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We present the requirements, design, and evaluation of the cryogenic continuously rotating half-wave plate (CHWP) for the Simons Observatory (SO). SO is a cosmic microwave background polarization experiment at Parque Astronómico de Atacama in northern Chile that covers a wide range of angular scales using both small (⌀0.42 m) and large (⌀6 m) aperture telescopes. In particular, the small aperture telescopes (SATs) focus on large angular scales for primordial B-mode polarization. To this end, the SATs employ a CHWP to modulate the polarization of the incident light at 8 Hz, suppressing atmospheric 1/f noise and mitigating systematic uncertainties that would otherwise arise due to the differential response of detectors sensitive to orthogonal polarizations. The CHWP consists of a 505 mm diameter achromatic sapphire HWP and a cryogenic rotation mechanism, both of which are cooled down to ∼50 K to reduce detector thermal loading. Under normal operation, the HWP is suspended by a superconducting magnetic bearing and rotates with a constant 2 Hz frequency, controlled by an electromagnetic synchronous motor. We find that the number of superconductors and the number of magnets that make up the superconducting magnetic bearing are important design parameters, especially for the rotation mechanism's vibration performance. The rotation angle is detected through an angular encoder with a noise level of 0.07 μrad s. During a cooldown process, the rotor is held in place by a grip-and-release mechanism that serves as both an alignment device and a thermal path. In this paper, we provide an overview of the SO SAT CHWP: its requirements, hardware design, and laboratory performance.

Guoqiang Xu,1,2,* Xiaona Song,2,* Xiaotang Wang,1,2,* Rui Xue,1,2 Xiaoru Yan,1,2 Litao Qin,1,2 Xiaoqi Chang,1,2 Jiping Gao,1 Zhaoyang Chen,1 Guohua Song1 1Laboratory Animal Center Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Taiyuan, People’s Republic of China; 2School of Basic Medical Science, Shanxi Medical University, Taiyuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guohua Song, Laboratory Animal Center, Shanxi Key Laboratory of Experimental Animal Science and Human Disease Animal Model, Shanxi Medical University, Road Xinjian 56, Taiyuan, 030001, People’s Republic of China, Tel +86-351-4135919, Email ykdsgh@sxmu.edu.cnPurpose: Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods: We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results: The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion: Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future. Keywords: silver nanoparticles, nanocomposite, combination therapy, β-catenin signaling pathway

Yuan Wang, Xiaoyu Song, Ru Cui, Xinlin Luo, Juntian Dong, Hanqi Wang, Chengcheng Song, Yifa Zhou, Sisi Cui Engineering Research Center of Glycoconjugates, Ministry of Education, Jilin Provincial Key Laboratory of Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, People’s Republic of ChinaCorrespondence: Sisi Cui, Engineering Research Center of Glycoconjugates of Ministry of Education, Jilin Provincial Key Laboratory on Chemistry and Biology of Changbai Mountain Natural Drugs, School of Life Sciences, Northeast Normal University, Changchun, 130024, People’s Republic of China, Email cuiss100@nenu.edu.cnPurpose: Conventional oral formulations for inflammatory bowel disease (IBD) treatment are less than satisfactory, due to the poor controllability of drug release and lack of specificity to the inflammation sites in the gastrointestinal (GI) tract. To overcome these limitations, we developed a multiple carbohydrate-based nanosystem with pH/ROS dual responsibility and charge-mediated targeting ability for IBD-specific drug delivery.Methods: In view of the overproduction of ROS and overexpression of cationic proteins in the inflammatory colon, the designed nanosystem was composed of oxidation-sensitive cyclodextrin (OX-CD), chitosan (CS) and pectin (AHP). OX-CD was utilized to load dexamethasone (DM) by the solvent evaporation method. CS and AHP with opposite charges were sequentially coated onto OX-CD to generate the nanosystems by the electrostatic self-assembly method. The physicochemical properties, stability, dual-sensitive drug release behavior, cytotoxicity, cellular uptake and anti-inflammatory activity were investigated in vitro. In vivo bio-distribution and therapeutic efficacy of the nanosystem were further evaluated in the ulcerative colitis (UC) mice.Results: The obtained AHP/CS/OX-CD-DM nanosystem (ACOC-DM) could maintain stability under the GI pH environments, and release drug in the inflammatory colon with pH/ROS sensitivity. Dual polysaccharide-coated ACOC-DM exhibited higher cellular uptake and anti-inflammatory efficacy in macrophages than single polysaccharide-coated CS/OX-CD-DM nanosystem (COC-DM). Orally administrated ACOC-DM could enhance inflammation targeting ability and therapeutic efficacy of DM in the UC mice.Conclusion: This carbohydrate-based nanosystem with pH/ROS dual sensitivity and inflammation targeting capacity may serve as a safe and versatile nanoplatform for IBD therapy. Keywords: PH/ROS sensitivity, pectin, chitosan, oxidation-sensitive cyclodextrin, inflammation targeting, oral delivery

Li Zhou,1,* Youlin Wu,1,2,* Jiani Wang,1 Haiyun Wu,1 Yongjun Tan,1 Xia Chen,1,3 Xiaosong Song,1,4 Yu Ren,1 Qin Yang1 1Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Neurology, Chongzhou People’s Hospital, Sichuan, People’s Republic of China; 3Department of Neurology, the Seventh People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Neurology, the Ninth People’s Hospital of Chongqing, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qin Yang, Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-023-89012008, Fax +86-023-68811487, Email xyqh200@126.comBackground and Purpose: Ischemic stroke is a leading cause of mortality and disability globally, necessitating accurate prediction of intra-hospital mortality (IHM) for improved patient care. This study aimed to develop a practical nomogram for personalized IHM risk prediction in ischemic stroke patients.Methods: A retrospective study of 422 ischemic stroke patients (April 2020 - December 2021) from Chongqing Medical University’s First Affiliated Hospital was conducted, with patients divided into training (n=295) and validation (n=127) groups. Data on demographics, comorbidities, stroke risk factors, and lab results were collected. Stroke severity was assessed using NIHSS, and stroke types were classified by TOAST criteria. Least absolute shrinkage and selection operator (LASSO) regression was employed for predictor selection and nomogram construction, with evaluation through ROC curves, calibration curves, and decision curve analysis.Results: LASSO regression and multivariate logistic regression identified four independent IHM predictors: age, admission NIHSS score, chronic obstructive pulmonary disease (COPD) diagnosis, and white blood cell count (WBC). A highly accurate nomogram based on these variables exhibited excellent predictive performance, with AUCs of 0.958 (training) and 0.962 (validation), sensitivities of 93.2% and 95.7%, and specificities of 93.1% and 90.9%, respectively. Calibration curves and decision curve analysis validated its clinical applicability.Conclusion: Age, admission NIHSS score, COPD history, and WBC were identified as independent IHM predictors in ischemic stroke patients. The developed nomogram demonstrated high predictive accuracy and practical utility for mortality risk estimation. External validation and prospective studies are warranted for further confirmation of its clinical efficacy.Keywords: ischemic stroke, nomogram, predictors, lasso, intra-hospital mortality

Wenwu Zhang,1,2,* Yuhan Xiao,3,* Xin Zhu,1 Yanxia Zhang,1 Qin Xiang,1 Shunhong Wu,1 Xiaoyu Song,1 Junxiu Zhao,3 Ruanfei Yuan,1 Qiguang Li,1 Bin Xiao,1 Linhai Li1 1Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People’s Republic of China; 3School of Public Health, Dali University, Dali, 671000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linhai Li; Bin Xiao, Email mature303@126.com; xiaobin2518@163.comPurpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.Keywords: meiosis-specific protein, pan-cancer, prognosis biomarker, immune infiltration, cell cycle

Zheping Chen,1,* Zhenxiang Zuo,2,* Xinyu Song,1 Yaqun Zuo,1 Le Zhang,1 Yuyang Ye,1 Yufeng Ma,1 Lili Pan,3 Xin Zhao,1 Yanwu Jin1 1Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of China; 2Department of Gastroenterology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, People’s Republic of China; 3Department of Anesthesiology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xin Zhao; Yanwu Jin, Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Bei Yuan Street, Jinan, 250033, People’s Republic of China, Tel +86-17660085551 ; +86-17660085535, Email lujnzx@sohu.com; jinyanwu_aa@163.comBackground: Dexmedetomidine, an α2-adrenergic receptor (α2-AR) agonist, is extensively used in clinical and animal studies owing to its sedative, analgesic, and anxiolytic effects. The diverse range of research domains associated with dexmedetomidine poses challenges in defining pivotal research directions. Therefore, this study aimed to conduct a qualitative and quantitative bibliometric study in the field of dexmedetomidine over the past decade to establish current research trends and emerging frontiers.Methods: Relevant publications in the field of dexmedetomidine between 2014 and 2023 were extracted from the Web of Science Core Collection database. The bibliometric analysis, incorporating statistical and visual analyses, was conducted using CiteSpace (6.1.R6) and R (4.3.1).Results: The present study encompassed a total of 5,482 publications, exhibiting a consistent upward trend over the past decade. The United States and its institutions had the highest centrality. Ji, Fuhai, and Ebert, Thomas J. were identified as the most productive author and the most cited author, respectively. As anticipated, the most cited journal was Anesthesiology. Moreover, cluster analysis of cited references and co-occurrence of keywords revealed that recent studies were primarily focused on sedation, delirium, and opioid-free anesthesia. Finally, a timeline view of keywords clusters and keywords burst demonstrated that primary research frontiers were stress response, neuroinflammation, delirium, opioid-free anesthesia, peripheral nerve block, and complications.Conclusion: Current research trends and directions are focused on sedation, delirium, and opioid-free anesthesia, as evidenced by our results. The frontier of future research is anticipated to encompass basic investigations into dexmedetomidine, including stress response and neuroinflammation, as well as clinical studies focusing on delirium, opioid-free anesthesia, peripheral nerve block, and associated complications.Keywords: dexmedetomidine, bibliometric analysis, CiteSpace, delirium, opioid-free anesthesia

Zhaohua Xiao,1,* Jiangfeng Zhao,1,* Guanhong Ji,1 Xiangqing Song,1 Xia Xue,2 Wenhao Zhang,1 Guomeng Sha,1 Yongjia Zhou,1 Jie Zhou,1 Zhongxian Tian,1,3 Xiaogang Zhao,1,3 Ning Jiang1 1Department of Thoracic Surgery, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China; 2Department of Pharmacy, the Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Key Laboratory of Chest Cancer, Shandong University, the Second Hospital of Shandong University, Jinan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Jiang, Department of Thoracic Surgery, the Second Hospital of Shandong University, Jinan, 250033, People’s Republic of China, Tel +86-17660081908, Email sdujiangning@163.comBackground: Exosomal microRNAs (miRNAs) in the tumor microenvironment play crucial roles in tumorigenesis and tumor progression by participating in intercellular cross-talk. However, the functions of exosomal miRNAs and the mechanisms by which they regulate esophageal squamous cell carcinoma (ESCC) progression are unclear.Methods: RNA sequencing and GEO analysis were conducted to identify candidate exosomal miRNAs involved in ESCC development. Receiver operating characteristic curve analysis was performed to assess the diagnostic value of plasma exosomal miR-493-5p. EdU, tube formation and Transwell assays were used to investigate the effects of exosomal miR-493-5p on human umbilical vein endothelial cells (HUVECs). A subcutaneous xenograft model was used to evaluate the antitumor effects of miR-493-5p and decitabine (a DNA methyltransferase inhibitor). The relationship between miR-493-5p and SP1/SP3 was revealed via a dual-luciferase reporter assay. A series of rescue assays were subsequently performed to investigate whether SP1/SP3 participate in exosomal miR-493-5p-mediated ESCC angiogenesis.Results: We found that miR-493-5p expression was notably reduced in the plasma exosomes of ESCC patients, which showed the high potential value in early ESCC diagnosis. Additionally, miR-493-5p, as a candidate tumor suppressor, inhibited the proliferation, migration and tube formation of HUVECs by suppressing the expression of VEGFA and exerted its angiostatic effect via exosomes. Moreover, we found that SP1/SP3 are direct targets of miR-493-5p and that re-expression of SP1/SP3 could reverse the inhibitory effects of miR-493-5p. Further investigation revealed that miR-493-5p expression could be regulated by DNA methyltransferase 3A (DNMT3A) and DNMT3B, and either miR-493-5p overexpression or restoration of miR-493-5p expression with decitabine increased the antitumor effects of bevacizumab.Conclusion: Exosomal miR-493-5p is a highly valuable ESCC diagnosis marker and inhibits ESCC-associated angiogenesis. miR-493-5p can be silenced via DNA methylation, and restoration of miR-493-5p expression with decitabine increases the antitumor effects of bevacizumab, suggesting its potential as a therapeutic target for ESCC treatment.Keywords: esophageal squamous cell carcinoma, exosomes, miR-493-5p, VEGFA, angiogenesis

Yuan Yuan,1,* Mingyi Hou,2,* Xiaoning Song,1 Xintao Yao,1 Xuerui Wang,1 Xiangjun Chen,2 Shengnan Li1 1School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin, 300401, People’s Republic of China; 2School of Pharmacy, Shandong New Drug Loading & Release Technology and Preparation Engineering Laboratory, Binzhou Medical University, Yantai, 264003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shengnan Li; Xiaoning Song, School of Chemical Engineering and Technology, Hebei University of Technology, Xiping Road, Tianjin, 300401, People’s Republic of China, Email lisn027@hebut.edu.cn; songxn123@hebut.edu.cnBackground: With the rapid development of nanotechnology, constructing a multifunctional nanoplatform that can deliver various therapeutic agents in different departments and respond to endogenous/exogenous stimuli for multimodal synergistic cancer therapy remains a major challenge to address the inherent limitations of chemotherapy.Methods: Herein, we synthesized hollow mesoporous Prussian Blue@zinc phosphate nanoparticles to load glucose oxidase (GOx) and DOX (designed as HMPB-GOx@ZnP-DOX NPs) in the non-identical pore structures of their HMPB core and ZnP shell, respectively, for photothermally augmented chemo-starvation therapy.Results: The ZnP shell coated on the HMPB core, in addition to providing space to load DOX for chemotherapy, could also serve as a gatekeeper to protect GOx from premature leakage and inactivation before reaching the tumor site because of its degradation characteristics under mild acidic conditions. Moreover, the loaded GOx can initiate starvation therapy by catalyzing glucose oxidation while causing an upgradation of acidity and H2O2 levels, which can also be used as forceful endogenous stimuli to trigger smart delivery systems for therapeutic applications. The decrease in pH can improve the pH-sensitivity of drug release, and O2 can be supplied by decomposing H2O2 through the catalase-like activity of HMPBs, which is beneficial for relieving the adverse conditions of anti-tumor activity. In addition, the inner HMPB also acts as a photothermal agent for photothermal therapy and the generated hyperthermia upon laser irradiation can serve as an external stimulus to further promote drug release and enzymatic activities of GOx, thereby enabling a synergetic photothermally enhanced chemo-starvation therapy effect. Importantly, these results indicate that HMPB-GOx@ZnP-DOX NPs can effectively inhibit tumor growth by 80.31% and exhibit no obvious systemic toxicity in mice.Conclusion: HMPB-GOx@ZnP-DOX NPs can be employed as potential theranostic agents that incorporate multiple therapeutic modes to efficiently inhibit tumors. Keywords: Prussian Blue, glucose oxidase, co-delivery system, photothermal therapy, chemotherapy

Xingyue Gao,1 Sihao Shen,1 Wenzhong Xiang,2 Xiuzu Song2 1The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Wenzhong Xiang, Department of Dermatology, Hangzhou Third People’s Hospital, Westlake Ave 38, Hangzhou, 310002, People’s Republic of China, Email xiangwenzhong@126.comPurpose: Coronavirus disease (COVID-19) may trigger the reactivation of the latent varicella-zoster virus and may be a risk factor for herpes zoster (HZ). However, the causal relationship between COVID-19 and varicella-zoster infections remains controversial. This study aimed to estimate the causal inferences between COVID-19 and HZ.Methods: This study used a two-sample Mendelian randomization (MR) design. The inverse variance-weighted method was used as the primary method and sensitivity analyses were conducted, including the MR-Egger regression, weighted median and weighted mode. We searched at https://gwas.mrcieu.ac.uk/ using the keywords “COVID-19” for exposure data and “zoster” for outcome datasets.Results: We got 26 COVID-19 datasets and five zoster datasets. We used 26 COVID-19 datasets as exposure data corresponding to each zoster dataset for the MR analysis. There were nine datasets of COVID-19 where the number of SNPs was fewer than three in the MR analysis of the risk of HZ, varicella zoster virus (VZV) glycoprotein E and I antibody levels, anti-VZV IgG seropositivity, and post-zoster neuralgia. In addition, there were 10 datasets of COVID-19 where the number of SNPs was less than three in the MR analysis of anti-VZV IgG levels. The results of the MR analysis showed that all p-values were greater than 0.05. Sensitivity analysis revealed no evidence of horizontal pleiotropy in most two sample MR analyses.Conclusion: Our results indicate that there is no causal relationship between COVID-19 and varicella-zoster infection, HZ progression, and postherpetic neuralgia.Keywords: COVID-19, herpes zoster, varicella-zoster virus, chronic pain

Xiaofan Jin,1 Xiuzu Song2 1Zhejiang University School of Medicine, Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Hangzhou, People’s Republic of China; 2Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Xiuzu Song, Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital, Zhejiang University School of Medicine, Westlake Ave 38, Hangzhou, 310009, People’s Republic of China, Email songxiuzu@sina.comAbstract: Autophagy is recognized as a crucial regulatory process, instrumental in the removal of senescent, dysfunctional, and damaged cells. Within the autophagic process, lysosomal digestion plays a critical role in the elimination of impaired organelles, thus preserving fundamental cellular metabolic functions and various biological processes. Mitophagy, a targeted autophagic process that specifically focuses on mitochondria, is essential for sustaining cellular health and energy balance. Therefore, a deep comprehension of the operational mechanisms and implications of autophagy and mitophagy is vital for disease prevention and treatment. In this context, we examine the role of autophagy and mitophagy during hair follicle cycles, closely scrutinizing their potential association with hair loss. We also conduct a thorough review of the regulatory mechanisms behind autophagy and mitophagy, highlighting their interaction with hair follicle stem cells and dermal papilla cells. In conclusion, we investigate the potential of manipulating autophagy and mitophagy pathways to develop innovative therapeutic strategies for hair loss.Keywords: hair follicle, mitophagy, dermal papilla cell, hair follicle stem cell, alopecia

Yunpeng Feng,1 Shifeng Qiao,1 Jie Chen,1 Xin Wen,2 Yanlei Chen,3 Xiaoyu Song,1 Jiaxin Xu,1 Xiucheng Qiao,1 Jing Yang,2 Shenshen Zhang,1 Yang Feng,1 Yu Gao4 1The Second Ward of Colorectal Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of China; 3The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 4School of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning, 12100, People’s Republic of ChinaCorrespondence: Yu Gao, School of Basic Medical Sciences, Jinzhou Medical University, No. 40, Section 3 Songpo Road, Jinzhou, Liaoning, 121000, People’s Republic of China, Tel +86 15904161717, Email jzykdxgy@163.comPurpose: This research explored the association between CD163-labeled M2-type macrophages and cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) of 38 colorectal cancer (CRC) liver metastases. In addition, we investigated the correlation differences between M2-type macrophages and CAFs in the tumor microenvironments of 38 primary colorectal cancer patients with confirmed liver metastases and 946 colorectal cancer patients, as well as possible mechanisms of action between the two cells.Methods: The Immunohistochemistry (IHC) method was applied to detect the expression levels of M2-type macrophages and CAFs in the tissues of 984 cases of CRC and to analyze the correlation between M2-type macrophages and CAFs in colorectal cancer tissues. The IHC method was also applied to detect the expression levels of M2-type macrophages and CAFs in the liver metastases of 38 cases of CRC in the experimental group and to analyze the correlation between the two cells in liver metastases.Results: 1. M2-type macrophages and CAFs expression were significantly higher in 38 primary colorectal cancer patients compared to 946 controls, and the expression of M2-type macrophages was significantly positively correlated with CAFs. 2. In 984 CRC cases, M2-type macrophages and CAFs expression levels were significantly higher in the cancer tissues than in the paired paracancerous tissues. 3. The expression levels of M2-type macrophages and CAFs in primary colorectal cancer were significantly higher in the experimental group than in colorectal cancer tissues without distant metastasis.Conclusion: M2-type macrophages and CAFs are involved in the development of the colorectal cancer tumor microenvironment, and their interaction influences the initiation and progression of liver metastasis in colorectal cancer. It may provide new clinical ideas for early diagnosis of CRC liver metastases and searching for immune targets.Keywords: M2-type macrophages, cancer-associated fibroblasts, colorectal cancer, liver metastasis

Zhipeng Wang,1,* You Yin,2,* Yuhui Mu,1,3,* Lili Cui,1 Xinhua Song,1 Jianhua Zhuang,2 Shouhong Gao,1 Xia Tao,1 Wansheng Chen1 1Department of Pharmacy, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, People’s Republic of China; 2Department of Neurology, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), Shanghai, 200003, People’s Republic of China; 3College of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming, Yunnan, 650500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianhua Zhuang, Department of Neurology, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), No. 415, Fengyang Road, Shanghai, 200003, People’s Republic of China, Email jianhuazh11@126.com Xia Tao, Department of Pharmacy, Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital), No. 415, Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel/Fax +86– 21– 81886191, Email taoxia@smmu.edu.cnObjective: This study aims to explore the mechanism underlying the induction of phlebitis by aescinate and create an early-warning model of phlebitis based on metabolomics.Methods: Patients with cerebral infarction enrolled had been treated with aescinate. Plasma samples were collected either before administration of aescinate, upon the occurrence of phlebitis, or at the end of treatment. Non-targeted metabolomics and targeted amino acid metabolomics were carried out to analyze metabolic profiles and quantify the metabolites.Results: Untargeted metabolomics revealed six differential metabolites in baseline samples versus post-treatment samples and four differential metabolites in baseline samples from patients with or without phlebitis. Pathways of these differential metabolites were mainly enriched in amino acid metabolism. Ten differential amino acids with a VIP value of > 1 were identified in the baseline samples, enabling us to distinguish between patients with or without phlebitis. A logistic regression model was constructed (AUC 0.825) for early warning of phlebitis of grade 2 or higher.Conclusion: The occurrence of aescinate-induced phlebitis, which can be predicted early during onset, may be associated with perturbations of the endogenous metabolic profile, especially the metabolism of amino acids. Keywords: aescinate, diagnostic model, mechanism, metabolomics, phlebitis

Yakun Wang,1,* Xinyu Song,2,* Mulan Jin,1 Jun Lu1 1Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mulan Jin; Jun Lu, Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China, Email jinmulan2022@126.com; Lujun11101@126.comPurpose: Chronic rhinosinusitis is a prevalent condition in the field of otorhinolaryngology; however, its pathogenesis remains to be elucidated. The immunological defense of the nasal mucosa is significantly influenced by dendritic cells (DCs). We identified specific biological indicators linked to DCs and explored their significance in cases of chronic rhinosinusitis with nasal polyps (CRSwNP).Patients and Methods: We categorized cells using single-cell RNA (scRNA) sequencing, and combined transcriptome sequencing was used to identify potential candidate genes for CRSwNP. We selected three biomarkers based on two algorithms and performed enrichment and immune correlation analyses. Biomarkers were verified using training and validation sets, receiver operating characteristic curves, immunohistochemistry, and quantitative real-time reverse-transcription PCR (qRT-PCR). Variations in biomarker expression were validated using pseudotime analysis. The networks of competing transcription factor (TF)-mRNA and competing endogenous RNA (ceRNA) were established, and the protein drugs associated with these biomarkers were predicted.Results: Both scRNA-seq and transcriptome data showed that DCs immune infiltration was higher in the CRSwNP group than in the control group. Three DC-related biomarkers (NR4A1, CLEC4G, and CD163) were identified. In CRSwNP, NR4A1 expression decreased, whereas CLEC4G and CD163 expression increased. All biomarkers were shown to be involved in immunological and metabolic pathways by enrichment analysis. These biomarkers were associated with γδ T cells, effector memory CD4 + T cells, regulatory T cells, and immature DCs. According to pseudotime analysis, NR4A1 and CD163 expression decreased from high to low, whereas CLEC4G expression remained low.Conclusion: We screened and identified potential DC-associated biomarkers of CRSwNP progression by integrating scRNA-seq with whole transcriptome sequencing. We analyzed the biological pathways in which they were involved, explored their molecular regulatory mechanisms and related drugs, and constructed ceRNA, TF-mRNA, and biomarker–drug networks to identify new CRSwNP treatment targets, laying the groundwork for the clinical management of CRSwNP.Keywords: CRSwNP, dendritic cell, single-cell sequencing, transcriptomic sequencing, biomarker

Xinhuan Lei,1,* Xiaoting Song,1,* Yongyong Fan,1,* Zhen Chen,1 Liwei Zhang1,2 1Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, Zhejiang, People’s Republic of China; 2Bone Metabolism and Development Research Center, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liwei Zhang; Zhen Chen, Email medzlw@sina.com; chenzhen@enzemed.comPurpose: Fibromyalgia (FM) is a syndrome characterized by chronic musculoskeletal pain. Its clinical symptoms include both somatic and psychiatric symptoms, making the treatment of FM extremely challenging. The cause of FM is still unknown, and some patients do not improve their symptoms even after long-term active treatment. Thus, the development of new targeted therapies is important to reduce pain and improve quality of life for FM patients.Methods: In this study, we screened genes and secreted factors that play key roles in FM through bioinformatics and big data analysis. Furthermore, we performed CCK-8, qRT-PCR, glucose, ATP and lactate content testing, dual luciferase reporter gene assay to investigate the potential mechanism of complement factor D in fibromyalgia development.Results: In bioinformatics and big data analysis, we identified CFD was negatively correlated with the pro-inflammatory factor IL-6 and positively correlated with the anti-inflammatory factor IL-4, which suggested that CFD may be an anti-inflammatory factor. Through cellular assays, we verified that CFD reversed the decrease in IL-4 expression and the increase in IL-6 expression in BV2 cells caused by ATP.Conclusion: In summary, based on bioinformatic methods and big data mining we obtained a new target CFD for FM, and further experiments verified that CFD has significant inhibition of ATP-induced neuropathic pain. These findings provide a new theoretical basis for the clinical translation of CFD.Keywords: fibromyalgia, complement factor D, bioinformatics, inflammation

Yan Wang,1– 4,* Limei Cui,2– 4,* He Zhao,1– 4,* Huhuifen He,1– 4 Liang Chen,2– 4 Xicheng Song,2– 4 Dawei Liu,2– 4 Jingjing Qiu,2– 4 Yan Sun2– 4 1The Second Medical College, Binzhou Medical University, Yantai, Shandong, People’s Republic of China; 2Department of Otolaryngology and Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai, Shandong, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Sun, Department of Otorhinolaryngology & Head and Neck Surgery, Yuhuangding Hospital Affiliated to Qingdao University, No. 20 East, Yuhuangding Road, Yantai, Shandong, 264000, People’s Republic of China, Email entsunyan@126.comAbstract: Degenerative diseases affect people’s life and health and cause a severe social burden. Relevant mechanisms of microglia have been studied, aiming to control and reduce degenerative disease occurrence effectively. This review discussed the specific mechanisms underlying microglia in neurodegenerative diseases, age-related hearing loss, Alzheimer’s disease, Parkinson’s disease, and peripheral nervous system (PNS) degenerative diseases. It also reviewed the studies of microglia inhibitors (PLX3397/PLX5622) and activators (lipopolysaccharide), and suggested that reducing microglia can effectively curb the genesis and progression of degenerative diseases. Finally, microglial cells’ anti-inflammatory and pro-inflammatory dual role was considered the critical communication point in central and peripheral degenerative diseases. Although it is difficult to describe the complex morphological structure of microglia in a unified manner, this does not prevent them from being a target for future treatment of neurodegenerative diseases.Keywords: microglia, neurodegenerative diseases, neuroinflammation

Xianrui Song,1,* Danyang Li,1,* Lingling Gan,2,* Xiyu Xiong,1 Aobo Nie,1 Huanhuan Zhao,3 Yunfeng Hu,1 Guangming Li,4 Jun Guo1 1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 2Experiment Center for Science and Technology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 3Basic Medical Experiment Center, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China; 4Department of Anesthesiology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Guo, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, People’s Republic of China, Tel +86 13813909055, Email guoj@njucm.edu.cn Guangming Li, Department of Anesthesiology, Huaian First People’s Hospital, Nanjing Medical University, Huaian, Jiangsu, 223001, People’s Republic of China, Email ligm7681@163.comIntroduction: Extracellular protein nanoparticles (PNs) and ions perform synergistical functions in the control of transmembrane osmotic pressure (OP) under isotonic conditions. Intravenous injection may disrupt the ion balance and alter PN levels in blood plasma, changing transmembrane OP and damaging vascular endothelial cells.Methods: Na ions were injected into AngII–induced HUVECs to simulate cell injury in vitro, and tail vein infusion of Na ions into hypertensive rats was performed to assess vascular damage. Optical measurements using an intermediate filament (IF) tension probe were conducted to detect indicators related to transmembrane OP. Immunofluorescence, Western blotting and small interfering RNA (siRNA) transfection were employed to investigate inflammasomes and the relationship between Abl2 and inflammation.Results: Electrolyte injections with sodium ions (but not glucose and hydroxyethyl starch) induced the production of ASC and NLRP3 inflammasomes in Ang II–induced HUVECs; this in turn resulted in the disorder of calcium signals, and changes in transmembrane OP and cell permeability. Moreover, injection of Na ions into Ang II–induced HUVECs activated the mechanosensitive protein Abl2, involved in inflammation-induced transmembrane OP changes. A drug combination was identified that could induce OP recovery and block hyperpermeability induced by cytoplasmic inflammatory corpuscles in vivo and in vitro.Conclusion: Changes in extracellular PNs and ions following chemical stimuli (Ang II) participate in the regulation of transmembrane OP. Furthermore, injection of Na ions causes vascular endothelial injury in Ang II-induced cells in vitro and hypertension rats in vivo, suggesting it is not safe for hypertensive patients, and we propose a new drug combination as a solution. Keywords: Na ion injection, vimentin tension probe, protein-nanoparticles, transmembrane OP, Ang II-induced vascular endothelial injury, Abl2

Yaying Chen,1,2 Xiaojiao Li,2 Xiangyuan Song,2 Lin Cong,2 Yuyan Zhang1 1Department of Ophthalmology, Huadong Hospital, Fudan University School of Medicine, Shanghai, People’s Republic of China; 2Department of Ophthalmology, Huashan Hospital, Fudan University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Yuyan Zhang, Department of Ophthalmology, Huadong Hospital, Fudan University School of Medicine, No. 221 West Yan’an Road, Shanghai, 200040, People’s Republic of China, Tel +86 13162899051, Fax +86 21 62483180, Email yuyan8688@163.comPurpose: This study aimed to determine the relationship among microvascular changes, retinal nerve fiber layer (RNFL) thickness, and visual field loss in pituitary adenoma (PA) patients.Patients and Methods: Optic disc and macular vessel densities were measured, using optical coherence tomography angiography (OCTA) in the eyes from PA patients with radiographic chiasmal compression. Comparisons of retinal microvascular and structural parameters were conducted between PA patients and age/sex-matched healthy controls. The PA group was subdivided into PA with temporal visual field defects (perimetric PA) and PA without visual field defect (preperimetric PA) groups. The study determined correlation between microvascular parameters and optic nerve damage, including visual field and structural measurements. Subgroup analyses were performed to distinguish the different microcirculation characteristics of the perimetric PA eyes and preperimetric PA eyes.Results: Forty-five eyes from 40 PA patients and 24 eyes from 24 healthy controls were recruited prospectively. Eyes in the perimetric PA group had significantly decreased optic disc vessel density but slightly increased macular vessel density at superficial retinal capillary plexus (SCP) level. Eyes in the preperimetric PA group had significantly increased macular vessel density at SCP level. Optic disc vessel density was inversely correlated with visual field mean deviation and positively correlated with RNFL thickness.Conclusion: Significantly decreased optic disc vessel density in the perimetric stage but increased SCP macular vessel density in the preperimetric stage were found in PA patients. Our data suggest that increased SCP macular vessel density may serve as an early biomarker of preperimetric PA eyes, while decreased optic disc vessel density could be a late biomarker of perimetric PA eyes. Optic disc vessel density was correlated with RNFL thickness and visual field loss in PA eyes. OCTA is a useful tool to detect retinal microvascular changes and access the severity of neural impairments in chiasmal compression caused by PA.Keywords: optical coherence tomography angiography, pituitary adenoma, optic disc vessel density, macular vessel density, chiasmal compression

Zhanmei Song,1,* Jiayang Ye,2,* Xudong Song,3 Zheng Zhang,4 Peiyun Xu,5 Hongmei Shen6 1College of International Education, Wenzhou University, Wenzhou, People’s Republic of China; 2College of Education, Wenzhou University, Wenzhou, People’s Republic of China; 3School of Public Administration and Policy, Renmin University of China, Beijing, People’s Republic of China; 4Department of Psychiatry, the Second Xiangya Hospital of Central South University, National Center for Mental Disorders, and National Clinical Research Center for Mental Disorders, Changsha, People’s Republic of China; 5School of Public Affairs, Zhejiang University, Hangzhou, People’s Republic of China; 6School of Public Administration, Beihang University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong Song, School of Public Administration and Policy, Renmin University of China, No. 59 Zhongguancun Street, Haidian District, Beijing, 100872, People’s Republic of China, Tel +86 18001057285, Email psyamsong@ruc.edu.cn Zheng Zhang, Department of Psychiatry, Second Xiangya Hospital, Central South University, 139 Renmin Middle Road, Changsha City, Hunan Province, 410011, People’s Republic of China, Tel +8617806172110, Email hldzzz@foxmail.comPurpose: The purpose of this study is to develop and validate the Work Information Anxiety Questionnaire (WIAQ), and to report on the psychometric properties of the WIAQ.Methods: Based on the Approach-Avoidance Conflict theory, and combining previous literature reviews and open-ended interviews, initial scale items for the Work Information Anxiety Questionnaire were developed. Using 324 full-time corporate employees as subjects (Sample 1), an exploratory structural examination of work information anxiety was conducted, including item analysis, exploratory factor analysis, and network analysis. An additional 210 corporate employees were selected for formal testing (Sample 2), and the obtained data underwent structural validation, including confirmatory factor analysis, validity testing, and reliability testing.Results: The WIAQ (9 items) exhibited a two-factor structure of reception anxiety and missing out anxiety, with a cumulative variance contribution rate of 67.56%. The confirmatory factor model showed good model fit, with cross-group and cross-measurement stability. The Cronbach’s α of the WIAQ was 0.899, and the McDonald’s ω of the two factors were 0.906 and 0.831 respectively. The WIAQ demonstrated good criterion-related validity with the SAS and DASS.Conclusion: The factor structure of the WIAQ is clear, and its reliability and validity indicators meet psychometric requirements. It can serve as an effective tool for measuring work information anxiety.Keywords: work information anxiety, reception anxiety, missing out anxiety, approach-avoidance conflict theory, network analysis

Ling-Ling Xia,1,* Jun-Da Li,1,* Fan Duan,1,* Jing Zhang,1 Lin-Lin Mu,1 Li-Jin Wang,1 Chen-Yang Jiao,2 Xun Song,1 Ze Wang,1 Jin-Xuan Chen,1 Jing-Jing Wang,1 Yue Wang,1 Xiao-Chu Zhang,1,3 Dong-Liang Jiao1 1School of Mental Health, Bengbu Medical College, Bengbu, People’s Republic of China; 2School of Medical Imaging, Wannan Medical College, Wuhu, People’s Republic of China; 3CAS Key Laboratory of Brain Function and Disease and School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dong-Liang Jiao; Xiao-Chu Zhang, Email jdl3925697@163.com; zxcustc@ustc.edu.cnObjective: Learner dependence on short videos has many pitfalls for learning outcomes, but the negative effects of excessive short video use have been little discussed in the learning psychology literature. Therefore, this study investigated the effects of excessive short video use on anxiety, depression, prospective memory, and academically delayed gratification (ADOG) in relation to online gaming-related behaviours, and explored the possible mechanisms by which excessive online gaming and short video use may lead to decreased ADOG, to expand our understanding of excessive short video use.Methods: Based on the whole class random sampling method, a questionnaire survey was conducted among college students in Northern Anhui, China from May 7 to July 27, 2022. The questionnaires included the Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire Scale (PHQ-9), Prospective and Retrospective Memory (PRM) Questionnaire, and ADOG Scale.Results: A total of 1016 participants completed the survey. The study found that of all the internet behaviors, 20.8% of the college students mainly played online games, 43.9% mainly played short videos, and 35.3% conducted other online behaviors. When compared with other internet behaviors, online gaming and short video behaviors can cause more serious anxiety/depression and worse PRM and ADOG scores. As time spent playing online games and short videos increased, anxiety and depression became worse, and the scores for PRM and ADOG also declined. Anxiety, depression, and PRM mediate the relationship between time spent on online gaming/short videos and ADOG.Conclusion: Excessive short videos behaviour may produce the same psychological problems and learning problems as online gaming disorder. Excessive short video and online gaming behaviors may affect ADOG performance through anxiety, depression, and prospective memory. These findings could be used as a basis for future studies on the improvement of ADOG.Keywords: short video, online games, anxiety, depression, prospective memory, academic delay of gratification

Xueqi Wan,* Huan Zhang,* Jinfan Tian,* Peng Hao, Libo Liu, Yuquan Zhou, Jing Zhang, Xiantao Song, Changjiang Ge Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changjiang Ge; Xiantao Song, Email cjge1116@163.com; song0929@mail.ccmu.edu.cnAbstract: Atherosclerosis (AS), a category of cardiovascular disease (CVD) that can cause other more severe disabilities, increasingly jeopardizes human health. Owing to its imperceptible and chronic symptoms, it is hard to determine the pathogenesis and precise therapeutics for AS. A novel type of programmed cell death called ferroptosis was discovered in recent years that is distinctively different from other traditional cell death pathways in morphological and biochemical aspects. Characterized by iron overload, redox disequilibrium, and accumulation of lipid hydroperoxides (L-OOH), ferroptosis influences endothelial cells, vascular smooth muscle cells (VSMCs), and macrophages, as well as inflammation, partaking in the pathology of many cardiovascular diseases such as atherosclerosis, stroke, ischemia-reperfusion injury, and heart failure. The mechanisms behind ferroptosis are so sophisticated and interwoven that many molecules involved in this procedure are unknown. This review systematically depicts the initiation and modulation of ferroptosis and summarizes the contribution of ferroptosis to AS, which may open a feasible approach for target treatment in the alleviation of AS progression.Keywords: ferroptosis, iron overload, oxidation, lipid peroxidation, atherosclerosis