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Yangjia Chen,1,&ast; Zhaocheng Zhuang,1,&ast; Zhixiang Rao2 1Department of Preventive Medicine, School of Health, Quanzhou Medical College, Quanzhou, Fujian, 362011, People’s Republic of China; 2School of Humanities and Management, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangjia Chen, Department of Preventive Medicine, School of Health, Quanzhou Medical College, Quanzhou, Fujian, 362011, People’s Republic of China, Email 2015018@qzmc.edu.cnObjective: Epidemiological investigations have indicated an association between skin microbiota imbalance and psoriasis, however, the causal relationship has not been confirmed through Mendelian randomization (MR). MR employed genetic instrumental variables (IVs) to evaluate the causal relationship between skin microbiota and psoriasis, providing new insights for potential treatments.Methods: Summary statistics for psoriasis and related traits were available from FinnGen R10 and United Kingdom Biobank (UKB) consortium. The genome-wide association studies (GWAS) on skin microbiota in three skin microenvironments came from two population-based German cohorts. Several selection processes were used to determine the optimal instrumental variables. Five MR methods were performed and different sensitivity analyses approaches yield robustness evidence under different assumptions.Results: 449 SNPs were employed as IVs for 53 bacterial genera, with F-statistics between 20.18 and 42.44, indicating no evidence of weak instrument bias. Bacteroides was associated with psoriasis from UKB in IVW (OR, 95% CI: 0.914, 0.869– 0.961; P < 0.001, PB-H = 0.007). The taxon was also associated with psoriasis vulgaris (IVW: OR, 95% CI, 0.918, 0.872– 0.967; P = 0.001, PB-H = 0.054) and psoriasis and related disorders (IVW: OR, 95% CI, 0.915, 0.875– 0.957; P < 0.001, PB-H = 0.008). Consistent causal estimates were identified in terms of both magnitude and direction, indicating a protective effect of Bacteroides.Conclusion: The MR study found that Bacteroides in the antecubital fossa may protect against psoriasis, offering genetic proof that skin microbiota helps prevent the condition.Keywords: skin microbiota, psoriasis, Mendelian randomization, genus Bacteroides, autoimmune disease, AD

Yaonan Hong,1,2,&ast; Qi Liu,1,2,&ast; Chuanao Xin,1,2,&ast; Huijin Hu,1,2 Zhenchao Zhuang,1– 3 Hangping Ge,1,2,4 Yingying Shen,1,2,4 Yuechao Zhao,1,2,4 Yuhong Zhou,1,2,4 Baodong Ye,1,2,4 Dijiong Wu1,2,4,5 1Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 2The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 4National Traditional Chinese Medicine Clinical Research Base (Hematology), Hangzhou, Zhejiang, People’s Republic of China; 5Department of Oncology and Hematology, Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dijiong Wu, Department of Hematology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China, Tel +86-571-86620325, Email wudijiong@zcmu.edu.cnBackground: Limited data were available to understand the significance of ferroptosis in leukemia prognosis, regardless of the genomic background.Methods: RNA-seq data from 151 AML patients were analyzed from The Cancer Genome Atlas (TCGA) database, along with 70 healthy samples from the Genotype-Tissue Expression (GTEx) database. Ferroptosis-related genes (FRGs) features were constructed by multivariate COX regression analysis and risk scores were calculated for each sample and a novel prediction model was identified. The validation was carried out using data from 35 AML patients and 13 healthy controls in our cohort. Drug sensitivity analysis was conducted on various chemotherapeutic drugs.Results: A signature of 10 FRGs was identified, as prognostic predictors for AML, and the risk scores were calculated to constructed the prognostic features of FRGs. Significantly lower overall survival was observed in the high-risk group. The predictive ability of these features for AML prognosis was confirmed using Cox regression analysis, ROC curves, and DCA. The prediction model performed well in our clinical practices, and had its potential superiority when comparing to classical NCCN risk stratification. Multiple chemotherapy drugs, including paclitaxel, dactinomycin, cisplatin, etc. had a lower IC50 in FRGs high-risk group than low-risk group.Conclusion: The AML prognosis model based on FRGs accurately predicts AML prognosis and drug sensitivity, and the drugs identified worthy further investigation.Keywords: ferroptosis, prediction model, TCGA, acute myeloid leukemia, drug sensitivity

Dan Li,1 Fang Lv,2 Chenyuan Ding,3 Zhaohan Zhuang,3 Shijun Wang1 1Department of Obstetrics & Gynecology, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 2Department of Medical Record Statistics, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of China; 3Education Section, Xuanwu Hospital Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Shijun Wang, Department of Obstetrics & Gynaecology, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86-13601222289, Email wangshijun20158866@126.comPurpose: This case report aimed to summarize the risk factors, clinical characteristics, imaging changes, and maternal and fetal prognosis associated with Moyamoya disease in pregnant women and to explore effective management strategies and a comprehensive delivery plan.Case Presentation: The clinical data of four pregnant women who were diagnosed with Moyamoya disease and admitted to our hospital between January 2010 and January 2019 were retrospectively analyzed. Their diagnosis, treatment, delivery, and postpartum management during the pregnancy were analyzed. Among the four pregnant women, three were primipara and one was multipara. The age ranged from 27 to 41 years old. The gestational week of termination of pregnancy ranged between 8 and 39 weeks. During pregnancy, one case died in utero; one case was complicated with postpartum hemorrhage; one case was complicated with chronic hypertension, multiple cerebral artery stenosis and occlusion, bilateral middle cerebral artery occlusion, bilateral internal carotid artery occlusion, and Hashimoto’s thyroiditis. Under epidural anesthesia, two cases underwent a lower segment cesarean section; one case underwent artificial abortion; and one case underwent induced labor during late pregnancy. Two newborns survived.Conclusion: Moyamoya disease is a rare and serious complication of pregnancy. Pregnancy and childbirth may exacerbate the progression of this disease or induce cerebrovascular accidents, with a high mortality and disability rate, which seriously threatens the safety of mother and infant lives; however, with the close collaboration of a multidisciplinary team, it is possible to maximize a good pregnancy outcome.Keywords: pregnancy, cerebrovascular lesions, moyamoya disease

Donghao Wang,1,&ast; Yuting Zhang,1,&ast; Qiming Gan,1,&ast; Xiaofen Su,1,&ast; Haojie Zhang,1,2,&ast; Yanyan Zhou,1 Zhiyang Zhuang,1 Jingcun Wang,1 Yutong Ding,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang; Dongxing Zhao, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13600460056 ; +86-13650901411, Email nfzhanggird@163.com; rieast@163.comObjective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea–hypopnea index (AHI).Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR).Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07– 1.62, P < 0.01) and 1.45 (95% CI = 1.01– 2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02– 3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes.Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.Keywords: obstructive sleep apnea, arousal threshold, apnea–hypopnea index, hypertension, diabetes

Ruiwei Guo,1,2 Jin Wu,1,2 Yanmin Zheng,1,2 Xiaona Lin,1,2 Zelin Zhuang,1,2 Jingjing Yin,1,2 Zhirong Lin,1 Lei Xie,1,2 Shuhua Ma1,2 1Department of Radiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of China; 2Laboratory of Medical Molecular Imaging, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, People’s Republic of ChinaCorrespondence: Shuhua Ma; Lei Xie, Email shuhua6633@163.com; 13lxie1@stu.edu.cnBackground: Inflammatory Bowel Disease (IBD) patients may experience cognitive impairments in Visuospatial Working Memory (VSWM), significantly impacting their quality of life. However, the mechanisms underlying these impairments remain poorly understood.Methods: We studied functional MRI and graph theory analysis to investigate changes in functional connectivity networks during the Mental Rotation Task (MRT) in IBD patients. Twenty IBD patients (13 males, 7 females; mean age = 34.95 ± 13.80 years; mean disease duration = 2.43 ± 2.37 years) participated in the study. Exclusion criteria encompassed recent use of analgesics, 5-Aminosalicylate, corticosteroids, or immunosuppressants within the past three months. Additionally, we recruited 20 age-, gender-, and education-matched healthy controls for comparison.Results: Compared to a control group, IBD patients exhibited significantly longer reaction times and reduced accuracy during the MRT. Our analysis revealed abnormalities in multiple nodal attributes within the functional connectivity network, particularly in regions such as the bilateral orbitofrontal cortex, right supplementary motor area, bilateral parahippocampal gyrus, and bilateral anterior temporal lobe. We observed that the nodal efficiency in the left temporal pole is negatively correlated with Red Blood Cell Distribution Width (RDW) and positively correlated with response time of MRT.Conclusion: Our findings revealed notable abnormalities in multiple node attributes among IBD patients during MRT, providing evidence of cognitive impairments in VSWM in IBD patients. This study found RDW maybe can serve as a clinical indicator for predicting early VSWM impairment in patients with IBD.Keywords: inflammatory bowel disease, graph theory, visuospatial working memory, cognitive impairment, mental rotation task

Donghao Wang,1,&ast; Yating Chen,1,&ast; Yutong Ding,1,&ast; Yongkang Tang,1,&ast; Xiaofen Su,1,&ast; Shiwei Li,1 Haojie Zhang,1,2 Yanyan Zhou,1 Zhiyang Zhuang,1 Qiming Gan,1 Jingcun Wang,1 Yuting Zhang,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510160, People’s Republic of China, Tel +86-13600460056, Email nfzhanggird@163.comBackground: Obstructive sleep apnea (OSA) is a common chronic disease with various comorbidities. The cardiometabolic index (CMI) reflects visceral fat tissue distribution and function, assessing the risk of obesity-related conditions such as metabolic syndrome (MetS) and stroke, which are strongly connected to OSA. The relationship between CMI with OSA and OSA combined with MetS (OMS) remains unclear. This study aims to evaluate the screening value of CMI for OSA and OMS, compared to the lipid accumulation product (LAP).Methods: A total of 280 participants who underwent polysomnography were finally included, with the measurements of metabolic-related laboratory test results such as total cholesterol and triglyceride. Receiver operating curve (ROC) analysis and calculation of the area under the curve (AUC) were conducted to assess the screening potential of CMI, LAP, and the logistic regression models established based on them for OSA and OMS. The Youden index, sensitivity, and specificity were used to determine the optimal cutoff points.Results: ROC curve analysis revealed that the AUCs for CMI in screening OSA and OMS were 0.808 and 0.797, and the optimal cutoff values were 0.71 (sensitivity 0.797, specificity 0.776) and 0.89 (sensitivity 0.830, specificity 0.662), respectively, showing higher Youden index than LAP. The AUCs of screening models based on CMI for OSA and OMS were 0.887 and 0.824, respectively.Conclusion: CMI and LAP can effectively screen for OSA and OMS, while CMI has more practical cutoff values for identifying the diseased states. Screening models based on CMI demonstrate a high discriminatory ability for OSA and OMS, which needs verification in a large-scale population.Keywords: obstructive sleep apnea, metabolic syndrome, cardiometabolic index, lipid accumulation products, screening model

Zequn Zhuang,1,&ast; Peng Zhou,1,&ast; Jing Wang,2 Xiaojing Lu,1 Yigang Chen1– 3 1Department of General Surgery, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China; 2Jiangnan University Medical Center, Wuxi, People’s Republic of China; 3Wuxi Clinical College, Nantong University, Wuxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yigang Chen, Department of General Surgery, the Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, People’s Republic of China, Email 9862023226@jiangnan.edu.cnAbstract: Presently, obesity has emerged as a significant global public health concern due to its escalating prevalence and incidence rates. The gut microbiota, being a crucial environmental factor, has emerged as a key player in the etiology of obesity. Nevertheless, the intricate and specific interactions between obesity and gut microbiota, along with the underlying mechanisms, remain incompletely understood. This review comprehensively summarizes the gut microbiota characteristics in obesity, the mechanisms by which it induces obesity, and explores targeted therapies centered on gut microbiota restoration.Keywords: gut microbiota, obesity, dysbiosis, metabolism

Yang Zhang,1,2,&ast; Anqing Lu,2– 4,&ast; Zixuan Zhuang,1,2 Su Zhang,5 Sicheng Liu,5 Haining Chen,1,2 Xuyang Yang,1,2 Ziqiang Wang1,2 1Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Central Transportation, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4West China School of Nursing, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Research Laboratory of Tumor Epigenetics and Genomics, Department of General Surgery, Frontiers Science Center for Disease-Related Molecular Network and National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ziqiang Wang; Xuyang Yang, Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email wangziqiang@scu.edu.cn; yangxuyang@wchscu.cnAbstract: Extracellular vesicles (EVs) are small membrane-bound vesicles that are released by cells into the extracellular environment. The role of EVs in tumors has been extensively studied, and they have been shown to play a crucial role in tumor growth, progression, and metastasis. Past research has mainly used 2D-cultured cell line models to investigate the role of EVs in tumors, which poorly simulate the tumor microenvironment. Organoid technology has gradually matured in recent years. Organoids are similar in composition and behavior to physiological cells and have the potential to recapitulate the architecture and function of the original tissue. It has been widely used in organogenesis, drug screening, gene editing, precision medicine and other fields. The integration of EVs and organoids has the potential to revolutionize the field of cancer research and represents a promising avenue for advancing our understanding of cancer biology and the development of novel therapeutic strategies. Here, we aimed to present a comprehensive overview of studies using organoids to study EVs in tumors.Keywords: organoids, extracellular vesicles, tumors, model, review

Donghao Wang,1,&ast; Yingying Ren,2,&ast; Riken Chen,1,&ast; Xiangxia Zeng,1,&ast; Qiming Gan,1,&ast; Zhiyang Zhuang,1 Xiaofen Su,1 Kang Wu,1 Sun Zhang,1 Yongkang Tang,1 Shiwei Li,1 Haojie Zhang,1,3 Yanyan Zhou,1 Nuofu Zhang,1 Dongxing Zhao1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Medical Records and Statistics Room, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongxing Zhao; Nuofu Zhang, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13650901411 ; +86-13600460056, Email rieast@msn.com; nfzhanggird@163.comObjective: Obstructive sleep apnea (OSA) is a common sleep-disordered breathing disease. We aimed to establish an improved screening questionnaire without physical examinations for OSA named the CNCQ-OSA (Chinese community questionnaire for OSA).Methods: A total of 2585 participants who visited sleep medicine center and underwent overnight polysomnography were grouped into two independent cohorts: derivation (n = 2180) and validation (n = 405). The CNCQ-OSA was designed according to the baseline of patients in derivation cohort. We comprehensively analyzed the data to evaluate the predictive value of the CNCQ-OSA, compared to the GOAL questionnaire, STOP-Bang questionnaire (SBQ) and NoSAS questionnaire.Results: The CNCQ-OSA included seven variables: loud snoring, BMI ≥ 25 kg/m2, male gender, apnea, sleepiness, hypertension and age ≥ 30, with a total score ranging from 7 to 16.7 points (≥ 13.5 points indicating high risk of OSA, ≥ 14.5 points indicating extremely high risk). In the derivation and validation cohorts, the areas under the curve of the CNCQ-OSA were 0.761 and 0.767, respectively. In the validation cohort, the sensitivity and specificity of a CNCQ-OSA score ≥ 13.5 points for the apnea–hypopnea index (AHI) ≥ 5/h were 0.821 and 0.559, respectively (Youden index, 0.380), and the score ≥ 14.5 points were 0.494 and 0.887, respectively (Youden index, 0.375). The CNCQ-OSA had a better predictive value for AHI ≥ 5/h, AHI > 15/h and AHI > 30/h, with the highest Youden index, compared to the other questionnaires.Conclusion: The CNCQ-OSA can effectively identify the risk of OSA, which is appropriate for self-screening at home without physical examinations.Keywords: obstructive sleep apnea, screening, GOAL, STOP-Bang, NoSAS

Shougang Liu,1,&ast; Fanghua Liu,1,2,&ast; Zeqiao Zhang,1 Zhe Zhuang,1,2 Xiuqing Yuan,1 Yongfeng Chen1,2 1Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Dermatology, Guangdong Medical University, Zhanjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongfeng Chen, Dermatology Hospital of Southern Medical University, No. 2, LuJing Road, Guangzhou, Guangdong Province, 510091, People’s Republic of China, Tel +86 13802920269, Email gdcyf@163.comPurpose: Psoriasis and atherosclerosis are immunometabolic diseases. This study aimed to integrate bioinformatics and updated public resources to find potential biological markers associated with atherosclerosis that can cause psoriasis.Patients and Methods: Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened, and functional enrichment analysis was performed. We identified psoriasis and atherosclerosis common immune-related genes (PA-IRGs) by overlapping immune-related genes (IRGs) with genes in the module most associated with psoriasis and atherosclerosis obtained by weighted gene co-expression network analysis (WGCNAs). Receiver operating characteristic (ROC) was conducted to evaluate the predictive ability. The skin expression levels of diagnostic biomarkers were further verified by immunohistochemical staining. CIBERSORT, single-sample gene set enrichment analysis (ssGSEA), and Pearson’s correlation analysis were applied to evaluate immune and lipid metabolism relationships in psoriatic tissues. In addition, a lincRNA-miRNA-mRNA network was constructed to find the pathogenesis in which diagnostic markers may be involved.Results: Four PA-IRGs (SELP, CD93, IL2RG, and VAV1) demonstrated the optimal diagnostic value, with an AUC above 0.8. The immune cell infiltration analysis showed that dendritic resting cells, NK cell activation, neutrophils, macrophages M2, macrophages M0, and B-cell memory were highly abundant in psoriasis. Immune response analysis showed that TNF family members, chemokine receptors, interferons, natural killer cells, and TGF-β family members might be involved in psoriasis. Diagnostic biomarkers are strongly associated with various infiltrating immune cells, immune responses, and lipid metabolism. A lincRNA-miRNA-mRNA regulatory network consisting of 31 lincRNAs and 23 miRNAs was constructed. LINC00662 is involved in modulating four diagnostic biomarkers.Conclusion: This study identified atherosclerosis-related genes SELP, CD93, VAV1, and IL2RG as potential psoriasis diagnostic markers. Provide novel insights into the possible regulatory mechanisms involved in psoriasis.Keywords: psoriasis, atherosclerosis, biomarker, immune, lipid metabolism, ceRNA network

Ronghua Mu,1,2,&ast; Xiaoyan Qin,2,&ast; Zixuan Guo,1,2,&ast; Zhuoni Meng,1,2 Fuzhen Liu,2 Zeyu Zhuang,1,2 Wei Zheng,1,2 Xin Li,2 Peng Yang,2 Yuling Feng,2 Yanchun Jiang,3 Xiqi Zhu2 1Graduate School of Guilin Medical University, Guilin, 541004, People’s Republic of China; 2Department of Radiology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, 541004, People’s Republic of China; 3Department of Neurology, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Guilin, 541004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiqi Zhu, Tel +86 13737399757, Email xiqi.zhu@163.comPurpose: To study the variation tendency of cerebral small vessel disease (CSVD) imaging markers and total burden with aging and to research the relationship between aging, CSVD markers and cognitive function.Methods: Participants in local urban communities were recruited for neuropsychological and magnetic resonance imaging assessments. Montreal Cognitive Assessment (MoCA), Mini-mental State Examination (MMSE), Number Connection Test A (NCT-A) and Digital Symbol Test (DST) were adopted as neuropsychological scale. Age was stratified at 5-year intervals, and the variation tendency of imaging markers and variables of neuropsychological scales in different age groups was studied. We further studied the relationship between aging, image markers and neuropsychological scales by multi-linear regression.Results: Finally, a total of 401 stroke-free participants (age, 54.83± 7.74y; 45.9% were male) were included in the present analysis. With the increase of age, the incidence of imaging markers of CSVD were increased with aging except cerebral microbleeds. The performance results of NCT-A and DST were significant difference in 6 age groups (P < 0.001). In addition, linear decline of the neuropsychological function reflected by NCT-A and DST variables was observed. Linear regression found that age was an independent factor affecting the neuropsychological function reflected by NCT-A and DST variables, and the standard correction coefficients among different age groups increased gradually with age. In addition, brain atrophy is an independent factor affecting neuropsychological variables (odds ratio: − 2.929, 95% CI: [− 5.094 to − 0.765]). There was no correlation between the number of neuroimaging markers and neuropsychological variables after full adjustment.Conclusion: There are many CVSD markers even in younger people, the incidence rate and CVSD marker numbers increase with age. Aging and CSVD may eventually affect cognitive function through brain atrophy.Keywords: cerebral small vessel disease, aging, imaging marker, neuropsychological scales, community-based study

Huihui Ti,1– 3,* Zixi Zhuang,4,5,* Qian Yu,1 Shumei Wang2,3,6 1School of Clinical Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 2Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 3Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 4Key Laboratory of Molecular Target & Clinical Pharmacology, State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 5Guangdong Institute of Analysis (China National Analytical Center, Guangzhou), Guangzhou, 510070, People’s Republic of China; 6School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qian Yu; Shumei Wang Email qyu@gdpu.edu.cn; gdpuwsm@126.comAbstract: Viral infectious diseases are serious threats to human health in both developing and developed countries. Although there is the continued development of new drugs from synthetic sources as antiviral agents, medicinal plants continue to provide the basic raw materials for some of the most important antiviral drugs. Alkaloids are a class of pharmacologically active plant compounds that are usually alkaline in nature. In this review, we tried to summarize recent progress in herb-based antiviral research, the advantages of using active plant compounds as antiviral agents, and the inflammatory responses initiated by alkaloids, based on the literature from 2009 to 2019, for the treatment of conditions, including influenza, human immunodeficiency virus, herpes simplex virus, hepatitis, and coxsackievirus infections. Articles are retrieved from PubMed, Google Scholar, and Web of Science using relevant keywords. In particular, the alkaloids from medicinal plants responsible for the molecular mechanisms of anti-inflammatory actions are identified and discussed. This review can provide a theoretical basis and approaches for using various alkaloids as antiviral treatments. More research is needed to develop alkaloidal compounds as antiviral therapeutic agents and potential regulators of the anti-inflammatory response.Keywords: viral infectious diseases, alkaloids, antiviral, anti-inflammatory responses, antiviral therapeutic agents

Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 2Postdoctoral Research Workstation of Harbin Sport University, Harbin, 150001, People’s Republic of China; 3Department of Sport Science and Health, Harbin Sport University, Harbin, 150008, People’s Republic of China; 4Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 5Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Feng CaiHanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of ChinaEmail cangjiong1973@163.comBackground: Interleukin-1β (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown.Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation.Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice.Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.Keywords: mesenchymal stem cells, interleukin-1β, exosome, astrocyte, inflammation, Nrf-2

Chao Ma,1 Zongming Zhuang,1 Qisheng Su,2 Jianfeng He,1 Haoyu Li1 1Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Haoyu LiDepartment of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaEmail med.dr.lihy@gmail.comPurpose: This study focused on the mechanism underlying the therapeutic effect of curcumin against tongue cancer (TC).Methods: Target genes of TC and curcumin were identified, respectively. Three datasets of TC from Gene Expression Omnibus were included, and then the differentially expressed genes were collected. After combing the data from The Cancer Genome Atlas, bioinformatics analyses were performed to investigate hub genes in terms of the functions and correlations. The proliferation and migration of TC cells were evaluated with CCK-8 assay and scratch wound healing assay, respectively. Cell apoptosis was evaluated by TUNEL assay, flow cytometry and Western blot. Cell cycle was determined by flow cytometry.Results: In this study, 15 hub genes were identified (TK1, TDRD3, TAGLN2, RNASEH2A, PDE2A, NCF2, MAP3K3, GPX3, GPD1L, GBP1, ENO1, CAT, ALDH6A1, AGPS and ACACB). They were mainly enriched in oxygen-related processes, such as oxidation-reduction process, reactive oxygen species metabolic process, hydrogen peroxide catabolic process, oxidoreductase activity and Peroxisome-related pathway. The expression levels of hub gene mRNAs were positively correlated with each other’s expression levels. None of the hub genes was correlated with prognosis (P > 0.05). Curcumin significantly inhibited CAL 27 cell proliferation and migration (P < 0.05), but significantly promoted cell apoptosis (P < 0.05).Conclusion: Curcumin has potential therapeutic effect on treating TC by suppressing cell proliferation and migration, as well as promoting apoptosis through modulating oxygen-related signaling pathways.Keywords: tongue neoplasms, curcumin, proliferation, apoptosis, migration, computational biology

Yuantao Wu,1 Rui Xia,1 Chungang Dai,2 Suji Yan,2 Tao Xie,2 Bing Liu,2 Lei Gan,1 Zhixiang Zhuang,1 Qiang Huang2 1Department of Oncology, The Second Affiliated Hospital of Soochow University, Soochow, China; 2Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Soochow, China Objective: Dexamethasone (DEX) is a glucocorticoid that is commonly used in clinics. Previously, DEX has been shown to inhibit the function of immune system; however, DEX is often used to treat side reactions, such as nausea and vomiting caused by chemotherapy in clinics. Therefore, it is necessary to study the role of DEX in the treatment of cancer.Methods: The effects of DEX on HepG2 were studied in vitro by Cell Counting Kit-8 method, cell cycle, and scratch test. The transplanted tumor model of HepG2 was established in nude mice to study the anti-tumor effect of DEX in vivo. In addition, in order to study the effect of DEX on the immune system, we also established a transplanted tumor model of 4T1 in normal immunized mice to study treatment effect and mechanism of DEX in mice of normal immune function.Results: The results showed that DEX inhibited the proliferation of HepG2 in vitro and in vivo, affecting the cycle and migration of HepG2 cells, and the expression of c-Myc and the activation of mTOR signaling pathway were inhibited. The expression of key enzymes related to glucose metabolism is altered, especially that of phosphoenolpyruvate carboxykinase2 (PCK2). In normal immunized mice, DEX also inhibits the proliferation of tumor cells 4T1, while the proportion of CD4+CD45+T cells and CD8+CD45+ T cells in CD45+ cells in the lymph nodes upregulated, the proportion of Treg cells in CD4+ T cells downregulated in lymph nodes, and the proportion of MDSCs in tumor tissues downregulated.Conclusion: DEX can inhibit tumor cells in vitro and in vivo. The mechanism is to inhibit the activation of mTOR signaling pathway by inhibiting the expression of c-Myc, further affecting the expression of key enzymes involved in glucose metabolism, especially PCK2.In addition, DEX has an inhibitory effect on the immune system, which may be the reason why DEX still has anti-tumor effect in normal mice. Keywords: dexamethasone, glycolysis, Warburg effect, HepG2, 4T1, immune cells, immune system

Jiejing Li,1* Beiqi Jiang,1* Chao Lin,2 Zhigang Zhuang1 1Department of Breast Surgery, Shanghai First Maternity and Infant Hospital, 2The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Sentinel lymph node (SLN) mapping is a critical procedure for SLN biopsy and its diagnosis as tumor metastasis in clinical practice. However, SLN mapping agents used in the clinic frequently cause side effects and complications in the patients. Here, we report the development of a near-infrared (NIR) emitting polymeric nanogel with hydrodynamic diameter of ~28 nm – which is the optimal size for SLN uptake – for noninvasive fluorescence mapping of SLN in a mouse. This polymeric nanogel was obtained by coupling Cy7, an NIR dye, to the self-assembled nanogel from disulfide-linked dextran-deoxycholic acid conjugate with the dextran of 10 kDa, denoted as Dex–Cy7. Fluorescence imaging analysis showed that Dex–Cy7 nanogels had an enhanced photostability when compared to Cy7 alone. After intradermal injection of Dex–Cy7 nanogel into the front paw of a mouse, the nanogels were able to migrate into the mouse’s axillary lymph node, exhibiting longer retention time and higher fluorescence intensity in the node when compared to Cy7 alone. An immunohistofluorescence assay revealed that the nanogels were localized in the central region of lymph node and that the uptake was largely by the macrophages. In vitro and in vivo toxicity results indicated that the dextran-based nanogels were of low cytotoxicity at a polymer concentration up to 1,000 µg/mL and harmless to normal liver and kidney organs in mice at an intravenous dose of 1.25 mg/kg. The results of this study suggest that NIR-emitting polymeric nanogels based on bioreducible dextran-deoxycholic acid conjugates show high potential as fluorescence nanoprobes for safe and noninvasive SLN mapping. Keywords: nanogel, disulfide, dextran, lymph node, tomographic imaging

Interaction-powered supernovae (SNe) explode within an optically thick circumstellar medium (CSM) that could be ejected during eruptive events. To identify and characterize such pre-explosion outbursts, we produce forcedphotometry light curves for 196 interacting SNe, mostly of Type IIn, detected by the Zwicky Transient Facility between early 2018 and 2020 June. Extensive tests demonstrate that we only expect a few false detections among the 70,000 analyzed pre-explosion images after applying quality cuts and bias corrections. We detect precursor eruptions prior to 18 Type IIn SNe and prior to the Type Ibn SN 2019uo. Precursors become brighter and more frequent in the last months before the SN and month-long outbursts brighter than magnitude -13 occur prior to 25% (5-69%, 95% confidence range) of all Type IIn SNe within the final three months before the explosion. With radiative energies of up to 1049erg, precursors could eject ~1M⊙of material. Nevertheless, SNe with detected precursors are not significantly more luminous than other SNe IIn, and the characteristic narrow hydrogen lines in their spectra typically originate from earlier, undetected mass-loss events. The long precursor durations require ongoing energy injection, and they could, for example, be powered by interaction or by a continuum-driven wind. Instabilities during the neon- and oxygen-burning phases are predicted to launch precursors in the final years to months before the explosion; however, the brightest precursor is 100 times more energetic than anticipated.

Due to the limited self-repair ability of the annulus fibrosus (AF), current tissue engineering strategies tend to use structurally biomimetic scaffolds for AF defect repair. However, the poor integration between implanted scaffolds and tissue severely affects their therapeutic effects. To solve this issue, we prepared a multifunctional scaffold containing loaded lysyl oxidase (LOX) plasmid DNA exosomes and manganese dioxide nanoparticles (MnO2 NPs). LOX facilitates extracellular matrix (ECM) cross-linking, while MnO2 NPs inhibit excessive reactive oxygen species (ROS)-induced ECM degradation at the injury site, enhancing the crosslinking effect of LOX. Our results revealed that this multifunctional scaffold significantly facilitated the integration between the scaffold and AF tissue. Cells were able to migrate into the scaffold, indicating that the scaffold was not encapsulated as a foreign body by fibrous tissue. The functional scaffold was closely integrated with the tissue, effectively enhancing the mechanical properties, and preventing vascular invasion, which emphasized the importance of scaffold-tissue integration in AF repair.

Abstract Bletilla striata has been used in traditional Chinese medicine for thousands of years to treat a variety of health diseases. Currently, metabolic causes of differences in medicinal values are unknown, due to the lack of a large-scale and comprehensive investigation of metabolites in Bletilla species. In order to gain a better understanding of the major chemical constituents responsible for the medicinal value, this study aimed to explore the metabolomic differences among three Bletilla species (Bletilla striata: Bs, Bletilla ochracea: Bo and Bletilla formosana: Bf). There were 258 different metabolites between ‘Bo’ and ‘Bf’, the contents of 109 metabolites had higher abundance, while 149 metabolites showed less accumulation. There were 165 different metabolites between the ‘Bs’ and ‘Bf’, content of 72 metabolites was increased and content of 93 metabolites was decreased. There were 239 different metabolites between the ‘Bs’ and ‘Bo’, content of 145 metabolites was increased and content of 94 metabolites was decreased. In the Bo_vs_Bf, Bs_vs_Bf and Bs_vs_Bo groups, the major differential categories were flavonoids, phenolic acids, organic acids and alkaloids. Moreover, the differential metabolites were clustered into clear and distinct profiles via K-means analysis. In addition, the major differential categories were flavonoids, phenolic acids, organic acids and alkaloids. The ‘Flavonoid biosynthesis’ (ko00941) and ‘Phenylalanine metabolism’ (ko00360) pathways were significantly enriched in Bo_vs_Bf, Bs_vs_Bf and Bs_vs_Bo comparisons. These results clarify the metabolomics in different Bletilla species, as well as providing basis for the phamaceutical value of novel species of Bletilla.

[Objective] Codon usage bias of four Zygophyllum chloroplast genomes, and their main patterns and causes were analyzed for better understanding of the codon optimization, preference mechanism, and genetic evolution relationship of Zygophyllum . [Methods] The parity preference (PR2-plot) analysis, effective number of codons (NEC-plot), neutrality plot, and RSCU cluster analysis of 40 genes from four Zygophyllum species were carried out using CodonW, EMBOSS, and other softwares in this study. [Results] The codon usage patterns in the plastomes of four Zygophyllum species were similar, the GC content of codon was followed by GC1> GC2> GC3, the average ENC values were more than 35, and the CAI was 0.17, indicating that gene expression of the chloroplast genome of Zygophyllum species was low and codon preference was weak. The results of neutral mapping analysis, ENC-plot selection, and PR2- plot analysis showed that the codon usage pattern was predominantly affected by natural selection. RSCU cluster analysis showed that Z. fabago, Z. obliquum , Z. xanthoxylum , and Z. kaschgaricum had 19, 13, 14, and 14 optimal codons, respectively. By constructing the high and low gene expression library of the target genes, four optimal genes were selected that were ending with A/U. [Conclusion] Codon bases of the chloroplast genome from four Zygophyllum species are mostly ended with A/U. The preference is weak and the main influencing factor is natural selection. Four optimal codons, including CGA, GAA, UAU and UUA, are identified in this study.

Objective This study examines the effectiveness of integrating problem-based learning (PBL) and situational teaching in laser-assisted ultrasound-guided radial artery puncture training to enhance students′ practical and clinical skills. Methods Forty anesthesiology residents from the First Hospital of Jilin University (2022 - 2023) were randomly assigned to traditional teaching (control group) (n = 18) or PBL with situational teaching (combined group) (n = 22) . The latter group engaged in problem-based scenarios. Assessments included the control knowledge and direct observation of procedural skills (DOPS) . Results The PBL combined group outperformed the control group in preparation, aseptic technique, and puncture skills (P < 0.05) . In Mini-CEX assessments, the combined group excelled in medical interview skills, humanistic care, clinical diagnosis, and overall clinical ability (P < 0.05). Survey results indicated higher agreement on improved clinical thinking and operational abilities in the combined group (P < 0.05). Conclusion This teaching mode is obviously better than the traditional teaching group, and it is leading in clinical ability and skill operation. Students have achieved remarkable teaching results in practice through this teaching mode.