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Beilei Zhang,1,&ast; Bin Guo,1,&ast; Hancun Kong,2,&ast; Linwei Yang,2 Hui Yan,2 Jierui Liu,2 Yichen Zhou,2 Ruifang An,1 Fu Wang2– 4 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 2Department of Medical Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710004, People’s Republic of China; 3Department of Biophysics, School of Basic Medical Sciences, Xi’an Jiaotong University, Xi’an, Shaanxi, 710061, People’s Republic of China; 4School of Pharmacy, Shaanxi University of International Trade & Commerce, Xianyang, Shaanxi, 712046, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruifang An; Fu Wang, Email anruifang@163.com; wangfu@xjtu.edu.cnBackground: Ovarian cancer is a type of gynecological cancer with extremely high fatality rate. Ferroptosis, an iron-dependent regulated cell death, inhibits the immune infiltration of tumor cells. Therefore, it is worthwhile to explore the effects of ferroptosis-related gene signatures and immune infiltration patterns on the clinical prognosis of ovarian cancer.Methods: In this study, we used the mRNA expression matrix and related medical information of those who suffer from ovarian cancer in the TCGA database. After that, we established a ferroptosis-related gene signature based on LASSO Cox regression model, and employed several specific enrichment analyses to explore the bioinformatics functions of differentially expressed genes (DEGs). Additionally, we analyzed the link between ferroptosis and immune cells by single-sample gene set enrichment analysis (ssGSEA) to create a heatmap of gene-immune cell correlation. We then examined the expression of immune checkpoints and verified the gene expression in ovarian cancer tissues by qPCR assays. Finally, we induced ferroptosis in ovarian cancer cells using drugs and analyzed their migration, invasion and gene expression.Results: According to LASSO Cox regression analysis, 9 prognostic DEGs were in association with overall survival (OS), which was utilized to construct a 9-gene signature for patients. Patients were divided into two groups, in which high-risk group’s OS was markedly shorter than that of low-risk group (Log−rank p< 0.001). KEGG enrichment analysis showed that these DEGs were linked to human cytomegalovirus (HCMV) infection. The ssGSEA analysis revealed significant differences in immune cell type and expression between ALOX12 and GLRX5 groups (p< 0.05). Heatmap showed high correlation of prognostic genes with various immune cells. qPCR assay confirmed the 9 gene expression signature in ovarian cancer tissues. The ovarian cancer cell invasion and migration were significantly inhibited after induction of ferroptosis.Conclusion: We decoded the ferroptosis-related gene signatures and immune infiltration patterns that can be used to predict the prognosis of ovarian cancer patients.Keywords: ovarian cancer, ferroptosis, tumor prognosis, gene signature, immune infiltration

Xian He,1,2 Xueping Wen,3 Peng Ming He,3 Dan Liang,2 Lihong Yang,2 Yuping Ran,1 Zhixin Zhang3 1Department of Dermatovenereology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2Department of Allergy, Chengdu First People’s Hospital, Chengdu, People’s Republic of China; 3Chengdu ExAb Biotechnology, LTD, Chengdu, People’s Republic of ChinaCorrespondence: Yuping Ran; Zhixin Zhang, Email ranyuping@vip.sina.com; zhangzhixin@med.uestc.edu.cnObjective: Studies establish a link between autoimmune factors and chronic spontaneous urticaria (CSU). T cells are crucial in immune-mediated diseases like CSU, and T-cell receptor (TCR) diversity could be pivotal in autoimmune responses. The clinical relevance of TCR variations in CSU is unknown, but understanding them may offer insights into CSU’s pathogenesis and treatment.Methods: This cross-sectional study included 132 chronic urticaria (CU) patients versus 100 age-matched healthy donors (HD), with subgroup analyses on CU type, angioedema, allergic comorbidities, and anti-IgE therapy efficacy. Peripheral TCRβ repertoires were analyzed by high-throughput sequencing.Results: CSU patients showed reduced TCR diversity (lower D50) and increased large clone proportions than HD. Moreover, TCR diversity in CSU patients was significantly lower than in those with Chronic Inducible Urticaria (ClndU). There were also differences in variable (V) and joining (J) gene usage between CU and HD groups as well as CSU and ClndU groups. However, in subgroup analyses regarding angioedema, allergic comorbidities, and the efficacy of anti-IgE treatment, no significant differences were found in TCR diversity or large TCRβ clones. Notably, patients with treatment relapse or poor response to anti-IgE therapy had a higher proportion of positively charged CDR3. Additionally, age affected TCR diversity, but TIgE value, EOS counts, CU duration, and UAS7 score did not associate significantly with D50.Conclusion: CSU patients exhibit reduced TCR diversity and increased large clone proportions, indicating abnormal T cell activation. The TCR diversity differences and distinct V and J gene usage between CSU and ClndU may indicate different mechanisms in T lymphocyte-associated immune responses for these two subtypes of CU. The higher positive charge in CDR3 of relapsed or poorly responsive patients to anti-IGE treatment may indicate more antigen charge involvement. These findings provide new insights into the pathogenesis of CSU and potential future treatments.Keywords: T-cell receptor, T-cell receptor repertoire, T-cell receptor diversity, chronic spontaneous urticaria, high-throughput sequencing

Xiangqun Zhang,1,2 Long Yang,1,3,&ast; Junyuan Wu,1,3,&ast; Xue Mei1,2 1Emergency Medicine Clinical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Clinical Center for Medicine in Acute Infection. Capital Medical University, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junyuan Wu; Xue Mei, Email wu007838@sina.com; meixue91@yeah.netBackground: Community-acquired pneumonia (CAP) is a significant global health issue, leading to high morbidity and mortality rates. Despite the existence of various severity scoring systems, accurately predicting patient outcomes remains challenging. The CAP-PIRO (Predisposition, Insult, Response, and Organ dysfunction) scoring system offers a comprehensive approach to evaluating CAP severity and prognosis.Objective: This study aimed to assess the effectiveness of the CAP-PIRO scoring system in predicting the prognosis and severity of CAP patients, focusing on the development of acute respiratory distress syndrome (ARDS) and 28-day mortality.Methods: A total of 875 CAP patients were prospectively enrolled from the emergency department of Beijing Chao-yang Hospital between November 2017 and December 2023. Clinical data, including patient demographics, medical history, vital signs, and laboratory findings, were collected within 6 hours of admission. CAP-PIRO, CURB-65, and PSI scores were calculated. Patients were stratified based on ARDS development, 28-day mortality, and PaO2/FiO2 categories (≤ 100 mmHg, 100– 200 mmHg, 200– 300 mmHg).Results: Significant differences were observed in PCT, blood lactate (Lac), CURB-65, PSI, and CAP-PIRO scores between patients with and without ARDS, as well as between survivors and non-survivors at 28 days (P< 0.05). CAP-PIRO and Lac were identified as independent predictors for ARDS development and 28-day mortality. The area under the ROC curve (AUC) for CAP-PIRO was higher than that for CURB-65 and PSI in predicting 28-day mortality. The combination of CAP-PIRO and Lac demonstrated improved predictive accuracy for ARDS. Notably, significant differences in CAP-PIRO scores were observed across different PaO2/FiO2 groups.Conclusion: CAP-PIRO demonstrates strong predictive ability for adverse outcomes and, when combined with lactate, shows enhanced predictive power. These findings underscore the value of CAP-PIRO for clinical risk stratification in CAP patients.Keywords: CAP, CAP-PIRO scoring system, prognosis prediction, ARDS, risk stratification

Lin Yang,1,2 Xiaoyu Pan,2 Zhenyu Pan,3 Haina Gao,4 Jiangli Ban,4 Shuchun Chen2,5,6 1Department of Internal Medicine, Hebei North University, Zhangjiakou, Hebei, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Internal Medicine, Shandong Medical College, Linyi, Shandong, People’s Republic of China; 4Department of Endocrinology, The Second Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China; 5Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 6Hebei Key Laboratory of Metabolic Diseases, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Shuchun Chen, Department of Internal Medicine, Hebei Medical University, People’s Republic of China, Tel +86 31185988406, Email chenshuc2014@163.comIntroduction: Obesity-induced inflammation and oxidative stress can cause damage to cardiomyocytes. Semaglutide has the potential to reduce glucose levels and weight, while hydroxysteroid dehydrogenase-like protein 2 (HSDL2) also plays a role in regulating lipid metabolism. This study aimed to investigate the expression of oxidative stress markers and HSDL2 in myocardium and serum under high-fat conditions, in order to elucidate the mechanism of obesity-induced myocardial injury and evaluate the impact of semaglutide on myocardial injury through HSDL2.Methods: Mouse models of obesity were established with semaglutide treatment. Palmitic acid-cultured mouse cardiomyocytes with HSDL2 knockout were used, as well as palmitic acid-induced high-fat environment models followed by semaglutide treatment. The levels of inflammatory and oxidative stress markers in serum and cardiomyocytes were measured. Additionally, the expression of HSDL2 and autophagy levels in different cell groups were assessed to evaluate the effect of semaglutide on high-fat diet-induced cardiomyocyte injury mediated by HSDL2.Results: Obesity increased oxidative stress, which was alleviated by intervention with semaglutide. Furthermore, semaglutide down-regulated HSDL2 expression in obese individuals. Moreover, palmitic acid-induced oxidative stress and autophagy were reduced when using cells with knocked out HSDL2 gene.Conclusion: These findings suggest that semaglutide may mitigate cardiomyocyte injury caused by a high-fat diet through regulation of HDLSDSLEP-1 expression. These discoveries are expected to unveil novel molecular mechanisms and provide new targets for clinical treatment.Keywords: obesity, inflammation, oxidative stress, semaglutide, HSDL2

Yueyue Fu,1 Yuling Xing,2 Linlin Yang,3 Jing Liu,2 Huijuan Ma3 1Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Jing Liu, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 13673186039, Email liujing981531@163.com Huijuan Ma, Department of Endocrinology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comPurpose: To explore the correlation between fasting C-peptide to diabetes duration ratio (FCP/DD) and diabetic peripheral neuropathy (DPN).Methods: The study was conducted on 816 patients with type 2 diabetes (T2DM). Subjects were classified into a diabetic peripheral neuropathy group (DPN, n=408) and a non-diabetic peripheral neuropathy group (NDPN, n=408) depending on the presence of DPN. Collected patients’ baseline data, calculated the FCP/DD ratio, and analyzed the correlation between FCP/DD and DPN.Results: A comparative analysis of general characteristics revealed that the DPN group exhibited higher values for age, DD, proportion of hypertension, proportion of DN, and proportion of DR compared to the NDPN group, Conversely, the DPN group demonstrated lower proportions of eGFR, FCP/DD, FCP, and fatty liver relative to the NDPN group, with all differences achieving statistical significance (P < 0.05). Compared to the high FCP/DD group, the low FCP/DD group exhibited higher values in age, DD, the proportion of DPN, DN, DR, and hypertension, as well as elevated levels of HDL-C and NEUT (P< 0.05). Conversely, the low FCP/DD group demonstrated a lower proportion of patients who smoked and those with fatty liver, along with reduced BMI, ALB, FBG, UA, eGFR, TC, TG, and LDL-C levels (P < 0.05). In patients with T2DM, after adjusting for confounding factors, high levels of FCP/DD were found to be a protective factor for DPN (P < 0.05). The area under the curve of the FCP/DD Model predicting DPN (AUC=0.737) was higher than that of single FCP (AUC=0.587), DD (AUC=0.665).Conclusion: The high FCP/DD ratio was a protective factor for T2DM with DPN. Additionally, the FCP/DD ratio was found to be a better predictor for the occurrence of DPN in T2DM compared to FCP and DD alone.Keywords: Diabetic peripheral neuropathy, type 2 diabetes, FCP/DD

Lukun Yang,1,2,&ast; Ling Li,3,&ast; Peiping Li,1,&ast; Jiafan Chen,1 Chaonong Cai,1 Yingbin Jia,1 Jian Li,1 Baojia Zou1 1Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong Province, People’s Republic of China; 2Department of Anesthesiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, People’s Republic of China; 3Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baojia Zou; Jian Li, Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, 52 Mei Hua East Road, Zhuhai, 519000, People’s Republic of China, Tel +86-756-252-8781, Fax +86-756-252-8166, Email zoubj6@mail.sysu.edu.cn; lijian5@mail.sysu.edu.cnPurpose: Both Ku80 and Ku70 are promising drug targets for hepatocellular carcinoma (HCC) and crucial for immune regulation. However, their correlation with HCC immune signatures has not yet been investigated. Therefore, we aimed to investigate the relationship between Ku80, Ku70, and immune signatures in HCC and validate their significance in cytotoxic lymphocyte (CTL) immunotherapy.Patients and Methods: Analyses of Ku70, Ku80, and immune signatures in public datasets was performed using R software, an online Kaplan-Meier plotter, g:Profiler, GeneTrail, and Metascape. Uniform manifold approximation and projection, correlation chord diagrams, Pearson’s correlation tests, and Spearman correlation tests were used to describe various correlation levels. HCC mRNA sequencing data (n=373 tumor samples and n=50 para-tumor samples) were drawn from The Cancer Genome Atlas (TCGA) public database. Immunofluorescent staining was used to validate Ku70/Ku80 and CD8+CTL expression in 120 HCC patients from our center. Survival analysis was performed using the Kaplan-Meier survival analysis with the Log rank test and was adopted to analyze immunotherapy outcomes correlated with Ku70/Ku80 expression in various solid tumors. Multivariate analysis of HCC patient data from our center was performed using a Cox proportional hazards model.Results: Increased Ku70/Ku80 expression positively correlated with more enriched immune microenvironment signatures, indicating increased immune infiltration in HCC. Upregulation of Ku70/Ku80 indicated better anti-PD1 and anti-PDL1 treatment outcomes in various solid tumors. Higher Ku70/Ku80 expression with lower CD8+CTL signatures indicated worse survival outcomes, whereas lower Ku70/Ku80 expression with higher CD8+CTL signatures indicated the best prognosis.Conclusion: Higher Ku70/Ku80 expression indicated an immune-hot infiltration signature in HCC. Patients with increased Ku70/Ku80 expression and high CD8+CTL signatures may potentially benefit from CTL-centered immunotherapies.Keywords: hepatocellular carcinoma, XRCC6/Ku70, XRCC5/Ku80, CTL-centered immunotherapy, tumor immune microenvironment

Changhong Xu,1,&ast; Yun Deng,1,&ast; Xinyi Gong,2,&ast; Huabin Wang,1 Jiangwei Man,1 Hailong Wang,1 Kun Cheng,1 Huiming Gui,1 Shengjun Fu,1 Shenghu Wei,3 Xiaoling Zheng,4 Tuanjie Che,4 Liyun Ding,3 Li Yang1 1Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China; 2The Second Clinical Medical College of Lanzhou University, Lanzhou, Gansu, 730030, People’s Republic of China; 3School of Physical Science and Technology, Lanzhou University, Lanzhou, 730000, People’s Republic of China; 4Innovation Center of Functional Genomics and Molecular Diagnostics Technology of Gansu Province, Lanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Liyun Ding, Email ery_yangli@lzu.edu.cn; dingly@lzu.edu.cnBackground: Renal ischemia-reperfusion injury (RIRI) is a significant cause of acute kidney injury, complicating clinical interventions such as kidney transplants and partial nephrectomy. Recent research has indicated the role of cuproptosis, a copper-dependent cell death pathway, in various pathologies, but its specific involvement in RIRI remains insufficiently understood. This study aims to investigate the role of cuproptosis-related genes in RIRI and establish robust diagnostic models.Methods: We analyzed transcriptomic data from 203 RIRI and 188 control samples using bioinformatics tools to identify cuproptosis-related differentially expressed genes (CRDEGs). The relationship between CRDEGs and immune cells was explored using immune infiltration analysis and correlation analysis. Gene Set Enrichment Analysis (GSEA) was conducted to identify pathways associated with CRDEGs. Machine learning models, including Least Absolute Shrinkage and Selection Operator(LASSO) logistic regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), Clustering analysis, and weighted gene co-expression network analysis (WGCNA), were used to construct diagnostic gene models. The models were validated using independent datasets. Experimental validation was conducted in vivo using a mouse bilateral RIRI model and in vitro using an HK-2 cell hypoxia-reoxygenation (HR) model with copper chelation intervention. HE, PAS, and TUNEL staining, along with plasma creatinine and blood urea nitrogen (BUN) measurements, were used to evaluate the protective effect of the copper chelator D-Penicillamine (D-PCA) on RIRI in mice. JC-1 and TUNEL staining were employed to assess apoptosis in HK-2 cells under hypoxia-reoxygenation conditions. Immunofluorescence and Western blot (WB) techniques were used to verify the expression levels of the SDHB and NDUFB6 genes.Results: A total of 18 CRDEGs were identified, many of which were significantly correlated with immune cell infiltration. GSEA revealed that these genes were involved in pathways related to oxidative phosphorylation and immune response regulation. Four key cuproptosis marker genes (LIPA, LIPT1, SDHB, and NDUFB6) were incorporated into a Cuproptosis Marker Gene Model(CMGM), achieving an area under the curve (AUC) of 0.741– 0.834 in validation datasets. In addition, a five-hub-gene SVM model (MOAP1, PPP2CA, SYL2, ZZZ3, and SFRS2) was developed, demonstrating promising diagnostic performance. Clustering analysis revealed two RIRI subtypes (C1 and C2) with distinct molecular profiles and pathway activities, particularly in oxidative phosphorylation and immune responses. Experimental results showed that copper chelation alleviated renal damage and cuproptosis in both in vivo and in vitro models.Conclusion: Our study reveals that cuproptosis-related genes are significantly involved in RIRI, particularly influencing mitochondrial dysfunction and immune responses. The diagnostic models developed showed promising predictive performance across independent datasets. Copper chelation demonstrated potential therapeutic effects, suggesting that cuproptosis regulation may be a viable therapeutic strategy for RIRI. This work provides a foundation for further exploration of copper metabolism in renal injury contexts.Keywords: cuproptosis, renal ischemia-reperfusion injury, RIRI, gene diagnostic models, copper chelators, bioinformatics analysis

Yashi Ruan,1,&ast; Lixia Guan,2,&ast; Yuting Wang,2 Yifei Geng,2 Xiaoran Wang,2 Miao-Miao Niu,2 Li Yang,1 Cen Xu,1 Zhen Xu1 1Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 2Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing, 211198, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Cen Xu, Department of Urology, Reproductive Medicine and Oncology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou, 225300, People’s Republic of China, Email proyangli@163.com; cenxu263128@163.comPurpose: Dual inhibition of ataxia telangiectasia mutated (ATM) and histone deacetylase 2 (HDAC2) may be a potential strategy to improve antitumor efficacy in testicular cancer.Methods: A combined virtual screening protocol including pharmacophore modeling and molecular docking was used for screening potent dual-target ATM/HDAC2 inhibitors. In order to obtain the optimal lead compound, the dual ATM/HDAC2 inhibitory activity of the screened compounds was further evaluated using enzyme inhibition methods. The binding stability of the optimal compound to the dual targets was verified by molecular dynamics (MD) simulation. MTT assay and in vivo antitumor experiment were performed to validate antitumor efficacy of the optimal compound in testicular cancer.Results: Here, we successfully discovered six potent dual-target ATM/HDAC2 inhibitors (AMHs 1– 6), which exhibited good inhibitory activity against both ATM and HDAC2. Among them, AMH-4 showed strong inhibitory activity against both ATM (IC50 = 1.12 ± 0.03 nM) and HDAC2 (IC50 = 3.04 ± 0.08 nM). MD simulation indicated that AMH-4 binds to ATM and HDAC2 with satisfactory stability. Importantly, AMH-4 had significant antiproliferative activity on human testicular tumor cells, especially NTERA-2 cL.D1 cells, and no inhibitory effect on normal human testicular cells. In vivo experiments exhibited that AMH-4 was more effective than lartesertib and vorinostat in inhibiting the growth of NTERA-2 cL.D1 xenograft tumors with low toxicity.Conclusion: Overall, these results suggest that AMH-4 is an effective and low toxicity candidate for the treatment of testicular germ cell tumors.Keywords: ataxia telangiectasia mutated, histone deacetylase 2, dual-targeting inhibitors, testicular germ cell tumors, structure-based virtual screening

Haoran Chen,1 Meng Wang,2,3 Lin Yang,1,4 Jiao Li,1,4,&ast; Zixiao Li2,3,5,&ast; 1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 4Key Laboratory of Medical Information Intelligent Technology, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 5Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Li, Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 3 Yabao Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Email li.jiao@imicams.ac.cn Zixiao Li, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Road, Southern Fourth Ringroad, Fengtai District, Beijing, 100070, People’s Republic of China, Email lizixiao2008@hotmail.comAim: The interaction between inflammatory biomarkers (high-sensitivity C-reactive protein, hsCRP) and antioxidants (uric acid, UA) regarding prognosis after ischemic stroke or transient ischemic attack (TIA) remains inadequately explored. This study aimed to assess (1) the individual and joint effects of hsCRP and UA, and (2) the neuroprotective role of UA in patients with elevated hsCRP levels concerning poor functional outcomes at 90 days.Methods: A prospective cohort study was conducted involving 2140 consecutive ischemic stroke or TIA patients with hsCRP and UA levels. The primary outcome was defined as a poor functional outcome, indicated by a modified Rankin Scale (mRS) score of 3– 6 at 90 days, with a shift in the mRS score as a secondary outcome. Logistic regression and propensity score (PS) analyses were employed to ensure robustness.Results: Poor functional outcome occurred in 345 (16.1%) patients. Individual effects found that the highest quartiles of hsCRP (adjusted OR = 3.090; 95% CI 2.150– 4.442) and UA (adjusted OR = 0.671; 95% CI 0.551– 0.883) were associated with increased or decreased risk of poor functional outcome, respectively. Joint effects (adjusted OR = 3.994; 95% CI 2.758– 5.640) between hsCRP and UA on the primary outcome were more apparent in patients with high hsCRP levels (hsCRP > 1.60 mg/L) and low UA levels (UA ≤ 291.85 μmol/L). For the patients with high hsCRP levels, patients with low UA levels had a higher risk of primary and secondary outcomes, compared with those with high UA levels, after unadjusted or adjusted for hsCRP. Similar and reliable results were observed in PS-based models.Conclusion: In patients with ischemic stroke or TIA, joint high levels of hsCRP and low UA levels significantly correlate with increased risk of poor functional outcome at 90 days. In addition, high UA levels could reduce the risk of poor functional outcome for patients with high hsCRP levels. Keywords: biomarkers, ischemic stroke, poor functional outcome, joint effects, neuroprotective effects

Yu Sun,1 Zhaoyong Li,1 Jiahao Duan,1 Enxu Liu,1 Fei Sun,1 Lei Yang,2 Long Chen,2 Shaofeng Yang2 1Graduate School of Hunan University of Chinese Medicine, Changsha, Hunan, 410208, People’s Republic of China; 2Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Shaofeng Yang, Department of Orthopedics, the First Affiliated Hospital of Hunan University of Chinese Medicine, No. 300 Xue-Shi Road, Yuelu District, Changsha, 410007, Hunan, People’s Republic of China, Tel +86 18391076233, Email a18391076233@163.comAbstract: The gut microbiome (GM), often referred to as the second genome of the human body, plays a crucial role in various metabolic processes and mediates the development of numerous diseases. Intervertebral disc degeneration (IDD) is an age-related degenerative spinal disease characterized by the loss of disc height, hydration, and integrity, leading to pain and reduced mobility. Although the pathogenesis of IDD is not fully understood, recent studies suggest that dysbiosis of the gut microbiome may accelerate the progression of IDD through multiple mechanisms. This article begins by discussing the potential relationship between GM dysbiosis and human diseases, followed by a comprehensive review of the regulatory mechanisms of GM in skeletal diseases within the gut-disc axis framework. Furthermore, it explores three potential pathways through which GM dysbiosis may mediate the development of IDD: immunomodulation, bacterial translocation and colonization, and the decomposition and absorption of intestinal metabolites. These pathways can disrupt disc cell homeostasis and promote degenerative changes. Finally, this paper summarizes for the first time the potential therapeutic approaches for delaying IDD by targeting the gut-disc axis, providing new insights into the pathogenesis and regenerative repair strategies for IDD.Keywords: intervertebral disc degeneration, microbiome, inflammation, immunity, metabolism

Guoxin Zhang,1,&ast; Liqin Yang,2,&ast; Fang Zhao,1 Xiaoyun Zhao1 1Respiratory and Critical Care Medicine Department, Tianjin Chest Hospital, Tianjin, People’s Republic of China; 2Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyun Zhao, Respiratory and Critical Care Medicine Department, Tianjin Chest Hospital, Tianjin, 300222, People’s Republic of China, Tel +86 8818 2075, Email zxydoctor@163.comObjective: To explore the characteristics of elderly patients with central sleep apnea (CSA).Methods: This retrospective study divided 123 patients with CSA into elderly and non-elderly groups, and compared them in terms of demographic characteristics (age, BMI, etc), underlying diseases (hypertension, coronary heart disease, and cardiac arrhythmias, etc). and polysomnography parameters. Multiple linear regression analysis was conducted to investigate the potential risk factors of central apnea index (CAI).Results: Compared with the non-elderly group, patients in the elderly group had lower body mass index, a higher proportion of comorbidities of coronary heart disease, arrhythmias, and diabetes, lower apnea-hypopnea index (AHI), obstructive apnea index (OAI) and oxygen desaturation index (ODI). CAI of the elderly group showed a trend higher than that of the non-elderly group with no statistical difference. However, the ratio of CAI to AHI in the elderly group was significantly higher (0.264 vs 0.154, P=0.003). True CSA was less prevalent than companion CSA in both groups. The results of multiple regression analysis indicated CAI was independently associated with age (β=0.256, P=0.005), OAI (β=− 0.543, P< 0.001), MAI (β=− 0.267, P=0.005), ODI (β=0.538, P< 0.001), heart failure (β=0.300, P< 0.001).Conclusion: CSA typically coexists with other types of sleep apnea. Elderly CSA patients have characteristics such as a lower BMI, and a milder decrease in blood oxygen saturation, along with higher prevalence of arrhythmia and coronary heart disease. Age may be a potential risk factor for CSA.Keywords: elderly people, sleep apnea, heart failure, oxygen desaturation index

Maoting Zhou, Peng Zhang, Qi Mao, Yue Shi, Lin Yang, Xiaoming Zhang Medical Imaging Key Laboratory of Sichuan Province, Science and Technology Innovation Center, Interventional Medical Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of ChinaCorrespondence: Lin Yang, Medical Imaging Key Laboratory of Sichuan Province, Science and Technology Innovation Center, Interventional Medical Center, Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, 637000, People’s Republic of China, Email linyangmd@163.comObjective: To develop a model for predicting the overall survival (OS) of hepatocellular carcinoma (HCC) patients after transarterial chemoembolization (TACE) on the basis of multisequence MRI radiomic features and clinical variables.Methods: The DCE-MRI and clinical data of 116 HCC patients treated with TACE for the first time were retrospectively analyzed. The included patients were randomly divided into training and validation cohorts at a ratio of 7:3. Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors that affect the OS of patients with HCC after TACE. Radiomic features were extracted from the sequences of FS-T2W images and arterial-phase (A) and portal venous-phase (P) axial DCE-MR images. The LASSO method was used to select the best radiomic features. Logistic regression was used to establish a radiomic model of each sequence, a joint model of MRI features (M model) combined the radiomic features of all the sequences, and a radiomic-clinical model (M-C model) that integrated the radiomic signatures and clinically independent predictors. The diagnostic performance of each model was evaluated as the area under the receiver operating characteristic (ROC) curve (AUC).Results: The Child–Turcotte–Pugh (CTP) score and neutrophil-to-lymphocyte ratio (NLR) –platelet–to–lymphocyte ratio (PLR) were found to be independent risk factors that affect the OS of patients with HCC treated with TACE. The AUCs of the FS-T2WI, A, P, M, and M-C models for predicting the OS of HCC patients after TACE treatment were 0.779, 0.803, 0.745, 0.858 and 0.893, respectively, in the training group and 0.635, 0.651, 0.644, 0.778 and 0.803, respectively, in the validation group. The M-C model had the best predictive performance.Conclusion: Multiparameter MRI-based radiomic features may be helpful for predicting OS after TACE treatment in HCC patients. The inclusion of clinical indicators such as inflammation scores can improve the predictive performance.Keywords: magnetic resonance imaging, radiomics, hepatocellular carcinoma, transcatheter arterial chemoembolization, inflammatory indices, overall survival

Maolin Hou,1,&ast; Jinghua Chen,2,&ast; Le Yang,3,&ast; Lei Qin,3 Jie Liu,4 Haibo Zhao,5 Yujin Guo,6 Qing-Qing Yu,6 Qiujie Zhang5 1Department of Internal Medicine, Siziwangqi People’s Hospital, Wulancabu, 011800, People’s Republic of China; 2Department of Oncology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer Institute, Jinan, 250000, People’s Republic of China; 3Department of Gastrointestinal Surgery, Jining, 272000, People’s Republic of China; 4Department of Pediatric Intensive Care Unit, Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao University, Jinan, 250000, People’s Republic of China; 5Department of Oncology, Jining, 272000, People’s Republic of China; 6Department of Clinical Pharmacology, Jining, 272000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Zhang, Department of Oncology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email zhangqiujie86@163.com Qing-Qing Yu, Department of Clinical Pharmacology, Jining No. 1 People’s Hospital, Jining, 272000, People’s Republic of China, Email yuqingqing_lucky@163.comIntroduction: Gastric cancer, the fifth most common malignant tumor in the world, poses a serious threat to human health. However, the role of fatty acid metabolism (FAM) in gastric cancer remains incompletely understood. We aim to provide guidance for clinical decisions by utilizing public database of gastric adenocarcinoma to establish an FAM-related gene subtypes via machine learning algorithm.Methods: The intersection of FMGs from KEGG, Hallmark, and Reactome bioinformatics databases and the DEGs of the TCGA-STAD cohort was used to decompose the gene matrix related to establish FAM-related gene subtypes by NMF. Comparison of immune infiltrating differences between subtypes using ESTIMATE and Cibersort algorithms. The multifactor Cox regression to identify independent risk genes for patient prognosis based on the subtypes. A prognostic model including independent risk genes was built using random survival forest and Cox regression. IHC validation in gastric cancer and adjacent tissues confirmed the above gene expression level.Results: 71 DEGs related to FMGs of STAD were identified, which was used to established the FAM-related gene subtypes, C1 and C2. The immune infiltrating analysis showed that most immune features of C2 were significantly upregulated compared to C1. The independent risk genes were CGβ 8, UPK1B, and OR51G based on the subtypes. A gastric cancer prognostic model consisting of independent risk genes was constructed and patients were classified into high-risk and low-risk groups with survival differential analysis. Finally, IHC showed that CGβ 8 and UPK1B expression were upregulated in gastric cancer, while OR51G2 did not detect differences in expression.Conclusion: The study developed a machine learning-based gastric cancer prognosis risk model using FMGs. This model effectively stratifies patients according to their risk levels and provides valuable insights for clinical decision-making, enabling accurate evaluation of patient prognosis.Keywords: Gastric cancer, fatty acid metabolism-related genes, machine learning, genomics, signature

Jing Yang,1,&ast; Mei Liu,1,&ast; Lei Yang,1 Shujing Fang,2 Guangling Wang,2 Zejuan Gu1 1Nursing Department, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China; 2Orthopedics Department, Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zejuan Gu, Nursing Department, Jiangsu province hospital and the First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, Tel +8602568305379, Email jassicagu@163.comObjective: To analyze the current utilisation of delirium risk assessment and screening for older patients after hip fracture surgery in tertiary hospitals in Jiangsu Province, China.Methods: This cross-sectional study was conducted from April 1 to April 30, 2023 among nurses working in orthopedics from Level III hospitals in Jiangsu Province, China. Data were collected using a self-designed questionnaire that focused on the utilisation of delirium risk assessment and prevention measures for older patients after hip fracture surgery. The questionnaire was administered through the online platform Questionnaire Star. Differences between data were analyzed using chi-square and rank-sum tests.Results: A total of 616 nurses from 48 hospitals in Jiangsu province responded to the survey. Among them, 50.17% reported having no training in delirium management, 66.88% did not assess patients for delirium risk, and 73.21% did not screen patients for delirium in their clinical practice. It was observed that nurses with longer tenure, nurses specialising in orthopaedics, and nurses with ICU experience were more attentive to delirium risk assessment and delirium screening of patients (P< 0.001).Conclusion: Medical institutions must focus on strengthening nurses’ training in delirium management for older patients after hip fracture surgery, improve their ability to undertake risk assessment and risk screening, unify delirium management norms, and ultimately improve nurses’ delirium management ability.Keywords: risk assessment and screening, delirium, older patients, postoperative Hip fracture

Yaxin Wang,1 Ziyang Wang,2 Yin Sun,1 Lin Yang,2 Liangkun Ma,1 Jiao Li,2 Suhan Zhang,1 Xuanjin Yang1 1Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, PUMC Hospital, CAMS and PUMC, Beijing, People’s Republic of China; 2Institute of Medical Information/Medical Library, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100020, People’s Republic of ChinaCorrespondence: Yin Sun, Peking Union Medical College Hospital, 1 Shuaifuyuan, Dongcheng District, Beijing, People’s Republic of China, Email sunyin@pumch.cnObjective: The study aimed to obtain more evidence on the association of gestational weight gain and pre-pregnancy body mass index (BMI) with macrosomia.Methods: The data on 5409 live births delivered at Peking Union Medical College Hospital from July 2020 to June 2022 were collected. Group analyses were performed according to the presence or absence of macrosomia. Multivariable binary logistic regression and incidence heatmaps was used to analyze the related factors of macrosomia.Results: The following variables were significantly associated with macrosomia: overweight (odds ratio [OR]: 2.24, 95% confidence interval [CI]: 1.62– 3.10), obesity (OR: 4.56, 95% CI: 2.93– 6.98), excessive gestational weight gain (OR: 2.39, 95% CI: 1.67– 3.43), gestational age at delivery at 39– 41 weeks (OR: 3.83, 95% CI: 2.56– 5.95), gestational age at delivery over 41 weeks (OR: 7.88, 95% CI: 4.37– 14.19), education level of junior college or below (OR: 1.95, 95% CI: 1.19– 3.09), and multipara (OR: 1.62, 95% CI: 1.09– 2.42). “v” represents the mean weekly weight gain during the second and third trimesters. A higher v value increased the risk of macrosomia by 2.6-fold (95% CI: 1.37– 4.89, P = 0.003). Compared to normal weight women, after adjustment for different pre-pregnancy BMI subgroups, overweight pregnant women had higher weekly weight gain in the second and third trimesters (OR: 4.57, 95% CI: 2.27– 9.10, P < 0.001). Obese pregnant women had higher average weekly weight gain during the second and third trimesters, and the OR value for macrosomia was 11.33 (95% CI: 4.95– 25.18, P < 0.001). To reduce the incidence of macrosomia in overweight pregnant women, v = 0.32 could be considered the critical threshold of average weekly weight gain in these women in the second and third trimesters of pregnancy.Conclusion: Pre-pregnancy BMI and weight gain during pregnancy are closely related to macrosomia. The introduction of average weekly weight gain values in the second and third trimesters of pregnancy probably help pregnant women minimizing adverse pregnancy-related outcomes.Plain Language Summary: What is already known about this topic?Pre-pregnancy BMI and GWG are both risk factors for macrosomia. It is very important to develop effective interventions based on pathogenic factors to promote the health of mothers and children. However, the threshold for maternal weight control in the second and third trimesters of pregnancy is unclear.What is added by this report?Our data suggest that the critical threshold of average weekly weight gain in overweight pregnant women during the second and third trimesters 0.32kg per week is beneficial to reduce the incidence of macrosomia.What are the implications for public health practice?The results of this study highlight the importance of weight management in women in the second and third trimesters, especially those who are overweight, and reasonable control of weight gain will contribute to maternal and fetal health.Keywords: pregnancy, pre-pregnancy BMI, gestational weight gain, macrosomia, critical threshold of weight gain

Sumei Chen,1,&ast; Lingrong Yang,2,&ast; Bing Xia,3 Haitao Zhu,4 Zhenghao Piao,5 Youssef Jounaidi6 1Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China; 2Department of Hangzhou Cancer Institution, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China; 3Department of Thoracic Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People’s Republic of China; 4Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China; 5Department of Basic Medical Science, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, People’s Republic of China; 6Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA&ast;These authors contributed equally to this workCorrespondence: Youssef Jounaidi, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA, 02114, USA, Email yjounaidi@mgh.harvard.eduBackground: Enhancing NK cells’ antitumor activity requires sustained cytokine signaling. Interleukin-15 (IL-15) is a potent immunostimulatory cytokine used to armor CAR-NK and CAR-T cell immunotherapies. However, strategies to increase IL-15 expression and antitumor effect may trigger systemic toxicity with the potential to promote oncogenesis and autoimmune diseases.Methods: To overcome these limitations, we developed a new platform (IL15RB) whereby IL-15 with IL-2 signal peptide is tethered to its receptor, IL2Rβ.Results: NK92-expressing IL15RB (NK92IL15RB) cells expand indefinitely without exogenous cytokines and have significantly higher anticancer activity than NK-92 stimulated by IL-15, IL-2, or expressing tethered IL-2. NK92IL5RB showed resistance to irradiation and IL-4. However, TGFβ 1 substantially reduced NK92IL5RB killing, suggesting the need to inhibit TGFβ 1 in IL-15-mediated immunotherapies. IL15RB induced strong STAT3 but weaker STAT5 and STAT1 activation compared to IL-2. Chronic exposure of NK92IL15RB cells to cancer cells reduced STAT3 and STAT1 activation irreversibly, suggesting a role in exhaustion. Combination with CAR-CD19 enhanced NK92IL15RB antitumor activity against leukemia and increased its STAT5 activation. NK92IL15RB anti-tumors activity was further enhanced by combination with anti-PD1.Conclusion: Our data suggest that the tethering of IL-15 to its receptor IL2Rβ empowers NK cell cytolytic activity. Additionally, the tethering of IL-15 will prevent any systemic risk of toxicity.Keywords: IL-15, IL2RB receptor, natural killer cells, cancer immunotherapy, IL15RB

Hui Jiang,1 Zhihui Xie,1 Liu Yang,1 Huiting Wang2 1Department of Emergency Medical Service, The First People’s Hospital of Changde City, Changde, Hunan Province, People’s Republic of China; 2Department of Emergency, The First People’s Hospital of Changde City, Changde, Hunan Province, People’s Republic of ChinaCorrespondence: Liu Yang, Department of Emergency Medical Service, The First People’s Hospital of Changde City, Changde, Hunan Province, People’s Republic of China, Email 908464348@qq.com Huiting Wang, Department of Emergency, The First People’s Hospital of Changde City, Changde, Hunan Province, People’s Republic of China, Email 19173601726@163.comPurpose: To investigate a correlation between the central venous minus arterial CO2 pressure to arterial minus central venous O2 content ratio (Pcv-aCO2/Ca-cvO2) combined with optic nerve sheath diameter (ONSD) in predicting prehospital elevated intracranial pressure (ICP) in traumatic brain injury (TBI) patients.Patients and Methods: This was a prospective observational study of all adult TBI patients from the surgical intensive care unit who underwent invasive ICP monitoring between January 2023 and December 2023. Using a Delica MVU-6300 machine with 14– 5 MHz linear probe to measure ONSD. We drew blood samples for arterial and central venous blood gases to measure and calculate the following indicators such as Pcv-aCO2, Ca-cvO2, and Pcv-aCO2/Ca-cvO2 ratio. ONSD and Pcv-aCO2/Ca-cvO2 were recorded during the first 3 days after admission. Simultaneous ICP values were gained from the invasive monitoring. Associations between ONSD, Pcv-aCO2/Ca-cvO2 and simultaneous ICP were explored by Spearman correlation analysis. We constructed an ROC curve to identify the ONSD and Pcv-aCO2/Ca-cvO2 cutoff for the evaluation of elevated ICP.Results: We included 54 patients aged mean 57.13 (standard deviation 4.02) years and 24 (44%) were male. A significant correlation was observed between ONSD and ICP (r = 0.74, P < 0.01). The AUC was 0.861 (95% CI: 0.727– 0.951), with a best cutoff value of 5.62 mm. Using a cutoff of 5.62mm, ONSD had a sensitivity of 92.8%, specificity of 80.4%. The Pcv-aCO2/Ca-cvO2 ratio also significantly correlated with ICP (r = 0.70, P < 0.01). The AUC was 0.791 (95% CI: 0.673– 0.889). The optimal Pcv-aCO2/Ca-cvO2 value for predicting elevated ICP was 1.98 mmHg/mL. Using a cutoff of 1.98 mmHg/mL, Pcv-aCO2/Ca-cvO2 had a sensitivity of 87.3%, specificity of 77.2%. The AUC for ONSD combined with Pcv-aCO2/Ca-cvO2 was 0.952 (95% CI: 0.869– 0.971), which had a sensitivity of 95.1%, specificity of 93.9%.Conclusion: Pcv-aCO2/Ca-cvO2 combined with ONSD performed best in predicting elevated intracranial pressure of patients with TBI in a prehospital setting. Our findings provide a crucial tool to improve earlier management of these patients in prehospital care, where the availability and utilization of invasive monitoring is limited. It could lead to significant changes in how TBI patients are monitored and treated before reaching a hospital.Keywords: intracranial pressure, traumatic brain injury, Pcv-aCO2/Ca-cvO2, optic nerve sheath diameter, prehospital

Li Yang,1 Jing Yang,2 Guosen Bu,3 Rui Han,1 Jiamila Rezhake,1 Xiaolin La1 1Center of Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of China; 2Department of Gynaecology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi, 830011, People’s Republic of China; 3Department of Neurology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, People’s Republic of ChinaCorrespondence: Xiaolin La, Center of Reproductive Medicine, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Liyushannan Road, Urumqi, 830054, People’s Republic of China, Tel +86-991-4362889, Email 909232905@qq.comPurpose: Screening of pathological copy number variations (CNVs) is important for early-diagnosis of hereditary disease. This study was designed to investigate the efficiency of non-invasive prenatal testing (NIPT) in detecting fetal CNVs.Methods: This retrospective analysis included fetuses with CNVs between January 2018 and December 2020. Karyotype analysis and CNV sequencing (CNV-seq) were performed. We then analyzed the positive predictive values of the subchromosomal microdeletions and microduplications.Results: Fifty-eight subjects with aberrant CNVs were screened after NIPT, among which 44 finally underwent amniocentesis. CNV-seq confirmed the presence of CNVs in 24 cases. This indicated that false positivity rate of NIPT was 45.5%. Among 24 cases with CNVs after CNV-seq, only 4 showed consistent findings with karyotype analysis, which showed that karyotyping analysis yielded a missed diagnosis rate of 83.3% for the genome CNV. Positive predictive value (PPV) was 50.0% for CNVs with a length of < 5 Mb after NIPT screening. PPV for CNVs with a length of 5 Mb-10 Mb was 33.3%, while that for CNVs with a length of ≥ 10Mb was 60%. For CNVs duplication after NIPT, the PPV was 65.2%, while that for deletion was 36.4%.Conclusion: For CNVs detected after NIPT, it should be combined with ultrasonographic findings, karyotype analysis, CNV-seq or CMA to determine the pregnancy outcome. Expanding NIPT may increase the risk of unnecessary invasive surgery and unintended selective termination of pregnancy.Keywords: non-invasive prenatal screening, genome copy number variation, next-generation sequencing, prenatal diagnosis

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

Changhong Xu,1,&ast; Yun Deng,1,&ast; Jiangwei Man,1,&ast; Huabin Wang,1 Tuanjie Che,2 Liyun Ding,3 Li Yang1 1Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China; 2Innovation Center of Functional Genomics and Molecular Diagnostics Technology of Gansu Province, Lanzhou, People’s Republic of China; 3School of Physical Science and Technology, Lanzhou University, Lanzhou, 730000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang, Department of Urology, Institute of Urology, Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China, Email ery_yangli@lzu.edu.cnObjective: This study investigates the targets, pathways, and mechanisms of Schisandrin B (Sch B) in alleviating renal ischemia-reperfusion injury (RIRI) using RNA sequencing and network pharmacology.Methods: The effects of Sch B on RIRI were assessed using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining, along with measurements of blood creatinine and urea nitrogen (BUN). Differential gene expression in mouse models treated with RIRI and Sch B+RIRI was analyzed through RNA-Seq. Key processes, targets, and pathways were examined using network pharmacology techniques. The antioxidant capacity of Sch B was evaluated using assays for reactive oxygen species (ROS), mitochondrial superoxide, and JC-1 membrane potential. Molecular docking was employed to verify the interactions between key targets and Sch B, and the expression of these targets and pathway was confirmed using qRT-PCR, Western blot, and immunofluorescence.Results: Sch B pre-treatment significantly reduced renal pathological damage, inflammatory response, and apoptosis in a mouse RIRI model. Pathological damage scores dropped from 4.33 ± 0.33 in the I/R group to 2.17 ± 0.17 and 1.5 ± 0.22 in Sch B-treated groups (p < 0.01). Creatinine and BUN levels were also reduced (from 144.6 ± 21.05 μmol/L and 53.51 ± 2.34 mg/dL to 50.44 ± 5.61 μmol/L and 17.18 ± 0.96 mg/dL, p < 0.05). Transcriptomic analysis identified four key targets (AKT1, ALB, ACE, CCL5) and the PI3K/AKT pathway. Experimental validation confirmed Sch B modulated these targets, reducing apoptosis and oxidative stress, and enhancing renal recovery.Conclusion: Sch B reduces oxidative stress, inflammation, and apoptosis by modulating key targets such as AKT1, ALB, ACE, and CCL5, while activating the PI3K/AKT pathway, leading to improved renal recovery in RIRI.Keywords: renal ischemia-reperfusion injury, schisandrin B, transcriptomics, network pharmacology, PI3K/AKT pathway

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

Mengyi Shen,1,&ast; Leyu Zhou,1,&ast; Xiaoli Fan,1 Ruiqi Wu,1 Shuyun Liu,2 Qiaoyu Deng,1 Yanyi Zheng,1 Jingping Liu,2 Li Yang1 1Department of Gastroenterology and Hepatology and Laboratory of Gastrointestinal Cancer and Liver Disease, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 2NHC Key Laboratory of Transplant Engineering and Immunology, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Yang; Jingping Liu, Email yangli_hx@scu.edu.cn; liujingping@scu.edu.cnBackground: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4+ T-cell overactivation and liver injury in AIH.Methods: The metabolic changes of CD4+ T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4+ T cells was also explored.Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4+ T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4+ T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4+ T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4+ T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4+ T cells.Conclusion: Disordered glucose metabolism promotes CD4+ T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH.Keywords: autoimmune hepatitis, extracellular vesicles, metabolic reprogramming, mitochondria, inflammation

Peiran Guo,1,2,&ast; Yuting Tan,1,2,&ast; Li Feng,3 Cui Liu,4 Jin Sun,5 Rong Cheng,1,2 Yanling Xiao,1 Xingxin Zhan,6 Lingjie Yang,1 Zhixia Zhang1 1Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Wuhan University of Science and Technology School of Medicine, Institute of Nursing Research, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan, Hubei, People’s Republic of China; 3School of Public Health and Nursing, Hubei University of Science and Technology, Xianning, Hubei, People’s Republic of China; 4Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Yiling Hospital of Yichang City, Yichang, Hubei, People’s Republic of China; 6School of Public Health, Xinyu University, Xinyu, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixia Zhang, Tianyou Hospital, Wuhan University of Science and Technology, No. 9, Tujialing, Dingzhiqiao, Wuchang District, Wuhan, Hubei, People’s Republic of China, Tel +8613476805827, Email zzx13476805827@126.comPurpose: The development of “Internet + nursing services” can effectively solve the problem of population aging, and grassroots nurses are the primary providers of such services in rural areas. This study aimed to analyze the factors affecting grassroots nurses’ risk perception of “Internet + nursing services” and construct a predictive model.Patients and Methods: A multicenter cross-sectional study of 2220 nurses from 27 secondary hospitals and 36 community health centers in Hubei Province was conducted from August to December 2023 using a multi-stage cluster sampling method. Information was collected through a structured anonymous questionnaire. A Chi-square test, a Welch t-test, and binary logistic regression analyses were employed to determine independent risk factors for grassroots nurses’ risk perception of “Internet + nursing services”, and a nomogram was constructed. Receiver operating characteristic curves, calibration curves, and decision curves were plotted to evaluate the discrimination, calibration, and clinical effectiveness of the nomogram.Results: A total of 2050 valid questionnaires were collected, demonstrating that 51.95% of grassroots nurses thought that “Internet + nursing services” was a medium-high risk. Age, other sources of income, knowledge about “Internet + nursing services”, personal safety, physical function, occupational exposure, social psychosocial, and time risk (P< 0.05) were independent risk factors for grassroots nurses’ risk perception. The area under the receiver operating characteristic curve of the nomogram was 0.939. The calibration and decision curve analyses demonstrated good calibration ability and clinical application values.Conclusion: The prediction model constructed in this study has good prediction ability. Most grassroots nurses believe that “Internet + nursing services” are risky and influenced by several factors. It is suggested that the government and hospitals should formulate a unified charging standard, improve the safety guarantee, and gradually eliminate the concerns of grassroots nurses.Keywords: grassroots nurse, Internet + nursing services, risk perception, predictive model

Shiyu Zhang, Fanting Kong, Lei Zheng, Xiaowei Li, Lining Jia, Lixian Yang Department of Breast Surgery, Xingtai People’s Hospital, Xingtai, Hebei, 054000, People’s Republic of ChinaCorrespondence: Lixian Yang, Department of Breast Surgery, Xingtai People’s Hospital, No. 818 Xiangdu District, Xingtai, Hebei, 054000, People’s Republic of China, Email yanglixian@hebmu.edu.cnBackground: The role of Semaphorin 7a (SEMA7A) in the initiation and progression of different types of cancerous lesions has been extensively studied. However, the prognostic significance of SEMA7A, specifically in breast cancer (BC), lacks clarity.Methods: We conducted an evaluation on the relationship between SEMA7A and the prognosis, immune invasion and tumor mutation burden in different types of cancer by analyzing data from The Cancer Genome Atlas database. The present study focused on investigating the expression level, mutation, immune correlation and coexpression of SEMA7A in BC, utilizing various databases such as the University of Alabama at Birmingham Cancer data analysis portal, cBioPortal and tumor immune estimation resource. Survival analysis was carried out using the Kaplan-Meier Plotter. Furthermore, we employed the R software package to generate receiver operating characteristic (ROC) curves and nomograms. Notably, P< 0.05 was considered to indicate statistical significance.Results: Using pancancer analysis, it has been observed that the expression of SEMA7A is elevated in various types of cancer and is strongly correlated with the prognosis of different cancer types. SEMA7A also exhibits a significant association with the tumor mutation burden of diverse types of cancer. Moreover, SEMA7A displays a notable increase in BC cases, and was indicated to have a substantial association with the abundance of immune infiltration. In-depth survival analysis demonstrated that elevated levels of SEMA7A expression are notably linked to shorter overall survival and distant metastasis-free survival among patients with BC. The efficiency of SEMA7A as a reliable prognostic biomarker for BC has been substantiated by the validation of ROC curves and nomograms.Conclusion: SEMA7A has the potential to function as a prognostic indicator for BC, and its correlation with immune infiltration in BC is significant.Keywords: SEMA7A, breast cancer, biomarker, prognosis, methylation, immune infiltration, nomogram, bioinformatics

Jia Wei,1,&ast; Mingfen Song,1,&ast; Hong Jing Mao,1 Ruobing Qi,1 Lili Yang,1 You Xu,1 Pan Yan,1 Linlin Hu2 1Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310013, People’s Republic of China; 2Sleep Medicine Center, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310013, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Jing Mao, Email maohongjing@hz7hospital.comBackground: The effectiveness of medication combined with smartphone-delivered cognitive behavioral therapy for insomnia (CBT-I) has been well verified, but there are few studies on the sequence of remission of insomnia symptoms. This study aims to understand the sequence of symptom improvement and the factors influencing the treatment effectiveness in patients with insomnia.Methods: Smartphone-delivered CBT, as a form of Online CBT, allows for training through mobile devices at any time and place. We utilized the Good Sleep 365 app to conduct a survey, involving 2820 patients who met the baseline inclusion criteria. These patients were assessed using a general demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI) to evaluate general demographic information and insomnia symptoms, and subsequently underwent CBT training using the Good Sleep 365 app. A total of 1179 patients completed follow-ups at 4 weeks, 8 weeks, 16 weeks, and 24 weeks.Results: At 4 weeks and 8 weeks, the descending order of the reduction rates of PSQI components (excluding component 6: use of sleeping medication) was: sleep latency, subjective sleep quality, sleep efficiency, sleep disturbance, sleep maintenance, and daytime dysfunction. At 16 weeks and 24 weeks, the descending order was subjective sleep quality, sleep latency, sleep efficiency, daytime dysfunction, sleep maintenance, and sleep disturbance. There were significant differences in the reduction rates of PSQI components (excluding component 6: use of sleeping medication) both at the same follow-up times and at different follow-up times (all P< 0.05). Multivariable logistic regression analysis showed that patients older than 30 years and those with a college degree or above had better treatment outcomes, whereas those with a disease duration of more than three years had worse outcomes.Conclusion: The sequence of symptom improvement in patients with insomnia changes over time, and age, educational level, and duration of disease are factors influencing treatment outcomes.Keywords: insomnia, CBT-I, PSQI, influencing factors

Mingyan Wang,1– 3,&ast; Siyuan Yang,1– 3,&ast; Linxin Yang,1– 3 Ning Lin1– 3 1Ultrasound Department of Shengli Clinical Medical College of Fujian Medical University, Fuzhou City, Fujian Province, 350001, People’s Republic of China; 2Ultrasound Department of Fujian Provincial Hospital, Fuzhou City, Fujian Province, 350001, People’s Republic of China; 3Ultrasound Department of Fuzhou University Affiliated Provincial Hospital, Fuzhou City, Fujian Province, 350001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Lin, Ultrasound Department of Fujian Provincial Hospital, 134 East Street, Fuzhou City, 350001, Fujian Province, People’s Republic of China, Tel +86 0591-87557768, Email NingLin2413@163.comAim: The study aimed to compare the diagnostic performance of AI-SONICTM Thyroid System (AI-SONICTM) with six thyroid nodule ultrasound risk stratification systems, as well as the interobserver agreement among different-year ultrasound examiners using the same diagnostic approach.Methods: This retrospective study included patients who underwent thyroid ultrasound examination and surgery between 2010 and 2022. Three ultrasound examiners with 2, 5, and 10 years of experience, respectively, used AI-SONICTM and six guidelines to risk-stratify the nodules. The diagnostic performance and interobserver agreement were assessed.Results: A total of 370 thyroid nodules were included, including 195 papillary thyroid carcinomas (PTC) and 175 benign nodules. For physicians of varying seniority from low to high, AI-SONICTM had a moderate sensitivities of 82.56%, 83.08%, 84.62%, respectively, while AACE/ACE/AME had the highest diagnostic sensitivities (96.41%, 95.38%, 96.41%, respectively); And relatively higher specificities were 85.14%, 85.71%, 85.71% for KSThR, while moderate specificities with values of 84.0%, 85.14%, and 85.71%, respectively were found for AI-SONICTM; The accuracy was highest for ATA (excluding non-classifiable nodules), with values of 87.26%, 87.93%, and 88.82%, respectively, while the accuracy for AI-SONICTM were 83.24%, 84.05%, and 85.14%, respectively. The Kendall’s tau coefficient indicated strong or moderate interobserver agreement among all examiners using different diagnostic methods (Kendall’s tau coefficient > 0.6, P< 0.001). AI-SONICTM showed the highest interobserver agreement (Kendall’s tau coefficient=0.995, P< 0.001). A binary probit regression analysis showed that nodules with cystic components had a significantly higher regression coefficient value of 0.983 (P=0.002), indicating that AI-SONICTM may have higher accuracy for nodules with cystic components.Conclusion: AI-SONICTM and the six thyroid nodule ultrasound risk stratification systems showed high diagnostic performance for papillary thyroid carcinoma. All examiners showed strong or moderate interobserver agreement when using different diagnostic methods. AI-SONICTM may have higher accuracy for nodules with cystic components.Keywords: AI-SONICTM thyroid system, six thyroid risk stratification guidelines, papillary thyroid cancer

Dong Wang,&ast; Xinsheng Yan,&ast; Luo Yang, Litao Zhang Department of Clinical Laboratory, Wuhan Asia General Hospital, Wuhan Asia General Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, 430056, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang; Litao Zhang, Email wangdongwuhan001@163.com; whyxzyyzlt@163.comPurpose: Human papillomavirus (HPV) infection is a prevalent sexually transmitted infection worldwide, with its persistence being a significant factor in the development of cervical cancer and precancerous lesions. Understanding the prevalence and genotypes distribution of HPV can aid in the implementation of more focused strategies for cervical cancer prevention and treatment. This study aimed to investigate the prevalence and genotype distribution of HPV infection among outpatient-based populations in Wuhan, China.Methods: Our study retrospectively analyzed the results of cervical HPV screening in 14,492 outpatient women. The cervicovaginal infection of 18 high-risk genotypes and 10 low-risk genotypes were analyzed by PCR and reverse dot hybridization techniques.Results: The overall prevalence of HPV infection in the outpatient female population was 15.33%, with a predominance of single infection and a predominance of dual infection among multiple infections. The top five genotypes in terms of prevalence of HR-HPV and LR-HPV were HPV-52 (3.77%), 53 (1.46%), 16 (1.31%), 58 (1.19%), 39 (1.18%) for HR-HPV, and HPV-54 (1.23%), 61 (1.08%), 81 (1.04%), 42 (0.87%), 44 (0.70%) for LR-HPV. Two peaks of HPV infection prevalence were observed among women under 25 years (22.88%) and over 56 years (24.26%). The prevalence and genotype distribution of HPV infection varied among different outpatient populations, with higher rates of HPV single infection, multiple infections, and infection across all ages observed in the gynecology outpatient population compared to the health check-up population.Conclusion: This study revealed the HPV prevalence and genotype distribution among different outpatient populations in Wuhan city, which may provide guidance for HPV vaccination and cervical cancer prevention strategies in the region.Keywords: human papillomavirus, prevalence, genotype, high-risk HPV, low-risk HPV, cervical cancer

Dongyuan Qin,1 Lin Wang,2 Yahui Ni,1 Zhangtao Shan,1 Lifang Yang1 1Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Lin Wang, Department of Pathology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China, Email 13613411069@139.comBackground: Chronic gastritis affects more than half of the global population to varying extents.Objectives: This study aimed to investigate the knowledge, attitude, and practice (KAP) of patients admitted to the gastroenterology department in the Shanxi region concerning chronic gastritis.Methods: This study was conducted in Shanxi between April and July 2023. The participants were enrolled when they consulted at the clinic. Demographic characteristics and KAP scores were collected through a self-administered questionnaire. KAP scores > 60% were considered good. Structural equation modeling (SEM) was utilized to examine the relationships among the dimensions of knowledge, attitude, and practice.Results: A total of 416 valid questionnaires were collected. The median knowledge score was 28 (0– 60) (with possible values of 0– 60), the median attitude score was 60 (28– 77) (with possible values of 16– 80), and the median practice score was 45 (12– 60) (with possible values of 12– 60). Hence, 133, 379, and 343 participants had knowledge, attitude, and practice scores, respectively, above the 60% threshold. Significant positive correlations were found between knowledge and attitude (r=0.300, P< 0.001), knowledge and practice (r = 0.297, P< 0.001), and attitude and practice (r=0.353, P=0.004) through correlation analysis. Structural Equation Modeling (SEM) revealed that knowledge directly and significantly influenced attitude (β=0.643, P< 0.001), as well as practice (β=0.095, P=0.034), and attitude had a direct effect on practice (β=0.094, P=0.009).Conclusion: Insufficient knowledge, positive attitudes, and proactive practices concerning chronic gastritis were observed in patients in the gastroenterology department. Prioritizing patient education and addressing patient attitudes during clinical consultations can enhance healthcare practices and improve the management of chronic gastritis.Keywords: knowledge, attitude, practice, Helicobacter pylori, chronic gastritis, cross-sectional study

Mengjie Xie,1,&ast; Fansu Meng,2,&ast; Panpan Wang,3,&ast; Alicia Marcelina Díaz-García,4 Marina Parkhats,5 Ralph Santos-Oliveira,6 Mulazim Hussain Asim,7 Nazish Bostan,8 Honghui Gu,9 Lina Yang,9 Qi Li,9 Zhenjiang Yang,9 Haibiao Lai,2 Yu Cai1 1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China / Guangdong Key Laboratory of Traditional Chinese Medicine Informatization / International Science and Technology Cooperation Base of Guangdong Province/School of Pharmacy, Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 2Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, Guangdong, 528400, People’s Republic of China; 3The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510632, People’s Republic of China; 4Bioinorganic Laboratory, Faculty of Chemistry, University of Havana, Havana, 1400, Cuba; 5B. I. Stepanov Institute of Physics, National Academy of Sciences of Belarus, Minsk, 220072, Belarus; 6Brazilian Nuclear Energy Commission, Nuclear Engineering Institute, Laboratory of Nanoradiopharmacy and Synthesis of New Radiopharmaceuticals, Rio de Janeiro, RJ, 21941906, Brazil; 7College of Pharmacy, University of Sargodha, Punjab, 40100, Pakistan; 8Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan; 9Shenzhen Traditional Chinese Medicine Hospital, Shenzhen, Guangdong, 518033, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cai; Haibiao Lai, Email caiyu8@sohu.com; lhb8829@163.comAbstract: Data published in 2020 by the International Agency for Research on Cancer (IARC) of the World Health Organization show that breast cancer (BC) has become the most common cancer globally, affecting more than 2 million women each year. The complex tumor microenvironment, drug resistance, metastasis, and poor prognosis constitute the primary challenges in the current diagnosis and treatment of BC. Magnetic iron oxide nanoparticles (MIONPs) have emerged as a promising nanoplatform for diagnostic tumor imaging as well as therapeutic drug-targeted delivery due to their unique physicochemical properties. The extensive surface engineering has given rise to multifunctionalized MIONPs. In this review, the latest advancements in surface modification strategies of MIONPs over the past five years are summarized and categorized as constrast agents and drug delivery platforms. Additionally, the remaining challenges and future prospects of MIONPs-based targeted delivery are discussed. Keywords: Nanopreparations, Organic Nanomaterials, Inorganic Nanomaterials, Surface Engineering, Targeted Delivery

Wei Zhang,1,&ast; Jiayu Zhang,2,&ast; Dian Jiao,1,&ast; Qisheng Tang,1 Xiaoping Gao,1 Zhenyu Li,1 Fa Yang,3 Zhiguang Zhao,1 Longfei Yang4 1Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 2Department of Urology, Air Force Hospital of Southern Theater Command, Guangzhou, Guangdong, 510062, People’s Republic of China; 3Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710032, People’s Republic of China; 4Department of Transfusion Medicine, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Longfei Yang; Zhiguang Zhao, Email y68lf@163.com; zzg13991809889@163.comPurpose: Lichen sclerosus urethral stricture disease (LS USD) is a refractory and progressive disease primarily affecting the anterior urethra in males. Various potential etiological factors, such as genetics, autoimmunity, infection, and exposure to infectious urine, have been suggested. However, the accurate etiology of LS in the male urethra remains unclear.Patients and Methods: In this study, we conducted single-cell RNA sequencing to identify the transcriptional profiles of three patients with LS USD and three patients with non-LS USD. Immunofluorescence was used to confirm the single-cell sequence results.Results: Our study revealed distinct subsets of vein endothelial cells (ECs), smooth muscle cells (SMCs), and fibroblasts (FBs) with high proportions in LS USD, contributing to the tissue microenvironment primarily involved in proinflammatory and immune responses. In particular, FBs displayed a unique subset, Fib7, which is exclusively present in LS USD, and exhibited high expression levels of SAA1 and SAA2. The accumulation of macrophages, along with the dysregulated ratios of M1/M2-like phenotype macrophages, may be engaged in the pathogenesis of LS USD. Through cell–cell communication analysis, we identified significant interactions involving CXCL8/ACKR1 and CCR7/CCL19 in LS USD. Remarkably, Fib7 exhibited exclusive communication with IL-1B macrophages through the SAA1/FPR2 receptor–ligand pair.Conclusion: Our study provides a profound understanding of the tissue microenvironment in LS USD, which may be valuable for understanding the pathogenesis of LS USD. Keywords: lichen sclerosus, urethral stricture disease, single-cell RNA sequencing, heterogeneity, fibroblasts, macrophages

Liu Yang,1 Kaijie Gao,1 Weihua Gong,1 Ci Li,1 Nan Chen,1 Tiewei Li,1 Shan Wang,1 Jiajia Ni,2,3 Junmei Yang1 1Department of Clinical Laboratory, Children’s Hospital Affiliated to Zhengzhou University, Zhengzhou Key Laboratory of Children’s Infection and Immunity, Zhengzhou, Henan, People’s Republic of China; 2Research and Development Center, Guangdong Meilikang Bio-Science Ltd, Foshan, Guangdong People’s Republic of China; 3Department of Detection and Diagnosis Technology Research, Guangzhou National Laboratory, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Junmei Yang, Email yangjunmei7683@163.comPurpose: Although allergic diseases in children are on the rise, there has been no comprehensive investigation of the allergens affecting children with allergic diseases in central China. Therefore, we aimed to analyze the distribution of serum allergen species among children with allergic conditions in central China to inform the prevention, diagnosis, and treatment of childhood allergies.Patients and Methods: A total of 9213 children (5543 males with 2.88 ± 0.04 years old and 3670 females with 2.91 ± 0.05 years old) underwent allergen screening, and serum allergen-specific IgE (sIgE) antibodies were detected using an automated fluorescent enzyme immunoassay system.Results: Our findings revealed a total sIgE-positive rate (sIgE-PR) of 57.83%, with mixed food (42.10%), egg whites (30.83%), milk (28.97%), mixed dust mites (24.57%), and mixed molds (23.20%) being the most prevalent source of allergens. The sIgE-PR for common sources of allergens exhibited significant sex-based differences, with males having greater susceptibility than females (p< 0.05). Dust mites were the primary source of inhaled allergens, whereas egg white was the predominant source of food allergens. Sources of food allergens were most dominant among infants (0– 3 years old); sIgE-PRs for most source of food allergens decreased with age, whereas those for most source of inhaled allergens increased. The autumn sIgE-PRs for mixed molds, weed pollen combinations, and tree pollen combinations were significantly higher than those found in other seasons (p< 0.05).Conclusion: Our findings suggest that sources of allergens profiles in children with allergies vary across age groups and seasons. Understanding these patterns can improve the effective prevention of childhood allergies.Keywords: allergen, childhood allergies, IgE antibodies, source of food allergens, allergy prevention

Hailing Yu,1,&ast; Yongquan Huang,2,&ast; Zhisheng Nong,3,&ast; Xi Lin,1 Kexin Tang,1 Zeyu Cai,1 Kaichen Huang,4 Ting Yu,1 Huimin Lan,1 Qianqian Zhang,1 Qiang Wang,5 Lei Yang,6 Jingchuan Zhu,7 Lili Wu,8 Hui Luo1 1Guangdong Provincial Engineering Research Center of Molecular Imaging, Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine, The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Ultrasound, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3School of Materials Science and Engineering, Shenyang Aerospace University, Shenyang, Liaoning, People’s Republic of China; 4Department of Clinical laboratory, The Third People’s Hospital of Zhuhai, Zhuhai, Guangdong, People’s Republic of China; 5The Green Aerotechnics Research Institute of Chongqing Jiaotong University, Chongqing, People’s Republic of China; 6Center for Composite Materials and Structures, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 7School of Materials Science and Engineering, Harbin Institute of Technology, Harbin, Heilongjiang, People’s Republic of China; 8Key Laboratory for Photonic and Electronic Bandgap Materials, Ministry of Education, School of Physics and Electronic Engineering, Harbin Normal University, Harbin, Heilongjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Luo; Lili Wu, Email luoh53@mail.sysu.edu.cn; wll790107@hotmail.comIntroduction: Traditional cancer treatment strategies often have severe toxic side effects and poor therapeutic efficacy. To address the long-standing problems related to overcoming the complexity of tumors, we develop a novel nanozyme based on the in situ oxidation of 2D Ti3C2 structure to perform simultaneous phototherapy and sonodynamic therapy on tumors. Ti3C2 nanozymes exhibit multi-enzyme activity, including intrinsic peroxidase (POD) activities, which can react with H2O2 in the tumor microenvironment. This new material can construct Ti3C2/TiO2 heterostructures in vivo.Methods: Photothermal (PTT), sonodynamic (SDT) effects, and photoacoustic (PA) image-guided synergy therapy can be achieved. Finally, anticancer immune responses occur with this nanozyme. In vivo experiments revealed that the Ti3C2/TiO2 heterostructure inhibited tumor growth.Results: Complementarily, our results showed that the Ti3C2/TiO2 heterostructure enhanced the immunogenic activity of tumors by recruiting cytotoxic T cells, thereby enhancing the tumor ablation effect. Mechanistic studies consistently indicated that Reactive Oxygen Species (ROS) regulates apoptosis of HCC cells by modulating NRF2/OSGIN1 signaling both in vitro and in vivo. As a result, Ti3C2 nanozyme effectively inhibited tumor through its synergistic ability to modulate ROS and enhance immune infiltration of cytotoxic T cells in the tumor microenvironment.Discussion: These findings open up new avenues for enhancing 2D Ti3C2 nanosheets and suggest a new way to develop more effective sonosensitizers for the treatment of cancer.Keywords: nanozyme, sonodynamic therapy, Ti3C2/TiO2, ROS

Wenliang Liu, Gongying Li, Mengya Zhu, Lin Yang Department of Psychological, Huai’an No. 3 People’s Hospital, Huaian, People’s Republic of ChinaCorrespondence: Gongying Li, Department of Psychological, Huai’an No. 3 People’s Hospital, No. 272, Huaihai West Road, Huaian, 223001, People’s Republic of China, Tel +86-517-83285124, Email ligongying2005@126.comObjective: To investigate the association between single nucleotide polymorphisms (SNPs) of tryptophan hydroxylase 2 (TPH2) (rs11178997, rs11178998, and rs120074175) and negative life events in adolescent depression with Non-suicidal self-injury (NSSI).Methods: Genomic DNA was extracted from 197 adolescents with depression (participants group, including NSSI group and non-NSSI group), as well as from 100 healthy controls (control group), in northern China. PCR technology was utilized to amplify DNA fragments and detect genotypes in both groups. The Adolescent Life Event Scale (ASLEC) was employed to conduct a questionnaire survey among the participants and control groups. Differences in allele and genotype frequency distribution between the two groups were analyzed using the X^2 test, while generalized multifactor dimensionality reduction (GMDR) was used to analyze gene-environment interactions.Results: Significant differences were observed in ASLEC scores between the control group and both the NSSI group and non-NSSI group (P< 0.05). Additionally, significant differences were found in the interpersonal relationship factor and punishment factor between the NSSI group and non-NSSI group (P < 0.05). Moreover, a significant difference was identified in SNP genotype of rs11178997 between the depression group (NSSI group + non-NSSI group) and control group (P< 0.05). GMDR analysis revealed an interaction among rs11178997, rs11178998, and ASLEC.Conclusion: Adolescents with depression, particularly females, may exhibit a tendency to employ NSSI as an emotional coping mechanism when confronted with greater family and interpersonal challenges. The AT genotype of TPH2 gene locus rs11178997 is more prevalent among adolescents with depression. Furthermore, the occurrence of NSSI may be associated with an interaction involving polymorphic sites rs11178997 and rs11178998 along with life events.Keywords: adolescent depression, non-suicidal self-injury, tryptophan hydroxylase 2, gene polymorphism, life events in adolescence

Weimin Xu,1 Xinyu Wang,2 Lei Yang,2 Muzi Meng,3,4 Chenyu Sun,1 Wanwan Li,1 Jia Li,1 Lu Zheng,1 Tong Tang,1 WenJun Jia,1 Xiao Chen1 1Department of Thyroid and Breast Surgery, The Affiliated Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2School of Second Clinical Medicine, AnHui Medical University, Hefei, People’s Republic of China; 3School of Medicine, American University of the Caribbean, Sint Maarten, Kingdom of the Netherlands; 4General Surgery, BronxCare Health System, New York, NY, USACorrespondence: WenJun Jia; Xiao Chen, Email jiawenjun@smail.nju.edu.cn; chenxiao950616@Gmai.comBackground: The Chinese Society of Clinical Oncology Artificial Intelligence System (CSCO AI) serves as a clinical decision support system developed utilizing Chinese breast cancer data. Our study delved into the congruence between breast cancer treatment recommendations provided by CSCO AI and their practical application in clinical settings.Methods: A retrospective analysis encompassed 537 breast cancer patients treated at the Second Affiliated Hospital of Anhui Medical University between January 2017 and December 2022. Proficient senior oncology researchers manually input patient data into the CSCO AI system. “Consistent” and “Inconsistent” treatment categories were defined by aligning our treatment protocols with the classification system in the CSCO AI recommendations. Cases that initially showed inconsistency underwent a second evaluation by the Multi-Disciplinary Treatment (MDT) team at the hospital. Concordance was achieved when MDTs’ treatment suggestions were in the ‘Consistent’ categories.Results: An impressive 80.4% concurrence was observed between actual treatment protocols and CSCO AI recommendations across all breast cancer patients. Notably, the alignment was markedly higher for stage I (85.02%) and stage III (88.46%) patients in contrast to stage II patients (76.06%, P=0.023). Moreover, there was a significant concordance between invasive ductal carcinoma and lobular carcinoma (88.46%). Interestingly, triple-negative breast cancer (TNBC) exhibited a high concordance rate (87.50%) compared to other molecular subtypes. When contrasting MDT-recommended treatments with CSCO AI decisions, an overall 92.4% agreement was established. Furthermore, a logistic multivariate analysis highlighted the statistical significance of age, menstrual status, tumor type, molecular subtype, tumor size, and TNM stage in influencing consistency.Conclusion: In the realm of breast cancer treatment, the alignment between recommendations offered by CSCO AI and those from MDT is predominant. CSCO AI can be a useful tool for breast cancer treatment decisions.Keywords: Chinese Society of clinical oncology artificial intelligence system, CSCO AI, breast cancer, multi-disciplinary treatment, MDT, consistency

Ziwei Jiang,&ast; Lianglong Chen,&ast; Lei Huang, Shengxiang Yu, Jiabao Lin, Mengyao Li, Yanbin Gao, Lei Yang Department of Burns, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Yang, Department of Burns, Nanfang Hospital, Southern Medical University, Jingxi Street, Baiyun District, Guangzhou, 510515, People’s Republic of China, Tel +86-20-6164-1841, Email yuanyang@smu.edu.cnAbstract: Endogenous stem cell homing refers to the transport of endogenous mesenchymal stem cells (MSCs) to damaged tissue. The paradigm of using well-designed biomaterials to induce resident stem cells to home in to the injured site while coordinating their behavior and function to promote tissue regeneration is known as endogenous regenerative medicine (ERM). ERM is a promising new avenue in regenerative therapy research, and it involves the mobilizing of endogenous stem cells for homing as the principal means through which to achieve it. Comprehending how mesenchymal stem cells home in and grasp the influencing factors of mesenchymal stem cell homing is essential for the understanding and design of tissue engineering. This review summarizes the process of MSC homing, the factors influencing the homing process, analyses endogenous stem cell homing studies of interest in the field of skin tissue repair, explores the integration of endogenous homing promotion strategies with cellular therapies and details tissue engineering strategies that can be used to modulate endogenous homing of stem cells. In addition to providing more systematic theories and ideas for improved materials for endogenous tissue repair, this review provides new perspectives to explore the complex process of tissue remodeling to enhance the rational design of biomaterial scaffolds and guide tissue regeneration strategies.Keywords: endogenous stem cell homing, in situ tissue regeneration, biomimetic design, wound healing, bioactive materials

Zhihong Cheng,1,&ast; Song Feng,1,2,&ast; Linfeng Yang,1 Jing Huang,3 Xilei Chen,4 Yang Guo,1 Yu Xiang,1 Bin Peng1 1Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 2Department of Neurosurgery, Dazhou Third People’s Hospital, Dazhou, Sichuan, People’s Republic of China; 3Innovation Center for Science and Technology, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 4Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Peng, Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College, No. 234 Fujiang Road, Shunqing District, Nanchong, Sichuan, People’s Republic of China, Tel/Fax +86-817-2242781, Email binpeng01@sina.comPurpose: The spinal nerve ligation (SNL) model is a typical peripheral neuropathic pain model. During its construction, the removal of paraspinal muscles and transverse processes typically occurs, resulting in additional trauma that may potentially affect the pathophysiologic process of neuropathic pain. This study aimed to investigate the feasibility of establishing a more reliable SNL model using an oblique lateral approach.Methods: 36 adult male Sprague-Dawley rats were randomly divided into three groups: the traditional SNL (T-SNL) group, the new SNL (N-SNL) group (where the left L5 spinal nerve was ligated with a titanium clip via an oblique lateral approach), and the sham-operated (Sham) group. The operation time, Intraoperative bleeding, the number of rats that died, gait behavior, mechanical and cold pain threshold were recorded and measured. Stereology technology was used to calculate the number of microglia in spinal dorsal horn, and the Enzyme-linked immunosorbent assay (ELISA) technology was used to detect the expression of TNF-α and IL-1β in spinal cord as well as C-reactive protein (CRP) in serum in order to assess the effect of surgery on animal inflammation.Results: Compared with the T-SNL group, operative time and intraoperative bleeding were significantly decreased in the N-SNL group. Within 14 days postoperation, one rat in the N-SNL group was died, two rats in the T-SNL group were died. Compared with the Sham group, the N-SNL group showed obvious spontaneous pain behavior, decreased the pain thresholds, the number of microglia and the expression of TNF-α and IL-1β were significantly increased, and there was no significant difference in these indexes compared with T-SNL group. There was no significant difference in serum CRP levels among the three groups.Conclusion: This study suggests that the oblique lateral approach SNL model is a reliable NP model with the advantages of good reproducibility, accessibility, and low trauma.Keywords: animal model, mechanical pain threshold, hyperpathia, microglial, peripheral nerve injury, inflammatory

Kaixin Wang,1 Lingfei Yang,2 Qingsheng Li,2 Xuan Yang,1 Ziyi Chen,2 Yongyan Zhou,3 Yanjie Jia,1 Zhe Gong1 1Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Academy of Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 3Department of Electrocardiogram, Zhoukou Center Hospital, Zhoukou, People’s Republic of ChinaCorrespondence: Yanjie Jia; Zhe Gong, The First Affiliated Hospital of Zhengzhou University, Department of Neurology, Postal FfCode 450052, No. 1 Jianshe East Road, Zhengzhou, People’s Republic of China, Email jiayanjie1971@aliyun.com; gongzhe1415@163.comBackground: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes.Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed.Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol.Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.Keywords: cerebral ischemia, chronic ethanol exposure, pericytes, TLR4, NLRP3 inflammasome

Tinghua Hu,1,&ast; Shanshan Dai,2,&ast; Lan Yang,1 Bo Zhu1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, 710000, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Xi’an No. 9 Hospital, Xi’an, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Zhu, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta West Road, Xi’an, Shaanxi, 710061, People’s Republic of China, Email zhubo685689@163.comBackground: COPD, combined with Osteoporosis, has a high incidence and potential for great harm. Choosing an optimal diagnostic method to achieve bone mineral density (BMD) screening is crucial for COPD patients. Studies on COPD patients with BMD reduction are lacking.Purpose: To identify the risk factors of BMD reduction and osteoporosis in COPD patients.Patients and Methods: We included a total of 81 patients with AECOPD, who were admitted to the hospital from July 1, 2019, to January 31, 2020. Patients were grouped into BMD normal group, BMD reduced group and OP group. The areas under ROC curve were used to explore the value of CT values in the diagnosis of bone abnormality, and clinical indicators were collected.Results: The CT value of the vertebral cancellous bone is highly correlated with the T value of BMD (R > 5.5, P < 0.0001). Using multivariate Logistic regression analysis, we showed that COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid were independent factors affecting different BMD levels in COPD patients. No significant difference in bone formation indexes between groups. β-crossL was negatively correlated with serum IL-6 (r=− 0.254, P=0.022), and ALP was positively correlated with serum TNF-α (r=0.284, P=0.023).Conclusion: Thoracolumbar vertebral cancellous bone CT has potential value in the diagnosis of bone abnormality. COPD duration, BMI, 25-hydroxyvitamin D3, and long-term inhaled glucocorticoid may contribute to the BMD reduction in COPD patients, and serum IL-6 and TNF-α regulate bone metabolism in COPD patients.Keywords: chronic obstructive pulmonary disease, osteoporosis, bone mineral density, chest CT

Weijian Liu,&ast; Liangzi Yang,&ast; Hongjuan Qin, Peize Zhang Department of Pulmonary Medicine and Tuberculosis, The Third People’s Hospital of Shenzhen, Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peize Zhang, Email 82880246@qq.comAbstract: Tuberculosis(TB) is a serious infection that affects transplant recipients, particularly in high TB burden countries. Clinical presentation of these patients is atypical, and the care and management are frequently tricky as multi-drug interaction and intolerable adverse effects. Contezolid, a novel oxazolidinone antibacterial agent, had been demonstrated to be effective for TB in vitro and had been shown in some clinical cases with a more favorable safety profile than linezolid, the first-generation oxazolidinone, which had a commonly seen myelosuppression and neuropathy. Additionally, Contezolid has a unique metabolic mechanism that leads to less drug interaction. Here, we report a case of multi-system TB in a transplant recipient with chronic kidney allograft dysfunction. She was intolerant to most first and second-line anti-TB drugs and repeatedly developed ascites and nocturnal low-grade fever. She finally achieved good efficacy and safety results after enhanced anti-TB treatment with the addition of contezolid. Given the increased risk of TB in patients with organ transplantation and multi-drug interaction in patients with severe comorbidities, further clinical studies are needed to investigate the application and appropriate dosage of contezolid in patients with active TB.Keywords: tuberculosis, contezolid, kidney dysfunction, kidney transplantation, tuberculous peritonitis

Liu Yang,1 Yan Xu,1 Jian Pan,2– 4 Renjie Li,1 Chao Lan,1 Dongshan Zhang2– 4 1Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 3Emergency Medicine and Difficult Diseases Institute, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 4Department of Nephrology, Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Chao Lan, Department of Emergency Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, People’s Republic of China, Tel +86 13663855629, Email fcclanc@zzu.edu.cn Dongshan Zhang, Department of Emergency Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86 138 7589 9625, Email dongshanzhang@csu.edu.cnBackground: Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity, as well as increased medical expenses. The molecular mechanisms underlying ischemia-reperfusion (I/R)-induced AKI remain unclear.Methods and Results: We applied an RT-qPCR assay to measure the expression of mmu-lncRNA129814, hsa-lncRNA582795, and miRNA-494-5p, immunoblotting to detect IL-1α and cleaved caspase-3 expression, and TUNEL staining and flow cytometry (FCM) to evaluate apoptosis. The experiments were conducted using BUMPT and HK-2 cells, as well as C57BL/6J mice. Mechanistically, mmu-lncRNA129814 could sponge miRNA-494-5p and upregulate IL-1α expression to promote cell apoptosis. Furthermore, knockdown of mmu-lncRNA129814 ameliorated I/R-induced progression of AKI by targeting the miRNA-494-5p/IL-1α pathways. Interestingly, hsa-lncRNA582795, a homolog of mmu-lncRNA129814, also promoted I/R-stimulated HK-2 cell apoptosis and AKI progression by regulating the miRNA-494-5p/IL-1α axis. Finally, we found that patients with I/R-induced AKI exhibited significantly elevated plasma and urinary levels of hsa-lncRNA582795 compared to those who underwent ischemia-reperfusion without developing AKI. Spearman’s test demonstrated a significant correlation between serum creatinine and plasma hsa-lncRNA582795 in I/R patients. Plasma hsa-lncRNA582795 showed high sensitivity but low specificity (86.7%) compared to urinary hsa-lncRNA582795.Conclusion: The mmu-lncRNA129814/hsa-lncRNA582795/miRNA-494-5p/IL-1α axis was found to modulate the progression of ischemic AKI, and hsa-lncRNA582795 could act as a diagnosis biomarker and potential therapy target of I/R-induced AKI. Keywords: AKI, mmu-lncRNA129814, hsa-lncRNA582795, apoptosis, biomarker

Min Wang,1,&ast; Lin Yang,1,&ast; Suhan Zhang,2 Meng Wu,1 Zhenfeng Sun,3 Liu Shen,1 Xiaowei Xu,1 Liangkun Ma,2 Jiao Li1 1Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China; 2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 3Daxing District Maternal and Child Health Hospital, Beijing, 102699, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Li, Institute of Medical Information & Library Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100020, People’s Republic of China, Tel +8618618461596, Email li.jiao@imicams.ac.cnBackground: Maternity health management has always been the area of concern and considering, and considering its complexity and multidisciplinary, it is necessary to provide effective training for healthcare workers.Purpose: To evaluate the impact of a multidisciplinary experiential training model on the knowledge, attitude, and practice of healthcare workers in maternity health management.Patients and Methods: We conducted a novel educational model, Multidisciplinary Maternity Health Experiential Training based on Knowledge, Attitude and Practice (MMHET), which combined theoretical knowledge, practical skills, and human-centred humanistic care, offering a comprehensive offline education program supported by online teaching materials structured around knowledge graphs. Pre- and post-test surveys were used to assess the changes in participants’ knowledge, attitudes, and practices.Results: From May to July 2023, a total of 322 participants attended the course, and only a small percentage had participated in experiential training. For all topics, the vast majority of participants endorsed the course, and the attitude content had the highest percentage of participants who said they agreed. Among the groups with different years of working life, the highest percentage of participants in the > 20 years group strongly endorsed the course.Conclusion: The preliminary findings indicate that the MMHET model is well-received and feasible, demonstrating its potential to enhance maternity health management education.Keywords: continuing education, pregnancy health, assessment, healthcare, medical education

Zhou Zhu,1– 3,&ast; Huizi Gong,4,&ast; Mingjuan Liu,1– 3 Hanlin Zhang,1,2 Leyan Yang,1,2 Xinyi Zhang,5 Heyi Zheng,1,2 Yanfeng Li,6 Mingli Li,7 Jun Li1,2 1Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Dermatology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 5Departments of Internal Medicine and Cellular & Molecular Physiology, Yale School of Medicine, New Haven, CT, USA; 6Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingli Li, Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email limingli@pumch.cn Jun Li, Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan Wangfujing Dongcheng District, Beijing, 100730, People’s Republic of China, Email lijun35@hotmail.comBackground: Tabes dorsalis is a late manifestation of neurosyphilis, characterized by progressive ataxia, lightning pains, loss of proprioception, and urinary incontinence. The absence of a definitive diagnostic standard and the non-specific clinical manifestations have led to a significant rate of misdiagnoses.Methods: Hospitalized patients with tabes dorsalis at Peking Union Medical College Hospital between January 2010 and December 2023 were reviewed.Results: A total of 13 patients were included, with 10 males and 3 females. The median age was 50 years (range, 34– 64). The most frequent initial symptoms were limb numbness (30.8%) and lightning pains (30.8%). Eleven patients (84.6%) received misdiagnoses prior to the final diagnosis. The most frequently observed physical sign was positive Romberg’s sign (84.6%). Notably, Argyll Robertson pupil was presented in 7 subjects (53.8%). Serological tests revealed positive rapid plasma regain (RPR) and Treponema pallidum particle agglutination (TPPA) for all patients. All CSF samples were TPPA-reactive. Intramedullary hyperintensity on T2-weighted imaging of spinal MRI was found in 5 patients (38.5%). All patients received anti-syphilitic treatment, with effective treatment recorded in five cases.Conclusion: This study underscores the importance of neurological symptoms and signs in diagnosing tabes dorsalis. Individuals with progressive ataxia and positive Romberg’s sign should be closely monitored for potential neurosyphilis. Integrating clinical features, laboratory tests, and neuroimaging could reduce misdiagnosis and expedite the initiation of anti-syphilitic therapy.Keywords: tabes dorsalis, neurosyphilis, ataxia, cerebrospinal fluid

Luxun Yang,1,&ast; Haiying Ran,2,&ast; Yaru Yin,1 Jing Liu,1 Binghui Lu,1 Xi Ran,3 Shenglin Luo,1 Weidong Wang,4 Zhangyou Yang,5 Rong Li1 1Institute of Combined Injury, National Key Laboratory of Trauma and Chemical Poisoning, Army Key Laboratory of Nanomedicine, Department of Military Preventive Medicine, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Biomedical Analysis Center, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Department of Medical Laboratory, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 4Department of Radiation Oncology, Sichuan Cancer Hospital, Chengdu, 610041, People’s Republic of China; 5Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhangyou Yang, Chongqing Medical University, No. 1, Yixueyuan Road, Chongqing, 400016, People’s Republic of China, Email yangzhangyou@cqmu.edu.cn Rong Li, Army Medical University, No. 30, Gaotanyan Street, Chongqing, 400038, People’s Republic of China, Tel +86-13883996627, Fax +8623-68753127, Email lrong361@126.comPurpose: Mitochondrial oxidative stress is an important factor in cell apoptosis. Cerium oxide nanomaterials show great potential for scavenging free radicals and simulating superoxide dismutase (SOD) and catalase (CAT) activities. To solve the problem of poor targeting of cerium oxide nanomaterials, we designed albumin-cerium oxide nanoclusters (TPP-PCNLs) that target the modification of mitochondria with triphenyl phosphate (TPP). TPP-PCNLs are expected to simulate the activity of superoxide dismutase, continuously remove reactive oxygen species, and play a lasting role in radiation protection.Methods: First, cerium dioxide nanoclusters (CNLs), polyethylene glycol cerium dioxide nanoclusters (PCNLs), and TPP-PCNLs were characterized in terms of their morphology and size, ultraviolet spectrum, dispersion stability and cellular uptake, and colocalization Subsequently, the anti-radiation effects of TPP-PCNLs were investigated using in vitro and in vivo experiments including cell viability, apoptosis, comet assays, histopathology, and dose reduction factor (DRF).Results: TPP-PCNLs exhibited good stability and biocompatibility. In vitro experiments indicated that TPP-PCNLs could not only target mitochondria excellently but also regulate reactive oxygen species (ROS)levels in whole cells. More importantly, TPP-PCNLs improved the integrity and functionality of mitochondria in irradiated L-02 cells, thereby indirectly eliminating the continuous damage to nuclear DNA caused by mitochondrial oxidative stress. TPP-PCNLs are mainly targeted to the liver, spleen, and other extramedullary hematopoietic organs with a radiation dose reduction factor of 1.30. In vivo experiments showed that TPP-PCNLs effectively improved the survival rate, weight change, hematopoietic function of irradiated animals. Western blot experiments have confirmed that TPP-PCNLs play a role in radiation protection by regulating the mitochondrial apoptotic pathway.Conclusion: TPP-PCNLs play a radiologically protective role by targeting extramedullary hematopoietic organ-liver cells and mitochondria to continuously clear ROS.Keywords: radioprotective effect, ceria nanoclusters, mitochondria targeting, oxidative stress, superoxide dismutase

Dazhen Wang,1,&ast; Zhengfeng Zhang,2,&ast; Liu Yang,1 Lu Zhao,1 Ze Liu,1 ChangJie Lou1 1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Hematopathology, The Second Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: ChangJie Lou, Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, Heilongjiang, 150081, People’s Republic of China, Email 601245@hrbmu.edu.cnPurpose: Comparing the efficacy and safety of programmed cell death protein-1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs) with or without hepatic artery infusion chemotherapy (HAIC) in HBV-related advanced HCC and exploring prognostic predictors of the combined regimen.Patients and Methods: A total of 194 patients diagnosed with HBV-related advanced HCC between 2020 and 2022 were included in the study, including 99 in the HAIC combined with PD-1 inhibitors plus TKIs (HPT group) and 95 in the PD-1 inhibitors plus TKIs (PT group). The efficacy was evaluated according to the tumor response rate and survival, and the safety was evaluated according to the adverse events.Results: The HPT group showed higher overall response rate and disease control rate than the PT group. The median overall survival (OS) of the HPT group and the PT group were 18.10 months and 12.57 months, respectively, and the difference was statistically significant (hazard ratio (HR) = 0.519, 95% confidence interval (CI): 0.374– 0.722, P

Lin Tang,1,&ast; Jian Liu,2,&ast; Hui Yang,2,&ast; Hong-Qing Zhao,3 Chao Hu,4 Si-Jing Ma,5 Yu-Hui Qing,6 Lei Yang,1 Rong-Rong Zhou,5 Shui-Han Zhang6 1Hospital-Made Preparations Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 2Medical Innovation Experiment Center, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 3Science & Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 4Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 5The Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan Province, People’s Republic of China; 6Institute of Chinese Medicine Resources, Hunan Academy of Chinese Medicine, Changsha, Hunan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-Rong Zhou; Shui-Han Zhang, Tel +86-0731-85920129, Email rrzhou0823@163.com; zhangshuihan0220@126.comPurpose: The Baihe Dihuang decoction (BDD) is a representative traditional Chinese medicinal formula that has been used to treat anxiety disorders for thousands of years. This study aimed to reveal mechanisms of anxiolytic effects of BDD with multidimensional omics.Methods: First, 28-day chronic restraint stress (CRS) was used to create a rat model of anxiety, and the open field test and elevated plus maze were used to assess anxiety-like behavior. Enzyme-linked immunosorbent assay (ELISA), hematoxylin–eosin staining, and immunofluorescence staining were used to evaluate inflammatory response. Besides, 16S rRNA gene sequencing assessed fecal microbiota composition and differential microbiota. Non-targeted metabolomics analysis of feces was performed to determine fecal biomarkers, and targeted metabolomics was used to observe the levels of hippocampus neurotransmitters. Finally, Pearson correlation analysis was used to examine relationships among gut microbiota, fecal metabolites, and neurotransmitters.Results: BDD significantly improved anxiety-like behaviors in CRS-induced rats and effectively ameliorated hippocampal neuronal damage and abnormal activation of hippocampal microglia. It also had a profound effect on the diversity of microbiota, as evidenced by significant changes in the abundance of 10 potential microbial biomarkers at the genus level. Additionally, BDD led to significant alterations in 18 fecal metabolites and 12 hippocampal neurotransmitters, with the majority of the metabolites implicated in amino acid metabolism pathways such as D-glutamine and D-glutamate, alanine, arginine and proline, and tryptophan metabolism. Furthermore, Pearson analysis showed a strong link among gut microbiota, metabolites, and neurotransmitters during anxiety and BDD treatment.Conclusion: BDD can effectively improve anxiety-like behaviors by regulating the gut–brain axis, including gut microbiota and metabolite modification, suppression of hippocampal neuronal inflammation, and regulation of neurotransmitters. Keywords: Baihe Dihuang decoction, 16S rRNA, metabolomics, anxiety, neurotransmitter

Yiyue Xu,1,&ast; Haoqian Li,1,&ast; Xiaoqing Wang,2 Butuo Li,1 Aiqin Gao,1 Qian Zhao,1 Linlin Yang,1 Wenru Qin,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Portal Hypertension, Shandong Public Health Clinical Center, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, 250117, People’s Republic of China, Tel +86-13793187739, Email wanglinlinatjn@163.comBackground: COVID-19 has spread worldwide, becoming a global threat to public health and can lead to complications, especially pneumonia, which can be life-threatening. However, in lung cancer patients, the prediction of pneumonia and severe pneumonia has not been studied. We aimed to develop effective models to assess pneumonia after SARS-CoV-2 infection in lung cancer patients to guide COVID-19 management.Methods: We retrospectively recruited 621 lung cancer patients diagnosed with COVID-19 via SARS-CoV-2 RT-PCR analysis in two medical centers and divided into training and validation group, respectively. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of all-grade pneumonia and ≥ grade 2 pneumonia in the training group. Nomograms were established based on independent predictors and verified in the validation group. C-index, ROC curves, calibration curve, and DCA were used to evaluate the nomograms. Subgroup analyses in immunotherapy or thoracic radiotherapy patients were then conducted.Results: Among 621 lung cancer patients infected with SARS-CoV-2, 203 (32.7%) developed pneumonia, and 66 (10.6%) were ≥ grade 2. Multivariate logistic regression analysis showed that diabetes, thoracic radiotherapy, low platelet and low albumin at diagnosis of COVID-19 were significantly associated with all-grade pneumonia. The C-indices of the prediction nomograms in the training group and validation group were 0.702 and 0.673, respectively. Independent predictors of ≥ grade 2 pneumonia were age, KPS, thoracic radiotherapy, platelet and albumin at COVID 19 diagnosis, with C-indices of 0.811 and 0.799 in the training and validation groups. In the thoracic radiotherapy subgroup, 40.8% and 11% patients developed all-grade and ≥grade 2 pneumonia, respectively. The rates in the immunotherapy subgroup were 31.3% and 6.6%, respectively.Conclusion: We developed nomograms predicting the probability of pneumonia in lung cancer patients infected with SARS-CoV-2. The models showed good performance and can be used in the clinical management of COVID-19 in lung cancer patients. Higher-risk patients should be managed with enhanced protective measures and appropriate intervention.Keywords: COVID-19, pneumonia, lung cancer, risk factor, nomogram

Min Liu,1,2 Bo Liu,2 Ziyang Liu,3 Zhen Yang,2 Thomas J Webster,4 Huan Zhou,2 Lei Yang2 1School of Materials Science and Engineering, Hebei University of Technology, Tianjin, People’s Republic of China; 2Center for Health Science and Engineering, Hebei Key Laboratory of Biomaterials and Smart Theranostics, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China; 3Department of Orthopedics, Tianjin Hospital, Tianjin, People’s Republic of China; 4School of Engineering, Saveetha University, Chennai, IndiaCorrespondence: Huan Zhou; Lei Yang, Center for Health Science and Engineering, School of Health Sciences and Biomedical Engineering, Hebei University of Technology, Tianjin, 300131, People’s Republic of China, Email zhouhuan@hebut.edu.cn; ylei@hebut.edu.cnIntroduction: Lumbar interbody fusion is widely employed for both acute and chronic spinal diseases interventions. However, large incision created during interbody cage implantation may adversely impair spinal tissue and influence postoperative recovery. The aim of this study was to design a shape memory interbody fusion device suitable for small incision implantation.Methods: In this study, we designed and fabricated an intervertebral fusion cage that utilizes near-infrared (NIR) light-responsive shape memory characteristics. This cage was composed of bisphenol A diglycidyl ether, polyether amine D-230, decylamine and iron oxide nanoparticles. A self-hardening calcium phosphate-starch cement (CSC) was injected internally through the injection channel of the cage for healing outcome improvement.Results: The size of the interbody cage is reduced from 22 mm to 8.8 mm to minimize the incision size. Subsequent NIR light irradiation prompted a swift recovery of the cage shape within 5 min at the lesion site. The biocompatibility of the shape memory composite was validated through in vitro MC3T3-E1 cell (osteoblast-like cells) adhesion and proliferation assays and subcutaneous implantation experiments in rats. CSC was injected into the cage, and the relevant results revealed that CSC is uniformly dispersed within the internal space, along with the cage compressive strength increasing from 12 to 20 MPa.Conclusion: The results from this study thus demonstrated that this integrated approach of using a minimally invasive NIR shape memory spinal fusion cage with CSC has potential for lumbar interbody fusion.Keywords: shape memory, interbody fusion cage, NIR responsive, calcium phosphate cement, minimally invasive

Yuanhang Pan,1,&ast; Di Zhao,1,&ast; Xinbo Zhang,1,&ast; Na Yuan,1 Lei Yang,1 Yuanyuan Jia,2 Yanzhao Guo,3 Ze Chen,1 Zezhi Wang,1 Shuyi Qu,1 Junxiang Bao,4 Yonghong Liu1 1Department of Neurology, Xijing Air Force Medical University, Xi’an, People’s Republic of China; 2Encephalopathy Department No.2, Baoji Hospital of Traditional Chinese Medicine, Baoji, People’s Republic of China; 3Encephalopathy Department No.10, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, People’s Republic of China; 4Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Liu, Department of Neurology, Xijing hospital, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 13991236602, Email liuyhong@fmmu.edu.cn Junxiang Bao, Department of Aerospace Hygiene, Air Force Medical University, Xi’an, People’s Republic of China, Tel +86 02984711241, Email baojunx@fmmu.edu.cnBackground: Excessive daytime sleepiness (EDS) forms a prevalent symptom of obstructive sleep apnea (OSA) and narcolepsy type 1 (NT1), while the latter might always be overlooked. Machine learning (ML) models can enable the early detection of these conditions, which has never been applied for diagnosis of NT1.Objective: The study aimed to develop ML prediction models to help non-sleep specialist clinicians identify high probability of comorbid NT1 in patients with OSA early.Methods: Totally, clinical features of 246 patients with OSA in three sleep centers were collected and analyzed for the development of nine ML models. LASSO regression was used for feature selection. Various metrics such as the area under the receiver operating curve (AUC), calibration curve, and decision curve analysis (DCA) were employed to evaluate and compare the performance of these ML models. Model interpretability was demonstrated by Shapley Additive explanations (SHAP).Results: Based on the analysis of AUC, DCA, and calibration curves, the Gradient Boosting Machine (GBM) model demonstrated superior performance compared to other machine learning (ML) models. The top five features used in the GBM model, ranked by feature importance, were age of onset, total limb movements index, sleep latency, non-REM (Rapid Eye Movement) sleep stage 2 and severity of OSA.Conclusion: The study yielded a simple and feasible screening ML-based model for the early identification of NT1 in patients with OSA, which warrants further verification in more extensive clinical practices.Keywords: obstructive sleep apnea, narcolepsy, machine learning, prediction model, sleep disorder

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

Xue Bai,1,2,&ast; LiTing Yang,1,2,&ast; Ruxin Liu,1,2 YuJiao Tang,1,2 Long Yang,1,2 Lingna Ma,1,2 MengFei Chen,2 Ling Zhang2 1Department of Emergency, The Third Clinical Medical College of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Emergency, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: MengFei Chen; Ling Zhang, Tel +86 13389513801 ; +86 13895318660, Email prayer_821@sina.com; zhangling_7015@sina.comObjective: Cellular pyroptosis is a pro-inflammatory mode of programmed cell death that has been identified in recent years, and studies have shown that the LncRNA SOX2OT regulates myocardial injury during sepsis, but the exact regulatory mechanism is unclear. The aim of this study was to assess the role of SOX2OT in regulating cardiomyocyte injury during sepsis cardiomyopathy.Methods: Rat cardiomyocytes, C57BL/6 mice, and transgenic mice were divided into four groups: control, LPS, LPS+ knockout LncRNA SOX2OT, and LPS+ overexpression LncRNA SOX2OT. Inflammatory factor levels were detected by qPCR. Associated proteins and gene expression were detected by Western blotting and qPCR. Dual luciferase was used to detect the target genes of SOX2OT. Nrf2 and EZH2 knockdown and overexpression cell lines were established, and the expression of related genes was detected by qPCR.Results: Results In this study, we found that SOX2OT knockdown exacerbated LPS-induced levels of inflammatory factors and procalcitoninogen (PCT), and increased the expression of pyroptosis-related proteins and LDH. The results of dual luciferase reporter gene assay showed that EZH2 is the target gene of SOX2OT, and overexpression of SOX2OT decreased the expression of EZH2; we also found that knockdown of EZH2 in H9c2 cells decreased the expression of Nrf2, which was positively correlated with the expression level of NLRP3. Further in vivo results showed that overexpression of SOX2OT attenuated SIMD (sepsis-induced myocardial dysfunction), as evidenced by improved myocardial structural integrity and reduced inflammatory cell infiltration. The expression of pyroptosis-related proteins and LDH was significantly increased in the mice in the LPS group; this effect was reversed by overexpression of SOX2OT, and potentiated by knockdown of SOX2OT.Conclusion: Our data reveal a novel mechanism by which SOX2OT inhibits cardiomyocyte sepsis through the EZH2/Nrf-2/NLRP3 pathway, thereby attenuating septic myocardial injury, which may contribute to the development of new therapeutic strategies.Keywords: SOX2OT, EZH2, Nrf2, sepsis, pyroptosis