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Jiamin Long,1,2,* Jiali Chen,3,* Yue Yuan,4,* Shaozhen Yang,5,* Xinya Xie,1,2 Xuelian Wu,1,2 Yuan Liu,1,2 Jinpeng Guo,2 Yong Chen,1,2 Changjun Wang,1,2 Xiong Liu2 1School of Public Health, China Medical University, Shenyang, 110122, People’s Republic of China; 2Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, People’s Republic of China; 3School of Medicine, NanKai University, Tianjin, 300071, People’s Republic of China; 4Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 5School of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiong Liu; Changjun Wang, Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, People’s Republic of China, Email liuxiong714@163.com; science2008@hotmail.comBackground: Klebsiella michiganensis is an emerging human pathogen that causes nosocomial infections. Its prevalence and spread in the environment should not be ignored. This study identified and characterized Klebsiella michiganensis co-harboring blaKPC-2 and TmexCD2-ToprJ2 in hospital wastewater samples.Methods: Twelve K. michiganensis strains were isolated from wastewater samples collected at a tertiary hospital in Beijing, China. The genomic characteristics of K. michiganensis strains were analyzed using whole-genome sequences, providing information on the comparison between the genome of K. michiganensis strains and the reference genome, antibiotic resistance genes (ARGs), virulence genes, secretion systems, and mobile genetic elements (plasmids, insertion sequences [ISs], and prophages).Results: Genome analysis showed that the twelve multi-drug resistant (MDR) strains carried a variety of ARGs and virulence genes, as well as four macromolecular secretion systems (T1SS, T2SS, T5aSS, T5bSS, and T4aP). The genetic environments of both the TmexCD2-ToprJ2 gene cluster and blaKPC-2 gene contained ISs. The plasmids carrying TmexCD2-ToprJ2 gene cluster of nine strains in clade 1 and two strains in clade 2 were annotated as IncR plasmid and rep_cluster_1254 type, respectively. The plasmids carrying blaKPC-2 in 10 strains in clade 1 were identified as IncU, and the plasmids carrying blaKPC-2 in the k11 and k12 strains in clade 2 were IncU and IncX6. The phylogenetic tree and heatmap revealed that the secretion system of type VI (T6SSi) existed in 10 strains in clade 1, and Type IV (T4SS) only existed in the k11 strain in clade 2. In addition, K. michiganensis strains carried 13 plasmids, 14 ISs, and 138 prophages.Conclusion: In this study, the whole genome sequencing demonstrated the diversity of K. michiganensis genome despite 12 K. michiganensis strains from a hospital wastewater, which lays the foundation for further genetic research and drug resistance gene transmission.Keywords: Klebsiella michiganensis, hospital wastewater, whole-genome sequencing, blaKPC-2, TmexCD2-ToprJ2

Lin Chen,1,* Zhan Zhang,2,* Xueyong Liu1 1Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xueyong Liu, Department of Rehabilitation, Shengjing Hospital of China Medical University, No. 16, Puhe Street, Shenyang, Liaoning, People’s Republic of China, Tel +86 18940112266, Email liusjh@sj-hospital.orgAbstract: Osteoarthritis (OA) is one of the most prevalent degenerative joint diseases, and the knee joint is particularly susceptible to it. It typically affects the entire joint and is marked by the erosion of cartilage integrity, chondrocytopenia, subchondral bone sclerosis and the mild synovial inflammation. Pathological changes in the subchondral bone often serve as initiating factors for joint degeneration. Various predisposing factors, including metabolic disorders, oxidative stress, and abnormal mechanical loading, regulate OA pathogenesis. Of them, mechanical loading is closely associated with the maintenance of the subchondral bone. Disrupted mechanical loading, leading to subchondral bone remodeling, can potentially trigger OA, whereas appropriate loading might ameliorate its progression. Therefore, this narrative review aimed to discuss existing knowledge and explore how mechanical loading mediates changes in the subchondral bone, influencing the development of knee osteoarthritis. Special emphasis is placed on its role and underlying mechanisms in maintaining joint homeostasis.Keywords: mechanical load, bone remodeling, homeostasis, osteogenic differentiation

Yongfeng Fan, Xiulun Liu, Zhongkui Li, Daokang Xiang Department of Cardiac Surgery, Guizhou Provincial People’s Hospital, Guizhou, 550499, People’s Republic of ChinaCorrespondence: Daokang Xiang, Email dao57115973@163.comObjective: To investigate the impact of surgical intervention on hemodynamic parameters and postoperative delirium in Stanford Type A aortic dissection patients.Methods: A retrospective analysis was conducted on 139 patients who underwent surgery for Stanford Type A aortic dissection from February 2022 to February 2024. Hemodynamic parameters, including maximum ascending aortic diameter (MAAD), left ventricular end-diastolic diameter (LVEDd), and ejection fraction (LVEF), were compared pre- and post-surgery. Patients were divided into two groups based on delirium occurrence postoperatively: Group A (n=49, with delirium) and Group B (n=90, without delirium). Differences in surgical factors and intensive care conditions were analyzed, and risk factors for postoperative delirium were identified. Group sizes differ due to retrospective categorization based on observed outcomes rather than controlled sampling.Results: ① Hemodynamic parameters: Postoperative MAAD and LVEDd were significantly reduced, while LVEF increased compared to preoperative levels (P < 0.05). ② Surgical and postoperative conditions: Group A had longer surgery, cardiopulmonary bypass, and deep hypothermic circulatory arrest times than Group B (P < 0.05). ③ Univariate analysis of baseline data: Group A had higher rates of patients aged ≥ 60, hypertension, history of stroke, and elevated preoperative D-dimer levels (P < 0.05). ④ Multivariate logistic analysis: Independent risk factors for postoperative delirium included age ≥ 60, hypertension, history of stroke, surgery time > 6 hours, cardiopulmonary bypass time > 3 hours, and deep hypothermic circulatory arrest time > 40 minutes (OR > 1, P < 0.05).Conclusion: Surgical treatment of Stanford Type A aortic dissection has a good effect, significantly improving long-term cardiac function. However, the incidence of postoperative delirium is relatively high and is closely related to factors such as age, hypertension, history of stroke, surgery time, cardiopulmonary bypass time, and deep hypothermic circulatory arrest time.Keywords: Stanford Type A aortic dissection, surgical intervention, hemodynamic parameters, postoperative delirium, impact, investigation

Xiangjun Chen,&ast; Weiwei Li,&ast; Qing Fan, Xiao Liu, Xuanxiang Zhai, Xiaoyi Shi, Wenting Li, Wei Hong School of Pharmacy, Shandong Engineering Research Center of New-Type Drug Loading & Releasing Technology and Preparation, Binzhou Medical University, Yantai, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Hong; Wenting Li, Email hongwei_sy@bzmc.edu.cn; liwenting1003@163.comIntroduction: Pseudomonas aeruginosa (P. aeruginosa)-induced pneumonia is marked by considerable infiltration of inflammatory cells and biofilm formation, which causes acute and transient lung inflammation and infection. Nevertheless, the discovery of alternative preventative and therapeutic methods is essential due to the high mortality rates in clinical settings and the resistance of P. aeruginosa infection to multiple medications.Purpose: In this research, we constructed amphiphilic Janus nanoparticles (JNPs, denoted as SSK1@PDA/CaP@CIP), loaded with hydrophobic SSK1, a β-galactosidase (β-gal)-activated prodrug for reducing macrophages, and hydrophilic ciprofloxacin (CIP), a classic antibiotic for treating infection. SSK1@PDA/CaP@CIP was designed to effectively attenuate inflammation, eradicate biofilms, and combat planktonic P. aeruginosa.Results: As expected, SSK1@PDA/CaP@CIP was able to target the infection site and demonstrated outstanding efficacy in treating P. aeruginosa strain PAO1-induced pneumonia by regulating macrophage infiltration to reduce inflammation and removing planktonic bacteria and biofilms to control infection. Additionally, the primary organs did not exhibit any discernible pathological changes following treatment with SSK1@PDA/CaP@CIP, which indicates superior biocompatibility throughout the treatment course.Discussion: In conclusion, our investigation introduced a promising approach to the treatment of pneumonia associated with PAO1.Keywords: Pseudomonas aeruginosa, pneumonia, inflammatory responses, β-galactosidase (β-gal)-activated prodrug, amphiphilic Janus nanoparticles

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

Shuai Tang,1– 4 Wenyu Feng,2– 4 Zekun Li,1 Xinjuan Liu,1 Tong Yang,1– 4 Fulan Wei,2– 4 Gang Ding1 1School of Stomatology, Shandong Second Medical University, Weifang, Shandong, 261053, People’s Republic of China; 2Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Shandong Key Laboratory of Oral Tissue Regeneration, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Gang Ding, School of Stomatology, Shandong Second Medical University, Baotong West Street No. 7166, Weifang, Shandong, 261053, People’s Republic of China, Email dinggang@sdsmu.edu.cn Fulan Wei, Department of Orthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Wenhua West Road No. 44-1, Jinan, Shandong, 250012, People’s Republic of China, Email weifl@sdu.edu.cnIntroduction: Inflammatory bowel disease is a complex chronic inflammatory condition characterized by dysbiosis of the gut microbiota and dysregulation of immune system. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells have garnered significant attention for their beneficial potentials in immune modulation and tissue repair. This study aims to evaluate the therapeutic effects and underlying mechanisms of EVs derived from lipopolysaccharide (LPS)-pretreated periodontal ligament stem cells (PDLSCs) in mice with colitis.Methods: A mouse model of colitis was established using 3.0% dextran sulfate sodium (DSS). Following the induction of colitis, mice were treated via tail vein injection with either conventional PDLSC-derived EVs (P-EVs) or LPS-pretreated PDLSC-derived EVs (LPS pre-EVs). The EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and Western blot analysis. The therapeutic effects and mechanisms were evaluated through a combination of small animal live imaging, disease activity index (DAI) scoring, histopathological staining, qRT-PCR, 16S rRNA gene sequencing, and mass spectrometry analysis.Results: The LPS pre-EVs exhibited typical EVs characteristics in terms of morphology, particle size distribution, and marker protein expression. Compared to P-EVs, LPS pre-EVs significantly ameliorated weight loss, DAI scores, colon length, and perianal symptoms in DSS-induced murine colitis. Additionally, LPS pre-EVs up-regulated the expression of Arginase-1, a typical M2 macrophage marker, and tight junction proteins, including ZO-1, Occludin, and Claudin-1, enhanced gut microbial diversity, and significantly regulated intestinal protein expression and activation of the PI3K/AKT signaling pathway.Conclusion: LPS pre-EVs exhibit significant anti-inflammatory and tissue repair effects in a mouse model of colitis. The underlying mechanisms may involve the regulation of macrophage polarization, maintenance of intestinal barrier function, modulation of the gut microbiota, and activation of the PI3K/AKT signaling pathway. Keywords: inflammatory bowel disease, periodontal ligament stem cells, extracellular vesicles, gut microbiota, PI3K/AKT signaling pathway

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

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

Shuang Wang,1– 4,&ast; Xuexia Liu,5 Xinhua Lin,1– 4,&ast; Xiaojing Lv,2– 4 Hua Zhang2– 4 1School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 4Yantai Key Laboratory of Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Qingdao University, Yantai, People’s Republic of China; 5Shandong Stem Cell Engineering Technology Research Center, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuexia Liu; Hua Zhang, Department of Otorhinolaryngology & Head and Neck Surgery, Yuhuangding Hospital Affiliated to Qingdao University, No. 20 East, Yuhuangding Road, Yantai, Shandong, 264000, People’s Republic of China, Tel +86-15154502782, Email xue6er6@163.com; zhang0hua@163.comAbstract: Allergic rhinitis (AR), which presents symptoms like sneezing and a runny nose, is categorized as an upper respiratory condition of type 2. Recent progress in comprehending AR has revealed the significant role played by type 2 cytokines, specifically interleukin (IL)-13, IL-4, and IL-5. These cytokines are released by helper T cells 2 (Th2) and innate lymphoid cells (ILC2s). ILC2s have the ability to interact with various immune cells and are essential in promoting both type 2 immune response and tissue repair, contributing to normal homeostatic functions within the body. This article presents a summary of the latest advancements in comprehending the activity of ILC2s, with particular emphasis on their potential role involvement in AR. It explores how they collaborate with Th2 cells to exacerbate nasal inflammation and interact with regulatory T cells (Tregs) to counteract the suppressive role mediated by Tregs during allergic inflammation. The significance of ILC2s in allergen-specific therapy is highlighted. A comprehensive understanding of ILC2s biology establishes a robust foundation for unraveling the pathogenesis of AR and devising innovative therapeutic approaches for its management.Keywords: allergic rhinitis, group 2 innate lymphoid cells, cytokines, Treg cells, Th2 cells

Zibin Cui,1,&ast; Xiangdong Liu,2,&ast; Zehua Feng,3 Zhengzong Huang4 1School of Management, Guangdong University of Technology, Guangzhou, People’s Republic of China; 2Faculty of Humanities and Social Sciences, Macao Polytechnic University, Macao, People’s Republic of China; 3School of Law, Guangdong University of Technology, Guangzhou, People’s Republic of China; 4College of Humanities and Social Science, Shenzhen Technology University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zehua Feng; Zhengzong Huang, Email zehuafeng@gdut.edu.cn; huangzhengzong@sztu.edu.cnBackground: The emerging risk of personalized medicine is driving drug manufacturers to seek collaborations with advanced diagnostic firms, aiming to improve detection and treatment outcomes. However, the government’s regulated pricing in personalized medicine affects manufacturers’ strategic decisions, particularly regarding the selection of diagnostic partners. In this context, this study investigates whether the government should regulate the price of personalized medicine and how the government’s regulated pricing decisions affect drug manufacturers’ diagnostic test choices.Methods: A stylized analytical model was developed, employing game-theoretic analysis. Numerical studies are also conducted to validate our results.Results: The study reveals that in the absence of the government’s regulated pricing, drug manufacturers benefit from partnering with high-level diagnostic firms, enhancing consumer surplus and social welfare. However, when the government regulates pricing, the choice of partnering with a high-level diagnostic firm depends on specific conditions, such as low patient sensitivity to treatment failure and a low unit cost coefficient of diagnostic effort. The government’s decision to regulate prices is influenced by three key parameters: patients’ sensitivity to treatment failure, the unit cost coefficient of the diagnostic test effort, and the proportion of the price of specialized drugs in the regulated pricing.Conclusions: The findings underscore the importance of legal frameworks in the personalized medicine industry. The absence of the government’s regulated pricing incentivizes collaborations with high-level diagnostic firms, enhancing consumer surplus and social welfare. However, government intervention in pricing makes such decisions contingent on specific conditions, requiring nuanced regulatory policies that balance the interests of patients, manufacturers, and diagnostic firms.Keywords: personalized medicine, partnership, government, regulated pricing, game theory

Yihe Ma,1– 3,&ast; Xiaojun Xiao,2,&ast; Yutao Wang,3,&ast; Jie Sun,4 Ping Tang,5 Jing Li,3 Xizhuo Sun,5 Damo Xu,1,2 Zifeng Yang,3 Shiguo Chen,4 Xiaoyu Liu2 1Department of Respiratory and Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 2State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4Nanshan District Key Laboratory for Biopolymers and Safety Evaluation, Shenzhen Key Laboratory of Polymer Science and Technology, Guangdong Research Center for Interfacial Engineering of Functional Materials, College of Materials Science and Engineering, Shenzhen University, Shenzhen, People’s Republic of China; 5Department of General Practice, Third Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyu Liu, State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen Key Laboratory of Allergy & Immunology, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China, Email lxy0901@szu.edu.cnPurpose: Synthesis and characterization of silver (Ag)/titanium dioxide (TiO2) nanocomposite (ATA) to investigate its antiviral activity against the H1N1 influenza virus and antiviral mechanisms.Materials and Methods: A water-dispersible ATA was prepared by a photocatalytic reduction process from AgNO3 and TiO2. The characterization of ATA was performed by ultraviolet-visible spectroscopy, X-ray diffraction, high-resolution transmission electron microscopy and energy-dispersive X-ray spectroscopy. The antiviral activities and the antiviral mechanism of ATA were investigated in detail by light microscopy, transmission electron microscopy and biological techniques such as cell cytotoxicity, 50% tissue culture infectious dose detection, western blot and reverse transcription-polymerase chain reaction.Results: These results showed the successful synthesis of ATA nanocomposite with uniform particle size and distribution. It demonstrated the highly efficient antiviral activity of ATA in a dose- and time-dependent manner, as indicated by the reduction of viral titer and the reduction of cytopathic effects caused by viral infection. In the presence of ATA, the structure of the H1N1 influenza virus is directly destroyed and even disintegrated, with the damaged surface membrane proteins and fuzzy contour. It reduces the infection efficiency of influenza by suppressing the activity and expression of hemagglutinin and neuraminidase. The results of mechanistic studies suggested that ATA nanocomposite primarily interferes with virus attachment to viral receptors on the cell surface.Conclusion: Our study suggests that ATA may be a good antiviral candidate against the influenza virus. Compared with AgNPs alone, our synthesized ATA nanocomposites can achieve similar viral inactivation rates using only a much smaller concentration of AgNPs, greatly reducing the amount of AgNPs and their potential side effects. It has great practical value for attaching ATA to the high-efficiency particulate air network in the air purifier, which can kill the virus attached to it and limit its spread.Keywords: silver, titanium dioxide, nanocomposites, antivirus, H1N1 influenza virus

Haoxiang Wen,1,2,&ast; Ruiming Liang,3,&ast; Xiaofei Liu,4 Yang Yu,1 Shuirong Lin,1 Zimin Song,1 Yihao Huang,1 Xi Yu,1 Shuling Chen,5 Lili Chen,6 Baifeng Qian,1 Jingxian Shen,7 Han Xiao,8 Shunli Shen1 1Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Guangdong Province, People’s Republic of China; 3Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 4Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-senUniversity, Guangzhou, Guangdong Province, People’s Republic of China; 5Precision Medicine Institute, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 6Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 7Department of Radiology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China; 8Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunli Shen, Center of Hepato-Pancreatico-Biliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhong-Shan Road2, Guangzhou, Guangdong Province, People’s Republic of China, Email Shenshli@mail.sysu.edu.cn Han Xiao, Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, No. 58 Zhongshan Road2, Guangzhou, Guang- Dong Province, People’s Republic of China, Email xiaoh69@mail.sysu.edu.cnPurpose: Predicting the pathological response after neoadjuvant conversion therapy for initially unresectable hepatocellular carcinoma (HCC) is essential for surgical decision-making and survival outcomes but remains a challenge. We aimed to develop a radiomics model to predict pathological responses.Methods: We included 203 patients with HCC who underwent hepatectomy after neoadjuvant conversion therapy between 2015 and 2023 and separated them into a training set (100 patients from Center A) and a validation set (103 patients from Center B). Pathological complete response (pCR)-related radiomic features were extracted from the largest tumor layer in the arterial and portal vein phases of the CT. A synthetic minority oversampling technique (SMOTE) was used to balance the minority groups in the training set. The SMOTE radiomics model was constructed using a logistic regression model in the SMOTE training set and its performance was verified in the validation set.Results: The AUC of the preoperative modified response evaluation criteria in solid tumors (mRECIST) assessment for pCR was 0.656 and 0.589 in the training and validation sets, respectively. The SMOTE radiomics model was established based on ten radiomic features and showed good pCR-predictive performance in the SMOTE training set (AUC, 0.889; accuracy, 87.7%) and the validation set (AUC: 0.843, accuracy: 86.4%). The RFS of the radiomics-predicted-pCR group was significantly better than that of the predicted-non-pCR group in the training cohort (P = 0.001, 2-year RFS: 69.5% and 30.1% respectively) and the validation cohort (P = 0.012, 2-year RFS: 65.9% and 38.0% respectively).Conclusion: The SMOTE radiomics model has great potential for predicting pathological response and evaluating RFS in patients with unresectable HCC after neoadjuvant conversion therapy.Keywords: hepatocellular carcinoma, radiomics, pathological complete response, neoadjuvant conversion therapy

Yanyan Lu,1,&ast; Qiang Wang,2,&ast; Xuzhen Liu,1 Shuzhan Gao,1 Sulin Ni,1 Jing Sun,1 Xijia Xu1 1Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, People’s Republic of China; 2Department of Medical Psychology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xijia Xu, Department of Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing Brain Hospital, Nanjing, People’s Republic of China, Tel +86-13739192705, Email xuxijia@c-nbh.comPurpose: Acute and transient psychotic disorder (ATPD), a psychosis frequently diagnosed, can potentially evolve into chronic conditions like schizophrenia (SCZ) and other mental disorders. This study aimed to develop a predictive model based on clinical data to forecast the transition from ATPD to SCZ and to identify the predictive factors.Methods: According to the diagnostic criteria issued by the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10), 396 inpatients diagnosed with ATPD were collected in this study. The Cox proportional-hazards regression model was performed using demographic data, clinical characteristics, and inflammatory markers to identify independent predictors for subsequent diagnostic transition (SDT) to SCZ.Results: During the follow-up period, 43.69% (n = 173) of ATPD patients had their diagnoses revised to SCZ. The multivariate Cox regression analysis identified post-treatment monocyte count, post-treatment monocyte/lymphocyte ratio (MLR), and the presence of schizophreniform symptoms as significant predictors for the diagnostic revision. Time-dependent receiver operating characteristic (TimeROC) analyses were developed. The AUC value at the 5-year follow-up was 0.728 for combined predictors, 0.702 for post-treatment monocyte count, 0.764 for post-treatment MLR, and 0.535 for the presence of schizophreniform symptoms.Conclusion: The combined predictors had good predictive ability for the diagnostic transition from acute and transient psychotic disorder to schizophrenia.Keywords: acute and transient psychotic disorder, Schizophrenia, inflammation, subsequent-diagnostic-transition, monocyte count, monocyte–lymphocyte ratio

Lei Zhang,&ast; Peng Sun,&ast; Xin Liu, Ya Yang, Ruo-Nan Sun, Xu-Dong Wang Department of Emergency Medicine, Aerospace Center Hospital, Beijing, 100049, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xu-Dong Wang, Department of Emergency Medicine, Aerospace Center Hospital, 15 Yuquan Road, Haidian District, Beijing, 100049, People’s Republic of China, Tel +86 01059975120, Email wxundong@126.comObjective: We aimed to analyze the clinical characteristics and prognostic factors of patients with severe hyperkalemia in the emergency department.Methods: This retrospective cohort study included adult patients diagnosed with severe hyperkalemia who sought medical care at the emergency department of Aerospace Center Hospital between January 2018 and May 2022. Clinical data, including demographics, comorbidities, laboratory findings, and outcomes, were systematically collected. Patients were categorized into survival and deceased groups based on in-hospital mortality. Comparative analysis between these groups identified significant differences, highlighting key clinically covariates. Binary logistic regression was employed to determine the primary factors influencing patient outcomes.Results: Of 90 patients diagnosed with severe hyperkalemia, 64 were in the survival group, and 26 in the deceased group. Binary logistic regression identified several significant predictors of mortality, including higher APACHE II scores (odds ratio [OR] 1.41, P = 0.02), widened QRS wave on electrocardiogram (ECG) (OR 79.39, P = 0.04), and elevated serum potassium levels (OR 1.3, P = 0.04). In contrast, emergency blood purification was associated with a reduced mortality rate (OR 0.29, P = 0.03).Conclusion: Key risk factors for mortality in patients with severe hyperkalemia include widened QRS wave on ECG, elevated APACHE II score, and high serum potassium level. Timely correction of hyperkalemia through emergency blood purification significantly improves patient outcomes.Keywords: clinical manifestation, prognosis, risk factors, severe hyperkalemia, treatment

Xiaoyu Liu, Pengyun Du, Jianing Xu, Wei Wang, Chenggang Zhang School of Life Sciences, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Chenggang Zhang, School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, People’s Republic of China, Email jxs@bucm.edu.cnPurpose: This study aims to assess the therapeutic potential of combining Shen-Ling-Bai-Zhu-San (SLBZS) or prebiotics with intermittent fasting (IF) in type 2 diabetes mellitus (T2DM) mice and to investigate the synergistic effects and underlying mechanisms.Methods: Type 2 diabetic mouse models were induced using high-fat diet (HFD) and streptozotocin (STZ), followed by IF treatment. Mice were then grouped for combined therapy with different doses of SLBZS and prebiotics. Fasting blood glucose (FBG) levels, body weight variations, and oral glucose tolerance tests were assessed to elucidate metabolic alterations. The hepatic and renal parameters were evaluated to determine systemic changes in T2DM mice, while the insulin levels were quantified by ELISA to assess glucose homeostasis. Gut microbiota alterations were examined via 16S rRNA sequencing. Alterations of the genes in relevant signaling pathways were analyzed using RT-qPCR.Results: IF improved FBG, body weight, insulin levels, and other diabetes indicators. Combined IF with SLBZS or prebiotics yielded similar effects. Furthermore, it ameliorated dyslipidemia and mitigated hepatic and renal parameters in T2DM mice. Pancreatic tissue histopathology showed islet cell restoration post-intervention. IF therapy reduced the abnormally elevated GSK-3β gene expression and increased the abnormally reduced GLUT2 genes. Further analysis indicated that the combination of IF with prebiotics and high doses of SLBZS upregulated the expression of the INSR and IRS1 genes. Gut microbiota analysis revealed restored diversity and structure, with notable changes in specific bacterial families. At the family level, the contents of Akkermansiaceae and Bifidobacteriaceae were restored. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) analysis suggested metabolic pathway alterations.Conclusion: IF improved type 2 diabetic symptoms, with combined SLBZS and prebiotics showing similar effects. IF with high concentration of SLBZS and prebiotics doses upregulated the INSR and IRS1 genes and had superior effects on gut microbiota compared to IF alone.Keywords: [type 2 diabetes mellitus, intermittent fasting, prebiotics, Shen-Ling-Bai-Zhu-San]

Yuxuan Yao,1– 3 Hong Zhao,4 Hua Lu,5 Xiaoli Liu,6 Hui Liu,7 Zhanli Fu,8 Chunyue Li,1 Fude Zhou,1– 3 Wanyin Hou,1– 3 Sufang Shi1– 3 1Department of Nephrology, Peking University First Hospital, Peking University Institute of Nephrology, Beijing, People’s Republic of China; 2Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, People’s Republic of China; 3Research Units of Diagnosis and Treatment of Immune-Mediated Kidney Diseases, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Department of Infectious Disease, Center for Liver Disease, Peking University First Hospital, Beijing, People’s Republic of China; 5Department of Nephrology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 6Department of Pathology, Xingtai People’s Hospital, Xingtai, Hebei, People’s Republic of China; 7Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 8Department of Nuclear Medicine, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Wanyin Hou; Hong Zhao, Peking University First Hospital, Xicheng District, Beijing, People’s Republic of China, Tel +86 10-83575685, Email helenwanyin@bjmu.edu.cn; zhaohong_pufh@bjmu.edu.cnAbstract: Q fever, an infectious zoonotic disease caused by Coxiella burnetii, remains prevalent in China. Systemic infections can result in renal or hepatic complications; however, it is rare for both the kidneys and liver to be simultaneously affected. We present a case of a patient who exhibited fever, rapid deterioration in renal function, thrombocytopenia, and severe ascites. Renal biopsy revealed crescentic glomerulonephritis, while liver biopsy demonstrated non-cirrhotic portal hypertension. Metagenomic next-generation sequencing (mNGS) identified the presence of Coxiella burnetii in both venous blood and liver tissue samples. Notably, the patient’s renal insufficiency and ascites showed a positive response to treatment for chronic Q fever. These findings provide valuable insights into the limited understanding of kidney and liver diseases associated with Q fever. Advanced diagnostic technologies, including mNGS and positron emission tomography/computed tomography (PET/CT), have been employed to identify Coxiella burnetii infection.Keywords: Coxiella burnetii, acute kidney injury, non-cirrhotic portal hypertension, biopsies

Jia Zhang,1,&ast; Xi Liu,2,&ast; Jin Huang,3 Songbin Huang,1 Zuolian Zhang4 1Department of Nursing, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China; 2Department of Neurology, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China; 3Department of Cardiovascular Medicine, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China; 4Department of Neurosurgery, Heyuan People’s Hospital, Heyuan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jia Zhang, Email 562232317@qq.comObjective: To analyze research trends, frontiers, and hot topics in specialty nurse training over the past 20 years, and provide a reference for researchers to understand the current research landscape in this field.Methods: Studies from the core collection of Web of Science were used. Furthermore, CiteSpace 6.3 R3 was utilized to analyze information on country, institution, authors, keywords and burst words.Results: A total of 296 articles were included in the analysis. The United States had the highest number of articles, and there was limited cooperation between authors and institutions. The research hotspots in this field included “clinical education models for specialist nurses”, “APN role training”, and “interprofessional education”.Conclusion: The future research trend is to explore the effective integration of training models suitable for different regions and cultural backgrounds and cross-professional education models. It is suggested that researchers pay attention to the innovation and development of specialized nursing clinical practice under different cultural backgrounds, and strengthen international exchanges and cooperation.Keywords: specialty nurse, train, bibliometric analysis, CiteSpace, data visualization

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

Pranjyan Dash,1 Senthilkumar Thirumurugan,1 Nandini Nataraj,1 Yu-Chien Lin,1– 3 Xinke Liu,4,5 Udesh Dhawan,6 Ren-Jei Chung1,7 1Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), Taipei, 10608, Taiwan; 2School of Materials Science and Engineering, Nanyang Technological University, Singapore, 639798, Singapore; 3ZhongSun Co., LTD, New Taipei City, 220031, Taiwan; 4College of Materials Science and Engineering, Chinese Engineering and Research Institute of Microelectronics, Shenzhen University, Shenzhen, 518060, People’s Republic of China; 5Department of Electrical and Computer Engineering, National University of Singapore, Singapore, 117583, Singapore; 6Centre for the Cellular Microenvironment, Division of Biomedical Engineering, James Watt School of Engineering, Mazumdar-Shaw Advanced Research Centre, University of Glasgow, Glasgow, G116EW, UK; 7High-Value Biomaterials Research and Commercialization Center, National Taipei University of Technology (Taipei Tech), Taipei, 10608, TaiwanCorrespondence: Ren-Jei Chung, Department of Chemical Engineering and Biotechnology, National Taipei University of Technology (Taipei Tech), No. 1, Sec. 3, Zhongxiao E. Road, Taipei, 10608, Taiwan, Tel +886-2-2771-2171 ext. 2547, Email rjchung@ntut.edu.twBackground: Phototherapy based on photocatalytic semiconductor nanomaterials has received considerable attention for the cancer treatment. Nonetheless, intense efficacy for in vivo treatment is restricted by inadequate photocatalytic activity and visible light response.Methods: In this study, we designed a photocatalytic heterostructure using graphitic carbon nitride (g-C3N4) and tin disulfide (SnS2) to synthesize g-C3N4/SnS2 heterostructure through hydrothermal process. Furthermore, Au nanoparticles were decorated in situ deposition on the surface of the g-C3N4/SnS2 heterostructure to form g-C3N4/SnS2@Au nanoparticles.Results: The g-C3N4/SnS2@Au nanoparticles generated intense reactive oxygen species radicals under near-infrared (NIR) laser irradiation through photodynamic therapy (PDT) pathways (Type-I and Type-II). These nanoparticles exhibited enhanced photothermal therapy (PTT) efficacy with high photothermal conversion efficiency (41%) when subjected to 808 nm laser light, owing to the presence of Au nanoparticles. The in vitro studies have indicated that these nanoparticles can induce human liver carcinoma cancer cell (HepG2) apoptosis (approximately 80% cell death) through the synergistic therapeutic effects of PDT and PTT. The in vivo results demonstrated that these nanoparticles exhibited enhanced efficient antitumor effects based on the combined effects of PDT and PTT.Conclusion: The g-C3N4/SnS2@Au nanoparticles possessed enhanced photothermal properties and PDT effect, good biocompatibility and intense antitumor efficacy. Therefore, these nanoparticles could be considered promising candidates through synergistic PDT/PTT effects upon irradiation with NIR laser for cancer treatment.Keywords: g-C3N4, SnS2, Gold nanoparticles, Photodynamic therapy, Photothermal therapy

Xinqiang Liu,1,&ast; Hongguang Ding,2,&ast; Miner Chen,1,&ast; Xusheng Li,2 Yan Xiao,1 Yongli Han,1 Hongke Zeng1 1Department of Intensive Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510800, People’s Republic of China; 2Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongke Zeng, Department of Intensive Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2nd Road, Guangzhou, People’s Republic of China, 510080, Tel/Fax +8602083827812-60810, Email zenghongke@gdph.org.cnBackground: Shenfu injection (SF) has demonstrated its potential to enhance cellular immunity and induce clinical regression in patients suffering from sepsis or infectious shock. However, the therapeutic effect of SF on sepsis-induced cognitive dysfunction (SAE) and the mechanisms involved are still unclear. We aimed to investigate the mechanism of SF in mice with SAE.Methods: Sepsis was constructed by caecal ligation and puncture. Mice were injected intraperitoneally with SF or NLRP3 inhibitor. The hippocampus injury of brain tissues was evaluated, and the levels of inflammatory cytokines (IL-1β, IL-18) and NLRP3 and Caspase 1 were measured. The active ingredients of SF were analyzed using network pharmacology, and molecular docking of the active ingredients of SF with NLRP3 and Caspase 1 was performed. BV-2 cells were treated with LPS or norcoclaurine. CCK-8 detected the cell viability, and the levels of inflammatory cytokines and NLRP3 and Caspase 1 were measured.Results: SF and NLRP3 inhibitor increased survival rate and the number of crossing the platform and decreased the escape latency time of sepsis mice. Moreover, SF and NLRP3 inhibitor improved neuronal damage and apoptosis in hippocampus of sepsis mice. In addition, SF and NLRP3 inhibitor reduced the levels of inflammatory cytokines, as well as inflammasomes in sepsis mice. There were 43 active ingredients in SF. Among them, 22 were Renshen and 21 were Fuzi. Renshen and Fuzi, the main active components of SF, form a complex regulatory network with NLRP3 and Caspase 1. (R)-norcoclaurine was most closely bound to NLRP3 with binding energy of − 7.2 kJ·mol− 1, ignavine was most closely bound to Caspase 1 with binding energy of − 8.3 kJ·mol− 1. Norcoclaurine increased the cell viability and decreased inflammation and pyroptosis.Conclusion: SF regulated NLRP3/Caspase 1 through (R)-norcoclaurinee to prevent SAE.Keywords: shenfu injection, NLRP3, caspase 1, pyroptosis, sepsis-associated encephalopathy

XingYun Liu,1,&ast; JingDuo Zhao,2,&ast; FuRong Liu,1 ZhiZhong Xie,2 XiaoYong Lei,2 Zhe Wang,3 Zerui Yang,4 YuSheng Zhou,1,3 GuoTao Tang2 1The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 2Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, 421001, People’s Republic of China; 3The Second Affiliated Hospital, Department of Pharmacy, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China; 4NMPA Key Laboratory for Technology Research and Evaluation of Pharmacovigilance, Guangdong Pharmaceutical University, Guangzhou, 510086, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: YuSheng Zhou, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China, Email yszhou08@126.com GuoTao Tang, Institute of Pharmacy and Pharmacology, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hengyang Medical School, Hengyang, Hunan, 421001, People’s Republic of China, Email tgtzq@163.comBackground: Breast cancer treatment has been a global puzzle, and targeted strategies based on the hypoxic tumor microenvironment (TME) have attracted extensive attention. As a signature transcription factor overexpressed in hypoxia tumor, hypoxia-inducible factor-1 (HIF-1) contribute to cancer progression. Compound 7-(3-(2-chloro-1H-benzo[d]1midazole-1-yl) propoxy)-2-(3,4,5-trime-thoxyphenyl)-4H-chromen-4-one, synthesized and named FB15 in our earlier research, a potential inhibitor of HIF-1α signaling pathway, has been proved a promising drug candidate for many kinds of cancer chemotherapy. However, the poor solubility and undesirable pharmacokinetics of FB15 leads to limited treatment efficacy of tumor, which ultimately restricts its potential clinical applications. Carbonic anhydrase IX (CAIX), a tumor cell transmembrane protein, was overexpressed in hypoxia tumor site. Acetazolamide (AZA), a highly selective ligand targeting CAIX, can be utilized to delivery FB15 to hypoxia tumor site.Methods: In this study, we prepared and characterized FB15 loaded nano-mixed micelles with the AZA conjugated poloxamer 188 (AZA-P188) and D-a-Tocopherol Polyethylene 1000 Glycol Succinate (TPGS), denoted as, AZA-P188/TPGS@FB15. Its delivery efficiency in vitro and in vivo was assessed by in vitro drug release, cytotoxicity assay, cellular uptake, and in vivo pharmacokinetics and fluorescence imaging. Finally, therapeutic effect of AZA-P188/TPGS@FB15 was investigated using a preclinical breast cancer subcutaneous graft model in vivo.Results: In vitro studies revealed that AZA-P188/TPGS@FB15 could efficiently target breast cancer cells mediated by CAIX receptor, trigger FB15 release in response to acidic condition, and enhance cellular uptake and cytotoxicity against breast cancer cells. The pharmacokinetic studies showed that FB15-loaded AZA-functionalized micelles exhibited significantly increased AUC0-t over free FB15. In vivo imaging demonstrated that AZA-functionalized micelles significantly increased the drug distribution in the tumor site. In vivo experiments confirmed that AZA-P188/TPGS@FB15 exhibited superior inhibition of tumor growth in nude mice with good biosafety.Conclusion: AZA-P188/TPGS@FB15 hold promise as a potentially effective therapeutic way for breast cancer. Its targeted delivery system utilizing AZA as a carrier shows potential for improving the efficacy of FB15 in cancer therapy.Keywords: carbonic anhydrase IX-targeting, FB15, hypoxia inducible factor-1, nano-mixed micelles, pH-responsive

Bohao Dai,1,&ast; Xiaorong Peng,1,&ast; Jia Sun,1 Xueling Zhu,1 Xiang Liu,1 Ye Xiong,1 Zhikai Wan,1 Dairong Xiang,1 Jiangjin Hui,1 Chenxi Ying,2 Huiting Liu,1 Biao Zhu1,&ast; 1The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Cardivascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Biao Zhu, The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qing Chun Road, Hangzhou, 310006, People’s Republic of China, Email zhubiao1207@zju.edu.cnBackground: HIV-1 CRF01_AE is becoming the predominant HIV-1 subtype among patients in China. The distribution and characteristics of transmission clusters of HIV-1 CRF01_AE in Zhejiang, Eastern China remains unclear. This study analyzed the epidemiologic characteristics and transmission clusters of HIV-1 CRF01_AE in Zhejiang.Methods: Plasma samples obtained from 152 patients of HIV-1 CRF01_AE not undergoing ART were used to amplify HIV-1 pol and env gene. CRF01_AE drug resistance mutations (DRM) prevalence was analysed using Stanford University’s HIV Drug Resistance Database. A phylogenetic tree was constructed using FastTree (version 2.1.11) based on the GTR nucleotide substitution model and visualized using Figtree (version 1.4.4) and The Interactive Tree of Life; the Chinese HIV Gene Sequence Data Platform was used to construct genetic transmission networks.Results: Majority samples could be grouped into CRF01_AE transmission Clusters 1 (11.2%), 4 (64.5%), and 5 (7.2%). The CD4+ T-cell counts in Cluster 1, 4a, 4b are lower than 5 were 15, 38, 30, and 248 cells/mm3, respectively (P < 0.05). The high X4 tropism rates were 13.2%, 11.8%, 20.0%, and 0.0% in Clusters 1, 4a, 4b, and 5, respectively. DRM rates in Clusters 4a and 4b were 17.6%, and 25.45% respectively (P < 0.05), whereas they were 17.6% and 18.2% in Clusters 1 and 5, respectively. In total, 24 transmission genetic networks, comprising 72 sequences and 61 links, were discovered; of them, 61.2%, 11.7%, and 18.2% were from Clusters 4, 1, and 5, respectively (P < 0.05).Conclusion: In Zhejiang, different CRF01_AE clusters displayed unique clinic features. Cluster 4, particularly Cluster 4b, was considered a high-risk transmission cluster. The surveillance of epidemiology of HIV-1 should be enhanced to minimize its transmission.Keywords: HIV-1 CRF01_AE, drug resistance mutation, transmission cluster

Qian Meng,1,&ast; Xiaowei Yang,1,&ast; Zhongcheng Liu,2 Guoxing You,3 Wanyi Chen,3 Bing Zhao,1 Huizi Zhu,4 Liang Xu,1 Yan Zhou,1 Xiang Liu,1 Chunjuan Zhai,5 Rong Wang,1 Lian Zhao,3 Jing Sun1 1Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Department of Cardiovascular, The North City Hospital of Jinan, Jinan, Shandong, 250031, People’s Republic of China; 3Academy of Military Medical Sciences, Beijing, 100850, People’s Republic of China; 4Department of Nephrology, Fuyang People’s Hospital, Fuyang, Anhui, 236000, People’s Republic of China; 5Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Sun, Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 151 6888 6367, Email sunj5708@126.com Lian Zhao, Academy of Military Medical Sciences, 27 Taiping Road, Beijing, 100850, People’s Republic of China, Tel +8613671217095, Email zhaolian@bmi.ac.cnPurpose: Chronic kidney disease (CKD) is associated with persistent systemic inflammation. Reduced red blood cell (RBC) survival in patients with CKD has been identified for several decades. The purpose of this study is to explore whether excessive erythrophagocytosis exists and contributes to systemic inflammation in CKD.Patients and methods: A CKD rat model was induced by 5/6 nephrectomy. Erythrocyte osmotic fragility was determined with hypotonic NaCl solutions. Erythrocyte deformability was evaluated by filterability. RBC cell death was quantified using fluorescence-activated cell sorting analyses of fluorescent annexin V–bound surface phosphatidylserine (PS). Erythrophagocytosis was evaluated in vivo and in vitro. RT-qPCR and immunohistochemistry were used to determine the inflammatory effects after erythrophagocytosis.Results: Erythrocyte osmotic fragility and deformability progressively declined, and the percentage of PS-exposing RBCs progressively increased in CKD rats. Levels of erythrophagocytosis in vivo were evaluated by autologous injection of CFSE-labeled erythrocytes. In comparison with the control group, higher fluorescence intensity of CFSE was detected in the spleen homogenates of rats with CKD. In vitro, more of erythrocytes from 5/6Nx rats were phagocytosed by peritoneal macrophages in comparison to those from control rats. Compared with macrophages phagocytosed control erythrocytes, macrophages phagocytosed CKD erythrocytes exhibited higher mRNA levels of IL-6, CXCL-10, CXCL-11, iNOS, IL-1β, ICAM-1 and MCP-1. Compared with the control group, the red pulp of rats with CKD exhibited higher levels of p-NFκB, IL-6, iNOS and CXCL-10. ELISA results showed significantly increased plasma levels of both IL-6 and CXCL-10 in patients with long-term hemodialysis compared with those in healthy controls (2.30 ± 1.38 pg/mL vs 1.33 ± 0.65 pg/mL, P=0.01; 78.11 ± 27.34 pg/mL vs 37.45 ± 7.08 pg/mL, P=0.001).Conclusion: Our results indicated that excessive erythrophagocytosis may contribute to systemic inflammation in CKD. Keywords: chronic kidney disease, chronic inflammation, erythrocyte, phagocytosis

Anni Zhao,1,&ast; Xiaomei Liu,1,&ast; Xiping Chen,1,&ast; Sha Na,1,&ast; Hui Wang,1 Xuan Peng,1 Peizhong Kong,1 Lu Li1,2 1Department of Biochemistry and Molecular Biology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peizhong Kong; Lu Li, Department of Biochemistry and Molecular Biology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, No. 350, Longzihu Road, Xinzhan District, Hefei, Anhui, People’s Republic of China, Email kongpz@ahtcm.edu.cn; deerlyee@hotmail.comObjective: To identify the polar parts in Rhubarb that cause hepatotoxicity and explore the underlying mechanisms.Methods: The rat model of liver cancer was established by gavage of diethylnitrosamine (DEN; 0.002 g/rat) for 14 weeks. Starting from the 11th week, Rhubarb granule (4 g/kg), aqueous, ethyl acetate and n-butanol extract of Rhubarb or Rhein equivalent to a dose of 4 g/kg Rhubarb granule were administered intragastrically for 4 consecutive weeks. Liver tissues from rats treated with DEN and Rhubarb granules were used for non-targeted metabolomics analysis. The correlation between pyruvate kinase isozyme type M2 (PKM2) expression level and the progress and prognosis of hepatocellular carcinoma (HCC) was evaluated through bioinformatics analysis based on TCGA database. Liver tissues and blood samples from rats treated with DEN and aqueous, ethyl acetate and n-butanol extract of Rhubarb were used for the screening of hepatotoxic polar parts of Rhubarb. The liver injuries were evaluated by the changes in pathology, liver function, and the expression levels of proliferating cell nuclear antigen (PCNA) and transforming growth factor beta1 (TGF-β 1). The mechanism studies focus on PKM2 expression, and the metabolic reprogramming via detecting the activities of lactate dehydrogenase A (LDHA) and isocitrate dehydrogenase (ICDH). Furthermore, molecular docking analysis was performed to validate the target interaction between Rhein and PKM2, and the hepatotoxicity of Rhein was evaluated by testing liver function in the DEN-induced liver cancer model.Results: The non-targeted metabolomics analysis revealed that Rhubarb promoted aerobic glycolysis in the rat model of DEN-induced liver cancer. And bioinformatics analysis revealed that high PKM2 expression was closely related to the progression and poor prognosis of HCC. In vivo studies indicated that the aqueous extract of Rhubarb, but not ethyl acetate and n-butanol extract, promoted the liver injuries induced by DEN. The mechanism study showed that the aqueous extract of Rhubarb increased the expression of PKM2 and promoted aerobic glycolysis. Moreover, Rhein had a strong binding affinity for PKM2 and aggravated liver injury in the DEN-induced liver cancer model.Conclusion: Aqueous extract of Rhubarb promoted hepatotoxicity via facilitating PKM2-mediated aerobic glycolysis in the rat model of DEN-induced liver cancer. Keywords: aqueous extract of rhubarb, hepatotoxicity, PKM2, aerobic glycolysis, Rhein

Ling Zhao,1– 3,&ast; Shichao Li,1,2,4,&ast; Xiaoyu Wang,1,2 Lingyan Zhang,1,2 Jingge Zhang,1,2 Xiyun Liu,1,2 Yuyan Hu,1,2 Xiaohui Xian,1,2 Feng Zhang,5 Wenbin Li,1,2 Min Zhang1,2,6 1Department of Pathophysiology, Hebei Medical University, Shijiazhuang, Hebei Province, 050017, People’s Republic of China; 2Hebei Key Laboratory of Critical Disease Mechanism and Intervention, Shijiazhuang, Hebei Province, 050017, People’s Republic of China; 3Department of Obstetrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 4Experimental Diagnostic Center for Infectious Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 5Department of Rehabilitation Medicine, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050051, People’s Republic of China; 6The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Shijiazhuang, Hebei Province, 050017, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhang, Department of Pathophysiology, Key Laboratory of Critical Disease Mechanism and intervention of Hebei Province, The Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang, Hebei, 050017, People’s Republic of China, Email hebmuzhangmin@hebmu.edu.cnBackground: Obesity is recognized as a primary risk factor for cerebral ischemia, which has shown a significant increase in its incidence among obese patients. The exact mechanism by which obesity exacerbates cerebral ischemic injury is not fully understood though. The present study validated the hypothesis that obesity mediates pyroptosis by the AGEs/RAGE signaling pathway to exacerbate cerebral ischemic injury.Methods: Leptin receptor knockout (Lepr−/−) rats were used in this study to construct an obesity model, and the middle cerebral artery occlusion (MCAO) models of ischemic stroke were established in Lepr−/− obese rats and their wild-type (WT) littermates respectively. Zea-Longa score, TTC and H&E staining were utilized to evaluate the neurological impairment. Western Blot, immunohistochemistry, and immunofluorescence were used to detect protein expressions. Transmission electron microscopy was used to observe the pores in the neuronal cell membrane in the ischemic penumbra cortex.Results: Compared with WT littermates, Lepr−/− obese rats exhibited exacerbated neuronal injury after MCAO, with higher expressions of NLRP3 inflammasome and pyroptosis-related proteins in the cortical tissue of the penumbra. Moreover, more GSDMD pores were observed on the neuronal cell membranes of Lepr−/− obese rats according to the electron microscopy. Inhibition of NLRP3 inflammasome expression with MCC950 inhibited neuronal pyroptosis after cerebral ischemia in Lepr−/− obese rats, thus reducing neuronal injury. We also found that compared with WT littermates, the levels of AGEs and RAGE in the cortex of Lepr−/− obese rats are significantly higher, with further increase after cerebral ischemia. Inhibition of AGEs/RAGE signaling pathway with FPS-ZM1 reduced the NLRP3 inflammasome-mediated neuronal pyroptosis in Lepr−/− obese rats, thereby mitigating the neuronal damage after cerebral ischemia.Conclusion: The AGEs/RAGE signaling pathway is involved in the exacerbation of cerebral ischemic injury in Lepr−/− obese rats via regulating NLRP3-mediated neuronal pyroptosis. Keywords: MCAO, neuronal pyroptosis, NLRP3, Lepr−/− obese rats, AGEs/RAGE signaling pathway

Minghui Wang,1,&ast; Zhiwei Lai,1,&ast; Hua Zhang,1,&ast; Weiqi Yang,2 Fengping Zheng,1 Dehua He,2 Xiaofang Liu,2 Rong Zhong,2 Mulan Qahar,1,2 Guang Yang1– 3 1Division of Renal Medicine, Peking University Shenzhen Hospital, Peking University, Shenzhen, 518036, People’s Republic of China; 2Department of Burn and Plastic Surgery, Shenzhen Institute of Translational Medicine, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China; 3Department of Life Sciences, Yuncheng University, Yuncheng, 044011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang Yang; Mulan Qahar, Email yakoaka@foxmail.com; mulanqahar@126.comBackground: Diabetes mellitus (DM) is known to inhibit skin self-renewal and hair follicle stem cell (HFSC) activation, which may be key in the formation of chronic diabetic wounds. This study aimed to investigate the reasons behind the suppression of HFSC activation in DM mice.Methods: Type 1 DM (T1DM) was induced in 6-week-old mice via streptozotocin, and hair follicle growth was subsequently monitored. RNA sequencing, bioinformatics analyses, qRT‒PCR, immunostaining, and cellular experiments were carried out to investigate the underlying mechanisms involved.Results: T1DM inhibited HFSC activation, which correlated with an increase in caspase-dependent programmed cell death. Additionally, T1DM triggered apoptosis and pyroptosis, predominantly in HFSCs and epidermal regions, with pyroptosis being more pronounced in the inner root sheath of hair follicles. Notably, significant cutaneous immune imbalances were observed, particularly in macrophages. Cellular experiments demonstrated that M1 macrophages inhibited HaCaT cell proliferation and induced cell death, whereas high-glucose environments alone did not have the same effect.Conclusion: T1DM inhibits HFSC activation via macrophage reprogramming-mediated caspase-dependent pyroptosis, and there is a significant regional characterization of cell death. Moreover, T1DM-induced programmed cell death in the skin may be more closely related to immune homeostasis imbalance than to hyperglycemia itself. These findings shed light on the pathogenesis of diabetic ulcers and provide a theoretical basis for the use of hair follicle grafts in wound repair.Keywords: diabetes mellitus, caspases, hair follicle stem cells, chronic wounds, cutaneous immune disorder

Xiaoxue Liu,1 Jiawei Gao,2 Liuxin Yang,2 Xingxing Yuan2,3 1Department of Paediatrics, Harbin Hospital of Traditional Chinese Medicine, Harbin, 150010, People’s Republic of China; 2Heilongjiang University of Chinese Medicine, Harbin, 150040, People’s Republic of China; 3Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, 150006, People’s Republic of ChinaCorrespondence: Xingxing Yuan, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, 150040, People’s Republic of China, Email yuanxingxing80@163.comAbstract: Asthma is a chronic inflammatory disorder of the airways, characterized by a complex interplay of genetic, environmental, and immunological factors that contribute to its onset and progression. Recent advances in researches have illuminated the critical role of exosomal microRNAs (miRNAs) in the pathogenesis and development of asthma. Exosomes are nano-sized extracellular vesicles that facilitate intercellular communication by transporting a variety of bioactive molecules, including miRNAs, and play a crucial role in regulating gene expression and immune responses, which are central to the inflammatory processes underlying asthma. Exosomal miRNAs are emerging as key players in asthma due to their involvement in various aspects of the disease, including the regulation of inflammation, airway hyperresponsiveness, and remodeling. Their ability to influence the behavior of target cells and tissues makes them valuable both as diagnostic biomarkers and as potential therapeutic targets. This review aims to provide a comprehensive overview of the biogenesis of exosomes, the functional roles of exosomal miRNAs in asthma, and their clinical potential. It will explore the mechanisms by which these miRNAs contribute to asthma pathophysiology, discuss their utility in diagnosing and monitoring the disease, and highlight ongoing research efforts to harness their therapeutic potential.Keywords: asthma, exosome, miRNA, biomarker, therapy

Ke-Qian Chen,1,&ast; Shu-Zhi Wang,2,&ast; Hai-Bo Lei,1 Xiang Liu1 1Department of Clinical Pharmacy, Xiangtan Central Hospital, Xiangtan, 411100, People’s Republic of China; 2Institute of Pharmacy and Pharmacology, School of Pharmaceutical Sciences, Hengyang Medical School, University of South China, Hengyang, 421001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hai-Bo Lei; Xiang Liu, Department of Clinical Pharmacy, Xiangtan Central Hospital, Xiangtan, 411100, People’s Republic of China, Email 286200571@qq.com; LX19890@163.comBackground: Dauricine is an important natural organic compound in Menispermum dauricum, which often has significant biological activity.Purpose: The purpose of this review is to systemically summarize and discuss the pharmacological activity and underlying mechanisms of dauricine in recent years.Methods: Web of Science (121 articles) and PubMed databases (97 articles) were used to search for articles related to “dauricine” published from 2000 to 2024. Meanwhile, we classified the pharmacological activity of dauricine by screening these articles.Results: Emerging evidence suggests that dauricine possesses numerous pharmacological activities, including neuroprotection, anti-cancer, anti-arrhythmia, anti-inflammatory and anti-diabetes.Conclusion: Dauricine has a potential value in the treatment of many diseases. We hope that this review will contribute to therapeutic development and future studies of dauricine.Keywords: menispermum dauricum, dauricine, toxicity, pharmacology, pharmacokinetics

Xiaoqing Liu,1,2 Qiaoqiao Ma,1 Jianfei Li,1 Zijun Huang,3 Xin Tong,2 Ting Wang,2 Hualong Qin,2 Wenjie Sui,2 Jing Luo2 1School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 3School of Computer Science and Technology, Soochow University, Suzhou, People’s Republic of ChinaCorrespondence: Jing Luo, Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Gusu District, Suzhou, Jiangsu, 215006, People’s Republic of China, Email luobojenny@163.comBackground: Rapid recovery after lung cancer surgery is challenging. Exercise is a low-cost, effective method to expedite recovery. Despite numerous exercise interventions, many fail to consider patient perspectives, leading to low adherence and short-term effects. Understanding lung cancer patients’ perspectives on postoperative exercise and exploring their exercise-related concerns and needs are crucial for enhancing the effectiveness of exercise-based rehabilitation programs.Objective: This study aims to analyze lung cancer patients’ perspectives on postoperative exercise in their daily lives, exploring their concerns and needs related to postoperative exercise to help healthcare professionals develop personalized exercise plans.Methods: An internet crawling technique collected online inquiries from Baidu webpages about postoperative physical activity in lung cancer patients, using “lung cancer”, “surgery”, and ”exercise” as keywords. The data was encoded, categorized, and analyzed using a large-scale semantic analysis platform in natural language processing and information retrieval to examine term frequency, sentiment tendencies, and attributes in the inquiry texts.Results: Initially, 2727 queries were retrieved; after screening, deduplication, and cleansing, 201 unique queries were identified. Queries related to “modes of exercise” constituted the largest proportion. The most frequently occurring words in the word frequency analysis were “lung”, “ cancer”, “should”, “can”, “long”, “early”, and “surgery”, “exercise”, “respiratory”. Postoperative lung cancer patients demonstrate significant interest in whether they should engage in exercise, as well as in the appropriate types and duration of such activities, indicating a strong need for detailed guidance and knowledge related to exercise. The sentiment analysis showed a positive score of 87.5% and a negative score of 12.5%, indicating that postoperative lung cancer patients view exercise positively and have an enthusiastic attitude towards it. Among the positive sentiment attributes, “good” was the most frequently mentioned term, whereas “bad” and “surprising” were the most prevalent terms within the negative sentiment attributes.Conclusion: Postoperative physical activity receives limited attention from lung cancer patients, who emphasize their preferences for exercise modalities. Their inquiries often reflect psychological concerns, such as fear and helplessness caused by symptoms. Understanding patients’ perspectives on postoperative physical activity within their real-life contexts can help integrate psychological support into exercise plans. This integration could guide healthcare professionals in developing more personalized postoperative exercise regimens for lung cancer patients.Keywords: lung cancer, surgery, exercise, web crawling technology, needs, concern

Xiaoyi Liu,1,&ast; Zhiwei Lin,2,&ast; Yiwen Li,3 Zhiwei Zhong,1 Aiwu Wu,1 Yueting Jiang3 1KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Clinical Laboratory of the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, People’s Republic of China; 3Department of Clinical Laboratory, the Key Laboratory of Advanced Interdisciplinary Studies Center, the First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aiwu Wu; Yueting Jiang, Email aiwwu66@163.com; jyting8899@126.comPurpose: The clinical distribution characteristics of nontuberculous mycobacteria (NTM) in general hospital were explored to guide the clinical diagnosis and treatment of NTM infection.Methods: Samples with positive mycobacterium culture in the First Affiliated Hospital of Guangzhou Medical University were collected and identified through PCR. Phenotypic drug sensitivity experiments were conducted on 44 Mycobacteroides abscessus isolated from clinical departments with broth microdilution method, and rrl, rrs and erm (41) genes associated with drug resistance were detected.Results: From September 2020 to July 2023, 314 mycobacterium-positive isolates were separated from patients in the First Affiliated Hospital of Guangzhou Medical University, with 147 (46.8%) NTM isolates were included in our study. The samples were respiratory tract specimens mainly, with 64% bronchoalveolar lavage fluid. Of 144 cases identified, samples were from 133 patients (60 males and 73 females; gender ratio of 0.82:1). NTM was mainly isolated from the people aged 40 and above, especially females (χ2 = 10.688, P = 0.014). M. abscessus (61, 42.36%), M. intracellulare (35, 24.31%) were the two most NTMs in this hospital. Clinical strains of M. abscessus exhibited high resistance to antibiotics, except for cefoxitin (31.8%), linezolid (25.0%), amikacin (0%), and clarithromycin (18.2%). Among 8 strains of M. abscessus with clarithromycin acquired resistance, just 4 strains (50.0%) showed mutations (A2270G, A2271G) in rrl gene, but a new mutation (C2750T) was detected in 1 strain. Among 14 strains of M. abscessus with clarithromycin-induced resistance, 13 (93.0%) strains had T28 erm (41) gene and 1 (7.0%) strain had C28 erm (41) gene.Conclusion: M. avium–intracellulare complex was gradually becoming predominant strain in Guangzhou area. The resistant situation of M. abscessus in general hospital had shown severe. Potential mutation in rrl gene associated with clarithromycin acquired resistance of M. abscessus were found, but drug-resistant mechanism remained unclear.Keywords: nontuberculous mycobacterium, drug resistance, clarithromycin, Mycobacteroides abscessus

Jiong Li,1 Dongqin Lei,1 Yanbing Cao,2,3 Fuli Xin,2,3 Zhenxi Zhang,1 Xiaolong Liu,2,3 Ming Wu,2,3 Cuiping Yao1 1Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, People’s Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 3Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, People’s Republic of ChinaCorrespondence: Ming Wu, Mengchao Hepatobiliary Hospital of Fujian Medical University, 312 Xi Hong Road, Fuzhou, 350025, People’s Republic of China, Email wmmj0419@163.com Cuiping Yao, School of Life Science and Technology, Xi’an Jiaotong University, 28 Xian Ning West Road, Xi’an, 710049, People’s Republic of China, Email zsycp@xjtu.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors.Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively.Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy.Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.Keywords: 2D porphyrin MOF, hypoxic relief, Pt nanozyme, photodynamic therapy

Yun Zhu,1,&ast; Lingyan Li,2,&ast; Wenxiao Wang,3,&ast; Xiaodan Liu,1 Meng Xue Zhang,1 Xiumin Chen,4 Xiaofeng Hou,5 Weimei Wang,6 Tuo Min,7 Jinmei Liu,8 Lecui Liu,9 Chengjun Liu,10 Zhong Jiang,11 Yanping Wang,12 Dayun Chang,13 Hua Pan1 1Department of Pediatric Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Department of Pediatrics, Zibo Maternal and Child Health Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Pediatrics, Yantai Yuhuangding Hospital, Yantai, Shandong, People’s Republic of China; 4Department of Pediatrics, Qingzhou People’s Hospital, Weifang, Shandong, People’s Republic of China; 5Department of Pediatrics, Laizhou City People’s Hospital, Laizhou, Shandong, People’s Republic of China; 6Department of Pediatrics, Haiyang People’s Hospital, Haiyang, Shandong, People’s Republic of China; 7Department of Pediatrics, Jining First People’s Hospital, Jining, Shandong, People’s Republic of China; 8Department of Pediatrics, West Coast New District Hospital of Chinese Medicine, Huangdao, Shandong, People’s Republic of China; 9Department of Neonatology, People’s Hospital of Wulian, Wulian, Shandong, People’s Republic of China; 10Department of Pediatrics, Linyi Central Hospital, Linyi, Shandong, People’s Republic of China; 11Department of Pediatrics, Rehabilitation University Qingdao Central Hospital, Qingdao, Shandong, People’s Republic of China; 12Department of Pediatrics, Qingdao Traditional Chinese Medicine Hospital, Qingdao, Shandong, People’s Republic of China; 13Department of Pediatrics, Weihai Municipal Hospital, Weihai, Shangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Pan, Department of Pediatric Intensive Care Unit, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, Shandong, 266003, People’s Republic of China, Tel +8618366205226, Email panhua1881@163.comIntroduction: The Omicron variant is the present predominant COVID-19 strain worldwide. Accurate mortality prediction can facilitate risk stratification and targeted therapies. The study aimed to evaluate the feasibility of the difference in hematocrit and albumin (HCT-ALB) levels, alone or combined with the pediatric Sequential Organ Failure Assessment (pSOFA) score and lactate level, to predict the in-hospital mortality of COVID-19 Omicron variant-infected pediatric patients.Methods: A multicenter retrospective cohort study was performed for children with COVID-19 Omicron variant infection between December 2021 and January 2022. The demographics, clinical characteristics, hospital admission laboratory test results, and treatments were recorded. The in-hospital mortality was documented. The associations between HCT-ALB levels and mortality, and between HCT-ALB+pSOFA+lactate and mortality were analyzed.Results: A total of 119 children were included. The median age was 1.6 (interquartile range: 0.5– 6.2) years old. There were 70 boys and 49 girls. The mortality rate was 14.3% (17/119). The univariate and multivariate Cox regression analysis revealed that HCT-ALB was associated to in-hospital mortality (hazard ratio: 1.500, 95% confidence interval: 1.235– 1.822, p< 0.001). The receiver operating characteristic curve analysis revealed that HCT-ALB can be used to accurately predict in-hospital mortality at a cut-off value of − 0.7 (area under the curve: 0.888, sensitivity: 0.882, specificity: 0.225, Youden index: 0.657, p< 0.001). These patients were assigned into three groups based on the HCT-ALB level, pSOFA score, and lactate level (low-, medium-, and high-risk groups). The Kaplan-Meier analysis revealed that the mortality increased in the high-risk group, when compared to the medium-risk group (p< 0.01). The latter group had a higher mortality, when compared to the low-risk group (p< 0.01).Conclusion: The HCT-ALB level can be applied to predict the in-hospital mortality of children infected with the COVID-19 Omicron variant. Its combination with other variables can improve prediction performance.Keywords: COVID-19, omicron variant, hematocrit, albumin, mortality

Xi Huang,1,2,&ast; Yu Peng,1,2,&ast; Lingfei Lu,1,&ast; Liwen Gao,1,2 Shanshan Wu,1,2 Jiandong Lu,1 Xinhui Liu1 1Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China; 2The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhui Liu, Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, 518033, People’s Republic of China, Email liuxinhui0317@163.comBackground: Huangqi-Danshen decoction (HDD) is a Chinese medicinal herb pair with good efficacy in treating chronic kidney disease, but its mechanism needs to be clarified.Aim: To uncover the underlying mechanism of HDD antagonizing renal fibrosis through network pharmacology (NP) analysis and experimental validation.Materials and Methods: The chemical components of water extract of HDD were analyzed by combining the ultra-high performance liquid chromatography coupled with Q-Exactive mass spectrum analysis (UHPLC-QE-MS) and HERB database. NP was used to identify core common targets of HDD components and renal fibrosis. Subsequently, male C57BL/6 mice were divided into Sham, unilateral ureteral obstruction (UUO) and UUO+HDD groups. Renal function, histopathology, Western blotting, and immunohistochemistry analyses were used to evaluate the protective effect of HDD on UUO mice. The effects of HDD on signaling pathways were validated in both UUO mice and transforming growth factor-β 1 (TGF-β 1)-induced HK-2 cells.Results: By combining UHPLC-QE-MS analysis and HERB database, 25 components were screened in HDD extract. There were 270 intersection targets of the 25 components and renal fibrosis. Based on their scores in protein-protein interaction analysis and degree values in component-pathway-target triadic network, 6 core common targets of the 25 components and renal fibrosis were identified, namely phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription 3 (Stat3), non-receptor tyrosine kinase Src (Src), epidermal growth factor receptor (EGFR), matrix metalloproteinase 9 (MMP9), and MMP2. HDD ameliorated renal tubular damage and collagen deposition and downregulated fibrosis-related proteins expression in UUO mice. Furthermore, HDD was demonstrated to reduce PI3K, Stat3, Src, EGFR, and MMP2 expressions, and enhance MMP9 expression in the kidney of UUO mice and in TGF-β 1-induced HK-2 cells.Conclusion: HDD can alleviate renal fibrosis which may be related to regulating the expression of essential proteins in the epithelial-mesenchymal transition and extracellular matrix production/degradation signaling pathways. Keywords: renal fibrosis, chronic kidney disease, Huangqi-Danshen decoction, network pharmacology, signaling pathway

Jiangping Zhang,&ast; Xinran Liu,&ast; Xiaorong Zhou, Yumei Li, Ke Chen, Tingting Kang, Wenting Du, Rongfei Suo The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai City, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Zhou, The Fifth Affiliated Hospital of Sun Yat-sen University, Meihua Road, Xiangzhou District, Zhuhai City, Guangdong Province, People’s Republic of China, Tel +86-756-15916286566, Email joxiaoro@163.comObjective: To explore the relationships among benefit finding (BF), self-management, and quality of life (QOL) among patients with COPD.Methods: A total of 205 patients with COPD were selected via a convenient sampling method. BF refers to the ability to find meaning or benefit from difficult situations. The Benefit Finding Scale (BFS), self-management scale, and 36-item Short-Form Health Survey (MOS SF-36) were used to investigate BF, self-management and QOL (including a physical component summary (PCS) and a psychological component summary (MCS)). Structural equation modeling was used to examine the relationships among BF, self-management and QOL in patients with COPD and to analyze the effects of BF and self-management on QOL.Results: The total QOL score of patients with COPD was 61.38± 21.15, and the PCS and MCS scores were 57.67± 23.60 and 65.09± 21.24, respectively. BF and self-management had positive predictive effects on both the PCS (βBF = 0.519, PBF = 0.012; βself-management = 0.473, Pself-management = 0.012) and MCS (βBF = 0.425, PBF = 0.013; βself-management = 0.535, Pself-management = 0.016) of patients with COPD, and self-management mediated the relationships of BF with the PCS (β = 0.144, P = 0.008) and MCS (β = 0.162, P = 0.007).Conclusion: The QOL of patients with COPD needs to be improved, especially in terms of physical aspects. Helping COPD patients obtain better BF not only helps them improve their PCS and MCS directly but also indirectly through enhancing self-management to improve their PCS and MCS.Keywords: COPD, benefit finding, self-management, quality of life

Jiafeng Lu,1,&ast; Zhaoyan Li,2,&ast; Xingjing Liu,2 Bin Xu,1 Weiyu Zhang2 1Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China; 2Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiyu Zhang, Department of Traditional Chinese Medicine, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, People’s Republic of China, Tel +86-021-67888394 ; Tel +86-13818103558, Email zhangweiyu33@163.com Bin Xu, Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, 200025, People’s Republic of China, Tel +86-021-67888176 ; Tel +86-18917762607, Email xb40291@rjh.com.cnBackground: The resistance to endocrine therapy can lead to recurrence and metastasis of breast cancer (BC), affecting the survival period. Tiaogan Bushen Xiaoji (TGBSXJ) Formula, a traditional Chinese medicine (TCM) decoction, has been widely used in the treatment of estrogen receptor-positive (ER+) BC. However, the underlying mechanism of TGBSXJ Formula in ER+BC treatment has not been totally elucidated.Methods: Network pharmacology (NP) and RNA sequencing were used to predict the candidate ingredients and explore the potential targets of TGBSXJ Formula. Then, the results of NP and RNA sequencing were investigated by in vitro experiments.Results: Active ingredients of TGBSXJ Formula mainly included Mangiferin, Rutin, Anemarrhena asphodeloides saponin BII, Ganoderic acid A and Acacetin, etc. A protein-protein interaction (PPI) network was created based on the active ingredients of TGBSXJ Formula and target genes of ER+ BC, in which TGF-β, MMP2 and SMAD3 were defined as the hub genes. In vitro experiments showed that TGBSXJ Formula significantly inhibited the viability, colony ability and migration of ER+ BC cells, and significantly increased the sensitivity to TAM. Western blot analysis showed that TGBSXJ Formula significantly downregulated TGF-β, E-cadherin, MMP2, MMP9, N-cadherin, p-Smad2 and p-Smad3 in ER+ BC cells.Conclusion: TGBSXJ Formula increases the sensitivity of ER+ BC cells to TAM by inhibiting the TGF-β/Smad signaling pathway.Keywords: estrogen receptor-positive breast cancer, network pharmacology, traditional Chinese medicine, endocrine resistance

Lijing Huo,1 Xuexin Liu,2 Changmei Wei,1 Fang Yu,1 Luping Ren,3 Yanqing Tie1 1Department of Medical Laboratory, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 2Health Check-up Centers, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Lijing Huo, Department of Medical Laboratory, Hebei General Hospital, 348 Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, People’s Republic of China, Email huolijing1979@126.comAim: This study was intended to establish the reference intervals of bone turnover markers (BTMs) for healthy populations.Methods: According to the Clinical Laboratory Standards Institute (CLSI) EP28-A3c, we recruited 774 healthy Chinese and investigated their clinical characteristics and relationships among gender, age, season and BTMs. The reference intervals of BTMs for healthy populations in Hebei of China were established through defining the central 95% range of all observations.Results: We found that gender were associated with 25(OH)D, OC, β-CTX, and P1NP (P < 0.05), but not PTH1-84 (P=0.138). All serum BTMs showed differences among different age groups (P < 0.01). The level of 25 (OH) D in winter showed statistical differences with spring, summer, and autumn (P< 0.05). The OC level showed statistical difference between summer and winter (P=0.000). The P1NP levels showed statistical difference between spring and winter (P=0.019), summer and winter (P=0.000), and summer and autumn (P=0.012), respectively. The PTH1-84 levels in winter showed statistical differences with spring, and summer (all P=0.000), while there was no statistically significant difference in β- CTX levels between seasons.Conclusion: We have established the reference intervals of several BTMs for healthy individuals in Hebei of China, which have statistical significance across different age groups and genders, and there are also significant differences between different seasons. Therefore, the Chinese medical laboratories in different locations should group individuals according to gender and age groups in different seasons, and establish corresponding biological reference intervals.Keywords: 25-hydroxyvitamin D, 25(OH)D, osteocalcin, OC, β-carboxy-terminal cross-linking telopeptide of type I collagen, β-CTX, N-terminal procollagen of type I collagen, P1NP, parathyroid hormone 1-84, PTH1-84

Jialin Ma, Xiaojing Liu, Yongxin Li Faculty of Education, Henan University, Kaifeng, Henan Province, People’s Republic of ChinaCorrespondence: Yongxin Li, Faculty of Education, Henan University, Kaifeng, Henan Province, 475000, People’s Republic of China, Tel +8613503780519, Email liyongxin@henu.edu.cnBackground: Studies have shown that elderly individuals have significantly worse facial expression recognition scores than young adults. Some have suggested that this difference is due to perceptual degradation, while others suggest it is due to decreased attention of elderly individuals to the most informative regions of the face.Methods: To resolve this controversy, this study recruited 85 participants and used a behavioral task and eye-tracking techniques (EyeLink 1000 Plus eye tracker). It adopted the “study-recognition” paradigm, and a mixed experimental design of 3 (facial expressions: positive, neutral, negative) × 2 (subjects’ age: young, old) × 3 (facial areas of interest: eyes, nose, and mouth) was used to explore whether there was perceptual degradation in older people’s attention to facial expressions and investigate the differences in diagnostic areas between young and older people.Results: The behavioral results revealed that young participants had significantly higher facial expression recognition scores than older participants did; moreover, the eye-tracking results revealed that younger people generally fixated on faces significantly more than elderly people, demonstrating the perceptual degradation in elderly people. Young people primarily look at the eyes, followed by the nose and, finally, the mouth when examining facial expressions. The elderly participants primarily focus on the eyes, followed by the mouth and then the nose.Conclusion: The findings confirmed that young participants have better facial expression recognition performance than elderly participants, which may be related more to perceptual degradation than to decreased attention to informative areas of the face. For elderly people, the duration of gaze toward the facial diagnosis area (such as the eyes) should be increased when recognizing faces to compensate for the disadvantage of decreased facial recognition performance caused by perceptual aging.Keywords: facial expressions, age, areas of interest, eye movement

Yan Tang,1,&ast; Xiaoling Liu,1,&ast; Wang Zhou,2 Xiachuan Qin3 1Department of Ultrasound, Beijing Anzhen Hospital Nanchong Hospital, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, 637000, People’s Republic of China; 2Department of Ultrasound, The First Affiliated hospital of Anhui medical University, Hefei, Anhui, 230022, People’s Republic of China; 3Department of Ultrasound, Chengdu Second People’s Hospital, Chengdu, Sichuan, 610000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiachuan Qin, Department of Ultrasound,Chengdu Second People’s Hospital,Chengdu, Sichuan, 610000, People’s Republic of China, Tel +86 18113917878, Email 11326636@qq.comPurpose: To assess the crescentic status of IgA nephropathy (IgAN) non-invasively using a superb microvascular imaging (SMI)-based radiomics machine learning (ML) model.Patients and Methods: IgAN patients who underwent renal biopsy from June 2022 to October 2023, with two-dimensional ultrasound (US) and SMI examinations conducted one day prior to the renal biopsy. The patients selected were divided randomly into a training group and a test group in a 7:3 ratio. Radiomic features were extracted from US and SMI images, then radiomic features were constructed and ML models were further established using logistic regression (LR) and extreme gradient boosting (XGBoost)XGBoost to determine the crescentic status. The utility of the proposed model was evaluated using receiver operating characteristics, calibration, and decision curve analysis. The SHapley Additive exPlanations (SHAP) was utilized to explain the best-performing ML model.Results: A total of 147 IgAN patients were included in the study, with 103 in the training group and 44 in the test group .Among them, the US-SMI based XGBoost model achieved the best results, with an the area under the curve (AUC) of 0.839 (95% CI,0.756– 0.910) and an accuracy of 78.6% in the training group.In the test group, the AUC was 0.859 (95% CI,0.721– 0.964), and the accuracy was 81.8%, significantly surpassing the ML model of a single modality and the clinical model established based on occult blood. Additionally, the decision curve analysis (DCA) demonstrated that the XGBoost model provided a higher overall net benefit in the both groups.Conclusion: The SMI radiomics ML model has the capability to accurately predict the crescentic status of IgAN patients, providing effective assistance for clinical treatment decisions.Keywords: IgA nephropathy, crescent, ultrasound, superb microvascular imaging, radiomics

Chuanjiang Dong,1,&ast; Yueqing Wang,2,3,&ast; Yi Cai,4,&ast; Yuhuang Wu,2,3 Wei Chen,2,3 Lu Wang,2,3 Xiaowen Liu,2 Lili Zou,2,3 Jun Wang5 1Department of Urology, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, Guangdong province, 523718, People’s Republic of China; 2Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China; 3Yichang Key Laboratory of Infection and Inflammation, College of Basic Medical Science, China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China; 4Department of Laboratory Medicine, Xiaogan Central Hospital, Xiaogan, Hubei Province, 432099, People’s Republic of China; 5The Second People’s Hospital of China Three Gorges University, Yichang, Hubei Province, 443002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lili Zou; Jun Wang, Email zoulili@ctgu.edu.cn; wangjfox@ctgu.edu.cnPurpose: Tuberculosis (TB) remains a major health threat worldwide, and the spread of drug-resistant (DR) TB impedes the reduction of the global disease burden. Ebselen (EbSe) targets bacterial thioredoxin reductase (bTrxR) and causes an imbalance in the redox status of bacteria. Previous work has shown that the synergistic action of bTrxR and sensitization to common antibiotics by EbSe is a promising strategy for the treatment of DR pathogens. Thus, we aimed to evaluate whether EbSe could enhance anti-TB drugs against Mycobacterium marinum (M. marinum) which is genetically related to Mycobacterium tuberculosis (Mtb) and resistant to many antituberculosis drugs.Methods: Minimum inhibitory concentrations (MIC) of isoniazid (INH), rifampicin (RFP), and streptomycin (SM) against M. marinum were determined by microdilution. The Bliss Independence Model was used to determine the adjuvant effects of EbSe over the anti-TB drugs. Thioredoxin reductase activity was measured using the DTNB assay, and its effects on bacterial redox homeostasis were verified by the elevation of intracellular ROS levels and intracellular GSH levels. The adjuvant efficacy of EbSe as an anti-TB drug was further evaluated in a mouse model of M. marinum infection. Cytotoxicity was observed in the macrophage cells Raw264.7 and mice model.Results: The results reveal that EbSe acts as an antibiotic adjuvant over SM on M. marinum. EbSe + SM disrupted the intracellular redox microenvironment of M. marinum by inhibiting bTrxR activity, which could rescue mice from the high bacterial load, and accelerated recovery from tail injury with low mammalian toxicity.Conclusion: The above studies suggest that EbSe significantly enhanced the anti-Mtb effect of SM, and its synergistic combination showed low mammalian toxicity in vitro and in vivo. Further efforts are required to study the underlying mechanisms of EbSe as an antibiotic adjuvant in combination with anti-TB drug MS.Keywords: Ebselen, antibiotic adjuvant, thioredoxin reductase, reactive oxygen species

Hanzhi Chen,1,&ast; Leting Zhou,1,&ast; Meilin Yan,1,&ast; Cheng Li,1 Bin Liu,1 Xiaobin Liu,1 Weiwei Shan,1 Ya Guo,2 Zhijian Zhang,1 Liang Wang1 1Department of Nephrology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, 214000, People’s Republic of China; 2Key Laboratory of Advanced Process Control for Light Industry (Ministry of Education), Jiangnan University, Wuxi, Jiangsu, 214122, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Zhang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email zzjwxyy@163.com Liang Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, 299 Qingyang Road, Wuxi, Jiangsu, 214000, People’s Republic of China, Email wangliang_wuxi@126.comBackground: End-stage kidney disease (ESKD) patients often face complications like anemia, malnutrition, and cardiovascular issues. Serological tests, which are uncomfortable and not frequently conducted, assist in medical assessments. A non-invasive, convenient method for determining these test results would be beneficial for monitoring patient health.Objective: This study develops machine learning models to estimate key serological test results using non-invasive cellular bioelectrical impedance measurements, a routine procedure for ESKD patients.Methods: The study employs two machine learning models, Support Vector Machine (SVM) and Random Forest (RF), to determine key serological tests by classifying cell bioelectrical indicators. Data from 688 patients, comprising 3,872 biochemical–bioelectrical records, were used for model validation.Results: Both SVM and RF models effectively categorized key serological results (albumin, phosphorus, parathyroid hormone) into low, normal, and high. RF generally outperformed SVM, except in classifying calcium levels in women.Conclusion: The machine learning models effectively classified serological test results for maintenance hemodialysis patients using cellular bioelectrical indicators, therefore can help in making judgments about physicochemical indicators using electrical signals, thereby reducing the frequency of serological tests.Keywords: serological test results, cellular bioelectrical indicators, machine learning, End-stage kidney disease

Zonglin Li,1,&ast; Xingming Shu,1,&ast; Xin Liu,1 Qiuyun Li,2 Yifu Hu,2 Bingbing Jia,2 Min Song3 1Department of General Surgery (Gastrointestinal Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Grade 2023, Clinical Medicine College, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Song, Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Tel +8615883059785, Email songminlele2007@126.comAbstract: Gastric cancer (GC) is one of the most common malignant tumors in the digestive tract, and chemotherapy plays an irreplaceable role in the comprehensive treatment of GC. However, chemoresistance makes it difficult for patients with GC to benefit steadily from chemotherapy in the long term, which ultimately leads to tumor recurrence, metastasis, and patient death. Elucidating the detailed mechanism of chemoresistance in GC and identifying specific therapeutic targets will help to solve the difficult problem of chemoresistance and improve the prognosis of patients with GC. This review summarizes and clarifies the cellular and molecular mechanisms underlying chemoresistance for GC.Keywords: gastric cancer, chemoresistance, cellular mechanisms, molecular mechanisms

Xueen Liu,1 Fang Pan,1 Qingmei Wang,1 Shuai Wang,1 Jiale Zhang2 1Department of Nursing, Beijing Hepingli Hospital, Beijing, People’s Republic of China; 2Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Jiale Zhang, Email zhang_tcm@163.comAbstract: Myofascial as a holistic structure emphasizes a holistic approach to intervention and treatment of fascial-related disorders such as neck pain (NP), low back pain (LBP), and knee pain. There are currently adverse effects of medication for diseases related to myofascial. Traditional Chinese rehabilitation exercise (TCRE) is a practical approach to traditional Chinese medicine and is a valuable option for intervening in myofascial-related pain. This article found some research evidence for Baduanjin, Wuqinxi, and Yijinjing in clinical studies of myofascial chain-related pain. The article summarizes the current evidence and finds that TCRE can enhance limb movement function through breathing and slow movements, increase joint movement and flexibility, and reduce joint pathology and stress-induced pain. As for future directions, focus on TCRE in improving the health of older adults and treating long-COVID syndrome, and integrate robotic and TCRE training to frame safe and effective exercise models. Relevant studies have already been registered in the Clinical Trials Registry, and some clinical study protocols have been published. TCRE can be an alternative nonpharmacological rehabilitation therapy to alleviate chronic rheumatic pain symptoms and augment public health management.Keywords: traditional Chinese rehabilitation exercise, pain, myofascial chain, rehabilitation

Jian Jiang,1,2,&ast; Xiaoyan Hou,1,&ast; Lili Gu,3 Xian Liu,1 Huiting Lv,1 Jiaxin Xiong,1 Hongmei Kuang,1,2 Xiaofeng Jiang,1 Shunda Hong1,2 1Department of Radiology, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China; 2Jiangxi Medical Imaging Research Institute, Nanchang, People’s Republic of China; 3Department of Pain, The First Affiliated Hospital, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shunda Hong, Department of Radiology, The First Affiliated Hospital, Nanchang University, 17 Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88693825, Email dyfy05441@ncu.edu.cnPurpose: This study aimed to explore the abnormal changes in short- and long-range functional connectivity density (FCD) in patients with herpes zoster (HZ) and postherpetic neuralgia (PHN).Patients and Methods: Twenty HZ patients, 22 PHN patients, and 19 well-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. We used FCD mapping, a data-driven graph theory method, to investigate local and global functional connectivity patterns. Both short- and long-range FCD were calculated and compared among the PHN, HZ, and HC groups. Then, the abnormal regions were used to calculate seed-based functional connectivity. Finally, correlation analyses were performed between the altered FCD values and clinical datas.Results: Compared with HCs, HZ patients showed significantly increased long-range FCD of the bilateral cerebellum, thalamus, parahippocampal gyrus, superior temporal gyrus and lingual gyrus. HZ patients also displayed significantly decreased short-range FCD of the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and left precuneus. Compared with HCs, PHN patients displayed significantly decreased long-range FCD of the bilateral superior frontal gyrus and decreased short-range FCD in the bilateral posterior cingulate gyrus, median cingulate/paracingulate gyri, and precuneus. However, there was no significant difference in either long-range or short-range FCD between the PHN and HZ patients. Long-range FCD deficit areas and the right insula showed altered functional connectivity in PHN patients. Furthermore, pain duration in patients with PHN was correlated with abnormal long-range FCD.Conclusion: Herpes zoster pain widely affects intra- and inter-regional functional connectivity, leading to disrupted short-range FCD and increased long-range FCD during different stages of the disease. Long-term chronic pain in PHN patients may impair the pain emotion regulation pathway. These findings could improve our understanding of the pathophysiological mechanisms of HZ and PHN and offer neuroimaging markers for HZ and PHN.Keywords: functional connectivity density, herpes zoster, postherpetic neuralgia, pain, functional magnetic resonance imaging

Jingfei Weng,1,2,&ast; Yuyao Xiao,1,&ast; Jing Liu,3,&ast; Xiaohua Liu,4 Yuqing He,2 Fei Wu,1 Xiaoyan Ni,1 Chun Yang1 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang; Xiaoyan Ni, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 18702135336 ; +86 15201803582, Email dryangchun@hotmail.com; nixiaoyan1103@126.comPurpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student’s t test, χ 2 test, and multivariable regression analysis.Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson–Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.Keywords: liver neoplasms, magnetic resonance imaging, P53-mutated

Jian Li,1,&ast; Li Liu,2,&ast; Zhiyun Gao,1 Xia Chuai,3 Xiaokun Liu,4 Xiaobo Zhang,2 Xinyu Zhang,2 Xiaoqing Su,2 Qian Xu,2 Zhuojun Deng2 1Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega Science, Chinese Academy of Sciences, Wuhan, Hubei, People’s Republic of China; 4Department of Ophthalmology, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuojun Deng, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email dengzhuojun@126.com; 37700469@hebmu.edu.cnPurpose: The incidence of visceral leishmaniasis (VL), a global infectious disease, has been on the rise in China’s Hebei province. When patients achieve clinical cure, they often do not reach an etiological cure, which may lead to recurrence of the disease. Here, we report a case of visceral leishmaniasis with a negative blood smear and bone marrow cytology.Patients and Methods: A 65-year-old man and bronchoalveolar lavage fluid mNGS.Results: A 65-year-old man developed a chronic fever, anorexia, splenomegaly, and pancytopenia. The blood metagenomic second-generation sequencing (mNGS) revealed Leishmania sequence readings, which led to the diagnosis of VL. After sodium antimony gluconate treatment, the blood smear and bone marrow cytology revealed no Leishmania bodies. However, pancytopenia and respiratory failure did not fully subside, and cardiotoxic damage emerged. The bronchoalveolar lavage fluid (BALF) mNGS was performed to detect the pathogen. Through BALF mNGS, Leishmania sequence was still detectable. Therefore, after the ECG returned to normal, antimony sodium gluconate was administered as a next course of treatment.Conclusion: BALF mNGS may assist in evaluating the therapeutic efficacy of VL with respiratory failure, especially in patients with negative blood and bone marrow cytology.Plain Language Summary: Accurate detection of visceral leishmaniasis is essential for clinical diagnosis.It is uncommon to use alveolar lavage fluid mNGS in etiological diagnosis.Patient with negative bone marrow cytology may refer to alveolar lavage fluid mNGS. Keywords: visceral leishmaniasis, metagenomic second-generation sequencing, bronchoalveolar lavage fluid, parasite diseases, case report

Xiaoming Liu,1 Xiaoni Yang2 1Department of Geriatric Medicine, The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 2Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, 250014, People’s Republic of ChinaCorrespondence: Xiaoni Yang, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, No. 16766 Jingshi Road, Jinan, 250014, People’s Republic of China, Email yangxiaoni1979@163.comAbstract: Global aging is rapidly accelerating, which significantly influences the health systems worldwide. Frailty emerges as the most conspicuous hallmark of aging, imposing novel global health challenges. Characterized by a multifaceted decline across physiological system, frailty diminishes an individual’s capacity to maintain equilibrium in the presence of stressors, which leads to adverse outcomes such as falls, delirium, and disability. Several screening tools and interventions have been developed to mitigate the harm caused by frailty to human health, but research on frailty in mainland China commences belatedly with scant studies conducted. Therefore, it is imperative to explore screening methods and treatment modalities tailored to the Chinese context, thereby enhancing the older adults’ quality of life and advancing social medicine. This review aims to elucidate the evolution, diagnosis, and management of frailty, alongside the challenges it poses, with the overarching goal of guiding future diagnostic and therapeutic endeavors. Specifically, we summarized the mechanisms of frailty and intervention strategies in elderly people, and meanwhile, we evaluated the advantages and disadvantages of different measurement tools.Keywords: frailty, geriatrics, pathogenesis, assessment, intervention

Yanyan Song, Bin Zhang, Xudong Liu Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of ChinaCorrespondence: Xudong Liu, Department of Cardiovascular Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqnfective shoingDistrict, Yinchuan, 750004, People’s Republic of China, Tel +869516743014, Fax +86 0951-6744302, Email xudong669@163.comObjective: To summarize the experience of surgical treatment and perioperative management of a case of infective endocarditis with aortic valve damage in a child with congenital heart disease.Methods: We retrospectively analyzed the treatment of a pediatric patient with infective endocarditis combined with aortic valve damage, who was admitted to the Department of Cardiovascular Surgery of our hospital in Yinchuan in March 2024. We summarize the case data and present a literature review.Results: The child recovered well after surgery, with echocardiographic re-examination, mild regurgitation of the aortic valve, and no recurrence of endocarditis. She recovered and was discharged from hospital.Conclusion: The surgical treatment of infective endocarditis in children has achieved satisfactory results, and the timing of and indications for surgery are very important to achieve the therapeutic effect.Keywords: infective endocarditis, congenital heart disease, cardiac surgical procedures, child

Xiao-Meng Xie,1 Sha Sha,1 Hong Cai,2 Xinyu Liu,1 Isadora Jiang,3 Ling Zhang,1 Gang Wang1 1The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & the Advanced Innovation Center for Human Brain Protection, Capital Medical University, School of Mental Health, Beijing, People’s Republic of China; 2Unit of Medical Psychology and Behavior Medicine, School of Public Health, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 3Bellarmine College of Liberal Arts, Loyola Marymount University, Los Angeles, CA, USACorrespondence: Gang Wang, Beijing Anding Hospital, Beijing, People’s Republic of China, Email gangwangdoc@gmail.comBackground: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals.Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated.Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05).Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction.Keywords: major depressive disorder, MDD, EEG, alpha power, cognition impairment

Linghong Guo,1,2 Xu Liu,1,2 Qingfeng Liu,1,2 Xiaoqin Xie,1,2 Xian Jiang1,2 1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Xian Jiang; Linghong Guo, West China Hospital, Sichuan University, &num;37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-028-85423315, Fax +86-028-85422560, Email jiangxian@scu.edu.cn; linhom.guo@foxmail.comObjective: This randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of tranexamic acid essence combined with iontophoresis in treating melasma.Methods: Thirty participants were recruited and randomly assigned to the experimental (Group A) or control group (Group B). Group A received tranexamic acid essence iontophoresis treatment twice weekly for three months, while Group B received placebo treatment. Melasma Area and Severity Index (MASI) scores and skin luminance (L) values were assessed at baseline and weeks 4, 8, and 12.Results: No significant differences in baseline characteristics were observed between the groups. The mean MASI score reduction rate was significantly higher in Group A (− 0.10± 0.12%) compared to Group B (− 0.02± 0.09%) (p< 0.05). Skin L values significantly increased in Group A from 61.32± 3.53 to 63.32± 1.78, while slightly decreasing in Group B (p=0.037).Conclusion: Tranexamic acid essence combined with iontophoresis significantly improved MASI scores and skin luminance compared to placebo, demonstrating its effectiveness in treating melasma. Further research with larger sample sizes and longer follow-up is warranted to validate long-term effects and recurrence rates.Keywords: tranexamic acid, iontophoresis, melasma, clinical trial

Zemin Ou, Yun You, Hong Yi, Xiaoqian Liu, Yan Tong, Dewen Liu, Jinyu Wang Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Dewen Liu; Jinyu Wang, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 10700, People’s Republic of China, Email dwliu@icmm.ac.cn; wangjinyu@icmm.ac.cnIntroduction: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra. The precise molecular mechanisms underlying neuronal loss in PD remain unknown, and there are currently no effective treatments for PD-associated neurodegeneration. Echinacoside (ECH) is known for its neuroprotective effects, which include scavenging cellular reactive oxygen species and promoting mitochondrial fusion. However, the blood-brain barrier (BBB) limits the bioavailability of ECH in the brain, posing a significant challenge to its use in PD treatment.Methods: We synthesized and characterized PEGylated ECH liposomes (ECH@Lip) and peptide angiopep-2 (ANG) modified liposomes (ECH@ANG-Lip). The density of ANG in ANG-Lip was optimized using bEnd.3 cells. The brain-targeting ability of the liposomes was assessed in vitro using a transwell BBB model and in vivo using an imaging system and LC-MS. We evaluated the enhanced neuroprotective properties of this formulation in a the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model.Results: The ECH@ANG-Lip demonstrated significantly higher whole-brain uptake compared to ECH@Lip and free ECH. Furthermore, ECH@ANG-Lip was more effective in mitigating MPTP-induced behavioral impairment, oxidative stress, dopamine depletion, and dopaminergic neuron death than both ECH@Lip and free ECH.Conclusion: The formulation used in our study significantly enhanced the neuroprotective efficacy of ECH in the MPTP-induced PD model. Thus, ECH@ANG-Lip shows considerable potential for improving the bioavailability of ECH and providing neuroprotective effects in the brain.Keywords: nanomedicine, brain delivery, angiopep-2, echinacoside, Parkinson’s disease, liposomes