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Hao Huang,1 Zhiping Long,2 Ying Deng,3 Zhicong Huang,3 Zhonghua Lv,4 Qian Sun,4 Hui Liu,4 Hongsheng Liang,5 Fulan Hu6 1Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Epidemiology, Public Health School of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, People’s Republic of China; 4Department of Neurosurgery, Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 6Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of ChinaCorrespondence: Fulan Hu, Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen, Guangdong, People’s Republic of China, Email hufu1525@163.com Hao Huang, Department of Preventive Medicine, Zhuhai Campus of Zunyi Medical University, Zhuhai, Guangdong, People’s Republic of China, Email hhxiaowo@163.comPurpose: Mitochondrial metabolism is essential for energy production and the survival of brain cells, particularly in astrocytes. Cuproptosis is a newly identified form of programmed cell death that occurs due to the disruption of mitochondrial metabolism caused by excessive copper toxicity. However, the relationship between cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) and the prognosis of gliomas remains unclear.Patients and Methods: In this study, we utilized 32,293 cells obtained from three in-house single-cell RNA sequencing (scRNA-seq) datasets, along with 6,148 cells acquired from the Chinese Glioma Genome Atlas (CGGA) involving 14 glioma patients, to identify and validate the TME of gliomas.Results: Based on an analysis of 32,293 single cells, we investigated intra-tumor heterogeneity, intercellular communication, and astrocyte differentiation trajectories in gliomas. Our findings revealed that the TGFβ signaling pathway exhibited a higher relative strength in astrocyte subpopulations. Additionally, we identified a novel three-gene signature (CDKN2A, SOX2, and MPC1) was identified for prognostic prediction. Furthermore, glioma patients with a high-risk score demonstrated poorer overall survival (OS) compared to those with a low-risk score in both training and testing datasets (Ptraining set < 0.001; Ptest set = 0.037).Conclusion: Our study revealed the prognostic value of the CRGs in astrocytes exhibiting tumor immunosuppressive characteristics in glioma. We established a novel three-gene prognostic model that offers new insights into the prognosis and treatment strategies for gliomas. Keywords: scRNA-seq, gliomas, astrocyte, cuproptosis, prognosis

Ying Chen,1,&ast; Hanyu Liang,2,&ast; Huaibin Jiang3 1School of Arts and Child Education, Yango University, Fuzhou, People’s Republic of China; 2School of Psychology, Inner Mongolia Normal University, Hohhot, People’s Republic of China; 3School of Education, Fujian Polytechnic Normal University, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaibin Jiang, School of Education, Fujian Polytechnic Normal University, No. 1 Campus New Village, Longjiang Street, Fuqing, 350300, People’s Republic of China, Email jianghuaibin@126.comPurpose: Non-suicidal self-injury (NSSI) is a growing public health concern among college students, with cybervictimization (CV) emerging as a significant contributing factor. Grounded in the experiential avoidance theory, this study investigates the mediating roles of cognitive fusion and negative emotions in the relationship between CV and NSSI, providing new insights into these key variables.Methods: A convenience sample of 457 undergraduate students (29% male; mean age 18.36± 0.66 years) from two universities in Fujian Province participated in this study. Data were collected using the Cyberbullying Victimization Scale, Cognitive Fusion Questionnaire, Positive and Negative Affect Schedule, and Non-Suicidal Self-Injury Scale. Descriptive statistics and Pearson correlation analysis were conducted using SPSS 25.0, while the mediating effects were analyzed using Process 3.5.Results: (1) Significant positive correlations were found among CV, cognitive fusion, negative emotions, and NSSI (p < 0.01). (2) CV was directly associated with NSSI (β = 0.22, p < 0.001) and positively predicted both cognitive fusion (β = 0.17, p < 0.001) and negative emotions (β = 0.15, p < 0.01). Additionally, cognitive fusion (β = 0.16, p < 0.01) and negative emotions (β = 0.11, p < 0.05) significantly predicted NSSI. (3) Mediation analyses revealed that cognitive fusion and negative emotions mediated the CV-NSSI relationship through three pathways: CV→cognitive fusion→NSSI (mediation effect = 0.026), CV→negative emotions→NSSI (mediation effect = 0.02), and CV→cognitive fusion→negative emotions→NSSI (mediation effect = 0.01).Conclusion: The study confirms that CV influences NSSI indirectly through cognitive fusion and negative emotions, supporting the experiential avoidance model. These findings underscore the importance of addressing cognitive and emotional processes in interventions aimed at reducing NSSI among college students.Keywords: cybervictimization, non-suicidal self-injury, cognitive fusion, negative emotions

Weixin Bei,1,2,&ast; Shuhui Dong,1,2,&ast; Guoying Liu,1,3,4,&ast; Lanfeng Lin,2,5,&ast; Yaofei Jiang,1,2 Nian Lu,1,2 Wangzhong Li,1,2 Hu Liang,1,2 Yanqun Xiang,1,2 Weixiong Xia1,2 1Department of Nasopharyngeal Carcinoma, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 3Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Radiation Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanqun Xiang; Weixiong Xia, Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Tel +86-20-87343643, Fax +86-20-87343392, Email xiangyq@sysucc.org.cn; xiawx@sysucc.org.cnBackground: We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy.Patients and Methods: We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR).Results: A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1– 28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3– 14.0] vs 5.0 months [95% CI 2.8– 7.2], P = 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, P = 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, P = 0.025).Conclusion: mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.Keywords: metastatic nasopharyngeal carcinoma, chemotherapy, PD-1 immune checkpoint inhibitors, second-line treatment strategies

Yufeng Yao,1,2 Zhenli Lin,3 Baikang Ye,1 Tingxi Long,1,4 Suting Li,1,4 Huixian Liang,1,4 Tianyi Luo,1,4 Xiaoyan Dou1 1Department of Ophthalmology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of China; 2Shantou University Medical College, Shantou, Guangdong Province, People’s Republic of China; 3Department of Ophthalmology, Shenzhen University General Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 4Shenzhen University Medical College, Shenzhen University, Shenzhen, Guangdong Province, People’s Republic of ChinaCorrespondence: Xiaoyan Dou, Department of Ophthalmology, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, No. 3002 Sungang West Road, Futian District, Shenzhen, Guangdong Province, 518035, People’s Republic of China, Tel/Fax +86 13600169183, Email douxy08@163.comPurpose: Previous studies simply linearized the relationship between low density lipoprotein (LDL) and diabetic macular edema’s (DME) probability, ignoring the possibility of a nonlinear relationship between them. We aimed to investigate the nonlinear relationship between LDL and DME probability in patients with type 2 diabetes mellitus (T2DM).Patients and methods: The study recruited 431 T2DM patients who attended Guangdong Provincial People’s Hospital from December 2017 to November 2018. A multivariate logistic regression model was conducted to evaluate the association between LDL and DME probability. The nonlinear relationship was identified by generalized additive model. Subgroup analyses were performed to assess the consistency of the association in different subgroups.Results: LDL was positively associated with DME probability (OR=1.60, 95% CI: 1.10~2.34, P=0.0145) after adjusting for covariates. A nonlinear relationship between LDL and DME probability was discovered, with an inflection point for LDL around 4.85 mmol/L (95% CI: 4.18~4.93, P=0.037). The effect sizes and the confidence intervals on the left and right sides of inflection point were 2.17 (1.31 to 3.58) and 0.26 (0.04 to 1.77), respectively. Subgroup analyses revealed other variables had no effect on the association between them.Conclusion: Our finding suggested LDL was positively correlated with DME probability in T2DM patients. And the relationship between LDL and DME probability was nonlinear. Our findings need to be confirmed by further causal researches.Keywords: low density lipoprotein, diabetic macular edema, nonlinearity, association

Hang Wang,1,&ast; Bobin Hu,1,&ast; Hengkai Liang,1 Rongming Wang,1 Lu Wei,1 Tumei Su,1 Qingmei Li,1 Qianbing Yin,1 Yanfei Feng,1 Minghua Su,1 Jianning Jiang1,2 1Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianning Jiang; Minghua Su, Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Tel +86-0771-5356531, Email gxjjianning@163.com; smh9292@163.comPurpose: Few studies have reported the integrated characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after long-term antiviral therapy. This study aimed to investigate the HBV integration features in HBV-HCC patients who had undergone long-term antiviral therapy, evaluate their impact on clinical indicators, and analyze the potential mechanisms involved.Patients and Methods: We utilized genome-wide association study (GWAS) to analyze liver cancer tissues and detect the presence of HBV integration. Seventeen patients with HBV integration were included in the integration (Int) group, while the remaining five patients were included in the non-integration (N-int) group. Clinical indicators were regularly monitored and compared between the two groups. The characteristics of HBV integration patterns were analyzed, and differences between the groups were explored at the chromosome and genomic levels.Results: After long-term antiviral therapy, although the frequency of HBV integration in HBV-HCC was reduced, residual HBV integration still accelerated the development of HCC. It affected the diagnosis, treatment, and prognosis of patients. HBV integration events led to changes in chromosome structure, which were closely related to HCC. Novel fusion genes were detected at a high frequency and had the potential to be specific detection sites for HBV-HCC.Conclusion: HBV integration events are synergistically involved in the human genome and HBV, which can lead to chromosome structural instability, gene rearrangement events closely related to HCC production, and the formation of new specific fusion genes.Keywords: hepatitis B virus, long-term antiviral therapy, hepatocellular carcinoma, integration, gene rearrangement

Kang Zhao,1,&ast; Hanfei Zhu,1,&ast; Lidong Huang,1,&ast; Ningli Yang,2 Saleh Mohammed Alhaj Othman,1 Wenbing Shi,1 Hongxia Hua,2 Hui Liang,2 Qin Xu1 1School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Xu, School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, 211166, People’s Republic of China, Tel +86 13601587208, Email qinxu@njmu.edu.cn Hui Liang, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +86 13951601358, Email lianghui@jsph.org.cnBackground: Diet and physical activity (PA) are pivotal behaviors for managing energy balance post-bariatric surgery. Given the need for dual behavioral management, understanding the interplay of cognitive factors influencing these behaviors is crucial. This study applied the compensatory carry-over action model (CCAM) to explore the impact of cognitive factors on behaviors and their subsequent effects on subjective health outcomes.Methods: This cross-sectional study was conducted among patients at the third month after bariatric surgery in China. Data on diet and PA status, behavioral cognitive factors (intention, self-efficacy, compensatory belief, transfer cognition), and subjective health outcomes (perceived stress, well-being, quality of life) were collected. Structural equation model (SEM) was employed to test hypotheses in CCAM and assess mediation relationships.Results: Analysis of data from 239 patients revealed the following: (1) Among antecedent cognitive factors, only compensatory belief significantly influenced diet (P< 0.001). (2) Intention and self-efficacy directly correlated with their respective behaviors, while compensatory belief affected intention, and transfer cognition impacted self-efficacy (P< 0.05), aligning with CCAM hypotheses. (3) PA demonstrated significant influence only on perceived stress (P=0.004), whereas diet significantly affected all subjective health outcomes (P< 0.05). (4) Mediation analysis indicated intention partially mediated the relationship between compensatory belief and diet and fully mediated the relationship between compensatory belief and PA. Self-efficacy completely mediated the relationship between transfer cognition and diet and PA.Conclusion: Transfer cognition’s carry-over effect did not directly influence behaviors among antecedent cognitions. Interventions should primarily target improving diet by mitigating compensatory belief. Moreover, diet exhibited a more pronounced impact on overall health compared to PA. Consequently, prioritizing dietary intervention over PA intervention is warranted based on the analysis of CCAM and the aim of promoting joint behaviors post-bariatric surgery.Keywords: bariatric surgery, compensatory carry-over action model, diet, physical activity, cognitive factors

Nengwen Wu,&ast; Xiaoqing Shen,&ast; Jianwei Li, Miaolian Chen, Guishen Wu, Haiming Niu, Hongkai Liang, Ting Yang Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongkai Liang; Ting Yang, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email 1019978382@qq.com; 53103334@qq.comAbstract: Septic cardiomyopathy (SCM) is often associated with bacterial infections but also occurs with infections with viruses such as influenza and spirochetes, including syphilis. However, there has been no systematic investigation into whether Aspergillus infections can cause septic cardiomyopathy. We report on such a case for the first time in a patient without immunodeficiency. Therefore, clinicians should be concerned with septic cardiomyopathy caused by some atypical or rare pathogens when admitting such patients.Keywords: septic cardiomyopathy, aspergillus, extracorporeal membrane oxygenation, metagenomic next-generation sequencing

Sheng Yin,1 YingRui Lin,1 Bingqi Wang,1 Yizhi Peng,2 Zeyou Wang,1 Xiaolin Zhu,1 Hao Liang,1 Xianping Li,1 Min Wang1 1Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China; 2Department of Laboratory Medicine, Hunan Cancer Hospital, Central South University, Changsha, Hunan, 410031, People’s Republic of ChinaCorrespondence: Min Wang, Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, People’s Republic of China, Tel +86 13298697558, Email wangmin0000@csu.edu.cnPurpose: Bloodstream infection(BSI) is linked with high mortality, underscoring the significance of prompt etiological diagnosis for timely and precise treatment. This study aims to investigate the diagnostic value of droplet digital polymerase chain reaction(ddPCR) in combination with conventional inflammatory markers [interleukin-6(IL-6) and procalcitonin(PCT)] concerning disease progression and treatment prognosis in BSI patients. Furthermore, the study aims to explore a more efficient clinical application strategy.Patients and Methods: This prospective case seried study centers on 176 patients suspected of or confirmed with BSI. Blood samples were collected to extract nucleic acids for identifying pathogens (bacteria, fungi, and viruses) and determining copy loads via ddPCR.Results: The sensitivity of ddPCR was markedly higher compared to the culture method (74.71% vs 31.03%). A positive correlation existed between bacterial load and levels of inflammatory markers [IL-6 (P= 0.0182), PCT (P= 0.0029), and CRP (P= 0.0005)]. In suspected BSI cases, the combination of ddPCR and inflammatory markers could predict sepsis risk [ROC: Area under the curve(AUC)=0.6071, P= 0.0383]. Within confirmed BSI patients, the ddPCR bacterial load of those with SOFA< 7 was lower than that of the SOFA≥ 7 (P= 0.0334). ddPCR (OR: 1.789, P= 0.035) monitoring combined with PCT (OR: 1.787, P= 0.035) holded predictive value for SOFA progression (AUC=0.7913, P= 0.0003). Similarly, BSI survivors displayed a lower burden than non-survivors (P= 0.0170). Additionally, ddPCR combinated with IL-6 provided a more accurate and expedited insight into clinical outcomes prediction for BSI confirmed patients (AUC=0.7352, P= 0.0030). Serial monitoring of bacterial load by ddPCR effectively mirrored the clinical course of BSI in patients. Notably, patients with positive ddPCR virus infection exhibited significantly reduced lymphocyte counts (P= 0.0003).Conclusion: In a clinical context, qualitative ddPCR results and quantitative continuous monitoring can more precisely assess sepsis progression and treatment prognosis in BSI patients. Furthermore, ddPCR results offer quicker and more accurate reference points for clinical antibacterial and antiviral interventions.Keywords: bloodstream infection, droplet digital polymerase chain reaction, interleukin-6, procalcitonin, prognosis

Zhongqi Sun,1 Xin Li,1 Hongwei Liang,1 Zhongxing Shi,2 Hongjia Ren3 1Department of Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 2Department of Interventional Radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, People’s Republic of China; 3School of Information Science and Engineering, Yanshan University, Qinhuangdao, 066004, People’s Republic of ChinaCorrespondence: Zhongqi Sun, Email sunzhongqi2021@163.com; Hongjia Ren, Email renhj@ysu.edu.cnBackground: To develop and validate an overall survival (OS) prediction model for transarterial chemoembolization (TACE).Methods: In this retrospective study, 301 patients with hepatocellular carcinoma (HCC) who received TACE from 2012 to 2015 were collected. The residual network was used to extract prognostic information from CT images, which was then combined with the clinical factors adjusted by COX regression to predict survival using a modified deep learning model (DLOPCombin). The DLOPCombin model was compared with the residual network model (DLOPCTR), multiple COX regression model (DLOPCox), Radiomic model (Radiomic), and clinical model.Results: In the validation cohort, DLOPCombin shows the highest TD AUC of all cohorts, which compared with Radiomic (TD AUC: 0.96vs 0.63) and clinical model (TD AUC: 0.96 vs 0.62) model. DLOPCombin showed significant difference in C index compared with DLOPCTR and DLOPCox models (P < 0.05). Moreover, the DLOPCombin showed good calibration and overall net benefit. Patients with DLOPCombin model score ≤ 0.902 had better OS (33 months vs 15.5 months, P < 0.0001).Conclusion: The deep learning model can effectively predict the patients’ overall survival of TACE.Keywords: deep learning, transarterial chemoembolization, hepatocellular carcinoma

Xiaobo Li,1,2 Chen Yu,1 Xuewei Liu,3 Yejia Chen,1 Yutian Wang,1 Hongbin Liang,1 ShiFeng Qiu,1 Li Lei,1 Jiancheng Xiu1 1Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Cardiology, Xiangdong Hospital, Hunan Normal University, Liling, Hunan, People’s Republic of China; 3The Tenth Affiliated Hospital of Southern Medical University (Dongguan People’s Hospital), Southern Medical University, Dongguan, Guangdong, People’s Republic of ChinaCorrespondence: Jiancheng Xiu, Tel +8613903064940, Email xiujch@163.comObjective: To evaluate the prognostic value of the systemic immune-inflammatory index (SII) for predicting in-hospital major adverse cardiovascular events (MACEs) in patients with acute myocardial infarction (AMI) and establish a relevant nomogram.Methods: This study included 954 AMI patients. We examined three inflammatory factors (SII, platelet to lymphocyte ratio (PLR) and neutrophil to lymphocyte ratio (NLR)) to see which one predicts in-hospital MACEs better. The predictors were subsequently screened using bidirectional stepwise regression method, and a MACE nomogram was constructed via logistic regression analysis. The predictive value of the model was evaluated using the area under the curve (AUC), sensitivity and specificity. In addition, the clinical utility of the nomogram was evaluated using decision curve analysis. We also compared the nomogram with the Global Registry of Acute Coronary Events (GRACE) scoring system.Results: 334 (35.0%) patients had MACEs. The SII (AUC =0.684) had a greater predictive value for in-hospital MACEs in AMI patients than the PLR (AUC =0.597, P< 0.001) or NLR (AUC=0.654, P=0.01). The area under the curve (AUC) of the SII-based multivariable model for predicting MACEs, which was based on the SII, Killip classification, left ventricular ejection fraction, age, urea nitrogen (BUN) concentration and electrocardiogram-based diagnosis, was 0.862 (95% CI: 0.833– 0.891). Decision curve and calibration curve analysis revealed that SII-based multivariable model demonstrated a good fit and calibration and provided positive net benefits than the model without SII. The predictive value of the SII-based multivariable model was greater than that of the GRACE scoring system (P< 0.001).Conclusion: SII is a promising, reliable biomarker for identifying AMI patients at high risk of in-hospital MACEs, and SII-based multivariable model may serve as a quick and easy tool to identify these patients.Keywords: systemic immune-inflammatory index, major adverse cardiovascular events, inflammation, acute myocardial infarction

Liang Fu,1,2,&ast; Wenfei Wang,2,3,&ast; Juan Xiong,4,&ast; Peize Zhang,2 Hui Li,2 Xilin Zhang,5 Hancheng Liang,6 Qianting Yang,2 Zhaoqin Wang,2 Xinchun Chen,3 Guofang Deng,2 Yi Cai,3 Shenjie Tang1 1Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, People’s Republic of China; 2Shenzhen Third People’s Hospital, National Clinical Research Center for Infectious Disease (Shenzhen), Shenzhen Clinical Research Center for Tuberculosis, Southern University of Science and Technology, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathogen Biology, Guangdong Key Laboratory of Regional Immunity and Diseases, Shenzhen University School of Medicine, Shenzhen, Guangdong, People’s Republic of China; 4Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 5Tuberculosis Prevention and Control Department, the Fourth People’s Hospital of Foshan, Foshan, Guangdong, People’s Republic of China; 6Division Two of Tuberculosis Diseases Department, the Sixth People’s Hospital of Dongguan, Dongguan, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shenjie Tang; Yi Cai, Email tangsj1106@hotmail.com; caiyi0113@szu.edu.cnBackground: The rising prevalence and limited efficacy of treatments for pre-extensively drug-resistant tuberculosis (pre-XDR-TB) underscore an immediate need for innovative therapeutic options. A combination of host-directed therapy (HDT) and anti-TB treatment presents a viable alternative for pre-XDR-TB management. Sulfasalazine (SASP), by targeting the amino acid transport system xc (xCT), potentially reduces the intracellular Mycobacterium tuberculosis load and mitigates lung pathology, positioning it as a promising TB HDT agent. This study aims to assess the efficacy of SASP as a supplementary therapy for pre-XDR-TB.Methods: A pilot study examined the safety and effectiveness of two 9-month short-course, all-oral regimens for pre-XDR-TB treatment: Bdq-regimen (consisting of Bdq, linezolid, cycloserine, clofazimine, and pyrazinamide) and SASP-regimen (comprising SASP, linezolid, cycloserine, clofazimine, and pyrazinamide). The primary endpoint was the incidence of unfavorable outcomes 12 months post-treatment.Results: Of the 44 participants enrolled, 43 were assessable 12 months post-treatment. Culture conversion rates stood at 73.2% by Month 2 and escalated to 95.1% by Month 6. Overall, 88.4% (38/43) of the participants exhibited favorable outcomes, 85.2% (19/23) for the Bdq-regimen and 93.8% (14/15) for the SASP-regimen. The SASP-regimen group recorded no deaths or treatment failures.Conclusion: Both 9-month short-course, all-oral regimens manifested commendable primary efficacy in treating pre-XDR-TB patients. The SASP-regimen emerged as effective, safe, well-tolerated, and cost-effective.Plain language summary: This study explored a new way to treat a hard-to-treat type of tuberculosis (TB) using a medicine called Sulfasalazine, alongside usual TB treatments. Over 9 months, two groups of patients were given different sets of medicines, one including Sulfasalazine. The results, checked 12 months after treatment, showed that most patients improved, especially those given Sulfasalazine. No one in the Sulfasalazine group died or had their treatment fail, suggesting that Sulfasalazine could be a promising addition to current treatments for this tough-to-treat TB.Keywords: Sulfasalazine, host-directed therapy, pre-extensive drug-resistant tuberculosis, short-course, treatment

Runing Zhou,1 Xiyu Sun,2 Mingyue Guo,1 Huimin Zhang,1 Xuanfu Chen,1 Meixu Wu,1 Haozheng Liang,1 Xiaoyin Bai,1 Gechong Ruan,1 Hong Yang1 1Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy Medical Sciences and Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Hong Yang, Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Wangfujing Street, Beijing, 100730, People’s Republic of China, Tel +86-10-69155014, Email yangh@pumch.cnAim: The diagnosis of inflammatory bowel disease (IBD) worldwide is complicated and results in diagnostic delay. However, the diagnostic interval of IBD and the factors associated with diagnostic delay in patients in China have not been determined.Methods: We retrospectively analyzed clinical data of hospitalized IBD patients in Peking Union Medical College Hospital from January 1998 to January 2018. Patients were divided into non-delayed and delayed groups according to their diagnostic interval.Results: A total of 516 and 848 patients were confirmed to have Crohn’s disease (CD) and ulcerative colitis (UC), respectively. The median diagnostic intervals were 6 and 20 months in patients with UC and CD, respectively (P< 0.05). A decreasing trend in the diagnostic interval for IBD was observed over time, from 9 months to 1 month in UC patients and from 30 months to 3 months in CD patients. The longest diagnostic interval was 29.5 months in CD patients with first symptoms at the age of 51– 60 years and 12.5 months in UC patients at the age of 41– 50 years. In patients with CD, intestinal obstruction (OR=2.71), comorbid diabetes (OR=4.42), and appendectomy history (OR=2.18) were risk factors for diagnostic delay, whereas having fever as the first symptom may reduce its risk (OR=0.39). In patients with UC, the misdiagnosis of chronic enteritis (OR=2.10) was a risk factor for diagnostic delay.Conclusion: The diagnostic interval for IBD has decreased over the years. Some clinical manifestations, such as initial symptoms and age at symptom onset, may help to shorten this interval. Diseases such as tuberculosis and infectious enteritis should be considered during differentiation.Keywords: inflammatory bowel disease, diagnostic delay, China

Huang Z, Liang H, Chen L. Onco Targets Ther. 2020;13:2193–2202. We, the Editor and Publisher of the journal OncoTargets and Therapy have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of 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”.

Wanqing Lin,1,&ast; Hanyu Liang,2,&ast; Huaibin Jiang,3,&ast; Mohd Azrin Mohd Nasir,1,&ast; Huiling Zhou2 1School of Applied Psychology, Social Work & Policy, UUM College of Arts & Sciences, University Utara Malaysia, Sintok, Malaysia; 2School of Medical Humanities, Guizhou Medical University, Guiyang, People’s Republic of China; 3Department of Psychology, Fujian Polytechnic Normal University, Fuqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaibin Jiang; Mohd Azrin Mohd Nasir, Email jianghuaibin@126.com; mohdazrin@uum.edu.myPurpose: Harsh parenting is positively correlated with adolescents’ smartphone addiction, according to a growing corpus of studies. The various mediating processes that could underlie this link, however, are not well understood. Based upon the experiential avoidance model, the current research aimed to identify the relation between harsh parenting and adolescents’ smartphone addiction and the mediating roles of adolescents’ depression and experiential avoidance.Methods: We recruited 456 adolescents (female = 52.6%; Mage = 13.19 years, SD = 0.85) at a public junior high school in China to complete the harsh discipline scale, 90-item Hopkins symptom checklist, acceptance and action questionnaire version II, and smartphone addiction scale short version. SPSS24.0 was used to conduct independent samples t-test, descriptive statistics, Pearson correlation analysis and common method bias test, PROCESS were used to conduct a significance test of the chain mediation effect on the data. Age, gender, and grade were used as con-founders that were controlled in order to make cautious predictions.Results: The results showed that (1) harsh parenting was positively correlated with adolescents’ depression, experiential avoidance, and smartphone addiction; (2) both depression and experiential avoidance fully mediated the link between harsh parenting and smartphone addiction; and (3) depression and experiential avoidance also sequentially mediated the link between harsh parenting and smartphone addiction. These findings have significant implications for the prevention and intervention of adolescents’ smartphone addiction.Conclusion: These findings suggested that harsh parenting may have an indirect impact on smartphone addiction in both a simple way (parallel mediation) and a complicated way (serial mediation). In addition, these studies shed light on smartphone addiction prevention and intervention.Keywords: harsh parenting, depression, experiential avoidance, smartphone addiction, adolescents

Xiaoqing Shen,&ast; Hongkai Liang,&ast; Guishen Wu, Miaolian Chen, Jianwei Li Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianwei Li, Department of Critical Care Medicine, Zhongshan People’s Hospital, Zhongshan, 528400, People’s Republic of China, Email lijwprof2005@163.comAbstract: Streptococcus dysgalactiae subspecies equlsimilis (SDSE) is considered an important bacterial pathogen, and attention has also increased with the increasing number of invasive SDSE infections. Here, we report a patient with S. dysgalactiae toxic shock syndrome complicated by symmetrical peripheral gangrene (SPG). Despite surviving active treatment, amputation severely impacts the quality of life of patients. Therefore, we should pay attention to the early treatment of SDSE infection and the prevention and treatment of related complications.Keywords: Streptococcus dysgalactiae subspecies equlsimilis, streptococcal poisoning shock syndrome, symmetric peripheral gangrene

Xun Lu,1– 3 Yue Yuan,4 Ning Cai,1– 3 Dean Rao,1– 3 Min Chen,4 Xiaoping Chen,1– 3 Bixiang Zhang,1– 3 Huifang Liang,1– 3 Lei Zhang3,5 1Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Clinical Medical Research Center of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Division of Gastroenterology, Department of Internal Medicine at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 5Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province (Preparatory), Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, People’s Republic of ChinaCorrespondence: Lei Zhang, Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province (Preparatory), Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Shanxi Medical University; Shanxi Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Taiyuan, 030032, People’s Republic of China, Email zhangl@tjh.tjmu.edu.cn Huifang Liang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, 430030, People’s Republic of China, Email lianghuifang1997@126.comPurpose: Tripartite motif containing 55 (TRIM55) is a member of the TRIM family and functions as an E3 ubiquitin ligase. It acts as a cancer promoter or suppressor in the malignant processes of multiple cancers. However, its proliferative function in hepatocellular carcinoma (HCC) has been poorly studied, and its underlying molecular mechanism remains unclear. In the present study, we investigated the role of TRIM55 in HCC and its mechanism of promoting HCC proliferation.Materials and Methods: Protein expression levels of TRIM55 were measured in paired HCC and normal tissue samples using immunohistochemical (IHC) staining. The correlation between TRIM55 and clinical features was evaluated by statistical analysis. At the same time, overexpression and knockdown experiments, cycloheximide (CHX) interference experiments, ubiquitination, co-immunoprecipitation and immunofluorescence staining experiments, as well as animal experiments were used to evaluate the potential mechanism that TRIM55 promotes proliferation of hepatocellular carcinoma in vitro and in vivo.Results: TRIM55 expression in HCC specimens was higher compared with the corresponding non-tumor tissues. The overall survival and disease-free survival time of patients with high TRIM55 expression were shorter than those with low expression of TRIM55. Functionally, TRIM55 promoted the proliferation of HCC cells and accelerated the growth of HCC xenografts. Mechanistically, TRIM55 interacted with thyroid receptor interacting protein 6 (TRIP6) and regulate its stability by influencing the ubiquitination process, thereby affecting the Wnt signaling pathway.Conclusion: Our results indicate that TRIM55 promotes HCC proliferation by activating Wnt signaling pathways by stabilizing TRIP6. Therefore, targeting TRIM55 may be an effective therapeutic strategy to inhibit HCC growth.Keywords: TRIM55, TRIP6, hepatocellular carcinoma, proliferation

Donglei Shi,&ast; Li Wei,&ast; Hongsen Liang, Dongqing Yan, Junhang Zhang, Zhaojun Wang Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, People’s Republic of China, Email wangzhj55@mail.sysu.edu.cnBackground: Malaria remains a substantial concern in the realm of public health on a worldwide level. Using information from the global burden of disease (GBD) 2019 for 204 countries and territories between 1990 and 2019, we assessed the burden of malaria.Methods: Data on malaria were derived from the GBD 2019 study between 1990 and 2019. We evaluated the number of incidence, deaths, disability-adjusted life years (DALYs), age-standardized incidence rates (ASIR), age-standardized mortality rates (ASMR), and age-standardized DALY rates (ASDR), examining them across variables such as age, year, gender, country, region, and socio-demographic index (SDI).Results: The burden of malaria decreased globally between 1990 and 2019. There were 2313.57× 105 incident cases and 6.43× 105 deaths in 2019, contributing to 464.38× 105 DALYs. Largest incident cases were observed in Western Sub-Saharan Africa [1151.72 (95% UI: 890.01– 1527.17)] × 105 in 2019. The only region where deaths increased between 1990 and 2019 was Western Sub-Saharan Africa. ASRs of malaria are distributed heterogeneously in different regions. The highest ASIR was observed in Central Sub-Saharan Africa [21,557.65 (95% UI: 16,639.4– 27,491.48)] in 2019. From 1990 to 2019, the ASMR of malaria declined. Compared to other age cohorts, the ASIR, ASMR, and ASDR for children aged between 1 to 4 years were found to be higher. Worst-affected regions by malaria infection were the low-middle SDI region and low SDI region.Conclusion: Malaria threatens global public health, especially in Central Sub-Saharan Africa and Western Sub-Saharan Africa. Children 1– 4 years old continue to bear the most significant burden of malaria. The study’s results will guide efforts to reduce malaria’s impact on the global population.Keywords: malaria, global burden of disease, ASIR, ASMR, ASDR

Xinwei Zhou,1,&ast; Ke Lin,2,&ast; Liangmin Fu,1,&ast; Fei Liu,3,&ast; Hansen Lin,1 Yuhang Chen,1 Bowen Zhuang,2 Hui Liang,4 Qiong Deng,4 Zhu Wang,4 Wei Chen,1 Junhang Luo,1,5 Jiazheng Cao,6 Pengju Li1 1Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Urology, Affiliated Longhua People’s Hospital, Southern Medical University, Shenzhen, People’s Republic of China; 5Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 6Department of Urology, Jiangmen Central Hospital, Jiangmen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengju Li, Department of Urology, The First Affiliated Hospital of Sun Yat-sen University, No. 58, Zhongshan Road II, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87618227, Email lipj25@mail.sysu.edu.cn Jiazheng Cao, Department of Urology, Jiangmen Central Hospital, Haibang Street 23, Jiangmen, 529030, People’s Republic of China, Tel +86-750-3165500, Email spotatos@163.comBackground: Triggering receptors expressed by myeloid cells-1 (TREM1) is a receptor belonging to the immunoglobulin superfamily and plays an important role in pro-inflammation in acute and chronic inflammatory disorders. However, the understanding of the immunomodulatory roles of TREM1 in the tumor microenvironment remains incomplete.Methods: The expression patterns of TREM1 mRNA in tumors and adjacent normal tissues were compared by analyzing data obtained from the Genotype-Tissue Expression and The Cancer Genome Atlas datasets. Survival analysis was performed to determine the prognostic value of TREM1. Functional enrichment analysis was applied to decipher the discrepancy in biological processes between high- and low-TREM1 groups across various cancers. The correlation between TREM1 and immune cell infiltration determined by using multiple algorithms was evaluated with the Pearson method. Four independent immunotherapy cohorts were adopted to validate the role of TREM1 as a biomarker.Results: TREM1 was elevated in most cancers as verified with clinical samples. Overexpression of TREM1 was linked with undesirable prognosis in patients. Further analysis revealed that TREM1 was positively correlated with immune response, pro-tumor pathways, and myeloid cell infiltration, while being negatively correlated with CD8+ T cell (including infiltration level and biological processes). Concordantly, tumors with high TREM1 levels were more resistant to immunotherapy. Through connective map analysis, therapeutically potential compounds like tozasertib and TPCA-1 were identified, which can be used synergistically with immunotherapy to improve the poor prognosis of patients with high TREM1 levels.Conclusion: Through a systematic and comprehensive pan-cancer analysis, we demonstrated that overexpression of TREM1 in tumors correlated closely with unfavorable outcome, infiltration of immune-suppressive cells, and immune regulation, which highlights its potential use as a tumor prognostic biomarker and a novel target for immunotherapy.Keywords: triggering receptors expressed by myeloid cells-1, pan-cancer, prognostic biomarker, tumor microenvironment, clear cell renal cell carcinoma, immunotherapy

Xin Su,1,&ast; Haifeng Li,2,&ast; Fajun Li,3 Hongsen Liang,4 Li Wei,4 Donglei Shi,4 Junhang Zhang,4 Zhaojun Wang4 1Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 2Department of Anesthesiology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Kunshan, People’s Republic of China; 4Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhang Zhang; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, No. 628, Zhenyuan Road, Guangming (New) Dist, Shenzhen, 518107, People’s Republic of China, Email zhangjh33@mail.sysu.edu.cn; wangzhj55@mail.sysu.edu.cnObjective: Exposure to ambient particulate matter (PM2.5) is the leading risk factor for developing chronic obstructive pulmonary disease (COPD) in China. The present study aimed to investigate the trends in COPD mortality attributable to ambient PM2.5 exposure in China from 1990 to 2019.Methods: Data on COPD burden attributable to ambient PM2.5 exposure in China were extracted from the Global Burden of Disease (GBD) study 2019. The estimated annual percentage change (EAPC) was used to assess COPD mortality from 1990 to 2019. The APC model was used to analyze the temporal trends in the rate of COPD mortality attributable to ambient PM2.5 exposure according to age, period, and cohort.Results: Exposure to ambient PM2.5 contributed to 192.4 thousand deaths in 1990 and 263.6 thousand deaths in 2019. The age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) due to ambient PM2.5 exposure showed a gradual downward trend, the ASMR and ASDR in 2019 decreased to 16.6 per 100,000 with an EAPC of − 2.82 (95% CI: − 8.61 to 3.34) and 278.6 per 100,000 with an EAPC of − 2.02 (95% CI: − 7.85 to 4.19), compared to those in 1990, respectively. The relative risk (RR) of COPD increased with age in females, while in males, mortality significantly increased from the levels among those in the 60– 64 age group to that among those in the 90– 94 age group. In the period group, the RR of COPD in males remained above 1.0 from the 2000 to 2004 period, but it gradually decreased in females. The cohort effect showed an overall downward trend.Conclusion: Although the ASMR and ASDR are decreasing in Chinese patients with COPD, the number of deaths due to COPD is increasing. Ambient PM2.5 exposure is more harmful in males and older people above 60 years of age.Keywords: chronic obstructive pulmonary disease, PM2.5, age-period-cohort model

Xianzhen Wei,&ast; Linlin Li,&ast; Meng Li, Hongjie Liang, Yu He, Shan Li Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shan Li, Email lis8858@126.comPurpose: The rising incidence of carbapenem-resistant Pseudomonas aeruginosa (PA) bloodstream infection (BSI) has made the selection of antibiotic therapy more difficult and caused high mortality. This study was aimed at exploring the risk factors for carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infection and identifying the risk factors for the outcomes of patients with PA-BSI.Methods: We performed a retrospective cohort study of patients with PA-BSI in a tertiary hospital from January 2017 to December 2021 in China. Epidemiological, clinical, and microbiological characteristics were described. Risk factors for CRPA-BSI and the outcomes of PA-BSI inpatients were identified, using multivariate logistic regression analysis.Results: A total of 198 PA-BSI inpatients were included. The negative outcome rate was significantly higher in patients infected with CRPA (15/34, 44.12%) than with carbapenem-susceptible Pseudomonas aeruginosa (CSPA) (35/164, 21.34%), and the difference was statistically significant (P=0.005). Multivariate logistic regression analysis showed that previous exposure to carbapenem (OR 3.519, 95% CI 1.359– 9.110, P=0.010) was an independent risk factor for CRPA-BSI. In addition, CRPA (OR 1.615, 95% CI 0.626– 4.171, P=0.32) was not an independent risk factor for negative outcome among PA-BSI inpatients.Conclusion: Our study showed that previous exposure to carbapenem was an independent risk factor for CRPA-BSI. CRPA was not an independent risk factor for a negative outcome in PA-BSI inpatients.Keywords: carbapenem-resistant, Pseudomonas aeruginosa bloodstream infection, risk factors, outcomes

Wenju Sun,1,&ast; Yuqing Cui,1,&ast; Xiaojuan Zhang,1,&ast; Yuze Wang,1 Zihao Zhang,2 Xianfei Ding,1 Huoyan Liang,1 Dong Wang,1 Yali Sun,1 Shaohua Liu,1 Xiaoguang Duan,1 Yibin Lu,3 Tongwen Sun1 1General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, 450052, People’s Republic of China; 2Department of Clinical Medicine, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Critical Care Medicine, Xinyang Hospital Affiliated to Zhengzhou University, Xinyang, 464000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongwen Sun, General ICU, The First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou, Henan Province, 450052, People’s Republic of China, Email suntongwen@163.comBackground: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. However, there is still no single drug that could reduce septic mortality. Previous studies have reported gabexate mesylate (GM) significantly reduced serum inflammatory factors, alleviated sepsis-induced lung injury and improved clinical outcomes. This study aimed to combine with microbiome sequencing and metabolomics analysis to explore the effects of GM administration in septic rats.Methods: Sixty SD rats were randomly divided into the sham control (SC), cecal ligation and puncture (CLP), and GM injection (GM) groups. The mortality was measured and colonic feces were collected to examine the gut microbiota and metabolism 24 h after the procedure. The lung tissues were collected for hematoxylin-eosin staining.Results: We observed the relative abundance of Pygmaiobacter, which contributed to short-chain fatty acids (SCFAs) promotion, Lactobacillus and Erysipelotrichaceae UCG-003 increased in the GM-treated rats, while Escherichia–Shigella and Akkermansia decreased compared to the sepsis-induced lung injury group. Furthermore, these 3 metabolites including Palmitoylethanolamide, Deoxycholic acid and Chenodeoxycholic acid correlated significantly to CLP- and GM-rich genus (P < 0.05). Besides, the lung tissues of CLP group showed more severe inflammatory infiltration and edema, and the mortality rate in the CLP group (10/20) was significantly higher than in the SC group (0/20) (P < 0.001) and GM group (4/20) (P < 0.05).Conclusion: Our findings showed that GM attenuated sepsis-induced lung injury rats and regulated metabolites related to gut microbiota, which may provide an effective treatment for sepsis patients.Keywords: sepsis, gabexate mesylate, gut microbiota, metabolomics, rats

Lin Gui,1 An-Biao Wang,2 Jie Zi,2 Ge-Yi Ai,3 Hui-Hui Wang,1 Mei Zhu,1 Hao Liang1 1Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Cardiovascular Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 3Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of ChinaCorrespondence: Mei Zhu; Hao Liang, Department of Ultrasound, Shandong Provincial Hospital Affiliated to Shandong First Medical University, No. 324, Jing Wu Road, Huai Yin District, Jinan, 250021, People’s Republic of China, Tel +86-15653101616 ; +86-13506411901, Email zhumeisph67@21cn.com; liamghaoo@outlook.comObjective: This study aimed to analyze the outcomes and risk factors of early postoperative death (within 30 days after surgery) in a single-center after repair of total anomalous pulmonary venous connection (TAPVC).Methods: The clinical data of 88 children who had been diagnosed with TAPVC and underwent radical operation in the Shandong Provincial Hospital Affiliated with Shandong First Medical University (China) from January 2015 to July 2021 were retrospectively analyzed. All the patients were divided into the survival group (n = 81) and the death group (n = 7) for the analysis of preoperative and postoperative clinical data. The variables associated with early postoperative death were statistically analyzed to obtain the risk factors for early postoperative death of TAPVC.Results: Of the 88 patients included in this study, 7 (7.95%) patients died early, including 4 supracardiac and 3 infracardiac cases. Recurrent pulmonary vein obstruction occurred in 2 patients after discharged from hospital, and both were intracardiac TAPVC. Delayed death occurred in 2 children, both of which were intracardiac TAPVC cases. According to univariate analysis, the risk factors statistically significantly associated with the early postoperative death included infracardiac type (P = 0.08), preoperative maximum pulmonary vein flow velocity (P = 0.031), preoperative mechanical ventilation (P = 0.043), preoperative maximum pulmonary artery pressure (P = 0.000), intraoperative cardiopulmonary bypass time (P = 0.003) and intraoperative aortic cross-clamp time (P = 0.000).Conclusion: Infracardiac type of TAPVC, preoperative maximum pulmonary vein flow velocity, preoperative mechanical ventilation, preoperative maximum pulmonary artery pressure, intraoperative cardiopulmonary bypass time and aortic cross-clamp time are the risk factors for early postoperative death.Keywords: congenital heart disease, TAPVC, cardiopulmonary bypass time, aortic cross-clamp time, risk factor, postoperative recurrent pulmonary venous obstruction

Hongbao Liang,1– 3,&ast; Chenghong Sun,2,3,&ast; Zhong Feng,2– 4 Xianzhen Wang,2 Lingpeng Kong,2,3 Feng Zhu,2,3 Jingchun Yao,2,3 Xiaomei Yuan,3 Zhong Liu,2,3 Guimin Zhang,2,3 Feng Li1 1School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China; 2Center for Drug Safety Evaluation, Shandong New Time Pharmaceutical Co., Ltd., Linyi, People’s Republic of China; 3State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co., Ltd., Linyi, People’s Republic of China; 4School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Li, Shandong University of Traditional Chinese Medicine, No. 4655 Daxue Road, Jinan, 250355, People’s Republic of China, Tel +86 139 6914 1796, Email 13969141796@163.com Guimin Zhang, Lunan Pharmaceutical Group Co., Ltd., State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, No. 209 Hongqi Road, Linyi, 276006, People’s Republic of China, Tel +86 539-5019206, Email lunanzhangguimin@yeah.netBackground: To improve the dissolution and bioavailability of the component-based Chinese medicine of Ginkgo biloba leaves (GBCCM), a novel nanocrystalline solid dispersion of GBCCM (GBCCM NC-SD) was first prepared.Methods: GBCCM mainly containing high pure flavonoid aglycones (FAs) and terpenoid lactones (TLs) was used as the model drug. PVP K30 and SDS were used as solubilizers, combined stabilizers and carriers, and GBCCM NC-SD was prepared by high-pressure homogenization combined with freeze-dryer. Morphology and crystal characteristic of GBCCM NC-SD were analyzed. The dissolution and bioavailability evaluation were performed to investigate the feasibility of GBCCM NC-SD by in vitro dissolution and in vivo integrated pharmacokinetic models.Results: After homogenizing for 30 cycles under the pressure of 650 bar and freeze-drying, GBCCM NC-SD with uniform quality would be obtained. The particle size, PDI and zeta potential were found to be 335.9 ± 32.8 nm, 0.29 ± 0.02 and − 28.4 ± 0.7 mV respectively. Based on charged aerosol detector (CAD) technology, a new chromatographic method for simultaneous detection of eight components in GBCCM was developed. In vitro drug release study showed that the cumulative dissolution of FAs and TLs in GBCCM NC-SD increased from 12.77% to 52.92% (P < 0.01) and 90.91% to 99.21% (P < 0.05) respectively. In comparison with physical mixture of GBCCM and stabilizer (PM), the integrated pharmacokinetics AUC0-t of FAs and TLs in GBCCM NC-SD were significantly increased (P < 0.05), and the T1/2 of TLs was also significantly prolonged (P < 0.05).Conclusion: This study demonstrated that novel GBCCM NC-SD was prepared using Polyvinylpyrrolidone K30 (PVP K30) and Sodium dodecyl sulfate (SDS) as a synergetic stabilizer and also provided a feasible way to improve the dissolution and oral bioavailability of poorly soluble candidate antihypertensive drugs.Keywords: Ginkgo biloba, flavonoid aglycones, terpenoid lactones, nanocrystalline solid dispersion, integrated pharmacokinetics, charged aerosol detector

Zhiman Xie,1,&ast; Jie Zhou,2,3,&ast; Fang Lu,2,3,&ast; Sufang Ai,1 Hao Liang,2– 4 Ping Cui,2,4 Jianyan Lin,1 Jiegang Huang2,3 1Nanning Infectious Disease Hospital Affiliated to Guangxi Medical University & The Fourth People’s Hospital of Nanning, Nanning, Guangxi, 530023, People’s Republic of China; 2Guangxi Key Laboratory of AIDS Prevention and Treatment & Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, Nanning, Guangxi, 530021, People’s Republic of China; 3School of Public Health, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 4Life Science Institute, Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiegang Huang; Jianyan Lin, Email jieganghuang@gxmu.edu.cn; linjianyan@126.comAbstract: We reported an HIV-naïve patient from a resource-limited area who was detected with multiple resistance sites associated with nucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) after the failure of the initial antiviral regimen dolutegravir/lamivudine (DTG/3TC) and subsequent Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). On May 8, 2021, a 53-year-old man was diagnosed with AIDS, Marneffei talaromycosis and fungal esophagitis, and was suspected of having tuberculosis (TB) in Guangxi, China. His baseline HIV RNA was 559,000 copies/mL and the CD4 count was 12 cells/μL, but resistance genotype testing was not performed. The patient remained immunosuppressed (CD4 count 3 cells/μL) after 12 weeks of initial antiviral treatment (ART) with DTG/3TC. After he was switched to BIC/FTC/TAF and started anti-TB treatment, the viral load (HIV RNA 163,200 copies/mL) was not effectively controlled, and there were multiple NRTIs drug-resistant mutations (D67N, K70R, M184V, T215V, K219Q) and INSTIs mutations (E138K, G140A, S147SG, Q148R). This suggested that in resource-limited areas, for HIV-naïve patients in advanced stages with active opportunistic infections, HIV RNA> 500,000 copies/mL, and low CD4 count, baseline resistance testing and increased HIV RNA testing frequency should be recommended, DTG/3TC was not recommended as initiation, and opportunistic infections should be treated promptly. In addition, switching to other INSTIs was not recommended in the absence of resistance testing and ineffective use of DTG.Keywords: HIV-naïve, DTG/3TC, BIC/FTC/TAF, resistance, resource-limited area

Hanyu Liang,1 Huaibin Jiang,2 Chengmian Zhang,2 Huiling Zhou,1 Bin Zhang,3 Anxie Tuo1 1Department Medical Humanities, Guizhou Medical University, Guiyang, People’s Republic of China; 2Department of Education, Fujian Normal University of Technology, Fuqing, People’s Republic of China; 3Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, People’s Republic of ChinaCorrespondence: Anxie Tuo, Email 1298253638@qq.comPurpose: With the widespread use of the Internet and mobile phone, cyberbullying has become a new type of bullying among adolescents. It is of great practical significance to explore the relevant factors affecting cyberbullying for prevention and intervention of adolescents’ cyberbullying. However, few studies have considered the effect of both the family and social factors on cyberbullying. Therefore, the current study examines whether the parent-adolescent conflict as a family factor and deviant peer affiliation as a social factor have an effect on adolescents’ cyberbullying, as well as the role of moral disengagement and gender.Methods: A total of 777 middle school students (females = 336; mean age = 13.57; SD = 0.98) were surveyed by using the Parent-child Relationship Questionnaire, Deviant Peer Affiliation Questionnaire, Moral Disengagement Questionnaire and Cyber Bullying Behavior Questionnaire. SPSS21.0 was used to conduct descriptive statistics, Pearson correlation analysis and T-test, PROCESS were used to conduct significance test of moderated mediation effect on the data.Results: Parent-adolescent conflict does not directly predict cyberbullying. Moral disengagement played a complete mediating role between parent-adolescent conflict and cyberbullying, and gender played a moderating role between moral disengagement and cyberbullying. Deviant peer affiliation directly predict cyberbullying. Moral disengagement played a partially mediating role between parent-adolescent conflict and cyberbullying, and gender played a moderating role between moral disengagement and cyberbullying.Conclusion: Attention should be paid to the effect of moral disengagement on cyberbullying in family and social factors, as well as the role of gender.Keywords: parent-adolescent conflict, deviant peer affiliation, moral disengagement, cyberbullying, gender

Haifeng Li,1,&ast; Hongsen Liang,2,&ast; Li Wei,2 Donglei Shi,2 Xin Su,3 Fajun Li,4 Junhang Zhang,2 Zhaojun Wang2 1Department of Anesthesiology, Guangdong Provincial People’s Hospitall, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 2Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Department of Respiratory, Hainan Hospital of PLA General Hospital, Sanya, People’s Republic of China; 4Department of Critical Care Medicine, The First People’s Hospital of Kunshan, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junhang Zhang; Zhaojun Wang, Department of Thoracic Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, 628 Zhenyuan Road, Shenzhen, People’s Republic of China, Tel/Fax +86-755-81206874, Email zhangjh33@mail.sysu.edu.cn; wangzhj55@gmail.sysu.edu.cnBackground: This study assessed health inequality in the global burden of chronic obstructive pulmonary disease (COPD) between 1990 and 2019 using data extracted from the Global Burden of Diseases (GBD 2019) study.Methods: Data were extracted from the GBD 2019 study. A series of comparative and descriptive analyses of the disease burden between women and men in countries with different socioeconomic development (SDI) status were performed. The slope index of inequality (SII), relative index of inequality (RII), and concentration index (CI) were calculated to measure the socioeconomic-related cross-national health inequity between 1990 and 2019.Results: The global health burden caused by COPD increased by 25.7% in terms of disability-adjusted life years (DALY) from 59.2 million years in 1990 to 74.4 million years in 2019. Global age-standardized DALY rate (ASDR) associated with COPD decreased by 40.0%, from 1537.7 per 100,000 population in 1990 to 926.1 per 100,000 population in 2019. The highest sex-specific DALY number was at age 70– 74 in male and female, and female is lower than male. However, after controlling for population size, the burden of COPD is more concentrated in the population living in low SDI countries, relative health inequality indicators (RII and CI) supported this conclusion.Conclusion: The health inequalities caused by the disparity of socioeconomic status are increasing, and the increasing concentration of wealth worldwide is likely to aggravate health inequalities associated with COPD.Keywords: chronic obstructive pulmonary disease, disease burden, health inequality

Jiahui Li,1 Sisi Li,1 Tiantian Jing,1 Mayangzong Bai,1 Zhiruo Zhang,1 Huigang Liang2 1School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of Business Information & Technology, Fogelman College of Business & Economics, University of Memphis, Memphis, TN, USACorrespondence: Zhiruo Zhang; Huigang Liang, Tel +86-21-63846590-776145, Email zhangzhiruo@shsmu.edu.cn; huigang.liang@gmail.comPurpose: The affective commitment of hospital staff is important for human resources management and the sustainable development of hospitals. Psychological safety is an important factor that contributes to an emotional connection to an organization among staff, yet its functional mechanism remains unclear. This study explored how psychological safety influenced affective commitment through the mediating roles of job satisfaction and job burnout.Methods: A battery of surveys were administered to all medical staff (n = 267) in a local second-grade comprehensive hospital. The surveys included the Psychological Safety Scale, Affective Commitment Scale, Minnesota Satisfaction Questionnaire, Maslach Burnout Inventory–Human Service Survey, and Perceived Organizational Support Scale.Results: Job satisfaction and job burnout fully mediated the relationship between psychological safety and affective commitment among hospital staff. In addition, perceived organizational support moderated the mediating path via job burnout, and the indirect effect of job burnout decreased when perceived organizational support increased.Conclusion: Psychological safety may enhance the affective commitment of hospital staff through improving job satisfaction or reducing job burnout. Perceived organizational support may counteract the deleterious effect of job burnout on affective commitment. Effective strategies to improve affective commitment among hospital staff may require consideration of job burnout and job satisfaction.Keywords: psychological safety, affective commitment, job burnout, job satisfaction, hospital management

Haishan Mo,1,&ast; Xu Lin,1,&ast; Ming Liu,2 Hui Liang1 1Department of General Surgery, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, People’s Republic of China; 2College of Oceanography, Hohai University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Liang, Department of General Surgery, Zhuhai People’s Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai, People’s Republic of China, Email zhlianghui@126.comAbstract: Cephalosporins and azithromycin are clinical antibiotics used to treat infections. Co-resistance to cephalosporins and azithromycin has been observed in some Enterobacterales, but it has only rarely been reported in Vibrio species. In this study, we isolated a cephalosporin- and azithromycin-resistant V. furnissii strain, VFN3, from hospital sewage. Whole-genome sequencing results showed that the strain VFN3 possesses an IncA/C2 plasmid, pVFN3-blaOXA-193K. This conjugative plasmid carries several clinically relevant drug resistance genes, including mph(A) and blaOXA-1. We also found that in the strain VFN3, mph(A) and blaOXA-1 are surrounded by insertion sequences and class I integrons, respectively. These data suggest that mobile elements mediate the transfer of mph(A) and blaOXA-1. This is the first reported Vibrio species that possesses an mph(A)- and blaOXA-1-bearing conjugative plasmid. The emergence of this conjugative multi-drug-resistance plasmid is of great concern to public health.Keywords: mph(A), blaOXA-1, conjugative plasmid, Vibrio furnissii

Yayuan Liu,1,&ast; Lizhi Lu,1,&ast; Xuemin Cheng,1 Qixiong Qin,1 Yunfei Wei,2 Dacheng Wang,3 Haihua Li,4 Guohui Li,5 Hongbin Liang,6 Shengyu Li,7 Zhijian Liang1 1Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, Guangxi Province, People’s Republic of China; 3Department of Neurology, The Ninth Affiliated Hospital of Guangxi Medical University, Beihai, 536000, Guangxi Province, People’s Republic of China; 4Department of Neurology, Fusui County People’s Hospital, Chongzuo, 532100, Guangxi Province, People’s Republic of China; 5Department of Neurology, Wuzhou Red Cross Hospital, Wuzhou, 543002, Guangxi Province, People’s Republic of China; 6Department of Neurology, Cenxi People’s Hospital, Cenxi, 543200, Guangxi Province, People’s Republic of China; 7Department of Neurology, The Affiliated Wuming Hospital of Guangxi Medical University, Nanning, 530100, Guangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijian Liang, Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530000, People’s Republic of China, Tel +86-771-5330705, Fax +86-771-5352627, Email liangzhijian@gxmu.edu.cnPurpose: To investigate independent risk factors for esophageal cancer-related ischemic stroke (ECIS) and to use them to develop an index of ECIS to help clinicians identify patients at high risk for ECIS or to identify ECIS from other types of ischemic stroke.Methods: We retrospectively enrolled active esophageal cancer (EC) patients with acute ischemic stroke (ECIS group) and patients with active EC without ischemic stroke (EC group), age- and sex-matched with ECIS patients, at seven centers from January 2011 to December 2020. Clinical data and laboratory and imaging findings were collected. Univariate and multivariate analyses were performed to analyze the independent risk factors for ECIS. Optimal cutoffs for sensitivities and specificities were obtained by Youden’s J statistic following a receiver operator characteristic (ROC) analysis of each risk factor and the product of the risk factors.Results: A total of 91 ECIS patients and 91 EC patients were included. Elevated levels of carcinoembryonic antigen (CEA) [odds ratio (OR) = 0.105, 95% confidence interval (CI): 1.051– 1.174, P < 0.001], D-dimer (DD) (OR = 0.003, 95% CI: 1.002– 1.004, P < 0.001), and neutrophil count (OR = 0.857, 95% CI: 1.628– 3.407, P < 0.001) were independent risk factors for ECIS. The area under the curve (AUC) of each independent risk factor and the product of the three independent risk factors were calculated by a receiver operator characteristic (ROC) curve, and the cutoff value from the largest AUC was called the ECIS index.Conclusion: It was suggested that elevated plasma DD and CEA levels and increased neutrophils in EC patients may altogether contribute to the development of ECIS. The index of ECIS may facilitate clinicians to identify patients at high risk for ECIS or to identify ECIS from other etiologic types of ischemic stroke.Keywords: independent risk factors, carcinoembryonic antigen, D-dimer, neutrophil count

Weixia Lai,1,2 Xixi Wu,2 Hao Liang1 1Department of Ophthalmology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Ophthalmology, First Affiliated Hospital of Guangxi Traditional Chinese Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Hao Liang, Department of Ophthalmology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Qingxiu District, Nanning, People’s Republic of China, Email liangh@stu.gxmu.edu.cnAim: High myopia (HM) is a global problem; however, the molecular pathogenesis of HM underlying lens remains largely unknown. The aims of the present study were to identify the potential key genes and pathways involved in lens changes of HM.Methods: Gene set enrichment analysis was carried out to identify the HM-specific pathway gene sets. The differentially expressed genes (DEGs) in lens epithelia of HM eyes compared to emmetropic control were screened using limma R package. A DEG-based protein–protein interaction network was constructed and used to identify hub genes and gene cluster analysis. The functional enrichment analysis was performed to reveal the potential biological functions for each gene cluster.Results: Multiple metabolism-related pathways were significantly enriched in lens epithelia of HM. The expression patterns of DEGs could accurately distinguish HM and emmetropic and CD34, CD40, EGF, IL1A, CD40LG, and CXCL12 maybe the potential key genes involved in HM. Three gene clusters were identified and involved in distinct pathways. MAPK signaling pathway and calcium signaling pathway were considered the key pathways involved in lens changes of HM, due to two gene clusters both involve in these two pathways.Conclusion: We identified potential key genes in pathological lens growth of HM eyes and proposed that the imbalances of MAPK signaling pathway and calcium signaling pathway may be the two crucial steps of pathological lens growth in HM.Keywords: high myopia, lens epithelia, hub genes, MAPK signaling pathway, calcium signaling pathway

Songyang Liu,1,&ast; Dongmei Luo,2,&ast; Jie Luo,2 Hanyin Liang,2 Yunfei Zhi,1 Dong Wang,3 Na Xu2 1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 2Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People’s Republic of China; 3Department of Bioinformatics, Basic Medical College of Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong Wang, Department of Bioinformatics, Basic Medical College of Southern Medical University, 1838 Guangzhou Da Dao North, Guangzhou, Guangdong, 510515, People’s Republic of China, Email wangdong79@smu.edu.cn Na Xu, Department of Hematology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Da Dao North, Guangzhou, 510515, Guangdong, People’s Republic of China, Email sprenaa@163.comBackground: Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood.Methods: We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups.Results: The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients’ OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups.Conclusion: A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.Keywords: acute myelogenous leukemia, pyroptosis, gene signature, tumor immune micro-environment, prognosis

Xiaolan Mo,1,2,&ast; Xiujuan Chen,3,&ast; Xianggui Wang,2,&ast; Xiaoli Zhong,2 Huiying Liang,3 Yuanyi Wei,1 Houliang Deng,1 Rong Hu,1 Tao Zhang,1 Yilu Chen,1 Xia Gao,4 Min Huang,2 Jiali Li2 1Department of Pharmacy, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, People’s Republic of China; 2Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Department of clinical Data Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 4Division of Nephrology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, 510623, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiali Li; Min Huang, Tel +86-20-39943034 ; +86-20-39943011, Fax +86-20-39943004 ; +86-20-39943000, Email lijiali5@mail.sysu.edu.cn; huangmin@mail.sysu.edu.cnPurpose: Tacrolimus (TAC) is a first-line immunosuppressant for patients with refractory nephrotic syndrome (NS). However, there is a high inter-patient variability of TAC pharmacokinetics, thus therapeutic drug monitoring (TDM) is required. In this study, we aimed to employ machine learning algorithms to investigate the impact of clinical and genetic variables on the TAC dose/weight-adjusted trough concentration (C0/D) in Chinese children with refractory NS, and then develop and validate the TAC C0/D prediction models.Patients and Methods: The association of 82 clinical variables and 244 single nucleotide polymorphisms (SNPs) with TAC C0/D in the third month since TAC treatment was examined in 171 children with refractory NS. Extremely randomized trees (ET), gradient boosting decision tree (GBDT), random forest (RF), extreme gradient boosting (XGBoost), and Lasso regression were carried out to establish and validate prediction models, respectively. The best prediction models were validated on a cohort of 30 refractory NS patients.Results: GBDT algorithm performed best in the whole group (R2=0.444, MSE=591.032, MAE=20.782, MedAE=18.980) and CYP3A5 nonexpresser group (R2=0.264, MSE=477.948, MAE=18.119, MedAE=18.771), while ET algorithm performed best in the CYP3A5 expresser group (R2=0.380, MSE=1839.459, MAE=31.257, MedAE=19.399). These prediction models included 3 clinical variables (ALB0, AGE0, and gender) and 10 SNPs (ACTN4 rs3745859, ACTN4 rs56113315, ACTN 4 rs62121818, CTLA4 rs4553808, CYP3A5 rs776746, IL2RA rs12722489, INF2 rs1128880, MAP3K11 rs7946115, MYH9 rs2239781, and MYH9 rs4821478).Conclusion: The association between the clinical and genetic variables and TAC C0/D was described, and three TAC C0/D prediction models integrating clinical and genetic variables were developed and validated using machine learning, which may support individualized TAC dosing.Keywords: tacrolimus, nephrotic syndrome, machine learning, prediction model, genetic polymorphism

Huaibin Jiang,1 Hanyu Liang,1 Huiling Zhou,1 Bin Zhang2 1Department of Education, Fujian Normal University of Technology, Fuqing, Fujian, People’s Republic of China; 2Department of Applied Psychology, Hunan University of Chinese Medicine, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Bin Zhang, Email zb303@163.comPurpose: Adolescent bullying has varying degrees of negative impact on both bullies and victims. Bullying in adolescents is complex, and the influence of individual factors and social factors should not be underestimated. Normative beliefs about aggression play an important role in adolescents’ bullying. However, the mediating and moderating mechanisms underlying this association remain largely unknown. The current study investigated the mediating role of moral disengagement between normative beliefs about aggression and bullying, as well as the moderating role of self-control in this relationship from the perspective of individual cognition.Methods: A sample of 491 Chinese adolescents (female = 38.9%; mean age = 13.05 years) were study participants. They completed questionnaires about normative beliefs about aggression, bullying, moral disengagement and self-control. SPSS21.0 statistical software was used to collate the obtained data, analyze descriptive statistics, and carry out reliability analysis and correlation analysis.Results: Moral disengagement mediated the relationship between normative beliefs about aggression and bullying (ab=0.13, 95% CI=[0.07, 0.21]). The association between normative beliefs about aggression and moral disengagement was moderated by self-control (β=− 0.08, t=− 2.25, p

Hanfei Zhu,1,&ast; Ziqi Ren,2,&ast; Hongxia Hua,3 Kang Zhao,1 Lingyu Ding,1 Shuqin Zhu,1 Ningli Yang,3 Hui Liang,3 Qin Xu1 1School of Nursing, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2School of Nursing, Fudan University, Shanghai, People’s Republic of China; 3Department of Bariatric and Metabolic Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin XuSchool of Nursing, Nanjing Medical University, 818 Tianyuan East Road, Jiangning District, Nanjing, Jiangsu, 210029, People’s Republic of ChinaTel +86-25-86869553; +86-13601587208Fax +86-25-86869555Email qinxu@njmu.edu.cnPurpose: This study was aimed to develop a questionnaire to assess the determinants of dietary adherence among patients after bariatric surgery based on the attitude-social influence-efficacy (ASE) model and to evaluate its psychometric properties.Patients and Methods: According to semi-structured interview, Delphi expert consultation and pilot study, the initial questionnaire was formed and applied to investigate 319 patients after bariatric surgery in a tertiary hospital in Jiangsu Province, China. The reliability and validity of the scale were tested.Results: The 28-item of the attitude-social influence-efficacy questionnaire after bariatric surgery (ASEQBS) was formed. The results of exploratory factor analysis showed that four factors, including intention, attitude, social influence, and self-efficacy, could be extracted, and the cumulative variance contribution rate reached 59.98%. Confirmatory factor analysis showed the model fit well. The content validity index of each item was 0.800– 1.000, and the content validity index of the ASEQBS was 0.857. The total Cronbach’s α of the ASEQBS was 0.920, the split-half reliability was 0.774, and the retest reliability was 0.922.Conclusion: The results suggest that ASEQBS is a valid and reliable measure of determinants of dietary adherence. It may be useful to evaluate the influence factors of dietary adherence and helpful to evaluate the efficacy of tailored dietary intervention programs.Keywords: bariatric surgery, dietary adherence, attitude-social influence-efficacy model, questionnaire, validation

Huan Long,1,2,&ast; Xiaojuan Qin,3,&ast; Rui Xu,1,2 Chunlei Mei,4 Zhiyong Xiong,5 Xuan Deng,1 Kaiyao Huang,1,2 Huageng Liang5 1Key Laboratory of Algal Biology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China; 3Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kaiyao Huang; Huageng Liang Email leonard19800318@hust.edu.cn; huangky@ihb.ac.cnIntroduction: Ultrasonic molecular imaging (UMI) technology has attracted increasing interest because of its low cost and capability to evaluate changes rapidly and noninvasively at the cellular and molecular levels. The key material of this technology is ultrasound-responsive gas vesicles (GVs). GVs synthesized by conventional chemical methods have several limitations, such as high costs, low yields, and complex production processes. In comparison, biosynthesized GVs have the advantages of high stability, a low risk of toxicity, genetic engineering characterization, easy post modification and drug loading potential. However, translational studies of their biosynthesis are still in their infancy; in particular, the duration of GVs in the circulatory system is essential for the usage of UMI in biomedicine and the clinic.Results: Here, we report novel GVs biosynthesized by the cyanobacterium Microcystis, which have a moderate size, a negative zeta potential, a rod-like morphology, and a protein-shelled gas-contained structure. These GVs without any chemical modifications could be detected in the mice circulatory system for more than 10 hours by clinically used ultrasound scanners. In particular, GVs can accumulate in tumors via the enhanced permeation and retention (EPR) effect 11 hours post-injection, and lasting at least 2 hours, which might be a potential aid for tumor diagnosis. Furthermore, pathological and hematological study suggested that GVs are safe for the host.Conclusion: We concluded that the GVs synthesized by Microcystis without any modifications have UMI potential for systemic evaluation as well as tumoral diagnosis after intravenous injection.Keywords: ultrasonic molecular imaging, gas vesicles, biosynthesis

Yiran Yan,1,&ast; Yan Chen,2,&ast; Zhongxun Liu,1 Feiyan Cai,3 Wanting Niu,4,5 Liming Song,1 Haifeng Liang,1 Zhiwen Su,1 Bo Yu,1 Fei Yan6 1Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 2Department of Ultrasonic Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, 510282, People’s Republic of China; 3Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China; 4VA Boston Healthcare System, Boston, MA, 02130, USA; 5Department of Orthopedics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA; 6CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, 518055, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei YanShenzhen Institutes of Advance Technology, Chinese Academy of Science, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, Guangdong, 518055, People’s Republic of ChinaTel +86 755 86392284Fax +86 755 96382299Email fei.yan@siat.ac.cnBo YuDepartment of Orthopedics, Zhujiang Hospital, Southern Medical University, 253 Gongye Avenue, Haizhu District, Guangzhou, Guangdong, 510280, People’s Republic of ChinaTel +86 20 67282573Fax +86 20 61643010Email gzyubo@163.comBackground: Parkinson’s disease (PD) is a progressive neurodegenerative disorder. Owing to the presence of blood–brain barrier (BBB), conventional pharmaceutical agents are difficult to the diseased nuclei and exert their action to inhibit or delay the progress of PD. Recent literatures have demonstrated that curcumin shows the great potential to treat PD. However, its applications are still difficult in vivo due to its poor druggability and low bioavailability through the BBB.Methods: Melt-crystallization methods were used to improve the solubility of curcumin, and curcumin-loaded lipid-PLGA nanobubbles (Cur-NBs) were fabricated through encapsulating the curcumin into the cavity of lipid-PLGA nanobubbles. The bubble size, zeta potentials, ultrasound imaging capability and drug encapsulation efficiency of the Cur-NBs were characterized by a series of analytical methods. Low-intensity focused ultrasound (LIFU) combined with Cur-NB was used to open the BBB to facilitate curcumin delivery into the deep brain of PD mice, followed by behavioral evaluation for the treatment efficacy.Results: The solubility of curcumin was improved by melt-crystallization methods, with 2627-fold higher than pure curcumin. The resulting Cur-NBs have a nanoscale size about 400 nm and show excellent contrast imaging performance. Curcumin drugs encapsulated into Cur-NBs could be effectively released when Cur-NBs were irradiated by LIFU at the optimized acoustic pressure, achieving 30% cumulative release rate within 6 h. Importantly, Cur-NBs combined with LIFU can open the BBB and locally deliver the curcumin into the deep-seated brain nuclei, significantly enhancing efficacy of curcumin in the Parkinson C57BL/6J mice model in comparison with only Cur-NBs and LIFU groups.Conclusion: In this work, we greatly improved the solubility of curcumin and developed Cur-NBs for brain delivery of curcumin against PD through combining with LIFU-mediating BBB. Cur-NBs provide a platform for these potential drugs which are difficult to cross the BBB to treat PD disease or other central nervous system (CNS) diseases.Keywords: nanobubbles, blood–brain barrier, low-intensity focus ultrasound, curcumin, Parkinson’s disease

Hailiang Liang,1,&ast; Jin Wang,2,&ast; Peng Zhang,1,&ast; Wei Yang,3 Yang Yang,4 Yin Zhi,1 Wei Wu,3 Xiaoqiang Dong1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 2Department of General Surgery, Suzhou Dushu Lake Hospital (Dushu Lake Hospital Affiliated to Soochow University), Suzhou, 215006, People’s Republic of China; 3Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China; 4Department of Anesthesiology, The Affiliated Hospital of Yangzhou University, Yangzhou, 225000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoqiang Dong; Wei Wu Email dongxq@hotmail.com; 306834397@qq.comIntroduction: Long non-coding RNAs (LncRNAs) play a critical role in development and progression of various cancers. More and more researchers pay attention to the effect of lncRNA on regulating the cancer. However, the function and mechanism of Duxap8 in colorectal cancer have not been studied.Methods: Reverse transcription quantitative PCR (RT-qPCR), cell counting kit-8 (CCK-8), 5-ethynyl-20-deoxyuridine (EdU), colony formation assay, flow cytometry, TdT-mediated dUTP nick-end labeling (TUNEL), Western blot, hematoxylin-eosin staining (HE), in situ hybridization (ISH) analysis, immunohistochemistry (IHC) and tumor transplantation experiment were performed to investigate the function and mechanism of Duxap8 in colorectal cancer.Results: We found that the expression level of Duxap8 in colorectal cancer was closely correlated with tumor size (P = 0.024), tumor depth (P = 0.035) and lymphatic invasion (P =0.067) among 50 colorectal cancer patients. Then, we proved that the expression level of Duxap8 was significantly increased in human colorectal cancer tissues and cell lines. Functionally, Duxap8 knockdown inhibited the proliferation and induced the apoptosis of colorectal cancer cells, while Duxap8 overexpression facilitated the proliferation and suppressed the apoptosis in colorectal cancer in vitro. Moreover, knockdown of Duxap8 inhibited the size and weight of tumors in mice injected with colorectal cancer cells, overexpression of Duxap8 promoted the growth of colorectal cancer cells in vivo. Mechanically, we found that Duxap8 was principally located in the cytoplasm. Furthermore, Duxap8 functioned as a competing endogenous RNA to induce the development and progression of colorectal cancer through sponging miR-519b-3p to upregulate ZNF277.Discussion: Taken together, our results demonstrated that Duxap8 enhanced the expression level of ZEB1 to promote via competing for miR-519b-3p, which might be a promising molecular therapeutic target of colorectal cancer.Keywords: Duxap8, miR-519b-3p, ZNF277, colorectal cancer

Xixuan Lu,1,&ast; Qiang Wang,2,&ast; Haiyan Liang,1 Li Xu,3 Liping Sha,1 Yuemei Wu,1 Liting Ma,1 Ping Yang,1 Hong Lei1 1Department of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, Yinchuan, Ningxia, People’s Republic of China; 2Department of Medical Office, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, People’s Republic of China; 3Department of Radiology, People’s Liberation Army’s Joint Service for the 942nd Hospital, Yinchuan, Ningxia, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xixuan LuDepartment of Endocrinology, Cardiovascular and Cerebrovascular Disease Hospital, Ningxia Medical University General Hospital, No. 804, Shengli South Street, Xingqing District, Yinchuan, 750004, Ningxia, People’s Republic of ChinaTel +860951-6746645Email xixuan86@163.comBackground: This study has been conducted to explore the correlation between phenotypes of obesity and metabolic comorbidities.Methods: This cross-sectional study recruited 14,724 adults aged ≥ 18 years with a randomized stratified sampling strategy. Obesity was classified into four types according to body mass index (BMI) and waist-to-height ratio (WHtR): normal weight with central obesity (NWCO) and without (NW) CO, and obese or overweight with (OBCO) and without (OB) central obesity. Uric acid (UA), fasting blood glucose (FBG), and lipid profile were measured.Results: The prevalence of hyperuricemia in the 4 groups (NW, NWCO, OB and OBCO) was 3.7%, 5.6%, 8.7% and 12.4%, whilst the prevalence of hypertriglyceridemia was 13.4%, 27.4%, 30.3% and 43.7%, separately. The prevalence of hypo-high-density lipoprotein cholesterolemia (hypo-HDL emia) was 20.1%, 21.4%, 30.8% and 27.9%, while the prevalence of hyper-low-density lipoprotein cholesterolemia (hyper-LDL emia) was 9.8%, 24.4%, 12.3% and 27.9%. The prevalence of hypercholesterolemia was 11.2%, 23.5%, 14.7%, 28.5% and the prevalence of hyperglycemia was 9.7%, 22.6%, 18.5%, and 27.0%, respectively. The prevalence of hypertension was 6.9%, 13.1%, 14.7%, and 20.6%. For various metabolic abnormalities, OBCO have the highest risks compared with NW (hyperuricemia: adjusted OR (aOR)= 2.60; hypertriglyceridemia: aOR= 3.19; hypercholesterolemia: aOR= 1.48; hyper LDLemia: aOR= 2.21; hypo HDLemia: aOR= 1.42; hyperglycemia: aOR= 1.95; hypertension: aOR= 2.16). The risk of hyper LDLemia, hypercholesterolemia and hyperglycemia in the NWCO group was higher than that in the OB group (hyperLDLemia: aOR: 1.69 vs 0.97; hypercholesterolemia: aOR: 1.27 vs 1.24; hyperglycemia: aOR: 1.62 vs 1.28).Conclusion: Different phenotypes of obesity are significantly associated with metabolic abnormalities. NWCO is more closely associated with hypercholesterolemia, hyperglycemia and hyper LDLemia. General obesity and central obesity have a synergistic effect on the diseases.Keywords: obesity, central obesity, metabolic abnormalities, BMI, WHtR