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This article aims to study the correlation between dietary magnesium intake and pulmonary function, utilizing data from the National Health and Nutrition Examination Survey (NHANES) database. This cross-sectional study examined representative samples of adults from the USA (n = 818; NHANES 2007-2012) to explore the correlation between magnesium intake and pulmonary function. We obtained the average magnesium intake over 2 days, as well as measured pulmonary function parameters, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, peak expiratory flow rate (PEF), and forced expiratory flow between 25 and 75% of FVC (FEF 25-75% ). Weighted multivariable linear regression was used to investigate the relationship between magnesium intake and pulmonary function. Additionally, subgroup analyses, interaction tests, and sensitivity analyses were conducted. Weighted multiple linear regression models revealed a significant positive correlation between magnesium and pulmonary function, even after adjusting for all included confounding variables. When we categorized magnesium intake into tertiles, we found that participants in the highest tertile of magnesium intake had significantly higher values for FVC (β: 898.54, 95%CI: 211.82-1585.25), FEV1 (β: 858.16, 95%CI: 212.41-1503.91), FEV1/FVC (β: 0.024, 95%CI: 0.004-0.044), PEF (β: 1324.52, 95%CI: 481.71-2167.33), and FEF 25-75% (β: 831.39, 95%CI: 84.93-1577.84). Upon stratifying the data by age and sex, it was observed that this positive correlation was particularly pronounced among men aged 40-79. At the same time, the stability of the results was further confirmed by sensitivity analyses. This study suggested that dietary magnesium intake may improve pulmonary function., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Jianpi-Huatan-Huoxue-Anshen formula [Tzu-Chi cancer-antagonizing & life-protecting II decoction (TCCL)] is a Chinese medical formula that has been clinically shown to reduce the gastrointestinal side effects of chemotherapy in cancer patients and improve their quality of life. However, its effect and mechanism on the intestinal microecology after chemotherapy are not yet clear., Aim: To discover the potential mechanisms of TCCL on gastrointestinal inflammation and microecological imbalance in chemotherapy-treated mice transplanted with hepatocellular carcinoma (HCC)., Methods: Ninety-six mice were inoculated subcutaneously with HCC cells. One week later, the mice received a large dose of 5-fluorouracil by intraperitoneal injection to establish a HCC chemotherapy model. Thirty-six mice were randomly selected before administration, and feces, ileal tissue, and ileal contents were collected from each mouse. The remaining mice were randomized into normal saline, continuous chemotherapy, Yangzheng Xiaoji capsules-treated, and three TCCL-treated groups. After treatment, feces, tumors, liver, spleen, thymus, stomach, jejunum, ileum, and colon tissues, and ileal contents were collected. Morphological changes, serum levels of IL-1β, IL-6, IL-8, IL-10, IL-22, TNF-α, and TGF-β, intestinal SIgA, and protein and mRNA expression of ZO-1, NF-κB, Occludin, MUC-2, Claudin-1, and IκB-α in colon tissues were documented. The effect of TCCL on the abundance and diversity of intestinal flora was analyzed using 16S rDNA sequencing., Results: TCCL treatment improved thymus and spleen weight, thymus and spleen indexes, and body weight, decreased tumor volumes and tumor tissue cell density, and alleviated injury to gastric, ileal, and colonic mucosal tissues. Among proteins and genes associated with inflammation, IL-10, TGF-β, SIgA, ZO-1, MUC-2, and Occludin were upregulated, whereas NF-κB, IL-1β, IL-6, TNF-α, IL-22, IL-8, and IκB-α were downregulated. Additionally, TCCL increased the proportions of fecal Actinobacteria , AF12 , Adlercreutzia , Clostridium , Coriobacteriaceae , and Paraprevotella in the intermediate stage of treatment, decreased the proportions of Mucipirillum , Odoribacter , RF32 , YS2 , and Rikenellaceae but increased the proportions of p_Deferribacteres and Lactobacillus at the end of treatment. Studies on ileal mucosal microbiota showed similar findings. Moreover, TCCL improved community richness, evenness, and the diversity of fecal and ileal mucosal flora., Conclusion: TCCL relieves pathological changes in tumor tissue and chemotherapy-induced gastrointestinal injury, potentially by reducing the release of pro-inflammatory factors to repair the gastrointestinal mucosa, enhancing intestinal barrier function, and maintaining gastrointestinal microecological balance. Hence, TCCL is a very effective adjuvant to chemotherapy., Competing Interests: Conflict-of-interest statement: The authors declare that there are no known competing financial interests or personal relationships among all authors of this article that could influence all studies reported in this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Bowel sounds can reflect the movement and health status of the gastrointestinal tract. However, the traditional manual auscultation method has subjective deviation and is time-consuming and labor-intensive. In order to better assist doctors in diagnosing bowel sounds and improve the reliability and efficiency of bowel sound detection, this study proposed a deep neural network model that combines a residual neural network (ResNet), a bidirectional long short-term memory network (BiLSTM), and an attention mechanism. Firstly, a large number of labeled clinical data was collected using the self-developed multi-channel bowel sound acquisition system, and the multi-scale wavelet decomposition and reconstruction method was used to preprocess the bowel sounds. Then, log Mel spectrogram features were extracted and sent to the network for training. Finally, the performance and effectiveness of the model were evaluated and verified by 10-fold cross-validation and an ablation experiment. The experimental results showed that the precision, recall, and F 1 score of the model reached 83%, 76%, and 79%, respectively, and it could effectively detect bowel sound segments and locate their start and end times, performing better than previous algorithms. This algorithm can not only provide auxiliary information for doctors in clinical practice but also offer technical support for further analysis and research of bowel sounds.

The RNA modification, 5-methylcytosine (m 5 C), has recently gained prominence as a pivotal post-transcriptional regulator of gene expression, intricately intertwined with various tumorigenic processes. However, the exact mechanisms governing m 5 C modifications during the onset and progression of colorectal cancer (CRC) remain unclear. Here, it is determined that the m 5 C methyltransferase NSUN2 exhibits significantly elevated expression and exerts an oncogenic function in CRC. Mechanistically, NSUN2 and YBX1 are identified as the "writer" and "reader" of ENO1, culminating in the reprogramming of the glucose metabolism and increased production of lactic acid in an m 5 C-dependent manner. The accumulation of lactic acid derived from CRC cells, in turn, activates the transcription of NSUN2 through histone H3K18 lactylation (H3K18la), and induces the lactylation of NSUN2 at the Lys356 residue (K356), which is crucial for capturing target RNAs. Together, these findings reveal an intriguing positive feedback loop involving the NSUN2/YBX1/m 5 C-ENO1 signaling axis, thereby bridging the connection between metabolic reprogramming and epigenetic remodeling, which may shed light on the therapeutic potential of combining an NSUN2 inhibitor with immunotherapy for CRC., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Objective: To investigate the treatment of internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma. Methods: The clinical data of 7 patients with internal carotid artery rupture after radiotherapy for nasopharyngeal carcinoma from March 2020 to March 2023 were retrospectively analyzed. Results: Skull base osteonecrosis with infection occurred in 4 cases, and tumor recurrence with infection in 3 cases. DSA showed that internal carotid artery rupture was located in the internal carotid artery petrosal segment in 6 cases, and in the paravicular segment in 1 case. Balloon occlusion test（BOT） was performed in 6 patients, of which 3 passed and 3 failed. Vascular treatment included internal carotid artery embolization（4 cases）, false aneurysm embolization 1 case（rebleeding）, coated stent 1 case（rebleeding）, muscle compression during operation（1 case）. Patients with rebleeding received high-flow bypass. Three cases developed cerebral infarction after embolization without severe sequelae after treatment, and no death occurred within 90 days. After bleeding control, all 3 patients with cranial base necrosis received surgical treatment to remove the necrotic bone and tissue flap repair, and 1 patient with recurrence received gamma knife and targeted therapy, 1 patient received immune and surgical therapy, and 1 patient received immune and targeted therapy. Conclusion: Rupture and hemorrhage of internal carotid artery after radiotherapy is related to tumor invasion, tissue injury and local infection after radiotherapy. For those caused by tumor invasion, it is recommended to sacrifice the responsible vessels. For those caused by infection, emergency surgery is recommended and blood vessels preserved. Emergency vascular occlusion remains a life-saving option., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Tumors that resist anoikis, a programmed cell death triggered by detachment from the extracellular matrix, promote metastasis; however, the role of anoikis-related genes (ARGs) in colorectal cancer (CRC) stratification, prognosis, and biological functions remains unclear., Methods: We obtained transcriptomic profiles of CRC and 27 ARGs from The Cancer Genome Atlas, the Gene Expression Omnibus, and MSigDB databases, respectively. CRC tissue samples were classified into two clusters based on the expression pattern of ARGs, and their functional differences were explored. Hub genes were screened using weighted gene co-expression network analysis, univariate analysis, and least absolute selection and shrinkage operator analysis, and validated in cell lines, tissues, or the Human Protein Atlas database. We constructed an ARG-risk model and nomogram to predict prognosis in patients with CRC, which was validated using an external cohort. Multifaceted landscapes, including stemness, tumor microenvironment (TME), immune landscape, and drug sensitivity, between high- and low-risk groups were examined., Results: Patients with CRC were divided into C1 and C2 clusters. Cluster C1 exhibited higher TME scores, whereas cluster C2 had favorable outcomes and a higher stemness index. Eight upregulated hub ARGs (TIMP1, P3H1, SPP1, HAMP, IFI30, ADAM8, ITGAX, and APOC1) were utilized to construct the risk model. The qRT-PCR, Western blotting, and immunohistochemistry results were consistent with those of the bioinformatics analysis. Patients with high risk exhibited worse overall survival (p < 0.01), increased stemness, TME, immune checkpoint expression, immune infiltration, tumor mutation burden, and drug susceptibility compared with the patients with low risk., Conclusion: Our results offer a novel CRC stratification based on ARGs and a risk-scoring system that could predict the prognosis, stemness, TME, immunophenotypes, and drug susceptibility of patients with CRC, thereby improving their prognosis. This stratification may facilitate personalized therapies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Circular RNAs (circRNAs) play important roles in colorectal cancer (CRC) development and progression. This study aimed to investigate the function and molecular mechanism of circPPP2R4 in CRC. Based on bioinformatic analyses and validation by qRT-PCR, we identified a novel circRNA, circPPP2R4, which was upregulated in CRC tissues. Receiver operating characteristic curve analysis implied a high diagnostic value of circPPP2R4 for CRC. Additionally, high circPPP2R4 levels were positively correlated with advanced clinical stage and lymph node metastasis. Functionally, circPPP2R4 overexpression facilitated CRC cells proliferation, migration and invasion, whereas circPPP2R4 knockdown attenuated the malignant behaviors. In mouse models, circPPP2R4 overexpression remarkably promoted tumor growth and lung metastasis. Mechanistically, a series of experiments containing RIP, RNA pull-down, and dual-luciferase reporter assays revealed the circPPP2R4/miR-646/FOXK1 axis in CRC. Further experiments were conducted to verify that circPPP2R4 reduced reactive oxygen species generation to exert its oncogenic function by sponging miR-646 to upregulate FOXK1 expression. For the first time, we identified the regulatory role of circPPP2R4 in CRC pathogenesis, providing a potential diagnostic biomarker and therapeutic strategy for CRC., (© 2023 Wiley Periodicals LLC.)

This study aimed to investigate the relationship between the dietary approaches to stop hypertension (DASH) dietary patterns and bone mineral density (BMD) in adults residing in the United States. To achieve this, data from the National Health and Nutrition Examination Survey (NHANES) database for 2011-2018 were utilized. This study utilized the NHANES database from 2011 to 2018, with a sample size of 8,486 US adults, to investigate the relationship between the DASH diet and BMD. The DASH diet was assessed based on nine target nutrients: total fat, saturated fat, protein, fiber, cholesterol, calcium, magnesium, sodium and potassium. The primary outcome measures were BMD values at the total BMD, thoracic spine, lumbar spine, and pelvis. Multivariable linear models were employed to analyze the association between the DASH diet and BMD. Interaction tests, subgroup, and sensitivity analysis were also followed. A negative correlation was observed between the DASH diet and total BMD (OR: - 0.003 [95%CI: - 0.005, - 0.001), pelvic (OR: - 0.005 [95%CI: - 0.007, - 0.002]), and thoracic BMD (OR: - 0.003 [95%CI: - 0.005, - 0.001]). However, the DASH diet does not appear to have a particular effect on lumbar spine BMD (OR: - 0.002 [95%CI: - 0.004, 0.001]). Similarly, when the DASH diet was categorized into tertiles groups, the relationship with total BMD, pelvic BMD, thoracic BMD, and lumbar spine BMD remained consistent. Furthermore, we performed a sensitivity analysis by converting BMD to Z-scores, and the results remained unchanged. Subgroup analyses and interaction tests indicated no significant dependence of BMI, gender, smoking, hypertension, and diabetes on the observed association (all p for interactions > 0.05). The DASH diet has been identified as potentially reducing total BMD, while specifically impacting thoracic and pelvic BMD. However, it appears to have no significant effect on lumbar spine BMD., (© 2024. The Author(s).)

Cancer immunotherapy is arguably the most rapidly advancing realm of cancer treatment. Glutathione peroxidase 4 (GPX4) has emerged as the vital enzyme to prevent lipid peroxidation and maintain cellular redox homeostasis. However, the mechanism of GPX4 in the regulation of cancer immunotherapy of colon adenocarcinoma (COAD) are incompletely understood. In pan-cancer analysis, we found that GPX4 showed remarkably upregulated expression and exhibited significant association with overall survival in multiple cancer types, especially COAD. Furthermore, upregulated GPX4 expression was positively correlated with increased immune cells infiltration and enhanced expression of immunomodulators. Mechanistically, RBM15B- and IGFBP2-mediated N6-methyladenosine (m6A) modification and NSUN5-mediated 5-methylcytosine (m5C) modification of GPX4 facilitated anticancer immunity via activation of cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) signaling by maintaining redox homeostasis in COAD. The risk model and nomogram model constructed based on the GPX4-derived genes further confirmed the prognostic and treatment-guiding value of GPX4. In all, our study demonstrated that m6A and m5C modification of GPX4 may be a promising target for cancer immunotherapy via activating the cGAS-STING signaling pathway in COAD., (© 2023. The Author(s).)

In this Letter, we propose a novel, to the best of our knowledge, dual-mode tunable absorber that utilizes quasi-bound states in the continuum (q-BIC) based on the periodically arranged silicon cylinders tetramer. By introducing asymmetry perturbation through manipulating the diameters of diagonal cylinders in the all-dielectric structure, the symmetry-protected BIC (SP-BIC) transforms into q-BIC, leading to the emergence of one transmission and one reflection Fano-like resonant mode. The relationship between the quality factor of each mode and the asymmetry parameter α is analyzed, revealing an exponential dependence with an exponent of -1.75, i.e., Q ∝ α -1.75 . To explain the underlying physics, multipole decomposition analysis and Aleksandra's theory are applied. Subsequently, a monolayer graphene is introduced to the all-dielectric structure to demonstrate the application of the dual-mode tunable absorber. When the critical coupling condition is satisfied, each mode can achieve the theoretical maximum absorption, demonstrating the distinctive capability of our proposed absorber for tuning and efficient light absorption. This research provides valuable insights into light-matter interactions and opens up possibilities for optical modulation and the development of graphene-based devices.

Colorectal cancer (CRC) is one of the most common malignant cancers worldwide and seriously threatens human health. The clustered regulatory interspaced short palindromic repeat/CRISPR-associate nuclease 9 (CRISPR/Cas9) system is an adaptive immune system of bacteria or archaea. Since its introduction, research into various aspects of treatment approaches for CRC has been accelerated, including investigation of the oncogenes, tumor suppressor genes (TSGs), drug resistance genes, target genes, mouse model construction, and especially in genome-wide library screening. Furthermore, the CRISPR/Cas9 system can be utilized for gene therapy for CRC, specifically involving in the molecular targeted drug delivery or targeted knockout in vivo. In this review, we elucidate the mechanism of the CRISPR/Cas9 system and its comprehensive applications in CRC. Additionally, we discussed the issue of off-target effects associated with CRISPR/Cas9, which serves to restrict its practical application. Future research on CRC should in-depth and systematically utilize the CRISPR/Cas9 system thereby achieving clinical practice., (© 2023. The Author(s).)

To explore the treatments for and manifestations of carotid blowout syndrome (CBS) and to further explore the critical role of high-flow bypass combined with parent artery isolation. The clinical data of nine patients with radiotherapy-related CBS who were admitted to our hospital from March 2020 to March 2023 were retrospectively analyzed. Relevant literature was reviewed. From March 2020 to March 2023, nine CBS patients were admitted to Tianjin Huanhu Hospital, including eight males and one female. Digital subtraction angiography was performed for all the patients; all the pseudoaneurysms were located at the petrous segment of the internal carotid artery. A balloon occlusion test was performed on four patients, which was tolerated by all patients. CT and MRI scans showed seven cases of osteonecrosis combined with infection and two cases of tumor recurrence. Emergency permanent parent artery occlusion was performed on six patients, aneurysm embolization was completed in one case, covered stent implantation was performed in one patient, and three cases were treated by cerebral bypass surgery (including two patients with failed interventional treatment). Rebleeding was found in two patients, and no rebleeding was found in the bypass group. Paralysis was found in three patients, and asymptomatic cerebral infarction without permanent neurologic impairment was found in three patients. Two patients died due to tumor progression. Emergency occlusion surgery is lifesaving in the acute phase of CBS. Endovascular therapy cannot prevent the progression of pseudoaneurysms or lower the recurrence rate of bleeding events. High-flow bypass combined with parent artery isolation is a safe and effective method that may facilitate further surgical treatment. Further research is warranted., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Real-time quantitative polymerase chain reaction (RT-qPCR) is the most common method to determine mRNA expression, and Minimum Information for Publication of RT-qPCR Experiments (MIQE) proposes that a panel of reference genes for RT-qPCR is conducive to obtaining accurate results. This study aimed to screen and verify the optimal panel of reference genes in colorectal cancer (CRC) and normal colonic cell lines. In the study, eight candidate reference genes (GAPDH, ACTB, 18S, PPIA, B2M, SDHA, GUSB, and YWHAZ) were selected for RT-qPCR to detect their expression in NCM460, HT29, HCT116, SW480, SW620, DLD-1, LOVO and RKO cell lines. The stability of reference genes and the optimal panel were evaluated by geNorm, NormFinder, and BestKeeper software. As results, the expression levels of candidate reference genes differed in the colonic epithelial cell lines, and the number of optimal panel of reference genes is two. B2M and YWHAZ were the two most stable reference genes for NCM460, HCT116, SW620, LOVO, and RKO cell lines, while only one of B2M and YWHAZ was most stable in HT29 and SW480 cells. In DLD-1 cells, the stability of B2M and YWHAZ ranked 3rd and 6th, PPIA and GUSB were the most stable two. Furthermore, the YWHZA + B2M performed smaller intragroup differences than other panel or single reference gene. In conclusion, this study indicates the optimal panel of reference genes is YWHZA + B2M for the NCM460, HCT116, SW620, LOVO, RKO, SW480, and HT29 cell lines, but it is PPIA + GUSB in DLD-1 cell lines., (© 2023. Springer Nature Limited.)

Sinonasal inverted papilloma（SNIP） is a kind of benign tumor originating from the nasal cavity and paranasal sinuses, accounting for 70% of papillomas. The incidence of the disease is more common in males, with an average age of 50-60 years. It is most likely to occur in unilateral maxillary sinus and ethmoid sinus, followed by sphenoid sinus and frontal sinus.It has the characteristics of local invasion, high recurrence rate and malignant tendency, and most malignant transformation into squamous cell carcinoma. Endoscopic nasal resection and appropriate adjuvant therapy can help to reduce the recurrence rate and inhibit further deterioration. We report the results of a 10-year follow-up of a SNIP patient, including the clinical manifestations, recurrence course and treatment plan during the 10 years. The patient underwent multiple nasal endoscopic surgeries, and had a recurrence of multiple focal attachment pattern, and finally had direct invasion and distant metastasis. Tumor recurrence and further deterioration persisted despite the use of a comprehensive treatment., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Little is known about the non-linear cumulative effects of temperature on blood pressure (BP) during pregnancy. We investigated the differing effects of daily ambient temperature on BP for up to 30 days in three trimesters., Methods: The first, second, and third trimester analyses included 2547, 2299, and 2011 pregnant women, respectively, from a prospective cohort in Nanjing from January 2017 to January 2020. BP was measured at each follow-up visit. The individual daily temperature exposures were calculated for 30 days prior to the follow-up date. The Distributed Lag Non-linear Model was used to investigate the relationship between temperature and BP in each trimester., Results: Temperatures under 15 °C elevate systolic, diastolic BP, and mean arterial pressure (SBP, DBP, and MAP) in the first trimester, while temperatures above 15 °C reduce SBP in the second and third trimesters. By using Distributed Lag Linear Models, we estimated that with a 1 °C decrease in daily temperature, the SBP and DBP increased by 0.32 (95 % CI: 0.12, 0.52) and 0.23 (95 % CI: 0.07, 0.39) mmHg, respectively, in the first trimester with a 20-day cumulative lag, while with a 1 °C increase in daily temperature, the SBP decreased by 0.23 (0.35, 0.10) mmHg in the third trimester with a 30-day cumulative lag. The significant effects of temperature mainly manifested between 2 and 4 weeks of exposure., Conclusions: Temperature has different effects on BP over three trimesters. Protective measures to reduce cold-related BP rise will help reduce the risk of hypertensive disorders of pregnancy., 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 © 2022. Published by Elsevier B.V.)

In this Letter, we theoretically study the topological plasmons in Su-Schrieffer-Heeger (SSH) model-based graphene nanoribbon (GNR) layers. We find that for the one-dimensional (1D) stacked case, only two topological modes with the field localized in the top or bottom layer are predicted to exist by the Zak phase. When we further expand the stacked 1D GNR layers to two-dimensional (2D) arrays in the in-plane direction, the topology is then characterized by the 2D Zak phase, which predicts the emergence of three kinds of topological modes: topological edge, surface, and corner modes. For a 2D ribbon array with Nx × Ny units, there are 4(Ny - 1), 4(Nx - 1), and 4 topological edge, surface, and corner modes, and the field is highly localized at the edge/surface/corner ribbons. This work offers a platform to realize topological modes in GNRs and could be important for the design of topological photonic devices such as lasers and sensors.

Background: Primary epistaxis (rupture of nasal artery vessels) is a common emergency, but the related factors are still controversial. This study collected the data on primary epistaxis patients and healthy people undergoing a physical examination at the same center to explore and classify primary epistaxis by its characteristics., Methods: Primary epistaxis was divided into septal epistaxis and non-septal epistaxis, and logistic regression was performed to determine the risk factors., Results: In total, 196 cases of septal epistaxis and 127 cases of non-septal epistaxis, and the control group was 182 healthy subjects. There were significant differences in sex, drinking history, hypertension history and hyperlipidemia between the bleeding group and the control group, but no correlation with smoking, diabetes, cardiovascular and cerebrovascular events, or anticoagulant drug use. In the age group of 26-40 years it was related to alcohol consumption and hypertension, for those aged 41-55 years it was related to hypertension, in the age group of 56-70 years it was related to hypertension, high triglyceride and high apolipoprotein B levels, and no related factors were found in the age group >70 years. The risk factors for non-septal cases were increased low-density lipoprotein (LDL) [P=0.035; odds ratio (OR), 2.450; 95% confidence interval (CI): 1.067-5.624], male sex (P=0.002; OR, 3.136; 95% CI: 1.501-6.554), and younger age (P=0.000; OR, 0.941; 95%CI: 0.920-0.962). All patients with nosebleed underwent nasal endoscopy and the bleeding site was successfully located and treated with electrocoagulation. No further bleeding or serious complications occurred after 6 months of follow-up., Conclusions: Primary epistaxis is more common in males and is related to alcohol consumption, hypertension, and hyperlipidemia. In the young age groups, male sex, and increased LDL were high risk factors for non-septal hemorrhage in winter and spring. Nasal endoscopy and electrocoagulation are safe and effective., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-6590/coif). The authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Colorectal cancer (CRC) is a common malignancy worldwide, and the gut microbiota and metabolites play an important role in its initiation and progression. In this study, we constructed a mouse model of inflammation-induced colorectal tumors, with fixed doses of azoxymethane/dextran sulfate sodium (AOM/DSS). We found that colorectal tumors only formed in some mice treated with certain concentrations of AOM/DSS (tumor group), whereas other mice did not develop tumors (non-tumor group). 16S rDNA amplicon sequencing and liquid chromatography-mass spectrometry (LC-MS)/MS analyses were performed to investigate the microbes and metabolites in the fecal samples. As a result, 1189 operational taxonomic units (OTUs) were obtained from the fecal samples, and the non-tumor group had a relatively higher OTU richness and diversity. Moreover, 53 different microbes were identified at the phylum and genus levels, including Proteobacteria , Cyanobacteria , and Prevotella . Furthermore, four bacterial taxa were obviously enriched in the non-tumor group, according to linear discriminant analysis scores (log 10 ) > 4. The untargeted metabolomics analysis revealed significant differences between the fecal samples and metabolic phenotypes. Further, the heatmaps and volcano plots revealed 53 and 19 dysregulated metabolites between the groups, in positive and negative ion modes, respectively. Styrene degradation and amino sugar-nucleotide sugar metabolism pathways were significantly different in positive and negative ion modes, respectively. Moreover, a correlation analysis between the metabolome and microbiome was further conducted, which revealed the key microbiota and metabolites. In conclusion, we successfully established a tumor model using a certain dose of AOM/DSS and identified the differential intestinal microbiota and characteristic metabolites that might modulate tumorigenesis, thereby providing new concepts for the prevention and treatment of CRC., 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 Hong, Chen, Zhai, Qian, Gui and Jiang.)

Background: Lymph node metastasis (LNM) is one of the most important factors affecting the prognosis of breast cancer. The accurate evaluation of lymph node status is useful to predict the outcomes of patients and guide the choice of cancer treatment. However, there is still lack of a low-cost non-invasive method to assess the status of axillary lymph node (ALN). Gene expression signature has been used to assess lymph node metastasis status of breast cancer. In addition, nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of its original tissues, so it may be used to evaluate the axillary lymph node status in breast cancer., Methods: In this study, we found that the cfDNA nucleosome footprints between the ALN-positive patients and ALN-negative patients showed different patterns by implementing whole-genome sequencing (WGS) to detect 15 ALN-positive and 15 ALN-negative patients. In order to further evaluate its potential for assessing ALN status, we developed a classifier with multiple machine learning models by using 330 WGS data of cfDNA from 162 ALN-positive and 168 ALN-negative samples to distinguish these two types of patients., Results: We found that the promoter profiling between the ALN-positive patients and ALN-negative patients showed distinct patterns. In addition, we observed 1071 genes with differential promoter coverage and their functions were closely related to tumorigenesis. We found that the predictive classifier based on promoter profiling with a support vector machine model, named PPCNM, produced the largest area under the curve of 0.897 (95% confidence interval 0.86-0.93)., Conclusions: These results indicate that promoter profiling can be used to distinguish ALN-positive patients from ALN-negative patients, which may be helpful to guide the choice of cancer treatment., (© 2022. The Author(s).)

Background: The RNA modification 5-methylcytosine (m5C) is one of the most prevalent post-transcriptional modifications, with increasing evidence demonstrating its extensive involvement in the tumorigenesis and progression of various cancers. Colorectal cancer (CRC) is the third most common cancer and second leading cause of cancer-related deaths worldwide. However, the role of m5C modulators in shaping tumor microenvironment (TME) heterogeneity and regulating immune cell infiltration in CRC requires further clarification., Results: The transcriptomic sequencing data of 18 m5C regulators and clinical data of patients with CRC were obtained from The Cancer Genome Atlas (TCGA) and systematically evaluated. We found that 16 m5C regulators were differentially expressed between CRC and normal tissues. Unsupervised cluster analysis was then performed and revealed two distinct m5C modification patterns that yielded different clinical prognoses and biological functions in CRC. We demonstrated that the m5C score constructed from eight m5C-related genes showed excellent prognostic performance, with a subsequent independent analysis confirming its predictive ability in the CRC cohort. Then we developed a nomogram containing five clinical risk factors and the m5C risk score and found that the m5C score exhibited high prognostic prediction accuracy and favorable clinical applicability. Moreover, the CRC patients with low m5C score were characterized by "hot" TME exhibiting increased immune cell infiltration and higher immune checkpoint expression. These characteristics were highlighted as potential identifiers of suitable candidates for anticancer immunotherapy. Although the high m5C score represented the non-inflammatory phenotype, the CRC patients in this group exhibited high level of sensitivity to molecular-targeted therapy., Conclusion: Our comprehensive analysis indicated that the novel m5C clusters and scoring system accurately reflected the distinct prognostic signature, clinicopathological characteristics, immunological phenotypes, and stratifying therapeutic opportunities of CRC. Our findings, therefore, offer valuable insights into factors that may be targeted in the development of precision medicine-based therapeutic strategies for CRC., 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 Chen, Xi, Zhao, Hong, Tian, Zhai, Chen, Ren, Fan, Xie and Jiang.)

Recent efforts for increasing the success in drug discovery focus on an early, massive, and routine mechanistic and/or kinetic characterization of drug-target engagement as part of a design-make-test-analyze strategy. From an experimental perspective, many mechanistic assays can be translated into a scalable format on automation platforms and thereby enable routine characterization of hundreds or thousands of compounds. However, now the limiting factor to achieve such in-depth characterization at high-throughput becomes the quality-driven data analysis, the sheer scale of which outweighs the time available to the scientific staff of most labs. Therefore, automated analytical workflows are needed to enable such experimental scale-up. We have implemented such a fully automated workflow in Genedata Screener for time-dependent ligand-target binding analysis to characterize non-equilibrium inhibitors. The workflow automates Quality Control (QC) / data modelling and decision-making process in a staged analysis: (1) quality control of raw input data-fluorescence signal-based progress curves - featuring automated rejection of unsuitable measurements; (2) automated model selection - one-step versus two-step binding model - using statistical methods and biological validity rules; (3) result visualization in specific plots and annotated result tables, enabling the scientist to review large result sets efficiently and, at the same time, to rapidly identify and focus on interesting or unusual results; (4) an interactive user interface for immediate adjustment of automated decisions, where necessary. Applying this workflow to first-pass, high-throughput kinetic studies on kinase projects has allowed us to surmount previously rate-limiting manual analysis steps and boost productivity; and is now routinely embedded in a biopharma discovery research process., Competing Interests: Declaration of Competing Interest The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: All authors are current or past employees of AstraZeneca or Genedata AG., (Copyright © 2022. Published by Elsevier Inc.)

In this paper, we combine the dielectric metasurface with monolayer graphene to realize a high quality(Q)-factor quasi-BIC-based optical modulator, and the corresponding modulation performances are investigated by using the finite-difference time-domain (FDTD) method, which can be well fitting by the Fano formula based on the temporal couple-mode theory. The results demonstrate that bound states in the continuum (BIC) will turn into the quasi-BIC with high Q-factor by breaking the symmetry of every unit of the metasurface. Meanwhile, the amplitude and bandwidth of transmission based on the quasi-BIC mode can be efficiently adjusted by changing the Fermi energy ( E F ) of monolayer graphene, and the maximum difference in transmission up to 0.92 is achieved. Moreover, we also discuss the influence of the asymmetry degree to further investigate the modulation effect of graphene on the quasi-BIC mode.

Objective: To evaluate the accuracy of preoperative computed tomographic cisternography（CTC） and magnetic resonance hydrography（MRH）in the diagnosis of cerebrospinal fluid（CSF） rhinorrhea. Methods: Retrospective analysis was made on the data of 38 patients diagnosed as cerebrospinal rhinorrhea who completed preoperative HRCT, CTC and MRH examinations in the Department of Otolaryngology Head and Neck Surgery of Tianjin Huanhu Hospital from October 2016 to January 2022. The diagnostic accuracy of preoperative imaging examinations was compared according to the leak location found during operation. Results: Among all the 38 cases with CSF rhinorrhea, the detection rates of HRCT, CTC, and cranial MRH were 31.58%, 89.47%, and 60.53%, respectively. The accuracy of CTC was significantlyhigher than that of MRH （ χ² =8.49, P =0.007）, and the accuracy of MRH was significantly higher than that of HRCT （ χ² =6.41, P =0.01）. Subgroup analyses were performed according to the precise positioning of cerebrospinal fluid rhinorrhea leakage. In patients with cerebrospinal fluid rhinorrhea located in ethmoid sinus, the accuracy of CTC（80.95% vs. 14.29%， P <0.01）and MRH（52.38% vs. 14.29%， P =0.02）were significantly higher than that of HRCT, but the accuracy but the difference between CTC and MRH between CTC and MRH was not statistically significant （ P =0.10）. The accuracy of CTC was significantly higher than that of MRH （100.00% vs. 61.54%, P =0.04） and HRCT （100.00% vs. 53.85%, P <0.01） in patients with CSF rhinorrhea located in sphenoid sinus. However, there was no significant difference in the accuracy between MRH and HRCT （ P =1.00）. However, There was no significant difference in the accuracy of CTC, MRH and HRCT in patients with cerebrospinal fluid rhinorrhea located in frontal sinus. The accuracy of CTC and MRH was 84.62% and 57.69% respectively in 26 patients who failed to detect a CSF rhinorrhea by HRCT, and the difference was not statistically significant（ χ² =4.59, P =0.06）. Conclusion: The comprehensive application of the multiple imaging methods has important guiding significance for the accurate treatment and prognosis evaluation. CTC and MRH could improve the accuracy of the localization diagnosis of cerebrospinal fluid rhinorrhea., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Human lysine methyltransferase 2D (hKMT2D) is an epigenetic writer catalyzing the methylation of histone 3 lysine 4. hKMT2D by itself has little catalytic activity and reaches full activation as part of the WRAD2 complex, additionally comprising binding partners WDR5, RbBP5, Ash2L, and DPY30. Here, a detailed mechanistic study of the hKMT2D SET domain and its WRAD2 interactions is described. We characterized the WRAD2 subcomplexes containing full-length components and the hKMT2D SET domain. By performing steady-state analysis as a function of WRAD2 concentration, we identified the inner stoichiometry and determined the binding affinities for complex formation. Ash2L and RbBP5 were identified as the binding partners critical for the full catalytic activity of the SET domain. Contrary to a previous report, product and dead-end inhibitor studies identified hKMT2D as a rapid equilibrium random Bi-Bi mechanism with EAP and EBQ dead-end complexes. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-ToF MS) analysis showed that hKMT2D uses a distributive mechanism and gives further insights into how the WRAD2 components affect mono-, di-, and trimethylation. We also conclude that the Win motif of hKMT2D is not essential in complex formation, unlike other hKMT2 proteins.

Circular RNAs (circRNAs) are a recently discovered kind of regulatory RNAs that have emerged as critical biomarkers of various types of cancers. Metabolic reprogramming has gradually been identified as a distinct hallmark of cancer cells. The pentose phosphate pathway (PPP) plays an indispensable role in satisfying the bioenergetic and biosynthetic demands of cancer cells. However, little is known about the role of circRNAs and PPP in colorectal cancer (CRC). The novel circ&#95;0003215 was identified at low levels in CRC and was negatively correlated with larger tumor size, higher TNM stage, and lymph node metastasis. The decreased level of circ&#95;0003215 was resulted from the RNA degradation by m6A writer protein YTHDF2. A series of functional assays demonstrated that circ&#95;0003215 inhibited cell proliferation, migration, invasion, and CRC tumor metastasis in vivo and in vitro. Moreover, circ&#95;0003215 regulated the expression of DLG4 via sponging miR-663b, thereby inducing the metabolic reprogramming in CRC. Mechanismly, DLG4 inhibited the PPP through the K48-linked ubiquitination of glucose-6-phosphate dehydrogenase (G6PD). Taken together, we have identified m6A-modified circ&#95;0003215 as a novel regulator of metabolic glucose reprogramming that inhibited the PPP and the malignant phenotype of CRC via the miR-663b/DLG4/G6PD axis., (© 2022. The Author(s).)

Warthin's tumors of the head and neck are more common in the parotid and salivary glands and are extremely rare in the nasopharynx. This paper reports the clinical data of a patient with a nasopharyngeal Warthin's tumor and posterior nostril atresia who underwent nasal endoscopic nasal mass resection combined with posterior nostriphoplasty, and the patient has no tumor recurrence during the postoperative follow-up of until 14 months. This case report, combined with a literature review, conducted an in-depth analysis of nasopharyngeal Warthin's tumors to enable more otolaryngology specialists to deepen their understanding of such diseases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Backgruound: It is well-established that serum testosterone in men decreases with age, yet the underlying mechanism of this change remains elusive., Methods: The expression patterns of Fancd2 opposite-strand (Fancd2os) in BALB/c male mice and testicular tissue derived cell lines (GC-1, GC-2, TM3, and TM4) were assessed using real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. The Fancd2os-overexpressing or knockdown TM3 cells were constructed by infecting them with lentivirus particles and were used to evaluated the function of Fancd2os. The testosterone production was measured using enzyme linked immunosorbent assay (ELISA) and the steroidogenic enzymes such as steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage (P450scc), and 3β-hydroxysteroid dehydrogenase (3β-HSD) were analysed using RT-PCR. The apoptosis of TM3 cells induced by ultraviolet light or testicular tissues was detected using flow cytometry, Western blot or dUTP-biotin nick end labeling (TUNEL) assays. Pearson correlation analysis was used to assess the correlation between the Fancd2os expression and TUNEL-positive staining in mouse testicular Leydig cells., Results: The Fancd2os protein was predominantly expressed in mouse testicular Leydig cells and its expression increased with age. Fancd2os overexpression inhibited testosterone levels in TM3 Leydig cells, whereas knockdown of Fancd2os elevated testosterone production. Fancd2os overexpression downregulated the levels of StAR, P450scc and 3β-HSD, while Fancd2os knockdown reversed this effect. Fancd2os overexpression promoted ultraviolet light-induced apoptosis of TM3 cells. In contrast, Fancd2os knockdown restrained apoptosis in TM3 cells. In vivo assays revealed that higher Fancd2os levels and mouse age were associated with increased apoptosis in Leydig cells and decreased serum testosterone levels. Pearson correlation analysis exhibited a strong positive correlation between the expression of Fancd2os and TUNEL-positive staining in mouse testicular Leydig cells., Conclusion: Our findings suggest that Fancd2os regulates testosterone synthesis via both steroidogenic enzymes and the apoptotic pathway.

In this paper, we developed an amplified fluorescence biosensor for acetylcholinesterase (AChE) activity detection by taking advantage of the mercury ion-mediated Mgzyme (Mg 2+ -dependent DNAzyme) activity. The catalytic activity of Mgzyme can be inhibited by the formation of T-Hg 2+ -T base pairs between the Mgzyme and mercury ions. Therefore, the Mgzyme-Hg 2+ complex has no activity on a molecular beacon (MB) substrate, which afforded a very weak fluorescence background for this biosensor. After the addition of acetylcholinesterase (AChE), the substrate acetylthiocholine could be hydrolyzed to thiocholine, which has a stronger binding power with mercury ions than T-Hg 2+ -T base pairs. Therefore, the Mgzyme activity was recovered. The activated Mgzyme could hybridize with the MB substrate and undergo many cleavage cycles, resulting in a significant increase of fluorescence intensity. This biosensor displayed high sensitivity with the detection limit as low as 0.01 mU mL -1 . Moreover, this design did not require complex composition and sequence design; thus it is simple and convenient. This biosensor was also applied for the determination of AChE in human blood and showed satisfactory results.

Objective: To investigate the surgical approach of transnasal endoscopic resection of benign lesions in the paramedian lateral skull base. Methods: Retrospectively analyze 40 cases of the clinical data of patients with benign lesions of the skull base from August 2018 to February 2021 with transnasal endoscopic surgery, including 9 cases of cholesteatoma, 6 cases of hemangioma, 1 case of hemangiopericytoma, 6 cases of schwannoma, 15 cases of sphenoid sinus lateral crypt meningocele and cerebrospinal fluid leak, 3 cases of nasopharyngeal carcinoma bone inflammation after radiotherapy. All patients underwent transnasal endoscopic surgery, and different surgical approaches were selected according to the lesion location. Results: The total resection rate was 100% in 40 patients. One patient had cerebrospinal fluid rhinorrhea, which was cured after repair. During the follow-up period of 3-30 months, 39 patients had different degrees of numbness in the maxillary or mandibular region, and the numbness disappeared from 2 weeks to 6 months; one patient with schwannoma still had numbness on one side of the upper lip one year after surgery. Conclusion: Transnasal endoscopic resection of benign lesions in the paramedian skull base has a high surgical safety and cure rate. The surgical approach selection mainly focuses on the pterygoid process and extends to the periphery. The shortest and least damaging approach should be selected according to the lesion location, and the endoscopic approach should also be selected according to the surgeon's expertise., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To evaluate the application value of magnetic resonance hydrography in determine the leak location of patients with cerebrospinal fluid rhinorrhea. Methods: Clinical data of 58 patients with cerebrospinal fluid rhinorrhea treated in Tianjin Huanhu Hospital from February 2015 to February 2021 were analyzed retrospectively. The leak position was judged by three methods: nasal sinus coronal CT, magnetic resonance hydrography and magnetic resonance hydrography combined with nasal sinus coronal CT. The consistency of the leak position among groups determined by different imageological examination pre-operation was compared with the real leak position found during the operation. Results: The positive rate of magnetic resonance hydrography combined with coronal CT in paranasal sinuses（91.4%） was significantly higher than that of magnetic resonance hydrography（74.1%）（ P >0.05）. The positive rate of magnetic resonance hydrography（74.1%） was higher than that of CT（43.1%）（ P >0.01）. Conclusion: The comprehensive application of imaging examination technology has important clinical guiding significance for the correct diagnosis of cerebrospinal fluid rhinorrhea. Magnetic resonance hydrography combined with coronal CT of paranasal sinus can effectively find the leak location, which was suggested as the first choice for preoperative localization of cerebrospinal fluid rhinorrhea., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Zornia diphylla (L.) Pers. (ZDP) is a traditional Chinese herbal medicine that has been used for several decades to treat patients with liver diseases. Whether ZDP is best administered as a single agent or adjunctive therapy has yet to be determined as does the mechanism whereby it exerts its effects on antagonizing acute liver injury (ALI). Aim of the study: To investigate the protective effects of ZDP on ALI induced by carbon tetrachloride (CCl 4 ) and the potential underlying mechanisms. Materials and Methods: Sixty adult mice were randomized into six study groups ( n = 10/group). Three groups were treated with different concentrations of ZDP (2.5, 1.25, 0.625 g/kg), one with bifendate (0.0075 g/kg) alone (positive control) and one with physiologic saline (normal, negative control). All groups were treated for 14 days. Two hours after the last administration, the normal group received an intraperitoneal injection of peanut oil, and the other five groups received an intraperitoneal injection of an equal dose of CCl 4 peanut oil solution. At 24 h, the liver index, histology and serum or tissue levels and/or protein expression of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), alkaline phosphatase (ALP), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione (GSH), Akt, phosphorylated Akt (p-Akt), nuclear factor kappa B p65 (NF-κB p65), inhibitor of NF-κB α (IκB-α), interleukin-1 β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), E-cadherin and vimentin were determined. Results: Compared to the model controls, the degree of inflammatory cell infiltration and hepatocyte injury of liver tissue was relieved in the bifendate and three ZDP groups; liver index in the ZDP (2.5, 1.25 g/kg) groups and serum liver function indices in the ZDP (2.5, 1.25 and 0.625 g/kg) groups were decreased; antioxidants SOD, CAT and GSH in liver tissue were increased but the lipid peroxidation index MDA was decreased; protein expression of inflammatory cytokines Akt, p-Akt, NF-κB p65, IκB-α, IL-1β, IL-6 and TNF-α in the liver was ameliorated, and E-cadherin expression was increased. The results of liver histopathology also showed that ZDP had a significant effect on ALI. Conclusion: ZDP has obvious protective effects on CCl 4 -induced ALI as a single therapy and appears to act by inhibiting oxidation, reducing the release of inflammatory factors and promoting hepatocyte repair., 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 © 2021 Xie, Zhai, Xi, Qiu, Zhang, Kong, Li, Zhu, Wang, Zhang, Huang, Lu and Wang.)

Breast cancer is the second cause of cancer-associated death among women and seriously endangers women's health. Therefore, early identification of breast cancer would be beneficial to women's health. At present, circular RNA (circRNA) not only exists in the extracellular vesicles (EVs) in plasma, but also presents distinct patterns under different physiological and pathological conditions. Therefore, we assume that circRNA could be used for early diagnosis of breast cancer. Here, we developed classifiers for breast cancer diagnosis that relied on 259 samples, including 144 breast cancer patients and 115 controls. In the discovery stage, we compared the genome-wide long RNA profiles of EVs in patients with breast cancer (n=14) and benign breast (n=6). To further verify its potential in early diagnosis of breast cancer, we prospectively collected plasma samples from 259 individuals before treatment, including 144 breast cancer patients and 115 controls. Finally, we developed and verified the predictive classifies based on their circRNA expression profiles of plasma EVs by using multiple machine learning models. By comparing their circRNA profiles, we found 439 circRNAs with significantly different levels between cancer patients and controls. Considering the cost and practicability of the test, we selected 20 candidate circRNAs with elevated levels and detected their levels by quantitative real-time polymerase chain reaction. In the training cohort, we found that BC ExoC , a nine-circRNA combined classifier with SVM model, achieved the largest AUC of 0.83 [95% CI 0.77-0.88]. In the validation cohort, the predictive efficacy of the classifier achieved 0.80 [0.71-0.89]. Our work reveals the application prospect of circRNAs in plasma EVs as non-invasive liquid biopsies in the diagnosis and management of breast cancer., Competing Interests: Author KL was employed by Guangzhou XGene Co., Ltd. The remaining 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. The reviewer LZ declared a shared affiliation, with no collaboration, with the authors to the handling editor at the time of the review, (Copyright © 2021 Lin, Cai, Zhai, Yang, Li, Li, Zhou, Liu, Han, Liu, Chen, Ye, Wu and Guo.)

Background: CSF rhinorrhea is a type of CSF leakage caused by an aseptic abnormal passage between the subarachnoid space and the adjacent sinus and nasal cavity due to a cranial dural defect. At present, the value of computed tomography cisternography (CTC) in locating CSF rhinorrhea has been widely recognized, and magnetic resonance hydrography (MRH), as a heavy T2-weighted water imaging, plays a pivotal role in showing the location of the leak. In this paper, we retrospectively summarize the imaging manifestations seen at our hospital of patients with clinically confirmed CSF rhinorrhea at the skull base and evaluate the diagnostic value of different imaging methods in the localization of CSF rhinorrhea by means of preoperative imaging analysis using CTC and MRH., Methods: Fifty-five patients with CSF rhinorrhea admitted to our department from October 2016 to January 2021 were retrospectively analyzed. The patients' conventional CT, CTC, and MRH imaging data were compared, and the location of the leak determined preoperatively matched the location of the leak found during surgery. Moreover, there was no recurrence during the follow-up period of 4 months to 3 years., Results: There were statistically significant differences between the diagnostic positivity rate of CTC and spiral CT (χ2=16.755, P<0.00), and between the diagnostic positivity rate of cranial MRH and spiral CT (χ2=6.338, 6.338=0.01), and no statistically significant difference between the diagnostic positivity rate of CTC and cranial MRH (χ2=2.625, P=0.1)., Conclusions: The combined use of imaging techniques has important practical significance for the proper treatment and prognostic evaluation of CSF rhinorrhea. CTC has the highest positive rate for the diagnosis of CSF rhinorrhea, followed by MRH, while spiral CT is safer. CTC and MRH can promote the diagnostic rate in determining the location of CSF rhinorrhea, and selective combined application can be an important guide to surgery.

KMT2 methyltransferases are important regulators of gene transcription through the methylation of histone H3 lysine 4 at promoter and enhancer regions. They reside in large, multisubunit protein complexes, which not only regulate their catalytic activities but also mediate their interactions with chromatin. The KMT2 family was initially associated with cancer due to the discovery of KMT2A translocations in mixed-lineage leukemia (MLL). However, emerging evidences suggest that the methyltransferase activity of KMT2 enzymes can also be important in cancer, raising the prospect of targeting the catalytic domain of KMT2 as a therapeutic strategy. In this review, we summarize recent advances in our understanding of KMT2 enzyme mechanisms and their regulation on nucleosomes, which will provide mechanistic insights into therapeutic discoveries targeting their methyltransferase activities., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To construct and validate a predicting genotype signature for pathologic complete response (pCR) in locally advanced rectal cancer (PGS-LARC) after neoadjuvant chemoradiation., Methods and Materials: Whole exome sequencing was performed in 15 LARC tissues. Mutation sites were selected according to the whole exome sequencing data and literature. Target sequencing was performed in a training cohort (n = 202) to build the PGS-LARC model using regression analysis, and internal (n = 76) and external validation cohorts (n = 69) were used for validating the results. Predictive performance of the PGS-LARC model was compared with clinical factors and between subgroups. The PGS-LARC model comprised 15 genes., Results: The area under the curve (AUC) of the PGS model in the training, internal, and external validation cohorts was 0.776 (0.697-0.849), 0.760 (0.644-0.867), and 0.812 (0.690-0.915), respectively, and demonstrated higher AUC, accuracy, sensitivity, and specificity than cT stage, cN stage, carcinoembryonic antigen level, and CA19-9 level for pCR prediction. The predictive performance of the model was superior to clinical factors in all subgroups. For patients with clinical complete response (cCR), the positive prediction value was 94.7%., Conclusions: The PGS-LARC is a reliable predictive tool for pCR in patients with LARC and might be helpful to enable nonoperative management strategy in those patients who refuse surgery. It has the potential to guide treatment decisions for patients with different probability of tumor regression after neoadjuvant therapy, especially when combining cCR criteria and PGS-LARC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: According to the global cancer burden data released in 2020, breast cancer (BC) has become the most common cancer in the world. Similar to those of other cancers, the present methods used in clinic for diagnosing early BC are invasive, inaccurate, and insensitive. Hence, new non-invasive methods capable of early diagnosis are needed., Methods: We applied next-generation sequencing and analyzed the messenger RNA (mRNA) profiles of plasma extracellular vesicles (EVs) derived from 14 BC patients and 6 patients with benign breast lesions. We used 3 regression models, namely support vector machine (SVM), linear discriminate analysis (LDA), and logistic regression (LR), to develop classifiers for use in making predictive BC diagnoses; and used 259 plasma samples, including those obtained from 144 patients with BC, 72 patients with benign breast lesions, and 43 healthy women, which were divided into training groups and validation groups to verify their performances as classifiers by quantitative reverse transcription polymerase chain reaction (RT-qPCR). The area under the curve (AUC) and accuracy, sensitivity, and specificity of the classifiers were cross-validated with the leave-1-out cross-validation (LOOCV) method., Results: Among all combinations assessed with the 3 different regression models, an 8-mRNA combination, named EXOB mRNA , exhibited high performance [accuracy =71.9% and AUC =0.718, 95% confidence interval (CI): 0.652 to 0.784] in the training cohort after LOOCV was performed, showing the largest AUC in the SVM model. The mRNAs in EXOB mRNA were HLA-DRB1, HAVCR1, ENPEP, TIMP1, CD36, MARCKS, DAB2, and CXCL14. In the validation cohort, the AUC of EXOB mRNA was 0.737 (95% CI: 0.636 to 0.837). In addition, gene function and pathway analyses revealed that different levels of gene expression were associated with cancer., Conclusions: We developed a high-performing predictive classifiers including 8 mRNAs from plasma extracellular vesicles for diagnosing breast cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/gs-21-275). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

A dynamically tunable anisotropic narrowband absorber based on monolayer black phosphorous (BP) is proposed in the terahertz (THz) band. The proposed absorber consists of a monolayer BP and a silicon (Si) grating, which is placed on a silica (SiO 2 ) isolation layer and a gold (Au) substrate. The benefit from the critical coupling mechanism with guided resonance is the efficiency of the absorption can reach 99.9% in the armchair (AC) direction and the natural anisotropy of BP makes it only 87.2% in the zigzag (ZZ) direction. Numerical and theoretical studies show that the absorption efficiency of the structure is operatively controlled by critical coupling conditions, including the geometric parameters of the Si grating, the electron doping of BP and the angle of incident light, etc. More importantly, in the absence of plasmon response, this structure greatly enhances the interaction between light and matter in monolayer BP. In particular, there are several advantages in this structure, such as extremely high-efficiency absorption, excellent tunability, outstanding intrinsic anisotropy and easy manufacturing, which will show unusual and promising potential applications in the design of BP-based tunable high-performance devices.

Background: Oropharyngeal squamous cell carcinoma (OPSCC) is a kind of squamous cell carcinoma of head and neck, and its incidence is on the rise in recent years. A variety of prognostic markers for OPSCC have been reported in many studies, but they are expensive or difficult to obtain. So, we retrospectively studied the prognostic significance of cytokeratin 19 soluble fragment (Cyfra21-1) in patients with OPSCC, in order to provide theoretical basis for accurate prognosis assessment., Methods: A retrospective analysis of the clinicopathological data of 85 OPSCC patients with concurrent radiotherapy and chemotherapy (CRT) admitted from January 2010 to June 2017. Serum Cyfra21-1 levels were measured before treatment. Analyze the relationship between Cyfra21-1 and clinical pathological characteristics of patients. The receiver operating characteristic (ROC) curve was used to calculate the cut-off value of Cyfra21-1. The Cox proportional hazard model was used to conduct univariate and multivariate analysis of related prognostic factors, and to determine the factors related to overall survival (OS) and progression-free survival (PFS)., Results: The cutoff value for Cyfra21-1 was 2.93 ng/mL. The baseline data of patients in different Cyfra21-1 groups were balanced and comparable. In the univariate and multivariate analyses, it was found that Cyfra21-1 was associated with OS and PFS. A measurement of Cyfra21-1 ≥2.93 ng/mL indicated poor OS (P<0.001) and PFS (P=0.001). After adjusting for age and disease stage, Cyfra21-1 can independently affect the OS (HR =3.57, 95% CI: 1.60-7.99, P=0.002) and PFS (HR =2.89, 95% CI: 1.41-5.91, P=0.004) of patients with OPSCC treated with CRT., Conclusions: Pre-treatment Cyfra21-1 can be used as a prognostic marker for patients with OPSCC treated with CRT, which has important clinical significance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6124). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother-to-child transmission (MTCT) in HBsAg- and HBeAg-positive mothers via a cohort study and a meta-analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [("HBV" or "hepatitis b" or "hepatitis b virus") and ("mother-to-infant transmission" or "vertical transmission")]. Studies were screened, and data were extracted. The fixed-effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7 months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>10 8  IU/mL; RR = 3.03, 95% CI: 1.41-6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR = 0.61) and nonbreastfeeding (RR = 0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR = 0.58, 95% CI: 0.46-0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR = 0.74, 95% CI: 0.56-0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg- and HBeAg-positive mothers who did not receive antiviral therapy during pregnancy., (© 2020 John Wiley & Sons Ltd.)

Background: Oropharyngeal cancer (OPC) is a type of head and neck squamous cell cancer, the incidence of which has increased in recent years. Many studies have reported a variety of prognostic markers of OPC, but they are either expensive or difficult to obtain. Therefore, we retrospectively studied the prognostic value of circulating neutrophil count (CNC) in patients with OPC, with the aim of providing a theoretical basis for further prognostic stratification., Methods: The clinicopathological data of 153 patients diagnosed with OPC from January 2010 to June 2017 were retrospectively analyzed. The CNC of each patient was measured before treatment. Then, the relationship between CNC and the clinicopathological characteristics of the patients was analyzed. The receiver operating characteristic (ROC) curve was used to calculate the cutoff value of CNC. The cox proportional hazards model was used to perform univariate and multivariate analysis of the relevant prognostic factors to determine the factors related to overall survival (OS) and progression-free survival (PFS)., Results: The cutoff value for CNC was 4.48. Neutrophilia was significantly associated with disease stage, P16 status, and the type of therapy. In the univariate and multivariate analyses, CNC was found to be correlated with OS and PFS. Increased neutrophil count was predictive of poor OS (P<0.001) and PFS (P=0.001). Neutrophil count was an independent risk factor for OS (HR =2.09, 95% CI: 1.25-3.51, P=0.005) and PFS (HR =1.78, 95% CI: 1.10-2.88, P=0.02) in patients with OPC., Conclusions: Pre-treatment CNC is an independent prognostic factor for OPC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-5702). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

High-contrast gratings (HCGs) can be designed as a resonator with high-quality factor and surface-normal emission, which are excellent characters for designing optical devices. In this work, we combine HCGs with plasmonic graphene structure to achieve an ultrathin five-band coherent perfect absorber (CPA). The presented CPA can achieve multi- and narrow-band absorption with high intensity under a relatively large incident angle. The good agreement between theoretical analysis and numerical simulated results demonstrates that our proposed HCGs-based structure is feasible to realize CPA. Besides, by dynamically adjusting the Fermi energy of graphene, we realize the active tunability of resonance frequency and absorption intensity simultaneously. Benefitting from the combination of HCGs and the one-atom thickness of graphene, the proposed device possesses an extremely thin feature. Our work proposes a novel method to manipulate coherent perfect absorption and is helpful to design tunable multi-band and ultrathin absorbers.

General plasmonic systems to realize plasmonically induced transparency (PIT) effect only exist one single PIT mainly because they only allow one single coupling pathway. In this study, we propose a distinct graphene resonator-based system, which is composed of graphene nanoribbons (GNRs) coupled with dielectric grating-loaded graphene layer resonators, to achieve two switchable PIT effects. By designing crossed directions of the resonators, the proposed system exists two different PIT effects characterized by different resonant positions and linewidths. These two PIT effects result from two separate and polarization-selective coupling pathways, allowing us to switch the PIT from one to the other by simply changing the polarization direction. Parametric studies are carried to demonstrate the coupling effects whereas the two-particle model is applied to explain the physical mechanism, finding excellent agreements between the numerical and theoretical results. Our proposal can be used to design switchable PIT-based plasmonic devices, such as tunable dual-band sensors and perfect absorbers.

In order to remarkably enhance the absorption capability of (CH 3 NH 3 )PbI 3 , a tunable narrow-band (CH 3 NH 3 )PbI 3 -based perfect absorber based on the critical coupling with guided resonance is proposed. By using the finite-difference time-domain (FDTD) simulations, a complete absorption peak is achieved at the wavelength of 1310 nm. Moreover, we have compared the simulation results with theoretical calculations, which agree well with each other. By changing related structural parameters, the wavelength of absorption peak can be tuned effectively. Furthermore, the proposed absorber can tolerate a relatively wide range of incident angles and demonstrate polarization-independence. In addition to (CH 3 NH 3 )PbI 3 , the complete optical absorption in the other halide perovskites can be realized by the same mechanism.