Incidence Trends, Clinicopathologic Characteristics, and Overall Survival Prediction in Retinoblastoma Children: SEER Prognostic Nomogram Analysis.

BACKGROUND: Retinoblastoma is the most common intraocular malignant tumor occurring among children, with an incidence rate of 1/15 000. This study built a joinpoint regression model to assess the incidence trend of retinoblastoma from 2004 to 2015 and constructed a nomogram to predict the overall survival (OS) in children. MATERIALS AND METHODS: Patients less than 19 years diagnosed with retinoblastoma from 2004 to 2015 were selected from the SEER database. Joinpoint regression analysis (version 4.9.0.0) was performed to evaluate the trends in retinoblastoma incidence rates from 2004 to 2015. Cox Regression Analysis was applied to investigate prognostic risk factors that influence OS. RESULTS: Joinpoint regression revealed that retinoblastoma incidence exhibited no significant increase or decrease from 2004 to 2015. As per the multiple Cox regression, tumor size, laterality, and residence (rural-urban continuum code) were correlated with OS and were used to construct a nomogram. The nomogram exhibited a good C-index of 0.71 (95% CI, 0.63 to 0.79), and the calibration curve for survival probability demonstrated that the predictions corresponded well with actual observations. CONCLUSIONS AND RELEVANCE: A prognostic nomogram integrating the risk factors for retinoblastoma was constructed to provide comparatively accurate individual survival predictions. If validated, this type of assessment could be used to guide therapy in patients with retinoblastoma.

Harmonic Phasor Estimation Method Considering Dense Interharmonic Interference.

Due to the limitation of frequency resolution and the spectrum leakage caused by signal windowing, the spectrums of harmonic and interharmonic components with close frequencies overlap each other. When the dense interharmonic (DI) components are close to the harmonic spectrum peaks, the harmonic phasor estimation accuracy is seriously reduced. To address this problem, a harmonic phasor estimation method considering DI interference is proposed in this paper. Firstly, based on the spectral characteristics of the dense frequency signal, the phase and amplitude characteristics are used to determine whether DI interference exists in the signal. Secondly, an autoregressive model is established by using the autocorrelation of the signal. Data extrapolation is performed on the basis of the sampling sequence to improve the frequency resolution and eliminate the interharmonic interference. Finally, the estimated values of harmonic phasor, frequency and rate of change of frequency are obtained. The simulation and some experimental results demonstrate that the proposed method can accurately estimate the parameters of harmonic phasors when DIs exist in the signal, and has a certain anti-noise capability and dynamic performance.

Permanent left bundle branch area pacing in a child with a third-degree atrioventricular block: A case report.

Permanent left bundle branch area pacing (LBBP) is a promising physiological pacing technique that has emerged in recent years. However, LBBP is almost exclusively clinically applied in adult patients. The feasibility and safety of the use of LBBP in children have not been well-assessed. Here, we report the case of a 6-year-old child with a third-degree atrioventricular block after surgical aortic valve replacement who successfully received a permanent LBBP.

[Association of TLR4 gene polymorphisms with large artery atherosclerotic stroke and vascular bed selectivity of atherosclerotic lesions].

OBJECTIVE: To assess the association of TLR4 gene polymorphisms with large artery atherosclerosis (LAA) stroke and liability to atherosclerosis in an ethnic Han population from northern China. METHODS: The study has involved 286 LAA stroke patients and 300 healthy controls. The LAA group has been divided 4 subsets according to angiostenosis conditions. Polymerase chain reaction-restriction fragment length polymorphism and pyrosequencing were employed to analyze three single nucleotide polymorphism (SNPs) (rs1927914, rs1927911 and rs2149356) of the TLR4 gene. A Haploview software package was used to analyze the haplotypes. RESULTS: SNPs rs1927911 and rs2149356 were associated with LAA stroke. Genotypic and allelic frequencies of rs1927914 did not differ significantly between the two groups. Genetic variants of the three SNPs did not vary significantly between all subsets. Haplotype analysis was revealed a significant difference between the LAA group and the control group. Compared with the controls, the frequencies of haplotypes H2 and H8 were lower, and that of H3 was greater in the LAA group. CONCLUSION: An association between the TLR4 gene polymorphisms and LAA stroke subtype in ethnic Han population in northern China has been found. However, no association of liability to atherosclerosis in different vascular bed has been found with these polymorphisms.

The Molecular Mechanism Underlying the Therapeutic Effect of Dihydromyricetin on Type 2 Diabetes Mellitus Based on Network Pharmacology, Molecular Docking, and Transcriptomics.

Type 2 diabetes mellitus (T2DM) is a chronic and complex disease, and traditional drugs have many side effects. The active compound dihydromyricetin (DHM), derived from natural plants, has been shown in our previous study to possess the potential for reducing blood glucose levels; however, its precise molecular mechanism remains unclear. In the present study, network pharmacology and transcriptomics were performed to screen the molecular targets and signaling pathways of DHM disturbed associated with T2DM, and the results were partially verified by molecular docking, RT-PCR, and Western blotting at in vivo levels. Firstly, the effect of DHM on blood glucose, lipid profile, and liver oxidative stress in db/db mice was explored and the results showed that DHM could reduce blood glucose and improve oxidative stress in the liver. Secondly, GO analysis based on network pharmacology and transcriptomics results showed that DHM mainly played a significant role in anti-inflammatory, antioxidant, and fatty acid metabolism in biological processes, on lipoprotein and respiratory chain on cell components, and on redox-related enzyme activity, iron ion binding, and glutathione transferase on molecular functional processes. KEGG system analysis results showed that the PI3K-Akt signaling pathway, IL17 signaling pathway, HIF signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and TNF signaling pathway were typical signaling pathways disturbed by DHM in T2DM. Thirdly, molecular docking results showed that VEGFA, SRC, HIF1A, ESR1, KDR, MMP9, PPARG, and MAPK14 are key target genes, five genes of which were verified by RT-PCR in a dose-dependent manner. Finally, Western blotting results revealed that DHM effectively upregulated the expression of AKT protein and downregulated the expression of MEK protein in the liver of db/db mice. Therefore, our study found that DHM played a therapeutic effect partially by activation of the PI3K/AKT/MAPK signaling pathway. This study establishes the foundation for DHM as a novel therapeutic agent for T2DM. Additionally, it presents a fresh approach to utilizing natural plant extracts for chemoprevention and treatment of T2DM.

Mind shift I: Fructus Aurantii - Rhizoma Chuanxiong synergistically anchors stress-induced depression-like behaviours and gastrointestinal dysmotility cluster by regulating psycho-immune-neuroendocrine network.

BACKGROUND: Researchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory. PURPOSE: MDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs. STUDY DESIGN: Acute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster. METHODS/RESULTS: Here, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling. CONCLUSION: Brain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.

High Body Mass Index Was Associated With Human Epidermal Growth Factor Receptor 2-Positivity, Histological Grade and Disease Progression Differently by Age.

Background: Breast cancer is the most commonly occurring cancer among women. The relationship between the obesity paradox and breast cancer is still unclear. The goal of this study is to elucidate the association between high body mass index (BMI) and pathological findings by age. Methods: We collected BMI information pertinent to breast cancer patients from the Gene Expression Omnibus (GEO) database. We use a BMI of 25 as a boundary, and those greater than 25 are defined as high BMI. Besides, we segregated the patients based on age into two age groups: < 55 years, and > 55 years. In this study, R × C Chi-square for trend and binary logistic regression was used to estimate the odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: Higher BMI was associated with less breast cancer incidence in females younger than 55 years of age (OR = 0.313, CI: 0.240 - 0.407). High BMI was associated with human epidermal growth factor receptor 2 (HER2) positivity in breast cancer patients of less than 55 years (P < 0.001), but not in the older patients. High BMI was associated with histological grade lower than 2 in the breast cancer patients older than 55 years, but not in younger patients (OR = 0.288, CI: 0.152 - 0.544). Besides, high BMI was associated with worse progression-free survival in younger breast cancer patients, but not in older patients (P < 0.05). Conclusions: Our results described a significant relationship between breast cancer incidence and BMI at different ages and benefit breast cancer patients to implement strategies to control their BMI for reducing the recurrence and distant recurrence.

Molecular classification of human papilloma virus-negative head and neck squamous cell carcinomas: Cell cycle-based classifier and prognostic signature.

The molecular classification of human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs) remains questionable. Differentially expressed genes were detected between tumor and normal tissues and GSEA showed they are associated with cell cycle pathways. This study aimed to classify HPV-negative HNSCCs based on cell cycle-related genes. The established gene pattern was correlated with tumor progression, clinical prognosis, and drug treatment efficacy. Biological analysis was performed using HNSCC patient sample data obtained from the Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Gene Expression Omnibus (GEO) databases. All samples included in this study contained survival information. RNA sequencing data from 740 samples were used for the analysis. Previously characterized cell cycle-related genes were included for unsupervised consensus clustering. Two subtypes of HPV-negative HNSCCs (C1, C2) were identified. Subtype C1 displayed low cell cycle activity, 'hot' tumor microenvironment (TME), earlier N stage, lower pathological grade, better prognosis, and higher response rate to the immunotherapy and targeted therapy. Subtype C2 was associated with higher cell cycle activity, 'cold' TME, later N stage, higher pathological grade, worse prognosis, and lower response rate to the treatment. According to the nearest template prediction method, classification rules were established and verified. Our work explored the molecular mechanism of HPV-negative HNSCCs in the view of cell cycle and might provide new sights for personalized anti-cancer treatment.

Recent Updates on the Efficacy of Mitocans in Photo/Radio-Therapy for Targeting Metabolism in Chemo/Radio-Resistant Cancers: Nanotherapeutics.

Conventional therapeutic modalities against the cancers such as surgery, chemotherapy (CT) and radiotherapy (RT) have limited efficacy due to drug resistance, and adverse effects. Recent developments in nanoscience emphasized novel approaches to overcome the aforementioned limitations and subsequently improve overall clinical outcomes in cancer patients. Photodynamic therapy (PDT), photothermal therapy (PTT), and radiodynamic therapy (RDT) can be used as cancer treatments due to their high selectivity, low drug resistance, and low toxicity. Mitocans are the therapeutic molecules that can produce anti-cancer effects by modulating mitochondria functions and they have significant implications in cancer therapy. Mitochondria- targeted therapy is a promising strategy in cancer treatment as these organelles play a crucial function in the regulation of apoptosis and metabolism in tumor cells and are more vulnerable to hyperthermia and oxidative damage. The aim of this review is used to explore the targeting efficacy of mitocans in the nanotherapeutic formulation when combined with therapies like PDT, PTT, RDT. We searched several databases include Pubmed, relemed, scopus, google scholar, Embase and collected the related information to the efficacy of mitocans in nanotherapeutics when combined with photo-radiotherapy to target chemo/radio-resisant tumor cells. In this review, we vividly described research reports pertinent to the selective delivery of chemotherapy molecules into specific sub-organelles which can significantly improve the efficiency of cancer treatment by targeting tumor cell metabolism. Furthermore, the rational design, functionalization and application of various mitochondrial targeting units, including organic phosphine/sulfur salts, quaternary ammonium salts, transition metal complexes, and mitochondria-targeted cancer therapy such as PDT, PTT, RDT, and others were summarized. Mainly, the efficacy of these modalities against mtDNA and additional nanotherapeutic strategies with photosensitizers, or radiotherapy to target mitochondrial metabolism in tumor cells with chemo/radio-resistance were delineated. This review can benefit nanotechnologists, oncologists, and radiation oncologists to develop rational designs and application of novel mitochondrial targeting drugs mainly to target metabolism in chemo/radio-resistant cancer cells in cancer therapy.

Insight into the mechanism of Xiao-Chai-Hu-Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut ß-GUS.

BACKGROUND: Irinotecan (CPT-11, Camptosar@) is a first-line drug for metastatic colorectal cancer. CPT-11-induced diarrhea, which is closely related to the concentrations of ß-glucuronidase (ß-GUS) and SN-38 in the gut, largely limits its clinical application. PURPOSE: Herein, Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for ß-GUS from the gut microbiota. METHODS: First, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of ß-GUS in intestine were examined. We also resolved the 3D structure of ß-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit ß-GUS. RESULTS: In XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of ß-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of ß-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT. CONCLUSIONS: Overall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.

Chinese Clinical Trial Registry 13-year data collection and analysis: geographic distribution, financial support, research phase, duration, and disease categories.

Objective: To evaluate the current status of trial registration on the Chinese Clinical Trial Registry (ChiCTR). Design: In this descriptive study, a multi-dimensional grouping analysis was conducted to estimate trends in the annual trial registration, geographical distribution, sources of funding, targeted diseases, and trial subtypes. Setting: We have analyzed all clinical trial records (over 30,000) registered on the Chinese Clinical Trial Registry (ChiCTR) from 2007 to 2020 executed in China. Main outcomes and measures: The main outcome was the baseline characteristics of registered trials. These trials were categorized and analyzed based on geographical distribution, year of implementation, disease type, resource and funding type, trial duration, trial phase, and the type of experimental approach. Results: From 2008 to 2017, a consistent upward trend in clinical trial registrations was observed, showing an average annual growth rate of 29.2%. The most significant year-on-year (yoy%) growth in registrations occurred in 2014 (62%) and 2018 (68.5%). Public funding represented the predominant source of funding in the Chinese healthcare system. The top five ChiCTR registration sites for all disease types were highly populated urban regions of China, including Shanghai (5,658 trials, 18%), Beijing (5,127 trials, 16%), Guangdong (3,612 trials, 11%), Sichuan (2,448 trials, 8%), and Jiangsu (2,196 trials, 7%). Trials targeting neoplastic diseases accounted for the largest portion of registrations, followed by cardio/cerebrovascular disease (CCVD) and orthopedic diseases-related trials. The largest proportions of registration trial duration were 1-2 years, less than 1 year, and 2-3 years (at 27.36, 26.71, and 22.46%). In the case of the research phase, the top three types of all the registered trials are exploratory research, post-marketing drugs, and clinical trials of new therapeutic technology. Conclusion and relevance: Oncological and cardiovascular diseases receive the highest share of national public funding for medical clinical trial-based research in China. Publicly funded trials represent a major segment of the ChiCTR registry, indicating the dominating role of public governance in this health research sector. Furthermore, the growing number of analyzed records reflect the escalation of clinical research activities in China. The tendency to distribute funding resources toward exceedingly populated areas with the highest incidence of oncological and cardiovascular diseases reveals an aim to reduce the dominating disease burden in the urban conglomerates in China.

Prognostic significance of lncRNA AP004608.1 in prostate cancer.

This study aimed to screen and determine the value of AP004608.1 expression as a biomarker for Prostate cancer (PCa) survival. We investigated the expression and prognosis of AP004608.1 through bioinformatics analysis. Low AP004608.1 expression predicted favorable Overall survival (OS) and Progression-free survival (PFS) in PCa patients, according to the Cancer Genome Atlas (TCGA) database. Cox regression demonstrated that low AP004608.1 expression were in-dependent biomarkers for OS. Moreover, Gene Expression Omnibus (GEO) database was utilized to verify the prognostic role of AP004608.1 in PCa, and the similar results were reached. A meta-analysis revealed that low AP004608.1 expression was closely relevant to better OS. AP004608.1 could constitute a promising prognostic biomarker, and probably plays an important role in PCa.

Chaihu-Shugan-San ameliorates tumor growth in prostate cancer promoted by depression via modulating sphingolipid and glycerinphospholipid metabolism.

Background: Psychologic depression is a pivotal pathological characteristic and has been shown to promote prostate cancer (PCa) progression. Chaihu-Shugan-San (CSS), a well-known Chinese herbal decoction, exhibits efficacy in the treatment of stress-accelerated PCa. However, the underlying mechanism of CSS in resisting PCa growth is still unknown, and further study is needed. Objective: To evaluate the effects of CSS on stress-accelerated PCa in a BALB/C nude mice model and to investigate the underlying mechanisms. Methods: PC-3 cells were implanted into BALB/C nude mice, and the stressed mice were exposed to chronic unpredictable mild stress (CUMS) to study the effects of CSS. The PCa growth were evaluated by tumor volume and tumor weight. Analyses of depression-like behaviors were evaluated by sucrose consumption test, tail suspension test and open field test. Network pharmacology was used to analyze the potential targets and signaling pathways of CSS against PCa. Untargeted lipidomics were used to analyze the serum lipid profiles and further elucidate the possible mechanism. Results: In the CUMS stressed PCa mice, CSS can restrain tumor growth with reduced tumor volume and tumor weight, and depression-like behaviors with increased sucrose consumption, reduced immobility duration, and increased total distance and center distance. Network pharmacology suggested that the lipid metabolism-related pathways are the most likely potential targets of CSS against PCa. Using untargeted lipidomics analysis, 62 lipids were found to have significant changes in PCa mice under CUMS treatment. The levels of glycerophospholipids containing phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylglycerol (PG), except PC (18:0_22:6) and PC (18:0_20:4), were significantly increased. Likewise, the levels of all sphingolipids (including sphingomyelin (SM), ceramides (Cer) and hexosyl-1-ceramide (Hex1Cer)) and diglyceride (DG) (32:1e) were significantly increased. CSS water extract was found to contribute to restore 32 lipids including 6 sphingolipids, 25 glycerophospholipids and 1 glyceride. Conclusion: This study is the first to delineate the lipid profile of stressed PCa BALB/C nude mice using untargeted lipidomics analysis. CSS restrained tumor growth and ameliorated depression-like behaviors by reprogramming lipid metabolism. Intervention of lipid metabolism could be a preventive and therapeutic approach for PCa patients with depression.

Noise spectrum characteristics of marine pump units induced by different excitation sources.

To study the noise spectrum characteristics of marine pump units induced by different excitation sources, a computational aeroacoustic (CAA) model of the internal and external field noise of a marine pump was established. The coupled acoustic-vibration method was used to obtain the spectrum characteristics of internal and external field noise. The accuracy and feasibility of the simulation method for noise prediction were confirmed through a noise test. Due to the different mediums in the internal and external fields of the marine pump, an external field acoustic model was established based on the automatically matched layer (AML) technology. The spectral characteristics of different excitation sources and the spatial distribution of the radiated sound field were analyzed, and the contribution of different sound source excitations to the internal and external sound field was revealed. The results show that the main frequency of the internal field noise generated by different excitations is at the blade passing frequency, and the internal field noise induced by the dipole acoustic excitations dominates at 180.6 dB. For the external field noise, the main frequency is still located at the blade passing frequency. The radiation noise induced by the fluid excitation (139.2 dB) is higher than that induced by the dipole excitations (surface dipole, 136.3 dB; rotating dipole, 137.3 dB).

Identification of absorbed compounds of Xiao Yao San Jia Wei and pharmacokinetic study in depressed rats by force swimming stress.

Xiao-Yao-San-Jia-Wei (XYSJW) is a commonly prescribed formulation for depression and anorexia in the Jiang Su Province Hospital of Chinese Medicine. Unfortunately, the proper dosage of this formulation is still unclear due to its limited chemical and pharmacokinetic profiles. Thus, in the present study, a sensitive, precise, and rapid procedure for the identification of absorbed compounds (Cs) in the plasma of depressed rats together with a pharmacokinetic analysis was established with the help of ultra-flow liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UFLC-Q-TOF MS/MS) and ultra-flow liquid chromatography coupled with electrospray ionization triple quadrupole tandem mass spectrometry (UFLC-QQQ MS/MS). Based on the characteristic fragmentation, neutral loss, mass defect filter, relevant literature and reference standards, 225 Cs in the XYSJW extract and 20 Cs in the plasma of the depressed rats were tentatively recognized via UFLC-Q-TOF MS/MS and UFLC-QQQ MS/MS. Then, the 12 major absorbed Cs in the depressed rats after oral XYSJW administration were chosen to further investigate its pharmacokinetic profile by UFLC-QQQ MS/MS. This study provides a systematic approach for the rapid and qualitative analysis of absorbed Cs in depressed rats and investigating the pharmacokinetics of XYSJW. More importantly, our work provides key information on the chemical and pharmacokinetic profiles of XYSJW in vitro and in vivo, which may benefit its therapeutic efficacy and further pharmacological studies involving this formulation.

Novel Implications of Nanoparticle-Enhanced Radiotherapy and Brachytherapy: Z-Effect and Tumor Hypoxia.

Radiotherapy and internal radioisotope therapy (brachytherapy) induce tumor cell death through different molecular signaling pathways. However, these therapies in cancer patients are constrained by dose-related adverse effects and local discomfort due to the prolonged exposure to the surrounding tissues. Technological advancements in nanotechnology have resulted in synthesis of high atomic elements such as nanomaterials, which can be used as radiosensitizers due to their photoelectric characteristics. The aim of this review is to elucidate the effects of novel nanomaterials in the field of radiation oncology to ameliorate dose-related toxicity through the application of ideal nanoparticle-based radiosensitizers such as Au (gold), Bi (bismuth), and Lu (Lutetium-177) for enhancing cytotoxic effects of radiotherapy via the high-Z effect. In addition, we discuss the role of nanoparticle-enhanced radiotherapy in alleviating tumor hypoxia through the nanodelivery of genes/drugs and other functional anticancer molecules. The implications of engineered nanoparticles in preclinical and clinical studies still need to be studied in order to explore potential mechanisms for radiosensitization by minimizing tumor hypoxia, operational/logistic complications and by overcoming tumor heterogeneity in radiotherapy/brachytherapy.

Immune Repertoire and Advancements in Nanotherapeutics for the Impediment of Severe Steroid Resistant Asthma (SSR).

Severe steroid-resistant asthma (SSR) patients do not respond to the corticosteroid therapies due to the heterogeneity, and genome-wide variations. However, there are very limited reports pertinent to the molecular signaling underlying SSR and making pharmacologists, and formulation scientists to identify the effective therapeutic targets in order to produce novel therapies using novel drug delivery systems (NDDS). We have substantially searched literature for the peer-reviewed and published reports delineating the role of glucocorticoid-altered gene expression, and the mechanisms responsible for SSR asthma, and NDDS for treating SSR asthma using public databases PubMed, National Library of Medicine (NLM), google scholar, and medline. Subsequently, we described reports underlying the SSR pathophysiology through several immunological and inflammatory phenotypes. Furthermore, various therapeutic strategies and the role of signaling pathways such as mORC1-STAT3-FGFBP1, NLRP3 inflammasomes, miR-21/PI3K/HDAC2 axis, PI3K were delineated and these can be considered as the therapeutic targets for mitigating the pathophysiology of SSR asthma. Finally, the possibility of nanomedicine-based formulation and their applications in order to enhance the long term retention of several antioxidant and anti-asthmatic drug molecules as a significant therapeutic modality against SSR asthma was described vividly.

High serum superoxide dismutase activity improves radiation-related quality of life in patients with esophageal squamous cell carcinoma.

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China. Intensity-modulated radiation therapy and volume-modulated arc therapy have become the main treatments for esophageal carcinoma; however, side effects caused by radiotherapy greatly impact the quality of life in these patients. This study aimed to explore the impact of serum superoxide dismutase (SOD) levels on the prognosis of patients with ESCC undergoing radiotherapy. METHODS: Patients aged between 18 and 80 years with lower-middle ESCC who underwent radiotherapy were eligible for this assessment. Adverse events, responses, treatment outcomes, and overall survival (OS) were assessed. Between 2012 and 2014, 195 patients were enrolled, of which 65 were assigned to the low- and high-SOD groups based on their serum SOD values. RESULTS: The baseline characteristics were similar between the two groups, except for the T staging. Adverse events in the low-SOD group were significantly higher than those in the high-SOD group (radiation esophagitis, p=0.007; radiation pneumonitis, p=0.032; leukopenia, p=0.023; thrombocytopenia, p=0.037; anemia, p=0.041). There were no significant differences in response, treatment outcomes, or OS. CONCLUSION: In conclusion, high serum SOD activity improved post-radiotherapy quality of life but did not impact the prognosis of patients with ESCC. To the best of our knowledge, this study is the first to report that serum SOD activity is associated with radiation-induced toxicity and moderately increased radiotherapeutic response in patients with ESCC undergoing radiotherapy.

Facile construction of Fe, N and P co-doped carbon spheres by carbothermal strategy for the adsorption and reduction of U(vi).

In this work, nitrogen and phosphorus co-doped magnetic carbon spheres encapsulating well-dispersed active Fe nanocrystals (Fe/P-CN) were fabricated via a simple copolymer pyrolysis strategy. Benefiting from heteroatoms doping, Fe/P-CN could primarily adsorb soluble U(vi) ions through abundant functional groups, and subsequently, the adsorbed U(vi) could be reduced to insoluble U(iv) by Fe nanocrystals. Fe/P-CN pyrolyzed at 800 °C (Fe/P-CN-800) exhibited excellent U(vi) removal capacity of 306.76 mg g-1, surpassing nitrogen and phosphorus co-doped carbon spheres and nano zero-valent iron. In addition, the magnetic separation and thermal reactivation properties endow Fe/P-CN-800 with excellent reusability. This research, especially, provides a promising synergistic adsorption and reduction strategy to effectively remove U(vi) using heteroatom-doped composites.

Artificial intelligence-assisted analysis on the association between exposure to ambient fine particulate matter and incidence of arrhythmias in outpatients of Shanghai community hospitals.

BACKGROUND: Recently, the impact of fine particulate matter pollution on cardiovascular system is drawing considerable concern worldwide. The association between ambient fine particulate and the cardiac arrhythmias is not clear now. OBJECTIVE: To study associations of ambient fine particulate with incidence of arrhythmias in outpatients. METHODS: Data was collected from the remote electrocardiogram (ECG) system covering 282 community hospitals in Shanghai from June 24th, 2014 to June 23rd, 2016. ECG was performed for patients admitted to above hospitals with complaining of chest discomfort or palpitation, or for regular check-ups. Air quality data during this time period was obtained from China National Environment Monitoring Center. A generalized additive quasi-Poisson model was established to examine the associations between PM2.5 and cardiac arrhythmias. RESULTS: Cardiac arrhythmias were detected in 202,661 out of 1,016,579 outpatients (19.9%) and fine particulate matter ranged from 6 to 219 µg/m3 during this period. Positive associations were evidenced between fine particulate matter level and prevalence of cardiac arrhythmia by different lag models. Per 10 µg/m3 increase in fine particulate matter was associated with a 0.584%(95%CI:0.346-0.689%, p < 0.001) increase of cardiac arrhythmia detected in these patient cohort at lag0-2. For different types of cardiac arrhythmias, an immediate arrhythmogenic effect of fine particulate matter (increase of the estimates of cardiac arrhythmia prevalence detected in daily outpatient visits) was found with paroxysmal supraventricular tachycardia; a lag effect was found with atrial fibrillation; and both immediate and lag effect was found with premature atrial contractions or atrial tachycardia, atrioventricular block. Moreover, the impact of fine particulate matter on cardiac arrhythmias was significantly greater in women (lag3 and lag0-4), and in people aged <65 years (lag0). CONCLUSION: Ambient exposure to fine particulate matter is linked with increased risk of arrhythmias in outpatients visiting Shanghai community hospitals, with an immediate or lag effect. The arrhythmogenic effect varies among different types of cardiac arrhythmias.