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Qu Zhao,1,2 Zeping Li,1,2 Dao Wen Wang,1,2 Fan Li,1,2 Li Zhang,3 Jiangang Jiang1,2 1Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, 430030, People’s Republic of China; 3Division of Cardiology, Minda Hospital of Hubei Minzu University, Enshi, 445099, People’s Republic of ChinaCorrespondence: Jiangang Jiang, Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China, Email jiangjg618@126.comBackground: Fulminant myocarditis (FM) is a critical manifestation of myocarditis. However, the clinical features and risk factors associated with its adverse outcomes are not fully understood. Given the high mortality and potential for long-term complications, it is crucial to identify factors that could predict the progression of FM to chronic persistent myocarditis. We hypothesize some clinical or laboratory markers may be predictive of this progression. This study aims to identify clinical factors that may help predict the progress of FM to chronic persistent myocarditis.Methods: A total of 82 patients with FM treated based on Chinese protocol were included. Kaplan–Meier curve and regression analysis were used to determine the clinical features and prognostic predictors of chronic persistent myocarditis in patients with 24 months of follow-up.Results: Chronic persistent myocarditis was observed in 20 patients during the follow-up. ROC curve showed that the critical value for chronic persistent myocarditis caused by lactate dehydrogenase (LDH) was 577.00U/L (sensitivity 75.0%, specificity 74.2%). Time from onset to admission over 6 days and LDH > 577.00U/L were identified as risk factors for chronic persistent myocarditis in patients with FM in both univariate and multivariate cox analysis. The hazard ratio and 95% Confidence intervals were 3.35 (1.32– 8.50) (p = 0.011) and 6.11 (2.02– 18.48) (p < 0.001), respectively. The per standard deviation of increment in LDH was associated with the 55% (1.55, 1.11– 2.18) in HR and 95% CI of the occurrence of chronic persistent myocarditis.Conclusion: About 24.4% of the patients with FM treated based on the life support measures proposed in the consensus of Chinese Society of Cardiology have been observed chronic persistent myocarditis. Time from onset to admission over 6 days and LDH levels > 577.00 U/L at admission may serve as risk factors for the progression from FM to chronic persistent myocarditis. Keywords: fulminant myocarditis, chronic persistent myocarditis, prognosis

Mengyu Zhang,1 Lei Wan,2 Haoxiang Fang,3 Xiaojun Zhang,4 Siyu Wang,1 Feng Li,1 Dawei Yan1 1Anhui University of Traditional Chinese Medicine First Clinical Medical College, Anhui, Hefei, People’s Republic of China; 2First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Anhui, Hefei, People’s Republic of China; 3Anhui University of Traditional Chinese Medicine, Anhui, Hefei, People’s Republic of China; 4Anhui University of Traditional Chinese Medicine Academic Affairs Office, Anhui, Hefei, People’s Republic of ChinaCorrespondence: Lei Wan; Xiaojun Zhang, Email yxwanlei@163.com; zhecho223@sohu.comIntroduction: Friend Leukemia Integration 1 Transcription Factor (FLI1) has attracted attention due to its involvement in rheumatoid arthritis (RA). Nevertheless, the precise mechanism through which FLI1 contributes to RA remains elusive. We investigated the potential role of FLI1 in RA through integrated bioinformatics, clinical experiments, and cellular experiments.Methods: Based on the GSE1919 and GSE12021 datasets, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses identified FLI1 as a differential gene in RA. Clinical validation was performed by measuring the FLI1 expression in the serum collected from RA patients. Correlational analysis between FLI1 and immune-inflammatory markers confirmed its association with RA inflammation. WGCNA analysis, along with the KnockTF, JASPAR, and ENCODE databases, was employed to predict the potential target genes of FLI1. Receiver operating characteristic analysis and gene-set enrichment analysis-KEGG were conducted to elucidate the biological functions of these target genes. Finally, cellular experiments were performed to validate FLI1’s regulatory effects on its target genes and its impact on synovial cell viability and apoptosis in RA.Results: FLI1 was upregulated in RA. FLI1 exhibited positive correlations with CRP, ESR, CCP, RF, IL-6, IL-10, IL-8, and TNF-α. The combined detection of FLI1 with CRP, ESR, CCP, and RF demonstrated the highest efficacy in evaluating RA disease activity. The target genes most strongly associated with FLI1 were AGA, DCK, LRRC15, MAN2A1, and TES, all of which exhibited positive correlations with FLI1. The suppression of FLI1 expression led to a decreased expression of AGA, DCK, LRRC15, MAN2A1, and TES. Furthermore, the inhibition of FLI1 reduced the viability of RA synovial cells and promoted their apoptosis.Discussion: FLI 1 is upregulated in RA and can promote inflammation, increase RA synovial cell viability, or inhibit synovial cell apoptosis. This finding suggests that FLI 1 and its target genes may serve as novel therapeutic targets in RA. The present findings integrate bioinformatics and experimental approaches to advance our current understanding of RA and open new avenues for targeted therapies.Keywords: ETS family, FLI1, rheumatoid arthritis, immunoinflammation, apoptosis

Yue Meng,1,&ast; Fang Li,2,&ast; Yan Gu,1 Ying Zhou,1 Yonggang Zhang,1 Yongbao Liu,1 Zhongchang Miao1 1Department of Imaging, Lianyungang First People’s Hospital, Lianyungang, Jiangsu, People’s Republic of China; 2Department of Nursing, Lianyungang Second People’s Hospital, Lianyungang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongchang Miao, Department of Imaging, Lianyungang First People’s Hospital, 1st Floor, Building 2, Gaoxin District, No. 6 East Zhenhua Road, Haizhou District, Lianyungang, Jiangsu, People’s Republic of China, Tel +86-18961326819, Email lygzhchmiao@163.comIntroduction: The traditional injection method of contrast media (CM) has limitations in terms of volume and imaging quality. Choosing the optimal CM injection method is crucial for ensuring high-quality images and accurate diagnosis in triple-rule-out computed tomography angiography (TRO-CTA). This study aims to investigate the application value of combining region of interest (ROI) with CM injection method alterations in TRO-CTA.Methods: A total of 596 patients with chest pain, chest tightness, and dyspnea as the primary clinical symptoms, underwent TRO-CTA examinations based on their clinical symptoms and test indicators. These patients were randomly assigned to one of three groups: the traditional group, the modified group, and the high-pitch helical scan (FLASH) group. Key parameters, including computed tomography (CT) values, vascular filling contrast numbers, image noise, signal-to-noise ratio, contrast noise ratio, image scores, CM volume, CM injection rate, radiation dose of the aorta, pulmonary artery, and coronary artery, were systematically compared across the three groups.Results: The CM volume and radiation doses were significantly higher in the traditional group compared to the other groups (P < 0.05). CT values for the aorta and coronary artery in the traditional group were higher than those in the modified and FLASH group, while CT values for the pulmonary artery were lower in the traditional group compared to the modified and FLASH groups (ALL P-value for traditional group versus FLASH group, P-value for modified group versus traditional group < 0.05, P-value for modified group versus FLASH group > 0.05).Conclusion: The combination of the modified CM injection method and FLASH scanning mode reduces the required CM volume by nearly 30 mL and significantly decreases radiation dose exposure during the examination. This approach shows valuable potential for improving both the safety and effectiveness of TRO-CTA, with significant implications for clinical practice.Keywords: triple-rule-out computed tomography angiography, chest pain, contrast injection methods

Dongdong Zhang,1 Minnan Deng,1 Fenfen Li,2 Ruile Shen1 1Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China; 2School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450001, People’s Republic of ChinaCorrespondence: Ruile Shen; Fenfen Li, Email haikuopingyuyuehu@outlook.com; liff@zzu.edu.cnBackground: Primary ventriculitis is a rare but serious brain infection characterized by inflammation of the ependyma and purulence within the ventricular system. Due to the challenges in early diagnosis and the potential for suboptimal treatment, this condition carries a significant risk of complications such as recurrence, hydrocephalus, and death. Metagenomic next-generation sequencing (mNGS) enables the rapid and broad-spectrum identification of pathogens, facilitating timely and precise diagnosis.Case Report: This study presents the first reported case of primary ventriculitis caused by Streptococcus constellatus. An 81-year-old female patient with hydrocephalus and clinical signs of central nervous system infection was diagnosed with primary ventriculitis based on brain magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) analysis using mNGS. The patient underwent external ventricular drainage (EVD) and received a five-week course of ceftriaxone and linezolid. Following timely and targeted therapy, she demonstrated significant clinical improvement and was discharged without residual symptoms.Conclusion: Key insights from this case include: 1) mNGS is an invaluable tool for the early and accurate diagnosis of primary ventriculitis; 2) MRI is indispensable for identifying characteristic radiological features of the condition; 3) prompt initiation and completion of appropriate antibiotic regimens significantly improve clinical outcomes.Keywords: primary pyogenic ventriculitis, Streptococcus constellatus, metagenomic next-generation sequencing, mNGS

Xia Li,1,&ast; Ben-Kai Wei,2,&ast; Fan Li,1 Huan-Huan Yan,1 Jun Shen1 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu Province, People’s Republic of China; 2Department of General Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of Xuzhou Medical University, Lianyungang, 222000, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Shen, Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, 222002, Jiangsu Province, People’s Republic of China, Tel +8618961325323, Email shenjun2257@126.comObjective: This study aims to develop and validate a predictive model for short-term post-treatment anxiety trajectories in patients with breast cancer, utilizing baseline patient characteristics and initial anxiety scores to inform precise clinical interventions.Methods: Baseline characteristics were collected from 424 patients diagnosed with breast cancer who underwent surgical treatment at our hospital between January 1, 2021, and December 30, 2022. Anxiety levels were assessed using the Self-Rating Anxiety Scale (SAS) scores at admission and at 3-, 6-, 9-, and 12-months post-treatment. Distinct trajectories of SAS score changes were identified and categorized. Variables were screened, and multiple models were developed. The optimal model was identified through comparative analysis, and a nomogram was generated following model simplification.Results: We found three distinct trends in the trajectory of anxiety, but we grouped them into two broad categories: gradual reduction of anxiety and persistent anxiety. LM Model was established by logistic regression, and Model 1 and Model 2 were established by Random Forest (RF) and eXtreme Gradient Boosting (Xgboost) screening variables. The ROC curve areas in the validation set were 0.822 (0.757– 0.887), 0.757 (0.680– 0.834) and 0.781 (0.710– 0.851), respectively. Model comparison, using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI), identified the Lm model as optimal, which underwent further simplification and value assignment. Decision Curve Analysis (DCA) and Clinical Impact Curve (CIC) analyses confirmed the superiority of model-based interventions over general interventions.Conclusion: Distinct anxiety trajectories are observed in patients diagnosed with breast cancer during the first 12 months post-treatment. Predictive modeling based on baseline characteristics is feasible although though further research is warranted.Keywords: anxiety, breast cancer, prediction model, self-rating anxiety scale score, trajectory analysis

Fan Li,1,2,&ast; Qi Huang,3,&ast; Lingling Xiong,1 Cheng Lei,4 Shaoyu Mou,5 Yujing Zhou,6 Ruichen Liang,7 Huiting Yu,8 Haihua Zhang,1 Xiaobo Ren,9 Qiuling Shi2 1Department of Otolaryngology-Head and Neck Surgery, Chongqing General Hospital, Chongqing University, Chongqing, People’s Republic of China; 2College of Public Health, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical, Chongqing, People’s Republic of China; 4Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliate Cancer Hospital of University of Electronic Science and Technology of China, Sichuan, People’s Republic of China; 5School of Nursing, Chongqing Medical University, Chongqing, People’s Republic of China; 6School of Nursing, Chongqing Medical & Pharmaceutical College, Chongqing, People’s Republic of China; 7Operating Room of Affiliated Hospital of Southwest Medical University, Sichuan, People’s Republic of China; 8Guang’an Vocational & Technical College Medical School, Sichuan, People’s Republic of China; 9Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiuling Shi, Email qshi@cqmu.edu.cnBackground: With the growing awareness of health and the expanding aging population, the demand for health services continues to rise. According to statistics from China, the number of professionals engaged in medical and health care services is insufficient to meet the public’s needs, particularly in terms of nursing human resources in medical institutions. Multi-site practice may offer a potential solution to this issue.Aim: To investigate the willingness and motivation of nursing students for multi-site practice of reference and nurse, and to lay a foundation for subsequent research.Research Questions: 1. How much do nursing students know about multi-site practice? What are the main sources of their knowledge of multi-site practice? 2. What are the main intentions and motivations of nursing students to participate in multi-site practice? For example, is it for financial gain, self-worth, or other reasons? 3. What are the potential barriers for nursing students to participate in multi-site practice in the future? For example, will inadequate laws and regulations, occupational safety issues or excessive work load affect their willingness?Methods: This cross-sectional study was conducted across eight provinces in China, involving 1014 nursing students who participated in an online survey between October and November 2021.Results: Among the 1014 nursing students surveyed, 61.74% were introduced to multi-site practice through their educational institutions, 75.25% expressed support for multi-site practice, and 53.75% indicated a willingness to engage in multi-site practice. However, a smaller percentage of students reported having a comprehensive understanding of multi-site practice. Notably, 61.74% of students cited their schools as the primary source of multi-site practice-related knowledge.Conclusion: Nursing students demonstrate positive attitudes toward multi-site practice and a willingness to participate. However, awareness of multi-site practice could be enhanced, and a standardized multi-site practice training system and model should be developed.Keywords: nursing students, multi-site practice, awareness, willingness

Tianxing Fang,1– 4 Liyu Hu,5 Tianshun Chen,4 Fei Li,6 Liu Yang,4 Bin Liang,7 Wenjun Wang,8 Fancai Zeng4 1Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, People’s Republic of China; 3Institute of Nuclear Medicine, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Laboratory of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, The Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of General Surgery (Breast Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan, People’s Republic of ChinaCorrespondence: Fancai Zeng; Wenjun Wang, Email zfcai@swmu.edu.cn; wenjunwang1213@126.comBackground: Breast cancer (BC) has become the main malignant tumor threatening the health of women worldwide. Previous studies have reported that Lactate dehydrogenase-A (LDHA) has critical roles in cancer development and progression. We aimed to explore the roles of LDHA and LDH5 isoenzyme activity in BC, which provides a new insight into LDHA for the treatment of BC.Methods: The expression of LDHA in BC and its relationship with clinicopathological features were obtained from various databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Breast Cancer-Gene Expression Miner (bc-GenExMiner), TNMplot, UALCAN. The Kaplan‒Meier Plotter was used to evaluate the prognostic value of LDHA. Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. The activities of LDH isoenzymes in serum and tissues were measured in patients with BC and healthy controls.Results: Compared to normal tissues, LDHA expression was significantly higher in BC tissues. Patients’ nodal status, histological types, TP53 mutation status and PAM50 subtypes were significant factors influencing the LDHA expression. By overexpressing or silencing LDHA gene in BT549 cells, it was confirmed that LDHA promoted cell proliferation, migration and invasion. LDH5 isoenzyme activity in patients with BC was higher than healthy controls. The increased activity of LDH5 isoenzymes was induced by overexpression of LDHA in BC. High expression of LDHA was found to be associated with poor prognosis in BC.Conclusion: LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.Keywords: LDHA, LDH5 isoenzyme, breast cancer, progression, prognosis

Yilu Zheng,1 Gareth R Williams,2 Ran Hu,1 Sen Tong,3 Jianxiang Xu,1 Tong Wang,1 Yanyan Zhang,1 Junzi Wu,3 Fan Li,4 Yingyu Cai,4 Li-Min Zhu1 1College of Biological Science and Medical Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, 201620, People’s Republic of China; 2UCL School of Pharmacy, University College London, London, WC1N 1AX, UK; 3The Key Laboratory of Microcosmic Syndrome Differentiation, Education Department of Yunnan, Yunnan University of Chinese Medicine, Kunming, 650500, People’s Republic of China; 4Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, People’s Republic of ChinaCorrespondence: Yingyu Cai, Department of Ultrasound, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, People’s Republic of China, Email yingyu.cai@shgh.cn Li-Min Zhu, College of Biological Science and Medical Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai, 201620, People’s Republic of China, Email lzhu@dhu.edu.cnBackground: The development of selective formulations able to target and kill tumor cells without the application of external energy has shown great promise for anti-tumor therapy.Methods: Here, we report a “nanobomb” that explosively increases Ca content within cells. It can selectively release Ca2+ and generate H2O2 in the tumor microenvironment (TME) by acid-triggered degradation of the two-layer protective shell (ie, unlocking the “double-lock”). This material, termed CaO2@ZIF8:CUR@PAA, comprises a CaO2 core coated with the ZIF-8 framework, which was then loaded with curcumin (CUR) and coated again with polyacrylic acid (PAA).Results: Under the slightly acidic conditions of the TME, the PAA shell (first lock) breaks down first exposing CaO2@ZIF8 and CUR inside the cell. Then, ZIF8 (second lock) is degraded in response to acid to deposit Ca2+, and H2O2. CUR can promote the release of Ca2+ from the endoplasmic reticulum to the cytoplasm, inhibit the outflow of Ca2+, and accumulates a large amount of Ca2+ intracellularly together with exogenous Ca2+ (calcium storms). The powerful calcium storm that causes mitochondrial dysfunction. The presence of a large amount of exogenous H2O2 causes further oxidative damage to tumor cell membranes and mitochondria where intracellular ROS production far exceeds clearance. CaO2@ZIF8:CUR@PAA NPs can induce cell S cycle arrest and apoptosis to inhibit tumor multiplication and growth. Oxidative damage-triggered immunogenic cell death (ICD) in turn leads to the polarization of macrophages to the M1 phenotype, inducing immunogenic cell death and inhibiting tumor cell proliferation and metastasis.Discussion: The acid two-step unlocking nanoplatform is a therapeutic modality that combines calcium storm and oxidative damage. The mode triggers apoptosis leading to ICD of tumor cells. The material induces cycle blockade during treatment to inhibit cell proliferation. Robust in vitro and in vivo data demonstrate the efficacy of this approach and CaO2@ZIF8:CUR@PAA as an anticancer platform, paving the way for nanomaterials in immune-triggered cancer therapy.Highlights: - A new calcium accumulation nanoplatform plays a role in activate antitumor immunity.- Double-locked structure slows down the premature decomposition of CaO2.- The platform allows Ca2+ and H2O2 to accumulate in tumor cells.- This leads to mitochondrial dysfunction, apoptosis, and M1 macrophage polarization.- Potent anti-tumor effects are seen both in vitro and in vivo.Keywords: Calcium ion load, controlled-release nanomaterials, two-layer protective shell, pH responsive drug release, reactive oxygen species, anti-cancer

Lin Li,&ast; Guangqi An,&ast; Fuzhen Li,&ast; Donghui Zhang, Xinyue Zhu, Chunyu Liang, Yu Zhao, Kunpeng Xie, Pengyi Zhou, Haiyan Zhu, Xuemin Jin,&ast; Liping Du&ast; Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Henan Province Eye Hospital, Henan International Joint Research Laboratory for Ocular Immunology and Retinal Injury Repair, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuemin Jin; Liping Du, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou, 450000, People’s Republic of China, Tel +8613603983193 ; +8613838191481, Email jinxuemin@zzu.edu.cn; dulplab@live.cnBackground: Associations between ulcerative colitis (UC) and ankylosing spondylitis (AS) have been reported in multiple studies, but the common etiologies of UC and AS remain unknown. Thus, in the current study, we aimed to investigate the shared genes and relevant mechanisms in UC and AS.Methods: Using datasets for UC (GSE113079) and AS (GSE1797879), we initially identified differentially expressed genes (DEGs) through differential expression analysis. The DEGs from both datasets were intersected to identify common DEGs, relevant to both UC and AS, which were used in receiver operating characteristic (ROC) curve analysis to confirm key genes in the shared pathway. Gene set enrichment analysis (GSEA) was used to obtain information on key gene pathways and interactions with UC or AS-related diseases, followed by immune infiltration analysis. Finally, peripheral blood samples of AS and UC were used to verify the mRNA expression of the eight key genes using reverse transcription-polymerase chain reaction (RT-PCR).Results: Our results revealed that GMFG, GNG11, CLEC4D, CMTM2, VAMP5, S100A8, S100A12 and DGKQ are potential diagnostic biomarkers of AS and UC. Rimegepant, eptinezumab, methotrexate, atogepant, and ubrogepant were identified as potential drugs for S100A12 and S100A8 in patients with UC and AS. GSEA showed that these key genes were associated with antigen processing and presentation, natural killer cell mediated cytotoxicity and the T cell receptor signaling pathway in AS and UC, and were significantly associated with immune cells in various immune-related pathways. Subsequent functional experiments revealed significant increases in the mRNA expressions of S100A12 and VAMP5 in patients with AS and UC. Additionally, CLEC4D mRNA expression was notably higher in patients with UC than in healthy controls.Conclusion: Key genes and shared pathways were identified in UC and AS, which may improve understanding of their relationship and guide diagnosis and treatment strategies.Keywords: ulcerative colitis, ankylosing spondylitis, diagnosis, etiology

Jun Wang,1,&ast; Yulong Li,1,&ast; Chunyu Tan,1,&ast; Jinlian Shao,1 Weitai Tang,2 Quan Kong,3 Wenqianjun Sheng,1 Zhiquan Ding,1 Feng Li,1 Jifeng Piao,1 Dingyi Lv,1 Libin Hu,1 Qinghua Wang,1 Xiaodan Jiang1 1Neuromedicine Center, The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, People’s Republic of China; 2Department of Neurosurgery, The People’s Hospital of Luoding & Affiliated Luoding Hospital of Guangdong Medical University, Luoding, 527200, People’s Republic of China; 3Neurosurgery Department of Zengcheng Campus, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qinghua Wang; Xiaodan Jiang, Email wqh1123@126.com; jiangxiao_dan@163.comBackground: Neuroinflammatory reactions are crucial factors in secondary brain damage following intracerebral hemorrhage (ICH). Although previous studies have shown that IRAK3 is involved in immune responses, the potential effects of IRAK3 on ICH remain unclear.Methods: Collagenase IV–induced ICH mouse model. Western blotting was used to determine the expression of IRAK3 at different time points following ICH. Immunofluorescence was used to investigate the cellular localization of IRAK3. The ICH model was treated with recombinant human IRAK3 (rh-IRAK3) or IRAK3 siRNA via an intracerebroventricular injection. The effect of IRAK3 on ICH mice was assessed by Western blotting and short-term and long-term neurological function evaluation. RNA-seq was performed to explore the mechanism by which IRAK3 promotes inflammation after ICH. The mechanisms of IRAK3 and neuroinflammation will be further investigated by Western blotting, qRT-PCR and immunofluorescence. Recombinant IL-17A was used to investigate the connection between IRAK3 and the NF-κB/IL-17A signaling pathway in vivo and in vitro experiments.Results: The expression of IRAK3 increased, peaking at 24 h, followed by a subsequent decrease after ICH. IRAK3 is mainly expressed in the microglia. RNA-seq analysis revealed 1,797 differentially expressed genes around the perihematomal brain tissue after IRAK3 siRNA treatment, with multiple inflammatory pathways being downregulated. Rh-IRAK3 treatment resulted in upregulation of the levels of inflammatory cytokines around the perihematomal tissue and exacerbated neurological function deficits. Furthermore, IRAK3 siRNA treatment markedly decreased the expression of inflammatory cytokines and microglial activation via the NF-κB/IL-17A signaling pathway. Recombinant IL-17A exacerbated the inflammatory response in vivo and in vitro; however, IRAK3 knockdown reversed this process.Conclusion: IRAK3 aggravates neuroinflammation by activating the NF-κB/IL-17A signaling pathway, thereby exacerbating neurological deficits following ICH. Therefore, inhibition IRAK3 may be a promising approach for treating ICH.Keywords: IRAK3, neuroinflammation, intracerebral hemorrhage, microglia, NF-κB/IL-17A pathway

Baoyue Ding,1,2,&ast; Mingjuan Li,2,&ast; Jie Zhang,2,&ast; Xiaojuan Zhang,2 Huan Gao,2 Jianqing Gao,3 Chunyan Shen,4 Yan Zhou,4 Fanzhu Li,5 Ailin Liu1 1Department of Pharmaceutical Analysis, Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, The School of Pharmacy, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics, Department of Pharmaceutics, Jiaxing University College of Medicine, Jiaxing, Zhejiang, People’s Republic of China; 3Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058 People’s Republic of China; 4Jiaxing Institute for Food, Drug and Product Quality Control, Jiaxing, Zhejiang, People’s Republic of China; 5Zhejiang Chinese Medical University, School of Pharmaceutical Science, Hangzhou, 310053, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fanzhu Li; Ailin Liu, Email lifanzhu@zcmu.edu.cn; ailinliu@mail.fjmu.edu.cnPurpose: The incidence of malignant melanoma (MM) has risen over the past three decades, and despite advancements in treatment, there is still a need to improve treatment modalities. This study developed a promising strategy for tumor-targeted co-delivery of Dacarbazine (DTIC) and miRNA 34a-loaded PHRD micelles (Co-PHRD) for combination treatment of MM.Methods: To construct the dual drug-loaded delivery system Co-PHRD, poly (L-arginine)-poly (L-histidine)-polylactic acid (PLA) was employed as a building block. In this system, poly (L-arginine) and PLA function as hydrophilic and hydrophobic blocks, respectively, which self-assemble into micelles in aqueous solution. Poly(L-arginine) and poly(L-histidine) are efficiently taken up by cells and perform efficient gene condensation, which facilitate the release of encapsulated miRNA 34a into the cytoplasm. Due to its lipophilic properties, PLA can effectively encapsulate DTIC. The polypeptide aptamer DR5-TAT (D21) was used as a targeting ligand. The properties of Co-PHRD and its in vitro release behaviour were characterized. Additionally, the synergetic effects of DTIC and miRNA 34a in melanoma therapy were investigated in vitro and in vivo.Results: Compared to DTIC treatment alone, Co-PHRD treatment exhibited 1.84-fold greater cytotoxicity in A375 cells, demonstrating that miRNA 34a enhanced the efficacy of DTIC. The particle size of Co-PHRD at an N/P ratio of 10 was 164.1 ± 4.5 nm, and the zeta potential of Co-PHRD was 27.3 ± 1.38 mV. The flow cytometry and CLSM results revealed both DTIC and miRNA 34a were avidly taken up by A375 cells at 1 h and 4 h in PHRD. In addition, in vivo results indicated that Co-PHRD micelles can significantly inhibit tumor growth without causing significant damage to major organs.Conclusion: Co-delivery of DTIC and miRNA 34a via polypeptide micelles showed synergistic effects against MM, offering a new strategy for gene and chemotherapy.Keywords: nano micelle, DTIC, miRNA 34a, co-delivery, malignant melanoma

Lin Zhu,1,&ast; Feiyong Jia,2,&ast; Aihua Cao,3,&ast; Yan Hao,4 Fei Li,5 Ruizhuo Liu,6 Honghua Li,2 Xiaoxiao Yu,3 Jinzhu Zhao,4 Feng Li,5 Yu Zhang,1 Yang Yu,1 Hua Wei,1 Ying Dai,1 Xuan Zhang,1 Xiao Liu,1 Bin Peng,7 Tingyu Li,1 Li Chen1 1Growth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Chongqing, 400014, People’s Republic of China; 2Department of Developmental and Behavioral Pediatric, the First Hospital of Jilin University, Changchun, 130021, People’s Republic of China; 3Department of Pediatrics, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China; 4Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 5Developmental and Behavioral Pediatric Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and Ministry of Education-Shanghai Key Laboratory for Children’s Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China; 6The Second Affiliated Hospital of Chengdu, Chengdu, 610017, People’s Republic of China; 7College of Public Health, Chongqing Medical University, Chongqing, 401331, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Chen, Growth, Development and Mental Health Center of Children and Adolescents, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, No. 136, Zhongshan 2nd Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Email chenli@cqmu.edu.cnPurpose: There is no consensus on whether cognitive measures among attention deficit hyperactivity disorder (ADHD) subtypes exhibit more similarities or differences, and most of them have been conducted on English-speaking subjects, lacking cross-cultural perspectives. The present study was aimed at investigating the intelligence structures of school-age children with ADHD who speak Chinese, using a multicenter and large sample size approach, offering some references for clinicians.Patients and Methods: 772 children aged 6 to 12 years with ADHD took part in the cross-sectional study. All participants underwent the Chinese Wechsler Intelligence Scale for Children-Third Edition assessment. Statistical Package for the Social Sciences (SPSS) Statistics 24 was used for statistical analyses.Results: No significant differences were found in full intelligence quotient (FIQ), verbal IQ (VIQ), performance quotient (PIQ), as well as most subtest scores among ADHD subtypes. The analysis of variance showed that the boys’ scores were higher than girls’ scores in PIQ (P < 0.05), information (P < 0.01), vocabulary (P < 0.05) and block design (P< 0.01) from the perspective of sex, but lower in the coding (P < 0.01). From the perspective of age, the senior group (aged 9– 12) scored higher in block design (P < 0.01) and object assembly (P < 0.05) than the junior one (aged 6– 8), but lower in VIQ (P < 0.05) and verbal comprehension (VC) factor.Conclusion: Our study supported that ADHD substyles shared more similarities in intelligence structures. Boys outperformed girls in PIQ and some subtests, suggesting that the importance to consider the gender differences and the distribution of intellectual strengths and weaknesses. Older children outperformed in block design and object assembly, but underperformed in VIQ and VC factor. This indicated the need to focus on language development and screen for specific learning disabilities in managing school-age children with ADHD.Keywords: school-age children, ADHD, intelligence structures, intellectual strengths and weaknesses, language development

Ping Huang,&ast; Lingsha Wu,&ast; Fang Li, Xiaoqin Meng, Ping He Department of Cardiovascular Medicine, The Second Hospital of JiaXing, Jia Xing, Zhe Jiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ping He, Email amnb1284sci@163.comBackground: To construct a risk factor intervention program for perimenopausal patients with coronary heart disease based on the health action process orientation theory, to provide a reference for perimenopausal women to reduce the controllable risk factors of coronary heart disease.Methods: By reviewing relevant literature, guidelines, and expert consensus, we performed a retrospective analysis of the factors influencing perimenopausal patients with coronary heart disease to engage in risk factor reduction behaviors in the preliminary stage, conducted qualitative interviews on patients’ cognition of and motivation for adherence to cardiac rehabilitation, and initially formulated an intervention program for perimenopausal patients with coronary heart disease regarding their risk factors based on the theoretical model of the process of action orientation to health and formed Expert Correspondence Form.Results: The positive response rate of experts in the 2 rounds of correspondence was 100%, the basis of expert judgment (Ca) was 0.955, the familiarity (Cs) was 0.964, the authority coefficient (Cr) was 0.960, and the Kendall’s W coefficients were 0.294 and 0.343, respectively (P< 0.05). The final result was a risk factor intervention program for perimenopausal patients consisting of coronary heart disease based on the health action process orientation theory with 3 level 1, 10 level 2, and 42 level 3 entries.Conclusion: Based on the health action process orientation theory of perimenopausal patients with coronary heart disease risk factor intervention program scientific construction process, the construction of the content around the perimenopausal patients with coronary heart disease characteristics, the development of targeted interventions.Keywords: perimenopause, coronary heart disease, health action process orientation theory, cardiac rehabilitation

Yaji Yang,1– 3,&ast; Haotian Zhou,1– 3,&ast; Runxing Kang,1– 3 Chen Zhao,1– 3 Jia Li,4 Feilong Li,1– 3 Yidong Shen,1– 3 Yuelong Chen,5 Wei Huang,1– 3 Leilei Qin1– 3 1Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Municipal Health Commission Key Laboratory of Musculoskeletal Regeneration and Translational Medicine, Chongqing, People’s Republic of China; 3Orthopaedic Research Laboratory of Chongqing Medical University, Chongqing, People’s Republic of China; 4Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 5Hospital of Chongqing University, Chongqing University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Huang; Leilei Qin, Department of Orthopaedics, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email huangwei68@263.net; qinleilei@stu.cqmu.edu.cnPurpose: Periprosthetic joint infection (PJI) is a severe complication following joint replacement surgery, and there is a current lack of rapid, accurate, and non-invasive diagnostic methods. This study aims to assess the effectiveness of using dual-energy computed tomography (DECT) to quantify the maximum long and short axes of the external iliac lymph nodes (LNs) as a diagnostic tool for PJI.Patients and Methods: In this prospective controlled study, 112 patients undergoing total hip or total knee revision surgery were enrolled. All patients underwent preoperative DECT scanning to measure the maximum long and short axes of the external iliac LNs on the affected side. The diagnostic value of lymph node size for PJI was assessed using receiver operating characteristic curves.Results: The AUC (Area Under the Curve) quantifies the diagnostic method’s ability to distinguish between positive and negative outcomes in this study. A value closer to 1.0 indicates better discriminatory performance. Compared to erythrocyte sedimentation rate (Area Under the Curve (AUC) = 0.834), percentage of polymorphonuclear leukocytes (AUC = 0.621), and C-reactive protein (AUC = 0.765), the maximum long axis (AUC =0.895) and maximum short axis (AUC = 0.858) of the external iliac LNs better differentiated PJI from aseptic failure. For diagnosing PJI, the threshold for the maximum long axis of the LNs was 20.5 mm, with a sensitivity of 84.21% and a specificity of 87.84%. For the maximum short axis, the threshold was 8.5 mm, with a sensitivity of 89.47% and a specificity of 82.43%. Combining the maximum long and short axes of the external iliac LNs enhanced the diagnostic accuracy for PJI.Conclusion: Measuring the long and short axes of external iliac LNs using DECT is an effective diagnostic approach for PJI, aiding in the differentiation between PJI and aseptic failure following joint replacement surgery.Keywords: periprosthetic joint infection, diagnosis, dual-energy CT, lymph nodes

Fang Li,1 Rong Xie,1 Tianlun Li,1 Shouzhong Ren2 1Department of Traditional Chinese Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, People’s Republic of China; 2College of Pharmacy, Hainan Medical University, HaiKou City, Hainan Province, People’s Republic of ChinaCorrespondence: Fang Li, Department of Traditional Chinese Medicine, The First Affiliated Hospital of Hainan Medical University, No. 33, Longhua Road, Longhua District, Haikou City, Hainan Province, 570102, People’s Republic of China, Tel +86-15308966331, Email doctor8988745@163.comBackground: Nonalcoholic fatty liver disease (NAFLD) refers to the liver pathological changes caused by excessive fat accumulation in hepatocytes owing to various reasons, which has become an emerging health challenge. Erhong Jiangzhi Decoction (EHJD) is a traditional Chinese medicine decoction. This study aims to investigate the therapeutic effect of EHJD on NAFLD.Methods: NAFLD model was constructed by high-fat diet (HFD)-induced mice and oleic acid-induced HepG2 cells. Mice were intragastrically administered with EHJD and HepG2 cells were treated with EHJD drug-containing serum. The effects of EHJD on NAFLD were explored in vivo and in vitro. Histological assessment was performed by hematoxylin-eosin and oil red O staining. ELISA was exploited to detect the expression of lipid accumulation, liver function, inflammation, and oxidative stress related indicators. The expression of Nrf2/HO-1 pathway was detected by qRT-PCR and Western blot.Results: In HFD-induced NAFLD mice, the body weight was increased, and liver/weight, inguinal fat/weight, and epididymal fat/weight were higher, while EHJD reduced them. Staining results exhibited that EHJD decreased inflammatory cell infiltration and oil red lipid droplets in HFD-induced mice. In addition, EHJD treatment suppressed TC, TG, ALT and AST levels; TNF-α, IL-1β, IL-6 and MDA levels were inhibited by EHJD, while GSH-Px, CAT and T-AOC levels were increased in NAFLD through the in vivo and in vitro experiments. The suppression of Nrf2 weakened the inhibitory effect of EHJD on lipid metabolism, liver injury, inflammation and oxidative stress.Conclusion: EHJD had a protective effect on NAFLD by alleviating lipid accumulation and liver injury, inhibiting inflammation, and oxidative stress, which was achieved by the restoration of Nrf2.Keywords: Erhong Jiangzhi Decoction, nonalcoholic fatty liver disease, lipid accumulation, Nrf2/HO-1 signaling pathway, oxidative stress

Ling Li,1 Jing Zhao,2 Fangxuan Li,3 Zhanyu Pan1 1Department of Integrated Traditional and Western Medicine, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 2Department of Ultrasound Diagnosis and Treatment, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People’s Republic of China; 3Department of Cancer prevention, Tianjin Medical University Cancer Institute & Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Zhanyu Pan, Department of Integrated Traditional and Western Medicine Tianjin Medical University Cancer Institute & Hospital, Huanhuxi Road, Hexi District, Tianjin, 300060, People’s Republic of China, Email pzytg1@126.com Fangxuan Li, Department of Cancer Prevention Center, Tianjin Medical University Cancer Institute and Hospital, Binshui Ave, Hexi District, Tianjin, 300060, People’s Republic of China, Email lifangxuan2008@126.com; lifangxuan@tjmuch.comIntroduction: This study aimed to compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in evaluating axillary lymph nodes (ALNs) status in breast cancer patients.Methods: We retrospectively analyzed 590 female breast cancer patients who had undergone both ultrasound and MRI to assess ALNs prior to any invasive procedures. Using pathological results as the standard, we compared the diagnostic performance of the two imaging modalities.Results: For differentiating between malignancy and benign ALNs, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of ultrasound were 68.98%, 38.14%, 86.67%, 62.12% and 70.96%, respectively. MRI demonstrated corresponding values of 72.03%, 38.60%, 91.20%, 71.55% and 72.15%. In assessing the burden status of ALNs (high vs low), ultrasound yielded values of 78.47%, 52.75%, 83.17%, 36.36% and 90.61%, while MRI showed corresponding values of 81.19%, 52.75%, 86.37%, 41.38% and 90.93%. There were no statistically significant differences between the two imaging modalities in their ability to evaluate ALN malignancy or burden status.Conclusion: Both ultrasound and MRI offer comparable value in assessing ALN status. Whether evaluating for metastatic involvement or determining ALN burden, it may not be necessary for patients to undergo both imaging tests.Plain Language Summary: 1. Both ultrasound and MRI have shown equally good value in assessing the ALNs status. 2. Whether evaluating for the metastatic ALNs or assessing the burden status of the ALNs, it is unnecessary for patients to undergo both tests.Keywords: breast cancer, axillary lymph node, ultrasound, magnetic resonance imaging, assessment value

Wenjun Chang,1 Zheng Li,2 Qianqian Liang,1 Wei Zhao,1 Fengsen Li2 1Department of Fourth Clinical College, Xinjiang Medical University, Urumqi, 830054, People’s Republic of China; 2Department of Respiratory, Unit Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, Urumqi, 830000, People’s Republic of ChinaCorrespondence: Fengsen Li, Department of Respiratory, Unit Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine, No. 119, Huang He Road, Urumqi, 830000, People’s Republic of China, Tel +86-13999980996, Email Fengsen602@163.comObjective: To assess the incidence and risk factors of tuberculosis-associated obstructive pulmonary disease (TOPD) in individuals with treatment-naive pulmonary tuberculosis (PTB) and develop a predictive model to enhance its management.Methods: The incidence of TOPD among patients with treatment-naive PTB in Xinjiang, China, was followed up for one year. Patient characteristics, such as demographics, medical histories, laboratory test results, lung radiological evidence, and pulmonary function, were collected upon hospital admission and throughout follow-up visits. Risk factors associated with TOPD were evaluated by multivariate logistic regression analysis, and then a predictive model was established using LASSO regression.Results: Of the 159 included patients, 69 (43.4%) developed TOPD during the follow-up period. Multivariate regression analysis identified age, body mass index, ESR, and symptom duration as significant risk factors. Subsequently, a model formula was derived from these factors to predict TOPD. Utilizing a cut-off value of 0.435, the model demonstrated a sensitivity of 89% and a specificity of 83%.Conclusion: In Xinjiang, the prevalence of TOPD appears notably high among treatment-naive PTB patients. Our findings, such as the risk factors and predictive model, may facilitate the early detection and improved interventions for TOPD among patients with PTB, potentially leading to better patient outcomes.Keywords: tuberculosis, tuberculosis-associated obstructive pulmonary disease, risk factor, predictive model, diagnosis

Dongjing Xie,1,&ast; Junfang Wan,2,3,&ast; Changwei Guo,1 Jie Yang,1 Jiacheng Huang,1 Zhouzhou Peng,1 Jiandi Huang,1 Linyu Li,1 Shitao Fan,1 Dahong Yang,1 Wenzhe Sun,1 Wenjie Zi,1 Fengli Li,1 Feng Peng,4 Jinrong Hu,1 Qingwu Yang1 1Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 2Department of Anesthesiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Anesthesiology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 4Department of Neurology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingwu Yang; Jinrong Hu, Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University (Third Military Medical University), No. 183 Xinqiao Main Street, Shapingba District, Chongqing, 400037, People’s Republic of China, Tel +86 23 68774270 ; +86 15183089810, Email yangqwmlys@tmmu.edu.cn; hujinrong1108@163.comBackground and Purpose: Many patients who gained successful recanalization by endovascular treatment (EVT) with acute large vessel occlusion (LVO) did not have the favorable outcome. The study aimed to assess the association between H-type hypertension and clinical prognosis in patients with LVO after receiving EVT.Methods: Our study enrolled patients from the Endovascular Treatment With versus Without Tirofiban for Stroke Patients with Large Vessel Occlusion (RESCUE BT) Trial. H-type hypertension is defined as patients with hypertension and homocysteine (Hcy) ≥ 10μmol/L. The primary outcome was a favorable functional outcome, defined as a score of 0– 2 on the modified Rankin Scale (mRS) at 90 days. The secondary outcomes were mortality, successful recanalization, futile recanalization, and symptomatic intracerebral hemorrhage (sICH).Results: The plasma homocysteine level was recorded for 215 patients with hypertension in our study. Among those patients, 172 patients (80%) were founded with Hcy ≥ 10μmol/L (H-type hypertension), and 43 patients (20%) with Hcy < 10μmol/L (non-H-type hypertension). The probability of favorable outcome decreased with homocysteine increasing in patients with hypertension. H-type hypertension was associated with a low probability of favorable outcome (adjusted odds ratio (aOR), 0.38 [95% confidence interval (CI), 0.18– 0.80]; p = 0.01) at 90 days. The effects of H-type hypertension on mortality (aOR, 1.90 [95% CI, 0.67– 5.39]; p = 0.23) and sICH (aOR, 0.55 [95% CI, 0.13– 2.29]; p = 0.41) were not significant.Conclusion: Our findings suggest that patients with H-type hypertension have a lower likelihood of achieving favorable outcomes but do not have an increased mortality rate within 90 days.Keywords: H-type hypertension, clinical prognoses, large vessel occlusion

Linsheng Wang,1,&ast; Yang Xu,2,&ast; Xudong Zhang,1 Jiahui Ding,1 Jingkun Jin,1 Jing Zong,1 Fangfang Li,1 Weidong Qian,3 Wenhua Li1,4 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Cardiology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3Department of Cardiology, Wujin Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, People’s Republic of China; 4Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Qian, Department of Cardiology, Wujin Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou, Jiangsu, People’s Republic of China, Email qwd213161@163.com Wenhua Li, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Email xzwenhua0202@163.comBackground: Contrast-induced acute kidney injury (CI-AKI) refers to the acute renal dysfunction caused by the injection of contrast agents. CI-AKI is currently a common complication after percutaneous coronary intervention (PCI).Objective: To investigate the predictive value of the combined systemic inflammatory index (SII) and urate/high-density lipoprotein cholesterol ratio (UHR) for CI-AKI after PCI in patients with AMI.Methods: A total of 1222 patients with AMI who underwent PCI were randomly divided into a training group and a validation group in an 8:2 ratio. According to the definition of CI-AKI diagnostic criteria, the training group was divided into CI-AKI group and non-CI-AKI group. Collect patient’s blood and biochemical data, then calculate SII and UHR. The risk factors for CI-AKI were identified using LASSO and multivariate logistic regression analyses. A predictive column was created by using R language.Evaluate the predictive value of SII, UHR and their combination for CI-AKI after PCI using the area under the ROC curve (AUC).Results: Diabetes, Cystatin C, Diuretics, UHR, and LnSII were independent risk factors for CI-AKI in AMI patients after PCI. The ROC curve showed that the AUC of UHR and SII combined for predicting CI-AKI in AMI patients after PCI was 0.761 (95% CI: 0.709– 0.812), with a sensitivity of 65.20% and a specificity of 76.70%, which was better than the prediction by either factor alone.Conclusion: High SII and high UHR are risk factors for AMI, and their combination can improve the accuracy of predicting CI-AKI in AMI patients after PCI.The prognosis of CI-AKI in AMI patients is worse than in the general population.Keywords: serum uric acid, high-density lipoprotein cholesterol, neutrophils, lymphocytes, systemic immune-inflammatory index, contrast-induced acute kidney injury

Yaqing Lin,1,&ast; Xuemei Ling,2,3,&ast; Linghua Li,2,&ast; Ruolei Xin,4 Fengyu Hu,1 Junbin Li,3 Jiaojiao Li,1 Feng Li,1,5 Yun Lan1 1Institute of Infectious Diseases, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Institute of Clinical Infectious Diseases, Infectious Disease Center, Guangzhou Eighth People’s Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Guangdong Center for Diagnosis and Treatment of AIDS, Guangzhou, People’s Republic of China; 4Institute of AIDS/STD Prevention and Control, Beijing Center for Disease Prevention and Control, Beijing, People’s Republic of China; 5Scientifc Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Li; Yun Lan, Email gz8h_lifeng@126.com; lanyun.vip@126.comBackground: The capsid inhibitor (CAI) lenacapavir (LEN) was approved for use in 2022, yet there are few reports about its drug resistance mutations (DRMs) and sensitivity.Purpose: To delineate the prevalence of CAI DRMs and drug susceptibility among HIV-1 infected individuals living in Guangdong, China.Patients and Methods: A total of 1035 individuals with HIV-1 infection, including 660 highly Active Anti-Retroviral Therapy (HAART) naive individuals and 375 hAART experienced individuals whose protease (PR)/ reverse transcriptase (RT) fragments were amplified successfully during drug resistance surveillance between October 2021 and December 2023, were randomly included in this study. The entire HIV-1 gag gene was amplified from plasma in LEN-naive individuals with or without antiretroviral therapy. The epidemiological and demographic information of the enrolled individuals were collected. The Stanford HIV Drug Resistance Database HIVdb program for Capsid was used to interpret the CAI DRMs and the LEN susceptibility.Results: Among 1035 samples, 805 gag sequences were amplified, sequenced and assembled successfully from 518 hAART drugs naive individuals and 287 hAART drugs experienced individuals. Among them, 0.50% (4/805) carried at least one CAI DRM, of which 0.19% (1/518) from HAART naive individuals and 1.05% (3/287) from HAART experienced individuals. Among the individuals with CAI DRMs, two patients carried CAI major mutations (Q67H) conferring intermediate resistance to LEN and two patients carried CAI accessory mutation (T107A) conferring low level resistance to LEN.Conclusion: Extremely low prevalence of CAI DRMs was detected among people living with HIV (PLWH) in Guangdong, China. Our observations indicate that LEN application may be promising when used in clinical practice in China. Before the administration of LEN, there is no need to consider detecting CAI mutations in PLWH through DRM examination for the time being.Keywords: HIV-1, capsid inhibitor, lenacapavir, drug resistance mutation, Guangdong

Haotian Xin,1,2 Beining Yang,1,2 Yulong Jia,1,2 Qunya Qi,1,2 Yu Wang,1,2 Ling Wang,1,2 Xin Chen,1,2 Fang Li,3 Jie Lu,1,2 Nan Chen1,2 1Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of China; 2Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, Beijing, 100053, People’s Republic of China; 3Department of Rehabilitation Medicine, Xuanwu Hospital, Capital Medical University, Beijing, 100053, People’s Republic of ChinaCorrespondence: Nan Chen, Department of Radiology and Nuclear Medicine, Xuanwu Hospital, Capital Medical University, Beijing Key Laboratory of Magnetic Resonance Imaging and Brain Informatics, No. 45 Chang-Chun St, Xicheng District, Beijing, People’s Republic of China, Tel +86 13910784187, Email chenzen8057@sina.comAbstract: Neuropathic pain (NP) is a common and persistent disease that leads to immense suffering and serious social burden. Incomplete understanding of the underlying neural basis makes it difficult to achieve significant breakthroughs in the treatment of NP. We aimed to review the functional and structural brain topological properties in patients with NP and consider how graph measures reveal potential mechanisms and are applied to clinical practice. Related studies were searched in PubMed and Web of Science databases. Topological property changes in patients with NP, including small-worldness, functional separation, integration, and centrality metrics, were reviewed. The findings suggest that NP was characterized by retained but declined small-worldness, indicating an insidious imbalance between network integration and segregation. The global-level measures revealed decreased global and local efficiency in the NP, implying decreased information transfer efficiency for both long- and short-range connections. Altered nodal centrality measures involve various brain regions, mostly those associated with pain, cognition, and emotion. Graph theory is a powerful tool for identifying topological properties of patients with NP. These specific brain changes in patients with NP are very helpful in revealing the potential mechanisms of NP, developing new treatment strategies, and evaluating the efficacy and prognosis of NP.Keywords: neuropathic pain, graph theory, brain network, magnetic resonance imaging

Xiyan Yu,1,&ast; Difei Wu,2,&ast; Fangzhou Li,3 Wei Qiao,4 Xujiao Chen3 1The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Geriatrics, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, People’s Republic of China; 4The First Department of Health Care, China-Japan Friendship Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xujiao Chen, Department of Geriatrics, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, 310003, People’s Republic of China, Email lily197459@163.com Wei Qiao, The First Department of Health Care, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China, Email viviqiao601@sina.comBackground: Cardiovascular disease (CVD) has become the leading cause of death worldwide. High muscle mass can reduce the incidence and mortality of CVD. In recent years, increasing attention has been given to the relationship between intrinsic capacity (IC) and CVD. This study aims to explore the relationship between the decline of IC, muscle strength, and muscle quality in older patients with CVD, providing a new method and basis for early recognition of IC decline in the older adults.Methods: This cross-sectional study included 475 older individuals from communities in Zhejiang. General data were collected, and a comprehensive geriatric assessment (CGA) was conducted. Participants with CVD were divided into three groups: IC retention, IC impairment, and IC significantly impaired. Bioelectrical impedance analysis (BIA) measurements were completed. Student’s t-test or non-parametric tests (Mann–Whitney) were used to analyze the correlation between IC and muscle-related indicators. The best cutoff values were obtained using ROC curve analysis.Results: Compared to non-CVD patients, CVD patients were older, more educated, and had higher rates of polypharmacy and comorbidity. IC decreased more significantly in CVD patients. Age (P=0.001), Fried (P=0.024), and GDS-5 (P=0.002) increased with the severity of IC decline. ADL (P=0.002), MMSE (P=0.000), MNA-SF (P=0.000), SARC-Calf (P=0.026), waist circumference (P=0.037), and muscle quality (P=0.010) decreased with the decline in IC. When IC decreased, the cutoff values for hand grip strength, waist circumference, and muscle quality were 25.45 kg, 72.55 cm, and 3.05, respectively. When IC decreased significantly, the cutoff values were 17.15 kg, 71.55 cm, and 2.28, respectively.Conclusion: The results of this study showed that in patients with CVD, the hand grip strength and muscle quality of patients with IC injury were lower than those of patients with IC retention.Keywords: CVD, intrinsic capacity, muscle quality

Yao Wang,1,&ast; Huilan Lv,1,&ast; Mingjun He,1 Peishan Wu,1 Fei Li,1 Yulong Wang2 1Department of Rehabilitation Medicine, Dapeng New District Nan’ao People’s Hospital, Shenzhen, 518121, People’s Republic of China; 2Department of Rehabilitation, The Second People’s Hospital of Shenzhen, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yulong Wang, Department of Rehabilitation, The Second People’s Hospital of Shenzhen; the First Affiliated Hospital of Shenzhen University, No. 3002, Sungang Road, Futian District, Shenzhen, 518035, People’s Republic of China, Tel +86 139 2344 8395, Fax +86 0755 83366388, Email wangy12013054@163.comObjective: This study examined the link between physical activity levels, as measured by the Longshi Scale, and cardiac function and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in stroke patients, aiming to find correlations with stroke risk factors.Methods: The study involved 123 apoplexy patients divided into four groups based on the Longshi Scale: bedridden (31), domestic (32), community (30), and health (30). Clinical data was collected, and hemodynamic assessments were performed using impedance cardiography.Results: Cardiac output time index (CTI) and estimated ejection fraction (EF est) were significantly reduced in both the domestic and community groups compared to the health group (P < 0.05), while diastolic arterial blood pressure (DABP) and systemic vascular resistance index (SVRi) were increased. In the bedridden group, stroke volume (SV), cardiac output (CO), CTI, left cardiac work index (LCWi), and EF est were all lower compared to the health group (P < 0.05), with SVRI and NT-proBNP levels being higher. Additionally, the bedridden group exhibited lower SV, CO, DABP, LCWi, CTI, and EF est when compared to the domestic and community groups (P < 0.05), but higher end-diastolic filling rate (EDFR) and NT-proBNP levels. The Longshi Scale grading positively correlated with SV (r = 0.536, P < 0.01), and NT-proBNP, EF, and cognitive dysfunction were found to be associated with activity levels in stroke patients.Conclusion: The Longshi Scale correlates with cardiac function indicators like NT-proBNP and EF, and can help identify stroke patients at risk of cardiac dysfunction. Moreover, cognitive dysfunction was identified as a significant factor influencing the range of activity in patients with stroke.Keywords: assessment, hemodynamic, Longshi Scale, stroke

Ciyi Hua,1 Feifei Li,1 Youyang Shi,2 Yuan Xu,1 Mengdie Zhu,1 Yang Wang,1 Xiqiu Zhou,2 Sheng Liu1,3 1Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Breast Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Sheng Liu, Institute of Chinese Traditional Surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China, Tel +86 18917763005, Fax +86-64385700, Email shengliu@shutcm.edu.cnBackground: Patients with clinically cured granulomatous lobular mastitis (GLM) still face a high probability of recurrence and new occurrence.Purpose: To evaluate the long-term efficacy of traditional Chinese medicine (TCM) in treating GLM and to hypothesize potential risk factors for recurrence or new occurrence.Patients and Methods: A retrospective analysis was conducted on GLM patients treated with TCM at Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine from January 2016 to July 2021. We analyzed general data, two-year recurrence and new occurrence rates, and 12 risk factors associated with recurrence or new occurrence.Results: This cross-sectional study included 261 GLM patients with an average age at onset of 31.95 years (primarily aged 31– 40). The two-year recurrence rate for GLM was 1.53%, and the new occurrence rate was 4.21%. Univariate and multivariate conditional logistic regression analyses revealed that a history of inverted nipples was associated with the risk of both recurrence and new occurrence of GLM (HR = 8.672, 5.375, P < 0.05), and menstrual irregularity was related to a higher risk of recurrence (HR = 13.172, P < 0.001).Conclusion: A history of inverted nipples is identified as a potential risk factor associated with the long-term recurrence and new occurrence of GLM, while menstrual irregularity is associated with recurrence. Despite this, patients with GLM undergoing TCM demonstrate low rates of long-term recurrence and new occurrence after achieving clinical cure, underscoring the effectiveness of TCM. This study lays the groundwork for a long-term effectiveness strategy to guide future GLM treatments.Keywords: granulomatous lobular mastitis, GLM, recurrence, new occurrence, risk factor

Dan Wu,1 Fang Li,2 Feifei Yang,3 Jun Liu4 1Department of Dermatology, Peking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan City, Ningxia Hui Autonomous Region, 750011, People’s Republic of China; 2Department of Pathology, Peking University First Hospital Ningxia Women and Children’s Hospital (Ningxia Hui Autonomous Region Maternal and Child Health Hospital), Yinchuan City, Ningxia Hui Autonomous Region, 750011, People’s Republic of China; 3Department of Dermatology, Tongzhou Maternal & Child Health Hospital of Beijing, Beijing City, 101101, People’s Republic of China; 4Department of Critical Care Medicine, the First People’s Hospital of Yinchuan, Yinchuan City, Ningxia Hui Autonomous Region, 750001, People’s Republic of ChinaCorrespondence: Jun Liu, Department of Critical Care Medicine, the First People’s Hospital of Yinchuan, No. 2 Liqun West Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, 750001, People’s Republic of China, Email JunLiunnu@outlook.comBackground: Numerous lines of evidence suggest that neuropeptide Y (NPY) is critically involved in the modulation of neuropathic pain. Postherpetic neuralgia (PHN) is characterized by prolonged duration, severe pain, and significant treatment resistance, substantially impairing patients’ quality of life. This study aims to evaluate the potential of plasma NPY levels in patients with PHN as a predictive biomarker for the development of this condition.Methods: Between February 2022 and December 2023, 182 patients with herpes zoster (HZ) were recruited. Thirty-eight volunteers with no history of HZ were also recruited as controls. Clinical factors, NPY, brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were assessed within 3 days of healing. Logistic regression analysis was used to predict the development of PHN.Results: NPY levels were lower and BDNF and NGF were higher in HZ patients than those in controls. Only NPY levels were lower in patients with PHN (n = 59) compared with those without PHN (n = 123). Age, acute pain severity, and rash area were independent predictors of PHN, as were NPY levels. The area under the curve (AUC) to predict the development of PHN based on the combination of NPY levels and clinical factors was 0.873 (95% CI: 0.805 to 0.940), and the AUC was 0.804 based on only clinical factors (AUC: 0.804, 95% CI: 0.728 to 0.881).Conclusion: Low plasma NPY levels are a predictor of developing PHN in patients with HZ. Combining clinical predictors with NPY levels may improve predictive accuracy.Keywords: neuropeptide Y, herpes zoster, postherpetic neuralgia, sensory neurons

Jing Wang,1,&ast; Yan Zhao,2,&ast; Cunming Lv,3,&ast; Feng Li1 1Department of Neurology, Lu’an Municipal People’s Hospital, Lu’an, People’s Republic of China; 2Department of Neurology, Jiangsu Provincial Medical Key Discipline (Laboratory), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing University, Nanjing, People’s Republic of China; 3Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, Medical College, China Three Gorges University, Yichang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Li, Department of Neurology, Lu’an Municipal People’s Hospital, No.21 Wanxi West Road, Jin’an District, Lu’an, Anhui Province, People’s Republic of China, Email lif0616@163.comBackground: Neutrophil-to-lymphocyte ratio (NLR) and Lymphocyte-to-monocyte ratio (LMR) have been reported to be associated with outcomes in acute ischemic stroke. However, research on elderly populations remains relatively scarce. We investigated the prognosis of NLR and LMR in elderly with acute ischemic stroke(AIS).Methods: Based on the modified Rankin Score (mRS) on the 90th day after stroke, patients were divided into group and bad prognosis groups. Multivariate logistic regression analysis and receiver operating curves were used to identify prognostic factors and their predictive powers.Results: In total, 824 elderly patients with AIS were enrolled between November 2021 and December 2023. Significant differences emerged in the NLR, LMR, and lymphocyte count between the two groups (P< 0.05). Binary logistic regression identified NLR, LMR and neutrophil count as independent risk factors for an unfavorable prognosis in elderly patients with AIS. The areas under the curve (AUCs) of NLR, LMR, and the combination of NLR and LMR to discriminate poor function prognosis were 0.703, 0.672, and 0.706, respectively. ROC analysis also showed that combination of NLR and LMR was superior to NLR and LMR alone for predicting AIS.Conclusion: NLR and LMR independently contribute to an unfavorable prognosis in elderly patients with AIS. The area under the ROC curve (AUC) for the combined NLR and LMR was higher than that for NLR and LMR individually, suggesting that combining these two indicators can improve the predictive ability for clinical outcomes in elderly patients with AIS.Keywords: neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, acute ischemic stroke, elderly patients

Song Wen,1,2 Yanyan Li,1 Chenglin Xu,1 Jianlan Jin,1 Zhimin Xu,1 Yue Yuan,1 Lijiao Chen,1 Yishu Ren,1 Min Gong,1 Congcong Wang,1 Meiyuan Dong,1 Yingfan Zhou,3 Xinlu Yuan,1 Fufeng Li,4 Ligang Zhou1,2,5 1Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China; 2Fudan Zhangjiang Institute, Fudan University, Shanghai, 201203, People’s Republic of China; 3Medical School of Tianjin University, Tianjin, 300072, People’s Republic of China; 4Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 5Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, People’s Republic of ChinaCorrespondence: Ligang Zhou, Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, 201399, People’s Republic of China, Tel +8613611927616, Email zhouligang1n1@163.com Fufeng Li, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email li_fufeng@aliyun.comObjective: We aim to examine and reestablish the correlational and linear regression relationships, as well as the predictive value, between the significant facial and tongue features and the metabolic parameters in type 2 diabetes mellitus (T2DM).Materials and Methods: From March to May 2024, we studied 269 patients with T2DM in the endocrinology department of Shanghai Pudong Hospital. The patients’ facial and tongue characteristics were sampling by a tongue imaging device equipped with artificial intelligence (AI) (XiMaLife, Sinology, China) of automated and advanced machine learning algorithms. Then, the imaging features were examined in relation to the blood examination.Results: Multiple facial and tongue features, as well as dimensional facial and tongue color parameters, were significantly correlated with glycated hemoglobin A1c (HbA1c) (r < 0.3, p < 0.05), glycated albumin (GA) (− 0.20 < 0.30, p < 0.05), C-peptide (− 0.20.20, p < 0.05), plasma insulin (r < 0.30, p < 0.05), fasting plasma glucose (FPG) (r < 0.3, p < 0.05), significant hepatic and renal function indicators (− 0.30 < r < 0.20, p< 0.05), cardiac injury markers (− 0.30 < r < 0.30, p < 0.05), tumor markers (− 0.5 < r < 0.5, p < 0.05), thyroid function (− 0.15 < r < 0.55, p < 0.05), and blood cell count, including white blood cells (r < 0.2, p < 0.05), and hemoglobin (Hb) (− 0.30 < r < 0.3, 0.0001. The correlational results demonstrated that the tongue’s characteristics and signs may be linked with the dynamic of the metabolic status of T2DM. In order to examine the causal relationships, we performed linear regression analyses, which revealed that various facial and tongue imaging parameters partially determined the metabolic indicators. The predictive value of imaging features was evaluated by receiver operating characteristic curve (ROC) to assess metabolic status in T2DM.Conclusion: This study demonstrated that metabolic status, renal and hepatic, cardiac, and thyroid function, the proportion of blood cells, and Hb in T2DM were intimately associated with facial and tongue features. The precise analysis of facial and tongue features through AI and advanced machine learning could be used to predict T2DM’s conditions and progression.Keywords: type 2 diabetes, tongue imaging, face imaging, cardiovascular disease, machine learning

Fan Li,1,&ast; Chuan-Guo Chen,2,&ast; Jiao-Fei Wei,1,3 Jia-Wen Lin,4 Zi-Ang Dou,3,4 Jun Shen,1 Shu-Qin Li1,3,4 1Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, People’s Republic of China; 2Department of General Surgery, Nanjing Meishan Hospital, Nanjing, Jiangsu, People’s Republic of China; 3Department of Clinical Medicine, Jinzhou Medical University, Jinzhou, Liaoning, People’s Republic of China; 4Department of clinical medicine, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jun Shen; Shu-Qin Li, Department of Breast Surgery, the First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, No. 6 Zhenhua East Road, High-tech Square, Lianyungang, Jiangsu Province, 222002, People’s Republic of China, Tel +861896132532 ; +8618961325781, Email shenjun2257@126.com; shuqinlilsh@126.comObjective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR).Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan–Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes.Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06– 6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66– 3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR.Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.Keywords: breast cancer, NACT, neoadjuvant chemotherapy, non-pCR, non-pathologic complete response, reg IV, risk factor

Ran Zhao,1,&ast; Dexiang Ji,1,&ast; Yulan Zhou,1,2 Ling Qi,1,2 Fei Li1,2 1Jiangxi Provincial Key Laboratory of Hematological Diseases, Department of Hematology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Jiangxi Clinical Research Center for Hematologic Disease, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Email yx021021@sina.comBackground: Immunosuppressive therapy (IST) with horse or rabbit anti-human thymocyte immunoglobulin (h-/r-ATG) and hematopoietic stem cell transplantation (HSCT) are two baseline treatments for severe aplastic anemia (SAA) and transfusion-dependent non-severe aplastic anemia (TD-NSAA) patients. Addition of thrombopoietin receptor agonists (TPO-RAs) to standard IST therapy (h-/r-ATG) has greatly improved the survival of SAA, whereas porcine anti-lymphocyte globulin (p-ALG) combined with TPO-RAs still had a matter of debate.Methods: We retrospectively compared the data of 48 AA patients in our center between 2020 and 2022, 23 AA patients received with p-ALG ± TPO-RAs, 25 AA patients underwent matched sibling donor (MSD-) or haploidentical (haplo-) HSCT.Results: For patients in the HSCT group, the ORR was 90.9% which was significantly higher than that in the IST±TPO-RAs group (45.5%, P = 0.001) at 3 months; moreover, patients who underwent HSCT achieved faster transfusion independence, better CR rate, shorter time of recovery normal blood routine, and the percentage of normal blood routine (all P < 0.05) compared with IST±TPO-RAs group. However, the ORR were similary at 6 months in the two groups (95.5% vs 81.8% P = 0.342), with a median follow up of 19.8 months (range, 0.3– 38.2 months), the 2-year FFS and OS in the two cohorts has no different. Subgroup analysis further indicated that the 2-year FFS and OS were similar between IST+TPO-RAs and haplo-HSCT subgroups, as well as in IST+TPO-RAs and MSD-HSCT cohorts. Moreover, the first-time hospitalizations were much more expensive in the HSCT group than in the IST±TPO-RAs group (402 756 vs. 292 902 yuan, P = 0.002).Conclusion: P-ALG-based-IST±TPO-RAs is a good treatment option with similar FFS and OS compared to allo- HSCT for AA patients without the opportunity of HSCT.Keywords: porcine anti-human thymocyte immunoglobulin, thrombopoietin receptor agonist, hematopoietic stem cell transplantation, aplastic anemia

Xu Tian,1,&ast; Fangrong Liu,2,&ast; Feili Li,3 Yi Ren,4 Hongcai Shang5 1Chongqing Center for Evidence-Based Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 2Outpatient Department, Chongqing University Cancer Hospital, Chongqing, 400030, People’s Republic of China; 3Department of Nursing, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 4Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 101121, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Ren, Department of Classic Traditional Chinese Medicine, Chongqing Traditional Chinese Medicine Hospital, No. 6 of 7th Branch of Panxi Road, Jiangbei District, Chongqing, People’s Republic of China, Tel/Fax +86 023 67776180, Email cqszyyrenyi@163.com Hongcai Shang, Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 of Haiyuncang, Dongcheng District, Beijing, People’s Republic of China, Tel/Fax +86 010 84013276, Email yxtx880919@163.comPurpose: While the benefits of exercises for chronic obstructive pulmonary disease (COPD) are well-established, the relative effectiveness of different exercise types for stable COPD remains unclear. This network meta-analysis aims to investigate the comparative effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in stable COPD.Methods: Electronic searches were performed in PubMed, Embase, and the Cochrane library to identify relevant randomized controlled trials (RCTs) investigating the effects of exercises on 6-minute walk test distance (6MWD), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC), and St. George’s Respiratory Questionnaire (SGRQ) score. Two authors screened the retrieved articles, extracted relevant data, and assessed the risk of bias. Network meta-analysis was conducted using Stata 14.0.Results: This study included a total of 19 studies involving 951 patients with stable COPD. HIIT emerged as the most favorable exercise type for enhancing 6MWD, with a probability of 82.9%. RT exhibited the greatest efficacy in reducing SGRQ scores, with probability of 49.8%. Notably, ET demonstrated superiority in improving FEV1 and FVC, with probabilities of being most effective at 78.1% and 42.0%, respectively.Conclusion: This study suggests that HIIT may be a viable intervention for improving exercise capacity in stable COPD patients, compared to AE, RR, and ET. RT may hold promise for improving quality of life, and ET may demonstrate superiority in improving pulmonary function. However, variation in response likely depends on patient characteristics, program parameters, and delivery context. Future research should explore the synergistic effects of combining RT with ET/HIIT, focusing on patient subgroups, optimal dosing, and settings, as current guidelines indicate this combination may offer the most significant benefits.Keywords: COPD, exercise, pulmonary function, quality of life, network meta-analysis

Chunrong Zuo,1,2 Nor Shafrin Ahmad,2 Lyu Zeng,1 Xiaogang Zhou,3 Feifei Li,2,4 Wuman Hong,2 Ping Gao1 1School of Education, Huainan Normal University, Anhui, 232038, People’s Republic of China; 2School of Educational Studies, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia; 3College of Physical Education and Health Science, Zhejiang Normal University, Jinhua, 321000, People’s Republic of China; 4Department of Art, Shandong Agricultural University, Shandong, 271000, People’s Republic of ChinaCorrespondence: Nor Shafrin Ahmad, School of Educational Studies, Universiti Sains Malaysia, Gelugor, Penang, 11800, Malaysia, Tel +60 465 325 69, Email sham@usm.my Xiaogang Zhou, College of Physical Education and Health Science, Zhejiang Normal University, Jinhua, 321000, People’s Republic of China, Tel +86 183 2904 0923, Email brucechou123456@gmail.comBackground and Objective: The mental health of economically disadvantaged college students in China is notably inferior to that of their non-disadvantaged peers. As such, these students necessitate a broader spectrum of psychological support beyond mere financial assistance. Seligman’s PERMA theory has established a compelling association between social support and positive emotions with subjective well-being. However, there is a scarcity of research focusing on character strengths within this framework, particularly the mechanisms that underlie their relationship. Hence, this study aims to examine the relationship between character strengths and subjective well-being among Chinese impoverished college students, while also delving into the chain mediating roles of perceived social support and positive emotions.Methods: A convenience sampling method was employed to collect cross-sectional data from impoverished college students. Participants (N=336, Mean age=20.67) were assessed using four instruments: the Chinese Virtues Questionnaire (CVQ-96), the Perceived Social Support Scale (PSSS), the Positive and Negative Affect Scale (PANAS), and the Satisfaction with Life Scale (SWLS).Results: Character strengths, perceived social support, positive emotions, and subjective well-being were all significantly positively correlated with each other (p< 0.01). In addition, regression analysis indicated that character strengths positively predicted perceived social support (β=0.71, p< 0.001), positive emotions (β=0.44, p< 0.001), and subjective well-being (β=0.52, p< 0.001). Perceived social support positively predicted positive emotions (β=0.34, p< 0.001), and subjective well-being (β=0.44, p< 0.001). Positive emotions positively predicted subjective well-being (β=0.88, p< 0.001). Furthermore, chain mediation analysis revealed that character strengths influenced subjective well-being both directly and indirectly through perceived social support and positive emotions.Conclusion: Perceived social support and positive emotions play a chain mediating role between character strengths and subjective well-being among impoverished college students.Keywords: character strengths, perceived social support, positive emotions, subjective well-being, Chinese, impoverished college students

Jie Yan,1,&ast; Jiandi Huang,2,&ast; Tianqiang Pu,3,&ast; Jiaxing Song,2 Jie Yang,2 Linyu Li,2 Fengli Li,2 Wenjie Zi,2 Changwei Guo,2 Zhouzhou Peng2 1Department of Neurology, The First People’s Hospital of Yongzhou City, Yongzhou City, Hunan Province, People’s Republic of China; 2Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University, Chongqing City, People’s Republic of China; 3Department of Neurology, The Central Hospital of Guangyuan City, Guangyuan City, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhouzhou Peng; Changwei Guo, Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Army Medical University, Shapingba District, Chongqing City, People’s Republic of China, Email peng_zhouzhou@163.com; changwei_guo@163.comBackground: Symptomatic intracranial hemorrhage (sICH) is a fatal complication after endovascular treatment (EVT) for acute large vessel occlusive (LVO) stroke. The aim of this study was to investigate the association between hyperglycemia and outcomes in patients with postprocedural sICH.Methods: Of the 2567 patients with AIS who underwent EVT from two large multicenter randomized trials and two prospective multicenter registry studies, 324 patients occurred sICH with documented admission glucose were included in this study. The primary outcome was functional independence (defined as a modified Rankin Scale score of 0 to 2) at 90 days. Secondary outcomes included mRS score of 0 to 3, 0 to 1, and mRS score at 90 days. Safety outcome was the mortality within 90 days. Admission hyperglycemia was defined as a plasma blood glucose ≥ 7.8 mmol/L (140 mg/dL) in our analysis.Results: Of 324 eligible participants included in this study, hyperglycemia was observed in 130 (40.1%) patients. The median age was 67 (IQR, 58– 75) years, and median blood glucose level was 7.1 (IQR, 6.0– 9.3) mmol/L. After adjusting for confounding variables, admission hyperglycemia was associated with decreased odds of functional independence (adjusted odds ratio[OR] 0.34; 95% CI 0.17– 0.68; P= 0.003), decreased odds of favorable outcome (adjusted OR 0.31; 95% CI 0.16– 0.58; P < 0.001) and increased odds of mortality (adjusted OR 2.56; 95% CI 1.47– 4.45; P = 0.001) at 90 days. After 1:1 propensity score matching analysis, the results were consistent with multivariable logistic regression analysis.Conclusion: In patients who suffered sICH after EVT for acute large vessel occlusive stroke, hyperglycemia is a strong predictor of poor clinical outcome and mortality at 90 days.Keywords: stroke, large vessel occlusion, endovascular treatment, symptomatic intracranial hemorrhage, hyperglycemia

Yan Wang,1,2,&ast; Fengmei Li,1,2,&ast; Shanshan Wei,1,2,&ast; Wenqun Li,1,2 Junyong Wu,1,2 Shengnan Li,1,2 Xiongbin Hu,1,2 Tiantian Tang,1,2 Xinyi Liu1,2 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institution of Clinical Pharmacy, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyi Liu, Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86-731-8529-2095, Email liuxinyi128@csu.edu.cnPurpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury.Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury.Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size.Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.Keywords: mitochondrial targeting, triphenylphosphonium cations, puerarin, ischemic myocardium-targeting peptide, liposomes

Lili Liu,1,&ast; Feifei Li,2,3,&ast; Xinyu Gu,2,3 Runkai Jiao4,5 1School of Education, Changchun Normal University, Changchun, Jilin, People’s Republic of China; 2College of Education, Wenzhou University, Wenzhou, Zhejiang, People’s Republic of China; 3Center for Psychological and Behavioral Research, Wenzhou University, Wenzhou, Zhejiang, People’s Republic of China; 4School of Psychology, Northeast Normal University, Changchun, Jilin, People’s Republic of China; 5National Training Center for Kindergarten Principals, Ministry of Education, Changchun, Jilin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feifei Li, Wenzhou University, Chashan Higher Education Park, Wenzhou, Zhejiang Province, 325035, People’s Republic of China, Tel +8615143003119, Email 20220053@wzu.edu.cnPurpose: Possessing a calling to teach is a core and essential quality of good kindergarten teachers, and it is critical to explore which factors positively impact kindergarten teachers’ career calling. Developing a career calling is a meaning-making process that can be influenced by the actions of others in the workplace. During the frequent parent-teacher interactions, parent-initiated support may serve as significant interpersonal cues for kindergarten teachers in developing their career calling. Thus, the present study examined the effect of parent-initiated support on kindergarten teachers’ career calling. Further, we investigated the multiple mediating roles of global and specific basic psychological need satisfaction based on the self-determination theory (SDT).Methods: Cross-sectional data were collected from 629 kindergarten teachers in China and analyzed using Mplus 8.3 software and the Process 3.5 macro of SPSS 26.0 software. Before testing the hypothesis, we used Mplus 8.3 to save factor scores from the Bifactor model of basic psychological need satisfaction and two uni-dimensional models of parent-initiated support and career calling. Subsequently, using the Process 3.5 macro within SPSS 26.0 software, we conducted path analysis to examine the total and mediating effects between parent-initiated support and kindergarten teachers’ career calling.Results: The results revealed a positive effect of parent-initiated support on teachers’ career calling. Teachers’ global and specific competence need satisfaction partially mediated this positive effect, while the mediating effects of teachers’ specific autonomy and relatedness need satisfaction were non-significant.Conclusion: These findings suggest that parent-initiated support is an important job resource for kindergarten teachers’ development of career calling. In addition to satisfying global psychological needs, satisfying specific needs (eg, competence need) provides additional benefits to kindergarten teachers’ experience of career calling.Keywords: parent-initiated support, career calling, basic psychological need satisfaction, kindergarten teacher, self-determination theory

Jun Yan,1 Rongrong Zheng,1 Zhongdong Zhang,1 Jinchuan Shi,1 Tingbo Yan,2 Hong Liu,3 Feng Li1 1The Second Infectious Disease Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 2Radiology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 3Pathology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Feng Li, The Second Infectious Disease Department, Xixi Hospital of Hangzhou, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, 310023, People’s Republic of China, Email lfnice@foxmail.comBackground: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging.Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient’s uncomfortable symptoms had resolved, and he is currently undergoing further review.Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.Keywords: non-tuberculous mycobacteria, Mycobacterium paracondontium, lymph nodes, case report

Fuming Li,1,2 Shimeng Liu,1,2 Yuanyuan Gu,3 Shunping Li,4 Ying Tao,1,2 Yan Wei,1,2 Yingyao Chen1,2 1School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2National Health Commission Key Laboratory of Health Technology Assessment (Fudan University), Shanghai, People’s Republic of China; 3Macquarie University Centre for the Health Economy, Macquarie Business School & Australian Institute of Health Innovation, Macquarie University, Macquarie Park, Macquarie Park, New South Wales, Australia; 4Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Shimeng Liu; Yingyao Chen, School of Public Health, Fudan University, 130 Dongan Road, Xuhui, Shanghai, 200032, People’s Republic of China, Tel +86 198 2182 4471 ; +86 135 6450 8981, Email smliu19@fudan.edu.cn; yychen@shmu.edu.cnPurpose: Discrete choice experiment (DCE) and profile case (case 2) best-worst scaling (BWS) present uncertainties regarding the acceptability of quantifying individual healthcare preferences, which may adversely affect the validity of responses and impede the reflection of true healthcare preferences. This study aimed to assess the acceptability of these two methods from the perspective of patients with type 2 diabetes mellitus (T2DM) and examine their association with specific characteristics of the target population.Patients and Methods: This cross-sectional study was based on a nationally representative survey; data were collected using a multistage stratified cluster-sampling procedure between September 2021 and January 2022. Eligible adults with confirmed T2DM voluntarily participated in this study. Participants completed both the DCE and case 2 BWS (BWS-2) choice tasks in random order and provided self-reported assessments of acceptability, including task completion difficulty, comprehension of task complexity, and response preference. Logistic regression and random forest models were used to identify variables associated with acceptability.Results: In total, 3286 patients with T2DM were included in the study. Respondents indicated there was no statistically significant difference in completion difficulty between the DCE and BWS-2, although the DCE scores were slightly higher (3.07 ± 0.68 vs 3.03 ± 0.67, P = 0.06). However, 1979 (60.2%) respondents found the DCE easier to comprehend. No significant preferences were observed between the two methods (1638 (49.8%) vs 1648 (50.2%)). Sociodemographic factors, such as residence, monthly out-of-pocket costs, and illness duration were significantly associated with comprehension complexity and response preference.Conclusion: This study yielded contrasting results to most of previous studies, suggesting that DCE may be less cognitively demanding and more suitable for patients with T2DM from the perspective of self-reported acceptability of DCE and BWS. This study promotes a focus on patient acceptability in quantifying individual healthcare preferences to inform tailored optimal stated-preference method for a target population.Plain Language Summary: Stated preference methodologies such as the discrete choice experiment (DCE) and case 2 best-worst scaling (BWS-2) are gaining popularity as methods for quantifying individual preferences in healthcare. However, the acceptability of the two methods to participants must be considered in practice to reduce cognitive burden and ensure the validity of preference elicitation.DCE was perceived to be less cognitively burdensome than BWS-2. In contrast to patients who thought that DCE was more acceptable, BWS-2 was more accepted by rural patients, patients who lived with the disease for a longer period, and those who had lower monthly out-of-pocket costs.These findings demonstrate potential differences in the acceptability of DCE and BWS-2 for patients with type 2 diabetes mellitus. To improve efficiency, it would be useful for researchers to consider the optimal stated preference method for identifying target populations according to sociodemographic and disease-related characteristics.Keywords: patient-reported outcomes, acceptability, discrete choice experiment, best-worst scaling, preference, type 2 diabetes

Shixin Ma,1,2 Fei Li,2 Lunqing Wang2 1Graduate School, Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Department of Thoracic Surgery, Qingdao Municipal Hospital, Qingdao, Shandong, 266071, People’s Republic of ChinaCorrespondence: Lunqing Wang, Department of Thoracic Surgery, Qingdao Municipal Hospital, No. 5 Donghai Middle Road, Qingdao, People’s Republic of China, Tel +86 532 87077952, Email wanglunqing1973@163.comPurpose: The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work.Patients and Methods: Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis. The results were visualized by a nomogram, and the performance of the model was judged by indicators such as the area under the subject operating characteristic curve (AUC) and C-index. The patients were divided into high- and low-risk groups by PILE score, and the prognosis of patients in different risk groups was evaluated.Results: Multivariate Cox regression analysis showed that immune-related adverse events (irAEs) were prognostic factors for overall survival (OS) improvement, and ECOG PS score ≥ 2, bone metastases before treatment, and high PIV expression were independent risk factors for OS. The C index of OS predicted by the nomogram model is 0.750 (95% CI: 0.677– 0.823), and the Calibration and ROC curves show that the model has good prediction performance. Compared with the low-risk group, patients in the high-risk group of PILE were associated with a higher inflammatory state and poorer physical condition, which often resulted in a poorer prognosis.Conclusion: PIV can be used as a prognostic indicator for patients with advanced NSCLC treated with ICIs, and a nomogram prediction model can be constructed to evaluate the survival prediction of patients, thus contributing to better clinical decision-making and prognosis assessment.Keywords: non-small cell lung cancer, immune checkpoint inhibitors, pan-immune-inflammation value, prognosis, nomogram

Xin Liu,1,&ast; Ruofan Xi,1,&ast; Xinran Du,1 Yi Wang,1 Linyan Cheng,1 Ge Yan,1 Hanzhi Lu,1 Te Liu,2 Fulun Li1 1Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Te Liu; Fulun Li, Email liute1979@shutcm.edu.cn; drlifulun@163.comBackground: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota.Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration.Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group.Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.Keywords: psoriasis, thymopentin, 16S rRNA sequencing, T-cell subsets

Fengfeng Li,1 Yang Jia,1 Jun Fang,2 Linqiang Gong,3 Yazhou Zhang,4 Shanshan Wei,5 Linlin Wu,6 Pei Jiang5 1Neurosurgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 2Anesthesiology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 3Gastroenterology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 4Foot and Ankle Surgery Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China; 5Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China; 6Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of ChinaCorrespondence: Linlin Wu, Oncology Department, Tengzhou Central People’s Hospital Affiliated to Xuzhou Medical University, Tengzhou, Shandong, 277500, People’s Republic of China, Tel +86 632-5513457, Email linlinliff@163.com Pei Jiang, Translational Pharmaceutical Laboratory, Jining First People’s Hospital, Jining, Shandong, 272000, People’s Republic of China, Tel +86 537-2106208, Email jiangpeicsu@sina.comBackground: Traumatic brain injury (TBI) is a condition characterized by structural and physiological disruptions in brain function caused by external forces. However, as the highly complex and heterogenous nature of TBI, effective treatments are currently lacking. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown notable antinociceptive and anti-inflammatory effects, yet its detailed neuroprotective effects and mode of action remain incompletely understood. This study investigated the neuroprotective effects and the underlying mechanisms of MOTS-c.Methods: Adult male C57BL/6 mice were randomly divided into three groups: control (CON) group, MOTS-c group and TBI group. Enzyme-linked immunosorbent assay (ELISA) kit method was used to measure the expression levels of MOTS-c in different groups. Behavioral tests were conducted to assess the effects of MOTS-c. Then, transcriptomics and metabolomics were performed to search Differentially Expressed Genes (DEGs) and Differentially Expressed Metabolites (DEMs), respectively. Moreover, the integrated transcriptomics and metabolomics analysis were employed using R packages and online Kyoto Encyclopedia of Genes and Genomes (KEGG) database.Results: ELISA kit method showed that TBI resulted in a decrease in the expression of MOTS-c. and peripheral administration of MOTS-c could enter the brain tissue after TBI. Behavioral tests revealed that MOTS-c improved memory, learning, and motor function impairments in TBI mice. Additionally, transcriptomic analysis screened 159 differentially expressed genes. Metabolomic analysis identified 491 metabolites with significant differences. Integrated analysis found 14 KEGG pathways, primarily related to metabolic pathways. Besides, several signaling pathways were enriched, including neuroactive ligand–receptor interaction and retrograde endocannabinoid signaling.Conclusion: TBI reduced the expression of MOTS-c. MOTS-c reduced inflammatory responses, molecular damage, and cell death by down-regulating macrophage migration inhibitory factor (MIF) expression and activating the retrograde endocannabinoid signaling pathway. In addition, MOTS-c alleviated the response to hypoxic stress and enhanced lipid β-oxidation to provide energy for the body following TBI. Overall, our study offered new insights into the neuroprotective mechanisms of MOTS-c in TBI mice.Keywords: MOTS-c, TBI, transcriptomics, metabolomics, neuroprotective

Siyu Pan,1 Yixiao Wang,1 Yuchen Zhang,1 Xiaoyu Ma,1 Jingfeng Peng,1 Fangfang Li,1,2 Wenhao Qian,1,2 Jing Zong1,2 1Institute of Cardiovascular Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of ChinaCorrespondence: Jing Zong, Department of Cardiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China, Tel +8618205000580, Email xyfyzongjing@126.comObjective: To investigate the Levels of Nucleotide-binding, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) and Adiponectin (APN) and their relationship with the severity of coronary artery disease in patients with Unstable Angina (UA) and Type 2 Diabetes (T2D).Methods: Two hundred and thirty-one patients with UA were diagnosed by CAG in the Department of Cardiology of the Affiliated Hospital of Xuzhou Medical University from July 2022 to May 2023 were included, and 74 healthy subjects were included as the control group. The levels of NLRP3 and APN in each group were detected by ELISA and the Gensini score in each patient according to the results of CAG. The correlations between NLRP3, APN, and Gensini score were analyzed. According to whether complicated with T2D or not, we further analyze the effect of NLRP3 and APN levels of patients with UA and T2D on the severity of coronary artery stenosis.Results: The levels of NLRP3 in UA with T2D group were the highest, followed by simple UA group, and the lowest in the control group, and the level of APN was the opposite. Spearman Correlation analysis showed that the level of NLRP3 was positively correlated with Gensini score (ρ1=0.688, P

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

Han Luo,1,&ast; Xiaofei Wang,1,&ast; Mengqi Fang,1 Huifan Yu,1 Lili Gui,1 Zhengkun Wu,1 Jianyong Sheng,2 Fei Li1 1Hubei Key Laboratory of Wudang Local Chinese Medicine Research, School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, Hubei, People’s Republic of China; 2Key Laboratory of Smart Drug Delivery, Ministry of Education, Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Li, Hubei University of Medicine, 30 Renmin South Road, Shiyan, Hubei, 442000, People’s Republic of China, Email piaopodexinlifei@163.comIntroduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1± 16.8 nm, zeta potential of about − 23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.Keywords: Hydroxyethyl starch, nanocrystals, stabilizer, luteolin, oral bioavailability, anti-hyperuricemia

Dan Qi,1– 9 Xi Zhang,1– 8 Fangli Li,10 Shengrui Zhao,2– 8 Qiumin Wang,1– 8 Wen Liu,2– 8 Lei Yan,1– 8 Yanbo Du1– 8 1State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, People’s Republic of China; 2National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, People’s Republic of China; 3Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, People’s Republic of China; 4Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 5Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, People’s Republic of China; 6Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 7Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No. 2021RU001), Jinan, Shandong, People’s Republic of China; 8Medical Integration and Practice Center, Shandong University, Jinan, Shandong, People’s Republic of China; 9Weifang People’s Hospital, Weifang, Shandong, People’s Republic of China; 10Department of Gynecology and Obstetrics, Public Health Clinical Center Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Yanbo Du, Center for Reproductive Medicine, Shandong University, Jinan, 250012, Shandong, People’s Republic of China, Tel +86 1 301 173 4515, Email duyanboivf@163.comPurpose: The objective of this study was to assess reproductive outcomes of D6 blastocysts transferred on day 6 in comparison to those transferred on day 7 of progesterone exposure in frozen-thawed embryo transfer cycles.Patients and Methods: This retrospective cohort study included 2029 D6 single blastocysts from the first frozen-thawed embryo transfer cycles of patients at the Hospital for Reproductive Medicine Affiliated to Shandong University from February 2017 to January 2020. Participants were divided into Group A (blastocyst transferred on the 6th day of progesterone exposure, n=1634) and Group B (blastocyst transferred on the 7th day of progesterone exposure, n=395).Results: The live birth rate was comparable between Group A and Group B (38.7% versus 38.7%, P=0.999). Subgroup analysis revealed a significantly higher preterm birth rate in D6 single blastocysts transferred on the 7th day than in those transferred on the 6th day of progesterone exposure for natural cycle frozen-thawed embryo transfer (5.2% versus 11.3%, P=0.020). After adjustment for potential confounders, the differences in the preterm birth rate in natural cycles persisted (adjusted odds ratio 2.347, 95% confidence interval 1.129– 4.877, P=0.022).Conclusion: In frozen-thawed embryo transfer cycles, transferring on the 6th or 7th day of progesterone exposure of D6 blastocysts did not affect the live birth rate; however, when a natural cycle protocol is adopted, the possible preterm risk of transferring D6 blastocysts on the 7th day of progesterone exposure should be noted.Keywords: frozen-thawed embryo transfer, blastocyst transfer, endometrium preparation, live birth rate

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

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

Yanhua Liu,1,2,&ast; Fuxing Li,1,2,&ast; Youling Fang,2,3 Qiaoshi Zhong,1,2 Yanping Xiao,1,2 Yunwei Zheng,1,2 Junqi Zhu,2,3 Chuwen Zhao,2,3 Xingwei Cao,1,2 Jianqiu Xiong,4 Longhua Hu1,2 1The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 2Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 3School of Public Health, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 4Department of Nursing, the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianqiu Xiong, Department of Nursing, The Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email 1773014059@qq.com Longhua Hu, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email longhuahu@163.comObjective: This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by Enterobacter cloacae complex (ECC).Methods: The clinical data of patients with bloodstream infections caused by Enterobacter cloacae complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum β-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (β-lactam/β-lactamase inhibitor combinations (BLICs) or carbapenems).Results: The proportion of ESBL-producing Enterobacter cloacae complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055– 0.662], P = 0.009; adjusted HR [95% CI] 0.106 [0.013– 0.863], P = 0.036).Conclusion: This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤ 6.0).Keywords: Enterobacter cloacae complex, extended-spectrum β-lactamase, bloodstream infection, risk factors, β-lactam/β- lactamase inhibitor combinations, carbapenems

Jiali Lu,1,2,&ast; Fei Li,3,&ast; Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 2Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China; 3Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei Ye, Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China, Email wumeiye08@163.comBackground: Ulcerative colitis (UC) is an autoimmune inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), including PANoptosis and autophagy, plays roles in inflammation and immunity. This study aimed to investigate the molecular signature and immune landscape of the PANoptosis- and autophagy-related differentially expressed genes (DEGs) in UC.Methods: Analyzing UC dataset GSE206285 yielded DEGs. Differentially expressed PANoptosis- and autophagy-related genes were identified using DEGs and relevant gene collections. Functional and pathway enrichment analyses were conducted. A protein-protein interaction (PPI) network was established to identify hub genes. TRRUST database predicted transcription factors (TFs), pivotal miRNAs, and drugs interacting with hub genes. Immune infiltration analysis, UC-associated single-cell sequencing data analysis, and construction of a competing endogenous RNA (ceRNA) network for hub genes were conducted. Machine learning identified key candidate genes, evaluated for diagnostic value via receiver operating characteristic (ROC) curves. A UC mice model verified expression of key candidate genes.Results: Identifying ten PANoptosis-related hub DEGs and four autophagy-related hub DEGs associated them with cell chemotaxis, wound healing and positive MAPK cascade regulation. Immune infiltration analysis revealed increased immunocyte infiltration in UC patients, with hub genes closely linked to various immune cell infiltrations. Machine learning identified five key candidate genes, TIMP1, TIMP2, TIMP3, IL6, and CCL2, with strong diagnostic performance. At the single-cell level, these genes exhibited high expression in inflammatory fibroblasts (IAFs). They showed significant expression differences in the colon mucosa of both UC patients and UC mice model.Conclusion: This study identified and validated novel molecular signatures associated with PANoptosis and autophagy in UC, potentially influencing immune dysregulation and wound healing, thus opening avenues for future research and therapeutic interventions.Keywords: ulcerative colitis, PANoptosis, autophagy, immune cell infiltration, inflammatory fibroblasts, bioinformatics analysis

Guang-Hong Xie,1,&ast; Jun Shen,2,&ast; Fan Li,2 Huan-Huan Yan,2 Ying Qian3 1Department of Operating Room, The First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 2Department of Breast Surgery, The First People’s Hospital of Lianyungang, The Affiliated Hospital of XuZhou Medical University, Lianyungang, Jiangsu, 222002, People’s Republic of China; 3Department of Operating Room, Wuxi People’s Hospital, Wuxi, Jiangsu, 214063, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Qian Department of Operating Room, Wuxi People’s Hospital, No. 299 Qingyang Road, Liangxi District, Wuxi, 214063, Jiangsu, People’s Republic of China, Tel +8615190209358, Email qianying_q06@126.comObjective: We aimed to analyze the factors related to delay in transfer of patients in the post-anesthesia care unit (PACU) and to develop and validate a prediction model for understanding these factors to guide precise clinical intervention.Methods: We collected data from two cohorts of 1153 and 297 patients who underwent surgery and were treated in the PACU at two time points. We examined their clinical features and anesthesia care data using analytical methods such as logistic regression, Random Forest, and eXtreme Gradient Boosting (Xgboost) to screen out variables and establish a prediction model. We then validated and simplified the model and plotted a nomogram. Using LASSO regression, we reduced the dimensionality of the data. We developed multiple models and plotted receiver operating characteristic (ROC) and calibration curves. We then constructed a simplified model by pooling the identified variables, which included hemoglobin (HB), alanine transaminase (ALT), glucose levels, duration of anesthesia, and the minimum bispectral index value (BIS_min).Results: The model had good prediction performance parameters in the training and validation sets, with an AUC of 0.909 (0.887– 0.932) in the training set and 0.939 (0.919– 0.959) in the validation set. When we compared model 6 with other models, the net reclassification index (NRI) and the integrated discriminant improvement (IDI) index indicated that it did not differ significantly from the other models. We developed a scoring system, and it showed good prediction performance when verified with the training and validation sets as well as external data. Additionally, both the decision curve analysis (DCA) and clinical impact curve (CIC) demonstrated the potential clinical efficacy of the model in guiding patient interventions.Conclusion: Predicting transfer delays in the post-anesthesia care unit using predictive models is feasible; however, this merits further exploration.Keywords: delayed transfer, machine learning, nomogram, post-anesthesia care unit, predictive model

Chenxi Ouyang,1,2 Changjiang Meng,3 Fei Li,3 Shanshan Nie,3 Liying Gong,4 Yu Cao,5 Hong Yuan,3,5 Zeying Feng6 1School of Pharmacology, University of South China, Hengyang, Hunan, People’s Republic of China; 2The Affiliated Nanhua Hospital, Department of Pharmacy, Hengyang Medical School University of South China, Hengyang, Hunan, People’s Republic of China; 3Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 5Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 6Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, Liuzhou, Guangxi, People’s Republic of ChinaCorrespondence: Zeying Feng, Clinical Trial Institution Office, Liuzhou Hospital of Guangzhou Women and Children’s Medical Center, No. 50 Boyuan Avenue, Liuzhou, Guangxi, 545000, People’s Republic of China, Email fengzeying@foxmail.comPurpose: Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators.Patients and Methods: Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis.Results: Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42– 5.28, false discovery rate adjusted-P =3.55&ast;10− 209). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI.Conclusion: The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.Keywords: P2Y12 receptor inhibitors, morphine, kidney injury, Mendelian randomization

Fei Li,1,&ast; Feifei Yan,2,&ast; Shengnan Liu,1,&ast; Rewaan Baheti,1 Yujia Feng,1 Jing Wan1 1Department of Cardiovascular Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China; 2Cardiac Ultrasound Department, Zhongnan Hospital of Wuhan University, Wuhan, 430000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Wan, Department of Cardiology, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, Hubei Province, 430071, People’s Republic of China, Tel +86-027-67813477, Email wanjing_zn@163.comPurpose: In essential hypertensive patients, cardiac remodeling may be associated with the risk of renal damage in the future which can be reflected by the estimated glomerular filtration rate (eGFR). Through retrospective analysis, we evaluated the potential of cardiac remodeling based on echocardiographic measurements to predict the risk of renal damage in the future with hypertensive patients.Methods: We retrospectively analyzed the relationship between the changes of left heart structure and function and renal damage for 510 patients with hypertension, who were diagnosed between 2016 to 2022. Demography data, clinical data, blood samples and echocardiographic variables were used for survival analysis, and the Cox proportional hazards regression model was used.Results: In our study, we found that age, serum creatinine (SCR), creatine kinase isoenzyme MB (CK MB), abnormal high-sensitivity troponin I (TNI), interventricular septum thickness (IVST) and left ventricular ejection fraction (LVEF) could be used as independent predictors in risk of renal impairment in hypertensive patients (p< 0.05). Combined in a score where one point was given for the presence of each of the parameters above, this score could strongly predict renal function damage in the future (p< 0.05). In receiver operating characteristics (ROC) curve analyses, the area under the curve of the risk factor score was 0.849 (P< 0.001).Conclusion: In essential hypertensive patients, LVEF and IVST can predict the risk of future adverse renal outcomes. Moreover, combining risk variables into a simplified score may enable to assess the risk of renal impairment in hypertensive patients at an early stage.Keywords: hypertension, echocardiography, changes of cardiac structure and function, progression of renal damage, hypertensive nephropathy