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Caina Liu,1,&ast; Qingqing Zhang,1,2,&ast; Yiming Liu,1 Zixu Wang,1 Fangchen Chen,1 Yitian Li,1 Yami Zhao,1 Jing Zhu,1 Dandan Li,1,3– 5 Chunyan Zhu1– 4,6 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, 230032, People’s Republic of China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, 230000, People’s Republic of China; 3Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, 230032, People’s Republic of China; 4Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, 230032, People’s Republic of China; 5Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 6Department of Psychology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dandan Li; Chunyan Zhu, Email 799200213@qq.com; ayswallow@126.comPurpose: Higher rates of depression are associated with autistic traits; however, the precise association between autistic traits and depression has yet to be fully elucidated. Good interpersonal emotional regulation and social self-efficacy are crucial for mental health; therefore, in this study, we investigated the relationships between autistic traits, interpersonal emotional regulation, social self-efficacy, and depression.Patients and Methods: In total, 1024 participants (613 females and 411 males) aged 16 to 23 years old (M = 19.03, SD = 0.95) completed questionnaires that were designed to evaluate their autistic traits, interpersonal emotion regulation, social self-efficacy and depression. Data were analyzed by Spearman correlation and mediation effects analyses.Results: Autistic traits were significantly and positively correlated with depression (r = 0.39, p < 0.001), and autistic traits were shown to positively predict depression (B = 0.28, p < 0.001). Interpersonal emotion regulation and social self-efficacy were found to play a serial mediating role between autistic traits and depression (indirect effect = 0.020, p = 0.006).Conclusion: This study is a supplement to the mechanism of the relationship between autistic traits and depression. Interpersonal emotion regulation and social self-efficacy are important predictors of possible depression in individuals with high autistic traits. These findings suggest combining interpersonal emotional regulation training and exploring the clinical value of interpersonal emotional regulation interventions in individuals with high autistic traits and autism spectrum disorder, aiming to build social confidence, reduce negative moods, restore social functioning, and other aspects.Keywords: autistic traits, depression, interpersonal emotion regulation, social self-efficacy, chain mediation

Jin-hui Xu,1,* Xiang-long Chen,1,* Qian Zhang,1,* Zhiwei Zhuang,2 Yun-long Yuan,3 Lu-fen Duan,1 Lu Shi,1 Chenqi Zhu,1 Jing-Jing Li,1 Jian Lu,4 Yan-xia Yu,1 Lian Tang1,5 1Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 2Emergency Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 3Medical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 4Intensive Care Unit, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, People’s Republic of China; 5Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian Tang; Yan-xia Yu, Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, No. 26 Daoqian Street, Gusu District, Suzhou, 215002, People’s Republic of China, Tel +86 512 6236 2325, Email tanglian716@aliyun.com; yuyxsz@163.comPurpose: The optimal treatment strategy in patients with hospital-acquired pneumonia (HAP) due to Gram-positive bacteria and renal insufficiency remains challenging. The objective of this study was to compare the outcomes of linezolid versus teicoplanin in HAP patients with renal insufficiency and to explore optimal dosage strategy for linezolid.Methods: The retrospective study enrolled adult patients treated with intravenous linezolid or teicoplanin at Suzhou Municipal Hospital between July 2018 and August 2023. For the comparative pharmacodynamic study, effectiveness, safety and target attainment of trough concentration (Cmin) for teicoplanin versus linezolid treatment in HAP patients with document Gram-positive bacteria and renal insufficiency were compared. For the population pharmacokinetics (PPK) analyses, linezolid concentrations collected exclusively from HAP patients with renal insufficiency were used and the optimal dosage strategy was investigated using Monte Carlo simulations.Results: Linezolid-treated patients had a higher bacterial eradication rate than teicoplanin-treated patients (88.5% vs 63.4%, P < 0.001). A higher proportion of patients in the linezolid group experienced at least one adverse reaction (42.0% vs 25.0%, P = 0.025). Significantly more supratherapeutic Cmin, less therapeutic Cmin were achieved in the linezolid group (adjusted P < 0.05). A total of 207 linezolid concentrations from 166 patients with renal insufficiency were available for the PPK analysis. Age and creatinine clearance (CrCL) were identified as significant covariates that influenced clearance. Simulations show that 300 mg q12h provide the optimal exposure in patients with a CrCL of 60 or 45 mL/min, and 200 mg q12h was recommended for patients with a CrCL of 30 or 15 mL/min.Conclusion: Linezolid-treated patients with HAP and renal insufficiency had higher bacterial eradication rates, supratherapeutic exposure and adverse reactions than teicoplanin-treated patients. Linezolid dose reduction in patients with renal insufficiency improved the probability of achieving optimal exposure.Keywords: linezolid, population pharmacokinetic, pharmacodynamic, renal insufficiency, hospital-acquired pneumonia

Jan Hillert,1 Helmut Butzkueven,2,3 Melinda Magyari,4 Stig Wergeland,5,6 Nicholas Moore,7 Merja Soilu-Hänninen,8 Tjalf Ziemssen,9 Jens Kuhle,10 Luigi Pontieri,11 Lars Forsberg,1 Jan Harald Aarseth,5 Chao Zhu,2 Nicholas Sicignano,12 Vasili Mushnikov,13 Irene Bezemer,14 Meritxell Sabidó15 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 2Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia; 3The Alfred Hospital, Melbourne, Victoria, Australia; 4Danish Multiple Sclerosis Center and Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 5Norwegian MS Registry and Biobank, Department of Neurology, Haukeland University Hospital, Bergen, Norway; 6Department of Clinical Medicine, University of Bergen, Bergen, Norway; 7Bordeaux PharmacoEpi (BPE), Université de Bordeaux, Bordeaux, France; 8Turku University Hospital Neurocenter and Division of Clinical Neurosciences, University of Turku, Turku, Finland; 9Center of Clinical Neuroscience, Department of Neurology, University Clinic Carl Gustav Carus, Dresden University of Technology, Dresden, Germany; 10MS Centre and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Neurology, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland; 11Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; 12Health ResearchTx LLC, Trevose, PA, USA; 13IQVIA, Helsinki, Finland; 14IQVIA, Amsterdam, the Netherlands; 15Merck Healthcare KGaA, Darmstadt, GermanyCorrespondence: Meritxell Sabidó, Merck Healthcare KGaA, Frankfurter Str. 250, Darmstadt, 64293, Germany, Email meritxell.sabido-espin@merckgroup.comPurpose: Understanding the long-term safety of disease-modifying therapies for multiple sclerosis (MS) in routine clinical practice can be undertaken through registry-based studies. However, variability of data quality across such sources poses the challenge of data fit for regulatory decision-making. CLARION, a non-interventional cohort safety study of cladribine tablets, combines aggregated data from MS registries/data sources, except in Germany (which utilizes primary data collection). We describe the application of key data quality indicators (DQIs) within CLARION to evaluate data quality over time, as recommended by the European Medicines Agency (EMA) guideline on registry-based studies.Methods: DQIs were defined with participating registries/sources; they were used to assess data quality according to the EMA Data Quality Framework, addressing consistency, accuracy, completeness, and study representativeness. DQIs were associated with potential remedial measures if data quality was not met. DQIs were summarized overall and for individual MS registries/data sources to November 1, 2022.Results: A total of 28 DQIs were analyzed using data from 5069 patients arising from eight MS registries/data sources and 14 countries. The Representativeness DQIs showed that 72.0% of patients were female, median age at MS diagnosis was 29.0 to 43.3 years, and 93.5% had relapsing-remitting MS. Consistency DQIs showed a total of 2899 patients had achieved at least two years of follow-up; 6.9% did not have any recorded visits during this timeframe. Discrepant values were assessed as part of Accuracy DQIs, and improvements over time were noted for recorded dates of MS onset and diagnosis. Regarding Completeness DQIs, 191/5069 (3.8%) patients were lost to follow-up.Conclusion: The application of 28 DQIs within the CLARION study has helped with understanding, not only intrinsic and question-specific determinants of data quality, but also tracking the quality of post-authorization safety data obtained from MS registries/data sources, thereby providing a foundation for the regulatory decision-making process.Keywords: cladribine tablets, multiple sclerosis, safety, fingolimod

Wei Zu,1,&ast; Shaojiong Zhou,2,&ast; Tao Du,1 Chenyanwen Zhu,3 Siyue Nie,4 Hongwei Zhu1 1Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, People’s Republic of China; 3 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 4Chinese PLA Medical School; Department of Oncology, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongwei Zhu, Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China, Email zhuhongwei@xwh.ccmu.edu.cnIntroduction: This study aims to investigate the potential causal effects of modifiable risk factors on Fibromyalgia (FM).Methods: Genetic variants associated with 34 exposure factors were obtained from Genome-wide association studies (GWAS). Summary statistics for FM were acquired from the FinnGen consortium. Bidirectional Mendelian randomization (MR) analysis was conducted between all exposures and outcomes. The inverse-variance weighted (IVW) method was employed as the primary estimation technique. Heterogeneity and pleiotropy were assessed using MR-PRESSO global test, the weighted median, Cochran’s Q statistic and MR-Egger.Results: Depression (OR=2.087, 95% CI: 1.466– 2.971), alcohol consumption (OR=1.489, 95% CI: 1.094– 2.028), body fat percentage (OR=1.524, 95% CI: 1.153– 2.013) and body mass index (BMI) (OR=1.542, 95% CI: 1.271– 1.872) were associated with an increased risk of FM among genetically susceptible individuals. Conversely, higher education level (OR=0.404, 95% CI: 0.297– 0.549), longer years of education (OR=0.489, 95% CI: 0.290– 0.825) and higher household income (OR=0.328, 95% CI: 0.215– 0.502) were protective against FM. Additionally, rheumatoid arthritis (OR=1.138, 95% CI: 1.061– 1.221) and ankylosing spondylitis (OR=1.079, 95% CI: 1.021– 1.140) were identified as important risk factors for FM.Conclusion: This MR study unveiled a complex causal relationship between modifiable risk factors and FM. Psychosocial factors significantly increase the odds of FM, while obesity and some autoimmune diseases that frequently coexist with FM demonstrate causal associations. Additionally, lifestyle habits such as alcohol consumption are causally related to FM. Further investigation is needed to determine whether risk factors contribute to the pathogenesis of FM through mechanisms involving central sensitization, inflammatory, and hyperalgesia. This study enhances our understanding of the factors that drive FM onset and progression, offering valuable insights for future targeted prevention and treatment strategies.Keywords: fibromyalgia, modifiable risk factors, causal association, Mendelian randomization

Shangtao Wang,1 Chenghao Zhu,1 Shurui Zhang,1 Siyu Ma,1 Baoshan Li,1 Shengbo Zhao,2 Wei Zhang,3 Zhirong Sun1 1School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Ningqiang Tianma Research Institution Limited Liability Company, Hanzhong, Shaanxi, People’s Republic of China; 3Ningqiang County Traditional Chinese Medicinal Industry Development Center, Hanzhong, Shaanxi, People’s Republic of ChinaCorrespondence: Zhirong Sun, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Northeast Corner of the Intersection of Yangguang South Street and Baiyang East Road, Fangshan District, Beijing, 102401, People’s Republic of China, Email szrbucm67@163.comBackground: Hypertension (HTN) is closely related to endothelial damage. While tianma (TM) and gouqizi (GQZ) have the potential to be effective in the treatment of HTN in traditional Chinese medicine, their main active ingredients and whether its exert synergistic effects and the underlying mechanisms of synergistic effects are still unclear.Objective: This study screened the active ingredients of TM and GQZ, investigated the synergistic effects of the active ingredients and explored possible mechanisms.Methods: The potential targets and mechanisms of TM and GQZ were screened using network pharmacology, and gastrodin (GAS) and gallic acid (GA) were identified as compounds with significant antihypertensive activity. The synergistic effects of the combination of GAS and GA was assessed by measuring biomarkers of AngII-induced human umbilical vein endothelial cell (HUVECs) dysfunction model. Furthermore, the anti-apoptotic and anti-inflammatory effects were evaluated by measuring inflammatory cytokine secretion, and apoptosis-related markers. Finally, key targets of the sphingolipid signaling pathway were experimentally validated by Western blotting.Results: In network pharmacology, the herb-pair exerted a synergetic effect by regulating sphingolipid pathways. The GAS and GA exerted synergistic protective effects in AngII-induced HUVECs injury by improving Nitric Oxide Content (NO) levels, alleviating lactate Endothelin-1 (ET-1), and Thromboxane B2 (TX-B2) release, reducing the secretion of inflammatory factors like interleukin-6 (IL-6), interleukin-1β (IL-1β), Tumor Necrosis Factor Alpha (TNF-α)), decreasing the pro-apoptotic protein BAX, and increasing the anti-apoptotic protein BCL-2. Furthermore, the results showed that the GAS and GA combination could elevate the level of S1PR1 and inhibit the expression of ROCK2 and the phosphorylation of NF-κB, which are key targets involved in sphingolipid pathways.Conclusion: Our study revealed that the combination of GAS and GA could suppress inflammation and apoptosis, which are highly correlated with sphingolipid signaling pathways, making it a potential candidate for the treatment of HTN. Keywords: gastrodin, gallic acid, synergistic effects, inflammation, apoptosis, sphingolipid pathways

Chan Li,1,2,&ast; Chen Zhu,3,&ast; Genghong Tu,4,&ast; Zhijie Chen,1 Zhixian Mo,1,5 Chaohua Luo1,5 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Life Sciences, Guangzhou University, Guangzhou, People’s Republic of China; 3The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Department of Sports Medicine, Guangzhou Sport University, Guangzhou, Guangdong, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixian Mo, Mo; Chaohua, Luo, School of Traditional Chinese Medicine, Southern Medical University, 1023-1063 Shatai South Road, Guangzhou, 510515, People’s Republic of China, Tel +020-61648261 ; +020-61648244, Email cherrymo@fimmu.com; 120557369@qq.comObjects: Ketamine is a drug of abuse worldwide and current treatments for ketamine abuse are inadequate. It is an urgent need to develop novel anti-addictive strategy. Since gut microbiota plays a crucial role in drug abuse, the present study investigates the impact and mechanisms of the gut microbiota in addictive behaviors induced by ketamine addiction.Methods: Conditioned place preference (CPP) was employed to assess addiction, followed by 16S rRNA gene sequencing to elucidate alterations in the gut microbiota. Furthermore, qRT-PCR, ELISA, and immunohistochemistry were conducted to evaluate the expression levels of crucial genes and proteins associated with the gut-brain axis. Additionally, we investigated whether ketamine addiction is regulated through the gut microbiota by orally administering antibiotics to establish pseudo-germ-free mice.Results: We found that repeated ketamine administration (20 mg/kg) induced CPP and significantly altered gut microbiota diversity and composition, as revealed by 16S rRNA gene sequencing. Compared to the control group, ketamine exposure exhibited differences in the relative abundance of 5 microbial families, with 4 (Lachnospiraceae, Ruminococcaceae, Desulfovibrionaceae and Family-XIII) showing increases, while one (Prevotellaceae) displayed a decrease. At the genus level, five genera were upregulated, while one was downregulated. Furthermore, COG analysis revealed significant differences in protein functionality between the two groups. Additionally, axis series studies showed that ketamine dependence reduced levels of tight junction proteins, GABA and GABRA1, while increasing BDNF and 5-HT. Moreover, an oral antibiotic cocktail simulating pseudo germ-free conditions in mice did not enhance the addictive behavior induced by ketamine.Conclusion: Our study supports the hypothesis that ketamine-induced CPP is mediated through the gut microbiota. The present study provides new insights into improvement of efficient strategy for addiction treatment.Keywords: ketamine abuse, BDNF, GABRA1, gut microbiota, gut-brain axis

Shanshan Ai,1,&ast; Yue Wang,2 Pengli Niu,2 Wenjun Xiao,2 Guojun Xu,2 Chang Zhu3,&ast; 1Department of Nursing, Linping District Hospital of Integrated Traditional Chinese and Western Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Nursing, The First Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Expanded Program on Immunisation, Linping District Centre for Disease Control and Prevention, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guojun Xu, Department of Nursing, The First Affiliated Hospital of Dalian Medical University, No. 222, Zhongshan Road, Xigang District, Dalian, Liaoning, 116011, People’s Republic of China, Email xgj1973@163.comPurpose: This study aimed to investigate the correlation between preoperative pain catastrophizing and social support, and acute post-surgical pain in patients who underwent knee arthroplasty. The study also aimed to determine whether social support moderates the role of pain catastrophizing psychologically in acute post-surgical pain after knee arthroplasty.Patients and Methods: This study recruited participants to survey a tertiary hospital in Dalian, China, between November 2022 and October 2023. Participants completed pain catastrophizing scales and social support reevaluated scales one day (T1) before they were confirmed to undergo knee arthroplasty, and finished the Numeric Rating Scale at 24h (T2), 48h (T3), and 72h (T4) postoperatively. Pearson correlation analyses were used to explore the relationship between social support, pain catastrophizing, and acute post-surgical pain, hierarchical regression analysis was used to test the moderating role of social support between pain catastrophizing and acute post-surgical pain.Results: This study recruited 178 knee arthroplasty patients. The results of the t-test or one-way ANOVA indicated that there were statistically significant differences in gender, age, education, occupation, disease duration, whether the knee replacement was performed for the first time, preoperative pain scores, and operation time in patients with knee arthroplasty (P < 0.05). The correlation analysis of social support, pain catastrophization, and acute post-surgical pain in knee arthroplasty patients showed that social support was negatively correlated with acute post-surgical pain (r=− 0.584, P< 0.01), and pain catastrophizing was positively correlated with postoperative acute pain (r=0.601, P< 0.01); The hierarchical regression analysis revealed that social support had a significant moderating effect on the relationship between pain catastrophizing and acute post-surgical pain (ΔR2=0.606, P< 0.05).Conclusion: The acute post-surgical pain of knee arthroplasty patients was affected by gender, age, education, occupation, disease duration, whether the knee arthroplasty was performed for the first time, preoperative pain scores, and operation time. Acute Post-surgical pain in patients with knee arthroplasty was affected by social support and pain catastrophizing, and social support had a moderating effect on the relationship between pain catastrophizing and acute post-surgical pain.Keywords: knee arthroplasty, pain, pain catastrophizing, social support

Fangqian Du,1,&ast; Yuwei Xie,1,&ast; Shengze Wu,1 Mengling Ji,2 Bingzi Dong,3 Chengzhan Zhu1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima, Japan; 3Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chengzhan Zhu, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel +86 0532-82919552, Fax +86 0532-82911885, Email zhuchengz@qduhospital.cn Bingzi Dong, Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China, Tel/Fax +86-82911383, Email dongbingzi@hotmail.comAbstract: Hepatobiliary and pancreatic diseases are becoming increasingly common worldwide and associated cancers are prone to recurrence and metastasis. For a more accurate treatment, new therapeutic strategies are urgently needed. The claudins (CLDN) family comprises a class of membrane proteins that are the main components of tight junctions, and are essential for forming intercellular barriers and maintaining cellular polarity. In mammals, the claudin family contains at least 27 transmembrane proteins and plays a major role in mediating cell adhesion and paracellular permeability. Multiple claudin proteins are altered in various cancers, including gastric cancer (GC), esophageal cancer (EC), hepatocellular carcinoma (HCC), pancreatic cancer (PC), colorectal cancer (CRC) and breast cancer (BC). An increasing number of studies have shown that claudins are closely associated with the occurrence and development of hepatobiliary and pancreatic diseases. Interestingly, claudin proteins exhibit different effects on cancer progression in different tumor tissues, including tumor suppression and promotion. In addition, various claudin proteins are currently being studied as potential diagnostic and therapeutic targets, including claudin-3, claudin-4, claudin-18.2, etc. In this article, the functional phenotype, molecular mechanism, and targeted application of the claudin family in hepatobiliary and pancreatic diseases are reviewed, with an emphasis on claudin-1, claudin-4, claudin-7 and claudin-18.2, and the current situation and future prospects are proposed.Keywords: claudins, hepatocellular carcinoma, cholangiocarcinoma, pancreatic cancer, targeted therapy

Jianqun Yin,&ast; Jiawei Chen,&ast; Ting Wang, Huiming Sun, Yongdong Yan, Canhong Zhu, Li Huang, Zhengrong Chen Respiratory Department, Children’s Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhengrong Chen; Li Huang, Respiratory Department, Children’s Hospital of Soochow University, No. 303 Jingde Road, Gusu District, Suzhou City, Jiangsu Province, People’s Republic of China, Tel +86-13771721180 ; +86-18962183510, Email chenzhengrong@suda.edu.cn; huanglilcy@163.comObjective: To investigate the significance of VISTA in bronchial asthma and its impact on the disease.Methods: Human peripheral blood of asthma children was gathered. The expression concentrations of VISTA, IL-4, IL-6, CD25, CD40L, and PD-L2 in peripheral blood plasma were detected by ELISA. We established the mouse model of asthma and intervened with agonistic anti-VISTA mAb (4C11) and VISTA fusion protein. ELISA, flow cytometry, and Western blotting were performed to detect the expression levels of Th1, Th2, and Th17 cell subsets and related characteristic cytokines, as well as the protein levels of MAPKs, NF-κB, and TRAF6 in lung tissues. In addition, the infiltration of eosinophils and inflammatory cells, airway mucus secretion, and VISTA protein expression in lung histopathological sections of different groups of mice were analyzed.Results: The concentration of VISTA in human asthma group decreased significantly (p < 0.05); A positive correlation was observed between VISTA and CD40L. The intervention of 4C11 mAb and fusion protein respectively during the induction period increase the differentiation of Th1 cells and the secretion of IFN-γ, and inhibit the differentiation of Th2 and Th17 cells, as well as the secretion of IL-4, IL-5, IL-13 and IL-17, partially reduce the pathological changes of asthma in mouse lungs and correct the progress of asthma. The MAPK, NF-κB, and TRAF6 protein levels were the middle range in the 4C11 mAb and fusion protein groups (p < 0.05).Conclusion: The findings suggest VISTA may play a negative regulatory role in the occurrence and development of bronchial asthma.Keywords: VISTA, bronchial asthma, Th2 cells, cytokines, anti-VISTA mAb, VISTA fusion protein

Zhanjie Li,1,&ast; Jian Li,2,&ast; Chuanlong Zhu,3 Shengyuan Jiao1,2 1Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China; 2Department of Disease Prevention and Control, Air Force Hospital of Eastern Theater, Nanjing, People’s Republic of China; 3Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shengyuan Jiao, Department of Infection Control, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8618021136781, Email 17319884906@163.com Chuanlong Zhu, Department of Infections Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +8617714316539, Email zhuchuanlong@jsph.org.cnBackground: To identify risk factors for acquiring HAIs in COVID-19 patients and establish visual prediction model.Methods: Data was extracted from Xinglin Hospital Infection Monitoring System to analyze COVID-19 patients diagnosed between December 1, 2022, and March 1, 2023. Univariate and multivariate analyses were conducted to identify risk factors. Predictive signature was developed by selected variables from lasso, logistic regression, and their intersection and union. Models were compared using DeLong’s t-tests. Likelihood ratio (LR) and Youden’s index was used to evaluate the predictive performance. Nomogram was constructed using optimal variables ensemble, prediction accuracy was evaluated using AUC, DCA and calibration curve.Results: Total of 739 patients met the criteria, of which 53 (7.2%) were HAIs. NSAIDs, surgery, fungi and MDRO detected, hormone drugs and LYMR were independent risk factors. Lasso model screened seven variables, and logistic model identified six risk factors. Union model performed the best with the maximum of the Youden’s index is 0.703, the sensitivity is 95.6%, the specificity is 74.7%, the LR is 3.778. The best AUC of union model is 0.953 (0.928– 0.978), and the accuracy is 87.5%. DCA indicated that the union model provided the best net benefits and calibration curve demonstrated good predictive agreement.Conclusions: HAIs prediction in COVID-19 patients is feasible and beneficial to improve prognosis. Physicians can use this nomogram to identify high-risk COVID-19 populations for HAIs and tailor follow-up strategies.Keywords: risk factors, healthcare-associated infection, COVID-19, nomogram, prediction model

Jiaying Lao,1,2,&ast; Hang Tan,3,&ast; Yuyu Wu,2,&ast; Ting Ding,4 Xinqian Liu,1 Lanrong Sun,2 Xiyi Chen,2 Chongrong Zhu,2 Yiming Kang,5 Yu-Hsin Chen,2,6 Chonghui Tang,1 Fan Wang,7 Yanlong Liu2,6 1Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of neurosurgery, Hangzhou Mingzhou Brain Rehabilitation Hospital, Hangzhou, People’s Republic of China; 4Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, People’s Republic of China; 5Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 7Beijing Hui−Long−Guan Hospital, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlong Liu, School of Mental Health, Medical University, Wenzhou, 325035, People’s Republic of China, Email benjaminlyl@wmu.edu.cn Chonghui Tang, Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, People’s Republic of China, Email tangegg@163.comObjective: Cigarette smoking and low peripheral nitric oxide synthase (NOS) levels are strongly associated with sleep disorders. However, whether cerebrospinal fluid (CSF) NOS relates to sleep disorders and whether CSF NOS mediates the relationship between cigarette smoking and sleep disorders is unclear.Methods: We measured CSF levels of total NOS (tNOS) and its isoforms (inducible NOS [iNOS] and constitutive NOS [cNOS]) in 191 Chinese male subjects. We applied the Pittsburgh Sleep Quality Index (PSQI).Results: The PSQI scores of active smokers were significantly higher than those of non-smokers, while CSF tNOS, iNOS, and cNOS were significantly lower (all p < 0.001). CSF tNOS, iNOS, and cNOS were negatively associated with PSQI scores in the general population (all p < 0.001). Mediation analysis suggested that CSF tNOS, iNOS, and cNOS mediate the relationship between smoking and PSQI scores, and the indirect effect accounted for 78.93%, 66.29%, and 81.65% of the total effect, respectively.Conclusion: Cigarette smoking is associated with sleep disorders. Active smokers had significantly lower CSF levels of tNOS, iNOS, and cNOS. Furthermore, tNOS, iNOS, and cNOS mediate the relationship between cigarette smoking and sleep quality. This study provides insights into how cigarette smoke affects sleep disorders.Keywords: cerebrospinal fluid nitric oxide synthase, cigarette smoking, Pittsburgh Sleep Quality Index, sleep disorders, mediation

Yingze Hou,1,2 Can Zhu,3 Ge Ban,1 Zhean Shen,4 Yingbing Liang,5 Kun Chen,1 Chenbo Wang,1 Heng Shi4 1School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 2Clinical Medical College, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Urology, The Second Clinical Medical College of Anhui Medical University, Hefei, 230032, People’s Republic of China; 4Heart Center, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China; 5Department of Chemistry and Biotechnology, Graduate School of Engineering Tottori University Koyama-Minami 4-101, Tottori, 680-8552, JapanCorrespondence: Ge Ban, School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China, Email bange119@qq.comAbstract: Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.Keywords: metal-organic frame, oncotherapy, photothermal effect, tumor immunity, drug delivery

Tingting Shao,1 Chengwei Zhu,2 Hanning Lei,2 Yiru Jiang,3 Haitao Wang,4 Cai Zhang2 1Institute of Early Childhood Education, Faculty of Education, Beijing Normal University, Beijing, People’s Republic of China; 2Collaborative Innovation Center of Assessment for Basic Education Quality, Beijing Normal University, Beijing, People’s Republic of China; 3School of Education Science, Shangrao Normal University, Shangrao, People’s Republic of China; 4Department of education, Ocean University of China, Qingdao, People’s Republic of ChinaCorrespondence: Cai Zhang, Collaborative Innovation Center of Assessment for Basic Education Quality, Beijing Normal University, No. 19 Xinjiekouwai Street, Beijing, 100875, People’s Republic of China, Email caizhangbj@163.comPurpose: With the increasing ubiquity of smartphones in our daily lives, technoference has emerged as a novel threat to family relationships and child development. This study explored the impact of parent-child technoference on child problematic smartphone use and its underlying mechanism and potential gender difference among children.Participants and Methods: The participants were 3032 fourth-grade students (42.6% female; 80.6% one-child families; 32.9% lower income level families, 33.3% middle income level families; Mage = 10.59 years, SD=0.32) from 535 primary schools. Students in the target classes were invited to participate anonymously in the questionnaire survey in classrooms. Then, SPSS, AMOS and other software were used to analyze the data.Results: 1) Parent-child technoference, negative parenting styles and child problematic smartphone use were positively correlated with each other, while they were negatively correlated with parent-child relationship; 2) Parent-child technoference can not only directly and positively predict child problematic smartphone use, but also indirectly and positively predict child problematic smartphone use through parent-child relationship and negative parenting styles respectively; 3) Parent-child relationship and negative parenting styles play a chain mediating role between parent-child technoference and child problematic smartphone use; 4) There are significant gender differences in the chain mediation model.Conclusion: The results showed that parent-child technoference significantly affected child problematic smartphone use through a chain mediation of parent-child relationship and negative parenting styles. Gender differences were observed, with girls experiencing a more pronounced disruption in the parent-child relationship, while boys were more likely to develop problematic smartphone use. In cases of strained parent-child relationships due to technoference, girls also tended to perceive more negative parenting styles. These findings promote parents’ understanding of the influencing factors and mechanisms of child problematic smartphone use, especially helpful for follow-up measures to prevent and intervene child problematic smartphone use from the perspective of families and parents.Keywords: parent-child technoference, parent-child relationship, negative parenting styles, child problematic smartphone use, gender difference

Caizhi Sun,1,2,&ast; Yongpeng Xie,1,&ast; Chenchen Zhu,2 Lei Guo,2 Jingjing Wei,2 Bowen Xu,2 Yang Song,2 Haidong Qin,2 Xiaomin Li1 1Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang City, Lianyungang, Jiangsu, 222000, People’s Republic of China; 2Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing City, Jiangsu Province, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaomin Li, Department of Emergency Medicine, Lianyungang Clinical College of Nanjing Medical University, The First People’s Hospital of Lianyungang City, 182 Tongguan North Road, Haizhou District, Lianyungang City, Jiangsu Province, People’s Republic of China, Email lyglxmsj@163.com Haidong Qin, Department of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing City, Jiangsu Province, People’s Republic of China, Tel/Fax +8602552271264, Email icuqhd@163.comBackground: To date, there are no studies regarding the Mrp 8/14 in predicting the occurrence of acute respiratory distress syndrome (ARDS) induced by sepsis. Thus, the objective of this study was to investigate the expression of Myeloid-related proteins 8 and 14 (Mrp 8/14) and its role in ARDS induced by sepsis.Methods: A total of 168 septic patients were enrolled in the observational study. The baseline information and clinical outcomes were obtained retrospectively. Serum Mrp 8/14 level was determined by enzyme linked immunosorbent assay (ELISA). The patients were categorized into sepsis and ARDS group based on whether they developed ARDS during the intensive care unit (ICU) hospitalization.Results: There was significant difference in the level of Mrp 8/14 between the sepsis group and ARDS groups (P < 0.05). Mrp 8/14 correlated positively with procalcitonin (PCT), interleukin-6 (IL-6), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score on day 1, mechanical ventilation time, length of ICU stay and hospitalization expenses in ICU (all P < 0.05). Logistic regression analysis showed Mrp 8/14 was the independent factor for forecasting the occurrence of sepsis- induced ARDS (P < 0.05). The areas under receiver operating characteristic curves for Mrp 8/14 were higher than that of PCT, APACHE II score and SOFA score on day 1 (P < 0.05).Conclusion: The serum Mrp 8/14 level at admission may be a potential marker for predicting the occurrence of ARDS induced by sepsis. Early detection of serum Mrp 8/14 could help clinicians to identify and evaluate the severity of ARDS induced by sepsis.Keywords: sepsis, acute respiratory distress syndrome, Mrp 8/14, inflammation, intensive care unit

Liguo Lu,1,2 Chengdong Zhu,3 Jian Xu,4 Yulan Hu,2 Juxiang Dai,2 Sheng Wang,2 Tao Wei1,5 1Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Shuyang Hospital, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian, People’s Republic of China; 3Department of Traditional Chinese Medicine, Shuyang Hospital, The Affiliated Shuyang Hospital of Xuzhou Medical University, Suqian, People’s Republic of China; 4Taian Maternal and Child Health Hospital, Tai An, Shandong, People’s Republic of China; 5Public Experimental Research Center, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of ChinaCorrespondence: Tao Wei, 209 Tongshan Road, Xuzhou City, Jiangsu Province, People’s Republic of China, Tel +8613815303574, Email weitaoxy@126.comIntroduction: The Lifei Decoction (LD) is a commonly utilized Chinese medicine for the treatment of sepsis and bronchial inflammation. However, its therapeutic potential in chronic obstructive pulmonary disease (COPD) remains unknown. Therefore, the objective of this study was to investigate the therapeutic efficacy and underlying mechanism of LD in a mouse model of COPD induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS).Methods: Hematoxylin-eosin (H&E) staining was employed to observe the pathological alterations in lung tissue, while ELISA was utilized for the detection of levels of inflammatory factors in both lung tissue and bronchoalveolar lavage fluid (BALF). Additionally, Western blot analysis was conducted to assess the expression of p-NF-κB, GDF11, ZO-1, and Occludin-1 proteins. The changes in intestinal flora were evaluated using the viable bacteria count method.Results: The administration of LD demonstrates significant efficacy in mitigating pulmonary tissue damage in a murine model, while concurrently inhibiting the activation of the inflammatory pathway NF-κB to attenuate the levels of pro-inflammatory factors. Moreover, LD exhibits the capacity to enhance the expression of intestinal functional proteins ZO-1 and Occludin-1, thereby rectifying dysbiosis within the gut microbiota.Conclusion: The LD shows great promise as a potential treatment for COPD.Keywords: COPD, lifei decoction, inflammation, intestinal flora

Jun’e Ma,1,* Zhenhui Wang,1,* Chuanjin Luo,2 Jin’ou Xi,1 Xiaojing Wang,1 Yan Hu,1 Chengliang Zhu,3 Zhengjiang Jin1 1Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China; 2State Key Laboratory of Virology College of Life Sciences, Wuhan University, Wuhan, 430060, People’s Republic of China; 3Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengjiang Jin, Department of Clinical Laboratory, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430070, People’s Republic of China, Email king199735@126.com Chengliang Zhu, Department of Clinical Laboratory, Institute of Translational Medicine, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China, Email zhuchengliang@whu.edu.cnPurpose: To understand the epidemiology and clinical features of Ureaplasma urealyticum (UU) infection in hospitalized neonates due to vertical transmission from mother to child.Methods: Respiratory secretions were collected from neonates hospitalized in the neonatology department of the Maternal and Child Health Hospital of Hubei Province from July 2020 to June 2022, and PCR was used to detect UU-DNA in respiratory secretions. The neonates were divided into UU-positive and UU-negative groups, the epidemiological and clinical characteristics of two groups, were statistically analyzed.Results: A total of 7257 hospitalized neonates were included in this study, of whom 561 were UU positive and 6696 were UU negative, with a UU detection rate of 7.73%. The detection rate among female neonates was higher than male neonates, and the highest detection rate was found in the period from 1– 7 days after birth; the detection rate was highest in spring and fall, and the lowest in winter, but the overall difference was not statistically significant (P> 0.05). Compared with the UU-negative group, neonates in the UU-positive group were more likely to be preterm, have a lower birth weight, be delivered vaginally, and have maternal preterm rupture of membranes. In addition, neonates in the UU-positive group were more likely to be co-infected with pathogens and to have complications related to UU infections, which were all statistically significant (P< 0.05).Conclusion: Neonatal UU infections are detected more frequently in female infants, with the highest detection rate occurring in 1– 7 days after birth, and the most prevalent periods for infection being spring and fall. Vaginal delivery and premature rupture of membranes may lead to an increased risk of vertical UU transmission from mother to child, and UU infection is strongly associated with preterm labor, low birth weight, pathogen co-infection, and related complications.Keywords: Ureaplasma urealyticum, neonates, infection, epidemiology, clinical characteristics, co-infection

Guanming Shao,&ast; Yonghui Ma,&ast; Chao Qu, Ruiqian Gao, Chengzhan Zhu, Linlin Qu, Kui Liu, Na Li, Peng Sun, Jingyu Cao Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Sun; Jingyu Cao, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, 266000, People’s Republic of China, Email psun1@qdu.edu.cn; cjy7027@163.comBackground: Circulating eosinophils are associated with tumor development. An eosinophil-related index, the neutrophil to eosinophil ratio (NER), can be used to predict the prognosis of patients with tumors. However, there is still a lack of efficient prognostic biomarkers for HCC. In this study, we aimed to investigate the predictive value of the NER and develop an optimal machine learning model for the recurrence of HCC patients. Patients and methods: A retrospective collection of 562 patients who underwent hepatectomy with a pathologic diagnosis of HCC was performed. The relationship between NER and progression-free survival (PFS) was investigated. We developed a new machine learning framework with 10 machine learning algorithms and their 101 combinations to select the best model for predicting recurrence after hepatectomy. The performance of the model was assessed by the area under the curve (AUC) of characteristics and calibration curves, and clinical utility was evaluated by decision curve analysis (DCA).Results: Kaplan‒Meier curves showed that the PFS in the low NER group was significantly better than that in the high NER group. Multivariate Cox regression analysis showed that NER was an independent risk factor for recurrence after surgery. The random survival forests (RSF) model was selected as the best model that had good predictive efficacy and outperformed the TNM, BCLC, and CNLC staging systems.Conclusion: The NER has good predictive value for postoperative recurrence in patients with hepatocellular carcinoma. Machine learning model based on NER can be used for accurate predictions.Keywords: hepatocellular carcinoma, liver resection, recurrence, machine learning, neutrophil-to-eosinophil ratio

Fang-Yi Yu,&ast; Kua Zheng,&ast; Yin-Fang Wu,&ast; Shen-Wei Gao, Qing-Yu Weng, Chen Zhu, Yan-Ping Wu, Miao Li, Zhong-Nan Qin, Jia-Fei Lou, Zhi-Hua Chen, Song-Min Ying, Hua-Hao Shen, Wen Li Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Li, Tel +86-571-87783729, Fax +86-571-87068001, Email liwen@zju.edu.cnPurpose: This study aimed to explore the effect of Rapamycin (Rapa) in Staphylococcus aureus (S. aureus) pneumonia and clarify its possible mechanism.Methods: We investigated the effects of Rapa on S. aureus pneumonia in mouse models and in macrophages cultured in vitro. Two possible mechanisms were investigated: the mTOR-RPS6 pathway phosphorylation and phagocytosis. Furthermore, for the mechanism verification in vivo, mice with specific Mtor knockout in myeloid cells were constructed for pneumonia models.Results: Rapa exacerbated S. aureus pneumonia in mouse models, promoting chemokines secretion and inflammatory cells infiltration in lung. In vitro, Rapa upregulated the secretion of chemokines and cytokines in macrophages induced by S. aureus. Mechanistically, the mTOR-ribosomal protein S6 (RPS6) pathway in macrophages was phosphorylated in response to S. aureus infection, and the inhibition of RPS6 phosphorylation upregulated the inflammation level. However, Rapa did not increase the phagocytic activity. Accordingly, mice with specific Mtor knockout in myeloid cells experienced more severe S. aureus pneumonia.Conclusion: Rapa exacerbates S. aureus pneumonia by increasing the inflammatory levels of macrophages. Inhibition of mTOR-RPS6 pathway upregulates the expression of cytokines and chemokines in macrophages, thus increases inflammatory cells infiltration and exacerbates tissue damage.Keywords: Staphylococcus aureus, pneumonia, macrophage, rapamycin, mTOR- ribosomal protein S6 signaling pathway

Jie Huang,1,&ast; Wenqiang Zhu,1,&ast; Qiangzhi Duan,2,&ast; Chaomang Zhu,1 Xueling Shi,1 Hongyu Zhao,1 Peng Cai,1 Duojie Li1 1Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China; 2Department of Radiotherapy, The 2nd Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Duojie Li, Department of Radiotherapy, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, 233000, People’s Republic of China, Tel/Fax +86-139-5633-2626, Email liduojie@163.comPurpose: To explore the efficacy and safety of pyrotinib combined with different radiotherapy modes in human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) patients with brain metastasis (BM).Patients and Methods: This study is a retrospective analysis of patients diagnosed with BM who underwent treatment with pyrotinib between November 2018 and April 2023. A total of 66 patients were administered radiotherapy in conjunction with pyrotinib (Group A), while 26 patients received pyrotinib as a standalone treatment (Group B). Within Group A, 18 patients underwent conventional fractionated radiotherapy (2Gy/F), while 48 patients received hyperfractionated radiotherapy (HFRT) (≥ 3Gy/F). The primary endpoints were intracranial progression-free survival (IC-PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR) and clinical benefit rate (CBR).Results: The ORR of Group A was 54.5% (36/66), while the ORR of Group B was 34.6% (9/26) (P= 0.047). The CBR of Group A was 89.4% (59/66) and that of Group B was 69.2% (18/26) (P= 0.041). The IC-PFS between Group A and Group B were 12 months and 8 months, respectively (P< 0.001), and the OS were 20 months and 16 months, respectively (P= 0.065). In Group A, the IC-PFS and OS between the conventional fractionation radiotherapy group and the HFRT group were 10 months and 12 months, respectively (P= 0.001) and 16 months and 24 months, respectively (P< 0.001). No serious adverse reactions were observed in Group A and Group B.Conclusion: For HER2-positive BC patients with BM, it is recommended to adopt the treatment mode of HFRT combined with pyrotinib, which can improve the local control and survival of patients.Keywords: breast cancer, human epidermal growth factor receptor type 2, brain metastasis, pyrotinib, radiation therapy, hyperfractionated radiotherapy

Zhiwei Chen,1,&ast; Chuling Zhu,2,&ast; Lingna Huang,1,&ast; Yuanjie Qi,1 Xiaoyao Guo,1 Li Xie,1 Hua Li1 1Department of Gynecologic, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, People’s Republic of China; 2Department of Women’s health Department, QuanZhou Women and Children’s Hospital, Quanzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Li, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-18005016206, Email fjsfylihua@163.com Li Xie, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, Fujian, 350001, People’s Republic of China, Tel +86-13635281861, Email 309381162@qq.comObjective: Excessive pain will have adverse effects on the mother and fetus. Labor epidural analgesia greatly reduces the pain, which is widely carried out abroad. Labor epidural anesthesia-associated fever (LEAF) is the biggest problem for labor epidural anesthesia. This study aimed to evaluate the clinical value of serum magnesium levels to predict the LEAF.Methods: Overall 528 singleton term-pregnant women who underwent labor epidural anesthesia in Fujian Provincial Maternity and Children’s Health Hospital, affiliated hospital of Fujian Medical University from January 2019 to June 2019, were analyzed retrospectively. The serum magnesium level was detected using venous blood samples. The relationship between the serum magnesium level and LEAF was interpreted, and the optimal cut-off values of the serum magnesium level to predict LEAF were calculated.Results: Overall, 65 (12.30%) participants had LEAF. And a higher rate of the bulging membrane, gestational hypertension, neonatal intensive care unit (NICU) admission, and the different mode of delivery was significantly associated with LEAF. Also, the serum magnesium level demonstrated higher significantly in presence of LEAF than absence (P< 0.05). What is more, it indicated that the area under the receiver operating characteristic curve (AUC) for the serum magnesium level was 0.825, and an optimal cut-off of the serum magnesium level was 0.855 mg/dl. Furthermore, it demonstrated that the serum magnesium level had the highest OR (OR= 7.49; 95% CI (4.58– 14.35)) (P< 0.001). The bulging membrane is an independent risk factor presence of LEAF (OR = 1.55; 95% CI (1.01– 2.43)) (P=0.038).Conclusion: This study demonstrated that the baseline of serum magnesium can provide a suitable biomarker to predict LEAF. It can help to provide a useful target for LEAF treatment and enhance surveillance before fever.Keywords: serum magnesium level, labor epidural anesthesia associated fever, inflammation, risk, therapy

Yixin Ding,1,&ast; Kongjia Wang,2,&ast; Shufen Zhao,1 Yu Li,3 Wensheng Qiu,1 Chunyang Zhu,1 Yan Wang,1 Chen Dong,1 Jiani Liu,1 Yangyang Lu,1 Weiwei Qi1 1Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Urology, Qingdao Municipal Hospital, Qingdao University, Qingdao, People’s Republic of China; 3Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiwei Qi, Email qwwqdfy@126.comPurpose: Kinetochore scaffold 1 (KNL1), a crucial protein during cell mitosis participating in cell division, was widely expressed in multiple kinds of cancers. However, the expression profile, the effect on cell biological function, tumor immune microenvironment, and predictive value of clinical prognosis in pan-cancer of KNL1 still require a comprehensive inquiry.Methods: The mRNA and protein expression profile of KNL1 was validated in pan-cancer using different databases. Six algorithms were used to explore the correlation between KNL1 and immune infiltration and the relationship between KNL1 and tumor mutation burden (TMB), microsatellite instability (MSI), and TIDE score were calculated. The diagnostic and clinical prognostic predictive ability of KNL1 was assessed. Differentially expressed genes (DEGs) of KNL1 were screened out and function enrichment analyses were performed in pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and bladder urothelial carcinoma (BLCA). Finally, 8 cases of pancreatic adenocarcinoma tissues and paired adjacent tissues were collected for immunohistochemical (IHC) staining and the histological score (H-score) was calculated. Real-time PCR was performed in gastric cancer and bladder cancer cell lines.Results: KNL1 was abnormally upregulated in more than half of cancers across different databases. IHC and real-time PCR verified the up-regulated expression in cancer tissues in PAAD, gastric cancer, and BLCA. The satisfactory diagnostic value of KNL1 was indicated in 30 cancers and high KNL1 expression was associated with poorer overall survival (OS) in 12 cancers. The prognostic role of KNL1 as a predictive biomarker of PAAD was clarified. KNL1 played an active part in the cell cycle and cell proliferation. Moreover, KNL1 was likely to mold the Th2-dominant suppressive tumor immune microenvironment and was associated with TMB, MSI, and immune checkpoint-related genes in pan-cancer.Conclusion: Our study elucidated the anomalous expression of KNL1 and revealed that KNL1 was a promising prognostic biomarker in pan-cancer.Keywords: KNL1, bioinformatics, pan-cancer, immune infiltration, prognosis, clinical prognostic model

Manjiao Zhuang,1,&ast; Lei Rao,2,3,&ast; Yadi Chen,1 Shangying Xiao,1 Haishan Xia,1 Jiangyong Yang,2 Xiaohua Lv,1 Dongyun Qin,1 Chunjie Zhu1 1Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China; 2Medical College, Shaoguan University, Shaoguan, 512026, People’s Republic of China; 3Department of Biomedicine, Chengdu Medical College, Chengdu, 610500, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Manjiao Zhuang, Guangdong Provincial Key Laboratory of Research and Development of Natural Drugs, and School of Pharmacy, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email manjiao@163.com Chunjie Zhu, School of Basic Medicine, Guangdong Medical University, Dongguan, 523808, People’s Republic of China, Email zhuchunjie718@163.comIntroduction: Quercetin has an ideal therapeutic effect on islet function improvement in type 2 diabetes mellitus (T2DM). However, the therapeutic benefit of quercetin is hindered by its poor bioavailability and limited concentration in pancreatic islets. In this study, superparamagnetic iron oxide nanoparticle (SPION)-modified exosomes were prepared to load quercetin, hoping to endow quercetin with enhanced water solubility and active targeting capacity with the help of magnetic force (MF).Methods: Transferrin-modified SPIONs (Tf-SPIONs) were synthesized by exploiting N-hydroxysuccinimidyl (NHS) conjugation chemistry, and quercetin-loaded exosomes (Qu-exosomes) were acquired by electroporation. Tf-SPION-modified quercetin-loaded exosomes (Qu-exosome-SPIONs) were generated by the self-assembly of transferrin (Tf) and the transferrin receptor (TfR). The solubility of quercetin was determined by high-performance liquid chromatography (HPLC) analysis. The pancreatic islet targeting capacity and insulin secretagogue and antiapoptotic activities of Qu-exosome-SPIONs/MF were evaluated both in vitro and in vivo.Results: The Qu-exosome-SPIONs were well constructed and harvested by magnetic separation with a uniform size and shape in a diameter of approximately 86.2 nm. The water solubility of quercetin increased 1.97-fold when loaded into the SPION-modified exosomes. The application of SPIONs/MF endowed the Qu-exosomes with favorable targeting capacity. In vitro studies showed that Qu-exosome-SPIONs/MF more effectively inhibited or attenuated β cell apoptosis and promoted insulin secretion in response to elevated glucose (GLC) compared with quercetin or Qu-exosome-SPIONs. In vivo studies demonstrated that Qu-exosome-SPIONs/MF displayed an ideal pancreatic islet targeting capacity, thereby leading to the restoration of islet function.Conclusion: The Qu-exosome-SPIONs/MF nano-delivery system significantly enhanced the quercetin concentration in pancreatic islets and thereby improved pancreatic islet protection.Keywords: quercetin, exosome, SPION, solubility, targeted delivery, islet function

Yuxi He,1,&ast; Shike Geng,1,&ast; Qing Mei,1,&ast; Lei Zhang,1,&ast; Tianjun Yang,1 Chunyan Zhu,1 Xiaoqin Fan,1 Yinzhong Wang,1 Fei Tong,1 Yu Gao,1 Xiaowei Fang,1 Renren Bao,2 Ximei Sheng,3 Aijun Pan1– 3 1Department of Intensive Care Unit, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China; 2Department of Intensive Care Unit, the Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Intensive Care Unit, the Training Center of Anhui Provincial Hospital, Wannan Medical College, Wuhu, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Pan; Qing Mei, Department of Intensive Care Unit, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, No. 17, Lu Jiang Road, Hefei, Anhui Province, People’s Republic of China, Tel +86-0551-62286175, Email aijunpan868@ustc.edu.cn; meiqing@ustc.edu.cnObjective: To evaluate the diagnostic value and clinical application of metagenomic next-generation sequencing (mNGS) for infections in critically ill patients.Methods: Comparison of diagnostic performance of mNGS and conventional microbiological testing for pathogens was analyzed in 234 patients. The differences between immunocompetent and immunocompromised individuals in mNGS-guided anti-infective treatment adjustment were also analyzed.Results: The sensitivity and specificity of mNGS for bacterial and fungal detection were 96.6% (95% confidence interval [CI], 93.5%– 99.6%) and 83.1% (95% CI, 75.2%– 91.1%), and 85.7% (95% CI, 71.9%– 99.5%) and 93.2% (95% CI, 89.7%– 96.7%), respectively. Overall, 152 viruses were detected by mNGS, but in which 28 viruses were considered causative agents. The proportion of mNGS-guided beneficial anti-infective therapy adjustments in the immunocompromised group was greater than in the immunocompetent group (48.5% vs 30.1%; P=0.008). In addition, mNGS-guided anti-infective regimens with peripheral blood and BALF specimens had the highest proportion (39.0%; 40.0%), but the proportion of patients not helpful due to peripheral blood mNGS was also as high as 22.0%.Conclusion: mNGS might be a promising technology to provide precision medicine for critically ill patients with infection.Keywords: next-generation sequencing, critically ill patients, community-acquired infection, hospital-acquired infection, immunosuppression

Yongzhen Zhou,1,2,&ast; Chenjie Qiu,3,&ast; Qingsheng Fu,2 Tao Li,1 Xudong Zhang,1 Chunfu Zhu,1 Xihu Qin,1 Baoqiang Wu1,2 1Department of General Surgery, the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, 213000, People’s Republic of China; 2Graduate School, Bengbu Medical College, Bengbu, 233003, People’s Republic of China; 3Department of General Surgery, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, 213000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baoqiang Wu, Email yddf999@163.comBackground: RAD54L is a prominent member of the SWI2/SNF2 protein family, primarily involved in the homologous recombination repair (HRR) process, thereby playing a pivotal role in the repair of DNA double-strand breaks (DSBs). RAD54L has been implicated in the development of numerous tumors. Consequently, we aimed to investigate the potential contribution of RAD54L in pan-cancer.Methods: Various databases and analytical tools were employed for bioinformatics analysis. Moreover, in vitro experiments were conducted to corroborate the findings from the bioinformatics analysis and delve deeper into the role of RAD54L in hepatocellular carcinoma (HCC).Results: RAD54L expression demonstrated a significant elevation in the majority of tumors, and its overexpression was strongly associated with unfavorable survival outcomes. RAD54L displayed robust correlations with the infiltration levels of various immune cells, including cancer associated fibroblasts (CAFs), endothelial cells, and myeloid-derived suppressor cells (MDSCs). Additionally, associations were observed between RAD54L and key factors such as tumor mutation burden (TMB), microsatellite instability (MSI), multiple immune checkpoints, and immune cell infiltration. Moreover, a close relationship was observed between RAD54L expression levels in HCC and clinicopathological characteristics, as well as immune cell infiltration. Experimental techniques including qRT-PCR, Western blotting, colony-forming, Cell Counting Kit-8 (CCK-8), wound-healing, and transwell assays were employed, which collectively demonstrated that RAD54L promoted the proliferation and migration of HCC cells.Conclusion: RAD54L exhibits robust expression in both pan-cancer and HCC, exerting a significant influence on the proliferation and migration of HCC cells. These findings highlight its potential as a promising biomarker for pan-cancer and a prospective target for immunotherapy.Keywords: RAD54L, pan-cancer, tumor microenvironment, malignant behavior

Suling Jiang,1,&ast; Jian Wang,2,3,&ast; Zhiyi Zhang,4,&ast; Jie Zhan,1 Ruifei Xue,1 Yuanwang Qiu,5 Li Zhu,6 Shaoqiu Zhang,2 Yifan Pan,1 Xiaomin Yan,2 Yuxin Chen,3,7 Jie Li,1– 4 Xingxiang Liu,8 Chuanwu Zhu,6 Rui Huang,1– 4 Chao Wu1– 4 1Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 3Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 5Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 7Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 8Department of Clinical Laboratory, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chao Wu, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Tel +86-25-83105890, Fax +86-25-83307115, Email dr.wu@nju.edu.cn Rui Huang, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People’s Republic of China, Email doctor_hr@126.comBackground: Noninvasive diagnosis of liver inflammation is important for patients with chronic hepatitis B (CHB). This study aimed to develop a nomogram to predict significant liver inflammation for CHB patients.Methods: CHB patients who underwent liver biopsy were retrospectively collected and randomly divided into a development set and a validation set. The least absolute shrinkage and selection operator regression and logistic regression analysis were used to select independent predictors of significant liver inflammation, and a nomogram was developed. The performance of nomogram was assessed by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA).Results: A total of 1019 CHB patients with a median age of 39.0 years were included. Alanine aminotransaminase (ALT, P = 0.018), gamma-glutamyl transpeptidase (P = 0.013), prothrombin time (P < 0.001), and HBV DNA level (P = 0.030) were identified as independent predictors of significant liver inflammation in the development set. A model namely AGPD-nomogram was developed based on the above parameters. The area under the ROC curve in predicting significant inflammation was 0.765 (95% CI: 0.727– 0.803) and 0.766 (95% CI: 0.711– 0.821) in the development and validation sets, which were significantly higher than other indexes. The AGPD-nomogram had a high predictive value in patients with normal ALT. Moreover, the nomogram was proven to be clinically useful by DCA.Conclusion: A visualized AGPD-nomogram which incorporated routine clinical parameters was proposed to facilitate the prediction of significant liver inflammation in CHB patients. This nomogram had high accuracy in the identification of significant liver inflammation and would be a useful tool for the better management of CHB patients, especially for those with normal ALT.Keywords: chronic hepatitis B, liver inflammation, prediction, nomogram, alanine aminotransferase

Tongtong Wang,1,&ast; Yingchu Liu,2,&ast; Chunyu Zhu,1,&ast; Siyuan Yang,3 Di Yang,4 Jiang Xiao,4 Guiju Gao4 1Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2School of General Practice and Continuing Education, Capital Medical University, Beijing, People’s Republic of China; 3Laboratory of Infectious Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guiju Gao, Professor of Medicine Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8, Jingshun Dongjie, Chaoyang District, Beijing, 100015, People’s Republic of China, Email guiju.gao@163.comBackground: Rifampicin is a known inducer of the cytochrome P450 (CYP2B6) enzyme, which can lead to a decrease in the concentration of efavirenz. Therefore, we conducted a study to evaluate the effect of daily rifampicin intake on efavirenz 600mg pharmacokinetics and HIV-1 virological suppression.Methods: Patients receiving antiretroviral therapy containing efavirenz (600mg daily), and we collected efavirenz concentration at four visit points: ART day 14 (PK1), ART day 42 (PK2), ART day 140 (PK3), and ART day 336 (PK4), and performed pharmacokinetics analysis.Results: From February 2017 to November 2020, 29 HIV/TB co-infection patients were included. Ninety percent of patients had a concentration of ≥ 1000ng/mL of efavirenz during the study. All patients had efavirenz Cmax ≥ 1000ng/mL, 86% patients showed good virology response.Conclusion: Our study shows that the use of rifampicin in HIV/TB co-infection patients does not affect efavirenz drug concentrations, that virological suppression is good and that no efavirenz dose adjustment is required.Keywords: HIV/TB, rifampicin, efavirenz, pharmacokinetics

Guangbin Yu,1 Shuping Luo,1 Cuilian Zhu,1 Li Chen,1 Hao Huang,2 Bin Nie,1,3 Jianhao Gu,4 Jianxin Liu1 1Fifth Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou City, People’s Republic of China; 2First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou City, People’s Republic of China; 3Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou City, People’s Republic of China; 4Clinical Medical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou City, People’s Republic of ChinaCorrespondence: Bin Nie, Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou City, People’s Republic of China, Tel +86 13826067459, Email niebing26@163.comPurpose: Recent studies have shown that acupuncture may have great potential in the treatment of Bell’s palsy. However, the bibliometric analysis of this field has not been summarized properly. Thus, the purpose of this study is to analyze the hotspot of acupuncture for Bell’s Palsy.Methods: The core collection database of Web of Science was searched for relevant publications from 2000 to 2023, and countries, institutions, authors, keywords, and literature were analyzed and visualized by bibliometric softwareCiteSpace 5.1.R6, Vosviewer, BICOMB, and gCLUTO to explore the scientific achievements, research collaboration networks, research hot spots, and research trends.Results: 229 publications were included in this study. The most cited journal is Journal of Otolaryngology-Head & Neck Surgery; the most prolific country is China; the most prolific author is Li Ying, moreover, the collaboration among scholars is poor; Kyung Hee University is the most prolific institution studying acupuncture for Bell’s Palsy. Reference burst detection indicates that traditional Chinese Medicine philosophy, the role of acupuncture in the prognosis of facial palsy, mechanism of acupuncture to improve facial nerve function, and the use of electroacupuncture are starting to become new research hotspots.Conclusion: The field of acupuncture for Bell’s Palsy has developed rapidly in recent years, and new research trends are mainly: combination with traditional Chinese medicine, the role of acupuncture in the prognosis of facial palsy, mechanism of acupuncture to improve facial nerve function, and the use of electroacupuncture. However, research in this field is still dominated by case reports and clinical trials, and there is a lack of large-scale, multicenter clinical trials and animal experiments there are still many problems in institutional cooperation and experimental design, which requires relevant researchers to strengthen cooperation and improve experimental design.Keywords: acupuncture, Bell’s palsy, CiteSpace, bibliometric analysis, Vosviewer

Shenglan Ma,1– 3,&ast; Peijun Ju,4,&ast; Qingrong Xia,1– 3 Zhongde Pan,5 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Hua Gao,1– 3 Junwei Yan,1– 3 Jie Zhang,1– 3 Keming Wang,1– 3 Chao Li,1– 3 Wen Xie,1– 3,&ast; Cuizhen Zhu1– 3,&ast; 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, 230022, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Traditional Chinese Medicine for Mental Health, Shanghai, People’s Republic of China; 5Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aims to clarify the negative psychological state and resilience impairments of schizophrenia (SCZ) with metabolic syndrome (MetS) while evaluating their potential as risk factors.Patients and Methods: We recruited 143 individuals and divided them into three groups. Participants were evaluated using the Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD)-24, Hamilton Anxiety Rating Scale (HAMA)-14, Automatic Thoughts Questionnaire (ATQ), Stigma of Mental Illness scale and Connor–Davidson Resilience Scale (CD-RISC). Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: The score of ATQ was highest in the MetS group (F = 14.5, p < 0.001), and the total score of CD-RISC, subscale tenacity score and subscale strength score of CD-RISC were lowest in the MetS group (F = 8.54, p < 0.001; F = 5.79, p = 0.004; F = 10.9, p < 0.001). A stepwise regression analysis demonstrated that a negative correlation was observed among the ATQ with employment status, high-density lipoprotein (HDL-C), and CD-RISC (β=− 0.190, t=− 2.297, p = 0.023; β=− 0.278, t=− 3.437, p = 0.001; β=− 0.238, t=− 2.904, p = 0.004). A positive correlation was observed among the ATQ with waist, TG, WBC, and stigma (β=0.271, t = 3.340, p = 0.001; β=0.283, t = 3.509, p = 0.001; β=0.231, t = 2.815, p = 0.006; β=0.251, t=− 2.504, p = 0.014). The area under the receiver-operating characteristic curve analysis showed that among all independent predictors of ATQ, the TG, waist, HDL-C, CD-RISC, and stigma presented excellent specificity at 0.918, 0.852, 0.759, 0.633, and 0.605, respectively.Conclusion: Results suggested that the non-MetS and MetS groups had grievous sense of stigma, particularly, high degree of ATQ and resilience impairment was shown by the MetS group. The TG, waist, HDL-C of metabolic parameters, CD-RISC, and stigma presented excellent specificity to predict ATQ, and the waist showed excellent specificity to predict low resilience level.Keywords: years of education, negative symptoms, waist circumstance

Song Z, Wang H, Zong F, Zhu C, Tao Y. Cancer Manag Res. 2019;11:8419–8429. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Following publication of the article, concerns were raised about the duplication of images from Figures 4 and 6 with images from other unrelated articles. Specifically, Images for Figures 4A and 4B have been duplicated with images for Figures 4A and 4B from Zhong R, et al (2019); Figure 4A from Cai C, et al (2019); Figures 4A and 4B from Li M, Meng X, Li M. MiR-126 promotes esophageal squamous cell carcinoma via inhibition of apoptosis and autophagy. Aging (Albany NY). 2020;12:12107-12118. https://doi.org/10.18632/aging.103379 and Figure 4A from Si H, Zhang Y, Song Y, Li L. Overexpression of adrenomedullin protects mesenchymal stem cells against hypoxia and serum deprivation‑induced apoptosis via the Akt/GSK3β and Bcl‑2 signaling pathways. International Journal of Molecular Medicine. 2018;41:3342-3352. https://doi.org/10.3892/ijmm.2018.3533. Images for Figure 4C and 4D have been duplicated with images for Figure 4B from Cai C, Min S, Yan B, et al. MiR-27a promotes the autophagy and apoptosis of IL-1β treated-articular chondrocytes in osteoarthritis through PI3K/AKT/mTOR signaling. Aging (Albany NY). 2019;11:6371-6384. https://doi.org/10.18632/aging.102194 (RETRACTED) and Figures 4c and 4d from Zhong R, Li S, Fang K, Yang L, Wang L. microRNA-1225 inhibit apoptosis of pancreatic cancer cells via targeting JAK1. Cell Cycle. 2019;18(9):990-1000. https://doi.org/10.1080/15384101.2019.1608127. Images for Figures 6A and 6B have been duplicated with images for Figure 3C from Zhou J, Zhang Y, Han Z, et al. RETRACTED ARTICLE: miR-506 contributes to malignancy of cutaneous squamous cell carcinoma via targeting of P65 and LAMC1. Cell Cycle. 2019;18(3):333-345. https://doi.org/10.1080/15384101.2019.1568747; Figure 4C from Ouyang L, Yi L, Li J, et al. SIRT6 overexpression induces apoptosis of nasopharyngeal carcinoma by inhibiting NF-κB signaling. Onco Targets Ther. 2018;11:7613-7624. https://doi.org/10.2147/OTT.S179866; Figures 6a and 6b from Zhong R, Li S, Fang K, Yang L, Wang L. (2019) microRNA-1225 inhibit apoptosis of pancreatic cancer cells via targeting JAK1. Cell Cycle. 2019;18(9):990-1000. https://doi.org/10.1080/15384101.2019.1608127, and Figure 8A from Huang L, Jian Z, Gao Y, et al. RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways. Aging (Albany NY). 2019;11:6674-6690. https://doi.org/10.18632/aging.102167. The authors did not respond to our queries and were unable to provide an explanation for the duplicated images or provide data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Yuxuan Xu,&ast; Zhihui Lin,&ast; Chenxi Zhu,&ast; Dongyan Song, Bosen Wu, Kangting Ji, Jin Li Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kangting Ji; Jin Li, Department of Cardiology, Key Laboratory of Panvascular Diseases of Wenzhou, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Xueyuanxi Road, No. 109, Wenzhou, 325027, People’s Republic of China, Tel/Fax +86-577-85676627, Email jikt@wmu.edu.cn; lijin1982@wzhealth.comObjective: The present study aimed to evaluate the relationship between all-cause mortality and the neutrophil percentage-to-albumin ratio (NPAR) in patients with atrial fibrillation (AF).Methods: We obtained clinical information from patients with AF from the Medical Information Mart for Intensive Care-IV version 2.0 (MIMIC-IV) database and the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (WMU). The clinical endpoints were all-cause death measured at 30-day, 90-day, and one-year intervals. For endpoints associated with the NPAR, logistic regression models were used to calculate odds ratios (OR) with 95% confidence intervals (CI). Receiver operating characteristic (ROC) curves and area under the curve (AUC) were developed to compare the ability of different inflammatory biomarkers to predict 90-day mortality in patients with AF.Results: Higher NPAR was associated with a higher risk of 30-day (OR 2.08, 95% CI 1.58– 2.75), 90-day (OR 2.07, 95% CI 1.61– 2.67), and one-year mortality (OR 1.60, 95% CI 1.26– 2.04) in patients with AF in 2813 patients from MIMIC-IV. The predictive performance of NPAR (AUC = 0.609) for 90-day mortality was better than that of neutrophil-to-lymphocyte ratio (NLR) (AUC = 0.565, P < 0.001), and platelet-to-lymphocyte ratio (PLR) (AUC = 0.528, P < 0.001). When NPAR and sequential organ failure assessment (SOFA) were combined, the AUC increased from 0.609 to 0.674 (P < 0.001). Higher NPAR was associated with a higher risk of 30-day mortality (OR 2.54, 95% CI 1.02– 6.30) and 90-day mortality (OR 2.76, 95% CI 1.09– 7.01) in 283 patients from WMU.Conclusion: An increased 30-day, 90-day, and one-year mortality risk among patients with AF were linked to a higher NPAR in MIMIC-IV. NPAR was thought to be a good predictor of 90-day all-cause mortality. Higher NPAR was associated with a higher risk of 30-day and 90-day mortality in WMU.Keywords: atrial fibrillation, neutrophil percentage-to-albumin ratio, mortality, inflammatory biomarker

Xiachuan Qin,1,2 Xiaomin Hu,2 Weihan Xiao,2 Chao Zhu,3 Qianqin Ma,1 Chaoxue Zhang1 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of ChinaCorrespondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People’s Republic of China, Tel +86-13955158023, Email zcxay@163.comObjective: Distinguishing the degree of differentiation, hepatocellular carcinoma (HCC) has important clinical significance in the therapeutic decision-making and patient prognosis evaluation.Methods: We developed a deep-learning radiomics (DLR) model based on contrast-enhanced ultrasound (CEUS) to evaluate the differentiation of HCC noninvasive. We retrospectively analyzed HCC patients who had undergone resection and CEUS one week preoperatively between November 2015 and August 2022. Enrolled patients were randomly divided into training (n=190) and testing (n=82) cohorts in a 7:3 ratio. The depth of learning and radiological characteristics reflecting the differentiation degree of HCC were extracted, and the least absolute shrinkage and selection operator(LASSO) was used for feature selection to obtain the most valuable features and then build a DLR model based on the useful features.Results: The deep-learning Radiomics model could accurately predict the degree of differentiation of HCC; the area under the curve of the DLR model in the training and testing cohorts was 0.969 and 0.932, respectively. The accuracy, sensitivity, and specificity of the CEUS-based DLR model for predicting the differentiation of HCC were 0.915, 0.938, and 0.900, respectively, in the testing cohort. The decision curve analysis confirmed that the combined model predicted good overall net income for differentiation.Conclusion: The CEUS-based DLR model provides an easy-to-use, visual, and personalized tool for predicting the differentiation of HCC and can help doctors formulate more favorable treatment plans for patients.Keywords: hepatocellular carcinoma, differentiated, contrast-enhanced ultrasound, deep-learning, radiomics

Xiachuan Qin,1,2,&ast; Linlin Xia,1,&ast; Chao Zhu,3 Xiaomin Hu,2 Weihan Xiao,2 Xisheng Xie,4 Chaoxue Zhang1 1Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Ultrasound, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Anhui Medical university, Hefei, Anhui, People’s Republic of China; 4Department of Nephrology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaoxue Zhang, Department of Ultrasound, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zcxay@163.com Xisheng Xie, Department of Nephrology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College (University), Nan Chong, Sichuan, People’s Republic of China, Email xishengx@163.comIntroduction: To explore whether ultrasonic radiomics extracted by machine learning method can noninvasively evaluate lupus nephritis (LN) activity.Materials and Methods: This retrospective study included 149 patients with LN diagnosed by renal biopsy. They were divided into a training cohort (n=104) and a test cohort (n=45). Ultrasonic radiomics features were extracted from the ultrasound images, and the radiomics features were constructed. Furthermore, five machine learning algorithms were compared to evaluate LN activity. The performance of the binary classification model was evaluated by the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).Results: The average AUC of the five machine learning models was 79.4, of which the MLP model was the best. The AUC of the training group was 89.1, with an accuracy of 81.7%, a sensitivity of 83%, a specificity of 80.7%, a negative predictive value of 85.2%, and a positive predictive value of 78%. The AUC of the test group was 82.2, the accuracy was 73.3%, the sensitivity was 78.9%, the specificity was 69.2%, the negative predictive value was 81.8%, and the positive predictive value was 65.2%.Conclusion: Machine learning classifier based on ultrasonic radiomics has high accuracy for LN activity. The model can be used to noninvasively detect the activity of LN and can be an effective tool to assist the clinical decision-making process.Keywords: systemic lupus erythematosus, lupus nephritis, activity, ultrasound, machine learning

Dandan Li,1– 3,&ast; Long Zhang,4,&ast; Tongjian Bai,4,&ast; Bensheng Qiu,5 Chunyan Zhu,1– 3 Kai Wang1,2,4,6,7 1School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, People’s Republic of China; 2Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, People’s Republic of China; 3Research Center for Translational Medicine, Second Hospital of Anhui Medical University, Hefei, People’s Republic of China; 4Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 5Hefei National Laboratory for Physical Sciences at the Microscale and the Centers for Biomedical Engineering, University of Science and Technology of China., Hefei, People’s Republic of China; 6Anhui Province Key Laboratory of Cognition and Neuropsychiatric Disorders, Hefei, People’s Republic of China; 7Collaborative Innovation Center of Neuropsychiatric Disorders and Mental Health, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunyan Zhu; Kai Wang, Email ayswallow@126.com; wangkai1964@126.comIntroduction: Empathy traits are highly heritable and linked with reward processing. It is implicated that common variations of the oxytocin-receptor gene (OXTR) play a modulatory effect on empathic performance. However, it is unclear about the neural substrates underlying the modulatory effect of the OXTR genotype on empathic performance. This study aimed to characterize the modulatory effect of common OXTR variations on reward-circuitry function and its relationship with empathy.Methods: Based on the seed of the nucleus accumbens (NAcc; a key hub of reward circuitry), we examined differences in spontaneous local activity and functional connectivity between OXTR rs2268493 genotype groups and their relationship with empathic performance among 402 high-homogeneity participants.Results: Comparing with C carriers (CC/CT) group, the individuals with the rs2268493 TT genotype exhibited lower functional connectivity of the right NAcc with the medial prefrontal cortex (mPFC) and inferior frontal gyrus. Similarly lower functional connectivity was found between the left NAcc and mPFC. Consequently, no significant difference was found in the spontaneous local activity of NAcc.Discussion: Our findings suggested that common OXTR variations have a modulatory effect on the connection of the NAcc with the hub of empathic networks (mPFC and IFG), which may provide insight on the neural substrate underlying the modulatory effect of OXTR on empathic behavior.Keywords: empathy, oxytocin-receptor gene, reward network, RS-fMRI, rs2268493

Xianhu Zeng,1 Yi Teng,1 Chunrong Zhu,2 Zhipeng Li,1 Tian Liu,3 Yong Sun,1 Shangcong Han1 1Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, People’s Republic of China; 2Department of Pharmacy Intravenous Admixture Service, Weifang Maternal and Child Health Hospital, Weifang, People’s Republic of China; 3Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of ChinaCorrespondence: Shangcong Han; Yong Sun, Department of Pharmaceutics, School of Pharmacy, Qingdao University, Qingdao, People’s Republic of China, Tel/Fax +86 532 82991508, Email hsc00111@163.com; sunyong@qdu.edu.cnIntroduction: Sunitinib, a first-line therapy with a certain effect, was utilized in the early stages of renal cell carcinoma treatment. However, its clinical toxicity, side effects, and its limited bioavailability, resulted in inadequate clinical therapeutic efficacy. Building neoteric, simple, and safe drug delivery systems with existing drugs offers new options. Therefore, we aimed to construct a micelle to improve the clinical efficacy of sunitinib by reusing ibuprofen.Methods: We synthesized the sialic acid-poly (ethylene glycol)-ibuprofen (SA-PEG-IBU) amphipathic conjugate in two-step reaction. The SA-PEG-IBU amphiphilic conjugates can form into stable SPI nanomicelles in aqueous solution, which can be further loaded sunitinib (SU) to obtain the SPI/SU system. Following nanomicelle creation, sialic acid exposed to the nanomicelle surface can recognize the overexpressed E-selectin receptor on the membrane of cancer cells to enhance cellular uptake. The properties of morphology, stability, and drug release about the SPI/SU nanomicelles were investigated. Confocal microscopy and flow cytometry were used to assess the cellular uptake efficiency of nanomicelles in vitro. Finally, a xenograft tumor model in nude mice was constructed to investigate the body distribution and tumor suppression of SPI/SU in vivo.Results: The result showed that SPI nanomicelles exhibited excellent tumor targeting performance and inhibited the migration and invasion of tumor cell in vitro. The SPI nanomicelles can improve the accumulation of drugs in the tumor site that showed effective tumor inhibition in vivo. In addition, H&E staining and immunohistochemical analysis demonstrated that the SPI/SU nanomicelles had a superior therapeutic effect and lower biotoxicity.Conclusion: The SPI/SU nanomicelles displayed excellent anti-tumor ability, and can suppress the metastasis of tumor cell by decreasing the expression of Cyclooxygenase-2 due to the ibuprofen, providing an optimistic clinical application potential by developing a simple but safe drug delivery system.Keywords: kidney cancer, nanomicelles, sialic acid, sunitinib, ibuprofen, anti-tumor therapy

Jiamin Li,1 Chen Zhu,1 Ying Liu,1 Baoyun Song,2 Jingfen Jin,3 Yilan Liu,4 Xianxiu Wen,5 Shouzhen Cheng,6 Xinjuan Wu1 1Department of Nursing, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Nursing, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Zhejiang University School of Medicine Second Affiliated Hospital, Hangzhou, People’s Republic of China; 4Department of Nursing, Wuhan Union Hospital, Jianghan District, Wuhan, People’s Republic of China; 5Department of Nursing, Sichuan Academy of Medical Sciences and Sichuan People’s Hospital, Chengdu, People’s Republic of China; 6Department of Nursing, Sun Yat-sen University First Affiliated Hospital, Guangzhou, People’s Republic of ChinaCorrespondence: Xinjuan Wu, Email wuxinjuan@sina.comBackground: Pressure injury is a common problem in intensive care units. Critical care nurses play an important role in multidisciplinary teams performing pressure injury treatment. Identifying the clinical status of pressure injury treatment may contribute to improving care quality.Aim: To identify the knowledge, attitudes, and practices regarding pressure injury treatment in critical care nurses.Design: A cross-sectional survey.Methods: Secondary data were extracted from a multicenter clinical trial. Knowledge and attitudes toward pressure injury treatment were assessed through a self-administered eight-item questionnaire. The observed practices were recorded using a case report form. The report was in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement.Results: A total of 950 critical care nurses in 15 hospitals from six provinces/municipalities of China were investigated. The mean knowledge score was 2.89 ± 1.16 (95% confidence interval: 2.82– 2.97) out of a possible total of 5 points. The correct rates of selecting wound dressings and pain management were 34.4% and 45.6%, respectively. The mean attitude score was 9.07 ± 1.09 (95% confidence interval: 9.00– 9.13) out of a possible total of 12 points. A total of 2092 patient days of pressure injury treatment practices were observed and recorded. Repositioning was the most commonly employed treatment measure (98.8%). Foam dressing was the common dressing for stage I (53.6%), stage II (47.5%), and more severe pressure injury (67.9%), including stage III, IV, unstageable, and suspected deep tissue injury.Conclusion: Critical care nurses exhibited a generally low level of knowledge and moderate attitudes regarding pressure injury treatment. Practices of pressure injury treatment were generally acceptable.Keywords: pressure injury, treatment, knowledge, attitude, practice, evidence implementation

Fan Ye,1,&ast; Yucui Jiang,1,2,&ast; Jian Zhang,1 Yingxin Zong,1 Mei Yu,1,3 Cuihua Chen,2 Chan Zhu,1 Yan Yang,1 Keke Jia,1 Gongxi Chen,4 Zongxiang Tang1 1School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 3Department of Pharmacy, Taizhou Hospital of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Taizhou, People’s Republic of China; 4School of Pharmaceutical Sciences, Jishou University, Jishou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gongxi Chen; Zongxiang Tang, Email chengongxi2011@163.com; zongxiangtang@njucm.edu.cnBackground: Senecio scandens Buch.-Ham (S. scandens) belongs to the Compositae family. As a Traditional Chinese medicine, S. scandens has been used in China to treat conjunctivitis, mastitis and vaginitis, it also has the function of antibacterial and relieving itching.Methods: Water extract of S. scandens (WSS) was prepared and its quality was controlled by HPLC. The antipruritic effects of WSS were evaluated by itch behavioral experiments. The oxazolone and compound 48/80 were induced to mice scratch behavior, scratch was recorded 30 min after sensitization. The relationship between the antipruritic mechanism and MrgprB2 on mast cell was studied by using mast cell-deficient Kit (W-sh) “Sash” mice and MrgprB2−/− mice. The mast cells were observed by toluidine blue staining. In vitro, the effects of WSS on MrgprB2 were studied by calcium imaging; The whole-cell patch clamp method recorded the MrgprB2 mediate voltage-dependent currents in mast cells.Results: The content of rutin (0.012%) and hyperin (0.014%) in the WSS were determined. WSS could ameliorate the pruritus induced by Oxazolone (inhibition was 41.19%, p = 0.004) and compound 48/80 (inhibition was 50.29%, p = 0.001). Meanwhile, WSS could reduce the number of mast cells in mice skin tissue with allergic contact dermatitis (ACD) (p = 0.002) or compound 48/80 (p = 0.013). In addition, WSS could inhibit the calcium influx (1 mg/mL: p = 0.001, 3 mg/mL: p < 0.0001) and the voltage-dependent currents induced by activation of MrgprB2 on mast cell. WSS also attenuated the calcium influx induced by compound 48/80 in HEK293 cells overexpressing MrgprB2/X2.Conclusion: These results showed that WSS could ameliorate pruritus by inhibiting MrgprB2 receptor on mast cells.Graphical Abstract: Keywords: Senecio scandens Buch.-Ham, pruritus, mast cell, MrgprB2 receptor

Zhao Zhou,1,2,&ast; Xiaohan Cui,1,2,&ast; Peng Gao,2 Xudong Zhang,2 Chunfu Zhu,2 Beicheng Sun1 1Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunfu Zhu, The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China, Email zcfmlm@njmu.edu.cn Beicheng Sun, Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China, Email sunbc@nju.edu.cnObjective: Recently, emerging studies have validated that circular RNAs participate in multiple biological progresses in various human malignant tumors, including hepatocellular carcinoma (HCC). However, until now, the elucidated mechanism of circular RNAs is only the tip of the iceberg. In this study, we firstly identify a novel circular RNA circRASSF5 (the only circular RNA derived from the RASSF5 gene), and attempt to investigate its biological function and underlying mechanism in HCC.Methods: qRT-PCR, Western blotting and IHC were applied to detect the expression of related genes. CCK-8 assay, EdU staining, wound healing and transwell assays were used to investigate HCC proliferation, migration and invasion abilities. Animal model studies were included to investigate the function of circRASSF5 in HCC tumorigenesis and metastasis. RNA pull-down assay, luciferase reporter assay and FISH (fluorescence in situ hybridization) assay were performed to explore the potential biological mechanism underlying circRASSF5 function in HCC.Results: CircRASSF5 is obviously downregulated in both HCC tissues and cell lines. Low level of circRASSF5 is negatively associated with larger tumor size, severe vascular invasion, more portal vein tumor embolus and unfavorable prognosis. Loss-of-function assay reveals that circRASSF5 remarkably impedes the growth and metastasis of HCC cells in vitro and in vivo. Mechanistically, circRASSF5 directly interacts with miR-331-3p as a sponge, and then enhances the expression of PH domain and leucine-rich repeat protein phosphatase (PHLPP), thus restraining the progression of HCC cells.Conclusion: Altogether, we validate that circRASSF5 is a tumor suppressor in HCC, which competitively sponges with miR-331-3p and then enhances the tumor inhibitory effect of PHLPP, indicating the potential application value of circRASSF5 for HCC diagnosis and clinical treatment.Keywords: circRASSF5, miR-331-3p, PHLPP, HCC

Rui Wang,1– 4 Wei Zhang,1– 3 Yuanyuan Li,1– 3 Yuting Jiang,1– 3 Hongqi Feng,1– 3 Yang Du,1– 3 Zhe Jiao,1– 3 Li Lan,4 Xiaona Liu,1– 3 Bingyun Li,1– 3 Chang Liu,1– 3 Xingbo Gu,5 Fang Chu,1– 3 Yuncheng Shen,1– 3 Chenpeng Zhu,1– 3 Xinhua Shao,1– 3 Simeng Tong,1– 3 Dianjun Sun1– 3 1Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, People’s Republic of China; 2National Health Commission & Education Bureau of Heilongjiang Province, Key Laboratory of Etiology and Epidemiology, Harbin Medical University (23618504), Harbin, 150081, People’s Republic of China; 3Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, 150081, People’s Republic of China; 4Harbin Center for Disease Control and Prevention, Harbin, 150056, People’s Republic of China; 5Department of Biostatistics, School of Public Health, Hainan Medical University, Haikou, 571199, People’s Republic of ChinaCorrespondence: Dianjun Sun, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Baojian Road 157, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86-13313685318, Fax +86 45186612695, Email hrbmusdj@163.comPurpose: To investigate the environmental, immune, and inflammatory factors associated with chronic obstructive pulmonary disease (COPD) in middle-aged and older Chinese individuals.Patients and Methods: A community-based case–control study was conducted among 471 patients with COPD and 485 controls. The information on COPD of the participants was collected through face-to-face interviews, and serum samples were measured at the laboratory. The main risk factors for COPD were analyzed using principal component analysis (PCA) and logistic regression.Results: Nine hundred and fifty-six respondents were included in the analysis. The results of the PCA-logistic regression analysis showed significant differences in the environmental factors, medical history, and serum C-reactive protein (CRP) levels between patients and controls. COPD was markedly more usual in those with smoking index > 200 (OR, 1.42; 95% CI, 1.28– 1.57); exposure to outdoor straw burning (OR, 1.64; 95% CI, 1.47– 1.83); use of coal, wood, and straw indoors (OR, 2.31; 95% CI, 1.92– 2.78); history of respiratory disease and coronary heart disease (OR, 3.58; 95% CI, 3.12– 4.10), congestive heart failure (OR, 1.23; 95% CI, 1.09– 1.38), and cerebrovascular disease (OR, 1.15; 95% CI,1.02– 1.31); and higher serum level of CRP (OR, 1.20; 95% CI, 1.11– 1.30). Compared to the logistic regression analysis, PCA logistic regression analysis identified more important risk factors for COPD.Conclusion: PCA-logistic regression analysis was first utilized to explore the influencing factors among rural residents in Northeast China Environmental aged 40 years and above, it was found that environmental factors, medical history, and serum CRP levels mainly affected the prevalence of COPD.Keywords: chronic obstructive pulmonary disease, collinearity, principal component, logistic regression

Hu L, Wang H, Rao M, et al. Int J Nanomedicine. 2014;9(1):1127–1138. We, the Editors and Publisher of International Journal of Nanomedicine, have retracted the following article. Following publication, the authors raised concerns about the duplication of images within the article. Specifically, The images for Figure 4C and 4F have been duplicated, as have the images for Figure 4D and 4E. The images for Figure 6A and 6B have been duplicated, as have the images for Figure 6C and 6D. It was noted that some images for Figures 2 and 10 may have duplicated regions, however, this was caused by an error during the publication process. When approached for an explanation, the authors were cooperative but wereg unable to provide an adequate explanation for the duplicated images and not all the original data for the study was available. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors agreed with this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Jianyun Yin,1 Changtai Zhu,2 Gaofeng Wang,3 Jianwei Gu1 1Thyroid Breast Surgery, Kunshan Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Kunshan, People’s Republic of China; 2Department of Transfusion Medicine, Shanghai Sixth Peoples’ Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Gastroenterology, Kunshan Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Kunshan, People’s Republic of ChinaCorrespondence: Jianyun Yin, Thyroid Breast Surgery, Kunshan Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Kunshan, People’s Republic of China, Tel +86-0512-57310000, Email yinjianyun99@sina.comPurpose: In recent years, many meta-analyses of triple-negative breast cancer (TNBC) treatment have been published; however, these studies still lack systematic summary. Therefore, the aim of this study is to summarize and evaluate the evidence level and efficacy of treatment for TNBC.Materials and Methods: Retrospective and prospective studies on treatment of TNBC were searched in the PubMed, Embase, and Cochrane Library databases. The literature search deadline was June 30, 2021. Two investigators independently screened the literature and extracted the data. In addition, the joint World Health Organization–United Nations Food and Agriculture Organization expert consultation was used to evaluate the validity of the evidence.Results: A total of 28 meta-analyses were included in this study. The treatment interventions for TNBC mainly included surgery, chemotherapy (CT), radiotherapy, molecular targeted therapy, immunotherapy, zoledronic acid, and gonadotropin-releasing hormone (GnRH) analog. Platinum improves the pathological complete response (PCR) rate of patients treated with neoadjuvant chemotherapy (NACT), the objective remission rate (ORR) and overall survival (OS) in patients with metastatic triple-negative breast cancer. Capecitabine improves disease-free survival (DFS) and OS in patients treated with adjuvant CT. Bevacizumab was added to NACT to improve the PCR rate in patients. Immunotherapy improves the PCR rate in patients treated with NACT. The improvement in PCR rate in patients with high Ki67 expression treated with neoadjuvant therapy is highly suggestive. Other interventions had suggestive or weak evidence.Conclusion: Among the strategies for treating TNBC, platinum, bevacizumab, and immunotherapy can lead to better PCR rates as part of a NACT regimen. Capecitabine as adjuvant CT and platinum in the treatment of metastatic TNBC can benefit patients’ survival. However, the effectiveness of other interventions for TNBC is not yet clear. Further research is needed in the future to obtain more reliable clinical evidence.Keywords: triple-negative breast cancer, treatment, meta-analysis, umbrella review

Xueying Zhang,1– 3,* Chen He,1– 3,* Peijun Ju,4,* Qingrong Xia,1– 3 Jianliang Gao,1– 3 Loufeng Zhang,1– 3 Xuequan Chen,1– 3 Hui Yuan,1– 3 Hua Gao,1– 3 Yang Zhang,1– 3 Junwei Yan,1– 3 Wen Xie,1– 3,* Cuizhen Zhu1– 3,* 1Affiliated Psychological Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Clinical Center for Psychiatry and Mental Health, Hefei Fourth People’s Hospital, Hefei, People’s Republic of China; 3Anhui Mental Health Center, Hefei, People’s Republic of China; 4Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Psychotic Disorders, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen Xie; Cuizhen Zhu, Affiliated Psychological Hospital of Anhui Medical University, No. 316 Huangshan Road, Shushan District, Hefei, Anhui, People’s Republic of China, Tel +86 13339102285 ; +86 13705535258, Fax +86 055163616000, Email xiewen0808@sina.com; zhucuizhen88@126.comPurpose: The study aimed to clarify the cognitive impairments of schizophrenia with metabolic syndrome while evaluating their potential as risk factors.Patients and Methods: We recruited 153 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria and the guideline standards for the prevention and treatment of dyslipidemia in Chinese adults in 2007 for metabolic syndrome, as follows: healthy control group (n = 47); nonmetabolic syndrome group (n = 58); and metabolic syndrome group (n = 48). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Cognitive function and automatic thinking were estimated using the Montreal Cognitive Assessment Scale, Verbal Fluency Test, and Automatic Thoughts Questionnaire. Serum biochemical parameters were measured by automatic biochemistry analyzer.Results: One-way ANOVA analysis revealed that differential cognition impairments in schizophrenia patients compared to controls. Furthermore, results of multiple comparisons showed that more serious barriers in orientation, language fluency, and negative automatic thinking existed in the metabolic syndrome group than in the healthy and non-metabolic syndrome groups. Spearman correlation and stepwise linear regression analyses showed that psychopathological symptoms, high waist circumference, and high triglyceride were the predictive factors for negative automatic thoughts, orientation, and language fluency. Those results collectively revealed that high waist circumference, high triglyceride and negative automatic thinking had validity and effectiveness in predicting the cognitive function impairments of the metabolic syndrome group.Conclusion: The present findings strongly supported the notion that aberrant parameters of high waist circumference, high triglyceride and high negative automatic thoughts had validity and effectiveness predictive role for cognitive impairments in the schizophrenics with metabolic syndrome. The schizophrenia patients with metabolic syndrome should receive regular monitoring and adequate treatment for metabolic and psychological risk factors.Keywords: second-generation antipsychotics, negative symptoms, diet, Montreal Cognitive Assessment Scale, Verbal Fluency Test

Feng Qian,1– 3,&ast; Song Hu,4,&ast; Yueping Zhu,2,3 Yinling Wang,2,3 Jin Liu,2,3 Jialu Qiao,4 Xiji Shu,4 Yong Gao,5 Binlian Sun,4 Chuanwu Zhu1– 3 1Department of Infectious Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, People’s Republic of China; 2Department of Infectious Diseases, The Affiliated Infectious Disease Hospital of Soochow University, Suzhou, 215131, People’s Republic of China; 3Department of Infectious Diseases, The Fifth People’s Hospital of Suzhou, Suzhou, 215131, People’s Republic of China; 4Wuhan Institute of Biomedical Sciences, School of Medicine, Jianghan University, Wuhan, 430056, People’s Republic of China; 5The First Affiliated Hospital, Department of Life Science and Medicine, University of Science and Technology of China, Hefei, 230001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanwu Zhu; Binlian Sun, Tel/Fax +86 512 87806206 ; +86 27 84225149, Email zhuchw@126.com; binlian17@jhun.edu.cnPurpose: To investigate factors involved in T-cell depletion in combination antiretroviral therapy (cART)-treated human immunodeficiency virus 1 (HIV-1)-positive patients.Patients and Methods: 29 HIV-1-positive patients were enrolled. The CD4+, CD8+ T cell subsets and CD56dim NK cells were detected by flow cytometry. The concentrations of cytokines were measured by enzyme-linked immunosorbent assay. Extraction, amplification, and viral load quantification of specimens were performed using the Roche Cobas Ampliprep/Cobas TaqMan HIV-1 test.Results: Compared with IR group, the total number of red blood cells (RBCs) and lymphocytes (LCs) in INR group was significantly reduced, and there was a significant positive correlation between the number of RBCs and that of LCs. The overall production rates of T cells-related cytokines were lower in INR group. However, the cell-surface expression of programmed death-1 (PD-1) on CD4+ T and CD8+ T cells were markedly elevated in INR group. Moreover, it was found that the proportion and the killing ability of CD56dim NK cells significantly increased in INR patients, and significantly correlated with apoptosis of T lymphocytes.Conclusion: A poor immune reconstitution in HIV-positive patients might result from multiple factors, including bone marrow suppression, high PD-1 expression on the surface of CD4+ T cells, and over-activation of T and NK cells. Besides, the activity of NK cells and RBCs count might be important auxiliary indicators for immune reconstitution and provided a reliable guidance for developing strategies to improve immune reconstitution.Keywords: AIDS, T-cells, CD56dim NK cells, antiretroviral therapy, immune reconstitution

Xu Yin,1 Xiang Zhong,2 Jun Li,1 Ma Le,1 Shiting Shan,1 Chunfu Zhu1 1Department of Hepatobiliary and Pancreatic Surgery, Changzhou No.2 People’s Hospital Affiliated with Nanjing Medical University, Changzhou, Jiangsu, 213000, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226000, People’s Republic of ChinaCorrespondence: Chunfu Zhu, Email zcfmlm@njmu.edu.cnObjective: To explore the value of modified RANSON score in predicting mortality from severe acute pancreatitis (SAP).Methods: In this retrospective study, 461 SAP patients hospitalized from January 2016 to January 2020 were enrolled. AP (acute pancreatitis) patients from our hospital were employed as the training set. In addition, AP patients from the affiliated hospital of Nantong University were set as the validation set. The clinical characteristics of patients were compared between the two sets. The independent risk factors for SAP were determined through logistic regression. Moreover, the risk factors were derived for various prediction models by logistic regression. Multiple methods were adopted to assess the predictive ability of various models.Results: A total of 338 patients were assigned into the training set, while 123 patients were assigned into the validation set. The patients in the training and validation sets showed the consistent distribution trends (P> 0.05). In the training set, significant differences between patients in the non-survival and survival groups were BMI, PCT, platelets (PLT), direct bilirubin (DBil) and RANSON scores (P< 0.05). In further multivariate analysis, BMI, PCT and RANSON score were found as the independent risk factors for the mortality of SAP (OR=1.12, 1.25, 1.28, 95% CI:1.06– 1.19, 1.08– 1.44, 1.12– 1.47, P< 0.05). In the training set and validation set, ROC curve analysis showed that AUC of BMI+RANSON score was 0.778 and 0.789, respectively. In the calibration curve, the fitting degree of RANSON score+BMI and ideal assessment model was 0.975 and 0.854, respectively. The decision curve suggested that the net benefit per patient increased with the lengthening of the RANSON score+ BMI model curve. As revealed by the results of NRI and IDI indicators, RANSON score+BMI was optimized based on RANSON score (P< 0.05).Conclusion: BMI+RANSON was confirmed as a modified model effective in predicting the mortality from SAP.Keywords: SAP, BMI, RANSON score, mortality, model

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

Li Zhu,1– 3,&ast; Jin Li,4,5,&ast; Junchi Xu,4,5 Fan Chen,2,3 Xunxun Wu,2,3 Chuanwu Zhu1– 3 1Department of Infectious Diseases, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2Department of Hepatology, the Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 3Department of Hepatology, the Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China; 4Central Laboratory, the Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 5Central Laboratory, the Fifth People’s Hospital of Suzhou, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuanwu Zhu, Department of Infectious Diseases, the Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, 215004, People’s Republic of China, Email zhuchw@126.comIntroduction: The adaptive immune response may reflect the immunomodulatory efficacy during peginterferon alfa-2a (PEG-IFN α-2a) treatment in chronic hepatitis B (CHB) patients. We evaluated the predictive efficiency of T-cell subsets on patient’s response to PEG-IFN α-2a treatment.Methods: The proportions of CD8+PD-1+, CD8+Tim-3+ and CD4+CD25high T-cells were measured at baseline and week 52 in CHB patients who underwent PEG-IFN α-2a treatment. The proportions of T-cell subsets were compared among different responders and non-responders (determined by biochemical, serological, and virological responses).Results: The baseline proportions of the three T-cell subsets were significantly higher in CHB patients (65 cases) than in healthy controls (28 cases), while the proportions declined significantly after 52 weeks of PEG-IFN treatment. Responders (ALT < 40 IU/L, 89.2% [58/65]; HBV DNA < 2.7 log10 IU/ml, 66.2% [43/65]; and HBeAg seroconversion [SR], 53.9% [35/65]) experienced more pronounced declines in the proportion of T-cell subsets compared to non-responders. In particular, the baseline proportions of CD4+CD25high T-cells displayed significant difference between SR and non-SR groups. The stepwise logistic regression analysis identified that CD4+CD25high T-cells combined with baseline HBV DNA and ALT can predict SR and CR (ALT < 40 IU/L, HBV DNA < 2.7 log10 IU/mL and HBeAg seroconversion) after 52 weeks of PEG-IFN treatment with high accuracy.Conclusion: PEG-IFN therapy induces significant declines in the proportion of some key T-cell subsets in HBeAg-positive patients. The model constructed with CD4+CD25high T-cells combined with ATL and HBV DNA may help to predict the efficacy of PEG-IFN α-2a therapy.Keywords: PEG-IFN α-2a, chronic hepatitis B, clinical response, HBeAg seroconversion, T-cell subsets

Liqi Zhu,1,2 Zhihao Wu,1,2 Chen Zhu,1,2 Jun Yin,1,2 Yuzheng Huang,3,4 Jie Feng,5 Quan Zhang1,2 1Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 2Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China; 3National Health Commission Key Laboratory of Parasitic Disease Control and Prevention, Jiangsu Provincial Key Laboratory on Parasite and Vector Control Technology, Jiangsu Institute of Parasitic Diseases, Wuxi, Jiangsu Province, 214064, People’s Republic of China; 4Public Health Research Center, Jiangnan University, Wuxi, Jiangsu Province, 214122, People’s Republic of China; 5Shanghai Laboratory Animal Research Center, Shanghai Quality Monitoring Center of Laboratory Animals, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Quan Zhang, Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, People’s Republic of China, Tel +86 138-1584-1244, Email zquan@yzu.edu.cnObjective: IL-17 is a key regulator of the inflammatory response, and as such, it is involved in the constraint and clearance of pathogens. The mechanism of IL-17 in the pathogenesis of inflammatory bowel disease (IBD) caused by microbial infection is still unclear. Helicobacter hepaticus infection can induce colitis in many mouse strains, and thus, it has been widely used in the study of IBD pathogenesis.Methods: In this study, male C57BL/6, BALB/c, Il-10−/−, and Il-17a−/− mice were infected with H. hepaticus for several weeks. Histopathology, H. hepaticus colonization and distribution, expression of inflammatory cytokines and lysozyme, and distribution of mucus in proximal colon were examined.Results: The colonic colonization of H. hepaticus was abnormally high in Il-17a−/− mice. H. hepaticus infection caused only mild to moderate colitis symptoms in Il-17a−/− mice, including low levels of lymphocyte infiltration, epithelial cell defects, goblet cell reduction, and crypt atrophy without obvious hyperplasia in the later stage of infection. Furthermore, many inflammatory genes were significantly increased in the proximal colon of H. hepaticus-infected Il-17a−/− mice compared with C57BL/6 mice. In addition, the reduction of colonic mucus and the down-regulation of ZO-1, Claudin-1, and IL-22 were observed in Il-17a−/− mice compared with C57BL/6 mice post H. hepaticus infection.Conclusion: These results demonstrated that the deletion of IL-17A impaired the integrity of the intestinal epithelium, weakened the secretion of mucus, attenuated colonic mucosal regeneration, reduced the ability to resist microbial infection, and finally led to colitis caused by H. hepaticus.Keywords: Helicobacter hepaticus, IL-17A, colitis, crypt atrophy

Hai Zhao,1,&ast; Yaqiong Huang,1,&ast; Hao Wang,2 Juan Zhao,1 Shanshan Tian,1 Haixia Bai,1 Mufang Guo,1 Caiping Dong,1 Yongliang Shi,1 Xia Li,1 Chengjun Zhu,1 Tao Feng,1 Xia Ma,3 Zhifei Hou1,4 1Department of Pulmonary and Critical Care Medicine, Sinopharm Tongmei General Hospital, Datong, People’s Republic of China; 2School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Department of Respiratory and Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4China-Japan Friendship Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhifei Hou; Xia Ma, Tel +86 18811189252 ; +86 15103510398, Email houzhifei1898@126.com; maxialn007@sina.comPurpose: CWP is an untreatable but preventable fibrotic lung disease caused by the chronic inhalation of coal dust. Genetic factors such as polymorphisms play an important role in the development of CWP. The present study investigated the association between the polymorphisms of SMAD4 and NLRP3 and CWP risk in a Chinese Han population.Patients and Methods: SMAD4 rs10502913 and NLRP3rs1539019 polymorphisms were examined in 292 CWP subjects and 315 coal dust-exposed controls. The genotypes were analyzed using direct sequencing. The allele and genotype proportion between the cases and controls were compared using the chi-square test.Results: The AG and GG genotypes of SMAD4 rs10502913 were not associated with altered CWP risk compared with AA genotype (adjusted OR = 1.535 and 1.426, 95% CI = 0.785– 3.000 and 0.732– 2.781, p = 0.210 and 0.297, respectively). Also, the NLRP3 rs1539019 heterozygous and homozygous variants CA and CC genotypes were not associated with the risk of CWP compared with the AA genotype (adjusted OR = 0.985 and 1.127, 95% CI = 0.652– 1.489 and 0.713– 1.782, p = 0.944 and 0.608, respectively). In addition, there was no interaction between SMAD4 rs10502913 and NLRP3 rs1539019 genotypes and smoking status on CWP risk in the stratified analyses.Conclusion: In this present study, SMAD4 rs10502913 and NLRP3 rs1539019 genotypes were not associated with altered CWP risk in the Chinese Han population. Large sample sizes and multicenter studies are needed to elucidate these results in the future.Keywords: CWP, polymorphisms, SMAD4 rs10502913, NLRP3 rs1539019

Xiangyang Zhang,1 Bin Qin,1 Min Wang,1 Junyi Feng,1 Chenglin Zhang,1 Chengshen Zhu,2 Suqin He,2 Hao Liu,2 Yaohe Wang,1 Saadyah E Averick,3 Nga TN Vo,4 Lei Huang,5 Wentao Liu,2 Zhimin Wang1 1Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 2School of Material Science and Engineering, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China; 3Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital, Pittsburgh, PA, USA; 4School of Engineering, Newcastle University, Newcastle Upon Tyne, NE1 7RU, UK; 5Inflammations Immunity Research Theme, Translational and Clinical Research Institute, FMS, Newcastle University, Newcastle Upon Tyne, NE1 7RU, UKCorrespondence: Zhimin Wang; Wentao Liu, Email wangzhimin1975@hotmail.com; wtliu@zzu.edu.cnPurpose: In order to overcome the biological barriers at all levels and enhance the delivery efficiency of siRNA, we have prepared a multifunctional siRNA delivery system (CHCE/siRNA nanoparticles) through self-assembly of the carboxymethyl chitosan modified with histidine, cholesterol, and anti-EGFR antibody (CHCE).Methods: The morphology of CHCE/siRNA NPs was detected by dynamic light scattering and scanning electron microscope. In vitro, we assessed the tumor-targeting, cellular uptake, and endosomal escape by flow cytometry and confocal laser scanning microscopy, confirming the CHCE/siRNA NPs functions in gene silencing and cell killing ability. In vivo, we examined the biodistribution of the CHCE/siRNA NPs by the IVIS imaging system and confirmed the therapeutic effect of NPs in the nude-mouse tumor model.Results: The CHCE/siRNA NPs exhibited nanosized spherical with narrow size distribution. In vitro, the CHCE/siRNA NPs incorporated a dual capability of tumor targeting and pH response that could facilitate cellular bind, cellular uptake, and endosomal escape. The CHCE/siRNA NPs could effectively silence the vascular endothelial growth factor A (VEGFA) to cause cell apoptosis and inhibit proliferation. In vivo, the CHCE/siRNA NPs could target tumor sites to knock down VEGFA and achieve a better anti-tumor effect.Conclusion: We successfully prepared a novel siRNA delivery system with the double capability of tumor targeting and pH response, which can break through the biological barriers to penetrate deep into tumors and achieve better therapeutic tumor effects, providing a new ideal delivery platform for siRNA.Keywords: multifunctional carboxymethyl chitosan, targeting delivery, endosomal escape, gene silencing, anti-tumor therapy

Wenfang Zhu,1,&ast; Yao Ma,2,&ast; Wen Guo,1 Jing Lu,1 Xiaona Li,1 Juan Wu,1 Pei Qin,1 Chen Zhu,1 Qun Zhang1 1Department of Health Management Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China; 2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qun Zhang Tel +86 25 68303925Fax +86 25 68303925Email lucyqzhang@126.comIntroduction: Lactate dehydrogenase (LDH) is an important oxidoreductase in the anaerobic metabolic pathway. The role of LDH in arterial stiffness (AS) and 10-year cardiovascular disease (CVD10) risk has not been established.Methods: This retrospective, cross-sectional, and observational study evaluated the relationships between the LDH level and AS and CVD10 risk in 12,597 health-examined people (6988 men and 5609 women; mean age, 49.49 years) in China. Brachial–ankle pulse wave velocity (baPWV) was used to estimate AS. The Framingham CVD 10-year risk prediction model was used to calculate the CVD10 risk score.Results: In both sexes, an increased LDH level was associated with increased AS and CVD10 (men: β = 0.032, P < 0.001; women: β = 0.025, P < 0.001). Half of the population with a high LDH level (≥ 172 U/L) showed significantly increased AS and CVD10 risk score. Men and women with baPWV ≥ 1400 cm/s had a higher LDH level, and the latter was significantly different from that of the group with baPWV < 1400 cm/s (men: 176.93± 30.99 vs 173.00± 33.36, P < 0.001; women: 189.10± 34.20 vs 171.39± 31.08, P < 0.001). In both sexes, a higher level of LDH was noted in groups with higher CVD10 risk score (men: 176.65± 32.51 vs 172.94± 32.46, P < 0.001; women: 202.51± 44.05 vs 175.73± 32.39, P < 0.001).Discussion: An increased LDH level may be associated with AS and CVD10 risk. The LDH level could be a new predictor of AS and CVD10 risk in health-examined populations.Keywords: lactate dehydrogenase, arterial stiffness, 10-year cardiovascular disease risk, brachial–ankle pulse wave velocity, Framingham CVD 10-year risk prediction model

Chao Zhu,1 Yongmei Yu,2 Shihui Wang,2 Xia Wang,1 Yankun Gao,1 Cuiping Li,1 Jianying Li,3 Yaqiong Ge,3 Xingwang Wu1 1Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241001, People’s Republic of China; 3GE Healthcare China, Shanghai, 210000, People’s Republic of ChinaCorrespondence: Xingwang WuDepartment of Radiology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Shushan District, Hefei, Anhui Province, 230022, People’s Republic of ChinaTel +86 138 56919001Email duobi2004@126.comPurpose: To establish a clinical radiomics nomogram to differentiate Crohn’s disease (CD) from intestinal tuberculosis (ITB).Patients and Methods: Ninety-three patients with CD and 67 patients with ITB were recruited (111 in training cohort and 49 in test cohort). The region of interest (ROI) for the lesions in the ileocecal region was delineated on computed tomography enterography and radiomics features extracted. Radiomics features were filtered by the gradient boosting decision tree (GBDT), and a radiomics score was calculated by using the radiomics signature-based formula. We constructed a clinical radiomics model and nomogram combining clinical factors and radiomics score through multivariate logistic regression analysis, and the internal validation was undertaken by ten-fold cross validation. Analyses of receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the prediction performance. DeLong test was applied to evaluate the performance of the clinical, radiomics and combined model.Results: The clinical radiomics nomogram, which was based on the 9 radiomics signature and two clinical factors, indicated that the clinical radiomics model had an area under the ROC curve (AUC) value of 0.96 (95% confidence interval [CI]: 0.93– 0.99) in the training cohort and 0.93 (95% CI: 0.86– 1.00) in validation cohort. The clinical radiomics model was superior to the clinical model and radiomics model, and the difference was significant (P = 0.006, 0.004) in the training cohort. DCA confirmed the clinical utility of clinical radiomics nomogram.Conclusion: CTE-based radiomics model has a good performance in distinguishing CD from ITB. A nomogram constructed by combining radiomics and clinical factors can help clinicians accurately diagnose and select appropriate treatment strategies between CD and ITB.Keywords: Crohn’s disease, intestinal tuberculosis, computed tomography, radiomics, nomogram