol were identified in the PubChem and Swiss Target Prediction databases, and gene information about macrophage polarization was retrieved from the GeneCards, OMIM, and PharmGKB databases. Analysis of protein-protein interactions was performed with STRING, and Cytoscape was used to construct a component-target-disease network. GO and KEGG enrichment analyses were performed to ascertain significant molecular biological processes and signaling pathways. LPS was used to construct the inflammatory cell model. ELISA and qRTâPCR were used to examine the expression levels of inflammationassociated factors, immunofluorescence was used to examine macrophage markers (CD86 and CD206), and western blotting was used to examine protein expression levels. RESULTS: The hub target genes of magnolol that act on macrophage polarization were MDM2, MMP9, IL-6, TNF, EGFR, AKT1, and ERBB2. The experimental validation results showed that magnolol treatment decreased the levels of proinflammatory factors (TNF-α, IL-1ß, and IL-6). Moreover, the levels of anti-inflammatory factors (IL-10 and IL-4) were increased. In addition, magnolol upregulated the expression of M2 markers (Agr-1, Fizzl, and CD206) and downregulated M1 markers (CD86). The cell experiment results supported the network pharmacological results and demonstrated that magnolol alleviated inflammation by modulating the PI3k-Akt and P62/keap1/Nrf2 signaling pathways. CONCLUSION: According to network pharmacology and experimental validation, magnolol attenuated inflammation in LPS-induced RAW264.7 cells mainly by inhibiting M1 polarization and enhancing M2 polarization by activating the PI3K/Akt and P62/keap1/Nrf2 signaling pathways.
RESUMEN
Abnormal B cell differentiation plays a critical role in IgG4-related disease (IgG4-RD), but the underlying mechanism remains largely unknown. We investigated the cell landscape from three IgG4-RD retroperitoneal tissues and three control tissues using single-cell RNA-sequencing. Critical cell type or markers were further validated in the peripheral blood from the patients with IgG4-RD and healthy controls via flow cytometry as well as in the IgG4-RD and control tissue via immunofluorescence staining. The increases in B cells, plasma cells, and CD4+ T cells were found in IgG4-RD retroperitoneal tissue. Importantly, among CD4+ T cells, an increase in CD4+CXCR5-PD1hi peripheral T helper (Tph) cells with a high expression of IL-21 and TIGIT was discovered in IgG4-RD tissue, which was further validated in peripheral blood of the patients with IgG4-RD. The Tph cell and TIGIT+ Tph cell proportion were remarkably higher in active IgG4-RD patients and correlated with disease activity. Moreover, TIGIT+CD4+ cells were able to promote B cell differentiation via IL-21. Our study revealed that Tph cells are increased in IgG4-RD and probably play critical roles in B cell differentiation through TIGIT-IL-21 axis. Peripheral Tph cell and TIGIT+Tph cell are potential markers for IgG4-RD disease activity.
Asunto(s)
Enfermedad Relacionada con Inmunoglobulina G4 , Humanos , Enfermedad Relacionada con Inmunoglobulina G4/genética , Linfocitos T Colaboradores-Inductores , Diferenciación Celular , Linfocitos T CD4-Positivos , ARNRESUMEN
Background: Surgery is the best way to cure the retroperitoneal leiomyosarcoma (RLMS), and there is currently no prediction model on RLMS after surgical resection. The objective of this study was to develop a nomogram to predict the overall survival (OS) of patients with RLMS after surgical resection. Methods: Patients who underwent surgical resection from September 2010 to December 2020 were included. The nomogram was constructed based on the COX regression model, and the discrimination was assessed using the concordance index. The predicted OS and actual OS were evaluated with the assistance of calibration plots. Results: 118 patients were included. The median OS for all patients was 47.8 (95% confidence interval (CI), 35.9-59.7) months. Most tumor were completely resected (n=106, 89.8%). The proportions of French National Federation of Comprehensive Cancer Centres (FNCLCC) classification were equal as grade 1, grade 2, and grade 3 (31.4%, 30.5%, and 38.1%, respectively). The tumor diameter of 73.7% (n=85) patients was greater than 5 cm, the lesions of 23.7% (n=28) were multifocal, and 55.1% (n=65) patients had more than one organ resected. The OS nomogram was constructed based on the number of resected organs, tumor diameter, FNCLCC grade, and multifocal lesions. The concordance index of the nomogram was 0.779 (95% CI, 0.659-0.898), the predicted OS and actual OS were in good fitness in calibration curves. Conclusion: The nomogram prediction model established in this study is helpful for postoperative consultation and the selection of patients for clinical trial enrollment.
Asunto(s)
Leiomiosarcoma , Nomogramas , Humanos , Leiomiosarcoma/cirugía , Pronóstico , Estadificación de Neoplasias , Estimación de Kaplan-MeierRESUMEN
Recently, the polarization effect has been receiving tremendous attention, as it can result in improved stability and charge transfer efficiency of metal-halide perovskites (MHPs). However, realizing the polarization effect on CsPbX3 NCs still remains a challenge. Here, metal ions with small radii (such as Mg2+, Li+, Ni2+, etc.) are introduced on the surface of CsPbX3 NCs, which facilitate the arising of electric dipole and surface polarization. The surface polarization effect promotes redistribution of the surface electron density, leading to reinforced surface ligand bonding, reduced surface defects, near unity photoluminescence quantum yields (PLQYs), and enhanced stability. Moreover, further introduction of hydroiodic acid results in the in situ formation of tert-butyl iodide (TBI), which facilitates the successful synthesis of pure iodine-based CsPbI3 NCs with high PLQY (95.3%) and stability under ambient conditions. The results of this work provide sufficient evidence to exhibit the crucial role of the surface polarization effect, which promotes the synthesis of high-quality MHPs and their applications in the fields of optoelectronic devices.
RESUMEN
BACKGROUND: The impact of sarcopenia on the outcome of patients with left-sided colon and rectal cancer has not been exhaustively investigated. Thus, the present study was performed to evaluate the effect of sarcopenia on the outcome of patients with left-sided colon and rectal cancer. METHODS: Patients with pathologically diagnosed stage I, II and III left-sided colon or rectal cancer who had undergone curative surgery between January 2008 and December 2014 were retrospectively reviewed. The psoas muscle index (PMI) identified by 3D-image analysis of computed tomographic images was the criterion used to diagnose sarcopenia. The cut-off value recommended by Hamaguchi (PMI value < 6.36 cm2/m2 for men and < 3.92 cm2/m2 for women) was adopted to confirm the diagnosis of sarcopenia. According to the PMI, each patient was divided into the sarcopenia group (SG) or the nonsarcopenia group (NSG). Then, the SG was compared with the NSG in terms of postoperative outcomes. RESULTS: Among the 939 patients included, 574 (61.1%) were confirmed to have preoperative sarcopenia. Initially, it was demonstrated that the SG was not significantly different from the NSG in terms of most baseline characteristics except for a lower body mass index (BMI) (P < 0.001), a larger tumour size (P < 0.001) and more weight loss (more than 3 kg in the last three months) (P = 0.033). The SG had a longer hospital stay after surgery (P = 0.040), more intraoperative blood transfusions (P = 0.035), and higher incidence of anastomotic fistula (P = 0.027), surgical site infection (SSI) (P = 0.037) and hypoalbuminemia (P = 0.022), 30-day mortality (P = 0.042) and 90-day mortality (P = 0.041). The SG had significantly worse overall survival (OS) (P = 0.016) and recurrence-free survival (RFS) (P = 0.036) than the NSG. Subsequently, Cox regression analysis revealed that preoperative sarcopenia was an independent predictive factor for worse OS (P = 0.0211, HR = 1.367, 95% CI: 1.049-1.782) and RFS (P = 0.045, HR = 1.299, 95% CI: 1.006-1.677). CONCLUSION: Preoperative sarcopenia adversely affects the outcome of patients with left-sided colon and rectal cancer, and preoperative nutrition supplementation may help us improve their long-term and short-term outcomes.
Asunto(s)
Neoplasias del Recto , Sarcopenia , Masculino , Humanos , Femenino , Estudios Retrospectivos , Sarcopenia/complicaciones , Sarcopenia/diagnóstico , Neoplasias del Recto/complicaciones , Neoplasias del Recto/cirugía , Anastomosis Quirúrgica , ColonRESUMEN
Dissolved inorganic carbon (DIC) in mine water generated during coal mining is a large and potential source of atmospheric CO2, however its geochemical behaviors under the influence of AMD in relation to CO2 degassing and carbonate buffering are not well known. In this study, water temperature, pH, DO, alkalinity, Ca2+ concentration, and the carbon isotope of DIC were measured monthly from November 2020 to November 2021 and carbonate chemistry and CO2 emission flux were calculated to reveal the processes of DIC evolution and CO2 degassing from the Chetian River draining a karst region, which is materially affected by the input of large quantities of AMD. The results showed that carbonate erosion, the mineralization of terrestrial organic matter, and domestic sewage input are all identified to contribute DIC to different degrees to the river. Throughout the year, the Chetian River undergoes high-intensity CO2 degassing, which is dominated by HCO3--neutralized degassing and proton-enhanced degassing in different reaches. The pCO2 in the river under the influence of AMD is as high as 237,482 µatm, while the F-CO2 approaches 316.9 g C m-2 d-1. Meanwhile, the carbonate system in the downstream karst river buffers an average of 85.2 % of DIC release at the river's outlet. The input of AMD significantly altered the carbon cycle of the surface watershed in the headwaters of tributaries, and greatly enhanced the release of CO2 from surface water to the atmosphere; meanwhile, the buffering of carbonates on acidity in the water of main streams causes pCO2 to rapidly reduce over a short distance. Obviously, the carbon emission effect generated by the interaction between AMD and carbonate mainly occurs in the tributary water system. Considering the huge amount of AMD worldwide, this large potential source of atmospheric CO2 requires a specific and precise quantitative analysis based on actual observations.
RESUMEN
Introduction: The exploration of lipid metabolism dysregulation may provide novel perspectives for retroperitoneal liposarcoma (RPLS). In our study, we aimed to investigate potential targets and facilitate further understanding of immune landscape in RPLS, through lipid metabolism-associated genes (LMAGs) based prognostic model. Methods: Gene expression profiles and corresponding clinical information of 234 cases were enrolled from two public databases and the largest retroperitoneal tumor research center of East China, including cohort-TCGA (n=58), cohort-GSE30929 (n=92), cohort-FD (n=50), cohort-scRNA-seq (n=4) and cohort-validation (n=30). Consensus clustering analysis was performed to identify lipid metabolism-associated molecular subtypes (LMSs). A prognostic risk model containing 13 LMAGs was established using LASSO algorithm and multivariate Cox analysis in cohort-TCGA. ESTIMATE, CIBERSORT, XCELL and MCP analyses were performed to visualize the immune landscape. WGCNA was used to identify three hub genes among the 13 model LMAGs, and preliminarily validated in both cohort-GSE30929 and cohort-FD. Moreover, TIMER was used to visualize the correlation between antigen-presenting cells and potential targets. Finally, single-cell RNA-sequencing (scRNA-seq) analysis of four RPLS and multiplexed immunohistochemistry (mIHC) were performed in cohort-validation to validate the discoveries of bioinformatics analysis. Results: LMS1 and LMS2 were characterized as immune-infiltrated and -excluded tumors, with significant differences in molecular features and clinical prognosis, respectively. Elongation of very long chain fatty acids protein 2 (ELOVL2), the enzyme that catalyzed the elongation of long chain fatty acids, involved in the maintenance of lipid metabolism and cellular homeostasis in normal cells, was identified and negatively correlated with antigen-presenting cells and identified as a potential target in RPLS. Furthermore, ELOVL2 was enriched in LMS2 with significantly lower immunoscore and unfavorable prognosis. Finally, a high-resolution dissection through scRNA-seq was performed in four RPLS, revealing the entire tumor ecosystem and validated previous findings. Discussion: The LMS subgroups and risk model based on LMAGs proposed in our study were both promising prognostic classifications for RPLS. ELOVL2 is a potential target linking lipid metabolism to immune regulations against RPLS, specifically for patients with LMS2 tumors.
Asunto(s)
Neoplasias Retroperitoneales , Humanos , Neoplasias Retroperitoneales/genética , Ecosistema , Metabolismo de los Lípidos , Pronóstico , Ácidos GrasosRESUMEN
Spontaneous deamidation of asparaginyl residues in proteins, if not repaired or cleared, can set in motion a cascade that leads to deteriorated health. Previously, we have discovered that deamidated human serum albumin (HSA) is elevated in the blood of patients with Alzheimer's disease and other neurodegenerative diseases, while the level of endogenous antibodies against deamidated HSA is significantly diminished, creating an imbalance between the risk factor and the defense against it. Endogenous antibodies against deamidated proteins are still unexplored. In the current study, we employed the SpotLight proteomics approach to identify novel amino acid sequences in antibodies specific to deamidated HSA. The results provide new insights into the clearance mechanism of deamidated proteins, a possible avenue for prevention of neurodegeneration.
Asunto(s)
Proteómica , Albúmina Sérica Humana , Humanos , Proteómica/métodos , Proteínas , Secuencia de Aminoácidos , AnticuerposRESUMEN
Background: Although surgery plays a key role in the treatment of the primary retroperitoneal sarcoma (RPS), there remain few reports on the primary multifocal RPS. Aims: This study aimed to identify the prognostic factors for the primary multifocal RPS in an effort to optimize the clinical management of this malignancy. Methods: A retrospective analysis was conducted on a cohort of 319 primary RPS patients who underwent radical resection from 2009 to 2021, with post-operative recurrence as the primary endpoint of this study. COX regression was performed to identify the risk factors for post-operative recurrence, and a comparison was made to baseline and prognostic differences between multivisceral resection (MVR) and non-MVR groups with multifocal disease. Results: There were 31 (9.7%) patients with multifocal disease, the mean tumor burden placed on them was 24.1 ± 11.9 cm, and nearly half of the patients (48.4%) had MVR. Dedifferentiated liposarcoma, well-differentiated liposarcoma, and leiomyosarcoma accounted for 38.7%, 32.3%, and 16.1%, respectively. The 5-year recurrence-free survival rate reached 31.2% (95% CI, 11.2-51.2%) in the multifocal group and 51.8% (95% CI, 44.2-59.4%) in the unifocal group (P = 0.010). Age (heart rate [HR] = 0.916; P = 0.039) and complete resection (HR = 1.861; P = 0.043) were identified as the independent risk factors for the post-operative recurrence of multifocal primary RPS. Conclusions: Regarding primary multifocal RPS, the overall treatment strategy can be adopted for the treatment of the primary RPS, and MVR remains effective in boosting the chance of disease control for a selected group of patients. Relevance for Patients: This study is relevant to patients as it highlights the importance of receiving appropriate treatment for the primary RPS, especially for those with multifocal disease. The treatment options should be evaluated carefully to ensure that the patients receive the most effective treatment for their specific type and stage of RPS. The potential risk factors for post-operative recurrence should be well understood to minimize those risks. Ultimately, this study underscores the importance of ongoing research to optimize the clinical management of RPS and improve outcomes for patients.