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Zhidi Zhang, Qiang Zuo, Yali Du, Hailing Jiang, Furong Ma, Yinghong Zhang Department, Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of ChinaCorrespondence: Yinghong Zhang, Department, Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China, Email yinghongzhang@bjmu.edu.cn Furong Ma, Department, Otolaryngology Head and Neck Surgery, Peking University Third Hospital, Beijing, 100191, People’s Republic of China, Email furongma@126.comObjective: Osteitis is more prevalent in patients with chronic rhinosinusitis with nasal polyps (CRSwNP), making the disease refractory and prone to recurrence. However, the pathophysiologic mechanism of osteitis formation in CRS has not been fully elucidated, and this study aimed to further elucidate the association of eosinophils and type 2 inflammatory mediators with osteitis in patients with CRSwNP.Methods: This retrospective study collected clinical data on 125 cases of CRSwNP. The participants were categorized into two groups based on the presence or absence of osteitis in their sinus CT scan. The groups were classified as the osteitis group and the non-osteitis group. The clinical baseline data, type 2 inflammatory mediators, and eosinophils were compared between the two groups. The correlation between these factors and the Global Osteitis score scale (GOSS) was also evaluated.Results: There were 69 cases in the osteitis group and 56 cases in the non-osteitis group of CRSwNP patients. The prevalence of concomitant asthma (P=0.009), SNOT-22 score, LUND-MAKAY score, and LUND-KEDENY score were significantly higher in the osteitis group than in the non-osteitis group (All P values were < 0.001); the absolute values of IL-13 (P< 0.001), periosteal proteins (P< 0.001), and tissue eosinophils (P < 0.05) were significantly higher in the osteitis group as compared with the non-osteitis group. Logistic regression analysis showed that IL-13 and periosteal proteins were risk factors for CRSwNP osteitis (P< 0.001). ROC curve analysis revealed that IL-13 had the highest predictive value (AUC=0.786) with a cut-off value of 5.8059 pg/mL, the sensitivity of 58.0%, and a specificity of 89.3% respectively.Conclusion: Osteitis could indicate the more severe symptoms of chronic rhinosinusitis with nasal polyps (CRSwNP), and elevated IL-13, periosteal proteins, and tissue eosinophils are risk factors for osteitis formation in patients with CRSwNP.Keywords: chronic rhinosinusitis, osteitis, eosinophils, type 2 inflammatory mediators

Yan Zhang,1,&ast; Senlu Wang,1,&ast; Xinqi Wang,2 Nianqiang Liu,2 Le Wang,2 Xiaomin Wang,1 Zhichao Liang,1 Junan Wang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingqin Cao, Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, 830011, People’s Republic of China, Tel +86-13319912419, Email 573596229@qq.comObjective: To analyze the effectiveness of the “Xinjiang Model” for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the policy implementation effect.Methods: The registration data of pulmonary tuberculosis (PTB) patients in Kashgar Prefecture from 2012 to 2021 were collected to describe the temporal trend of registered incidence. A questionnaire survey was conducted among PTB patients registered and treated in the tuberculosis management information system in Zepu and Shache Counties from January 2022 to July 2023 to collect and analyze “Xinjiang model” determinants of effectiveness.Results: The PTB registered incidence in Kashgar Prefecture showed a significant increasing trend from 2012 to 2018 (APC=18.7%) and a significant decreasing trend from 2018– 2021 (APC=− 28.8%). Among the Kashgar Prefecture, compared with average registered incidence in 2012– 2017, registered incidence in 2021 in Shufu, Maigaiti, and Zepu Counties had a greater decline rate of 58.68%, 57.16%, and 54.02%, respectively, while the registered incidence in 2021 in Shache County increased by 6.32%. According to the comprehensive analysis of the factors affecting the effect of policy implementation, the proportion of PTB patients in Zepu County whose health status has now significantly improved compared with that before treatment was significantly greater than that in Shache County (P< 0.05); patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular reviews during treatment; the factors that accounted for the greater proportion of heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively.Conclusion: The “Xinjiang model” can effectively control the epidemic situation of tuberculosis in Kashgar, and the knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs were the determinants of the effectiveness of policy implementation.Keywords: pulmonary tuberculosis, implementation effect, registered incidence, determinants, Xinjiang

Li Zhang,1,2 Zimu Yu,3 Yunfeng Zhang,1 Hengyu Wang,4,5 Juntao Cheng,6 Chao Shi1 1Department of Oncology, Gaoxin Branch Of The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 2First School of Clinical Medicine, Jiangxi Medical College, Nanchang University, Nanchang, 330031, People’s Republic of China; 3Medical College of Zhengzhou University, Zhengzhou University, Zhengzhou, 450001, People’s Republic of China; 4Queen Mary College, Nanchang University, Nanchang, 330031, People’s Republic of China; 5School of Biological and Biomedical Sciences, Queen Mary University of London, London, UK; 6Peking University First Hospital, Peking University, Beijing, 100034, People’s Republic of ChinaCorrespondence: Chao Shi, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 151 7049 8679, Email ndyfy4540@ncu.edu.cnPurpose: Although brain metastasis (BM) from gastric cancer (GC) is relatively uncommon, its incidence has been increasing owing to advancements in treatment modalities. Unfortunately, patients diagnosed with BM from gastric cancer have poor life expectancy. Our study aims to establish a predictive model for brain metastasis in advanced gastric cancer patients, thus enabling the timely diagnosis of brain metastasis.Patients and Methods: The clinicopathological features of a cohort which included 40 GC patients with brain metastasis, 32 of whom from the First Affiliated Hospital of Nanchang University, 2 from Gaoxin Branch of the First Affiliated Hospital of Nanchang University, remaining 6 from Anyang District Hospital, and 80 non-metastatic advanced GC patients from the First Affiliated Hospital of Nanchang University between 2018 and 2022. Data were retrospectively analyzed.Results: Age, tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, carbohydrate antigen 199 (CA199), lactate dehydrogenase (LDH), and human epidermal growth factor receptor 2 (Her-2) were associated with BM. A nomogram integrated with nine risk factors (tumor size, differentiation, lymph node grade, tumor location, Lauren classification, liver metastasis, CA-199, LDH, and Her-2) showed good performance (Area Under Curve 0.95, 95% CI: 0.91– 0.98).Conclusion: We developed and validated a nomogram that achieved individualized prediction of the possibility of BM from GC. This model enables personalized imaging review schedules for timely brain metastasis detection in advanced gastric cancer patients.Keywords: brain metastasis, gastric cancer, nomogram, risk factors

Yuan Zhuang,1,2 Ru Zhang,3,4 Miaomiao Li,3,4 Yaru Zou,1 Shui Jiang,1 Yanan Zhang,1 Shiguo Liu,3,4 Bo Yu1 1Dermatological Department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China; 2dermatological department, Women and Children’s hospital, Qingdao University, Qingdao, People’s Republic of China; 3Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 4Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Bo Yu, Dermatological department, The Affiliated Hospital of QingdaoUniversity, Qingdao, People’s Republic of China, Email yubo@qduhospital.cn Shiguo Liu, Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Email liushiguo@qdu.edu.cnIntroduction: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that influences structures of ectodermal origin, such as teeth, hair, and sweat glands. Compared with autosomal recessive and dominant modes of inheritance, the X-linked HED (XLHED) characterized by Hypodontia/Oligodontia teeth, Absent/sparse hair, Anhidrosis/hypohidrosis, and characteristic facial features, is the most frequent and its primary cause is the mutation of ectodysplasin A (EDA) gene. This research aimed to expound the clinical and molecular features of a Chinese male with XLHED and to summarize and compare several previous findings.Methods: Genomic DNA was obtained from the peripheral blood of the proband and his family members, then Sanger sequencing was used to perform a mutational analysis of EDA. Real-time quantitative PCR and Western blotting were used to detect EDA expression. The transcriptional activity of NF-κB was detected using a luciferase assay.Results: The probandwith XLHED was identified a novel EDA mutation, c.1119G>C(p.M373I), that affected the molecular analysis of transmembrane protein exon8 mutations, inherited from the mother. He showed a severe multiple-tooth loss, with over 20 permanent teeth missing and sparse hair and eyebrows, dry, thin, and itching skin. Furthermore, his sweating function was abnormal to a certain extent.Discussion: The functional study showed that this novel mutant led to a significant decrease in the EDA expression level and transcriptional activity of NF-κB. Our findings extend the range of EDA mutations in XLHED patients, which provides the basis and idea for further exploring the pathogenesis of XLHED.Keywords: EDA, X-linked hypohidrotic ectodermal dysplasia, gene mutation

Zaiyan Wang,1 Yuan Zhang,2 Xiaoning Li3 1Department of Pulmonary and Critical Care Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China; 3Department of Geriatric Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of ChinaCorrespondence: Xiaoning Li, Department of Geriatric Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, People’s Republic of China, Email xihao5182020@163.com Yuan Zhang Department of Pulmonary and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, People’s Republic of China, Email zhs0905@126.comAbstract: Idiopathic pulmonary fibrosis (IPF) poses a formidable clinical challenge, characterized by the thickening of alveolar septa and the onset of pulmonary fibrosis. The pronounced activation of oxidative stress emerges as a pivotal hallmark of inflammation. Traditional application of exogenous antioxidants proves inadequate in addressing oxidative stress, necessitating exploration into strategies to augment their antioxidant efficacy. Exosomes, nano-sized extracellular vesicles harboring a diverse array of bioactive factors, present as promising carriers with the potential to meet this challenge. Recent attention has been directed towards the clinical applications of exosomes in IPF, fueling the impetus for this comprehensive review. We have compiled fresh insights into the role of exosomes in modulating oxidative stress in IPF and delved into their potential as carriers for regulating endogenous reactive oxygen species generation. This review endeavors to bridge the divide between exosome research and IPF, traversing from bedside to bench. Through the synthesis of recent findings, we propose exosomes as a novel and promising strategy for improving the outcomes of IPF therapy.Keywords: oxidative stress, idiopathic pulmonary fibrosis, exosomes, treatment

Yan Zhang,1,&ast; Qixing Wu,2,&ast; Mingming Han,2 Chengwei Yang,2 Fang Kang,2 Juan Li,2 Chengwen Hu,1 Xia Chen1 1Department of Nursing, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xia Chen; Chengwen Hu, Email chenxiaahslyy@163.com; huchengwen318@126.comObjective: Frailty, representing the physiological reserve and tolerance of the body, serves as a crucial evaluation index of the overall status of the older adults. This study aimed to investigate the prevalence of preoperative frailty and its impact on postoperative outcomes among older adults with lumbar degenerative disease in China.Patients and Methods: In this prospective study, a total of 280 patients aged 60 and above, diagnosed with lumbar degenerative disease and scheduled for surgical intervention were enrolled. The prevalence of frailty pre-surgery was evaluated using the Tilburg Frailty Indicator (TFI) and the modified Frailty Index 11 (mFI-11). The primary outcome was postoperative complication within 30 days post-surgery. The secondary outcomes were the length of hospital stay, hospital costs, reoperation within 30 days post-surgery and unplanned readmission within 30 days post-discharge. Both univariable and multivariable logistic regression were employed to screen and identify the risk factors predisposing patients to postoperative complications.Results: A total of 272 older adults were included in the study ultimately. The frailty detection rates of TFI and mFI-11 were 15.8% (43/272) and 10.7% (29/272) respectively. Thirty-four patients (12.5%) encountered complications. Significantly elevated rates of complications, prolonged hospital stays, increased hospital costs, and heightened readmission rates were observed in the frail group compared to the non-frail group (P< 0.05). Univariable analysis showed that the potential factors related to complications are TFI, mFI-11 and albumin. Multivariable logistic regression revealed that TFI was an independent risk factor for postoperative complications (OR=5.371, 95% CI: 2.338– 12.341, P < 0.001).Conclusion: Frailty was an independent predictor of postoperative complications in older adults undergoing lumbar fusion surgery. Frailty assessment should be performed in such patients to improve preoperative risk stratification and optimize perioperative management strategies.Keywords: lumbar degenerative disease, older adults, frailty, postoperative outcome

Changxiu Ma,1 Ying Zhang,1 Tingchao Tian,2 Ling Zheng,1 Jing Ye,1 Hui Liu,1 Dahai Zhao1 1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Anhui Medical University, Hefei, 230601, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Huoqiu First People’s Hospital, Huoqiu, 237400, People’s Republic of ChinaCorrespondence: Dahai Zhao, Second Affiliated Hospital, Anhui Medical University, 678 Furong Road, Hefei, Anhui Province, 230601, People’s Republic of China, Tel +86-13721027959, Email zhaodahai@ahmu.edu.cnPurpose: To explore the role of the mean apnea–hypopnea duration (MAD) and apnea–hypopnea duration per hour (HAD) in hypoxemia and evaluate whether they can effectively predict the occurrence of hypoxemia among adults with OSA.Patients and Methods: A total of 144 participants underwent basic information gathering and polysomnography (PSG). Logistic regression models were conducted to evaluate the best index in terms of hypoxemia. To construct the prediction model for hypoxemia, we randomly divided the participants into the training set (70%) and the validation set (30%).Results: The participants with hypoxemia tend to have higher levels of obesity, diabetes, AHI, MAD, and HAD compared with non-hypoxemia. The most relevant indicator of blood oxygen concentration is HAD (r = 0.73) among HAD, MAD, and apnea–hypopnea index (AHI). The fitness of HAD on hypoxemia showed the best. In the stage of establishing the prediction model, the area under the curve (AUC) values of both the training set and the validation set are 0.95. The increased HAD would elevate the risk of hypoxemia [odds ratio (OR): 1.30, 95% confidence interval (CI): 1.13– 1.49].Conclusion: The potential role of HAD in predicting hypoxemia underscores the significance of leveraging comprehensive measures of respiratory disturbances during sleep to enhance the clinical management and prognostication of individuals with sleep-related breathing disorders.Keywords: mean apnea–hypopnea duration, obstructive sleep apnea, apnea–hypopnea duration per hour, polysomnography, apnea–hypopnea index

Haotian Zhou,1,2,&ast; Yaji Yang,1,2,&ast; Yanhao Zhang,3 Feilong Li,1,2 Yidong Shen,4 Leilei Qin,1,2 Wei Huang1,2 1Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Orthopedic Laboratory of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 3College of Pharmacy, Army Military Medical University, Chongqing, 400038, People’s Republic of China; 4Department of Orthopaedics, The First People’s Hospital of Yancheng, Yancheng, 224000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leilei Qin; Wei Huang, Email 253505921@qq.com; huangwei68@263.netAbstract: Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery, posing significant challenges to orthopedic surgeons. Due to the lack of a definitive diagnostic gold standard, timely treatment initiation is problematic, resulting in substantial economic burdens on patients and society. In this review, we thoroughly analyze the complexities of PJI and emphasize the importance of accurate diagnosis and effective treatment. The article specifically focuses on the advancements in diagnostic techniques, ranging from traditional pathogen culture to advanced molecular diagnostics, and discusses their role in enhancing diagnostic accuracy. Additionally, we review the latest surgical management strategies, including everything from debridement to revision surgeries. Our summary aims to provide practical information for the diagnosis and treatment of PJI and encourages further research to improve diagnostic accuracy and treatment outcomes.Keywords: arthroplasty, periprosthetic joint infection, PJI, molecular diagnosis, pathogenesis diagnosis, antibiotic application, recurrence of infection

Wensheng Lu,1 JianFeng Wang,2 YuanJing Zhang,1 Ruixue Chang,1 Jun Zhao3 1Department of Dermatology, The No. 1 Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Dermatology, The No. 1 Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, People’s Republic of China; 3Department of Dermatology, The Lu’an Hospital Affiliated to Anhui Medical University, Lu’an, Anhui, People’s Republic of ChinaCorrespondence: Wensheng Lu; Jun Zhao, Email 492051693@qq.com; 13085092159@163.comIntroduction: This study observed the effectiveness of ustekinumab and reactivation risk of concurrent latent tuberculosis infection (LTBI) and inactive hepatitis B virus (HBV) infection in Chinese mainland psoriasis patients on ustekinumab treatment.Methods: This retrospective, multicenter, observational study was conducted in three centers in China. Adult patients with moderate to severe plaque psoriasis were treated with ustekinumab for 28 weeks. The effectiveness endpoint included 75% and 90% improvement in Psoriasis Area Severity Index (PASI75/90) response rate, percentage of PASI improvement, change of absolute PASI score and body surface area involvement (BSA) score, absolute PASI ≤ 1/3 and Physicians’ Global Assessment (PGA)=0/1, as well as Dermatology life quality index (DLQI)=0/1 response rate at week 4, 16 and 28. Screening of tuberculosis and hepatitis were performed at baseline and week 28.Results: A total of 82 patients were enrolled between March 2021 and May 2023 and the number of patients combined with LTBI and inactive HBV infection was 20 and 21 respectively. The PASI75 and PASI90 response rate at week 28 was 95.1% and 81.7% respectively. The mean PASI score decreased from 14.93 ± 12.07 at baseline to 0.78 ± 1.86 at week 28, and the mean BSA score decreased from 21% ± 18% at baseline to 1% ± 2% at week 28 (both P< 0.001 compared with baseline). DLQI 0/1 response rate at week 28 was 73.2%. No reactivation of LTBI and inactive HBV infection and also no new-onset tuberculosis and hepatitis B occurred in patients without LTBI and inactive HBV infection at baseline.Conclusion: Ustekinumab demonstrated great effectiveness in Chinese plaque psoriasis patients and good safety in psoriasis concurrent with LTBI and inactive HBV infection under the real-world setting.Keywords: ustekinumab, plaque psoriasis, real-world effectiveness, LTBI, inactive HBV infection

Jingwen Xu,1,2 Yue Zhang,1,2 Xiaolin Yao,1 Sijuan Wang,1,2 Kaiqiang Lv,1,2 Guangwen Luo,1,2 Jiaqi Wang,1,2 Guoliang Li1 1School of Food Science and Engineering, School of Biological and Pharmaceutical Sciences, Shaanxi University of Science & Technology, Xi’an, 710021, People’s Republic of China; 2Xi’an Key Laboratory of Antiviral and Antimicrobial-Resistant Bacteria Therapeutics Research, Xi’an, 710021, People’s Republic of ChinaCorrespondence: Guoliang Li, Email 61254368@163.comIntroduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging.Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release.Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1.Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res. Keywords: trans-resveratrol, seleno-alginate, synergistic antioxidant, mucoadhesion, intestinal targeted delivery

Miao-Miao Hua,1 Jia Li,2 Jie Zheng,2 Jing-Jing Wang,2 Chang Liu,2 Yan Zhang,2 Zhi-Feng Zhang,2 Xiao-Li Cao,1,2 Han Shen1,2 1Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China; 2Department of Laboratory Medicine, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, People’s Republic of ChinaCorrespondence: Xiao-Li Cao; Han Shen, Email cao-xiao-li@163.com; shenhan10366@sina.comObjective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital.Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays.Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates.Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.Keywords: Salmonella enteritidis, bloodstream infections, serovars, antibiotic-resistance genes, virulence factors, sequence type

Shuaiwei Song,1– 5,&ast; Xintian Cai,1– 5,&ast; Junli Hu,1– 5 Qing Zhu,1– 5 Di Shen,1– 5 Huimin Ma,1– 5 Yingying Zhang,1– 5 Rui Ma,1– 5 Wenbo Yang,1– 5 Jing Hong,1– 5 Delian Zhang,1– 5 Nanfang Li1– 5 1Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830001, People’s Republic of China; 2Xinjiang Hypertension Institute, Urumqi, Xinjiang, 830001, People’s Republic of China; 3NHC Key Laboratory of Hypertension Clinical Research, Urumqi, Xinjiang, 830001, People’s Republic of China; 4Key Laboratory of Xinjiang Uygur Autonomous Region ”Hypertension Research Laboratory”, Urumqi, Xinjiang, 830001, People’s Republic of China; 5Xinjiang Clinical Medical Research Center for Hypertension (Cardio-Cerebrovascular) Diseases, Urumqi, Xinjiang, 830001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nanfang Li, Hypertension Center of People’s Hospital of Xinjiang Uygur Autonomous Region, No. 91 Tianchi Road, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 8,564,818, Email lnanfang2016@sina.comObjective: While the role of aldosterone in bone metabolism is well established, the specific effects of the widely used aldosterone antagonist, spironolactone, on bone health are not fully understood. This study aimed to investigate the effects of spironolactone on osteoporosis and future fracture risk in middle-aged and elderly hypertensive patients, revealing its potential benefits for bone health.Methods: Propensity score matching was employed in this study to create matched groups of spironolactone users and non-users at a 1:4 ratio. We investigated the association between spironolactone use and the risk of osteoporosis using multivariate logistic regression analysis. Furthermore, we conducted multivariate linear regression analysis to explore the relationship between cumulative dosage and the FRAX score. Subgroup analysis was also performed to assess the effects under different stratification conditions.Results: In both pre-match and post-match analyses, multivariable logistic regression revealed a significant reduction in the risk of osteoporosis in the spironolactone usage group (pre-match: odds ratios [OR] 0.406, 95% confidence interval [CI], 0.280– 0.588; post-match: OR 0.385, 95% CI, 0.259– 0.571). Furthermore, post-match multivariable linear regression demonstrated a clear negative correlation between cumulative spironolactone dosage and the FRAX score. Subgroup analyses consistently supported these findings.Conclusion: This study offers evidence supporting the significant positive impact of the antihypertensive drug spironolactone on bone health, resulting in a substantial reduction in the risk of osteoporosis and future fractures in hypertensive patients. Future research should consider conducting large-scale, multicenter, randomized controlled trials to further investigate the long-term effects of spironolactone on bone health in hypertensive patients.Keywords: hypertensive, spironolactone, aldosterone, osteoporosis, FRAX score

Wenying Qiao,1– 3,&ast; Yiqi Xiong,1,&ast; Kang Li,4 Ronghua Jin,2,3 Yonghong Zhang1,5 1Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 3Changping Laboratory, Beijing, 102206, People’s Republic of China; 4Research Center for Biomedical Resources, Beijing You’an Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Beijing Research Center for Respiratory Infectious Diseases, Beijing, 100006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Zhang, Interventional Therapy Center for Oncology, Beijing You’an Hospital, Capital Medical University, 8 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, People’s Republic of China, Tel +86-13810108505, Email zhangyh@ccmu.edu.cn Ronghua Jin, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, People’s Republic of China, Tel +86-13811611118, Email ronghuajin@ccmu.edu.cnPurpose: We explored the role of tumor size and number in the prognosis of HCC patients who underwent ablation and created a nomogram based on machine learning to predict the recurrence.Patients and Methods: A total of 990 HCC patients who underwent transcatheter arterial chemoembolization (TACE) combined ablation at Beijing Youan Hospital from January 2014 to December 2021 were prospectively enrolled, including 478 patients with single small HCC (S-S), 209 patients with single large (≥ 30mm) HCC (S-L), 182 patients with multiple small HCC (M-S), and 121 patients with multiple large HCC (M-L). S-S patients were randomized in a 7:3 ratio into the training cohort (N=334) and the validation cohort (N=144). Lasso-Cox regression analysis was carried out to identify independent risk factors, which were used to construct a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves. Patients in the training and validation cohorts were divided into low-risk, intermediate-risk, and high-risk groups based on the risk scores of the nomogram.Results: The median recurrence-free survival (mRFS) in S-S patients was significantly longer than the S-L, M-S, and S-L patients (P< 0.0001). The content of the nomogram includes age, monocyte-to-lymphocyte (MLR), gamma-glutamyl transferase-to-lymphocyte (GLR), International normalized ratio (INR), and Erythrocyte (RBC). The C-index (0.704 and 0.71) and 1-, 3-, and 5-year AUCs (0.726, 0.800, 0.780, and 0.752, 0.761, 0.760) of the training and validation cohorts proved the excellent predictive performance of the nomogram. Calibration curves the DCA curves showed that the nomogram had good consistency and clinical utility. There were apparent variances in RFS between the low-risk, intermediate-risk, and high-risk groups (P< 0.0001).Conclusion: S-S patients who underwent ablation had the best prognosis. The nomogram developed and validated in the study had good predictive ability for S-S patients.Keywords: hepatocellular carcinoma, HCC, transcatheter arterial chemoembolization, TACE, ablation, nomogram, recurrence

Ying Wang,1,&ast; Yiyan Xu,2,&ast; Jiayu Song,1 Xueting Liu,1 Sijia Liu,1 Nan Yang,1 Le Wang,1 Yujie Liu,1 Yiwei Zhao,1 Wenhu Zhou,3,4 Yunyan Zhang1 1Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyan Zhang, Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13604843878, Fax +86 451 85718392, Email zhangyunyan@hrbmu.edu.cn Wenhu Zhou, Xiangya School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 15111469284, Fax +86 731 88710591, Email zhouwenhuyaoji@163.comPurpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Yuelin Zhang, Xue Lin, Xinxin Chen, Weixiang Fang, Kailing Yu, Wenting Gu, Yinghui Wei, Hangsheng Zheng, Jigang Piao, Fanzhu Li School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of ChinaCorrespondence: Fanzhu Li; Ji-Gang Piao, Email lifanzhu@zcmu.edu.cn; jgpiao@zcmu.edu.cnAbstract: Mesoporous silica nanoparticles (MSNs) have attracted extensive attention as drug delivery systems because of their unique meso-structural features (high specific surface area, large pore volume, and tunable pore structure), easily modified surface, high drug-loading capacity, and sustained-release profiles. However, the enduring and non-specific enrichment of MSNs in healthy tissues may lead to toxicity due to their slow degradability and hinder their clinical application. The emergence of degradable MSNs provided a solution to this problem. The understanding of strategies to regulate degradation and clearance of these MSNs for promoting clinical trials and expanding their biological applications is essential. Here, a diverse variety of degradable MSNs regarding considerations of physiochemical properties and doping strategies of degradation, the biodistribution of MSNs in vivo, internal clearance mechanism, and adjusting physical parameters of clearance are highlighted. Finally, an overview of these degradable and clearable MSNs strategies for biosafety is provided along with an outlook of the encountered challenges. Keywords: mesoporous silica nanoparticles, degradation, clearance, biodistribution, strategies

Yi Zhang,1,2,&ast; Zhang-Rui Liang,1,3,&ast; Yang Xiao,4 Yi-Shi Li,4 Bin-Jie Fu,1 Zhi-Gang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Radiology, Chongqing Jiangjin Second People’s Hospital, Chongqing Jiangjin Cancer Hospital, Chongqing, 402260, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 4Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin-Jie Fu; Zhi-Gang Chu, Department of Radiology, The First Affiliated Hospital of Chongqing Medical, University, 1&num; Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 18883851162 ; +86 18723032809, Fax +86 23 68811487, Email binjie_fu@163.com; chuzg0815@163.comPurpose: To explore the computed tomography (CT) features of bronchopneumonia caused by pepper aspiration to improve the diagnosis.Materials and Methods: 28 adult patients diagnosed with obstructive pneumonia caused by pepper aspiration from January 2016 to September 2022 were enrolled. The CT characteristics of bronchial changes and pulmonary lesions caused by pepper were analyzed and summarized.Results: Among 28 patients, the most common symptom was cough (26, 92.9%), followed by expectoration (23, 82.1%). Bronchoscopy revealed that peppers were mainly found in the bronchus of the right lower lobe (n = 18, 64.3%), followed by the bronchus of the left lower lobe (n = 5, 17.9%). In combination with bronchoscopy results, the pepper in the bronchus manifested as circular or V/U-shaped high-density, localized soft tissue, and flocculent opacification in 8 (28.6%), 16 (57.1%), and 3 (10.7%) cases on CT images, respectively. The bronchial wall around the pepper was thickened with localized occlusion (n = 19, 67.9%) and stenosis (n = 9, 32.1%). Regarding adjacent bronchi without peppers, extensive wall thickening with stenosis and/or occlusion was found in 23 (82.1%) cases. Distal pulmonary lesions frequently involved two or three segments (21, 75.0%) and mainly presented as patchy consolidation or atelectasis (24, 85.7%).Conclusion: In combination to a history of eating peppers and clinical symptoms, bronchopneumonia caused by pepper should be highly suspected if U/V-shaped and annular high-density or localized soft tissue density is detected in the bronchi of the lower lobes, accompanied by extensive bronchial wall thickening, stenosis, or occlusion, and consolidation or atelectasis in multiple distal lung segments.Keywords: obstructive pneumonia, foreign body, pepper, computed tomography

Zheping Chen,1,&ast; Changli Gao,1,2,&ast; Yingchao Zhang,1,3 Yongxu Gao,1,4 Le Zhang,1 Shanshan Zhao,1 He Zhang,1 Xin Zhao,1 Yanwu Jin1 1Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Anesthesiology, Laoling People Hospital, Laoling, People’s Republic of China; 3Department of Anesthesiology, Shouguang People Hospital, Weifang, People’s Republic of China; 4Department of Anesthesiology, Jinan Third People’s Hospital, Laoling, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanwu Jin, Department of Anesthesiology, the Second Hospital, Cheeloo College of Medicine, Shandong University, 247 Bei Yuan Street, Jinan, 250033, People’s Republic of China, Tel +86-17660085535, Email jinyanwu_aa@163.comBackground: Thoracic paravertebral block (TPVB) analgesia can be prolonged by local anesthetic adjuvants such as dexmedetomidine. This study aimed to evaluate the two administration routes of dexmedetomidine on acute pain and chronic neuropathic pain (NeuP) prevention compared with no dexmedetomidine.Methods: A total of 216 patients were randomized to receive TPVB using 0.4% ropivacaine alone (R Group), with perineural dexmedetomidine 0.5 μg·kg− 1 (RD0.5 Group) or 1.0 μg·kg− 1 (RD1.0 Group), or intravenous (IV) dexmedetomidine 0.5 μg·kg− 1·h− 1 (RDiv Group). The primary outcome was the incidence of chronic NeuP, defined as a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain score > 12 points at 3-month after surgery.Results: (1) For the primary outcome, RD0.5 Group and RD1.0 Group demonstrated a decreased incidence of chronic NeuP at 3-month after surgery; (2) Compared with R Group, RDiv Group, RD0.5 Group, and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of oral morphine equivalent (OME) and improve QOD-15 at POD1; (3) Compared with RDiv Group, RD0.5 Group and RD1.0 Group can reduce VAS scores at rest and movement and Prince-Henry Pain scores at 12 and 24-h after surgery, the consumption of postoperative OME and improve QOD-15 at POD1; (4) Compared with RD0.5 Group, RD1.0 Group effectively reduced VAS scores at rest at 12 and 24-h after surgery, VAS scores in movement and Prince-Henry Pain scores at 12-h after surgery. However, RD1.0 Group showed an increased incidence of drowsiness.Conclusion: Perineural or IV dexmedetomidine are similarly effective in reducing acute pain, but only perineural dexmedetomidine reduced chronic NeuP. Moreover, considering postoperative complications such as drowsiness, perineural dexmedetomidine (0.5 μg·kg− 1) may be a more appropriate choice.Clinical Trial Registration: Chinese Clinical Trial Registry (ChiCTR2200058982).Keywords: dexmedetomidine, thoracic paravertebral nerve block, neuropathic pain, thoracoscopic surgery

Jieyang Yu,1,2 Yanan Zhang,1 Lijia Cai,1 Qingqing Sun,1 Wanru Li,1 Junfang Zhou,1 Jianmin Liang,2 Zan Wang1 1Sleep Centre, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Jianmin Liang, Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email liangjm@jlu.edu.cn Zan Wang, Sleep Centre, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China, Email wangzan@jlu.edu.cn; wangzanprof@163.comPurpose: This study aimed to evaluate nocturnal sleep structure and anxiety, depression, and fatigue in patients with narcolepsy type 1 (NT1).Methods: Thirty NT1 patients and thirty-five healthy controls were enrolled and evaluated using the Epworth sleepiness scale (ESS), Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Fatigue Severity Scale (FSS), polysomnography, multiple sleep latency test, and brain function state monitoring. Statistical analyses were performed using SPSS Statistics for Windows, version 23.0. Benjamini-Hochberg correction was performed to control the false discovery rate.Results: Apart from typical clinical manifestations, patients with NT1 are prone to comorbidities such as nocturnal sleep disorders, anxiety, depression, and fatigue. Compared with the control group, patients with NT1 exhibited abnormal sleep structure, including increased total sleep time (Padj=0.007), decreased sleep efficiency (Padj=0.002), shortening of sleep onset latency (Padj< 0.001), elevated wake after sleep onset (Padj=0.002), increased N1% (Padj=0.006), and reduced N2%, N3%, and REM% (Padj=0.007, Padj< 0.001, Padj=0.013). Thirty-seven percent of patients had moderate to severe obstructive sleep apnea-hypopnea syndrome. And sixty percent of patients were complicated with REM sleep without atonia. Patients with NT1 displayed increased anxiety propensity (Padj< 0.001), and increased brain fatigue (Padj=0.020) in brain function state monitoring. FSS scores were positively correlated with brain fatigue (Padj< 0.001) and mean sleep latency was inversely correlated with FSS scores and brain fatigue (Padj=0.013, Padj=0.029). Additionally, ESS scores and brain fatigue decreased after 3 months of therapy (P=0.012, P=0.030).Conclusion: NT1 patients had abnormal nocturnal sleep structures, who showed increased anxiety, depression, and fatigue. Excessive daytime sleepiness and fatigue improved after 3 months of treatment with methylphenidate hydrochloride prolonged-release tablets in combination with venlafaxine.Keywords: narcolepsy, sleep structure, excessive daytime sleepiness, anxiety, depression, fatigue

Chunhua Wang,1 Haifeng Jin,1 Hua Xue,1 Yanwei Zhang2 1Department of Gastroenterology, Bethune International Peace Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Diagnostic Radiology, Bethune International Peace Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Chunhua Wang; Haifeng Jin, Department of Gastroenterology, Bethune International Peace Hospital, No. 398 Zhongshan West Street, Qiaoxi Disctrict, Shijiazhuang, Hebei, People’s Republic of China, Email crown99@126.com; jinhfhfjin@163.comPurpose: Hepatic portal venous gas is not a specific disease and is often only an imaging manifestation in patients with acute abdomen. However, its appearance often indicates serious disease and poor prognosis. It is not difficult to distinguish typical portal venous gas from biliary tract gas on computed tomography because of their relatively different distribution within the liver. But the difference is not absolute.Case Description: An 82-year-old female was admitted to the emergency department due to epigastric pain, nausea and vomiting for 1 day. Intrahepatic gas was found on computed tomography (CT), which was initially diagnosed as portal venous gas, and contrast-enhanced abdominal CT was performed 3 hours after the first plain CT scan and revealed a significant reduction of intrahepatic gas, then diagnosed as biliary tract gas. Two days later, enhanced abdominal CT showed that biliary tract gas had disappeared. Continuous gastrointestinal decompression, anti-infection, rehydration and other treatments were given. After treatment, abdominal pain, nausea, vomiting and other symptoms of the patient were gradually relieved. The patient refused gastroenteroscopy and was discharged after 13 days of hospitalization.Conclusion: Portal venous gas and biliary tract gas may have similar CT findings and be misdiagnosed, and enhanced CT examination is necessary to confirm the diagnosis.Keywords: hepatic portal venous gas, biliary tract gas, acute gastroenteritis, computed tomography, case report

Juan Bu,1 Yeledan Mahan,1 Yanmin Zhang,2 Shengnan Zhang,1 Xuanxia Wu,1 Xiaoling Zhang,1 Ling Zhou1 1Medical and Translational Research Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of China; 2Scientific Research and Education Center, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, People’s Republic of ChinaCorrespondence: Ling Zhou, Medical and Translational Research Center, People’s Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Tianshan District, Urumqi, Xinjiang, 830001, People’s Republic of China, Tel +86 991 8562 317, Email zlrmyy@sina.comBackground: Acacetin is a natural flavonoid known for its anti-tumor, antioxidant, and anti-inflammatory properties. Our previous studies have shown its protective effects against cerebral ischemia-reperfusion injury (IRI), but the underlying molecular mechanisms remain unclear.Purpose: The study delves into acacetin’s mechanism in mitigating cerebral IRI, with a focus on transcriptomic insights.Methods: We established the oxygen-glucose deprivation/re-oxygenation (OGD/R) model in BV2 microglia, treating them with 10μM acacetin. Then we assessed cell proliferation using CCK-8 and measured Lactate Dehydrogenase (LDH) release. High-throughput RNA sequencing (RNA-seq) underpinned the analysis of differentially expressed genes (DEGs) and long non-coding RNAs (lncRNAs), functional enrichment, and alternative splicing events (ASEs), validated by reverse transcription–quantitative polymerase chain reaction (RT-qPCR).Results: OGD/R injury significantly impaired cell proliferation and increased LDH release, effects mitigated by acacetin. RNA-seq identified 2148 upregulated and 2135 downregulated DEGs post-OGD/R. In contrast, the acacetin-treated group showed 248 upregulated and 240 downregulated DEGs compared to the OGD/R group. All DEGs were enriched in both Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Overlapping analysis indicated that acacetin treatment reversed the expression of 203 genes affected by OGD/R, including inflammation-related genes such as Isg15, Fcgr1, Il1b, and Parp12. Moreover, the oxidative stress-related gene, Mt2, was downregulated post-OGD/R but upregulated following acacetin treatment. We further found that OGD/R and acacetin treatment could modulate gene splicing events, impacting cell apoptosis or inflammatory responses, such as the A3SS splicing event in the Trim47 gene. RNA-seq also highlighted differential expression of numerous lncRNAs, particularly the upregulation of lncRNA Rmrp and Terc post-OGD/R and their subsequent downregulation post-acacetin treatment. These lncRNAs might regulate cell proliferation through mediating target gene expressions. RT-qPCR validation confirmed these findings.Conclusion: Significant upregulation of genes and ASEs linked to oxidative stress and inflammatory response is observed in cerebral IRI. Acacetin intervention reverses these effects, highlighting its mechanism in alleviating the injury by modulating gene expression and splicing events.Keywords: acacetin, ischemic stroke, inflammation, genome-wide analysis, differentially expressed genes, alternative splicing, long non-coding RNA, RNA sequencing

Gan Cao,1 Xiaoqi Yue,1 Shuhong Chi,2 Yanli Zhang1 1Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China; 2Department of Rheumatology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of ChinaCorrespondence: Yanli Zhang, Department of Pathogen Biology and Immunology, School of Basic Medical Sciences, Ningxia Medical University, 1160 Shengli Street, Yinchuan, Ningxia, 750004, People’s Republic of China, Tel/Fax +86951-6980122, Email zhangyl@nxmu.edu.cnBackground: Rheumatoid arthritis (RA) is a chronic autoimmune disease with abnormal differentiation of follicular helper T (Tfh) cells, Total alkaloids of Sophora alopecuroides Linn. (Leguminosae) (TASA) have potential effects on collagen-induced arthritis (CIA) mice, while the mechanism needs further elucidation. The purpose of this study is to explore the regulation of TASA on rheumatoid arthritis and related mechanism.Methods: The proportion of Tfh and B lymphocytes in peripheral blood lymphocytes of RA patients was examined by flow cytometry. We constructed the collagen induced arthritis DBA/1J mice model. Between days 15 and 45 following the first immunization, the mice were treated intraperitoneally with saline, TASA (100, 50, and 25 mg/kg), and dexamethasone (DXM) for 30 days. Molecular biological techniques such as FCM, PCR, ELISA, and Western-blotting were used to examine Tfh cells and associated signal pathways.Results: Our results indicated that the follicular helper T cells and B lymphocytes in rheumatoid arthritis patients were significantly increased compared with the healthy control. The percentage of Tfh cells are correlated with RA related inflammatory factors. Total alkaloids of Sophora alopecuroides Linn. could significantly attenuate joint swelling. Meanwhile, it reduced the frequencies of spleen Tfh, B lymphocytes and the expression of TLR2, TLR9, p-NF-κBp65, CXCR5, Bcl-6, ICOS of ankle joints in CIA mice.Conclusion: Total alkaloids of Sophora alopecuroides Linn. may down-regulate the frequency and function of Tfh cells and inhibit GCB cells via TLRs/NF-κB signal pathway to relieve the immune-pathological progression of CIA mice.Keywords: collagen-induced arthritis, C-X-C chemokine receptor type 5, total alkaloids of Sophora alopecuroides Linn., toll-like receptors

You Zhang,1,&ast; Chi Geng,1,&ast; Yulun Zhou,1,&ast; Feng Li,1 Siliang Peng,1 Xinru Guo,1 Xiaosong Gu,1 Jing Li,2 Hui Li1 1Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China; 2Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Li, Department of Cardiology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215006, People’s Republic of China, Email 9911263@163.com Jing Li, Department of Intensive Care Medicine, The First Affiliated Hospital of Soochow University, No. 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Email 18862130763@163.comBackground: Vascular adhesion protein-1 (VAP-1), an inflammation-inducible endothelial cell molecule, was reported to be implicated in a variety of cardiovascular diseases. However, the clinical significance of circulating VAP-1 levels in patients with coronary heart disease (CHD) remains less studied.Patients and Methods: We retrospectively analyzed clinical data of 336 hospitalized patients in the Second Affiliated Hospital of Soochow University from May 2020 to September 2022, 174 of which were diagnosed with CHD. Serum VAP-1 was measured by enzyme-linked immunosorbent assay at enrollment. The primary end point of this study was the occurrence of major adverse cardiovascular events (MACE). The coronary stenosis and clinical manifestations of CHD were assessed and recorded from medical records or follow-up calls. The relevant results were obtained, and the reliability of the conclusions was verified through regression analysis, curve fitting, and survival curve.Results: After adjusting for potential confounders, higher serum VAP-1 level was associated with increased risk of MACE in patients with CHD [(HR = 5.11, 95% CI = 1.02– 25.59), (HR = 5.81, 95% CI = 1.16– 29.11)]. The results of curve fitting and survival analysis were consistent with those of regression analysis. However, no significant association was observed between VAP-1 and MACE in the entire study population [(HR = 5.11, 95% CI = 0.41– 1.93), (HR = 1.17, 95% CI = 0.52– 2.62)]. Furthermore, the level of VAP-1 did not show a significant correlation with coronary stenosis and the clinical manifestations of CHD.Conclusion: These findings suggested that CHD patients with higher serum levels of VAP-1 are at a higher risk of adverse cardiovascular outcomes.Keywords: vascular adhesion protein-1, atherosclerosis, coronary heart disease, major adverse cardiovascular events

Yongchao Li,1,&ast; Jinfeng Gao,2,&ast; Shuhua Liu,1 Shijian Chen,3 Xiaoyue Wei,3 Yalun Guan,1 Xuejiao Li,1 Yunfeng Li,1 Zhongqiang Huang,1 Ge Li,1 Yuhong Zhao,3 Pinghua Liu,4 Yu Zhang1 1Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, 510663, People’s Republic of China; 2Guangdong Quality Supervision and Testing Station for Medical and Health Care Appliances, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou, 510632, People’s Republic of China; 3School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People’s Republic of China; 4Department of Chemistry, Boston University, Boston, MA, 02215, USA&ast;These authors contributed equally to this workCorrespondence: Yu Zhang; Pinghua Liu, Email zhangyugzh@hotmail.com; pinghua@bu.eduBackground: Ergothioneine (EGT) is an antioxidant, which could be detected in human tissues, and human skin cells could utilize EGT and play an anti-oxidative role in keratinocytes. And in this study we are going to elucidate whether EGT could protect the skin from photoaging by Ultraviolet (UV) exposure in mice and its molecule pathway.Methods: Histological analysis was performed for evaluating the skin structure change. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured with biological assay for evaluating oxidative and antioxidative ability of skin exposed to UV light. And the level of marker molecules in mouse skin were detected by hydroxyproline (Hyp) assay, immunohistochemical analysis, Western blot, and quantitative real-time PCR (qRT-PCR). The markers of skin aging and cell death were tested by cell culture and treatment, Western blot and qRT-PCR.Results: EGT decreased the levels of inflammatory factors induced by UV exposure in mouse skin. MDA and SOD activity detection showed that EGT decreased MDA levels, increased SOD activity, and upregulated PI3K/Akt/Nrf2 signals in mouse skin exposed to UV, which further activated Nrf2 in the nucleus and enhanced the expression of Nrf2 target genes. In the cell model, we revealed that EGT could inhibit the increase in senescence-associated β-galactosidase-positive cells and p16 and γ-H2A.X positive cells induced by etoposide and activate PI3K/Akt/Nrf2 signaling. Moreover, a PI3K inhibitor blocked EGT protection against etoposide-induced cell death.Conclusion: The study showed EGT may play an important protective role against cell damage or death through the PI3K/Akt/Nrf2 signaling pathway in skin.Keywords: ergothioneine, skin aging, PI3K/Akt, Nrf2

Hao Du,1 Wentao Li,1 Xueyi Li,2 Zhiyuan Qiu,1 Jie Ding,2 Yi Zhang1 1Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jie Ding; Yi Zhang, Email dingjie711@seu.edu.cn; yizhangcir@126.comBackground: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions—a phenomenon described as the “stealth effect”. In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored.Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA).Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site.Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted. Keywords: vascular stent, Poly-L-lactic acid, albumin, biomimetic coating, stealth effect

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

Jing-Xian Hu,1,&ast; Dong-Xia Wu,2,&ast; Xuan Wang,3,&ast; Yu-Ling Zhang,4 Hui-Min Guo,1 Jian-Hong Ma,2 Yun Zhang,2 Xiao-Jing Lian,5 Xin Wang,1 Lili Zhang1 1Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Infection, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 3Second Department of Hepatology Center for Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 4Department of Anesthesiology and Surgery, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 5Integrated Traditional Chinese and Western Medicine Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Zhang; Xin Wang, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmen Wai, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86 10 8399 7143, Email zhanglyliy@163.com; 13521101275@mail.ccmu.edu.cnObjective: To analyze the relevant research publications on infectious disease nursing in China to understand the current research status of infectious disease in nursing.Methods: Retrieve relevant literature on infectious disease in nursing from the establishment of the Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang Database until May 10, 2021. Conduct bibliometric analysis using CiteSpace software. Key words were analyzed using cluster analysis.Results: A total of 4693 relevant literature on infectious disease research in nursing care were included in this study. The overall number of publications on infectious disease research in nursing showed an increasing trend, with a peak in 2010. There were 324 papers funded by scientific research funds, mainly from provincial-level fund projects. The core journal with the most published articles was Nursing Research. The research on infectious disease in nursing mainly focused on various aspects of infectious disease in nursing and infection control. CiteSpace cluster analysis of keywords showed that a total of six clusters were formed: infectious diseases, infectious disease care, health education, mental health, infectious disease nurses, and etiology. After 2015, high-mutation keywords included “quality nursing” and “infection control”.Conclusion: Chinese research on infectious disease research in nursing closely follows clinical reality and has developed rapidly. Currently, research focuses on infectious disease research in nursing and infection control. Future research trends will further broaden the depth and breadth of the research, enhance research on infection control and quality nursing, and improve the breadth and depth of the research.Keywords: infectious disease in nursing, bibliometrics, CiteSpace, nursing care

Yixuan Zhang,1,&ast; Min Wang,2,&ast; Ting Zhang,3 Honghua Wang,2 Ying Chen,1 Tao Zhou,1 Rui Yang1 1Research Institute for Reproductive Medicine and Genetic Diseases, Wuxi Maternity and Child Health Care Hospital, Wuxi, 214002, People’s Republic of China; 2Center for Reproductive Medicine, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi, 214002, People’s Republic of China; 3Department of Laboratory Medicine, Wuxi Maternity and Child Health Care Hospital, Jiangnan University, Wuxi, 214002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Zhou; Rui Yang, Email zhoutao@njmu.edu.cn; ruiyang826@163.comAbstract: Sperm quality is declining dramatically during the past decades. Male infertility has been a serious health and social problem. The sperm cell driven biohybrid nanorobot opens a new era for automated and precise assisted reproduction. Therefore, it is urgent and necessary to conduct an updated review and perspective from the viewpoints of the researchers and clinicians in the field of reproductive medicine. In the present review, we first update the current classification, design, control and applications of various spermbots. Then, by a comprehensive summary of the functional features of sperm cells, the journey of sperms to the oocyte, and sperm-related dysfunctions, we provide a systematic guidance to further improve the design of spermbots. Focusing on the translation of spermbots into clinical practice, we point out that the main challenges are biocompatibility, effectiveness, and ethical issues. Considering the special requirements of assisted reproduction, we also propose the three laws for the clinical usage of spermbots: good genetics, gentle operation and no contamination. Finally, a three-step roadmap is proposed to achieve the goal of clinical translation. We believe that spermbot-based treatments can be validated and approved for in vitro clinical usage in the near future. However, multi-center and multi-disciplinary collaborations are needed to further promote the translation of spermbots into in vivo clinical applications. Keywords: assisted reproduction, biohybrid nanorobot, clinical translation, male infertility, spermbot

Donghao Wang,1,&ast; Yuting Zhang,1,&ast; Qiming Gan,1,&ast; Xiaofen Su,1,&ast; Haojie Zhang,1,2,&ast; Yanyan Zhou,1 Zhiyang Zhuang,1 Jingcun Wang,1 Yutong Ding,1 Dongxing Zhao,1 Nuofu Zhang1 1State Key Laboratory of Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2The Clinical Medicine Department, Henan University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nuofu Zhang; Dongxing Zhao, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Sleep Medicine Center, Guangzhou Institute of Respiratory Health, National Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-13600460056 ; +86-13650901411, Email nfzhanggird@163.com; rieast@163.comObjective: Compared to low arousal threshold (AT), high AT is an easily overlooked characteristic for obstructive sleep apnea (OSA) severity estimation. This study aims to evaluate the relationship between high AT, hypertension and diabetes in OSA, compared to those with apnea–hypopnea index (AHI).Methods: A total of 3400 adults diagnosed with OSA were retrospectively recruited. Propensity score matching (PSM) was conducted to further categorize these patients into the low and high AT groups based on the strategy established by previous literature. The different degrees of AHI and quantified AT (AT score) were subsequently measured. The correlation of AT and AHI with the occurrence of various comorbidities in OSA was estimated by logistic regression analysis with odds ratio (OR).Results: After PSM, 938 pairs of patients arose. The median AT score of high and low AT group was 21.7 and 12.2 scores, and the adjusted OR of high AT for hypertension and diabetes was 1.31 (95% CI = 1.07– 1.62, P < 0.01) and 1.45 (95% CI = 1.01– 2.08, P < 0.05), respectively. Compared to low AT score group, the OR significantly increased in patients with very high AT score (30 ≤ AT score), especially for diabetes (OR = 1.79, 95% CI = 1.02– 3.13, P < 0.05). The significant association was not observed in AHI with increasing prevalent diabetes.Conclusion: Higher AT is significantly associated with increased prevalence of hypertension and diabetes in patients with OSA. Compared with AHI, AT score is a potentially comprehensive indicator for better evaluating the relationship between OSA and related comorbidities.Keywords: obstructive sleep apnea, arousal threshold, apnea–hypopnea index, hypertension, diabetes

Yali Zhang,1 Ruohan Bu,1 Xiaoli Li2 1College of Education, Hebei Normal University, Shijiazhuang, 050024, People’s Republic of China; 2School of Educational Science, Zhengzhou Normal University, Zhengzhou, 450044, People’s Republic of ChinaCorrespondence: Xiaoli Li, School of Educational Science, Zhengzhou Normal University, Zhengzhou, 450044, People’s Republic of China, Email lixiaoli197302@163.comBackground: Short video apps are very popular among Chinese college students, and some students even rely on them. Most of the current research has focused only on Internet addiction and has seldom focused on the phenomenon of short video addiction. Its influencing factors and formation mechanism are worth exploring.Objective: This study aimed to explore the relationship between social exclusion and short video addiction among college students and the mediating roles of boredom and self-control.Methods: This study adopted a multistage investigation and investigated 532 college students (39% male; mean age 19.32 ± 1.23 years) with a social exclusion scale, boredom proneness scale, self-control scale, and short video addiction scale. The mediating effect was tested with Process 3.1.Results: The results showed that social exclusion has a positive predictive effect on college student’s short video addiction. The impact of social exclusion on college student’s short video addiction was mediated by boredom and self-control, and the chained mediation of boredom and self-control.Conclusion: Theoretically, this study modified the I-PACE model, indicating that personal and distant social factors should be considered in individuals with behavioral addictions, such as short video addiction. Practically, the results suggested that schools should reduce peer rejection and improve students’ mental health literacy to reduce boredom and enhance self-control, thus effectively preventing short video addiction.Keywords: social exclusion, boredom, self-control, short video addiction

Yating Zhang,1 Hongyan Wang,1 Jie Yang,2 Sanchun Wang,1 Weifang Tong,1 Bo Teng1 1Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of China; 2Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Bo Teng, Department of Otorhinolaryngology Head and Neck Surgery, the Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun, Jilin Province, 130000, People’s Republic of China, Email tengbo1975@163.comPurpose: This investigation sought to elucidate the genetic underpinnings that connect obesity indicators, circulating blood lipid levels, adipokines levels and obstructive sleep apnea syndrome (OSAS), employing a bidirectional two-sample Mendelian randomization (MR) analysis that utilizes data derived from extensive genome-wide association studies (GWAS).Methods: We harnessed genetic datasets of OSAS available from the FinnGen consortium and summary data of four obesity indices (including neck circumference), seven blood lipid (including triglycerides) and eleven adipokines (including leptin) from the IEU OpenGWAS database. We primarily utilized inverse variance weighted (IVW), weighted median, and MR-Egger methods, alongside MR-PRESSO and Cochran’s Q tests, to validate and assess the diversity and heterogeneity of our findings.Results: After applying the Bonferroni correction, we identified significant correlations between OSAS and increased neck circumference (Odds Ratio [OR]: 3.472, 95% Confidence Interval [CI]: 1.954– 6.169, P= 2.201E-05) and decreased high-density lipoprotein (HDL) cholesterol levels (OR: 0.904, 95% CI: 0.858– 0.952, P= 1.251E-04). Concurrently, OSAS was linked to lower leptin levels (OR: 1.355, 95% CI: 1.069– 1.718, P= 0.012) and leptin receptor levels (OR: 0.722, 95% CI: 0.530– 0.996, P= 0.047). Sensitivity analyses revealed heterogeneity in HDL cholesterol and leptin indicators, but further multiplicative random effects IVW method analysis confirmed these correlations as significant (P< 0.05) without notable heterogeneity or horizontal pleiotropy in other instrumental variables.Conclusion: This investigation compellingly supports the hypothesis that OSAS could be a genetic predisposition for elevated neck circumference, dyslipidemia, and adipokine imbalance. These findings unveil potential genetic interactions between OSAS and metabolic syndrome, providing new pathways for research in this domain. Future investigations should aim to delineate the specific biological pathways by which OSAS impacts metabolic syndrome. Understanding these mechanisms is critical for developing targeted prevention and therapeutic strategies.Keywords: sleep disorders, metabolic syndrome, causal inference, GWAS

Chenxi Yu,1,&ast; Yifeng Zhang,1,&ast; Hui Chen,2,&ast; Zhongli Chen,3 Ke Yang1 1Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China; 3State Key Laboratory of Cardiovascular Disease, Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ke Yang, Department of cardiovascular medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai, 200025, People’s Republic of China, Tel/Fax +86 21 64370045, Email ykk_ykkk@126.com Zhongli Chen, State Key Laboratory of Cardiovascular Disease, Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Tel/Fax +861088392295, Email zhonglichen555@126.comBackground: Aortic valve sclerosis (AVS) is a pathological state that can progress to aortic stenosis (AS), which is a high-mortality valvular disease. However, effective medical therapies are not available to prevent this progression. This study aimed to explore potential biomarkers of AVS-AS advancement.Methods: A microarray dataset and an RNA-sequencing dataset were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened from AS and AVS samples. Functional enrichment analysis, protein–protein interaction (PPI) network construction, and machine learning model construction were conducted to identify diagnostic genes. A receiver operating characteristic (ROC) curve was generated to evaluate diagnostic value. Immune cell infiltration was then used to analyze differences in immune cell proportion between tissues. Finally, immunohistochemistry was applied to further verify protein concentration of diagnostic factors.Results: A total of 330 DEGs were identified, including 92 downregulated and 238 upregulated genes. The top 5% of DEGs (n = 17) were screened following construction of a PPI network. IL-7 and VCAM-1 were identified as the most significant candidate genes via least absolute shrinkage and selection operator (LASSO) regression. The diagnostic value of the model and each gene were above 0.75. Proportion of anti-inflammatory M2 macrophages was lower, but the fraction of pro-inflammatory gamma-delta T cells was elevated in AS samples. Finally, levels of IL-7 and VCAM-1 were validated to be higher in AS tissue than in AVS tissue using immunohistochemistry.Conclusion: IL-7 and VCAM-1 were identified as biomarkers during the disease progression. This is the first study to analyze gene expression differences between AVS and AS and could open novel sights for future studies on alleviating or preventing the disease progression.Keywords: aortic stenosis, aortic valve sclerosis, diagnostic genes, machine learning, immune infiltration, immunohistochemistry

Xiaoliang Liu,1,&ast; Kecheng Lou,2,&ast; Yunmeng Zhang,3 Chuanxiao Li,1 Shenghong Wei,1 Shangzhi Feng1 1Department of Urology, Jiujiang University Clinic College/Hospital, Jiujiang, Jiangxi, People’s Republic of China; 2Department of Urology, Lanxi People’s Hospital, Jinhua, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, Jiujiang College Hospital, Jiujiang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shangzhi Feng, Email 1131718266@qq.comAbstract: Botanical preparations for herbal medicine have received more and more attention from drug researchers, and the extraction of active ingredients and their successful clinical application have become an important direction of drug research in major pharmaceutical companies, but the complexity of extracts, multiple side effects, and significant individual differences have brought many difficulties to the clinical application of herbal preparations. It is noteworthy that extracellular vesicles as active biomolecules extracted from medicinal plants are believed to be useful for the treatment of a variety of diseases, including cancer, inflammation, regenerative-restorative and degenerative diseases, which may provide a new direction for the clinical utilization of herbal preparations. In this review, we sort out recent advances in medicinal plant extracellular vesicles and discuss their potential as disease therapeutics. Finally, future challenges and research directions for the clinical translation of medicinal plant extracellular vesicles are also discussed, and we expect that continued development based on medicinal plant extracellular vesicles will facilitate the clinical application of herbal preparations.Keywords: plant-derived extracellular vesicles, Chinese medicine preparation, nanoparticle, drug delivery nanoplatforms, nanotherapeutics

Liying Ma,1,2 Yansong Gao,1 Ge Yang,1 Lei Zhao,2 Zijian Zhao,1 Yujuan Zhao,1 Yuhang Zhang,2 Shenhui Li,2 Shengyu Li1 1Institute of Agricultural Products Processing Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), Changchun, 130033, People’s Republic of China; 2School of Pharmaceutical Sciences, Changchun University of Chinese Medicine, Changchun, 130117, People’s Republic of ChinaCorrespondence: Shengyu Li, Institute of Agro-Food Technology, Jilin Academy of Agricultural Sciences (Northeast Agricultural Research Center of China), No. 1363 Sheng-Tai Street, Changchun, Jilin Province, 130033, People’s Republic of China, Tel +86 431 87063289, Fax +86 431 87063075, Email lisy720@126.comAim: The inflammatory response plays a pivotal role in the occurrence, progression, and plaque formation of atherosclerosis. The study was performed to investigate the impacts of notoginsenoside R1 on the development of atherosclerosis (AS) and the potential mechanisms.Methods: Rats induced with AS by a high-fat-diet and vitamin D3 were treated with notoginsenoside R1 for six weeks. The ameliorative effect of NR1 on AS rats was assessed by detecting pathological changes in the abdominal aorta, biochemical indices in serum and protein expression in the abdominal aorta, as well as by analysing the gut microbiota.Results: The NR1 group exhibited a noticeable reduction in plaque pathology. Notoginsenoside R1 can significantly improve serum lipid profiles, encompassing TG, TC, LDL, ox-LDL, and HDL. Simultaneously, IL-6, IL-33, TNF-α, and IL-1β levels are decreased by notoginsenoside R1 in lowering inflammatory elements. Notoginsenoside R1 can suppress the secretion of VCAM-1 and ICAM-1, as well as enhance the levels of plasma NO and eNOS. Furthermore, notoginsenoside R1 inhibits the NLRP3/Cleaved Caspase-1/IL-1β inflammatory pathway and reduces the expression of the JNK2/P38 MAPK/VEGF endothelial damage pathway. Fecal analysis showed that notoginsenoside R1 remodeled the gut microbiota of AS rats by decreasing the count of pathogenic bacteria (such as Firmicutes and Proteobacteria) and increasing the quantity of probiotic bacteria (such as Bacteroidetes).Conclusion: Notoginsenoside R1, due to its unique anti-inflammatory properties, may potentially prevent the progression of atherosclerosis. This mechanism helps protect the vascular endothelium from damage, while also regulating the imbalance of intestinal microbiota, thereby maintaining the overall health of the body. Keywords: notoginsenoside R1, inflammation, endothelial damage, gut microbiota

Mengnan Li,1,2,&ast; Xifeng Yang,1,2,&ast; Ru Li,1,2 Baofeng Wu,1,2 Jinxuan Hao,1,2 Yijie Qi,1,2 Tao Bai,1 Luyang Yang,1 Yi Zhang,3 Yunfeng Liu1,4 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China; 4Clinical Research Center of Endocrine and Metabolic Diseases in Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email yizhang313@163.comPurpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids.Patients and Methods: 50 patients with newly diagnosed Graves’ disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis.Results: The results showed that the following indexes changed significantly at different time points: visceral fat area, subcutaneous fat area, free triiodothyronine, free thyroxine, thyroid stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, body weight, neck circumference, body mass index, waist circumference, and drug dose (All P< 0.001). We found that free triiodothyronine and free thyroxine were significantly negatively associated with abdominal fat area (P< 0.01). There was no significant correlation between drug dose and abdominal fat area (P> 0.05). Total cholesterol and low-density lipoprotein were significantly positively associated with abdominal fat area (P< 0.01). However, high-density lipoprotein (P=0.06) was not correlated with abdominal fat area. Moreover, the results showed a significant negative correlation between thyroid hormones and lipids (P< 0.001).Conclusion: After anti-thyroid medicine treatment, patients had elevated visceral fat area and subcutaneous fat area and altered lipid profiles. These changes may be one of the reasons why metabolic and cardiovascular diseases remain increased after thyroid function is restored.Keywords: visceral fat area, subcutaneous fat area, thyroid hormones, lipids, Graves’ disease

Yunfang Zhang,1,&ast; Ming Zhang,2,&ast; Yuan Li,3 Huaji Wang3 1The Department of Oncology, Hainan Provincial Hospital of TCM, Haikou, Hainan, People’s Republic of China; 2Department of Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 3Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaji Wang; Yuan Li, Department of Cosmetic Dermatology, The Fifth People’s Hospital of Hainan Province, No. 8 Longhua Road, Longhua District, Haikou, Hainan, 570100, People’s Republic of China, Email 13876838737@163.com; liyuanskin@hotmail.comAbstract: Restricted pagetoid reticulosis, also known as Woringer-Kolopp disease, represents a rare cutaneous lymphoproliferative disorder categorized as an isolated variant of mycosis fungoides. This report presents a case involving limited pagetoid reticulosis affecting the right upper extremity in a 25-year-old female. The patient had been experiencing plaques on the right upper extremity for a decade. Dermatologic examination revealed well-defined scaly plaques on the right forearm, surrounded by hyperpigmented patches. Skin histopathology demonstrated atypical mononuclear cell infiltration in the lower part of the epidermis, forming nests. Immunohistochemistry indicated CD3+, CD4+, CD5+, CD7+, CD8+, CD30+, and Ki-67-positive staining. Additionally, CD20, CD79α, and PD-1 were negative. Monoclonal rearrangement of T-cells was identified in TCR β and TCR γ through clonality assessment. The diagnosis of limited paget-like reticulocyte hyperplasia was established, leading to surgical resection. A review of the literature affirmed the variable immunophenotype of pagetoid reticulosis, with atypical cells exhibiting four types: (1) CD3+, CD4+, CD8+-type; (2) CD3+, CD4-, CD8+-type; (3) CD3+, CD4-, CD8-type; and (4) CD3+, CD4+, CD8+-type—relatively uncommon in the restrictive type. This case report details the clinical features, histologic and morphologic characteristics, immunohistochemical phenotype, diagnosis, and differential diagnosis of a rare CD3+, CD4+, CD8+ limited pagetoid reticulosis. The lesion was surgically resected, and the patient underwent a 3-year follow-up to observe its prognosis.Keywords: pagetoid reticulosis, restricted type, tunica granulosa, CD4+, CD8+

Jiao Zhang,1,2 Yi Yin,3,4 Jiliang Tang,5 Yingrong Zhang,1,2 Yanan Tian,1,2 Fengkai Sun1,2,6 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Paediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 4Department of Paediatrics, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5Emergency Department, Rizhao Central Hospital, Rizhao, People’s Republic of China; 6College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of ChinaCorrespondence: Fengkai Sun, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jingwu Road 324&num;, Jinan, 250021, People’s Republic of China, Tel +86-531-68776902, Fax +86-531-68776072, Email sunfengkai2016@126.com; sunfengkai@sdfmu.edu.cnBackground: Effective biomarkers are needed to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy in hepatocellular carcinoma (HCC). We evaluated the early changes in serum interleukin-8 (IL-8) levels as a biomarker of response to ICIs in patients with unresectable HCC.Methods: Eighty patients who received ICIs therapy alone or in combination with other treatments for unresectable HCC were included. Serum was collected at baseline and 2– 4 weeks after the first dose. Serum IL-8 levels were measured using by ELISA.Results: In the progressive disease (PD) group, serum IL-8 levels increased significantly before the second dose of ICIs therapy compared with baseline levels (P < 0.001). Early changes in serum IL-8 levels were significantly associated with the response to ICIs therapy (P < 0.001). A cutoff value of 8.1% increase over the baseline most effectively predicted the response to ICIs. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy in patients with unresectable HCC. Patients with increases in serum IL-8 levels > 8.1% had significantly shorter overall survival (OS) and progression-free survival (PFS) than those with increases in serum IL-8 levels ≤ 8.1% (P < 0.001). Increases in serum IL-8 levels > 8.1% were independent prognosticators of worse OS (P = 0.003) and PFS (P < 0.001).Conclusion: Early changes in serum IL-8 levels, measured only 2– 4 weeks after starting therapy, could predict the response to ICIs therapy, as well as OS and PFS of patients with unresectable HCC. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy and predicted worse OS and PFS.Keywords: interleukin-8, immune checkpoint inhibitor, response, serum biomarker, hepatocellular carcinoma

Xinfang Cao, Jie Shao, Yonggang Zhang, Li Zheng, Jun Zhang Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Jun Zhang, Department of Ophthalmology, Hangzhou MSK Eye Hospital, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +86 571 85068587, Email zhangjun@mskyk.onaliyun.comPurpose: To examine the visual outcomes, particularly at 33 cm, and assess patient satisfaction following the implantation of a diffractive trifocal intraocular lens (IOL) and its toric variant.Patients and Methods: This prospective single-arm observational study involved 45 Chinese patients (90 eyes) underwent bilateral cataract surgery and PanOptix or PanOptix toric intraocular lenses (IOLs) implantation. Postoperatively, visual acuity was evaluated at various distances, including 40 cm and 33 cm, for both monocular and binocular outcomes. Patient satisfaction was evaluated using the VF-14 questionnaire.Results: 72 eyes underwent PanOptix IOLs implantation, and 18 eyes received PanOptix toric IOLs. At 3-month postoperative mark, the mean monocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were − 0.02± 0.09, 0.00± 0.07, 0.02± 0.07, and 0.07± 0.14 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 96.7%, 96.7%, 94.4%, and 74.4%, respectively. The mean binocular UDVA, UIVA, and UNVA at 40 cm and 33 cm were − 0.05± 0.06, − 0.03± 0.05, 0.00± 0.05, and 0.04± 0.07 logMAR, respectively, with proportions of visual acuity exceeding 0.1 logMAR were 97.8%, 100.0%, 100.0%, and 91.1%, respectively. When the near point shifted from 40cm to 33cm, some patients showed a decline for UDVA, but the average reduction was less than one line. The overall VF-14 questionnaire score was 4.02± 4.19.Conclusion: PanOptix can provide Chinese patients with a full range of satisfying visual acuity, near to 33cm. Though the visual acuity of some patients at 33 cm did not match the level at 40 cm, the gap of one line may not carry clinical significant.Keywords: trifocal IOL, PanOptix, visual acuity at 33 cm

Fanfan Zhao,1 Min Zhou,2 An Mao,3 Yingjiao Zhang,4 Yao Chen2 1Center for Rehabilitation Medicine, Department of Radiology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang Province, People’s Republic of China; 2Department of Radiology, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Outpatient, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Gastroenterology, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Yao Chen, Department of Radiology, 903 Hospital of the Joint Service Support Force of the Chinese People’s Liberation Army, Hangzhou, Zhejiang Province, People’s Republic of China, Email chenyao19970712@163.comBackground: Kimura disease (KD) is a rare chronic inflammatory disease that affects mainly young Asian men and is characterized by painless subcutaneous masses, lymphadenopathy, and elevated serum IgE levels. Despite its benign nature, KD poses a diagnostic and therapeutic challenge due to its rarity and clinical variability.Objective: This study aimed to provide a comprehensive analysis of the clinical and radiological features of KD in a retrospective case series, to assess treatment outcomes, and to discuss the implications for diagnosis and management.Methods: We retrospectively analyzed four histologically confirmed cases of KD admitted to Zhejiang Provincial People’s Hospital from January 2018 to October 2023. Clinical and radiological data were retrospectively analyzed, and imaging findings were analyzed by two neuroradiologists to determine lesion characteristics and contrast enhancement patterns.Results: Our findings showed that the patients were predominantly male, with a mean age of 43 years and an age range of 13– 71 years. All patients presented with painless subcutaneous masses and three of them had peripheral blood eosinophilia and elevated serum IgE levels. Radiographically, the lesions were predominantly ill-defined with heterogeneous enhancement, accompanied by subcutaneous fat atrophy. Complete surgical excision and oral corticosteroids were effective treatments, and no recurrence was noted during follow-up.Conclusion: KD should be considered in the differential diagnosis of painless subcutaneous masses in the head and neck region, especially in the presence of eosinophilia and elevated IgE levels. Our findings contribute to the understanding of KD’s clinical and radiological spectrum and highlight the need for long-term follow-up due to the risk of recurrence.Keywords: Kimura disease, computed tomography, CT, magnetic resonance imaging, MRI, eosinophilia

Zhengjun Ma,1 Yanmei Zhang,1 Yupu Zhu,2 Minxuan Cui,2 Yutao Liu,2 Yun-You Duan,1 Li Fan,2 Li Zhang1 1Department of Ultrasound Medicine, Tangdu Hospital, Air Force Medical University, Xi’an, People’s Republic of China; 2Department of Pharmaceutical Chemistry and Analysis, School of Pharmacy, Air Force Medical University, Xi’an, People’s Republic of ChinaCorrespondence: Li Fan; Li Zhang, Email xxfanny@fmmu.edu.cn; lilyzhang319_20@hotmail.comIntroduction: Recently, nanobubbles (NBs) have gained significant traction in the field of tumor diagnosis and treatment owing to their distinctive advantages. However, the application of NBs is limited due to their restricted size and singular reflection section, resulting in low ultrasonic reflection.Methods: We synthesized a nano-scale ultrasound contrast agent (IR783-SiO2NPs@NB) by encapsulating SiO2 nanoparticles in an IR783-labeled lipid shell using an improved film hydration method. We characterized its physicochemical properties, examined its microscopic morphology, evaluated its stability and cytotoxicity, and assessed its contrast-enhanced ultrasound imaging capability both in vitro and in vivo.Results: The results show that IR783-SiO2NPs@NB had a “donut-type” composite microstructure, exhibited uniform particle size distribution (637.2 ± 86.4 nm), demonstrated excellent stability (30 min), high biocompatibility, remarkable tumor specific binding efficiency (99.78%), and an exceptional contrast-enhanced ultrasound imaging capability.Conclusion: Our newly developed multiple scattering NBs with tumor targeting capacity have excellent contrast-enhanced imaging capability, and they show relatively long contrast enhancement duration in solid tumors, thus providing a new approach to the structural design of NBs.Keywords: ultrasound contrast agents, nanobubbles, CEUS, scattering cross-section, SiO2 NPs

Dawei Ren,1 Yan Zhang,1 Bo Du,1 Lina Wang,2 Meiheng Gong,1 Wei Zhu1 1Department of Otorhinolaryngology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pediatric Respiration, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Wei Zhu, Email zhuwei@jlu.edu.cnBackground: Electrical stimulation (ES) can effectively promote skin wound healing; however, single-electrode-based ES strategies are difficult to cover the entire wound area, and the effectiveness of ES is often limited by the inconsistent mechanical properties of the electrode and wound tissue. The above factors may lead to ES treatment is not ideal.Methods: A multifunctional conductive hydrogel dressing containing methacrylated gelatin (GelMA), Ti3C2 and collagen binding antimicrobial peptides (V-Os) was developed to improve wound management. Ti3C2 was selected as the electrode component due to its excellent electrical conductivity, the modified antimicrobial peptide V-Os could replace traditional antibiotics to suppress bacterial infections, and GelMA hydrogel was used due to its clinical applicability in wound healing.Results: The results showed that this new hydrogel dressing (GelMA@Ti3C2/V-Os) not only has excellent electrical conductivity and biocompatibility but also has a durable and efficient bactericidal effect. The modified antimicrobial peptides V-Os used were able to bind more closely to GelMA hydrogel to exert long-lasting antibacterial effects. The results of cell experiment showed that the GelMA@Ti3C2/V-Os hydrogel dressing could enhance the effect of current stimulation and significantly improve the migration, proliferation and tissue repair related genes expression of fibroblasts. In vitro experiments results showed that under ES, GelMA@Ti3C2/V-Os hydrogel dressing could promote re-epithelialization, enhance angiogenesis, mediate immune response and prevent wound infection.Conclusion: This multifunctional nanocomposite hydrogel could provide new strategies for promoting infectious wound healing. Keywords: MXene, GelMA, electrical stimulation, antimicrobial peptides, wound healing

Longjun Sun,1,&ast; Wenjuan Chen,2,&ast; Peixi Zhao,3 Bin Zhao,4 Guangyan Lei,1 Le Han,1,&ast; Yili Zhang2,&ast; 1Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 2Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 3Department of Department of Pharmacy, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 4Department of Epidemiology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Le Han, Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email millyhan1@sohu.com Yili Zhang, Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email doctor_z2023@stu.xjtu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is a common and deadly malignancy. Traditional Chinese medicine, such as the compound Astragalus (wild Baicalin), has shown promise in improving outcomes for HCC patients. This study aimed to investigate the effects of wild Baicalin on the human hepatoma cell line HepG2 and elucidate the underlying mechanisms, particularly the role of the AKR1B10 and PI3K/AKT signaling pathways.Methods: HepG2 cells were treated with varying concentrations of wild Baicalin. Cell proliferation, apoptosis, migration, invasion, and cell cycle were evaluated using CCK-8, flow cytometry, scratch, Transwell, and clonogenic assays, respectively. Transcriptome sequencing was performed to analyze gene expression changes induced by wild Baicalin. Differentially expressed genes were identified and analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The expression of AKR1B10 and PI3K was validated by qPCR.Results: Wild Baicalin inhibited HepG2 cell proliferation, induced apoptosis, suppressed migration and invasion, and caused cell cycle arrest in a dose-dependent manner. Transcriptome sequencing revealed 1202 differentially expressed genes, including 486 upregulated and 716 downregulated genes. GO analysis indicated that biological processes were pivotal in the anticancer mechanism of wild Baicalin, while KEGG analysis identified metabolic pathways as the most significantly regulated. AKR1B10 and PI3K, key genes in metabolic pathways, were downregulated by wild Baicalin, which was confirmed by qPCR.Discussion: The findings suggest that wild Baicalin exhibits potent anticancer effects against HepG2 cells by inducing apoptosis, inhibiting proliferation, migration, and invasion, and causing cell cycle arrest. The regulatory effects of wild Baicalin on the AKR1B10 and PI3K/AKT signaling pathways appear to be critical for its inhibitory effects on HCC cell proliferation. These results provide new insights into the mechanism of action of wild Baicalin and support its potential as a therapeutic approach for HCC treatment. Keywords: hepatocellular carcinoma, wild baicalin, transcriptome sequencing, apoptosis

Qiuyue Zhang,1– 5,&ast; Qi Zhang,6,&ast; Zhiyu Duan,2– 5,7 Pu Chen,2– 5 Jing-jing Chen,2– 5 Ming-xv Li,8 Jing-jie Zhang,9 Yan-hong Huo,10 Wu-xing Zhang,11 Chen Yang,12 Yu Zhang,12 Xiangmei Chen,2– 5 Guangyan Cai2– 5 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Key Laboratory of Kidney Diseases, Beijing, People’s Republic of China; 4National Clinical Research Center for Kidney Diseases, Beijing, People’s Republic of China; 5Beijing Key Laboratory of Kidney Diseases Research, Beijing, People’s Republic of China; 6Department of Nephrology, Capital Medical University Electric Power Teaching Hospital, Beijing, People’s Republic of China; 7Department of Nephrology, Fourth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 8Department of Nephrology, Sixth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 9Department of Nephrology, Third Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 10Department of Nephrology, Seventh Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 11Department of Nephrology, Eighth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 12School of Medicine, Nankai University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangyan Cai, Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Hospital 28 Fuxing Road, Beijing, 100853, People’s Republic of China, Email caiguangyan@sina.comPurpose: The International IgA Nephropathy Prediction Tool (IIgAN-PT) can predict the risk of End-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) decline ≥ 50% for adult IgAN patients. Considering the differential progression between older adult and adult patients, this study aims to externally validate its performance in the older adult cohort.Patients and Methods: We analyzed 165 IgAN patients aged 60 and above from six medical centers, categorizing them by their predicted risk. The primary outcome was a ≥ 50% reduction in estimated glomerular filtration rate (eGFR) or kidney failure. Evaluation of both models involved concordance statistics (C-statistics), time-dependent receiver operating characteristic (ROC) curves, Kaplan–Meier survival curves, and calibration plots. Comparative reclassification was conducted using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).Results: The study included 165 Chinese patients (median age 64, 60% male), with a median follow-up of 5.1 years. Of these, 21% reached the primary outcome. Both models with or without race demonstrated good discrimination (C-statistics 0.788 and 0.790, respectively). Survival curves for risk groups were well-separated. The full model without race more accurately predicted 5-year risks, whereas the full model with race tended to overestimate risks after 3 years. No significant reclassification improvement was noted in the full model without race (NRI 0.09, 95% CI: − 0.27 to 0.34; IDI 0.003, 95% CI: − 0.009 to 0.019).Conclusion: : Both models exhibited excellent discrimination among older adult IgAN patients. The full model without race demonstrated superior calibration in predicting the 5-year risk.Keywords: IgAN Progression, statistical validation, risk analysis, progression risk, prediction models, older adults

Peng Wu,1,&ast; Xiaoyong Wang,2,&ast; Min Yin,1,&ast; Wenjie Zhu,3,&ast; Zheng Chen,1 Yang Zhang,1 Ziyu Jiang,4 Longqing Shi,5 Qiang Zhu1 1Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2The People’s Hospital of Rugao, Nantong, People’s Republic of China; 3Kangda College of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210028, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Longqing Shi, Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China, Email 20204135017@stu.suda.edu.cn Qiang Zhu, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China, Email zhu20081023@yeah.netBackground: Liver cancer remains to be one of the leading causes of cancer worldwide. The treatment options face several challenges and nanomaterials have proven to improve the bioavailability of several drug candidates and their applications in nanomedicine. Specifically, chitosan nanoparticles (CNPs) are extremely biodegradable, pose enhanced biocompatibility and are considered safe for use in medicine.Methods: CNPs were synthesized by ionic gelation, loaded with rutin (rCNPs) and characterized by ultraviolet–visible spectroscopy (UV-Vis), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS) and transmission electron microscopy (TEM). The rCNPs were tested for their cytotoxic effects on human hepatoma Hep3B cells, and experiments were conducted to determine the mechanism of such effects. Further, the biocompatibility of the rCNPs was tested on L929 fibroblasts, and their hemocompatibility was determined.Results: Initially, UV–vis and FTIR analyses indicated the possible loading of rutin on rCNPs. Further, the rutin load was quantitatively measured using Ultra-Performance Liquid Chromatography (UPLC) and the concentration was 88 μg/mL for 0.22 micron filtered rCNPs. The drug loading capacity (LC%) of the rCNPs was observed to be 13.29 ± 0.68%, and encapsulation efficiency (EE%) was 19.55 ± 1.01%. The drug release was pH-responsive as 88.58% of the drug was released after 24 hrs at the lysosomal pH 5.5, whereas 91.44% of the drug was released at physiological pH 7.4 after 102 hrs. The cytotoxic effects were prominent in 0.22 micron filtered samples of 5 mg/mL rutin precursor. The particle size for the rCNPs at this concentration was 144.1 nm and the polydispersity index (PDI) was 0.244, which is deemed to be ideal for tumor targeting. A zeta potential (ζ-potential) value of 16.4 mV indicated rCNPs with good stability. The IC50 value for the cytotoxic effects of rCNPs on human hepatoma Hep3B cells was 9.7 ± 0.19 μg/mL of rutin load. In addition, the increased production of reactive oxygen species (ROS) and changes in mitochondrial membrane potential (MMP) were observed. Gene expression studies indicated that the mechanism for cytotoxic effects of rCNPs on Hep3B cells was due to the activation of Unc-51-like autophagy-activating kinase (ULK1) mediated autophagy and nuclear factor kappa B (NF-κB) signaling besides inhibiting the epithelial–mesenchymal Transition (EMT). In addition, the rCNPs were less toxic on NCTC clone 929 (L929) fibroblasts in comparison to the Hep3B cells and possessed excellent hemocompatibility (less than 2% of hemolysis).Conclusion: The synthesized rCNPs were pH-responsive and possessed the physicochemical properties suitable for tumor targeting. The particles were effectively cytotoxic on Hep3B cells in comparison to normal cells and possessed excellent hemocompatibility. The very low hemolytic profile of rCNPs indicates that the drug could be administered intravenously for cancer therapy.Keywords: rCNPs, Hep3B, ROS, qPCR, mechanism

Longfei Fan,1 Zhongqiang Qin,1 Di Wu,1 Yunchuan Yang,2 Yigang Zhang,2 Bo Xie,1 Jingyu Qian,1 Jianzhu Wei,1 Zhaoying Wang,1 Peipei Yang,1 Zhen Qian,1 Mu Yuan,1 Ziyi Zhu,1 Yulin Tan,1 Yi Tan2 1Department of Interventional Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of China; 2Department of Hepatobiliary Surgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu, 233000, People’s Republic of ChinaCorrespondence: Yi Tan, Email doctortanyi2007@126.comPurpose: To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC).Patients and Methods: The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators.Results: In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators.Conclusion: LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.Keywords: hepatocellular carcinoma, leucyl-tRNA synthetase 1, bioinformatics analysis, biomarker, the cancer genome atlas

Minmin Han,1,2,&ast; Xiaoming Cao,3,&ast; Jian Zhang,1,2 Xifeng Yang,1,2 Yi Zhang,4,5 Yunfeng Liu1,2 1Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 2First Clinical Medical College, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 3Department of Urology, First Hospital of Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 4Department of Pharmacology, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China; 5Medicinal Basic Research Innovation Center of Chronic Kidney Disease, Ministry of Education, Shanxi Medical University, Taiyuan, 030000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, No. 85, Jiefang Nan Road, Taiyuan, 030000, People’s Republic of China, Tel +86-18703416196, Fax +86-351-4639756, Email nectarliu@163.com Yi Zhang, Department of Pharmacology, Shanxi Medical University, No. 56, Xinjian Nan Road, Taiyuan, 030000, People’s Republic of China, Tel +86-18835102847, Fax +86-351-4135971, Email yizhang313@163.comPurpose: This study aimed to investigate the glycometabolism, fat mass, and lean mass in primary aldosteronism (PA) during disease progression.Patients and Methods: Patients diagnosed with PA and healthy controls (HCs) were enrolled. A flash glucose monitoring system (FGMS) and dual-energy X-ray absorptiometry (DEXA) were used to measure glucose variability and glucose target rate along with fat mass and lean mass. Comparative analysis of FGMS- or DEXA-derived parameters along with correlation analyses between these parameters and PA progression were performed.Results: Increased glucose variability and poor glucose target rate, along with an increased proportion of truncal fat mass, and decreased proportion of appendicular lean mass, were identified in PA group compared to those in HCs. Plasma aldosterone concentration was positively correlated with glucose variability and poor glucose target rate. Plasma renin concentration was positively correlated with the proportion of truncal fat mass and lean mass, and negatively correlated with the proportion of appendicular fat mass. Aldosterone-to-renin ratio was negatively correlated with the proportion of truncal fat mass and lean mass, and positively correlated with the proportion of appendicular fat mass.Conclusion: Patients with PA presented significant differences in glycometabolism, fat mass, and lean mass compared with HCs, and these alterations correlated with PA progression.Keywords: glucose variability, fat mass, lean mass, aldosterone, renin, ARR, correlation analysis

Jie Chen,1,&ast; Yan Xiao,2,&ast; Chaofang Yan,1 Xiaoju Li,1 Yafang Zhang,1 Ying Chen,1 Yuan Huang,1 Rui Deng1 1School of Public Health, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Foreign Languages Department, Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Deng; Yuan Huang, Email dengruirita@126.com; huangyuan@kmmu.edu.cnPurpose: With population aging, individuals in underdeveloped areas may experience a higher prevalence of chronic non-communicable diseases (NCDs), a lower level of health-related quality of life (HRQoL), and distinct lifestyles. However, this triadic association remains inadequately studied, particularly regarding the role of health lifestyle. This study aims to examine the relationship between the number of NCDs and HRQoL, while considering the moderating effect of health lifestyle among middle-aged and older adults residing in resource-limited areas.Methods: This cross-sectional study was conducted in Yunnan Province from July to December 2022. Participants completed a self-report questionnaire related to socio-demographic information, NCDs conditions, health lifestyle status, and HRQoL, which was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) scale. Hierarchical regression and simple slope tests were used to examine the moderating effect of health lifestyle.Results: Out of the total 2704 participants, 57.91% presented at least one NCD. The mean scores for health lifestyle and health utility value were 11.109 and 0.944 respectively. The number of NCDs was negatively associated with health utility value, while positively correlated with the health lifestyle score (P< 0.001). The results of hierarchical regression indicated that health lifestyle exerted a negative moderating effect on the relationship between the number of NCDs and HRQoL (β=0.006, P< 0.001), which was also observed for specific health-related behaviors such as sleep duration (β=0.013, P< 0.001), physical examination attendance (β=0.006, P< 0.05) and physical activity (β=0.013, P< 0.001).Conclusion: These findings highlight the crucial role of a healthy lifestyle in attenuating the association between the number of NCDs and HRQoL. Recognizing the potential modulating influence of a healthy lifestyle in this relationship could be pivotal for developing effective interventions for this population, even within resource-constrained rural settings.Keywords: chronic non-communicable diseases, health-related quality of life, health lifestyle, health-related behavior, rural, moderating effect

Yonggui Zhang,1 Xianzhong Lin,2 Chen Ye,2 Peiling Zhang3 1Department of Anesthesiology, The Second Hospital of Longyan, Fujian, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, People’s Republic of ChinaCorrespondence: Xianzhong Lin, Department of Anesthesiology, the First Affiliated Hospital of Fujian Medical University, 20 Chazhong Road, Fuzhou, People’s Republic of China, Email lxzyjs@fjmu.edu.cnBackground: With the aging of the population and the increasing incidence of neurological diseases, amnestic mild cognitive impairment (aMCI) has attracted attention. Hyperbaric oxygen (HBO) has gradually shown the potential in the treatment of aMCI as an emerging treatment method in recent times. This study is to observe the effect of HBO on the long-term learning memory of aMCI rats, and investigate the associated mechanisms.Methods: Seventy-two male rats (4-month-old) were randomly divided into control (CON) group, aMCI group, HBO group, 24 rats in each group. Each group was randomly divided into CON1, CON7, CON28; aMCI1, aMCI7, aMCI28; HBO1, HBO7, HBO28, 8 rats in each group. The aMCI model rats were established in aMCI and HBO groups. HBO group was treated with HBO for 7 days. The ethological and cytopathology which include Morris water maze (MWM) test, HE staining, TUNEL staining and the expression of Fas/FasL on neuron membrane were conducted to evaluate the effects of HBO on day 1, day 7 and day 28 after HBO treatment.Results: MWM test showed that the spatial learning and memory ability of the rats decreased in aMCI group, and recovered in HBO group; Compared with aMCI group, the pathological damage of hippocampal nerve cells was alleviated, the number of apoptotic cells was significantly reduced (P < 0.05), and the expression of Fas/FasL on the surface of nerve cell membrane was significantly weakened in HBO group (P < 0.05). There were no significant changes in the spatial learning and memory ability, pathological damage of hippocampal neurons, the number of apoptotic cells, and the changes of Fas/FasL on the surface of hippocampal neurons in HBO1, HBO7, and HBO28 groups (P > 0.05). However, in aMCI1, aMCI7, and aMCI28 groups gradually aggravated (P < 0.05).Conclusion: 1. HBO can improve the long-term learning and memory impairment by attenuating neuronal apoptosis in aMCI rats. 2. Fas/FasL mediated cell receptor death pathway is involved in the apoptosis of hippocampal neurons.Keywords: amnesic mild cognitive impairment, hyperbaric oxygen, apoptosis, learning and memory impairment

Jiawen Hu,1,2 Yiwen Wang,1 Xiaojian Ji,1 Yinan Zhang,1 Kunpeng Li,1 Feng Huang1 1Department of Rheumatology and Immunology, First Medical Center of Chinese PLA General Hospital, Beijing, China; 2Medical School of Chinese PLA, Beijing, ChinaCorrespondence: Feng Huang, Department of Rheumatology and Immunology, First Medical Center of Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, 100853, China, Email frankfhuang@126.comAbstract: This article focuses on a range of non-pharmacological strategies for managing sarcopenia in chronic diseases, including exercise, dietary supplements, traditional Chinese exercise, intestinal microecology, and rehabilitation therapies for individuals with limited limb movement. By analyzing multiple studies, the article aims to summarize the available evidence to manage sarcopenia in individuals with chronic diseases. The results strongly emphasize the role of resistance training in addressing chronic diseases and secondary sarcopenia. Maintaining the appropriate frequency and intensity of resistance training can help prevent muscle atrophy and effectively reduce inflammation. Although aerobic exercise has limited ability to improve skeletal muscle mass, it does have some positive effects on physical function. Building upon this, the article explores the potential benefits of combined training approaches, highlighting their helpfulness for overall quality of life. Additionally, the article also highlights the importance of dietary supplements in combating muscle atrophy in chronic diseases. It focuses on the importance of protein intake, supplements rich in essential amino acids and omega-3, as well as sufficient vitamin D to prevent muscle atrophy. Combining exercise with dietary supplements appears to be an effective strategy for preventing sarcopenia, although the optimal dosage and type of supplement remain unclear. Furthermore, the article explores the potential benefits of intestinal microecology in sarcopenia. Probiotics, prebiotics, and bacterial products are suggested as new treatment options for sarcopenia. Additionally, emerging therapies such as whole body vibration training, blood flow restriction, and electrical stimulation show promise in treating sarcopenia with limited limb movement. Overall, this article provides valuable insights into non-pharmacological strategies for managing sarcopenia in individuals with chronic diseases. It emphasizes the importance of a holistic and integrated approach that incorporates exercise, nutrition, and multidisciplinary interventions, which have the potential to promote health in the elderly population. Future research should prioritize high-quality randomized controlled trials and utilize wearable devices, smartphone applications, and other advanced surveillance methods to investigate the most effective intervention strategies for sarcopenia associated with different chronic diseases.Keywords: sarcopenia, resistance training, nutrition, chronic disease, inflammation

Gang Fan,1,&ast; Jingfen Lu,2,&ast; Jinhui Zha,3,&ast; Weiming Guo,1 Yifei Zhang,4 Yuxin Liu,5 Liyuan Zhang1 1Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, People’s Republic of China; 2The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 510006, People’s Republic of China; 3Shenzhen University, Shenzhen, 518000, People’s Republic of China; 4The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, People’s Republic of China; 5College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyuan Zhang; Gang Fan, Department of Urology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518000, People’s Republic of China, Email liyuan.zhang@uszh.org.cn; gang.fan.med@qq.comAbstract: The maintenance of normal vascular function and homeostasis is largely dependent on the signaling mechanisms that occur within and between cells of the vasculature. TGF-β-activated kinase 1 (TAK1), a multifaceted signaling molecule, has been shown to play critical roles in various tissue types. Although the precise function of TAK1 in the vasculature remains largely unknown, emerging evidence suggests its potential involvement in both physiological and pathological processes. A comprehensive search strategy was employed to identify relevant studies, PubMed, Web of Science, and other relevant databases were systematically searched using keywords related to TAK1, TABs and MAP3K7.In this review, we discussed the role of TAK1 in vascular signaling, with a focus on its function, activation, and related signaling pathways. Specifically, we highlight the TA1-TABs complex is a key factor, regulating vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) involved in the processes of inflammation, vascular proliferation and angiogenesis. This mini review aims to elucidate the evidence supporting TAK1 signaling in the vasculature, in order to better comprehend its beneficial and potential harmful effects upon TAK1 activation in vascular tissue.Keywords: TGF-β-activated kinase 1, vascular disease, mitogen-activated protein kinase, transforming growth factor-β, smooth muscle cell, endothelial cell

Siyao Wang,1 Yong Zhang,1,2 Xiaoya Qi,1 Xiaoyang Xu1 1Health Medicine Center, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, People’s Republic of China; 2School of Public Health, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xiaoyang Xu, Health Medicine Center, The Second Hospital Affiliated to Chongqing Medical University, Chongqing, People’s Republic of China, Email 302500@hospital.cqmu.edu.cnPurpose: Disagreements about the risk of non-obese, non-alcoholic fatty liver disease for cardiometabolic outcomes occurred widely. This study aims to characterize the cardiometabolic and metabolic profile of lean/normal, overweight and obese patients with nonalcoholic fatty liver disease on a big sample.Patients and methods: Appeared healthy adults who participated in health examinations during the year of 2019– 2022 were screened for fatty liver diagnosis. BMI classified fatty livers as lean, overweight and obese. Eleven cardiometabolic metrics (SBP: systolic blood pressure; DBP: diastolic blood pressure; TC: total cholesterol; TG: triglycerides; HDL: high-density lipoprotein cholesterol; LDL: low-density lipoprotein cholesterol) and metabolic metrics (GLU: blood glucose; GHB: glycated haemoglobin; UA: uric acid; AST: aspartate aminotransferase; ALT: alanine aminotransferase) were included, described and compared among BMI categories.Results: There were 56,496 fatty livers diagnosed by ultrasound in this study. In total, the lean fatty liver had lowest mean SBP, DBP, GLU, TG, UA, AST, and ALT but highest TC and HDL among BMI categories (all p < 0.001). The number of abnormal metrics in total was 2.5, 2.9 and 3.4 in lean, overweight, and obesity, respectively (p < 0.001, p_trend < 0.001). Visualized data showed that lean fatty liver was similar but milder in all metabolic metrics than overweight and obesity at the young ages. However, lean fatty liver had higher coefficients of age and risk of metabolic abnormality regression (p < 0.001 for SBP, DBP, GLU, GHB, TC).Conclusion: The lean type of fatty livers at a younger age has a relatively favourable cardiometabolic and metabolic profile compared to overweight and obese fatty livers. Due to the possible catch-up effect of metabolic dysfunctions in young lean fatty liver, lean fatty liver may have the same health outcomes as overweight/obesity fatty liver in long term. The evaluation and intervention may be critical for young lean fatty liver management to slowdown the rapid progress of metabolic dysfunction.Keywords: fatty liver, cardiometabolic profile, metabolic profile, body mass index