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Yongming Xu,1,&ast; Junzhen Wu,1,&ast; Qingqing Jiang,2 Yingying Lv,1 Jin Zhou,1 Zhiyu Wang,3 Hui Zhao,3 Dongping Du1 1Department of Pain Management Center, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Neurology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Internal Oncology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongping Du, Department of Pain Management Center, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China, Tel +86-21-24058896, Email dudp@sjtu.edu.cn Hui Zhao, Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86-21-24058328, Fax +86-21-240598328, Email zhao-hui@sjtu.edu.cnObjective: Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy and it is currently intractable We compared the efficacy of transcutaneous electrical acupoint stimulation (TEAS) against non-TEAS groups and investigated the variables that predict effective relief of upper extremity pain in cancer survivors with CIPN.Methods: We retrospectively collected data of cancer survivors who developed CIPN between May 2017 to March 2022. All eligible CIPN patients were divided into TEAS group (received TEAS) and non-TEAS group (did not receive TEAS) in our department. A 1:1 ratio propensity score matching (PSM) was used to balance the baseline features. The change of numerical rating scale (NRS), Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and sympathetic skin response (SSR) parameters are all assessed after treatment. The procedure was considered a clinically effective relief if the patients’ NRS scores were reduced by 50% or more, and overall patients with effective relief were all counted after treatment. Furthermore, a multivariable logistic regression model was utilized to evaluate the predictors of effective relief following CIPN treatment.Results: : A total of 102 cancer survivors with CIPN were analyzed after PSM (51 in each group). The change of NRS, SF-MPQ-2, SSR latency and SSR amplitude in TEAS group were significantly higher than those in non-TEAS group at 3 weeks after therapy (all P< 0.01). In addition, the effective relief rate was significantly higher in TEAS group than in non-TEAS group (P=0.026). Multivariate logistic regression on the total study cohort showed that TEAS group (OR 2.783, P = 0.025) and the baseline SSR amplitude of the upper extremity < 1265 μV (OR 12.191, P = 0.000) were independent predictive factors for the clinical efficacy.Conclusions: : TEAS significantly decreased the severity of CIPN. TEAS group and baseline SSR amplitude of the upper extremity < 1265 μV were the independent predictive factors for the clinical efficacy after treatment.Keywords: transcutaneous electrical acupoint stimulation, chemotherapy-induced peripheral neuropathy, sympathetic skin response, cancer survivors, neuropathic pain

Shuzhe Xiao,1,* Yue Ding,1,* Chen Du,1,* Yiting Lv,1 Shumei Yang,1,2 Qi Zheng,3 Zhiqiu Wang,3 Qiaoli Zheng,3 Meifang Huang,1 Qingyan Xiao,1 Zhuxiao Ren,2 Guangliang Bi,1 Jie Yang1,2 1Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Department of Neonatology, Guangdong Women and Children Hospital, Guangzhou, 511442, People’s Republic of China; 3The First Clinical Medical College of Southern Medical University, Guangzhou, 510515, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jie Yang; Guangliang Bi, Email Jieyang0830@126.com; bader515@163.comBackground: Autophagy and immunity play important regulatory roles in lung developmental disorders. However, there is currently a lack of bioinformatics analysis on autophagy-related genes (ARGs) and immune infiltration in bronchopulmonary dysplasia (BPD). We aim to screen and validate the signature genes of BPD by bioinformatics and in vivo experiment.Methods: GSE8586 was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using the R program. Using cell-type identification with CIBERSORT to analyze the inflammatory and immune status of BPD. Subsequently, the hub genes were identified by Lasso and Cytoscape with three machine-learning algorithms (MCC, Degree and MCODE). In addition, hub genes were validated with ROC, single-cell sequence and IHC in hyperoxia mice. Finally, we searched the drug targets of these hub genes, and established a nomogram model for predicting the risk of BPD.Results: There were 73 the differentially expressed and autophagy-related genes (DE-ARGs) by overlapping the DEGs in GSE8586 and ARGs. Five hub genes, BRIX1, JUN, PES1, NR4A1 and RRP9, were lowly expressed in the BPD group and had high diagnostic value in the diagnostic model. All hub genes are mainly located in B cell, epithelial cell, fibroblast, endothelial cell, smooth muscle cell and pneumocyte in lung single-cell sequencing. Moreover, immune infiltration analysis showed immune cells were higher in the BPD group and were closely associated with hub genes. We also predict the drug targets of the genes. Finally, the IHC result in mice showed that expression of PES1, BRX1, RRP9, JUN, NR4A1 was lower in the hyperoxia group compared to the normoxia group.Conclusion: BRIX1, JUN, PES1, NR4A1, RRP9, may be promising therapeutic targets for BPD. Our findings provided researchers and clinicians with more evidence regarding immunotherapeutic strategies for BPD treatment.Keywords: BPD, autophagy, immune cell infiltration, single cell sequencing, biomarkers

Ziqing Yang,1,&ast; Bingsong Li,2,3,&ast; Dan Ma,1,4 Yitong Lv,1 Xinhui Qiu,5 Wenge Zhang,6 Jianye Wang,7 Yanlin Zhang,8 Chunming Xu,9 Yuxin Deng,9 Jinyang Li,10 Xuemei Zhen,2,3 Jun Zhang1 1Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical Research Center for Oral Diseases, Jinan, Shandong, People’s Republic of China; 2Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, Shandong, 250012, People’s Republic of China; 4Department of Orthodontics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 5The second Hospital of Shandong University, Jinan, Shandong, 250033, People’s Republic of China; 6School of Management, Shandong University, Jinan, Shandong, 250100, People’s Republic of China; 7Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 8School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 9Department of Pediatrics, Xinjiang Medical University, Urumqi, People’s Republic of China; 10Faculty of Nursing, Shihezi University, Shihezi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemei Zhen; Jun Zhang, Email zhenxuemei@sdu.edu.cn; zhangj@sdu.edu.cnObjective: Existing research has yet to adequately examine the correlation between sleep time, body pain, and depressive symptoms. This study seeks to elucidate the interconnections between these three elements.Methods: The study used 2020 CHARLS data for analysis. To assess the intricate association among sleep time, body pain, and depressive symptoms, the study employed Spearman correlation analysis, multiple logistic regression, restricted cubic splines, and mediation effect analysis based on bootstrap testing.Results: Risk factors for depressive symptoms in middle-aged and elderly Chinese include physical pain and reduced sleep duration. Results from the RCS suggest that the lowest risk of depressive symptoms occurs when the sleep time for the middle-aged and elderly population is approximately 7.5 hours. Body pain accounts for a 19.05% mediating effect between sleep time and depressive symptoms, and even after controlling confounding factors, there remains a 7.5% mediating effect.Conclusion: The research findings indicate that there is a significant correlation among sleep time, body pain, and depressive symptoms. Insufficient sleep time and body pain can lead to depressive symptoms. Body pain plays a partial mediating role between sleep time and depressive symptoms.Keywords: middle-aged and elderly people, sleep time, body pain, depressive symptoms

Jiaqi Wang, Yujing Jiang, Yamin Yuan, Xin Ma, Tongqin Li, YaTing Lv, Jing Zhang, Liao Chen, Jinquan Zhou, Yanfei Meng, Bei Zhang, Xiaorong Dong, Li Ma Department of Critical Care Medicine, Lanzhou University Second Hospital, Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Li Ma, Email ery_mali@lzu.edu.cnAim: Sepsis is a potentially fatal condition characterized by organ failure resulting from an abnormal host response to infection, often leading to liver and kidney damage. Timely recognition and intervention of these dysfunctions have the potential to significantly reduce sepsis mortality rates. Recent studies have emphasized the critical role of serum exosomes and their miRNA content in mediating sepsis-induced organ dysfunction. The objective of this study is to elucidate the mechanism underlying the impact of miR-122-5p on sepsis-associated liver and kidney injury using inhibitors for miR-122-5p as well as GW4869, an inhibitor targeting exosome release.Materials and Methods: Exosomes were isolated from serum samples of septic rats, sepsis patients, and control groups, while liver and kidney tissues were collected for subsequent analysis. The levels of miR-122-5p, inflammation indices, and organ damage were assessed using PCR, ELISA, and pathological identification techniques. Immunohistochemistry and Western blotting methods were employed to investigate the activation of inflammatory pathways. Furthermore, big data analysis was utilized to screen potential targets of miR-122-5p in vivo.Key Findings: Serum exosomal levels of miR-122-5p were significantly elevated in septic patients as well as in LPS-induced septic rats. Inhibition of miR-122-5p reduced serum pro-inflammatory factors and ameliorated liver and kidney damage in septic rats. Mechanistically, miR-122-5p upregulated TAK1, downregulated SIRT1, and facilitated NF-κB activation.Conclusion: Serum exosomal miR-122-5p promotes inflammation and induces liver/kidney injury in LPS-induced septic rats by modulating the TAK1/SIRT1/NF-κB pathway, highlighting potential therapeutic targets for sepsis management.Keywords: sepsis, exosome, miR-122-5p, NF-κB signaling pathway, sepsis-related liver and kidney injury

Weiwei Du, Wentao Ji, Tian Luo, Yinying Zhang, Weihong Guo, Jianping Liang, Yanhua Lv Department of Respiratory and Critical Care Medicine, Zhongshan City People’s Hospital, Zhongshan, Guangdong Province, People’s Republic of ChinaCorrespondence: Yanhua Lv, Department of Respiratory and Critical Care Medicine, Zhongshan City People’s Hospital, No. 2 Sunwen East Road, Zhongshan, 528400, Guangdong Province, People’s Republic of China, Tel/Fax +86-760-89880256, Email lyh009001@163.comBackground: The incidence of invasive pulmonary aspergillosis (IPA) is progressively rising in the nonneutropenic population, but studies investigating relevant prognostic factors remain scarce.Methods: Participants who were hospitalized at Zhongshan City People’s Hospital from January 2018 to May 2023 and diagnosed with nonneutropenic deficient IPA were included in this study. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression methods were used to select variables for constructing the predictive model. The performance of the predictive model was evaluated using the concordance index (C-index), calibration curve, time-dependent receiver operating characteristic (T-ROC) curve, area under the curve (AUC), and decision curve analysis (DCA). Finally, prognostic risk stratification was performed for nonneutropenic IPA patients, transforming the nomogram into a risk-stratified prognostic model.Results: A total of 210 participants were included in this study, divided into training and validation cohorts at a ratio of 7.5:2.5. Lasso regression identified seven potential predictive factors, including age, comorbid bacterial pneumonia, pleural effusion, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), invasive mechanical ventilation and ICU treatment. Multivariate Cox regression analysis showed age (HR=1.02), comorbid bacterial pneumonia (HR=3.36), NLR (HR=1.02), LDH (HR=1.001), and invasive mechanical ventilation (HR=4.86) as independent predictive factors and constructed nomogram. The calibration curves show that the nomogram performs well in terms of consistency between predictions and actual observations. The T-ROC curves and DCA of the nomogram model show that the recognition ability of the nomogram model was outstanding. Participants could be classified into high and low-risk groups based on the final score of this nomogram, demonstrating the excellent risk stratification performance of our model.Conclusion: The nomogram model developed in this study is an effective tool for predicting mortality risk in nonneutropenic IPA patients, aiding clinicians in identifying high-risk patients and optimizing early treatment strategies.Keywords: invasive pulmonary aspergillosis, pulmonary fungal infections, overall survival, risk stratification, nomogram, model

Ying Lv,1,&ast; Kun Zou,2,&ast; Shanshan Zhuang,3 Yang Zhou,1 Yaping Weng,3 Enna Mi,1 Minzhu Xie,1 Long Wang1 1Department of Nephrology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang,People’s Republic of China; 2Department of Neurology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3Department of Hemodialysis Center, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Lv, Department of Nephrology, The First Affiliated Hospital of Ningbo University, 59 Liuting Street, Ningbo, Zhejiang, 315010, People’s Republic of China, Email lvying0721@hotmail.comBackground: Hemodialysis-related restless legs syndrome (HD-RLS) is a common sensorial and motor disorder. The diagnosis of this disease is based on clinical criteria, and it has recently been proposed to use physiological parameters of the nerves related to the duration of the F wave as a supplementary diagnostic modality. The aim of the study is to determine the value of these parameters in the diagnosis of HD-RLS by comparing the differences between patients with HD-RLS and hemodialysis patients without RLS (HD-nRLS).Methods: A total of 20 HD-RLS patients, 33 HD-nRLS patients, and 30 age-and gender-matched healthy controls (HCs) were included in the study. The motor nerve conduction of the median and ulnar nerves in the upper limbs, as well as the tibial and peroneal nerves in the bilateral lower limbs, and the sensory nerve conduction of the sural nerve bilaterally and the superficial peroneal nerve, along with the F waves of the ulnar nerves, median nerve, and bilateral tibial nerve, were assessed.Results: Both groups of HD patients had variable levels of axonal degeneration and demyelination, with the HD-RLS patients having more severe lower limb involvement. The HD-RLS patients showed an extension of the F-wave duration (FWD) of the bilateral tibial, median, and ulnar nerves, along with an increased ratio between FWD and compound muscle action potential duration (CMAPD).Conclusion: Peripheral neuropathy occurs in patients with HD-RLS, and the FWD/CMAPD ratio could potentially serve as an adjunctive diagnostic tool for HD-RLS.Keywords: Restless legs syndrome, F wave hemodialysis, peripheral neuropathy

Bo Yang, Changhu Xie, Yuxing Lv, Yinquan Wang Department of Hernia and Abdominal Wall Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Science, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030032, People’s Republic of ChinaCorrespondence: Yinquan Wang, Department of Hernia and Abdominal Wall Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongi Shanxi Hospital, Third Hospital of Shanxi Medical University, No. 99 Longcheng Street, Xiaodian District, Taiyuan, Shanxi, 030032, People’s Republic of China, Tel +86-13834046996, Email Wangyinquan6996@163.comObjective: To unravel the effects of different laparoscopic inguinal hernia repairs (IHRs) on inflammatory factors, oxidative stress, and postoperative recovery of inguinal hernia (IH) patients.Methods: A total of 88 patients for laparoscopic treatment of IH were studied in a retrospective cohort, and were randomized into the transabdominal preperitoneal (TAPP) repair group (n = 44) and the total extraperitoneal (TEP) repair group (n = 44) according to the method of treatment. Patients in the TAPP group underwent laparoscopic TAPP IHR, while patients in the TEP group underwent laparoscopic TEP IHR. Visual analogue scores (VAS) were measured at 1, 3, and 7 d after repair. Gastrin (GAS), motilin (MTL), matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assessed by enzyme-linked immunosorbent assay. Superoxide dismutase (SOD) was tested by spectrophotometry and malondialdehyde (MDA) and β-endorphin (β-EP) were examined by radioimmunoprecipitation. Total antioxidant capacity (T-AOC) was evaluated by chemical colorimetry, quality of life was evaluated by SF-36, and fibrinogen (FIB), C-reactive protein (CRP), antitrypsin (al-AT), and interleukin-6 (IL-6) levels were determined by immunoturbidimetry. Complications and postoperative recurrence were recorded.Results: VAS scores in the TEP group were lower than those in the TAPP group. Operative time, hospital stay, time for postoperative activity out of bed, and time taken to exhaust were shorter in the TEP group than in the TAPP group. Intraoperative blood loss was less in the TEP group than in the TAPP group. GAS, MTL, SOD, and T-AOC were higher, and MDA, β-EP, CRP, FIB, alAT, IL-6, MMP-2, MMP-9, and TIMP-1 were lower in the TEP group than the TAPP group. Quality of life was improved in the TEP group compared with the TAPP group. There was no significant difference in the rate of postoperative complications and recurrence rates between both groups of patients.Conclusion: For IHs, laparoscopic TEP repair can effectively relieve pain, reduce inflammatory factors and oxidative stress indices, and facilitate postoperative recovery.Keywords: laparoscopic transabdominal preperitoneal inguinal hernia repair, laparoscopic total extraperitoneal inguinal hernia repair, inguinal hernia, inflammatory factors, oxidative stress

Xiaoling Shang,1,&ast; Chenyue Zhang,2,&ast; Yuanyuan Lv,3,&ast; Xiaoxiao Zhang,3,&ast; Kaiyue Guo,4 Huijuan Li,3 Haiyong Wang5 1Shandong Cancer Hospital and Institute, Shandong University, Jinan, 250117, People’s Republic of China; 2Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, People’s Republic of China; 3Department of Clinical Drug Research, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China; 4Department of Radiation Oncology, Qilu Hospital of Shandong University, Shandong University, Jinan, 250117, People’s Republic of China; 5Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huijuan Li, Department of Clinical Drug Research, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Email ywb234@126.com Haiyong Wang, Department of internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China, Tel +860531-87984777, Fax +86531-87984079, Email wanghaiyong6688@126.comBackground: Immune checkpoint inhibitors (ICIs) has prolonged survival in patients with extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment. However, whether ICI rechallenge could bring survival benefit to patients with ES-SCLC following its failure as first-line treatment remains unknown. Therefore, we aim to address the issue and identify the cohort of patients that may derive such benefit.Methods: Patients with ES-SCLC from both the IMpower133 study and Shandong Cancer Hospital and Institute (shanzhong cohort) who failed first-line ICI were included. Kaplan Meier analysis was performed to compare overall survival (OS). Both univariate and multivariate Cox regression analyses were conducted to identify factors affecting survival. Tumor immune cell infiltration was evaluated by the CIBERSORT algorithm and detected by multiplex immunofluorescence (mIF).Results: A total of 125 ES-SCLC patients undergoing atezolizumab and 161 patients undergoing ICI as first-line treatment were recruited from IMpower133 and shanzhong cohort. Those receiving ICI rechallenge had a longer OS than those without in IMpower133 (P = 0.08) and shanzhong cohort (P = 0.013). In IMpower133 cohort, subgroup analyses found that patients with < 4 metastatic sites derived more survival benefit from atezolizumab (P = 0.008). For patients with ES-SCLC harboring < 4 metastatic sites, there was significant OS difference between atezolizumab versus non-atezolizumab as retreatment (P = 0.036). Moreover, for ES-SCLC patients with < 4 metastatic sites, atezolizumab improved survival compared with non-atezolizumab (hazard ratio [HR]: 0.457; 95% CI: 0.256– 0.817; P = 0.008). These findings were confirmed in shanzhong cohort. Those harboring < 4 metastatic sites had fewer M2 macrophage and more CD4 naïve T cells infiltration, which was further confirmed by mIF of ES-SCLC samples from shanzhong cohort.Conclusion: Our study provides rationale for ICI rechallenge among ES-SCLC patients with < 4 metastatic sites, suggesting beneficial outcome by reshaping TME.Keywords: extensive stage small cell lung cancer, ICI rechallenge, survival, metastatic sites, tumor microenvironment

Yuyan Sun,1 Bing Lu,1 Yuanwen Hu,2 Yingqi Lv,3 Shao Zhong1 1Department of Endocrinology, Gusu School, Nanjing Medical University, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China; 2Department of Gastroenterology, The First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China; 3Division of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, People’s Republic of ChinaCorrespondence: Shao Zhong, Department of Endocrinology, Gusu School, Nanjing Medical University, the First People’s Hospital of Kunshan, Kunshan, 215300, People’s Republic of China, Tel +86 13328056828, Email drzhong@163.comAbstract: In recent years, pancreatogenic diabetes mellitus has garnered significant attention due to its high incidence, complications, and mortality rates. Glycemic variability (GV) can increase the risk of pancreatogenic diabetes mellitus and its associated complications; however, the precise mechanism remains unclear. The effective control of GV is crucial for preventing the onset of pancreatic diabetes mellitus and improving prognosis. Both diet and antidiabetic medications have substantial effects on GV. However, many patients are prescribed suboptimal or even harmful drugs. Therefore, to provide a comprehensive treatment basis for clinicians to prevent and treat pancreatogenic diabetes mellitus, this study aimed to elucidate the relationship between GV and pancreatogenic diabetes mellitus; investigate the potential mechanisms (such as oxidative stress, inflammatory response, insulin resistance, and lipid metabolism disorders); provide lifestyle guidance; and recommend drug selections to reduce the GV in patients with pancreatogenic diabetes mellitus. Keywords: pancreatogenic diabetes, glucose fluctuation, glycemic variability, therapy, antihyperglycemic drug

Yangting Lv,1 Yiwen Yin2 1Department of Neurology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Department of Electromyography, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, People’s Republic of ChinaCorrespondence: Yangting Lv, Department of Neurology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, NO. 318 Chaowang Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +8619538649581, Email lvyangting@yeah.netAbstract: Myofascial release (MFR) therapy is widely used in clinical practice to treat various musculoskeletal and pain-related conditions. However, there is a lack of comprehensive reviews that systematically evaluate its effectiveness across different medical conditions, leading to inconsistent applications and understanding of its therapeutic potential. This review aims to synthesize the current applications of myofascial release therapy in the treatment of various diseases, highlighting its efficacy and identifying areas where further research is needed. The review covers the application of myofascial release therapy in conditions such as chronic pain, fibromyalgia, post-surgical recovery, and neurological disorders. It evaluates the outcomes of existing studies, identifies gaps in the literature, and discusses the mechanisms through which myofascial release exerts its effects. Additionally, the review provides insights into the limitations of current research and suggests directions for future studies to enhance the clinical application of myofascial release therapy.Keywords: myofascial release, chronic pain, cancer pain, stroke

Yangting Lv,1 Guliziba Aihemaiti,2 Huirong Guo3 1Department of Neurology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, 311500, People’s Republic of China; 2Department of Medicine, Changji Branch of the First Affiliated Hospital of Xinjiang Medical University, Changji City, Xinjiang Province, 831100, People’s Republic of China; 3Department of Scientific Research and Teaching, Changji Branch of the First Affiliated Hospital of Xinjiang Medical University, Changji City, Xinjiang Province, 831100, People’s Republic of ChinaCorrespondence: Huirong Guo, Department of scientific Research and Teaching, Changji Branch of the First Affiliated Hospital of Xinjiang Medical University, No. 743 Qingnian Road, Changji City, Xinjiang Province, 831100, People’s Republic of China, Tel + 86 13579646668, Email guohr2024hr@163.comAbstract: Metabolic syndrome (MS) is more prevalent in chronic diseases and, if left untreated, can lead to serious consequences, such as cardiovascular disease (CVD), cerebrovascular disease and type 2 diabetes, which have become significant public health issues globally. Metabolic syndrome is significantly influenced by the daily diet of patients. The dietary approaches to stop hypertension (DASH) diet, originally designed to prevent or control hypertension, offers additional metabolic benefits due to its nutrient composition. The DASH diet recommends the intake of potassium, magnesium, calcium and fibre while limiting total fat, saturated fat and sodium, which is beneficial for patients with MS. Due to its limited fat content and high levels of fibre and calcium, individuals following the DASH diet are less prone to being overweight and obese and have lower concentrations of total and low-density lipoprotein cholesterol. Moreover, the DASH diet can reduce blood pressure and is effective in correcting glucose and insulin abnormalities. This review comprehensively summarises the health benefits of the DASH diet on the risk factors of MS and describes the potential mechanisms based on available evidence.Keywords: DASH diet, metabolic syndrome, metabolomics

Wennuo Huang,1,&ast; Yuanzhe Li,2,&ast; Zhuqing Bao,3,&ast; Jing Ye,1 Wei Xia,1 Yan Lv,1 Jiahui Lu,4 Chao Wang,1 Xi Zhu1 1Department of Radiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225002, People’s Republic of China; 2Department of CT/MRI, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, People’s Republic of China; 3Department of Emergency, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, Jiangsu, 225002, People’s Republic of China; 4School of Medical Imaging, Hangzhou Medical College, Hangzhou, Zhejiang, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Zhu, Department of Radiology, Northern Jiangsu People’s Hospital Affiliated to Yangzhou University, Yangzhou, 225002, Jiangsu, People’s Republic of China, Tel +8618051062318, Email yzdxlcyxyzhuxi@qq.comPurpose: This study aimed to investigate the knowledge, attitudes, and practice (KAP) of radiologists regarding artificial intelligence (AI) in medical imaging in the southeast of China.Methods: This cross-sectional study was conducted among radiologists in the Jiangsu, Zhejiang, and Fujian regions from October to December 2022. A self-administered questionnaire was used to collect demographic data and assess the KAP of participants towards AI in medical imaging. A structural equation model (SEM) was used to analyze the relationships between KAP.Results: The study included 452 valid questionnaires. The mean knowledge score was 9.01± 4.87, the attitude score was 48.96± 4.90, and 75.22% of participants actively engaged in AI-related practices. Having a master’s degree or above (OR=1.877, P=0.024), 5– 10 years of radiology experience (OR=3.481, P=0.010), AI diagnosis-related training (OR=2.915, P< 0.001), and engaging in AI diagnosis-related research (OR=3.178, P< 0.001) were associated with sufficient knowledge. Participants with a junior college degree (OR=2.139, P=0.028), 5– 10 years of radiology experience (OR=2.462, P=0.047), and AI diagnosis-related training (OR=2.264, P< 0.001) were associated with a positive attitude. Higher knowledge scores (OR=5.240, P< 0.001), an associate senior professional title (OR=4.267, P=0.026), 5– 10 years of radiology experience (OR=0.344, P=0.044), utilizing AI diagnosis (OR=3.643, P=0.001), and engaging in AI diagnosis-related research (OR=6.382, P< 0.001) were associated with proactive practice. The SEM showed that knowledge had a direct effect on attitude (β=0.481, P< 0.001) and practice (β=0.412, P< 0.001), and attitude had a direct effect on practice (β=0.135, P< 0.001).Conclusion: Radiologists in southeastern China hold a favorable outlook on AI-assisted medical imaging, showing solid understanding and enthusiasm for its adoption, despite half lacking relevant training. There is a need for more AI diagnosis-related training, an efficient standardized AI database for medical imaging, and active promotion of AI-assisted imaging in clinical practice. Further research with larger sample sizes and more regions is necessary.Keywords: artificial intelligence, medical imaging, knowledge, attitude, practice, radiologists, cross-sectional study

Jing Ye,1,2 Yunhui Lv,2 Hui Xie,3 Kun Lian,4 Xiufeng Xu1 1Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Sleep Medicine Center, The First People’s Hospital of Yunnan, Kunming, Yunnan, People’s Republic of China; 3Department of Traumatology, The First People’s Hospital of Yunnan, Kunming, Yunnan, People’s Republic of China; 4Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of ChinaCorrespondence: Xiufeng Xu, Department of Psychiatry, The First Affiliated Hospital of Kunming Medical University, No. 295 of Xichang Road, Kunming City, Yunnan Province, People’s Republic of China, Email xfxu2004@sina.comBackground: Obstructive sleep apnea (OSA) patients commonly experience high rates of depression. This study aims to examine the oral microbiota characteristics of OSA and those with comorbid major depressive disorder (OSA+MDD) patients.Methods: Participants were enrolled from Aug 2022 to Apr 2023. Polysomnography, psychiatrist interviews, and scales were used to diagnose OSA and MDD. Oral samples were collected from participants by rubbing swabs on buccal mucosa, palate, and gums. Oral microbiota was analyzed via whole-genome metagenomics and bioinformatic analysis followed sequencing. Venous blood was drawn to detect plasma inflammatory factor levels.Results: The study enrolled 33 OSA patients, 28 OSA+MDD patients, and 28 healthy controls. Significant differences were found in 8 phyla, 229 genera, and 700 species of oral microbiota among the three groups. Prevotellaceae abundance in the OSA and OSA+MDD groups was significantly lower than that in healthy controls. Linear discriminant analysis effect size (LEfSe) analysis showed that Streptococcaceae and Actinobacteria were the characteristic oral microbiota of the OSA and OSA+MDD groups, respectively. KEGG analysis indicates 30 pathways were changed in the OSA and OSA+MDD groups compared with healthy controls, and 23 pathways were changed in the OSA group compared with the OSA+MDD group. Levels of IL-6 in the OSA+MDD group were significantly higher than in the healthy group, correlating positively with the abundance of Schaalia, Campylobacter, Fusobacterium, Alloprevotella, and Candidatus Nanosynbacter in the oral, as well as with Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale scores.Conclusion: Significant differences in oral microbiota populations and gene function were observed among the three groups. OSA patients were characterized by a decreased abundance of Prevotellaceae and an increased abundance of Streptococcaceae. OSA+MDD patients had an increased abundance of Actinobacteria. IL-6 might regulate the relationship between depression and the oral microbiota in OSA+MDD patients.Keywords: obstructive sleep apnea, major depressive disorder, oral microbiota, whole-genome metagenomic analysis, inflammatory factors

Jiajia Zhou,1,2,&ast; Shuang Song,2,3,&ast; Senlin Xue,2 Yingxing Zhu,3 Boyin Xu,4 Ping Ma,2,3 Yanguan Lv,1 Haiquan Kang2,3 1The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, People’s Republic of China; 2Medical Technology School, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Department of Infection Control, Affiliated Hospital of Nantong University, Nantong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiquan Kang, Department of Clinical Laboratory, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, People’s Republic of China, Tel +86-516 85802759, Email hqk811029@163.com Yanguan Lv, The Huai’an Maternity and Child Clinical College of Xuzhou Medical University, Huai’an, 223001, People’s Republic of China, Tel +86-517 89687770, Email lvyanguan@163.comBackground: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has garnered international concern due to its significant antibiotic resistance. Notably, children exhibit distinct resistance mechanisms compared to adults, necessitating a differential approach to antibiotic selection. A thorough analysis of CRKP’s epidemiology and drug resistance mechanisms is essential for establishing a robust foundation for clinical anti-infection strategies and precise prevention and control measures.Methods: This study involved the collection of 31 non-repetitive strains from pediatric and adult patients at a tertiary hospital in China, spanning from July 2016 to July 2022, testing for resistance genes, antimicrobial susceptibility, and homology analysis.Results: Infants (0– 1 year) were the largest pediatric CRKP group, with 61.3% of cases. The neonatal intensive care unit (NICU) and pediatrics were the main departments affected. Adults with CRKP had a mean age of 67 years, with the highest prevalence in neurology and emergency ICU. Antimicrobial susceptibility testing revealed that adult CRKP strains exhibited higher resistance to amikacin, ciprofloxacin, cotrimoxazole, and aztreonam compared to pediatric strains. Conversely, pediatric strains showed a higher rate of resistance to ceftazidime/avibactam. The predominant resistance genes identified were blaNDM-5 in children (58.1%) and blaKPC-2 in adults (87.1%), with over 93% of both groups testing positive for extended-spectrum beta-lactamase (ESBL) genes. Multilocus Sequence Typing (MLST) indicated ST2735 and ST11 as the predominant types in children and adults, respectively. Pulsed-field gel electrophoresis (PFGE) identified clonal transmission patterns of ST11 blaKPC-2 and ST15 blaOXA-232 across both age groups. Notably, this study reports the first instance of ST1114-type CRKP co-producing blaNDM-5 and blaOXA-181 in the NICU.Conclusion: This study reveals distinct resistance mechanisms and epidemiology in CRKP from children and adults. The identified clonal transmission patterns emphasize the need for improved infection control to prevent the spread of resistant strains.Keywords: children, adults, Klebsiella pneumoniae, carbapenemases, drug resistance mechanisms

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

Yan Lv, Zheren Huang, Yan Ma Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of ChinaCorrespondence: Yan Ma, Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China, Tel +86-0-13813693377, Email mayan19820117@126.comBackground: We aimed to investigate the association between maternal neutrophil ratio and histological chorioamnionitis (HCA) risk in pregnant women with premature rupture of membranes (PROM) in late pregnancy.Methods: A retrospective analysis was conducted on 95 cases of women with PROM in their late pregnancy between March 2018 and August 2021. These women were divided into two groups based on the presence of HCA. General clinical data and laboratory indicators were compared between the two groups. A generalized additive model was used for curve fitting, and a segmented regression model was used to explain further the non-linear relationship between neutrophil ratio and HCA risk.Results: After adjusting for confounding factors, the curve fitting showed a “U”-shaped curve relationship between the neutrophil ratio and the risk of HCA. When the neutrophil ratio was < 76.3%, the risk of HCA exhibited a decreasing trend, but the difference was not statistically significant (adjusted OR = 0.884, 95% CI: 0.781– 1.001, P = 0.053). However, when the neutrophil ratio was > 76.3%, the HCA risk was significantly increased (adjusted OR = 1.339, 95% CI: 1.067– 1.680, P = 0.012). Furthermore, we equally divided the neutrophil ratio into three groups. The risk of HCA was significantly increased in the low-ratio group (OR = 4.292, 95% CI: 1.247– 14.706, P = 0.021) compared with the middle-ratio group, which was used as the reference group. Similarly, the HCA risk of the high-ratio group (OR = 13.145, 95% CI: 1.796– 96.233, P = 0.011) was also significantly enhanced. However, there was no significant difference in HCA risk between the high-ratio and low-ratio groups (OR = 1.182, 95% CI: 0.357– 3.909, P = 0.784).Conclusion: There was a significant “U”-shaped relationship between maternal neutrophil ratio and HCA risk in women with PROM in late pregnancy.Keywords: premature rupture of membranes, late pregnancy, neutrophil ratio, histological chorioamnionitis, non-linear relationship

Chang Su,1– 3 Zeyu Wang,4 Zhen Qin,1– 3 Yan Lv,1– 3 Yachen Hou,1– 3 Ge Zhang,1– 3 Mengdie Cheng,1– 3 Xinyue Cui,1– 3 Zhiyu Liu,1– 3 Pengchong Du,1– 3 Tianding Liu,1– 3 Peiyu Yuan,1– 3 Junnan Tang,1– 3 Jinying Zhang1– 3 1Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, People’s Republic of China; 4Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Junnan Tang; Jinying Zhang, Department of Cardiology, First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166 ; +86 13503830283, Email fcctangjn@zzu.edu.cn; jyzhang@zzu.edu.cnBackground: The triglyceride-glucose (TYG) index is a novel and reliable marker reflecting insulin resistance. Its predictive ability for cardiovascular disease onset and prognosis has been confirmed. However, for advanced chronic heart failure (acHF) patients, the prognostic value of TYG is challenged due to the often accompanying renal dysfunction (RD). Therefore, this study focuses on patients with aHF accompanied by RD to investigate the predictive value of the TYG index for their prognosis.Methods and Results: 717 acHF with RD patients were included. The acHF diagnosis was based on the 2021 ESC criteria for acHF. RD was defined as the eGFR < 90 mL/(min/1.73 m2). Patients were divided into two groups based on their TYG index values. The primary endpoint was major adverse cardiovascular events (MACEs), and the secondary endpoints is all-cause mortality (ACM). The follow-up duration was 21.58 (17.98– 25.39) months. The optimal cutoff values for predicting MACEs and ACM were determined using ROC curves. Hazard factors for MACEs and ACM were revealed through univariate and multivariate COX regression analyses. According to the univariate COX regression analysis, high TyG index was identified as a risk factor for MACEs (hazard ratio = 5.198; 95% confidence interval [CI], 3.702– 7.298; P < 0.001) and ACM (hazard ratio = 4.461; 95% CI, 2.962– 6.718; P < 0.001). The multivariate COX regression analysis showed that patients in the high TyG group experienced 440.2% MACEs risk increase (95% CI, 3.771– 7.739; P < 0.001) and 406.2% ACM risk increase (95% CI, 3.268– 7.839; P < 0.001). Kaplan-Meier survival analysis revealed that patients with high TyG index levels had an elevated risk of experiencing MACEs and ACM within 30 months.Conclusion: This study found that patients with high TYG index had an increased risk of MACEs and ACM, and the TYG index can serve as an independent predictor for prognosis.Keywords: TyG index, advanced chronic heart failure, renal dysfunction, prognosis factor

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

Guang Chen,1,&ast; Caohua Lv,2,&ast; Qing Nie,3 Xin Li,1 Yinyi Lv,1 Guoyan Liao,1 Shuangchun Liu,4 Weiwei Ge,2 Jinguang Chen,1 Yunting Du5 1Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, 318000, People’s Republic of China; 2Department of Dermatology, Taizhou Second People’s Hospital, Taizhou, 317200, People’s Republic of China; 3Weifang Centers for Disease Control and Prevention, Weifang, 261061, People’s Republic of China; 4Municipal Hospital Affiliated to Medical School of Taizhou University, Taizhou, 318000, People’s Republic of China; 5Department of Laboratory Medicine, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinguang Chen; Yunting Du, Tel/Fax +86 576 88661988, Email tongly0422@126.com; m15840557769@163.comBackground: The traditional Matricaria chamomilla L. has been used to treat dermatitis for thousands of years. Due to emerging trends in alternative medicine, patients prefer natural remedies to relieve their symptoms. Therefore, finding safe and effective plant medicines for topical applications on the skin is an important treatment strategy for dermatologists. German chamomile (Matricaria chamomilla L.) from the Compositae family is a famous medicinal plant, often known as the “star of medicinal species.”However, the function of Matricaria chamomilla essential oil on skin inflammation has not been thoroughly examined in earlier research.Methods: GC-MS analyzed the components of MCEO, and this study explored the anti-inflammation effects of MCEO on psoriasis with network pharmacological pathway prediction. Following this, we used clinical samples of psoriasis patients to confirm the secretory characteristic of relative inflammatory markers. The therapeutic effect of MCEO on skin inflammation was detected by examination of human keratinocytes HaCaT. At the same time, we prepared imiquimod-induced psoriatic-like skin inflammation in mice to investigate thoroughly the potential inhibition functions of MCEO on psoriatic skin injury and inflammation.Results: MCEO significantly reduced interleukin-22/tumor necrosis factor α/lipopolysaccharide-stimulated elevation of HaCaT cell inflammation, which was correlated with downregulating PI3K/Akt/mTOR and p38MAPK pathways activation mediated by MCEO in HaCaT cells treated with IL-22/TNF-α/LPS. Skin inflammation was evaluated based on the PASI score, HE staining, and relative inflammatory cytokine levels. The results showed that MCEO could significantly contribute to inflammatory skin disease treatment.Conclusion: MCEO inhibited inflammation in HaCaT keratinocytes induced by IL-22/TNF-α/LPS, the potential mechanisms associated with inhibiting excessive activation and crosstalk between PI3K/Akt/mTOR and p38MAPK pathways. MCEO ameliorated skin injury in IMQ-induced psoriatic-like skin inflammation of mice by downregulating the levels of inflammatory cytokines but not IL-17A. Thus, anti-inflammatory plant drugs with different targets with combined applications were a potential therapeutic strategy in psoriasis.Keywords: Matricaria chamomilla, essential oil, psoriasis, HaCaT, IMQ, mouse

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

Tao Huang,1,&ast; Yongling Lv,2,&ast; Wei Wang,1 Yunyao Chen,1 Lixin Fan,1 Zhaowei Teng,3 Xianfeng Zhou,2,4 Hexiao Shen,2 Guang Fu1 1Gastrointestinal Surgery, Wuhan Puren Hospital, Wuhan, People’s Republic of China; 2Maintainbiotech. Ltd. (Wuhan), Wuhan, People’s Republic of China; 3Central Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, People’s Republic of China; 4School of Life Sciences and Health Engineering, Hubei University of Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hexiao Shen; Guang Fu, Email shenhxmyt@163.com; fuguang71@163.comAbstract: Adverse skin reactions caused by the COVID-19 vaccine have attracted considerable attention. As we all know, the development mechanism of some skin diseases is related to the gut and skin microbiome. A 78-year-old male patient who received the COVID-19 vaccine developed generalized eczema with multiple dense black patches over the body, a widespread rash, erosion, and scabs on his limbs, as well as facial edema. The patient experienced recurrent flare-ups after conventional treatment, but then recovered well without recurrence after undergoing three fecal microbial transplantation (FMT) treatments. This rare case is reported for the first time in this study. This report demonstrates the possible potential of FMT in targeting refractory skin diseases, such as eczema, as well as diseases associated with gut microbiota disturbance after vaccination.Keywords: FMT, eczema, COVID-19 vaccine

Yuhan Wang,1,&ast; Ping Zhang,1,&ast; Yu Lv,1 Yu Deng,2 Ming Yao,3 Lin Wang,1 Guangtao Pan3 1College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan, Hubei Province, People’s Republic of China; 2Department of Encephalopathy, Guangzhou Hospital of Integrated Traditional and West Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 3Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangtao Pan, Department of Dermatology, Yancheng Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, No. 53, Renmin North Road, Tinghu District, Yancheng, Jiangsu Province, People’s Republic of China, Tel +86-17612738767, Email panguangtaowuhan@foxmail.comAbstract: This literature review systematically searched relevant literature from the past 10 years using various medical databases, including PubMed, Medline, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. As a chronic inflammatory disease, psoriasis is associated with various cells and cytokines of the body’s immune system, making them more susceptible to various systemic comorbidities than the general population. At a time when conventional regimens are ineffective and there is a lack of personalized treatment options for such comorbidities, the development of biologics has revolutionized the treatment of psoriasis comorbidities, and a number of biologic combination therapies have been incorporated into first-line treatments in many countries. The focus of this review was to investigate the relationship between psoriasis and comorbidities, such as metabolic syndrome, psoriatic arthritis, cardiovascular diseases, mental disorders, infectious diseases, digestive system diseases, and renal diseases. Furthermore, the study explored the significance of biologic therapies in the management of these comorbidities. Also this paper suggests current conditions and precautions for the use of biologic therapies to minimize the occurrence of adverse effects. This review was performed to provide guidance for clinical drug selection in patients with psoriasis and comorbidities, as well as serve as a reference for the development and application of biologic therapies.Keywords: psoriasis, biologics, comorbidity, research advancements

Wentao Zhong,1– 3,&ast; Qianyu Wang,2,&ast; Xiaofei Shen,4,&ast; Yuan Lv,2,3 Liang Sun,2 Ran An,5 Hongyan Zhu,5 Huiyun Cai,2 Gang Chen,2,3 Aijun Liu,5 Junfeng Du1– 3 1The Second School of Clinical Medicine, Southern Medical University, Guangdong, 510515, People’s Republic of China; 2Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 3Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 5Department of Pathology, the 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Liu, Department of Pathology, The 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email aliu301@126.com Junfeng Du, Department of General Surgery, the 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email dujf66@126.comPurpose: To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms.Patients and Methods: We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3.Results: NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial–mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response.Conclusion: NET was an independent prognostic factor in LARC that were associated with patients’ survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.Keywords: NETs, tumor microenvironment, locally advanced rectal cancer, outcome

Subei Zhao, Zheng Yang, Meng Yu, Linyu Xiang, Yuhuan Lv, Chunyan Tian, Rong Li Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of ChinaCorrespondence: Rong Li, Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86 13508385198, Email rongli@hospital.cqmu.edu.cnPurpose: Subclinical inflammation may be involved in the pathogenesis of diabetic cardiac autonomic neuropathy (DCAN). The purpose of the study is to explore the relationship between novel inflammation biomarkers fibrinogen-albumin ratio (FAR), fibrinogen-prealbumin ratio (FPR), and DCAN in type 2 diabetes mellitus (T2DM).Patients and Methods: A total of 715 T2DM patients were enrolled in this retrospective study, divided into non-DCAN (n=565) and DCAN (n=150) groups by Ewing’s test. Serum fibrinogen, albumin, prealbumin, routine inflammatory and other biochemical markers were measured.Results: Patients with versus without DCAN had higher FAR (10.29 ± 4.83 vs 7.22 ± 2.56 g/g, P < 0.001) and FPR (2.19 ± 1.85 vs 1.43 ± 0.93 g/mg, P < 0.001). As FAR and FPR quartiles increased, the incidence of DCAN increased (Quartile 1 vs Quartile 4: 8.4 vs 42.7%, 9.6 vs 39.2%, respectively, P < 0.001), heart rate variability parameters decreased (P < 0.001); the incidence of diabetic nephropathy, retinopathy and peripheral neuropathy tended to be higher and inflammation factors were more active (P < 0.01). FAR (OR, 95% CI: 1.16, 1.08– 1.25, P < 0.001) and FPR (OR, 95% CI: 1.22, 1.03– 1.44, P = 0.021) were independent determinants of DCAN; the risk of DCAN increased by approximately 65% and 27% with each increase in the standard deviation (SD) of FAR (OR per SD, 95% CI: 1.65, 1.29– 2.11, P < 0.001) and FPR (OR per SD, 95% CI: 1.27, 1.04– 1.56, P = 0.021).Conclusion: FAR and FPR are independent risk factors and may influence DCAN development through inflammation.Keywords: type 2 diabetes mellitus, diabetic cardiac autonomic neuropathy, inflammation, fibrinogen-albumin ratio, fibrinogen-prealbumin ratio

Qiongyang Zhou,1,&ast; Yue Ji,2,&ast; Yanzhu Lv,3 Jing Xue,3 Yuhui Wang,3 Yin Huang4 1Department of Acupuncture and Moxibustion, The First People’s Hospital of Wenling, Wenling, People’s Republic of China; 2First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 4Department of Acupuncture, Changshu Hospital Affiliated to Nanjing University of Chinese Medicine, Changshu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yin Huang, Email colbycovington@163.comBackground: Acupuncture may be effective to treat post-stroke cognitive impairment (PSCI). We aimed to evaluate the reliability of the systematic reviews/meta-analyses (SRs/MAs) evidence regarding acupuncture treatment of PSCI.Methods: The methodological quality was appraised with Methodological Quality of Systematic Reviews 2 (AMSTAR-2). We evaluated reporting quality with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and evidence quality with Grade of Recommendation, Assessment, Development and Evaluation (GRADE) system.Results: The inclusion criteria were met by fifteen reviews. All studies assessed by AMSTAR-2 had critically poor methodological quality due to the limitations on the lack of the provision of the list of excluded trails, screening of duplicate study, and protocol registration. For reporting quality, response rate of “yes” was less than 50% in Q5 (protocol and registration topic), Q8 (Search) and Q23 (Additional analysis). Evidence quality of outcome measures was low or worse with GRADE because when the data was qualitatively synthesized, low quality and small sample size trials provided the data.Conclusion: Acupuncture may be beneficial for PSCI. Because of limitations and inconsistent conclusions, further research is needed to provide higher evidence for acupuncture on PSCI.Keywords: acupuncture, treatment, cognitive impairment, stroke, evidence

Shaopeng Chen,1,2,&ast; Mindan Wu,3,&ast; Zhilin Xiong,1,&ast; Jiewen Huang,1 Yingying Lv,1 Yuyan Li,4 Minjuan Zeng,5 Tianwen Lai1 1Institute of Respiratory Diseases, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China; 2Blood Donation Service Department, Zhanjiang Blood Center, Zhanjiang, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shantou Central Hospital, Shantou, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Dongguan Hospital of Southern Medical University, Dongguan, People’s Republic of China; 5Laboratory Animal Center, Guangdong Medical University, Zhanjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianwen Lai; Minjuan Zeng, Email laitianwen2011@163.com; mjzeng@gdmu.edu.cnPurpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages.Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo.Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure.Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.Keywords: particulate matter, SIRT6, macrophage, lung inflammation

Zeyi Liang,&ast; Jiahao Shen,&ast; Jing Liu, Xu Sun, Yayuan Yang, Yanan Lv, Juanshan Zheng, Xiaoqing Mou, Hongsheng Li, Xuezhi Ding, Feng Yang Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, Gansu, 730050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of Serratia marcescens isolates from clinical bovine mastitis in Ningxia Hui Autonomous Region of China.Methods: S. marcescens was identified by the polymerase-chain reaction of 16S rRNA gene and sequencing. Antimicrobial susceptibility was tested by the disk diffusion method. Genes of resistance and virulence were determined by the PCR.Results: Overall, S. marcescens were confirmed from 32 of 2897 (1.1%) mastitis milk samples. These isolates showed high resistance to cefazolin (30/32, 93.8%) and chloramphenicol (28/32, 87.5%). A 12.5% (4/32) of the isolates displayed multidrug resistance (MDR). The most prevalent resistant genes found in S. marcescens were TEM (32/32, 100%) and CTX-M (24/32, 75.0%; CTX-M-15, 14/32, 43.8%; CTX-M-14, 8/32, 25.0%; CTX-M-65, 2/32, 6.3%) for extended-spectrum beta-lactamase, cmlA (28/32, 87.5%) and floR (16/32, 50.0%) for chloramphenicol resistance, SIM-1 (2/32, 6.3%) for carbapenemases, and sdeB (28/32, 87.5%), sdeY (26/32, 81.3%), sdeR (26/32, 81.3%) and sdeD (20/32, 62.5%) for efflux pumps. Moreover, all isolates carried virulence genes flhD, entB, and kpn, and most of them contained mrkD (30/32, 93.8%), ycfM (26/32, 81.3%), bsmB (26/32, 81.3%), pigP (26/32, 81.3%), kfu (24/32, 75.0%) and shlB (24/32, 75.0%).Conclusion: To our knowledge, this is the first report of genetic determinants for antimicrobial resistance and virulence in S. marcescens isolated from bovine mastitis cases in China. These findings are useful for developing strategies for prevention and treatment of bovine mastitis caused by S. marcescens in China.Keywords: Serratia marcescens, bovine mastitis, antimicrobial resistance, virulence

Chunjiao Lu,&ast; Yi Liu,&ast; Yao Liu, Guanhua Kou, Yang Chen, Xuewei Wu, Yuhang Lv, Jiahao Cai, Renyuan Chen, Juanjuan Luo, Xiaojun Yang Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, 515041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juanjuan Luo; Xiaojun Yang, Guangdong Provincial Key Laboratory of Infectious Disease and Molecular Immunopathology, Shantou University Medical College, Shantou, 515041, People’s Republic of China, Tel +86-754-88900236, Fax +86-754-88900276, Email lujj770@163.com; yangx@stu.edu.cnIntroduction: Silver nanoparticles (AgNP) are widely used as coating materials. However, the potential risks of AgNP to human health, especially for neural and vascular systems, are still poorly understood.Methods: The vascular and neurotoxicity of various concentrations of AgNP in zebrafish were examined using fluorescence microscopy. In addition, Illumina high-throughput global transcriptome analysis was performed to explore the transcriptome profiles of zebrafish embryos after exposure to AgNP. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to elucidate the top 3000 differentially expressed genes (DEGs) between AgNP-exposed and control groups.Results: We systematically investigated the neural and vascular developmental toxicities of AgNP exposure in zebrafish. The results demonstrated that AgNP exposure could cause neurodevelopmental anomalies, including a small-eye phenotype, neuronal morphology defects, and inhibition of athletic abilities. In addition, we found that AgNP exposure induces angiogenesis malformation in zebrafish embryos. Further RNA-seq revealed that DEGs were mainly enriched in the neuroactive ligand-receptor interaction and vascular endothelial growth factor (Vegf) signaling pathways in AgNP-treated zebrafish embryos. Specifically, the mRNA levels of the neuroactive ligand-receptor interaction pathway and Vegf signaling pathway-related genes, including si:ch73-55i23.1, nfatc2a, prkcg, si:ch211-132p1.2, lepa, mchr1b, pla2g4aa, rac1b, p2ry6, adrb2, chrnb1, and chrm1b, were significantly regulated in AgNP-treated zebrafish embryos.Conclusion: Our findings indicate that AgNP exposure transcriptionally induces developmental toxicity in neural and vascular development by disturbing neuroactive ligand-receptor interactions and the Vegf signaling pathway in zebrafish embryos.Keywords: silver nanoparticles, neurological development, vascular development, developmental toxicity, zebrafish

Yonghui Lv,1 Yuanwei Liu,1 Kaiguo Li,1 Zhiling Liu,1 Tong Zhang,1 Mingguang Duan,1 Yunchao Chen,1 Teng Ma,1 Guanghui Huang,2,&ast; Zhaoqin Huang1,&ast; 1Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250000, People’s Republic of China; 2Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guanghui Huang, Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 9677 Jingshi Road, Lixia District, Jinan, Shandong, 250012, People’s Republic of China, Email hgh3612@163.com Zhaoqin Huang, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jingwu Road, Huaiyin District, Jinan, Shandong, 250012, People’s Republic of China, Email devin813@163.comPurpose: This study aims to investigate the prognostic value of preoperative absolute lymphocyte count (preALC) for non-small cell lung cancer (NSCLC) after microwave ablation (MWA) and build a combined nomograph with clinical features to predict the local recurrence.Patients and Methods: A total of 118 NSCLC patients who underwent microwave ablation were enrolled in this study. The median local recurrence-free survival (LRFS) was 35.5 months. Independent prognostic factors obtained by multivariate analysis were included in the prediction model. The prognostic value of the model was assessed by the area under the time-dependent receiver operating characteristic curve (T-AUC).Results: Histological subtype and preALC were independent risk factors for local relapse-free survival. According to the time-dependent receiver operating characteristic curve (T-ROC), the optimal cut-off value of preALC was 1.965× 109/L, the sensitivity was 0.837, and the specificity was 0.594. The area under the T-ROC curve (AUC) of preALC was 0.703. To establish a nomogram to predict the local recurrence rate of NSCLC after MWA based on the prognostic factors revealed by Cox regression.Conclusion: Preoperative lymphocyte count reduction is associated with poor prognosis of NSCLC. The nomogram model combined with preALC can provide a good individualized prediction of local recurrence after microwave ablation.Keywords: non-small cell lung cancer, microwave ablation, nomogram, preoperative absolute lymphocyte count

Shenghan Gao,1,2 Xinyu Zhang,1,2 Jie Liu,3 Fuqing Ji,2 Zhihao Zhang,2 Qingjie Meng,2 Qi Zhang,1 Xiaogang Han,2 He Wu,2 Yulong Yin,2 Yonggang Lv,2 Wenzhen Shi3 1The College of Life Sciences, Northwest University, Xi’an, 710069 People’s Republic of China; 2Department of Thyroid Breast Surgery, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China; 3Clinical Medical Center, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of ChinaCorrespondence: Yonggang Lv, Department of Thyroid Breast Surgery, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China, Email lvygwytt@163.com Wenzhen Shi, Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, School of Life Sciences and Medicine, Northwest University, Xi’an, People’s Republic of China, Tel +8615037916770, Email shiwenzhen736@163.comBackground: Breast cancer is a common cancer worldwide. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by a poor prognosis. Icariin (ICA) is a flavonoid glycoside purified from the natural product Epimedium, which is reported to exert an inhibitory effect on a variety of cancers. However, molecular mechanisms behind ICA suppressed TNBC remain elusive.Methods: The curative effects of ICA on TNBC cells and potential targets were predicted by network pharmacology and molecular biology methods screening, and the mechanism of inhibition was explained through in vitro experiments such as cell function determination, Western blot analysis, molecular docking verification, etc.Results: This study showed that ICA inhibits TNBC cell functions such as proliferation, migration, and invasion in a dose-dependent manner. ICA could induce redox‐induced apoptosis in TNBC cell, as shown by ROS upregulation. As a result of network pharmacology, ICA was predicted to be able to inhibit the MAPK signaling pathway. ICA treatment inhibited the expression of JNK and c-Jun and downregulated the antiapoptotic gene cIAP-2. Our results suggested that ICA could induce apoptosis by inducing an excessive accumulation of ROS in cells and suppress TNBC cell invasion via the JNK/c-Jun signaling pathway.Conclusion: We demonstrated that ICA can effectively inhibit cell proliferation and induced apoptosis of TNBC cells. In addition, ICA could inhibit TNBC cell invasion through the JNK/c-Jun signaling pathway. The above suggests that ICA may become a potential drug for TNBC.Keywords: triple-negative breast cancer, icariin, JNK/c-Jun, apoptosis, ROS, invasion

Delian Kong,1,&ast; Junrong Li,1,&ast; Yingying Lv,1,&ast; Man Wang,2,&ast; Shenghua Li,1 Baoxin Qian,3 Yusheng Yu2 1Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, People’s Republic of China; 2Department of Radiology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, People’s Republic of China; 3Huiying Medical Technology (Beijing); Huiying Medical Technology Co., Ltd, Beijing City, 100192, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Delian Kong; Yusheng Yu, Email xykdl@163.com; yayiba2063@163.comObjective: To develop a radiomics nomogram model based on time-of-flight magnetic resonance angiography (TOF-MRA) images for preoperative prediction of true microaneurysms.Methods: 118 patients with Intracranial Aneurysm Sac (40 positive and 78 negative) were enrolled and allocated to training and validation groups (8:2 ratio). Findings of clinical characteristics and MRA features were analyzed. A radiomics signature was built on the basis of reproducible features by using the least absolute shrinkage and selection operator (LASSO) regression algorithm in the training group. The radiomics nomogram model was constructed by combining clinical risk factors and radiomics signature. In order to compare the classification performance of clinical models, radiomics model and radiomics nomogram model, AUC was used to evaluate them. The performance of the radiomics nomogram model was evaluated by calibration curve and decision curve analysis.Results: Eleven features were selected to develop radiomics model with AUC of 0.875 (95% CI 0.78– 0.97), sensitivity of 0.84, and specificity of 0.68. The radiomics model achieved a better diagnostic performance than the clinic model (AUC = 0.75, 95% CI: 0.53– 0.97) and even radiologists. The radiomics nomogram model, which combines radiomics signature and clinical risk factors, is effective too (AUC = 0.913, 95% CI: 0.87– 0.96). Furthermore, the decision curve analysis demonstrated significantly better net benefit in the radiomics nomogram model.Conclusion: Radiomics features derived from TOF-MRA can reliably be used to build a radiomics nomogram model for effectively differentiating between pseudo microaneurysms and true microaneurysms, and it can provide an objective basis for the selection of clinical treatment plans.Keywords: machine learning, radiomics, microaneurysms, nomogram

Yuhuan Lv, Zheng Yang, Linyu Xiang, Meng Yu, Subei Zhao, Xiaoru Zhang, Rong Li Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of ChinaCorrespondence: Rong Li, The Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, YouYi Road 1&num;, Yuzhong District, Chongqing, People’s Republic of China, Email rongli@hospital.cqmu.edu.cnBackground: As an early manifestation of diabetic peripheral neuropathy (DPN), sudomotor dysfunction significantly increases the risk of diabetic foot ulcer. The pathogenesis of sudomotor dysfunction is still unclear. Lower limb ischemia may be related to sudomotor dysfunction, but few studies have explored it. The purpose of this study is to explore the relationship between sudomotor function and comprehensive lower limb arterial ischemia including large arteries, small arteries and microvascular in type 2 diabetes mellitus (T2DM).Patients and Methods: 511 T2DM patients were enrolled in this cross-sectional study. Sudomotor function was assessed qualitatively and quantitatively by Neuropad. Lower limb arterial ischemia was defined as any abnormality of the ankle brachial index (ABI), toe brachial index (TBI) or transcutaneous oxygen tension (TcPO2).Results: In this study, 75.1% of patients had sudomotor dysfunction. Compared with normal sudomotor function, patients with sudomotor dysfunction had a higher incidence of lower limb arterial ischemia (51.2% vs 36.2%, p = 0.004). Similarly, compared with the non-arterial ischemia group, the proportion of sudomotor disorders was higher in the arterial ischemia group (p = 0.004). Low TBI and low TcPO2 groups also had a higher proportion of sudomotor disorders (all p < 0.05).Compare with normal groups, low ABI, low TBI, and low TcPO2 groups had lower Slop4 which quantitatively reflecting Neuropad discoloration. Arterial ischemia was an independent risk factor for sudomotor dysfunction [OR = 1.754, p = 0.024]. Low TcPO2 also independently increased the risk of sudomotor disorders [OR = 2.231, p = 0.026].Conclusion: Lower limb arterial ischemia is an independent risk factor of sudomotor dysfunction. Especially below the ankle (BTA) small arteries and microvascular ischemia may also be involved in the occurrence of sudomotor disorders.Keywords: sudomotor function, lower limb arterial ischemia, ankle brachial index, toe brachial index, transcutaneous oxygen tension

Wusheng Deng,1,&ast; Yun Jiang,2,&ast; Jiaoxia Qin,1,&ast; Gang Chen,3,&ast; Yongjie Lv,1 Yanmei Lei,1 Jing Luo,1 Kangkang Hong,1 Bing Huang,1 Luhai Qin,4 Xiujia Tang,1 Liumei Ye,1 Yuhai Dang,1 Chao Wang,1 Feiyang Long,1 Ke Wang,1 Jinliang Kong1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Pulmonology, Hechi Traditional Chinese Medicine Hospital, Hechi, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@163.com; keewang@hotmail.comBackground: Aspergillus fumigatus is an opportunistic fungal pathogen, which is commonly found in lungs and rarely causes infections in mediastinum. Mediastinal Aspergillus abscess is a serious infectious condition, and is characterized by difficult diagnosis due to its clinical manifestations being nonspecific.Case Presentation: Here, we report a case of a mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. The patient was a 45-year-old woman who presented with a 20-day history of sore throat without any underlying diseases. Chest computed tomography (CT) showed a mass in the anterior superior mediastinum. Metagenomic next-generation sequencing (mNGS) identified Aspergillus fumigatus sequences in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) tissue, indicating the mediastinal Aspergillus fumigatus infection of this patient. The following mediastinal biopsy histological analysis and tissue fungi culture also suggested Aspergillus fumigatus infection, confirming the mNGS detection. The patient was diagnosed with mediastinal aspergillosis caused by Aspergillus fumigatus. After timely voriconazole treatment, the patient was discharged with good condition.Conclusion: Our study presented a rare case with mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. As a new clinical diagnostic method, mNGS could assist timely diagnosis and precise treatment of Aspergillus infection.Keywords: mediastinal abscess, Aspergillus fumigatus, metagenomic next-generation sequencing, diagnosis, case report

Qiuxue Sun,1,&ast; Hailian Xu,2,&ast; Wenyue Zhang,3 Yuqiu Zhou,1 Yumei Lv1 1School of Nursing, Harbin Medical University (Daqing), Daqing, People’s Republic of China; 2School of Medical, Quzhou College of Technology, Quzhou, People’s Republic of China; 3Department of Rehabilitation, People’s Hospital of Daqing, Daqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yumei Lv, School of Nursing, Harbin Medical University (Daqing), No. 39 Xinyang Road, Longfeng District, Daqing, People’s Republic of China, Email lymktz@163.comBackground: Subthreshold depression (SD) is known to be a major risk factor for the development of post-stroke depression (PSD). Appropriate intervention to prevent the transition from SD to PSD is thus imperative. As a form of short-term psychotherapy adapted for individuals with cognitive and communication impairments, behavioral activation therapy (BAT) may be a suitable choice. However, the effects of BAT on psychological outcomes in stroke patients with SD has not been established. This study investigated the feasibility and effectiveness of BAT in reducing the development of depressive symptoms in this patient population.Methods: A double-blind, randomized controlled trial was performed. Seventy participants were randomized to either a BAT group (n=35) or a control group (n=35). Participants in the BAT group received a six-week BAT intervention. The feasibility of BAT was assessed by the number of sessions attended by participants, and the acceptability of BAT to participants and the incidence of adverse events were recorded. The primary clinical outcome measure was the Center for Epidemiological Studies Depression Scale (CES-D) and the 17-item Hamilton Depression Scale (HAMD-17) at baseline, six weeks, and three months after the group allocation. Secondary outcomes included behavioral activation and the incidence of depression.Results: The intervention was feasible and acceptable, with 94.3% of participants in the BAT group (33 of 35) attending at least five sessions. No adverse events were reported in either group. Compared with the control group, the BAT group showed significant improvements in the CES-D (F=67.689, P< 0.05), HAMD-17 (F=4.170, P< 0.05), and behavioral activation (F=25.355, P< 0.05) scores after intervention, and these differences were maintained at the three-month assessment.Conclusion: BAT appears to be feasible and efficacious for reducing depressive symptoms and increasing behavioral activation among stroke patients with SD. The findings of this study may contribute to the primary prevention of PSD.Keywords: stroke, subthreshold depression, post-stroke depression, behavioral activation therapy

Gangtie Liu,1,2 Guanglei Wang,2 Zhan Yang,2 Guangfu Liu,3 Haijun Ma,3 Yong Lv,2 Feiyan Ma,2 Weiwei Zhu1 1Department of Pediatrics, Jinan Central Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Pediatrics, Taian Maternity and Child Health Care Hospital, Taian, People’s Republic of China; 3Department of Radiology, Taian Maternity and Child Health Care Hospital, Taian, People’s Republic of ChinaCorrespondence: Weiwei Zhu, Department of Pediatrics, Jinan Central Hospital, Shandong University, No. 105 Jiefang Road, Jinan, 250013, People’s Republic of China, Tel +86-538-6620622, Email 198651020311@email.sdu.edu.cnPurpose: Early diagnosis of refractory Mycoplasma pneumoniae pneumonia (RMPP) is challenging because of the lack of practical diagnostic imaging tools. Lung ultrasound (LUS) is an emerging tool for diagnosing childhood pneumonia. Hence, we evaluated the role of a nomogram combining LUS findings, clinical features, and laboratory indices in the early prediction of RMPP in children.Patients and Methods: We retrospectively analyzed 225 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to our hospital between Dec 2018 and Aug 2021. Logistic regression analysis incorporated LUS findings and clinical predictors into the nomogram. Ninety patients hospitalized from Sep 2021 to Dec 2021 were used for external validation of the prediction model. Receiver operating characteristics (ROC) and calibration curves were used to evaluate the performance of the nomogram in the early diagnosis of RMPP.Results: Ultimately, Consolidation size /BSA (odds ratio (OR) 1.015, 95% confidence interval (CI) 1.536– 2.446), Pleural Effusion (OR 3.551, 95% CI 1.921– 15.600), LDH (OR 1.044, 95% CI 1.006– 1. 021) and CRP (OR 3.293, 95% CI 1.019– 1.098) were independent risk factors for the development of RMPP. The prediction model was represented visually as a nomogram. The area under the ROC curve for the predictive nomogram was 0.955 (95% CI 0.919– 0.978) in the training cohort and 0.916 (95% CI 0.838– 0.964) in the validation cohort. The calibration curve is close to the diagonal.Conclusion: This is the first-time lung ultrasound was added to the predicted nomogram, which can more comprehensively assess the condition and more accurately predict the occurrence of RMPP early. Therefore, this nomogram can be widely used in the early diagnosis of RMPP, especially in primary care hospitals.Graphical Abstract: Keywords: predictive model, risk factors, diagnosis, Mycoplasma pneumoniae pneumonia

Min Zhang,1 Yao Lv,2 Haokui Liu3 1Department of Nephrology, Bayannur Hospital, Bayannur, Inner Mongolia, People’s Republic of China; 2Department of Orthopedics, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 3Department of Traumatic Orthopedics, Bayannur Hospital, Bayannur, Inner Mongolia, People’s Republic of ChinaCorrespondence: Haokui Liu, Department of Traumatic Orthopedics, Bayannur Hospital, No. 98 Wulan Buhe Road, Linhe District, Bayannur City, Inner Mongolia, 015000, People’s Republic of China, Tel +86-15047899415, Email liuhaokui123@163.comObjective: To investigate the efficacy of cyclophosphamide combined with prednisone in membranous nephropathy (MN) patients with different cytochrome P450 (CYP) 2B6 gene polymorphisms and explore the factors influencing the efficacy.Methods: We performed a prospective and interventional study including 153 outpatients diagnosed with membranous nephropathy from April 2020 to June 2020 in the Bayannur Hospital. Based on the results of CYP2B6 gene polymorphisms, patients were divided into CYP2B6&ast;4 group (785A>G) with 93 cases and CYP2B6&ast;5 group (1459C>T) with 60 cases, and all patients were treated with cyclophosphamide and prednisone. The efficacy of the two groups was compared, and the serum levels of antibody against thrombospondin type-1 domain-containing 7A (THSD7A-Ab), 8-hydroxy-2’-deoxyguanosine (8-OHdG) and antibody against the M-type phospholipase A2 receptor (PLA2R-Ab) determined by the enzyme-linked immunosorbent method were analyzed in the two groups before and after treatment.Results: After the treatment with cyclophosphamide and prednisone, serum levels of THSD7A-Ab, 8-OHdG, and PLA2R-Ab were higher in the CYP2B6&ast;4 group than those in the CYP2B6&ast;5 group (All three P< 0.001). The univariate Logistic regression analysis showed that CYP2B6&ast;4 (OR = 1.727, 95% CI: 1.028– 2.654. P=0.012), CYP2B6&ast;5 (OR = 1.802, 95% CI: 1.179– 2.752. P=0.031), THSD7A-Ab (OR = 1.832, 95% CI: 0.871– 2.348. P=0.023), 8-OHdG (OR = 1.661, 95% CI: 1.123– 2.231. P=0.009), PLA2R-Ab (OR = 1.649, 95% CI: 1.083– 2.761. P=0.017) were independent influencing factors on the efficacy of MN. The multivariate Logistic regression analysis showed that CYP2B6&ast;4 (OR = 2.009, 95% CI: 1.327– 2.703. P< 0.001), CYP2B6&ast;5 (OR = 3.009, 95% CI: 1.467– 5.231. P=0.005), THSD7A-Ab (OR = 1.396, 95% CI: 1.002– 1.897. P=0.019), 8-OHdG (OR = 0.704, 95% CI: 0.591– 0.742. P< 0.001), PLA2R-Ab (OR = 2.761, 95% CI: 1.231– 3.918. P=0.017) were independent factors influencing the efficacy of cyclophosphamide and prednisone on MN.Conclusion: Cyclophosphamide combined with prednisone was effective in treating MN with different CYP2B6 gene polymorphisms. CYP2B6&ast;4, CYP2B6&ast;5, and serum levels of THSD7A-Ab, 8-OHdG, and PLA2R-Ab were independent influencing factors on the outcome of MN.Keywords: cyclophosphamide, prednisone, gene polymorphisms, membranous nephropathy, influencing factor

Yijie Lv,1 Junnan Kan,1 Mingfang Luo,2 Changfeng Yang,1 Xunrong Luo,2 Xiaoqian Lin,1 Hao Li,1 Xueming Li,1 Yuping Li,1 Caixia Yang,1 Yan Liu,1 Xianglin Li1 1School of Medical Imaging, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 2Department of Radiology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 610072, People’s Republic of ChinaCorrespondence: Yan Liu; Xianglin Li, School of Medical Imaging, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China, Tel +86 535 6919135 ; +86 535 6919175, Email liuericyan@hotmail.com; xlli@bzmc.edu.cnIntroduction: Accurate tumor diagnosis is essential to achieve the ideal therapeutic effect. However, it is difficult to accurately diagnose cancer using a single imaging method because of the technical limitations. Multimodal imaging plays an increasingly important role in tumor treatment. Photodynamic therapy (PDT) has received widespread attention in tumor treatment due to its high specificity and controllable photocytotoxicity. Nevertheless, PDT is susceptible to tumor microenvironment (TME) hypoxia, which greatly reduces the therapeutic effect of tumor treatment.Methods: In this study, a novel multifunctional nano-snowflake probe (USPIO@MnO2@Ce6, UMC) for oxygen-enhanced photodynamic therapy was developed. We have fabricated the honeycomb-like MnO2 to co-load chlorin e6 (Ce6, a photosensitizer) and ultrasmall superparamagnetic iron oxide (USPIO, T1-T2 double contrast agent). Under the high H2O2 level of tumor cells, UMC efficiently degraded and triggered the exposure of photosensitizers to the generated oxygen, accelerating the production of reactive oxygen species (ROS) during PDT. Moreover, the resulting USPIO and Mn2+ allow for MR T1-T2 imaging and transformable PAI for multimodal imaging-guided tumor therapy.Results: TEM and UV-vis spectroscopy results showed that nano-snowflake probe (UMC) was successfully synthesized, and the degradation of UMC was due to the pH/ H2O2 responsive properties. In vitro results indicated good uptake of UMC in 4T-1 cells, with maximal accumulation at 4 h. In vitro and in vivo experimental results showed their imaging capability for both T1-T2 MR and PA imaging, providing the potential for multimodal imaging-guided tumor therapy. Compared to the free Ce6, UMC exhibited enhanced treatment efficiency due to the production of O2 with the assistance of 660 nm laser irradiation. In vivo experiments confirmed that UMC achieved oxygenated PDT under MR/PA imaging guidance in tumor-bearing mice and significantly inhibited tumor growth in tumor-bearing mice, exhibiting good biocompatibility and minimal side effects.Conclusion: The multimodal imaging contrast agent (UMC) not only can be used for MR and PA imaging but also has oxygen-enhanced PDT capabilities. These results suggest that UMC may have a good potential for further clinical application in the future.Graphical Abstract: Keywords: photodynamic therapy, oxygen generation, magnetic resonance imaging, photoacoustic imaging, theranostics, nanoprobe

Zhen Qin,1– 3 Shuai Xu,1– 3 Ruixia Yuan,4 Zeyu Wang,1– 3 Yongzheng Lu,1– 3 Yanyan Xu,1– 3 Yan Lv,1– 3 Fengyi Yu,1– 3 Jing Bai,1– 3 Hui Zhang,1– 3 Li Zhang,1– 3 Jinying Zhang,1– 3 Junnan Tang1– 3 1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 2Henan Province Key Laboratory of Cardiac Injury and Repair, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, 450018, People’s Republic of China; 4Clinical Big Data Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Junnan Tang, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 15890696166, Email fcctangjn@zzu.edu.cn Jinying Zhang, Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13503830283, Email jyzhang@zzu.edu.cnObjective: We aimed to investigate the prognostic value of the triglyceride-glucose (TyG) index combined the with Global Registry of Acute Coronary Events (GRACE) score in adult acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) who underwent percutaneous coronary intervention (PCI).Methods: The study enrolled total 899 ACS patients with T2DM who underwent PCI. TyG index and the GRACE risk score were calculated and assessed by median. The correlation was analyzed by Spearman’s rank correlation coefficient. The cumulative major adverse cardiovascular event (MACE) curve was generated using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of MACEs. Additionally, the receiver operating characteristic curve (ROC), net reclassification index (NRI) and Integrated Discrimination Improvement (IDI) were applied to analyze the performance of each single factor index and combined multivariate index in predicting MACE.Results: In the ACS patients with T2DM after PCI, there were significant differences in the TyG index and GRACE risk score between the MACE group and the MACE-free group (P < 0.001). Kaplan–Meier analysis showed that the TyG index combined with the GRACE risk score was positively correlated with the occurrence of MACEs (log rank P < 0.001). Multivariate Cox regression analyses showed that the TyG index, the GRACE risk score, and the TyG index combined with the GRACE risk score were independent predictors of long-term MACEs (adjusted HR: 1.805; 95% CI: 1.479– 2.203, P < 0.001; adjusted HR: 1.012; 95% CI: 1.009– 1.016, P < 0.001; and adjusted HR: 2.337; 95% CI: 1.805– 3.025, P < 0.001, respectively). Correlation analysis indicated that the TyG index was positively correlated with the GRACE risk score (R = 0.140, P < 0.001). The analysis of AUC, NRI and IDI revealed that the combined multivariate index performed better prognostic role than each single factor index in predicting the occurrence of MACE.Conclusion: Both the GRACE risk score and the TyG index could be significant and independent predictors of clinical outcomes in ACS patients with T2DM after PCI. A combination of them could be enhanced predictions of clinical outcomes in these patients.Keywords: triglyceride-glucose index, GRACE risk score, predictive biomarker, acute coronary syndrome, type 2 diabetes mellitus, percutaneous coronary intervention

Yuyu Lv,1,2 Ru Ren,1– 3 Chengxiang Tang,4 Kuimeng Song,5 Shunping Li,1– 3 Haipeng Wang1,2 1Center for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2NHC Key Laboratory of Health Economics and Policy Research (Shandong University), Jinan, People’s Republic of China; 3Center for Health Preference Research, Shandong University, Jinan, People’s Republic of China; 4Macquarie University Centre for the Health Economy, Macquarie University Business School & Australian Institute of Health Innovation, Macquarie University, Sydney, NSW, Australia; 5School of Health Care Security, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaCorrespondence: Shunping Li; Haipeng Wang, Centre for Health Management and Policy Research, Wenhua Xi Road 44, Jinan, Shandong Province, 250012, People’s Republic of China, Tel +86-131-8893-4998, +86-186-6899-6362, Email lishunping@sdu.edu.cn; wanghaipeng@sdu.edu.cnPurpose: To evaluate preferences for medications among patients with type 2 diabetes mellitus (T2DM) from urban community health stations or rural village clinics in Shandong province, China.Methods: We use a discrete choice experiment (DCE) to measure the medication preferences. Each patient completed six DCE choice sets. The attributes for the DCE questionnaire include mode of administration, out-of-pocket medication cost per month, fasting blood glucose control effect and frequency of hypoglycemia events. The conditional logit model (Clogit) and mixed logit model (MXL) were used to evaluate choice data.Results: A total of 887 patients with T2DM completed the survey. The mean age of participants was 64 years, 36.42% experienced complications, and the mean duration of diabetes was about 8 years. Overall, patients’ ideal medication would not have hypoglycemia events, provide normal fasting glucose levels, have oral medication three times a day and lower monthly medication cost. Patients prioritized the frequency of hypoglycemia events (β=15.055, P < 0.01) and were willing to spend CNY 393.10 per month to avoid hypoglycemia events. For patients with higher educational levels and with longer diagnosis time, the effect of fasting blood glucose was more relevant than all other outcomes.Conclusion: This study provides information on T2DM patients’ preference for medications. Our results suggest that clinical doctors should present patients with a variety of pharmaceutical characteristics and include their preference into medication decision, which will improve patient adherence and health outcomes.Keywords: type 2 diabetes mellitus, patients’ preference, medication, discrete choice experiment

Yongming Xu,1,&ast; Qingqing Jiang,2,&ast; Xiaoliang Xu,3,&ast; Shaofeng Pu,1 Yingying Lv,1 Chen Li,1 Junzhen Wu,1,&ast; Dongping Du1,&ast; 1Department of Pain Management Center, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Neurology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 3Department of Anesthesiology, Cixi People’s Hospital, Cixi, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongping Du; Junzhen Wu, Department of Pain Management Center, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86-21-24058896, Fax +86-21-240598896, Email dudp@sjtu.edu.cn; analgesia@sjtu.edu.cnBackground: Neuropathic pain is the most common clinical sign of complex regional pain syndrome (CRPS). Currently, lumbar sympathetic block (LSB) is commonly utilized in lower extremity CRPS that has failed to respond to medication therapy and physical therapy, but its effectiveness is unknown. The tourniquet ischemia test (IT) can distinguish between two types of CRPS: IT-positive CRPS and IT-negative CRPS.Objective: The aim of the study was to investigate whether LSB improves pain scores in patients with lower extremity CRPS-1 and to screen factors to predict its efficacy.Study Design: Prospective clinical observational study.Setting: Pain management center.Subjects: Forty-three patients diagnosed with lower extremity CRPS-1 using the Budapest criteria were included as participants.Methods: Forty-three CRPS-1 patients were treated with LSB therapy, and all of them underwent a tourniquet ischemia test (IT) before undergoing LSB therapy. LSB therapy was performed using a combination of ultrasonography and fluoroscopy. Then, numeric rating scale (NRS) scores and the symptom relief rates of patients were evaluated at 1, 4, and 12 weeks. Finally, peripheral blood inflammatory cytokine samples were collected before and after the LSB treatment.Results: At 4 weeks after the treatment, the total effective symptom relief rate of LSB on CRPS-1 was 25.6% (11/43), with 52.6% (10/19) of IT(+) patients and 4.2% (1/24) of IT(-) patients. There was a significant difference between the IT(-) and IT(+) groups (P = 0.001). The multivariate binary logistic regression analysis revealed that the response to the tourniquet IT was the only significant independent predictor of sympathetic block success (p = 0.007).Conclusion: Tourniquet IT is a simple, safe and effective test to distinguish patients with lower extremity CRPS-1. The response to the tourniquet IT is a reliable predictor of LSB effectiveness in lower extremity CRPS-1 patients.Keywords: complex regional pain syndrome, lumbar sympathetic block, tourniquet ischemia test, predict

Lv Y, Kan J, Luo M, et al. Int J Nanomedicine. 2022;17:4619-4638. The equal contribution statement was missing from the author list on page 4619. The correct author and affiliation list is as follows: Yijie Lv1,*, Junnan Kan1,*, Mingfang Luo2, Changfeng Yang1, Xunrong Luo2, Xiaoqian Lin1, Hao Li1, Xueming Li1, Yuping Li1, Caixia Yang1, Yan Liu1, Xianglin Li1 1School of Medical Imaging, Binzhou Medical University, Yantai, Shandong, 264003, People’s Republic of China; 2Department of Radiology, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 610072, People’s Republic of China *These authors contributed equally to this work The authors apologize for this error.

Runan Zuo,1 Yan Zhang,1 Xiaorong Chen,1 Shiheng Hu,1 Xinhao Song,1 Xiuge Gao,1 Jiahao Gong,1 Hui Ji,1 Fengzhu Yang,1 Lin Peng,1 Kun Fang,2 Yingjun Lv,1 Junren Zhang,1 Shanxiang Jiang,1 Dawei Guo1 1Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, People’s Republic of China; 2The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of ChinaCorrespondence: Dawei Guo; Shanxiang Jiang, Engineering Center of Innovative Veterinary Drugs, Center for Veterinary Drug Research and Evaluation, MOE Joint International Research Laboratory of Animal, Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing, 210095, People’s Republic of China, Tel +86 25-84396215, Fax +86-25-84398669, Email gdawei0123@njau.edu.cn; nauvy@sina.comBackground: Halofuginone (HF)-loaded TPGS polymeric micelles (HTPM) were successfully fabricated using the thin-film hydration technique. HTPM via intravenous injection have been demonstrated to exert an excellent anticancer effect against triple-negative breast cancer (TNBC) cells and subcutaneous xenografts. In the present study, we further explored the potential treatment effect and mechanism of orally administered HTPM alone and in combination with surgical therapy on TNBC in subcutaneous and orthotopic mouse models.Methods: Herein, the stability and in vitro release behavior of HTPM were first evaluated in the simulated gastrointestinal fluids. Caco-2 cell monolayers were then used to investigate the absorption and transport patterns of HF with/without encapsulation in TPGS polymeric micelles. Subsequently, the therapeutic effect of orally administered HTPM was checked on subcutaneous xenografts of TNBC in nude mice. Ultimately, orally administered HTPM, combined with surgical therapy, were utilized to treat orthotopic TNBC in nude mice.Results: Our data confirmed that HTPM exhibited good stability and sustained release in the simulated gastrointestinal fluids. HF was authenticated to be a substrate of P-glycoprotein (P-gp), and its permeability across Caco-2 cell monolayers was markedly enhanced via heightening intracellular absorption and inhibiting P-gp efflux due to encapsulation in TPGS polymeric micelles. Compared with HF alone, HTPM showed stronger tumor-suppressing effects in subcutaneous xenografts of MDA-MB-231 cells when orally administered. Moreover, compared with HTPM or surgical therapy alone, peroral HTPM combined with partial surgical excision synergistically retarded the growth of orthotopic TNBC. Fundamentally, HTPM orally administered at the therapeutic dose did not cause any pathological injury, while HF alone led to weight loss and jejunal bleeding in the investigated mice.Conclusion: Taken together, HTPM could be applied as a potential anticancer agent for TNBC by oral administration.Graphical Abstract: Keywords: triple-negative breast cancer, Halofuginone hydrobromide, TPGS polymeric micelles, subcutaneous xenografts, orthotopic xenografts, oral administration

Guanyu Chi,&ast; Yinghua Lv,&ast; Shuang Chao,&ast; Chenxi Hou, Yuxin Pei, Zhichao Pei Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhichao Pei, Shaanxi Key Laboratory of Natural Products and Chemical Biology, College of Chemistry and Pharmacy, Northwest A&F University, Yangling, Shaanxi 712100, People’s Republic of China, Tel/Fax +86 29 8709-2769, Email peizc@nwafu.edu.cnBackground: Multifunctional nanocarriers based on tumor targeting and intracellular monitoring have received much attention and been a subject of intensive study by researchers in recent years. In this study, we report multifunctional glyconanoparticles with activatable near-infrared probes for tumor imaging and targeted drug delivery.Methods: Disulfide-functionalized dicyanomethylene-4H-pyran (DCM-SS-NH2) and amino-functionalized lactose were modified and loaded onto the surfaces of polydopamine nanoparticles (NPs) by Michael addition or Schiff-base reaction as GSH stimulation–responsive fluorescent probes and tumor-targeting moieties, respectively. Doxorubicin (DOX), a model anticancer drug, was loaded onto polydopamine through π–π interactions directly to prepare multifunctional PLDD (PDA@Lac/DCM/DOX) NPs.Results: Experimental results showed that PLDD NPs had been successfully prepared. DCM, the fluorescence of which was quenched in PLDD NPs, was able to restore red fluorescence in a solution with a GSH concentration of 5 mM. The amount of DOX released from PLDD NPs was 44% over 72 hours in a weak-acid environment (pH 5). The results of CLSM and flow cytometry indicated that the PLDD NPs had good HepG2-targeting ability due to the special recognition between lactose derivative of NPs and overexpressed asialoglycoprotein receptors on HepG2 cell membrane. More importantly, the disulfide bond of DCM-SS-NH2 was broken by the high concentration of GSH inside cancer cells, activating the near-infrared fluorescence probe DCM for cancer-cell imaging. MTT assays indicated that PLDD NPs exhibited higher anticancer efficiency for HepG2 cells and had reduced side effects on normal cells compared with free DOX.Conclusion: The fluorescence of modified DCM loaded onto PLDD NPs is able to be restored in the high-concentration GSH environment within cancer cells, while improving the effectiveness of chemotherapy with reduced side effects. It provides a good example of integration of tumor imaging and targeted drug delivery.Keywords: near-infrared probes, targeted drug delivery, GSH-responsive, tumor-cell imaging, polydopamine

Mengyao Yan, Bo Zheng, Yun Li, Yuan Lv Institute of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yun Li; Yuan Lv, Institute of Clinical Pharmacology, Peking University First Hospital, Xueyuan Road 38, Haidian District, Beijing, 100191, People’s Republic of China, Tel +86-10-82802315, Fax +86-10-62072817, Email liyun19702@sina.com; lvyuan0901@sina.comPurpose: The antimicrobial resistance profiles of gram-negative bacilli causing bloodstream infections have changed over time, while comprehensive and real-time surveillance data are limited in China. This study aimed to review the antimicrobial susceptibility trends among main gram-negative bacilli isolated from blood specimens in China.Methods: From 2011 to 2020, a total of 4352 non-duplicate isolates were collected from 21 tertiary hospitals in 18 provinces or cities across China. Antimicrobial susceptibility testing was conducted by the agar dilution method recommended by the Clinical and Laboratory Standards Institute (CLSI), and the results were interpreted using CLSI criteria.Results: During this 10-year surveillance period, meropenem and imipenem were the most effective agents against Escherichia coli (resistance remaining < 5%). The proportion of ESBL-producing isolates in carbapenem-susceptible E. coli displayed a decreasing trend (from 72.9% to 51.2%). The resistance rates of Klebsiella pneumoniae to meropenem and imipenem increased from 3.3% and 1.6% in the 2011– 12 period to 15.0% and 15.4% in the 2019– 20 period, respectively. Carbapenems and amikacin were the most active agents against Enterobacter cloacae. The resistance rates of Pseudomonas aeruginosa to meropenem and imipenem increased from 13.1% and 17.7% in the 2015– 16 period to 24.5% and 21.0% in the 2019– 20 period, respectively. Few agents showed activity against Acinetobacter baumannii. The frequency of imipenem-non-susceptible A. baumannii remained stable (remaining ∼ 70%).Conclusion: The rapid spread of carbapenem-resistant K. pneumoniae has been serious in recent years. Conversely, the prevalence of ESBL-producing isolates was decreased. Carbapenems are still effective against gram-negative bacilli causing BSIs, except for A. baumannii. More attention should be given to A. baumannii, considering its high resistance against different classes of antimicrobials.Keywords: Enterobacterales, P. aeruginosa, A. baumannii, ESBL, carbapenem-resistance

Shanshan Peng,1 Na Liu,1 Kai Wei,1 Gang Li,2 Zheng Zou,3 Tao Liu,3 Meifang Shi,3 Yuan Lv,1 Yong Lin1 1Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Baoshan Renhe Hospital, Shanghai, People’s Republic of China; 3Youyi Road Community Health Service Centre for Baoshan District, Shanghai, People’s Republic of ChinaCorrespondence: Yong Lin, Department of Laboratory Medicine, Huashan Hospital, Fudan University, No. 12 the Middle of Urumqi Road, Shanghai, People’s Republic of China, Tel +86 13916553198, Email linyong7007@163.comPurpose: Recent studies have focused on whether kidney injury molecule-1 (KIM-1) might serve as a marker of acute kidney tubular injury. Our study analyzed the levels of KIM-1 in the healthy population of different ages to explore the correlation between KIM-1 and age. Moreover, we constructed a model to predict kidney age.Methods: A cross-sectional study was conducted by Huashan Hospital, Shanghai, China, between April 2020 and December 2020. KIM-1 and other kidney biomarkers were measured in 176 healthy individuals ranging from 26 to 91 years old. Statistical correlated analyses for urinary KIM-1, creatinine (uCREA), potassium (K), sodium (Na) and chlorine (Cl), plasmic renin, angiotensin-2 (AngII) and aldosterone (ALD), and serum microalbuminuria (MALB), β 2-microglobulin (B2MG), cystatin C (CYSC), urea nitrogen (BUN), creatinine (CREA), and glucose (GLU) were performed to assess the correlation between age and kidney biomarkers. All variables were selected as independent variables for the prediction of age by multiple linear regression.Results: KIM-1 positively correlated with age in kidney healthy people (r = 0.41, p < 0.05), whether among females (r = 0.51, p < 0.05) or males (r = 0.27, p < 0.05). It was much related to K (r = 0.34), B2MG (r = 0.28), and CL (r = 0.23). The predicted model was constructed with eGFR, Cl, ALD, CYSC, KIM-1, BUN, GLU and AngII, reaching an adjusted R2 of 69.5% and a standard error of the estimated 7.84 years.Conclusion: The level of urinary KIM-1 increases with age in healthy people. The model constructed by KIM-1 and the other 7 biomarkers can predict kidney age in healthy people.Keywords: aging, kidney biomarkers, KIM-1, healthy

Cheng Ma,1,&ast; He Li,1,&ast; Teng Zhang,1 Yifan Wei,1 Helong Zhang,1 Fenglei Yu,1 You Lv,2 Yongxin Ren1 1Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu, People’s Republic of China; 2Department of Orthopaedics, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang, Lianyungang, 222061, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yongxin Ren, Tel +86 13585162283, Email renyongxinjsph@163.comPurpose: Both percutaneous endoscopic lumbar discectomy (PELD) and open fenestration discectomy (OFD) are effective and safe surgical procedures for the treatment of LDH. The purpose of this retrospective study was to compare the surgical outcomes of percutaneous endoscopic interlaminar discectomy (PEID) and OFD for single-segment huge lumbar disc herniation (HLDH).Patients and Methods: We retrospectively analyzed 91 patients diagnosed with single-segment HLDH and treated with OFD or PEID. Visual analog scale (VAS), modified Japanese orthopedic association (mJOA) and Oswestry disability index (ODI) were used to assess clinical outcomes at preoperation and postoperatively at 3, 6, 12, and 24months. Modified Macnab criteria were applied to evaluate clinically satisfaction at the final follow-up.Results: In both groups, the VAS and ODI scores at 3, 6, 12, and 24months postoperatively showed a significant decrease and the mJOA score at 3, 6, 12, and 24months postoperatively was significantly increased compared to preoperative results (P< 0.001). According to Macnab criteria at the final follow-up, the overall clinically satisfactory rate was 86.67% in the OFD group and 86.96% in the PEID group. There were no significant differences in VAS, ODI, and mJOA scores between the two groups at preoperation and postoperative 3, 6, 12, and 24months, respectively. In the PEID group, the length of hospitalization and the length of incision were significantly shorter than that in the OFD group (P< 0.0001). However, there was no significant difference in operative time between groups (P=0.81).Conclusion: Collectively, postoperative clinical results were equally favorable for both procedures, with no statistically significant difference between PEID and OFD at the two-year of follow-up. No serious complication was observed in two groups. Compared with the traditional surgery, PEID has the following benefits: less trauma, less bleeding, speedy recovery, and shorter hospitalization. Therefore, PEID may be a promising alternative to traditional surgery.Keywords: percutaneous endoscopic lumbar discectomy, percutaneous endoscopic interlaminar discectomy, open fenestration discectomy, single-segment, huge lumbar disc herniation

Liu S, Jiang J, Huang L, et al. Cancer Manag Res. 2019;11:8005–8022. We, the Editors and Publisher of Cancer Management and Research, have retracted the published article. Concerns were raised following the authors request to correct Figure 4. It was found images in Figure 4 had been duplicated. Specifically, The images for Figure 4C, 0h, 0 µmol/l and 25 µmol/l, have been duplicated. When approached for an explanation, the authors were cooperative and provided some original data for their study, however, the provided data was not satisfactory, and the results could not be adequately verified. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors do not agree with this decision. We have been informed in our decision-making by our editorial policies and the COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yongmei Lv, Yamei Gao, Na Lan, Minghui Sun, Chenchen Zhang, Jing Gao, Na Wang, Xingyu Yang Departments of Dermatology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of ChinaCorrespondence: Yongmei Lv, Department of Dermatology, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei Economic and Technological Development Zone, Hefei, Anhui Province, 230601, People’s Republic of China, Email yongmei_lv830@163.comPurpose: To understand the distribution characteristics of onset time, onset age and gender of pityriasis alba (PA) patients in the dermatology clinic of our hospital and to further explore the pathogenesis of the disease to provide a scientific basis for the prevention and treatment of this disease.Patients and Methods: The clinical data of 2726 outpatients with PA diagnosed for the first time from January 2016 to December 2020 were collected and descriptively analyzed.Results: The number of patients with PA was less from January to March. The peak was reached in July and August. The number of cases affected by the COVID-19 epidemic in 2020 was significantly lower than that in previous years. Furthermore, the onset age of the patients ranged from 0 to 64 years old, and the median age of the total population was 7 (3, 13) years old, including 1566 males (57.45%) and 1160 females (42.55%). The ratio of male to female was 1.35:1. The number of male patients before 18 years old was higher than that of female patients, especially in the high paroxysmal age group.Conclusion: PA can be seen all the year round, and the onset peak of the disease is from July to August every year. It occurs frequently at the age of 1 to 14 before puberty. In the season of high incidence of PA, the protection from sun and moisture retention should be strengthened for infants and adolescents.Keywords: pityriasis alba, epidemic characteristics, pathogenic factors

Shaofeng Pu,1 Yiyang Wu,1 Qingjian Han,2 Jie Chen,3 Yongming Xu,1 Yingying Lv,1 Chen Li,1 Jing Lu,4 Junzhen Wu,1,&ast; Dongping Du1,&ast; 1Department of Pain Management, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 2Institutes of Brain Science, Fudan University, Shanghai, 200032, People’s Republic of China; 3Shanghai Institute of Ultrasound in Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 4Radiology Department, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongping Du, Department of Pain Management, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China, Tel +86 21 2405 8896, Fax +86 21 2405 8330, Email dudp@sjtu.edu.cnPurpose: Thoracic nerve root (TNR) block is performed primarily under computed tomography or X-ray fluoroscopy but is associated with radiation exposure. Ultrasound requires no radiation and distinguishes vessels, nerves, pleura, and other tissues. Few reports of ultrasound-guided TNR (US-TNR) block have been described, and the puncture end point has not been clearly defined. Herein, we evaluated the feasibility of US-TNR block using the midpoint of the inferior articular process (IAP) and parietal pleura (PP) as the puncture end point.Patients and Methods: A prospective series of 10 patients with Herpes Zoster-associated pain underwent US-TNR-guided block performed using an in-plane technique with the midpoint of thoracic IAP and PP as the puncture end points of ultrasonography. The US-TNR block procedure was performed with ultrasound as the primary imaging tool followed by fluoroscopic confirmation.Results: In all patients, the needle tips were visible at the lateral margin of the pedicle in the anteroposterior view and at the extraforaminal zone in the lateral view. The TNR and dorsal root ganglion (DRG) were delineated in all 10 patients. Furthermore, 2 mL of radiopaque agent could delineate the epidural space in 8 patients and the thoracic paravertebral (TPV) space in the other 2 patients. All patients developed numbness along the corresponding dermatome 30 min after injection of local anesthetics. The numeric rating scale (NRS) score at baseline, and at two- and four-week follow-ups were 6.50 ± 1.35, 3.50 ± 0.85 (vs NRS at baseline, P < 0.01), and 4.00 ± 0.82 (vs NRS at baseline, P < 0.01), respectively.Conclusion: This study demonstrated the feasibility of US-TNR block using the in-plane technique with the midpoint of thoracic IAP and PP as the puncture end point to effectively block the TNR and DRG. This technique is an accurate clinical application of TPV nerve block and provides a potential therapeutic option for the treatment of neuropathic pain.Keywords: ultrasound-guided, thoracic nerve root, thoracic paravertebral, midpoint, neuropathic pain

Ayodele Olaolu Oladejo,1,2 Yajuan Li,1 Bereket Habte Imam,1,3 Xiaoyu Ma,1 Wenxiang Shen,1 Xiaohu Wu,1 Wei Jiang,1 Jie Yang,1 Yanan Lv,1 Xuezhi Ding,1 Shengyi Wang,1 Zuoting Yan1 1Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, 730050, People’s Republic of China; 2Department of Animal Health Technology, Oyo State College of Agriculture and Technology, Igboora, 201103, Nigeria; 3Department of Veterinary Science, Hamelmalo Agricultural College, Keren, 397, EritreaCorrespondence: Zuoting YanKey Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, 730050, People’s Republic of China, Tel +8613919067215, Email yanzuoting@caas.cnPurpose: Endometritis is a female reproductive disease that affects the cattle industries development and microRNAs (miRNAs) play a pivotal role and critical regulators of the innate immune response in varieties of diseases. The present study intends to investigate the regulatory role of miR‐24-3p in the innate immune response involved in endometritis and evaluate its therapeutic potential.Methods: Whole mice uteri and bovine endometrial epithelial cells (BEECs) were separately stimulated with LPS. The BEECs were also transfected with miR-24-3p mimic and negative control; siTRAF6 and siNC; pcDNA3.1 empty and pcDNA3.1(+)TRAF6 separately with LPS stimulation. The expression levels of miR‐24-3p and TRAF6 were measured via quantitative real‐time polymerase chain reaction (qRT-PCR) and Western blot, respectively. LPS‐induced inflammatory response assessed by inflammatory cytokines secretion and expression via ELISA and qRT-PCR. Bioinformatics analysis and luciferase reporter assay validated the interaction between miR‐24-3p and TRAF6. The activation of the NF‐&kgreen;B/MAPK pathway and p65 phosphorylation was investigated by Western blot and immunofluorescence assay, respectively.Results: The expression of miR‐24-3p was decreased, and TRAF6 was elevated with an increased level of pro-inflammatory cytokines in LPS‐treated BEECs and mice uterus. The overexpression of miR‐24-3p suppressed LPS‐induced secretion of inflammatory cytokines (IL‐1β, IL‐6, IL-8 and TNF-α) and deactivation of NF‐&kgreen;B/MAPK pathways. The downregulation of TRAF6 inhibited LPS‐induced inflammatory response in BEECs. TRAF6 is validated as a target of miR‐24-3p, and miR‐24-3p reversed the overexpression of cloned TRAF6 on inflammation response in BEECs.Conclusion: Our findings demonstrate that the overexpression of miR‐24-3p attenuates endometrial inflammation and the expression of pro-inflammatory mediators via suppressing TRAF6. Therefore, modulating the pathogenesis of endometritis and possibly, a therapeutic potential against endometritis.Keywords: endometritis, miR-24-3p, TRAF6, NF-&kgreen;B/MAPK, inflammation