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Wenbin Guo,1,&ast; Lin Sun,1,&ast; Huijun Yue,1,&ast; Xueqin Guo,1 Lin Chen,1 Jinhong Zhang,1 Zhuqi Chen,1 Yiming Wang,1 Jiao Wang,2 Wenbin Lei1 1Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Wang, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email wangj836@mail.sysu.edu.cn Wenbin Lei, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email leiwb@mail.sysu.edu.cnPurpose: Clinical studies focusing on the association between the gut microbiota and obstructive sleep apnea (OSA) are limited. This study aimed to explore the relationship between intermittent hypoxia and the composition of gut microbiota in adults by analyzing the differences in the characteristics and functional distribution of gut microbiota between patients with different severities of OSA and healthy individuals.Patients and Methods: A cohort of 113 individuals from the First Affiliated Hospital of Sun Yat-sen University underwent overnight polysomnography from July 2019 to August 2021. The individuals included 16 healthy controls and 97 patients with OSA, categorized by the apnea-hypopnea index into mild, moderate, and severe groups. Fecal samples were analyzed using high-throughput sequencing of the 16S rRNA V3–V4 region to assess gut microbiota composition and function. Correlation analysis was used to evaluate the association between clinical indicators and microbiota markers.Results: In patients with OSA, the gut microbiota diversity and the abundance of specific microbes that produce short-chain fatty acids decreased (P< 0.05). The phyla Verrucomicrobia and Candidatus Saccharibacteria, genera Gemmiger and Faecalibacterium, and the species Gemmiger formicilis exhibited decreasing abundance with increasing OSA severity. Correlation analysis revealed a robust association between the proportion of total sleep time, characterized by nighttime blood oxygen saturation below 90%, and the alterations in the gut microbiota, demonstrating that elevated levels of desaturation are correlated with pronounced microbiota dysbiosis (P< 0.05).Conclusion: Compared to the control group, the intermittent hypoxia exhibited by patients with OSA may be related to alterations in the composition and structure of the gut microbiota. Our results demonstrate the importance of monitoring hypoxia indicators in future clinical practice.Keywords: obstructive sleep apnea, gut microbiota, 16S rRNA, intermittent hypoxia

Mengmeng Huo,&ast; Wanying Guo,&ast; Liqiong Ding Department of Pharmaceutics, School of Pharmacy, Hubei University of Science and Technology, Xianning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liqiong Ding, Email dinglq2021@163.comIntroduction: NLRP3, ASC, and procaspase-1 form the multiprotein complex known as the NLRP3 inflammasome. Following the priming of NLRP3 by TLR4 ligand, the activation of the NLRP3 inflammasome causes caspase-1 maturation, which results in the release of IL-1β. Calcium channel antagonists are commonly employed as antihypertensive medications and have anti-inflammatory properties through the inhibition of cytokine release, specifically IL-1β. The impact of calcium channel antagonists on NLRP3 inflammasomes, however, has not been well studied. This study aimed to investigate the effect of the calcium channel blocker benidipine hydrochloride on LPS-induced NLRP3 inflammasome activation in THP-1 macrophages and its possible mechanism.Methods: Firstly, the cytotoxicity of benidipine hydrochloride was determined by MTT. The effect of benidipine hydrochloride on LPS-induced IL-1β release was determined by ELISA. Then, the effect of benidipine hydrochloride on the expression of IL-1β, NLRP3, ASC, and Caspase-1 induced by LPS was determined by QPCR, and the expression of IL-1β, GSDMD, Caspase-1, and their active forms was determined by Western blot, and the activation of NF-κB was determined by Western blot and immunofluorescence. Finally, the production of ROS was determined by flow cytometry and fluorescence microscopy.Results: Benidipine hydrochloride was found to drastically lower the expression of NLRP3, ASC, and caspase 1, which in turn decreased the amount of IL-1β secreted by THP-1 macrophages. Benidipine hydrochloride dramatically reduced the phosphorylation level of NF-κB p65 and its nuclear translocation in THP-1 macrophages. Furthermore, benidipine hydrochloride significantly decreased the generation of ROS.Discussion: Based on these results, we deduced that benidipine hydrochloride prevents ROS formation in THP-1 macrophages and LPS-induced NF-κB signaling, which in turn prevents the activation of NLRP3 inflammasomes and the release of IL-1β.Keywords: benidipine hydrochloride, NLRP3, NF-κB, ROS, THP-1

Wei Guo,1 Jing Tian,1 Yajing Wang,1 Yajing Zhang,1 Jingjing Yan,2 Yutao Du,2 Yanbo Zhang,2,3 Qinghua Han1,4 1Department of Cardiology, the 1st Hospital of Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 2Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China; 3Shanxi Provincial Key Laboratory of Major Diseases Risk Assessment, Taiyuan, Shanxi Province, People’s Republic of China; 4Key Laboratory of Cellular Physiology at Shanxi Medical University, Ministry of Education, Taiyuan, Shanxi Province, People’s Republic of ChinaCorrespondence: Qinghua Han, Department of Cardiology, the 1st Hospital of Shanxi Medical University, No. 85 South JieFang Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email syhqh@sohu.com Yanbo Zhang, Department of Health Statistics, School of Public Health, Shanxi Medical University, No. 56 South XinJian Road, Yingze District, Taiyuan, Shanxi, People’s Republic of China, Email sxmuzyb@126.comPurpose: This study aimed to develop an integrative dynamic nomogram, including N-terminal pro-B type natural peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), for predicting the risk of all-cause mortality in HFmrEF patients.Patients and Methods: 790 HFmrEF patients were prospectively enrolled in the development cohort for the model. The least absolute shrinkage and selection operator (LASSO) regression and Random Survival Forest (RSF) were employed to select predictors for all-cause mortality. Develop a nomogram based on the Cox proportional hazard model for predicting long-term mortality (1-, 3-, and 5-year) in HFmrEF. Internal validation was conducted using Bootstrap, and the final model was validated in an external cohort of 338 consecutive adult patients. Discrimination and predictive performance were evaluated by calculating the time-dependent concordance index (C-index), area under the ROC curve (AUC), and calibration curve, with clinical value assessed via decision curve analysis (DCA). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) were used to assess the contributions of NT-proBNP and eGFR to the nomogram. Finally, develop a dynamic nomogram using the “Dynnom” package.Results: The optimal independent predictors for all-cause mortality (APSELNH: A: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitor (ACEI/ARB/ARNI), P: percutaneous coronary intervention/coronary artery bypass graft (PCI/CABG), S: stroke, E: eGFR, L: lg of NT-proBNP, N: NYHA, H: healthcare) were incorporated into the dynamic nomogram. The C-index in the development cohort and validation cohort were 0.858 and 0.826, respectively, with AUCs exceeding 0.8, indicating good discrimination and predictive ability. DCA curves and calibration curves demonstrated clinical applicability and good consistency of the nomogram. NT-proBNP and eGFR provided significant net benefits to the nomogram.Conclusion: In this study, the dynamic APSELNH nomogram developed serves as an accessible, functional, and effective clinical decision support calculator, offering accurate prognostic assessment for patients with HFmrEF.Keywords: heart failure with mildly reduced ejection fraction, all-cause mortality, risk prediction model, risk strategy, dynamic nomogram

Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Longyi Zheng,1,&ast; Chengjing Zhang,2,&ast; Shichang Bu,1,&ast; Wencheng Guo,3,&ast; Tongtong Li,4 Ying Xu,5 Yunan Liu,4 Caimei Yuan,4 Chengwu Feng,4 Geng Zong,4 Jingwen Zhu,4 Maoying Xing,5 Xin Geng5 1Department of Endocrinology, Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China; 2Department of Nutrition, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, People’s Republic of China; 3Department of General Surgery and Vascular Surgery, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 4CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China; 5National Center for Liver Cancer, Naval Medical University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Maoying Xing; Xin Geng, Email xmyxing@sina.com; gxouc@hotmail.comBackground: Neuregulin 4 (NRG4) was known to be associated with serum lipid levels and atherosclerosis. However, it is unknown whether the role of NRG4 in lipid homeostasis is causal to atherosclerosis and whether the effect is beneficial across different atherosclerosis subtypes.Methods: We investigated the causal role of the levels of serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides regulated by NRG4 in subtypes of atherosclerosis through two sample Mendelian randomization. Aggregated genome-wide association study (GWAS) summary data for serum lipid level of 1.32 million individuals with European ancestry were obtained from the Global Lipids Genetics Consortium. GWAS summary data for four atherosclerosis subtypes (peripheral, coronary, cerebral and the other atherosclerosis) were obtained from FinnGen Consortium. Generalized inverse-variance–weighted Mendelian randomization and several sensitivity analyses were used to obtain the causal estimates.Results: A 1-SD genetically elevated LDL-C level mediated by NRG4 was validated to be nominally associated with the risk of peripheral atherosclerosis (log (odds ratio)= 4.14, 95% confidence interval 0.11 to 8.17, P = 0.04), and the other associations were not significant or could not be validated by sensitivity analyses.Conclusion: LDL-C lowering mediated by NRG4 is likely to prevent peripheral atherosclerosis.Keywords: Mendelian randomization analysis, NRG4, atherosclerosis, lipid

Guoqin Wang,1,&ast; Xiaoying Hu,1,&ast; Nan Ye,1 Xiaoyi Xu,1 Weiyi Guo,1 Lijun Sun,1 Hongrui Dong,1 Xiaoyi Zhao,2 Hong Cheng1 1Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Cheng, Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Beijing, 100029, People’s Republic of China, Email drchengh@163.comPurpose: In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.Patients and Methods: A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.Results: 19 patients in our center’s MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).Conclusion: The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.Keywords: malignancy, membranous nephropathy, PLA2R, THSD7A, NELL-1

Xiuwen Chen,1,&ast; Meiyan Zou,1,&ast; Siquan Liu,1 Weilin Cheng,1 Weihong Guo,2 Xiaoli Feng1 1Stomatology Hospital, School of Stomatology, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weihong Guo; Xiaoli Feng, Email drguowh@163.com; dentistfxl226@163.comAbstract: Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis. Keywords: graphene, graphene oxide, regenerative medicine, scaffold, anti-inflammatory, bone regeneration, nerve, angiogenesis, dental pulp stem cells

Tingting Wang,1 Yang Wang,2 Qingyue Liu,1 Wenbin Guo,1 Hongliang Zhang,1 Liangliang Dong,3 Jiajun Sun1 1Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 2Department of Laboratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of China; 3Department of Respiratory Medicine, The Second People’s Hospital of Liaocheng, Linqing, Shandong Province, 252600, People’s Republic of ChinaCorrespondence: Jiajun Sun, Department of Intensive Care Unit, The Second People’s Hospital of Liaocheng, No. 306 Jiankang Road, Linqing, Shandong, People’s Republic of China, Tel +86-13793092818, Email 13793092818@126.comBackground: Malnutrition adversely affects prognosis in various medical conditions, but its implications in older adults with Chronic Obstructive Pulmonary Disease (COPD) in the ICU are underexplored. The geriatric nutritional risk index (GNRI) is a novel tool for assessing malnutrition risk. This study investigates the association between GNRI and 90-day mortality in this population.Methods: We selected older adults with COPD admitted to the ICU from Medical Information Mart for Intensive Care (MIMIC)-IV 2.2 database. A total of 666 patients were categorized into four groups based on their GNRI score: normal nutrition (> 98), mild malnutrition (92– 98), moderate malnutrition (82– 91), and severe malnutrition (≤ 81) groups. We employed a restricted cubic spline (RCS) analysis to assess the presence of a curved relationship between them and to investigate any potential threshold saturation effect.Results: In multivariate Cox regression analyses, compared with individuals had normal nutrition (GNRI in Q4 > 98), the adjusted HR values for GNRI in Q3 (92– 98), Q2 (82– 91), and Q1 (≤ 81) were 1.81 (95% CI: 1.27– 2.58, p=0.001), 1.23 (95% CI: 0.84– 1.79, p=0.296), 2.27 (95% CI: 1.57– 3.29, p< 0.001), respectively. The relationship between GNRI and 90-day mortality demonstrates an L-shaped curve (p=0.016), with an approximate inflection point at 101.5.Conclusion: These findings imply that GNRI is a useful prognostic tool in older adults with COPD in the ICU. An L-shaped relationship was observed between GNRI and 90-day mortality in these patients.Keywords: geriatric nutritional risk index, 90-day mortality, older adults, chronic obstructive pulmonary disease, MIMIC-IV

Gang Fan,1,&ast; Jingfen Lu,2,&ast; Jinhui Zha,3,&ast; Weiming Guo,1 Yifei Zhang,4 Yuxin Liu,5 Liyuan Zhang1 1Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, People’s Republic of China; 2The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 3Shenzhen University, Shenzhen, 518000, People’s Republic of China; 4The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China; 5College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyuan Zhang; Gang Fan, Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000, People’s Republic of China, Email liyuan.zhang@uszh.org.cn; gang.fan.med@qq.comAbstract: The maintenance of normal vascular function and homeostasis is largely dependent on the signaling mechanisms that occur within and between cells of the vasculature. TGF-β-activated kinase 1 (TAK1), a multifaceted signaling molecule, has been shown to play critical roles in various tissue types. Although the precise function of TAK1 in the vasculature remains largely unknown, emerging evidence suggests its potential involvement in both physiological and pathological processes. A comprehensive search strategy was employed to identify relevant studies, PubMed, Web of Science, and other relevant databases were systematically searched using keywords related to TAK1, TABs and MAP3K7.In this review, we discussed the role of TAK1 in vascular signaling, with a focus on its function, activation, and related signaling pathways. Specifically, we highlight the TA1-TABs complex is a key factor, regulating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) involved in the processes of inflammation, vascular proliferation and angiogenesis. This mini review aims to elucidate the evidence supporting TAK1 signaling in the vasculature, in order to better comprehend its beneficial and potential harmful effects upon TAK1 activation in vascular tissue.Keywords: TGF-β-activated kinase 1, vascular disease, mitogen-activated protein kinase, transforming growth factor-β, smooth muscle cell, endothelial cell

Lili Zhang,1– 3 Yunshu Zhang,2,3 Wentao Guo,2,3 Qi Ma,1,4 Feng Zhang,2,3 Keqing Li,2,3 Qizhong Yi1,4 1The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Hebei Provincial Mental Health Center, Baoding, Hebei Province, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioural Disorders, Baoding, Hebei Province, People’s Republic of China; 4Xinjiang Clinical Research Center for Mental (Psychological) Disorder, Urumqi, People’s Republic of ChinaCorrespondence: Qizhong Yi, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushan Road, Urumqi, 830054, People’s Republic of China, Tel +86 13079911689, Email qizhongyi@126.com Keqing Li, Hebei Provincial Mental Health Center, No. 572, Dongfeng East Road, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13703288007, Email like2125@sina.comPurpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress.Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups.Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1.Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.Keywords: depressive disorder, chronic stress, hippocampus, functional connectivity

Jia Li,1,2 Wenjing Guo,1,2 Jieru Wang,1,2 Xiaomeng Feng,1,2 Qingsong Lin,1,2,&ast; Yizhou Zheng,1,2 Fengkui Zhang,1,2 Yingchang Mi,1,2 Xiaofan Zhu,1,2 Erlie Jiang,1,2 Zhijian Xiao,1,2 Jianxiang Wang,1,2 Sizhou Feng1,2,&ast; 1State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, People’s Republic of China; 2Tianjin Institutes of Health Science, Tianjin, 301600, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sizhou Feng, Hematopoietic Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Tel +86-022-23909162, Fax +022-23909047, Email doctor_szhfeng@163.com; szfeng@ihcams.ac.cnObjective: This study aimed to assess the impact of colonization status on the outcomes of Acinetobacter spp. bloodstream infection (BSI) and investigate the homology and within-host evolution between colonizing and bloodstream carbapenem-resistant Acinetobacter spp. (CRA) to inform antibiotic therapeutic decisions.Methods: We analyzed clinical outcomes of 46 hematological patients with Acinetobacter spp. BSI and performed whole-genome sequencing on the remaining CRA isolates.Results: Among the patients, 39.1% (n=18) had prior Acinetobacter spp. colonization. Colonized patients had higher rates of polymicrobial BSI (50.0% vs 21.4%, P=0.044) and CRA BSI (72.2% vs 17.9%, P< 0.001), resulting in elevated inflammatory markers and increased 30-day mortality. Each of the eight pairs of the remaining respiratory colonizing and bloodstream CRA strains belonged to the same genomospecies. Each pair exhibited definitive agreement in at least 21 of the 22 most representative antibiotic susceptibility tests. The minimum spanning tree based on multilocus sequence typing (MLST) and phylogenetic trees based on MLST and single nucleotide polymorphism (SNP) all indicated that each pair shared the same minimum branch. Very few non-synonymous SNPs in genic regions were identified during the transition from respiratory colonization to bloodstream infection, with minimal changes in virulence genes. Homology analysis suggested that CRA BSI originated from colonizing isolates in the respiratory tract.Conclusion: Strict infection control measures are needed to manage Acinetobacter spp. colonisation in hematological patients. Appropriate empirical therapy can be administered for suspected CRA BSI based on the antimicrobial minimum inhibitory concentration of CRA colonising the respiratory tract.Keywords: Acinetobacter, colonization, bloodstream infections, homology, therapy, carbapenem-resistant

Mengjin Hao,1,2 You Lv,1 Siyuan Liu,1 Weiying Guo1 1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 2Department of Endocrinology, Jining No. 1 People’s Hospital, Jining, Shandong, 272000, People’s Republic of ChinaCorrespondence: Weiying Guo, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China, Email guowy@jlu.edu.cnAbstract: In recent years, obesity has become one of the major diseases that affect human health and consume human health resources, especially when it causes comorbidities such as hypertension, diabetes, cardiovascular disease and kidney disease. Many studies have demonstrated that obesity is associated with the development of chronic kidney disease and can exacerbate the progression of end-stage renal disease. This review described the mechanisms associated with the development of obesity-associated nephropathy and the current relevant therapeutic modalities, with the aim of finding new therapeutic targets for obesity-associated nephropathy. The mechanisms of obesity-induced renal injury include, in addition to the traditional alterations in renal hemodynamics, the involvement of various mechanisms such as macrophage infiltration in adipose tissue, alterations in adipokines (leptin and adiponectin), and ectopic deposition of lipids. At present, there is no “point-to-point” treatment for obesity-induced kidney injury. The renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporter 2 (SGLT-2) inhibitors and bariatric surgery described in this review can reduce urinary protein to varying degrees and delay the progression of kidney disease. In addition, recent studies on the therapeutic effects of intestinal flora on obesity may reduce the incidence of obesity-related kidney disease from the perspective of primary prevention. Both of these interventions have their own advantages and disadvantages, so the continuous search for the mechanism of obesity-induced related kidney disease will be extremely helpful for the future treatment of obesity-related kidney disease.Keywords: obesity, kidney injury, inflammation, oxidative stress, adiponectin, leptin

Jianmei Lu,1,2,&ast; Yongzhu Zeng,1,&ast; Huashuai Zhong,1 Wei Guo,1 Yuyan Zhang,1 Wanting Mai,3 Yucui Qin,4 Xiaodan Su,3 Bo Zhang,5 Weisen Wu,1 Yu Zhu,1 Qiujie Huang,6 Yong Ye1,7– 9 1Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2The Second Nanning People’s Hospital, Nanning, People’s Republic of China; 3The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 4Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Scientific Research Center, Guilin Medical University, Guilin, People’s Republic of China; 6Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 7Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, People’s Republic of China; 8Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Nanning, People’s Republic of China; 9Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Huang, Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China, Email hqj8@163.com Yong Ye, Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China, Email yong-ye@163.comBackground and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.Results: The nanoparticles prepared in this study have an average particle size of (255.9± 5.10) nm, with an encapsulation rate of (72.83± 2.13) % and a drug loading of (4.65± 0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.Keywords: nanoparticles, colonic targeting, metabolic disorders, gut microbiota

Qi Wang,1,2,&ast; Min Wen,2,3,&ast; Shaohang Fan,2,4 Jinning Liu,2 Xiaowen Wang,5 Wentao Guo,2 Jinyun Hu,6 Jialan Zhang,2 Bing Li,2,7 Lili Zhang,2,7 Yunshu Zhang,1,2,7 Keqing Li2,7 1Clinical Medicine College, Hebei University, Hebei, People’s Republic of China; 2Hebei Provincial Mental Health Center, Hebei, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4School of Psychology and Mental Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 5Psychosomatic Medicine Department, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of China; 6Psychiatric Department, The Second People’s Hospital of Yuxi, Yunnan, People’s Republic of China; 7Hebei Provincial Key Laboratory of Major Mental and Behavioral Disorders, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Li, Hebei Provincial Mental Health Center, Hebei, People’s Republic of China, Email like2125@sina.com Yunshu Zhang, Hebei Provincial Mental Health Center, Hebei, People’s Republic of China, Email yunshucoffee@sina.comObjective: Suicidal behavior is strongly correlated with depressive symptoms and the degree of suicidal ideation. Cognitive impairment may have varying degrees of influence on suicidal ideation (SI) and suicidal attempts (SA). The aim of this study was to identify the cognitive biomarkers that distinguish suicidal ideation from suicidal attempts in adolescents.Methods: The cross-sectional sample comprised 54 adolescents with major depressive disorder (MDD) and 32 healthy controls (HC). The THINC-it was utilized to assess cognitive function of all the samples. Suicidal ideation was examined by the Positive and Negative Suicide Ideation Scale (PANSI). Based on the type of data, one-way ANOVA or Kruskal–Wallis was performed to investigate group differences. Bonferroni post-hoc analysis was employed for regulating type I error for pairwise comparisons. Network analysis was used to compare the networks associated with suicidal ideation, depression symptoms, and cognitive function between SA and SI.Results: The depression symptoms (HAMD-17) (F=72.515, P< 0.001) and suicidal ideation (PANSI) (F=267.952, P< 0.001) in the SA were higher than those in the SI. Analysis of between-group differences showed SA performed worse in THINC-it, especially in “Spotter (SP)” (P=0.033), “Objective cognition score (OS)” (P=0.027) and “Composite score (CS)” (P=0.017). Compared with SI, network analysis revealed that SA had a unique network of cognitive function, depressive symptoms, and suicidal ideation. Nevertheless, both networks exhibit comparable performance concerning the node strength of cognitive function. Within their separate networks, the aspects of CS, OS, and SP have emerged as the three most crucial elements.Conclusion: Adolescents with SI or SA exhibit a broad spectrum of cognitive impairments. Attention impairment can be beneficial in discerning between SI and SA. Future interventions for adolescent suicide can center on attention and the comprehensive cognitive ability that it represents.Keywords: attention impairment, suicide ideation, suicide attempts, adolescent, THINC-it tool, network analysis

Hongjie Cai,1 Song Chen,2 Zhiqiang Wu,1 Fan Wang,1 Shuangyan Tang,1 Ludan Chen,1 Wenbo Guo1 1Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510062, People’s Republic of China; 2Department of Minimally Invasive Interventional Therapy, Sun Yat-Sen University Cancer Center and Sun Yat-Sen University State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of ChinaCorrespondence: Wenbo Guo, Email guowenbo@mail.sysu.edu.cnPurpose: Local in combination with systemic therapy might be an option for patients with advanced unresectable hepatocellular carcinoma (uHCC). This study examined the clinical benefits and adverse events (AEs) of first-line transarterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC) combined with atezolizumab (Atezo) and bevacizumab (Bev) in patients with uHCC of a diameter larger than 8 cm.Patients and methods: This retrospective study included patients with uHCC of a diameter larger than 8 cm who were treated with first-line Atezo-Bev and TAE+HAIC at the First Affiliated Hospital of Sun Yat-Sen University between September 30, 2019, and September 30, 2022. Progression-free survival (PFS), overall survival (OS), tumor response according to mRECIST, and AEs were analyzed. Multivariable Cox analyses were performed to examine the factors associated with PFS.Results: Thirty patients were included. The objective response rate (ORR) was 74.4% (95% confidence interval [CI], 59.3%-89.5%), and the disease control rate (DCR) was 93.3% (95% CI, 85.4%-98.6%). The median follow-up was 11.4 (inter-quartile range [IQR], 5.5– 17.9) months. The median PFS was 6.8 (95% CI, 2.6– 11.1) months. The 3-, 6-, 9-, and 12-month survival rates were 86.2%, 82.5%, 68.6%, and 60%, respectively. The median OS was not estimated. Extrahepatic metastasis was independently associated with PFS (hazard ratio [HR]=3.468, 95% CI, 1.001– 12.023). The most common AEs were fever (46.7%). Grade 4 AEs occurred one time as hematemesis but no 5 AEs were observed.Conclusion: Atezo-Bev combined with TAE and HAIC might benefit patients with uHCC of a diameter larger than 8 cm, with manageable AEs.Keywords: immune checkpoint inhibitors, tyrosine kine inhibitors, local therapy, systemic therapy, large unresectable hepatocellular carcinoma

Wenhui Guo,1,&ast; Xiang Lian,2,&ast; Hong Li,2 Lushun Jiang,1 Yingsha Chen,3 Ping Shen,1 Wei Yu1 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University; Xiangshan First People’s Hospital Medical and Health Group; Ningbo Fourth Hospital, Ningbo, People’s Republic of China; 3Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Shen; Wei Yu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel/Fax +86 571 87236421, Email shenping123451@126.com; wyu@zju.edu.cnObjective: To evaluate the characteristics of immunocytes and cytokines associated with bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).Methods: Patients with BSIs K. pneumoniae (BSIs-Kpn) were enrolled in our hospital between 2015 and 2022. Whole blood and serum samples were collected on the first day after diagnosis. Immunocytes and cytokines profiles were assessed using multicolor flow cytometry and multiplex immunoassays, respectively. The test cytokines included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2, IL-4, IL-6, IL-10, and IL-17A.Results: A total of 313 patients had BSIs-Kpn, including 145 with CRKP, 43 with extended-spectrum β-lactamases (ESBL) producing Kpn (ESBL-Kpn) and 125 with non-CRKP or non-ESBL-Kpn (susceptible Kpn, S-Kpn). Absolute number of leukomonocyte (CD45+) in CRKP, ESBL-Kpn and S-Kpn were 280.0 (138.0– 523.0) cells/μL, 354.5 (150.3– 737.3) cells/μL, and 637.0 (245.0– 996.5) cells/μL, respectively. Compared with S-Kpn group, the absolute numbers of leukomonocyte (including T lymphocytes, B lymphocytes and natural killer cells) in patients with CRKP were significantly lower than that in patients with S-Kpn (P

Hongqi Meng,1 Ying Zhao,1 Hang Cai,2 Di You,3 Ying Wang,4 Siyu Wu,1 Yixin Wang,5 Wenlai Guo,1 Wenrui Qu1,6 1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 2Department of Pharmacy, The Second Hospital of Jilin University, Changchun, 130041, People’s Republic of China; 3Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun, 130031, People’s Republic of China; 4Institute of Neural Tissue Engineering, Mudanjiang College of Medicine, Mudanjiang, 157011, People’s Republic of China; 5Department of Plastic Surgery, First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 6Joint International Research Laboratory of Ageing Active Strategy and Bionic Health in Northeast Asia of Ministry of Education, Jilin University, Changchun, 130041, People’s Republic of ChinaCorrespondence: Wenlai Guo, Email guowl19@jlu.edu.cnPurpose: Persistent Infections and inflammation are associated with impaired wound healing in diabetic patients. There is a pressing demand for innovative antimicrobial strategies to address infections arising from antibiotic-resistant bacteria. Polymer-modified gold nanoparticles (AuNPs) show broad-spectrum antibacterial properties and significant biocompatibility. This study investigated the antibacterial and wound healing efficacy of hydrogel dressings conjugated with chitosan-AuNPs in diabetic model rats.Methods: Chitosan (CS)-functionalized gold nanoparticles (CS-AuNPs) were incorporated into hydrogel dressings (Gel/CS-AuNPs), which were formulated through the chemical cross-linking of gelatin with sodium alginate (SA). The basic characteristics of Gel/CS-AuNPs were analyzed by TEM, SEM, XRD, and UV-visible spectra. Rheological, swelling, degradation, and adhesive properties of Gel/CS-AuNPs were also determined. In vitro anti-bactericidal effects of the Gel/CS-AuNPs were analyzed with E. coli, S. aureus, and MRSA. In vitro biocompatibility of the Gel/CS-AuNPs was evaluated using NIH3T3 cells. The in vivo antibacterial and wound healing efficacy of the Gel/CS-AuNPs was analyzed in the diabetic wound model rats. Histological and immunofluorescence staining were performed to determine the status of angiogenesis, epithelization, inflammation response, and collagen deposition.Results: Gel/CS-AuNPs demonstrated significant high biodegradability, water absorption bactericidal, and biocompatibility, and slight adhesiveness. Gel/CS-AuNPs exhibited pronounced antibacterial efficacy against gram-negative, gram-positive, and MRSA in a CS-AuNPs-dose-dependent manner. In the diabetic wound model rats, Gel/CS-AuNPs effectively killed MRSA, reduced inflammation, and promoted angiogenesis and collagen deposition and remodeling at the wound site. As a result, Gel/CS-AuNPs expedited the recovery process for infected diabetic wounds. Among the hydrogels with different CS-AuNPs concentrations, Gel/CS-Au25 with 25% CS-AuNPs showed the best bactericidal and wound healing performance.Conclusion: Gel/CS-AuNPs significantly improve the healing of MRSA-infected diabetic wounds in the rat model. Therefore, Gel/CS-AuNPs show great promise for the treatment of diabetic infection wound healing. Keywords: MRSA, infection, diabetic wounds, hydrogels, CS-AuNPs, antimicrobial

Hongyi Yang,1,&ast; Linbin Lu,1,&ast; Wanting Guo,2 Baocuo Gong,2 Xuewen Wang,1 Yaying Chen,1 Xiong Chen1 1Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Oncology, The 900th Hospital of Joint Logistic Support Force, People’s Liberation Army (PLA), Fuzong Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Chen, Tel +1-216-612-2438, Fax +86-591-24937089, Email cxiongzpc@fjmu.edu.cnBackground: Previous studies have shown that the alpha-fetoprotein (AFP) response has been a key tumour marker in hepatocellular carcinoma (HCC), but its definition remains controversial. Recently, a new study has explored and defined the AFP serological response and used it to explain the subclass of intermediate-stage hepatocellular carcinoma (IM-HCC) with “sharp-falling” AFP change after transarterial chemoembolization (TACE). It may be a new and simple tool for assessing the prognosis of patients. This study aims to explore a simplified AFP trajectory and its impact on overall survival (OS) and disease-free survival (DFS) for IM-HCC after hepatectomy.Patients and Methods: Between January 2007 and May 2012, data from the Sun Yat-sen University Cancer Center was examined in this longitudinal, retrospective cohort study. A generalized additive model was applied to distinguish potential AFP dynamic trajectories. The Kaplan-Meier method was applied to analyze OS and DFS, and multivariate Cox models were used to calculate adjusted hazard ratios (aHRs) and 95% CIs for overall survival.Results: 144 patients who had IM-HCC with at least three AFP repeat measurements were included in the study. Three similar trajectories are displayed using the generalized additive model: low-stable (35.4%; n = 51), high-rising (36.1%; n = 52), and sharp-falling (28.5%; n = 41). Compared with the low-stable class, the aHRs for death were 2.84 (1.50, 5.41) and 0.59 (0.25, 1.40) for the high-rising and sharp-falling classes, adjusted by age and log AFP. Simplified AFP trajectory had higher relative importance than sex, intrahepatic tumor number, Child-Pugh class, and baseline AFP.Conclusion: The simplified AFP trajectory is a promising biomarker for IM-HCC patients undergoing hepatectomy. In the future, it should be verified by a larger population containing various stages of HCC.Keywords: hepatocellular carcinoma, hepatectomy, AFP trajectory, AFP serological response, overall survival

Zilong Yin,1,&ast; Wanying Guo,2,&ast; Yue Wang3 1School of Teacher Education, Jiangsu University, Zhenjiang, People’s Republic of China; 2Overseas Education College, Jiangsu University, Zhenjiang, People’s Republic of China; 3College of Education, Chungnam National University, Daejeon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Zilong Yin, School of Teacher Education, Jiangsu University, No. 301 Xuefu Road, Zhenjiang, Jiangsu Province, 212013, People’s Republic of China, Email yinzilong1@hotmail.comPurpose: The relationship between psychological distress (PD) and academic engagement (AE) in adolescents is widely recognized. However, there is a lack of research on the mechanisms behind this correlation, especially in COVID-19 pandemic policy liberalization. This study proposed a moderated mediation model to determine the mediating role of social-emotional competence (SEC) between PD and AE and the moderating role of teachers’ caring behavior (TCB).Patients and methods: The moderated mediation model was tested by PROCESS macro developed based on SPSS with Chinese adolescents aged 13– 18 years (n = 8625; male 50.5%) as survey respondents. Multiple scales, including the 6-item Kessler PD Scale, SEC Scale, TCB Scale, and AE Scale, were used in this test.Results: Adolescent PD negatively predicted AE. In addition, SEC partially mediated the relationship between adolescent PD and AE. TCB moderated the direct and indirect relationships between PD and AE, which mitigated the negative effect of PD on AE and enhanced the positive effect of SEC on AE.Conclusion: Adolescent SEC and TCB are essential in mediating PD and AE. This study provided instructions for schools and teachers to intervene in adolescents’ PD and academic problems, such as improving SEC and engaging in TCB in an adequate and timely manner. In addition, these findings provided vital references for adolescent mental health interventions in future large-scale public health events.Keywords: psychological distress, academic engagement, social-emotional competence, teachers’ caring behavior, adolescents, COVID-19 policy liberalization

Xiaojuan Wang,1,&ast; Lingling Huang,1,&ast; Wenbin Guo,2,&ast; Langlang Tang,1 Aiyu Wu,3 Peng Wu,4 Xiance Zhao,4 Qi Lin,1 Lian Yu3 1Department of Radiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China; 2Department of Pathology, Pingtan Comprehensive Experimental Area Hospital, Fuzhou, Fujian, 350400, People’s Republic of China; 3Department of Rheumatology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan, Fujian, 364000, People’s Republic of China; 4Philips Healthcare, Shanghai, 200000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qi Lin, Department of Radiology, Longyan First Affiliated Hospital of Fujian Medical University, No. 105, Jiu Yi North Road, Xin Luo District, Longyan City, 364000, People’s Republic of China, Tel + 86 13950881931, Email linqii8m@126.com Lian Yu, Department of Rheumatology, Longyan First Affiliated Hospital of Fujian Medical University, No. 105, Jiu Yi North Road, Xin Luo District, Longyan City, 364000, People’s Republic of China, Email yulianian@126.comPurpose: The purpose of this study was to observe cerebral microstructure and microcirculation features, as well as changes in white matter (WM) and gray matter (GM) among patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE).Methods: We compared 36 female patients with non-NPSLE and 20 age- and gender-matched healthy controls (HCs) who underwent 3.0T MRI imaging with diffusion kurtosis imaging (DKI) and 3D pseudo-continuous Arterial Spin Labeling (pCASL). Mean kurtosis (MK), mean kurtosis tensor (MKT), and cerebral blood flow (CBF) values were obtained from 25 brain regions, including WM and GM. We analyzed the correlation between imaging indicators and clinical data.Results: When compared with HCs, patients with non-NPSLE had reduced MK and MKT values in regional WM, deep GM, and the left frontal lobe cortical GM, and increased CBF in the right parietal lobe WM and right semioval center (SOC). The MK and MKT values were weakly correlated with CBF in some regions, including WM and GM. Complement 3 (C3) and Complement 4 (C4) showed a weak positive correlation with MK and MKT in some regions, including WM and deep GM, while platelet (PLT) was positively correlated with MKT in the left frontal lobe WM; dsDNA antibody was correlated negatively with MK in the right occipital lobe WM; and erythrocyte sedimentation rate (ESR) was correlated negatively with CBF in the left SOC.Conclusion: Our findings revealed the presence of brain microstructural and microvascular abnormalities in non-NPSLE patients, indicating microstructural damage in the cortical GM, which was less commonly reported. We found DKI and pCASL useful in detecting early brain lesions, and MK was a more sensitive and beneficial indicator.Keywords: arterial spin labeling, cerebral blood flow, diffusion kurtosis imaging, gray matter, systemic lupus erythematosus, white matter

Yanmei Song,&ast; Huiyuan Chu,&ast; Fang Liu, Wenjie Guo, Na Gao, Che Chen, Shisan Bao Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Che Chen; Shisan Bao, Department of Clinical Laboratory Diagnostics, School of Public Health Gansu University of Chinese Medicine, 35, Dingxi East Road, Chengguan, Lanzhou, Gansu, 730000, People’s Republic of China, Tel +86 187 09312856 ; +81 180 176 84959, Email chen72123@163.com; profbao@hotmail.comPurpose: To investigate the role of IL-36 in the tumorigenesis of hepatocellular carcinoma (HCC). IL-36 composed of a natural antagonist (IL-36Ra) and three agonists (IL-36α, -β, -γ) that stimulate inflammation by binding to a common receptor consisting of IL-36R and IL-1RAcP. HCC is a common malignancy associated with high morbidity and mortality, often diagnosed at later stages. Although the exact role of IL-36α in HCC remains controversial, it is hypothesized that it may play a significant role in the development and progression of this cancer.Materials and Methods: In the current study, we measured both circulating and intrahepatic levels of IL-36α from HCC patients and healthy controls, using ELISA. The association between IL-36 and the differentiation of HCC was determined. Furthermore, the role IL-36 in both HCC and non-HCC cell lines was evaluated in vitro.Results: Circulating and intra-hepatic IL-36α was inversely correlated with differentiation of HCC, suggesting that IL-36α contribute to protection during the development of HCC. Based on bioinformatics, miR-27b-3p is closely related to downstream IL-36α. Thus, we determined miR-27b-3p expression in HCC tissues, showing upregulated miR-27b-3p was inversely correlated with IL-36α in HCC, perhaps via CXCL1 in HCC cells. It was confirmed that IL-36α inhibited HCC proliferation, viability and migration in vitro, consistent with reduced the expression of cytokines IL-1β, IL-18, implying that IL-36α inhibited the possible involvement of pyroptosis.Conclusion: Our data suggests that IL-36α may be a potential therapeutic target and a prediction biomarker for the management of HCC.Keywords: hepatocellular carcinoma, interleukin-36α, prognosis, biomarker

Baocuo Gong,1,2,&ast; Xuewen Wang,1,3,&ast; Wanting Guo,1 Hongyi Yang,1 Yanhong Shi,1 Yaying Chen,1 Simiao Gao,1 Jialin Chen,1 Lifang Liu,2 Linbin Lu,1 Xiong Chen1 On behalf of Fujian HCC-biomarker Study Group1Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, 350025, People’s Republic of China; 2Department of Oncology, Oriental Hospital Affiliated to Xiamen University, Fuzhou, Fujian, 350025, People’s Republic of China; 3Department of Histology and Embryology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linbin Lu; Xiong Chen, Department of Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, 321 Xihong Road, Fuzhou, Fujian, 350025, People’s Republic of China, Email doctorxiaolin@fjmu.edu.cn; cxiongzpc@fjmu.edu.cnBackground: Transarterial chemoembolization (TACE) is the recommended first-line treatment for intermediate-stage Hepatocellular carcinoma (HCC) patients. However, predicting the survival of HCC patients receiving TACE remains challenging.Methods: In this retrospective study, we analyzed a total of 1805 HCC patients who received TACE. The patients were randomly divided into a training set (n = 1264) and a validation set (n = 541). We examined various prognostic factors within the training set and developed a simple ALFP (ALBI grade, AFP, and Prothrombin time) score, which was subsequently validated using the independent validation set.Results: Our multivariate analysis revealed that baseline ALBI grade 2 or 3, AFP ≥ 100 ng/mL, and PT > 13.1 s were independent unfavorable prognostic factors for HCC patients receiving TACE (p 13.1 s. The score has a range of 0 to 3, and higher scores are associated with poorer outcomes. The median overall survival (OS) varied significantly among different ALFP score groups, both in the training set and the validation set (p

Song Chen,1 Feng Shi,2 Zhiqiang Wu,3 Liguang Wang,4 Hongjie Cai,3 Ping Ma,5 Yuanmin Zhou,5 Qicong Mai,2 Fan Wang,3 Shuangyan Tang,3 Wenquan Zhuang,3 Jiaming Lai,6 Xiaoming Chen,2 Huanwei Chen,4 Wenbo Guo3 1Department of Minimally Invasive Interventional Therapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Interventional Radiology, Guangdong Provincial People’s Hospital, Guangzhou, People’s Republic of China; 3Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China; 5Department of Oncology, the Twelfth People’s Hospital of Guangzhou, Guangzhou, People’s Republic of China; 6Center of Hepato-Pancreato-Biliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Huanwei Chen, Department of Hepatopancreatic Surgery, the First People’s Hospital of Foshan, Foshan, People’s Republic of China, Email chwei_fsyyy@163.com Wenbo Guo, Department of Interventional Radiology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China, Email guowenbo@mail.sysu.edu.cnPurpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load.Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9– 14.8) and 5.0 months (95% CI, 4.2– 5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients.Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.Keywords: hepatocellular carcinoma, transhepatic arterial embolization, hepatic arterial infusion chemotherapy, lenvatinib, tislelizumab

Yuyi Zhang,1 Suzhen Wang,1 Chunmei Zhou,1 Yao Zhang,2 Jue Pan,2 Baishen Pan,1 Beili Wang,1 Bijie Hu,2 Wei Guo1 1Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Infectious Disease, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Wei Guo, Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64041990-2376, Email guo.wei@zs-hospital.sh.cn Bijie Hu, Department of Infectious Disease, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86-21-64041990-2328, Email hu.bijie@zs-hospital.sh.cnBackground: Aspergillus species are becoming a major public health concern worldwide due to the increase in the incidence of aspergillosis and emergence of antifungal resistance. In this study, we surveyed all Aspergillus species isolated from aspergillosis patients in Zhongshan Hospital Fudan University, Shanghai, China, from 2019 to 2021.Methods: We characterized the susceptibility profiles of these Aspergillus species to medical azoles (voriconazole, itraconazole and posaconazole) using YeastOneTM broth microdilution system. To determine the underlying antifungal resistance mechanisms in azole-resistant A. fumigatus (ARAf) isolates, we characterized mutations in the cyp51A gene. Genotypic diversity of sampled A. fumigatus was investigated using CSP-typing.Results: A total of 112 Aspergillus isolates (81 A. fumigatus, 17 A. flavus, 5 A. niger, 2 A. terreus, 2 A. lentulus, 2 A. oryzae, 1 A. nidulans, 1 A. versicolor and 1 A. sydowii) from 105 patients diagnosed with aspergillosis (including proven or probable invasive aspergillosis, chronic pulmonary aspergillosis, allergic bronchopulmonary aspergillosis and cutaneous aspergillosis) were obtained. Eight isolates (7 A. fumigatus and 1 A. niger) from seven patients were either azole non-susceptible or non-wild type. Azole non-susceptible or non-wild type rate was 7.1%/isolate and 6.7%/patient analysed. Four ARAf harbored TR34/L98H mutation, whereas one carried TR46/Y121F/T289A allele. The 81 A. fumigatus isolates were spread across 8 CSP types with t01 to be the predominant type (53.1%). ARAf isolates were distributed over CSP types t01, t02, t04A and t11.Conclusion: Results from this study provided us with an understanding of the antifungal resistance and related characteristics of Aspergillus species in Eastern China. Further comparisons of our results with those in other countries reflect potential clonal expansion of A. fumigatus in our region. Further surveillance study is warranted to guide antifungal therapy and for epidemiological purposes.Keywords: Aspergillus fumigatus, aspergillosis, antifungal susceptibility profile, non-susceptible, non-wild type, CSP-typing

Changjiang Yu,1,&ast; Wei Guo,1,2,&ast; Zhulai Zhang,1,&ast; Yuting Ma,3,&ast; Xiaobei Cao,1 Na Sun,1 Yingyao Cui,1 Yunshen Wang,1 Wenyu Cui,1 Yongsheng Xu,1 Jianghua Zhan2,4 1Department of Pediatric Respiratory Medicine, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, People’s Republic of China; 2Graduate School of Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Infection, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, People’s Republic of China; 4Department of Pediatric Surgery, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongsheng Xu, Department of Pediatric Respiratory Medicine, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, 300134, People’s Republic of China, Email xxyyss@126.com Jianghua Zhan, Graduate School of Tianjin Medical University, Department of Pediatric Surgery, Tianjin Children’s Hospital, Tianjin University Children’s Hospital, Tianjin, 300134, People’s Republic of China, Email zhanjianghuatj@163.comPurpose: Metagenomic next-generation sequencing (mNGS) is an emerging technique for pathogen detection. However, most literature on the clinical application of pediatrics generally comprises case reports or small-scale cohort studies.Patients and Methods: A total of 101 children with community-acquired severe pneumonia admitted to Tianjin Children’s Hospital from November 2021 to February 2022 were included. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected using mNGS. The performances of mNGS and conventional tests on pulmonary infection diagnosis and pathogen identification were compared.Results: According to our data, mNGS had a broader spectrum for pathogen detection. The mNGS results of BALF showed that the number of children with severe pneumonia hospitalized for mycoplasma pneumoniae infection was more than that for other bacterial infections during the COVID-19 epidemic. In addition, 43 cases (42.6%) had been identified with mixed infection, including 36 cases (35.6%) of Mycoplasma pneumoniae mixed with other pathogenic bacteria. Analytically, the mNGS exhibited significantly enhanced detection in the BALF as compared with the conventional laboratory pathogenic detection approaches (P < 0.05). The Pearson correlation analysis revealed positive correlation between the time of fever during hospitalization and the number of mycoplasma sequences (P < 0.05).Conclusion: Compared with traditional methods, mNGS has a higher etiological detection rate and can comprehensively detect various pathogens of severe pneumonia. Therefore, mNGS of bronchoalveolar lavage fluid should be performed in children with severe pneumonia, which is of great significance for guiding treatment.Keywords: mNGS, severe pneumonia, pathogen, BALF, children

Jie Chen,1,&ast; Weichang Guo,2,&ast; Hejia Yin,1 Liju Ma,3 Shaoyou Li,4 Huifang Li1 1Department of Diabetes, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Department of Physical Education, Kunming Medical University, Kunming, 650032, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 4Department of The Scientific Research Laboratory Center, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huifang Li, Department of Diabetes, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District, Kunming, 650032, People’s Republic of China, Email lhfkm2021@163.comBackground: This study aimed to explore relationship among RANTES − 28 (rs2280788) C/G polymorphism or CCR5 59029 (rs1799987) A/G polymorphism, level of self-expression, and type 2 diabetes mellitus (T2DM).Materials and Methods: Clinical data were collected from 92 subjects with normal blood glucose (NC) and 97 patients with T2DM (DM). CCR5 levels on the surface of monocyte/lymphocyte and plasma RANTES levels were detected by flow cytometry. TaqMan real-time fluorescent quantitative PCR was used to detect genetic polymorphisms of RANTES rs2280788 and CCR5 rs1799987.Results: There were no significant differences in frequencies of CCR5 rs1799987 genotype and A/G allele and frequencies of RANTES rs2280788 genotype and C/G allele, between subjects in NC and DM group (P > 0.05). Plasma RANTES level in DM group was significantly lower than NC group (P < 0.05), and difference came from patients with T2DM using insulin and subjects with normal blood glucose. CCR5 levels on the surface of monocytes and lymphocytes of patients in DM group were higher than NC group (P < 0.05). There was no significant difference in CCR5 level on the surface of monocytes and lymphocytes (or plasma RANTES level) among different genotypes of CCR5 rs1799987 (or RANTES rs2280788) (P > 0.05). RANTES level was positively correlated with age and TC and negatively correlated with diabetes course and HbA1c. CCR5 level on the surface of monocytes was positively correlated with drinking years, HbA1c, course of diabetes, and negatively correlated with TC. CCR5 on lymphocyte surface was positively correlated with diabetes course, smoking years, HbA1c, and negatively correlated with LDL, TC, HDL (P < 0.05).Conclusion: RANTES -28 (rs2280788) C/G polymorphism or CCR5 59029 (rs1799987) A/G polymorphism may not be associated with T2DM of Han nationality in Kunming and cannot affect RANTES and CCR5 expression. RANTES and CCR5 levels may be related to T2DM but may also be affected by age, blood lipids, HbA1c, diabetes course, drugs, and other factors.Keywords: type 2 diabetes, inflammation, cytokines, gene polymorphism, RANTES, CCR5

Huanhuan Zhang,1 Meinv Liu,1 Wenchang Guo,2 Jinhua He,1 Jianli Li1 1Department of Anesthesiology, Hebei General Hospital, Shijiazhuang City, Hebei Provence, People’s Republic of China; 2Department of Neurosurgery, Hebei General Hospital, Shijiazhuang City, Hebei Provence, People’s Republic of ChinaCorrespondence: Jianli Li, Department of Anesthesiology, Hebei General Hospital, 348 Heping Road West, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel +86 311 8598 8447, Email hblijianli@163.comBackground: Trigeminal neuralgia (TN) is a facial neuropathic pain, which is defined as unilateral brief shock-like paroxysmal pain. Percutaneous balloon compression (PBC) was widely used to treat TN under general anesthesia. However, trigeminocardiac reflex (TCR) as a brainstem reflex can induce bradycardia or even cardiac arrest during PBC, which may result in catastrophic consequences in elderly patients. The aim of the present study was to investigate the effect of trigeminal ganglion block on TCR in elderly patients with TN during PBC.Materials and Methods: Eighty-two elderly patients undergoing PBC were recruited to this randomized controlled study. The participants were randomly allocated to the control group (C group, n=41) and study group (S group, n=41). After anesthesia induction, 2% lidocaine 0.5 mL or an equal volume of normal saline was injected into Meckel’s cave. HR and MAP were recorded at seven time-points, and the TCR incidence was compared.Results: HR decreased in the C group at the time of foramen ovale puncture (T5) and at the time of ganglion compression (T6) compared with that at the moment of needle puncture (T4) (P< 0.05), but almost no change in the S group. HR was lower in the C group compared with the S group at T5 and T6 (P< 0.05). MAP increased significantly at T5 and T6 compared with that at T4 in the C group (P< 0.05), but almost no increase in the S group. Compared with the C group, MAP was lower at T5 and T6 in the S group (P< 0.05). There were no significant differences in HR and MAP between the two groups at T1, T2, T3, T4 and T7. The incidence of bradycardia was higher in the C group than that in the S group (P< 0.05).Conclusion: Trigeminal ganglion block was an effective approach to prevent TCR in elderly patients during PBC.Keywords: trigeminal neuralgia, trigeminocardiac reflex, trigeminal ganglion block, elderly patients

Junxian Ren,1,&ast; Rongcheng Yu,1,&ast; Jingyan Xue,1 Yiqi Tang,1 Sihui Su,1 Chenxi Liao,1 Quanyi Guo,2 Weimin Guo,3 Jinxuan Zheng1 1Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, 510055, People’s Republic of China; 2Institute of Orthopedics, Chinese PLA General Hospital, Key Laboratory of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, 100853, People’s Republic of China; 3Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimin Guo, Department of Orthopedic Surgery, Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, 510080, People’s Republic of China, Tel +86 20 87755766&num;6236, Email guowm5@mail.sysu.edu.cn Jinxuan Zheng, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, 56 Lingyuan West Road, Guangzhou, 510055, People’s Republic of China, Tel +86 20 83802802, Email zhengjx27@mail.sysu.edu.cnAbstract: The maintenance of bone homeostasis includes both bone resorption by osteoclasts and bone formation by osteoblasts. These two processes are in dynamic balance to maintain a constant amount of bone for accomplishing its critical functions in daily life. Multiple cell type communications are involved in these two complex and continuous processes. In recent decades, an increasing number of studies have shown that osteogenic and osteoclastic extracellular vesicles play crucial roles in regulating bone homeostasis through paracrine, autosecretory and endocrine signaling. Elucidating the functional roles of extracellular vesicles in the maintenance of bone homeostasis may contribute to the design of new strategies for bone regeneration. Hence, we review the recent understandings of the classification, production process, extraction methods, structure, contents, functions and applications of extracellular vesicles in bone homeostasis. We highlight the contents of various bone-derived extracellular vesicles and their interactions with different cells in the bone microenvironment during bone homeostasis. We also summarize the recent advances in EV-loaded biomaterial scaffolds for bone regeneration and repair.Keywords: bone, homeostasis, metabolism, extracellular vesicles, regeneration

Na Ta,1,2 Jingchuan Mi,2 Xiaoyan Li,2 Wei Guo,2 Gaowa Yu,3 Guojun Li,4 Shuchun Pang,5 Wuyun Bai,6 Qingjie Liu,7 Haijun Zhao,8 Guangjun Wei,9 Mengguang Fan,2 Yongjun Wen1 1School of Veterinary Medicine, Inner Mongolia Agricultural University, Hohhot, People’s Republic of China; 2Inner Mongolia Center for Disease Control and Research, Hohhot, People’s Republic of China; 3Tong Liao Center for Endemic Disease Control and Research, Tong Liao, People’s Republic of China; 4Chi Feng Center for Disease Control and Research, Chi Feng, People’s Republic of China; 5Xingan Meng Center for Disease Control and Research, Xingan Meng, People’s Republic of China; 6Keyouqian QI Center for Disease Control and Research, Xingan Meng, People’s Republic of China; 7Zhalute Qi Center for Disease Control and Research, Chi Feng, People’s Republic of China; 8Alukerqin Qi Center for Disease Control and Research, Chifeng, People’s Republic of China; 9Balinzuo Qi Center for Disease Control and Research, Chi Feng, People’s Republic of ChinaCorrespondence: Yongjun Wen, School of Veterinary Medicine, Inner Mongolia Agricultural University, No. 306, Zhaowuda Road, Saihan District, Hohhot, 010018, Inner Mongolia, People’s Republic of China, Email wenyongjun2022@163.comObjective: To investigate the distribution, epidemiology, and clinical symptoms of brucellosis and Q fever in northeastern Inner Mongolia.Methods: In this study, 64 townships of Bairin left flag and Alukerqin flag, Jarud flag and Horqin right front flag in four counties with frequent brucellosis and Q fever were selected. Epidemiological characteristics, clinical features, and exposure to risk factors were identified and descriptively analyzed in patients from these areas.Results: There were 367 brucellosis cases in the four regions and 78 positive cases of Q-fever infection. In addition, 24 cases of brucellosis and Q-fever co-infection were identified, with a co-infection rate of 1.13%. Brucellosis and Q fever were mainly concentrated in the 30– 65 and 40– 55 age groups. For brucellosis, the difference between age groups was statistically significant (χ2 = 29.121, P < 0.05). The sex distribution for brucellosis was 225 men (61.31%) and 142 women (38.69%), and 45 men (57.69%) and 33 women (42.31%) had Q fever. Those with brucellosis and Q fever were mainly farmers, accounting for 79.19% and 78.38% of the total number, respectively. Of the 367 cases of brucellosis infection, the main symptoms were joint pain (52.59%), fatigue (47.14%), lower back pain (38.96%), fever (33.24%), hyperhidrosis (28.88%), and muscle pain (20.44%). Of the 78 cases of Q-fever infection, the main symptoms were joint pain (35.90%), fatigue (30.77%), lower back pain (26.92%), fever (21.79%), and hyperhidrosis (17.95%). Muscle pain also accounted for 12.82%.Conclusion: Occupational distribution suggests that we should strengthen the protection measures against diseases infected through animal husbandry. Among the clinical symptoms, fever, hyperhidrosis and fatigue were associated with brucellosis, while fever, headache, and fatigue were significantly associated with Q fever.Keywords: distribution, clinical characteristics, brucellosis, Q fever, northeastern Inner Mongolia

Shaoqin Zheng1,2 &ast;, Yuan Liang2 &ast;, Zhaojia Wang,1 Min Liu,1 Yingyi Chen,1 Ying Ai,1 Wenfeng Guo,1,3 Guoming Li,1 Yueming Yuan,1,2 Zhiyong Xu,2 Wanting Wu,1 Xinan Huang,1,3 Zhibing Wu,3 Qin Xu,1,3 Jianping Song,1,3 Changsheng Deng1,3 1Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Science and Technology Institute, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Song; Changsheng Deng, Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China, Tel +86-20-3658 5633 ; +86-20-8746 1723, Email songjp@gzucm.edu.cn; dcs19811202@163.comIntroduction: Artemisinin-based combination therapies (ACTs) act as first-line antimalarial drugs and play a crucial role in the successful control of falciparum malaria. However, the recent emergence of resistance of Plasmodium falciparum to ACTs in South East Asia is of particular concern. Hence, there is an urgent need to identify the genetic determinants of and understand the molecular mechanisms underpinning such resistance. Artemisinin resistance (AR) is primarily driven by the mutations in the P. falciparum K13 protein, which is widely recognized as the major molecular marker of AR. However, association of K13 mutations with in vivo AR has been ambiguous due to the absence of a tractable model.Methods: In this study, we have successfully produced artemisinin- and piperaquine-resistant P. berghei K173 following drug administrations. Prolonged parasite clearance and early recrudescence were found following daily exposure to high doses of artemisinin and piperaquine. We have also sequenced the DNA of artemisinin-resistant strains and piperaquine-resistant strains of P. berghei K173 to explore the relationship between PfK13 and AR.Results: The resistance index of P. berghei K173 reached 12.4 after 30 artemisinin-resistant generations, but AR declined gradually after 30 generations. On the 50th generation, the resistance index of artemisinin-resistant strains was only 5.0 compared with the severe drug resistance of piperaquine-resistant strains (I90=148.8). DNA sequencing of artemisinin-resistant strains showed that there were 9 meaningful mutations at P. berghei K13-propeller domain, but the above mutations did not include common clinical point mutations.Conclusion: Our data show that artemisinin is less susceptible to severe resistance compared with other antimalarial drugs. In addition, mutation on P. berghei K13 has a multi-drug-resistant phenotype and may be used as a biomarker to monitor its resistance. More studies need to be conducted on the new mutations detected so as to understand their association, if any, with ACT resistance.Keywords: malaria, Plasmodium berghei, P. berghei K13 gene, artemisinin resistance

Xin Sun, Jie Xu, Lu Xie, Wei Guo Department of Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, 100044, People’s Republic of ChinaCorrespondence: Wei Guo, Department of Musculoskeletal Tumor Center, Peking University People’s Hospital, No. 11, Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Tel +86 13810548607, Email bonetumor@163.comObjective: This study was to investigate the effectiveness and tolerability of anlotinib plus PD-1 inhibitors for patients with previously treated metastatic soft tissue sarcoma (STS).Methods: Patients with previously treated metastatic STS who were administered with anlotinib plus PD-1 inhibitors in clinical practice were included for analysis retrospectively. All the common subtypes of advanced STS were appropriate for analysis. Efficacy of the regimen was assessed according to the change of target lesion radiologically, and all the patients were followed up regularly. Safety profile during the combination administration was recorded and documented specifically. Clinical significance according to different STS subtypes was analyzed accordingly.Results: From September 2018 to January 2022, a total of 32 patients with previously treated metastatic STS who received anlotinib plus PD-1 blockades were screened for the analysis in this study. The best overall response during the combination administration indicated that partial response was observed in 11 patients, stable disease was noted in 16 patients and progressive disease was found in 6 patients, yielding an objective response rate (ORR) of 34.4% (95% CI: 18.6– 53.2%) and a disease control rate (DCR) of 84.4% (95% CI: 67.2– 94.7%). Furthermore, the median PFS of 32 patients with metastatic STS was 7.6 months (95% CI: 3.31– 11.89) and the median OS was 14.9 months (95% CI: 8.36– 21.44). Besides, adverse reactions related to the treatment during anlotinib plus PD-1 inhibitors administration were observed in 29 patients (90.6%), of whom, a total of 13 patients (40.6%) were deemed as grade 3– 4 adverse reactions and no grade 5 adverse reaction was found. Specifically, the most common adverse reactions were fatigue, hypertension, hand-foot syndrome, diarrhea and dermal toxicity.Conclusion: Anlotinib plus PD-1 inhibitors demonstrated durable and promising efficacy and tolerable safety for patients with metastatic STS in real world. Further prospective clinical trials were warranted to validate the feasibility of anlotinib plus PD-1 blockades clinically.Keywords: soft tissue sarcoma, anlotinib, PD-1 inhibitors, effectiveness, tolerability

Yanrui Liang,1,&ast; Weihong Guo,1,&ast; Chuangji Li,1,&ast; Guodong Shen,1,&ast; Haoxian Tan,2 Peiwen Sun,2 Zhian Chen,1 Huilin Huang,1 Zhenhao Li,1 Zhenyuan Li,1 Yingxin Ren,1 Guoxin Li,1 Yanfeng Hu1 1Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2The First School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoxin Li; Yanfeng Hu, Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Ave, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1681 ; +86-20-6164-1682, Fax +86-20-6164-1681, Email yfenghu@qq.com; gzliguoxin@163.comPurpose: Lymphadenectomy with lymph node (LN) mapping is essential for surgical removal of solid tumors. Existing agents do not provide accurate multimodal mapping and antitumor therapy for metastatic LNs; therefore, we fabricated a polydopamine (PDA) nanoparticle (NP)-based tumor-targeted LN mapping agent capable of multimodal mapping and guided photothermal therapy (PTT) for metastatic LNs.Materials and Methods: PDA NPs modified with polyethylene glycol (PEG) were obtained by polymerization under alkaline conditions. The PEG-PDA NPs were loaded with the circular tripeptide Arg-Gly-Asp (cRGD) to achieve tumor-targeting capacity and with the fluorescent dye IR820 and magnetic resonance imaging (MRI) contrast Gd(NH2)2 for in situ detection. The resulting cRGD-PEG-PDA@IR820/Gd(NH2)2 (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αvβ 3 integrin-mediated endocytosis.Results: This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice.Conclusion: In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.Keywords: multimodal imaging, lymph node mapping, metastatic lymph node, photothermal therapy

Wenmei Guo,1,2 Junli Wan,1,2 Feng Zhang,1,2 Mingqiong Liu,1,2 Mingqiong Tan,1,2 Wei Bian1,2 1Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, People’s Republic of ChinaCorrespondence: Wei Bian, Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China, Tel +8615922933012, Email bianwei@Tmmu.edu.cnObjective: We described the development and pilot-testing of an application based patient decision-making aid (PDA) for nutrition in age-related macular degeneration (AMD). Alpha-testing and beta-testing were performed to explore the PDA’s usability, acceptability, and comprehensibility in the design stage and in “real-life” conditions.Methods: A nutrition PDA was developed in this study by a multidisciplinary steering committee that consisted of ophthalmologists, nurses, nutritionists, and methodologists using a systematic development process. The PDA was based on a smartphone native installation and a free-to-use app. First, based on information from literature reviews and focus group interviews for needs assessment, we developed a decision aid prototype. Second, we conducted the alpha testing to explore the acceptability, usability, and comprehensibility of the PDA prototype among 18 AMD patients. Third, a before/after study was conducted to assess changes in the attitudes, risk perceptions, intentions, knowledge, decisional conflicts, and decision self-efficacy of 33 AMD patients.Results: The alpha test proved that the nutrition PDA is acceptable and usable. In the beta test, after the AMD participants used the PDA, their scores for knowledge [mean = 13.3, standard deviation (SD) = 2.92], attitude (mean = 18.97, SD = 2.19), decision self-efficacy (mean = 23.94, SD = 6.04), and preparation significantly increased (mean = 26.30, SD = 4.90), and their score for decisional conflict significantly decreased (mean = 10.15, SD = 3.66). There was no significant difference in anxiety (mean = 2.64, SD = 1.08) before and after the use of the PDA. The mean score in the system usability scale was above 70 (mean = 72.61; SD = 5.38), which indicates the good usability of the PDA. With regard to the PDA acceptability, the scores for satisfaction with its comprehensibility, satisfaction with its attractiveness, and satisfaction with its emotional support were 5.49 (SD = 1.03), 5.30 (SD = 1.40), and 4.91(SD = 1.07), respectively, which show its adequate acceptability.Conclusion: Our study showed that the nutrition PDA was an acceptable and suitable instrument for AMD patients and fit the values of all its stakeholders. This study is an important step in supporting shared decision-making, which has the potential to provide a more patient-centered and value-based nutrition health system for individuals with different types of AMD.Keywords: age-related macular degeneration, nutrition, decision-making aid

Yanwan Shangguan,&ast; Zhongkang Ji,&ast; Wanru Guo, Wenjuan Hu, Xiaomeng Li, Kaijin Xu State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaijin Xu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Tel/Fax +86-0571-87236440, Email zdyxyxkj@zju.edu.cnAbstract: Linezolid-induced black hairy tongue is a self-limiting benign disease that is rare. Here, we report three patients who developed black hairy tongue after linezolid treatment. The severe dysbiosis of oral bacterial communities was observed in all these patients. Proteobacteria was the most prevalent phylum (over 90%) at the black tongue stage. Furthermore, the dramatic oral bacterial alteration took a long time to reverse after the BHT resolved.Keywords: tuberculosis infection, linezolid, treatment, side-effect, black-hairy tongue, microorganism metabolism

Yunzhen Shi,1,&ast; Wanru Guo,2,&ast; Wenjuan Hu,2 Xiaomeng Li,2 Yanwan Shangguan,2 Xuewen Feng,2 Ming Hu,2 Jiafeng Xia,2 Shuting Wang,2 Jingnan Li,1 Li Hong,1 Bin Lu,1 Kaijin Xu2 1Department of Infectious Diseases, Dongyang People’s Hospital, Dongyang, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaijin Xu, Email zdyxyxkj@zju.edu.cnAbstract: Tuberculous aortitis (TA) is a rare disease with a high mortality rate. Aortic pseudoaneurysm is the most common vascular pattern of TA, and isolated arterial wall thickening and arterial stenosis can also be seen in TA. We report two cases of disseminated tuberculosis involving the aorta with clinical improvement after treatment. One patient who had an aortic ulcer and intermural hematoma received anti-tuberculosis along with steroids therapy. The other patient, who developed a tubercular abdominal aortic pseudoaneurysm during anti-tuberculosis therapy, successfully received endovascular stent implantation. Clinicians should be aware that TA should be considered in patients with aortitis and active tuberculosis.Keywords: tuberculosis aortitis, aortic pseudoaneurysm, anti-tuberculosis therapy, steroids, endovascular stent implantation

Xudong Liu,1– 3 Jie Gao,1– 3 Yaohui Sun,1– 3 Feng Zhang,1– 3 Wenzhi Guo,1– 3 Shuijun Zhang1– 3 1Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2Henan Research & Development International Joint Laboratory for Organ Transplantation Immunomodulation, Zhengzhou, Henan Province, People’s Republic of China; 3National Regional Medical Treatment Centre of Henan Organ Transplantation, Zhengzhou, Henan Province, People’s Republic of ChinaCorrespondence: Shuijun Zhang, Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jian She Road, Zhengzhou, 450052, Henan Province, People’s Republic of China, Tel/Fax +8637166913032, Email zhangshuijun@zzu.edu.cnPurpose: Hepatocellular carcinoma (HCC), has a very high mortality rate and is the most common type of liver cancer. Clotrimazole, a traditional antifungal drug, has garnered considerable attention as a therapeutic strategy for HCC. However, its effects against the migration and invasion of HCC cells as well as the associated underlying mechanisms remain unclear. Therefore, in this study, we investigated its effects on HCC and attempted to elucidate the underlying molecular mechanisms.Methods: CCK-8 was used to investigate the inhibitory effect of clotrimazole on the proliferation of different types of HCC cells, and wound healing and transwell assays were performed to investigate its inhibitory effect on the invasion and migration of the HCC cells. Further, western blotting was employed to detect changes in the expression levels of epithelial mesenchymal transition (EMT)-related proteins, extracellular-regulated protein kinases (ERK), p-ERK, p65, and p-p65. We also used ERK activators in combination with clotrimazole to treat the HCC cell lines.Results: Clotrimazole inhibited the invasion and migration of HCC cells, and mechanistically, it exerted these anti-tumor effects via EMT by repressing ERK phosphorylation.Conclusion: These findings suggest that clotrimazole inhibits HCC metastasis by repressing EMT in an ERK dephosphorylation-dependent manner.Keywords: hepatocellular carcinoma, clotrimazole, extracellular-regulated protein kinases, migration, invasion, cancer

Nickel smelting produces a large amount of nickel slag which contains a lot of Fe in the form of FeO. The effect of FeO content on the melting properties and structure of nickel slag is investigated by thermodynamic calculations and experiments, using the nickel slag of water quenching furnace as raw material, which is simplified to CaO-SiO2-FeO-MgO slag system. The results are as follows: with increasing FeO content, the precipitated primary phase changes from melilite to olivine. The liquidus temperature, softening temperature, hemispherical temperature, flow temperature, viscosity, and critical viscosity temperature of the slag system tend to decrease gradually, but the solid phase temperature tends to decrease first and then increase. The centre of the symmetric stretching vibration band of the [SiO4]4 tetrahedron -in the slag system shifts to the low wavenumber region. The mole fraction of O0 in the slag continuously decreases, and the mole fraction of O- and O2- increases. The complex silicon-oxygen tetrahedron structure gradually disintegrates and the structural unit tends to be simple.

Wenfang Zhu,1,&ast; Yao Ma,2,&ast; Wen Guo,1 Jing Lu,1 Xiaona Li,1 Juan Wu,1 Pei Qin,1 Chen Zhu,1 Qun Zhang1 1Department of Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Zhang Tel +86 25 68303925Fax +86 25 68303925Email lucyqzhang@126.comIntroduction: Lactate dehydrogenase (LDH) is an important oxidoreductase in the anaerobic metabolic pathway. The role of LDH in arterial stiffness (AS) and 10-year cardiovascular disease (CVD10) risk has not been established.Methods: This retrospective, cross-sectional, and observational study evaluated the relationships between the LDH level and AS and CVD10 risk in 12,597 health-examined people (6988 men and 5609 women; mean age, 49.49 years) in China. Brachial–ankle pulse wave velocity (baPWV) was used to estimate AS. The Framingham CVD 10-year risk prediction model was used to calculate the CVD10 risk score.Results: In both sexes, an increased LDH level was associated with increased AS and CVD10 (men: β = 0.032, P < 0.001; women: β = 0.025, P < 0.001). Half of the population with a high LDH level (≥ 172 U/L) showed significantly increased AS and CVD10 risk score. Men and women with baPWV ≥ 1400 cm/s had a higher LDH level, and the latter was significantly different from that of the group with baPWV < 1400 cm/s (men: 176.93± 30.99 vs 173.00± 33.36, P < 0.001; women: 189.10± 34.20 vs 171.39± 31.08, P < 0.001). In both sexes, a higher level of LDH was noted in groups with higher CVD10 risk score (men: 176.65± 32.51 vs 172.94± 32.46, P < 0.001; women: 202.51± 44.05 vs 175.73± 32.39, P < 0.001).Discussion: An increased LDH level may be associated with AS and CVD10 risk. The LDH level could be a new predictor of AS and CVD10 risk in health-examined populations.Keywords: lactate dehydrogenase, arterial stiffness, 10-year cardiovascular disease risk, brachial–ankle pulse wave velocity, Framingham CVD 10-year risk prediction model

Hua Ye,1 Mengxia Sun,2 Shiliang Huang,1 Feng Xu,1 Jian Wang,3 Huiwei Liu,1 Liangshun Zhang,1 Wenjing Luo,1 Wenying Guo,1 Zhe Wu,1 Jie Zhu,4 Hong Li4 1Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China; 2Department of Clinical Medicine, Medical School of Ningbo University, Ningbo, Zhejiang, 315211, People’s Republic of China; 3Department of Dermatology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China; 4Department of Hepatobiliary Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaCorrespondence: Hua YeDepartment of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaTel/Fax +86 57483023687Email yh-med@163.comHong LiDepartment of Hepatobiliary Surgery, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of ChinaEmail lancet2017@163.comBackground: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. HCC transcriptome has been extensively studied; however, the progress in disease mechanisms, prognosis, and treatment is still slow.Methods: A rank-based module-centric workflow was introduced to analyze important modules associated with HCC development, prognosis, and drug resistance. The currently largest HCC cell line RNA-Seq dataset from the LIMORE database was used to construct the reference modules by weighted gene co-expression network analysis.Results: Thirteen reference modules were identified with validated reproducibility. These modules were all associated with specific biological functions. Differentially expressed module analysis revealed the crucial modules during HCC development. Modules and hub genes are indicative of patient survival. Modules can differentiate patients in different HCC stages. Furthermore, drug resistance was revealed by drug-module association analysis. Based on differentially expressed modules and hub genes, six candidate drugs were screened. The hub genes of those modules merit further investigation.Conclusion: We proposed a reference module-based analysis of the HCC transcriptome. The identified modules are associated with HCC development, survival, and drug resistance. M3 and M6 may play important roles during HCV to HCC development. M1, M3, M5, and M7 are associated with HCC survival. High M4, high M9, low M1, and low M3 may be associated with dasatinib, doxorubicin, CD532, and simvastatin resistance. Our analysis provides useful information for HCC diagnosis and treatment.Keywords: HCV, IC50, microarray, module preservation, WGCNA

Ao Duan,1,&ast; Zemeng Ma,2,&ast; Wanshun Liu,1,&ast; Kai Shen,1,&ast; Hao Zhou,1,&ast; Shunbing Wang,3 Renyi Kong,4 Yuqi Shao,5 Yunzi Chen,2 Wei Guo,6 Feng Liu1 1Department of Orthopedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 2Key Laboratory of Immune Microenvironment and Disease, Department of Immunology, Nanjing Medical University, Nanjing, 211100, People’s Republic of China; 3Department of Rheumatology and Immunology, Affiliated Hospital of Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 4Department of Orthopedics, Xincheng Hospital of Traditional Chinese Medicine, Maanshan, 243131, Anhui, People’s Republic of China; 5Department of Orthopedics, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221006, Jiangsu, People’s Republic of China; 6Department of Urology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi, 214002, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Guo; Feng Liu Email weiguo_gavin@163.com; njliuf@163.comBackground: Osteoarthritis (OA) is the most prevalent chronic joint disease globally. Loss of extracellular matrix (ECM) by chondrocytes is a classic feature of OA. Inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), secreted mainly by macrophages, promote expression of matrix degrading proteins and further aggravate progression of OA. 1,25-dihydroxyvitamin D (1,25VD) modulates inflammation thus exerting protective effects on cartilage tissue. However, the underlying mechanisms of 1,25VD activity have not been fully elucidated.Methods: The destabilization of the medial meniscus (DMM)-induced mice model of OA was established to investigate the protective effects of 1,25VD by micro-CT and Safranin-O and Fast Green staining. And the co-culture system between THP-1 cells and primary chondrocytes was constructed to explore the effects of vitamin D receptor (VDR) and 1,25VD on chondrogenic proliferation, apoptosis, and migration. The immunofluorescence staining and Western blot analysis were used to detect the expressions of ECM proteins and matrix degradation-associated proteases. Enzyme-linked immunosorbent assay (ELISA) was used to examine the expression levels of inflammatory cytokines.Results: The findings of the study showed that 1,25VD prevented cartilage degeneration and osteophyte formation by inhibiting secretion of inflammatory cytokines in OA mice model. These protective effects were exerted through the vitamin D receptor (VDR). Further studies showed that 1,25VD increased ubiquitination level of NLRP3 by binding to VDR, resulting in decrease in IL-1β and IL-18 secretion. These findings indicate that 1,25VD binds to VDR thus preventing chondrogenic ECM degradation by modulating macrophage NLRP3 activation and secretion of inflammatory cytokines, thus alleviating OA progression.Conclusion: Here, our study suggests that 1,25VD, targeting to VDR, prevents chondrogenic ECM degradation through regulating macrophage NLRP3 activation and inflammatory cytokines secretion, thereby alleviating OA. These findings provide information on a novel molecular mechanism for application of 1,25VD as OA therapy.Keywords: osteoarthritis, 1,25-dihydroxyvitamin D, vitamin D receptor, NLRP3, inflammatory cytokines

Dong Zhang,1– 3 Hailong Zhang,1– 3 Xuanlin Li,1– 3 Siyuan Lei,1– 3 Lu Wang,1– 3 Wen Guo,1– 3 Jiansheng Li1– 3 1Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China; 3Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, 450003, People’s Republic of ChinaCorrespondence: Jiansheng Li Tel/Fax +86-371-65676568Email li_js8@163.comObjective: To evaluate the efficacy and safety of early pulmonary rehabilitation (PR) (ie, < 3 days of hospitalization) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: Embase, Web of Science, PubMed and Cochrane Library were searched from their inception to 1 April 2021. Randomized controlled trials were included if they observed the efficacy of early PR in AECOPD patients. Study selection, data extraction, risk of bias and quality of evidence were assessed by two researchers independently. Assessment of the risk of bias and eidence quality were evaluated by the Cochrane Collaboration’s tool and Grading of Recommendations, Assessment, Development and Evaluation system, respectively.Results: Fourteen trials (829 participants) were identified. Significant improvement was found in the 6-minute walk distance (6MWD; mean difference (MD): 69.64; 95% CI: 40.26 to 99.01; Z = 4.65, P < 0.0001, low quality). In the subgroup analysis, the exercise-training group showed marked improvement (MD: 96.14; 95% CI: 20.24 to 172.04; Z = 2.48, P = 0.001). The Saint George’s Respiratory Questionnaire (SGRQ) total score was low (MD: − 12.77; 95% CI: − 16.03 to − 9.50; Z = 7.67, P < 0.0001, moderate quality). Significant effects were not found for the duration of hospital stay, quadriceps muscle strength or five times sit to stand test. Only one serious adverse event was reported in experimental group, which was not associated with early PR.Conclusion: PR initiated < 3 days of hospitalization may increase exercise capacity and improve quality of life, but the results should be interpreted prudently and dialectically, and the role of early PR in AECOPD needs further exploration.Keywords: chronic obstructive pulmonary disease, acute exacerbation, pulmonary rehabilitation, meta-analysis

Bing Xu, Mengmeng Yan, Fei Zhou, Desheng Cai, Wenbo Guo, Xiaohui Jia, Runping Liu, Tao Ma, Tong Li, Feng Gao, Penglong Wang, Haimin Lei School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of ChinaCorrespondence: Penglong Wang; Haimin Lei Email wpl581@126.com; hm_lei@126.comBackground: The clinical utility of camptothecin (CPT) is restricted by poor aqueous solubility, high lipophilicity, active lactone ring instability, and off-targeted toxicities. We report here a prostate-specific membrane antigen (PSMA) and esterase dual responsive self-assembled nanoparticles (CPT-WT-H NPs) for highly efficient CPT delivery and effective cancer therapy.Methods and Results: In this study, smart self-assembled nanoparticles CPT-WT-H NPs were elaborately designed and synthesized by combing hydrophobic CPT with hydrophilic PSMA-responsive penta-peptide via a cleavable ester bond. This dual responsive nanoparticle with negatively charged surface first respond to the extracellular PSMA and then to the intracellular esterase, achieving a programmable release of CPT at the tumor site and producing the byproducts of biocompatible glutamic acid and aspartic acid. Our data demonstrated that CPT-WT-H NPs exhibited greatly improved water solubility and stability. Results from MTT and flow cytometry showed CPT-WT-H NPs exhibited significantly higher cytotoxicity as well as apoptosis-inducing activity against PSMA-expressing LNCaP-FGC cells than the non-PSMA-expressing cancer cells, showing excellent cytotoxic selectivity. Moreover, the unique nanostructure provided the efficient transportation of CPT to tumor site, which resulted in the effective inhibition of tumor growth and low systemic toxicity in vivo.Conclusion: CPT-WT-H NPs exhibited excellent in vitro PSMA-response ability and in vivo antitumor activity and safety, holding the promise to become a new and potent anticancer drug. The current research presents a promising strategy for efficient drug delivery.Keywords: CPT prodrug, dual responsive, sequential drug release, prostate-specific membrane antigen, self-assembly

Hui Yu,1 Weikang Guo,2 Yunduo Liu,2 Yaoxian Wang2 1Cardiopulmonary Function Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Gynecological Department, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of ChinaCorrespondence: Yaoxian WangGynecological Department, Harbin Medical University Cancer Hospital, No. 150 Haping Road, Nangang District, Harbin, Heilongjiang, 150081, People’s Republic of ChinaTel +86-0451-86298578Email wyxxs012@126.comPurpose: The variation in inflammation in chronic obstructive pulmonary disease (COPD) between individuals is genetically determined. This study aimed to identify gene signatures of COPD through bioinformatics analysis based on multiple gene sets and explore their immune characteristics and transcriptional regulation mechanisms.Methods: Data from four microarrays were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) between COPD patients and controls. Weighted gene co-expression network analysis was applied to identify trait-related modules and then select key module-related DEGs. The optimized gene set of signatures was obtained using the least absolute shrinkage and selection operator (LASSO) regression analysis. The CIBERSORT algorithm and Pearson correlation test were used to analyze the relationship between gene signatures and immune cells. Finally, public databases were used to predict the transcription factors (TFs) and upstream miRNAs.Results: A total of 127 DEGs in COPD were identified from the combined dataset. By considering the intersection of DEGs and genes in two trait-related modules, 83 key module-related DEGs were identified, which were mainly enriched in interleukin-related pathways. Seven-gene signatures, including MTHFD2, KANK3, GFPT2, PHLDA1, HS3ST2, FGG, and RPS4Y1, were further selected using the LASSO algorithm. These gene signatures showed the predictive potential for COPD risks and were significantly correlated with 18 types of immune cells. Finally, nine miRNAs and three TFs were predicted to target MTHFD2, GFPT2, PHLDA1, and FGG.Conclusion: We proposed the seven-gene-signature to predict COPD risk and explored its potential immune characteristics and regulatory mechanisms.Keywords: COPD, gene signatures, immune infiltration, transcriptional regulation

Xiaobo Shi,1 Xiaoxiao Liu,1 Shupei Pan,1 Yue Ke,1 Yuxing Li,1 Wei Guo,1 Yuchen Wang,1 Qinli Ruan,1 Xiaozhi Zhang,2 Hongbing Ma1 1Department of Radiation Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Hongbing MaDepartment of Radiation Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, Xi Wu Road, Xi’an, 710004, Shaanxi, People’s Republic of ChinaTel +86 13991845066Email mhbxian@126.comBackground: Considering the significance of autophagy and long non-coding RNAs (lncRNAs) in the biology of esophageal squamous cell carcinoma (ESCC), the present study aimed to identify a new autophagy-related lncRNA signature to forecast the clinical outcomes of ESCC patients and to guide individualized treatment.Methods: The expression profiles were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. We extracted autophagy-related genes from the Human Autophagy Database and identified autophagy-related lncRNAs through Spearman correlation analysis. Univariate, least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed on GSE53625 to construct an autophagy-related lncRNAs prognostic signature. The model was subjected to bootstrap internal validation, and the expression levels of lncRNAs were verified by TCGA database. The potential molecular mechanism of the model was explored by gene set enrichment analysis (GSEA). Spearman correlation coefficient examined the correlation between risk score and ferroptosis-associated genes as well as the response to immunotherapy and chemotherapy.Results: We identified and validated an autophagy-related lncRNAs prognostic signature in 179 patients with ESCC. The prognosis of patients in the low-risk group was significantly better than that in the high-risk group (p-value < 0.001). The reliability of the model was verified by Brier score and ROC. GSEA results showed significant enrichment of cancer- and autophagy-related signaling pathways in the high-risk group and metabolism-related pathways in the low-risk group. Correlation analysis indicated that the model can effectively forecast the effect of immunotherapy and chemotherapy. About 35.41% (74/209) ferroptosis-related genes were significantly correlated with risk scores.Conclusion: In brief, we constructed a novel autophagy-related lncRNAs signature (LINC02024, LINC01711, LINC01419, LCAL1, FENDRR, ADAMTS9-AS1, AC025244.1, AC015908.6 and AC011997.1), which could improve the prediction of clinical outcomes and guide individualized treatment of ESCC patients.Keywords: autophagy, esophageal squamous cell carcinoma, lncRNA, prognosis, therapeutic response

Xiaowei Zhou,1,&ast; Weichang Guo,2,&ast; Hejia Yin,1 Jie Chen,1 Liju Ma,3 Qiuping Yang,4 Yan Zhao,1 Shaoyou Li,5 Weijun Liu,1 Huifang Li1 1Department of Diabetes, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 2Department of Physical Education, Kunming Medical University, Kunming, People’s Republic of China; 3Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4Department of Geriatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 5Department of NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huifang LiDepartment of Diabetes, The First Affiliated Hospital of Kunming Medical University, No. 295 Xichang Road, Wuhua District, Kunming, 650032, People’s Republic of ChinaEmail lhfkm2003041@protonmail.comBackground: Type 2 diabetes mellitus (T2DM) is characterized by β cell decline in the pancreas and insulin resistance. This study aimed to investigate the possible pathogenic gene mutation sites of T2DM patients using whole exome sequencing.Materials and Methods: We recruited a Chinese family with 3-generation history of diabetes. The whole blood genomic DNA of seven members of the family was extracted and sent for whole exome sequencing. Biological information was analyzed with in silico prediction methods, including significance analysis of single nucleotide polymorphism (SNP)/Indel site, and analysis of specific SNP/Indel proteins and their potential mechanisms.Results: Six out of seven members of the family were diagnosed with diabetes. All DNA samples (23 kb) met quality requirements of library construction. Clean reads of each sample demonstrated high Q20 and Q30 (> 80%), indicating good sequencing quality of sequencing data. A total of 130,693 SNPs and 15,928 Indels were found in DNA samples. A total of 22 significant SNPs and Indel mutation sites located on 19 genes were obtained, including ZCCHC3, SYN2, RPL14, SRRD, AMD1, CAMKK2, ZNF787, RNF157, NPIPB15, ALG3, KIAA0040, MAST2, ESRRA, C8orf58, PNLIPRP1, DACH1, MACC1, CAPN9 and DMKN. An rs2305205 mutation of PNLIPRP1 gene and an rs778701848 mutation of CAMKK2 gene may be associated with the pathogenesis of T2DM in this family.Conclusion: Exons of these diabetic patients demonstrated an rs2305205 mutation in PNLIPRP1 gene and an rs778701848 mutation in CAMKK2 gene. These two mutations might promote T2DM occurrence through reducing sensitivity of peripheral tissue to insulin and reducing insulin secretion.Keywords: type 2 diabetes, gene mutation, whole exome sequencing, PNLIPRP1, CAMKK2

Xiaoxiao Liu,1 Xiaobo Shi,1 Wei Guo,1 Yue Ke,1 Yuxing Li,1 Shupei Pan,1 Xiaona Li,2 Mei Liu,3 Mingzhu Liu,4 Yuchen Wang,1 Qinli Ruan,1 Hongbing Ma1 1Department of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 2Department of Dermatology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of China; 4Department of Gastroenterology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of ChinaCorrespondence: Hongbing MaDepartment of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, People’s Republic of ChinaTel +86 13991845066Email mhbxian@126.comPurpose: Ferroptosis and long non-coding RNA (lncRNA) expression signatures have been associated with the clinical progression and immune-contexture of different solid tumors. The study aimed to identify a prognostic signature of ferroptosis-related lncRNAs (falncRNAs) to forecast the immune scenery and immunotherapy response in esophageal cancer (EC).Patients and Methods: Gene expression profiles of EC were extracted from The Cancer Genome Atlas (TCGA) database, and ferroptosis-related genes were downloaded from the FerrDb database, which identified differentially expressed falncRNAs (DEfalncRNAs) via differential analysis. DEfalncRNA pairs associated with prognosis were identified by constructing a matrix, univariate and least absolute shrinkage and selection operator (LASSO) analysis. The prognostic signature was constructed by multivariate analysis. We appraised the forecasting capability of prognostic signature in survival, clinicopathological features, immune landscape, efficacy of immunotherapy, and drug sensitivity. The potential molecular mechanism of signature was investigated by gene set enrichment analysis (GSEA).Results: We obtained 18 DEfalncRNA pairs to define a novel prognostic signature that was determined on a discovery cohort of 158 tumor samples and 11 adjacent normal tissues from TCGA and internally validated, with the definition of high- vs low-risk groups based on 3 years overall survival. We demonstrated that the high- vs low-risk groups differed for clinical parameters and computationally predicted drug sensitivity and tumor immune contexture, with the high-risk group having worse survival, more aggressive disease (node involvement, metastasis), reduced drug sensitivity, higher tumor mutation load, and gene signatures of infiltration of pro-tumoral immune cell subsets. The GSEA results revealed that ferroptosis and immunoregulatory pathways were significantly enriched in the high-risk group.Conclusion: The prognostic signature based on falncRNAs has the potential to forecast the survival, immune scenery, efficacy of immunotherapy, and drug sensitivity of EC, which is helpful for clinical prediction and individualized treatment.Keywords: esophageal cancer, ferroptosis, lncRNA, immune, signature, prognosis

Xiehui Chen,1 Weichao Huang,2 Lingyue Zhao,3 Yichong Li,2 Lili Wang,2 Fanrui Mo,4 Wenqin Guo2 1Department of Cardiology, Shenzhen Longhua District Central Hospital, Shenzhen, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 3Department of Ambulatory Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, People’s Republic of China; 4Department of Cardiology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, People’s Republic of ChinaCorrespondence: Lingyue ZhaoDepartment of Ambulatory Surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Nanshan District, Shenzhen, People’s Republic of ChinaTel/Fax +86 755-26553111Email z07198102755@163.comFanrui MoDepartment of Cardiology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, People’s Republic of ChinaTel +86 772-3815284Fax +86 772-3815384Email 9313902@qq.comPurpose: The aim of this study was to assess the value of the eosinophil/monocyte ratio (EMR) for predicting the prognosis of decompensated heart failure (HF).Patients and Methods: This was a retrospective cohort study. We included adults (≥ 18 years old) diagnosed with decompensated HF for whom EMR data were available. The patients were divided into three groups according to EMR tertiles (T1 [EMR≤ 0.15], T2 [0.15 0.32]). The primary endpoint was the composite outcome of cardiovascular death or HF rehospitalization.Results: Initially, the records of 2264 patients with decompensated HF were screened; 1883 of these patients had EMR data and were therefore included in the study. There were 627 patients in the T1 group, 628 in the T2 group, and 628 in the T3 group. The risk of cardiovascular death or HF rehospitalization was significantly different among the three groups (Log rank test, P=0.007). Compared with the T3 group, both the T1 group (hazard ratio [HR]: 1.50, 95% confidence interval [CI]: 1.16– 1.94, P=0.002) and the T2 group (HR: 1.34, 95% CI: 1.03– 1.74, P=0.030) had significantly higher rates of cardiovascular death or HF rehospitalization. A Cochran-Armitage test for trend showed a positive correlation between the EMR and the composite outcome of cardiovascular death or HF. There was a significant difference between the three groups in terms of cardiovascular death (Log rank test, P< 0.001) and HF rehospitalization (Log rank test, P=0.03).Conclusion: The EMR is positively correlated with the risk of cardiovascular death or HF rehospitalization in patients with decompensated HF. Specifically, the lower the EMR, the higher the risk of cardiovascular death or HF rehospitalization.Keywords: decompensated heart failure, eosinophil/monocyte ratio, prognosis, cardiovascular death, heart failure rehospitalization

Xiacan Chen,1 Wanjun Guo,2 Liangming Yu,2 Dan Luo,2 Leling Xie,2 Jiajun Xu2 1Institute of Forensic Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, People’s Republic of China; 2Mental Health Centre, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Jiajun XuMental Health Centre, West China Hospital, Sichuan University, 610041, People’s Republic of ChinaEmail xujiajun120@126.comObjective: The findings of olfaction are inconsistent in anxiety disorders, and few studies have reported on the olfactory performance in generalized anxiety disorder (GAD). Therefore, we aim to investigate the olfactory function of patients with GAD and the association between olfactory function and anxiety symptoms.Methods: We conducted a case–control study by selecting 107 patients with GAD and 107 healthy controls matched for sex and age, to investigate olfaction deficits in GAD and the association between anxiety severity and olfaction. All patients were treatment-naïve prior to the inclusion. Anxiety severity and olfaction were assessed by the Hamilton anxiety rating scale (HAM-A) and the Sniffin’ Sticks test (SST), respectively. Partial correlations were used to analyze the relationship between olfaction and anxiety severity. False discovery rate (FDR) correction was used in multi-correlation analyses.Results: Compared with healthy controls, patients in the GAD group demonstrated odor threshold, discrimination and identification deficits. In the moderate/severe anxiety subgroup, discrimination score was significantly and inversely correlated with the somatic anxiety score (γ=− 0.44, q = 0.03), and identification score was significantly and inversely correlated with the HAM-A total score (γ=− 0.42, q= 0.04). The TDI score (the sum of threshold, discrimination and identification scores) was significantly and inversely correlated with the somatic (γ=− 0.44, q = 0.04) and psychic (γ=− 0.45, q = 0.04) anxiety scores in the moderate/severe anxiety subgroup.Conclusion: This study demonstrated the olfactory impairment in patients with GAD and that poorer odor discrimination was correlated with greater severity of somatic anxiety.Keywords: GAD, olfaction, symptom

Hao Ren,1,2,&ast; Jie Liu,1,3,&ast; Jiwei Zhang,4 Baixi Zhuang,5 Weiguo Fu,6 Danming Wu,7 Feng Wang,8 Yu Zhao,9 Pingfan Guo,10 Wei Bi,11 Shenming Wang,12 Wei Guo1,3 1Medical School of Chinese PLA, Beijing, 100853, People’s Republic of China; 2Department of Vascular Surgery, Dalian Municipal Central Hospital, Dalian, 116033, People’s Republic of China; 3Department of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Department of Vascular Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200120, People’s Republic of China; 5Department of Vascular Surgery, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100080, People’s Republic of China; 6Department of Vascular Surgery, Zhongshan Hospital Fudan University, Shanghai, 200032, People’s Republic of China; 7Department of Vascular Surgery, The People’s Hospital of Liaoning Province, Shenyang, 110016, People’s Republic of China; 8Department of Interventional Therapy, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People’s Republic of China; 9Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, People’s Republic of China; 10Department of Vascular Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 11Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, 050073, People’s Republic of China; 12Department of Vascular Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei GuoDepartment of Vascular and Endovascular Surgery, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of ChinaTel +86-10-66938049Fax +86-10-66938149Email Guoweiplagh@sina.comObjective: To evaluate the long-term outcomes after drug-coated balloon (DCB) angioplasty dissection in patients with complex femoropopliteal artery disease.Methods: Two hundred patients with femoropopliteal peripheral artery disease were enrolled in the AcoArt I trial and randomly assigned to either the DCB or percutaneous transluminal angioplasty (PTA) group. A total of 86 patients with post-balloon angioplasty dissection were reanalyzed. The primary endpoint was clinically driven target lesion revascularization (CD-TLR) over five years. Kaplan–Meier curve estimates were used to evaluate the association between the treatment and CD-TLR. Interaction and stratified analyses were also performed.Results: Over five years, patients treated with DCB angioplasty demonstrated an acceptable effect with a numerically higher but not statistically significant rate of freedom from CD-TLR compared with those treated by PTA (Kaplan–Meier estimate of 77.6% vs 64.4%; log-rank P = 0.08). Among the patients who underwent TLR, the mean time from intervention to TLR in the DCB group was significantly prolonged compared to the PTA group (P < 0.001). The stratified analysis showed that the Rutherford classification played an interactive role in the association between the DCB angioplasty and low CD-TLR rate at five years. No significant difference in the all-cause mortality was found in the patients with post-balloon angioplasty dissection between the two treatment groups.Conclusion: The five-year follow-up outcomes of the post-balloon angioplasty dissection in the AcoArt I trial demonstrated that DCB angioplasty is more trustworthy than PTA, with a higher rate of freedom than CD-TLR and sustained improvement in clinical symptoms. However, the all-cause mortality rate in patients with femoropopliteal lesions is similar after both DCB angioplasty and PTA.Clinical Trial Registration: http://www.clinicaltrials.gov.Unique Identifier: NCT01850056.Keywords: balloon angioplasty, dissection, femoropopliteal artery disease, long-term outcomes, drug-coated balloon, percutaneous transluminal angioplasty

Xiaoning Cen,1,&ast; Yunmei Huang,2,&ast; Zhuangnian Lu,3,&ast; Wenjun Shao,4 Chenyi Zhuo,1 Chongchan Bao,5 Shi Feng,5 Cheng Wei,5 Xiqiang Tang,5 Lijun Cen,5 Wenwen Guo,5 Xinru Tian,5 Qianli Tang,5 Xusen Huang1 1General Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 4Medical college of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 5YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianli TangYouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail htmgx@163.comXusen HuangGeneral Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail hxsfy@163.comBackground: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified.Methods: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The “limma” package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| > 1 and P < 0.05. The “Survival” package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients.Results: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial–mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells.Conclusion: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.Keywords: IGFL2-AS1, lncRNA, colon cancer, immune