Search

Xinyu Zhao,1 Yang Wang,2,3 Xiaoyi Li,1 Peiqun Hu,2 Xiong-Fei Pan,4– 6 Benxiang He,7 Yunlu Liu,8 Yushi Hu,2 Tianmin Zhu9 1School of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 3Postdoctoral Workstation, Affiliated Sport Hospital of Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China; 4Section of Epidemiology and Population Health & Department of Gynecology and Obstetrics, Ministry of Education Key Laboratory of Birth Defects and Related Diseases of Women and Children & National Medical Products Administration Key Laboratory for Technical Research on Drug Products in vitro and in vivo Correlation, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Shuangliu Institute of Women’s and Children’s Health, Shuangliu Maternal and Child Health Hospital, Chengdu, Sichuan, People’s Republic of China; 7Sichuan Academy of Chinese Medicine Science, Chengdu, Sichuan, People’s Republic of China; 8Institute of Laboratory Animal Sciences, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People’s Republic of China; 9School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Tianmin Zhu, School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email tianminzhu@cdutcm.edu.cn Yushi Hu, School of Sports Medicine and Health, Chengdu Sport University, Chengdu, Sichuan, People’s Republic of China, Email huyushi@cdsu.edu.cnObjective: This study aims to evaluate the efficacy of acupuncture as an adjunct to lifestyle interventions on weight loss in simple obesity.Methods: Potentially eligible studies that assessed anthropometric outcomes as well as glucose and lipid metabolism following acupuncture combined with lifestyle interventions in simple obesity patients were searched from eight databases from inception to October 2023. All analyses were performed using the Review Manager software v5.4 and Stata software v17.0.Results: Herein, 25 randomized controlled trials (RCTs) involving 2018 patients were included. Generally, acupuncture combined with lifestyle interventions outperformed lifestyle interventions alone in terms of body weight (MD = − 4.73, 95% CI [− 6.32, − 3.13], p < 0.00001), body mass index (BMI) (MD = − 2.11, 95% CI [− 2.75, − 1.48], p < 0.00001), waist circumference (WC) (MD = − 4.96, 95% CI [− 6.89, − 3.03], p < 0.00001), body fat percentage (BF %) (MD = − 2.61, 95% CI [− 4,51, − 0.71], p = 0.007), fasting plasma glucose (FPG) (SMD = − 0.66, 95% CI [− 1.02, − 0.31], p = 0.0002), fasting serum insulin (FINS) (SMD = − 1.12, 95% CI [− 1.44, − 0.81], p < 0.00001), homeostasis model assessment-insulin resistance (HOMA-IR) (MD = − 1.22, 95% CI [− 1.50, − 0.94], p < 0.00001), total cholesterol (TC) (SMD = − 1.14, 95% CI [− 1.83, − 0.45], p = 0.001), triglyceride (TG) (SMD = − 1.31, 95% CI [− 2.07, − 0.56], p = 0.0006), and low-density lipoprotein cholesterol (LDL-C) (SMD = − 1.81, 95% CI [− 3.11, − 0.51], p = 0.006). Subgroup analysis based on three subgroup variables (types of acupuncture and lifestyle interventions as well as treatment durations) could partially explain the heterogeneity of the results.Conclusion: Acupuncture demonstrated an enhancing effect on the benefits of lifestyle interventions for weight loss in patients with simple obesity, including reducing body weight and improving glucose and lipid metabolism. This finding suggests its potential value as a complementary therapy alongside lifestyle interventions in a clinical setting. However, further validation with rigorously designed and high-quality RCTs is still needed in the future.Keywords: obesity, acupuncture, acupuncture therapy, meta-analysis, systematic review

Pilong Shi,1,&ast; Yuetong Sha,1,&ast; Xinran Wang,1,&ast; Tao Yang,1 Jiawei Wu,1 Jiajun Zhou,1 Kai Liu,1 Xue Guan,2 Song Wang,1 Yongsheng Liu,1 Jingquan Gao,3 Hongli Sun,1 Tao Ban,1 Yonggang Cao1 1Department of Pharmacology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Morphological Experiment Center, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Nursing, School of Medicine, Lishui University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonggang Cao; Hongli Sun, Email 437343482@qq.com; sunhongli@hmudq.edu.cnPurpose: Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods: In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results: Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion: Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2. Keywords: myocardial ischemia-reperfusion injury, lutein, ROS, MDM2, NDUFS1, ferroptosis

Yunfeng Jia,1 Yayi Liu,1 Yiming Zuo,1 Junping Zhang,1 Yanyang Li,2,3 Xuezheng Liu,1 Shichao Lv1 1Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion), Tianjin, 300381, People’s Republic of China; 2Department of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, People’s Republic of China; 3Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of ChinaCorrespondence: Shichao Lv; Xuezheng Liu, Department of Geriatrics, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, No. 88 Changling Street, Xiqing District, Tianjin, 300193, People’s Republic of China, Email dr_lv@foxmail.com; drhare1975@163.comAbstract: Heart failure (HF) represents a serious manifestation or advanced stage of various cardiac diseases. HF continues to impose a significant global disease burden, characterized by high rates of hospitalization and fatality. Furthermore, the pathogenesis and pathophysiological processes underlying HF remain incompletely understood, complicating its prevention and treatment strategies. One significant pathophysiological mechanism associated with HF is the systemic inflammatory response. PANoptosis, a novel mode of inflammatory cell death, has been extensively studied in the context of infectious diseases, neurodegenerative disorders, cancers, and other inflammatory conditions. Recent investigations have revealed that PANoptosis-related genes are markedly dysregulated in HF specimens. Consequently, the PANoptosis-mediated inflammatory response may represent a potential mechanism and therapeutic target for HF. This paper conducts a comprehensive analysis of the molecular pathways that drive PANoptosis. We discuss its role and potential therapeutic targets in HF, thereby providing valuable insights for clinical treatment and the development of novel therapies.Keywords: PANoptosis, pyroptosis, apoptosis, necroptosis, cell death, heart failure

Tianjie Zhang,1 Yan Liu,1 Dongwei Xu,2 Rui Dong,1 Ye Song1 1Department of Ultrasonography, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318,People’s Republic of China; 2Department of Critical Care Medicine, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Ye Song, Email songy_18@sumhs.edu.cnBackground: This study aims to evaluate the predictive value of bedside ultrasound evaluation of diaphragmatic dynamics in determining successful extubation outcomes for patients eligible for weaning.Methods: This prospective observational study was conducted on patients who were mechanically ventilated and ready for weaning during the spontaneous breathing trial (SBT). The diaphragm contraction and motion-related parameters of patients such as end inspiratory diaphragm thickness (DT-insp), end respiratory diaphragm thickness (DT-exp), diaphragm thickening fraction (DTF), diaphragmatic thickening fraction rapid shallow breathing index (DTF-RSBI), diaphragmatic excursion (DE), diaphragmatic excursion rapid shallow breathing index (DE-RSBI) were recorded and the association with failure in ventilatory extubation was analyzed. A receiver operating characteristic (ROC) curve was conducted to analyze the prediction of successful weaning.Results: Out of 95 patients, 14 (14.74%) died, and 68 (71.58%) were successfully extubated. There were significant differences between the two groups in all parameters except DT-exp. The results indicated that duration of mechanical ventilation (OR = 0.850, 95% CI: 0.770– 0.938, P = 0.001), DTF (OR = 1.214, 95% CI: 1.108– 1.330, P = 0.000), DTF-RSBI (OR = 0.917, 95% CI: 0.880– 0.954, P = 0.000), DE (OR = 127.02, 95% CI: 15.004– 1075.291, P = 0.000), DE-RSBI (OR = 0.752, 95% CI: 0.657– 0.861, P = 0.000) had predictive value for weaning. DTF and DE had a high sensitivity of 91.18%, 100%, respectively. Whereas, duration of mechanical ventilation, DTF-RSBI, DE-RSBI showed a high specificity of 81.48,85.19%, 81.48%. Considering all the above factors, the sensitivity was 88.24% and the specificity was 88.89%.Conclusion: Bedside ultrasound assessment of diaphragmatic parameters enables the detection of diaphragmatic dysfunction, thus proving valuable in predicting extubation success and facilitating a favorable weaning outcome.Keywords: diaphragmatic dynamics, bedside ultrasound, extubation, intensive care unit

Jingkai Di,1,2,&ast; Liying Song,2,3,&ast; Yaru Liu,2,4,&ast; Zhibo Zhang,1,2 Yawen Wu,2 Tingting Chen,2,5 Chuan Xiang1 1The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Shanxi Medical University, Taiyuan, People’s Republic of China; 3The First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 4The Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 5The Fifth Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuan Xiang, The Second Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 15903410351, Email chuanxiang@sxmu.edu.cnPurpose: Despite the association between peripheral blood inflammatory biomarkers and a range of inflammatory diseases, the role of these biomarkers in osteoarthritis (OA) progression remains unclear. Additionally, whether alterations in these inflammatory markers impact the prognosis of OA patients remains an understudied area. The aim of our study was to investigate the specific associations between peripheral blood inflammatory markers and OA progression and OA-related mortality.Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database from 1999 through 2018. The primary outcomes were all-cause mortality, cardiac mortality, and renal disease mortality, with information on the corresponding mortality rates for each participant obtained through association with the National Death Index (NDI). Multivariate logistic regression models were used to examine the relationship between peripheral blood lymphocyte counts and OA, and restricted cubic spline (RCS) analysis was utilized to assess whether there was a nonlinear relationship with OA and mortality of OA patients. Interaction and stratified analyses were employed to explore the association between peripheral blood leukocyte counts and OA.Results: This study included 1077 OA patients and 21,612 non-OA participants. In model 3 fully adjusted for covariates, eosinophil-to-lymphocyte ratio (ELR) and eosinophil (EOS) were positive risk factors promoting the development of OA (OR = 3.26, 95% CI: 1.49– 7.14; OR = 1.79, 95% CI: 1.12– 2.88). In stratified models for age, sex, BMI, smoking status, and alcohol consumption, the associations of ELR and EOS with OA were significantly different. RCS curves showed a J-shaped relationship between ELR and EOS and all-cause mortality in patients with OA. ELR was also found to significantly up-regulate cardiac mortality and renal mortality in patients with OA (OR = 3.92, 95% CI: 1.68– 9.14; OR = 22.55, 95% CI: 6.55– 77.70), while EOS was only significantly positively correlation (OR = 3.68, 95% CI: 1.94– 7.01).Conclusion: A significant relationship was found between ELR, EOS and OA. In addition, ELR and EOS were identified as potential predictors of mortality from different causes in patients with OA.Keywords: eosinophil to lymphocyte ratio, osteoarthritis, eosinophil, all-cause mortality

Chengran Wang,&ast; Xiaoqing Zhao,&ast; 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&ast;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

Weichao Li,1,2 YuYan Liu,2 Xunhu Gu1 1Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Anesthesiology, Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, QingYuan, Guangdong, People’s Republic of ChinaCorrespondence: Xunhu Gu, Doctor of Medicine (MD), Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email 540523118@qq.comBackground: Catecholamine vasopressors are commonly used for intra- or post-operative hypotension for cardiac surgery, which have a side effect of new-onset atrial fibrillation (AF) and myocardial ischemia. However, it is not entirely clear whether catecholamine vasopressors increase the risk of new-onset AF after noncardiac surgery.Aim: The aim of this study was to analyze the association between the use of catecholamine vasopressors and the risk of developing new-onset AF after noncardiac surgery.Methods: In this prospective trial, available data from eligible elderly individuals receiving noncardiac surgery at a single center from November 2022 to January 2024 were gathered. Propensity score matching (PSM) was used to balance patient baseline characteristics and to control for confounders. To determine the association between catecholamine vasopressors and the risk of new-onset AF, univariate and multivariate logistic regression analyses were performed.Results: A total of 6000 subjects were included in this study (mean [SD] age, 70.73 [6.37] years; 910 [50.9%] males). After PSM, the patients were stratified into catecholamine vasopressor (n = 357) and comparator groups (n = 1432). A total of 18/357 patients in the catecholamine vasopressor group developed AF, and 25/1432 patients in the comparator group developed AF (incidence rate, 5.0% vs 1.7%). Compared with the comparator group, the catecholamine vasopressor group had an increased risk of new-onset AF (aOR, 2.77; 95% CI, 1.28– 5.89). Some sensitivity analyses also revealed consistent findings of increased new-onset AF risk associated with catecholamine vasopressor treatment.Conclusion: The findings from this study suggest that catecholamine vasopressor treatment is associated with an increased risk of new-onset AF and may help physicians select a modest medication for patients while also assessing the risk of new-onset AF. Keywords: catecholamine vasopressors, new-onset atrial fibrillation, risk, prospective trial, noncardiac procedures

Caina Liu,1,&ast; Qingqing Zhang,1,2,&ast; Yiming Liu,1 Zixu Wang,1 Fangchen Chen,1 Yitian Li,1 Yami Zhao,1 Jing Zhu,1 Dandan Li,1,3– 5 Chunyan Zhu1– 4,6 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230000, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230032, People’s Republic of China; 4Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230032, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 6Department of Psychology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dandan Li; Chunyan Zhu, Email 799200213@qq.com; ayswallow@126.comPurpose: Higher rates of depression are associated with autistic traits; however, the precise association between autistic traits and depression has yet to be fully elucidated. Good interpersonal emotional regulation and social self-efficacy are crucial for mental health; therefore, in this study, we investigated the relationships between autistic traits, interpersonal emotional regulation, social self-efficacy, and depression.Patients and Methods: In total, 1024 participants (613 females and 411 males) aged 16 to 23 years old (M = 19.03, SD = 0.95) completed questionnaires that were designed to evaluate their autistic traits, interpersonal emotion regulation, social self-efficacy and depression. Data were analyzed by Spearman correlation and mediation effects analyses.Results: Autistic traits were significantly and positively correlated with depression (r = 0.39, p < 0.001), and autistic traits were shown to positively predict depression (B = 0.28, p < 0.001). Interpersonal emotion regulation and social self-efficacy were found to play a serial mediating role between autistic traits and depression (indirect effect = 0.020, p = 0.006).Conclusion: This study is a supplement to the mechanism of the relationship between autistic traits and depression. Interpersonal emotion regulation and social self-efficacy are important predictors of possible depression in individuals with high autistic traits. These findings suggest combining interpersonal emotional regulation training and exploring the clinical value of interpersonal emotional regulation interventions in individuals with high autistic traits and autism spectrum disorder, aiming to build social confidence, reduce negative moods, restore social functioning, and other aspects.Keywords: autistic traits, depression, interpersonal emotion regulation, social self-efficacy, chain mediation

Guangtong Cao,1 Mingmin Ye,2 Haiyan Wang,3 Yi Liu,1,&ast; Mengzhi Li4,&ast; 1Department of Burns and Plastic Surgery & Wound Repair Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu, 730030 People’s Republic of China; 2Department of Plastic Surgery, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Department of Ultrasound Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 4Department of Hand, Foot, and Microsurgical Reconstruction, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Liu; Mengzhi Li, Email liuyi196402@163.com; sweetlife00@163.comAbstract: Pathological scars, including hypertrophic scar and keloid are the result of excessive tissue repair and are influenced by biomechanical forces like tension, mechanical pressure, and stiffness. These forces significantly impact scar development and progression, affecting wound healing, collagen deposition, and tissue remodeling. Understanding how these mechanical stimuli contribute to scar development is essential for devising effective therapeutic interventions. Clinically, reducing wound tension and applying mechanical pressure are key strategies for managing pathological scars. Techniques like super-tension-reduction suturing, stress-shielding polymers, and force-modulating tissue bridges (FMTB) have been shown to effectively alleviate tension and reduce scar proliferation. Additionally, Pressure Garment Therapy (PGT) is widely used to treat hypertrophic scars by reducing tissue stiffness, limiting collagen buildup, and promoting collagen realignment. Despite challenges such as discomfort and uneven pressure application, ongoing research focuses on enhancing these therapies through mechanosensitive technologies to improve both efficacy and patient comfort. This review highlights the role of biomechanical forces in scar formation and discusses therapeutic approaches that target these forces to improve clinical outcomes.Keywords: pathological scars, biomechanical forces, hypertrophic scar, keloid, tissue remodeling

Liyan Wu,1 Zhenyan Yuan,1 Min Wang,1 Xiaomeng Fu,1 Xiaohui Liu,1 Bing Wei,2 Yugeng Liu1 1Department of Infectious Diseases and Clinical Microbiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, People’s Republic of China; 2Emergency Medicine Clinical Research Center, Beijing Chaoyang Hospital, Capital Medical University, & Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Clinical Center for Medicine in Acute Infection, Capital Medical University, Beijing, 100043, People’s Republic of ChinaCorrespondence: Bing Wei; Yugeng Liu, Email dr_weibing@126.com; yugeng_liu@126.comPurpose: Sepsis is a life-threatening condition associated with acute organ dysfunction. Iron is an essential trace element for multicellular organisms and almost all microorganisms, and its role in sepsis has been increasingly recognized. The aim of this study was to investigate the changes in iron metabolism in caecal ligation and puncture solution (CLP) -induced septic mice and the effects of hepcidin pretreatment on serum inflammatory marker levels and liver iron metabolism in CLP-induced septic mice.Methods: C57BL/6 mice were given normal saline, CLP (peritonitis model) or 100 μg of hepcidin via intraperitoneal injection. The experimental animals were divided into 4 groups: the control group, model group (CLP), hepcidin pretreatment Groups CLP+hepcidin-2h and CLP+hepcidin-24 h. Blood samples were collected at 6, 12 and 24 hours after CLP surgery, and the mice were euthanized and livers were obtained.Results: ELISA revealed that hepcidin pretreatment, especially 2 hours in advance (p< 0.01), increased the serum hepcidin, TNF-a and IL-6 in CLP-induced septic mice; the serum iron content of CLP-related septic mice decreased (P< 0.01), while the liver iron content increased (P< 0.01); Hepcidin pretreatment reduced the serum iron (P< 0.05) at 6 h and 12 h and liver iron concentrations (P< 0.01) at 6 h, 12 h and 24 h in CLP-related septic mice. Western blotting revealed that the hepatic iron absorption-related proteins transferrin receptor-2 (TFR2), ZRT/IRT-like protein 14 (ZIP14) and divalent meta lion transporter-1 (DMT1) were elevated (P< 0.01); The iron-exporting protein ferroportin (SLC40A1) was decreased (P< 0.01) throughout CLP and CLP+hepcidin sepsis. Compared with CLP group, the protein expressions in the CLP+ hepcidin-2 h group were more obvious than that in the CLP+ hepcidin-24 h group.Conclusion: Hepcidin has proinflammatory effect. Hepcidin exacerbates iron metabolism imbalances in sepsis by influencing the expression of iron absorption-related proteins and iron export-related proteins.Keywords: hepcidin, sepsis, iron metabolism, SLC40A1, liver

Minghui Li,1,&ast; Yuelin Liu,1,&ast; Xu Han,1,&ast; Tao Li,2 Zhizheng Zhang,1 Ningyi Xue,1 Mengdi Liang,1 Ge Ma,1 Tiansong Xia1 1Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiansong Xia; Ge Ma, Department of Breast Surgery, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Tel +86-25-83718836, Email xiatsswms@163.com; ntmage@sina.comBackground: Aneuploid circulating endothelial cells (CECs) are an indicator in breast cancer (BC). Significant changes of aneuploid CECs occurred during neoadjuvant chemotherapy (NCT). This study aimed to explore the predictive and prognostic values of aneuploid CECs in locally advanced breast cancer (LABC) patients with different NCT responses.Methods: Breast cancer patients received an EC4-T4 NCT regimen. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for the detection of CECs (CD45–/CD31+/DAPI+). Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of aneuploid CEC counts in distinguishing NCT-resistant patients from sensitive ones. All patients were observed for progression-free survival (PFS) and overall survival (OS).Results: The CEC counts at any time point did not show the ability to predict the efficacy of NCT. The difference in the CECs between post-chemotherapy levels and baseline could be sufficient to distinguish chemotherapy-resistant cases from other cases in Hormone+Her-2-/+ (HR+) BC patients. Patients with reduction of CECs after all courses of NCT were associated with higher probability of PFS.Conclusion: Variations in aneuploid CECs during NCT may predict chemotherapy response in patients with HR+ breast cancer. The decrease in the number of aneuploid CECs after all courses of NCT indicates better treatment outcomes in patients with LABC.Keywords: circulating endothelial cells, aneuploidy, neoadjuvant chemotherapy, prognosis, locally advanced breast cancer

Dou Zhang,1,2,&ast; Xuyi Liu,1,2,&ast; Xiong Li,3,&ast; Xinyi Cai,1,2 Zhenying Diao,1,2 Long Qiu,1,2 Xuelin Chen,1,2 Yuyu Liu,1,2 Jianbo Sun,1 Daxiang Cui,1,4 Qiaoyuan Ye,5 Ting Yin1,2 1Research Center of Nano Technology and Application Engineering, The First Dongguan Affiliated Hospital, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 2Dongguan Biomedical Nano Engineering Technology Research Center, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China; 3Department of Pharmacy, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong, 519000, People’s Republic of China; 4School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 5Department of Dermatology and Venereology, Second Clinical Medical College of Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiaoyuan Ye, Department of Dermatology and Venereology, Second Clinical Medical College of Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China, Email 13650248189@163.com Ting Yin, Research Center of Nano Technology and Application Engineering, School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong, 523808, People’s Republic of China, Email wsyt132@163.comPurpose: Melanoma is a highly aggressive and dangerous malignant skin tumor and there is an urgent need to develop effective therapeutic approaches against melanoma. The main objective of this study was to construct a multifunctional nanomedicine (GNR@PEG-Qu) to investigate its therapeutic effect on melanoma from the oxidative stress pathway.Methods: First, the nanomedicine GNR@PEG-Qu was synthesized and characterized, and its photothermal and antioxidant properties were confirmed. In addition, in vivo imaging capabilities were observed. Finally, the tumor inhibitory effects of GNR@PEG-Qu in vivo and in vitro as well as its biosafety were observed.Results: GNR@PEG-Qu shows good photothermal and anti-oxidation properties. Following exposure to 1064 nm laser irradiation in the second near-infrared II (NIR-II) window, GNR@PEG-Qu shows anti-tumor ability through low-temperature photothermal therapy (PTT) adjuvant drug chemotherapy. GNR@PEG-Qu makes full use of the antioxidant capacity of quercetin, reduces ROS levels in melanoma, alleviates oxidative stress state, and achieves “oxidative stress avoidance” at the tumor site. Quercetin can also downregulate the expression of the heat shock protein Hsp70, which will improve the thermal sensitivity of the tumor site and enhance the efficacy of low-temperature PTT.Conclusion: GNR@PEG-Qu nanoagent exhibits synergistic treatment and high tumor inhibition effects, which is a promising strategy developed to achieve oxidative stress avoidance and synergistic therapy of melanoma using quercetin (Qu)-coated gold nanorod (GNR@PEG).Keywords: melanoma, gold nanorods, quercetin, chemo-photothermal therapy, oxidative stress

Jifeng Li, Yifei Zeng, Mengjie Wang, Yongxin Liu, Yubo Guo, Wenjie Zhao, Qiao Huang, Dongxiao Zhang Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Dongxiao Zhang, Department of Galactophore Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, No. 23, Art Museum Back Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Tel +8617864190977, Email Tzdx_thinking@126.comPurpose: Granulomatous lobular mastitis (GLM) has seen a rising incidence, though its pathogenesis remains unclear, posing challenges for treatment and contributing to high recurrence rates with conventional therapies. While the role of inflammatory and immune factors in GLM has been recognized, a comprehensive clinical evaluation of these markers is still lacking. This study aims to identify potential diagnostic markers and therapeutic targets by comparing immune markers and cytokine levels in GLM patients and healthy controls.Methods: Conducted at Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from July 2023 to May 2024, this study enrolled 30 GLM patients and 15 healthy female controls in a 2:1 ratio. Serum levels of immune markers and cytokines were analyzed to explore their potential association with GLM.Results: The study population comprised 30 GLM patients with a mean age of 33.40 ± 4.12 years and 15 healthy female controls with a mean age of 32.13 ± 6.19 years. Significantly elevated levels of C-reactive protein (CRP), Immunoglobulin A (IgA), Complement Component 3 (C3), Complement Component 4 (C4), Compliment Component 1q (C1q), Alpha1-antit-rypsin (AAT), α 1-acidglycoprotein (AGP), Anti-histone antibodies (Anti-HIS), Anti-Ro52 antibodies (Anti-Ro52), Anti-double stranded DNA antibodies (Anti-dsDNA), Interleukin-6 (IL-6), Interleukin-10 (IL-10), and Tumor Necrosis Factor-α (TNF-α) were observed in GLM patients compared to controls (all P < 0.05). Subgroup analysis revealed higher levels of CRP, C3, C1q, AAT, and AGP in patients with larger mass areas and those with erythema nodosum (all P < 0.05). No significant differences were found in subgroups based on disease duration or recurrence (both P > 0.05).Conclusion: Serum levels of CRP, IgA, AAT, AGP, Anti-HIS, Anti-Ro52, Anti-dsDNA, C3, C4, C1q, IL-6, IL-10, and TNF-α may serve as diagnostic and prognostic indicators for GLM, with CRP, AAT, AGP, and C1q being particularly indicative of disease severity. These markers offer potential therapeutic targets for GLM.Keywords: granulomatous lobular mastitis, peripheral serology, immune markers, cytokine

Lixin Xie,1,&ast; Lihua Feng,1,&ast; Xiaomin Tang,1 Yunping Xu,1 Hengyi Xu,2 Yang Liu1 1Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of China; 2State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hengyi Xu, State Key Laboratory of Food Science and Resources, Nanchang University, 235 Nanjing East Road, Nanchang, 330047, People’s Republic of China, Tel +0086-791-8830-4447-ext-9520, Fax +0086-791-8830-4400, Email kidyxu@163.com; HengyiXu@ncu.edu.cn Yang Liu, Department of Pediatrics, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1 minde Road, Nanchang, 330006, People’s Republic of China, Tel +86-791-8631-1209, Email ocean3166@yeah.netPurpose: To evaluate the therapeutic effect of oral administration of Lactiplantibacillus plantarum P101 (P101) on skeletal injury in young rats exposed to titanium dioxide nanoparticles (TiO2 NPs), and explore the potential mechanism.Methods: Four-week-old male rats were orally administration to TiO2 NPs and supplemented with P101 2 hours later for 4 weeks. The growth and development, food intake, bone metabolism and serum inflammatory markers of the rats were evaluated. Their tibias were observed and evaluated using microcomputed tomography (micro-CT), tartrate-resistant acid phosphatase (TRAP) staining, immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR). We observed the tibia growth plate using safranin and fast green staining. 16S rDNA sequence analysis of fecal samples was performed to observe changes in the gut microbiota.Results: Our results showed that TiO2 NPs can lead to bone growth inhibition and osteoporosis, induce intestinal flora imbalance, and induce inflammation in young rats. Further mechanistic studies suggested that TiO2 NPs disrupts intestinal flora and increases serum IL-1β levels, which increased the expression of RANKL in bone, thereby enhancing osteoclast differentiation and function, leading to bone loss. Through a P101 supplementation experiment, we found that P101 ameliorated the inflammation and osteoporosis on bone caused by TiO2 NPs.Conclusion: This study showed that the mechanism by which P101 alleviates bone damage caused by TiO2 NPs may be through restoring intestinal microbial homeostasis and inhibiting inflammatory response. Keywords: TiO2 NPs, P101, young rats, intestinal flora, bone injury, IL-1&#x03B2

Yuting Wang,&ast; Yan Liu,&ast; Kan Liu, Yuan He, Hui Ding Department of Pulmonary and Critical Care Medicine, Yixing People’s Hospital Affiliated to Jiangsu University, Yixing, Jiangsu Province, 214200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Ding, Email dh1350519@163.comAbstract: Chronic obstructive pulmonary disease (COPD) is one of the most common clinical respiratory illnesses, defined by permanent pathological deterioration that leads to respiratory failure. Regarding COPD treatment, oxygen therapy is very important. Non-invasive positive pressure ventilation (NPPV) is a technique for non-invasive mechanical ventilation that enables patients to get positive pressure support without the need of an artificial airway. Instead, it merely employs the mask by covering the mouth and nose, or simply the nose of patients. NPPV has been shown to be beneficial for COPD patients experiencing respiratory failure. High-flow nasal cannula (HFNC) oxygen therapy shows some advantages, including the reduction of anatomical dead space, the prompt correction of low oxygen levels as well as the improvement of patients’ tolerance. Owing to its continuous progress, ventilation technology strongly improves COPD treatment. In this study, the authors analyze the application of NPPV and HFNC in COPD so as to provide recommendations for mechanical ventilation treatment.Keywords: chronic obstructive pulmonary disease, high flow nasal cannula, non-invasive positive pressure ventilation, respiratory failure

Zijun Wu,1,&ast; Ruijing Wang,1,&ast; Yuanjun Liu,1 Bin Yang,2 Huiping Wang1 1Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, People’s Republic of China; 2Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Yang, Department of Burn and Plastic Surgery, General Hospital of Central Theater Command, Wuhan, Hubei, People’s Republic of China, Email sszxkyb1@163.com Huiping Wang, Department of Dermatovenereology, Tianjin Medical University General Hospital/Tianjin Institute of Sexually Transmitted Disease, Tianjin, People’s Republic of China, Email huiping1208@163.comBackground: Psoriasis is characterized by accelerated proliferation of epidermal keratinocytes. IL-27 is relevant to psoriasis pathogenesis. We previously found that IL-27 stimulates the proliferation of keratinocytes. However, the mRNAs involved in the process have not been fully studied. This study aims to identify potential pathways and hub genes associated with proliferation in keratinocytes with IL-27 intervention by bioinformatics analysis.Methods: The mRNA expression profiles from HaCaT cells with or without IL-27 treated were analyzed by bioinformatics tools. The protein–protein interaction (PPI) network was constructed to screen gene clusters and hub genes associated with proliferation. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were used to identify the function of the mRNAs. The GEO database and quantitative real-time PCR (qPCR) were used to verify the expression levels of hub genes in psoriatic skin lesions and IL-27-treated psoriasiform keratinocytes, respectively.Results: We found 1257 differentially expressed genes and screened 2 crucial gene clusters. GO analysis revealed that Cluster 1 was mainly enriched in “Mitotic sister chromatid segregation” and “Spindle”. Cluster 2 was mainly enriched in the “Pyruvate metabolic process” and “Oxidoreductase complex”. KEGG analysis showed that Cluster 1 and Cluster 2 were mainly enriched in “Cell cycle” and “Glycolysis/Gluconeogenesis”, respectively. We then identified 6 hub genes enriched in the two pathways, including CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA. GSEA complemented the role of the mitochondrial “Oxidative phosphorylation” pathway. Moreover, we found that 6 hub genes were upregulated in psoriasis skin lesions and IL-27 elevated the hub genes expression in M5-induced psoriasiform keratinocytes.Conclusion: IL-27 possibly promotes glycolysis, mitochondrial oxidative phosphorylation, and cell cycle progression in keratinocytes. Additionally, we identified CCNB1, PTTG1, CDC20, PLK1, PKM, and LDHA as hub genes that may be involved in the mechanism of IL-27 facilitating keratinocyte proliferation in psoriasis.Keywords: psoriasis, glycolysis, oxidative phosphorylation, bioinformatics

Zhiyang Wu,1,&ast; Wenjun Lu,2,&ast; Xin Zhang,1 Qiaoying Xia,2 Han Zuo,2 Xi Guo,1 Yu Liu,1 Fan Zhang,3 Xin Zhang,4 Luyao Zhang2 1Department of Critical Care Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 2Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 3Department of Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China; 4Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luyao Zhang, Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China, Email zhangluyao@njucm.edu.cn Xin Zhang, Department of General Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, Shandong, People’s Republic of China, Email 514557061@qq.comPurpose: Protectin D1 (PD1), a biologically active molecule derived from docosahexaenoic acid (DHA), plays a major role in the body’s endogenous lipid-mediated inflammatory response. The study aims to explore the relationship between PD1, inflammatory response and the severity of acute pancreatitis (AP).Patients and Methods: Sixty consecutive AP patients within 72h of disease onset were enrolled as the study group, a further thirty healthy people were enrolled as the control group. General demographics collected at the time of enrollment. Serum PD1, Citrullinated Histone 3 (CitH3), myeloperoxidase-Deoxyribonucleic acid (MPO-DNA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) level were measured in AP patients on enrollment day 0, day 1, day 3 and day 7. Meanwhile, the Acute Physiology and Chronic Health evaluation II (APACHE II) scores, Sequential Organ Failure Assessment (SOFA) scores were also evaluated on day 0, day 1, day 3 and day 7.Results: AP was severe in 29 patients (48.3%), moderately severe acute pancreatitis (MSAP) was found in 9 patients (15%), and mild acute pancreatitis (MAP) was found in 22 patients (36.7%). The level of PD1, CitH3 and MPO-DNA were statistically significantly higher in AP patients than in the healthy population. Serum PD1, CitH3 and MPO-DNA concentration increased with AP severity. In AP patients, PD1 has a strong linear association with TNF-α, CitH3 and MPO-DNA. The AUC for SAP predicted by PD1 was 0.938. The calculated cut-off point for prognosis SAP is 7.94 pg/mL. The AUC for infected pancreatic necrosis (IPN) predicted by PD1 was 0.836 and the cut-off point was 8.65 pg/mL. The AUC for organ failure (OF) predicted by PD1 was 0.719 and the cut-off point was 7.94 pg/mL.Conclusion: PD1 is associated with both the presence of AP and the severity of pancreatitis.Keywords: PD1, acute pancreatitis, CitH3, MPO-DNA, infected pancreatic necrosis, organ failure

Minghui Li,1,&ast; Jiabi Wu,1,&ast; Tao Yang,1 Yuhang Zhao,1 Ping Ren,1 Lingling Chang,2 Pilong Shi,1 Jing Yang,1 Yuhang Liu,2 Xiaolei Li,3 Peng Wang,2 Yonggang Cao1 1Department of Pharmaceutics, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 2Department of Physiology, Harbin Medical University, Heilongjiang, 163319, People’s Republic of China; 3Department of Pathology, Jiangsu College of Nursing, Jiangsu, 223003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Wang, Department of Physiology, Harbin Medical University, Xinyang Road 39, Gaoxin District, Daqing, Heilongjiang, People’s Republic of China, Email wangpeng810122@126.com Yonggang Cao, Department of Pharmaceutics, Harbin Medical University, Xinyang Road 39, Gaoxin District, Daqing, Heilongjiang, People’s Republic of China, Email caoyonggang@hmudq.edu.cnBackground: Cardiac microvascular damage is substantially related with the onset of myocardial ischaemia-reperfusion (IR) injury. Reportedly, allicin (AL) effectively protects the cardiac microvascular system from IR injury. However, the unsatisfactory therapeutic efficacy of current drugs and insufficient drug delivery to the damaged heart are major concerns. Here, inspired by the natural interaction between neutrophils and inflamed cardiac microvascular endothelial cells (CMECs), a neutrophil membrane-camouflaged nanoparticle for non-invasive active-targeting therapy for IR injury by improving drug delivery to the injured heart is constructed.Methods: In this study, we engineered mesoporous silica nanoparticles (MSNs) coated with a neutrophil membrane to act as a drug delivery system, encapsulating AL. The potential of the nanoparticles (named AL@MSNs@NM) for specific targeting of infarcted myocardium was assessed using small animal vivo imaging system. The cardiac function of AL@MSNs@NM after treatment was evaluated by Animal Ultrasound Imaging system, HE staining, and Laser Speckle Imaging System. The therapeutic mechanism was analyzed by ELISA kits, immunofluorescence, and PCR.Results: We discovered that AL@MSNs@NM significantly improves cardiac function index, reduced infarct size and fibrosis, increased vascular perfusion in ischemic areas, and also promoted the function of CMECs, including migration, tube formation, shear stress adaptation, and nitric oxide production. Further research revealed that AL@MSNs@NM have cardio-protective functions in IR rats by inhibiting CMEC ferroptosis and increasing platelet endothelial cell adhesion molecule-1 (PECAM-1) expression.Conclusion: Our results indicated that AL@MSNs@NM significantly reversed CMEC ferroptosis and increased PECAM-1 expression, enhanced cardiac function, and reduced myocardial infarction size. Therefore, this strategy demonstrates that engineered biomimetic nanotechnology effectively delivers AL for targeted therapy of myocardial infarction.Keywords: neutrophil membrane, ischemia-reperfusion, allicin, cardiac microvascular endothelial cells, ferroptosis

Xiaoping Xu, Han Wu, Yang Liu Department of Obstetrics and Gynecology, Deyang People’s Hospital, Deyang, Sichuan, People’s Republic of ChinaCorrespondence: Yang Liu, Department of Obstetrics and Gynecology, Deyang People’s Hospital, 173 North Taishan Road Taishan North Road, Deyang, Sichuan, 61800, People’s Republic of China, Email 18783861321@163.comPurpose: To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis in American women.Methods: The study adopted a cross-sectional design, incorporating 3862 women aged over 20 years, selected from the National Health and Nutrition Examination Survey (NHANES) dataset from 2001 to 2006. Six dietary antioxidants were taken into account in calculating CDAI. Endometriosis was determined based on self-report. To evaluate the association between CDAI and the risk of endometriosis, we employed models with multivariable logistic variables. For subgroup assessment in relation to CDAI, a stratified multivariate logistic regression model was utilized.Results: Among all participants, 273 participants (7.1%) were found to exhibit endometriosis. The preliminary analysis showed a reverse association between CDAI and the likelihood of endometriosis (odds ratio [OR] = 0.95; 95% confidence interval [CI]: 0.92~0.98). Upon full adjustment within the multivariable logistic regression, the ORs (95% CI) for endometriosis prevalence per unit increase in CDAI were estimated to be 0.96 (0.93~1). When the CDAI levels were divided into quartiles, it was found that the ORs for endometriosis with CDAI levels in Q2 (− 2.131– 0.023), Q3 (0.023– 2.650), and Q4 (2.650– 42.854) were 0.74 (0.52, 1.05), 0.76 (0.53, 1.1), and 0.53 (0.36, 0.79), respectively, compared to those with CDAI levels in Q1 (− 7.151–− 2.131). We evaluated the association between CDAI and endometriosis using subgroups stratified by age, race/ethnicity, education level, body mass index (BMI), oral contraceptive, and menopausal status, revealing a substantial negative relationship.Conclusion: In this cross-sectional study, increasing CDAI was proportionally associated with a reduced risk of endometriosis among American women, suggesting a diet high in antioxidants may play an important role in reducing the risk of endometriosis. The findings of NHANES data spanning 2001 to 2006 suggest that promoting antioxidant-rich diets could be an important prevention strategy for endometriosis.Keywords: composite dietary antioxidant index, endometriosis, National Health and Nutrition Examination Survey, cross-sectional study

Linqiong Liu,1– 3,&ast; Pengfei Huang,1,2,&ast; Changsong Wang,1,2,&ast; Yuxi Liu,1– 3 Yan Gao,3 Kaijiang Yu1,2 1Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 2Heilongjiang Provincial Key Laboratory of Critical Care Medicine, Harbin Medical University, Harbin, People’s Republic of China; 3Departments of Critical Care Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Gao, Departments of Critical Care Medicine, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email icugaoyan@163.com Kaijiang Yu, Departments of Critical Care Medicine, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China, Email drkaijiang@163.comPurpose: We aimed to identify the association between heart failure (HF) with sepsis and its mortality through Mendelian randomization (MR) and observational studies.Patients and Methods: In MR study, we utilized public summary statistics from genome-wide association studies (GWAS). We conducted univariable, multivariable and network MR analyses to investigate causal relationships between HF and sepsis, and mediating roles of cytokines and growth factors. We performed an observational analysis using the MIMIC-IV database. Propensity score matching (PSM) and logistic regression models were employed to explore causal relationships between HF and sepsis, besides short-, medium-, and long-term mortality associated with sepsis.Results: In univariable MR analysis, there was a causal relationship between genetically predicted HF (OR = 1.15, 95% CI = 1.02– 1.29, P = 0.025) and sepsis. In multivariable and network MR analyses, βNGF was independently associated with sepsis. And it mediated 17.6% (95% CI 2.45– 30.72%) of HF effect on sepsis. In the real-world observational study, acute on chronic diastolic (congestive) heart failure (DCHF) (OR = 1.59, 95% CI = 1.31– 1.93, P < 0.001), acute DCHF (OR = 2.52, 95% CI = 1.61– 3.95, P = 0.010), and acute diastolic heart failure (DHF) (OR = 1.52, 95% CI = 1.06– 2.19, P = 0.024) after PSM were associated with occurrence of sepsis. Chronic systolic (congestive) heart failure (SCHF) was associated with increased 28-day (OR = 1.75, 95% CI = 1.06– 2.91, P = 0.030), 1-year (OR = 1.80, 95% CI = 1.08– 3.00, P = 0.023), and 2-year (OR = 1.86, 95% CI = 1.12– 3.10, P = 0.018) mortality in sepsis.Conclusion: Observational and MR analyses showed a causal relationship between HF and sepsis. Chronic SCHF was related to increased short/long-term mortality in sepsis. Our study indicated βNGF a key factor in HF-induced sepsis.Keywords: βNGF, MIMIC-IV, PSM, GWAS

Ruixue Zhang,1 Hui Xu,1 Xiaoxue Zhang,1 Hui Xiong,2 Fei Tang,3 Liping Lv,3 Xiangdong Mu,4 Wei Tian,5 Yueguang Cheng,6 JianRong Lu,6 Xiuhong Nie,7 Yang Guo,8 Yingying Liu,9 Zhi Zhang,10 Lianjun Lin1 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Emergency, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Interventional Pulmonology, Anhui Province Chest Hospital, Hefei, People’s Republic of China; 4Department of Respiratory, Tsinghua Changgung Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Jishuitan Hospital, Beijing, People’s Republic of China; 6Department of Emergency, Jingmei Group General Hospital, Beijing, People’s Republic of China; 7Department of Respiratory, Xuanwu Hospital, Beijing, People’s Republic of China; 8Department of Endoscopic Diagnosis &treatment, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 9CapitalBio Technology Co., Ltd, Beijing, People’s Republic of China; 10Bio Biological Group Co., Ltd, Beijing, People’s Republic of ChinaCorrespondence: Lianjun Lin, Department of Geriatrics, Peking University First Hospital, No. 8 Xishiku Avenue, Beijing, 100034, People’s Republic of China, Email 06474@pkufh.comPurpose: The detection of pathogenic microorganisms plays a significant role in the diagnosis and management of pneumonia that are responsible for a substantial number of deaths worldwide. However, conventional microbiological tests (CMT) have low accuracy and are time-consuming. In this study, we aim to evaluate the clinical value of Chips for Complicated Infection Detection (CCID) in detecting pneumonia pathogens.Patients and Methods: This study was conducted at nine hospitals in China from January 2021 to September 2022. Respiratory samples from adult pneumonia patients were collected from each patient. CMT and CCID were performed in parallel to identify the pathogens.Results: A total of 245 patients were included, with 73% being elderly. CCID identified pathogenic microbes in 78.0% of patients and conventional microbiological tests (CMT) in 57.1% of the patients (p< 0.001). The overall positive and negative percent agreements between CCID and CMT for pathogen detection were 90.07% and 38.46%, respectively. 38.8% of patients were diagnosed with mixed infections with at least two pathogens by CCID. Bacterial infections identified by CCID accounted for 60.0% of 245 patients, with the top 3 being Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterococcus faecium, respectively. K. pneumoniae was the most common pathogen in elderly patients, with a significantly higher prevalence compared to non-elderly patients (p = 0.0011). Among the 197 patients who had used antibiotics before sample collection, the positive rate of CCID was significantly higher than that of CMT (p < 0.001).Conclusion: This study indicates that compared to CMT, this novel chip has significant advantages in detecting pathogens in pneumonia patients, especially in the elderly.Keywords: pneumonia, elderly, pathogens, chip, LAMP

Nan Chen, Jiadi Gao, Hanshu Zhao, Sihan Liu, Yubing Zhou, Yushuang Liu, Zhongling Zhang, Shanshan Yang Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of ChinaCorrespondence: Shanshan Yang; Zhongling Zhang, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Stree, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China, Tel +86-451-85553681 ; + 86-451-85555918, Fax +86-451-85555918, Email yangshanshan81@163.com; zhangzhongling7@126.comObjective: Stroke is a leading cause of disability and mortality worldwide, posing a significant public health challenge. While treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA) is effective but increases the risk of hemorrhagic transformation (HT). This study aimed to explore the determinants of HT in AIS patients treated with rt-PA and investigate the association between blood glucose levels and HT risk.Methods: We conducted a prospective cohort study at the First Affiliated Hospital of Harbin Medical University from January 2018 to December 2021. Patients with AIS and who received rt-PA within 4.5 hours of symptom onset were included. Demographic, clinical, laboratory, and imaging data were collected.Results: Of the 426 patients, 15% experienced HT post-rt-PA, occurred more frequently in patients with a history of cardiac embolism, higher prethrombolysis NIHSS scores, and elevated fasting blood glucose (FBG) levels. The frequency of HT was higher in non-diabetic patients with FBG levels ≥ 7.0 mmol/L compared to diabetic patients. Elevated blood glucose levels were significantly associated with HT, regardless of diabetes history.Conclusion: The findings suggest importance of precise glycemic control during AIS management to improve patient outcomes, particularly in non-diabetic patients. Future protocols for AIS treatment should incorporate these findings to reduce HT risks. Further large-scale studies are needed to confirm these associations and guide clinical practices.Keywords: Acute ischemic stroke, thrombolytic therapy, rt-PA, hemorrhagic transformation, blood glucose, outcomes

Min Li,1,2 Song Zhao,2 Yan Liu,1 Qian Wang,2 Yongzhe Chen,2 Yaru Zhou1 1Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China; 2Department of Nephrology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaCorrespondence: Yaru Zhou, Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, Ziqiang Road 139, Hebei, 050051, People’s Republic of China, Tel +86-0311-88603031, Email zyrydsy@hebmu.edu.cnBackground: Diabetes kidney disease (DKD) is a common complication of diabetes and is currently considered the primary cause of end-stage renal disease. Ferroptosis has been found to participate in the development of DKD. However, no ferroptosis-related markers have been evaluated in human DKD samples. This study aimed to examine the ferroptosis-related pathological alterations in DKD samples.Methods: This study enrolled patients with DKD at the Third Hospital of Hebei Medical University between January 2018 and December 2022, of whom 30 were diagnosed with DKD and 10 with non-DKD (CON). Clinical data of patients were collected, and hematoxylin-eosin staining (H&E), PASM, and immunohistochemical staining were performed to evaluate pathological changes and the expression of ferroptosis-related proteins, including GPX4, ACSL4, Nrf2, TfR1, FTH, and FTL.Results: Compared with the CON group, patients with DKD exhibited significantly elevated serum creatinine levels and reduced eGFR (P < 0.05). Iron content and the expression of the ferroptosis-related protein ACSL4 were significantly increased, while the expression of Nrf2 was significantly decreased in the renal tissues of patients with DKD (P all < 0.05). There were no differences in the expression of GPX4, TfR1, FTH, or FTL between the two groups. Nrf2 and ACSL4 expression were influential factors in the occurrence of DKD and both exhibited diagnostic value for DKD. Nrf2 was a protective factor (OR, < 1), whereas ACSL4 was a risk factor (OR, > 1).Conclusion: Ferroptosis-promoting gene profile was identified in DKD renal samples, indicating that ferroptosis may participate in the pathogenesis of DKD. The expression levels of Nrf2 and ASCL4 in the kidneys are related to the severity and progression of DKD.Keywords: diabetes kidney disease, ferroptosis, iron overload, lipid peroxidation

Wenhao Chen,1 Yuanliang Liu,2 Xunwei Deng,3 Bin Li,1 Hao Wang,1 Guoliang Wei,1 Kehui Chen,1 Shen Wang1 1Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Computer Tomography, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 3Research Experimental Center, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Wenhao Chen, Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 18319255493@163.comObjective: Cytochrome P450 2C19 (CYP2C19) is a major enzyme involved in the biotransformation and metabolism of various substances. Loss-of-function of the CYP2C19 gene represents downregulation of CYP2C19 enzyme indication limited or no enzymatic function, which may be, in turn, associated with some disease susceptibility. The relationship between CYP2C19 polymorphisms and susceptibility to premature coronary artery disease (PCAD) is not fully understood. This study aimed to assess this relationship.Methods: This study included 635 PCAD patients, and 548 age-matched non-CAD individuals as controls, from November 2019 to August 2023. The CYP2C19 rs4244285 (681G > A, &ast;2) and rs4986893 (636G > A, &ast;3) were genotyped, and the distribution of CYP2C19 polymorphisms between patients and controls and the relationship between CYP2C19 polymorphisms and PCAD risk were analyzed.Results: A total of 442 (37.4%), 543 (45.9%), and 198 (16.7%) individuals had CYP2C19 extensive metabolizer (EM) (&ast;1/&ast;1), intermediate metabolizer (IM) (&ast;1/&ast;2 and &ast;1/&ast;3), and poor metabolizer (PM) (&ast;2/&ast;2, &ast;2/&ast;3, and &ast;3/&ast;3) phenotypes, respectively. CYP2C19 &ast;2/&ast;2 genotype frequency was higher, &ast;1/&ast;1 genotype was lower in PCAD patients than controls. Individuals with CYP2C19 PM phenotype had higher triglyceride (TG) levels than those with CYP2C19 EM or IM phenotypes. Logistic regression analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (≥ 24.0 kg/m2 vs 18.5– 23.9 kg/m2, odds ratio (OR): 1.326, 95% confidence interval (CI): 1.041– 1.688, p = 0.022), smoking (OR: 1.974, 95% CI: 1.283– 3.306, p = 0.002), hypertension (OR: 1.327, 95% CI: 1.044– 1.687, p = 0.021), diabetes mellitus (OR: 1.390, 95% CI: 1.054– 1.834, p = 0.020), CYP2C19 PM phenotype (PM phenotype vs EM phenotype, OR: 1.701, 95% CI: 1.200– 2.411, p = 0.003), and CYP2C19 IM+PM phenotypes (IM+PM vs EM phenotype, OR: 1.369, 95% CI: 1.077– 1.740, p = 0.010) were associated with PCAD.Conclusion: CYP2C19 PM or IM+PM phenotypes, overweight, smoking, hypertension, and diabetes mellitus were associated with PCAD.Keywords: premature coronary artery disease, cytochrome P450, CYP2C19, loss-of-function

Yang Liu,1,&ast; Chunan Wang,1,&ast; Sitong Liu,1,&ast; Hangzhan - Ma,2 Jiayun Xu,3 Kai Jiang,1 Ruitao Lu,4 Xintao Shuai,5 Jinming Wang,3 Zhong Cao1 1School of Biomedical Engineering, Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Orthopedics, Panyu Hospital of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3Department of Oral Implantology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, People’s Republic of China; 4Shenzhen International Institute for Biomedical Research, Shenzhen, Guangdong, People’s Republic of China; 5Nanomedicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong Cao; Jinming Wang, Email caozhong@mail.sysu.edu.cn; wjinm@mail.sysu.edu.cnBackground: As a burgeoning cancer treatment modality, photothermal therapy (PTT) has shown robust anti-tumor effects. However, it still faces numerous challenges, such as triggering an inflammatory response and potentially increasing the risk of cancer recurrence. To address these concerns, integration of PTT with anti-inflammatory therapies presents a promising approach to enhance the efficacy of cancer treatment and meanwhile reduce the risk of recurrence.Methods: In this study, Gd3+ was first chelated with dopamine to create Gd-DA chelates, and then the mesoporous dopamine nanoparticles MX@Arg-Gd-MPDA (MAGM NPs) were synthesized by combining arginine (Arg) and the anti-inflammatory medication meloxicam (MX). The photothermal properties of MAGM NPs were then defined and examined; the in vivo MRI imaging effect, as well as MAGM NPs’ anti-cancer and anti-inflammatory efficiency, were tested in a mouse model of breast cancer.Results: The incorporation of Arg doping into MAGM NPs was intended to boost its photothermal conversion efficiency and reactive oxygen species (ROS) scavenging ability. Additionally, synergizing with the anti-inflammatory agent meloxicam (MX) within the nanoparticles aimed to enhance the anti-inflammatory effect following photothermal therapy. Furthermore, gadolinium ions (Gd3+) were chelated into the nanostructure to enable precise T1-T2 dual-mode magnetic resonance imaging (MRI) of the intratumor accumulation profile. This imaging capability was leveraged to guide the implementation of photothermal therapy. Animal experiments demonstrated that MAGM NPs exerted a notable anticancer effect in a 4T1 breast cancer mouse model, under the precise guidance of MRI.Keywords: magnetic resonance imaging, photothermal therapy, anti-inflammatory therapy, mesoporous polydopamine, cancer therapy

Lingling Ding,1,&ast; Guowan Zheng,1– 3,&ast; Aoni Zhou,4 Fahuan Song,1– 3 Lei Zhu,5 Yefeng Cai,6 Yehao Guo,1 Tebo Hua,7 Yunye Liu,1 Wenli Ma,1 Yiqun Hu,1– 3 Yawen Guo,1– 3 Chuanming Zheng1– 3 1Otolaryngology & Head and Neck Center, Cancer Center, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 2Zhejiang Provincial Clinical Research Center for Malignant Tumor, Hangzhou, Zhejiang, 310000, People’s Republic of China; 3Zhejiang Key Laboratory of Precision Medicine Research on Head & Neck Cancer, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4Hangzhou Normal University, Hangzhou, Zhejiang, 311121, People’s Republic of China; 5Department of Thyroid Surgery, The Fifth Hospital Affiliated to Wenzhou Medical University, Lishui Central Hospital, Lishui, Zhejiang, 323000, People’s Republic of China; 6Department of Thyroid Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 7Department of Thyroid Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo, Zhejiang, 315000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yawen Guo; Chuanming Zheng, Department of Head and Neck Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, No. 158, Shangtang Road, Hangzhou, Zhejiang, People’s Republic of China, Email mingdoc@163.com; gyw20072644@126.comBackground: The incidence of papillary thyroid cancer (PTC) has been increasing annually; however, early diagnosis can improve patient outcomes. Pyroptosis is a programmed cell death modality that has received considerable attention recently. However, no studies have reported using pyroptosis-related genes in PTC diagnosis.Methods: Analyzed 33 pyroptosis-related genes in PTC transcriptome data from the Gene Expression Omnibus database. Subsequently, used the Least Absolute Shrinkage and Selection Operator (LASSO) model to construct a PTC molecular diagnostic model. Furthermore, confirmed differences in the expression of five genes between PTC and non-tumor tissues using immunohistochemistry. Collected 338 PTC and control samples to construct a five-gene PTC diagnostic model, which was then validated using a training set and underwent correlation analysis with immune cell infiltration. Additionally, validated the biological functions of the core gene NOD1 in vitro.Results: The five-gene PTC diagnostic model demonstrated good diagnostic value for PTC. Moreover, identified three reliable subtypes of pyroptosis and found that NOD1 is involved in tumor-suppressive microenvironment formation. Notably, patients with high NOD1 expression had lower Progression-Free Survival (PFS). Additionally, NOD1 expression was positively correlated with immune markers such as CD47, CD68, CD3, and CD8. Lastly, inhibiting NOD1 showed significant anti-PTC activity in vitro.Conclusion: Our results suggest that pyroptosis-related genes can be used for PTC diagnosis, and NOD1 could be a promising therapeutic target.Keywords: pyroptosis-related genes, papillary thyroid cancer, PTC, immune cell infiltration, bioinformatic, diagnosis model

Peng Liu,1,2,&ast; Tingting Lv,1,&ast; Yuanwei Liu,1,&ast; Xiaofei Zhang,1 Fei She,1 Rong He,1 Dan Li,1 Lianfeng Liu,1 Ping Zhang1 1Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, People’s Republic of China; 2Department of Cardiology, Ordos Central Hospital, Ordos School of Clinical Medicine, Inner Mongolia Medical University, Inner Mongolia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping Zhang, Email zhpdoc@126.comObjective: Atrial fibrillation (AF) is known to increase the risk of thromboembolic events and major adverse cardiovascular events (MACE). The impact of paroxysmal atrial tachycardia (PAT) on these risks remains unclear.Methods: This retrospective cohort study was conducted involving 889 patients diagnosed with PAT and 1106 control patients without PAT, all of whom underwent their initial 24-hour ECG monitoring between 2015 to 2020. Kaplan–Meier survival analysis and Cox regression analysis were used to evaluate the association between PAT and the study endpoints, including thromboembolic events and MACE.Results: Over a mean follow-up period of 50.3 months, the incidence of thromboembolic events and MACE was significantly higher in the PAT group compared to the control group (6.5% vs 1.7% and 19.1% vs 9.9%, respectively). After adjusting for common risk factors and baseline imbalances, the PAT group exhibited a significantly elevated risk of thromboembolic events (hazard ratio [HR] 3.782, 95% confidence interval [CI] 2.212– 6.467; P < 0.001) and MACE (HR 1.795, 95% CI 1.398– 2.305; P < 0.001). However, the frequency of PAT episodes, heart rate, and maximum heart rate were not significantly associated with these outcomes. Within the PAT group, a history of stroke, transient ischemic attack, and chronic renal failure were identified as independent risk factors for thromboembolic events, while hypertension, coronary heart disease, heart failure, and chronic renal failure were independently associated with MACE.Conclusion: PAT, as detected by 24-hour dynamic ECG, is associated with an increased risk of thromboembolic events and MACE.Keywords: paroxysmal atrial tachycardia, thromboembolic events, ischemic stroke, transient ischemic attack, systemic thromboembolism, major adverse cardiovascular events

Yi Zhou,1 Xinyu Xiong,1 Zhe Cheng,1 Zekai Chen,1 Shizhen Wu,2 Yan Yu,3 Yujin Liu,4 Guang Chen,1 Lingli Li5 1Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2College of Acupuncture and Bone Injury, Hubei University of Chinese Medicine, Wuhan, 430061, People’s Republic of China; 3Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 4Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Traditional Chinese Medicine, Wuhan Fourth Hospital, Wuhan, 430033, People’s Republic of ChinaCorrespondence: Lingli Li, Department of Traditional Chinese Medicine, Wuhan Fourth Hospital, Wuhan, 430033, People’s Republic of China, Email 379994890@qq.com Guang Chen, Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email guangchen@tjh.tjmu.edu.cnPurpose: Ginseng (Panax ginseng Meyer) is an herbal medicine used in traditional Chinese medicine (TCM), has the effects of treating colitis and other diseases. Ginsenoside Rb1 (GRb1), a major component of ginseng, modulates autoimmunity and metabolism. However, the mechanism underlying GRb1 treatment of ulcerative colitis (UC) has not yet been elucidated. UC is a refractory inflammatory bowel disease (IBD) with a high recurrence rate, and researches on new drugs for UC have been in the spotlight for a long time.Methods: Mice with DSS-induced UC were treated with GRb1 or 0.9% saline for 10 days. Colon tissue of UC mice was collected to detect the levels of intestinal inflammatory cytokines and integrity of the intestinal barrier. RNA-seq and network pharmacology were used to predict the therapeutic targets of GRb1 during UC treatment.Results: GRb1 treatment alleviated intestinal inflammation and improved intestinal barrier dysfunction in UC mice. Specifically, GRb1 downregulated the levels of pro-inflammatory cytokines such as TNF-α and IL-6, while upregulating the level of the anti-inflammatory cytokine IL-10. Additionally, GRb1 treatment increased the levels of tight junction proteins including ZO-1, Occludin, and E-cadherin, which are crucial for maintaining intestinal barrier integrity. Further analyses using RNA-seq and network pharmacology suggested that these effects might involve the regulation of GRb1 in the signal transduction network of VDR, PPARγ, and NF-κB.Conclusion: The study demonstrated that GRb1 effectively alleviated UC by modulating intestinal inflammation and protecting the integrity of the intestinal barrier through the signal transduction network of VDR, PPARγ, and NF-κB.Keywords: ginsenoside Rb1, ulcerative colitis, intestinal barrier, vitamin D receptor, nuclear factor-kappa B

Yao Liu, Cunsheng Wei Department of Neurology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, 211100, People’s Republic of ChinaCorrespondence: Cunsheng Wei, Department of Neurology, Affiliated Jiangning Hospital with Nanjing Medical University, 169 hushan Road, Nanjing, Jiangsu, 211100, People’s Republic of China, Tel +86 18262637236, Email weicunsheng1988@126.comObjective: To explore the relevant factors affecting the prognosis of subarachnoid hemorrhage.Methods: 284 patients with subarachnoid hemorrhage who were hospitalized in our hospital from January 1, 2022 to June 30, 2024 were selected and divided into a good prognosis group and a poor prognosis group according to the modified Rankin Scale (mRS) score. The general clinical data of the patients were also collected, and the independent risk factors affecting the poor prognosis of the patients were screened by univariate logistic regression analysis.Results: Patients with a favorable prognosis had a lower incidence rate of rebleeding (4.72% vs 17.65%; P =0.001), electrolyte disturbances (21.46% vs 41.18%; P < 0.001), lower respiratory tract infection (5.58% vs 35.29%; P < 0.001), urinary tract infection (1.72% vs 15.69%; P < 0.001) and gastrointestinal infection (2.15% vs 11.76%; P < 0.001) than patients with an unfavorable prognosis. Therefore, coinfection is an independent risk factor for prognosis. After adjusting for covariates, logistic regression analysis identified the prognosis of subarachnoid hemorrhage was related to coinfections (adjusted odds ratio =2.057; 95% CI: 1.516~2.791; P< 0.001).Conclusion: Coinfection is a very important independent risk factor affecting prognosis, and clinical care should focus on how to reduce coinfection during hospitalization in patients with subarachnoid hemorrhage and treat it aggressively to reduce mortality and disability and improve patient prognosis.Keywords: subarachnoid hemorrhage, prognosis, infections, risk factors, treatment

Yuan Liu,1,2,&ast; Xingchen Shang,1,&ast; Wenyi Du,1,&ast; Wei Shen,1 Yanfei Zhu1 1Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of General Surgery, Tengzhou Central People’s Hospital, Jining Medical College, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Shen; Yanfei Zhu, Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China, Tel +8613385110723 ; +8617852061572, Email shenweiijs@outlook.com; wxsrmyy@outlook.comPurpose: The reappearance of gastric cancer, a frequent postoperative complication following radical gastric cancer surgery, substantially impacts the near-term and far-reaching medical outlook of patients. The objective of this research was to create a machine learning algorithm that could recognize high-risk factors for gastric cancer recurrence and anticipate the correlation between gastric cancer recurrence and Helicobacter pylori (H. pylori) infection.Patients and Methods: This investigation comprised 1234 patients diagnosed with gastric cancer, and 37 characteristic variables were obtained. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), k-nearest neighbor algorithm (KNN), and multilayer perceptron (MLP), were implemented to develop the models. The k-fold cross-validation technique was utilized to perform internal validation of the four models, while independent datasets were employed for external validation of the models.Results: In contrast to the other machine learning models, the XGBoost algorithm demonstrated superior predictive ability regarding high-risk factors for gastric cancer recurrence. The outcomes of Shapley additive explanation (SHAP) analysis revealed that tumor invasion depth, tumor lymph node metastasis, H. pylori infection, postoperative carcinoembryonic antigen (CEA), tumor size, and tumor number were risk elements for gastric cancer recurrence in patients, with H. pylori infection being the primary high-risk factor.Conclusion: Out of the four machine learning models, the XGBoost algorithm exhibited superior performance in predicting the recurrence of gastric cancer. In addition, machine learning models can help clinicians identify key prognostic factors that are clinically meaningful for the application of personalized patient monitoring and immunotherapy.Keywords: gastric tumor, gastrectomy, helicobacter pylori, immunotherapy, risk factor, machine learning

Wenyi Li,1,2 Zhenguo Liu,1 Min Song,1 Zhenpeng Shi,1 Jihang Zhang,3 Junyu Zhou,1 Yidan Liu,1 Yun Qiao,4 Deshan Liu4 1First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Research Center for Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 3Traditional Chinese Medicine College, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 4Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Deshan Liu, Department of Traditional Chinese Medicine, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Tel +86 18560087381, Email liudeshan@sdu.edu.cnContext: Diabetic nephropathy (DN) and cognitive dysfunction (CD) are common complications of diabetes. Yi-Qi-Bu-Shen Recipe (YQBS) can effectively reduce blood glucose, improve insulin resistance, and delay the progression of diabetic complications. The underlying mechanisms of its effects need to be further studied.Objective: This study elucidates the mechanism of YQBS in DN with CD through network pharmacology and experimental validation.Materials and Methods: Protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Male Sprague-Dawley (SD) rats were divided into 6 groups: model, YQBS (2, 4, 8 g/kg), positive control (metformin, 200 mg/kg), and control; the DN model was established by high sugar and high fat diet combined with intraperitoneal streptozotocin injection. After the DN model was established, the rats were gavaged for 10 weeks. Serum, kidneys, and hippocampus tissues were collected to measure the expression levels of TLR4, NF-κB, TNF-α, and IL-6.Results: The network pharmacology analysis showed that quercetin and kaempferol were the main active components of YQBS. TNF and IL-6 were the key targets, and TLR4/NF-κB pathway was crucial to YQBS in treating DN complicated with CD. Experimental validation showed that the intervention of YQBS can reduce TNF-α and IL-6 in serum, and also significantly decreases the protein expression of TLR4 and NF-κB.Conclusion: YQBS exerts anti-inflammatory effects on DN with CD through TLR4/NF-κB pathway. This study provides a biological basis for the scientific usage of YQBS in inflammation diseases and supplies experimental evidence for future traditional Chinese medicine development.Keywords: Yiqi Bushen Recipe, diabetes nephropathy, cognitive dysfunction, network pharmacology, inflammation

Yijia Guo,1– 3,&ast; Ruyun Zhang,4,&ast; Xinling Gan,5 Erli Wang,6 Shuihua Lu,7 Hui Jiang,3 Hongfei Duan,8 Zhengzhou Yuan,9 Weimin Li,2,3,10 Yong Liu1 1Department of Neurology, Chengdu Medical College, The First Affiliated Hospital, Chengdu, People’s Republic of China; 2Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 3Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Department of Emergency, Beijing Chest Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Key Laboratory of Rehabilitation Medicine in Sichuan Province, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 6Department of Radiology, The First People’s Hospital of Longquanyi District, Chengdu, People’s Republic of China; 7National Clinical Research Center for Infectious Diseases, Guangdong Provincial Clinical Research Center for Tuberculosis, Shenzhen Third People’s Hospital, Southern University of Science and Technology, Shenzhen, People’s Republic of China; 8Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 9Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 10National Tuberculosis Clinical Laboratory of China, Beijing Key Laboratory in Drug Resistance Tuberculosis Research, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China&ast;These authors contributed equally to this work as first authorsCorrespondence: Yong Liu, Chengdu Medical College, The First Affiliated Hospital, No. 278, Middle Section, Baoguang Avenue, Xindu District, Chengdu, 610500, People’s Republic of China, Email 410578100@qq.comBackground: The predictors associated with clinical outcomes in patients with tuberculous meningitis (TBM) remain unclear. We aimed to analyse the relationship between systemic inflammation and clinical outcomes, as well as to explore whether systemic inflammation level influences the effectiveness of dexamethasone on treatment.Methods: Between January 2011 and December 2021, TBM patients admitted to five hospitals were observed consecutively. Baseline and post-treatment systemic inflammation levels were calculated using the neutrophil-lymphocyte-ratio (NLR). Generalized linear mixed models were employed to identify predictors of clinical outcomes. Propensity score matching and subgroup analyses were conducted to evaluate the effect of dexamethasone on treatment outcomes across different NLR levels.Results: A total of 1203 TBM patients were included in the study. During the follow-up, 144 (13.6%) participants experienced early neurological deterioration within 7 days after admission, and 345 (28.67%) exhibited poor functional outcome at the 12-month follow-up. Multivariate analysis revealed that post-treatment NLR was significantly associated with early neurological deterioration (OR=1.25; 95% CI, 1.14– 1.33; P< 0.001), and poor outcome (OR=1.34; 95% CI, 1.26– 1.45; P< 0.001). After propensity score matching, dexamethasone treatment was not associated with early neurological deterioration (OR=0.83; 95% CI, 0.42– 1.66; P=0.610) or poor outcome (OR=1.22; 95% CI, 0.49– 2.11; P=0.490) in the highest quartile of post-treatment NLR. The effect of dexamethasone on treatment outcomes did not significantly vary with disease severity stratification.Conclusion: Elevated systemic inflammation is an independent risk factor for neurological outcome in TBM patients. Further studies are required to investigate systemic inflammation in more severely affected population to better predict the outcomes following anti-inflammatory therapies.Keywords: tuberculous meningitis, systemic inflammation, neurological outcome

Chuxiao Zhang, Yuelan Qin, Yangguang Song, Yingying Liu, Xiaodong Zhu Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation OncologyGuangxi Medical University Cancer Hospital, No. 71 hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xdzhu1466@hotmail.comPurpose: There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.Methods: From 2011 to 2018, a cohort of individuals (age ≥ 70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.Results: The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20– 0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.Conclusion: In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.Keywords: elderly patients, hepatocellular carcinoma, transcatheter arterial chemoembolization, microwave ablation, treatment modality

Xiaoyue Feng,1,&ast; Jianli Shang,1,&ast; Zhengping Gu,1 Junhua Gong,1 Yong Chen,1,2 Youting Liu1,2 1R&D Department, Beijing UPROVEN Medical Technology Co., Ltd., Beijing, Daxing, People’s Republic of China; 2Beijing UPROVEN Institute of Dermatology, Beijing, Daxing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youting Liu, R&D Department, Beijing UPROVEN Medical Technology Co., Ltd., Yard 5, Tianhua Avenue, Beijing, Daxing, 102699, People’s Republic of China, Tel +86 18510256963, Email YtLiu.adpt@outlook.comAbstract: AZA is a non-phenolic, saturated dicarboxylic acid with nine carbon atoms, naturally produced by the yeast Malassezia. It has diverse physiological activities, including antibacterial, anti-keratinizing, antimelanogenic, antioxidant and anti-inflammatory effects. AZA is widely used in dermatology and is FDA-approved for treating papulopustular rosacea. It also shows significant efficacy in acne vulgaris and melasma. This review summarizes the mechanisms of action and clinical applications of AZA, aiming to provide theoretical support for its clinical and cosmetic use and to facilitate further research.Keywords: azelaic acid, mechanism, rosacea, acne, melasma, safety

Jiali Wang,1,2 Yiqing Liu,3 Chengkui Xiu,1 Xue Wang,1 Yinan Liu,1 Yanhong Hu,1 Jing Yang,1 Yan Lei1 1Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin, People’s Republic of China; 3National Resource Center for Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Yan Lei; Jing Yang, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Tel +13651217893 ; +15901070286, Email 13651217893@163.com; yangjingdr@163.comObjective: To explore the mechanism of the traditional Chinese medicine (TCM), Zhizhu granule (ZZG), in treating metabolic syndrome (MS) based on network pharmacology and pharmacodynamic experiment.Materials and Methods: Network pharmacology combined with a pharmacodynamic experiment was used to elucidate the therapeutic mechanism of ZZG in MS. Serum samples were collected from rats with MS, induced by a high-sugar-fat-salt diet (HSFSD) combined with streptozotocin (STZ), to measure the levels of biochemical markers. The glucose (GLU), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were detected. The liver tissue of rats was used for histological examination and Western blot analysis.Results: Network pharmacology analysis generated 69 drug-disease common targets and 10 hub genes closely related to ZZG against MS. KEGG pathway analysis revealed that the PI3K/AKT signaling pathway was the most potential pathway, which took part in the therapeutic mechanisms. In the animal experiments section, the therapeutic effect of ZZG on MS and the therapeutic pathway of ZZG on MS were verified. ZZG could significantly decrease the body weight, TC, TG, LDL-C and GLU levels in MS rats (all p< 0.01), alleviate hepatocyte steatosis and decrease liver lipid droplet deposition. Western blot analysis indicated that compared with the model group, the expression levels of PI3K, AKT, and IRS-1 protein were significantly increased (all p< 0.05), and the FOXO-1 was significantly decreased (all p< 0.05) in the ZZG group.Conclusion: ZZG can improve glucose-lipid metabolism disorder in rats with metabolic syndrome. The reported results provide experimental evidence for ZZG in the treatment of MS.Keywords: metabolic syndrome, network pharmacology, Zhizhu granule, pharmacodynamic experiment, PI3K/AKT pathway

Jiamin Mao,1,2 Xiaoyuan Liu,2 Lie Zhang,1 Yu Chen,2 Shiyu Zhou,2 Yujiao Liu,2 Jing Ye,2 Xiaohong Xu,2 Quan Zhang1– 4 1Department of Neurosurgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 2Sichuan Higher Education Institute Key Laboratory of Structure-Specific Small Molecule Drugs, Institute of Materia Medica, School of Pharmacy, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 3Development and Regeneration Key Laboratory of Sichuan Province, Department of Anatomy and Histoembryology, Chengdu Medical College, Chengdu, 610500, People’s Republic of China; 4Chengdu Nature’s Grace Biological Technology Co., Ltd., Chengdu, 610213, People’s Republic of ChinaCorrespondence: Quan Zhang, Email zhangquancdmc@126.comPurpose: Acute alcohol intoxication (AAI) is a life-threatening medical condition resulting from excessive alcohol consumption. Our research revealed the potential of morin (MOR) in treating AAI. However, MOR’s effectiveness against AAI was hindered by its poor solubility in water and low bioavailability. In this study, our aim was to develop a self-nanoemulsifying drug delivery system (SNEDDS) to enhance MOR’s solubility and bioavailability, evaluate its anti-AAI effects, and investigate the underlying mechanism.Methods: The composition of MOR-loaded self-nanoemulsifying drug delivery system (MOR-SNEDDS) was determined by constructing pseudo-ternary phase diagrams, and its formulation proportion was optimized using the Box-Behnken design. Following characterization of MOR-SNEDDS, we investigated its pharmacokinetics and biodistribution in healthy animals. Additionally, we assessed the anti-AAI effects and gastric mucosal protection of MOR-SNEDDS in an AAI mice model, exploring potential mechanisms.Results: After breaking down into tiny droplets, the optimized mixture of MOR-SNEDDS showed small droplet size on average, even distribution, strong stability, and permeability. Pharmacokinetic studies indicated that MOR-SNEDDS, compared to a MOR suspension, increased the area under the plasma concentration-time curve (AUC0-t) by 10.43 times. Additionally, studies on how drugs move and are distributed in the body showed that MOR-SNEDDS had an advantage in passively targeting the liver. Moreover, in a mouse model for alcohol addiction, MOR not only decreased alcohol levels by boosting the activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the stomach and liver, which counteracted the loss of righting reflex (LORR), but also reduced alcohol-induced damage to the stomach lining by lowering malondialdehyde (MDA) levels and increasing superoxide dismutase (SOD) levels. Furthermore, MOR-SNEDDS notably amplified these effects.Conclusion: MOR exhibits significant potential as a new medication for treating AAI, and utilizing MOR-SNEDDS with high oral bioavailability represents a promising new strategy in combating AAI.Keywords: Morin, self-nanoemulsifying drug delivery system, acute alcohol intoxication, oral bioavailability, alcohol-induced tissue injury

Liu Liang,1 Xuemin Guo,1 Wei Ye,1 Yuxiang Liu2 1Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Medical Oncology, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Liu Liang, Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 19926117315@163.comBackground: The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC.Methods: Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed.Results: 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥ 65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287– 3.016, p=0.002), and high SII level (≥ 807.81 vs < 807.81, OR: 1.915, 95% CI: 1.120– 3.272, p=0.018) were independently associated with KRAS mutation.Conclusion: Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.Keywords: colorectal cancer, KRAS, systemic immune inflammation index, tumor budding

Youwen Gong,1 Yongyi Chen,2 Yang Liu3 1Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The First People’s Hospital of Changde City), Changde, People’s Republic of China; 2Department of Nursing, Hunan Cancer Hospital, Changsha, People’s Republic of China; 3School of Nursing, University of South China, Hengyang, People’s Republic of ChinaCorrespondence: Youwen Gong, Department of Nursing, Changde Hospital, Xiangya School of Medicine, Central South University (The first People’s hospital of Changde city), Changde, People’s Republic of China, Email 1755144149@qq.comPurpose: To identify the factors affecting Chinese oncology nurses’ competency in coping with death, and their relationship with death attitudes and educational needs.Methods: A national cross-sectional descriptive study was conducted using an online survey of Chinese oncology nurses. Data were collected using the Coping with Death, Death Attitude Profile–Revised, and Death Education Needs Scales. A Pearson’s correlation analysis was used to examine the relationships among the research variables. A multiple linear regression analysis was used to analyze the factors influencing coping with death.Results: The total score of coping with death was 133.57± 26.78, showing a moderate coping level among Chinese oncology nurses. The Pearson’s correlation analysis showed that death attitude was significantly and positively correlated with coping with death competence, and there was a statistically significant positive relationship between coping with death competence and death education needs. Years of oncology care experience, bereavement experience, death attitude, and death education needs were identified as statistically significant factors influencing competency in coping with death. These factors explained 30.6% of the differences in coping with death.Conclusion: This study found that oncology nurses in China exhibited moderate levels of death coping competence, which needs to be improved to provide higher-quality end-of-life care. Further, death attitude and education needs were important factors affecting participants’ coping with death competence. Tailored death education programs and continuing education on death should be provided for oncology nurses, to encourage them to actively participate in death competence-related training and promote an attitude of natural acceptance of death and positive care for terminally ill patients. In the future, virtual reality technology could complete course implementation designs with immersive, conceptual, and interactive characteristics, to enhance the death-coping education program. Nurses with less experience in oncology care and bereavement should improve their competency in coping with death.Keywords: death competence, death attitudes, death education, oncology nurses

Fengting Wang,1,&ast; Limin Rong,1,&ast; Linlin Luo,2 Fuqin Mu,1 Liju Qian,3 Yandan Qian,4 Xinyao Zhang,1 Yuying Lang,1 Weijia Wang,1 Yan Liu,5,6 Ying Zhang,7 Jianli Wang1,8 1School of Mental Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Department of Hematology, Tai’an Central Hospital, Tai’an, Shandong, People’s Republic of China; 3Shandong Daizhuang Hospital, Jining, Shandong, People’s Republic of China; 4The Third People’s Hospital of Jiashan County, Jiashan, Zhejiang, People’s Republic of China; 5School of Public Health, Jining Medical University, Jining, Shandong, People’s Republic of China; 6Center of Evidence-Based Medicine, Jining Medical University, Jining, Shandong, People’s Republic of China; 7School of Public Health, University of Sydney, Sydney, NSW, Australia; 8Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada&ast;These authors contributed equally to this workCorrespondence: Fengting Wang, School of Mental Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email wft.0810@163.com Yan Liu, School of Public Health, Jining Medical University, Jining, Shandong, 272013, People’s Republic of China, Email hakunaly@163.comBackground: Youth and young adults have a high prevalence of major depressive disorder (MDD). Limited longitudinal research has explored the relationship between different dimensions of psychological stress and MDD. This study aimed to estimate the effect of psychological stress on the risk of first onset MDD in a sample of Chinese freshmen.Methods: Using a longitudinal design, 8079 Chinese first-year students were recruited at baseline, and 6985 were followed up one year later. The Psychological Stress Scale for College Students was utilized to evaluate the levels of psychological stress. MDD was evaluated using the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0). Logistic regression modeling was utilized to estimate the associations between dimensions of psychological stress and the risk of MDD.Results: Two dimensions of psychological stress, namely learning stress (OR=1.05, 95% CI:1.01– 1.09, P=0.017) and economic stress (OR=1.11, 95% CI:1.04– 1.19, P=0.001), were significantly associated with the risk of MDD. Other dimensions of psychological stress (specify family stress, interpersonal stress, intimate relationship stress, employment stress and appearance stress) were not associated with MDD.Conclusion: Psychological stress, especially learning and economic stresses, could increase the risk of MDD in university students. These factors should be incorporated into mental health prevention and intervention programs at universities to reduce the risks of MDD.Keywords: major depressive disorder, psychological stress, longitudinal study, freshmen

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

Yanfen Liu, Xueyong Lou Department of Endocrinology at Zhejiang University School of Medicine, Jinhua Hospital, Jinhua, People’s Republic of ChinaCorrespondence: Xueyong Lou, Email jhszxyy0710@163.comBackground: The rapid global spread of a new coronavirus disease known as COVID-19 has led to a significant increase in mortality rates, resulting in an unprecedented worldwide pandemic.Methods: The impact of COVID-19, particularly its long-term effects, has also had a profound effect on the health and well-being of individuals.Metabolic syndrome increases the risk of heart and brain diseases, presenting a significant danger to human well-being.Purpose: The prognosis of long COVID and the progression of metabolic syndrome interact with each other, but there is currently a lack of systematic reports.In this paper, the pathogenesis, related treatment and prognosis of long COVID and metabolic syndrome are systematically reviewed.Keywords: Long COVID, Metabolic syndrome, Cardiovascular disease, pathway, drugs

Luqian Zhan,1,&ast; Ye Zhang,2,&ast; Yanwei Li,3 Chenhui Lin,3 Heyu Zhang,3 Yuntao Liu,3 Jincai He3 1Department of Neurology, Integrated Traditional Chinese and Western Medicine Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Third Department of Cerebrovascular Disease, Cangzhou Central Hospital, Cangzhou, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jincai He; Yuntao Liu, Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Email hjc@wmu.edu.cn; 18267850815@163.comPurpose: Acute ischemic stroke (AIS) patients with COVID-19 have severe neurological symptoms and high mortality. It remains unclear how COVID-19 causes unfavorable outcomes. This study aimed to explore the possible mechanism focusing on inflammation and coagulation.Patients and Methods: 109 AIS patients were recruited and followed up 3 months after stroke. We used binary logistic regression to investigate if COVID-19 infection is an independent prognostic factor. To analyze the link between inflammation, coagulation, and neurological outcomes, we used mediation analysis.Results: Compared to the non-COVID-19 group, the COVID-19 group had significantly higher fibrinogen (FIB) (P < 0.001), APTT ratio (P < 0.001), D-dimer (P < 0.001), CRP (P < 0.001). Patients with unfavorable outcomes had a higher incidence of COVID-19 infection (P = 0.002), along with elevated levels of INR (P = 0.005), D-dimer (P < 0.001), and CRP (P = 0.012). The significant association between 3-month functional outcomes and COVID-19 tends to be insignificant (P = 0.294) after adding the covariates of inflammation and coagulation. The mediation analyses showed the APTT ratio mediated the association between COVID-19 and the 3-month outcome (percent mediation = 56.3%). The integrated pathway analysis implicated that the path of COVID-19 infection→CRP→APTT ratio→ 3-month outcome was significant (percent mediation = 18.7%).Conclusion: AIS with COVID-19 had a poorer prognosis. We delineated a more accurate mechanism by which COVID-19 influences functional outcomes: COVID-19 infection→inflammation→endogenous coagulation pathway→poor stroke outcome. This study provided new insight into the pathway mechanisms of AIS with COVID-19.Keywords: COVID-19, Omicron, stroke, mediation analysis, APTT ratio

Mengyao Shi,1,&ast; Xueyu Mao,2,&ast; Xuechun Wu,2 Min Chu,2 Huicong Niu,2 Lulu Sun,1 Xinyue Chang,1 Yu He,1 Yi Liu,1 Daoxia Guo,3 Yonghong Zhang,1 Zhengbao Zhu,1 Jing Zhao2,4 1Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 4Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Zhao, Department of Neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China, Email zhao_jing@fudan.edu.cn Zhengbao Zhu, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province, 215123, People’s Republic of China, Email zbzhu@suda.edu.cnBackground: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study.Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS.Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59– 0.85; Ptrend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (Ptrend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036).Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.Keywords: prealbumin, ischemic stroke, prognosis, cohort study

Ying Liu,1,&ast; Li Wang,2,&ast; Er-Hao Bao,1,&ast; Jia-Hao Wang,1 Lin Yang,1 Lei Wang,1 Long Xia,1 Ben Wang,1 Ping-Yu Zhu1 1Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping-Yu Zhu, Email zhupingyu@nsmc.edu.cnPurpose: The prevalence of Obstructive Sleep Apnea (OSA) is high, and there are many complications. Few studies have reported the relationship between OSA and kidney stones. The purpose of this study is to explore whether people at risk of OSA will increase the risk of kidney stones.Methods: This was a cross-sectional study, and information was collected through the National Health and Nutrition Examination Survey conducted from 2015 to 2018. Multiple logistic regression analyses were employed to calculate the odds ratios (ORs) and their 95% confidence intervals (CIs) for the link between obstructive sleep apnea and the presence of kidney stones. Additionally, to assess causality and reduce observational biases, five distinct two-sample Mendelian randomization techniques were applied.Results: Following the adjustment for relevant confounders, findings indicated a statistically significant correlation between obstructive sleep apnea (OSA) and higher prevalence of kidney stones (OR = 1.29; 95% CI: 1.00– 1.66). Additionally, using the inverse-variance weighted approach in Mendelian randomization, results suggested a genetic predisposition to OSA might be causally linked to an elevated risk of developing kidney stones (OR: 1.00221, 95% CI 1.00056– 1.00387).Conclusion: OSA promotes the formation of kidney stones, and the treatment and management of OSA can improve or mitigate the occurrence of kidney stones.Keywords: obstructive sleep apnea, kidney stones, national health and nutrition examination survey, Mendelian randomization

Na Yu,1,&ast; Mingqin Su,1,&ast; Juan Wang,2 Yakun Liu,1 Jingya Yang,1 Jingyi Zhang,1 Meimei Wang1 1Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Department of Public Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei, 230032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Meimei Wang, Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, No. 81, Mei-Shan Road, Hefei, 230032, People’s Republic of China, Email wangmm@ustc.edu.cnBackground: Tumor development and progression is a long and complex process influenced by a combination of intrinsic (eg, gene mutation) and extrinsic (eg, environmental pollution) factors. As a detoxification organ, the liver plays an important role in human exposure and response to various environmental pollutants including nanomaterials (NMs). Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and remains a serious threat to human health. Whether NMs promote liver cancer progression remains elusive and assessing long-term exposure to subtoxic doses of nanoparticles (NPs) remains a challenge. In this study, we focused on the promotional effects of nano zinc oxide (nZnO) on the malignant progression of human HCC cells HepG2, especially aged nZnO that has undergone physicochemical transformation.Methods: In in vitro experiments, we performed colony forming efficiency, soft agar colony formation, and cell migration/invasion assays on HepG2 cells that had been exposed to a low dose of nZnO (1.5 μg/mL) for 3 or 4 months. In in vivo experiments, we subcutaneously inoculated HepG2 cells that had undergone long-term exposure to nZnO for 4 months into BALB/c athymic nude mice and observed tumor formation. ZnCl2 was administered to determine the role of zinc ions.Results: Chronic low-dose exposure to nZnO significantly intensified the malignant progression of HCC cells, whereas aged nZnO may exacerbate the severity of malignant progression. Furthermore, through transcriptome sequencing analysis and in vitro cellular rescue experiments, we demonstrated that the mechanism of nZnO-induced malignant progression of HCC could be linked to the activation of Claudin-2 (CLDN2), one of the components of cellular tight junctions, and the dysregulation of its downstream signaling pathways.Conclusion: Long-term exposure of fresh and aged nZnO promotes hepatocellular carcinoma malignancy by up-regulating CLDN2. The implications of this work can be profound for cancer patients, as the use of various nanoproducts and unintentional exposure to environmentally transformed NMs may unknowingly hasten the progression of their cancers. Keywords: nano zinc oxide, environmental transformation of NPs, long-term exposure, malignant progression of tumors, CLDN2

Rong Hong,1,2,&ast; Xiaoxia Ping,2,3,&ast; Yuanying Liu,2 Feiwen Feng,2 Su Hu,2,3 Chunhong Hu2,3 1Department of Radiology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, Jiangsu, 215100, People’s Republic of China; 2Department of Radiology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, People’s Republic of China; 3Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Hu; Su Hu, Department of Radiology, The First Affiliated Hospital of Soochow University; Institute of Medical Imaging, Soochow University, Suzhou, Jiangsu, People’s Republic of China, Email sdhuchunhong@sina.com; husu@suda.edu.cnPurpose: The clinical, pathological, gene expression, and prognosis of invasive mucinous adenocarcinoma (IMA) differ from those of invasive non-mucinous adenocarcinoma (INMA), but it is not easy to distinguish these two. This study aims to explore the value of combining CT-based radiomics features with clinic-radiological characteristics for preoperative diagnosis of solitary-type IMA and to establish an optimal diagnostic model.Methods: In this retrospective study, a total of 220 patients were enrolled and randomly assigned to a training cohort (n = 154; 73 IMA and 81 INMA) and a testing cohort (n = 66; 31 IMA and 35 INMA). Radiomics features and clinic-radiological characteristics were extracted from plain CT images. The radiomics models for predicting solitary-type IMA were developed by three classifiers: linear discriminant analysis (LDA), logistic regression-least absolute shrinkage and selection operator (LR-LASSO), and support vector machine (SVM). The combined model was constructed by integrating radiomics and clinic-radiological features with the best performing classifier. Receiver operating characteristic (ROC) curves were used to evaluate models’ performance, and the area under the curve (AUC) were compared by the DeLong test. Decision curve analysis (DCA) was conducted to assess the clinical utility.Results: Regarding CT characteristics, tumor lung interface, and pleural retraction were the independent risk factors of solitary-type IMA. The radiomics model using the SVM classifier outperformed the other two classifiers in the testing cohort, with an AUC of 0.776 (95% CI: 0.664– 0.888). The combined model incorporating radiomics features and clinic-radiological factors was the optimal model, with AUCs of 0.843 (95% CI: 0.781– 0.906) and 0.836 (95% CI: 0.732– 0.940) in the training and testing cohorts, respectively.Conclusion: The combined model showed good ability in predicting solitary-type IMA and can provide a non-invasive and efficient approach to clinical decision-making.Keywords: computed tomography, invasive mucinous adenocarcinoma, radiomics, machine learning

Fengsong Chen,1,&ast; Yanhua Huang,1,&ast; Yongxia Liu,2 Yanwen Zhuang,3 Xiaowei Cao,3 Xiaogang Qin2 1Department of Gastroenterology, Nantong Haimen People’s Hospital, Nantong, Jiangsu, 226100, People’s Republic of China; 2Department of gastroenterology, Traditional Chinese Medicine Hospital of Tongzhou District, Nantong, Jiangsu, 226300, People’s Republic of China; 3Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogang Qin, Email tzqinxiaogang@163.comBackground: Colorectal cancer (CRC) has become a significant global public health challenge, demanding immediate attention due to its high incidence and mortality rates. Regular CRC screening is essential for the early detection of precancerous lesions and CRC.Methods: : We developed a novel surface-enhanced Raman scattering (SERS) analysis platform that employs high-throughput microarray chips as carriers and Au/SnO2 nanoring arrays (Au/SnO2 NRAs) as substrates. This platform utilizes an aptamer recognition-release strategy to achieve efficient and sensitive detection of protein tumor markers. In the detection process, the strong affinity and high specificity between the aptamer and the target protein result in competitive replacement of the SERS nanoprobes originally bound to the substrate surface. As a result, the SERS nanoprobes carrying Raman reporter genes are dislodged, leading to a reduction in the SERS signal intensity.Results: The platform demonstrated excellent detection performance, with rapid detection completed within 15 minutes and limits of detection (LOD) as low as 6.2× 10− 12 g/mL for hnRNP A1 and 6.51× 10− 12 g/mL for S100P. Clinical samples analyzed using the SERS platform showed high consistency with enzyme-linked immunosorbent assay (ELISA) results.Conclusion: This platform offers strong support for the early detection, risk assessment, and treatment monitoring of colorectal cancer precancerous lesions, with broad potential for clinical applications.Keywords: colorectal cancer, precancerous lesions, surface enhanced raman scattering, aptamer, microarray chip

Ruien Chen,1,&ast; Huamei Zou,1,&ast; Xiuwen Ye,1,&ast; Bailing Xie,2 Aizhi Zhang,3 Lihua Mo,4 Yu Liu,4 Huanping Zhang,5 Gui Yang,1 Pingchang Yang2 1Department of Otolaryngology, Longgang Central Hospital affiliated to Guangzhou University of Chinese Traditional Medicine Shenzhen Clinical College, Shenzhen, 518116, People’s Republic of China; 2State Key Laboratory of Respiratory Diseases Allergy Division at Shenzhen University and Institute of Allergy & Immunology, Shenzhen University School of Medicine, Shenzhen, 518055, People’s Republic of China; 3Department of Critical Care Medicine, Second Hospital, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China; 4Department of General Medicine Practice, Third Affiliated Hospital, Shenzhen University, Shenzhen, 518005, People’s Republic of China; 5Department of Allergy Medicine, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pingchang Yang; Gui Yang, Email pcy2356@163.com; guiyang1981@hotmail.comIntroduction: The therapeutic efficacy for airway allergies needs to be improved. Th2 polarization is a primary pathological feature of airway allergies. We constructed chimeric antigen-LgDNA (Lactobacillus rhamnosus DNA) nanoparticles (CAP-NPs). The effects of CAP-NPs on reconciling airway Th2 polarization were tested.Methods: In this study, disulfide bond-linked antigen-major histocompatibility complex II (MHC II)-LgDNA nanoparticles (NPs) were constructed and designated CAP-NPs. An airway Th2 polarization mouse model was established to test the effects of CAP-NPs on suppressing the Th2 response.Results: The CAP-NP components of ovalbumin (OVA), major histocompatibility complex II (MHC II), and LgDNA were confirmed in a series of laboratory tests. The CAP-NPs remained stable at pH7.2 for at least 96 h. In in vitro experiments, CAP-NPs bound to the surface of OVA-specific CD4+ T cells, which resulted in apoptosis of the antigen-specific CD4+ T cells. Removal of any of the three components from the NPs abolished the induction of apoptosis of antigen specific CD4+ T cells. CAP-NPs increased the expression of lysine-specific demethylase 5A (KDM5A) in CD4+ T cells. Histone H3K9 and the gene promoter of caspase 8 were demethylated by KDM5A, which led to transcription and expression of the caspase 8 gene. Administration of CAP-NPs significantly alleviated experimental airway Th2 polarization through activating the caspase 8-apoptosis signaling pathway.Discussion: In this paper, we constructed CAP-NPs that could induce antigen-specific CD4+ T cell apoptosis. Administration of CAP-NPs efficiently alleviated experimental airway Th2 polarization.Keywords: airway allergy, T cell, therapy, vaccine, nanoparticle

Mengyue Sun,1 Yuanyuan Liu,2 Shan Tang,2 Yiming Li,2 Ridong Zhang,2 Li Mao2 1Department of Geratology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of China; 2Department of Endocrinology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu, 223300, People’s Republic of ChinaCorrespondence: Li Mao, Email maoli_mail@126.comAim: This study investigated differences in gut flora between osteoporosis (OP) patients and healthy individuals using 16S rDNA sequencing. The correlation between differential flora abundance and bone mineral density (BMD) was analyzed, and key flora and potential mechanisms associated with OP were explored.Methods: Forty-three OP patients and twenty-four healthy volunteers were recruited. Gender, age, height, weight, and BMD data were collected. DNA from fecal samples was extracted for 16S rDNA sequencing. The Kruskal–Wallis test assessed differences in gut flora composition, while LEfSe analysis identified significant flora. Spearman correlation analysis examined the relationship between differential flora and BMD, and PICRUSt predicted pathways involved in OP.Results: Significant differences in microbial composition were found between the two groups. Klebsiella, Escherichia-Shigella, and Akkermansia were biomarkers in OP patients, with Faecalibacterium in the healthy group. Akkermansia abundance negatively correlated with lumbar BMD, while Klebsiella and Escherichia-Shigella negatively correlated with femoral neck and hip BMD. Faecalibacterium showed a positive correlation with BMD. Functional predictions indicated differences in metabolism-related pathways between the groups.Conclusion: Gut flora differed significantly between OP patients and healthy individuals. Akkermansia, Klebsiella, and Escherichia-Shigella could serve as diagnostic biomarkers for OP, highlighting the potential of gut flora in OP diagnosis and treatment.Keywords: osteoporosis, intestinal flora, 16S rDNA

Longfei Lin,1,&ast; Yuling Liu,1,&ast; Ruying Tang,1 Shilan Ding,1 Hongmei Lin,2,3 Hui Li1,4 1Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3National Medical Products Administration Key Laboratory for Research Evaluation of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Institute of Traditional Chinese Medicine Health Industry, China Academy of Chinese Medical Sciences, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li, Institute Chinese Materia Medica China Academy of Chinese Medical Sciences, Beijing, 100700, People’s Republic of China, Email lihuizys@126.com Hongmei Lin, Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China, Email lhmtcm@126.comAbstract: Evodiamine (EVO) is a tryptamine indole alkaloid and the main active ingredient in Evodia rutaecarpa. In recent years, the antitumor, cardioprotective, anti-inflammatory, and anti-Alzheimer’s disease effects of EVO have been reported. EVO exerts antitumor effects by inhibiting tumor cell activity and proliferation, blocking the cell cycle, promoting apoptosis and autophagy, and inhibiting the formation of the tumor microvasculature. However, EVO has poor solubility and low bioavailability. Several derivatives with high antitumor activity have been discovered through the structural optimization of EVO, and new drug delivery systems have been developed to improve the solubility and bioavailability of EVO. Current research found that EVO could have toxic effects, such as hepatotoxicity, nephrotoxicity, and cardiac toxicity. This article reviews the pharmacological activity, derivatives, drug delivery systems, toxicity, and pharmacokinetics of EVO and provides research ideas and references for its further in-depth development and clinical applications.Keywords: evodiamine, pharmacology, derivatives, drug delivery systems