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Jingjing Li,1 Yu Zhang,2 Rui Wu,1 Guodong Ma,1 Li Sheng,1 Yun Feng,1 Yang Han,1 Lina Zhang,1 Janfeng Guo,1 Rongbo Li1 1Department of Infectious Diseases, Hohhot First Hospital, Hohhot, Inner Mongolia Autonomous Region, 010000, People’s Republic of China; 2Department of Dermatology and Venereology, Hohhot, Inner Mongolia Autonomous Region People’s Hospital, 010000, People’s Republic of ChinaCorrespondence: Jingjing Li, Department of Infectious Diseases, Hohhot First Hospital, No. 148, South Second Ring Road, Zhaojun Road, Yuquan District, Hohhot, Inner Mongolia Autonomous Region, 010000, Tel +86-18047422188, Email 1151664990@qq.comPurpose: To explore the value of different inflammatory markers in predicting the severity of coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 116 patients with COVID-19 in patients with T2DM were collected from December 2022 to March 2023 and were divided into a mild case group (77 cases) and a severe case group (39 cases). The ratio of neutrophil to lymphocyte (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil to lymphocyte × platelet ratio (NLPR), lymphocyte ratio to monocyte (LMR), systemic inflammatory response index (SIRI), systemic inflammatory index (SII), systemic inflammatory composite index (AISI), procalcitonin (PCT), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were compared between the two groups. The screening effect of each variable on the progression of the disease was analyzed using receiver operating characteristic (ROC) curves.Results: NLR, PLR, NLPR, MLR, SIRI, SII, AISI, LDH, CRP and PCT in severe case group were higher than those in mild case group (P< 0.05), and LMR was lower than those in mild case group (P< 0.05). ROC curve analysis further demonstrated the diagnostic performance of these biomarkers, with PCT having the largest area under the ROC curve (AUCROC) of 0.83.Conclusion: NLR, PLR, NLPR, SIRI, SII, LDH, CRP and PCT demonstrate greater reliability in diagnostic value and clinical utility for predicting the severity of COVID-19 in patients with T2DM.Keywords: COVID-19, T2DM, inflammatory index, LDH, CRP, PCT

In this paper, some properties of a BPFR were studied. Also, level sets of BPFRs were studied with their properties. Some results were given and, in some cases, examples and counter-examples were constructed. In particular, we have shown that if a BPFR Q is a subset of another BPFR ρ, (s, t)-level (or strong level) subsets of Q are classical subsets of the (s, t)-level (or strong level) subsets of ρ and that the strong level subsets of a BPFR is a subset of the ordinary level subset of the same among others. By these, we have improved on some of the results in the previous work and have laid the right foundation for further works on these concepts.

Yijuan Feng,1,&ast; Yan Wang,1,&ast; Li Li,1,&ast; Yan Yang,1 Xiaoqiu Tan,1– 3 Tangting Chen1,2 1Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Cardiology, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Department of Physiology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tangting Chen; Xiaoqiu Tan, Key Laboratory of Medical Electrophysiology of the Ministry of Education, Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email ctt@swmu.edu.cn; tanxiaoqiu@swmu.edu.cnAbstract: Recanalization therapy can significantly improve the prognosis of patients with acute myocardial infarction (AMI). However, infarction or reperfusion-induced cardiomyocyte death, immune cell infiltration, fibroblast proliferation, and scarring formation lead to cardiac remodeling and gradually progress to heart failure or arrhythmia, resulting in a high mortality rate. Due to the inability of cardiomyocytes to regenerate, the healing of infarcted myocardium mainly relies on the formation of scars. Cardiac fibroblasts, as the main effector cells involved in repair and scar formation, play a crucial role in maintaining the structural integrity of the heart after MI. Recent studies have revealed that exosome-mediated intercellular communication plays a huge role in myocardial repair and signaling transduction after myocardial infarction (MI). Exosomes can regulate the biological behavior of fibroblasts by activating or inhibiting the intracellular signaling pathways through their contents, which are derived from cardiomyocytes, immune cells, endothelial cells, mesenchymal cells, and others. Understanding the interactions between fibroblasts and other cell types during cardiac remodeling will be the key to breakthrough therapies. This review examines the role of exosomes from different sources in the repair process after MI injury, especially the impacts on fibroblasts during myocardial remodeling, and explores the use of exosomes in the treatment of myocardial remodeling after MI.Keywords: exosomes, myocardial infarction, myocardial fibrosis, cardiac fibroblasts

Yali Liang,1,&ast; Yunxin Zhang,1,&ast; Yong Feng,2 Yuying Huang,2 Cuiling Zhang1 1Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cuiling Zhang, Nursing Department, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13753482546, Email sxbqezcl@163.comPurpose: To assess abusive supervision and organizational silence among nurses and investigate the mediating influence of psychological capital and fear.Background: Since the end of 2019, China’s National Development and Reform Commission (NDRC) department has decided to start the construction of regional medical centers in Shanxi, reducing cross-provincial and cross-regional medical care. In order to improve the overall standard of care in a hospital in a short period of time, health care leadership decision makers may adopt various effective leadership management practices to achieve the set goals and have high work pressure at the same time. In this case, abusive management may occur.Methods: A cross-sectional survey design was employed. In January -March 2024, a convenience sampling method was used to collect data from 470 nurses in a total of 5 hospitals in Shanxi province they were required to complete the questionnaires online anonymously. The chain mediation model was tested using the PROCESS macro program in the SPSS software and multiple linear regression model was used to verify the mediating effect.Results: Psychological capital and fear mediate the relationship between abusive supervision and nurses’ organizational silence, playing indirect mediating roles. Abusive supervision was positively associated with nurses’ organizational silence. Additionally, psychological capital plays a negative mediating role, accounting for 48.48% of the indirect effect, and fear plays a positive mediating role, accounting for 45.83% of the indirect effect. They form a chain intermediary, accounting for 5.69% of the indirect effect.Conclusion: Psychological capital and fear mediate the impact of abusive supervision on nurses’ organizational silence. Positive leadership training should be conducted to help reducing the level of head nurses’ abusive supervision behaviors, while also fostering actions that elevate nurses’ psychological capital levels.Keywords: Abusive supervision, Nurses’ organizational silence, psychological capital, fear, mediating effect

Yilin Feng,1 Nandini Venkateswaran,1 Amanda Steele,2 Eric D Rosenberg,3 Preeya K Gupta2,4 1Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 2Triangle Eye Consultants, Raleigh, NC, USA; 3Department of Ophthalmology, New York Medical College, Valhalla, NY, USA; 4Department of Ophthalmology, Tulane University, New Orleans, LA, USACorrespondence: Preeya K Gupta, Email preeyakgupta@gmail.comPurpose: To evaluate the impact of TearCare (TC) treatment on clinical, quality of life, and functional visual outcome metrics in patients with dry eye disease (DED) and meibomian gland disease (MGD).Methods: This is a prospective, single-center clinical trial. Adults with MGD and a DED diagnosis and tear break-up time (TBUT) < 10 seconds were included. All subjects had at least 20/40 vision and no surgery or new treatment for DED within 60 days prior to enrollment. All patients had one baseline visit prior to undergoing TC and one follow-up visit 1 month after TC. At each visit, the meibomian gland secretion score (MGSS), TBUT, and corneal fluorescein staining (KFL) were assessed. DED symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Visual Function Questionnaire 25 (VFQ-25), and the Fatigue Severity Scale. Reading speed was determined through the International Reading Speed Texts (IReST), Minnesota Low Vision Reading Test (MNREAD), and Wilkins Rate of Reading Test (WRRT).Results: Thirty-two subjects were included. The average age was 55.9 years. Sixteen (52%) participants had a clinically significant improvement in reading speed after treatment with TC, defined as > 10 words per minute increase in their IReST score. Improvement on the IReST and the MNREAD reached statistical significance (p = 0.012 and p = 0.028, respectively). OSDI scores significantly decreased and VFQ-25 scores significantly increased after TC treatment (p < 0.001). All of the clinical exam parameters showed statistically significant improvements after treatment (p < 0.001).Conclusion: TC is an effective treatment both clinically and with respect to visual function. Patients who had TC exhibited improvements in quality of life and improved reading speed after a single treatment. This treatment should be frequently considered and utilized to reduce the disease burden of DED related to MGD.Keywords: thermal pulsation, tearcare, meibomian gland dysfunction, dry eye disease, reading speed

Yan Liu,1 Yunlai Liu,2 Yunpeng Feng3 1School of Media and Communication, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 2School of Media, Anqing Normal University, Anqing, 246000, People’s Republic of China; 3School of Communication and Media, Guangzhou Huashang College, Guangzhou, 511300, People’s Republic of ChinaCorrespondence: Yunpeng Feng, School of Communication and Media, Guangzhou Huashang College, Guangzhou, 511300, People’s Republic of China, Tel +8618719800593, Email ifeng1987@sina.comBackground: Digital hoarding refers to the continuous acquisition of digital content and the difficulty in disposing of it. This behavior is increasingly common among today’s youth. This study aims to explore the impact of mindfulness on digital hoarding behavior, investigating self-control as a mediator and upward social comparison via social media as a moderator.Methods: A total of 956 young individuals participated in this cross-sectional study. The research instruments used included the Mindfulness Measure, the Self-Control Scale, the Social Comparison Scale, and the Digital Hoarding Behavior Questionnaire. Data analysis included descriptive statistics and correlation analysis. For more complex analyses, we examined the mediating role of self-control and the moderating effects of upward social comparison via social media in the relationship between mindfulness and digital hoarding behavior.Results: 1) Mindfulness significantly negatively predicted digital hoarding. 2) Self-control mediated the relationship between mindfulness and digital hoarding. 3) Upward social comparison via social media moderated the relationship between mindfulness and self-control, specifically the first segment of the mediation pathway.Discussion: This research is pioneering in exploring mindfulness as a protective factor against digital hoarding, offering fresh insights into this nascent field. The findings also suggest prevention and intervention strategies for digital information management disorder in young people.Keywords: social media, digital hoarding, mindfulness, self-control, upward social comparison via social media

Yunze Feng,1,&ast; Wencan Zhang,1,&ast; Kunpeng Li,1 Xiangyu Lin,1 Chen Liu,1 Chongyi Wang,1 Bingtao Hu,1 Kaibin Wang,1 Wanlong Xu,1 Haipeng Si1,2 1Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong, 250000, People’s Republic of China; 2Key Laboratory of Qingdao in Medicine and Engineering, Department of Orthopedics, Qilu Hospital (Qingdao), Shandong University, Qingdao, Shandong, 266035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haipeng Si, Key Laboratory of Qingdao in Medicine and Engineering, Department of Orthopedics, Qilu Hospital (Qingdao), Shandong Universityl, Qingdao, Shandong, 266035, People’s Republic of China, Email sihaipeng1978@email.sdu.edu.cn Wanlong Xu, Department of Orthopedics Qilu Hospital, Shandong University, Jinan, Shandong, 250000, People’s Republic of China, Email xuwanlong20082008@163.comPurpose: One-hole Split Endoscopy (OSE) is a newer surgical modality that can be applied to posterior cervical foraminotomy (PCF), lumbar discectomy, laminectomy, and decompression. It incorporates intervertebral foraminotomy, open surgery, and other lumboendoscopic techniques with a wide observation field, free space, and compatibility with various spinal surgical techniques and instruments. This study investigated the clinical efficacy of minimally invasive posterior cervical nucleus pulposus removal for cervical spondylotic radiculopathy (CSR) by OSE-Keyhole technique.Patients and Methods: This was a retrospective study of 63 patients treated with OSE keyhole treatment for CSR between May 2021 and September 2023 at Qilu Hospital of Shandong University, Qilu Hospital of Shandong University (Qingdao, China), and Second Hospital of Shandong University, respectively. Clinical outcomes included patients’ preoperative and postoperative visual analogue scale (VAS) - arm and neck, Japanese Orthopaedic Association Assessment Treatment Score (JOA) - cervical spine, which were collected at baseline, two days postoperatively, one month postoperatively, and three months postoperatively after the last follow-up visit for evaluation, and perioperative indicators, including intraoperative bleeding, length of hospital stay, postoperative complications, and reoperations, which were also collected.Results: Statistical analyses were performed for the baseline data and follow-up results of 63 patients. Compared to the preoperative baseline values, the follow-up results two days, one month and three months after surgery showed significant improvements in vas-arm, neck and JOA scores in the operated patients (P< 0.05) as well as a reduction in all perioperative-related indices.Conclusion: In the treatment of cervical pain and disability due to radiculopathy, OSE keyhole removal of the posterior cervical nucleus pulposus is a better clinical option as it is less invasive and recovers better postoperatively.Keywords: nerve root type cervical spondylosis, unilateral cervical disc herniation, posterior cervical laminectomy, single-channel endoscopy

Chunrong Huang,1,2,&ast; Yulian Gao,1,2,&ast; Hongxia Lin,1– 3,&ast; Qinmei Fan,4,&ast; Ling Chen,1,2 Yun Feng1,2 1Department of Respiratory and Critical Care Medicine, Ruijin Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Institute of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, 610000, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, The First People’s hospital of Jin Zhong, JinZhong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Chen; Yun Feng, Email co840608@hotmail.com; fy01057@163.comBackground: To evaluate the clinical features of patients with Acinetobacter baumannii bloodstream infection (BSI).Methods: Totally 200 inpatients with Acinetobacter baumannii BSI were included, clinical features of Acinetobacter baumannii BSI inpatients between 90-day survival and 90-day mortality groups, between 30-day survival and 30-day mortality groups, between patients infected with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) were analyzed. The prognostic factors of 90-day mortality were analyzed by univariate logistic regression and multivariate logistic regression. The survival curve in bloodstream infectious patients with multidrug-resistant (MDR group) and sensitive Acinetobacter baumannii (sensitive group) was analyzed by Kaplan–Meier analysis.Results: The 90-day mortality patients had significantly higher carbapenem-resistant bacterial infection and critical care unit (ICU) admission. The 90-day and 30-day mortality groups showed higher C-reactive protein (CRP) and serum creatinine (Scr) levels and lower red blood cells (RBC) and albumin (ALB) levels than their survival counterparts, respectively. Critical surgery, ICU admission and delayed antibiotic treatment were independently prognostic risk predictors for 90-day mortality in Acinetobacter baumannii BSI patients, while critical surgery and diabetes were independently prognostic risk predictors for 90-day mortality in carbapenem-resistant Acinetobacter baumannii BSI patients. Compared with sensitive group, MDR group showed significantly longer ICU and whole hospital stay, lower levels of lymphocytes, RBC, hemoglobin, lactate dehydrogenase and ALB, higher frequency of infection originating from the skin and skin structure. Moreover, patients in the MDR group had a significantly worse overall survival than the sensitive group.Conclusion: We identified the prognostic factors of Acinetobacter baumannii BSI and carbapenem-resistant Acinetobacter baumannii BSI patients. Critical surgery, ICU admission, delayed antibiotic treatment or diabetes were significantly associated with the mortality of those patients. Moreover, aggressive measures to control MDR Acinetobacter baumannii could lead to improved outcomes. Keywords: Acinetobacter baumannii, bloodstream infection, mortality, prognostic predictors, multidrug-resistance

Yang Gou,1,2 Ping Wang,1,2 Wucheng Yang,1,2 Yimei Feng,1,2 Xiangui Peng,1,2 Hong Liu,1,2 Shuiqing Liu,1,2 Xi Zhang1,2 1Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 2Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Hong Liu; Shuiqing Liu, Email 1241580141@qq.com; liushuiqing062@tmmu.edu.cnAbstract: Hereditary spherocytosis (HS) is the most common hereditary hemolytic disease with defects in red blood cells (RBC) membrane proteins caused by mutations in membrane protein genes, like SPTB, SPTA1 and ANK1. Gilbert syndrome (GS) is a disease characterized by a mild deficiency of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) enzyme activity and unconjugated hyperbilirubinemia, largely caused by UGT1A1 mutations. The two inherited diseases HS and GS are rarely occurred in the same patient and are easy to be misdiagnosed, resulting in excessive diagnosis and treatment. Here, we report a rare case of HS combined with GS due to mutations in the SPTB and UGT1A1 genes. A 50-year-old man who had an over 40-year history of jaundice was admitted to our hospital owing to fatigue and fever. His blood analysis showed low hemoglobin (74 g/L), high reticulocyte (23.5%) and high serum bilirubin (65 μmol/L); abdominal ultrasound revealed calculous cholecystitis and splenomegaly. Considering a possible diagnosis of hemolytic anemia, further examinations showed 42% spherocytes in blood smears and high erythroid lineage hyperplasia in bone marrow. Subsequently, 151 jaundice-related genes panel sequencing was done and results showed SPTB p.N1260fs and UGT1A1 p.G71R mutations. Then the patient was diagnosed with HS complicated with GS. Anti-infection and supportive treatments were providing to the patient, while infection removed, the hemoglobin recovered to normal, and no additional treatment was given. These findings of this report indicate that patients who are considered hemolytic anemia presenting with jaundice and anemia, genetic testing is a crucial method for the final diagnosis and bilirubin metabolic disease should also be concerned.Keywords: hereditary spherocytosis, Gilbert syndrome, SPTB, UGT1A1

Tong Guo,1,2 Yuan Feng,1,2 Jingjing Zhou,1,2 Linghui Meng,1,2 Xuequan Zhu,1,2 Xu Chen,1,2 Le Xiao,1,2 Lei Feng,1,2 Ling Zhang,1,2 Yu-Tao Xiang,3,4 Yan-Jie Zhao,1,2 Gang Wang1,2 1Beijing Key Laboratory of Mental Disorders, National Clinical Research Center for Mental Disorders & National Center for Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Unit of Psychiatry, Department of Public Health and Medicinal Administration, Faculty of Health Sciences, Institute of Translational Medicine, University of Macau, Taipa, Macao SAR, People’s Republic of China; 4Centre for Cognitive and Brain Sciences, University of Macau, Taipa Macao SAR, People’s Republic of ChinaCorrespondence: Yan-Jie Zhao; Gang Wang, Email yzhao118@126.com; gangwangdoc@ccmu.edu.cnBackground: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD.Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire – 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence.Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between “mood” (delta-QLES2) and “anhedonia” (delta-DEP1), between “physical health” (delta-QLES1) and “sleep problems” (delta-DEP3), and between “physical health” (delta-QLES1) and “sad mood” (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. “Anhedonia” (delta-DEP1), “sad mood” (delta-DEP2) and “loss of energy” (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants’ satisfaction with function in daily life.Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.Keywords: network analysis, patients with MDD, acute phase treatment, depressive symptoms, quality of life

Xiaoyan Huang,1,2 Xiangrong Zhao,1,2 Yaping Li,1,2 Yangmeng Feng,1,2 Guoan Zhang,3 Qiyu Wang,4 Cuixiang Xu1,2 1Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 2Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 3Department of Cardiovascular Surgery, Shaanxi Provincial People’s Hospital, Xi’an, People’s Republic of China; 4Department of Graduate School, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Cuixiang Xu, Email xucuixiang1129@163.comBackground: Dilated cardiomyopathy (DCM) is the second leading cause of heart failure, with intricate pathophysiological underpinnings. In order to shed fresh light on the mechanistic research of DCM, we combined bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data to examine significant cells and genes implicated in the disease.Methods: This analysis employed publicly accessible bulk RNA-seq and scRNA-seq DCM datasets. The scRNA-seq data underwent normalization, principal component, and t-distribution stochastic neighbor embedding analysis. Cell-to-cell communication networks and activity analysis were conducted using CellChat. Utilizing enrichment analysis, the marker genes’ role in the active cells was evaluated. After screening by limma software and weighted gene co-expression network analysis, the differentially expressed genes (DEGs) served as hub genes. Furthermore, these hub genes were subjected to immunological studies, transcription factor expression, and gene set enrichment. Lastly, the expression of the four hub genes and their connection to DCM were verified using the rat models.Results: Fibroblasts and monocytes were chosen as hub cells from among the eight identified cell clusters; their marker genes intersected with DEGs to yield six hub genes. In addition, the six hub genes and the essential module genes intersected to yield four essential genes (ASPN, SFRP4, LUM, and FRZB) that were connected to the Wnt signaling pathway and highly expressed in fibroblast. The four hub DEGs had an expression pattern in the DCM rat model experiment results that was in line with the findings of the bioinformatics study. Additionally, there was a strong correlation between decreased cardiac function and the up-regulation of ASPN, SFRP4, LUM, and FRZB.Conclusion: Ultimately, bulk RNA-seq and scRNA-seq data identified fibroblasts and monocytes as the main cell types implicated in DCM. The highly expressed genes ASPN, FRZB, LUM, and SFRP4 in fibroblasts may aid in the mechanistic investigation of DCM.Keywords: dilated cardiomyopathy, single cell RNA-seq, bulk RNA-seq, weighted gene co-expression network analysis, wnt signaling pathway, fibroblasts

Xin Qiu,1,2,&ast; Shuang Shen,1,&ast; Donghong Lu,2 Nizhen Jiang,3 Yifei Feng,3 Jindu Li,1 Chenglei Yang,1 Bangde Xiang1,4,5 1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 3Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 4Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bangde Xiang; Chenglei Yang, Email xiangbangde@gxmu.edu.cn; chenglei2017yang@163.comBackground: Hepatocellular carcinoma (HCC) presents a significant global health challenge due to its poor prognosis and high recurrence rates post-surgery. This study examines the predictive efficacy of the Advanced Lung Cancer Inflammation Index (ALI) in assessing the post-hepatectomy prognosis of patients with HCC.Methods: A cohort comprising 1654 HCC patients who underwent hepatectomy at Guangxi Medical University Cancer Hospital from 2013 to 2019 was enrolled. Patients were stratified into two groups according to the median ALI level, and then subjected to propensity score matching (PSM) in a 1:1 ratio. Kaplan-Meier survival curves, the traditional Cox proportional hazards (CPH) model, and machine learning (ML) models were employed to analyze and evaluate ALI’s prognostic significance. Furthermore, ALI’s prognostic value in digestive system tumors was validated via analysis of the National Health and Nutrition Examination Survey (NHANES) database.Results: After applying PSM, a final cohort of 1284 patients, categorized into high and low ALI groups, revealed a significantly reduced survival time in the low ALI cohort. Univariate and multivariate Cox analyses identified ALI, BCLC stage, CK19, Hepatitis B virus (HBV) DNA, lymph node metastasis, and microvascular invasion (MVI) as independent predictors of prognosis. Both traditional CPH and ML models incorporating ALI demonstrated excellent predictive accuracy, validated through calibration curves, time-dependent ROC curves, and decision curve analysis. Furthermore, the prognostic value of ALI in digestive tumors was confirmed in the NHANES database.Conclusion: The ALI exhibits potential as a prognostic predictor in patients with HCC following hepatectomy, providing valuable insights into postoperative survival.Keywords: advanced lung cancer inflammatory index, ALI, hepatocellular carcinoma, HCC, prognosis, Cox regression, machine learning, ML

Wenbin Wang,1 Lin Liu,2 Weida Qiu,1 Chaolei Chen,1 Yuqing Huang,1 Anping Cai,1 Zhiqiang Nie,1 Yanqiu Ou,1 Yicheng Zhu,1 Yingqing Feng1 1Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 2Department of Medicine, The University of Hong Kong, Hong Kong, ChinaCorrespondence: Yingqing Feng; Yicheng Zhu, Department of Cardiology, Hypertension Research Laboratory, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, People’s Republic of China, Email fengyingqing@gdph.org.cn; zhuyicheng@gdph.org.cnIntroduction: Traditional clinical risk factors are insufficient to estimate the residual risk of large-vessel ischemic stroke. Non-targeted lipidomic techniques provide an opportunity to evaluate these risks.Methods: Plasma samples were collected from 113 hypertensive individuals, including 55 individuals at high risk of ischemic stroke and 58 matched individuals, in a prospective nested case-control cohort. To identify dysregulated lipid metabolites, we conducted multivariate and univariate analyses. A classifier based on a cross-validated procedure was employed to select the optimal combination of lipid species and their ratios.Results: We identified 23 dysregulated lipid species in patients with and without ischemic stroke, including 16 (69.6%) up-regulated and 7 (30.4%) down-regulated lipid species. Through internal cross-validation, the optimal combination of two lipid features (phosphatidylcholine 34:2 and triglyceride 18:1/18:1/22:1 / phosphatidylcholine 34:2, referred to as ischemic stroke-related 2 lipid features - IS2LP) was selected, leading to a more precise prediction probability for ischemic stroke within 3.9 years. In the comparison of different risk factors, the traditional risk score, the IS2LP risk score, and the combination of the traditional risk score with IS2LP yield AUC values of 0.613(95% CI:0.509– 0.717), 0.833(95% CI:0.755– 0.911), and 0.843(95% CI:0.777– 0.916), respectively. The combination of the traditional risk score and IS2LP exhibited significantly improved discriminative performance, with an integrated discrimination improvement (IDI) of 0.31 (p< 0.001) and a continuous net reclassification improvement (NRI) of 1.06 (p < 0.001) compared to the traditional risk score.Conclusion: We identified new lipidomic biomarkers associated with the futural event of large-vessel ischemic stroke. These lipid species could serve as potential blood biomarkers for assessing the residual risk of ischemic stroke in hypertensive individuals.Keywords: hypertension, lipidomics, ischemic stroke, risk factors

Qiying Zeng,1,&ast; Wenjun Xue,2,&ast; Zhicheng Wei,1 Hangdong Shen,1 Huajun Xu,1 Huaming Zhu,1 Jian Guan,1 Hongliang Yi,1 Yunhai Feng,2 Xinyi Li,1 Haibo Ye1 1Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai Jiao Tong University, Shanghai, 200233, People’s Republic of China; 2Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Eighth People’s Hospital Affiliated to Jiangsu University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Li; Haibo Ye, Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Sleep Disordered Breathing, Otorhinolaryngology Institute of Shanghai JiaoTong University, Shanghai, 200233, People’s Republic of China, Tel/Fax +86-2164834143, Email lixinyilixinyi123@163.com; yehaibo_2012@163.comBackground: Sleep-disordered breathing is more prevalent in individuals with allergic rhinitis (AR) than in those without AR. In addition to increased risk for sleep-disordered breathing, AR is associated with greater severity of obstructive sleep apnea (OSA) symptoms. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in AR with sleep- and breathing-related parameters in men with OSA.Methods: Men who had complained of snoring were consecutively enrolled in the Shanghai Sleep Health Study of Shanghai Sixth People’s Hospital from 2007 to 2018. After rigorous screening, 5322 men were included in the analysis. Anthropometric, fasting biochemical, and polysomnographic parameters, along with 27 AR-associated SNPs were analyzed. The associations between AR-related genetic polymorphisms and OSA were determined via linear, binary, and multinomial logistic regression analyses.Results: Rs12509403 had significantly positive associations with most sleep-breathing parameters. While the risk for OSA was increased by rs12509403, it was decreased by rs7717955 [odds ratio (OR) = 1.341, 95% confidence interval [CI] = 1.039– 1.732, P = 0.024; OR = 0.829, 95% CI = 0.715– 0.961, P = 0.013, respectively]. A graded increase in the risk of being in the highest quartile (Q4) vs the reference category (Q1) for sleep breathing indicators, especially REM-AHI and NREM-AHI, was identified by rs12509403 (OR = 1.496, 95% CI = 1.175– 1.904, P = 0.001; OR = 1.471, 95% CI = 1.151– 1.879, P < 0.001, respectively).Conclusion: The association of multiple AR SNPs with OSA-related hypoxia and sleep indices provides a genetic explanation for the higher AR susceptibility of OSA patients. Understanding the AR-related genetic underpinnings of OSA may lead to more personalized treatment approaches.Keywords: allergic rhinitis, obstructive sleep apnea, single nucleotide polymorphism, polysomnography

Tiantian Guo,1 Yao Wang,1 Dixuan Chen,2 Sifan Cui,2 Shuyue Guo,1 Yixing Feng,1 Jialin Zhu,1 Luchen Chang,1 Jiawei Zhang,2 Xiujun Gao,2 Xi Wei1 1Department of Diagnostic and Therapeutic Ultrasonography, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, 300060, People’s Republic of China; 2School of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin, 300070, People’s Republic of ChinaCorrespondence: Xi Wei, Department of Diagnostic and Therapeutic Ultrasonography, 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, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060, People’s Republic of China, Email weixi@tmu.edu.cn Xiujun Gao, School of Biomedical, Engineering and Technology, Tianjin Medical University, No. 22, Meteorological Station Road, Tianjin, 300070, People’s Republic of China, Email gaoxiujun12242@tmu.edu.cnPurpose: Chemotherapy remains the primary therapeutic approach for advanced Hepatocellular Carcinoma (HCC). The therapeutic effect of chemotherapy is limited and the toxic side effects are serious. The aim of this study is to develop a nanobubble that is ultrasonically responsive to reduce the toxic side effects of direct chemotherapy.Methods: We developed curcumin/doxorubicin-cis-aconitic anhydride-polyethylene glycol nanobubble (C/DCNB) surface modified with acid-sensitive polyethylene glycol (PEG). And it is loaded with curcumin (CUR) and doxorubicin (DOX), as liposomes at the nanoscale for diagnosis and therapy of tumors.Results: In this study, the acid-sensitive PEG on the surface layer of nanobubbles serves to stabilize them in the blood circulatory system and in normal tissues, while peeling off in the acidic tumor microenvironment (pH 6.8). C/DCNB can identify tumor sites through contrast-enhanced ultrasound (CEUS). And ultrasound-mediated nanobubbles promote permeability of the tumor vascular, thus improving the enhanced permeability and retention (EPR) effects in the tumor, leading to the accumulation of nanobubbles in the tumor. After endocytosis of nanobubbles, drugs are released and curcumin generates reactive oxygen species (ROS) under ultrasound conditions. CUR can enhance the sensitivity of tumor cells to DOX by inhibiting the expression of P-glycoprotein. In vitro and vivo experiments demonstrate that C/DCNB can facilitate contrast-enhanced ultrasound imaging while simultaneously delivering drugs, enabling both imaging and treatment.Conclusion: The combination of C/DCNB and ultrasound provides an effective strategy for improving the efficiency of HCC therapy and imaging. Keywords: combination of sonodynamic therapy and chemotherapy, the synergistic effect of two drugs, integration of diagnosis and treatment, ultrasound

Yinping Feng,&ast; Jing Guo, Shuirong Luo, Guangnao Zhou&ast; Department of Tuberculosis, Lishui Hospital of traditional Chinese Medicine Affiliated to Zhejiang University of traditional Chinese Medicine, Lishui, 323000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangnao Zhou, Email zgn198615@163.comBackground: Pulmonary tuberculosis (PTB) with tracheobronchial tuberculosis (TBTB) can lead to tracheal stenosis and atelectasis, but the specific risk factors are currently unclear. Therefore, the goal of this retrospective study is to address this issue and help with the early diagnosis of TBTB.Methods: Please include PTB hospitalized in our hospital from January 2021 to October 2023 in the study. After conducting bronchoscopy examinations, the patients were divided into two groups: the PTB group and the PTB&TBTB group. We used the propensity score matching (PSM) to align the baseline data of the two groups of patients, and then performed multiple logistic regression analysis to identify risk factors.Results: 643 patients with PTB were included in the study, 227 of whom (35.30%) were diagnosed with TBTB. A total of 204 pairs of patients were successfully matched using the PSM. After matching, there were no statistically significant differences in basic information between the two groups of patients (P> 0.05). Multivariate logistic regression analysis revealed that disease course ≥ 1 month (OR=1.85, 95% CI: 1.21– 2.83), complicated with diabetes (OR=3.00, 95% CI: 1.91– 4.70), and concomitant pulmonary cavity (OR=3.46, 95% CI: 2.23– 5.36) were risk factors for PTB accompanied by TBTB (all P< 0.05).Conclusion: After adjusting for various influencing factors using PSM, the analysis demonstrated that disease course ≥ 1 month, complicated with diabetes, and concomitant pulmonary cavity are risk factors for PTB combined with TBTB. This emphasizes the significance of improving screening and implementing early intervention measures.Keywords: pulmonary tuberculosis, tracheobronchial tuberculosis, propensity score matching, risk factors

Yanan Li,1 Yahui Feng,2 Dongmei Li,3 Dongmei Shi,2,4 Guanzhi Chen1 1Department of Dermatology, Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2The Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, Shandong, People’s Republic of China; 3Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC, USA; 4Department of Dermatology, Jining No.1 People’s Hospital, Jining, Shandong, People’s Republic of ChinaCorrespondence: Guanzhi Chen, Department of Dermatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266000, People’s Republic of China, Email chenguanzhiqd@hotmail.comObjective: The increasing incidence of chronic skin infections caused by Mycobacterium marinum, coupled with the time-consuming and low detection rates nature of traditional culture and histological-based diagnostic methods, underscores the need for an expedited approach. The study aims to develop a rapid and efficient method for detecting M. marinum with PCR technology.Methods: We designed four pairs of primers based on DNA sequences from GeneBank and prior studies, we utilized both PCR and Real-time PCR to identify M. marinum. Specificity and sensitivity assessments were conducted in vitro by DNAs extracted from M. marinum and other bacterial or fungal cultures. Further validation was performed through the implementation of a mouse skin infection model to optimize and confirm the efficacy of the detection method in both fresh and paraffin-embedded skin tissues. The same PCR testing system was further confirmed with paraffin-embedded skin tissues samples from patients as well.Results: The results of the study indicate promising outcomes for the four-pair primers system. It demonstrated 100% sensitivity in detecting M. marinum from purified cultures, including typical strains and nine clinical isolates, while achieving a specificity of 100%. This specificity was evidenced by the absence of PCR products from 12 bacterial species, 12 fungi species, and six other non-tuberculous mycobacterium (NTM) species. In the animal model, the PCR assay exhibited high detection efficacy for both infected fresh tissues and paraffin-embedded tissues, with a slight superiority observed in fresh tissues. However, the PCR assay exhibited high detection efficacy for clinical paraffin-embedded tissues. These findings collectively underscore the robust detection capabilities of our four-pair primers in both in vitro and in vivo settings.Conclusion: A sensitive and highly specific rapid detection system has been successfully developed that can be used to detect M. marinum in both infected fresh tissues and paraffin-embedded tissues.Keywords: Mycobacterium marinum, bacteria, infected tissue, paraffin-embedded tissue, PCR technique

Yaxu Feng,&ast; Qing Sun,&ast; Pei Liu, Wei Fan, Bing Fan The State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Fan; Bing Fan, Email weifan@whu.edu.cn; bingfan@whu.edu.cnBackground: Enterococcus faecalis (E. faecalis) is one of the main pathogens responsible for refractory root canal infections in the teeth and shows resistance against various antibacterial managements. Effective control of E. faecalis infection is a prerequisite for successful treatment of refractory apical periodontitis. This study aimed to analyze the antibacterial activity and mechanisms of Au@Ag nanoparticles (NPs) combined with photothermal therapy (PTT) against the original and Ag+-resistant E. faecalis.Methods: Au@AgNPs with optimal shell thicknesses were synthesized and characterized. The antibacterial activity of Au@AgNPs with PTT against the original or Ag+-resistant E. faecalis was evaluated, and the antibiofilm activity was tested on E. faecalis biofilm on the dentin of teeth. The potential antibacterial mechanisms of Au@AgNPs combined with PTT against E. faecalis have also been studied. Moreover, its influence on dentin microhardness and cytotoxicity was assessed.Results: This study revealed that Au@AgNPs combined with PTT showed enhanced antibacterial and antibiofilm effects, no negative effects on dentin microhardness, and low cytotoxicity toward human periodontal ligament cells (hPDLCs). Moreover, Au@AgNPs combined with PTT effectively inhibited the growth of Ag+-resistant E. faecalis. Its antibacterial effects may be exerted through the release of silver ions (Ag+), destruction of the cell membrane, production of reactive oxygen species (ROS) and inhibition of adenosine triphosphate (ATP) production. Hyperthermia generated by Au@AgNPs with PTT reduced membrane fluidity and enhanced Ag+ sensitivity by downregulating fabF expression. The upregulated expression of heat shock genes demonstrated that the Ag+ released from Au@AgNPs compromised the heat adaptation of E. faecalis.Conclusion: PTT significantly enhanced Ag+ sensitivity of the original and Ag+-resistant E. faecalis. Au@AgNPs combined with PTT may have the potential to be developed as a new antibacterial agent to control E. faecalis infections in teeth.Keywords: Au@AgNPs, resistance, photothermal therapy, antibacterial, silver ions, E. faecalis

Yuting Xiang,1,2,&ast; Li Tang,1,&ast; Hua Pang,3 Han Xu,1,2 Yiman He,1,2 Yuyue Feng,3 Linjun Ju,3 Liang Zhang,1 Dong Wang1 1Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Nuclear Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Zhang; Dong Wang, Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400042, People’s Republic of China, Email zhangliang338@cqmu.edu.cn; wang57554@163.comBackground: The inadequate perfusion, frequently resulting from abnormal vascular configuration, gives rise to tumor hypoxia. The presence of this condition hinders the effective delivery of therapeutic drugs and the infiltration of immune cells into the tumor, thereby compromising the efficacy of treatments against tumors. The objective of this study is to exploit the thermal effect of ultrasound (US) in order to induce localized temperature elevation within the tumor, thereby facilitating vasodilation, augmenting drug delivery, and enhancing immune cell infiltration.Methods: The selection of US parameters was based on intratumor temperature elevation and their impact on cell viability. Vasodilation and hypoxia improvement were investigated using enzyme-linked immunosorbent assay (ELISA) and immunofluorescence examination. The distribution and accumulation of commercial pegylated liposomal doxorubicin (PLD) and PD-L1 antibody (anti-PD-L1) in the tumor were analyzed through frozen section analysis, ELISA, and in vivo fluorescence imaging. The evaluation of tumor immune microenvironment was conducted using flow cytometry (FCM). The efficacy of US-enhanced chemotherapy in combination with immunotherapy was investigated by monitoring tumor growth and survival rate after various treatments.Results: The US irradiation condition of 0.8 W/cm2 for 10 min effectively elevated the tumor temperature to approximately 40 °C without causing any cellular or tissue damage, and sufficiently induced vasodilation, thereby enhancing the distribution and delivery of PLD and anti-PD-L1 in US-treated tumors. Moreover, it effectively mitigated tumor hypoxia while significantly increasing M1-phenotype tumor-associated macrophages (TAMs) and CD8+ T cells, as well as decreasing M2-phenotype TAMs. By incorporating US irradiation, the therapeutic efficacy of PLD and anti-PD-L1 was substantially boosted, leading to effective suppression of tumor growth and prolonged survival in mice.Conclusion: The application of US (0.8 W/cm2 for 10 min) can effectively induce vasodilation and enhance the delivery of PLD and anti-PD-L1 into tumors, thereby reshaping the immunosuppressive tumor microenvironment and optimizing therapeutic outcomes.Keywords: ultrasound, thermal effect, vasodilatation, drug delivery, tumor microenvironment

Qin Zhang,1 Rui Zhao,1 Yaqing Wu,2 Liming Zhang,1 Yi Feng2 1Endoscopy Center, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yi Feng, Department of Anesthesiology, Peking University People’s Hospital, Beijing, 100044, People’s Republic of China, Email doctor_yifeng@sina.comPurpose: Remimazolam is a novel short-acting benzodiazepine used for sedation and general anesthesia. This study aimed to evaluate the efficacy and safety of remimazolam besylate in elderly patients who underwent diagnostic gastrointestinal endoscopy.Patients and Methods: A total of 120 patients aged 60– 75 years were randomly allocated to one of two groups. Remifentanil 0.3μg/kg was used for analgesia. Patients were administered remimazolam besylate 7 mg (R group) or etomidate 0.1 mg/kg combined with 1% propofol 0.5 mg/kg (EP group) for induction, supplemental repeated doses were given as needed. Some time metrics, vital signs, adverse events were evaluated. Patients’ Mini-cog score and recovery questionnaires were compared.Results: Compared to the EP group, the induction time was slightly longer in the R group (1.50 VS 1.15 minutes) (P< 0.05), the time spent in the post-anesthesia care unit (PACU) was shorter (15.17 VS 17.40 minutes) (P< 0.05). Compare with EP group, SBP was lower in R group at T15 and T25 time point, but heart rate was higher in T2, T3, T5 (P< 0.05). The Mini-Cog score was higher after the procedure (2.83 VS 2.58) (P< 0.05). The incidence of respiratory adverse events was higher in the EP group than R group (18.3% VS 5.0%, P < 0.05). The most common adverse event in R group was hiccups. The sedation satisfaction rate and degree of amnesia were higher in the R group (66.7% VS 11.7%) (P < 0.05), and the effect on patient’s life within 24 hours was lower (12.0% VS 30.5%) (P < 0.05).Conclusion: The safety and efficacy of remimazolam besylate are not inferior to those of etomidate combined with propofol, rendering it a safe option for sedation during gastrointestinal endoscopy in ASA I-II elderly patients, but care should be taken to monitor the occurrence of hiccups.Keywords: gastrointestinal endoscopy, anesthesia, remimazolam besylate, etomidate, propofol

Yanxia Guo,&ast; Zhihua Yao,&ast; Yan Feng, Dan Wang, Yizheng Wang, Jingyan Lin Department of Anesthesiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingyan Lin, Email linjingyan@nsmc.edu.cnBackground: The novel short-acting benzodiazepine drug, remimazolam tosilate, has been employed for sedation during endoscopic procedures. The optimal loading dosage of remimazolam tosilate in gastroscopy for elderly patients when co-administered with fentanyl remains unclear. Therefore, the primary objective of our research was to ascertain the median effective dose (ED50) and the 95% effective dose (ED95) of remimazolam tosilate in combination with various fentanyl dosages for elderly patients undergoing painless gastroscopy.Methods: Seventy-five patients aged ≥ 65 years and American Society of Anesthesiologists (ASA) class I–III were recruited to undergo elective painless gastroscopy. All patients were randomized assigned to group F1, group F2, and group F3, and were injected intravenously with different doses of fentanyl (0.5 ug/kg, 1 ug/kg, and 1.5 ug/kg) 3 minutes prior to the administration of remimazolam tosilate, respectively. The initial preset dose of remimazolam tosilate was 0.3 mg/kg in group F1, 0.2 mg/kg in group F2, 0.15 mg/kg in group F3. The dose gradient was 0.02 mg/kg per group according to the up-and-down sequential method. Probibt regression model was employed to determine the ED50 and ED95 of remimazolam tosilate.Results: The ED50 of remimazolam tosilate in group F3 was lower than that in group F1 and F2 (0.095 [0.088– 0.108] mg/kg vs 0.162 [0.153– 0.171] mg/kg; 0.258 [0.249– 0.266] mg/kg, p < 0.05). The ED95 of remimazolam tosilate was 0.272 mg/kg (95% CI: 0.264– 0.295 mg/kg) in group F1, 0.175 mg/kg (95% CI: 0.167– 0.200 mg/kg) in group F2 and 0.109 mg/kg (95% CI: 0.101– 0.135 mg/kg) in group F3. The total dosage of remimazolam tosilate decreased gradually with the increasing of fentanyl (p < 0.001). The frequency of injection pain was higher in group F1 compared to groups F2 and F3 (p < 0.05). The patients in group F3 had a lower incidence of hypotension than in groups F1 and F2 (p < 0.05). There was no respiratory depression, intraoperative consciousness, dizziness or delirium in the three groups.Conclusion: The concurrent use of fentanyl reduces the dosage of remimazolam tosilate required for sedative gastroscopy in elderly patients in a dose-dependent manner. Moreover, 1.5 ug/kg fentanyl combined with remimazolam tosilate may reduce the incidence of hypotension and injection pain. These findings should be confirmed in a large-scale study.Keywords: painless gastroscopy, elderly patients, median effective dose, fentanyl, remimazolam tosilate

Yanzhi Feng,1– 4,&ast; Litao Liang,1– 4,&ast; Wenbo Jia,1– 4 Jinyi Wang,1– 4 Chao Xu,1– 4 Deming Zhu,1– 4 Bin Xu,1– 4 Wenhu Zhao,1– 4 Xiangyu Ling,1– 4 Yongping Zhou,5 Lianbao Kong,1– 4,&ast; Wenzhou Ding1– 4,&ast; 1Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, National Health Commission Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Provincial Medical Innovation Center, Nanjing, Jiangsu, People’s Republic of China; 4Jiangsu Provincial Medical Key Laboratory, Nanjing, Jiangsu, People’s Republic of China; 5Jiangnan University Medical Center, JUMC, Department of Hepatobiliary, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhou Ding; Lianbao Kong, Hepatobiliary Centre, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email dingwenzhou@njmu.edu.cn; lbkong@njmu.edu.cnBackground: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown.Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed.Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial–mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment.Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients. Keywords: hepatocellular carcinoma, circ_0007386, miR-507, CCNT2, Lenvatinib

Hongmei Sun,1,2 Chao Lv,2,3 Xiaoxue Zhang,1,2 Xuan Sun,1,3,4 Siyu Chen,1,3,4 Ke Li,3,4 Yazhuo Hu,2,3 Yuxin Feng,1,2 Tong Yin,2,3 Jianjun Jia2,3 1Medical School, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Institute of Geriatrics, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Geriatric Neurology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianjun Jia; Tong Yin, Institute of Geriatrics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, Haidian District, 100853, People’s Republic of China, Email jiajianjun301@126.com; yintong301@163.comBackground: Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer’s disease continuum (ADC).Objective: This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC.Material and Methods: According to 2018 National Institute on Aging and Alzheimer’s Association (NIA-AA) standard, amyloid β-protein positive (Aβ+) and negative (Aβ-) patients were recruited according to the Aβ-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aβ+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aβ+ and 73 Aβ– patients using a logistic regression analysis.Results: The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64– 28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28– 4.95).Conclusion: The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.Keywords: Alzheimer’s disease, pharmacogenomics, variant, gene, donepezil

Peng Zhou,1,2,&ast; Ling Li,3,&ast; Zehua Lin,1,2,&ast; Xiaoping Ming,1,2 Yiwei Feng,1,2 Yifan Hu,1,2 Xiong Chen1,2 1Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Sleep Medicine Centre, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiong Chen, Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuhan, Hubei, 430071, People’s Republic of China, Email zn_chenxiong@whu.edu.cnPurpose: The reciprocal comorbidity of obstructive sleep apnea (OSA) and body mass index (BMI) has been observed, yet the shared genetic architecture between them remains unclear. This study aimed to explore the genetic overlaps between them.Methods: Summary statistics were acquired from the genome-wide association studies (GWASs) on OSA (Ncase = 41,704; Ncontrol = 335,573) and BMI (Noverall = 461,460). A comprehensive genome-wide cross-trait analysis was performed to quantify global and local genetic correlation, infer the bidirectional causal relationships, detect independent pleiotropic loci, and investigate potential comorbid genes.Results: A positive significant global genetic correlation between OSA and BMI was observed (rg = 0.52, P = 2.85e-122), which was supported by three local signal. The Mendelian randomization analysis confirmed bidirectional causal associations. In the meta-analysis of cross-traits GWAS, a total of 151 single-nucleotide polymorphisms were found to be pleiotropic between OSA and BMI. Additionally, we discovered that the genetic association between OSA and BMI is concentrated in 12 brain regions. Finally, a total 134 expression-tissue pairs were observed to have a significant impact on both OSA and BMI within the specified brain regions.Conclusion: Our comprehensive genome-wide cross-trait analysis indicates a shared genetic architecture between OSA and BMI, offering new perspectives on the possible mechanisms involved.Keywords: genome-wide cross-trait analysis, Mendelian randomization, genetic architecture

Hang Wang,1,&ast; Bobin Hu,1,&ast; Hengkai Liang,1 Rongming Wang,1 Lu Wei,1 Tumei Su,1 Qingmei Li,1 Qianbing Yin,1 Yanfei Feng,1 Minghua Su,1 Jianning Jiang1,2 1Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianning Jiang; Minghua Su, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Tel +86-0771-5356531, Email gxjjianning@163.com; smh9292@163.comPurpose: Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.Patients and Methods: We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.Results: After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.Conclusion: HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.Keywords: hepatitis B virus, long-term antiviral therapy, hepatocellular carcinoma, integration, gene rearrangement

Fei Li,1,&ast; Feifei Yan,2,&ast; Shengnan Liu,1,&ast; Rewaan Baheti,1 Yujia Feng,1 Jing Wan1 1Department of Cardiovascular Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China; 2Cardiac Ultrasound Department, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wan, Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, People’s Republic of China, Tel +86-027-67813477, Email wanjing_zn@163.comPurpose: In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.Methods: We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.Results: In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p< 0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p< 0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P< 0.001).Conclusion: In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.Keywords: hypertension, echocardiography, changes of cardiac structure and function, progression of renal damage, hypertensive nephropathy

Menglu Dong,1 Xili Liang,1 Tian Zhu,1 Ting Xu,1 Liwei Xie,2,3 Yuan Feng1,4,5 1Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, People’s Republic of China; 3Department of Endocrinology and Metabolism, Zhujiang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 4Institute of Brain Disease, Nanfang Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Science, Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Liwei Xie, Email xielw@gdim.cn; Yuan Feng, Sleep Medicine Center, Department of Psychiatric, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Baiyun District, Guangzhou, 510515, People’s Republic of China, Email yuanstar@126.comBackground: Obstructive sleep apnea (OSA) is a prevalent sleep breathing disorder characterized by intermittent hypoxia (IH), with continuous positive airway pressure (CPAP) as its standard treatment. However, the effects of intermittent hypoxia/reoxygenation (IH/R) on weight regulation in obesity and its underlying mechanism remain unclear. Gut microbiota has gained attention for its strong association with various diseases. This study aims to explore the combined influence of IH and obesity on gut microbiota and to investigate the impact of reoxygenation on IH-induced alterations.Methods: Diet-induced obese (DIO) rats were created by 8-week high-fat diet (HFD) feeding and randomly assigned into three groups (n=15 per group): normoxia (NM), IH (6% O2, 30 cycles/h, 8 h/day, 4 weeks), or hypoxia/reoxygenation (HR, 2-week IH followed by 2-week reoxygenation) management. After modeling and exposure, body weight and biochemical indicators were measured, and fecal samples were collected for 16S rRNA sequencing.Results: DIO rats in the IH group showed increased weight gain (p=0.0016) and elevated systemic inflammation, including IL-6 (p=0.0070) and leptin (p=0.0004). Moreover, IH rats exhibited greater microbial diversity (p< 0.0167), and significant alterations in the microbial structure (p=0.014), notably the order Clostridiales, accompanied by an upregulation of bile acid metabolism predicted pathway (p=0.0043). Reoxygenation not only improved IH-exacerbated obesity, systemic inflammation, leptin resistance, and sympathetic activation, but also showed the potential to restore IH-induced microbial alterations. Elevated leptin levels were associated with Ruminococcaceae (p=0.0008) and Clostridiales (p=0.0019), while body weight was linked to Blautia producta (p=0.0377). Additionally, the abundance of Lactobacillus was negatively correlated with leptin levels (p=0.0006) and weight (p=0.0339).Conclusion: IH leads to gut dysbiosis and metabolic disorders, while reoxygenation therapy demonstrates a potentially protective effect by restoring gut homeostasis and mitigating inflammation. It highlights the potential benefits of CPAP in reducing metabolic risk among obese patients with OSA.Keywords: intermittent hypoxia, reoxygenation, high-fat diet-induced obese, gut microbiota, 16S rRNA

Guiqing Liu,1 Yuanyuan Yi,1 Yanni Wang,1 Yuru Feng,1 Minyi Lin,1 Xu Yan,1 Jinghua Wang,2 Xianjia Ning,2 Nan Ma1 1Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 2Center of Clinical Epidemiology, Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Nan Ma, Department of Liver Surgery (Liver Transplantation), Shenzhen Third People’s Hospital and the Second Hospital Affiliated with the Southern University of Science and Technology, 29 Bulan Road, Longgang District, Shenzhen, Guangdong Province, 518112, People’s Republic of China, Tel +86-755-61222333, Fax +86-755-61238928, Email manan133@163.comObjective: We aimed to explore the status of nutritional and frailty in patients undergoing liver transplantation and the associated influencing factors.Methods: We conducted a follow-up analysis of 44 patients who underwent liver transplantation between 2021 and 2022. We followed up and recorded the nutritional status and risk of weakness at different time-points (days 1, 2, 3, 6, 9, and 12) postoperatively. Patient information regarding demographics, physical examination, medical history, and perioperative blood tests were collected. Binary logistic regression was applied to identify risk factors for weakness after liver transplantation.Results: The cohort comprised 44 liver transplant recipients, with a mean age of 47.66 years (standard deviation=9.49 years). Initial analysis revealed that, compared to the group without nutritional risks, the group with nutritional risks displayed elevated age and preoperative blood ammonia levels one week post-surgery. Moreover, this group had reduced levels of albumin and total bile acid preoperatively. Patients with preoperative nutritional risks were also prone to similar risks 2 weeks postoperatively. Further, a correlation was observed between preoperative pulmonary infections and increased frailty risk 6 days postoperatively. At both 9 and 12 days postoperatively, patients with frailty risk exhibited higher preoperative white blood cell counts and ammonia levels than those without. Multivariable analysis, controlling for confounding factors, indicated a significant association between preoperative nutritional status and nutritional risk 2 weeks postoperatively, as well as a link between preoperative white blood cell count and frailty risk at 12 days postoperatively.Conclusion: There was a significant correlation between preoperative nutritional status and nutritional risk 2 weeks after liver transplantation, and preoperative white blood cell count was an independent risk factor for weakness 12 days postoperatively. Preoperative nutritional management for patients could potentially mitigate the likelihood of adverse clinical outcomes.Keywords: malnutrition, frailty, liver transplantation, risk factors, epidemiology

Xiaoqi Chen,1,2,&ast; Zhuang Li,1,&ast; Yanying Feng,3 Zhijun Yang,1,2 Bingbing Zhao1,2 1Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Cardiopulmonary Center, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bingbing Zhao; Zhijun Yang, Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email zhaobingbing@gxmu.edu.cn; yzj7528@126.comPurpose: Evidence has indicated that PDZD11 is involved in regulating adherens junction. However, the distinct effect of its aberrant expression on epithelial ovarian cancer (EOC) awaits clarification.Methods: In this study, public databases (Gene Expression Omnibus, The Cancer Genome Atlas, and The Genotype-Tissue Expression), online analysis tools (Kaplan-Meier plotter and TIMER), and data analysis methods (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and the CIBERSORT algorithm) were fully utilized to analyze the differential expression, diagnostic efficiency, prognostic significance, potential function, and correlation with immune infiltration of PDZD11. The differential expression of PDZD11 was tested by immunohistochemistry in EOC tissues (78 cases) and control tissues (37 cases).Results: Our results indicate that PDZD11 was remarkably overexpressed in EOC, which was associated with advanced cancer stages, no lymphatic metastasis status, and poor prognosis. Moreover, PDZD11 played a role in cell adhesion, cell proliferation, and immune responses. Also, PDZD11 was significantly related to the abundances of infiltrating immune cells in EOC, including neutrophils, macrophages, dendritic cells, CD8+ T cells, and CD4+ T cells, and its expression was positively co-expressed with well-known immune checkpoints, including TIGIT, TIM3, LAG3, CTLA4, and PD-1.Conclusion: These results suggest that PDZD11 could be a potential diagnostic and prognostic biomarker associated with immune infiltration in EOC, and our findings might help elucidate the function of PDZD11 in carcinogenesis. Keywords: PDZD11, epithelial ovarian cancer, prognostic biomarker, immune infiltration, immune checkpoint

Yinping Feng, Jing Guo, Shuirong Luo, Zunjing Zhang, Zhongda Liu Department of Tuberculosis, Lishui Hospital of Traditional Chinese Medicine Affiliated to Zhejiang University of Traditional Chinese Medicine, Lishui Tuberculosis Clinical Medical Research Center, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Zhongda Liu, Email liu_zd0578@126.comObjective: Exploring the risk factors for readmission of elderly patients with pulmonary tuberculosis (PTB) within one month using the propensity score matching(PSM).Methods: A retrospective analysis was conducted on the clinical data of elderly patients with PTB who were admitted to the Tuberculosis Department of Lishui Hospital of Traditional Chinese Medicine from January 2020 to October 2023. The patients were divided into two groups: non-readmission group and readmission group based on whether they were readmitted within one month after discharge. The PSM method was used to match the baseline data of the two groups of patients, and multivariate logistic regression analysis was conducted to explore the risk factors for readmission of elderly patients with PTB within one month after discharge.Results: A total of 1268 hospitalized elderly patients with PTB were included in the study, comprising 977 readmitted patients and 291 newly admitted patients (22.95%). Using the PSM, 288 pairs of patients were successfully matched. Following matching, there were no statistically significant differences between the two groups in terms of gender, age, occupation, body mass index(BMI), past medical history, etc. (all P> 0.05). Multivariate logistic regression analysis indicated that infection, drug-induced liver injury(DILI), acute heart failure(AHF), chronic kidney disease(CKD), and extrapulmonary tuberculosis(EPTB) were all identified as risk factors for readmission of elderly patients with PTB.Conclusion: After controlling for confounding factors through PSM, the study revealed that infection, DILI, AHF, CKD, and EPTB are risk factors for readmission among elderly patients with PTB, highlighting the need for early intervention.Keywords: elderly patients with pulmonary tuberculosis, aged, readmission, propensity score matching, risk factors

Yisong Feng,1 Jing Cui2 1College of Public Health, Chongqing Medical University, Chongqing, People’s Republic of China; 2Human Resources Office, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Jing Cui, Human Resources Office, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-13708360542, Fax +862368480072, Email cuijing@cqmu.edu.cnPurpose: This study aimed to examine the role of personal emotions and emotional contagion within organizations on the behavior and attitudes of healthcare personnel. This study is expected to provide a theoretical foundation for reducing resignation behaviors and improving healthcare quality.Materials and Methods: This study adopted a quantitative research method with a cross-sectional survey through an online questionnaire. The bootstrap method with 5000 iterations was used to validate the role of variables within a 95% confidence interval. SPSS 26.0 and Model 5 in Process 3.4 for SPSS were used for the data analysis.Results: This research involved 459 healthcare personnel, whose levels of role overload (3.821± 0.925), emotional exhaustion (3.436± 1.189), and turnover emotional contagion (3.110± 1.099) were notably high. Role overload was positively related to turnover intention, with emotional exhaustion as a mediator. Notably, turnover emotional contagion exerted a positive moderating effect.Conclusion: This study emphasizes the adverse effects of emotional exhaustion and turnover emotional contagion in the Chinese context, offering practical recommendations for medical organizational managers to navigate turnover intention among healthcare personnel. This study suggests paying attention to the emotional state of healthcare personnel and providing adequate support resources. Managers should routinely assess and track turnover emotional contagion within the organization, fostering a positive emotional atmosphere.Keywords: emotional contagion, emotional exhaustion, role overload, turnover intention, job demands-resources model

Guodong Yang,1– 3 Shuang Zhou,4 Yue Feng,5 Jiaran Lang,1– 3 Yaxin Chen,1– 3 Huipeng Ren1– 3 1Mental Health Center, Hebei Medical University and Hebei Technical Innovation Center for Mental Health Assessment and Intervention, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Psychiatry, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 4The Sixth People’s Hospital of Hebei Province, Baoding, Hebei, 071000, People’s Republic of China; 5Maternity & Child Care Center of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Huipeng Ren, The First Hospital of Hebei Medical University, 89 Donggang Road, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email renhuipeng@126.comPurpose: In clinical work, it has been found that the prevalence of hyperuricemia (HUA) is significantly higher in younger patients with psychiatric disorders, but there are few studies in this area. The present study aims to evaluate the prevalence of HUA and the relationship between the HUA and age in hospitalized patients with psychiatric disorders in the real world, and to provide a theoretical basis for clinical staff to pay attention to the metabolic indicators of younger patients and for future related studies.Methods: This is a cross-sectional evaluation of a cohort of 1761 patients with psychiatric disorders of hospitalized. The categories of disorders designed for study included: Depression, Bipolar disorder, Schizophrenia, Anxiety, Obsessive-Compulsive disorder, Acute and transient psychotic disorder, Dissociative(conversion) disorders, Conduct disorders and Tic disorders. In addition, based on age, the participants are stratified into three groups. The authors used Kruskal–Wallis tests, chi-square tests, and multiple linear logistic regression to verify the relationship between HUA and age among hospitalized patients with psychiatric disorders.Results: Overall, the estimated prevalence of HUA was 35.4%. The prevalence of HUA was significantly higher in individuals with 17 years and under compared to those with 45 years and above (P < 0.001). After adjusting for confounders, the prevalence of HUA remained higher at 17 years and under than at 45 years and above. Bipolar disorder can lead to an increased prevalence of HUA (P< 0.05).Conclusion: The prevalence of HUA was higher in hospitalized patients with psychiatric disorders, and the prevalence was inversely proportional to age.Keywords: hyperuricemia, uric acid, age, psychiatric disorders, bipolar disorder

Yan Feng,&ast; Jia-Feng Sun,&ast; Hai-Chao Wei,&ast; Ying Cao, Lei Yao, Bo-Xiang Du The Affiliated Hospital 2 of Nantong University, Nantong City, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo-Xiang Du; Lei Yao, Email boxiang_du@163.com; yaoleijiangsu1987@163.comPurpose: This study aims to investigate how the type of anesthesia used during major orthopedic surgery may impact adverse short-term postoperative outcomes depending on frailty.Methods: To conduct this investigation, we recruited individuals aged 65 years and older who underwent major orthopedic surgery between March 2022 and April 2023 at a single institution. We utilized the FRAIL scale to evaluate frailty. The primary focus was on occurrences of death or the inability to walk 60 days after the surgery. Secondary measures included death within 60 days; inability to walk without human assistance at 60 days; death or the inability to walk without human assistance at 30 days after surgery, the first time out of bed after surgery, postoperative blood transfusion, length of hospital stay, hospital costs, and the occurrence of surgical complications such as dislocation, periprosthetic fracture, infection, reoperation, wound complications/hematoma.Results: In a study of 387 old adult patients who had undergone major orthopedic surgery, 41.3% were found to be in a frail state. Among these patients, 262 had general anesthesia and 125 had neuraxial anesthesia. Multifactorial logistic regression analyses showed that anesthesia type was not linked to complications. Instead, frailty (OR 4.04, 95% CI 1.04 to 8.57, P< 0.001), age (OR 1.05, 95% CI 1.00– 1.10, P= 0.017), and aCCI scores, age-adjusted Charlson Comorbidity Index, (OR 1.36, 95% CI 1.12 to 1.66, P= 0.002) were identified as independent risk factors for death or new walking disorders in these patients 60 days after surgery. After adjusting for frailty, anesthesia methods was not associated with the development of death or new walking disorders in these patients (P > 0.05).Conclusion: In different frail populations, neuraxial anesthesia is likely to be comparable to general anesthesia in terms of the incidence of short-term postoperative adverse outcomes.Keywords: anesthesia, frailty, major orthopedic surgery, death, impaired walking ability

Yuanyuan Ding,&ast; Linjiang Chen,&ast; Jing Xu, Yuhan Feng, Qiong Liu Department of Ophthalmology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiong Liu, Department of Ophthalmology, Nanfang Hospital, Southern Medical University, No. 1838, North Guangzhou Avenue, Baiyun District, Guangzhou, Guangdong Province, 510515, People’s Republic of China, Tel +86-13922442109, Email nanfanglq2023@163.comObjective: Diabetic retinopathy (DR) can cause permanent blindness with unstated pathogenesis. We aim to find novel biomarkers and explore the mechanism of apoptotic protease activating factor 1 (APAF1) in DR.Methods: Differential expression genes (DEGs) were screened based on GSE60436 dataset to find hub genes involved in pyroptosis after comprehensive bioinformatics analysis. DR mice model was constructed by streptozotocin injection. The pathological structure of retina was observed using hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was applied to assess inflammatory factors, vascular endothelial growth factor (VEGF), and oxidative stress. The mRNA and protein expression levels were detected using quantitative real-time polymerase-chain reaction and Western blot. Cell counting kit and flow cytometry were employed to detect proliferation and apoptosis in high glucose-induced ARPE-19 cells.Results: Total 71 pyroptosis-related DEGs were screened. BIRC2, CXCL8, APAF1, PPARG, TP53, and CYCS were identified as hub genes of DR. APAF1 was selected as a potential regulator of DR, which was up-regulated in DR mice. APAF1 silencing alleviated retinopathy and inhibited pyroptosis in DR mice with decreased levels of inflammatory factors, VEGF, and oxidative stress. Moreover, APAF1 silencing promoted proliferation while inhibiting apoptosis and caspase-3/GSDME-dependent pyroptosis with a decrease in TNF-α, IL-1β, IL-18, and lactate dehydrogenase in high glucose-induced ARPE-19 cells. Additionally, caspase-3 activator reversed the promotion effect on proliferation and inhibitory effect on apoptosis and pyroptosis after APAF1 silencing in high glucose-induced ARPE-19 cells.Conclusion: APAF1 is a novel biomarker for DR and APAF1 silencing inhibits the development of DR by suppressing caspase-3/GSDME-dependent pyroptosis.Keywords: diabetic retinopathy, APAF1, caspase-3, GSDME, pyroptosis

Yue Wang,1 Jie Chen,1 Han Dong,2 Rui-Lin Ma,1 Ying Zou,3 Wei Wang,4 Qingmei Zheng,5 Ying Feng,6 Zhangyun Tan,7 Xiaoqin Zeng,8 Yinqing Zhao,7 Yan Deng,1 Yanfang Wang,1 Bei Gu,9 Aijun Sun1,10 1National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Women and Children’s Hospital of Jinzhou, Jinzhou, Liaoning, 121000, People’s Republic of China; 3Department of Obstetrics and Gynecology, Hunan Provincial Maternal and Child Health Care Hospital, Changsha, Hunan, 410008, People’s Republic of China; 4Department of Reproductive Medicine, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 5Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266500, People’s Republic of China; 6Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 7Department of Obstetrics and Gynecology, Xinhui Maternity and Children’s Hospital, Nanning, Guangxi, 529100, People’s Republic of China; 8Department of Gynecology, Guangzhou Women and Children’s Medical Center, Guangzhou, Guangdong, 510000, People’s Republic of China; 9Department of Obstetrics and Gynecology, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing, 100038, People’s Republic of China; 10Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100010, People’s Republic of ChinaCorrespondence: Aijun Sun, Email saj@pumch.cnBackground: The basic medical education stage is not enough to support physicians to fully diagnose and evaluate polycystic ovary syndrome (PCOS). The study aims to discover the difference in treatment choice between participants with different annual consultation number of PCOS, to promote lifelong learning, and drive balanced development within healthcare.Methods: This is a multicenter cross-sectional survey. Participants’ basic information, knowledge of PCOS and treatment options were collected online. According to the annual consultation number of patients with PCOS, physicians were divided into three groups: 0– 50 people/yr, 50– 200 people/yr, and > 200 people/yr, and the results were derived from χ2 test, Fisher exact test, and multivariate logistic regression analysis.Results: The study analyzed 1689 questionnaires, and 1206 physicians (71.4%) received less than 50 women per year, 388 physicians (30.0%) with an annual number of 50– 200 women, and 95 physicians (5.6%) with patient turnover for more than 200 people. Reproductive endocrinologists generally have higher access to the clinic. As the number of visits increases, more and more physicians would perceive patients as more likely to have abnormal blood glucose and heavy weight. Physicians with large numbers of consultations are more likely to use Asian or Chinese standards to assess obesity. The multivariate analysis involved variables such as age, hospital level, specialty, and patient turnover annually, and more young doctors actively assessed lipid profile (odds ratio (OR) 1.56, 95% confidence interval (CI) (1.16, 2.16)), and primary hospitals (OR 0.65 CI (0.44, 0.89)) chose OGTT for blood glucose assessment less than tertiary hospitals. Physicians in secondary hospitals are more aggressive in evaluating androgens.Conclusion: Our survey found differences in endocrine assessment, metabolic screening, and treatment in PCOS women in terms of the number of obstetrician-gynecologists who received different patient consultation numbers. The importance of continuing education for physicians is emphasized, to promote lifelong learning.Keywords: polycystic ovary syndrome, consultation number, lifelong learning, insulin resistance, obesity, hyperandrogenemia, metformin

Xinyi Long,1 Fangfang Li,1 Sishi Tang,1 Jing Liu,1 Yunfeng Fu,2 Yanhui Feng3 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of China; 3Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of ChinaCorrespondence: Yanhui Feng, Department of Oncology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Hexi, Changsha, Hunan Province, People’s Republic of China, Tel +86-13549656766, Email fengyanhui900@sohu.comPurpose: Immunological regimens are an important area of research for treating multiple myeloma (MM). Plasma cells play a crucial role in immunotherapy.Patients and Methods: In our study, we used both single-cell RNA sequencing (scRNA-seq) and bulk sequencing techniques to analyze MM patients. We analyzed each sample using gene set variation analysis (GSVA) based on immune-related gene sets. We also conducted further analyses to compare immune infiltration, clinical characteristics, and expression of immune checkpoint molecules between the H-S100A9 and L-S100A9 groups of MM patients.Results: We identified eight subpopulations of plasma cells, with S100A9 plasma cells being more abundant in patients with 1q21 gain and 1q21 diploid. CellChat analysis revealed that GAS and HGF signaling pathways were prominent in intercellular communication of S100A9 plasma cells. We identified 14 immune-related genes in the S100A9 plasma cell population, which allowed us to classify patients into the H-S100A9 group or the L-S100A9 group. The H-S100A9 group showed higher ESTIMATE, immune and stroma scores, lower tumor purity, and greater immune checkpoint expression. Patients with 1q21 gain and four or more copies had the lowest ESTIMATE score, immune score, stroma score, and highest tumor purity. Drug sensitivity analysis indicated that the H-S100A9 group had lower IC50 values and greater drug sensitivity compared to the L-S100A9 group. Quantitative reverse transcription (RT-q) PCR showed significantly elevated expression of RNASE6, LYZ, S100A8, S100A9, and S100A12 in MM patients compared to the healthy control group.Conclusion: Our study has identified a correlation between molecular subtypes of S100A9 plasma cells and the response to immunotherapy in MM patients. These findings improve our understanding of tumor immunology and provide guidance for developing effective immunotherapy strategies for this patient population.Keywords: multiple myeloma, single-cell sequencing, bulk transcription, tumor immune microenvironment, S100A9

Yuting Feng, Xue Bao, Jinxuan Zhao, Lina Kang, Xuan Sun, Biao Xu Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Xuan Sun; Biao Xu, Department of Cardiology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email sunxuan891119@163.com; xubiao62@nju.edu.cnIntroduction: Acute inflammatory storm is a major cause of myocardial ischemia/reperfusion (I/R) injury, with no effective treatment currently available. The excessive aggregation of neutrophils is correlated with an unfavorable prognosis in acute myocardial infarction (AMI) patients. Exosomes derived from mesenchymal stromal cells (MSC-Exo) have certain immunomodulatory potential and might be a therapeutic application. Therefore, we investigated the protective role of MSC-Exo in modulating neutrophil infiltration and formation of neutrophil extracellular traps (NETs) following myocardial I/R injury.Methods: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. We used flow cytometry, histochemistry, and immunofluorescence to detect the changes of neutrophils post-intravenous MSC-Exo injection. Additionally, cardiac magnetic resonance (CMR) and thioflavin S experiments were applied to detect microvascular obstruction (MVO). The NLR family pyrin domain containing 3 (NLRP3) inflammasome was examined for mechanism exploration. Primary neutrophils were extracted for in vitro experiment. Antibody of Ly6G was given to depleting the neutrophils in mice for verification the effect of MSC-Exo. Finally, we analyzed the MiRNA sequence of MSC-Exo and verified it in vitro.Results: MSC-Exo administration reduced neutrophil infiltration and NETs formation after myocardial I/R. MSC-Exo treatment also could attenuate the activation of NLRP3 inflammasome both in vivo and in vitro. At the same time, the infarction size and MVO following I/R injury were reduced by MSC-Exo. Moreover, systemic depletion of neutrophils partly negated the therapeutic effects of MSC-Exo. Up-regulation of miR-199 in neutrophils has been shown to decrease the expression of NETs formation after stimulation.Discussion: Our results demonstrated that MSC-Exo mitigated myocardial I/R injury in mice by modulating neutrophil infiltration and NETs formation. This study provides novel insights into the potential therapeutic application of MSC-Exo for myocardial ischemia/reperfusion injury. Keywords: myocardial ischemia/reperfusion injury, mesenchymal stromal cells, exosomes, neutrophil extracellular traps, mir-199

Qiong Ge,1,&ast; Zhewen Zhang,2,&ast; Zhiming Cao,2 Dan Wu,3 Changping Xu,1 Jianbiao Yao,3 Jian Gao,1 Yan Feng1 1Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, 310057, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Feng, Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China, Tel/Fax +86-571-87115204, Email yfeng@cdc.zj.cnPurpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components.Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments.Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds.Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.Keywords: antiviral effects, material basis analysis, component-target-pathway-disease network, protein–protein interaction network, core targets, rosmarinic acid

Zhongxu Jing,&ast; Wenqing Li,&ast; Wei Liao, Ying Lv, Yuwei Liu, Haibo Jiang, Yufei Feng Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yufei Feng, Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Harbin, 150040, People’s Republic of China, Tel +86-18503653988, Email fuf-002@163.comPurpose: The aim of the present study was to fabricate a Fructus Xanthii and Magnolia liliiflora volatile oils liposomes-loaded thermosensitive in situ gel (gel/LIP/volatile oil) for effectively treating allergic rhinitis via intranasal administration.Patients and Methods: Particle size, polymer dispersity index (PDI), entrapment effectiveness, and cumulative drug permeation of the developed liposomes were assessed. Then, a thermoreversible in situ gel was created using the liposomes loaded with volatile oils of Fructus Xanthii and Magnolia liliiflora. The effectiveness of this treatment for allergic rhinitis was confirmed by evaluating nasal symptoms, and hematological results, after injecting the formulation into the ovalbumin (OVA)-sensitized mice, we conducted hematoxylin-eosin staining (HE) and immunohistochemistry to evaluate the outcomes. The effects of the gel/LIP/volatile oil formulation for nasal delivery of volatile oil in the treatment of rhinitis were then assessed.Results: The average particle size was 95.1 ± 3.6 nm, and the encapsulation efficiencies of Fructus Xanthii and Magnolia liliiflora volatile oils were 70.42 ± 5.41% and 67.10 ± 6.08%, respectively. Drug loadings of Fructus Xanthii and Magnolia liliiflora volatile oils were 9.10 ± 0.98% and 16.10 ± 1.03%, respectively. The binary formulation produced a gel rapidly in the nasal cavity with a strong mucosal adherence at a temperature of delivering volatile oil to the nasal mucosa steadily and continuously. After nasal administration, the gel/LIP/volatile oil sustained the volatile oil delivery into the mucosa. In comparison to the monolithic formulations, the gel/LIP/volatile oil binary formulation exhibited superior performance in terms of drug delivery capability and pharmacodynamic effects.Conclusion: This binary preparation displayed the ability to deliver drugs to the nasal mucosa and exhibited positive pharmacodynamic effects in treating OVA-induced rhinitis in mice. As a result, it has the potential to serve as a delivery platform for Traditional Chinese medicine in the treatment of allergic rhinitis.Keywords: volatile oil of Magnolia liliiflora, volatile oil of Fructus Xanthii, liposomes, thermosensitive gel, allergic rhinitis

Leyao Shi,1 Yahui Feng,2 Dongmei Shi2,3 1The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2The Laboratory of Medical Mycology, Jining No. 1 People’s Hospital, Jining, Shandong, People’s Republic of China; 3Department of Dermatology, Jining No. 1 People’s Hospital, Jining, Shandong, People’s Republic of ChinaCorrespondence: Dongmei Shi, Department of Dermatology, Jining No. 1 People’s Hospital, No. 6 Jiankang Road, Jining, Shandong Province, 272000, People’s Republic of China, Tel +86 537-6051008, Email shidongmei28@163.comAbstract: The clinical manifestation of superficial candidiasis varies depending on the infectious sites and causative Candida species that brings a great challenge to diagnose or treat without mycological or pathological evidence in clinical settings. Oral mucosal candidiasis and onychomycosis are most common types of superficial candidiasis. Typically, oral mucosal candidiasis manifests as white or erythematous thrush coated on the tongue and other interior oral cavity; and onychomycosis caused by Candida spp. presents with thick, fragile, or cracked fingernails or toenails in yellow or white discoloration. Here, we report one case of patient with a black hairy tongue caused by Candida tropicalis and one case of greenish discolored onychomycosis caused by Candida parapsilosis. The cases of superficial candidiasis with the same discolored lesions were searched in literature and compared with our cases in clinical manifestation, causative pathogen and treatment. These cases highlight the importance of mycological diagnosis for identifying non-Candida albicans Candida species (NCAC) in superficial infections to guide an effective therapy.Keywords: Candida tropicalis, Candida parapsilosis, onychomycosis, black hairy tongue, nail discoloration

Jiawei Lu,1 Lebin Song,1 Jiaochen Luan,2 Yifei Feng,1 Yidan Wang,1 Xuechen Cao,1 Yan Lu1 1Department of Dermatology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Yan Lu, Department of Dermatology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 13913967126, Email luyan6289@163.comBackground: Vitiligo and Hashimoto’s thyroiditis (HT) are concomitant autoimmune diseases characterized by the destruction of melanocytes or thyrocytes. We aimed to explore the immunological mechanism of this comorbidity and screen their potential biomarkers.Methods: We downloaded the microarray datasets from the GEO database. Differentially expressed genes (DEGs) and immune-related genes (IRGs) were selected. The immune-related differentially expressed genes (IRDEGs) were obtained by taking the intersection. Candidate biomarkers were elected by Cytoscape software. CIBERSORT was used to depict immune cell infiltration prospects. Correlation analysis was conducted between infiltrating cells and several indicators. The results were validated by real-time quantitative PCR (RT-qPCR).Results: Three datasets and 60 IRDEGs were obtained in total. Pathway enrichment analysis showed that the T cell receptor signaling pathway, IL-17 signaling pathway, receptor-ligand activity, and signaling receptor activator activity were significantly enriched. We screened out four hub genes, including IFNG, STAT1, IL1B, and CXCL10. The ROC curve indicated the highest diagnostic value of CXCL10 in both vitiligo and HT. Immuno-infiltration analysis revealed significant changes in T cell subsets and macrophage subtypes, which were correlated with four hub genes, melanocyte markers, and thyroid-specific antigens. qPCR validated the hub genes in peripheral blood mononuclear cells from patients with comorbidity.Conclusion: IFNG, STAT1, IL1B, and CXCL10, were the key IRDEGs to vitiligo and HT. These genes may participate in the comorbidity by remodeling the immune cell infiltration pattern, and cross-expressed antigens may mediate the common damage of melanocytes and thyroid tissues.Keywords: depigmenting skin disorder, autoimmune thyroiditis, immune cell infiltration, bioinformatics analysis

Ying Lv, Wenqing Li, Wei Liao, Haibo Jiang, Yuwei Liu, Jiansheng Cao, Wenfei Lu, Yufei Feng Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education, Harbin, 150040, People’s Republic of ChinaCorrespondence: Yufei Feng, 150040, Tel +86-18503653988, Email fuf-002@163.comAbstract: Natural products have proven to have significant curative effects and are increasingly considered as potential candidates for clinical prevention, diagnosis, and treatment. Compared with synthetic drugs, natural products not only have diverse structures but also exhibit a range of biological activities against different disease states and molecular targets, making them attractive for development in the field of medicine. Despite advancements in the use of natural products for clinical purposes, there remain obstacles that hinder their full potential. These challenges include issues such as limited solubility and stability when administered orally, as well as short durations of effectiveness. To address these concerns, nano-drug delivery systems have emerged as a promising solution to overcome the barriers faced in the clinical application of natural products. These systems offer notable advantages, such as a large specific surface area, enhanced targeting capabilities, and the ability to achieve sustained and controlled release. Extensive in vitro and in vivo studies have provided further evidence supporting the efficacy and safety of nanoparticle-based systems in delivering natural products in preclinical disease models. This review describes the limitations of natural product applications and the current status of natural products combined with nanotechnology. The latest advances in nano-drug delivery systems for delivery of natural products are considered from three aspects: connecting targeting warheads, self-assembly, and co-delivery. Finally, the challenges faced in the clinical translation of nano-drugs are discussed. Keywords: natural products, nanotechnology, drug delivery, targeting

Zongfeng Zhao,1,&ast; Jie Cheng,2,&ast; Wanqun Sun,1 Jian Zhu,3 Sheng Lu,3 Yanyan Feng,4 Zhendong Song,5 Yali Yang,6 Xiujuan Wu3 1Department of Scientific Research, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, People’s Republic of China; 4Chengdu Second People’s Hospital, Chengdu, Sichuan Province, People’s Republic of China; 5WLSA Shanghai Academy, Shanghai, People’s Republic of China; 6Department of Dermatology, Shanghai Ninth Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yali Yang, Department of Dermatology, Shanghai Ninth Hospital affiliated to Shanghai Jiao Tong University, School of Medicine, No. 639, Manufacturing Bureau Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Email ky7812@126.com Xiujuan Wu, Department of Dermatology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, No. 966, Huaihai Middle Road, Xuhui District, Shanghai, 200031, People’s Republic of China, Email xjwuxj@sina.comPurpose: Psoriasis is an incurable chronic inflammatory skin disease. The exact function and regulatory mechanism of non-coding RNA upregulation in psoriasis remains to be elucidated. The aim of this study was to analyse the role of the lncRNA-miRNA-mRNA network of psoriasis and LINC01176 in the pathogenesis of psoriasis.Patients and Methods: We performed miRNA, lncRNA, and mRNA sequencing analysis in pretreatment and treatment psoriatic tissues and normal tissues, constructed an lncRNA-miRNA-mRNA coexpression network and screened mRNA-associated pathways using bioinformatics analysis. We further validated the regulatory role of LINC01176-miR-218-5p on the proliferation and inflammation of the psoriatic model by dual-luciferase reporter assay, cell transfection, CCK-8 method, TUNEL staining and animal model construction method. An lncRNA-miRNA-mRNA coexpression network was successfully constructed by RNA-seq data analysis.Results: We obtained the relationship between LINC01176, miR-218-5p and IL36-G. Analysis of the apoptotic and proliferative capacity of the transfected cells showed that miR-218-5p up-regulation significantly inhibited cell proliferation and promoted apoptosis. A mouse model of psoriasis was successfully established. Phenotypic observations revealed that keratin-forming cells in mice coated with LINC01176-shRNA emulsifier were significantly lower than those in the model group and close to those in the normal group. HE and immunohistochemical experiments were performed, and the results showed the role and mechanism of action of LINC01176-shRNA. Suppression of LINC01176 significantly inhibited the expression of IL-36G in psoriatic tissues. LINC01176 showed a targeting and positive correlation with IL36-G expression.Conclusion: Our study shows that LINC01176 promotes the proliferation and invasion of keratinocytes and inhibits apoptosis by targeting miR-218-5p, which acts as a repressor of the psoriasis-associated IL-36G. The shRNA-LINC01176 emulsion showed potential treatment capability in alleviating symptoms of psoriasis.Keywords: psoriasis, LINC01176, IL-36G, inflammation

Xuan Zhao,1,&ast; Yang Niu,1,&ast; Xue-Lin Zhao,1,&ast; Hui-Juan Ruan,1 Yi Xiang,1 Ling-Yu Wang,1 Yi Feng,1,2 Qing-Ya Tang1,2 1Department of Clinical Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Digestion and Nutrition, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Ya Tang; Yi Feng, Email tangqingya@xinhuamed.com.cn; fengyi@xinhuamed.com.cnPurpose: To explore the relationships between serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) levels and glucolipid metabolism disorders (GLMD) in obese children and adolescents.Patients and Methods: In this cross-sectional study, 105 obese children and adolescents were selected for the detection of TNF-α, IL-6, hs-CRP, and glycolipid metabolism indicators. All participants were divided into elevated TNF-α group (≥ 8.1 pg/mL; n=49) and normal TNF-α group (< 8.1 pg/mL; n=56), elevated IL-6 group (≥ 5.9 pg/mL; n=13) and normal IL-6 group (< 5.9 pg/mL; n=92), elevated hs-CRP group (≥ 3.0 mg/L; n=44) and normal hs-CRP group (< 3.0 mg/L; n=61), respectively.Results: Low-density lipoprotein cholesterol (LDL-C) in the elevated TNF-α group was higher than that in the normal TNF-α group (P=0.010). TNF-α was positively correlated with LDL-C (P=0.005). Fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) in the elevated IL-6 group were higher than those in the normal IL-6 group (all for P < 0.05), while high-density lipoprotein cholesterol (HDL-C) in the elevated IL-6 group was lower than that in the normal IL-6 group (P< 0.001). IL-6 was positively correlated with FINS, 2-hour postprandial insulin, HOMA-IR and triglyceride (all for P < 0.01), while was negatively correlated with HDL-C (P=0.006). Moreover, hs-CRP was positively correlated with FINS and HOMA-IR (all for P < 0.05).Conclusion: There may be correlations between serum TNF-α, IL-6, hs-CRP levels and GLMD in obese children and adolescents. Attention should be paid to monitoring serum inflammatory factors and preventing their elevation in obese children and adolescents, thus reducing the occurrence of GLMD.Keywords: tumor necrosis factor-alpha, interleukin-6, high-sensitivity C-reactive protein, glucolipid metabolism disorders, obesity, children and adolescents

Cuiling Zhang,1,&ast; Ziyan Yang,2,&ast; Rongxin Du,3 Yong Feng,4 Xiaohong Zhang,5 Junyan Zhang6 1Department of Digestive Oncology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2College of Nursing, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Urology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4College of Nursing, Shanxi University of Chinese Medicine, Taiyuan, People’s Republic of China; 5Nursing Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 6Department of Clinical Epidemiology and Evidence-Based Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaohong Zhang, Nursing Department, Third Hospital of Shanxi Medical University, Shanxi, Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, NO. 99, Longcheng Street, Xiaodian District, Taiyuan, 030032, People’s Republic of China, Tel +86-13453443366, Email zxhxb2013@126.comPurpose: Elucidation of the cardio-oncologic knowledge among the oncology nurses of tertiary hospitals in Shanxi Province to provide better insights and directions for management by nursing managers.Background: China’s National Health and Wellness Commission issued the Action Plan for Further Improving Nursing Services in June 2023, which requires nurses to provide patients with physical and mental holistic nursing services, such as medical care, condition observation, assistance with treatment, and health guidance. Most oncology patients are treated with chemotherapy, but the modality can cause greater harm to patients, especially cardiotoxicity. How to provide precise care for chemotherapy patients is a problem for nursing managers.Methods: In order to investigate the level of cardio-oncologic knowledge among the oncology nurses of tertiary care hospitals in Shanxi Province, China, a questionnaire was created based on the relevant literature and the provided instructions on cardio-oncology. The chi-squared test was performed for multiple comparisons of the level of knowledge of disease observation, health guidance, and implementation of treatment. Spearman correlation analysis was performed to analyze the correlation between the levels of cardio-oncologic knowledge and general information of hospitals and nurses.Results: Cardio-oncology awareness among the oncology nurses was 0.1%– 44.7%, the awareness rate of single dimension was 0 to 3.9%, and overall awareness rate was 0. A partially significant difference was revealed in the two-by-two comparisons of the awareness rates of the three dimensions of disease observation, health guidance, and implementation of treatment (P < 0.05). A correlation was observed between the cardio-oncologic knowledge and some of the hospital and the nurses’ general information data (P < 0.05).Conclusion: Oncology nurses exhibited a low rate of awareness related to cardio-oncology. Hospitals could establish oncology nursing teams to train the oncology nurses to promote their cardio-oncologic knowledge and ensure the quality of daily care provided by these nurses.Keywords: oncology nurse, cardio-oncology, cardiotoxicity, awareness, precision nursing care, nursing management

Decheng Meng,1 Fengxia Zhang,2 Wenfei Yu,1 Xin Zhang,1 Guoliang Yin,1 Pengpeng Liang,3 Yanan Feng,1 Suwen Chen,1 Hongshuai Liu1 1The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China; 2Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China; 3Shenzhen Hospital, Shanghai University of Traditional Chinese Medicine, Shenzhen, 518001, People’s Republic of ChinaCorrespondence: Fengxia Zhang, Department of Neurology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250011, People’s Republic of China, Tel +86-131-5317-5246, Email fxzhang0987@163.comAbstract: Non-alcoholic fatty liver disease(NAFLD) is an umbrella term for a range of diseases ranging from hepatic fat accumulation and steatosis to non-alcoholic steatohepatitis (NASH) in the absence of excessive alcohol consumption and other definite liver damage factors. The incidence of NAFLD has increased significantly in recent years and will continue to grow in the coming decades. NAFLD has become a huge health problem and economic burden. SIRT1 is a member of Sirtuins, a group of highly conserved histone deacetylases regulated by NAD+, and plays a vital role in regulating cholesterol and lipid metabolism, improving oxidative stress, inflammation, and insulin resistance through deacetylating some downstream transcription factors and thus improving NAFLD. Although there are no currently approved drugs for treating NAFLD and some unresolved limitations in developing SIRT1 activators, SIRT1 holds promise as a proper therapeutic target for NAFLD and other metabolic diseases. In recent years, natural products have played an increasingly important role in drug development due to their safety and efficacy. It has been discovered that some natural products may be able to prevent and treat NAFLD by targeting SIRT1 and its related pathways. This paper reviews the mechanism of SIRT1 in the improvement of NALFD and the natural products that regulate NAFLD through SIRT1 and its associated pathways, and discusses the potential of SIRT1 as a therapeutic target for treating NAFLD and the effectiveness of these related natural products as clinical drugs or dietary supplements. These works may provide some new ideas and directions for finding new therapeutic targets for NAFLD and the development of anti-NAFLD drugs with good pharmacodynamic properties. Keywords: NAFLD, SIRT1, natural products, FFA, TG

Zhimin Ding,1,&ast; Jing Gao,2,&ast; Yixuan Feng,1,&ast; Mengyu Wang,1 Huandong Zhao,1 Ruonan Wu,1 Xinyue Zheng,1 Xiaodong Feng,1,2 Mingyin Lai3 1School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Department of Rehabilitation Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3School of Traditional Chinese Medicine, Hainan Medical University, Haikou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Feng; Mingyin Lai, Email fxd0502@163.com; dearl_0524@163.comBackground: Post-stroke depression (PSD) is one of the most common complications of stroke. Electroacupuncture (EA) is an effective traditional Chinese medicine treatment for PSD, which is widely used in clinical settings. EA has a significant therapeutic effect against PSD, but the mechanism is still unclear. This study aimed to determine whether EA ameliorates depression-like behaviors in PSD rats by regulating the adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK)-mediated mitochondrial function.Methods: Middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS) were used to develop a PSD rat model. To elucidate the role of AMPK in EA treatment, compound C, a selective inhibitor of AMPK, was injected into the lateral ventricle of rats before EA treatment. EA treatment was performed for 14 consecutive days for 30 min per day after PSD modeling. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. Behavioral tests were conducted to evaluate depression-like phenotypes in rats. Depression-like behaviors were tested by sucrose preference test (SPT), novelty suppressed feeding test (NSFT), and open-field test (OFT). The structure and morphology of the prefrontal cortex were observed by histopathological hematoxylin-eosin (HE) and Nissl staining. The mitochondrial morphology and function were analyzed by colorimetry, chemiluminescence, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR).Results: EA treatment successfully ameliorated depression-like behaviors, upregulated AMPK expression, and improved mitochondrial function. However, AMPK inhibition by Compound C exacerbated depression-like behaviors and aggravated neuronal and mitochondrial injury in PSD rats.Conclusion: EA treatment improved depression-like behaviors in PSD rats and promoted mitochondrial function by activating AMPK.Keywords: electroacupuncture, post-stroke depression, mitochondria, AMPK

Yang Gou,&ast; Yongjie Tang,&ast; Shuiqing Liu, Siyu Cheng, Xiaojuan Deng, Qin Wen, Yimei Feng, Xiangui Peng, Ping Wang, Xi Zhang Medical Center of Hematology, Xinqiao Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Wang, Medical Center of Hematology, The Xinqiao Hospital of Army Medical University, Chongqing, People’s Republic of China, Email wpii_2002@sina.comAbstract: The ETV6::PDGFRB fusion gene is commonly reported in chronic myelomonocytic leukemia with eosinophilia, yet patients with ETV6::PDGFRB presenting myeloid and lymphoid neoplasms successively have not been reported. Here, we report the first case of a 35-year-old man with myeloid and lymphoid neoplasms harboring an ETV6::PDGFRB fusion gene who demonstrated poor response to imatinib. The patient was diagnosed with an ETV6::PDGFRB fusion gene myeloid neoplasm on initial diagnosis at our hospital. After 5 months of treatment with imatinib, he was diagnosed with T-cell lymphoblastic lymphoma. ETV6::PDGFRB turned negative after increasing the dose of imatinib, but enlarged superficial lymph nodes reappeared the following year. Notably, the patient exhibited a worse response to imatinib treatment. This study describes this rare case and speculates on a possible mechanism.Keywords: ETV6, PDGFRB, fusion, myeloid/lymphoid neoplasms, imatinib

Xue Wang,1– 3 Xiaomei Liu,2 Radouil Tzekov,4 Chaofeng Yu,1 Jiasong Yang,1,5 Yuliang Feng,1 Yajun Wu,1 Yali Xu,1 Shiying Li,6 Wensheng Li1,5,7 1Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of China; 2Suzhou Institute of Biomedical Engineering and Technology, University of Science and Technology of China, Suzhou, People’s Republic of China; 3Department of Ophthalmology, Second Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Ophthalmology, University of South Florida, Tampa, FL, USA; 5Shanghai Aier Eye Hospital, Shanghai, People’s Republic of China; 6Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of China; 7Shanghai Aier Eye Insititute, Shanghai, People’s Republic of ChinaCorrespondence: Wensheng Li, Shanghai Aier Eye Hospital, 83 Wuzhong Road, Shanghai, People’s Republic of China, Email drlws@qq.com Shiying Li, Department of Ophthalmology, Xiang’an Hospital of Xiamen University, Xiamen University, Xiamen, People’s Republic of China, Email shiying_li@126.comPurpose: This study aimed to determine the effect and its mechanism of fenofibrate on retinal pigment epithelium (RPE) injury induced by excessive fat in vitro and in vivo.Methods: ARPE-19 cells were co-incubated with palmitic acid (PA) and fenofibric acid (the active form of fenofibrate after metabolism in vivo) and mice fed with high-fat diet (HFD) were supplemented with fenofibrate. The following methods were used: Western blot and immunofluorescent staining to determine expressions of reactive oxygen species (ROS)–associated factors and proinflammatory cytokines; electroretinogram (ERG) c-wave to evaluate RPE function; TUNEL staining to detect the apoptotic cell in RPE tissue. Additionally, ARPE19 cells were treated with PI3K/AKT inhibitor or agonist to investigate the mechanism of fenofibric acid inhibiting PA-induced RPE damage.Results: We found that the application of PA inhibited RPE cell viability in a dose-dependent manner, and increased the levels of NAPDH oxidase 4 (NOX4), 3-nitrotyrosin (3-NT), intracellular adhesion molecule-1(ICAM1), tumor necrosis factor alpha (TNFα) and vascular endothelial growth factor (VEGF) at 400μM. The application of fenofibric acid resulted in the inhibition of NOX4, 3-NT, TNFα, ICAM1 and VEGF expression in ARPE-19 cells treated with PA. Moreover, wortmannin, as a selective inhibitor of PI3K/AKT pathway, abolished the effects of fenofibrate on the oxidative stress and inflammation in ARPE-19 cells. In addition, 740Y-P, a selective agonist of PI3K/AKT pathway, enhanced the protective action of fenofibrate. Meanwhile, in vivo dosing of fenofibrate ameliorated the downregulated amplitudes of ERG c-wave in HFD-fed mice and suppressed the HFD-induced oxidative injury and inflammatory response in RPE tissues.Conclusion: Our results suggested that fenofibrate ameliorated RPE cell damage induced by excessive fat in vitro and in vivo, in part, through activation of the PI3K/AKT signaling pathway.Keywords: fenofibrate, RPE, palmitic acid, high-fat diet, oxidative stress, inflammation

Xiaosi Li,1 Yan Feng,2 Dan Li,3 Liyang Chen,1 Mengli Shen,1 Hongsheng Li,1 Shuo Li,3 Xiaoyan Wu,1 Lingling Lu3 1Department of Clinical Laboratory, The Second Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China; 2Department of Clinical Laboratory, Jiaxing Maternity and Child Health Care Hospital Affiliated to Jiaxing University, Jiaxing, People’s Republic of China; 3Key laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Dian Diagnostics Group Co, Ltd, Hangzhou, People’s Republic of ChinaCorrespondence: Lingling Lu, Key laboratory of Digital Technology in Medical Diagnostics of Zhejiang Province, Dian Diagnostics Group Co, Ltd, No. 329, Jinpeng Street, Sandun Town, West Lake District, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Tel +86-13587528187, Email lull1@dazd.cn Xiaoyan Wu, Department of Clinical Laboratory, the Second Affiliated Hospital of Jiaxing University, No. 1518, North Huancheng Road, Nanhu District, Jiaxing, Zhejiang Province, 314000, People’s Republic of China, Tel +86-13586330218, Email wxy87751@163.comPurpose: Nocardia gipuzkoensis is a novel species that solely identified in patients with pulmonary infections by far. Growing evidence showed the excellent performance of metagenomics next-generation sequencing (mNGS) on pathogenic identification, especially for new species. Here, we described the first case of an elderly female patient suddenly suffering from neurological disorders owing to N. gipuzkoensis infection. And linezolid could effectively treat N. gipuzkoensis infection.Patients and Methods: The results of imaging, laboratory cultures, and mNGS, as well as therapeutic process are shared.Results: An elderly female patient suddenly suffered from neurological disorders with dysphasia and right limb trembles under no obvious causes. Subsequently, she was diagnosed as intracranial space-occupying lesions by magnetic resonance imaging (MRI). The isolate from brain secretion was further identified as N. gipuzkoensis through mNGS. The targeted therapy with linezolid according to the antimicrobial susceptibility was used to treat cerebral abscess induced by N. gipuzkoensis. During the follow-up, no relapse was observed for the patient after surgery for 104 days.Conclusion: Cerebral abscess induced by N. gipuzkoensis is rare disorder with high mortality. mNGS has been identified as a promising tool in pathogen diagnosis for timely therapy. Linezolid as one of the antimicrobial drugs could effectively treat N. gipuzkoensis infection and prevent adverse outcomes.Keywords: Nocardia gipuzkoensis, cerebral abscess, metagenomics next-generation sequencing, linezolid, mNGS