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Tao Su,1,2,&ast; Ling Liu,3,&ast; Fan Meng,4,&ast; Hongzhen Wu,1,2 Tao Liu,1,2 Jun Deng,1,2 Xiang Peng,1,2 Min Zhi,1,2 Jiayin Yao1,2 1Department of Gastroenterology, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 4Digestive System Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhi; Jiayin Yao, Department of Gastroenterology, The Sixth Affiliated Hospital, Sun Yat-Sen University, 26th Yuancun the Second Road, Guangzhou, Guangdong Province, 510655, People’s Republic of China, Email zhimin@mail.sysu.edu.cn; yjyin@mail3.sysu.edu.cnBackground: Ustekinumab (UST) is recommended as the first-line treatment for patients with moderate to severe Crohn’s disease (CD). However, the efficacy of certain patients may be suboptimal and necessitate intensive treatment or modification of the treatment regimen. We sought to establish a nomogram model to predict the short-term effectiveness of UST in moderate to severe CD patients.Methods: We established a derivation cohort comprising patients diagnosed with CD and treated with UST at the Sixth Affiliated Hospital of Sun Yat-sen University from May 2020 to July 2023. The patient data, including demographic and clinical characteristics as well as treatment details, were systematically collected. The achievement of clinical remission (defined as Crohn’s Disease Activity Index, CDAI < 150, without corticosteroid usage) after induction therapy was the endpoint observed during follow-up. Potential predictors were identified through the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Subsequently, a multivariate logistic regression analysis was conducted to construct a nomogram model. The predictive accuracy and discriminative power of the model were assessed by Receiver Operating Characteristics (ROC) curves and calibration curves. Decision curve analysis (DCA) was employed to assess the clinical application value of the model.Results: 162 patients were included in the derivation cohort. The predictor’s selection was according to the minimum criteria. Prognostic factors, including duration, body mass index (BMI), smoking, extraintestinal manifestations (EIMs), perianal lesions (P), history of Vedolizumab therapy, and albumin levels (ALB), were identified and included in the nomogram. The model showed good discrimination and calibration on internal validation based on the bootstrap method (C-index: 0.843, 95% confidence interval: 0.768– 0.903). Moreover, DCA demonstrated that the nomogram was clinically beneficial.Conclusion: We constructed a practical tool to assist clinicians in identifying moderate to severe CD patients who are expected to have a good clinical response to UST, promoting personalized treatment and the development of precision medicine.Keywords: Ustekinumab, Crohn’s disease, clinical remission, nomogram

Huixin Cheng,1 Xuehan Wang,1 Juyi Yao,2 Chunbo Yang,3 Jian Liu1,4 1The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China; 2Traditional Chinese Medicine Hospital of Xinjiang Uygur Autonomous Region, Urumqi, People’s Republic of China; 3Department of Critical Medicine Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 4Department of Intensive Care Unit, Gansu Provincial Maternity and Child Health Hospital/Gansu Provincial General Hospital, Lan Zhou, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, The First Clinical Medical College of Lanzhou University, No. 222 Tianshui South Road, Lanzhou, Gansu Province, 730013, People’s Republic of China, Email medecinliujian@163.comAbstract: Sepsis is a common critical illness characterized by high mortality rates and a significant disease burden. In the context of sepsis-induced organ dysfunction, the lungs are among the initial organs affected, which may progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent studies have highlighted the crucial roles of mitophagy and ferroptosis in the development and progression of sepsis-induced ALI/ARDS. Identifying key convergence points in these processes may provide valuable insights for the treatment of this condition. In recent years, certain herbs and their bioactive compounds have demonstrated unique benefits in managing sepsis-induced ALI/ARDS by modulating mitophagy or ferroptosis. This review summary the mechanisms of mitophagy and ferroptosis, explores their interactions, and emphasizes their regulatory roles in the progression of sepsis-induced ALI/ARDS. Additionally, it offers a novel perspective on treatment strategies by summarizing various herbs and their bioactive compounds relevant to this condition.Keywords: sepsis, acute lung injury, acute respiratory distress syndrome, mitophagy, ferroptosis

Yurou Shi,1,2,&ast; Yingjie Zhang,1,&ast; Yaxuan Zhang,2 Jiali Yao,2 Junping Guo,3 Xiaoling Xu,2 Lijun Wang1 1Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310015, People’s Republic of China; 2Shulan International Medical College, Zhejiang Shuren University, Hangzhou, 310015, People’s Republic of China; 3Rainbowfish Rehabilitation and Nursing School, Hangzhou Vocational & Technical College, Hangzhou, 310018, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoling Xu, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cn Lijun Wang, Geriatric Medicine Center, Department of Endocrinology, Zhejiang Provincial People’s Hospital, No. 158 Shangtang Road, Hangzhou, Zhejiang, 310015, People’s Republic of China, Email wanglijun@hmc.edu.cnAbstract: Aging is an inevitable process in the human body, and cellular senescence refers to irreversible cell cycle arrest caused by external aging-promoting mechanisms. Moreover, as age increases, the accumulation of senescent cells limits both the health of the body and lifespan and even accelerates the occurrence and progression of age-related diseases. Therefore, it is crucial to delay the periodic irreversible arrest and continuous accumulation of senescent cells to address the issue of aging. The fundamental solution is targeted therapy focused on eliminating senescent cells or reducing the senescence-associated secretory phenotype. Over the past few decades, the remarkable development of nanomaterials has revolutionized clinical drug delivery pathways. Their unique optical, magnetic, and electrical properties effectively compensate for the shortcomings of traditional drugs, such as low stability and short half-life, thereby maximizing the bioavailability and minimizing the toxicity of drug delivery. This article provides an overview of how nanomedicine systems control drug release and achieve effective diagnosis. By presenting and analyzing recent advances in nanotherapy for targeting senescent cells, the underlying mechanisms of nanomedicine for senolytic and senomorphic therapy are clarified, providing great potential for targeting senescent cells. Keywords: senescent cells, calcium carbonate nanoparticles, liposomes, nanoemulsions, mesoporous silica nanoparticles

Chen Kong,1,&ast; Meifeng Yang,2,&ast; Ningning Yue,3,&ast; Yuan Zhang,4 Chengmei Tian,5 Daoru Wei,6 Ruiyue Shi,1 Jun Yao,1 Lisheng Wang,1 Defeng Li1 1The Second Clinical Medical College, Jinan University; Shenzhen, Guangdong, People’s Republic of China; 2Department of Hematology, Yantian District People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Gastroenterology, Shenzhen People’s Hospital (the Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 4Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, Guangdong, People’s Republic of China; 5Department of Emergency, Shenzhen People’s Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 6Department of Rehabilitation, Shenzhen People’s Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lisheng Wang; Defeng Li, Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 755 25533018, Email wanglsszrmyy@163.com; ldf830712@163.comAbstract: The intestinal barrier maintained by various types of columnar epithelial cells, plays a crucial role in regulating the interactions between the intestinal contents (such as the intestinal microbiota), the immune system, and other components. Dysfunction of the intestinal mucosa is a significant pathophysiological mechanism and clinical manifestation of inflammatory bowel disease (IBD). However, current therapies for IBD primarily focus on suppressing inflammation, and no disease-modifying treatments specifically target the epithelial barrier. Given the side effects associated with chronic immunotherapy, effective alternative therapies that promote mucosal healing are highly attractive. In this review, we examined the function of intestinal epithelial barrier function and the mechanisms of behind its disruption in IBD. We illustrated the complex process of intestinal mucosal healing and proposed therapeutic approaches to promote mucosal healing strategies in IBD. These included the application of stem cell transplantation and organ-like tissue engineering approaches to generate new intestinal tissue. Finally, we discussed potential strategies to restore the function of the intestinal barrier as a treatment for IBD.Keywords: inflammatory bowel disease, intestinal barrier, pathophysiology, treatment

Xianjun Xiao,1,&ast; Peiwen Xue,1,&ast; Xiangyun Yan,2,&ast; Yanqiu Li,2,&ast; Yunzhou Shi,2 Haiyan Qin,2 Di Qin,2 Wei Cao,2 Zihao Zou,2 Lu Wang,2 Rongjiang Jin,1 Ying Li,2 Junpeng Yao,2 Juan Li1,3 1School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 3Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Chengdu, Sichuan, 611135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Yao; Juan Li, Email yjp@cdutcm.edu.cn; 785939016@qq.comBackground: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research.Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness.Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of − 22%, − 24.9%, and − 24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of − 21.7% and − 23.7%, respectively.Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs’ potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.Keywords: urticaria, short-chain fatty acids, gut microbiota, gut-skin axis, Mendelian randomization

Wei Tang,1,2,&ast; Ying Liu,3,&ast; Xin Li,2 Guiyun Leng,2 Ju Gao,2 Yawu Wang,2 Jie Yao,2 Zhou Liu,2 Qiang Zhou,2 Yuanhong Xu1 1Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China; 3High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuanhong Xu, Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Shushan District, Hefei, Anhui, 230022, People’s Republic of China, Tel +86 135 0569 4447, Fax +86 551 6292 2125, Email xyhong1964@ahmu.edu.cnPurpose: This study aimed to investigate the microbiological characteristics of clinically isolated Staphylococcus aureus with different hemolytic phenotypes in China.Materials and Methods: Using the three-point inoculation method, the hemolytic phenotypes of 1295 clinically isolated S. aureus strains were detected and categorized. Antimicrobial susceptibility testing of all strains was performed using a VITEK 2 Compact System. After sample size matching, plasma coagulase activity, catalase activity, mRNA expression of hemolysin genes (hla, hlb, hlc, and hld), biofilm formation, growth kinetics, inflammatory response of macrophages and cytotoxicity of S. aureus with different hemolytic phenotypes using the rabbit plasma kit, the catalase test on slides, qRT-PCR, crystal violet staining, the microcultivation assay, the ELISA kits, and the CCK-8 assay, respectively.Results: Seven categories of hemolytic phenotypes were identified. Accordingly, strains were categorized into seven different groups, including S. aureus with complete hemolytic phenotype (SCHP), S. aureus with weak hemolytic phenotype (SWHP), S. aureus with incomplete hemolytic phenotype 1 (SIHP-1), SIHP-2, SIHP-3, SIHP-4 and SIHP-5, the last three of which were reported for the first time. Except for the hemolytic phenotype, all seven groups differed in clinical isolation rates, antibiotic resistance profile, plasma coagulase activity, mRNA expression of hemolysin genes, biofilm formation, growth kinetics, inflammatory response of macrophages, and cytotoxicity.Conclusion: S. aureus with different hemolytic phenotypes have distinctive microbiological characteristics. Clinical microbiologists need to be vigilant about the hemolytic phenotypes when culturing S. aureus strains, and actively enhance communication with clinicians to optimize the treatment of infection.Keywords: Staphylococcus aureus, hemolytic phenotype, hemolysin, microbiological characteristics, antibiotic resistance

PurposeThe ongoing lack of data standardization severely undermines the potential for automated learning from the vast amount of information routinely archived in electronic health records (EHRs), Radiation Oncology Information Systems (ROIS), treatment planning systems (TPSs), and other cancer care and outcomes databases. The effort sought to create a standardized ontology for clinical data, social determinants of health (SDOH), and other radiation oncology concepts and interrelationships.Methods and materialsThe American Association of Physicists in Medicine's (AAPM's) Big Data Science Committee (BDSC) was initiated July of 2019 to explore common ground from the stakeholders' collective experience of issues that typically compromise the formation of large inter- and intra- institutional databases from EHRs. The BDSC adopted an iterative, cyclical approach to engaging stakeholders beyond its membership to optimize the integration of diverse perspectives from the community.ResultsWe developed the Operational Ontology for Oncology (O3) which identified 42 key elements, 359 attributes, 144 value sets, and 155 relationships ranked in relative importance of clinical significance, likelihood of availability in EHRs, or the ability to modify routine clinical processes to permit aggregation. Recommendations are provided for best use and development of the O3 to four constituencies: device manufacturers, centers of clinical care, researchers, and professional societies.ConclusionsO3 is designed to extend and interoperate with existing global infrastructure and data science standards. The implementation of these recommendations will lower the barriers for aggregation of information that could be used creating large, representative, findable, accessible, interoperable and reusable (FAIR) datasets supporting the scientific objectives of grant programs. The construction of comprehensive "real world" datasets and application of advanced analytic techniques, including artificial intelligence (AI), holds the potential to revolutionize patient management and improve outcomes by leveraging increased access to information derived from larger, more representative datasets.

Jun Mei Teng,1 Shuiqing Qin,2 Danyu Lu,1 Yefa Gu,3 Shi Jie Tang,3 Qiong Yan,1 Jiawei Yao,1 Chao Zhang1 1Laboratory Department, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Science and Education, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Psychiatry, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Danyu Lu, Laboratory Department, The Fifth People’s Hospital of Nanning, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China, Tel +86 13457087740, Email 297459717@qq.comPurpose: To investigate the CYP2C19 genotype distribution and allelic frequency among the Zhuang and Han schizophrenic populations in Guangxi, examine the correlation between CYP2C19 genetic variants and standardized blood levels of Valproic Acid (VPA) in schizophrenic patients, and evaluate the effects of age, gender, and Body Mass Index (BMI) on standardized VPA blood concentrations.Patients and Methods: Between February and December 2022, 192 Zhuang and Han schizophrenia patients treated with VPA were studied. Steady-state VPA concentrations were determined using homogeneous enzyme immunoassays, and CYP2C19 &ast;1, &ast;2, and &ast;3 loci via q-PCR. CYP2C19 genotype distributions between Zhuang and Han groups in Nanning were compared using chi-square tests and contrasted with other ethnicities. Non-parametric tests analyzed VPA variations, identifying critical factors through multivariate stepwise regression.Results: The study identified five CYP2C19 genotypes at the &ast;2 and &ast;3 loci, with the &ast;3/&ast;3 genotype absent in both cohorts. The CYP2C19 distribution in Guangxi Zhuang and Han mirrors, yet diverges significantly from Hui and Kazakh groups. Among 192 subjects, VPA blood levels remained consistent across metabolic types and ages 18– 60 but varied significantly by gender. Multivariate analysis revealed gender and BMI as significant factors, overshadowing CYP2C19 genotype and age.Conclusion: In Guangxi, CYP2C19 genetic variants in Zhuang and Han schizophrenia patients demonstrate statistically indistinguishable allelic and metabolic distributions. Gender and BMI can influence standardized VPA blood concentrations in schizophrenia patients. However, in our study cohort, the CYP2C19 genotype and age are not the primary determinants of standardized VPA blood levels.Keywords: CYP2C19 gene, valproic acid, blood drug concentration, Zhuang Chinese, Han Chinese

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

Hui Yu,1 Xinyi He,1 Jinmeng Yao,1 Xiaoya Gu,1 Lin Zhou,1 Li Gao,1,2 Jia Wang1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Health Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Jia Wang; Li Gao, Email wangjia_80@163.com; gaoli23@mail.xjtu.edu.cnBackground: Molybdenum diselenide (MoSe2), as a nano near-infrared absorber, has been widely studied in the field of photothermal therapy of cancer. However, there is little research on its application in the treatment of human choriocarcinoma.Methods and Results: In this paper, a new type of carbon-coated MoSe2 (MEC) nanoparticles was prepared by a one-step hydrothermal method. The chemical characterization including SEM, TEM, EDS, XRD, FT-IR, TGA, Roman, and XPS showed that MEC was successfully synthesized. MEC exhibited a high photothermal conversion efficiency (50.97%) and extraordinary photothermal stability under laser irradiation. The cell experiment results showed that MEC had good biocompatibility on normal cells while significant photothermal effect on human choriocarcinoma (JEG-3) cells, achieving a good anticancer effect. The level of reactive oxygen species (ROS) in JEG-3 cells was significantly increased under the combination of MEC nanoparticles and near-infrared radiation. MEC nanoparticles could induce apoptosis of JEG-3 cells in combination with near-infrared radiation. Finally, transcriptomic analysis verified that MEC combined with laser radiation could inhibit DNA replication and induce apoptosis, thus improving its therapeutic effect on human choriocarcinoma.Conclusion: MEC nanoparticles exert an excellent photothermal effect and may become an important candidate drug for the treatment of human choriocarcinoma.Keywords: MoSe2, carbon-coated, biocompatibility, human choriocarcinoma, photothermal therapy

Qiong Ge,1,&ast; Zhewen Zhang,2,&ast; Zhiming Cao,2 Dan Wu,3 Changping Xu,1 Jianbiao Yao,3 Jian Gao,1 Yan Feng1 1Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China; 2College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine Pharmaceutical Technology, Zhejiang Conba Pharmaceutical Co., Ltd, Hangzhou, Zhejiang, 310057, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Feng, Key Laboratory of Public Health Detection and Etiological Research of Zhejiang Province, Department of Microbiology, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, 310051, People’s Republic of China, Tel/Fax +86-571-87115204, Email yfeng@cdc.zj.cnPurpose: This study aims to investigate the in vitro antiviral effects of the aqueous solution of Changyanning (CYN) tablets on Enterovirus 71 (EV71), and to analyze its active components.Methods: The in vitro anti-EV71 effects of CYN solution and its herbal ingredients were assessed by testing the relative viral RNA (vRNA) expression level and the cell viability rates. Material basis analysis was performed using HPLC-Q-TOF-MS/MS detection. Potential targets and active components were identified by network pharmacology and molecular docking. The screened components were verified by in vitro antiviral experiments.Results: CYN solution exerted anti-EV71 activities as the vRNA is markedly reduced after treatment, with a half maximal inhibitory concentration (IC50) of 996.85 μg/mL. Of its five herbal ingredients, aqueous extract of Mosla chinensis (AEMC) and leaves of Liquidambar formosana Hance (AELLF) significantly inhibited the intracellular replication of EV71, and the IC50 was tested as 202.57 μg/mL and 174.77 μg/mL, respectively. Based on HPLC-Q-TOF-MS/MS results, as well as the comparison with the material basis of CYN solution, a total of 44 components were identified from AEMC and AELLF. Through network pharmacology, AKT1, ALB, and SRC were identified as core targets. Molecular docking performed between core targets and the components indicated that 21 components may have anti-EV71 effects. Of these, nine were selected for in vitro pharmacodynamic verification, and only rosmarinic acid manifested in vitro anti-EV71 activity, with an IC50 of 11.90 μg/mL. Moreover, rosmarinic acid can stably bind with three core targets by forming hydrogen bonds.Conclusion: CYN solution has inhibitory effects on EV71 replication in vitro, and its active component was identified as rosmarinic acid. Our study provides a new approach for screening and confirmation of the effective components in Chinese herbal preparation.Keywords: antiviral effects, material basis analysis, component-target-pathway-disease network, protein–protein interaction network, core targets, rosmarinic acid

Jiapei Yao,1,2 Xindie Zhou,1,3 Dongmei Xu,1 Ting Liu,1 Yuanyuan Gui,4 Yong Huang1,3 1Department of Orthopedics, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Hunan Normal University, Changsha, People’s Republic of China; 3Changzhou Medical Center, Nanjing Medical University, Changzhou, People’s Republic of China; 4Department of Psychogeriatric Intensive Care Medicine, Xianlin Campus, Tongde Hospital of Zhejiang Province, Hangzhou, People’s Republic of ChinaCorrespondence: Yuanyuan Gui; Yong Huang, Email Guiyuanyuansltd@163.com; huangyong@njmu.edu.cnObjective: Secondary traumatic stress (STS) is stress caused by helping or wanting to help someone who has suffered a traumatic event. STS has adverse effects on nurses and their work, such as reduced career achievement, an increased staff turnover rate, inability to complete work, avoidance of contact with patients, mental exhaustion, negative emotions which seriously affect the quality of their work and life. The study to investigate secondary traumatic stress in emergency and intensive care nurses and analyze factors that influence it.Material and Methods: The study was a cross-sectional survey. Convenience sampling was used to select hospital emergency and intensive care department nurses (n=434) who met the inclusion and exclusion criteria from August to October 2021 to participate in this study. They provided demographic data and completed measures of secondary traumatic stress, emotional intelligence, anxiety and depression. Data analysis included independent samples t-tests, one-way analysis of variance, Pearson correlation analysis and multiple linear regression analysis.Results: Almost one-third (30.7%) of participants were at moderate risk for Secondary Traumatic Stress Scale or above, with high average scores on measures of anxiety (GAD-7 average = 6.05 ± 4.13), and depression (PHQ-9 average = 6.35 ± 4.85). The results of multiple linear regression analysis showed that the average daily amount of sleep in the past week, the number of night shifts in the past month, emotional intelligence, anxiety, and depression influenced secondary traumatic stress, explaining 70.8% of the variance.Conclusion: The STS of emergency and intensive care nurses in Changzhou is at a high level. Sleep time, number of night shifts and emotional intelligence are related to secondary traumatic stress and anxiety and depression significantly predicted the degree of secondary traumatic stress. Nurses need to master effective treatment methods for secondary traumatic stress, to improve their work efficiency and nursing quality and ensure nursing safety.Keywords: secondary traumatic stress, emergency and intensive care department nurses, anxiety, depression, emotional intelligence

Congcong Guo,1– 4 Mingwen Jiao,5 Yuying Cui,1– 4 Pingjiang Li,6 Jinming Yao,1– 3 Jianjun Dong,7 Lin Liao1– 4 1Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, People’s Republic of China; 2Shandong Key Laboratory of Rheumatic Disease and Translational medicine, Shandong Institute of Nephrology, Jinan, Shandong, People’s Republic of China; 3Shandong Institute of Nephrology, the First Affiliated Hospital of Shandong First Medical University& Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, People’s Republic of China; 4Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 5Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, People’s Republic of China; 6Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 7Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Lin Liao, Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Jinan, Shandong, People’s Republic of China, Tel +86 15168888260, Email liaolin@sdu.edu.cn Jianjun Dong, Department of Endocrinology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China, Tel +86 13791122910, Email dongjianjun@sdu.edu.cnPurpose: Proximal tubular epithelial cell (PTEC) is vulnerable to injury in diabetic kidney disease (DKD) due to high energy expenditure. The injured PTECs-derived profibrotic factors are thought to be driving forces in tubulointerstitial fibrosis (TIF) as they activate surrounding fibroblasts. However, the mechanisms remain unclear.Methods: The diabetes with uninephrectomy (DKD) rats were used to evaluated renal histological changes and the expression of Claudin-2 by immunofluorescence staining. Then, Claudin-2 expression in PTECs were modulated and subsequently determined the proliferation and activation of fibroblasts by building a transwell co-culture system in normal glucose (NG)or high glucose (HG) condition.Results: Decreased expression of Claudin-2 in PTECs accompanied by tight junction disruption and increased interstitial fibrosis, were detected in DKD rats. In vitro, downregulated Claudin-2 in PTECs promoted proliferation and activation of fibroblasts, which coincided with elevated expression of profibrotic connective tissue growth factor (CTGF) in PTECs. Silenced CTGF inhibited the profibrotic of PTECs via Claudin-2 inhibition. Fibroblasts co-cultured with PTECs transitioned more to myofibroblasts and generated extracellular matrix (ECM) significantly in response to high glucose (HG) stimulation whereas overexpression of Claudin-2 in PTECs reversed the above results. Upregulating CTGF disrupted the beneficial anti-fibrosis effects obtained by overexpression of Claudin-2 in HG condition.Conclusion: Our study suggested that Claudin-2 in PTECs, a key mediator of paracellular cation and water transport, promotes the activation and proliferation of surrounding fibroblasts significantly via CTGF in a paracrine manner.Keywords: proximal tubular epithelial cell, fibroblast, crosstalk, diabetic kidney disease, Claudin-2

Xiulin Huo,1,2 Peiying Huang,1 Hexuan Di,3 Tianxiao Ma,3 Sufang Jiang,1 Jie Yao,4 Lining Huang1 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Orthopaedic Surgery, The Key Laboratory of Orthopedic Biomechanics of Hebei Province, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei, People’s Republic of ChinaCorrespondence: Lining Huang, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China, Email 15803213730@163.comPurpose: Postamputation neuropathic pain is a common disease in patients with malignant tumor amputation, seriously affecting amputees’ quality of life and mental health. The objective of this study was to identify independent risk factors for phantom limb pain in patients with tumor amputation and to construct a risk prediction model.Methods: Patients who underwent amputation due to malignant tumors from 2013 to 2023 were retrospectively analyzed and divided into phantom limb pain group and non-phantom limb pain group. To determine which preoperative factors would affect the occurrence of phantom limb pain, we searched for candidate factors by univariate analysis and used multivariate logistic regression analysis to identify independent factors and construct a predictive model. The receiver operating characteristic curve (ROC) was drawn to further evaluate the accuracy of the prediction model in evaluating the phantom limb pain after amputation of bone and soft tissue tumors.Results: Multivariate analysis showed that age (OR, 1.054; 95% CI, 1.027 to 1.080), preoperative pain (OR, 5.773; 95% CI, 2.362 to 14.104), number of surgeries (OR, 3.425; 95% CI, 1.505 to 7.795), amputation site (OR, 5.848; 95% CI, 1.837 to 18.620), amputation level (OR, 8.031; 95% CI, 2.491 to 25.888) were independent risk factors for phantom limb pain for bone and soft tissue tumors. The the area under the curve (AUC) of this model was 0.834.Conclusion: Risk factors for postoperative phantom limb pain were the site of amputation, proximal amputation, preoperative pain, multiple amputations, and older age. These factors will help surgeons to individualize and stratify phantom limb pain and help patients with risk counseling. In particular, an informed clinical decision targeting those modifiable factors can be considered when needed.Keywords: neuropathic pain, phantom limb pain, bone and soft tissue tumors, amputation, risk factors, prediction model

Jiali Yao, Kun Chen, Hongjie Tong, Ruixin Liu Department of Critical Care Medicine, Jinhua Hospital Affiliated to Zhejiang University, Zhejiang, People’s Republic of ChinaCorrespondence: Kun Chen; Hongjie Tong, Department of Critical Care Medicine, Jinhua Hospital Affiliated to Zhejiang University, 365 Renmin East Road, Wucheng District, Zhejiang, 321000, People’s Republic of China, Email 13957970707@sina.com; 444370182@qq.comPurpose: Sepsis patients with persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have a poor prognosis, and early detection of biomarkers to predict its prognosis is particularly important. The purpose of this study is to investigate the predictive value of glycemic variability (GV) and high density lipid-cholesterol (HDL-C) for secondary PICS in patients with sepsis.Patients and Methods: One hundred and sixty-five patients with sepsis were enrolled in the retrospective study and divided into sepsis secondary PICS and non-PICS group. The daily blood glucose levels from 1 to 7 days after the diagnosis of sepsis were recorded, and GV was calculated. Logistic regression was used to analyze the risk factors of sepsis with PICS, receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of GV, and HDL-C for the prognosis of sepsis with PICS.Results: In a study of 165 patients, PICS group tended to have higher GV and lower HDL-C levels than those in the non-PICS group. Logistic regression analysis identified GV and HDL-C as independent risk factors for the secondary PICS of sepsis. The results of ROC curve showed that GV and HDL-C had a certain predictive value for the secondary PICS of sepsis, the sensitivity of GV was 77.5%, specificity of 81.8%, the sensitivity of HDL-C was 76.6%, and specificity of 74.8%.Conclusion: GV and HDL are risk factors for PICS secondary to sepsis and have predictive value for patients’ prognosis.Keywords: glycemic variability, high density lipid-cholesterol, sepsis, persistent inflammatory immunosuppressed catabolic syndrome