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Chengran Wang,* Xiaoqing Zhao,* Keyan Wang, Huixin Liang, Shuhan Chen, Yajie Liu, Hua Yao, Jinlan Jiang Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua Yao; Jinlan Jiang, Department of Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Tel\Fax +86-13596102816, Email yao_hua@jlu.edu.cn; jiangjinlan@jlu.edu.cnAbstract: Disseminated intravascular coagulation (DIC) is an acquired disorder characterized by systemic activation of blood coagulation, which can arise from various causes. Owing to its abrupt onset, rapid progression, and high mortality rate, DIC presents a major clinical challenge. Anticoagulant drugs, such as heparin or low-molecular-weight heparin, are the current gold standard of treatment; however, these interventions pose considerable bleeding risks. Thus, safer and more effective therapeutic strategies are urgently required. Owing to their strong anti-inflammatory and tissue repair capabilities, mesenchymal stem cell-derived exosomes (MSC-Exos) have gained considerable attention as novel therapeutic options for numerous disorders, including DIC. Their stability in diverse pathological states highlights their potential as promising candidates for DIC therapy. This review presents the latest insights on the pathogenesis of DIC and anti-inflammatory and anticoagulant properties of MSC-Exos. We aimed to elucidate the potential mechanisms by which MSC-Exos influence DIC pathogenesis. We speculate that MSC-Exos offer a multifaceted approach to DIC treatment by attenuating neutrophil extracellular trap formation, modulating M1/M2 macrophage polarization, altering Nrf2/NF-κB signalling pathway to downregulate pro-inflammatory factors, and correcting imbalances in the coagulation-fibrinolysis system through anticoagulant routes. This suggests that MSC-Exos are a potential paradigm in DIC therapy, offering novel targets and treatment modalities for DIC management. Keywords: disseminated intravascular coagulation, mesenchymal stem cell-derived exosomes, anticoagulant therapy, neutrophil extracellular traps, macrophage polarization

Yuan Hu,1,* Shao-Bo Wang,1,* Kun Wang,2 Ming-Jie He2 1Suining Central Hospital, Suining, Sichuan, People’s Republic of China; 2First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming-Jie He, Email hmj15238917691@163.comIntroduction: Vitiligo is an autoimmune disease characterized by the loss of skin pigmentation. This study aims to explore genetic associations between vitiligo and 21 autoimmune diseases using Mendelian randomization (MR) analysis, with a focus on identifying potential risk and protective factors.Methods: We performed univariable and multivariable Mendelian randomization analyses to assess the causal associations between 21 autoimmune diseases and vitiligo. Confounding factors, including smoking, alcohol consumption, and Body Mass Index (BMI), were integrated into the multivariable analysis. Strongly associated single nucleotide polymorphisms (SNPs) were mapped to genes, followed by Summary-data-based Mendelian Randomization (SMR) analysis with expression Quantitative Trait Loci (eQTL) and methylation Quantitative Trait Loci (mQTL) data. Risk and protective factors were further identified by evaluating inflammatory mediators and immune cell phenotypes.Results: The MR analysis identified seven autoimmune diseases with potential causal associations with vitiligo. However, after accounting for confounding factors, only Hashimoto’s thyroiditis and type 1 diabetes maintained genetic associations with vitiligo. Gene mapping revealed 25 intersecting genes between these two diseases and vitiligo. SMR analysis confirmed Sulfite Oxidase (SUOX) as a protective gene across multiple tissues. Furthermore, several inflammatory factors were identified as risk factors, including C-X-C motif chemokine ligand 9 (CXCL9), C-X-C motif chemokine ligand 10 (CXCL10), Tumor Necrosis Factor (TNF), and Signaling Lymphocytic Activation Molecule (SLAM). In contrast, Osteoprotegerin (OPG) was identified as a protective factor.Discussion: This study provides novel insights into the shared molecular mechanisms linking vitiligo with other autoimmune diseases. The identification of SUOX as a common protective gene and the discovery of specific inflammatory and immune-related factors may facilitate future therapeutic strategies.Keywords: autoimmune diseases, causality, Mendelian randomization, sulfite oxidase, vitiligo

Yingli Wang,1,2,* Yalin Jiang,2,* Meiling Xie,1,2,* Bin Qi,2 Kunpeng Pu,2 Wenjie Du,2 Qingqing Zhang,2 Mengmeng Ma,2 Ziyong Chen,2 Yongxia Guo,2 Hui Qian,2 Kaiqin Wang,2 Tulei Tian,2 Lin Fu,3 Xiaofei Zhang2 1Bengbu Medical University Graduate School, Bengbu, Anhui, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lin Fu, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230601, People’s Republic of China, Tel +86 551 6516 7923, Email fulindev@126.com Xiaofei Zhang, Department of Respiratory and Critical Care Medicine, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou, Anhui, 236800, People’s Republic of China, Email zhangxiaofeibz@163.comBackground: Leucine-rich α-2 glycoprotein 1 (LRG1) is associated with various inflammatory lung diseases. Nevertheless, the connection between LRG1 and adult community-acquired pneumonia (CAP) individuals was still not well understood. Through a prospective cohort study, the correlations of serum LRG1 with severity and prognosis were evaluated in CAP patients.Methods: The study encompassed 327 patients who received the diagnosis of CAP. We collected fasting venous blood and clinical features. Serum LRG1 was detected by ELISA. CAP severity was assessed using various scoring systems. The prognostic outcomes were observed through follow-up visits.Results: The level of serum LRG1 at admission was gradually increased with CAP severity scores. Serum LRG1 level shown positive associations with inflammatory indices, including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Linear and logistic regression analyses suggested that serum LRG1 at admission was positively associated with severity scores and the risk of death in CAP patients. Serum LRG1 in combination with CAP severity scores significantly increased the predictive powers for severity and death compared with single serum LRG1 or severity scores.Conclusion: The study revealed positive connections of serum LRG1 levels with severity and poor prognosis in CAP patients, suggesting LRG1 partakes into the physiological processes of CAP. Serum LRG1 may be regarded as a potential biomarker in predicting the severity and death among CAP patients.Keywords: community-acquired pneumonia, LRG1, severity, outcomes, cohort study

Kai Wang,1,2,&ast; Qin Gao,3,&ast; Yelong Bai,1 Rong Yu,1 Qing Luo1 1Department of Otorhinolaryngology, FirstAffiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Otorhinolaryngology, the 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Nanchang, Jiangxi, People’s Republic of China; 3Department of Otorhinolaryngology, Central Theater Command General Hospital of the People’s Liberation Army of China, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing Luo; Rong Yu, Department of Otorhinolaryngology, FirstAffiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86-18170846190, Email luoq@ncu.edu.cn; yurong1982@ncu.eud.cnObjective: To study the role of transforming growth factor beta 1 (TGF-β 1) and tumor necrosis factor receptor related factor 6 (TRAF6) in the progression of epithelial mesenchymal transformation (EMT) in allergic rhinitis (AR).Methods: A total of 30 patients underwent nasal endoscopic surgery at our Hospital were selected for 15 patients in each group based on their allergy status. Inferior turbinate mucosa tissue was obtained and analyzed using immunohistochemical (IHC) tests, real-time quantitative PCR (qRT-PCR) detection, and Western blotting (WB) tests to measure TGF-β 1, TRAF6, E-cadherin, Vimentin, and α-Smooth Muscle Actin (α-SMA) expression levels.Results: The expression levels of TGF-β 1, TRAF6, Vimentin, and α-SMA were significantly higher in the AR group compared to the control group as shown by IHC, qRT-PCR, and WB (P < 0.05). E-cadherin expression was significantly lower group than in the control group (P < 0.05). Protein expression of TGF-β 1 showed significantly positive correlations with TRAF6 (r = 0.8188, P = 0.0002), α-SMA (r = 0.8076, P = 0.0003), and Vimentin (r = 0.6917, P = 0.0043). There was a significantly negative correlation between protein expression of TGF-β 1 and E-cadherin (r = − 0.8032, P = 0.0003). Protein expression of TRAF6 showed a significantly negative correlation with E-cadherin (r = − 0.6405, P = 0.0101) but positive correlations with α-SMA (r = 0.5809, P = 0.0231) and Vimentin (r = 0.555, P = 0.0318).Conclusion: TGF-β 1, TRAF6, and EMT-related markers (Vimentin, α-SMA) were highly expressed in the nasal mucosa of AR patients. TGF-β 1 and TRAF6 may be involved in the epithelial-mesenchymal transition in allergic rhinitis.Keywords: allergic rhinitis, transforming growth factor β 1, tumor necrosis factor receptor associated factor 6, epithelial-mesenchymal transition, immunohistochemical

Hui-Hui Yang,1,&ast; Jie Dou,1,&ast; Ruo-Ling Guo,1 Jie Gao,1 Hui-Zhe Li,2 Kun Wang,2 Tian-Hua Hou,2 Tie-Jun Wei,2 Jing-Tao Guo,2 Jian-Wei Liu,3 Dong-Lei Luo2 1Chengde Medical University, Chengde, People’s Republic of China; 2Department of Cardiology, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, People’s Republic of China; 3Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Lei Luo, Department of Cardiology, Chengde Central Hospital/Second Clinical College of Chengde Medical, Chengde, People’s Republic of China, Email dongleiluocn@aliyun.com Jian-Wei Liu, Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, People’s Republic of China, Email Ljw2112@126.comObjective: The study aimed to explore the clinical diagnostic significance of lipoprotein(a) [Lp(a)] and neck circumference (NC) in patients with coronary heart disease (CHD).Methods: This cross-sectional study was conducted at Chengde Central Hospital from September 2021 to June 2023, enrolling 791 patients with suspected CHD who underwent selective coronary angiography (CAG). Patients were categorized into CHD and non-CHD groups based on the severity of arterial narrowing. Subsequently, the diagnostic value of Lp(a) combined with NC in patients with CHD was assessed using receiver operating characteristic (ROC) curves. Based on the results of multivariate logistic regression, a nomogram was constructed, and its clinical applicability was validated using decision curve analysis (DCA) and clinical impact curve (CIC).Results: Multivariate logistic regression proved that high Lp(a) and high NC are risk factors for CHD, with OR of 1.836 (95% CI: 1.282– 2.630) and 1.383 (1.0.978– 1.955), respectively. Patients in the high NC or Lp(a) group exhibited a higher prevalence of multi-vessel disease. The area under the ROC curve (AUC) of the predictive model combining high Lp(a) and high NC was 0.710 (95% CI: 0.670– 0.751) and also demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P value=0.494). The DCA and CIC confirmed the clinical utility of the nomogram developed to predict CHD based on the combination of high Lp(a) and high NC.Conclusion: The levels of Lp(a) and NC exhibit a significant correlation with the presence of CHD, and their combined assessment holds specific clinical value in the diagnosis of CHD.Keywords: coronary heart disease, lipoprotein(a), neck circumference, sensitivity, specificity

Ye Zhao,1,&ast; Xi Chen,1,&ast; Yuhan Huang,2,&ast; Zhihan Zhang,3 Kui Wang,1 Duowu Zou,1 Teng Ma2 1Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Teng Ma, Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of China, Email mrmateng@126.com Duowu Zou, Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, People’s Republic of China, Email zdw_pi@163.comPurpose: This study aimed to investigate gene expression profiles, identify potential hub genes, and predict drugs for patients with erosive esophagitis (EE). Despite its clinical significance, molecular-level exploration of this condition has been limited.Patients and Methods: RNA sequencing was performed on clinical biopsy samples from eight EE patients and eight healthy controls. Integrated bioinformatic tools were then utilized to analyze the data, including functional enrichment analysis, protein-protein interaction network analysis, weighted gene co-expression network analysis, immune infiltration analysis, and identification of small-molecule compounds. Additionally, the expressions of the identified hub genes were assessed in clinical samples.Results: A total of 2801 genes with differential expression were identified, including four potential hub genes: SOX9, SPP1, TIMP1, and TLR4. Moreover, the overexpression of these hub genes was verified in clinical samples. Analysis of Immune infiltration indicated an imbalance in the distribution of immune cell types in patients with EE. Correlation analysis between immune cells and hub genes unveiled noteworthy relationships. Specifically, SOX9 exhibited a negative correlation with CD8 T cells but a positive correlation with resting memory CD4 T cells. SPP1 displayed a positive correlation with naïve B cells, while TIMP1 exhibited a negative correlation with resting dendritic cells. Furthermore, the study identified ten small-molecule drugs with potential therapeutic effects for EE, including loreclezole and mercaptopurine.Conclusion: This study provides valuable insights into the molecular understanding of EE, offering new perspectives on disease mechanisms. The findings may inspire further research leading to the development of novel treatment strategies for EE.Keywords: erosive esophagitis, RNA sequencing, bioinformatics analysis, immune infiltration, drug prediction

Wei Xu,1,2 Keren Wang,2 Ke Wang,3 Ye Zhao,4 Zhaoying Yang,2 Xiuying Li1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3Gynecology and Obstetrics Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 4Dermatological Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Xiuying Li; Zhaoying Yang, Email lixiuying@jlu.edu.cn; zyyang@jlu.edu.cnIntroduction: Exosomes (Exos) are promising drug delivery systems due to their low immunogenicity, minimal toxicity, high biocompatibility, and effective delivery capabilities. However, addressing the cardiotoxicity and other toxic side effects associated with anthracyclines has proven challenging.Methods: In this study, we loaded doxorubicin (Dox) into Exos derived from human placental mesenchymal stem cells (MSCs) and modified them with carboxylated Fe3O4 nanoparticles (NPs) to create an Exo-Dox-NP delivery system. Using an external magnetic force (MF), we regulated the distribution of Exos for targeted Dox delivery in breast cancer treatment. We characterized and determined the drug-loading efficiency of Exo-Dox-NPs, their uptake by tumor cells, and the modulation of drug release. The therapeutic efficacy of Exo-Dox-NPs was evaluated through both in vitro and in vivo anti-tumor experiments.Results: Our results indicated that Exo-Dox-NPs remain stable in the bloodstream while releasing the drug in the acidic environment of tumor cells and their lysosomes. As a drug delivery system, Exo-Dox-NPs enhanced Dox absorption by tumor cells, demonstrating high targeting specificity. Moreover, Exo-Dox-NPs inhibited the migration of breast cancer cells, as confirmed by scratch migration and Transwell Matrigel invasion assays. In vivo experiments confirmed the effective targeting and delivery of Dox to malignant tumors using Exo-Dox-NPs/MFs, with the Exo-Dox-NP/MF formulation exhibiting the most potent anti-tumor activity.Conclusion: The utilization of Exos as carriers for Dox showed promising efficacy in breast cancer management. Carboxylated Fe3O4 NPs demonstrated to be suitable targeting agents, potentially advancing the development of natural nanocarriers for combination cancer therapy.Keywords: breast cancer, doxorubicin, exosomes, carboxylated Fe3O4 nanoparticles, magnetic targeting

Kaijie Wang,1 Weiwei Wu,2 Yongbao Wei,3 Xianwei Cao1 1Department of Dermatology, the 1st affiliated hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2Department of Neurology, Union Hospital, Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Urology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, 350001, People’s Republic of ChinaCorrespondence: Xianwei Cao; Yongbao Wei, Email ndyfycxw@126.com; weiyb@fjmu.edu.cnObjective: To analyze the influencing factors of male cutaneous melanoma (CM) patients dying from genitourinary diseases (GUD).Methods: We searched the surveillance, epidemiology, and end results (SEER) database and extracted data on male CM patients according to the inclusion and exclusion criteria, including male patients whose cause of death was CM (cohort A) or GUD (cohort B). Comparisons between the two cohorts were performed before and after propensity score matching (PSM). An interaction analysis between age and year of diagnosis was also conducted. Cox regression analysis were performed to find the risk factors for death from GUD.Results: Seven thousand seventy-eight CM patients were included, including 6415 (90.6%) in cohort A and 663 (9.4%) in cohort B. Compared with cohort A, cohort B patients were older (median age 74 ys. vs 65 ys.) and were more under the localized stage and had longer survival time no matter before or after PSM (all p< 0.001). The stage was an inhibitory factor for cohort B (p < 0.001). After PSM, only age and year of diagnosis were found to be cohort B’s promoting factors (p< 0.001). The interaction analysis showed that older patients diagnosed in later years (2009– 2020) had a higher risk of dying from GUD compared to those diagnosed earlier (p< 0.05). Patients with a later year of diagnosis (2009– 2020) had a lower median survival time than patients with an earlier year of diagnosis (2000– 2008) (p< 0.001). When the patient’s year of diagnosis was earlier (2000– 2008), older patients (> 75 ys.) had a higher risk of dying from GUD than younger patients (≤ 75 ys.) (p< 0.001).Conclusion: We first reported a significant interaction between age and year of diagnosis in male CM patients dying from GUD, highlighting the increased risk in older patients diagnosed more recently. We may pay attention to the possibility of dying from genitourinary diseases for CM patients.Keywords: cutaneous melanoma, genitourinary diseases, non-cancer mortality, genitourinary cancer, cohort study

Biao Tao,&ast; Dian Gu,&ast; Kai Wang,&ast; Yinan Li, Xianlin Xu, Jiexun Chen Department of Urology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, 211100, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiexun Chen; Xianlin Xu, Department of Urology, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Jiangning District, Nanjing, Jiangsu Province, 211100, People’s Republic of China, Email cjx128619@yeah.net; xianlinxu@njmu.edu.cnBackground and Aims: Metabolic syndrome (MetS) is associated with the development of several diseases. However, the correlation between MetS and size of renal cysts remains unclear. This research aims to explore the potential connection between them, offering theoretical guidance for clinical prevention and treatment of renal cysts.Methods: A total of 467 patients diagnosed with renal cysts and admitted to Sir Run Run Hospital, Nanjing Medical University from September 2019 to September 2020 were eventually included in this study. They were divided into the small cyst group (cyst volume≤ 1.5cm³) and the large cyst group (cyst volume> 1.5cm³) based on the median value of cyst volume. Multivariate logistic regression analysis was used to evaluate the association between MetS and size of renal cysts.Results: Our results indicated that MetS (OR 1.941, 95% CI 1.286– 2.927, P=0.002) was positively associated with the size of renal cysts. Additionally, multiple renal cysts (OR 2.259, 95% CI 1.402– 3.640, P=0.001) and serum globulin (OR 0.945, 95% CI 0.905– 0.987, P=0.011) were positively and negatively related to size of renal cysts, respectively.Conclusion: Our study reveals the association between MetS and the size of renal cysts. Patients with MetS are more likely to have larger renal cysts. The administration of MetS may help limit the development of renal cysts. Further prospective studies are needed to explore the causal relationship between MetS and renal cysts.Keywords: size of renal cysts, metabolic syndrome, metabolic disease, renal cyst

Kang Wang,1 Fengchang Yang,1 Changxing Feng,1 Fuhao Xu,1 Li Li,1 Jinghao Duan,1 Shuanghu Yuan1,2 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 2Department of Radiation Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Shuanghu Yuan, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No. 440 Jiyan Road, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626931, Fax +86-531-87984079, Email yuanshuanghu@sina.comPurpose: This study aims to identify risk factors associated with symptomatic radiation pneumonitis (RP, Grade ≥ 2) following immunotherapy preceding thoracic radiotherapy (ICI-TRT) and establish safe dose constraints.Patients and Methods: This retrospective study enrolled patients diagnosed with non-small-cell lung cancer (NSCLC) who underwent thoracic radiotherapy (TRT) following immune checkpoint inhibitors (ICIs) treatment. The primary endpoint was the occurrence of symptomatic RP (Grade ≥ 2), as defined by the Common Terminology Criteria for Adverse Events version 5.0. Clinical and lung dosimetric parameters were analyzed to determine their associations with symptomatic RP. Dosimetric parameters included mean lung dose (MLD) and the percentage of lung volume receiving ≥ 10 Gy (V10), ≥ 20 Gy (V20), ≥ 30 Gy (V30), and ≥ 40 Gy (V40). Receiver operating characteristic curves were used to predict the risk of developing symptomatic RP to establish optimal threshold values for each dosimetric predictor.Results: Among the 118 patients included, the incidence of symptomatic RP was 25.4%. Tumor locations, intervals between immunotherapy and radiotherapy, and MLD, V10, V20, V30, and V40 were identified as independent risk factors for symptomatic RP. The area under the curve (AUC) values for MLD, V10, V20, V30, and V40 were 0.788 (95% confidence interval [CI] 0.704– 0.873), 0.789 (95% CI 0.705– 0.874), 0.791 (95% CI 0.706– 0.876), 0.784 (95% CI 0.697– 0.871), and 0.749 (95% CI 0.656– 0.842), respectively. The optimal threshold values for MLD, V10, V20, V30, and V40 were 9.7 Gy, 26.3%, 15.9%, 13.3%, and 8.6%, respectively. These thresholds are lower than current guideline recommendations, and maintaining dosimetric parameters below these values resulted in a cumulative symptomatic RP incidence of < 12%.Conclusion: The recommended dose thresholds for MLD, V10, V20, V30, and V40 are lower than the current guidelines, underscoring the importance of radiotherapy planning to minimize symptomatic RP occurrence in patients receiving ICI-TRT.Keywords: radiation therapy, immunotherapy, non-small-cell lung cancer, radiation pneumonitis, risk factors

Shanshan Liu, Ju Li, Zhongyuan Zhang, Deqian Meng, Kai Wang Department of Rheumatology and Immunology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of ChinaCorrespondence: Kai Wang, Department of Rheumatology and Immunology, The affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of China, Tel/Fax +86-17551710317, Email morrosun@hotmail.comObjective: To evaluate belimumabf’s efficacy in refractory lupus nephritis (LN) patients and identify predictive serum biomarkers for treatment response.Methods: In this single-arm retrospective study, we assessed clinical responses in LN patients at baseline and six months after initiating belimumab. Serum cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were quantified using multiplex magnetic bead flow immunoassay before and after treatment.Results: Fourteen patients with various subtypes of refractory LN participated in the study: seven with class III and V LN, three with type V alone, two with class III, and two with class IV+V and V LN. Post six months of belimumab therapy, all participants exhibited a reduction in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores from their respective baseline values. Notably, most patients showed a decrease in the dosage of prednisone, levels of 24-hour urinary protein, immunoglobulins, erythrocyte sedimentation rate (ESR), and anti-double-stranded DNA antibody IgM, along with serum levels of IL-4, IL-6, IL-10, and IFN-γ. Meanwhile, levels of C3, C4, IL-2, and TNF-α were observed to increase. Of the participants, nine (64.29%) achieved a complete renal response, one (7.14%) showed a partial response, and four (28.57%) exhibited no response. Significantly, higher baseline serum IFN-γ levels were found in patients who did not achieve complete renal response (CR) compared to those who did (p = 0.009). Receiver operating characteristic (ROC) curve analysis demonstrated that baseline IFN-γ levels had an area under curve (AUC) of 0.96 (0.70– 1.00), with a sensitivity of 0.89 and a specificity of 1.00 (p < 0.001).Conclusion: Belimumab shows potential efficacy in treating refractory LN. Baseline serum IFN-γ levels may predict response to belimumab therapy, potentially enabling more targeted treatment approaches for this challenging condition.Keywords: refractory lupus nephritis, belimumab, treatment, biomarker, IFN-&#x03B3

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

Longqing Xia,1 Mengmeng Yang,1 Nan Zang,1– 4 Jia Song,1– 4 Jun Chen,1– 4 Huiqing Hu,1 Kewei Wang,1 Yingyue Xiang,1 Jingwen Yang,1 Liming Wang,1 Ying Zou,1 Xiaoyu Lv,1 Xinguo Hou,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Disease, Jinan, 250012, People’s Republic of ChinaCorrespondence: Li Chen, Department of Endocrinology, Qilu Hospital of Shandong University, Shandong, People’s Republic of China, Email chenli3@email.sdu.edu.cnBackground: The depletion of β cell mass is widely recognized as a significant contributor to the progression of type 2 diabetes mellitus (T2DM). Exosomes derived from mesenchymal stem cells (MSC-EXOs) hold promise as cell-free therapies for treating T2DM. However, the precise effects and mechanisms through which MSC-EXO affects β cell function remain incompletely understood, and the limited ability of MSC-EXO to target β cells and the short blood circulation time hampers its therapeutic effectiveness.Methods: The effects of MSC-EXO were investigated in T2DM mice induced by a high-fat diet combined with STZ. Additionally, the high glucose-stimulated INS-1 cell line was used to investigate the potential mechanism of MSC-EXO. Michael addition reaction-mediated chemical coupling was used to modify the surface of the exosome membrane with a β-cell-targeting aptamer and polyethylene glycol (PEG). The β-cell targeting and blood circulation time were evaluated, and whether this modification enhanced the islet-protective effect of MSC-EXO was further analyzed.Results: We observed that the therapeutic effects of MSC-EXO on T2DM manifested through the reduction of random blood glucose levels, enhancement of glucose and insulin tolerance, and increased insulin secretion. These effects were achieved by augmenting β cell mass via inhibiting nuclear factor erythroid 2–related factor 2 (NRF2)-mediated ferroptosis. Mechanistically, MSC-EXOs play a role in the NRF2-mediated anti-ferroptosis mechanism by transporting active proteins that are abundant in the AKT and ERK pathways. Moreover, compared to MSC-EXOs, aptamer- and PEG-modified exosomes (Apt-EXOs) were more effective in islet protection through PEG-mediated cycle prolongation and aptamer-mediated β-cell targeting.Conclusion: MSC-EXO suppresses NRF2-mediated ferroptosis by delivering bioactive proteins to regulate the AKT/ERK signaling pathway, thereby improving the function and quantity of β cells. Additionally, Apt-EXO may serve as a novel drug carrier for islet-targeted therapy.Keywords: exosome, type 2 diabetes mellitus, β-cell-targeting, polyethylene glycol modification, ferroptosis

Lei Wang,1,&ast; Kai Wang,2,&ast; Yuwen Chen,1 Xiaoyu Zhang,1,3 Wenhao Xu,1,3 Zhong Dong,1,3 Yu Wang1,3,4 1Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People’s Republic of China; 2Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People’s Republic of China; 3Department of Neurology, Anhui Public Health Clinical Center, Hefei, Anhui Province, 230000, People’s Republic of China; 4Department of Neurology, Anqing First People’s Hospital Affiliated to Anhui Medical University, Anqing, Anhui Province, 246000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Wang, Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, 230000, People’s Republic of China, Email yw4d@hotmail.comObjective: To investigate the effects of inhibiting the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome on neuronal damage and chronic pro-inflammatory responses during epileptogenesis in a mouse model of pilocarpine-induced status epilepticus (SE).Methods: Mice were randomly allocated into three groups: control, SE, and SE + MCC 950. The expression patterns of M1 and M2 microglial biomarkers in the hippocampus were quantified using Western blotting, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and immunofluorescence staining. Additionally, seizure susceptibility, video-electroencephalography recording, Morris water maze test, and brain immunofluorescence staining were performed to evaluate the epileptic brain 4 weeks post-SE.Results: Within 72 hours post-SE, hippocampal microglia demonstrated a preferential polarization towards the M1 phenotype, a trend that was mitigated by NLRP3 inflammasome inhibition. During epileptogenesis, SE mice treated with NLRP3 inflammasome inhibition exhibited reduced neuronal damage, improved cognitive function, decreased seizure susceptibility, and attenuated chronic pro-inflammatory responses.Conclusion: Inhibition of NLRP3 inflammasome post-SE effectively ameliorates neuronal loss, seizure susceptibility, and cognitive dysfunction during epileptogenesis. This neuroprotective effect may be mediated through the mitigation of chronic pro-inflammatory responses within the epileptic brain.Keywords: NLRP3 inflammasome, microglial polarization, M1 microglia, epileptogenesis, chronic pro-inflammatory response

Kun Li,1,2 Kun Wang,3 Shu-Xian Xu,1 Xin-Hui Xie,1 Yan Tang,3 Lihong Zhang,2 Zhongchun Liu1,4 1Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Clinical Laboratory, Affiliated Hospital of West Anhui Health Vocational College, Lu’an, Anhui, People’s Republic of China; 3Department of Psychiatry, Affied Hospital of West Anhui Health Vocational College, Lu’an, Anhui, People’s Republic of China; 4Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, People’s Republic of ChinaCorrespondence: Zhongchun Liu, Department of Psychiatry, Renmin Hospital of Wuhan University, No. 99 Jiefang Road, Wuchang District, Wuhan, Hubei, 430060, People’s Republic of China, Email zcliu6@whu.edu.cnPurpose: To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels.Patients and Methods: Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. BDNF levels were quantified in both ADEVs and plasma. ALG-2-interacting protein X (Alix) and cluster of differentiation 81 (CD81) levels, two established extracellular vesicle markers, were measured in ADEVs.Results: After false discovery rate correction, patients with MDD exhibited higher CD81 levels (PFDR = 0.040) and lower BDNF levels (PFDR = 0.043) in ADEVs than HCs at baseline. BDNF levels in ADEVs normalized to CD81 (PFDR = 0.002) and Alix (PFDR = 0.040) remained consistent with this finding. Following four weeks of selective serotonin reuptake inhibitor treatment (n=10), CD81 levels in ADEVs decreased (PFDR = 0.046), while BDNF levels normalized to CD81 increased (PFDR = 0.022). BDNF levels in ADEVs were more stable than in plasma. Exploratory analysis revealed no correlation between BDNF levels in ADEVs and plasma (ρ=0.117, P = 0.334).Conclusion: This study provides human in vivo evidence supporting the neuroplasticity hypothesis of depression by demonstrating altered BDNF levels in ADEVs. ADEVs may be more suitable for developing biomarkers of depression than plasma-derived biomarkers.Keywords: major depressive disorder, ADEV, BDNF, biomarker, treatment

Donglin Jiang,1 Yangxue Wu,1 Ling Liu,1 Yajing Shen,1 Tiandong Li,1 Yin Lu,1 Peng Wang,2 Changqing Sun,2 Kaijuan Wang,2 Keyan Wang,3 Hua Ye1 1College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Hua Ye, College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86 186-3853-6001, Fax +86 371-67781018, Email yehua@zzu.edu.cnBackground: Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021).Methods: The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI).Results: In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors.Conclusion: The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.Keywords: Asia, gastrointestinal tumors, burden, trends

Ke Wang, Xuelu Wang, Chenying Xu, Lina Bai Operating Room, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of ChinaCorrespondence: Xuelu Wang; Chenying Xu, Operating Room, Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, 2699 West Gaoke Road, Pudong New Area, Shanghai, People’s Republic of China, 200092, Email wangxuelu@51mch.com; xuchenying@51mch.comObjective: Reasonable surgical scheduling management is crucial to optimize the utilization rate of operating room. This study aims to understand the context, frontier and hot spots of surgical scheduling management research, in order to provide reference for surgical scheduling optimization.Methods: Literature on operation scheduling management collected in Web of Science core collection database was searched from the database establishment to June 21, 2023. HisCite Pro 2.1 software was used to analyze the publication time, countries, research institutions, journals, authors, keywords and highly cited papers.Results: A total of 1383 literatures were included, and research institutions in the United States, Canada and other countries played a leading role in this field. Among them, the combination of machine algorithm and system model optimization to improve the accuracy of surgical duration prediction is the future research focus in this field.Conclusion: Improving operation efficiency is one of the key issues in operating room management. Managers should find the best operation scheduling plan from a more detailed and comprehensive perspective to improve operation efficiency.Keywords: surgery, schedule, manage

Xiao-Ling Shen,1,&ast; Zhuo-Yi Li,1,&ast; Qing Li,1 Kai Wang2 1Department of Women Health Care, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China; 2Department of Aristogenesis, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Qing Li, Email wangkai111909@163.com; lq5090@126.comPurpose: To verify whether there is lower incidence of adverse pregnancy outcomes after high-intensity focused ultrasound (HIFU) treatment than loop electrosurgical excision procedure (LEEP) in young women of childbearing age.Patients and Methods: This retrospective cohort study enrolled 46 patients treated with HIFU and 46 patients treated with LEEP. To compare the differences between the two groups, Fisher’s exact test or the Kruskal–Wallis (K-W/H) test was used in the univariate analysis, while the logistic regression method was applied for further verification.Results: Basic characteristics showed no differences between the two groups (P > 0.05) except for parity (P < 0.001). Preterm birth rates were 6.52% and 0.00% in patients with cervical high-grade squamous intraepithelial lesions (HSIL) treated with LEEP and HIFU, respectively. The incidence rates of premature rupture of membranes (PROM) were respectively 15.22% and 21.74% in the two groups. There was no significant difference in pregnancy outcomes between the two groups (P > 0.05).Conclusion: This study is the first to compare the pregnancy outcomes of patients with cervical HSIL who treated with LEEP and HIFU procedures. Both HIFU treatment and LEEP are available options for patients of reproductive age with cervical HSIL. Therefore, it is necessary to conduct prospective single-center or multicenter randomized controlled studies.Keywords: cervical high-grade squamous intraepithelial lesions, high-intensity focused ultrasound, loop electrosurgical excision procedure, pregnancy outcome

Kaixin Wang,1 Lingfei Yang,2 Qingsheng Li,2 Xuan Yang,1 Ziyi Chen,2 Yongyan Zhou,3 Yanjie Jia,1 Zhe Gong1 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Electrocardiogram, Zhoukou Center Hospital, Zhoukou, People’s Republic of ChinaCorrespondence: Yanjie Jia; Zhe Gong, The First Affiliated Hospital of Zhengzhou University, Department of Neurology, Postal FfCode 450052, No. 1 Jianshe East Road, Zhengzhou, People’s Republic of China, Email jiayanjie1971@aliyun.com; gongzhe1415@163.comBackground: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes.Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed.Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol.Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.Keywords: cerebral ischemia, chronic ethanol exposure, pericytes, TLR4, NLRP3 inflammasome

Kang Wang,1,&ast; Zihui Yang,1,&ast; Boyu Zhang,1,&ast; Song Gong,2 Yiping Wu1 1Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Division of Endocrinology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Song Gong, Division of Endocrinology, Tongji Hospital, Tongji Medical College, Wuhan, Hubei, People’s Republic of China, Email gongsong@tjh.tjmu.edu.cn Yiping Wu, Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Wuhan, Hubei, People’s Republic of China, Email tongjiplastic@163.comAbstract: Wound healing in diabetic patients is frequently hampered. Adipose-derived stem cell exosomes (ADSC-eoxs), serving as a crucial mode of intercellular communication, exhibit promising therapeutic roles in facilitating wound healing. This review aims to comprehensively outline the molecular mechanisms through which ADSC-eoxs enhance diabetic wound healing. We emphasize the biologically active molecules released by these exosomes and their involvement in signaling pathways associated with inflammation modulation, cellular proliferation, vascular neogenesis, and other pertinent processes. Additionally, the clinical application prospects of the reported ADSC-eoxs are also deliberated. A thorough understanding of these molecular mechanisms and potential applications is anticipated to furnish a theoretical groundwork for combating diabetic wound healing.Keywords: diabetes, wound healing, ADSC-exos, tissue regeneration, skin cells, inflammation

Chenxiao Hu,&ast; Mingwei Sheng,&ast; Ke Wang,&ast; Zi Yang, Shiping Che Solicitation Office, The First Hospital of Lanzhou University, Lanzhou, Gansu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiping Che, The First Hospital of Lanzhou University, No. 1 Donggang West Road, Lanzhou, Gansu, 730000, People’s Republic of China, Email ldyycheshiping@163.comObjective: Identify the collaborations between authors, countries, and institutions, respectively, and explore the hot issues and prospects for research on hospital medication management.Materials and Methods: Publications on hospital medication management were retrieved from the Web of Science Core Collection. Bibliometric analyses were performed using CiteSpace 6.1.R3, HistCite 2.1, and VOSviewer 1.6.16. The network maps were created between authors, countries institutions, and keywords.Results: A total of 18,723 articles related to hospital medication management studies were identified. Rapid growth in the number of publications since 2017. The high papers were published in AM J HEALTH-SYST PH, while JAMA-J AM MED ASSOC was the most co-cited journal. Manias E and WHO ranked first in the author and cited author. There were active collaborations among the top authors. Bates DW was the key author in this field. The authors have active collaborations in adverse drug events, acute coronary syndrome, in-hospital major bleeding, and so on. The US was the leading contributor in this field. The UK, Australia, and China are also very active. Active cooperation between countries and between institutions was observed. The main hot topics included matters related to outcome indicators, hospital pharmacy service behaviors, and medication use in pain management. More recent keywords focus on chronic disease medication management and clinical medication management.Conclusion: Hospital medication management studies have significantly increased after 2017. There was active cooperation between authors, countries, and institutions. The application of hospital medication management in the emergency department and the relationship between medication management and medication adherence are current research hotspots. In addition, with the continuous progress of society, chronic diseases have become an important factor affecting people’s health, and medication management is becoming more and more subdivided, so the direction of chronic disease medication management as well as precise medication may become the development direction of future research.Keywords: bibliometric analysis, medication management, hospital, development trends, hot topics

Zhida Bian,1– 3,&ast; Bo Wang,2,4,&ast; Xingqi Wu,3,5,6,&ast; Kai Wang,3,5– 7 Yi Jiang1,8 1Anhui Medical University School of Basic Medicine, Hefei, 230032, People’s Republic of China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230088, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230022, People’s Republic of China; 4State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, People’s Republic of China; 5Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 6Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230022, People’s Republic of China; 7The School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China; 8State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang, Department of Neurology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email wangkai1964@126.com Yi Jiang, Anhui Medical University School of Basic Medicine, Hefei, 230032, People’s Republic of China, Tel +86 10 64879639, Fax +86 10 64856521, Email yijiang@psych.ac.cnIntroduction: Conventional methods like patient history, neuropsychological testing, cerebrospinal fluid examination, and magnetic resonance imaging are widely used to diagnose cases in the current clinical setting but are limited in classifying Alzheimer’s disease (AD) stages. Patients with AD exhibit visual perception deficits, which may be a potential target to assess the severity of the disease according to visual paradigms. However, owing to the inconsistent forms of perceived objects, the defects of current visual processing paradigms often lead to inconsistent results and a lack of sensitivity and specificity.Methods: We develop two paradigms based on global-first topological approach of visual perception, which avoids inconsistent results and lack of sensitivity and specificity owing to the inconsistent forms of perceived objects in traditional paradigms, delineate a unique detection strategy from perception organization (Experiment 1) and visual working memory (VWM) (Experiment 2).Results: Except for the significant differences of the reaction times (RTs) between groups, significant differences were found when AD subjects recognize small figures due to the consistency of global and local figures in similarity test. The difference of RTs between recognizing global and local figures can be recognized in AD and mild cognitive impairment (MCI) group compared to healthy elderly (HE) in similarity test (Experiment 1). The memory capacity of AD patients was significantly lower than MCI group. Topological interference effect was observed in MCI and HE group, whereas MCI patients may have a greater difference trend in non-topological and topological changes than HE (Experiment 2).Conclusion: Our paradigms provide a new strategy, which can assist clinical severity staging and linking topological approach of visual perception with pathophysiological processes in AD.Keywords: Alzheimer’s disease, visual perception deficits, paradigm, working memory, perceptual organization

Kaiyu Wang,1,&ast; Yan Gao,1,&ast; Shan Wu,1,&ast; Jin Zhang,1 Manfang Zhu,2 Xiayu Chen,1 Xizi Fu,1 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.com Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.comBackground: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments.Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (&epsiv;-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates.Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models.Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.Keywords: mRNA gene therapy, dual-mRNA delivery, tumor cell lysates, Bim and IL-23A mRNAs, immune response

Yanling Li,&ast; Li Ji,&ast; Tian Liu, Guang Xu, Kaihe Wang, Leixin Mu, Yuying Guo, Qun Ma School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Ma, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email maqun99@126.comBackground: Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant Pseudomonas aeruginosa (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.Materials and Methods: Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.Results: QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as Tmax, t1/2, MRT, Vd/F, CL/F and PD parameters such as MIC, AUC0-24h/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.Conclusion: These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.Keywords: multidrug-resistant Pseudomonas aeruginosa infection, combination therapy, PK/PD model, Qiguiyin decoction, levofloxacin

Kun Wang,1 Wei Zhu,2 Wei Huang,3 Kangkang Huang,1 Huidan Luo,1 Lu Long,1 Bin Yi1 1Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 2Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 3Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Bin Yi, Tel +86-13707495781, Email xyyibin@163.comObjective: Ubiquitination is an important post-translational modification. However, the significance of the TRIM family of E3 ubiquitin ligases in head and neck squamous cell carcinoma (HNSCC) has not been determined. In this study, the roles of TRIM E3 ubiquitin ligases in lymphovascular invasion in head and neck squamous cell carcinoma (HNSCC) were evaluated.Materials and Methods: TRIM expression and related parameters were obtained from UbiBrowser2.0, UALCAN, TIMER, TISIDB, LinkedOmics, STRING, and GeneMANIA databases. Immunohistochemistry was used to confirm their expression.Results: TRIM2, TRIM11, TRIM28, and TRIM56 were upregulated in HNSCC with lymphovascular invasion. TRIM expression was strongly associated with immune infiltration, including key treatment targets, like PD-1 and CTL4. Co-expressed genes and possible ubiquitination substrates included tumor-related factors. The TRIMs had predicted roles in ubiquitination-related pathways and vital signaling pathways, eg, MAPK, PI3K-Akt, and JAK-STAT signaling pathways.Conclusion: Ubiquitination mediated by four TRIMs might be involved in the regulation of tumor immunity, laying the foundation for future studies of the roles of the TRIM family on the prediction and personalized medicine in HNSCC. The four TRIMs might exert oncogenic effects by promoting lymphovascular invasion in HNSCC.Keywords: ubiquitination, TRIM, head and neck squamous cell carcinoma, bioinformatic analysis, lymphovascular invasion

Boyu Zhang,1,&ast; Yajun Bi,2,&ast; Kang Wang,1,&ast; Xingjun Guo,3 Zeming Liu,1 Jia Li,1 Min Wu1 1Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Pediatrics, Dalian Municipal Women and Children’s Medical Center (Group), Dalian Medical University, Dalian, Liaoning Province, 116011, People’s Republic of China; 3Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia Li; Min Wu, Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of China, Tel +86 18846818658 ; +86 13554254796, Email 4338311@qq.com; wumin@hust.edu.cnAbstract: Wound healing is a sophisticated and orderly process of cellular interactions in which the body restores tissue architecture and functionality following injury. Healing of chronic diabetic wounds is difficult due to impaired blood circulation, a reduced immune response, and disrupted cellular repair mechanisms, which are often associated with diabetes. Stem cell-derived extracellular vesicles (SC-EVs) hold the regenerative potential, encapsulating a diverse cargo of proteins, RNAs, and cytokines, presenting a safe, bioactivity, and less ethical issues than other treatments. SC-EVs orchestrate multiple regenerative processes by modulating cellular communication, increasing angiogenesis, and promoting the recruitment and differentiation of progenitor cells, thereby potentiating the reparative milieu for diabetic wound healing. Therefore, this review investigated the effects and mechanisms of EVs from various stem cells in diabetic wound healing, as well as their limitations and challenges. Continued exploration of SC-EVs has the potential to revolutionize diabetic wound care. Keywords: diabetes, wound healing, stem cells, EVs, ncRNAs, regeneration

Ke Wang,1,2,3 Yuying Kou,4 Xing Rong,1,2 Lingling Wei,5 Jingyuan Li,6 Hongrui Liu,1,2 Minqi Li,1,2 Hui Song31Department of Bone Metabolism, 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, People’s Republic of China; 2Center of Osteoporosis and Bone Mineral Research, Shandong University, Jinan, People’s Republic of China; 3Department of Health Care (Department of General Dentistry II), 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, People’s Republic of China; 4School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 5Department of Pediatric Dentistry, 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, People’s Republic of China; 6Department of Oral Mucosal Disease, 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, People’s Republic of ChinaCorrespondence: Hui Song, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration No.44-1 Wenhua Road West, Jinan, Shandong, 250012, People’s Republic of China, Tel +0086-531-88382912, Email songhui@sdu.edu.cnPurpose: Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71.Methods: In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H2O2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot.Results: ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts.Conclusion: ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.Keywords: osteoporosis, eldecalcitol, osteoclasts, EphrinB2-EphB4, osteoblasts, RANKL/RANK/OPG

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

Wei Zhang,1,&ast; Yufei Wang,1,&ast; Kaiying Wang,2,&ast; Jinhui Li,2 Jia Liu,1 Shulei Li,1 Lijie Song,1 Chunchen Liao,2 Xiaoli Yang,1 Peng Li,2 Xiong Liu2 1Department of Clinical Laboratory, The Third Medical Center, PLA General Hospital, Beijing, 100039, China; 2Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, China&ast;These authors contribute equally to this workCorrespondence: Peng Li; Xiong Liu, Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, China, Email jiekenlee@126.com; liuxiong714@163.comBackground: Urinary tract infection (UTI) associated with Klebsiella pneumoniae poses a serious threat for inpatients. This study aimed to describe the genomic characteristics of K. pneumoniae causing UTI in a tertiary-care hospital in Beijing, China.Methods: A total of 20 K. pneumoniae strains collected from 2020 to 2021 were performed whole-genome sequencing. The Antibiotic susceptibility of 19 common antimicrobial agents was tested against all strains. The multi-locus sequence types (MLSTs) and serotypes were determined from the WGS data. De novo assemblies were used to identify resistance and virulence genes. The presence and characteristics of the plasmids were detected using hybrid assembly of long and short-read data.Results: These K. pneumoniae strains were clustered into nine sequence types (STs) and twelve K-serotypes. All the carbapenem-resistant K. pneumoniae (CRKP) strains acquired carbapenemase blaKPC-2 (n=7). Two CRKP strains exhibited increased resistance to Polymyxin B with MIC ≥ 4 mg/L due to insertion of an IS5-like sequence in the mgrB gene, and they were also involved in a transmission event in Intensive Care Unit. Long-read assemblies identified many plasmids co-carrying multiple replicons. Acquisition of a new IncM2_1 type blaCTX-M-3 positive plasmid was observed after transfer from ICU to neurovascular surgery by comparing the two strains collected from the same patient.Conclusion: K. pneumoniae is a significant pathogen responsible for urinary tract infections. The ST11-KL47 strain, prevalent at our hospital, exhibits a combination of high drug resistance and hypervirulence. It is imperative to enhance ongoing genomic surveillance of urinary tract infection-causing pathogens.Keywords: Antimicrobial resistance, Klebsiella pneumoniae, urinary tract infections

Jianxia Ma,&ast; Ke Wang,&ast; Jun Wang, Qinlian Zeng, Kangwei Liu, Songbai Zheng, Yuanwen Chen, Jianfeng Yao Department of Gastroenterology, Hua Dong Hospital of Fu Dan University, Shanghai, 200040, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianfeng Yao, Department of Gastroenterology, HuaDong Hospital of Fu Dan University, No. 221. Road West Yanan, Shanghai, 200040, People’s Republic of China, Tel +8602162483180, Email yjf1966@126.comObjective: The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD.Methods: Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn’s disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis.Results: There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly.Conclusion: There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.Keywords: inflammatory bowel disease, ulcerative colitis, Crohn’s disease, gut microbiota, 16S rRNA gene sequencing

Baogen Zhang,1,&ast; Biqing Huang,2,&ast; Fan Yang,3,&ast; Jiandong Yang,1 Man Kong,1 Jing Wang,1 Yaoxian Xiang,1 Kangjie Wang,1 Ruchen Peng,4 Kun Yang,4 Chao An,5 Dong Yan1 1Department of Oncology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Interventional Radiology and Vascular Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 3Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, People’s Republic of China; 4Department of Medical Imaging, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, 101149, People’s Republic of China; 5Department of Minimal Invasive Intervention, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative, Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Yan, Department of Oncology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, 101149, People’s Republic of China, Tel/Fax +86-10-69543901, Email dongyan@mail.ccmu.edu.cn Chao An, Department of Minimal invasive intervention, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative, Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China, Tel/Fax +86-20-87343272, Email anchao-1983@163.comObjective: To compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with transarterial chemoembolization (TACE) for the treatment of high-risk hepatocellular carcinoma (hHCC) patients.Methods: Between January 2014 and August 2022, a total of 1765 consecutive patients with hHCC who underwent initial intra-arterial therapies were reviewed and divided into a TACE group (n, 507) and a HAIC group (n, 426). The study used propensity score matching (PSM) to reduce selectivity bias. Overall survival (OS) and progression-free survival (PFS) were compared using Kaplan‒Meier curves with the Log rank test. The objective response rate (ORR), conversion surgery rate (CSR) adverse event (AE) comparison and subgroup analysis were performed between the two groups.Results: After PSM 1:1, 444 patients were divided into two groups. The patients with hHCC who received HAIC had higher median PFS (6.1 vs 3.3 months, P < 0.001) and OS (10.3 vs 8.2 months, P=0.303) than TACE. Higher ORR (24.8% vs 11.7%) and CSR (15.5% vs 8.9%) were found in the HAIC group than in the TACE group (both P < 0.05). The incidence of grade 3/4 AE was 23.9% and 8.1% in the TACE and HAIC groups, respectively. The subgroup analysis suggest that HAIC appeared to particularly benefit patients with tumor diameter of more than 10 centimeters (hazard ratio [HR], 0.6; 95% CI, 0.47– 0.77; p, 0.00) and PVTT Vp4 (HR, 0.56; 95% CI, 0.39– 0.8; P, 0.01) for PFS outperforming TACE.Conclusion: HAIC can provide better disease control for hHCC than cTACE, with a comparable long-term OS and safety.Keywords: hepatocellular carcinoma, transarterial chemoembolization, hepatic artery infusion chemotherapy, high risk

Jiandong Yang,1 Yaoqin Lu,2 Yanggui Chen,2 Yida Wang,1 Kai Wang3 1School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China; 2Department of Tuberculosis Control and Prevention, Urumqi Center for Disease Control and Prevention, Urumqi, 830026, People’s Republic of China; 3State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of ChinaCorrespondence: Kai Wang, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, School of Public Health, Xinjiang Medical University, Urumqi, 830017, People’s Republic of China, Email wangkaimath@sina.comObjective: This study aims to analyze the drug resistance spectrum, genetic diversity, and transmission dynamics to provide a basis for the prevention and control of drug-resistant (DR) tuberculosis (TB) epidemics.Methods: This retrospective study is based on routine national drug resistance surveillance. The demographic, epidemiological, and clinical information on DR-TB patients from 2016 to 2021 was collected and used for phenotypic drug susceptibility testing and whole-genome sequencing.Results: It was indicated that L2.2.1 was the dominant lineage in Urumqi. The drug resistance spectrum in Urumqi was narrow, which means more drug combinations can be used for clinical treatment. Furthermore, mutations identification of drug-resistance gene katG, rpoB, embA/B, rrs, rpsL, eis, gyrA/B, folC and tryA are important for clinical drug use. However, mutations in cross-resistance genes rrs have limited guidance for clinical selection of KM, CPM and AK. Moreover, there is an increased risk of cluster transmission of DR-TB, and the difference in clustering rate among L2, L3, and L4 was not statistically significant (χ2 = 2.6410, p = 0.2670).Conclusion: In the Urumqi, DR-TB has a complex prevalence state, a narrow drug resistance spectrum, and a high clustering rate and burden of drug resistance. To reduce the burden of DR-TB, related research should be strengthened, and the development of prevention, control, and treatment strategies should be accelerated.Keywords: Mycobacterium tuberculosis, resistance, whole genome sequencing, transmission dynamics, Urumqi

Jiahui Ma,1– 4,&ast; Xue Yang,5,&ast; Zhiming Liu,1– 4 Hao Fu,1– 4 Sizhou Fan,1– 4 Kai Wang,1– 4 Yan Li,1– 4 Lvzhen Huang,1– 4 Mingwei Zhao1– 4 1Department of Ophthalmology, Peking University People’s Hospital, Beijing, People’s Republic of China; 2Eye Diseases and Optometry Institute, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Diagnosis and Therapy of Retinal and Choroid Diseases, Beijing, People’s Republic of China; 4College of Optometry, Peking University Health Science Center, Beijing, People’s Republic of China; 5Department of Ophthalmology, Peking University International Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Yan Li, Email wang_kai@bjmu.edu.cn; 13801153660@163.comPurpose: To investigate the impact of vergence dysfunction on myopia progression in children with Defocus incorporated multiple segments (DIMS) spectacle lenses.Patients and Methods: We retrospectively enrolled children prescribed DIMS spectacle lenses to slow myopic progression. Baseline vergence dysfunction was determined according to phoria at distance and near. Axial length (AL) measurement and cycloplegic subjective refraction were performed before fitting the lenses and at six-month and one-year follow-ups. The six-month and one-year AL and spherical equivalent (SE) change from baseline were calculated and compared in subgroups stratified with the type of vergence dysfunction.Results: Two hundred and ninety-two myopic children were included. Significant AL elongation and SE progression were observed at six months and one year (P < 0.05 for all comparisons). Multiple regression demonstrated that AL elongation at six months (P < 0.001) and one year (P < 0.001) was negatively correlated with age, and SE progression at six months was associated with age (P = 0.002). The AL elongation at six months in children with convergence excess was significantly greater than in normal myopic subjects (P = 0.011) and subjects with convergence insufficiency (P = 0.008), divergence excess (P = 0.007), divergence insufficiency (P = 0.024) and basic esophoria (P = 0.048) at six months.Conclusion: The present research demonstrated that vergence dysfunction influences myopia progression for myopic children with DIMS, and the children with convergence excess suffer from the greatest myopia progression among different types of vergence dysfunction.Keywords: myopia, vergence dysfunction, defocus spectacles, axial length

Huimin Du,1 Kexin Wang2 1First Affiliated Hospital of Huzhou University, Huzhou, Zhejiang People’s Republic of China; 2Gynecology Department, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumchi, People’s Republic of ChinaCorrespondence: Huimin Du, First Affiliated Hospital of Huzhou University, 158, Square Back Road, Huzhou, Zhejiang Province, 313000, People’s Republic of China, Email huimindu@naver.com

Kongjia Wang,1 Shufei Wang,2 Yixin Ding,3 Zengshun Kou,1 Bo Jiang,1 Sichuan Hou1 1Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 2College of Clinical and Basic Medical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Jiang; Sichuan Hou, Email jiangboqdy@126.com; housichuandoctor@126.comBackground: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased susceptibility to cancer, including bladder urothelial carcinoma (BLCA). This study investigates the shared molecular mechanisms and gene signatures between SLE and BLCA, shedding light on potential biomarkers and therapeutic targets.Methods: We compiled gene datasets related to SLE and BLCA from various databases and identified common genes. Differential gene expression analysis, protein-protein interaction networks, and hub gene identification were performed. We studied functional enrichment, immune infiltration, and transcription factor/miRNA regulation networks. We also explored gene-disease interactions and protein-chemical/drug networks. Hub gene expression levels and diagnostic values were validated in TCGA and GEO databases. Prognostic analysis was performed on the core gene MMP9 in the TCGA-BLCA database to study its prognostic value. Finally, the mRNA expression of MMP9 was verified in bladder cancer cell lines and BLCA patient blood. The diagnostic value of MMP9 for BLCA was verified by receiver operating characteristic(ROC) curve analysis of the expression of MMP9 in patients’ blood.Results: We identified 524 common genes between SLE and BLCA, enriched in pathways related to apoptosis and cytokine regulation. Immune infiltration analysis for two diseases. Transcription factors and microRNAs were implicated in regulating these common genes. The gene-disease network linked hub genes with various diseases, emphasizing their roles in autoimmune disease and cancer. Protein-chemical/drug networks highlighted potential treatment options. Finally, our study found that MMP9 is a potential therapeutic target with diagnostic and prognostic value and Immune-related biomarkers in patients with BLCA and SLE.Conclusion: Our study reveals shared molecular mechanisms, genetic signatures, and immune infiltrates between SLE and BLCA. MMP9 emerges as a potential diagnostic and prognostic biomarker in BLCA, warranting further investigation. These findings provide insights into the pathogenesis of SLE-associated BLCA and may guide future research and therapeutic strategies.Keywords: systemic lupus erythematosus, bladder urothelial carcinoma, gene signatures, immune response, MMP9

Chenxi Zeng,1,&ast; Qi Wang,2,&ast; Xuhan Liu,3,&ast; Kai Wang,1 Congjian Wang,1 Xuetao Ju,1 Tianlai Wang,1 Qing Zhou,4 Xiangning Fu,1 Jun Yu,1 Yi Wang4 1Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 3Department of Emergency Medicine, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Wang, Department of Pulmonary and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, People’s Republic of China, Email wangyi@tjh.tjmu.edu.cn Jun Yu, Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, People’s Republic of China, Email junyu2018@hotmail.comBackground: Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by chronic lung injury leading to macrophage infiltration and fibroblast activation. However, there is no effective therapeutic strategy targeting the crucial crosstalk between macrophages and fibroblasts to halt IPF progression.Methods: Studies were conducted in IPF patients and fibrotic mice models to elucidate the role of Bcar3 in the pathogenesis of pulmonary fibrosis. The effect of Bcar3 on macrophage polarization, fibroblast activation, and related signaling pathways were next investigated to unravel the underlying mechanisms.Results: Our study elucidates a marked increase in Bcar3 expression in lung tissues from IPF patients and fibrotic mice, recording 1.7 and 7.8-fold increases compared to control subjects, respectively. Additionally, Bcar3 was found to significantly enhance macrophage activation and fibroblast differentiation, observable in both in vivo and in vitro settings. Mechanistically, the upregulation of Bcar3 in macrophages was reliant on Stat6, while in fibroblasts, it depended on TGFβR1/Smad3. Furthermore, Bcar3 augmented IL-4/Stat6 pathway in macrophages and TGF-β/Smad3 pathway in fibroblasts, supporting a synergistic activation loop that expedited lung fibrogenesis. Notably, intratracheal injection of liposomes containing Bcar3 siRNA precisely delivered gene therapeutics to lung macrophages and fibroblasts, effectively reducing Bcar3 expression to 59% of baseline levels. Importantly, this intervention protected mice from lung fibrosis induced by either FITC or bleomycin, as well as human precision-cut lung slices against TGF-β 1 stimulation.Conclusion: Our study underscores the pivotal role of Bcar3 in orchestrating the macrophage-fibroblast crosstalk during pulmonary fibrosis progression. Targeting Bcar3 emerges as a novel therapeutic avenue to halt IPF progression and enhance patient prognosis.Keywords: idiopathic pulmonary fibrosis, Bcar3, liposomes, macrophages, fibroblasts

Haijun Wei,&ast; Ke Wang,&ast; Wei Huang, Yang Liu Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang Liu, Department of Vascular Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China, Email zjobliu@163.comAbstract: Pyoderma gangrenosum (PG) is a rare autoinflammatory neutrophilic dermatosis clinically characterized by painful nodules, red papules or plaques that rapidly erode into ulcers. We report a 53-year-old febrile male patient with acute peripheral arterial disease who underwent transtibial amputation after failed thrombolysis. Five days after amputation, an ulcer developed around the cannulation site of the right internal jugular vein that was indicative of pathergy. The patient’s fever did not improve after surgery, and purpuric discoloration and punctate ulcers of the skin near the amputation site became apparent, leading to re-debridement. Finally, consultation with a dermatologist raised the possibility of postoperative PG, and additional laboratory tests revealed positive anticardiolipin autoantibodies consistent with antiphospholipid syndrome. The patient was treated with intravenous glucocorticosteroids and antibiotics, and the amputation wound and cannulation site ulcer were found to have healed at the 2-month follow-up. The current report raises the need for vascular surgeons to be aware of this uncommon etiology of arterial thrombosis, and the postoperative appearance of dermatosis and pathergy should alert for PG.Keywords: antiphospholipid syndrome, case report, peripheral artery disease, pyoderma gangrenosum

Jie Bai,1 Jinxia Zheng,1 Nafei Guo,2 Yueyan Dong,1 Ke Wang,1 Cheng Cheng,3 Hui Jiang,2 Lin Qian4 1Shanghai Key Laboratory of Maternal-Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 3School of Nursing, Fudan University, Shanghai, People’s Republic of China; 4Nursing Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Hui Jiang, Nursing Department, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China, Tel/Fax +86 21-20261221, Email jianghuitest@163.com Lin Qian, Nursing Department, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China, Email lc699536@126.comPurpose: Receiving assisted reproductive technology is stressful due to its long-lasting process, which might pose negative impacts on clients’ psychological well-being and quality of life. This study was to investigate coping profiles among couples undergoing assisted reproductive technology and examine their associations with psychological distress and quality of life.Methods: This cross-sectional study was conducted at the IVF center of a specialized hospital in Shanghai, China. Of 502 eligible clients completed a structured, online survey of socio-demographic information, Dyadic Coping Inventory, Kessler Psychological Stress Scale, and Fertility quality of life. Coping profiles were identified using latent profile analysis and differences between identified profiles on psychological distress and quality of life were examined using analyses of covariance.Results: A three-profile solution was supported: low dyadic coping group (n = 168, 33.50%), moderate dyadic coping group (n = 241, 48.00%), and high dyadic coping group (n = 93, 18.50%). Significant differences between those groups were found in psychological distress and quality of life.Conclusion: The findings of this study have revealed dyadic coping profiles in clients undergoing assisted reproductive technology, which are differentially associated with psychological distress and quality of life.Keywords: assisted reproductive technology, coping, latent profile analysis, psychological distress, quality of life

Xun Qiu,1,2,&ast; Libin Dong,1,2,&ast; Kai Wang,1,2 Xinyang Zhong,1,2 Hanzhi Xu,1,2 Shengjun Xu,2 Haijun Guo,2 Xuyong Wei,1,2 Wei Chen,2,3 Xiao Xu1,2 1Department of Surgery, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Hangzhou, 310006, People’s Republic of China; 3Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chen; Xiao Xu, Email jackweichen@zju.edu.cn; zjxu@zju.edu.cnBackground: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Accumulating evidence indicates that hypoxia and lactate metabolism play critical roles in tumor progression and therapeutic efficacy. This study aimed to construct a hypoxia- and lactate metabolism-related prognostic model (HLPM) to evaluate survival and treatment responses for HCC patients and develop a nomogram integrated with HLPM and clinical characteristics for prognosis prediction in HCC.Methods: Expression profile and clinical data of HCC were obtained from TCGA and ICGC databases. The univariate, LASSO and stepwise multivariate Cox analyses were used to identify the hypoxia- and lactate metabolism-related biomarkers, whose expression levels were then validated in 14 pairs tissue samples and single-cell RNA sequencing dataset. Kaplan–Meier survival curves were utilized to assess the prognostic values of biomarkers or models. Analyses of ImmuCellAI, TIDE and drug sensitivity were conducted to evaluate the therapeutic responses of patients. Furthermore, the nomogram integrated with hypoxic and lactate metabolic characteristics was established through univariate and multivariate Cox analyses. ROC curves, C-index, and calibration curves were depicted to evaluate the performance of the nomogram.Results: Five hypoxia- and lactate metabolism-related biomarkers (KIF20A, IRAK1, ADM, PPARGC1A and EPO) were used to construct HLPM. The expression of five prognostic biomarkers was validated in 14 pairs tissue samples and single-cell RNA sequencing dataset. Analyses of ImmuCellAI, TIDE and drug sensitivity implied that patients with low-risk score were more sensitive to immunotherapy and major chemotherapeutic agents. The nomogram that contained age, histological grade and risk score of HLPM was developed and exhibited a better capacity in prognosis prediction than HLPM only.Conclusion: A novel nomogram integrated with hypoxic and lactate metabolic characteristics was developed and validated for prognosis prediction in HCC, providing insight into personalized decision-making in clinical management.Keywords: hepatocellular carcinoma, nomogram, prognosis, lactate metabolism, hypoxia, immunotherapy

Ke Wang,1,2,&ast; Te Liu,1,&ast; Yucheng Zhang,1 Huiying Lv,1 Hua Yao,1 Ye Zhao,3 Jing Li,1 Xiuying Li1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Gynecology and Obstetrics Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3Dermatological Department, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuying Li; Jing Li, Email lixiuying@jlu.edu.cn; lijing1029@jlu.edu.cnBackground: Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus and constitutes the primary cause of mortality in affected patients. Previous studies have shown that placental mesenchymal stem cells (PL-MSCs) can alleviate kidney dysfunction in animal models of DN. However, the limited ability of mesenchymal stem cells (MSCs) to home to damaged sites restricts their therapeutic potential. Enhancing the precision of PL-MSCs’ homing to target tissues is therefore vital for the success of cell therapies in treating DN.Methods: We developed Fe3O4 coated polydopamine nanoparticle (NP)-internalized MSCs and evaluated their therapeutic effectiveness in a mouse model of streptozotocin- and high-fat diet-induced DN, using an external magnetic field.Results: Our study confirmed that NPs were effectively internalized into PL-MSCs without compromising their intrinsic stem cell properties. The magnetic targeting of PL-MSCs notably improved their homing to the kidney tissues in mice with DN, resulting in enhanced kidney function compared to the transplantation of PL-MSCs alone. Furthermore, the anti-inflammatory and antifibrotic attributes of PL-MSCs played a role in the recovery of kidney function and structure.Conclusion: These results demonstrate that magnetically targeted therapy using PL-MSCs is a promising approach for treating diabetic nephropathy.Keywords: diabetic nephropathy, magnetic targeting, mesenchymal stem cells, iron oxide nanoparticles

Lei Lei, Ke Wang Henan Provincial Chest Hospital, Zhengzhou, 450008, Henan, People’s Republic of ChinaCorrespondence: Ke Wang, Email 13837178129@163.comBackground: Preserving nephrons while avoiding tumor recurrence during the treatment of renal cell carcinoma remains as a challenge in clinic. To achieve desired therapeutic outcome, we developed specific nanozymes based on the tumor microenvironment and evaluated its efficacy in combination with radiotherapy.Methods: Herein, a hybrid nanozyme CeO2@Au-PEG nanocomposite nanoparticle (NPs) was developed for the treatment of renal tumor. It was composed of gold nanozyme decorated CeO2 nanorods and exhibited both glucose-oxidase like by gold nanozyme and peroxidase-like catalytic activities. Due to the high metabolic rate of tumor cells, they take up a huge amount of glucose to survive and proliferate. Therefore, we generated CeO2@Au-PEG NPs, which exhausted glucose in the tumor tissue and generated hydrogen peroxide, depleting the source of energy and causing tumor cell death. Then the generated hydrogen peroxide was degraded by the peroxidase-mimicking properties of CeO2@Au-PEG NPs, elevating oxidative stress and thus enhancing tumor cell death. Moreover, due to the high mass nuclei of gold and cerium, they could further sensitize the tumors to radiotherapy and thus thoroughly eliminate tumors.Results: With enough biocompatibility, CeO2@Au-PEG NPs showed superior ability to deplete glucose as well as enhance oxidative stress by producing reactive oxygen species in RENCA cells under ionizing irradiation. Moreover, CeO2@Au-PEG NPs greatly improved radiotherapy mediated tumor ablation in tumor bearing mice.Conclusion: Systematic experiments demonstrated the synergistic therapeutic effects of the combination of CeO2@Au-PEG NPs and radiotherapy in renal tumor model, which may serve as a promising strategy for treating renal cancer patients in the clinic.Keywords: nanozyme, radiotherapy, glucose consumption, reactive oxygen species, renal cell carcinoma

Ying Yin,1 Ke Wang,1,2 Yan Xu,2,3 Xin Huang,1 Jinxia Zheng,1 Yuping Fan,1 Jie Bai1 1Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 2School of Medicine, Tongji University, Shanghai, 200092, People’s Republic of China; 3School of International Medical Technology, Sanda University, Shanghai, 201206, People’s Republic of ChinaCorrespondence: Ke Wang, Email wangkeyfy@126.comObjective: To analyze the mental health and erectile function status of men using sperm donor during pregnancy after ICSI failure in severe oligoasthenospermia and to provide reference for clinical implementation of more targeted psychological intervention and nursing for this group.Methods: A total of 410 sterile men who received assisted pregnancy treatment in our hospital from December 2020 to December 2022 and met the inclusion and exclusion criteria were collected as the study subjects. Among them, 68 patients with severe oligoasthenospermia who used donor assisted pregnancy after ICSI failure were used as the study group. Sixty-eight patients with severe oligoasthenospermia who continued to receive ICSI assisted pregnancy were matched by propensity score 1:1 as control group. General data questionnaire, self-rating Anxiety Scale (SAS), self-rating Depression Scale (SDS), Chinese version of perceived Stress Scale (CPSS) and International Erectile Function Index Rating Scale (IIEF-5) were used to conduct a cross-sectional investigation to compare the mental health and erectile function status of the two groups.Results: There were statistical differences in age and occupational status between the two groups before PSM (P < 0.05), but there was no statistical significance in social demographic data between the two groups after matching (P > 0.05). The incidence of anxiety, depression, stress and erectile dysfunction (ED) in the study group was higher than that in the control group, and there were statistical differences between the two groups (P < 0.05).Conclusion: The use of donor sperm to assist pregnancy has a great impact on the mental health and erectile function of infertile men. Medical personnel should pay attention to the mental health and erectile function of these men, and formulate targeted measures to help these patients actively cope with infertility, so as to improve the life and marriage quality of this group and improve their mental health status.Keywords: sterile male, supply semen, erectile function, mental health, propensity score

Jing Huang,1,&ast; Kaiyu Wang,1,&ast; Xizi Fu,1,&ast; Manfang Zhu,2 Xiaohua Chen,1 Yan Gao,1 Pingchuan Ma,3 Xingmei Duan,2 Ke Men1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China; 3State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comBackground: Messenger ribonucleic acid (mRNA)-based gene therapy has great potential in cancer treatment. However, the application of mRNA-based cancer treatment could be further developed. Elevated delivery ability and enhanced immune response are advantages for expanding the application of mRNA-based cancer therapy. It is crucial that the prepared carrier can cause an immune reaction based on the efficient delivery of mRNA.Methods: We reported DMP nanoparticle previously, which was obtained by the self-assembly of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and (ethylene glycol)-b-poly (&epsiv;-caprolactone) (mPEG-PCL). Research demonstrated that DMP can deliver mRNA, siRNA, and plasmid. And it is applied to various tumor types. In our work, the tumor cell lysate was introduced to the internal DMP chain, fusing cell-penetrating peptides (CPPs) modification on the surface forming the CLSV system. And then mixed encoded IL-22BP (interleukin-22 binding protein) mRNA and CLSV to form CLSV/IL-22BP complex.Results: The size of the CLSV system was 213.2 nm, and the potential was 45.7 mV. The transfection efficiency of the CLSV system is up to 76.45% in C26 cells via the micropinocytosis pathway. The CLSV system also could induce an immune response and significantly elevate the expression of CD80, CD86, and MHC-II in vivo. Then, by binding with IL-22BP (Interleukin-22 binding protein) mRNA, the CLSV/IL-22BP complex inhibited tumor cell growth, with an inhibition rate of up to 82.3% in vitro. The CLSV/IL-22BP complex also inhibited tumor growth in vivo, the tumor cell growth inhibition up to 75.0% in the subcutaneous tumor model, and 84.9% in the abdominal cavity metastasis tumor model.Conclusion: Our work demonstrates that the CLSV system represents a potent potential for mRNA delivery.Keywords: mRNA, cell-penetrating peptide, gene therapy, tumor cell lysate, immune response

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

Diane N Sayah,1– 3 Itika Garg,1,2 Raviv Katz,1,2 Ying Zhu,1,4 Ying Cui,1,5 Rebecca Zeng,1,2 Rachel Tandias,1,2 Jade Y Moon,1,2 Filippos Vingopoulos,1,2 Hannah E Wescott,1,2 Grace Baldwin,1,2 Kira Wang,1,2 Tobias Elze,1,2 Cassie Ann Ludwig,1,2 Demetrios G Vavvas,1,2 Joan W Miller,1,2 Deeba Husain,1,2 Leo A Kim,1,2 Nimesh A Patel,1,2 John B Miller1,2 1Harvard Retinal Imaging Lab, Boston, MA, USA; 2Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA; 3College of Optometry, University of Houston, Houston, TX, USA; 4Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Guangdong Eye Institute, Department of Ophthalmology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of ChinaCorrespondence: John B Miller, Retina Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, 243 Charles St, Boston, MA, 02114, USA, Tel +1 617 573-3750, Fax + 1 617 573-3698, Email John_Miller@meei.harvard.eduPurpose: Visual prognosis and treatment burden for macular neovascularization (MNV) can differ between myopic macular degeneration (MMD) and age-related macular degeneration (AMD). We describe and compare MNV associated with MMD and AMD using swept-source (SS)-OCTA.Patients and Methods: Adult patients with documented MNV associated with MMD or AMD were consecutively recruited. Qualitative and quantitative features were assessed from 6x6mm angiograms, including the MNV area and vessel density (VD). Descriptive statistics and linear regression analyses were carried out.Results: Out of 75 enrolled eyes with diagnosed MNV (30 MMD-MNV and 45 AMD-MNV; mean age 55± 19 and 75± 8 years, respectively), 44 eyes had discernible MNV (11 MMD-MNV and 33 AMD-MNV) on SS-OCTA at the time of the study and were included in the analysis. The MMD-MNV group exhibited a three-fold smaller sized MNV (p=0.001), lower greatest linear dimension (p=0.009) and greatest vascular caliber (p< 0.001) compared to AMD-MNVs, and had a higher prevalence of tree-in-bud pattern. Eyes with AMD showed a higher prevalence of type 1 MNVs with medusa pattern. There was no difference in the location of the MNV, shape’s regularity, margins, presence of core vessel, capillary fringe, peripheral loops, or perilesional dark halo (p> 0.05) between both conditions. After adjustment, decreased MNV area and increased VD were associated with the tree-in-bud pattern, whereas the diagnosis did not significantly influence those parameters.Conclusion: While larger studies are warranted, this study is the first to describe and compare MMD-MNV and AMD-MNV using SS-OCTA, providing relevant clinical insight on MNV secondary to MMD and AMD. These findings also further validate OCTA as a powerful tool to detect and characterize MNV non-invasively.Keywords: macular neovascularization, age-related macular degeneration, high myopia, swept source, OCT angiography

Ziwei Meng,1,&ast; Rongxin Chen,1,&ast; Shujuan Cao,2,&ast; Xinyue Yu,1 Shu Liu,3 Yu Hu,1 Jing Li,1 Meiqing Chen,1 Kerui Wang,1 Xuanwei Liang1 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, Guangzhou, 510060, People’s Republic of China; 2Ophthalmologic Center, The Affiliated Kashi Hospital of Sun Yat-sen University, The First People’s Hospital of Kashi Prefecture, Kashi, 844000, People’s Republic of China; 3Department of Pharmacy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuanwei Liang; Rongxin Chen, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangdong Provincial Clinical Research Center for Ocular Diseases, Sun Yat-sen University, 54 South Xianlie Road, Guangzhou, 510060, People’s Republic of China, Email liangxuanwei@163.com; rongxinchan@foxmail.comPurpose: To assess the quality of vision (QOV) of patients with chronic dacryocystitis and explore the impact of endoscopic dacryocystorhinostomy (En-DCR) on patients’ QOV, with the aim of increasing clinicians’ attention to the potential QOV changes in patients with chronic dacryocystitis.Patients and Methods: Chronic dacryocystitis patients who attended the Department of Oculoplastics, Zhongshan Ophthalmic Center, Sun Yat-sen University from January 2022 to June 2022 and had En-DCR were included. The QOV was evaluated preoperatively and postoperatively using the Quick-contrast sensitivity function test (qCSF) and the OPD ScanIII comprehensive visual quality analyser, and the contrast sensitivity function (CSF), higher-order aberrations (HOAs), and modulation transfer function (MTF) data were recorded.Results: Thirty-eight patients with chronic dacryocystitis were included. QOV analysis of those with monocular chronic dacryocystitis revealed that HOAs were significantly higher in affected eyes than in contralateral eyes (P < 0.05), and CSF and MTF were significantly lower in affected eyes than in contralateral eyes (P < 0.05). One month after En-DCR, patients’ HOAs, CSF, and MTF were significantly improved (P < 0.05), and there was no statistically significant difference in the effect of intraoperative combined silicone intubation versus no intubation on QOV (P > 0.05).Conclusion: Chronic dacryocystitis can significantly affect the QOV of patients. Successful En-DCR significantly improves the CSF, HOAs and MTF, which can effectively improve the QOV.Keywords: chronic dacryocystitis, contrast sensitivity function, higher-order aberrations, modulation transfer function, endoscopic dacryocystorhinostomy

Dongmei Guo,1 Yue Huang,2 Kun Wang,2 Chenguang Yang,2 Lili Ma,2 Yu Zhang,2 Haiyang Yu,2 Manhua Cui,1 Zhaohui Tang2 1Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, Jilin Province, 130041, People’s Republic of China; 2Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of ChinaCorrespondence: Manhua Cui, Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, 218 Ziqiang Road, Changchun, Jilin Province, 130041, People’s Republic of China, Email cuimanhua@126.com Yue Huang, Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, People’s Republic of China, Tel/Fax +86 431 85262116, Email huangyue@ciac.ac.cnPurpose: Cervical cancer (CC) is a highly vascularized tumor with abundant abnormal blood vessel, which could be targeted by therapeutic strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential as nano vascular disrupting agents (VDAs) in the realm of synergistic cancer therapy.Methods: In this study, we investigated the nanocharacteristics of CB-NPs, focusing on active pharmaceutical ingredients (API), as well as lyophilized samples combining API with protective agents (PAs). The in vivo efficacy of final sample (API + PAs) was evaluated.Results: The assembled sphere of API with complex core and thin-shell structure was confirmed. PAs were found to significantly influence in vivo efficacy. Collaborative efforts between API and PAs, namely mannitol and lactose, resulted in the most promising lyophilized sample, ie, the final sample (FS2) for CC therapy. Impressively, FS2 demonstrated an exceptional 100% cure rate on the CC U14-bearing mice model.Conclusion: FS2 has provided significant insights for cervical cancer therapy. It is also crucial to develop a comprehensive evaluation strategy for the formulation of nanomedicine, which has the potential to serve as a guideline for future clinical trials. Keywords: combretastatin A4, BLZ945, glutamic acid, nano character, cervical cancer

Yixin Ding,1,&ast; Kongjia Wang,2,&ast; Shufen Zhao,1 Yu Li,3 Wensheng Qiu,1 Chunyang Zhu,1 Yan Wang,1 Chen Dong,1 Jiani Liu,1 Yangyang Lu,1 Weiwei Qi1 1Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Qi, Email qwwqdfy@126.comPurpose: Kinetochore scaffold 1 (KNL1), a crucial protein during cell mitosis participating in cell division, was widely expressed in multiple kinds of cancers. However, the expression profile, the effect on cell biological function, tumor immune microenvironment, and predictive value of clinical prognosis in pan-cancer of KNL1 still require a comprehensive inquiry.Methods: The mRNA and protein expression profile of KNL1 was validated in pan-cancer using different databases. Six algorithms were used to explore the correlation between KNL1 and immune infiltration and the relationship between KNL1 and tumor mutation burden (TMB), microsatellite instability (MSI), and TIDE score were calculated. The diagnostic and clinical prognostic predictive ability of KNL1 was assessed. Differentially expressed genes (DEGs) of KNL1 were screened out and function enrichment analyses were performed in pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and bladder urothelial carcinoma (BLCA). Finally, 8 cases of pancreatic adenocarcinoma tissues and paired adjacent tissues were collected for immunohistochemical (IHC) staining and the histological score (H-score) was calculated. Real-time PCR was performed in gastric cancer and bladder cancer cell lines.Results: KNL1 was abnormally upregulated in more than half of cancers across different databases. IHC and real-time PCR verified the up-regulated expression in cancer tissues in PAAD, gastric cancer, and BLCA. The satisfactory diagnostic value of KNL1 was indicated in 30 cancers and high KNL1 expression was associated with poorer overall survival (OS) in 12 cancers. The prognostic role of KNL1 as a predictive biomarker of PAAD was clarified. KNL1 played an active part in the cell cycle and cell proliferation. Moreover, KNL1 was likely to mold the Th2-dominant suppressive tumor immune microenvironment and was associated with TMB, MSI, and immune checkpoint-related genes in pan-cancer.Conclusion: Our study elucidated the anomalous expression of KNL1 and revealed that KNL1 was a promising prognostic biomarker in pan-cancer.Keywords: KNL1, bioinformatics, pan-cancer, immune infiltration, prognosis, clinical prognostic model

Jingmei Li,1,&ast; Jin Zhang,1,&ast; Yan Gao,1 Sibei Lei,1 Jieping Wu,1 Xiaohua Chen,1 Kaiyu Wang,1 Xingmei Duan,2 Ke Men1 1Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Men, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu, 610041, People’s Republic of China, Email mendingbob@hotmail.com Xingmei Duan, Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, People’s Republic of China, Email duanxingmei2003@163.comIntroduction: Cell-membrane nanocarriers are usually constructed by modifying the nanoparticle surface with cell membrane extracts, which has a direct benefit in endowing targeting capacity to nanocarriers based on their original cell types. However, delivering nucleic acid cargos by cell membrane–based nanoparticles is difficult owing to the strong negative charge of the cell membrane fraction. In this study, we developed a cancer cell membrane–based drug delivery system, the cMDS, for efficient siRNA delivery. Meanwhile, the cancer-specific immune response stimulated by the gene vector itself could offer synergistic anti-cancer ability.Methods: The cMDS was prepared by ultrasound, and its transfection efficiency and anti-cancer ability were examined using cultures of CT26 cells. MTT and red blood cell hemolysis tests were performed to assess the safety of cMDS, while its targeted gene delivery and strong immune stimulation were investigated in a subcutaneous tumor model. Moreover, the detailed anti-cancer immune stimulation mechanisms of cMDS are uncovered by protein chip analysis.Results: The cMDS was spherical core-shell structure. It showed high transfection efficiency and anti-cancer ability in vitro. In animal experiments, intravenously administered cMDS/siStat3 complex efficiently suppress the growth of colon cancer. Moreover, the result of protein chip analysis suggested that cMDS affect the migration and chemotaxis of immune cells.Conclusion: The cMDS shows obvious tumor tissue-specific accumulation properties and strong immune stimulation ability. It is an advanced targeted gene delivery system with potent immunotherapeutic properties.Keywords: bioinspired material, cancer cell membrane, targeted siRNA delivery, immunotherapeutic, colon cancer

Meiyan Sun,1,2,&ast; Xiaoyong Zhao,2,&ast; Xingyue Li,2 Chunling Wang,2 Lili Lin,3 Kaifang Wang,2 Yingui Sun,2 Wei Ye,3 Haiyan Li,3 Ye Zhang,1 Chaolu Huang2,4 1Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, 261053, People’s Republic of China; 3The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 4Department of Clinical Medicine, Qiandongnan Ethnic Vocational and Technical College, Kaili, 556000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Zhang, Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China, Email zhangy@ahmu.edu.cn Chaolu Huang, Department of Clinical Medicine, Qiandongnan Ethnic Vocational and Technical College, Kaili, 556000, People’s Republic of China, Email huangzhaolu2020@163.comObjective: Diabetes mellitus (DM) implicates oxidative stress, apoptosis, and inflammation, all of which may contribute liver injury. Aerobic exercise is assured to positively regulate metabolism in the liver. This project was designed to investigate whether and how aerobic exercise improves DM-induced liver injury.Methods: Seven-week-old male db/db mice and age-matched m/m mice were randomly divided into a rest control group or a group that received 12 weeks of aerobic exercise by treadmill training (10 m/min). Haematoxylin and eosin (HE) staining, electron microscopy, Oil Red O staining and TUNEL assays were used to evaluate the histopathological changes in mouse liver. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TRIG), cholesterol (CHOL) were analyzed by serum biochemical analysis. Interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and tissue levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed via ELISA. Nuclear factor E2-associated factor-2 (Nrf2), nuclear factor κB (NF-κB) and JAK2/STAT3 pathway-related proteins were measured by immunofluorescence, Western blotting and q-PCR. F4/80 expression in liver tissues was assessed by immunohistochemistry.Results: In diabetic mice, exercise training significantly decreased the levels of serum TRIG, CHOL, IL-6, TNF-α, ALT and AST; prevented weight gain, hyperglycaemia, and impaired glucose and insulin tolerance. Morphologically, exercise mitigated the diabetes-induced increase in liver tissue microvesicles, inflammatory cells, F4/80 (macrophage marker) levels, and TUNEL-positive cells. In addition, exercise reduced the apoptosis index, which is consistent with the results for caspase-3 and Bax. Additionally, exercise significantly increased SOD activity, decreased MDA levels, activated Nrf2 and decreased the expression of NF-kB, phosphorylated JAK2 and STAT3 proteins in the livers of diabetic mice.Conclusion: This study demonstrated that aerobic exercise reversed liver dysfunction in db/db mice with T2DM by reducing oxidative stress, apoptosis and inflammation, possibly by enhancing Nrf2 expression and inhibiting the JAK2/STAT3 cascade response.Keywords: db/db mice, aerobic exercise, inflammation, apoptosis, Nrf2, JAK2/STAT3