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To address the environmental hazards of electrolytic manganese residue (EMR) accumulation and the urgent need for ecological restoration in mining areas, we developed an innovative method for creating pit restoration materials (S-EMRs) using alkaline-excited EMR via mechanical ball milling. Black liquid (BL) was used as a base exciter and EMR as the precursor. With a BL dosage of 35 %, alumina as the milling medium, a speed of 500 rpm, and milling for 20-35 min, we achieved an S-EMR compressive strength of approximately 30 MPa after 14 d-six times higher than that in conventional cement curing (C-EMR). This method also stabilized contaminants such as Mn and NH 4 + by over 10-fold. The self-cementation and formation mechanisms of the S-EMR were clarified through chemical characterization and geochemical modeling. Over 3 y of monitoring and plant experiments have shown that S-EMR ensured the long-term stability and ecological restoration of mining areas. Remarkably, it enhanced microbial diversity and biophilicity, improving tomato seed germination by over 90 % compared with that in control. This study presents a sustainable and innovative solution for the green cycle rehabilitation of Mn mining areas with significant potential for engineering applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Treatment of lung cancer leptomeningeal carcinomatosis (LM) remains challenging partly due to the biological nature of the blood-brain barrier (BBB). Cisplatin has limited effects on LM, and it is notorious for neurotoxicity. Aptamers are small oligonucleotides considered as antibody surrogates. Here we report a DNA therapeutics, AptBCis1. AptBCis1 is a cisplatin-conjugated, BBB-penetrating, and cancer-targeting DNA aptamer. Its backbone, AptB1, was identified via in vivo SELEX using lung cancer LM orthotopic mouse models. The AptB1 binds to EAAT2, Nucleolin, and YB-1 proteins. Treatment with AptBCis1 1 mg/kg (equivalent to cisplatin 0.35 mg/kg) showed superior tumor suppressive effects compared to cisplatin 2 mg/kg in mice with lung cancer LM diseases. The cerebrospinal fluid platinum concentration in the AptBCis1 group was 10% of that in the cisplatin group. The data suggested the translational potential of AptBCis1 in lung cancer with LM and in cancers in which platinum-based chemotherapy remains as the standard of care.

Exploring novel targets for non-small cell lung cancer (NSCLC) remains of utmost importance. This study focused on ORC6 (origin recognition complex subunit 6), investigating its expression and functional significance within NSCLC. Analysis of the TCGA-lung adenocarcinoma database revealed a notable increase in ORC6 expression in lung adenocarcinoma tissues, correlating with reduced overall survival, advanced disease stages, and other key clinical parameters. Additionally, in patients undergoing surgical resection of NSCLC at a local hospital, ORC6 mRNA and protein levels were elevated in NSCLC tissues while remaining low in adjacent normal tissues. Comprehensive bioinformatics analyses across various cancers suggested that ORC6 might play a significant role in crucial cellular processes, such as mitosis, DNA synthesis and repair, and cell cycle progression. Knocking down ORC6 using virus-delivered shRNA in different NSCLC cells, both primary and immortalized, resulted in a significant hindrance to cell proliferation, cell cycle progression, migration and invasion, accompanied by caspase-apoptosis activation. Similarly, employing CRISPR-sgRNA for ORC6 knockout (KO) exhibited significant anti-NSCLC cell activity. Conversely, increasing ORC6 levels using a viral construct augmented cell proliferation and migration. Silencing or knockout of ORC6 in primary NSCLC cells led to reduced expression of several key cyclins, including Cyclin A2, Cyclin B1, and Cyclin D1, whereas their levels increased in NSCLC cells overexpressing ORC6. In vivo experiments demonstrated that intratumoral injection of ORC6 shRNA adeno-associated virus markedly suppressed the growth of primary NSCLC cell xenografts. Reduced ORC6 levels, downregulated cyclins, and increased apoptosis were evident in ORC6-silenced NSCLC xenograft tissues. In summary, elevated ORC6 expression promotes NSCLC cell growth., (© 2024. The Author(s).)

The leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and their phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the LRRK2-regulated RAB GTPase in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brain through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes through enhancing the phosphorylation of RAB10 and recruiting RILPL1, while the functions of RAB12 require a direct interaction with LRRK2 and LRRK2 activity. Furthermore, the ciliary and centrosome defects caused by the PD-linked LRRK2-G2019S mutation are prevented by Rab12 deletion in astrocytes. Thus, our study reveals a physiological function of the RAB12-LRRK2 complex in regulating ciliogenesis and centrosome homeostasis. The RAB12-LRRK2 structure offers a guidance in the therapeutic development of PD by targeting the RAB12-LRRK2 interaction., (© 2024. The Author(s).)

Objective: To analyze the relationship between serum cystatin C (CysC), β 2 -microglobulin (β 2 -MG) and the efficacy of demethylation therapy in patients with acute myeloid leukemia (AML)., Methods: A prospective cohort study was conducted on 98 AML patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from February 2019 to January 2022. All patients were treated with decitabine (DAC) + HAG regimen, 28 days as a course and treated for 3-4 courses. At the end of each course of treatment, the treatment effect of the patients was evaluated, and the patients who achieved complete remission (CR) transferred to consolidation therapy, while the patients who did not reach CR at the end of the course of treatment were considered as treatment failure. The examination items before treatment include routine blood parameters, serum CysC, and β 2 -MG, and general clinical data of the patients were collected. According to the statistical results, logistic regression model was used to analyze the relationship between serum CysC, β 2 -MG and the efficacy of demethylation therapy in AML patients. The ROC curves were drawn, and the predictive efficacy of serum CysC, β 2 -MG on demethylation therapy in AML patients was evaluated by the area under the curve (AUC)., Results: Of the 98 AML patients enrolled in the study, 5 cases were excluded during the treatment period, and 93 cases finally completed the chemotherapy courses. Among them, 23 patients achieved CR after the initial induction chemotherapy (course 1-2), and 11 patients achieved CR after the re-induction chemotherapy (course 3-4). The success rate of demethylation therapy was 36.56 % (34/93). Compared with the patients in treatment success group, patients in treatment failure group had a higher proportion of intermediate- and adverse-risk, lower levels of platelet (PLT) and hemoglobin (Hb), and higher expression levels of serum CysC and β 2 -MG, all of which were statistically significant ( P < 0.05). Logistic regression analysis showed that high expression of serum CysC, β 2 -MG and adverse-risk were independent risk factors for failure of demethylation treatment in AML patients ( OR >1, P < 0.05). The ROC curves showed that the AUC values of serum CysC, β 2 -MG alone and combined in predicting the efficacy of demethylation therapy in AML patients were 0.788, 0.785 and 0.834, respectively., Conclusion: The failure of demethylation therapy in AML patients is related to the high expression of serum CysC and β 2 -MG, and detection of serum CysC and β 2 -MG before treatment can predict the risk of demethylation therapy failure in AML patients.

Microorganisms living with higher organisms are valuable sources of bioactive substances like antibiotics, which could assist them competing for more and better nutrients or space. Here, we focused on a marine animal-associated bacterium, 'Aliisedimentitalea scapharcae' KCTC 42119 T , which was isolated from ark shell collected from Gang-Jin bay of South Korea. We evaluated its biosynthetic potentials of medicinal secondary metabolites by de novo genome sequencing. The complete genome of strain KCTC 42119 T sequenced is 5,083,900 bp and is comprised of one circular chromosome and four circular plasmids. Functional genome analysis by antiSMASH v7.1.0 showed that there are nine biosynthetic gene clusters encoded on the chromosome. The annotated secondary metabolites include antibiotic corynecin, cytoprotective ectoine and antineoplastic ET-743 (Yondelis), which suggested strain KCTC 42119 T possesses potentials to synthesize a series of secondary metabolites of pharmaceutical utility. Genome analysis of 'A. scapharcae' also provides more insights into mining bioactive substances from animal-associated microorganisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and the phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brains through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis. Mechanistically, RAB12 cooperates with LRRK2 to inhibit primary ciliogenesis and regulate centrosome homeostasis in astrocytes through enhancing the phosphorylation of RAB10 and recruiting Rab interacting lysosomal protein like 1 (RILPL1), while the functions of RAB12 require a direct interaction with LRRK2 and LRRK2 kinase activity. Furthermore, the ciliary deficits and centrosome alteration caused by the PD-linked LRRK2-G2019S mutation are prevented by the deletion of Rab12 in astrocytes. Thus, our study reveals a physiological function of the RAB12-LRRK2 complex in regulating ciliogenesis and centrosome homeostasis. The RAB12-LRRK2 structure offers a guidance in the therapeutic development of PD by targeting the RAB12-LRRK2 interaction., Competing Interests: Competing interests The authors declare no competing interests.

There has been increasing attention given to nickel-cobalt tailings (NCT), which pose a risk of heavy metal pollution in the field. In this study, on site tests and sampling analysis were conducted to assess the physical and chemical characteristics, heavy metal toxicity, and microbial diversity of the original NCT, solidified NCT, and the surrounding soil. The research results show that the potential heavy metal pollution species in NCT are mainly Ni, Co, Mn, and Cu. Simultaneous solidification and passivation of heavy metals in NCT were achieved, resulting in a reduction in biological toxicity and a fivefold increase in seed germination rate. The compressive strength of the original tailings was increased by 20 times after solidification. The microbial diversity test showed that the abundance of microbial community in the original NCT was low and the population was monotonous. This study demonstrates, for the first time, that the use of NCT for solidification in ponds can effectively solidification of heavy metals, reduce biological toxicity, and promote microorganism diversity in mining areas (tended to the microbial ecosystem in the surrounding soil). Indeed, this study provides a new perspective for the environmental remediation of metal tailings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The study aims to investigate whether including the inflammation-related parameters would enhance the accuracy of a nomogram for local control (LC) prediction in lung cancer patients undergoing stereotactic body radiation therapy (SBRT)., Methods: 158 primary or metastatic lung cancer patients treated with SBRT were retrospectively analyzed. The clinical, dosimetric and inflammation-related parameters were collected for the Cox regression analysis. The ACPB model was constructed by employing the clinical and dosimetric factors. And the ACPBLN model was established by adding the inflammation-related factors to the ACPB model. The two models were compared in terms of ROC, Akaike Information Criterion (AIC), C-index, time-dependent AUC, continuous net reclassification index (NRI), integrated discrimination improvement (IDI), calibration plots and decision curve analysis (DCA)., Results: Multivariate Cox regression analysis revealed that six prognostic factors were independently associated with LC, including age, clinical stage, planning target volume (PTV) volume, BED of the prescribed dose (BEDPD), the lymphocyte count and neutrocyte count. The ACPBLN model performed better in AIC, bootstrap-corrected C-index, time-dependent AUC, NRI and IDI than the ACPB model. The calibration plots showed good consistency between the probabilities and observed values in the two models. The DCA curves showed that the ACPBLN nomogram had higher overall net benefit than the ACPB model across a majority of threshold probabilities., Conclusion: The inflammation-related parameters were associated with LC for lung cancer patients treated with SBRT. The inclusion of the inflammation-related parameters improved the predictive performance of the nomogram for LC prediction., (© 2024. The Author(s).)

Purpose: The study aims to develop and validate a combined model for predicting 3-year cancer-specific survival (CSS) in lung cancer patients treated with stereotactic body radiation therapy (SBRT) by integrating clinical and radiomic parameters., Methods: Clinical data and pre-treatment CT images were collected from 102 patients treated with lung SBRT. Multivariate logistic regression and the least absolute shrinkage and selection operator were used to determine the clinical and radiomic factors associated with 3-year CSS. Three prediction models were developed using clinical factors, radiomic factors, and a combination of both. The performance of the models was assessed using receiver operating characteristic curve and calibration curve. A nomogram was also created to visualize the 3-year CSS prediction., Results: With a 36-month follow-up, 40 patients (39.2%) died of lung cancer and 62 patients (60.8%) survived. Three clinical factors, including gender, clinical stage, and lymphocyte ratio, along with three radiomic features, were found to be independent factors correlated with 3-year CSS. The area under the curve values for the clinical, radiomic, and combined model were 0.839 (95% CI 0.735-0.914), 0.886 (95% CI 0.790-0.948), and 0.914 (95% CI 0.825-0.966) in the training cohort, and 0.757 (95% CI 0.580-0.887), 0.818 (95% CI 0.648-0.929), and 0.843 (95% CI 0.677-0.944) in the validation cohort, respectively. Additionally, the calibration curve demonstrated good calibration performance and the nomogram created from the combined model showed potential for clinical utility., Conclusion: A clinical-radiomic model was developed to predict the 3-year CSS for lung cancer patients treated with SBRT., (© 2024. The Author(s).)

Background: The study aims to identify the risk factors and develop a model for predicting grade ≥2 radiation pneumonitis (RP) for lung cancer patients treated with stereotactic body radiation therapy (SBRT)., Materials and Methods: Clinical data, dosimetric data, and laboratory biomarkers from 186 patients treated with lung SBRT were collected. Univariate and multivariate logistic regression were performed to determine the predictive factors for grade ≥2 RP. Three models were developed by using the clinical, dosimetric, and combined factors, respectively., Results: With a median follow-up of 36 months, grade ≥2 RP was recorded in 13.4% of patients. On univariate logistic regression analysis, clinical factors of age and lung volume, dosimetric factors of treatment durations, fractional dose and V 10 , and laboratory biomarkers of neutrophil, PLT, PLR, and Hb levels were significantly associated with grade ≥2 RP. However, on multivariate analysis, only age, lung volume, fractional dose, V 10 , and Hb levels were independent factors. AUC values for the clinical, dosimetric, and combined models were 0.730 (95% CI, 0.660-0.793), 0.711 (95% CI, 0.641-0.775) and 0.830 (95% CI, 0.768-0.881), respectively. The combined model provided superior discriminative ability than the clinical and dosimetric models (P < .05)., Conclusion: Age, lung volume, fractional dose, V 10 , and Hb levels were demonstrated to be significant factors associated with grade ≥2 RP for lung cancer patients after SBRT. A novel model combining clinical, dosimetric factors, and laboratory biomarkers improved predictive performance compared with the clinical and dosimetric model alone., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract: This study aimed to investigate the independent clinical, pathological, and radiological factors associated with extracapsular extension in radical prostatectomy specimens and to improve the accuracy of predicting extracapsular extension of prostate cancer before surgery., Methods: From August 2018 to June 2023, the clinical and pathological data of 229 patients with confirmed prostate cancer underwent radical prostatectomy from The Second Hospital of Yinzhou. The patients' multiparametric magnetic resonance imaging data were graded using the Likert scale. The chi-square or independent-sample T-test was used to analyze the related factors for an extracapsular extension. Multivariate analysis was used to identify independent factors associated with extracapsular extension in prostate cancer. Additionally, receiver operating characteristic curve analysis was used to calculate the area under the curve and assess the diagnostic performance of our model. The clinical decision curve was used to analyze the clinical net income of Likert scale, biopsy positive rate, biopsy GG, and combined mode., Results: Of the 229 patients, 52 had an extracapsular extension, and 177 did not. Multivariate analysis showed that the Likert scale score, biopsy grade group and biopsy positive rate were independent risk factors for extracapsular extension in prostate cancer. The area under the curves for the Likert scale score, biopsy grade group, and biopsy positive rate were 0.802, 0.762, and 0.796, respectively. Furthermore, there was no significant difference in the diagnostic efficiency for extracapsular extension (P>0.05). However, when these three factors were combined, the diagnostic efficiency was significantly improved, and the area under the curve increased to 0.905 (P<0.05). In the analysis of the decision curve, The clinical net income of the combined model is obviously higher than that of Likert scale, biopsy positive rate, and biopsy GG., Conclusion: The Likert scale, biopsy grade group and biopsy positive rate are independent risk factors for extracapsular extension in prostate cancer, and their combination can significantly improve the diagnostic efficiency for an extracapsular extension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Huang, Huang, Zhang, He and Chen.)

Background and Objective: The evidence on the risk of mortality after myocardial infarction (MI) among migrants compared with natives is mixed and limited. The aim of this study is to assess the mortality risk after MI in migrants compared to natives., Methods: This study protocol is registered with PROSPERO, number CRD42022350876. We searched the Medline and Embase databases, without time and language constraints, for cohort studies that reported the risk of mortality after MI in migrants compared to natives. The migration status is confirmed by country of birth, both migrants and natives are general terms and are not restricted to a particular country or area of destination or origin. Two reviewers separately screened searched studies according to selection criteria, extracted data, and assessed data quality using the Newcastle-Ottawa Scale (NOS) and risk of bias of included studies. Pooled estimates of adjusted and unadjusted mortality after MI were calculated separately using a random-effects model, and subgroup analysis was performed by region of origin and follow-up time., Result: A total of 6 studies were enrolled, including 34,835 migrants and 284,629 natives. The pooled adjusted all-cause mortality of migrants after MI was higher than that of natives ( OR , 1.24; 95% CI , 1.10-1.39; I 2   = 83.1%), while the the pooled unadjusted mortality of migrants after MI was not significantly different from that of natives ( OR , 1.11; 95% CI , 0.69-1.79; I 2   = 99.3%). In subgroup analyses, adjusted 5-10 years mortality (3 studies) was higher in the migrant population ( OR , 1.27; 95% CI , 1.12-1.45; I 2   = 86.8%), while adjusted 30 days (4 studies) and 1-3 years (3 studies) mortality were not significantly different between the two groups. Migrants from Europe (4 studies) ( OR , 1.34; 95% CI , 1.16-1.55; I 2   = 39%), Africa (3 studies) ( OR , 1.50; 95% CI , 01.31-1.72; I 2  = 0%), and Latin America (2 studies) ( OR , 1.44; 95% CI , 1.30-1.60; I 2   = 0%) had significantly higher rates of post-MI mortality than natives, with the exception of migrants of Asian origin (4 studies) ( OR , 1.20; 95% CI , 0.99-1.46; I 2   = 72.7%)., Conclusions: Migrants tend to have lower socioeconomic status, greater psychological stress, less social support, limited access to health care resources, etc., therefore, face a higher risk of mortality after MI in the long term compared to natives. Further research is needed to confirm our conclusions, and more attention should be paid to the cardiovascular health of migrants., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: r CRD42022350876., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zhu, Huang and Chen.)

Background: We aimed to investigate whether the pressure injury risk mediates the association of left ventricular ejection fraction (LVEF) with all-cause death in patients with acute myocardial infarction (AMI) aged 80 years or older., Methods: This retrospective cohort study included 677 patients with AMI aged 80 years or older from a tertiary-level hospital. Pressure injury risk was assessed using the Braden scale at admission, and three risk groups (low/minimal, intermediate, high) were defined according to the overall score of six different variables. LVEF was measured during the index hospitalization for AMI. All-cause death after hospital discharge was the primary outcome., Results: Over a median follow-up period of 1,176 d (interquartile range [IQR], 722-1,900 d), 226 (33.4%) patients died. Multivariate Cox regression analysis showed that reduced LVEF was associated with an increased risk of all-cause death only in the high-risk group of pressure injury (adjusted hazard ratios [ HR ]=1.81, 95% confidence interval [ CI ]: 1.03-3.20; P =0.040), but not in the low/minimal- (adjusted HR =1.29, 95% CI : 0.80-2.11; P =0.299) or intermediate-risk groups (adjusted HR =1.14, 95% CI : 0.65-2.02; P =0.651). Significant interactions were detected between pressure injury risk and LVEF (adjusted P =0.003). The cubic spline with hazard ratio plot revealed a distinct shaped curve relation between LVEF and all-cause death among different pressure injury risk groups., Conclusions: In older patients with AMI, the risk of pressure injury mediated the association between LVEF and all-cause death. The classification of older patients for both therapy and prognosis assessment appears to be improved by the incorporation of pressure injury risk assessment into AMI care management., Competing Interests: Conflicts of interest: None., (Copyright: © World Journal of Emergency Medicine.)

Aims: To investigate the risk factors, clinical features, and prognostic factors of patients with premature acute myocardial infarction (AMI)., Materials and Methods: A retrospective cohort study of patients with AMI included in data from the West China Hospital of Sichuan University from 2011 to 2019 was divided into premature AMI (aged < 55 years in men and < 65 years in women) and non-premature AMI. Patients' demographics, laboratory tests, Electrocardiography (ECG), cardiac ultrasound, and coronary angiography reports were collected. All-cause death after incident premature MI was enumerated as the primary endpoint., Results: Among all 8,942 AMI cases, 2,513 were premature AMI (79.8% men). Compared to the non-premature AMI group, risk factors such as smoking, dyslipidemia, overweight, obesity, and a family history of coronary heart disease (CHD) were more prevalent in the premature AMI group. The cumulative survival rate of patients in the premature AMI group was significantly better than the non-premature AMI group during a mean follow-up of 4.6 years (HR = 0.27, 95% CI 0.22-0.32, p < 0.001). Low left ventricular ejection fraction (LVEF) (Adjusted HR 3.00, 95% CI 1.85-4.88, P < 0.001), peak N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (Adjusted HR 1.34, 95% CI 1.18-1.52, P < 0.001) and the occurrence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCEs) (Adjusted HR 2.36, 95% CI 1.45-3.85, P = 0.001) were predictors of poor prognosis in premature AMI patients., Conclusion: AMI in young patients is associated with unhealthy lifestyles such as smoking, dyslipidemia, and obesity. Low LVEF, elevated NT-proBNP peak level, and the occurrence of in-hospital MACCEs were predictors of poor prognosis in premature AMI patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Shi, Zhang, Cheng, Yang, Zhang, Huang and Chen.)

Discovery of interventions that delay or minimize age-related diseases is arguably the major goal of aging research. Conversely discovery of interventions based on phenotypic screens have often led to further elucidation of pathophysiological mechanisms. Although most hypotheses to explain lifespan focus on cell-autonomous processes, increasing evidence suggests that in multicellular organisms, neurons, particularly nutrient-sensing neurons, play a determinative role in lifespan and age-related diseases. For example, protective effects of dietary restriction and inactivation of insulin-like signaling increase lifespan and delay age-related diseases dependent on Creb-binding protein in GABA neurons, and Nrf2/Skn1 in just 2 nutrient-sensing neurons in C. elegans. Screens for drugs that increase lifespan also indicate that such drugs are predominantly active through neuronal signaling. Our own screens also indicate that neuroactive drugs also delay pathology in an animal model of Alzheimer's Disease, as well as inhibit cytokine production implicated in driving many age-related diseases. The most likely mechanism by which nutrient-sensing neurons influence lifespan and the onset of age-related diseases is by regulating metabolic architecture, particularly the relative rate of glycolysis vs. alternative metabolic pathways such as ketone and lipid metabolism. These results suggest that neuroactive compounds are a most promising class of drugs to delay or minimize age-related diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Left ventricular hypertrophy (LVH) is prevalent in obese individuals. Besides, both of LVH and obesity is associated with subclinical LV dysfunction. The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease (CAD)., Methods: In this retrospective cohort study, a total of 2243 patients with angiographically proven CAD were included. Body fat and LV mass were calculated using established formulas. Patients were grouped according to body fat percentage and presence or absence of LVH. Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death., Results: Of 2243 patients enrolled, 560 (25%) had a higher body fat percentage, and 1045 (46.6%) had LVH. After a median follow-up of 2.2 years, the cumulative mortality rate was 8.2% in the group with higher body fat and LVH, 2.5% in those with lower body fat and no LVH, 5.4% in those with higher body fat and no LVH, and 7.8% in those with lower body fat and LVH (log-rank P < 0.001). There was a statistically significant interaction between body fat percentage and LVH ( P interaction was 0.003). After correcting for confounding factors, patients with higher body fat and LVH had the highest risk of all-cause death (HR = 3.49, 95% CI: 1.40-8.69, P = 0.007) compared with those with lower body fat and no LVH; in contrast, patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH (HR = 2.03, 95% CI: 0.70-5.92, P = 0.195)., Conclusion: A higher body fat percentage was associated with a different risk of all-cause death in patients with CAD, stratified by coexistence of LVH or not. Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH., (Copyright and License information: Journal of Geriatric Cardiology 2022.)

Purpose: Stereotactic body radiation therapy (SBRT) is a standard treatment for early primary lung cancer patients. However, there are few simple models for predicting the clinical outcomes of these patients. Our study analyzed the clinical outcomes, identified the prognostic factors, and developed prediction nomogram models for these patients., Materials and Methods: We retrospectively analyzed 114 patients with primary lung cancer treated with SBRT from 2012 to 2020 at our institutions and assessed patient's clinical outcomes and levels of toxicity. Kaplan-Meier analysis with a log-rank test was used to generate the survival curve. The cut-off values of continuous factors were calculated with the X-tile tool. Potential independent prognostic factors for clinical outcomes were explored using cox regression analysis. Nomograms for clinical outcomes prediction were established with identified factors and assessed by calibration curves., Results: The median overall survival (OS) was 40.6 months, with 3-year OS, local recurrence free survival (LRFS), distant disease-free survival (DDFS) and progression free survival (PFS) of 56.3%, 61.3%, 72.9% and 35.8%, respectively, with grade 3 or higher toxicity rate of 7%. The cox regression analysis revealed that the clinical stage, immobilization device, and the prescription dose covering 95% of the target area (D95) were independent prognostic factors associated with OS. Moreover, the clinical stage, and immobilization device were independent prognostic factors of LRFS and PFS. The smoking status, hemoglobin (Hb) and immobilization device were significant prognostic factors for DDFS. The nomograms and calibration curves incorporating the above factors indicated good predictive accuracy., Conclusions: SBRT is effective and safe for primary lung cancer. The prognostic factors associated with OS, LRFS, DDFS and PFS are proposed, and the nomograms we proposed are suitable for clinical outcomes prediction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Wang, Lin, Su and Huang.)

Purpose: Stereotactic body radiotherapy (SBRT) is an important treatment modality for lung cancer patients, however, tumor local recurrence rate remains some challenge and there is no reliable prediction tool. This study aims to develop a prediction model of local control for lung cancer patients undergoing SBRT based on radiomics signature combining with clinical and dosimetric parameters., Methods: The radiomics model, clinical model and combined model were developed by radiomics features, incorporating clinical and dosimetric parameters and radiomics signatures plus clinical and dosimetric parameters, respectively. Three models were established by logistic regression (LR), decision tree (DT) or support vector machine (SVM). The performance of models was assessed by receiver operating characteristic curve (ROC) and DeLong test. Furthermore, a nomogram was built and was assessed by calibration curve, Hosmer-Lemeshow and decision curve., Results: The LR method was selected for model establishment. The radiomics model, clinical model and combined model showed favorite performance and calibration (Area under the ROC curve (AUC) 0.811, 0.845 and 0.911 in the training group, 0.702, 0.786 and 0.818 in the validation group, respectively). The performance of combined model was significantly superior than the other two models. In addition, Calibration curve and Hosmer-Lemeshow (training group: P = 0.898, validation group: P = 0.891) showed good calibration of combined nomogram and decision curve proved its clinical utility., Conclusions: The combined model based on radiomics features plus clinical and dosimetric parameters can improve the prediction of 1-year local control for lung cancer patients undergoing SBRT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Luo, Huang, Chen, Wang, Su, Peng, Zeng, Wu, Wang, Huang and Qiu.)

Used as traditional Chinese medicine, Astragalus membranaceus (Fisch.) Bge. (A. membranaceus) roots are also used as tonic food material in a wide range of applications, while the leaves are left in the field, unused. Therefore, comprehensively exploring and utilizing the leaves will inevitably reduce the associated resource waste and environment pollution. In this study, the plant leaves were processed into tea using green tea processing technology. Bioactive components, antioxidant and antibacterial activities of the Leaf Tea (LT) and Dry Leaves (DL) were studied, and compared to that of the Dry Roots (DR). The results showed that the polysaccharides content (POL) in the DR (20.44%) was twice as high as the DL (10.18%) and LT (8.68%). However, the DL contained 36.85% more water-soluble extracts (WSE), 35.09% more ethanol-soluble extracts (ESE), 409.63% more total flavonoid content (TFC), 221.01% more total phenolic content (TPC) and 94.34% more proteins, and the LT contained 26.21% more WSE, 40.64% more ESE, 326.93% more TFC, 191.90% more TPC and 37.71% more proteins. The total amino acid (AA) content in the DR was 8.89%, while in that of the DL and LT were 24.18% and 28.96% respectively, nearly 3-times higher than that of the DR. The antioxidant activity of DR was much lower than those of DL and LT, both of which had antioxidant activity closer to that of Vitamin C (V C ) and the antioxidant activities were even stronger when the optimal concentration was reached. Except for Aspergillus niger and Staphylococcus aureus, the DL and DR exhibited inhibition activities to Salmonella, Bacillus subtilis, Escherichia coli and yeast, while the LT had antimicrobial activities against all the strains except for A. niger. In summary, compared with the most commonly used DR, the DL and LT from A. membranaceus contained higher bioactive components, and stronger antioxidant and antimicrobial activities. Producing leaf tea may be an appropriate way to economically and reasonably utilize the plant leaves which are by-products., (© 2021. The Author(s).)

A new nerve matrix membrane derived from decellularized porcine nerves has been shown to retain the major extracellular matrix components, and to be effective in preventing adhesion between the nerve anastomosis sites and the surrounding tissues in a rat sciatic nerve transection model, thereby enhancing regeneration of the nerve. The effectiveness of the membrane may be attributed to its various bioactive components. In this prospective, randomized, single-blind, parallel-controlled multicenter clinical trial, we compared the safety and efficacy of the new nerve matrix membrane with a previously approved bovine tendon-derived type I collagen nerve wrapping. A total of 120 patients with peripheral nerve injury were recruited from Beijing Jishuitan Hospital, The First Bethune Hospital of Jilin University, and Yantai Yuhuangding Hospital, China. The patients were randomly assigned to undergo end-to-end and tension-free neurorrhaphy with nerve matrix membrane (n = 60, 52 male, 8 female, mean age 41.34 years, experimental group) or tendon-derived collagen nerve wrapping (n = 60, 42 male, 18 female, mean age 40.17 years, control group). Patients were followed-up at 14 ± 5, 30 ± 7, 90 ± 10 and 180 ± 20 days after the operation. Safety evaluation included analyses of local and systemic reactions, related laboratory tests, and adverse reactions. Efficacy evaluation included a static 2-point discrimination test, a moving 2-point discrimination test, and a Semmes-Weinstein monofilament examination. Sensory nerve function was evaluated with the British Medical Research Council Scale and Semmes-Weinstein monofilament examination. The ratio (percentage) of patients with excellent to good results in sensory nerve recovery 180 ± 20 days after the treatment was used as the primary effectiveness index. The percentages of patients with excellent to good results in the experimental and control groups were 98.00% and 94.44%, respectively, with no significant difference between the two groups. There were no significant differences in the results of routine blood tests, liver and renal function tests, coagulation function tests, or immunoglobulin tests at 14 and 180 days postoperatively between the two groups. These findings suggest that the novel nerve matrix membrane is similar in efficacy to the commercially-available bovine-derived collagen membrane in the repair of peripheral nerve injury, and it may therefore serve as an alternative in the clinical setting. The clinical trial was approved by the Institutional Ethics Committee of Beijing Jishuitan Hospital, China (approval No. 20160902) on October 8, 2016, the Institutional Ethics Committee of the First Bethune Hospital of Jilin University, China (approval No. 160518-088) on December 14, 2016, and the Institutional Ethics Committee of Yantai Yuhuangding Hospital, China (approval No. 2016-10-01) on December 9, 2016. The clinical trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2000033324) on May 28, 2020., Competing Interests: None

EGFR is established as a driver of lung cancer, yet the regulatory machinery underlying its oncogenic activity is not fully understood. PTEN-induced kinase 1 (PINK1) kinase is a key player in mitochondrial quality control, although its role in lung cancer and EGFR regulation is unclear. In this study, we show that PINK1 physically directly interacts with EGFR via the PINK1 C-terminal domain (PINK1-CTD) and the EGFR tyrosine kinase domain. This interaction constituted an endogenous steric hindrance to receptor dimerization and inhibited EGFR-mediated lung carcinogenesis. Depletion of PINK1 from lung cancer cells promoted EGFR dimerization, receptor activation, EGFR downstream signaling, and tumor growth. In contrast, overexpression of PINK1 or PINK1-CTD suppressed EGFR dimerization, activation, downstream signaling, and tumor growth. These findings identify key elements in the EGFR regulatory cascade and illustrate a new direction for the development of anti-EGFR therapeutics, suggesting translational potential of the PINK1-CTD in lung cancer. SIGNIFICANCE: This study identifies PINK1 as a critical tumor suppressor that impedes EGFR dimerization and highlights PINK1-CTD as a potential therapeutic agent in EGFR-driven lung cancer., (©2021 American Association for Cancer Research.)

Background: Few studies from developed countries have quantitatively characterized the clinical characteristics and outcomes of patients receiving contemporary intensive cardiac care. We sought to investigate these data in patients admitted to a Chinese intensive cardiac care unit (ICCU)., Methods: We conducted a retrospective study using data from 2,337 consecutive admissions to the ICCU at a large centre in China from June 2016 to May 2017. Data were captured after systematic inspection of individual medical records regarding current demographics, primary diagnosis, comorbidities, illnesses severity, and in-hospital outcomes., Results: The mean age was 65.6 ± 14.2 years, and females accounted for 32.0% of patients. The Charlson Comorbidity Index and Oxford Acute Severity of Illness Score were 2.4 ± 1.8 and 22.5 ± 10.4, respectively. The top reason for admission was ST-segment elevation myocardial infarction (32.0%), and nonischaemic heart diseases accounted for 31.2% of all primary diagnoses. Noncardiovascular diseases were prevalent in the ICCU population, including chronic illnesses and acute noncardiovascular critical illnesses (ANCIs); in particular, 21.7% of patients were marked by acute respiratory failure (14.6%), acute kidney injury (13.7%), sepsis (4.2%), or gastrointestinal bleeding (3.3%). The median length of stay in the ICCU and hospital were 1.1 days [interquartile range (IQR): 0.8-2.6 days] and 6.3 days (IQR: 3.8-10.9 days), respectively. The overall incidence of in-hospital death or discharge against medical advice under extremely critical conditions was 7.6% ( n = 177). Multivariate logistic regression analysis showed that the complexity of chronic illnesses and incident ANCIs were strong independent determinants for in-hospital outcomes., Conclusions: Remarkable patient diversity and breadth of critical illnesses were observed in a Chinese ICCU population. Particularly, noncardiovascular diseases were prevalent and associated with adverse outcomes. Reformation of organization and staffing practices may be considered to adapt to the changed landscape., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Background: The relationship between renal function and outcomes among patients with hypertrophic cardiomyopathy (HCM) remains undefined. We sought to investigate the prevalence of renal dysfunction and its prognostic value in HCM patients., Methods: A total of 581 patients with HCM were consecutively recruited. The chronic kidney disease epidemiology equation was used to estimate the glomerular filtration rate (eGFR). Patients were divided into 2 eGFR categories: ≥60 or <60 ml/min/1.73 m 2 . The predictive value of renal function was assessed using Cox regression., Results: The proportions of eGFR 60-90 ml/min/1.73 m 2 and <60 ml/min/1.73 m 2 were 41.8% and 15.3%, respectively. Estimated GFR independently predicted the risk of all-cause mortality [HR 0.98, 95% confidence interval (CI) 0.96-0.99, P < 0.001]. Compared to those with eGFR ≥ 60 ml/min/1.73 m 2 , patients with eGFR < 60 ml/min/1.73 m 2 were independently associated with all-cause mortality (HR, 3.42 95% CI 1.86-6.28), cardiovascular mortality (HR 2.98, 95% CI 1.36-6.50) and combined adverse outcomes (HR 1.60, 95% CI 1.02-2.49). HRs for all-cause mortality with renal dysfunction were attenuated in patients with older ages (P for interaction = 0.034)., Conclusions: Renal dysfunction is a common comorbidity in HCM. Renal function is an independent predictor of outcomes in patients with HCM. These findings highlight the clinical importance of renal dysfunction in HCM., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fifty typical redevelopment industrial sites in the Putuo, Baoshan, Minhang, and Jiangding districts of Shanghai were chosen to evaluate the ecological risk of heavy metals in the soil. The contents of heavy metal (Hg, Cd, Pb, Cr, and As) in 1847 soil samples, taken from vertical sections, were determined, and their risks were evaluated using the Nemero composite index and Hakanson potential ecological risk index. The average contents of Hg, Cd, Pb, Cr, and As in topsoil samples were 0.33, 0.37, 74.55, 69.23, and 9.05 mg·kg -1 , respectively. The contents of Hg, Cd, and Pb exceeded the soil background values of Shanghai, which were 2.75, 2.85, and 2.93 times the background values, respectively. The contents of five heavy metals in soil decreased gradually with increased depth. The contents of heavy metals in deep and saturated soils were close to, or below, the background values, indicating that the anthropic activity disturbance was mainly confined to the topsoil. The accumulation of Hg, Cd, and Pb was the most obvious in Putuo topsoil, with the average contents being 4.25, 4.85, and 3.09 times the background values, respectively. The average contents of Hg and Pb in Baoshan were 4.92 and 6.43 times the background values, respectively. The Nemero Composite Index of Baoshan and Putuo districts were 3.70 and 3.20, respectively, representing heavy pollution level at these sites. The Hakanson potential ecological risk indexes of the Putuo and Baoshang districts were 398.59 and 303.08, respectively, with considerable ecological risk levels. The content and ecological risk of heavy metals at the Minhang and Jiading sites were relatively low. In summary, the pollution of heavy metal in the redeveloped industrial sites is influenced by the operating time, industry type, and past management level of the enterprises. The heavy metal accumulation in the Putuo and Baoshan districts, whose industries developed earlier, were higher than those in the Minhang and Jiading districts. The pollution of heavy metal Hg, Cd, and Pb in soil should be a focus of future work.

Background: C-reactive protein (CRP) has two natural isomers: C-reactive protein pentamer (pCRP) and C-reactive protein monomer (mCRP). The levels of CRP are significantly elevated in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). mCRP not only activates the endothelial cells, platelets, leukocytes, and complements, but also has a proinflammatory structural subtype that can localize and deposit in inflammatory tissues. Thus, it regulates a variety of clinical diseases, such as ischemia/reperfusion (I/R) injury, Alzheimer's disease, age-related macular degeneration, and cardiovascular disease. We hypothesized that plasma mCRP levels are related to cardiovascular disease in AAV., Methods: In this cross-sectional study, 37 patients with AAV were assessed. Brain natriuretic peptide (BNP) and mCRP in plasma were assessed by enzyme-linked immunosorbent assay (ELISA). The acute ST-segment elevation myocardial infarction (STEMI) was diagnosed by coronary angiography, and the Gensini score calculated. Echocardiography evaluated the ejection fraction (EF%), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), and left ventricular mass index (LVMI). Estimated glomerular filtration rate (eGFR) was calculated based on serum creatinine, age, and gender., Results: The plasma level of mCRP in AAV was significantly higher than that in healthy volunteers (P < 0.001). Then, mCRP and CRP levels were compared with and without STEMI complications in AAV. The plasma level of mCRP was higher, but that of CRP was lower in STEMI. The plasma level of mCRP was correlated with Birmingham vasculitis activity score (BVAS), eGFR, BNP, EF%, LVEDV, LVESV, LVMI, and STEMI complications' Gensini score in AAV; however, CRP did not correlate with BNP, EF%, LVEDV, LVESV, LVMI, and Gensini score., Conclusions: The plasma level of mCRP was related to cardiovascular diseases in AAV patients.

Dynamic fission and fusion events regulate mitochondrial shape, distribution, and rejuvenation, and proper control of these processes is essential for neuronal homeostasis. Here, we report that Gas7, a known cytoskeleton regulator, controls mitochondrial dynamics within neurons of the central nervous system. In this study, we generated an improved Gas7 -knockout mouse and evaluated its mitochondrial phenotype. We first identified Gas7 in mitochondrial fractions from wild-type brain tissue, and observed Gas7 colocalization with mitochondria in primary cortical neurons. In Gas7 -deficient brain tissue and neuronal cultures mitochondria were elongated with perinuclear clustering. These morphological abnormalities were associated with increased levels mitochondrial fusion proteins and increased PKA-dependent phosphorylation of Drp-1 in brain tissues, suggesting an imbalance of mitochondrial fusion and fission. Moreover, expression of mitochondrial quality control kinase, PINK1, and PINK1-specific phosphorylation of Mfn-2 (S442), Parkin (S65), and ubiquitin (S65) were all reduced in the knockout cells. Ectopic expression of Gas7 restored mitochondrial morphology and distribution, as well as PINK1 expression in Gas7 -null cortical neurons. Collectively, our results introduce a novel role of mouse Gas7 in determining the dynamics, morphology, and intracellular distribution of neuronal mitochondria, which are expected to be required for normal neuronal function., Competing Interests: The authors state that there are no actual or potential conflicts of interest., (© 2020 The Authors.)

Objective: The applicability of the linear quadratic (LQ) model to local control (LC) modeling after hypofractionated radiotherapy to treat lung cancer is highly debated. To date, the differences in predicted outcomes between the LQ model and other radiobiological models, which are characterized by additional dose modification beyond a certain transitional dose (d T ), have not been well established. This study aims to compare the outcomes predicted by the LQ model with those predicted by two other radiobiological models in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC). Methods: Computer tomography (CT) simulation data sets for 20 patients diagnosed with stage Ⅰ primary NSCLC were included in this study. Three radiobiological models, including the LQ, the universal survival curve (USC) and the modified linear quadratic and linear (mLQL) model were employed to predict the tumor control probability (TCP) data. First, the d T values for the USC and mLQL models were determined. Then, the biologically effective dose (BED) and the predicted TCP values from the LQ model were compared with those calculated from the USC and mLQL models. Results: The d T values from the USC model were 29.6 Gy, 33.8 Gy and 44.5 Gy, whereas the values were 90.2 Gy, 84.0 Gy and 57.3 Gy for the mLQL model for 1-year, 2-year and 3-year TCP prediction. The remarkable higher d T values obtained from the mLQL model revealed the same dose-response relationship as the LQ model in the low- and high-dose ranges. We also found that TCP prediction from the LQ and USC models differed by less than 3%, although the BED values for the two models were significantly different. Conclusion: Radiobiological analysis reveals small differences between the models and suggested that the LQ model is applicable for modeling LC using SBRT to treat lung cancer, even when an extremely high fractional dose is used., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: To calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P + ) function., Methods: Thirty-three patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose bin was multiplied by a certain percentage of the dose in that bin which ranged from 1 to 200% in steps of 1%. For each dose fraction, P + values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P + values corresponded to the optimal therapeutic gain. The IFR in 3 fractions was also calculated with the same method by converting the dose using the linear quadratic (LQ) model., Results: Thirty-three patients attained an IFR using the introduced methods. All the patients achieved a TCP value higher than 92.0%. The IFR ranged from 3 × 10.8 Gy to 3 × 12.5 Gy for 3 fraction regimes and from 4 × 9.2 Gy to 4 × 10.7 Gy for 4 fraction regimes. Four patients with typical tumor characteristics demonstrated that the IFR was patient-specific and could maximize the therapeutic gain. Patients with a large tumor had a lower TCP and UTCP and a smaller fractional dose than patients with a small tumor. Patients with a tumor adjacent to the organ at risk (OAR) or at a high risk of RIP had a lower UTCP and a smaller fractional dose compared with patients with a tumor located distant from the OAR., Conclusions: The proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation in clinical samples is required.

Rationale: The TNF-α pathway plays as a double-edged sword that simultaneously regulates cell apoptosis and proliferation. The dysregulated TNF-α signaling can trigger cytokine storms that lead to profound cell death during the phase of acute tissue injury. On the other hand, an optimal level of TNF-α signaling is required for tissue repair following the acute injury phase. The TNF-α pathway is commonly upregulated in acute lung injury (ALI) and acute liver failure (ALF). Previous studies investigated the feasibility of adopting protein-based TNF-α blockers as disease modifiers in ALI and ALF, but none of these came out with a positive result. One of the potential reasons that resides behind the failure of the trials might be the long half-life of these inhibitors that led to undesired side effects. Developing alternative TNF-α blockers with manageable half-lives remain an unmet need in this regard. Methods: In the current study, we developed a novel TNF-α-targeting aptamer (aptTNF-α) and its PEG-derivate (aptTNF-α-PEG) with antagonistic functions. We investigated the in vivo antagonistic effects using mouse ALI and ALF models. Results: Our data showed that aptTNF-α possessed good in vitro binding affinity towards human/mouse TNF-α and successfully targeted TNF-α in vivo . In the mouse ALI model, aptTNF-α/aptTNF-α-PEG treatment attenuated the severity of LPS-induced ALI, as indicated by the improvement of oxygen saturation and lung injury scores, the reduction of protein-rich fluid leakage and neutrophil infiltration in the alveolar spaces, and the suppression of pro-inflammatory cytokines/chemokines expressions in the lung tissues. In the mouse ALF model, we further showed that aptTNF-α/aptTNF-α-PEG treatment not only attenuated the degree of hepatocyte damage upon acute injury but also potentiated early regeneration of the liver tissues. Conclusion: The results implicated potential roles of aptTNF-α/aptTNF-α-PEG in ALI and ALF. The data also suggested their translational potential as a new category of TNF-α blocking agent., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Ageing is a risk factor for both coronary artery disease (CAD) and reduced renal function (RRF), and it is also associated with poor prognosis in patients with CAD or RRF. However, little is known about whether the impact of RRF on clinical outcomes are different in CAD patients at different age groups. This study aimed to investigate whether ageing influences the effect of RRF on long-term risk of death in patients with CAD., Methods: A retrospective analysis was conducted using data from a single-center cohort study. Three thousand and two consecutive patients with CAD confirmed by coronary angiography were enrolled. RRF was defined as an estimated glomerular filtration rate (eGFR) of less than 60 ml/min. The primary endpoint in this study was all-cause mortality., Results: The mean follow-up time was 29.1 ± 12.5 months and death events occurred in 275 cases (all-cause mortality: 9.2%). The correlation analysis revealed a negative correlation between eGFR and age (r = - 0.386, P < 0.001). Comparing the younger group (age ≤ 59) with the elderly one (age ≥ 70), the prevalence of RRF increased from 5.9 to 27.5%. Multivariable Cox regression revealed that RRF was independently associated with all-cause mortality in all age groups, and the relative risks in older patients were lower than those in younger ones (age ≤ 59 vs. age 60-69 vs. age ≥ 70: hazard ratio [HR] 2.57, 95% confidence interval [CI] 1.04-6.37 vs. HR 2.00, 95% CI 1.17-3.42 vs. HR 1.46, 95% CI 1.06-2.02). There was a significant trend for HRs for all-cause mortality according to the interaction terms for RRF and age group (RRF*age [≤59] vs. RRF*age [60-69] vs. RRF*age [≥70]: HR 1.00[reference] vs. HR 0.60, 95% CI 0.23-1.54 vs. HR 0.32, 95% CI 0.14-0.75; P for trend = 0.010)., Conclusions: RRF may have different impacts on clinical outcomes in CAD patients at different age groups. The association of RRF with the risk of all-cause mortality was attenuated with ageing.

Background: The role of triglyceride (TG) in secondary prevention of patients with coronary artery disease (CAD) was debated. In the present study, we assessed the association between admission TG levels and long-term mortality risk in CAD patients., Methods: A retrospective analysis was conducted from a single registered database. 3061 consecutive patients with CAD confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission serum TG levels. The primary end point in this study was all-cause mortality and the secondary end point was cardiovascular mortality., Results: The mean follow-up time was 26.9 ± 13.6 months and death events occurred in 258 cases and cardiovascular death events occurred in 146 cases. Cumulative survival curves indicated that the risk of all-cause death decreased with increasing TG level (Tertile 1 vs. Tertile 2 vs. Tertile 3 = 10.3% vs. 8.6% vs. 6.3%, log rank test for overall p = 0.001). Cox regression analysis showed an independent correlation between TG level and risk of all-cause mortality [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.86] and cardiovascular mortality (HR 0.67, 95% CI 0.51-0.89) in total patients with CAD. Subgroup analysis found the similar results in patients with acute coronary syndrome and acute myocardial infarction., Conclusions: This study found an inverse association between TG levels and mortality risk in CAD patients, which suggests that the "TG paradox" may exist in CAD patients., Trial Registration: ChiCTR, ChiCTR-OOC-17010433 . Registered 17 February 2017 - Retrospectively registered.

Background: The impact of renal function on the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) remains unclear in coronary artery disease (CAD). This study sought to investigate the value of using NT-proBNP level to predict prognoses of CAD patients with different estimated glomerular filtration rates (eGFRs)., Methods: A retrospective analysis was conducted from a single registered database. 2087 consecutive patients with CAD confirmed by coronary angiography were enrolled. The primary endpoint was allcause mortality., Results: The mean follow-up time was 26.4 ± 11.9 months and death events occurred in 197 cases. The NT-proBNP levels increased with the deterioration of renal function, as well as the optimal cutoff values based on eGFR stratification to predict endpoint outcome (179.4 pg/mL, 1443.0 pg/mL, 3478.0 pg/mL, for eGFR ≥ 90, 60-90 and < 60 mL/min/1.73 m2, respectively). Compared with the routine cut-off value or overall optimal one, stratified optimal ones had superior predictive ability for endpoint in each eGFR group (all with the highest Youden's J statistics). And the prognostic value became weaker as eGFR level decreased (eGFR ≥ 90 vs. 60-90 vs. < 60 mL/min/1.73 m2, odds ratio [OR] 7.7; 95% confidence interval [CI] 1.7-33.9 vs. OR 4.8; 95% CI 2.7-8.5 vs. OR 3.0; 95% CI 1.5-6.2)., Conclusions: This study demonstrated that NT-proBNP exhibits different predictive values for prognosis for CAD patients with different levels of renal function. Among the assessed values, the NT-proBNP cut-off value determined using renal function improve the accuracy of the prognosis prediction of CAD. Moreover, lower eGFR is associated with a higher NT-proBNP cut-off value for prognostic prediction.

Purpose: Associations between Asian lung cancer (LC) and breast cancer (BC) are unknown. This study evaluates associations between LC and BC in the Taiwan population., Methods: This study was based on the Taiwan National Health Insurance data and Taiwan Cancer Registry. The cohorts included women with newly diagnosed LC or BC between 2000 and 2011 and an age- and sex-stratified random sample as a noncancer comparison cohort during the same period. Cox proportional hazards regression analysis was used to determine the risks. The National Taiwan University Hospital (NTUH) cohort, which comprised patients with confirmed pathology diagnoses of double BC/LC, was reviewed., Results: In 32,824 women with LC, there were increased risks for synchronous BC in patients younger than age 50 years (hazard ratio, 5.80; 95% CI, 1.83 to 18.73), age 50 to 59 years (HR, 2.37; 95% CI, 1.02 to 5.54), and age 60 to 69 years (HR, 4.42; 95% CI, 1.91 to 10.2). In the 88,446 women with BC, there were increased risks for synchronous LC in patients age 40 to 59 years (HR, 5.86; 95% CI, 3.05 to 11.3) and older than 60 years (HR, 1.98; 95% CI, 1.04 to 3.77). In the 128-patient NTUH double LC/BC cohort, 77 (60%) had both cancers diagnosed within 5 years of each other., Conclusion: LC is associated with an increased risk for synchronous BC in Taiwan and vice versa. Radiotherapy might not be a major risk factor for LC in BC survivors. Etiology for double LC/BC deserves additional exploration and cross-racial genomic studies.

Background: Exercise-based cardiac rehabilitation (CR) has been recognized as an essential component of the treatment for coronary heart disease (CHD). Determining the efficacy of modern alternative treatment methods is the key to developing exercise-based CR programs., Methods: Studies published through June 6, 2016, were identified using MEDLINE, EMBASE, and the Cochrane Library. English-language articles regarding the efficacy of different modes of CR in patients with CHD were included in this analysis. Two investigators independently reviewed abstracts and full-text articles and extracted data from the studies. According to the categories described by prior Cochrane reviews, exercise-based CR was classified into center-based CR, home-based CR, tele-based CR, and combined CR for this analysis. Outcomes included all-cause mortality, cardiovascular death, recurrent fatal and/or nonfatal myocardial infarction, recurrent cardiac artery bypass grafting, recurrent percutaneous coronary intervention (PCI), and hospital readmissions., Results: Sixty randomized clinical trials (n = 19,411) were included in the analysis. Network meta-analysis (NMA) demonstrated that only center-based CR significantly reduced all-cause mortality (center-based: RR = 0.76 [95% CI 0.64-0.90], p = 0.002) compared to usual care. Other modes of CR were not significantly different from usual care with regard to their ability to reduce mortality. Treatment ranking indicated that combined CR exhibited the highest probability (86.9%) of being the most effective mode, but this finding was not statistically significant due to the small sample size (combined: RR = 0.50 [95% CI 0.20-1.27], p = 0.146)., Conclusions: Current evidence suggests that center-based CR is acceptable for patients with CHD. As home- and tele-based CR can save time, money, effort, and resources and may be preferred by patients, their efficacy should be investigated further in subsequent studies.

Background: Statins therapy in the secondary prevention of coronary artery disease (CAD) is associated with a lower risk of adverse cardiovascular events. However, little is known regarding the association of elderly patients with nutritional risk on statin therapy., Aims: To investigate whether older patients with CAD who were at nutritional risk gain similar survival benefit from statins therapy as their counterparts without nutritional risk., Methods: We conducted a retrospective hospital-based cohort study among 1705 patients with CAD who were older than 65 years of age, using coronary heart disease database from 2008 to 2012. Nutritional status of included patients was gauged using the geriatric nutritional risk index. After stratification by nutritional status, the hazard of all-cause death was compared between those with or without statins therapy., Results: Of the 1705 patients included in the study (mean age 72 years; 73% male), all-cause death occurred in 146 (9.2%) patients with statins use and in 33 (26.2%) patients without statins use. The rate of all-cause death was higher in patients not receiving statins irrespective of nutritional status. After adjustments for potential confounders, the HR with statins use was 0.33 (95% CI 0.20-0.55) in patients without nutritional risk and 0.47 (95% CI 0.22-1.00) in patients with nutritional risk. No interaction effect was detected between nutritional status and statins use in relation to all-cause death (P value for interaction effect 0.516)., Conclusion: Despite of the patient's nutritional status, statins therapy as a secondary prevention in elderly CAD patients was associated with decreased risk of all-cause death.

Edge morphology and lattice orientation of single-crystal molybdenum disulfide (MoS 2 ) monolayers, a transition metal dichalcogenide (TMD), possessing a triangular shape with different edges grown by chemical vapor deposition are characterized by atomic force microscopy and transmission electron microscopy. Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic edges of MoS 2 monolayers with localized midgap electronic states, which result in greatly enhanced optical second-harmonic generation (SHG). Microscopic S-zigzag edge and S-Mo Klein edge (bare Mo atoms protruding from a S-zigzag edge) terminations and the edge-atom dependent resonance energies can therefore be deduced based on SHG images. Theoretical calculations based on density functional theory clearly explain the lower energy of the S-zigzag edge states compared to the corresponding S-Mo Klein edge states. Characterization of the atomic-scale variation of edge-enhanced SHG is a step forward in this full-optical and high-yield technique of atomic-layer TMDs.

Background: Elderly patients with coronary artery disease (CAD) frequently complicated with more cardiovascular risk factors, but received fewer evidence-based medications (EBMs). This study explored the association of EBMs compliance in different age groups and the risk of long-term death., Methods: A retrospective analysis was conducted from a single registered database. 2830 consecutive patients with CAD were enrolled and grouped into 3 categories by age. The primary end point was all-cause mortality and secondary endpoint is cardiovascular mortality., Results: The mean follow-up time was 30.25 ± 11.89 months and death occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival curves indicated that the incidence rates of all-cause death and cardiovascular death increased with age (older than 75 years old vs. 60 to 75 years old vs. younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001; cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of elderly patients using no EBMs was significantly higher than the percentages in the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR] 0.15, 95% CI 0.08-0.27; cardiac mortality: HR 0.08, 95% CI 0.04-0.19) for older CAD patients. Similar trends were found about different kinds of EBMs in elderly patients., Conclusions: Elderly patients with CAD had higher risk of death but a lower degree of compliance with EBMs usage. Elderly CAD patients could receive more clinical benefits by using EBMs.

Background: TAVR is a rapidly spreading treatment option for severe aortic valve stenosis. Significant coronary artery disease (CAD) is present in 40% to 75% of patients undergoing TAVR. However, when to treat the concomitant coronary artery lesions is controversial., Methods: This is a systematic review comparing concomitant PCI and TAVR versus staged PCI and TAVR. The OVID database was systematically searched for studies reporting PCI in patients undergoing TAVR. A random effects model was used to calculate the pooled odds ratio (OR) with 95% confidence intervals., Results: Four observational studies and a total of 209 patients were included in this analysis. Overall 30-day mortality was similar between concomitant PCI and TAVR versus staged PCI and TAVR [OR: 1.47 (0.47-4.62); P = .51], renal failure was not significantly different between both groups [OR: 3.22 (0.61-17.12); P = .17], periprocedural myocardial infarction was not different between the 2 groups [OR: 1.44 (0.12-16.94); P = .77], life-threatening bleeding did not differ between both groups [OR: 0.45 (0.11-1.87); P = .27], and major stroke also was not significantly different [OR: 3.41 (0.16-74.2); P = .44]., Conclusion: These data did not show a significant difference in short-term outcomes between concomitant PCI and TAVR versus staged PCI and TAVR.

Tremendous effort has been invested in reducing the prevalence of atherosclerotic cardiovascular disease (ASCVD) in China. Meanwhile, accumulating evidence has emerged to show the benefits of statins in the prevention of cardiovascular disease. The present study investigated the change trends of statins prescription at discharge among patients with ASCVD in recent years, differences across subtypes of ASCVD, and associated factors. The study included 51,972 patients with a discharge diagnosis of ASCVD who were hospitalized in West China Hospital from 2008 to 2014. Trends of statins prescription rates between subtypes of ASCVD were compared and potential influential factors were explored. The overall statins prescription rate in patients with ASCVD was 58.8%. Adjusted odds ratios (ORs) of increase in prescription rate per year were 1.15 (95% CI 1.13-1.17, p < 0.001), 1.14 (95% CI 1.10-1.17, p < 0.001), 1.19 (95% CI 1.16-1.23; p < 0.001), 1.14 (95% CI 1.09-1.19; p < 0.001), and 1.13 (95% CI 1.09-1.17; p < 0.001) for ASCVD, coronary artery disease, cerebrovascular disease, peripheral arterial disease (PAD), and polyvascular disease, respectively; no significant differences in trends were detected among ASCVD subtypes. However, statins prescription rates were persistently lower in cerebrovascular disease and PAD than the other two subtypes. Discharge departments, together with other physician-related and patient-related characteristics were associated with statins utilization. In conclusion, between 2008 and 2014, statins prescription rate in patients with ASCVD was not optimal. The increasing trends in statins prescription among patients with ASCVD subtypes were similar but the differences did not decrease. Consciousness of integrated and successive medical care should be strengthened in China.

Objective: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines., Method: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS. Stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained from K562-R cells by RNA interference. K562-W, K562-R and K562-R-EphB4-sh cells (10 8 ) were respectively injected subcutaneously on the dorsal surface of BALB/C female nude mice to establish the xenografts models., Result: The mRNA/protein of EphB4 was overexpressed in the DAS-resistant A2-E2 in comparison with the A1-E1 human cell lines. Further, compared with K562-R cells, the expressions of EphB4 and p-Rac1/Cdc42 protein/mRNA were significantly downregulated in K562-R-EphB4-sh cells (P<0.01). K562-R cells showed the highest DAS resistance (IC50 10.54±0.67μg/ml), but K562-R-EphB4-sh cells became sensitive to DAS (IC50 1.02±0.1μg/ml, P<0.01). The expression of EphB4/p-RhoA/MCL-1 protein was gradually increased in the stimulating of EphrinB2-Fc, which partly made K562-R-EphB4-sh cells restore sensitivity to DAS (4.18±0.30μg/ml). Meanwhile, the K562-R-EphB4-sh xenografts group had relatively good efficacy compared to K562-R xenografts nude mice receiving the same dose of DAS. The analysis of xenografts tissue also suggested parallel results with the overexpression of EphB4/RhoA/ROCK1/PTEN/MCL-1 in K562-R xenografts, which decreased in the A2-R-EphB4-sh xenografts (P<0.01)., Conclusions: The present study found that a new DAS resistance pathway of EphB4 overexpression was triggered by EphrinB2-Fc, which induced the resistance to DAS by activating RhoA/ROCK1/PTEN/MCL-1 signaling., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Frequent premature atrial complexes (PACs) are universal in the general population; however, their clinical significance is unclear. We hypothesize that frequent PACs are associated with increased risk of stroke and death. The PubMed (from 1966 to April 2017) and Embase (from 1974 to April 2017) databases were searched for longitudinal studies that reported the relation of PACs with incidence of stroke and death with various etiologies. Study quality was evaluated, and the relative risks (RR) of unfavorable outcomes in subjects with frequent PACs vs those without were calculated. Eleven studies with overall high quality were eligible according to inclusion criteria. The meta-analysis demonstrated that frequent PACs were associated with an increased risk of stroke (unadjusted RR: 2.20, 95% confidence interval [CI]: 1.79-2.70; adjusted RR: 1.41, 95% CI: 1.25-1.60) and death from all causes (unadjusted RR: 2.17, 95% CI: 1.80-2.63; adjusted RR: 1.26, 95% CI: 1.13-1.41), cardiovascular diseases (unadjusted RR: 2.89, 95% CI: 2.20-3.79; adjusted RR: 1.38, 95% CI: 1.24-1.54), and coronary artery disease (unadjusted RR: 2.74, 95% CI: 1.64-4.58; adjusted RR: 1.74, 95% CI: 1.27-2.37). No significant publication bias was detected. The association was robust in sensitivity analysis, subgroup analysis, and pooled analysis of estimates adjusting for confounding factors. Frequent PACs are not benign phenomena; they are associated with higher risk of unfavorable outcomes. Further research on the optimal management of subjects with frequent PACs is urgently required., (© 2017 Wiley Periodicals, Inc.)

The successful translation of cytotoxic T lymphocyte antigen-4 (CTLA-4) blockade has revolutionized the concept of cancer immunotherapy. Although monoclonal antibody therapeutics remain the mainstream in clinical practice, aptamers are synthetic oligonucleotides that encompass antibody-mimicking functions. Here, we report a novel high-affinity CTLA-4-antagonizing DNA aptamer (dissociation constant, 11.84 nM), aptCTLA-4, which was identified by cell-based SELEX and high-throughput sequencing. aptCTLA-4 is relatively stable in serum, promotes lymphocyte proliferation, and inhibits tumor growth in cell and animal models. Our study demonstrates the developmental pipeline of a functional CTLA-4-targeting aptamer and suggests a translational potential for aptCTLA-4., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To develop and validate prediction models of overall survival (OS) for head and neck cancer (HNC) patients based on image biomarkers (IBMs) of the primary tumor and positive lymph nodes (Ln) in combination with clinical parameters., Material and Methods: The study cohort was composed of 289 nasopharyngeal cancer (NPC) patients from China and 298 HNC patients from the Netherlands. Multivariable Cox-regression analysis was performed to select clinical parameters from the NPC and HNC datasets, and IBMs from the NPC dataset. Final prediction models were based on both IBMs and clinical parameters., Results: Multivariable Cox-regression analysis identified three independent IBMs (tumor Volume-density, Run Length Non-uniformity and Ln Major-axis-length). This IBM model showed a concordance(c)-index of 0.72 (95%CI: 0.65-0.79) for the NPC dataset, which performed reasonably with a c-index of 0.67 (95%CI: 0.62-0.72) in the external validation HNC dataset. When IBMs were added in clinical models, the c-index of the NPC and HNC datasets improved to 0.75 (95%CI: 0.68-0.82; p=0.019) and 0.75 (95%CI: 0.70-0.81; p<0.001), respectively., Conclusion: The addition of IBMs from the primary tumor and Ln improved the prognostic performance of the models containing clinical factors only. These combined models may improve pre-treatment individualized prediction of OS for HNC patients., (Copyright © 2017. Published by Elsevier B.V.)

Few studies to date address the predictive ability of CHA 2 DS 2 -VASc and R 2 CHADS 2 in CAD patients. Our aim is to investigate the prognostic performance of CHADS 2 , CHA 2 DS 2 -VASc and R 2 CHADS 2 scores in patients with coronary artery disease (CAD). Angiographically obstructive CAD patients were enrolled. The prognostic performance of the three risk scores was evaluated using Cox hazards models. In addition, we compared their predictive values by calculating C statistics, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). The endpoints are death from any cause and cardiovascular death. Of 3295 subjects with CAD, the mean CHADS 2 , CHA 2 DS 2 -VASc and R 2 CHADS 2 scores are 1.2 ± 1.0, 2.4 ± 1.4, and 1.6 ± 1.4, respectively. The CHADS 2 -guided risk classification is markedly distinct from CHA 2 DS- 2 -VASc- and R 2 CHADS 2 -guided ones. Over a median follow-up of 24 months, a total of 290 (rate 4.00/100 person-year) deaths occurred, and 163 (rate 2.2/100 person-year) were attributed to cardiovascular deaths. Event rates increase by CHADS 2 , CHA 2 DS 2 -VASc and R 2 CHADS 2 (P for trend <0.001). The multivariate analyses show 60, 111 and 82% higher risk of mortality per unit increase of CHADS 2 , CHA 2 DS 2 -VASc and R 2 CHADS 2 scores, respectively. Comparing with CHADS 2 score (c-statistic = 0.61), CHA 2 DS 2 -VASc (c-statistic 0.65, NRI 0.52 and IDI 0.06, P for all <0.05) and R 2 CHADS 2 (c-statistic 0.66, NRI 0.43 and IDI 0.09, P for all <0.05) scores provide better discrimination and reclassification for mortality. Also, CHA 2 DS 2 -VASc and R 2 CHADS 2 have comparable predictive ability of mortality to the GRACE score. The CHADS 2 , CHA 2 DS 2 -VASc and R 2 CHADS 2 scores are simple yet robust prognostic tools in CAD patients.

Objective: Obesity is a risk factor for both coronary artery disease (CAD) and chronic renal insufficiency (RI); patients with CAD are prone to obesity and RI. In this study, we try to analyze the effect of body composition on death in CAD patients with mild RI., Design: Retrospective cohort study., Subjects: A total of 1,591 consecutive CAD patients confirmed by coronary angiography were enrolled and met the mild RI criteria by estimated glomerular filtration rate: 60-90 mL/min., Main Outcome Measurements: The influence of body composition on mortality of CAD was detected in different body compositions, including body mass index (BMI), body fat (BF), and lean mass index (LMI). The end points were all-cause mortality. Cox models were used to evaluate the relationship of quintiles of body compositions with all-cause mortality., Results: A survival curve showed that the risk of death was higher in the low BMI group than in the high BMI group (log-rank for overall P = .002); LMI was inversely correlated with risk of death, such that a lower LMI was associated with a higher risk of death (log-rank for overall P < .001). No significant correlation was observed between BF and risk of death. Multifactorial correction show that LMI was still inversely correlated with risk of death (quintile 1: reference; quintile 2: hazard ratio [HR]: 0.49, 95% confidence interval [CI]: 0.26-0.92; quintile 3: HR: 0.35, 95% CI: 0.17-0.70; quintile 4: HR: 0.41, 95% CI: 0.20-0.85; quintile 5: HR: 0.28, 95% CI: 0.12-0.67)., Conclusion: For CAD patients with mild RI, BMI or BF was unrelated to risk of death, while LMI was inversely correlated with risk of death. A weak "obesity paradox" was observed in this study., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation., Methods: Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed., Results: Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups., Conclusion: Radiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities., Competing Interests: Disclosure The authors report no conflicts of interest in this work.