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Guangjie Wang,1,&ast; Puhui Liu,2,&ast; Hui Xie,2 Chuanzhen Niu,2 Jie Lyu,1 Youzhong An,1 Huiying Zhao1 1Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Yantai Qishan Hospital, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiying Zhao, Department of Critical Care Medicine, Peking University People’s Hospital, No. 11, Southern Xizhimen Road, Beijing, 100044, People’s Republic of China, Tel +86 13811088270, Email zhaohuiying@pkuph.edu.cnPurpose: The high mortality rate associated with the critical stages of severe fever with thrombocytopenia syndrome (SFTS) does not have effective treatment. We aimed to evaluate the 28-day mortality and potential impact of glucocorticoid therapy in these patients.Patients and Methods: This retrospective observational study included participants from the intensive care unit between July 2019 and April 2023. The participants were categorized into glucocorticoid (GC) and non-GC groups. Propensity score matching (PSM) was employed to ensure comparability between groups. We used Cox proportional hazard models to examine mortality risk associated with GC use, Kaplan–Meier survival analyses for overall survival, stratified Cox proportional hazard models for subgroup analyses, and likelihood ratio tests to examine interactions between subgroups.Results: Of 218 patients with SFTS (median age, 71 years; male, 49.1%), 61.9% required mechanical ventilation, 58.3% received GC treatment, and the 28-day mortality rate was 61.5%. After PSM, there were 58 patients in each group; post-PSM analysis revealed improved 28-day mortality rates with GC treatment, particularly for patients with Glasgow coma scale (GCS) score < 13 (hazard ratio [HR], 95% confidence interval [CI] for GCS score: 9– 12: 0.39, 0.17– 0.88, p=0.024 and for GCS score: 3– 8: 0.09, 0.02– 0.35, p=0.001); lactate levels > 2 mmol/L (0.35, 0.15– 0.83, p=0.017); and norepinephrine usage (0.26, 0.13– 0.49, p< 0.001). Combining antiviral (0.41, 0.22– 0.78, p=0.006) or immunoglobulin therapy (0.22, 0.1– 0.51, p< 0.001) with GC treatment significantly decreased the 28-day mortality rates, compared with GC monotherapy.Conclusion: Using GCs reduced the high 28-day mortality rate in the patients, especially with low GCS score, high lactate levels, norepinephrine intake, and on antiviral or immunoglobulin therapy.Keywords: glucocorticoids, mortality, severe fever with thrombocytopenia syndrome, intensive care unit, virus infection

Shengyang Liu,1 Hui Zhao,2 Li Shi,1 Hongzhi Ji1 1Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Radiology, Shandong Second Provincial General Hospital, Jinan, People’s Republic of ChinaCorrespondence: Hongzhi Ji, Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, 4 Duanxing West Road, Jinan, 250000, People’s Republic of China, Email jhz_jx163@163.comAbstract: In this case report, we describe a 21-year-old man with recurrent hemangiomas in his left eye socket and nasal cavity. Traditional surgeries were unsuccessful, so we used Bevacizumab, a drug that inhibits blood vessel growth. This approach significantly reduced the tumor size and stopped frequent nosebleeds. Over two years, the tumor remained controlled without major side effects, suggesting Bevacizumab as a promising non-surgical treatment for recurrent hemangiomas.Keywords: Bevacizumab, orbital hemangioma, vascular endothelial growth factor, treatment efficacy

Yuxuan Yao,1– 3 Hong Zhao,4 Hua Lu,5 Xiaoli Liu,6 Hui Liu,7 Zhanli Fu,8 Chunyue Li,1 Fude Zhou,1– 3 Wanyin Hou,1– 3 Sufang Shi1– 3 1Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People’s Republic of China; 2Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People’s Republic of China; 3Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Pathology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 7Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of Nuclear Medicine, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wanyin Hou; Hong Zhao, Peking University First Hospital, Xicheng District, Beijing, People’s Republic of China, Tel +86 10-83575685, Email helenwanyin@bjmu.edu.cn; zhaohong_pufh@bjmu.edu.cnAbstract: Q fever, an infectious zoonotic disease caused by Coxiella burnetii, remains prevalent in China. Systemic infections can result in renal or hepatic complications; however, it is rare for both the kidneys and liver to be simultaneously affected. We present a case of a patient who exhibited fever, rapid deterioration in renal function, thrombocytopenia, and severe ascites. Renal biopsy revealed crescentic glomerulonephritis, while liver biopsy demonstrated non-cirrhotic portal hypertension. Metagenomic next-generation sequencing (mNGS) identified the presence of Coxiella burnetii in both venous blood and liver tissue samples. Notably, the patient’s renal insufficiency and ascites showed a positive response to treatment for chronic Q fever. These findings provide valuable insights into the limited understanding of kidney and liver diseases associated with Q fever. Advanced diagnostic technologies, including mNGS and positron emission tomography/computed tomography (PET/CT), have been employed to identify Coxiella burnetii infection.Keywords: Coxiella burnetii, acute kidney injury, non-cirrhotic portal hypertension, biopsies

Maolin Hou,1,&ast; Jinghua Chen,2,&ast; Le Yang,3,&ast; Lei Qin,3 Jie Liu,4 Haibo Zhao,5 Yujin Guo,6 Qing-Qing Yu,6 Qiujie Zhang5 1Department of Internal Medicine, Siziwangqi People’s Hospital, Wulancabu, 011800, People’s Republic of China; 2Department of Oncology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250000, People’s Republic of China; 3Department of Gastrointestinal Surgery, Jining, 272000, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250000, People’s Republic of China; 5Department of Oncology, Jining, 272000, People’s Republic of China; 6Department of Clinical Pharmacology, Jining, 272000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Zhang, Department of Oncology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email zhangqiujie86@163.com Qing-Qing Yu, Department of Clinical Pharmacology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email yuqingqing_lucky@163.comIntroduction: Gastric cancer, the fifth most common malignant tumor in the world, poses a serious threat to human health. However, the role of fatty acid metabolism (FAM) in gastric cancer remains incompletely understood. We aim to provide guidance for clinical decisions by utilizing public database of gastric adenocarcinoma to establish an FAM-related gene subtypes via machine learning algorithm.Methods: The intersection of FMGs from KEGG, Hallmark, and Reactome bioinformatics databases and the DEGs of the TCGA-STAD cohort was used to decompose the gene matrix related to establish FAM-related gene subtypes by NMF. Comparison of immune infiltrating differences between subtypes using ESTIMATE and Cibersort algorithms. The multifactor Cox regression to identify independent risk genes for patient prognosis based on the subtypes. A prognostic model including independent risk genes was built using random survival forest and Cox regression. IHC validation in gastric cancer and adjacent tissues confirmed the above gene expression level.Results: 71 DEGs related to FMGs of STAD were identified, which was used to established the FAM-related gene subtypes, C1 and C2. The immune infiltrating analysis showed that most immune features of C2 were significantly upregulated compared to C1. The independent risk genes were CGβ 8, UPK1B, and OR51G based on the subtypes. A gastric cancer prognostic model consisting of independent risk genes was constructed and patients were classified into high-risk and low-risk groups with survival differential analysis. Finally, IHC showed that CGβ 8 and UPK1B expression were upregulated in gastric cancer, while OR51G2 did not detect differences in expression.Conclusion: The study developed a machine learning-based gastric cancer prognosis risk model using FMGs. This model effectively stratifies patients according to their risk levels and provides valuable insights for clinical decision-making, enabling accurate evaluation of patient prognosis.Keywords: Gastric cancer, fatty acid metabolism-related genes, machine learning, genomics, signature

Ziyan Zhong,1,&ast; Jian Liu,2,&ast; Yan Luo,1 Mei Wu,1 Feng Qiu,1 Hongqing Zhao,1 Yang Liu,1 Yajing Wang,3 Hongping Long,2 Lei Zhao,4 Yuhong Wang,1 Yuanshan Han,2 Pan Meng1 1Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China; 3Office of Science & Technology, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 4School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanshan Han, The First Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of China, Email 121983755@qq.com Pan Meng, Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China, Email 004181@hnucm.edu.cnBackground: Depression, a leading cause of disability worldwide, is characterized by dysfunction of immature neurons, resulting in dysregulated calcium homeostasis and impaired structural plasticity. Jujuboside A (JuA), a biologically active compound derived from Semen Ziziphi Spinosae, has demonstrated anti-anxiety and anti-insomnia properties. Recent studies suggest that JuA may be a promising antidepressant, but its underlying mechanisms remain unclear.Methods: Sprague-Dawley rats were subjected to chronic unpredictable mild stress (CUMS) to induce a depression model. JuA (12.5 mg/kg, 25 mg/kg, 50 mg/kg) was administered orally for 4 weeks. Emotional and cognitive function were assessed. Monoamine neurotransmitter levels were measured using enzyme-linked immunosorbent assay (ELISA). The number of immature neurons and calcium homeostasis were evaluated by immunofluorescence. Western blotting and immunofluorescence were employed to detect the expression of Sonic hedgehog (Shh) signaling proteins. Additionally, lentiviral vector expressing Shh shRNA (LV-Shh-RNAi) were infused intracerebrally to investigate the role of Shh in JuA’s antidepressant effects.Results: JuA significantly ameliorated depressive-like behavior and cognitive dysfunction in CUMS rats, increased monoamine neurotransmitter levels in serum and hippocampal tissue, reduced the number of BrdU/DCX (bromodeoxyuridine/doublecortin)-positive immature neurons, and attenuated calcium ion (Ca2+) concentration and Ca2+/calmodulin-dependent protein kinase II (CaMKII) levels in immature neurons. JuA also markedly elevated synaptic density and prominence complexity, upregulated Shh, Gli family zinc finger 1 and 2 (Gli1/2), synaptophysin (Syn) and postsynaptic density protein-95 (PSD-95) expression in the ventral dentate gyrus (vDG). However, knockdown of Shh in the vDG counteracted JuA’s therapeutic effects.Conclusion: These findings collectively suggest that JuA improves depressive-like behavior in CUMS rats by modulating calcium homeostasis and synaptic structural plasticity in immature neurons through the Shh signaling pathway.Keywords: Jujuboside A, Sonic hedgehog, Immature neuron, Calcium homeostasis, Depression

Lili Wang,1 Le Cheng,1 Chenhui Lv,1 Jie Kou,1 Wenjuan Feng,1 Haoran Xie,1 Ruolin Yan,1 Xi Wang,1 Shuangzhi Chen,1 Xin Song,1 Lushan Xue,1 Cheng Zhang,1 Xuemin Li,2 Haifeng Zhao1,3 1Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Center for Disease Control and Prevention in Shanxi Province, Taiyuan, People’s Republic of China; 3MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, Taiyuan, People’s Republic of ChinaCorrespondence: Haifeng Zhao, Department of Nutrition & Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel/Fax +86-351-4135046, Email haifengzao75@163.comBackground: The present study aimed to explore the association between the inflammatory potential of diet, assessed by energy-adjusted dietary inflammatory index (E-DII) and reduced rank regression (RRR)-derived inflammatory dietary pattern, and the risk for cognitive impairment (CI) in community-dwelling older adults, especially in older adults with chronic diseases and multimorbidity.Methods: A total of 549 older adults from Taiyuan city were included in the present cross-sectional study. The Chinese Version of the Mini-Mental State Examination (CMMSE) was used for the evaluation of cognitive function. E-DII score was calculated based on semi-quantitative food frequency questionnaire (FFQ). Blood samples, including interleukin (IL)-1β, interleukin (IL)-18, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP), were tested for calculating RRR-derived inflammatory dietary pattern. Logistic regression was used to assess the association between inflammatory dietary pattern and risk of CI. In addition, patients with diabetes, hypertension, hyperlipidemia and multimorbidity were screened for further analysis among 549 older adults.Results: In those 549 older adults, adjusting for demographic characteristics and chronic disease status, there was no association between E-DII score tertile (ORT3VST1: 1.357, 95%CI:0.813~2.265, Ptrend = 0.267), RRR-derived inflammatory dietary pattern score tertile (ORT3VST1: 1.092, 95%CI:0.679~ 1.758, Ptrend = 0.737) and risk of CI. However, in older adults with diabetes and multimorbidity, the score tertile of E-DII and RRR-derived inflammatory dietary pattern were positively correlated with risk of CI in a dose-responsive manner (All Ptrend < 0.05). There is insufficient evidence to reach similar conclusion in patients with hypertension and hyperlipidemia (All Ptrend > 0.05).Conclusion: In the present study, pro-inflammatory diet contributed to the increased risk of CI in older adults with diabetes and multimorbidity. These results supplemented vital evidence for the prevention and treatment of CI in older adults with chronic diseases.Keywords: chronic diseases, multimorbidity, cognitive impairment, inflammatory dietary pattern, dietary inflammatory index, reduced rank regression

Mu Yuan,1,2,&ast; Weijun Wan,1,2,&ast; Wei Xing,1,2 Chengxiu Pu,1,2 Xiaofeng Wu,1,2 Zhikang Liao,3 Xiyan Zhu,3 Xueting Hu,1,2 Zhan Li,1,2 Qing Zhao,1,2 Hui Zhao,3,&ast; Xiang Xu1,2,&ast; 1Department of Stem Cell and Regenerative Medicine, National Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 2Central Laboratory, State Key Laboratory of Trauma, Burn and Combined Injury, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China; 3Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Xu, Stem Cell and Regenerative Medicine Department, Daping Hospital, Army Medical University, Chongqing, No. 10, Changjiang Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email xiangxu@tmmu.edu.cn Hui Zhao, Research Department Fourth Laboratory, Daping Hospital, Army Medical University, Chongqing, 400042, People’s Republic of China, Email Zhaohui@tmmu.edu.cnPurpose: We aimed to investigate whether peripheral blood biomarkers B2M related to immune response can serve as indicators of HAPE pathophysiological characteristics or disease progression.Patients and Methods: Bioinformatics technology was used to explore the peripheral blood pathophysiological mechanisms and immune hub genes related to the occurrence of HAPE. The hub gene was verified through animal experiments, and its function and correlation between its expression level and the diagnosis, treatment effect and prognosis of HAPE were explored.Results: The GSVA results showed that the occurrence of HAPE was related to the down-regulation of immune response pathways by RUNX3 and STING. WGCNA results showed that the peripheral blood immune gene module related to the development of HAPE was related to the decrease of immune function and the increase of immune checkpoint molecule PD-L1 gene expression, and the expression of immune checkpoint genes LILRB2 and SIGLEC15 increased. Cytoscape software, RT-qPCR and WB confirmed that the hub gene B2M is a specific peripheral blood biomarker of HAPE. ROC, DCA, RT-qPCR, HE and Masson results showed that the expression of peripheral blood B2M has the ability to indicate the diagnosis, treatment effect and prognosis of HAPE. The decreased expression of B2M protein in peripheral blood leukocytes may be a marker of HAPE. Single-gene GSEA confirmed that the reduced expression of B2M in peripheral blood may be involved in the down-regulation of the antigen presentation pathway mediated by MHC class I molecules, was positively correlated with the down-regulation of the TNF signaling pathway, and was negatively correlated with the expression of LILRB2 and SIGLEC15.Conclusion: The occurrence of HAPE may be related to decreased immune function and immune tolerance. Peripheral blood B2M may be involved in the related pathways, its expression level can prompt the diagnosis, treatment and prognosis of HAPE. Keywords: high altitude pulmonary edema, immune tolerance, biomarker, B2M, prognosis

Chengxin Luan,1 Ying Zhu,1 Hongguo Zhao2 1Department of Oncology and Hematology, The Fourth Division Hospital of Xinjiang Production and Construction Corps, Yining, People’s Republic of China; 2Department of Hematology, Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Chengxin Luan, Email luanchengxinxjb@163.comAbstract: Gynecomastia refers to the abnormal enlargement of the male breast caused by the proliferation of the glandular component of the breast, typically due to sexual hormone disturbance. Multiple medications have been linked to the development of gynecomastia with varying incidences. This adverse event has also been associated with TKIs such as imatinib, dasatinib, and rarely nilotinib. However, it is poorly described and regarded as a rare event. Herein, we present the first case of a CML patient who developed gynecomastia after switching from imatinib to flumatinib. The patient is an 82-year-old male. He was diagnosed with CML and initially treated with imatinib. However, the treatment response milestone after three months of imatinib was not achieved. Hence, flumatinib was used to replace imatinib. Unexpectedly, two weeks later, he developed gynecomastia. Gynecomastia usually causes distress to patients, and there are currently no clear mechanisms or management strategies for this condition. Inspired by this case and through a review of the literature, we propose possible mechanisms and management strategies for this rare adverse event associated with TKIs, along with future perspectives. This may assist others in dealing with this issue and stimulate research on it.Keywords: gynecomastia, chronic myeloid leukemia, flumatinib

Yao Sun, Huiying Zhao, Youzhong An Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Huiying Zhao; Youzhong An, Peking University People’s Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, People’s Republic of China, Email zhaohuiying109@sina.com; 2211110449@stu.pku.edu.cnAbstract: Guillain-Barré syndrome (GBS) stands out as the most prevalent and severe acute immune-mediated paralytic neuropathy. Approximately 30% of patients experience respiratory failure necessitating admission to the intensive care unit (ICU) and invasive mechanical ventilation. The management of diseases concomitant with acute respiratory distress syndrome (ARDS) poses significant challenges. This case report illustrates the swift development of ARDS in a patient with GBS, explores the utility of the biomarker neurofilament light chain, and highlights the unexpected advantages of proactive ARDS intervention.Keywords: Guillain-Barré syndrome, severe acute respiratory distress syndrome, case, ventilation

Yong Zhu,1,&ast; Yongzhe Zhang,2,&ast; Xiuli Yu,3 Huaqiang Zhao,1 Chuan Ma1 1Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of China; 2Department of Prosthodontics, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 3Department of Stomatology, Chengyang People’s Hospital, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Ma, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, No. 44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Fax +86 53188382923, Email machuan@sdu.edu.cnObjective: Tumor cells, inflammatory cells, and chemical factors collaboratively orchestrate a sophisticated signaling network, culminating in the formation of the inflammatory tumor microenvironment (TME). The present study sought to explore the nature of the inflammatory response in HNSCC and to decipher its influence on immunotherapeutic.Materials and Methods: A thorough analysis was performed utilizing the TCGA cohort along with two GEO cohorts. Unsupervised clustering of 200 inflammatory response-related genes (IRGs) was applied using the k-means algorithm to explore the heterogeneity of HNSCC. Additionally, a prognostic signature based on IRGs genes was constructed using Lasso regression. Meanwhiles, the expression of IRGs were identified in tumors and paracancerous tissues at the single-cell level. The crosstalk between IRGs was explored using CellChat and the patterns of incoming and outgoing signals were identified. Finally, qPCR was used to verify the expression of hub genes.Results: There were significant differences in immune-cell function and immune-cell infiltration among three inflammatory response clusters. Additionally, we also constructed a prognostic model which could predicted the responses of common chemotherapeutic drugs and immunotherapy. Furthermore, qPCR and sc-RNA seq corroborated that the expression profiles of the prognostic genes were largely in alignment with the findings from the bioinformatics analysis. Ultimately, the molecular docking demonstrated favorable binding affinities between the pivotal gene-SCC7 and four chemotherapeutic drugs.Conclusion: This research has uniquely shed light on the intricate connection between the inflammatory response profiles and the immune infiltration patterns in HNSCC.Keywords: HNSCC, TME, inflammatory response, immunotherapy, sc-RNA seq

Xuan Ma,1,2,&ast; Baolan Ji,2,&ast; Wenhua Du,2 Shuwei Shi,1,2 Hongyan Zhao,1,2 Jie Sheng,1,2 Xinghe Jiang,1,2 Bo Ban,3 Guanqi Gao2 1School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, 261000, People’s Republic of China; 2Department of Endocrinology, Linyi People’s Hospital Affiliated to Shandong Second Medical University, Linyi, Shandong, 276034, People’s Republic of China; 3Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanqi Gao, Department of Endocrinology, Linyi People’s Hospital, North Side of the Intersection of Wohushan Road and Wuhan Road in Lanshan District, Linyi, Shandong, 276034, People’s Republic of China, Email guanqi_gao@yeah.net Bo Ban, Department of Endocrinology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272029, People’s Republic of China, Email banbo2011@163.comPurpose: Substantial evidence has established a strong association between non-alcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM) and insulin resistance (IR). Insulin resistance metabolic score (METS-IR) is a new and more effective comprehensive indicator for measuring IR. Our aim was to investigate the relationship between METS-IR and NAFLD in T2DM population.Patients and methods: This cross-sectional study included 1097 adult patients with T2DM. Anthropometric measurements and biochemical indicators were collected, and the NAFLD was diagnosed by ultrasound. The METS-IR was calculated. Based on the presence of NAFLD, the population was divided into non-NAFLD and NAFLD groups. The relationship between METS-IR and NAFLD was evaluated.Results: Compared with the non-NAFLD group, the METS-IR was higher in the NAFLD group (P < 0.001). The incidence rate of NAFLD increased across the quartiles of the METS-IR (P < 0.001). Spearman correlation analysis showed that METS-IR was positively correlated with NAFLD (Correlation Coefficient: 0.441, P < 0.001). The binary logistic regression analysis indicated that METS-IR was independently associated with NAFLD (OR: 1.120, 95% CI 1.080– 1.161). Furthermore, the area under the receiver operating characteristic curve of the METS-IR was 0.781 (95% CI 0.746– 0.817) and relatively higher than other evaluation variables.Conclusion: In patients with T2DM, METS-IR is closely associated with NAFLD, and might be a valuable predictor of NAFLD. Further research is needed to verify this association.Keywords: Type 2 diabetes mellitus, NAFLD, insulin resistance, METS-IR

Caiyun Yin,1,2,&ast; Peiyun Hu,1,2,&ast; Lijing Qin,2 Zhicheng Wang,2 Hongguang Zhao1 1Department of Nuclear Medicine, The First Hospital of Jilin University, Changchun, People’s Republic of China; 2National Health Commission (NHC) Key laboratory of Radiobiology, School of Public Health, Jilin University, Changchun, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhicheng Wang; Hongguang Zhao, Email zhicheng@jlu.edu.cn; zhaohg@jlu.edu.cnAbstract: Molecular imaging is an advanced technology that utilizes specific probes or markers in conjunction with cutting-edge imaging techniques to observe and analyze the localization, distribution, activity, and interactions of biomolecules within living organisms. Tumor molecular imaging, by enabling the visualization and quantification of molecular characteristics of tumor cells, facilitates a deeper and more comprehensive understanding of tumors, providing valuable insights for early diagnosis, treatment monitoring, and cancer biology research. However, the image quality of molecular imaging still requires improvement, and nanotechnology has significantly propelled the advancement of molecular imaging. Currently, nanoparticle-based tumor molecular imaging technologies encompass radionuclide imaging, fluorescence imaging, magnetic resonance imaging, ultrasound imaging, photoacoustic imaging, and multimodal imaging, among others. As our understanding of the tumor microenvironment deepens, the design of nanoparticle probes for tumor molecular imaging has also evolved, offering new perspectives and expanding the applications of tumor molecular imaging. Beyond diagnostics, there is a marked trend towards integrated diagnosis and therapy, with image-guided treatment playing a pivotal role. This includes image-guided surgery, photodynamic therapy, and chemodynamic therapy. Despite continuous advancements and innovative developments in molecular imaging, many of these remain in the experimental stage and require breakthroughs before they can be fully integrated into clinical practice.Keywords: molecular imaging, nanoparticles, tumor, diagnosis, treatment

Hupo Bian,1 Shaoqi Zhu,2 Yonghua Zhang,3 Qiang Fei,4 Xiuhua Peng,1 Zanhui Jin,1 Tianxiang Zhou,5 Hongxing Zhao1,6 1Department of Radiology, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, The Wuxing District People’s Hospital, Huzhou, Zhejiang, People’s Republic of China; 4Department of Radiology, The Linghu People’s Hospital, Huzhou, Zhejiang, People’s Republic of China; 5Department of Urinary Surgery, The First Affiliated Hospital of Huzhou Normal University, Huzhou, Zhejiang, People’s Republic of China; 6Huzhou Key Laboratory of Precise Diagnosis and Treatment of Urinary Tumors, Huzhou, Zhejiang, 313000, People’s Republic of ChinaCorrespondence: Hongxing Zhao, Department of Radiology, The First Affiliated Hospital of Huzhou Normal University, No. 158, Plaza Back Road, Wuxing District, Huzhou City, Zhejiang Province, People’s Republic of China, Email zhx2113408@126.comObjective: A bibliometric analysis was conducted using VOSviewer and CiteSpace to examine studies published between 2009 and 2023 on the utilization of artificial intelligence (AI) in chronic obstructive pulmonary disease (COPD).Methods: On March 24, 2024, a computer search was conducted on the Web of Science (WOS) core collection dataset published between January 1, 2009, and December 30, 2023, to identify literature related to the application of artificial intelligence in chronic obstructive pulmonary disease (COPD). VOSviewer was utilized for visual analysis of countries, institutions, authors, co-cited authors, and keywords. CiteSpace was employed to analyze the intermediary centrality of institutions, references, keyword outbreaks, and co-cited literature. Relevant descriptive analysis tables were created using Excel2021 software.Results: This study included a total of 646 papers from WOS. The number of papers remained small and stable from 2009 to 2017 but started increasing significantly annually since 2018. The United States had the highest number of publications among countries/regions while Silverman Edwin K and Harvard Medical School were the most prolific authors and institutions respectively. Lynch DA, Kirby M. and Vestbo J. were among the top three most cited authors overall. Scientific Reports had the largest number of publications while Radiology ranked as one of the top ten influential journals. The Genetic Epidemiology of COPD (COPDGene) Study Design was frequently cited. Through keyword clustering analysis, all keywords were categorized into four groups: epidemiological study of COPD; AI-assisted imaging diagnosis; AI-assisted diagnosis; and AI-assisted treatment and prognosis prediction in the COPD research field. Currently, hot research topics include explainable artificial intelligence framework, chest CT imaging, and lung radiomics.Conclusion: At present, AI is predominantly employed in genetic biology, early diagnosis, risk staging, efficacy evaluation, and prediction modeling of COPD. This study’s results offer novel insights and directions for future research endeavors related to COPD.Keywords: chronic obstructive pulmonary disease, artificial intelligence, visual analysis, bibliometric analysis

Wensen Pi, Yang Liu, Haidan Chen, Hongwei Zhao Department of Spine Surgery of Yichang Central People’s Hospital, First Clinical Medical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Hongwei Zhao; Haidan Chen, Department of Spine Surgery of Yichang Central People’s Hospital, First Clinical Medical College of China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Email ycguke@sina.com; 147811399@qq.comAbstract: Cryptococcus neoformans is a type of fungal infection, which primarily affects the central nervous system and lungs of immunocompromised individuals. Spinal infections are known to be a rare manifestation of cryptococcosis. Herein, we report a case of a patient with isolated nonspecific spinal lesions at the T10 vertebra. The patient received non-surgical treatment with antifungal drugs, resulting in satisfactory clinical outcomes.Keywords: cryptococcal, thoracic spine

Longyin Zhu,&ast; Juan Cai,&ast; Jia Fang, Lingyu Ran, Huan Chang, Huhai Zhang, Jiamin Zeng, Qin Yang, Chunxiao Fu, Qingping Li, Qianguang Pan, Hongwen Zhao Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comObjective: Analyze risk factors for cardiac surgery-associated acute kidney injury (CSA-AKI) in adults and establish a nomogram model for CSA-AKI based on plasma soluble urokinase-type plasminogen activator receptor (suPAR) and clinical characteristics.Methods: In a study of 170 patients undergoing cardiac surgery with cardiopulmonary bypass, enzyme-linked immunosorbent assay (ELISA) measured plasma suPAR levels. Multivariable logistic regression analysis identified risk factors associated with CSA-AKI. Subsequently, the CSA-AKI nomogram model was developed using R software. Predictive performance was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). Internal validation was performed through the Bootstrap method with 1000 repeated samples. Additionally, decision curve analysis (DCA) assessed the clinical applicability of the model.Results: Multivariable logistic regression analysis revealed that being male, age ≥ 50 years, operation time ≥ 290 minutes, postoperative plasma suPAR at 2 hours, and preoperative left ventricular ejection fraction (LVEF) were independent risk factors for CSA-AKI. Employing these variables as predictive factors, a nomogram model was constructed, an ROC curve was generated, and the AUC was computed as 0.817 (95% CI 0.726– 0.907). The calibration curve indicated the accuracy of the model, and the results of DCA demonstrated that the model could benefit the majority of patients.Conclusion: Being male, age ≥ 50 years, operation time ≥ 290 minutes, low preoperative LVEF, and elevated plasma suPAR at 2 hours are independent risk factors for CSA-AKI. The nomogram model established based on these risk factors has high accuracy and clinical value, serving as a predictive tool for assessing the risk of CSA-AKI.Keywords: nomogram, acute kidney injury, prediction model, risk factors, cardiac surgery

Yannan Pan,1,2,&ast; Jiandan Qian,1,&ast; Guiqiang Wang,1 Hong Zhao1 1Department of Infectious Diseases, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiqiang Wang; Hong Zhao, Department of Infectious Diseases, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Email john131212@126.com; zhaohong_pufh@bjmu.edu.cnBackground: Infective endocarditis caused by Streptococcus sinensis is exceedingly rare, with only limited cases reported. Here, we present the first documented case of prosthetic valve endocarditis attributed to Streptococcus sinensis.Case Presentation: A 40-year-old Chinese female was admitted with a 45-day history of intermittent fever. The presumed diagnosis was a pulmonary infection and antibiotic therapies failed to alleviate her symptoms. On admission, infective endocarditis was suspected, considering the history of aortic valve replacement and recent dental procedure without prophylactic antibiotics. Transesophageal echocardiography disclosed a 3-millimeter vegetation in the prosthetic aortic valve, and metagenomic next-generation sequencing and mass spectrometry identified Streptococcus sinensis. The patient was diagnosed with infective endocarditis. Antibiotic treatments resulted in temporary clinical improvements, although fluctuations in temperature and inflammatory markers led to multiple attempts at antibiotic therapies. At last, the patient underwent an elective aortic valve replacement with a favorable prognosis.Conclusion: In this case, we demonstrated prosthetic valve endocarditis caused by Streptococcus sinensis, which is an extremely rare pathogen. All reported endocarditis cases caused by Streptococcus sinensis were reviewed and summarized. Most of these patients had rheumatic heart diseases or congenital heart diseases. Antibiotic prophylaxis is important for high-risk procedures. Timely identification of the bacterium is crucial for diagnosis and treatment. Overall, infective endocarditis caused by this bacterium had a good prognosis.Keywords: infective endocarditis, prosthetic valve, Streptococcus sinensis, metagenomic next-generation sequencing, case report

Yuan Gao,1– 3,&ast; Ce Zong,1,&ast; Ying Yao,4 Haixu Zhao,5 Yuan Song,4 Ke Zhang,1 Hongxun Yang,1 Hongbing Liu,1 Yunchao Wang,1 Yusheng Li,1– 3 Jing Yang,1– 3 Bo Song,1– 3 Yuming Xu1– 3 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, People’s Republic of China; 3Henan Key Laboratory of Cerebrovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4School of Health and Nursing, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 5School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuming Xu, Department of Neurology, the First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Erqi District, Zhengzhou, Henan Province, People’s Republic of China, 450052, Tel/Fax +86 13903711125, Email xuyuming@zzu.edu.cnPurpose: We aimed to explore the association between fibrinogen-to-albumin ratio (FAR) and the risk of incident stroke (IS) in a cohort of cerebral small vessel disease (CSVD) patients.Patients and Methods: Participants were screened from a prospective CSVD database. Clinical data, hematologic measures and imaging findings were collected. The primary outcome was IS during follow-up, with a secondary outcome of composite vascular events (CVE) including IS, myocardial infarction (MI), and vascular deaths. Univariate and multivariate COX proportional risk models, along with competing risk models, were employed to identify factors associated with outcomes. Restricted cubic spline (RCS) and subgroup analyses were conducted to assess the association between FAR and the risk of IS and CVE in CSVD patients.Results: In the final analysis of 682 CSVD patients over a median observation period of 34.0 [24.0– 53.0] months, there were 33 cases of IS (4.84%, 1.55/100 person-years), 4 incidents of MI (0.59%, 0.19/100 person-years), 15 non-vascular deaths (2.20%, 0.70/100 person-years), and 37 occurrences of CVE (5.43%, 1.74/100 person-years). Multivariate Cox regression analysis revealed a significant positive correlation between elevated FAR and both IS (HR 1.146; 95% CI 1.043– 1.259; P=0.004) and CVE (HR 1.156; 95% CI 1.063– 1.257; P=0.001) in CSVD patients. Multivariate competing risk model showed the similar results (IS: HR 1.16; 95% CI 1.06– 1.27; P=0.001, CVE: HR 1.15; 95% CI 1.05– 1.26; P=0.003). RCS analysis indicated a linear relationship between FAR and the risks of both IS (P for non-linearity =0.7016) and CVE (P for non-linearity =0.6475), with an optimal cutoff value of 8.69, particularly in individuals over 60 years of age.Conclusion: Elevated FAR demonstrated an independent and linear association with IS and the development of CVE in CSVD patients.Keywords: cerebral small vessel disease, incident stroke, fibrinogen-to-albumin ratio, inflammation

Xiaoyu Wu,1,2 Chun Liu,2 Yuqing Jiang,2 Ting Dai,1,2 Linxiang Zhang,1,2 Jiafeng Wang,1,2 Hongbin Zhao1,2 1Gansu Provincial Maternity and Child-Care Hospital, Gansu Provincial Central Hospital, Gansu, People’s Republic of China; 2Changzhou Medical Center, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of ChinaCorrespondence: Hongbin Zhao, Gansu Provincial Maternity and Child-care Hospital, Gansu Provincial Central Hospital, Gansu, 730070, People’s Republic of China, Email zhao761032@163.comBackground: Salidroside (SAL) is the most effective component of Rhodiola rosea, a traditional Chinese medicine. Cryptotanshinone (CT) is the main fat-soluble extract of Salvia miltiorrhiza, exhibiting considerable potential for application in osteogenesis. Herein, a polycaprolactone/gelatin nanofiber membrane loaded with CT and SAL (PSGC membrane) was successfully fabricated via coaxial electrospinning and characterized.Methods and Results: This membrane capable of sustained and controlled drug release was employed in this study. Co-culturing the membrane with bone marrow mesenchymal stem cells and human umbilical vein endothelial cells revealed excellent biocompatibility and demonstrated osteogenic and angiogenic capabilities. Furthermore, drug release from the PSGC membrane activated the Wnt/β-catenin signaling pathway and promoted osteogenic differentiation and vascularization. Evaluation of the membrane’s vascularization and osteogenic capacities involved transplantation onto a rat’s subcutaneous area and assessing rat cranium defects for bone regeneration, respectively. Microcomputed tomography, histological tests, immunohistochemistry, and immunofluorescence staining confirmed the membrane’s outstanding angiogenic capacity two weeks post-operation, with a higher incidence of osteogenesis observed in rat cranial defects eight weeks post-surgery.Conclusion: Overall, the SAL- and CT-loaded coaxial electrospun nanofiber membrane synergistically enhances bone repair and regeneration.Keywords: gelatin, coaxial electrospinning, vascularization and bone regeneration

Yanzhao Zhou,1,&ast; Jingzhong Ouyang,2– 4,&ast; Hongcai Yang,5,&ast; Zhengzheng Wang,2,&ast; Yi Yang,3,4,&ast; Qingjun Li,2 Haitao Zhao,6 Jinxue Zhou,2 Qiang Li1 1Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, People’s Republic of China; 3Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Key Laboratory of Gene Editing Screening and Research and Development (R&D) of Digestive System Tumor Drugs, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 6Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Li, Department of Hepatobiliary Cancer, Liver Cancer Research Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, People’s Republic of China, Email liqiang@tjmuch.com Jinxue Zhou, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, 450008, People’s Republic of China, Email zhoujx888@126.comPurpose: The impact of visceral adiposity on overall survival (OS) in hepatocellular carcinoma (HCC) receiving immunotherapy was unclear. We aimed to determine how visceral adiposity affected OS and explore the interrelationships between visceral adiposity, body mass index (BMI), and other body compositions.Patients and Methods: Data from three centers were retrospectively analyzed. Skeletal muscle index (SMI), skeletal muscle density (SMD), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were used to define each body composition. The BMI subgroups included the underweight, the normal weight, and the obesity. The Log rank test compared survival curves calculated by the Kaplan-Meier method. The relationships between body compositions and BMI with OS were examined using Cox proportional risk regression models.Results: A total of 305 patients who met the criteria were included. Patients with low VATI had significantly worse OS (P = 0.001). The protections of VATI (P = 0.011) on OS were independent of covariates. However, after additional adjustment of SMI, the effect of VATI on OS disappeared (P = 0.146), but the effect of SMD on OS did not (P = 0.021). BMI has a significant U-shaped relationship with OS, and the effect of BMI on OS equally disappeared after additional adjustment by SMI.Conclusion: This study first demonstrated that high VATI and mid-level BMI were protective for the survival of patients with HCC receiving immunotherapy. Skeletal muscle status (including SMI and SMD) may be the better predictor for outcomes of patients with HCC receiving immunotherapy.Keywords: hepatocellular carcinoma, immunotherapy, body mass index, body composition, obesity paradox

Yan Wang,1,&ast; Cuiying Liu,2,3,&ast; Yanhong Ren,3 Jibin Song,4 Kelong Fan,5 Lizeng Gao,5 Xunming Ji,3 Xiaoyuan Chen,6– 10 Heng Zhao3 1Institute of Medical Innovation and Research, Peking University Third Hospital, Beijing, People’s Republic of China; 2School of Nursing, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China; 4State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing, People’s Republic of China; 5CAS Engineering Laboratory for Nanozyme, Institute of Biophysics Chinese Academy of Sciences, Beijing, People’s Republic of China; 6Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore; 7Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 8Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 9Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore; 10Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A&ast;STAR), Singapore&ast;These authors contributed equally to this workCorrespondence: Heng Zhao; Xiaoyuan Chen, Email hengzhao@ccmu.edu.cn; chen.shawn@nus.edu.sgAbstract: This review article discusses the potential of nanomaterials in targeted therapy and immunomodulation for stroke-induced immunosuppression. Although nanomaterials have been extensively studied in various biomedical applications, their specific use in studying and addressing immunosuppression after stroke remains limited. Stroke-induced neuroinflammation is characterized by T-cell-mediated immunodepression, which leads to increased morbidity and mortality. Key observations related to immunodepression after stroke, including lymphopenia, T-cell dysfunction, regulatory T-cell imbalance, and cytokine dysregulation, are discussed. Nanomaterials, such as liposomes, micelles, polymeric nanoparticles, and dendrimers, offer advantages in the precise delivery of drugs to T cells, enabling enhanced targeting and controlled release of immunomodulatory agents. These nanomaterials have the potential to modulate T-cell function, promote neuroregeneration, and restore immune responses, providing new avenues for stroke treatment. However, challenges related to biocompatibility, stability, scalability, and clinical translation need to be addressed. Future research efforts should focus on comprehensive studies to validate the efficacy and safety of nanomaterial-based interventions targeting T cells in stroke-induced immunosuppression. Collaborative interdisciplinary approaches are necessary to advance the field and translate these innovative strategies into clinical practice, ultimately improving stroke outcomes and patient care.Keywords: ischemic stroke, neuroinflammation, T cells, immunosuppression, nanoparticles

Hongqing Zhao,1,2,&ast; Yang Liu,1,2,&ast; Na Cai,3 Xiaolin Liao,1,2 Lin Tang,2,4 Yuhong Wang1,2 1Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 2Hunan Key Laboratory of Traditional Chinese Medicine Prevention & Treatment of Depressive Diseases, Changsha, Hunan, People’s Republic of China; 3Outpatient Department, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China; 4Department of Pharmacy, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Tang; Yuhong Wang, Email tanglin0018@163.com; wangyh107@126.comAbstract: Over the past decade, the idea of targeting the endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone to various adverse effects due to their strong pharmacological activity and poor receptor selectivity, limiting their application in clinical research. Endocannabinoid hydrolase inhibitors are considered to be the most promising development strategies for the treatment of anxiety disorders. More recent efforts have emphasized that inhibition of two major endogenous cannabinoid hydrolases, monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), indirectly activates cannabinoid receptors by increasing endogenous cannabinoid levels in the synaptic gap, circumventing receptor desensitization resulting from direct enhancement of endogenous cannabinoid signaling. In this review, we comprehensively summarize the anxiolytic effects of MAGL and FAAH inhibitors and their potential pharmacological mechanisms, highlight reported novel inhibitors or natural products, and provide an outlook on future directions in this field.Keywords: endocannabinoid hydrolase inhibitors, endocannabinoid system, anxiety disorders, anxiolytic, MAGL, FAAH

Xingtong Chen,1,&ast; Qian Chen,1– 3,&ast; Zhigang Qin,1,&ast; Azeem Alam,3 Hailin Zhao,3 Raha West,3 Xianzhe Liu,1 Jieyu Li,1 Xin Li,1 Bin Yi,1 Daqing Ma,2,3 Jianteng Gu1 1Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Perioperative and Systems Medicine Laboratory, National Clinical Research Center for Child Health, Children’s Hospital, Zhejiang University School of Medicine, Zhejiang, People’s Republic of China; 3Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK&ast;These authors contributed equally to this workCorrespondence: Jianteng Gu, Department of Anesthesiology, Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Road, Chongqing, 400038, People’s Republic of China, Tel +86 23 68766122, Fax +86 23 65463270, Email jiantenggu@hotmail.com Daqing Ma, Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK, Email d.ma@imperial.ac.ukBackground: Dexmedetomidine (Dex) may have anti-inflammatory properties and potentially reduce the incidence of postoperative organ injury.Objective: To investigate whether Dex protects pulmonary and renal function via its anti-inflammatory effects in elderly patients undergoing prolonged major hepatobiliary and pancreatic surgery.Design and Setting: Between October 2019 and December 2020, this randomized controlled trial was carried out at a tertiary hospital in Chongqing, China.Patients: 86 patients aged 60– 75 who underwent long-duration (> 4 hrs) hepatobiliary and pancreatic surgery without significant comorbidities were enrolled and randomly assigned into two groups at a 1:1 ratio.Interventions: Patients were given either Dex or an equivalent volume of 0.9% saline (Placebo) with a loading dose of 1 μg kg− 1 for 10 min, followed by 0.5 μg kg− 1 hr− 1 for maintenance until the end of surgery.Main Outcome Measures: The changes in serum concentrations of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were primary outcomes.Results: At one hour postoperatively, serum IL-6 displayed a nine-fold increase (P< 0.05) in the Placebo group. Administration of Dex decreased IL-6 to 278.09 ± 45.43 pg/mL (95% CI: 187.75 to 368.43) compared to the Placebo group (P=0.019; 432.16 ± 45.43 pg/mL, 95% CI: 341.82 to 522.50). However, no significant differences in TNF-α were observed between the two groups. The incidence of postoperative acute kidney injury was twice as high in the Placebo group (9.30%) compared to the Dex group (4.65%), and the incidence of postoperative acute lung injury was 23.26% in the Dex group, lower than that in the Placebo group (30.23%), although there was no statistical significance between the two groups.Conclusion: Dex administration in elderly patients undergoing major hepatobiliary and pancreatic surgery reduces inflammation and potentially protects kidneys and lungs.Registration: Chinese Clinical Trials Registry, identifier: ChiCTR1900024162, on 28 June 2019.Keywords: dexmedetomidine, elderly patients, long-duration hepatobiliary and pancreatic laparotomy, perioperative renal function, perioperative pulmonary function

Xin Yang,1 Xiaoguang Cui,1 Xiao Yang,2 Bincheng Ren,1 Xiaojing Cheng,1 Xinrui Zhao,1 Shanshan Liu,1 Tian Tian,1 Hui Zhao,1 Li Qu,1 Xueyi Li1 1Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China; 2Scientific Research Center and Precision Medical Institute, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of ChinaCorrespondence: Xueyi Li, Department of Rheumatology, Xi’an Jiaotong University Second Affiliated Hospital, Xi’an, People’s Republic of China, Tel +86 13992891987, Fax +86 02987679832, Email li-xueyi@139.comPurpose: This study aimed to assess liver involvement and investigate its correlation with rapidly progressive interstitial lung disease (RP-ILD) and mortality in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 positive) DM patients.Patients and Methods: This retrospective study included 159 patients diagnosed with anti-MDA5 positive DM or anti-synthetase syndrome (ASyS). Clinical features and laboratory findings were compared between patients with anti-MDA5 positive DM and patients with ASyS. In the anti-MDA5 positive DM cohort, clinical features and laboratory findings between patients with liver involvement and without liver involvement were further compared. The effects of liver involvement on the overall survival (OS) and development of RP-ILD were also analyzed using Kaplan–Meier method and Cox regression analysis.Results: Levels of serum aspartate aminotransferase (AST), alanine transaminase (ALT), γ-glutamyl transferase (γGT) and alkaline phosphatase (ALP) were all significantly higher in patients with anti-MDA5 positive DM than those in patients with ASyS. In our cohort of anti-MDA5 positive DM patents, 31 patients (34.4%) were complicated with liver involvement. Survival analysis revealed that serum ferritin > 1030.0 ng/mL (p< 0.001), ALT > 103.0 U/l (p< 0.001), AST > 49.0 U/l (p< 0.001), γGT > 82.0 U/l (p< 0.001), ALP > 133.0 U/l (p< 0.001), lactate dehydrogenase (LDH)> 474.0 U/l (p< 0.001), plasma albumin (ALB) < 35.7 g/l (p< 0.001) and direct bilirubin (DBIL) > 2.80 μmol/l (p=0.002) predicted poor prognosis. The incidence of RP-ILD increased remarkably in patients with liver involvement compared to patients without liver involvement (58.1% vs 22.0%, p=0.001). Multivariate analysis revealed that elevated serum ALT level was an independent risk factor for mortality (HR 6.0, 95% CI 2.3, 16.2, p< 0.001) and RP-ILD (HR 5.9, 95% CI 2.2, 15.9, p< 0.001) in anti-MDA5 positive DM patents.Conclusion: Liver involvement is common in patients with anti-MDA5 positive DM. Elevated serum ALT level was an independent risk factor for RP-ILD and mortality in patients with anti-MDA5 positive DM.Keywords: anti-melanoma differentiation-associated gene 5 antibody, liver involvement, ferritin, macrophage, interstitial lung disease, dermatomyositis

Wang L, Li D, Hao Y, et al. Int J Nanomedicine. 2017;12:3059-3075. The authors have advised Figures 9 and 11 on pages 3070 and 3071, respectively, are incorrect. The H&E staining image of tumor tissue in the PLGA/DTX@MnO2 group in Figure 9C and the X-ray CT images in Figure 11C were inadvertently misused during data acquisition. The correct Figure 9 is as follows. Figure 9 Inhibition of tumor growth in vivo by the drug delivery system.Abbreviations: H&E, hematoxylin and eosin; AuNR, gold nanorod; DTX, docetaxel; MnO2, manganese dioxide; PLGA, poly(lactic-co-glycolic acid); RF, radiofrequency.Notes: (A) Relative volumes of tumor-bearing mice; (B) body weight of the mice models (mean ± standard deviation; n=6); (C) H&E-stained tumor tissue sections: (a) control, (b) DTX, (c) PLGA/DTX@MnO2, (d) PLGA/DTX@MnO2 + RF, (e) PLGA/AuNR/DTX@MnO2, and (f) PLGA/AuNR/DTX@MnO2 + RF. The correct Figure 11 is as follows. Figure 11 Dual-mode imaging in vivo.Abbreviations: MR, magnetic resonance; CT, computed tomography.Notes: (A, B) T1-weighted MR images; (C) X-ray CT images: (a) control; (b) 4 h; (c) 8 h. The authors apologize for these errors and advise they do not affect the results and conclusions of the paper.

Meiju Deng, Na Chen, Xiaojie Lao, Xiaolei Wang, Jiantao Fu, Lulu Xing, Hongxin Zhao Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Hongxin Zhao, Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Email drzhao66@ccmu.edu.cnPurpose: The study aimed to explore the reasons, efficacy, and safety of switching to dolutegravir (DTG) based regimens in virologically suppressed people living with HIV (PLWH) in tertiary hospitals in China. Therefore, the study could provide a valuable reference for the rational clinical use of DTG.Methods: PLWH’s basic information, treatment details, and reasons for switching were collected, through the electrical clinical medical record system and telephone follow-up. Data included the proportion of PLWH with HIV RNA < 50 copies/mL, changes in immunological indicators, and metabolic metrics at week 48 and week 96.Results: 319 PLWH were included in the analysis. The three major reasons for switching were neurological toxicity (16.30%), simplification (13.79%), and renal toxicity (11.29%). Our study showed high rates of virologic suppression in the per-protocol analysis (week 48: 99.69%; week 96: 99.29%) after switching to DTG-based regimens. The median CD4+ T cell count increased from 579 cells/μL (IQR 420.5– 758) to 642 cells/μL (IQR 466.5– 854) at week 96 (p< 0.0001). An improvement was observed in liver function (ALT: p< 0.0001; AST: p< 0.0001) and fasting glucose (p< 0.0001). However, there was an elevation in creatinine (Cr) (p< 0.0001) and a slight decrease in the estimated glomerular filtration rate (eGFR) (p< 0.0001). Regarding lipid profile, triglyceride (TG) levels declined, while total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels increased. Further analysis revealed that the increase in TC and LDL-C was associated with the withdrawal of tenofovir disoproxil fumarate (TDF). This observed increase in lipid parameters only concerned the PLWH who switched from a TDF-containing regimen to a non-TDF regimen.Conclusion: This study confirmed the virologic efficacy of switching to DTG-based regimens in virologically suppressed PLWH over a 96-week period. The findings also expanded the evidence of immune reconstitution and metabolic safety associated with this switch.Keywords: HIV, dolutegravir, switching, virologically suppressed, lipids profile

Chuihao Kong,1,2,&ast; Kaidi Wang,1,2,&ast; Lei Sun,1,3 Hongsu Zhao,1,2 Tongsheng Wang,1 Wuxi Zhou,1 Deling Wu,1,2 Fengqing Xu1,2 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China; 3Zhejiang CONBA Pharmaceutical Co. LTD, Hangzhou, 310052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuxi Zhou; Fengqing Xu, School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan District, Hefei, 230012, People’s Republic of China, Email zhouwuxi@ahtcm.edu.cn; xufengqing@ahtcm.edu.cnBackground: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics.Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo.Results: The results indicated that MC-CDs with a uniform spherical particle size of 1– 5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg.Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs. Keywords: Moutan Cortex, carbon dots, mangiferin, solubility, bioavailability

Zhuoyuan Zhang,1,2,&ast; Dan Liu,1,2,&ast; Rui Lv,1,2,&ast; Haoyan Zhao,1,2,&ast; Tianjing Li,1,2 Yutao Huang,2 Zhicheng Tian,2 Xiangyu Gao,2 Peng Luo,2 Xin Li3 1Biochemistry and Molecular Biology, College of Life Science, Northwest University, Xi’an, 710127, People’s Republic of China; 2Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China; 3Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Luo; Xin Li, Email pengluo@fmmu.edu.cn; li_xin_mail@126.comPurpose: Neuroinflammation occurs in response to central nervous system (CNS) injury, infection, stimulation by toxins, or autoimmunity. We previously analyzed the downstream molecular changes in HT22 cells (mouse hippocampal neurons) upon lipopolysaccharide (LPS) stimulation. We detected elevated expression of Fibrillarin (FBL), a nucleolar methyltransferase, but the associated proinflammatory mechanism was not systematically elucidated. The aim of this study was to investigate the underlying mechanisms by which FBL affects neuroinflammation.Methods: RT-real-time PCR, Western blotting and immunofluorescence were used to assess the mRNA and protein expression of FBL in HT22 cells stimulated with LPS, as well as the cellular localization and fluorescence intensity of FBL. BAY-293 (a son of sevenless homolog 1 (SOS1) inhibitor), SR11302 (an activator protein-1 (AP-1) inhibitor) and KRA-533 (a KRAS agonist) were used to determine the molecular mechanisms underlying the effect of FBL. AP-1 was predicted to be the target protein of FBL by molecular docking analysis, and validation was performed with T-5224 (an AP-1 inhibitor). In addition, the downstream signaling pathways of FBL were identified by transcriptome sequencing and verified by RT-real-time PCR.Results: LPS induced FBL mRNA and protein expression in HT22 cells. In-depth mechanistic studies revealed that when we inhibited c-Fos, AP-1, and SOS1, FBL expression decreased, whereas FBL expression increased when KRAS agonists were used. In addition, the transcript levels of inflammatory genes in the NF-kB signaling pathway (including CD14, MYD88, TNF, TRADD, and NFKB1) were elevated after the overexpression of FBL.Conclusion: LPS induced the expression of FBL in HT22 cells through the RAS/MAPK signaling pathway, and FBL further activated the NF-kB signaling pathway, which promoted the expression of relevant inflammatory genes and the release of cytokines. The present study reveals the mechanism by which FBL promotes neuroinflammation and offers a potential target for the treatment of neuroinflammation.Keywords: FBL, neuroinflammation, LPS, molecular docking, transcriptome sequencing

Shuzhou Liu,1,&ast; Hao Zhao,2,&ast; Xiaoyi Li2 1Department of Head & Neck Surgery, Hainan General Hospital, Haikou, 570311, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyi Li, Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 1 Shuai Fu Yuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email li.xiaoyi@263.netIntroduction: Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC.Methods: A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers.Results: The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management.Conclusion: Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.Keywords: medullary thyroid carcinoma, serum biochemical markers, calcitonin, carcinoembryonic antigen, procalcitonin

Yan Wang,1,2,&ast; Cong Li,1,2,&ast; Lei Liu,1,&ast; Yuan Yang,3,&ast; Xue He,1,2 Gang Li,3 Xianzhen Zheng,3 Yun Ren,1,4 Hanpeng Zhao,1,5 Zhenchao Du,1,4 Jianrong Jiang,1,5 Yu Kuang,1 Fujun Jia,3 Honghua Yu,1 Xiaohong Yang1,2 1Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China; 3Guangdong Mental Health Center, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, People’s Republic of China; 4Shantou University Medical College, Shantou, People’s Republic of China; 5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Yang; Honghua Yu, Email syyangxh@scut.edu.cn; yuhonghua@gdph.org.cnBackground: Identifying the fundus objective biomarkers for the major depressive disorders (MDD) may help promote mental health. The aim of this study was to evaluate retinal neurovascular changes and further investigate their association with disease severity in MDD.Methods: This cross-sectional study conducted in the hospital enrolled patients with MDD and healthy controls.The retinal neurovascular parameters for all subjects, including vessel density (VD), thickness of ganglion cell complex (GCC) and retinal nerve fiber layer (RNFL), and optic nerve head (ONH) eg are automatically calculated by the software in optical coherence tomography angiography (OCTA). The severity of MDD including depressive symptoms, anxiety, cognition, and insomnia was assessed by Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Scale (HAMA), Montreal Cognitive Assessment (MoCA), and Insomnia Severity Index (ISI) respectively.Results: This study included 74 MDD patients (n=74 eyes) and 60 healthy controls (HCs) (n=60 eyes). MDD patients showed significantly decreased VD of superficial and deep capillary plexus, thickness of GCC and RNFL, and volume of ONH (all p< 0.05) and increased vertical cup-to-disc ratio and global loss volume (GLV) (all p< 0.05) compared to HCs. Positive associations were found between HAMD scores and cup area (r=0.30, p=0.035), cup volume (r=0.31, p=0.029), and disc area (r=0.33, p=0.020) as well as ISI scores and RNFL thickness (r=0.34, p=0.047).Conclusion: We found the retinal neurovascular impairment and its association with disease severity in MDD patients. OCTA showed promise as a potential complementary assessment tool for MDD.Keywords: major depressive disorder, retinal neurovasculature, optical coherence tomography angiography, disease severity

Lujie Wei,1,&ast; Pingyang Li,2,&ast; Xiaofeng Liu,1 Yuxia Wang,1 Zhengping Tang,1 Hang Zhao,1 Lu Yu,3 Kaixiu Li,1 Jianping Li,1 Min Du,4 Xinzhu Chen,2 Xin Zheng,2 Yixiong Zheng,5 Yao Luo,2 Jing Chen,5 Xiamin Jiang,6 Xiaobing Chen,7 Huaicong Long1 1Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 2Medical College, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Nanbu County People’s Hospital, Nanbu, Sichuan, People’s Republic of China; 5College of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 6Clinical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaicong Long, Geriatric Intensive Care Unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86 18981838105, Fax +86-28-8779 5585, Email longhc69@163.comBackground: Chronic obstructive pulmonary disease (COPD) is closely associated with frailty, and prevention of acute exacerbations is important for disease management. Moreover, COPD patients with frailty experience a higher risk of acute exacerbations. However, the frailty instruments that can better predict acute exacerbations remain unclear.Purpose: (1) To explore the factors influencing frailty and acute exacerbations in stable COPD patients, and (2) quantify the ability of multidimensional frailty instruments to predict acute exacerbations within 1 year.Patients and methods: In this retrospective longitudinal study, stable COPD patients were recruited from the outpatient department of Sichuan Provincial People’s Hospital from July 2022 to June 2023. COPD patients reviewed their frailty one year ago and their acute exacerbations within one year using face-to-face interviews with a self-developed frailty questionnaire. Frailty status was assessed using the Frailty Index (FI), frailty questionnaire (FRAIL), and Clinical Frailty Scale (CFS). One-way logistic regression was used to explore the factors influencing frailty and acute exacerbations. Multivariate logistic regression was used to establish a prediction model for acute exacerbations, and the accuracy of the three frailty instruments was compared by measuring the area under the receiver operating characteristic curve (AUC).Results: A total of 120 individuals were included. Frailty incidence estimates using FI, FRAIL, and CFS were 23.3%, 11.7%, and 15.8%, respectively. The three frailty instruments showed consistency in COPD assessments (P< 0.05). After adjusting for covariates, frailty reflected by the FI and CFS score remained an independent risk factor for acute exacerbations. The CFS score was the best predictor of acute exacerbations (AUC, 0.764 (0.663– 0.866); sensitivity, 57.9%; specificity, 80.0%). Moreover, the combination of CFS plus FRAIL scores was a better predictor of acute exacerbations (AUC, 0.792 (0.693– 0.891); sensitivity, 86.3%; specificity, 60.0%).Conclusion: Multidimensional frailty assessments could improve the identification of COPD patients at high risk of acute exacerbations and facilitate targeted interventions to reduce acute exacerbations in these patients.Keywords: chronic obstructive pulmonary disease, frailty, acute exacerbations

Xiaoxiao Zhao,1 Hanjun Zhao,1 Runzhen Chen,1 Jiannan Li,1 Jinying Zhou,1 Nan Li,1 Shaodi Yan,2 Chen Liu,1 Peng Zhou,1 Yi Chen,1 Li Song,1 Hongbing Yan2 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, BeiJing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital Chinese Academy of Medical Sciences, ShenZhen, People’s Republic of ChinaCorrespondence: Hanjun Zhao, Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, No. 167, Beijing, 100037, People’s Republic of China, Tel +86-15210020808, Email 15210020808@163.com Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Shenzhen, 518000, People’s Republic of China, Tel +86-1301339287, Email hbyanfuwai2018@163.comBackground and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown.Methods: We studied 274 consecutive aged ≥ 18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019.Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723– 0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p= 0.033). A similar tendency was found in the cohort with hyperlipidemia (p= 0.016) and diabetes mellitus (p= 0.036).Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics.Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.Keywords: optical coherence tomography, triglyceride glucose index, trimethylamine N-oxide, high risk plaque feature, major adverse cardiovascular events, prospective study

Bo-Lun Zhang,1 Jia Liu,2 Guanghao Diao,2 Jianping Chang,1 Junshuai Xue,1 Zhen Huang,1 Hong Zhao,1 Lingxiang Yu,2 Jianqiang Cai1 1Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Hepatobiliary Surgery, the Fifth Medical Center of the PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianqiang Cai, Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, People’s Republic of China, Tel +86-10-87787100, Fax +86-10-67709698, Email caijianqiang@cicams.ac.cnPurpose: We developed a nomogram based on the liver function, nutrition, inflammation, and immunity (LFNII) score to predict recurrence-free survival (RFS) post-resection in patients with hepatocellular carcinoma (HCC) exhibiting alpha-fetoprotein (AFP) negativity (AFP ≤ 20 ng/mL).Patients and Methods: Clinical data of 661 patients diagnosed with alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) who underwent surgical resection at two medical centers between 2012 and 2021 were collected. A total of 462 and 199 patients served as the training and validation sets, respectively. Pre-operative blood markers were collected and analyzed for LFNII. The LFNII score was formulated using the least absolute shrinkage and selection operator Cox regression model. A nomogram model was developed using the training set to incorporate other relevant clinicopathological indicators and predict postoperative recurrence. Model discrimination was assessed using the receiver operating characteristic curve, calibration was evaluated using a calibration curve, and clinical applicability was assessed using clinical decision curve analysis. A comparison with liver cancer staging was performed using the nomogram model. Finally, a cohort study was conducted to validate our findings.Results: We derived the LFNII scores from nine indicators. Elevated LFNII scores correlated with unfavorable clinicopathological features. The LFNII score area under the curve revealed superior predictive efficacy at 1-, 2-, and 5-year RFS intervals, with values of 0.675, 0.658, and 0.633, respectively. Multivariate Cox analysis revealed that a high LFNII score independently increased RFS risk in patients with AFP-NHCC. The C-index of the LFNII-nomogram model was 0.686 (95% confidence interval [CI], 0.651– 0.721). The nomogram model’s clinical application value surpassed that of standard HCC staging systems.Conclusion: The LFNII score-derived nomogram effectively predicted the RFS of patients with AFP-NHCC after curative resection.Keywords: hepatocellular carcinoma, alpha-fetoprotein-negative, immunity, inflammation, nutrition, recurrence-free survival

Yan Hu,1,&ast; Jiawei Shen,2,&ast; Youzhong An,2 Yanwen Jiang,1 Huiying Zhao2 1Department of Respiratory and Critical Care Medicine, Peking University International Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huiying Zhao, Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China, Email zhaohuiying@pkuph.edu.cnObjective: We aim to identify the clinical phenotypes of immunocompromised patients with pneumonia-related ARDS, to investigate the lung microbiota signatures and the outcomes of different phenotypes, and finally, to develop a machine learning classifier for a specified phenotype.Methods: This prospective study included immunocompromised patients with pneumonia-related ARDS. We identified phenotypes using hierarchical clustering to analyze clinical variables and serum cytokine levels. We then compared outcomes and lung microbiota signatures between phenotypes. Based on lung microbiota markers, we developed a random forest classifier for a specified phenotype with worse outcomes.Results: This study included 92 patients, who were divided into three phenotypes, namely “type α” (N = 33), “type β” (N = 12), and “type γ” (N = 47). Compared to type α or type β, patients with type γ had no obvious inflammatory presentation and had significantly lower IL-6 levels and more severe oxygenation failure. Type γ was also related to higher 30-day mortality and lower ventilator free days. The microbiota signatures of type γ were characterized by lower alpha diversity and distinct compositions than those of other patients. We developed a lung microbiota-derived random forest model to differentiate patients with type γ from other phenotypes.Conclusion: Immunocompromised patients with pneumonia-related ARDS can be clustered into three clinical phenotypes, namely type α, type β, and type γ. Phenotypes were distinguished from each other with different outcomes and lung microbiota signatures. Type γ, which was characterized by insufficient inflammation response and worse outcomes, can be detected with a random forest model based on lung microbiota markers.Keywords: immunocompromised host, respiratory failure, microbiota

Meiju Deng,1,2,&ast; Yongqin Zeng,2,3,&ast; Ying Liu,2 Xiaolei Wang,1,2 Na Chen,1,2 Mengyuan Zhang,1,4– 6 Meiqing Jiang,1,4– 6 Hongxin Zhao,2 Juan Du1,4– 6 1Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Clinical Center for HIV/AIDS, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Department of Nephrology, The Affiliated Hospital Guizhou Medical University, Guiyang, Guizhou, 550004, People’s Republic of China; 4Beijing Institute of Infectious Diseases, Beijing, 100015, People’s Republic of China; 5National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 6National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing, 100015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Du; Hongxin Zhao, Email duj656@ccmu.edu.cn; Drzhao66@ccmu.edu.cnBackground: The aging of the immune system is associated with various diseases. It is worth exploring the changes of the immune system in aging. Previous studies have shown that aged T cells have enhanced expression of co-inhibitory molecules. However, it remains unclear whether aged NK cells exhibit similar characteristics to aged T cells. The objective of our research was to clarify this aspect.Patients and Methods: This study included 98 adults aged 24– 90 years (50 males and 48 females). We detected the subset of peripheral blood NK cells and the expression of various receptors on NK cells among donors of different age groups by flow cytometry. Immune subsets were initially defined by forward and side-scatter characteristics and then staining with the appropriate marker.Results: The absolute number and subset distribution of NK cells were not associated with age. However, CD57 expression and CD69 expression were correlated with age. Furthermore, we found that PD-1 was up-regulated on NK cells in older people, associated with aging, while no such change was observed in other co-inhibitory molecules, including 2B4, CTLA-4, TIM-3, BTLA, CD70, CD39, CD160, and TIGIT. PD-1+ NK cells expressed high levels of CD57 and CD69, indicating PD-1+ NK cells displayed a phenotype of over-activation and aging.Discussion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people.Conclusion: This study indicated that PD-1+ NK cells were one of the characteristics of NK cells in older people. Those findings provided new ideas to explore the underlying drivers of NK aging.Keywords: PD-1, NK cell, aging, co-inhibitory molecules

Yin-Gen Luo,&ast; Xiao-Wu Zhang,&ast; He Zhao, Jin-Gui Li, Jiay-Wei Tsauo, Tao Gong, Ai-Xin Ou, Tian-Hao Cong, Wen-Di Kang, Xiao Li Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao Li; He Zhao, Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China, Tel/Fax +86 010 8778 8502, Email simonlixiao@gmail.com; hezhaoo@gmail.comObjective: This study aimed to establish a rat model that simulates benign esophageal strictures induced by endoscopic submucosal dissection (ESD).Materials and Methods: Sixteen male Sprague-Dawley rats were randomly divided into mucosal resection (n = 8) and sham-operated groups (n = 8). The rats in the mucosal resection group underwent a 5-mm three-fourths mucosal resection by way of a 3-mm incision in the distal esophagus under direct visualization via laparotomy. Rats in the sham-operated group underwent a 3-mm incision of the muscularis propria layer in the distal esophagus via laparotomy without mucosal resection. Dysphagia score, weight gain, mucosal constriction rate, and histology were evaluated 2 weeks after surgery.Results: Technical success was achieved in all the animals. One rat in the mucosal resection group died of infection, and no other complications were observed. Weight gain (P < 0.001) and luminal diameter derived from the esophagograms (P < 0.001) were significantly lower in the mucosal resection group than those in the sham-operated group. Dysphagia score (P < 0.001) and mucosal constriction rate (P < 0.001) were significantly higher in the mucosal resection group than those in the sham-operated group. The inflammation grade (P = 0.002), damage to the muscularis propria (P < 0.001), number of nascent microvessels (P = 0.006), and degree of α-SMA positive deposition (P = 0.006) were significantly higher in the mucosal resection group.Conclusion: A rat model of benign esophageal stricture induced by ESD was successfully and safely established by mucosal resection.Keywords: esophageal stenosis, endoscopic mucosal resection, models, animal

Hua Zhao,1 Wen-Jing Geng,2 Rui-Hong Wu,3 Zhen-Zhen Li3 1College of Nursing, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, People’s Republic of China; 2Nursing Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, Shanxi, People’s Republic of China; 3Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of ChinaCorrespondence: Hua Zhao, College of Nursing, Shanxi University of Chinese Medicine, Jinzhong, Shanxi, 030619, People’s Republic of China, Tel +86 13903465019, Email zhshun7788@126.comPurpose: A better understanding of the factors that influence engagement is needed to provide a reference for conducting genetic testing in female relatives of patients with hemophilia (PWH). We therefore determined the perceptions and understanding of genetic testing among female relatives of PWH in China.Methods: We carried out a qualitative study using in-depth, semi-structured interviews with 11 female relatives of PWH in Shanxi Province, China. The resulting data were analyzed using thematic analyses.Results: This study extracted four topics: uncertainty about carrier genetic status; limited understanding of genetic testing; coexistence of positive and negative coping; and multi-aspect demands.Conclusion: Healthcare professionals should provide personalized and multidimensional health education and comprehensive decision-making support to female relatives of PWH, to enhance their motivation and willingness to undergo genetic testing. It is also important to actively improve relevant policies, strengthen the genetic testing service system, and promote the popularization of genetic testing in female relatives of PWH.Keywords: hemophilia, female, genetic testing, attitudes, qualitative study

Haopeng Wang,1,&ast; Hua Zhao,1,&ast; Zheng Chen,1,&ast; Xiaomin Cai,1 Xuhui Wang,1 Ping Zhou,1 Yinda Tang,1 Tingting Ying,1 Xin Zhang,1 Yiman Shen,1 Baimiao Wang,1 Wanchun Zhu,1 Jin Zhu,1 Xinjun Wang,2 Shiting Li1 1Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China; 2Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiting Li, Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai JiaoTong University School of Medicine, Shanghai, 200092, People’s Republic of China, Email lishiting@xinhuamed.com.cn Xinjun Wang, Department of Neurosurgery, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Email wangxj@zzu.edu.cnBackground: Facial nerves have the potential for regeneration following injury, but this process is often challenging and slow. Schwann cells (SCs) are pivotal in this process. Bone mesenchymal stem cells (BMSC)-derived exosomes promote tissue repair through paracrine action, with hypoxic preconditioning enhancing their effects. The main purpose of this study was to determine whether hypoxia-preconditioned BMSC-derived exosomes (Hypo-Exos) exhibit a greater therapeutic effect on facial nerve repair/regeneration and reveal the mechanism.Methods: CCK-8, EdU, Transwell, and ELISA assays were used to evaluate the functions of Hypo-Exos in SCs. Histological analysis and Vibrissae Movements (VMs) recovery were used to evaluate the therapeutic effects of Hypo-Exos in rat model. circRNA array was used to identify the significantly differentially expressed exosomal circRNAs between normoxia-preconditioned BMSC-derived exosomes (Nor-Exos) and Hypo-Exos. miRDB, TargetScan, double luciferase assay, qRT-PCR and WB were used to predict and identify potential exosomal cirRNA_Nkd2-complementary miRNAs and its target gene. The function of exosomal circRNA_Nkd2 in facial nerve repair/regeneration was evaluated by cell and animal experiments.Results: This study confirmed that Hypo-Exos more effectively promote SCs proliferation, migration, and paracrine function, accelerating facial nerve repair following facial nerve injury (FNI) compared with Nor-Exos. Furthermore, circRNA analysis identified significant enrichment of circRNA_Nkd2 in Hypo-Exos compared with Nor-Exos. Exosomal circRNA_Nkd2 positively regulates mediator complex subunit 19 (MED19) expression by sponging rno-miR-214-3p.Conclusion: Our results demonstrated a mechanism by which Hypo-Exos enhanced SCs proliferation, migration, and paracrine function and facial nerve repair and regeneration following FNI through the circRNA_Nkd2/miR-214-3p/Med19 axis. Hypoxic preconditioning is an effective and promising method for optimizing the therapeutic action of BMSC-derived exosomes in FNI. Keywords: hypoxic, BMSCs, exosomes, Schwann cells, facial nerve injury

Hui Feng,1 Yang Yue,1 Yan Zhang,1 Jingqi Liang,1 Liang Liu,1 Qiong Wang,1 Qian Feng,2 Hongmou Zhao1 1Department of Foot and Ankle Surgery, Honghui Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi, 710054, People’s Republic of China; 2Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of ChinaCorrespondence: Hongmou Zhao, Department of Foot and Ankle Surgery, Honghui Hospital of Xi’an Jiaotong University, Xi’an City, Shaanxi, 710054, People’s Republic of China, Email zhaohongmou@xiyi.edu.cn Qian Feng, Key Laboratory of Biorheological Science and Technology Ministry of Education College of Bioengineering, Chongqing University, Chongqing, 400044, People’s Republic of China, Email qianfeng@cqu.edu.cnAbstract: Tissue engineering holds great potential for tissue repair and rejuvenation. Plant-derived exosome-like nanoparticles (ELNs) have recently emerged as a promising avenue in tissue engineering. However, there is an urgent need to understand how plant ELNs can be therapeutically applied in clinical disease management, especially for tissue regeneration. In this review, we comprehensively examine the properties, characteristics, and isolation techniques of plant ELNs. We also discuss their impact on the immune system, compatibility with the human body, and their role in tissue regeneration. To ensure the suitability of plant ELNs for tissue engineering, we explore various engineering and modification strategies. Additionally, we provide insights into the progress of commercialization and industrial perspectives on plant ELNs. This review aims to highlight the potential of plant ELNs in regenerative medicine by exploring the current research landscape and key findings.Keywords: plant, exosome-like nanoparticles, nanomedicine, tissue engineering, cartilage, wound, bone

Zhao H, He Y, Li H, et al. Cancer Manag Res. 2019;11:4569–4576. We, the Editor and Publisher of the journal Cancer Management and Research have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Han Yu,1– 4 Na Ning,1– 3 Fujin He,5 Jiao Xu,6 Han Zhao,5 Shaofeng Duan,5,7 Yunqi Zhao1– 4 1College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang Province, 325060, People’s Republic of China; 2Wenzhou Municipal Key Laboratory for Applied Biomedical and Biopharmaceutical Informatics, Wenzhou-Kean University, Wenzhou, Zhejiang, 325060, People’s Republic of China; 3Zhejiang Bioinformatics International Science and Technology Cooperation Center, Wenzhou-Kean University, Wenzhou, Zhejiang, 325060, People’s Republic of China; 4Dorothy and George Hennings College of Science, Mathematics and Technology, Kean University, Union, NJ, 07083, USA; 5School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People’s Republic of China; 6Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang, 325001, People’s Republic of China; 7The First Affiliated Hospital of Henan University, Kaifeng, Henan, 475004, People’s Republic of ChinaCorrespondence: Yunqi Zhao, College of Science, Mathematics and Technology, Wenzhou-Kean University, Wenzhou, Zhejiang, 325060, People’s Republic of China, Tel +86 577 5587 0000, Fax +86 577 5587 0101, Email yuzhao@kean.edu Shaofeng Duan, School of Pharmacy, Henan University, Kaifeng, Henan, 475004, People’s Republic of China, Fax +86 371 2286 5974, Email sduan@henu.edu.cnBackground: Targeted delivery systems have been developed to improve cancer treatment by reducing side effects and enhancing drug efficacy. Geraniol, a natural product, has demonstrated promising anti-cancer effects in various cancer types, including prostate cancer, which is the most commonly diagnosed cancer in men. Hyaluronic acid (HA), a natural carrier targeting CD44-positive prostate cancer cells, can be utilized in a targeted delivery system.Purpose: This study investigated the efficacy of a conjugate of HA and geraniol linked via a disulfide bond linker (HA-SS-Geraniol) in prostate cancer.Materials and Methods: The cytotoxicity of HA-SS-Geraniol was evaluated on human PC-3 prostate cancer cells. Flow cytometry was used to assess its effects on mitochondrial membrane potential, apoptosis, and cell cycle arrest. Additionally, proteomic analysis was conducted to explore the underlying mechanism of action induced by HA-SS-Geraniol treatment. A subcutaneous xenograft tumor model was established in nude mice to evaluate the toxicity and efficacy of HA-SS-Geraniol in vivo.Results: The results demonstrated that HA-SS-Geraniol exhibited potent cytotoxicity against PC-3 prostate cancer cells by inducing mitochondrial membrane potential loss and apoptosis in vitro. The proteomic analysis further supported the hypothesis that HA-SS-Geraniol induces cell death through mitochondria-mediated apoptosis, as evidenced by differential protein expression. The in vivo mouse model confirmed the safety of HA-SS-Geraniol and its ability to inhibit tumor growth.Conclusion: HA-SS-Geraniol holds promise as a biologically safe and potentially effective therapeutic agent for prostate cancer treatment. Its targeted delivery system utilizing HA as a carrier shows potential for improving the efficacy of geraniol in cancer therapy.Keywords: geraniol, hyaluronic acid, prostate cancer, nanoparticle, proteomics

Hu Zhao,1,&ast; Jun Zhan,1,&ast; Qiong Wang,2 Shuqi Yang,1 Xue Xiao1 1Department of Gynecology and Obstetrics, Sichuan University West China Second University Hospital, Chengdu, Sichuan, People’s Republic of China; 2Department of Gynecology and Obstetrics, Chengdu Women and Children’s Central Hospital, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Xiao, Department of Gynecology and Obstetrics, Sichuan University West China Second University Hospital, No. 20, Section 3, Renmin Road South, Chengdu, Sichuan, 610041, People’s Republic of China, Email xue_xiao_west@163.comPurpose: LncRNA HCP5 has been reported to participate in high glucose-induced pathological processes, whereas its role in gestational diabetes mellitus (GDM) is unclear. This study aimed to explore the role of HCP5 in GDM.Methods: This study enrolled a total of 220 pregnant women (gestational age = 1 month). A follow-up study was performed until delivery. The occurrence of GDM was checked every month during follow-up. Plasma samples were collected from all participants and expression of HCP5 was determined with RT-qPCR. The 220 patients were divided into high and low GDM groups, and GDM-free curves were plotted for both groups and compared. The ROC curve was plotted to explore the predictive value of plasma HCP5 on the day of admission for GDM. INS-1 cells were transfected with HCP5 expression vector or siRNA, and cell viability under high glucose was determined by the MTT assay. An ELISA was applied to determine insulin levels in the cell culture medium.Results: During follow-up, the level of HCP5 was increased during pregnancy and the high HCP5 level group showed a significantly higher incidence of GDM. Plasma levels of HCP5 on the day of admission effectively separated GDM patients from healthy controls. HCP5 negatively regulated cell viability and insulin secretion under high glucose treatment.Conclusion: HCP5 may act as a predictor for GDM, and it negatively regulated INS-1 cell viability and insulin secretion under high glucose conditions.Keywords: HCP5, gestational diabetes mellitus, INS-1 cells, insulin

Ying Zhu,1 Liyuan Jiang,2 Tiantian Ye,3 Yan Liu,4 Li Sun,2 Lijuan Xiao,5 Jiayu Chen,6 Ting Wang,7 Yinghua Ren,8 Hongjun Xu,8 Huihui Zhao,8 Xiaozhen Mao,8 Tiantian Shen9 1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, 310005, People’s Republic of China; 3The 1st Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 5Department of Rehabilitation, Chun’an County Hospital of Traditional Chinese Medicine, Chun’an, 311799, People’s Republic of China; 6Department of Rehabilitation, Huzhou Central Hospital, Huzhou, 313099, People’s Republic of China; 7The 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 8Department of Acupuncture and Tuina, Community Health Service Center of Zhuantang Street, Hangzhou, 310024, People’s Republic of China; 9Department of Acupuncture and Rehabilitation, Shengzhou Municipal Hospital of Traditional Chinese Medicine, Hangzhou, 312499, People’s Republic of ChinaCorrespondence: Liyuan Jiang, Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Stadium Road, Xihu District, Hangzhou, 310005, People’s Republic of China, Tel +86-13018976755, Email Jiangliyuan520j@163.comPurpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women.Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann–Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis).Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group.Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.Keywords: risk factors, patient-reported outcome measures, diastasis recti abdominis, postpartum period

Gongxin Yang,1,&ast; Jikai Xia,2,&ast; Xiaoqing Dai,1,&ast; Hongbo Zhao,1 Weiqing Gao,1 Weilong Ding,1 Xiaofeng Tao,1 Ling Zhu1 1Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People’s Republic of China; 2Department of Radiology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, 264100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng Tao; Ling Zhu, Department of Radiology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200001, People’s Republic of China, Email cjr.taoxiaofeng@vip.163.com; zhuling011@126.comIntroduction: Magnetic resonance imaging (MRI) is an important tool for the accurate diagnosis of malignant tumors in clinical settings. However, the lack of tumor-specific MRI contrast agents limits diagnostic accuracy.Methods: Herein, we developed αv integrin receptor-targeting multi-crystalline manganese oxide (MCMO) as a novel MRI contrast agent for accurate diagnosis of tumors by coupling iRGD cyclopeptide PEGylation polymer onto the surface of MCMO (iRGD-pMCMO).Results: The MCMO consisted of numerous small crystals and exhibited an oval structure of 200 nm in size. The iRGD-pMCMO actively recognizes tumor cells and effectively accumulates at the tumor site, consequently releasing abundant Mn2+ ions in a weakly acidic and high-GSH-expressing tumor microenvironment. Subsequently, Mn2+ ions interact with cellular GSH to form Mn-GSH chelates, enabling efficient T1-weighted MR contrast imaging. In vivo experiments indicated that iRGD-pMCMO significantly improved T1-weighted images, achieving an accurate diagnosis of subcutaneous and orthotopic tumors. The results verified that the T1 contrast effect of iRGD-pMCMO was closely associated with the expression of GSH in tumor cells.Conclusion: Altogether, the novel tumor-targeting, highly sensitive MRI contrast agent developed in this study can improve the accuracy of MRI for tumor diagnosis. Keywords: multi-crystalline manganese oxide, MRI contrast agent, tumor targeting, tumor selectivity, accurate diagnosis

Dapeng Hu,1,2 Junwen Huang,1 Wenqu Zhao,1 Maosheng Xu,1 Yanyan Ma,1 Zhaoqian Gong,1 Qian Zhang,1 Haijin Zhao1 1Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, NanFang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Emergency Medicine, Dalian Municipal Friendship Hospital, Dalian, Liaoning, 116001, People’s Republic of ChinaCorrespondence: Haijin Zhao, Chronic Airway Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China, Tel/Fax +86-2062787112, Email zhjin@smu.edu.cnPurpose: Identifying prognosis for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is challenging. Eosinophils and platelet are involved in the development of COPD, which may predict adverse events. The objective of this study was to determine the effect of the eosinophil to platelet ratio (EPR) in predicting adverse events in patients with AECOPD who visited the emergency department.Patients and Methods: The records of patients with AECOPD treated at Dalian Municipal Friendship Hospital from January 2018 to December 2020 were retrospectively reviewed. The relationship between the clinical characteristics and EPR, as cut-off value of 0.755, was evaluated.Results: A total of 508 patients with an AECOPD (316 male, 192 female) were included. An optimal AUC cutoff of 0.755 for the EPR segregated the patients into 2 groups with significantly different mortality (25.3% vs 5.5%, P < 0.001). The same mortality risk with lower EPR was observed among the patients with emergency room attendance (35.6% vs 11.1%, P < 0.001). A model including EPR < 0.755, exacerbation history, PaO2 < 60mmHg, PaCO2 > 50 mm Hg, hypoalbuminemia and age ≥ 80 was developed to predict death risk and showed good performance.Conclusion: During severe COPD exacerbation, an EPR < 0.755 preceding therapy can predict worse outcomes in patients with an AECOPD.Keywords: eosinophil, COPD, eosinophil to platelet ratio, emergency department

Longyin Zhu,1,&ast; Huhai Zhang,1,&ast; Jia Fang,1 Shuang Xiao,2 Fu Xiong,3 Caixia Deng,3 Qin Yang,1 Chunxiao Fu,1 Qianguang Pan,1 Hongwen Zhao1 1Department of Nephrology, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China; 2Department of Infectious Disease, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, the First Hospital Affiliated to Army Military Medical University (Southwest Hospital), Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhao; Qianguang Pan, Email zhaohw212@126.com; panqianguang@163.comIntroduction: We report a fatal case of massive airway bleeding caused by pulmonary strongyloidiasis in a patient with a transplanted kidney.Case Presentation: A 47-year-old male, regularly taking immunosuppressants post-kidney transplant, visited our hospital with symptoms of abdominal bloating, nausea, and emesis persisting for three days. After hospitalization, he developed a cough, hemoptysis, and respiratory failure. Sputum analysis confirmed an infestation with Strongyloides stercoralis. Despite receiving albendazole therapy and bronchoscopic management for bronchial hemorrhage, the patient ultimately died due to acute respiratory and circulatory collapse triggered by severe airway bleeding.Conclusion: Patients undergoing immunosuppressive therapy following kidney transplantation are at increased risk for disseminated strongyloidiasis. Consequently, infectious disease screening prior to transplantation, along with essential preventive pharmacotherapy, is of paramount importance.Keywords: strongyloides stercoralis, kidney transplantation, airway bleeding, disseminated infection

Huajian Zhao,1 Ruifen Zhang,2 Yi Chen1 1School of Communication, Soochow University, Suzhou, Jiangsu Province, 215127, People’s Republic of China; 2School of Public Health, Soochow University, Suzhou, Jiangsu Province, 215127, People’s Republic of ChinaCorrespondence: Yi Chen, School of Communication, Soochow University, Suzhou, Jiangsu Province, 215127, People’s Republic of China, Email chenyisuda@suda.edu.cnPurpose: The use of traditional Chinese medicine (TCM) for disease prevention and healthcare has been strongly supported by the Chinese government in recent years, but public perception of TCM remains controversial or resistant, especially in preventing and treating COVID-19. It is therefore crucial to understand the factors that influence public attitudes.Methods: By applying a measure of attitudes towards TCM in epidemic prevention, this study conducted a nationwide survey (n=1192) on the relationships between attitudes towards TCM for the control of COVID-19 and trust, perceptions of risk, scientific literacy, policy endorsement, and cultural values.Results: The results of the study showed surprisingly that scientific literacy and risk perception did not dominate the Chinese public’s attitudes towards TCM for the control of COVID-19. Meanwhile, egalitarianism, policy endorsement, trust in scientist and healthcare personnel played a positive role. Moreover, egalitarianism positively regulates the relationship between trust in scientist and attitudes towards TCM epidemic prevention and control, while collectivism negatively regulates the relationship of the preceding variables.Conclusion: All these findings suggest that attitudes towards the use of TCM are not based on rational cognition and logical reasoning, but are mainly influenced by emotional and cultural factors. This study will help researchers and practitioners understand the importance of cultural values, trust, policy endorsement, and attitudes towards TCM epidemic prevention and control to TCM’s use in healthcare.Keywords: TCM, cultural values, policy endorsement, COVID-19

Runzhen Chen,1,2,&ast; Jiannan Li,1,3,&ast; Zhaoxue Sheng,4 Jinying Zhou,1,3 Ying Wang,1 Xiaoxiao Zhao,1,3 Nan Li,1 Weida Liu,5 Chen Liu,1,3 Peng Zhou,1,3 Yi Chen,1,3 Shaodi Yan,2 Li Song,1– 3 Hongbing Yan,2,3 Hanjun Zhao1,3 1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, People’s Republic of China; 3Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Cardiology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Medical Research Center, Peking Union Medical College Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongbing Yan, Fuwai Hospital, Chinese Academy of Medical Sciences, 12 Langshan Road, Nanshan District, Shenzhen, 510000, People’s Republic of China, Email hbyanfuwai2018@163.com; hbyanfuwai@aliyun.com Hanjun Zhao, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email 15210020808@163.comBackground: As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features.Results: The median RvD1 level was 129.7 (56.6– 297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥ 111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20– 3.66, P = 0.010), healed plaques (≥ 246.4 pg/mL, OR: 2.17, 95% CI: 1.11– 4.24, P = 0.023), and calcification (≥ 293.38 pg/mL, OR: 2.10, 95% CI: 1.21– 3.66, P = 0.008) at culprit lesions.Conclusion: Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.Keywords: resolvin D1, specialized pro-resolving lipid mediator, myocardial infarction, optical coherence tomography, atherosclerosis, inflammation

Yunbo Yan,1 Linqian Yu,1 Binyang Chen,1 Chang’an Cao,1 Hairong Zhao,1,2 Qiang Wang,1 De Xie,1 Yuemei Xi,1 Chenggui Zhang,2 Jidong Cheng1,3 1Department of Internal Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, People’s Republic of China; 3Xiamen Key Laboratory of Translational Medicine for Nucleic Acid Metabolism and Regulation, Xiamen, People’s Republic of ChinaCorrespondence: Jidong Cheng; Chenggui Zhang, Email jidongcheng36@hotmail.com; chenggui_zcg@hotmail.comBackground: Gouty arthritis is characterized by the accumulation of monosodium urate crystals (MSU) in the synovial joints and surrounding tissues. Mastoparan M (Mast-M) is a biologically active peptide composed of 14 amino acids, extracted from wasp venom. This study aims to assess the impact of Mast-M on in vitro and in vivo gouty arthritis induced by lipolyaccharide (LPS) plus MSU crystal stimulation.Methods: PMA-differentiated THP-1 macrophages were pre-treated with Mast-M or left untreated, followed by stimulation with LPS and MSU crystals. Cell lysates were collected to assess the expression of the NLRP3 inflammasome, inflammatory signaling pathways, and oxidative stress. Furthermore, to evaluate the in vivo anti-inflammatory effect of Mast-M, an experimental acute gouty arthritis mouse model was established through intra-articular injection of MSU crystals.Results: Mast-M treatment demonstrated significant inhibition of the phosphorylation of MAPKs/NF-κB signaling pathways and reduction in oxidative stress expression in LPS and MSU-induced THP-1 macrophages. This resulted in the suppression of downstream NLRP3 inflammasome activation and IL-1β release. In vivo, Mast-M effectively attenuated the inflammation induced by MSU in mice with gouty arthritis. Specifically, Mast-M reduced swelling in the paws, inhibited the infiltration of neutrophils and macrophages into periarticular tissue, and decreased the activation of the NLRP3 inflammasome and IL-1β production.Conclusion: Mast-M significantly improves gouty arthritis, and its potential mechanism may be achieved by inhibiting the MAPK/NF-κB pathway and alleviating oxidative stress, thus suppressing the activation of NLRP3 inflammasomes.Keywords: Mastoparan M, NLRP3, MAPKs, NF-κB, oxidative stress, gout

Yue Zhang,1,2,&ast; Meiyan Sun,2,&ast; Hongxiang Zhao,1,2,&ast; Zhengyan Wang,2 Yanan Shi,2 Jianxin Dong,2 Kaifang Wang,3 Xi Wang,4 Xingyue Li,5 Haiyan Qi,6 Xiaoyong Zhao1,2,7 1Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 3Department of Anesthesia, Tangdu Hospital, Fourth Military Medical University, Xian, Shanxi Province, People’s Republic of China; 4Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, People’s Republic of China; 6Department of Anesthesiology, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China; 7Department of Anesthesiology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyong Zhao; Haiyan Qi, Email xyzhao83@163.com; qihy123@163.comAbstract: Dichloroacetate (DCA) is an investigational drug used to treat lactic acidosis and malignant tumours. It works by inhibiting pyruvate dehydrogenase kinase and increasing the rate of glucose oxidation. Some studies have documented the neuroprotective benefits of DCA. By reviewing these studies, this paper shows that DCA has multiple pharmacological activities, including regulating metabolism, ameliorating oxidative stress, attenuating neuroinflammation, inhibiting apoptosis, decreasing autophagy, protecting the blood‒brain barrier, improving the function of endothelial progenitor cells, improving mitochondrial dynamics, and decreasing amyloid β-protein. In addition, DCA inhibits the enzyme that metabolizes it, which leads to peripheral neurotoxicity due to drug accumulation that may be solved by individualized drug delivery and nanovesicle delivery. In summary, in this review, we analyse the mechanisms of neuroprotection by DCA in different diseases and discuss the causes of and solutions to its adverse effects.Keywords: dichloroacetate, neuroprotection, mitochondria, energy metabolism, oxidative stress

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