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Yuhang Tian,1 Xiang He,1 Yanchi Yuan,1 Shijie Zhang,2 Chunyue Wang,1 Jialin Dong,1 Zhao Liu,1 Hui Jing1 1Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 2Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of ChinaCorrespondence: Hui Jing, Department of Ultrasound, Harbin Medical University Cancer Hospital, 150 Haping Road, Nangang District, Harbin, 150081, People’s Republic of China, Email jinghuihrb@163.comBackground: Triple negative breast cancer (TNBC) is one of the worst prognosis types of breast cancer that urgently needs effective therapy methods. However, cancer is a complicated disease that usually requires multiple treatment modalities.Methods: A tumor microenvironment (TME)-responsive PFC/TRIM37@Fe-TA@HA (abbreviated as PTFTH) nanoplatform was constructed by coating Fe3+ and tannic acid (TA) on the surface of TRIM37-siRNA loaded phase-transition perfluorocarbon (PFC) nanodroplets and further modifying them with hyaluronic acid (HA) to achieve tumor-specific mild photothermal/gene/ferroptosis synergistic therapy (MPTT/GT/ Ferroptosis) in vitro. Once internalized into tumor cells through CD44 receptor-mediated active targeting, the HA shell of PTFTH would be preliminarily disassembled by hyaluronidase (HAase) to expose the Fe-TA metal-phenolic networks (MPNs), which would further degrade in response to an acidic lysosomal environment, leading to HAase/pH dual-responsive release of Fe3+ and PFC/TRIM37.Results: PTFTH showed good biocompatibility in vitro. On the one hand, the released Fe3+ could deplete the overexpressed glutathione (GSH) through redox reactions and produce Fe2+, which in turn converts endogenous H2O2 into highly cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). On the other hand, the local hyperthermia generated by PTFTH under 808 nm laser irradiation could not only improve CDT efficacy through accelerating the Fe2+-mediated Fenton reaction, but also enhance TRIM37-siRNA delivery for gene therapy (GT). The consumption of GSH and accumulation of •OH synergistically augmented intracellular oxidative stress, resulting in substantial tumor cell ferroptosis. Moreover, PTFTH possessed outstanding contrast enhanced ultrasound (CEUS), photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) ability.Conclusion: This PTFTH based multiple-mode therapeutic strategy has successfully achieved a synergistic anticancer effect in vitro and has the potential to be translated into clinical application for tumor therapy in future.Keywords: mild photothermal therapy, gene therapy, ferroptosis, synergistic therapy, multimodal imaging

Mei Liu,1,* Sili Guo,1,* Xiaohan Li,1,* Yang Tian,1 Yanjie Yu,2 Lili Tang,1 Qimei Sun,1 Ting Zhang,1 Mingwei Fan,3 Lili Zhang,1 Yingjiang Xu,4 Jiajia An,5 Xiangqian Gao,6 Lei Han,7 Lei Zhang1 1Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 2Department of Ultrasound Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 4Department of Interventional Vascular Surgery, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 5Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 6Department of Pathology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 7Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email binzhouzhanglei@outlook.comBackground: GLP-1 receptor agonists (GLP-1 RA) have been proven to treat several metabolic diseases; however, the effects of GLP-1 RA on polycystic ovary syndrome (PCOS) remain unclear. Here, we aimed to investigate whether semaglutide, a novel GLP-1 RA, could alleviate ovarian inflammation in PCOS mice.Methods: Female C57BL/6J mice were subcutaneously injected with dehydroepiandrosterone for 21 days to establish the PCOS model. Then the mice were randomly divided into three groups: PCOS group (n = 6), S-0.42 group (semaglutide 0.42 mg/kg/w, n = 6), and S-0.84 group (semaglutide 0.84 mg/kg/w, n = 6). The remaining six mice were used as controls (NC). After 28 days of intervention, serum sex hormones and inflammatory cytokine levels were measured. Hematoxylin and eosin staining was used to observe the ovarian morphology. Immunohistochemical staining was used to detect the relative expression of CYP19A1, TNF-α, IL-6, IL-1β, and NF-κB in ovaries. CYP17A1 and StAR were detected using immunofluorescence staining. Finally, the relative expressions of AMPK, pAMPK, SIRT1, NF-κB, IκBα, pIκBα, TNF-α, IL-6, and IL-1β were measured using Western blotting.Results: First, after intervention with semaglutide, the weight of the mice decreased, insulin resistance improved, and the estrous cycle returned to normal. Serum testosterone and IL-1β levels decreased significantly, whereas estradiol and progestin levels increased significantly. Follicular cystic dilation significantly improved. The expression of TNF-α, IL-6, IL-1β, NF-κB, CYP17A1, and StAR in the ovary was significantly downregulated, whereas CYP19A1 expression was upregulated after the intervention. Finally, we confirmed that semaglutide alleviates ovarian tissue inflammation and improves PCOS through the AMPK/SIRT1/NF-κB signaling pathway.Conclusion: Semaglutide alleviates ovarian inflammation via the AMPK/SIRT1/NF‑κB signaling pathway in PCOS mice.Keywords: GLP-1 receptor agonist, polycystic ovary syndrome, semaglutide, inflammation

Yang Liu,1 Lanxi Zhang,2 Jie Zhao,1,3 Ruilong Lu,1 Xuejie Shao,1 Kexin Xu,1 Jiansheng Li,1,3,4,* Yange Tian1,3,* 1Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People’s Republic of China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, 450000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiansheng Li; Yange Tian, Email li_js8@163.com; yange0910@126.comPurpose: The main objective of this study was to explore the mechanism of effective component compatibility of Bufei Yishen formula III (ECC-BYF III) in inhibiting mitochondrial oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD).Methods: A549 cells exposed to cigarette smoke extract (CSE) were used to establish a model of mitochondrial oxidative damage. The cells were treated with the plasmid encoding Pkm2 and the enzymes and proteins involved in oxidative stress and mitochondrial function were measured. A rat model of COPD was established using CS and bacteria. Two different treatments were established, ECC-BYF III (5.5 mg/kg/d) and N-acetylcysteine (54 mg/kg/day). Animals were tested for pulmonary function (Vt, PEF, FVC, FEV0.1s and Cdyn) after eight weeks of therapy and were sacrificed. Pulmonary H&E staining was performed, and the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content were measured. The mitochondrial function was also examined. Furthermore, the Pkm2/Nrf2 signaling pathway was evaluated.Results: Overexpression of Pkm2 dramatically ameliorated the CS-induced mitochondrial oxidative damage. Further studies indicated that ECC-BYF III significantly improved mitochondrial function and inhibited oxidative stress in the lung tissues of COPD rats. Moreover, it can upregulate mitochondrial respiratory chain enzyme activity. ECC-BYF III also decreased the MDA content and increased T-SOD, GSH-Px, and T-AOC expression to facilitate oxidative homeostasis. Finally, our results indicated that the Pkm2/Nrf2 pathway is regulated by ECC-BYF III in A549 cells and lung tissue.Conclusion: These results indicate that ECC-BYF III exerts a strong effective therapeutic effect against cigarette smoke combined with bacteria-induced COPD in rats by activating the Pkm2/Nrf2 signaling pathway and restoring mitochondrial oxidative stress. Although more in vivo animal model research is needed to confirm these findings, this study contributes new data to support the conventional usage of ECC-BYF III.Keywords: chronic obstructive pulmonary disease, oxidative stress, ECC-BYF III, Pkm2, Nrf2

Kuocheng Yan,1,* Xiaohui Wang,2,* Yao Han,1,* Yuan Tian,1 Mengwei Niu,1 Xue Dong,1 Xiaowei Li,2 Hao Li,1 Yansong Sun1 1State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 2Department of Gastroenterology, the Sixth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hao Li, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China, Email lihao88663239@126.com Xiaowei Li, Department of Gastroenterology, the Sixth Medical Center of Chinese People’s Liberation Army General Hospital, Beijing, 100080, People’s Republic of China, Email lixwei12@126.comBackground: Infection caused by Helicobacter pylori (H. pylori) affects approximately 50% of the global population. It is a major pathogenic factor for chronic gastritis and gastric cancer. Besides, the resistance to antibiotics such as clarithromycin could reduce the eradication rate. Currently, there is an urgent need for a swift, easy to perform, and highly sensitive detection method for H. pylori and clarithromycin resistance.Methods: We used FAM/Digoxin labeled primers to amplify specific H. pylori 23S rRNA fragments by Recombinase Aided Amplification (RAA), and resistance mutations were distinguished using CRISPR/Cas13a system combined with lateral flow strip. Twenty-eight saliva samples were analyzed using qPCR, gene sequencing and this method to evaluate the detection efficiency.Results: We developed a simultaneous detection method for H. pylori and clarithromycin resistance mutations named sensitive H. pylori easy-read dual detection (SHIELD). The results showed both A2142G and A2143G mutant DNAs causing clarithromycin resistance could be distinguished from the wild type with a concentration of 50 copies/μL, and no cross-reaction with other 5 common gastrointestinal bacteria was observed. For the detection of H. pylori in 28 saliva samples, the positive predictive value of this method was 100% (19/19) in comparison with qPCR. For detecting clarithromycin resistance, the positive predictive value of this method was 84.6% (11/13) compared with gene sequencing.Conclusion: SHIELD assay showed high sensitivity and specificity in detecting H. pylori and clarithromycin resistance mutations. It could be a potential measure in the rapid detection of H. pylori, large-scale screening and guiding clinical medication.Keywords: Helicobacter pylori, clarithromycin resistance mutation, recombinase aided amplification, CRISPR/Cas13a, nucleic acid detection

Xia Cao,1 Yusheng Tian,2 Hui Chen,2 Sihong Li,2 Jiansong Zhou2 1Health Management Center, The Third Xiangya Hospital of Central South University, Changsha, People’s Republic of China; 2National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jiansong Zhou, National Clinical Research Center for Mental Disorders, and Department of Psychiatry, The Second Xiangya Hospital of Central South University, Renmin Road 139, Changsha, Hunan Province, People’s Republic of China, Tel +86-073185295888, Fax +86-073188618573, Email jasonzhou75@163.comObjective: The concept of intrinsic capacity (IC) revolves around healthy aging and active aging. Since the Introduction of the concept by the World Health Organization in 2015, a series of studies have been conducted by scholars from multiple fields. However, no bibliometric analysis has systematically investigated this issue. We aim to identify the current landscape and frontier trends of scientific achievements on IC in older adults through bibliometric approaches.Methods: Quantitative analysis of publications relating to IC in older adults from 2015 to 2023 was interpreted and graphed through the Web of Science Core Collection database on December 5, 2023. A variety of quantitative variables was analyzed, including publication and citation counts, H-index, and journal citation reports. Co-authorship, citation, co-citation, and co-occurrence analyses were performed for countries/regions, institutions, authors, and keywords using the VOSviewer and CiteSpace.Results: A total of 952 original and review articles in English were identified. The European countries possessed an absolute advantage in this field. The most contributive institution was the University of São Paulo. The most productive author is Cesari Matteo from France, followed by Qaisar Rizwan from the United Arab Emirates. However, a relatively low level of research cooperation existed between institutions and authors. Important topics mainly include the connotations, theoretical framework models, evaluation, screening tools, and application scenarios of IC. Among the promising hotspots, “biological aging”, “ICOPE”, “Covid-19”, “prevention”, “inflammation”, “caf22”, “prevalence”, and “randomized controlled trial” displayed relatively latest average appearing year.Conclusion: Global trends indicate a growing scientific output on IC in older adults, and developed countries are leading the way. There is still room for improvement in research team collaboration. The focus gradually shifts from theoretical research to empirical research. It is recommended to pay attention to the latest hot spots, such as “biological aging”, “ICOPE implementation”, “post-COVID-19 syndrome”, and “biomarkers”.Keywords: intrinsic capacity, old adults, bibliometrics, research frontier, visualization

Junjuan Li,1,* Yue Tian,2,* Qi Qin,2,* Zhaolei Ding,1 Xue Zhao,3 Wei Tan1 1Department of Respiratory Medicine, The First Affiliated Hospital of Weifang Medical University/Weifang People’s Hospital, Weifang, 261000, People’s Republic of China; 2School of Clinical Medicine, Weifang Medical University, Weifang, 261053, People’s Republic of China; 3Department of Laboratory Medicine, The First Affiliated Hospital of Weifang Medical University/Weifang People’s Hospital, Weifang, 261000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Tan, Department of Respiratory Medicine, Weifang People’s Hospital, 151 Guangwen Street, Weifang, Shandong Province, 261000, People’s Republic of China, Email 13863659099@126.com Xue Zhao, Department of Laboratory Medicine, Weifang People’s Hospital, 151 Guangwen Street, Weifang, Shandong Province, 261000, People’s Republic of China, Email 42281870@qq.comPurpose: Owing to its noninvasive nature, broad-spectrum effectiveness, minimal bacterial resistance, and high efficiency, phototherapy has significant potential for antibiotic-free antibacterial interventions and combating antibacterial biofilms. However, finding effective strategies to mitigate the detrimental effects of excessive temperature and elevated concentrations of reactive oxygen species (ROS) remains a pressing issue that requires immediate attention.Methods: In this study, we designed a pH-responsive cationic polymer sodium nitroside dihydrate/branched polyethylenimine–indocyanine green@polyethylene glycol (SNP/PEI-ICG@PEG) nanoplatform using the electrostatic adsorption method and Schiff’s base reaction. Relevant testing techniques were applied to characterize and analyze SNP/PEI-ICG@PEG, proving the successful synthesis of the nanomaterials. In vivo and in vitro experiments were performed to evaluate the antimicrobial properties of SNP/PEI-ICG@PEG.Results: The morphology and particle size of SNP/PEI-ICG@PEG were observed via TEM. The zeta potential and UV-visible (UV‐vis) results indicated the synthesis of the nanomaterials. The negligible cytotoxicity of up to 1 mg/mL of SNP/PEI-ICG@PEG in the presence or absence of light demonstrated its biosafety. Systematic in vivo and in vitro antimicrobial assays confirmed that SNP/PEI-ICG@PEG had good water solubility and biosafety and could be activated by near-infrared (NIR) light and synergistically treated using four therapeutic modes, photodynamic therapy (PDT), gaseous therapy (GT), mild photothermal therapy (PTT, 46 °C), and cation. Ultimately, the development of Gram-positive (G+) Staphylococcus aureus (S. aureus) and Gram-negative (G−) Escherichia coli (E. coli) were both completely killed in the free state, and the biofilm that had formed was eliminated.Conclusion: SNP/PEI-ICG@PEG demonstrated remarkable efficacy in achieving controlled multimodal synergistic antibacterial activity and biofilm infection treatment. The nanoplatform thus holds promise for future clinical applications.Keywords: cationic, mild photothermal, photodynamic, NO gas, antibacterial

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

Wenxue Liu,1 Yapeng Wang,2 Yi Jiang,2 Shan Lu,1 Jiawei Zhu,3 Yuhuan Tian,2 Jun Pan,1 Zhenjun Xu,1 Dongjin Wang1 1Institute of Cardiothoracic Vascular Disease, Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, People’s Republic of China; 3Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Dongjin Wang; Zhenjun Xu, Institute of Cardiothoracic Vascular Disease, Department of Cardio-Thoracic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China, Email wangdongjin@njglyy.com; xzj881225@163.comBackground: Postoperative delirium (POD) significantly impacts patient outcomes after acute type A aortic dissection (ATAAD) surgeries. This study investigates the role of Neuronal Pentraxin 2 (NPTX2) as a potential biomarker for POD in ATAAD patients.Methods: This secondary analysis involved ATAAD patients from a prospective observational study. Serum NPTX2 levels were measured preoperatively and immediately postoperatively using Enzyme-Linked Immunosorbent Assay (ELISA). Delirium was assessed using the Confusion Assessment Method (CAM) or CAM for the ICU (CAM-ICU). Statistical analyses included the Pearson Correlation Coefficient and multivariate logistic regression to evaluate the association between NPTX2 levels and POD.Results: Among the 62 patients included, 46.77% developed POD. Patients with POD had significantly lower preoperative and postoperative serum NPTX2 levels. The Receiver Operating Characteristic (ROC) curve analysis showed that postoperative NPTX2 had a strong predictive capability for POD (AUC = 0.895). The optimal cutoff for postoperative NPTX2 in predicting POD was less than 421.4 pg/mL. Preoperative NPTX2 also demonstrated predictive value, albeit weaker (AUC = 0.683).Conclusion: Serum NPTX2 levels, both preoperatively and postoperatively, are promising biomarkers for predicting POD in ATAAD patients. These findings suggest that NPTX2 could be instrumental in early POD detection and intervention strategies.Keywords: acute type a aortic dissection, postoperative delirium, NPTX2, biomarker

Xiaoxue Yang,1– 3 Lewei Liu,1– 3 Yinghan Tian,1– 3 Cheng Yang,1– 3 Chen Ling,1– 3 Huanzhong Liu2,3 1Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Huanzhong Liu, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China, Tel +86-551-82324616, Fax +86-551-82324252, Email huanzhongliu@ahmu.edu.cnPurpose: Insomnia is related to alexithymia in adults, but the relationship between insomnia and alexithymia in adolescents with major depressive disorder remains unclear. This study aimed to investigate the sex differences and the association between insomnia and alexithymia in adolescents with major depressive disorder.Patients and Methods: From October 2020 to April 2022, adolescent patients with major depressive disorder were recruited from psychiatric departments of seven hospitals in Anhui Province, China. Their general demographic and clinical information were collected. The 20-item Toronto Alexithymia Scale, the Center for Epidemiologic Studies of Depression Scale, and the Insomnia Severity Index Scale were used to assess their alexithymia, depression, and insomnia symptoms, respectively. The analysis of variance (ANOVA), Student’s t-test and Mann–Whitney U-test were used for continuous variables and chi-square tests for categorical variables. Pearson’s correlation analysis and Spearman correlation analysis were used to examine the correlation between ISI and demographic and clinical variables. Multiple binary logistic regression analyses with the “Enter” method were carried out to explore the correlations of insomnia.Results: The prevalence of insomnia in female adolescent patients was similar to that of male patients (χ2=1.84, p = 0.175). Compared with those without insomnia, patients with insomnia had worse family relationships (F = 7.71, p = 0.021), perceived heavier academic stress (F = 6.32, p = 0.012), more likely to take sedative-hypnotics (F = 5.51, p = 0.019), had higher levels of depression (F = 81.57, p < 0.001) and alexithymia (F = 28.57, p < 0.001). Correlation analysis showed that alexithymia was significantly associated with insomnia in adolescent patients (r = 0.360, p < 0.01). Binary logistic regression analyses showed that, alexithymia was significantly associated with insomnia in female patients (OR = 1.050, p < 0.05) but not male patients.Conclusion: In female adolescent patients, alexithymia is a risk factor of insomnia, which is of great importance in the understanding of the psychopathological mechanisms, treatments and psychological interventions of insomnia in adolescents with major depressive disorder.Keywords: adolescents, major depressive disorder, insomnia, alexithymia

Xin Gao,1 Jiale Xu,2 Musen Xu,2 Pengzhe Han,2 Jingchao Sun,2 Ruifeng Liang,1 Shaojian Mo,2,&ast; Yanzhang Tian2,&ast; 1School of Public Health, Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Biliary and Pancreatic Surgery, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaojian Mo; Yanzhang Tian, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +8619834514208 ; +8613903512030, Email 1009184648@qq.com; tyz2030@163.comPurpose: Acute pancreatitis is a common gastrointestinal emergency. Approximately 20% of patients with acute pancreatitis develop organ failure, which is significantly associated with adverse outcomes. This study aimed to establish an early prediction model for persistent organ failure in acute pancreatitis patients using 24-hour admission indicators.Patients and Methods: Clinical data and 24-h laboratory indicators of patients diagnosed with acute pancreatitis from January 1, 2017 to January 1, 2022 in Shanxi Bethune Hospital were collected. Patients from 2017 to 2021 were used as the training cohort to establish the prediction model, and patients from 2021 to 2022 were used as the validation cohort. Univariate logistic regression and LASSO regression were used to establish prediction models. The performance of the model was evaluated using area under the curve (AUC), calibration curves, and decision curve analysis (DCA), and subsequently validated in the validation group.Results: A total of 1166 patients with acute pancreatitis were included, a total of 145 patients suffered from persistent organ failure from 2017 to 2021. Data were initially selected for 100 variables, and after inclusion and exclusion, 46 variables were used for further analysis. Two prediction models were established and nomogram was drawn respectively. After comparison, the prediction values of the two models were similar (The univariate model AUC was 0.867, 95% CI (0.834– 0.9). The LASSO model AUC was 0.864, 95% CI (0.828– 0.895)), and the model established by LASSO regression was more parsimonious. A web calculator was developed using the model established by LASSO.Conclusion: Predictive model including 6 risk indicators can be used to predict the risk of persistent organ failure in patients with acute pancreatitis.Keywords: prediction model, LASSO regression, acute pancreatitis, nomogram, organ failure

Mei Liu,1,&ast; Xiangqian Gao,2,&ast; Yang Tian,1 Huiwei Li,3 Ziqi Yin,1 Lei Han,4 Lei Zhang1 1Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 2Department of Pathology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China; 3Department of Intensive Care Unit, the Fifth People’s Hospital of Jinan, Jinan, Shandong, People’s Republic of China; 4Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Zhang, Department of Endocrinology and Metabolism, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email binzhouzhanglei@outlook.com Lei Han, Department of Reproductive Medicine, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of China, Email hanleimm@126.comContext: Metrnl is a novel adipokine mainly produced by white adipose tissue, which plays important roles in insulin sensitization, and energy homeostasis. However, information about the function of Metrnl in Metabolic dysfunction-associated fatty liver disease (MAFLD) remains unclear.Methods: This is a control study, which enrolled 176 adults with MAFLD and 176 normal controls. They were matched in body mass index (BMI), age, and sex. Serum Metrnl was determined by ELISA. Other biochemical data were also collected.Results: Compared to the controls, circulating Metrnl was prominently decreased in the MAFLD adults (P< 0.001). Next, binary logistic regression model indicated that sex, waist circumference (WC), triglyceride, γ-gamma glutamyl transferase(γ-GGT), and Metrnl was independently associated with MAFLD. Further, as Metrnl levels elevated across its tertiles, the rate of MAFLD decreased (67.52, 66.95, and 15.38%; P value for trend< 0.001). Data from multivariate logistic regression models evidenced that compared with the lowest tertile of Metrnl, the odds ratio of MAFLD was 0.023(95% CI 0.006– 0.086, P< 0.001) for the highest tertile after adjusting for potential confounders. Besides, area under ROC curve of Metrnl for diagnosis MAFLD was 0.755(95% CI 0.705– 0.805). Metrnl was positively correlated with diastolic blood pressure, WC, BMI, systolic blood pressure, γ-GGT, and Creatinine in MAFLD. Finally, we found systolic blood pressure and Creatinine were independently related to serum Metrnl in MAFLD.Conclusion: Serum Metrnl is reduced in adult with MAFLD. The results suggest that Metrnl may be a protective factor associated with the pathogenesis of MAFLD.Keywords: metabolic dysfunction-associated fatty liver disease, metrnl, adipokine, adipose tissue

Zhao Guo,1,&ast; Haoyun Song,1,&ast; Yingxia Tian,2,&ast; Jie Xu,3 Guokun Zhang,1 Yanan Guo,1 Rong Shen,1 Degui Wang1 1Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, People’s Republic of China; 2Department of Internal Medicine, Gansu Provincial Academic Institute for Medical Research, Lanzhou, 730050, People’s Republic of China; 3Cuiying Biomedical Research Center, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Degui Wang; Rong Shen, Department of Anatomy and Histology, Lanzhou University School of Basic Medical Sciences, Lanzhou, 730000, People’s Republic of China, Tel +86 13893609120 ; +86 13909483373, Fax +86 931 8915023, Email wangdegui@lzu.edu.cn; shenr@lzu.edu.cnBackground: The evident side effects and decreased drug sensitivity significantly restrict the use of chemotherapy. However, nanoparticles based on biomaterials are anticipated to address this challenge.Methods: Through bioinformatics analysis and colon cancer samples, we initially investigated the expression level of RNF8 in colon cancer. Next, we constructed nanocarrier for delivering siRNF8 based on DNA tetrahedron (si-Tet), and Doxorubicin (DOX) was further intercalated into the DNA structure (si-DOX-Tet) for combination therapy. Further, the effects and mechanism of RNF8 inhibition on the sensitivity of colon cancer cells to DOX chemotherapy have also been studied.Results: RNF8 expression was increased in colon cancer. Agarose gel electrophoresis, transmission electron microscopy, and size distribution and potential analysis confirmed the successful preparation of the two nanoparticles, with particle sizes of 10.29 and 37.29 nm, respectively. Fluorescence imaging reveals that the carriers can be internalized into colon cancer cells and escape from lysosomes after 12 hours of treatment, effectively delivering siRNF8 and DOX. Importantly, Western blot analysis verified treatment with 50nM si-Tet silenced RNF8 expression by approximately 50% in colon cancer cells, and combined treatment significantly inhibited cell proliferation. Furthermore, the CCK-8 assay demonstrated that si-Tet treatment enhanced the sensitivity of colon cancer cells to the three chemotherapeutic drugs. Significant more DNA damage was detected after treatment with both si-Tet or si-DOX-Tet. Further flow cytometry analysis revealed that si-DOX-Tet treatment led to significantly more apoptosis, approximately 1.6-fold higher than treatment with DOX alone. Mechanistically, inhibiting RNF8 led to decreased ABCG2 expression and DOX efflux, but increased DNA damage, thereby enhancing the chemotherapeutic effect of DOX.Conclusion: We have successfully constructed si-DOX-Tet. By inhibiting the expression of RNF8, it enhances the chemotherapy sensitivity of DOX. Therefore, this tetrahedral FNA nanocarrier offers a new approach for the combined treatment of colon cancer. Keywords: DNA framework nucleic acid, RNF8, chemosensitivity, RNAi, colorectal cancer

Hao Yang,1– 3,&ast; Guanglin Lei,2,&ast; Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Yang Xu,1 Qinglin Chen,1,2 Yu Tian1 1Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, 610066, People’s Republic of China; 2Sichuan Key Laboratory of Psychology and Behavior of Discipline lnspection and Supervision (Sichuan Normal University), Chengdu, 610066, People’s Republic of ChinaCorrespondence: Yu Tian, Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, 610066, People’s Republic of China, Tel +86 13888583767, Email tianyu@sicnu.edu.cnIntroduction: The general deficit in inhibitory control of problematic social media users has received widespread attention. However, the neural correlates of problematic social media use (PSMU) and inhibitory control remain unclear. Additionally, the co-occurrence of the fear of missing out (FoMO) with social media use is common, yet its role in the relationship between PSMU and inhibitory control has not been investigated.Methods: This study aimed to examine the electrophysiological correlates of PSMU and inhibitory control using a modified two-choice oddball task combined with event-related potentials (ERPs), and to explore the role of FoMO in this relationship. A total of 66 participants with varying degrees of PSMU were included in the analysis based on the Problematic Mobile Social Media Usage Questionnaire.Results: The study found that PSMU could impact inhibitory control. Specifically, as the PSMU score increases, the N2 amplitude is greater for social media-related pictures, and the P3 amplitude is smaller, while no significant differences are observed for neutral pictures. This suggests that PSMU affects inhibitory control by consuming more cognitive resources in the early conflict detection stage and leading to insufficient cognitive resources in the later stages of the inhibitory process. Furthermore, FoMO played a mediating role between PSMU and inhibitory control. PSMU could further impact inhibitory control through FoMO.Conclusion: This study provides electrophysiological evidence for deficits in inhibitory control in PSMU and suggests that FoMO may further reduce inhibitory control in PSMU individuals.Keywords: problematic social media use, inhibitory control, fear of missing out, event-related potentials

Yuan Tian,1 Kang Tao,1 Shifei Li,1 Xiaoqiang Chen,2 Rupeng Wang,3 Mingwang Zhang,1 Zhifang Zhai1 1Department of Dermatology, The First Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Dermatology, General Hospital of Central Theater Command, Wuhan, People’s Republic of China; 3Department of Dermatology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Mingwang Zhang; Zhifang Zhai, Department of Dermatology, The First Affiliated Hospital, Army Medical University, No. 29 Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email mingwangzhang2@163.com; zhaizf1004@163.comBackground: Systemic Lupus Erythematosus (SLE), a prototypical autoimmune disorder, presents a challenge due to the absence of reliable biomarkers for discerning organ-specific damage within SLE. A growing body of evidence underscores the pivotal involvement of N6-methyladenosine (m6A) in the etiology of autoimmune conditions.Methods: The datasets, which primarily encompassed the expression profiles of m6A regulatory genes, were retrieved from the Gene Expression Omnibus (GEO) repository. The optimal model, selected from either Random Forest (RF) or Support Vector Machine (SVM), was employed for the development of a predictive nomogram model. To identify pivotal genes associated with SLE, a comprehensive screening process was conducted utilizing LASSO, SVM-RFE, and RF techniques. Within the realm of SLE susceptibility, Weighted Gene Co-expression Network Analysis (WGCNA) was harnessed to delineate relevant modules and hub genes. Additionally, MeRIP-qPCR assays were performed to elucidate key genes correlated with m6A targets. Furthermore, a Mendelian randomization study was conducted based on genome-wide association studies to assess the causative influence of MMP9 on ischemic stroke (IS), which is not only a severe cerebrovascular event but also a common complication of SLE.Results: Twelve m6A regulatory genes was identified, demonstrating statistical significance (p < 0.05) and utilized for constructing a nomogram model using the RF algorithm. EPSTI1, USP18, HP, and MMP9, as the hub genes, were identified. MMP9 uniquely correlates with m6A modification and was causally linked to an increased risk of IS, as indicated by our inverse variance weighting analysis showing an odds ratio of 1.0134 (95% CI=1.0004– 1.0266, p = 0.0440).Conclusion: Our study identified twelve m6A regulators, shedding light on the molecular mechanisms underlying SLE risk genes. Importantly, our analysis established a causal relationship between MMP9, a key m6A-related gene, and ischemic stroke, a common complication of SLE, thereby providing critical insights for presymptomatic diagnostic approaches.Keywords: systemic lupus erythematosus, N6-methyladenosine, m6A regulatory genes, MMP9, Mendelian randomization, bioinformatic analysis

Wenxiu Zhang,1,&ast; Yu Zhao,2,&ast; Yuchi Tian,1 Xiaoyun Liang,1 Chenghao Piao2 1Institute of Research and Clinical Innovations, Neusoft Medical Systems Co, Ltd, Shanghai, People’s Republic of China; 2Radiology Department, Second Affiliated Hospital of Shenyang Medical College, Shenyang, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenghao Piao, First Floor, Radiology Department, Second Affiliated Hospital of Shenyang Medical College, No. 64, Qishan West Road, Huanggu District, Shenyang, Liaoning, People’s Republic of China, Tel +0086-18002452977, Email doctor_pch@163.comPurpose: Quantitative computed tomography (QCT) techniques, focusing on airway anatomy and emphysema, may help to detect early structural changes of COPD disease. This retrospective study aims to identify high-risk COPD participants by using QCT measurements.Patients and Methods: We enrolled 140 participants from the Second Affiliated Hospital of Shenyang Medical College who completed inspiratory high-resolution CT scans, pulmonary function tests (PFTs), and clinical characteristics recorded. They were diagnosed Non-COPD by PFT value of FEV1/FVC > 70% and divided into two groups according percentage predicted FEV1 (FEV1%), low-risk COPD group: FEV1% ≥ 95%, high-risk group: 80% < FEV1% < 95%. The QCT measurements were analyzed by the Student’s t-test (or Mann–Whitney U-test) method. Then, feature candidates were identified using the LASSO method. Meanwhile, the correlation between QCT measurements and PFTs was assessed by the Spearman rank correlation test. Furthermore, support vector machine (SVM) was performed to identify high-risk COPD participants. The performance of the models was evaluated in terms of accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-score, and area under the ROC curve (AUC), with p < 0.05 considered statistically significant.Results: The SVM based on QCT measurements achieved good performance in identifying high-risk COPD patients with 85.71% of ACC, 88.34% of SEN, 84.00% of SPE, 83.33% of F1-score, and 0.93 of AUC. Further, QCT measurements integration of clinical data improved the performance with an ACC of 90.48%. The emphysema index (%LAA− 950) of left lower lung was negatively correlated with PFTs (P < 0.001). The airway anatomy indexes of lumen diameter (LD) were correlated with PFTs.Conclusion: QCT measurements combined with clinical information could provide an effective tool for an early diagnosis of high-risk COPD. The QCT indexes can be used to assess the pulmonary function status of high-risk COPD.Keywords: early diagnosis, QCT measurements, COPD, SVM

Yuchen Gao,1,&ast; Chunrong Wang,2,&ast; Wenhao Dong,3 Bianfang Li,3 Jianhui Wang,1 Jun Li,1 Yu Tian,1 Jia Liu,1 Yuefu Wang3 1Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Surgical Intensive Care Unit & Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuefu Wang, Department of Surgical Intensive Care Unit & Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing, People’s Republic of China, Email wangyuefu3806@bjsjth.cnBackground: To derive and validate a machine learning (ML) prediction model of acute kidney injury (AKI) that could be used for AKI surveillance and management to improve clinical outcomes.Methods: This retrospective cohort study was conducted in Fuwai Hospital, including patients aged 18 years and above undergoing cardiac surgery admitted between January 1, 2017, and December 31, 2018. Seventy percent of the observations were randomly selected for training and the remaining 30% for testing. The demographics, comorbidities, laboratory examination parameters, and operation details were used to construct a prediction model for AKI by logistic regression and eXtreme gradient boosting (Xgboost). The discrimination of each model was assessed on the test cohort by the area under the receiver operator characteristic (AUROC) curve, while calibration was performed by the calibration plot.Results: A total of 15,880 patients were enrolled in this study, and 4845 (30.5%) had developed AKI. Xgboost model had the higher discriminative ability compared with logistic regression (AUROC, 0.849 [95% CI, 0.837– 0.861] vs 0.803[95% CI 0.790– 0.817], P< 0.001) in the test dataset. The estimated glomerular filtration (eGFR) and creatine on intensive care unit (ICU) arrival are the two most important prediction parameters. A SHAP summary plot was used to illustrate the effects of the top 15 features attributed to the Xgboost model.Conclusion: ML models can provide clinical decision support to determine which patients should focus on perioperative preventive treatment to preemptively reduce acute kidney injury by predicting which patients are not at risk.Keywords: machine learning, acute kidney injury, cardiac surgery, shapley additive explanations, SHAP, prediction model

Jiao Sun,1,&ast; Lichao Fan,2,&ast; Yanping Zhao,3,&ast; Haoyu Wu,2 Ran Li,2 Yao Tian,2 Moxin Cheng,2 Xin Ma,1 Yingying Ma,1 Xinru Yang,1 Adong Shen,4 Yanhong Yu,1 Yu Chen2 1Tuberculosis Laboratory, Shenyang Tenth People’s Hospital/Shenyang Chest Hospital, Shenyang, People’s Republic of China; 2Department of Tuberculosis, Shenyang Tenth People’s Hospital/Shenyang Chest Hospital, Shenyang, People’s Republic of China; 3School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 4National Clinical Research Center for Respiratory Disease, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanhong Yu; Yu Chen, Email 438735174@qq.com; yuchensyxk@163.comObjective: Drug-resistant tuberculosis (DR-TB) in children seriously threatens TB control. Information on the epidemiology and characteristics of DR-TB in children in China is limited. We studied data in Shenyang Tenth People’s Hospital to understand the DR-TB epidemiology in children in Shenyang.Design or Methods: We retrospectively analyzed drug resistance testing data of pediatric TB patients between 2017 and 2021, and included 2976 clinically-diagnosed pediatric TB patients. We described the epidemiology of DR-TB and analyzed the trends of DR-TB incidence. The Kappa value was calculated to assess the agreement between MGIT 960 DST and Xpert MTB/RIF for detecting rifampicin resistance. Multivariate logistic regression was used to identify the risk factors for DR-TB in pediatric patients.Results: Of the 2976 TB patients, 1076 were confirmed by MGIT 960 culture and/or Xpert MTB/RIF. Among the 806 patients identified by MGIT 960 culture, 232 cases (28.78%) were DR-TB. Resistance to the six drugs was in the following order: streptomycin (21.09%), isoniazid (9.35%), rifampin (15.01%), levofloxacin (6.20%), ethambutol (4.22%), and amikacin (3.23%). Alarmingly, 12.90% were MDR-TB (104/806), including 28 (3.47%) pre-XDR-TB. Of the 1076 pediatric TB patients, 295 (27.4%) developed DR-TB to any one drug (including 69 rifampicin-resistant cases identified by Xpert MTB/RIF only). No difference was found in the incidence of pediatric DR-TB between 2017 and 2021. Among 376 patients who were positive for both methods, using the MGIT 960 DST results as the gold standard, Xpert MTB/RIF’s sensitivity for detecting rifampicin resistance was 91.38% and its specificity was 94.65%.Conclusion: Between 2017 and 2021, the DR-TB incidence in children remained unchanged in Shenyang. RR-TB, MDR-TB, and even Pre-XDR-TB require attention in children with drug-resistant TB. Xpert MTB/RIF helped to detect more rifampicin-resistant pediatric patients; thus Xpert MTB/RIF should be widely used as an important complementary tool to detect rifampicin-resistant TB in children.Keywords: tuberculosis, drug-resistant, children, rifampicin, Xpert MTB/RIF, drug susceptibility testing

Ling Chen,1,&ast; Zhe Meng,2,&ast; Zhiguo Zhou,1,&ast; Xiaomin Li,2 Liyan Zhao,2 Zhaohui Jia,2 Jingli Chen,3 Ye Tian,3 Qingju Meng,2 Yibing Liu1 1The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050011, People’s Republic of China; 2The First Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei Province, 054000, People’s Republic of China; 3Hebei Medical University, Shijiangzhuang, Hebei Province, 050011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yibing Liu, Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, 12 JianKang Road, Shijiazhuang, Hebei Province, 050011, People’s Republic of China, Tel +86-13831173220, Email lyb.he@163.com Qingju Meng, Department of Orthopedics, The First Affiliated Hospital of Xingtai Medical College, 376 Shun de Road, Qiaodong District, Xingtai, Hebei Province, People’s Republic of China, Tel +86-13780444436, Email qingjumeng@163.comAbstract: Metaplastic breast cancer (MBC) is a rare disease, and there was rarely reported the treatment after recurrence and metastasis. Here, we report the treatment of an adult patient who suffered from MBC with lung, lymph nodes and left pleura metastasis after radical surgery. The next-generation sequencing result demonstrated that it had tumor mutational burden (TMB) of 12.0 Muts/Mb and microsatellite stability. The patient received sintilimab, an immune checkpoint inhibitor, plus chemotherapy and achieved partial response (PR). This is a report of a good outcome of metastatic MBC achieving 24 months of progression-free survival (PFS) and 39 months of overall survival (OS) with a combination therapy of immune checkpoint inhibitor and chemotherapy. Immuno-chemotherapy may have antitumor activity for relapse MBC. TMB may serve as a potential predictor associated with PD-1 inhibitors in MBC and help clinicians make an optimum treatment strategy.Keywords: metaplastic breast cancer, tumor mutational burden, immunotherapy, chemotherapy, progression-free survival, overall survival

Yilin Li,1,&ast; Tingting Wang,2,&ast; Beibei Ma,2 Shangyue Yu,1 Hailuan Pei,1 Shiqiu Tian,1 Yingying Tian,1 Chuang Liu,1 Xinyue Zhao,1 Zeping Zuo,2 Zhibin Wang1,2 1School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Beijing Tongrentang Technology Co., LTD. Pharmaceutical Factory, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhibin Wang; Zeping Zuo, Beijing Tongrentang Technology Co., LTD. Pharmaceutical Factory, No. 20S 3rd Ring Road Middle, Beijing, 100071, People’s Republic of China, Email wangzhibin4804@126.com; zepingzuo@126.comPurpose: Xianglian Zhixie Tablet (XLZXT), a classical traditional Chinese medicine formulation, is commonly used to treat Ulcerative Colitis (UC) in China. However, the therapeutic mechanisms of XLZXT for UC have yet to be fully understood. This study aimed to investigate the curative benefits of XLZXT and its associated mechanisms for healing UC in mice.Methods: In the present study, the 1% dextran sulfate sodium (DSS) solution was used to establish the UC model in C57BL/6N mice. To investigate the therapeutic effects of XLZXT on DSS-induced UC mice, several parameters were measured, including DAI score, colon length, spleen index, pathological changes in colon tissue, and levels of inflammatory factors in plasma and colon tissue. By investigating the gut microbiota, assessing the levels of intestinal mucosal protein expression, and looking at the proteins involved in the TLR4/MyD88/NF-B p65 signaling pathway, the mechanisms of XLZXT impact on UC were investigated. Mouse feces were examined for patterns of gut microbiota expression using high-throughput sequencing of 16S rRNA.Results: XLZXT effectively alleviated UC symptoms and colon pathological damage in DSS-induced UC mice. It improved body weight loss, stool consistency, and hematochezia, while also repairing colon damage. Moreover, it down-regulated pro-inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), and up-regulated anti-inflammatory cytokines (such as IL-10). XLZXT also increased the expression of MUC-2, Occludin and ZO-1, while decreasing the expression of NF-κB, MyD88 and TLR4. Additionally, it regulated gut microbiota disorder by increasing the abundance of beneficial bacteria and reducing the adhesion of intestinal harmful bacteria.Conclusion: XLZXT demonstrated therapeutic effects on DSS-induced UC mice. The mechanisms may be associated with repairing the intestinal mucosal barrier, regulating the TLR4/MyD88/NF-κB p65 signaling pathway, and restoring the balance of gut microbiota.Plain Language Summary: This is the first study to probe the therapeutic potential of XLZXT for UC. Our findings indicated that XLZXT could effectively alleviate the clinical symptoms of UC and in-depth apparently modify the levels of relevant cytokines in the organism to maintain the system homeostasis. Our results suggested that XLZXT might treat DSS-induced UC by repairing the intestinal mucosa barrier, regulating the TLR4/MyD88/NF-κB p65 signaling pathway, and restoring gut microbiota balance.Graphical Abstract: Keywords: ulcerative colitis, TCM, TLR4/MyD88/NF-&kcy;B p65 signaling pathway, gut microbiota

Yuan Tian,1,&ast; Wenbiao Jin,1,&ast; Honghua Sun,1 Dehao Jin,2 Dongxu Kang,1 Zhiyu Li,1 Longzhen Piao1 1Department of Oncology, The Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People’s Republic of China; 2Department of Radiology, Yanbian Maternal and Child Health Hospital, Yanji, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyu Li; Longzhen Piao, Department of Oncology, The Affiliated Hospital of Yanbian University, No. 1327 Juzi Street, Yanji City, Jilin Province, People’s Republic of China, Tel +86 15526771578 ; +86 15526771162, Fax +86 433 2513610, Email 15526771578@163.com; plz1978@126.comBackground: Advanced-stage hepatocellular carcinoma (HCC), especially huge HCC or portal vein tumour thrombus (PVTT), is difficult to treat, and the prognosis is poor. The advantages of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunotherapy for this complex disease are gradually becoming apparent. However, HAIC still has some inevitable disadvantages, such as arterial perfusion therapy requiring a long time, which results in many patients having difficulty completing the procedure. Modified HAIC (mHAIC)-based oxaliplatin and S-1 is a new treatment option for huge HCC or PVTT that can reduce complications and improve patient compliance. We report two cases of huge HCC or PVTT that were successfully treated with mHAIC combined with lenvatinib and camrelizumab. The clinical presentations, treatment strategies, and outcomes of these cases are presented.Case Presentation: Case 1: A 52-year-old female was found to have a huge HCC with a size of 14× 11 cm. She was treated with one cycle of mHAIC combined with transcatheter arterial chemoembolization (TACE), lenvatinib and camrelizumab and 3 cycles of mHAIC in combination with lenvatinib and camrelizumab. The patient’s follow-up maintenance therapy with lenvatinib and camrelizumab has been evaluated for efficacy in achieving complete response (CR). Case 2: A 57-year-old man was diagnosed with advanced HCC in combination with PVTT. He achieved partial remission (PR) after four cycles of mHAIC combined with lenvatinib and camrelizumab. This was followed by treatment with lenvatinib and camrelizumab with an efficacy assessment for CR, and progression-free survival (PFS) was 7 months.Conclusion: For advanced HCC with a large mass or PVTT, mHAIC combined with lenvatinib and camrelizumab is a safe and effective treatment with good patient compliance.Keywords: huge HCC, PVTT, mHAIC, case report

Ran-Ran Zhang,1,2,&ast; Yu-Qing Meng,1,&ast; Yan Tian,1 Tao Zou3 1School of Medical Humanities, Guizhou Medical University, Guizhou, 550004, People’s Republic of China; 2Researcher, Guizhou Health Development Research Center, Guizhou, 550004, People’s Republic of China; 3Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guizhou, 550004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Zou, Department of Psychiatry, Affiliated Hospital of Guizhou Medical University, Guizhou, 550004, People’s Republic of China, Tel +8613985400734, Email zoutaozou@tom.comPurpose: Most studies have supported the view that individuals prefer to reward the in-group and discriminate against the out-group in response to unfair offers in the Ultimatum Game. However, the current study advanced a different view, that is, the “black sheep effect”, in which in-group members were punished more severely compared with out-group members. This study aimed to incorporate proposer identity and allocation motive as possible explanations for offer rejection.Methods: In the current study, the in-group and out-group identities were distinguished by their health condition, and the allocation motive was defined according to its benefit maximization. With a total of 89 healthy college student participants, a mixed design of 2 (proposer identity: out-group vs in-group) × 2 (allocation motive: selfish vs random) × 2 (offer type: unfair vs fair) was used in the Ultimatum Game. Event-related potential (ERP) technology was used, and ERPs were recorded while participants processed the task.Results: The behavioral result showed that the “black sheep effect” was found on the fair offer when a random allocation motive was used. Our ERP result suggested that feedback-related negativity (FRN) and P300 were modulated by proposer identity but not by allocation motive. However, the allocation motive interacted with proposer identity affecting FRN and P300 when the fair offer was proposed.Conclusion: These findings demonstrated that the “black sheep effect” was related to the experience of the out-group member, such as disadvantage or distress, but it was also modulated by allocation motive. Meanwhile, the out-group (depressed college students) captured more attention because they violated individual expectations, according to the P300. This finding plays an integral role in understanding the mechanism of response to the “black sheep effect”.Plain Language Summary: People prefer to receive fair offers compared to unfair offers, but they are more tolerant to in-group members compared with out-group members when facing unfair offers. However, what would you do if you knew the in-group members were making you the smallest offer possible with a self-interested motive to maximize their own gains? We used the Ultimatum Game (UG) to explore this issue. We invited 89 colleges to participate in this study, and they were randomly divided into in-group member, out-group member, selfish motive, and random motive groups. Then, we used event-related potential (ERP) technology to examine cognitive processing. We found the “back sheep effect” on the fair offer, which means that people prefer to accept the out-group member’s offer when they had a random motive. We also found different feedback-related negativity (FRN) and P300 between the in-group and out-group members. In addition, the “black sheep effect” was found in the fair offers when the proposer presented a random motive. This finding plays an important role in understanding the mechanism of response to fair or unfair offers.Keywords: in-group, out-group, ultimatum game, event-related potential technique, allocation motive, feedback-related negativity, P300

Yuan Tian,1,&ast; Zilin Wang,2,&ast; Feng Liang,3,&ast; Yi Wang1 1Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 2Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Heart Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Wang, Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, NO. 100 Haining Road, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 021 63241377, Email wangyi2016@sjtu.edu.cnPurpose: Myocardial remodeling after myocardial infarction (MI) is a complex repair process following myocardial injury, characterized by the infiltration of multiple types of immune cells. However, the underlying molecular mechanism of myocardial remodeling after MI remains obscure. This study aimed to identify the hub differential expression genes (DEGs) of myocardial remodeling after MI and determine the distribution of immune cells infiltrating the pathology.Methods: We downloaded GSE132143, GSE151834, and GSE176092 data from the GEO database. The GSE132143 dataset was used to identify DEGs, perform functional annotation, and screen hub genes based on protein-protein interaction (PPI) analysis. The GSE151834 dataset was used to validate the expression of hub genes. CIBERSORTx analysis was performed to explore the immune microenvironment in myocardial remodeling after MI. After conducting a literature review, we selected P3H3 to confirm the expression by utilizing immunohistochemistry and qRT-PCR. Finally, the snRNA-seq data in dataset GSE176092 was used for clarifying the expression of these hub genes in various cell clusters.Results: We found 975 DEGs in myocardial remodeling after MI. Four hub genes (P3H3, COL15A1, COL16A1, COL27A1) were identified and were verified in the GSE151834 dataset. According to immune infiltration analysis, CD4+ naive T cells, regulatory T cells, monocytes, M2 macrophages, and neutrophils were involved in the pathological process of myocardial remodeling after MI. Additionally, in vitro experiments verified that P3h3 expression was significantly elevated in myocardial remodeling after MI. The snRNA-seq data analyzed that P3h3, Col15a1, Col16a1, and Col27a1 were highly expressed in fibroblasts of post-MI.Conclusion: This study identified four hub genes P3H3, COL15A1, COL16A1, and COL27A1, particularly P3H3, as potential targets for targeted therapy in MI patients.Keywords: myocardial infarction, myocardial remodeling, hub genes, immune infiltration, bioinformatic analysis

Bo Li,1 Weiqing Wu,1 Aijun Liu,1 Lifeng Feng,1 Bin Li,1 Yong Mei,1 Li Tan,1 Chaoyang Zhang,2 Yangtao Tian1 1Department of Pancreatic Surgery, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of China; 2Department of Ultrasound Medicine, Shangluo Center Hospital, Shangluo, Shaanxi, 726000, People’s Republic of ChinaCorrespondence: Yangtao Tian, Department of Pancreatic Surgery, Shangluo Center Hospital, 37 Shangyang, Shangzhou, Shangluo, Shaanxi, 726000, People’s Republic of China, Email 928763821@qq.comBackground: Severe acute pancreatitis (SAP) can progress to lung and kidney dysfunction, and blood clotting within 48 hours of its onset, and is associated with a high mortality rate. The aim of this study was to establish a reliable diagnostic prediction model for the early stage of severe pancreatitis.Methods: The clinical data of patients diagnosed with acute pancreatitis from October 2017 to June 2022 at the Shangluo Central Hospital were collected. The risk factors were screened by least absolute shrinkage and selection operator (LASSO) regression analysis. A novel nomogram model was then established by multivariable logistic regression analysis.Results: The data of 436 patients with acute pancreatitis, 45 (10.3%) patients had progressed to SAP. Through univariate and LASSO regression analyses, the neutrophils (P < 0.001), albumin (P < 0.001), blood glucose (P < 0.001), serum calcium (P < 0.001), serum creatinine (P < 0.001), blood urea nitrogen (P < 0.001) and procalcitonin (P = 0.005) were identified as independent predictive factors for SAP. The nomogram built on the basis of these factors predicted SAP with sensitivity of 0.733, specificity of 0.9, positive predictive value of 0.458 and negative predictive value of 0.967. Furthermore, the concordance index of the nomogram reached 0.889 (95% CI, 0.837– 0.941), and the area under the curve (AUC) in receiver operating characteristic curve (ROC) analysis was significantly higher than that of the APACHEII and ABISAP scoring systems. The established model was validated by plotting the clinical decision curve analysis (DCA) and clinical impact curve (CIC).Conclusion: We established a nomogram to predict the progression of early acute pancreatitis to SAP with high discrimination and accuracy.Keywords: acute pancreatitis, prediction model, risk factor, nomogram, decision curve analysis

YiFu Tian,1 CaiXia Zhou,1 XiaoYang Bu,1 Qian Lv,1 Qin Huang1,2 1Department of Physiology of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education & School of Basic Medical Sciences, Guangxi Medical University, Nanning, People’s Republic of ChinaCorrespondence: Qin Huang, Department of Physiology, Guangxi Medical University, Building 102, 22 Shuangyong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email hqgxmu@163.comBackground: Inflammation plays a crucial role in the development of diabetic cardiomyopathy (DCM), including inflammation caused by high-glucose and high-lipid (HGHL). Targeting inflammation may provide a useful strategy for preventing and treating DCM. Puerarin has been shown to reduce the inflammation, apoptosis and hypertrophy of cardiomyocytes induced by HGHL, in which this study aims to investigate the underlying mechanisms.Methods: H9c2 cardiomyocytes cultured with HGHL were used to establish a cell model of DCM. Puerarin was then placed to these cells for 24 hours. The effects of HGHL and puerarin on cell viability and apoptosis were investigated by the Cell Proliferation, Toxicity Assay Kit (CCK-8) and flow cytometry. Morphological changes of cardiomyocytes was observed by HE staining. CAV3 proteins in H9c2 cardiomyocytes were altered by transient transfection of CAV3 siRNA. IL-6 was detected by ELISA. The Western blot was performed to determine the CAV3, Bcl-2, Bax, pro-Caspase-3, cleaved-Caspase-3, NF-κB (p65) and p38MAPK proteins.Results: Puerarin treatment reversed the cells viability, hypertrophy in morphology, inflammation (showed by p-p38 and p-p65 and IL-6) and apoptosis-related damage (showed by cleaved-Caspase-3/pro-Caspase-3/Bax, Bcl-2 and flow cytometry) of the H9c2 cardiomyocyte caused by HGHL. Puerarin treatment also restored the decrease of CAV3 proteins of the H9c2 cardiomyocyte caused by HGHL. When silenced the expression of CAV3 proteins with SiRNA, puerarin failed to decreased p-p38 and p-p65 and IL-6, and could not reversed cell viability and morphological damage. In contrast to the simple CAV3 silenced group, the CAV3 silenced with NF-κB pathway or p38MAPK pathway inhibitors, significantly downregulated the p-p38, p-p65 and IL-6.Conclusion: Puerarin upregulated CAV3 protein expression in H9c2 cardiomyocytes and inhibited the NF-κB and p38MAPK pathways, thereby reducing HGHL-induced inflammation and may related to the apoptosis and hypertrophy of cardiomyocytes.Keywords: puerarin, cardiomyocyte, inflammation, caveolin-3, siRNA, NF-κB, p38MAPK

Xing-Chen Zhou,&ast; Yu-Bo Huang,&ast; Zhen Liu,&ast; Hong-Jiao Wu, Hua-Zhi Huang, Yu Tian, Shuang-Wei Hong, Hui-Jie Hu, Li-Jiang Lv, Zhi-Zhen Lv The Third Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Zhen Lv; Li-Jiang Lv, The Third Clinical Medical College of Zhejiang Chinese Medical University, No. 548, Binwen Road, Hangzhou, 310053, People’s Republic of China, Tel +86 13750821128 ; +86 13958107858, Email lvzhizhen1992@163.com; lvlijiang0288@163.comBackground: Research on the brain mechanisms underlying manual therapy (MT)-induced analgesia has been conducted worldwide. However, no bibliometric analysis has been performed on functional magnetic resonance imaging (fMRI) studies of MT analgesia. To provide a theoretical foundation for the practical application of MT analgesia, this study examined the current incarnation, hotspots, and frontiers of fMRI-based MT analgesia research over the previous 20 years.Methods: All publications were obtained from the Science Citation Index-Expanded (SCI-E) of Web of Science Core Collection (WOSCC). We used CiteSpace 6.1.R3 to analyze publications, authors, cited authors, countries, institutions, cited journals, references, and keywords. We also evaluated keyword co-occurrences and timelines, and citation bursts. The search was conducted from 2002– 2022 and was completed within one day on October 7, 2022.Results: In total, 261 articles were retrieved. The total number of annual publications showed a fluctuating but overall increasing trend. Author B. Humphreys had the highest number of publications (eight articles) and J. E. Bialosky had the highest centrality (0.45). The United States of America (USA) was the country with the most publications (84 articles), accounting for 32.18% of all publications. Output institutions were mainly the University of Zurich, University of Switzerland, and the National University of Health Sciences of the USA. The Spine (118) and the Journal of Manipulative and Physiological Therapeutics (80) were most frequently cited. The four hot topics in fMRI studies on MT analgesia were “low back pain”, “magnetic resonance imaging”, “spinal manipulation”, and “manual therapy.” The frontier topics were “clinical impacts of pain disorders” and “cutting-edge technical capabilities offered by magnetic resonance imaging”.Conclusion: fMRI studies of MT analgesia have potential applications. fMRI studies of MT analgesia have linked several brain areas, with the default mode network (DMN) garnering the most attention. Future research should include international collaboration and RCTs on this topic.Keywords: manual therapy, analgesia, functional magnetic resonance imaging, CiteSpace, bibliometric analysis, web of science

Yang He,1 Huili Li,2 Rui Wang,3 Ning Ma,3 Lianyuan Liu,4 Rui Shi,5 Bohua Zhang,3 Ningning Lin,6 Yiming Tian3 1Hemodialysis Room, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, People’s Republic of China; 2Department of Endocrinology, The First Hospital of Qinhuangdao Affiliated to Hebei Medical University, Qinhuangdao, 066000, People’s Republic of China; 3Department of Endocrinology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, People’s Republic of China; 4Functional Examination Department, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, People’s Republic of China; 5Rheumatology and Immunology Department, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, People’s Republic of China; 6Department of Dermatology, The First Hospital of Qinhuangdao, Qinhuangdao, 066000, People’s Republic of ChinaCorrespondence: Yiming Tian, Department of Endocrinology, The First Hospital of Qinhuangdao, No. 258, Wenhua Road, Qinhuangdao, Hebei Province, 066000, People’s Republic of China, Email Yiming_Tian@foxmail.comBackground: Diabetic nephropathy (DN) is one of the most devastating microvascular complications of diabetes, with a high prevalence and poor prognosis. Early intervention is crucial to improve the outcomes of DN. CXCL8 is related to podocyte damage in incipient DN; however, the role and expression level of CXCL8 have never been elucidated, especially in those with undiminished creatinine clearance.Methods: Consecutive inpatients with type 2 diabetes were included in this study. Patients were assigned into four groups based on the Mogensen stage, reflecting pathological features through clinical manifestations: non-DN group, hyperfiltration group, microalbuminuria group and overt DN group. Clinical and laboratory data were retrospectively collected and analyzed. Urinary CXCL8 (uCXCL8) was measured using an enzyme-linked immunosorbent assay (ELISA) method and adjusted for urinary creatinine (Cr) from the same urine sample.Results: In total, 88 eligible consecutive inpatients with type 2 diabetes were included in this study. uCXCL8 was differentially expressed in different stages of incipient DN; it decreased in the hyperfiltration phase of incipient DN (1.40± 1.01 pg/μmol Cr) and was highly expressed in patients in the microalbuminuria stage (5.01± 4.01 pg/μmol Cr). uCXCL8 was positively correlated with age, diabetes course, cystatin C and urinary albuminuria-to-creatinine ratio, but negatively correlated with estimated glomerular filtration rate (P< 0.05). uCXCL8 was a risk factor for classic DN after adjusting for age, diabetes course and cystatin C (OR= 1.17, 95% CI 0.98– 1.4, P=0.045).Conclusion: CXCL8 played an important role in the progression of incipient DN. The unique expression profile of uCXCL8 may provide a reference for understanding the prognosis and mechanisms of incipient DN progression. uCXCL8 was an independent risk factor for the development of classic DN.Keywords: type 2 diabetes, diabetic nephropathies, interleukin-8, inflammation

Wenjun Zhu,&ast; Yaping Tian,&ast; Lin Xiang, Linna Cao, Lirong He Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lirong He, Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 18170905103, Fax +86 0791 86311242, Email hlr_ndefy@163.comAbstract: One of the most pressing emerging issues in bacterial resistance is multidrug-resistant Klebsiella pneumoniae. The treatment of K. pneumoniae infections is often problematic because of the lack of available therapeutic options, leading to negative effects on morbidity, mortality, and healthcare-associated costs. Carrimycin is a macrolide antibiotic with good antibacterial effects. In this study, we report a patient diagnosed with multidrug-resistant K. pneumoniae infection who was treated with carrimycin. The patient presented with cough, expectoration, dyspnea, and severe hypoxemia requiring noninvasive ventilation. We successively used a variety of antibiotics, including meropenem, tigecycline, and polymyxin, with unsatisfactory results. Finally, we used carrimycin, and the patient’s condition improved, resulting in hospital discharge. Therefore, for patients with multidrug-resistant K. pneumoniae infection that does not respond to conventional anti-infective treatments, carrimycin can be considered a treatment option.Keywords: carrimycin, Klebsiella pneumoniae, multidrug-resistant

Ying Cao,1,&ast; Heng Zhang,2,&ast; Gui-Lan Tu,3 Ye Tian,2 Xiao-Hu Tang,2 Lei Tang,1 Mu-Xia Luo,1 Yan-Dong Wang,2 Zhen Wang,2 Shu-Jie Xia,4 Guang-Heng Luo2 1Guizhou University Medical College, Guiyang, 550025, People’s Republic of China; 2Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China; 3Department of Pathology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China; 4Department of Urology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, 200080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guang-Heng Luo, Email luoguangheng1975@126.comObjective: The aim of the present study was to observe the effect of the stroma proportion in hyperplasia nodules on the clinical symptoms of benign prostatic hyperplasia (BPH) patients and to identify the different genes and pathways in prostatic hyperplasia nodules between patients with epithelial-dominated hyperplasia (EDH) and stromal-dominated hyperplasia (SDH) nodules.Methods: Sixty-seven BPH patient samples underwent transurethral resection of the prostate (TURP) were collected and retrospectively analyzed. The differences in clinical parameters between the EDH and SDH groups were investigated. Collagen fiber percentage was assessed, and the correlation with clinical parameters was evaluated. mRNA sequencing in hyperplasia nodules of 8 BPH patients was performed, and differentially expressed genes (DEGs) between the EDH and SDH groups were screened. These DEGs were analyzed using GO, KEGG and PPI analysis.Results: The results showed the IPSS was significantly higher in the SDH group than in the EDH group (p < 0.01). The collagen fiber percentage of BPH nodules was higher in the SDH group than in the EDH group (p < 0.05), and the collagen fiber percentage was positively correlated with the IPSS (r = 0.4058, p = 0.0007). A total of 172 DEGs were obtained, including 63 up-regulated genes and 109 down-regulated genes. GO and KEGG pathway enrichment analyses showed DEGs were mainly enriched in extracellular matrix structural constituents. The top 10 hub genes were associated to the components of extracellular matrix and fibrosis.Conclusion: These results suggested that the symptoms of BPH patients with SDH nodules may be associated with prostate fibrosis and fibrosis may be a significant contributing factor in BPH/LUTS patients with SDH nodules.Keywords: benign prostate hyperplasia, lower urinary tract symptoms, prostate fibrosis, stroma, pathology

Yuanxiao Li,1,&ast; Ying Tian,2,&ast; Shufen Pei,3 Baoyuan Xie,2 Xiaonan Xu,1 Bin Wang4 1Department of Pediatric Gastroenterology, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 2Department of Clinical Medicine, Lanzhou University Second Hospital, Lanzhou, People’s Republic of China; 3Department of Clinical Medicine, North Sichuan Medical College, Nanchong, People’s Republic of China; 4Department of Infectious Diseases, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Wang, 88 Jie Fang Lu, Shangcheng District, Hangzhou, Zhejiang, 310009, People’s Republic of China, Email wangbin2022@zju.edu.cnObjective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice.Methods: A retrospective analysis of 944 studies was performed on February 28, 2023.Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the “Brief Summary”. A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions.Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent.Keywords: real-world data, real-world evidence, real-world study, study design, ClinicalTrials.gov

Xiang He, Shentao Zhang, Yuhang Tian, Wen Cheng, Hui Jing Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of ChinaCorrespondence: Hui Jing; Wen Cheng, Department of Ultrasound, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, People’s Republic of China, Tel +86 13304504935 ; +86 13313677182, Email jinghuihrb@163.com; chengwen@hrbmu.edu.cnAbstract: With the booming development of nanomedicine, mild photothermal therapy (mPTT, 42– 45°C) has exhibited promising potential in tumor therapy. Compared with traditional PTT (> 50°C), mPTT has less side effects and better biological effects conducive to tumor treatment, such as loosening the dense structure in tumor tissues, enhancing blood perfusion, and improving the immunosuppressive microenvironment. However, such a relatively low temperature cannot allow mPTT to completely eradicate tumors, and therefore, substantial efforts have been conducted to optimize the application of mPTT in tumor therapy. This review extensively summarizes the latest advances of mPTT, including two sections: (1) taking mPTT as a leading role to maximize its effect by blocking the cell defense mechanisms, and (2) regarding mPTT as a supporting role to assist other therapies to achieve synergistic antitumor curative effect. Meanwhile, the special characteristics and imaging capabilities of nanoplatforms applied in various therapies are discussed. At last, this paper puts forward the bottlenecks and challenges in the current research path of mPTT, and possible solutions and research directions in future are proposed correspondingly.Keywords: nanomedicine, nanotechnology, mild photothermal therapy, tumor therapy

Miao Wang,1,&ast; Jin Shi,2,&ast; Kepei Zhang,1,&ast; Jie Hong,2,&ast; Xinwei Peng,2 Yu Tian,1 Wei Lu,3 Ke Li,2 Zengliang Wang,4 Feng Li,1 Zhijie Zhang,2 Guojiang Mei1 1Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Fudan University, Shanghai, People’s Republic of China; 3Department of Nursing, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijie Zhang, Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Xuhui District, School of Medicine Road, 130, Shanghai, People’s Republic of China, Tel +86-21-54237410, Email epistat@gmail.com; Guojiang Mei, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Tel + 86-21-64385700, Email mgj_761014@sina.comPurpose: This study aimed to evaluate the clinical efficacy of Longyizhengqi granule, a traditional Chinese medicine, in patients with mild COVID-19.Patients and Methods: We conducted a prospective study including mild COVID-19 participants conducted at Mobile Cabin Hospital in Shanghai, China. Participants were assigned to receive Longyizhengqi granule or conventional treatment. The primary outcome was the time for nucleic acid to turn negative and the secondary outcomes are hospital stay and changes in cycle threshold (Ct) values for N gene and Orf gene. Multilevel random-intercept model was performed to analyze the effects of treatment.Results: A total of 3243 patients were included in this study (Longyizhengqi granule 667 patients; conventional treatment 2576 patients). Age (43.5 vs 42.1, p< 0.01) and vaccination doses (not vaccinated: 15.8% vs 21.7%, 1 dose: 3.5% vs 2.9%, 2 doses: 27.9% vs 25.6%, 3 doses: 52.8% vs 49.8%. p< 0.01) show statistical difference between Conventional treatment group and LYZQ granules group. The use of Longyizhengqi granule could significantly reduce the time for nucleic acid to turn negative (14.2 days vs 10.7 days, p< 0.01), shorten hospital stay (12.5 days vs 9.9 days, p< 0.01), and increase the changes in Ct value for N gene (8.44 vs 10.33, p< 0.01) and Orf gene (7.31 vs 8.44, p< 0.01) to approximately 1.5. Moreover, the difference in the changes of Ct values on the 4th, 6th, 8th, and 10th days seem to increase between two groups. No serious adverse events were reported.Conclusion: Longyizhengqi granule might be a promising drug for the treatment of mild COVID-19, and it might be beneficial to effectively shorten the negative transition time of nucleic acid, the total days of hospitalization, and increase the changes of Ct values. Long-term randomized controlled trials with follow-up evaluations are required to confirm its long-term efficacy.Keywords: COVID-19, Omicron variant, traditional Chinese medicine, prospective study

Miao Tian,1,&ast; Zhijia Wang,2,&ast; Yanbin Zhu,1,3 Yunxu Tian,1 Kexin Zhang,1 Xiuting Li1 1Department of Orthopedic Surgery, the Third Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Joint Surgery, Huai ‘an Hospital of Huai‘an City, Huai‘an, People’s Republic of China; 3Hebei Orthopedic Research Institute, Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiuting Li; Yanbin Zhu, Email lixiuting2021@126.com; zhuyanbin111@126.comAim: The purpose of this study was to examine the incidence and cause of unplanned readmission after Surgically Treated Hip Fractures in Elderly Patients and identify the associated risk factors.Methods: This study retrospectively collected the data on elderly patients who underwent hip fracture surgery at two institutions from January 2020 to December 2021, and identified those who were readmitted within 12 months postoperatively. Based on the presence or not of postoperative readmission, they were divided into readmission and non-readmission groups. Demographics, surgery-related variables, and laboratory parameters were compared between groups. The specific causes for documented readmission were collected and summarized. Multivariate logistic regression analysis was performed to identify the associated risk factors.Results: There were 930 patients including 76 (8.2%) patients who were readmitted within 12 months postoperatively. Overall, cardiac and respiratory complications and new-onset fractures were the first three common causes of readmission, taking an overwhelming proportion of 53.9% (41/76). Over 60% (61.8%, 47/76) of readmissions occurred within 30 days after surgery, with medical complications taking a predominance (89.4%, 42/47). New-onset fractures accounted for a proportion of 18.4% (14/76), occurring at different time points; especially, at 90– 365 days, it accounted for 44.4% (8/18). Multivariate analysis revealed that age ≥ 80 years (OR, 1.0, 95% CI, 1.0 to 1.1; P=0.032), preoperative albumin level ≤ 21.5 g/L (OR, 1.1, 95% CI, 1.0 to 1.2; P=0.009), the postoperative occurrence of DVT (OR, 4.2, 95% CI, 2.5 to 7.2; P=0.001), and local anesthesia (OR, 2.1, 95% CI, 1.1 to 4.0; P=0.029) were independent risk factors for unplanned readmissions.Conclusion: This study identified several risk factors for unplanned readmissions after elderly hip fractures, and provided detailed information about unplanned readmissions.Keywords: hip fracture, the elderly, unplanned readmissions, cause, risk factors

Chang Liu,1,2,&ast; Kai Zhang,1,2,&ast; Ting Zhang,1,&ast; Xiaoling Sha,1 Yuhai Xu,3 Juanjuan Gu,1 Ye Tian,4 Yanhong Liu,1,2 Jiangbei Cao,1,2 Weidong Mi,1,2 Hao Li1,2 1Department of Anesthesiology, The First Medical Center, Chinese People’s Liberation Army (PLA) General Hospital, Beijing, People’s Republic of China; 2Medical School of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Anesthesiology Department, Air Force Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Anesthesiology Department, The Sixth Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weidong Mi; Hao Li, Medical School of Chinese PLA, Department of Anesthesiology, The First Medical Center, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, People’s Republic of China, Email wwdd1962@aliyun.com; lihao301@126.comBackground: Myocardial injury after noncardiac surgery (MINS) has been associated with worse outcomes. The aim of our study was to investigate the relationship between higher red blood cell distribution width (RDW) and postoperative 30-day MINS among advanced-age patients.Methods: This was a retrospective observational study including advanced-age patients (≥ 65 years old) who underwent noncardiac surgery between January 2017 and August 2019 at the First Medical Center of the Chinese People’s Liberation Army General Hospital. Patients were divided into two groups according to the cutoff value identified the lowest risk using Restricted Cubic Splines (RCS) model. The primary outcome was the incidence of MINS within 30 days after surgery. The relationship between RDW and MINS was investigated by univariable and multi-variable logistic regression analysis. Propensity score (PS) analysis, including propensity score matching (PSM) and inverse probability treatment weighting (IPTW), as well as subgroup analysis were also conducted to identify the effect of RDW.Results: The result of the RCS analysis showed that the risk of MINS in advanced-age patients increases when the baseline RDW is > 12.8%. In the univariate analysis, baseline RDW > 12.8% was a risk factor for postoperative MINS [odds ratio (OR)=2.11; 95% confidence interval (CI): 1.83– 2.44; p< 0.001]. After adjustment for all possible components, there was also a high risk of MINS for patients with elevated RDW [Adjusted OR (aOR)=1.43; 95% CI: 1.27– 1.61; p< 0.001). The relationship remained after PS analysis (aOR=1.24; 95% CI: 1.04– 1.47; p=0.016 in PSM; aOR=1.23; 95% CI: 1.05– 1.44; p=0.012 in IPTW, respectively). Significant differences between two groups were established in the incidence rate of postoperative cardiac complications and mortality.Conclusion: Elevated preoperative RDW is significantly associated with an increased risk of MINS within postoperative 30 days.Keywords: myocardial injury after noncardiac surgery, red blood cell distribution width, advanced-age patients

Ruijun Ju,1,2 Faliang Wu,2 Yanzhao Tian,1 Jiahao Chu,2 Xiaoming Peng,2 Xiaobo Wang1 1Pharmacy Department, the 967th Hospital of PLA Joint Logistics Support Force, Dalian, People’s Republic of China; 2Beijing Key Laboratory of Enze Biomass Fine Chemicals, Beijing Institute of Petrochemical Technology, Beijing, People’s Republic of ChinaCorrespondence: Xiaobo Wang, Pharmacy Department, the 967 th Hospital of PLA Joint Logistics Support Force, Dalian, People’s Republic of China, Tel/Fax +86-0411-85847131, Email wxbbenson0653@sina.comPurpose: Current chemotherapy fails to offer a desirable efficacy in clinical treatment against breast cancer due to the extensive multi-drug resistance. In this study, we developed dual sensitization anti-resistant nanoparticles to treat refractory breast cancer, aiming to benefit from photodynamic therapy and chemotherapy.Methods: Hyaluronic acid (HA) derivative and photosensitizer chlorin e6 (Ce6) derivative were synthesized and confirmed by mass spectrometry. These derivatives and the chemotherapy agent paclitaxel were incorporated into nanoparticles by an emulsion-solvent evaporation method. The prepared nanoparticles were characterized by dynamic laser scattering, atomic force microscopy, and high performance liquid chromatography (HPLC). The efficacy and mechanisms of the nanoparticles, both in vitro and in vivo, were investigated by flow cytometry, confocal/fluorescence microscopy, and a high-content screening system.Results: The prepared dual sensitization anti-resistant nanoparticles were round with a diameter of ~ 100 nm, exhibiting high encapsulation efficiency for the anticancer agent paclitaxel. The nanoparticles demonstrated a robust inhibitory effect against drug-resistant breast cancer cells by enhanced uptake, synergistic effect of photodynamic therapy and chemotherapy, and apoptosis-inducing via multiple pathways. In vivo efficacy, biocompatibility and safety were further confirmed acceptable in tumor-bearing mice.Conclusion: The prepared dual sensitization anti-resistant nanoparticles were promising to treat refractory breast cancer with a controllable treatment site and minimal side effects.Keywords: dual sensitization anti-resistant nanoparticles, drug-resistant breast cancer, apoptosis, photodynamic therapy, synergistic effect

Keyu Chen,1,&ast; Bin Xu,2,&ast; Yifan Tang,3 Juan Cao,1 Rong Wang,3 Yali Tian,3 Chunhong Gao,3 Ming Chu4 1Department of Thoracic Surgery, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Neurosurgical Intensive Care Unit, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 3Nursing Department, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 4Department of Nosocomial Infection, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhong Gao, Nursing Department, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, Tel +862568305379, Email gao22095@163.com Ming Chu, Department of Nosocomial Infection, Jiangsu Province Hospital and The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, People’s Republic of China, Tel +862568306917, Email chuming@njmu.edu.cnBackground: Community screening for SARS-CoV-2 Omicron variant plays a significant role in controlling the spread of infection. However, loopholes may exist in the current management of community screening in Shanghai, China. The objective of this study was to discover loopholes in the management of community screening for SARS-CoV-2 Omicron variant in Shanghai, China and provide targeted solutions.Methods: The cross-sectional study was carried out April 4 to April 30, 2021, among residential committee directors from the Putuo District, Pudong District, and Minhang District of Shanghai, China. Data were collected using a self-designed questionnaire about the management of nucleic acid testing (NAT) sampling in communities through the network platform powered by www.wjx.cn.Results: A total of 203 residential committee directors responded to the survey. Of them, 47.3% were not accepted training and 40.4% were not aware of cross-infection. Comparison among sampling sites and communities, high-risk group contained lower proportion of community training (P = 0.093~0.200), higher awareness of cross-infection (P = 0.039~0.777), more medical workers (P = 0.007~0.724) and more tests performed (P = 0.001~0.992). Larger communities had more medical workers, sampling sites, sampling tables (P = 0.000) and higher awareness of cross-infection (P = 0.009), but lower proportion of community training (P = 0.051).Conclusion: Overall, community training and awareness of infection control were inadequate. Government or institutions should organize the community training and raise the awareness of infection control. Significant differences exist in NAT management patterns between sampling sites, as well as communities of different sizes. Residential community directors minimize high-risk sampling point settings in the future. Special personnel designated by the government or institutions should tour to guide each sampling site.Keywords: community screening, SARS-CoV-2 Omicron variant, management, China

Weiping Li, Yanqing Liu, Xiaoling Xu, Qi Zhang, Xiao Zhang, Jie Zhang, Xiaochen Niu, Shiyao Yang, Xiaobo Zhang, Wenzhen Shi, Gejuan Zhang, Mingze Chang, Ye Tian Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, School of Life Sciences and Medicine, Northwest University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Ye Tian; Wenzhen Shi, Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, No. 10, East Section of Fengcheng Third Road, Weiyang District, Xi’an, Shaanxi Province, People’s Republic of China, Tel +86 29-61816515, Email chhty@sina.com; shiwenzhen736@163.comBackground: Ischemic stroke (IS) was a multifactorial disease, which was the main cause of death and adult disability. Genetic factors cannot be ignored.Objective: The present study discussed the relationship between MMP17 variants and the susceptibility of IS.Methods: Based on the Agena MassARRAY platform, we genotyped single nucleotide polymorphisms (SNPs) on the MMP17 gene in 1345 participants (670 controls and 675 cases). We used logistic regression analysis to analyze the association of MMP17 SNPs with the risk of IS in the Chinese population, with odds ratio (OR) and 95% confidence intervals (CIs). False-positive report probability (FPRP) detected false positives on the significant results. Besides, we detected the SNP–SNP interaction to predict IS risk by multi-factor dimensionality reduction (MDR) analysis.Results: In the total analysis, MMP17 rs7975920 conferred an increased susceptibility to IS. After a stratified analysis by age and gender, the significant association between rs7975920 and IS risk was displayed in the subjects aged > 55 years old and females. After stratified analysis by smoking and drinking, MMP17 rs6598163 was related to the risk of IS in smokers and rs7975920 was associated with the risk of IS in smokers and was in correlation with IS risk in drinkers.Conclusion: In short, we first observed that MMP17 rs7975920 and rs6598163 were related to the risk of IS. The above results provided a theoretical basis for the elaboration of the role of MMP17 in IS in the Chinese population.Keywords: ischemic stroke, MMP17, single nucleotide polymorphisms, population

Jia Liu,1 Chunrong Wang,1 Yuchen Gao,1 Yu Tian,1 Yuefu Wang,2 Sudena Wang1 1Department of Anesthesiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Anesthesiology and Surgical Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yuefu Wang, Department of Anesthesiology and Surgical Intensive Care Unit, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing, People’s Republic of China, Tel +86-10-88398082, Email wangyuefu3806@bjsjth.comBackground and Purpose: Chronic postoperative pain (CPSP) after cardiac surgery can cause severe health problems. As demonstrated in noncardiac surgeries, preoperative chronic pain can potentially lead to CPSP. However, the association between preoperative chronic pain and CPSP over follow-up in cardiac surgical settings in the context of sex differences is still lacking. This observational study aims to explore the role and sex differences of preoperative chronic pain in the occurrence and development of long-term CPSP and CPSP-related complications after cardiac surgery.Patients and Methods: This observational study enrolled 495 patients (35.3% women) who underwent cardiac surgery via median sternotomy in March 2019. Validated questionnaires were delivered to assess preoperative chronic pain and moderate to severe CPSP at 3 and 24 months following surgical procedures. The secondary outcomes included the occurrence of moderate to severe chronic pruritus, sleep disturbance, and daily activities interference at follow-up. Multivariable logistic regression was employed.Results: Of 495 patients analyzed, the incidences of preoperative chronic pain (29.7% versus 20.6%) and moderate to severe CPSP (14.8% versus 8.1%) were both higher in females than males. Female sex (P = 0.048) and preoperative chronic pain (P = 0.008) were identified as significant risk factors for CPSP occurrence. However, preoperative chronic pain contributed significantly to CPSP (P = 0.008), sleep disturbance (P =0.047), and daily activities interference (P =0.019) in females, but not in males.Conclusion: The 2-year prevalence of moderate to severe CPSP after cardiac surgery was 10.5%. Compared to males, females are more susceptible to CPSP and pain-related outcomes in the long term. In addition, preoperative chronic pain was associated with a higher risk of CPSP in females but not in males.Keywords: cardiac surgery, chronic postoperative pain, preoperative chronic pain, sex differences

Xiaoshi Sun, Tianlian Li, Yumeng Tian, Shuying Ren, Ling Li, Ping Li Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of ChinaCorrespondence: Ping Li, Email s6800@163.comPurpose: We investigated the association of omentin with metabolic syndrome (MetS), MetS components, and obesity in adolescents.Methods: A total of 742 middle-school students from Liaoyang City were enrolled in this cross-sectional study using the stratified cluster sampling method. Clinical information and blood samples were collected, and serum omentin levels were measured using enzyme-linked immunosorbent assay.Results: Mean plasma omentin levels were lower in male than in female participants (88.25 (interquartile range 63.02– 133.61) vs 99.46 (interquartile range 69.08– 188.35) ng/L, P = 0.004). The participants were divided into four groups according to the quartile (Q) values of omentin from low to high. With increasing omentin levels from Q1 to Q4, the age of adolescents and the proportion of males gradually increased (P < 0.05), whereas the body mass index (BMI) (P < 0.05) and prevalence of MetS (P > 0.05) tended to decrease. Omentin levels were significantly and negatively correlated with waist circumference and BMI (correlation coefficients of ˗0.099 and ˗0.115, respectively). Regression analysis showed that omentin level was independently associated with the risk of MetS (Odds ratio, OR = 0.639, 95% confidence interval, CI (0.432, 0.945)), which was attributed to the association with central obesity (OR = 0.775, 95% CI (0.605, 0.993)) among MetS components. Increased omentin levels also indicated a reduced risk of obesity (OR = 0.700, 95% CI (0.563, 0.870)).Conclusion: Omentin is an independent predictor of MetS and obesity among adolescents in northeast China.Keywords: metabolic syndrome, omentin, adolescents, obesity, insulin resistance

Chao Li,&ast; Lianlei Wang,&ast; Zheng Wang, Donglai Li, Yakubu Ibrahim, Yonghao Tian, Suomao Yuan, Xinyu Liu Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, 250012, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinyu Liu, Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Wenhua West Road 107&num;, Jinan, 250012, People’s Republic of China, Tel +86-18560082585, Fax +86-531-8216-9423, Email newyuliu@163.comObjective: To investigate the differences, correlations, and clinical significance of the paraspinal muscles among patients with isthmic spondylolisthesis (IS), degenerative lumbar spondylolisthesis (DLS), and age-matched healthy subjects.Methods: This study involved 159 age-matched patients with L4 anterior spondylolisthesis. The patients were divided into the IS group (n = 81) and DLS group (n = 78). Eighty-four age-matched healthy adults were enrolled as the control group. The cross-sectional area (CSA) of paraspinal muscles (multifidus [MF], erector spinae [ES], and psoas [PS]) and the relative CSA of the paraspinal muscles (paraspinal muscle CSA/vertebral CSA) were measured in the IS group, DLS group, and control group. The degree of fat infiltration was simultaneously observed.Results: There was no significant difference in age or sex among the three groups. The relative CSA of the MF and PS was higher in control group than in IS and DLS groups (p < 0.05). The relative CSA of ES was higher in IS and control groups than in DLS group (p < 0.05). The relative CSA of total paraspinal muscles decreased in the order of control group > IS group > DLS group (p < 0.05). Logistic regression analysis showed that the relative CSA of MF, and the degree of fat infiltration of ES were independent protective factors for IS (odds ratio < 1, p < 0.05). The relative CSA of MF was an independent protective factor for DLS (odds ratio < 1, p < 0.05), whereas BMI and the degree of fat infiltration of MF were independent risk factor for DLS (odds ratio > 1, p < 0.05).Conclusion: Compared with the control group, patients with IS and DLS showed varying degrees of degeneration, and the degree of degeneration in patients with DLS was more severe at the same age. Lower fat infiltration and higher paraspinal muscle CSA are protective factors for IS and DLS, whereas the higher BMI is risk factor for DLS.Keywords: lumbar vertebrae, spondylolysis, isthmus, degenerative lumbar spondylolisthesis, paraspinal muscle

Meng-Meng Zheng,1,&ast; Ming-Xing Guo,2,&ast; Li-Min Shang,1,&ast; Jian Zhang,1 Jun Lin,1 Ye Tian,1 Xiang-Li Cui,2,&ast; Yi-Chen Zhu1,&ast; 1Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang-Li Cui, Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, No. 95 Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email xianglicui@ccmu.edu.cn Yi-Chen Zhu, Department of Urology, Capital Medical University, Beijing Friendship Hospital, No. 95 Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email zhuyc@ccmu.edu.cnBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has proven to be difficult to control and typically presents with devastating effects.Methods: This retrospective study was conducted on the renal recipients at our institution between January 2021 to January 2022. Clinical data was collected to identify factors associated with CRKP infection and clinical outcomes.Results: There were 104 cases out of 186 total renal recipients who presented with at least one infection within 3 months after KT, and 14 cases developed unfavorable clinical outcomes. We identified 16 confirmed CRKP infected cases with the incidence of 8.60%. Possible donor derived infection (DDI) (OR = 6.743; 95% CI: 1.477– 30.786; P = 0.014) were independent risk factors for the occurrence of CRKP infection of renal recipients in our analysis, CRKP infection (OR = 20.723; 95% CI: 3.448– 124.547; P = 0.001) and pneumonia (OR = 28.458; 95% CI: 1.956– 413.984 P = 0.014) were independent risk factors for the occurrence of unfavorable clinical outcomes following KT, and the occurrence of unfavorable clinical outcomes following KT were significantly associated with CRKP infection (r = 0.535; P < 0.001) and antibiotic regimen containing ceftazidime/avibactam (CZA) (r = − 0.655; P = 0.006). The use of CZA was significantly different in the comparison of antibiotic regimens between the CRKP infected renal recipients with unfavorable outcomes and CRKP infected patients with favorable outcomes.Conclusion: It is possible that DDI can lead to CRKP infection, and CRKP infection and pneumonia were closely correlated with poor prognosis. The use of CZA may play a role in avoiding the unfavorable outcomes of CRKP infected recipients.Keywords: kidney transplant, carbapenem-resistant Klebsiella pneumoniae, early infections, risk factors, clinical outcomes

Yunming Tian,1 Wei-Zeng Huang,2 Lei Zeng,3 Li Bai,1 Fei Han,4,* Yuhong Lan1,* 1Department of Radiation Oncology, Huizhou Central People’s Hospital, Huizhou, Guangdong Province, People’s Republic of China; 2Department of Medical Oncology, Huizhou First Hospital, Huizhou, Guangdong Province, People’s Republic of China; 3Department of Medical Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jixiang Province, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen University Cancer Centre, State Key Laboratory of Oncology in South China, Guangzhou, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fei Han, Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China, Email hanfeisysucc@126.com Yuhong Lan, Department of Radiation Oncology, Hui Zhou Municipal Central Hostpital, Huizhou, Guangdong Province, People’s Republic of China, Email lanyuhonghzyy@126.comObjective: To investigate the treatment outcomes, failure patterns and surveillance strategy in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT).Methods: A cohort of patients with NPC who had received the full course of IMRT between 2008 and 2012 were retrospectively analyzed. The failure patterns, time to recurrence, and detection methods were recorded. The survival was calculated using the Kaplan–Meier method. Multivariate proportional hazard regression models were used to test the prognostic factors.Results: In total, 2607 patients with NPC treated with IMRT were recruited. After the median follow-up of 112 months, 402 (15.4%) patients experienced distant metastasis, 225 (8.6%) patients had local recurrence, and 77 (3.0%) patients had regional recurrences. The 10-year overall survival (OS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 74.5%, 90.1%, and 79.3%, respectively. The factors of male sex, age > 50 years, lactate dehydrogenase > 245 IU/L, advanced T classification, and advanced N classification were associated with poor OS. The N disease classification was the most important factor in predicting distant metastasis, and advanced T disease classification for high risk of local recurrence. For patients with T1 disease, the incidence of local recurrence was less than 2%, and the incidence of distant metastasis was less than 5% for patients with N0 disease. About 83% of the recurrence occurred in the first 5 years, and 20% of the recurrences showed no symptoms.Conclusion: High rate of local-regional control can be achieved for patients with NPC after IMRT, while distant metastasis remains as the major cause of failures. Patients with advanced N classification has high risk to develop distant metastasis, and most occurred within 5 years. Developing rational and individualized surveillance strategies based on the high risk factors of recurrence is helpful to balance the survival benefit and medical cost.Keywords: failure patterns, intensity-modulated radiotherapy, nasopharyngeal carcinoma, surveillance

Kai Wang, Yian Tian, Shanshan Liu, Zhongyuan Zhang, Leilei Shen, Deqian Meng, Ju Li Department of Rheumatology, the Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of ChinaCorrespondence: Ju Li; Deqian Meng, Department of Rheumatology, the affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, 223001, People’s Republic of China, Email liju198461@163.com; deqianmeng2016njmc@163.comBackground: Rapidly progressive interstitial lung disease (RP-ILD) is a significant complication that determines the prognosis of dermatomyositis (DM). Early RP-ILD diagnosis can improve screening and diagnostic efficiency and provide meaningful guidance to carry out early and aggressive treatment.Methods: A retrospective screening of 284 patients with DM was performed. Clinical and laboratory characteristics of the patients were recorded. The risk factors of RP-ILD in DM patients were screened by logistic regression (LR) and machine learning methods, and the prediction models of RP-ILD were developed by machine learning methods, namely least absolute shrinkage and selection operator (LASSO), random forest (RF), and extreme gradient boosting (XGBoost).Results: According to the result of univariate LR, disease duration is a protective factor for RP-ILD, and ESR, CRP, anti-Ro-52 antibody and anti-MDA5 antibody are risk factors for RP-ILD. The top 10 important variables of the 3 machine learning models were intersected to obtain common important variables, and there were 5 common important variables, namely disease duration, LDH, CRP, anti-Ro-52 antibody and anti-MDA5 antibody. The AUC of LASSO, RF and XGBoost test set were 0.661, 0.667 and 0.867, respectively. We further validated the performance of these three models on validation set, and the results showed that, the AUC of LASSO, RF and XGBoost were 0.764, 0.727 and 0.909, respectively. Based on the results of the models, XGBoost is the optimal model in this study.Conclusion: Disease duration, LDH, CRP, anti-Ro-52 antibody and anti-MDA5 antibody are vital risk factors for RP-ILD in DM. The prediction model constructed using XGBoost can be used for risk identification and early intervention in DM patients with RP-ILD and practical application.Keywords: dermatomyositis, interstitial lung disease, risk factor, predictive model, logistic regression, least absolute shrinkage and selection operator, random forest, extreme gradient boosting

Lingling Lu,1,&ast; Wei Gu,2,&ast; Hang Xie,3 Xu Wang,4 Liming Cao,1 Mingfeng Shan,1 Peng Wu,1 Ye Tian,1 Kai Zhou1 1Department of Infectious Disease, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Quality Management, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 3Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 4Department of Endocrinology, Children’s Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ye Tian; Kai Zhou, Department of Infectious Disease, Children’s Hospital of Nanjing Medical University, Guangzhou Road 72, Nanjing, 210000, People’s Republic of China, Tel +86-21-52862898, Email medtronic@163.com; 18951769720@163.comPurpose: The Chinese government has authorized the emergency use of an inactivated vaccine for COVID-19 in children and adolescents aged 3 to 17 years. This study aimed to investigate parents’ attitudes towards vaccinating their children against COVID-19 and influencing factors.Patients and Methods: Through an online questionnaire survey, we collected self-reported children’s demographic characteristics, physical conditions and parents’ attitudes towards COVID-19 vaccination for children. The parents in the unwilling group received online consultation about the benefits and risks of COVID-19 vaccine and were asked to complete the questionnaire again.Results: A total of 868 participants were recruited from July 2021 to August 2021 in Nanjing, China. Overall, 76.0% of parents were willing to accept vaccination for children. Parents’ willingness increased with children’s age (P=0.018) and height (P=0.034), but decreased if the children fell sick within previous one month (P=0.030). Most of the unwilling parents gave a higher score to the risk of vaccination (53.76 VS 40.18). Unsafety (63.8%) and unfamiliarity (24.0%) were their major concerns. After consultation with a health worker, 24% of the unwilling parents turned willing.Conclusion: Children’s age and recent physical condition are related to parents’ attitudes towards vaccination for children against COVID-19. The major concerns of parents are unsafety and unfamiliarity. Parents view health workers as a reliable source of vaccine information. A successful consultation with health workers to understand the benefits and risks of vaccination can increase parents’ willingness. This study provides insight into parents’ attitudes towards vaccination for children against COVID-19 in China and related influencing factors. Our findings could be referenced in establishing policies for vaccinating children against COVID-19 in China.Keywords: COVID-19, vaccine, vaccination willingness, children, China

Chunyue Wang, Yuhang Tian, Bolin Wu, Wen Cheng Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of ChinaCorrespondence: Wen Cheng; Bolin Wu, Department of Ultrasound, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, 150081, People’s Republic of China, Tel +86 13313677182 ; +86 15663615088, Fax +86 451 85718392 ; +86 451 86298651, Email chengwen@hrbmu.edu.cn; wubolin@hrbmu.edu.cnAbstract: Sonodynamic therapy (SDT) is a rapidly developing non-surgical therapy that initiates sensitizers’ catalytic reaction using ultrasound, showing great potential for cancer treatment due to its high safety and non-invasive nature. In addition, recent research has found that using different diagnostic and therapeutic methods in tandem can lead to better anticancer outcomes. Therefore, as essential components of SDT, sonosensitizers have been extensively explored to optimize their functions and integrate multiple medical fields. The review is based on five years of articles evaluating the combined use of SDT and imaging in treating cancer. By developing multifunctional sonosensitive particles that combine imaging and sonodynamic therapy, we have integrated diagnosis into the treatment of precision medicine applications, improving SDT cell uptake and antitumor efficacy utilizing different tumour models. This paper describes the imaging principle and the results of cellular and animal imaging of the multifunctional sonosensitizers. Efforts are made in this paper to provide data and design references for future SDT combined imaging research and clinical application development and to provide offer suggestions.Keywords: sonodynamic therapy, multifunctional sonosensitizers, imaging, ultrasound

Meng-meng Zheng,&ast; Li-min Shang,&ast; Chun-kai Du,&ast; Lei Zhang, Wen Sun, Zhi-peng Wang, Yi-chen Zhu, Ye Tian Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi-chen Zhu; Ye Tian, Department of Urology, Capital Medical University, Beijing Friendship Hospital, No. 95 Yong’an Road, Xicheng District, Beijing, 100050, People’s Republic of China, Email zhuyc82@sina.com; tianye166@126.comBackground: Potent immune-suppressive therapy has been demonstrated to increase the risk of infective endocarditis (IE) in renal recipients. Reports of Corynebacterium striatum (C. striatum) endocarditis in renal recipients are scarce, thus limiting understanding of the disease.Case Presentation: We describe a case of native valve endocarditis caused by C. striatum in a 35-year-old male patient. The young man with end-stage renal failure underwent kidney transplantation because of autosomal dominant polycystic kidney disease. Ceftazidime was administered after the surgery according to routine procedures, and the patient was discharged on the 14th day after the surgery without any evidence of infection. The patient experienced fever on the 56th day, and Corynebacterium was cultured from the patient’s blood, in agreement with the results of testing of the donor kidney preservation solution. On the 64th day, multiple thromboses were found in the right external iliac artery, particularly around the anastomotic orifice of the transplanted renal artery. Vegetation was found in the posterior mitral valve tip on the 65th day. The patient had symptoms of persistent angina pectoris and chest tightness and underwent mitral valve replacement and vegetative resection. The patient eventually died. C. striatum was detected in the mitral valve and vegetation tissue with metagenomic next-generation sequencing.Conclusion: C. striatum may cause endocarditis and endanger patients’ lives and thus warrants greater attention. Genotypic assays such as metagenomic next-generation sequencing are demonstrated to be effective in confirming species identity. Adequate anti-infection therapy and early surgery are required after IE is discovered.Keywords: kidney transplantation, infection, endocarditis, Corynebacterium striatum, case report

Jing Mao,1,&ast; Ya Li,2– 4,&ast; Qingqing Bian,3 Yinshuang Xuan,3 Jingmei Li,3 Zhikun Wang,3 Suxiang Feng,1,2,4 Xuefang Liu,2,4 Yange Tian,2,4 Suyun Li2– 4 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 3Institute for Respiratory Diseases, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Disease by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Suyun Li, Email lisuyun2000@126.comPurpose: Bufei Jianpi formula (BJF), a traditional Chinese medicine, is an effective and safe therapeutic formula for chronic obstructive pulmonary disease (COPD). BJF treatment is known to reduce the incidence of loose stools in rats with COPD. It is unclear whether BJF regulates gut microbiota. This study examined whether BJF improved mucosal immune function by remodeling the gut microbiota and modulating metabolites in COPD rats.Methods: Sixty Sprague Dawley (SD) rats were randomized into control, model, BJF, aminophylline (APL), and probiotics (PBT) groups. The stable COPD rat model was duplicated using repeated cigarette smoke inhalation and lipopolysaccharide (LPS) injection. Normal saline, BJF, APL, or PBT were intragastrically administered from weeks eight to twelve, and then the rats were sacrificed at week thirteen. Lung and colon tissues were removed; feces were collected. Pulmonary function, histopathology, levels of inflammatory factors, and activation of NF-κB in the lung tissues were evaluated. Gut microbiota were analyzed using 16S rRNA gene sequencing; fecal short-chain fatty acid (SCFA) concentrations were determined using gas chromatography/mass spectrometry. Mucosal immune response-related genes and proteins were determined using quantitative polymerase chain reaction and Western blotting.Results: BJF improved pulmonary function and reduced lung inflammation. Further, BJF treatment altered the gut microbiota composition and significantly increased the abundance of Firmicutes and the ratio of Firmicutes to Bacteroides, raising SCFA levels, including acetate, butyrate, and propionate levels. However, the abundance of Bacteroidetes, Proteobacteria, Spirochaetes, Clostridiaceae, and Treponema decreased after BJF administration. BJF decreased the gene and protein expression of NLRP3, Caspase-1, IL-8, and IL-1β, and increased GPR43 expression.Conclusion: Overall, BJF administration improved mucosal immune function by remodeling the gut microbiota and suppressing the SCFAs/GPR43/NLRP3 pathway in COPD rats. This study provides evidence for the mechanisms underlying BJF-induced improvements in COPD and supports clinical application of BJF.Keywords: Bufei Jianpi formula, chronic obstructive pulmonary disease, gut microbiota, gut-lung axis, short-chain fatty acids, mucosal immune function

Ye Tian,1,2 Heng Zhang,1,2 Ying Cao,2 Lu Yang,3 Guangheng Luo1 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, People’s Republic of China; 2Guizhou University School of Medicine, Guiyang, People’s Republic of China; 3Department of Urology, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Guangheng Luo, Tel +86-173-8501-5539, Fax +86-851-8562 1836, Email luoguangheng1975@163.comPurpose: Transurethral resection of the prostate (TURP) is often indicated for benign prostatic hyperplasia (BPH). Some patients, however, fail to adequately respond to these interventions. Accordingly, a powerful prediction model for TURP efficacy is warranted. This study aimed to create a nomogram with preoperative parameters for the prediction of individual TURP efficacy.Methods: Clinical data from 356 BPH subjects who underwent TURP were retrospectively collected between November 2015 and June 2021 for nomogram development. The prediction model was developed using multivariable logistic regression analysis and presented as a nomogram. Nomogram performance was assessed through calibration curves and the concordance index (C-index). An independent validation cohort containing 177 consecutive patients in the corresponding period was used for external validation. The optimal cutoff value was determined through receiver operating characteristic curve (ROC) analysis by maximizing the Youden index, and its accuracy was assessed through sensitivity, specificity and predictive values.Results: In multivariate analysis of the primary cohort, the independent factors for TURP efficacy were age, International Prostate Symptom Score (IPSS), intravesical prostatic protrusion (IPP), bladder wall thickness (BWT), peripheral zone thickness (PT) and transitional zone thickness (TT), all of which were included in the nomogram. The calibration curve for survival probability showed good agreement between the nomogram predictions and actual observations. The C-index for predicting TURP efficacy was 0.860 (95% confidence interval [CI], 0.808– 0.911). The optimal cutoff total nomogram score was 177, with a maximum Youden index of 0.643. The sensitivity, specificity, positive predictive value, and negative predictive value for predicting TURP efficacy were 70.6%, 75.6%, 90.6%, and 43.7% in the validation cohort, respectively. Logistic regression analysis in the validation cohort demonstrated that the area under the curve (AUC) was 0.806 (95% CI, 0.733– 0.879).Conclusion: The P.R.OS.T.A.T.E nomogram objectively and accurately predicted TURP efficacy, thereby facilitating the clinical decision-making process.Keywords: nomogram, benign prostatic hyperplasia, lower urinary tract symptoms, transurethral resection of prostate, efficacy

Ting Zhang,1– 3,&ast; Xiaohui Xie,2– 4,&ast; Qianqian Li,1– 3,&ast; Lei Zhang,2,3,5,6 Yue Chen,2,4 Gong-Jun Ji,2,3,5 Qiangqiang Hou,2– 4 Tianxia Li,7 Chunyan Zhu,2,3,5,6 Yanghua Tian,4,8,9 Kai Wang2– 5,9 1Department of Psychiatry, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 2Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, Anhui Province, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 5School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 6Department of Psychiatry, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 7Anhui Mental Health Center, Hefei, Anhui Province, People’s Republic of China; 8Department of Neurology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China; 9Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyan Zhu; Yanghua Tian, Email ayswallow@126.com; ayfytyh@126.comPurpose: Insomnia is a recognized feature of generalized anxiety disorder (GAD). The underlying neural substrate of insomnia in GAD is still unclear. Cortical folding is a reliable index and possibly an endophenotype of psychiatric disease. The aim of this study was to explore whether the aberrant cortical morphology was associated with insomnia in GAD.Patients and Methods: We enrolled 73 patients with GAD and 74 matched healthy controls (HCs) to undergo neuropsychiatric assessment and 3.0 T magnetic resonance imaging scanning. Neuropsychiatric batteries included the 14-item Hamilton Anxiety Rating Scale (HAMA) and the Insomnia Severity Index (ISI). Using FreeSurfer7.1.1, we calculated local gyrification index, cortical thickness and surface area and identified group differences in these parameters. Then, we calculated the functional connectivity of these identified regions and determined functional alterations. The relationship between these neuroimaging indicators and clinical measurement was explored.Results: Compared with HCs, the LGI in the bilateral orbitofrontal cortex (OFC), bilateral insula, left middle frontal gyrus, left temporal pole, and left fusiform area was significantly decreased in GAD. GAD patients had concurrent decreased surface area in the left OFC and thicker right OFC. GAD patients also exhibited increased functional connectivity between the left insula and frontoparietal control network. In addition, a negative relationship was observed between decreased LGI in these limbic regions and ISI score.Conclusion: GAD patients presented aberrant cortical folding in limbic network. Cortical morphology is a potential endophenotype in GAD, corresponding to an insomnia phenotype.Keywords: generalized anxiety disorder, cortical morphology, insomnia, limbic network, frontoparietal control network