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Xiujuan Chang,1,* Shumin Yu,2,* Jianzhi Pang,1 Wei Zhang,1 Huifang Kong,1 Jiagan Huang,1 Guojie Zhang,1 Huixin Zhang,1 Yueyue Gu,1,3 Yan Chen,1 Bin Yang,1 Jingping Liu,4 Zhen Zeng1– 3 1Department of Liver Disease Medicine, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 2 302 Clinical Medical School Peking University, Beijing, 100039, People’s Republic of China; 3The Fifth School of Clinical Medicine, Anhui Medical University, Hefei, Anhui Province, 230032, People’s Republic of China; 4Oncology Department, Electric Power Hospital of Beijing, Beijing, 100073, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen Zeng, Department of Liver Disease Medicine, The Fifth Medical Center of Chinese PLA General Hospital, No. 100 West 4th Ring Middle Road, Beijing, 100039, People’s Republic of China, Tel +86 15010540233, Email zengzhen1970@sina.comBackground: We explore the dose–efficacy relationship of lenvatinib plus anti-PD-1 in patients with unresectable hepatocellular carcinoma (u-HCC) infected with hepatitis B virus (HBV) in real-world practice. Furthermore, we identify the population sensitive to lenvatinib plus anti-PD-1 treatments.Methods: This retrospective study included 70 patients treated with lenvatinib plus at least 3 cycles of anti-PD-1 and 140 with lenvatinib alone. Stabilized inverse probability of treatment weighting (SIPTW) was used to balance clinical features between the two groups. The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed. Subpopulation treatment effect pattern plot (STEPP) estimated treatment-effect differences between the two groups.Results: The median age was 54 years, and 189 (90%) cases were male. A total of 180 (85%) patients were infected with HBV. A slowly increasing 12-month survival rate was with the cycles of anti-PD-1, and 5 cycles and more of anti-PD-1 appeared the most beneficial and stable survival rate. The lenvatinib plus at least 3 cycles anti-PD-1 group had better OS (21.4 vs 14 months, p = 0.041), PFS (8.0 vs 6.3 months, p = 0.015) than the lenvatinib alone group in unadjusted cohorts, and the SIPTW adjusted cohorts had confirmed it. For patients with portal vein trunk invasion (PVTI) or extrahepatic spread (EHS) combined with Child-Pugh class B (CPB), lenvatinib plus anti-PD-1 made the 12-month survival rate increase by 38%, while, in the other population, it did only 18%. The two groups had similar AEs (p ≥ 0.05).Conclusion: The lenvatinib combined with at least 3 cycles of anti-PD-1 was efficacy and safe for u-HCC patients infected with HBV. Especially, patients with PVTI or EHS combined with CPB may benefit most from the combination therapy.Graphical Abstract: Keywords: hepatocellular carcinoma, real-world study, anti-PD-1, lenvatinib

XiaoYan Zhang, Jifeng Liu Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital of Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Jifeng Liu, Department of Dermatology, Hangzhou Third People’s Hospital, Affiliated Hangzhou Dermatology Hospital of Zhejiang University School of Medicine, 38 West Lake Avenue, Hangzhou, 310009, People’s Republic of China, Tel +86-13758145226, Email fliu8166@126.comAbstract: This work reports a case of a 49-year-old male suffering from chronic tuberculosis who developed painful ulcers around the anus for approximately eight months. The colonoscopy revealed the presence of ulcers in the transverse colon, which were also found in the skin and intestine, as revealed by microscopic examination. The skin ulcer was positive for tuberculosis bacilli, leading to the final diagnosis of Tuberculosis cutis orificialis. The patient had a previous history of tuberculosis, which indicated that the infection in the lungs moved down to invade the intestines and finally the skin.Keywords: skin ulcers, tuberculosis, tuberculosis cutis orificialis

Jie Liu,1,&ast; Ke Zhao,2,&ast; Wei Kang,1,&ast; Siyu Tong,1 Yao Xu,1 Wei Jin,1 Mengxuan Qiao,1 Yuan Li,1 Lan Hong,3 Keqing Yao,4,5 Tiansheng Zheng6 1School of Mental Health, Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, People’s Republic of China; 3The Third Hospital of Quzhou, Quzhou, People’s Republic of China; 4Shenzhen Mental Health Center, Shenzhen, Guangdong, People’s Republic of China; 5Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China; 6The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Keqing Yao, Shenzhen Mental Health Center, Shenzhen Kangning Hospital, Shenzhen, Guangdong, People’s Republic of China, Tel +86-755-82927264, Email KQKangning@gmail.com Tiansheng Zheng, The Affiliated Kangning Hospital of Wenzhou Medical University Zhejiang Provincial Clinical Research Center for Mental Disorder, Wenzhou, People’s Republic of China, Email sky.tsh@163.comIntroduction: Non-suicidal self-injury (NSSI) is becoming an increasingly prevalent phenomenon among adolescents, endangering their health. The aims of this study were to 1) explore the associations between borderline personality features, alexithymia and NSSI and 2) examine if alexithymia mediates the relationships between borderline personality features and both the severity of NSSI and the various functions that maintain NSSI in adolescents.Methods: This cross-sectional study recruited 1779 outpatient and inpatient aged 12– 18 years from psychiatric hospitals. All adolescents completed a structured four-part questionnaire including demographic items, the Chinese version of the Functional Assessment of Self-Mutilation, the Borderline Personality Features Scale for Children and the Toronto Alexithymia Scale.Results: The structural equation modelling results indicated that alexithymia partially mediated the associations between borderline personality features and both the severity of NSSI and the emotion regulation function of NSSI (B = 0.058 and 0.099, both p < 0.001), after controlling for age and sex.Discussion: These findings suggest that alexithymia may play a role in the mechanism and treatment of NSSI among adolescents with borderline personality features. Further longitudinal studies are essential to validate these findings.Keywords: self-harm, health, emotion regulation, structural equation modelling

Xiaohui Wang,1,&ast; Bo Wu,2,&ast; Guogen Sun,3 Wenxi He,4 Jia Gao,1 Teng Huang,1 Jing Liu,1 Qing Zhou,1 Xiaoyu He,5 Shu Zhang,1 Zixiong Zhang,2 He Zhu1 1The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, Hubei, People’s Republic of China; 2The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, Enshi, Hubei, People’s Republic of China; 3Hubei Selenium and Human Health Institute, Enshi, Hubei, People’s Republic of China; 4Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 5Branch of National Clinical Research Center for Metabolic Diseases, Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zixiong Zhang, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei Selenium and Human Health Institute, No. 158, Muyang Avenue, Enshi, Hubei, People’s Republic of China, Email 596099670@qq.com He Zhu, The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei, People’s Republic of China, Email Zhuh@tjh.tjmu.edu.cnPurpose: Pancreatic adenocarcinoma (PAAD) presents an extremely high morbidity and mortality rate. Broccoli has excellent anti-cancer properties. However, the dosage and serious side effects still limit the application of broccoli and its derivatives for cancer therapy. Recently, extracellular vesicles (EVs) derived from plants are emerging as novel therapeutic agents. Thus, we conducted this study to determine the effectiveness of EVs isolated from Se-riched broccoli (Se-BDEVs) and conventional broccoli (cBDEVs) for the treatment of PAAD.Methods: In this study, we first isolated Se-BDEVs and cBDEVs by a differential centrifugation method, and characterized them by using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Then, miRNA-seq was combined with target genes prediction, and functional enrichment analysis to reveal the potential function of Se-BDEVs and cBDEVs. Finally, the functional verification was conducted in PANC-1 cells.Results: Se-BDEVs and cBDEVs exhibited similar characteristics in size and morphology. Subsequent miRNA-seq revealed the expression of miRNAs in Se-BDEVs and cBDEVs. Using a combination of miRNA target prediction and KEGG functional analysis, we found miRNAs in Se-BDEVs and cBDEVs may play an important role in treating pancreatic cancer. Indeed, our in vitro study showed that Se-BDEVs had greater anti-PAAD potency than cBDEVs due to increased bna-miR167a_R-2 (miR167a) expression. Transfection with miR167a mimics significantly induced apoptosis of PANC-1 cells. Mechanistically, further bioinformatics analysis showed that IRS1, which is involved in the PI3K-AKT pathway, is the key target gene of miR167a.Conclusion: This study highlights the role of miR167a transported by Se-BDEVs which could be a new tool for counteracting tumorigenesis.Graphical Abstract: Keywords: selenium, broccoli, extracellular vesicles, apoptosis, pancreatic cancer

Xiaoling Zhang, Xuting Jin, Jiajia Ren, Jueheng Liu, Haichang Ma, Xiaoming Fang, Huifan Zhang, Yujie Zhao, Yanli Hou, Yanni Luo, Lei Guo, Qi Ma, Ya Gao, Jingjing Zhang, Jiamei Li, Xiaochuang Wang, Gang Wang Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of ChinaCorrespondence: Xiaochuang Wang; Gang Wang, Department of Critical Care Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xi 5 Lu, Xi’an, Shaanxi, 710004, People’s Republic of China, Tel +86-029-8767-9630 ; +86-029-8767-9633, Email dr_xc_wang@163.com; gang_wang@xjtu.edu.cnPurpose: In patients with carbapenem-resistant Gram-negative bacteria (CRGNB) infection, the impact of appropriate empirical antibiotic treatment (AEAT) initialized before culture results were available remains controversial. We aimed to investigate the effect of AEAT on the prognosis of critically ill patients with hospital-acquired pneumonia (HAP) caused by CRGNB.Patients and Methods: Patients with CRGNB-infected HAP and received empirical antibiotic treatment (EAT) for at least 3 days in the intensive care unit (ICU) of a tertiary teaching hospital in China from February 2017 to September 2021 were included in the retrospective cohort study. Patients were categorized into AEAT and inappropriate empirical antibiotic treatment (IEAT) groups based on whether they received EAT covering CRGNB. The associations of AEAT with ICU and 28-day mortality were assessed using multivariable logistic regression model.Results: A total of 94 patients were enrolled, including 29 patients in AEAT group and 65 patients in IEAT group. Patients in AEAT group had a higher Sequential Organ Failure Assessment (SOFA) score (P = 0.003), levels of procalcitonin (PCT) (P = 0.001), and lactic acid (LAC) (P = 0.026); while patients in the IEAT group had a higher platelet count (PLT) (P = 0.001). There was no significant difference in the length of ICU stay between the two groups (P = 0.051). Compared with IEAT, AEAT was associated with an increased risk of 28-day mortality in the univariable logistic regression model (OR: 2.618, 95% CI: 1.063– 6.448). However, after adjusted for SOFA score, PLT, PCT, and LAC level, the association between AEAT and 28-day mortality diminished (OR: 1.028, 95% CI: 0.353– 2.996). AEAT showed no significant association with ICU mortality in neither univariable (OR: 1.167, 95% CI: 0.433– 3.142) nor multivariable (OR: 0.357, 95% CI: 0.097– 1.320) models.Conclusion: AEAT showed no significant influence on ICU or 28-day mortality in critically ill patients with HAP caused by CRGNB infection.Keywords: appropriate empirical antibiotics, hospital-acquired pneumonia, carbapenem-resistant, gram-negative bacteria, ICU mortality

Shuchi Lin,1,&ast; Xiaofan Huang,1,&ast; Ying Zhang,1 Xiaohan Zhang,1 Erhong Cheng,1 Jindong Liu1– 4 1Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jindong Liu, Department of Anesthesiology, the Affiliated Hospital of Xuzhou Medical University, Huaihai Road West, Quanshan District, Xuzhou, Jiangsu, People’s Republic of China, Tel +86-13951355136, Email liujindong1818@163.comPurpose: Myocardial injury after non-cardiac surgery is closely related to major adverse cardiac and cerebrovascular event and is difficult to identify. This study aims to investigate how to predict the myocardial injury of thoracic surgery and whether intraoperative variables contribute to the prediction of myocardial injury.Methods: The prospective study included adult patients with high cardiovascular risk who underwent elective thoracic surgery from May 2022 to October 2022. Multivariate logistic regression was used to establish a model with baseline variables and a model with baseline and intraoperative variables. We compare the predictive performance of two models for postoperative myocardial injury.Results: In general, 31.5% (94 of 298) occurred myocardial injury. Age ≥ 65 years old, obesity, smoking, preoperative hsTnT, and one-lung ventilation time were independent predictors of myocardial injury. Compared with baseline model, the intraoperative variables improved model fit, modestly improved the reclassification (continuous net reclassification improvement 0.409, 95% CI, 0.169 to 0.648, P< 0.001, improved integrated discrimination 0.036, 95% CI, 0.011 to 0.062, P< 0.01) of myocardial injury cases, and achieved higher net benefit in decision curve analysis.Conclusion: The risk stratification and anesthesia management of high-risk patients are essential. The addition of intraoperative variables to the baseline predictive model improved the performance of the overall model of myocardial injury and helped anesthesiologists screen out the patients at the greatest risk for myocardial injury and adjust anesthesia strategies.Keywords: prediction model, myocardial injury, thoracic surgery, cardiovascular risk, hsTnT

En Cao,1,&ast; Jun Xu,1,&ast; Yuanqi Gong,2,&ast; Jingjing Yuan,3 Anbang Chen,1 Jiayi Liu,4 Yunfei Fan,4 Xiangyang Fan,4 Xiaodong Kuang1 1Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of Critical Care Medicine/ICU (Intensive Care Unit), Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Physiology, School of Basic Medicine, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4The Basic Medical School of Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodong Kuang, Department of Pathology, Basic Medical College of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, Email xdssmu2005@163.comBackground: Macrophages are known to play a crucial role in the chronic inflammation associated with Chronic Obstructive Pulmonary Disease (COPD). BML-111, acting as a lipoxin A4 (LXA4) receptor agonist, has shown to be effective in protecting against COPD. However, the precise mechanism by which BML-111 exerts its protective effect remains unclear.Methods: In order to establish a cell model of inflammation, cigarette smoke extract (CSE) was used on the RAW264.7 cell line. Afterwards, an Enzyme-linked immunosorbent assay (ELISA) kit was employed to measure concentrations of tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), interleukin-18 (IL-18), and interleukin-10 (IL-10) in the cell supernatants of the RAW264.7 cells.In this study, we examined the markers of macrophage polarization using two methods: quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Additionally, we detected the expression of Notch-1 and Hes-1 through Western blotting.Results: BML-111 effectively suppressed the expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-18, as well as inflammasome factors NLRP3 and Caspase-1, while simultaneously up-regulating the expression of the anti-inflammatory cytokine IL-10 induced by CSE. Moreover, BML-111 reduced the expression of iNOS, which is associated with M1 macrophage polarization, and increased the expression of Arg-1, which is associated with M2 phenotype. Additionally, BML-111 downregulated the expression of Hes-1 and the ratio of activated Notch-1 to Notch-1 induced by CSE. The effect of BML-111 on inflammation and macrophage polarization was reversed upon administration of the Notch-1 signaling pathway agonist Jagged1.Conclusion: BML-111 has the potential to suppress inflammation and modulate M1/M2 macrophage polarization in RAW264.7 cells. The underlying mechanism may involve the Notch-1 signaling pathway.Keywords: BML-111, macrophage polarization, Notch-1 signaling pathway, COPD

Jin Zhang,1 Luxin Li,1 Jing Yu,2 Fan Zhang,1 Jiayi Shi,1 Meiyun LI,1 Jianyong Liu,3 Haitao Li,3 Jie Gao,4 Yan Wu1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2Department of Endocrinology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, 157011, People’s Republic of China; 3Department of Vascular Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Yan Wu, College of Life Science, Mudanjiang Medical University, Mudanjiang, Heilongjiang, 157001, People’s Republic of China, Tel/Fax +86-453-6984647, Email wuyan@mdjmu.edu.cn; Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21-31166666, Email jmsx2021@shu.edu.cnAbstract: Autophagy, a self-renewal mechanism, can help to maintain the stability of the intracellular environment of organisms. Autophagy can also regulate several cellular functions and is strongly related to the onset and progression of several diseases. Wound healing is a biological process that is coregulated by different types of cells. However, it is troublesome owing to prolonged treatment duration and poor recovery. In recent years, biomaterials have been reported to influence the skin wound healing process by finely regulating autophagy. Biomaterials that regulate autophagy in various cells involved in skin wound healing to regulate the differentiation, proliferation and migration of cells, inflammatory responses, oxidative stress and formation of the extracellular matrix (ECM) have emerged as a key method for improving the tissue regeneration ability of biomaterials. During the inflammatory phase, autophagy enhances the clearance of pathogens from the wound site and leads to macrophage polarization from the M1 to the M2 phenotype, thus preventing enhanced inflammation that can lead to further tissue damage. Autophagy plays important roles in facilitating the formation of extracellular matrix (ECM) during the proliferative phase, removing excess intracellular ROS, and promoting the proliferation and differentiation of endothelial cells, fibroblasts, and keratinocytes. This review summarizes the close association between autophagy and skin wound healing and discusses the role of biomaterial-based autophagy in tissue regeneration. The applications of recent biomaterials designed to target autophagy are highlighted, including polymeric materials, cellular materials, metal nanomaterials, and carbon-based materials. A better understanding of biomaterial-regulated autophagy and skin regeneration and the underlying molecular mechanisms may open new possibilities for promoting skin regeneration. Moreover, this can lay the foundation for the development of more effective therapeutic approaches and novel biomaterials for clinical applications.Keywords: wound healing, autophagy, biomaterial, antibacterial effects, inflammatory response, oxidative stress

Xiaojie Su,1,2 Ting Lei,1,2 Haichuan Yu,1,2 Lu Zhang,1,2 Zhouzhou Feng,1,2 Tiankui Shuai,1,2 Hong Guo,1,2 Jian Liu1,2 1The First Clinical Medical College of Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of China; 2Lanzhou University, Lanzhou City, Gansu Province, People’s Republic of ChinaCorrespondence: Jian Liu, Department of Clinical Medicine, the First Clinical Medical College of Lanzhou University, No. 1, Donggang West Road, Chengguan District, Lanzhou City, Gansu Province, People’s Republic of China, Tel +86 136 0935 4197, Email medecinliu@sina.comPurpose: NT-proBNP, a peptide biomarker synthesized and secreted by cardiomyocytes in response to cardiac load, has gained attention in recent years for its potential role in respiratory diseases. Chronic Obstructive Pulmonary Disease (COPD), a chronic and progressive inflammatory condition affecting the respiratory system, is frequently associated with comorbidities involving the cardiovascular system. Consequently, the aim of this systematic review and meta-analysis was to evaluate the variations in NT-proBNP levels across distinct patient groups with COPD and establish a foundation for future investigations into the precise clinical significance of NT-proBNP in COPD.Methods: The search databases for this study were conducted in PubMed, Excerpt Medica database (Embase), Web of Science (WOS), and Cochrane Library databases. Databases were searched for studies on the predictive value of NT-proBNP in adult COPD patients.Results: A total of 29 studies (8534 participants) were included. Patients with stable COPD exhibit elevated levels of NT-proBNP [standardized mean difference(SMD) [95CI%]=0.51 [0.13,0.89]; p=0.0092]. COPD patients with predicted forced expiratory volume in 1 s (FEV1) < 50% exhibit significantly elevated levels of NT-proBNP compared to those with FEV1 ⩾50%[SMD [95CI%]=0.17 [0.05,0.29]; p=0.0058]. NT-proBNP levels were significantly higher in acute exacerbations (AECOPD) compared to patients with stable COPD [SMD [95CI%]=1.18 [0.07,2.29]; p=0.037]. NT-proBNP levels was significantly higher in non-survivors than in survivors of hospitalised AECOPD patients [SMD [95CI%]=1.67 [0.47,2.88]; p=0.0063]. Both COPD patients with pulmonary hypertension(PH) [SMD [95CI%]=0.82 [0.69,0.96]; p< 0.0001] and chronic heart failure(CHF) [SMD [95CI%]=1.49 [0.96,2.01]; p< 0.0001] showed higher NT-proBNP level.Conclusion: NT-proBNP, a biomarker commonly used in clinical practice to evaluate cardiovascular disease, demonstrates significant variations in different stages of COPD and during the progression of the disease. The fluctuations in NT-proBNP levels could be indicative of the severity of pulmonary hypoxia and inflammation and cardiovascular stress among COPD patients. Therefore, assessing NT-proBNP levels in COPD patients can aid in making informed clinical decisions.Keywords: amino-terminal pro-brain natriuretic peptide, chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, chronic heart failure, meta-analysis

Zeyi Liang,&ast; Jiahao Shen,&ast; Jing Liu, Xu Sun, Yayuan Yang, Yanan Lv, Juanshan Zheng, Xiaoqing Mou, Hongsheng Li, Xuezhi Ding, Feng Yang Key Laboratory of New Animal Drug Project of Gansu Province/Key Laboratory of Veterinary Pharmaceutics Discovery, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, Lanzhou, Gansu, 730050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Yang; Xuezhi Ding, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of Chinese Academy of Agricultural Science, No. 335 Jiangouyan, Qilihe District, Lanzhou, Gansu, 730050, People’s Republic of China, Tel +86-931-2115262, Fax +86-931-2114180, Email yangfeng@caas.cn; dingxuezhi@caas.cnPurpose: This study aimed to investigate the prevalence and genetic characterization of Serratia marcescens isolates from clinical bovine mastitis in Ningxia Hui Autonomous Region of China.Methods: S. marcescens was identified by the polymerase-chain reaction of 16S rRNA gene and sequencing. Antimicrobial susceptibility was tested by the disk diffusion method. Genes of resistance and virulence were determined by the PCR.Results: Overall, S. marcescens were confirmed from 32 of 2897 (1.1%) mastitis milk samples. These isolates showed high resistance to cefazolin (30/32, 93.8%) and chloramphenicol (28/32, 87.5%). A 12.5% (4/32) of the isolates displayed multidrug resistance (MDR). The most prevalent resistant genes found in S. marcescens were TEM (32/32, 100%) and CTX-M (24/32, 75.0%; CTX-M-15, 14/32, 43.8%; CTX-M-14, 8/32, 25.0%; CTX-M-65, 2/32, 6.3%) for extended-spectrum beta-lactamase, cmlA (28/32, 87.5%) and floR (16/32, 50.0%) for chloramphenicol resistance, SIM-1 (2/32, 6.3%) for carbapenemases, and sdeB (28/32, 87.5%), sdeY (26/32, 81.3%), sdeR (26/32, 81.3%) and sdeD (20/32, 62.5%) for efflux pumps. Moreover, all isolates carried virulence genes flhD, entB, and kpn, and most of them contained mrkD (30/32, 93.8%), ycfM (26/32, 81.3%), bsmB (26/32, 81.3%), pigP (26/32, 81.3%), kfu (24/32, 75.0%) and shlB (24/32, 75.0%).Conclusion: To our knowledge, this is the first report of genetic determinants for antimicrobial resistance and virulence in S. marcescens isolated from bovine mastitis cases in China. These findings are useful for developing strategies for prevention and treatment of bovine mastitis caused by S. marcescens in China.Keywords: Serratia marcescens, bovine mastitis, antimicrobial resistance, virulence

Qing Xia,&ast; Yue Tang,&ast; Wang Li, Tingting Liang, Yue Zhou, Jun Liu, Feila Liu School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feila Liu, School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, People’s Republic of China, Tel +86-15123002638, Fax +86 2362563190, Email liufeila@cqut.edu.cnIntroduction: The immunosuppressive tumor microenvironment (TME) of solid tumors inhibits most drug delivery system-based nanomaterials from achieving deep penetration in tumor tissue and interferes with T cell activity in terms of differentiation and exhaustion, which is becoming a critical therapy hurdle for solid tumors. Therefore, developing a therapeutic strategy with abilities of rapid establishment of tumor-targeted cells, elimination of immune obstacles, and enhanced active immunization is very important, while is still a big challenge.Methods: A new strategy was explored to enhance immune therapy via the conjugation of microRNA155 (miR) to the surface of therapeutic monocyte with graphene quantum dots (GQDs).Results: TME was reversed using surface-engineered monocyte immunotherapy via reprogramming pro-tumoral M2 TAMs into antitumor M1, and thus tumor elimination was dramatically enhanced.Conclusion: Such a surface-engineered monocyte immunotherapy has been demonstrated to be well tolerated to intravenous administration and bio-compatible, showing the potential to be extended for the solid tumor treatment.Graphical Abstract: Keywords: solid tumor, surface-engineered monocyte, GQDs, miR155, immunotherapy

Bowen Li,&ast; Jinghang Liu,&ast; Liangzhi Xu, Qi Xu, Zhaohui Liu, Tiande Liu Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tiande Liu, Departments of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People’s Republic of China, Tel +8613479101447, Email liutd123@163.comBackground: The DNA binding protein NABP2 (nucleic acid binding protein 2) is a member of the SSB (single-stranded DNA-binding) protein family, which is involved in DNA damage repair. Its prognostic significance and relationship with immune infiltration in hepatocellular carcinoma (HCC), however, remain unknown.Methods: The purpose of this study was to estimate the prognostic value of NABP2 and to investigate its possible immune function in HCC. By applying multiple bioinformatics methods, we gathered and analysed data from The Cancer Genome Atlas (TCGA), Cancer Cell Lineage Encyclopedia (CCLE), and Gene Expression Omnibus (GEO) to investigate the potential oncogenic and cancer-promoting role of NABP2, including the differential expression, prognostic value, immune cell infiltration association, and drug sensitivity of NABP2 in HCC. Immunohistochemistry and Western blotting were used to validate the expression of NABP2 in HCC. The knockdown of NABP2 expression by siRNA was further used to validate its role in hepatocellular carcinoma.Results: Our findings indicated that NABP2 was overexpressed in HCC samples and was related to poor survival, clinical stage, and tumour grade in HCC patients. Analysis of functional enrichment indicated that NABP2 was potentially involved in the cell cycle, DNA replication, G2M checkpoint, E2F targets, apoptosis, P53 signalling, TGFA signalling via NF-κB, and so on. NABP2 was shown to be significantly linked to immune cell infiltration and immunological checkpoints in HCC. Analyses of drug sensitivity predict a number of drugs that could potentially be used to target NABP2. Moreover, in vitro experiments verified the promoting effect of NABP2 on the migration and proliferation of hepatocellular carcinoma cells.Conclusion: Based on these findings, NABP2 appears to be a candidate biomarker for HCC prognosis and immunotherapy.Keywords: bioinformatics analysis, NABP2, hepatocellular carcinoma, prognostic value, immune infiltration

Jinquan Liu,1 Ruihua Zhang,1 Tingting Lian,2 Zuoxi Chen,1 Rui-Li Zhang,3 Qianqiu Wang1 1Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, National Center for STD Control, China Centers for Disease Control and Prevention, Nanjing, 210042, People’s Republic of China; 2Department of Dermatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 3Department of Dermatology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210003, People’s Republic of ChinaCorrespondence: Rui-Li Zhang; Qianqiu Wang, Email reallyvictor@126.com; wangqianqiunj@126.comPurpose: Syphilis is a sexually transmitted bacterial infection caused by Treponema pallidum (T. pallidum), which can lead to chronic morbidity and adverse complications. In clinical practice, serofast status (SF) patients present with clinical symptoms that are very similar to those of healthy individuals or syphilis-cured patients, and often require prolonged follow-up for diagnosis. Currently, there is increasing interest in the potential of plasma exosome-derived miRNA as a biomarker for the detection of infectious diseases. In this study, we aimed to explore the diagnostic potential of miRNA in SF and its possible biological implications.Patients and Methods: Exosome-derived miRNAs were isolated from peripheral plasma samples obtained from 20 patients with secondary syphilis (SS), SF, serologically cured syphilis (SC), and healthy controls (HC), and differentially expressed miRNAs (DEmiRNAs) were identified by microarray analysis. Prediction of potential target genes, functional annotation, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were then performed. The expression of selected miRNAs was confirmed in 37 patients by quantitative reverse transcription polymerase chain reaction (RT-qPCR). A receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic performance of these miRNAs in differentiating syphilis from HC or SC.Results: The expression profile of plasma exosome-derived miRNA was discovered in individuals with SF through microarray analysis. The targeted genes of DEmiRNAs were found to be involved in diverse biological processes according to GO and KEGG analysis, such as regulation of transcription, mitochondria, Golgi, immune system, apoptosis, Ras signaling pathway, etc. Using RT-qPCR validation, miR-1273g-3p, miR-4485-5p, miR-197-3p, and miR-1908-3p showed significant upregulation in patients with SF. These miRNAs exhibited a superior diagnostic ability, either individually or combined, to distinguish SF from SC or HC.Conclusion: The DEmiRNAs in plasma exosomes may play a role in the pathogenesis of SF and have the potential to become a noble and effective diagnostic method.Keywords: serofast status, syphilis, microRNA, exosome, biomarker

Chunjie Han,1,&ast; Lingli Zhang,2,&ast; Jihong Liu,2 Ping Zhang3 1Department of Rehabilitation Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 2Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China; 3Department of Nursing, Beijing Rehabilitation Hospital, Capital Medical University, Beijing, 100144, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Liu, Department of Neurology, Beijing Luhe Hospital, Capital Medical University, No. 82 of Xin Hua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10-69543901-1041, Fax +86 10 69531069, Email l_jihong0@163.com Ping Zhang, Department of Nursing, Beijing Rehabilitation Hospital, Capital Medical University, No. 15 of Xixiazhuang South Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 10 5689 1513, Fax +86 10 5698 1555, Email doczp@163.comObjective: As an important hospital task, the quality and efficiency of nursing practice directly affect the medical quality and sustainable development of the hospital. Increasing attention is now paid by managers to nursing teamwork. From the level of the nursing team, this study explored the relationship between team roles, using teamwork as the intermediate variable, and team performance to provide a theoretical foundation for the human resource management of nursing managers.Methods: Taking 29 general inpatient areas of a tertiary general hospital in Beijing as research objects, a questionnaire survey was used to collect basic information on nursing staff, teamwork, team roles and team performance. The collected data were analysed. A pathway analysis based on a multiple regression analysis was used to interpret the effect of each team role on teamperformance.Results: ①The mean and maximum value of emotional type (Teamworker and Finisher) were the largest in the role combination of nursing team. In the team role combination, the average value of emotional type was 12.58 ± 1.48, with significant difference (P< 0.001). ② The average level of emotion, thinking and decision of team role combination is positively correlated with work performance; The average level and maximum value of emotion have a positive correlation with team cooperation; The average level of willingness was negatively correlated with team cooperation, job performance and satisfaction (P< 0.05). ③ Teamwork plays a certain intermediary role in the mean value of emotion to improve level of team satisfaction and performance.Conclusion: This study identified the important roles of different types of nursing staff in work performance and used a pathway analysis to create a path showing each role. Increasing the emotional-type nursing staff in a team can not only improve the mean level of team emotion but also effectively improve both teamwork and work performance.Keywords: nursing staff, teamwork, team role, team performance, intermediary role

Lingli Zhang,1,&ast; YaoYa Shu,2,&ast; Chunjie Han,3,&ast; Jihong Liu1 1Department of Neurology, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Department of Rehabilitation Medicine, Beijing Luhe Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jihong Liu, Department of Neurology, Beijing Luhe Hospital, Capital Medical University, No. 82 of Xin Hua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10-69543901-1041, Fax +86 10 69531069, Email l_jihong0@163.comObjective: To explore the relationship between family functioning and health beliefs in patients with stroke.Methods: A total of 253 patients with stroke were selected from Beijing Luhe Hospital, Capital Medical University from May 2021 to November 2021. All patients were of Chinese nationality, and 240 valid questionnaires were obtained. The Family Assessment Device and Champion’s Health Belief Model Scale were used to collect patients’ family functioning and health beliefs information, and correlation analysis was used to analyse it.Results: The total score for family functioning in patients with stroke was 130.5 (22). The highest mean score was 2.46 for behaviour control, and the lowest score was 2.00 for total function. The items were ranked from high to low in this order: behaviour control, emotional response, role, communication, emotional intervention, problem solving and total function. The total score of the patients’ health beliefs was 116 (33), The items were ranked from high to low in this order: were self-efficacy, health motivation, perceived benefit, susceptibility, severity and perceived impairment. The scores for family functioning were negatively correlated with the total scores for health beliefs (P < 0.05).Discussion: Stroke can reduce the self-care ability of the patients and aggravate the burden of family care. This can lead to abnormal function roles for patients and their families, emotional reactions in patients with stroke and weaker levels of family functioning.Conclusion: The health beliefs scores of patients with stroke were at the middle level, and family functioning was at the general level. There was a negative correlation between the family functioning score and the total score for health beliefs in patients with stroke.Keywords: health belief, family function, stroke

Xiaona Lang,1 Jinlei Liu,2 Guangzhong Zhang,3 Xin Feng,1 Wenchao Dan3 1Pharmacy Department, Tianjin Hospital, Tianjin, People’s Republic of China; 2Cardiology Department, Guang ‘anmen Hospital, Chinese Academy of Traditional Chinese Medicine, Beijing, People’s Republic of China; 3Dermatological Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wenchao Dan, Dermatological Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China, Tel +86 13652001152, Email dan9521@foxmail.comBackground: In recent years, the emergence of new diseases and resistance to known diseases have led to increasing demand for new drugs. By means of bibliometric analysis, this paper studied the relevant articles on drug repositioning in recent years and analyzed the current research foci and trends.Methodology: The Web of Science database was searched to collect all relevant literature on drug repositioning from 2001 to 2022. These data were imported into CiteSpace and bibliometric online analysis platforms for bibliometric analysis. The processed data and visualized images predict the development trends in the research field.Results: The quality and quantity of articles published after 2011 have improved significantly, with 45 of them cited more than 100 times. Articles posted by journals from different countries have high citation values. Authors from other institutions have also collaborated to analyze drug rediscovery. Keywords found in the literature include molecular docking (N=223), virtual screening (N=170), drug discovery (N=126), machine learning (N=125), and drug-target interaction (N=68); these words represent the core content of drug repositioning.Conclusion: The key focus of drug research and development is related to the discovery of new indications for drugs. Researchers are starting to retarget drugs after analyzing online databases and clinical trials. More and more drugs are being targeted at other diseases to treat more patients, based on saving money and time. It is worth noting that researchers need more financial and technical support to complete drug development.Keywords: drug repositioning, drug discovery, bibliometric, citation analysis, trend analysis

Xiyan Zhang,1,2 Hui Chen,1 Shengnan Liu,3 Xijuan Wang,2 Beibei Guo,2 Jingjing Liu,2 Shaojie Feng,2 Fengxia Liu2 1School of Clinical Medicine, Weifang Medical University, Weifang, People’s Republic of China; 2Department of Allergy, Weifang People’s Hospital, Weifang, People’s Republic of China; 3Department of Blood Transfusion, Affiliated Hospital of Weifang Medical University, Weifang, People’s Republic of ChinaCorrespondence: Shaojie Feng; Fengxia Liu, Email fengshaojie2020@163.com; wf_lfx@163.comBackground: Children are the age group with the highest prevalence of allergy diseases. There is currently a lack of knowledge regarding monosensitization and polysensitization characteristics in children. In this study, we investigated the characteristics and differences between monosensitization and polysensitization in children in Weifang, eastern China.Objective: To demonstrate the basic features of monosensitization and polysensitization in children. To explore the inherent and clinical parameter differences between monosensitized and polysensitized children.Material and Methods: A total of 6030 individuals with a physician-determined need for allergy testing were tested for 15 common allergens, including 9 aeroallergens and 6 food allergens. A total of 938 allergen-positive children aged 1 month to 18 years were eventually included in this analysis. Complete blood count results from the same time as the allergen test were derived from the computerized medical records. Intrinsic features such as age, gender, sIgE, T-IgE, and clinical parameters such as eosinophil percentage, eosinophil count, basophil percentage, and basophil count were compared.Results: The results showed that dust mite-related allergens, mould-related allergens, and tree and grass pollen-related allergens were the most prevalent allergens among monosensitized children. Additionally, the results of the combined pattern of polysensitive childhood allergens indicate the most common two allergens that were present together included dust mites and mould-related allergens, dust mite and Artemisia pollens, and dust mite and Humulus scandens pollens. Polysensitization can result in higher sIgE, T-IgE and eosinophil levels.Conclusion: In conclusion, we provide a basic overview of allergens in monosensitized and polysensitized children. These findings provide new insight into the management of allergic diseases, particularly from the standpoint of polysensitization.Keywords: allergic disease, children, monosensitization, polysensitization, eosinophils, T-IgE

Ziqing Li,&ast; Jiayuan Liu,&ast; Haotao Li, Yuankai Huang, Xiaoyu Xi The Research Center of National Drug Policy and Ecosystem, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuankai Huang; Xiaoyu Xi, The Research Center of National Drug Policy and Ecosystem, China Pharmaceutical University, Longmian Avenue 639, Jiangning District, Nanjing, 211198, People’s Republic of China, Email hyk@cpu.edu.cn; xixy@cpu.edu.cnPurpose: This study aims to explore the relationship between the four-dimensional structured perceived organizational support (emotional support, instrumental support, supervisor support, and coworker support) and the turnover intention of pharmacists in primary healthcare institutions. The gender differences between perceived organizational support and turnover intention will also be examined.Methods: A cross-sectional study was conducted in primary healthcare institutions of 31 cities in China from 2 July to 1 September 2021. And the binary logistic regression model was employed for data analysis.Results: 937 valid questionnaires are allocated from pharmacists in primary healthcare institutions. The regression results indicated that emotional support (b=0.073, p< 0.001) has a significant influence on pharmacists’ turnover intention, and the effect of supervisor support (b=0.173, p=0.046) on pharmacists’ turnover intention differs by gender.Conclusion: These findings offer suggestions for the management and stabilization of pharmacists in primary healthcare institutions. It is suggested that specific measures should be taken to increase pharmacists’ perceived organizational support and reduce their turnover intention. At the same time, gender differences need to be taken into consideration by the managers when providing perceived organizational support to reduce their turnover intention through adaptive management.Keywords: primary healthcare pharmacist, turnover intention, perceived organizational support, emotional support, supervisor support, gender

Jie Liu,1,&ast; Yilei Ma,2,&ast; Wanli Xie,1,&ast; Xia Li,1 Yanting Wang,1 Zhenzhen Xu,1 Yunxiao Bai,1 Ping Yin,2 Qingping Wu1 1Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingping Wu, Email wqp1968@126.comBackground: The predictive effect of systemic inflammatory factors on postoperative pulmonary complications in elderly patients remains unclear. In addition, machine learning models are rarely used in prediction models for elderly patients.Patients and Methods: We retrospectively evaluated elderly patients who underwent general anesthesia during a 6-year period. Eligible patients were randomly assigned in a 7:3 ratio to the development group and validation group. The Least logistic absolute shrinkage and selection operator (LASSO) regression model and multiple logistic regression analysis were used to select the optimal feature. The discrimination, calibration and net reclassification improvement (NRI) of the final model were compared with “the Assess Respiratory Risk in Surgical Patients in Catalonia” (ARISCAT) model.Results: Of the 9775 patients analyzed, 8.31% developed PPCs. The final model included age, preoperative SpO2, ANS (the Albumin/NLR Score), operation time, and red blood cells (RBC) transfusion. The concordance index (C-index) values of the model for the development cohort and the validation cohort were 0.740 and 0.748, respectively. The P values of the Hosmer–Lemeshow test in two cohorts were insignificant. Our model outperformed ARISCAT model, with C-index (0.740 VS 0.717, P = 0.003) and NRI (0.117, P < 0.001).Conclusion: Based on LASSO machine learning algorithm, we constructed a prediction model superior to ARISCAT model in predicting the risk of PPCs. Clinicians could utilize these predictors to optimize prospective and preventive interventions in this patient population.Keywords: older adult, postoperative complications, ANS, the albumin/NLR score, risk factors

Tao Rui,1,2 Kai Wang,1,2 Aizhai Xiang,1 Jufeng Guo,1 Ning Tang,1 Xin Jin,1 Yimou Lin,3 Jian Liu,1 Xiaobing Zhang1,2 1Department of Surgery, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 2Key Laboratory of Integrated Oncology and Intelligent Medicine of ZheJiang Province, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 3Department of Surgery, Collaborative Innovation Center for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University Hangzhou, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Tao Rui; Xiaobing Zhang, Email 11818248@zju.edu.cn; 11818341@zju.edu.cnBackground: Serum exosome-based liquid biopsy has significant advantages for screening and diagnosing hepatocellular carcinoma (HCC). P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are novel small silencing RNAs that have been identified to function in cancer-related signalling pathways. However, studies on the presence of piRNAs in serum exosomes from HCC patients and their diagnostic values in HCC are not well reported. Our aim is to validate serum exosome-derived piRNAs as the valuable component of liquid biopsy for diagnosing HCC.Methods: We used small RNA (sRNA) sequencing to profile piRNAs from serum exosomes and describe the base distribution characteristics of serum exosome-derived piRNAs. Serum exosomes from 125 HCC patients and 44 nontumor donors were included in this study.Results: We found that piRNAs were components of serum exosomes from HCC patients. A total of 253 differentially expressed serum exosome-derived piRNAs were screened from HCC compared with the piRNAs from nontumor donors. Serum exosome-derived piRNAs from HCC displayed a distinctive base distribution. To further confirm the potential diagnostic value of serum exosome-derived piRNAs in HCC, we detected the levels of the top 5 upregulated piRNAs in our Chinese cohort. The training set and validation set both showed that all 5 piRNAs were dramatically increased in the serum exosomes from HCC compared with the piRNAs from non-tumour donors. The piRNAs could strongly identify HCC patients from non-tumour donors according to the area under the receiver operating characteristic (AUROC) model. Additionally, the piRNAs could also present significant values for the diagnosis of HCC with low tumour burden.Conclusion: piRNAs enriched the components of serum exosomes from HCC and could serve as promising biomarkers for HCC diagnosis.Keywords: biomarker, exosome, sRNA-seq, HCC, piRNA

Shuchi Lin,1,&ast; Ying Zhang,1,&ast; Xiaofan Huang,1,&ast; Xiaohan Zhang,1 Erhong Cheng,1 Zhaoyun Zhou,2 Jindong Liu1,3– 5 1Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 2Department of Anesthesiology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, People’s Republic of China; 3Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 4Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 5NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jindong Liu, Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Huaihai Road West, Quanshan District, Xuzhou, Jiangsu, People’s Republic of China, Tel +86-13951355136, Email liujindong1818@163.comPurpose: This study aims to investigate whether the administration of salbutamol/budesonide reduced the incidence of myocardial injury in thoracic surgery.Methods: The randomized controlled trial included 298 patients over 45 and at high-risk for cardiovascular complications after lobectomy. Patients in the experimental group were treated with salbutamol/budesonide after anesthesia induction with fiberoptic bronchoscope. The primary outcome was the incidence rates of myocardial injury, assessed before and three days after the operation. The secondary outcome was respiratory function at each time point during the operation, including lung compliance and arterial partial pressure of oxygen, postoperative pulmonary and cardiovascular complications, hospital stay, pain score, and analgesic dosage.Results: In the control group, the incidence of myocardial injury was 57/150 (38%), while that in the experimental group was 33/148 (22%); compared between the two groups, the difference in the incidence of myocardial injury was statistically significant. The dynamic compliance and static compliance at half an hour after the start of surgery in the experimental group were significantly improved. Before leaving the operating room, the difference in arterial oxygen partial pressure between the two groups was statistically significant.Conclusion: Intraoperative administration of salbutamol/budesonide reduced the incidence of myocardial injury after thoracic surgery, improved lung function, and reduced the incidence of postoperative pulmonary complications.Keywords: salbutamol/budesonide, myocardial injury, thoracic surgery, cardiovascular risk, hsTnT, prediction model

Ziyuan Li,1,&ast; Yu Gan,1,&ast; Ting Kang,1,&ast; Yi Zhao,1 Tianguang Huang,2 Yuhao Chen,3 Jin Liu,1 Bowen Ke1 1Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Frontiers Science Center for Disease-Related Molecular Network, Sichuan University West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bowen Ke, Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Wuhou District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-85422114, Fax +86-28-85582944, Email bowenke@scu.edu.cnBackground: The treatment of neuropathic pain is still a major troublesome clinical problem. The existing therapeutic drugs have limited analgesic effect and obvious adverse reactions, which presents opportunities and challenges for the development of new analgesic drugs. Camphor, a kind of monoterpene, has been shown anti-inflammatory and analgesic effects in traditional Chinese medicine. But we know little about its effect in neuropathic pain. In this article, We have verified the reliable analgesic effect of camphor in the neuropathic pain model caused by different predispositions.Methods: The nociceptive response of mice was induced by transient receptor potential A1 (TRPA1) agonist to verify the effect of camphor on the nociceptive response. Multiple paclitaxel (PTX) injection models, Single oxaliplatin (OXA) injection models, Chronic constriction injury (CCI) models and Streptozotocin-induced (STZ) diabetic neuropathic pain models were used in this study. We verified the analgesic effect of camphor in mice by acetone test and conditioned place aversion test. At the same time, comparing the adverse reaction of nervous system between camphor and pregabalin at equivalent dose in locomotor activity test and rotarod test. Using patch clamp to verify the effect of camphor on dorsal root ganglion (DRG) excitability.Results: In behavioral test, compared with vehicle group, camphor significantly reduced the spontaneous nociception caused by TRPA1 agonist-formalina and allyl isothiocyanate (AITC). Compared with vehicle group, camphor significantly reduced the flinching and licking time in neuropathic pain model mice, including PTX, OXA, STZ and CCI induced peripheral neuralgia models. Compared with vehicle group, pregabalin significantly increased the resting time and reduced the average speed without resting and distance in locomotor activity test, reduced the time stayed on rotarod in rotarod test. In patch clamp test, compared with vehicle group, camphor significantly reduced the action potential (AP) firing frequency of DRG.Conclusion: Camphor can alleviate the symptoms of hyperalgesia in various neuropathic pain models, and has no obvious adverse reactions compared with pregabalin. This effect is related to the down-regulation of DRG neuron excitability.Keywords: camphor, neuropathic pain, TRPA1, hyperalgesia

Ruining Ma,&ast; Jida Liu,&ast; Shi An School of Management, Harbin Institute of Technology, Harbin, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jida Liu, School of Management, Harbin Institute of Technology, No. 92 West Dazhi Street, Nangang District, Harbin, 150001, People’s Republic of China, Email kittadada@yeah.netPurpose: During the early warning period of public health emergencies, the information released by whistleblowers on the risk posed by the given event can reduce uncertainty in the public’s risk perception and help governments take timely actions to contain the large-scale dissemination of risk. The purpose of this study is to give full play to whistleblowers and draw attention to the risk events, forming a pluralistic model of the risk governance during the early warning period of public health emergencies.Methods: We construct an evolutionary game model of the early warning of public health emergencies through whistleblowing that involves the government, whistleblowers, and the public, discussing the mechanism of interaction between these subjects under the uncertainty of risk perception. Furthermore, we use numerical simulations to analyze the influence of changes in the relevant parameters on the evolutionary trajectory of the subjects’ behaviors.Results: The results of the research are obtained by numerical simulation of the evolutionary game model. The results show that the public’s cooperation with the government encourages the latter to take a positive guidance strategy. Increasing the reward for whistleblowers within an acceptable cost, strengthening the propaganda of the mechanism and the higher level of risk perception of the government and whistleblowers will promote whistleblowers’ vocalization actively. When the government’s reward for whistleblowers is lower, the whistleblowers choose negative vocalization with the improvement of the public’s risk perception. If there is no mandatory guidance from the government at this point, the public is prone to passively cooperating with the government owing to a lack of risk-related information.Conclusion: Establishing an early warning mechanism through whistleblowing is important for containing risk in the early warning period of public health emergencies. Building the whistleblowing mechanism in daily work can improve the effectiveness of the mechanism and enhance the public’s risk perception better when the public health emergencies arise.Keywords: public health emergencies, early warning through whistleblowing, risk prevention, uncertainty in perception, evolutionary game

Miao Zhang, Jing Liu, Yu-Chen Pan, Hui-Li Liu, Jing Shu, Xiao-Ming Wu, Yang Yang Department of Pediatric Gynecology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, ChinaCorrespondence: Jing Liu, Department of Pediatric Gynecology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China, Tel +86 010 59616889, Email liujing2893@126.comObjective: The aim of this study was to analyze the prevalence of vaginal flora and drug resistance in bacterial vaginitis among girls.Methods: A total of 3099 girls (0– 10 years old) with vaginitis who visited the Beijing Children’s Hospital from January 2020 to December 2021 were included in the present study. The clinical data, results of bacterial culture of vaginal secretions, and drug sensitivity reports of the subjects were collected and analyzed.Results: Of the 3099 girls with vaginitis, 399 girls had a positive bacterial culture of vaginal secretions. Nineteen types of bacteria were cultured from the vaginal secretions of these 399 girls, with a total of 419 strains. The top three infective bacteria were Haemophilus influenzae (127 strains, 30.31%), Staphylococcus aureus (66 strains, 15.75%), and Streptococcus agalactiae (32 strains, 7.64%). Additionally, 20 girls were simultaneously infected with two types of bacteria. Staphylococcus aureus, Group G Streptococcus, Haemophilus parainfluenzae, and Pseudomonas aeruginosa more frequently occurred in mixed infections. The number and bacterial detection rate among school-age girls were higher than those of preschool-age girls. We found seasonal variation in infection rates, and vaginitis among girls was higher in summer. Recurrence of vaginitis in girls was not related to the type of pathogenic bacteria in the infection. Drug sensitivity analyses showed that the resistance rates of clindamycin and erythromycin were generally high, 70– 100%. After the coronavirus disease 2019 outbreak, the resistance rates of some antibiotics had decreased to varying degrees.Conclusion: Improving the understanding of vaginal flora and drug resistance in girls with vaginitis will facilitate the selection of highly effective and sensitive antibacterial drugs and reduce the production of drug-resistant strains.Keywords: drug sensitivity analysis, girls, pathogenic bacteria, vaginitis

Ting Liu,1 Jiaxing Liu,2 Jing Wu,1 Linghan Qin,1 Yuru Shi,1 Yingjie Qi1 1Department of Laboratory Medicine, Infection Hospital Area of the First Affiliated Hospital of University of Science and Technology of China (Hefei Infectious Disease Hospital), Hefei, Anhui Province, 230022, People’s Republic of China; 2Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, 210008, People’s Republic of ChinaCorrespondence: Yingjie Qi, Department of Laboratory Medicine, Infection Hospital Area of the First Affiliated Hospital of University of Science and Technology of China (Hefei Infectious Disease Hospital), No. 218 Susong Road, Hefei, Anhui Province, 230022, People’s Republic of China, Email 7yingjie@sina.comPurpose: Severe Fever with Thrombocytopenia Syndrome (SFTS) is an infectious disease with rapid onset and high case fatality rate. The study was to explore the clinical value by examining the serum level of 25-hydroxyvitamin D (25 (OH) D) in SFTS patients.Methods: One hundred and five patients and 156 healthy controls were included. Univariate and multivariate regression analyses were performed to identify independent risk factors for disease progression. Subject operating characteristics (ROC) curves were drawn, and the corresponding area under the curve (AUC) was calculated to assess the sensitivity and specificity of the diagnostic disease.Results: The 25 (OH) D level of disease group was lower than that of healthy control group (22.12 (18.43, 25.86) ng/mL vs 27.36 (23.20, 32.71) ng/mL; P< 0.05). The 25 (OH) D level of severe disease group was lower than that of mild disease group (20.55(16.30, 24.44) ng/mL vs 24.94(20.89, 31.91) ng/mL; P< 0.05). And there was no significant difference of 25 (OH) D level between the survival group and death group in severe disease group. Multivariate Logistic regression analysis showed that the 25 (OH) D level under 19.665 ng/mL was an independent risk factor for the development of SFTS (OR = 0.901, P=0.040). Furthermore, age more than 68.5 years old and lactate dehydrogenase (LDH) more than 1023.5U/L were independent risk factors for death in severe patients with SFTS.Conclusion: Patients with SFTS have reduced 25 (OH) D level, and 25 (OH) D is a risk factor for disease severity in patients with SFTS. Vitamin D supplementation may be an effective measure to reduce the risk of infection and improve the prognosis.Keywords: severe fever with thrombocytopenia syndrome, 25-hydroxyvitamin D, risk factor

Shenghan Gao,1,2 Xinyu Zhang,1,2 Jie Liu,3 Fuqing Ji,2 Zhihao Zhang,2 Qingjie Meng,2 Qi Zhang,1 Xiaogang Han,2 He Wu,2 Yulong Yin,2 Yonggang Lv,2 Wenzhen Shi3 1The College of Life Sciences, Northwest University, Xi’an, 710069 People’s Republic of China; 2Department of Thyroid Breast Surgery, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China; 3Clinical Medical Center, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of ChinaCorrespondence: Yonggang Lv, Department of Thyroid Breast Surgery, Xi’an NO.3 Hospital, the Affiliated Hospital of Northwest University, Xi’an, People’s Republic of China, Email lvygwytt@163.com Wenzhen Shi, Xi’an Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Xi’an No.3 Hospital, The Affiliated Hospital of Northwest University, School of Life Sciences and Medicine, Northwest University, Xi’an, People’s Republic of China, Tel +8615037916770, Email shiwenzhen736@163.comBackground: Breast cancer is a common cancer worldwide. Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by a poor prognosis. Icariin (ICA) is a flavonoid glycoside purified from the natural product Epimedium, which is reported to exert an inhibitory effect on a variety of cancers. However, molecular mechanisms behind ICA suppressed TNBC remain elusive.Methods: The curative effects of ICA on TNBC cells and potential targets were predicted by network pharmacology and molecular biology methods screening, and the mechanism of inhibition was explained through in vitro experiments such as cell function determination, Western blot analysis, molecular docking verification, etc.Results: This study showed that ICA inhibits TNBC cell functions such as proliferation, migration, and invasion in a dose-dependent manner. ICA could induce redox‐induced apoptosis in TNBC cell, as shown by ROS upregulation. As a result of network pharmacology, ICA was predicted to be able to inhibit the MAPK signaling pathway. ICA treatment inhibited the expression of JNK and c-Jun and downregulated the antiapoptotic gene cIAP-2. Our results suggested that ICA could induce apoptosis by inducing an excessive accumulation of ROS in cells and suppress TNBC cell invasion via the JNK/c-Jun signaling pathway.Conclusion: We demonstrated that ICA can effectively inhibit cell proliferation and induced apoptosis of TNBC cells. In addition, ICA could inhibit TNBC cell invasion through the JNK/c-Jun signaling pathway. The above suggests that ICA may become a potential drug for TNBC.Keywords: triple-negative breast cancer, icariin, JNK/c-Jun, apoptosis, ROS, invasion

Fei Gao,1,&ast; Yang Zhou,2,3,&ast; Xiaoming Yan,4,&ast; Haozhang Huang,2,3,5 Guoxiao Liang,2,3 Yongyi Xie,6 Qijiong Zhu,7 Ziming Chen,8 Bo Wang,2,3 Huanqiang Li,2,3 Ziling Mai,2,3,9 Ming Ying,2,3 Jin Liu,2,3 Shiqun Chen,2,3 Jiyan Chen2,3,10 1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4Department of Information Technology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 5The Second School of Clinical Medicine, Southern Medical University, Guangzhou, People’s Republic of China; 6School of Pharmacy, Guangdong Medical University, Dongguan, People’s Republic of China; 7School of Public Health, Guangdong Medical University, Dongguan, People’s Republic of China; 8School of Foreign Studies, Southern Medical University, Guangzhou, People’s Republic of China; 9School of Biology and Biological Engineering, South China University of Technology, Guangzhou, People’s Republic of China; 10Guangdong Provincial People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiqun Chen, Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Email shiqunchen@126.com Jiyan Chen, Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China, Tel +86 2083827812-10528, Fax +86 2083851483, Email chenjiyandr@126.comBackground: Diabetes mellitus (DM) patients with increased urinary albumin creatinine ratio (uACR) have higher risk of mortality, while it is unclear in DM patients with atherosclerotic cardiovascular disease (ASCVD).Methods: We analysed 2832 DM patients with ASCVD in this multi-center registry cohort study Cardiorenal ImprovemeNt II (CIN-II) in 5 Chinese tertiary hospitals from 2007 to 2020. Patients were divided into 3 groups according to their uACR level (normal group: uACR < 30mg/g, moderately increased group: 30mg/g≤ uACR < 300mg/g, severely increased group: 300mg/g≤ uACR). The main outcome of the study was cardiovascular mortality and all-cause mortality.Results: During a median follow-up of 2.1 years, among 2832 patients (mean age: 63.3 ± 9.9 years, 29.1% women), 434 patients (15.3%) had moderately increased uACR, and 203 patients (7.2%) had severely increased uACR. Compared to patients in normal group, patients had higher cardiovascular mortality in moderately increased group and severely increased group (2.5% vs 9.9% vs 16.7%, P < 0.001), as well as all-cause mortality. After adjusting confounders, the risk of cardiovascular mortality remained higher in moderately increased group (adjusted hazard ratio [aHR]: 3.13; 95% confidence interval [CI]: 2.04– 4.81) and severely increased group (aHR: 4.54; 95% CI: 2.58– 8.01) than in normal group, as well as all-cause mortality.Conclusion: In our study, we found nearly a quarter of DM patients with ASCVD had increased uACR, and they have over 2- or 3-fold risk of cardiovascular mortality than those with normal uACR. UACR is a helpful indicator for risk stratification and treatment target for DM patients with ASCVD.Keywords: diabetes mellitus, atherosclerotic cardiovascular disease, urinary albumin creatinine ratio, cardiovascular mortality

Shuang Guan,1,&ast; Ya-Nan Yu,1,&ast; Bing Li,2 Hao Gu,1 Lin Chen,1 Nian Wang,1 Bo Wang,1 Xi Liu,1 Jun Liu,1 Zhong Wang1 1Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong Wang; Jun Liu, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimennei, Beijing, People’s Republic of China, Email zhonw@vip.sina.com; franlj1104@aliyun.comBackground: The Xueyu Zheng (XYZ) phenome is central to coronary heart disease (CHD), but efforts to detect genetic associations in the XYZ phenome have been disappointing.Methods: The phenomic alteration-related genes (PARGs) for the XYZ phenome were screened using |ρ| > 0.4 and p < 0.05 after treatment with Danhong injection at day 14 and day 30. Then, the driver genes for the Protein-Protein Interaction (PPI) networks of the PARGs established using STRING 11.0 were detected using a personalized network control algorithm (PNC). Finally, the molecular correlations of the driver genes with the XYZ phenome were analyzed with the Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways from a holistic viewpoint.Results: A total of 525 and 309 PARGs in the XYZ phenome at day 14 and day 30 were identified. These genes were separately enriched in 48 and 35 pathways. Furthermore, five driver genes were detected. These genes were mainly correlated with endoplasmic reticulum stress-mediated apoptosis and autophagy regulation, which could suppress atherosclerosis progression.Conclusion: Our study detected the drug-responsive PARGs of the XYZ phenome in CHD and provides an exemplary strategy to investigate the genetic associations among this common phenome and its component symptoms in patients with CHD.Trial Registration: ClinicalTrials.gov, NCT01681316; registered on September 7, 2012.Graphical Abstract: Keywords: coronary heart disease, Xueyu Zheng phenome, phenomics strategy, driver gene

Hui Wu, Tao Li, Jian Cao, Dingwen He, Tianlong Wu, Jiahao Liu, Jinghong Yuan, Xigao Cheng Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Xigao Cheng, Department of Orthopaedics Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China, 330006, Email xigaocheng@hotmail.comObjective: This study aims to compare the efficacy of percutaneous endoscopic lumbar discectomy (PELD) in treating adolescent posterior ring apophysis fracture (APRAF) accompanied by lumbar disc herniation (LDH) and lumbar disc herniation alone.Methods: Herein we present a case series of adolescent patients who underwent PELD surgery from June 2017 to September 2021. All patients were divided into two distinct groups (ie Group A and B), based on their preoperative Computed tomography (CT) scans. Group A included patients with PRAF (type III) accompanied by LDH. Group B patients had LDH alone. The general clinical characteristics, clinical outcomes, and complications in patients from the two groups were assessed and compared.Results: Compared to before surgery, the back and leg visual analog scores (VAS) and Oswestry Disability Index (ODI) were markedly improved in both groups’ patients at all follow-ups. Notably, no significant differences were observed in the back and leg VAS scores, and ODI values between the two groups at different time points after surgery. The mean intraoperative blood loss was significantly lower in Group B, relative to Group A. The mean operation time was significantly shorter in Group B, compared to Group A. There was no statistically significant difference in complication and recurrence rates between the two groups.Conclusion: APRAF (type III) accompanied by LDH and LDH alone can obtain roughly equal surgical effects through PELD surgery and turns out to be a safe and effective surgical approach.Keywords: adolescent, posterior ring apophysis fracture, percutaneous endoscopic lumbar discectomy, lumbar disc herniation

Wenwen Xie, Jiayuan Liu,&ast; Yuankai Huang,&ast; Xiaoyu Xi The Research Center of National Drug Policy & Ecosystem, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoyu Xi, Email xixy@cpu.edu.cnBackground: In China, bypassing is becoming increasingly prevalent. Such behavior, as going directly to upper-level health-care facilities without a primary care provider (PCP) referral when facing non-critical diseases, contrasts to “expanding the role of PCPs as the first-contact of care”, may cause unneglectable damage to the healthcare system and people’s physical health.Objective: To examine the relationship between patient experience in primary health-care clinics (PHCs) and their bypass behavior.Methods: A cross-sectional study was designed for data collection. From July 2021 to August 2021, we conducted a questionnaire survey nationally. Fifty-three investigators were dispatched to 212 pre-chosen PHCs, around which 1060 interviewees were selected to gather information, using a convenience sampling. The primary independent variable was scores measured by Chinese Primary Care Assessment Tool (PCAT-C) to quantify patients’ experience at PHCs. The dependent variable was a binary variable measured by a self-developed instrument to identify whether participants actually practiced bypassing. Covariates were well-screened determinants of patients’ bypass behavior including socio-demographic factors, policy factors, and health-care suppliers. Binary logistic regression analysis was employed to evaluate the association of patients’ experience with their bypass behavior.Findings: A total of 928 qualified questionnaires were obtained. The first contact dimension (OR 0.961 [95% CI 0.934 to 0.988], P = 0.005) and continuity dimension (OR 1.034 [95% CI 1.000 to 1.068], P = 0.047) of patients’ experience were significantly associated with patients’ bypass behavior (P < 0.05). In addition, age (OR 1.072, [95% CI 1.015– 1.132], P = 0.013) and gender (OR 2.044, [95% CI 1.139– 3.670], P = 0.017) also made a statistically significant difference.Conclusion: Enhancement in patient experience at PHCs may help reduce their bypass behavior. Specifically, efforts are needed to improve primary care accessibility and utilization. The positive correlation between bypassing rates and continuity scores may require more attention on strengthening PCPs’ technical quality besides the quality of interpersonal interactions.Keywords: China, bypass behavior, patient experience, primary care, continuity

Jia Liu, Haixiao Zhang, Dan Feng, Jiali Wang, Mingyang Wang, Biao Shen, Yigeng Cao, Xiaoyu Zhang, Qingsong Lin, Fengkui Zhang, Yizhou Zheng, Zhijian Xiao, Xiaofan Zhu, Lei Zhang, Jianxiang Wang, Aiming Pang, Mingzhe Han, Sizhou Feng, Erlie Jiang State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People’s Republic of ChinaCorrespondence: Sizhou Feng; Erlie Jiang, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 288 Nanjing Road, Tianjin, 300020, People’s Republic of China, Email szfeng@ihcams.ac.cn; jiangerlie@163.comPurpose: Patients with hematological diseases are at high risk of carbapenem-resistant Enterobacteriaceae (CRE) infection, and CRE-related bloodstream infection (BSI) is associated with high mortality risk. Therefore, developing a predictive risk model for subsequent BSI in hematological patients with CRE isolated from perianal swabs could be used to guide preventive strategies.Methods: This was a single-center retrospective cohort study at a tertiary blood diseases hospital, including all hematological patients hospitalized from 10 October 2017 to 31 July 2021. We developed a predictive model using multivariable logistic regression and internally validated it using enhanced bootstrap resampling.Results: Of 421 included patients with CRE isolated from perianal swabs, BSI due to CRE occurred in 59. According to the multivariate logistic analysis, age (OR[odds ratio]=1.04, 95% CI[confidence interval]: 1.01– 1.06, P=0.004), both meropenem and imipenem minimal inhibitory concentration (MIC) of the isolate from perianal swabs> 8ug/mL (OR=5.34, 95% CI: 2.63– 11.5, P< 0.001), gastrointestinal symptoms (OR=3.67, 95% CI: 1.82– 7.58, P< 0.001), valley absolute neutrophil count (109/L)> 0.025 (OR=0.07, 95% CI: (0.02– 0.19, P< 0.001) and shaking chills at peak temperature (OR=6.94, 95% CI: (2.60– 19.2, P< 0.001) were independently associated with CRE BSI within 30 days and included in the prediction model. At a cut-off of prediction probability ≥ 21.5% the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 79.7%, 85.6%, 96.27% and 47.47%. The discrimination and calibration of the prediction model were good on the derivation data (C-statistics=0.8898; Brier score=0.079) and enhanced bootstrapped validation dataset (adjusted C-statistics=0.881; adjusted Brier score=0.083). The risk prediction model is freely available as a mobile application at https://liujia1992.shinyapps.io/dynnomapp/.Conclusion: A prediction model based on age, meropenem and imipenem MIC of isolate, gastrointestinal symptoms, valley absolute neutrophil count and shaking chills may be used to better inform interventions in hematological patients with CRE isolated from perianal swabs.Keywords: carbapenem-resistant Enterobacteriaceae, bloodstream infection, risk prediction model, hematological patients, perianal colonization

Na Wang,1,&ast; Minghua Zhan,2,&ast; Teng Wang,3 Jinlu Liu,1 Caiqing Li,1 Baoliang Li,1 Xuying Han,1 Huiying Li,4 Shuting Liu,5 Jing Cao,1 Xinran Zhong,1 Chunmei Lei,1 Wei Zhang,1 Zhihua Zhang6 1Microbiology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 2Clinical Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 3Otolaryngology Head and Neck Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 4Obstetrics and Gynecology Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 5Hemodialysis Department, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China; 6Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang; Zhihua Zhang, Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, No. 14, Changqing Road, Zhangjiakou City, Hebei Province, 075000, People’s Republic of China, Tel +86-03138043503, Fax +86-1088326317, Email 15369318318@163.com; zzh19641229@163.comPurpose: Through long-term and large sample size statistical analysis, we revealed the pattern of Klebsiella pneumoniae (KP) infection and drug resistance and provided epidemiological data for the treatment and prevention and control of multidrug-resistant bacterial infection in our hospital.Patients and Methods: Strains were identified using the BD PhoenixTM 100 system, minimal inhibitory concentration of antibiotics were determined by the broth method, and data were statistically analyzed using WHONET 5.6 and SPSS27.0.Results: The isolation rate of KP from Enterobacteriaceae (26.2%, 4547/17358) in our hospital showed an increasing annual trend, ranking second only to Escherichia coli. Carbapenem-resistant KP (CRKP) accounted for the highest proportion of carbapenem-resistant Enterobacteriaceae (72.2%, 431/597), showing an upward trend. Infected patients had a male-to-female ratio of approximately 2:1 and were mainly > 60 years of age (66.2%), with intensive care units being the most commonly distributed department. Sputum was the most common specimen type (74.0%). Compared with spring and summer, autumn and winter were the main epidemic seasons for KP and extended-spectrum β-lactamase KP (ESBL-KP). The resistance rate of KP to common antibiotics was low, but all showed an increasing trend each year. ESBL-KP was > 90% resistant to piperacillin, amoxicillin/clavulanic acid, and cefotaxime and less resistant to other common antibiotics, but showed an increasing trend in resistance to most antibiotics. CRKP resistance to common antibiotics was high, with resistance rates > 90%, excluding amikacin (64.1%), gentamicin (87.4%), cotrimoxazole (44.3%), chloramphenicol (13.6%), and tetracycline (30.5%).Conclusion: KP in our hospital mainly caused pulmonary infection in older men, which occurred frequently in autumn and winter, and the isolation and drug resistance rates showed an increasing trend. Age over 70 years, admission to intensive care unit, and urinary tract infection were found to be the risk factors for CRKP and ESBL-KP-resistance.Keywords: Klebsiella pneumoniae, antibacterial drugs, resistance trends, carbapenem-resistant, extended-spectrum β-lactamase, antimicrobial susceptibility surveillance

Siqin Chen,1,&ast; Minhong Su,2,&ast; Wei Lei,1,&ast; Zhida Wu,1 Shuhong Wu,1 Jing Liu,1 Xiaoyan Huang,1 Guiyang Chen,1 Qian Zhang,1 Hua Zhong,1 Fu Rong,1 Xi Li,1 Qiang Xiao1 1Pulmonary and Critical Care Medicine, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), Foshan, Guangdong, People’s Republic of China; 2Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Xiao; Xi Li, Pulmonary and Critical Care Medicine, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde Foshan), No. 1, Jiazi Road, Lunjiao Street, Shunde District, Foshan, Guangdong, 528300, People’s Republic of China, Tel +86-757-22318689 ; +86-757-22318690, Email xiaoqiang@smu.edu.cn; kamaneal@163.comPurpose: There is a high disease burden associated with community-acquired pneumonia (CAP) around the world. A timely and correct diagnosis of CAP can facilitate early treatment and prevent illness progression. The present study aimed to find some novel biomarkers of CAP by metabolic analysis and construct a nomogram model for precise diagnosis and individualized treatment of CAP patients.Patients and Methods: 42 CAP patients and 20 controls were enrolled in this study. The metabolic profiles of bronchoalveolar lavage fluid (BALF) samples were identified by untargeted LC-MS/MS analysis. With a VIP score ≥ 1 in OPLS-DA analysis and P < 0.05, the significantly dysregulated metabolites were estimated as potential biomarkers of CAP, which were further included in the construction of the diagnostic prediction model along with laboratory inflammatory indexes via stepwise backward regression analysis. Discrimination, calibration, and clinical applicability of the nomogram were evaluated by the C-index, the calibration curve, and the decision curve analysis (DCA) estimated by bootstrap resampling.Results: The metabolic profiles differed obviously between CAP patients and healthy controls, as shown by PCA and OPLS-DA plots. Seven metabolites significantly dysregulated in CAP were established: dimethyl disulfide, oleic acid (d5), N-acetyl-a-neuraminic acid, pyrimidine, choline, LPC (12:0/0:0) and PA (20:4/2:0). Multivariate logistic regression revealed that the expression levels of PA (20:4/2:0), N-acetyl-a-neuraminic acid, and CRP were associated with CAP. After being validated by bootstrap resampling, this model showed satisfactory diagnostic performance.Conclusion: A novel nomogram prediction model containing metabolic potential biomarkers in BALF that was developed for the early diagnosis of CAP offers insights into the pathogenesis and host response in CAP.Keywords: community-acquired pneumonia, biomarker, precision medicine, metabolomics, prediction model, logistic regression

Ying Li,1,2,&ast; Xiaomin Xia,1,2,&ast; Wenxue Hou,1,2 Hanlin Lv,1,2 Jie Liu,1,2 Xue Li1,2 1Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of China; 2School of Stomatology, Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Li, Department of Stomatology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of China, Tel +86-1 562 143 8983, Email lixue@qdu.edu.cnAbstract: The emergence of multidrug-resistant bacteria has been deemed a global crisis that affects humans worldwide. Novel anti-infection strategies are desperately needed because of the limitations of conventional antibiotics. However, the increasing gap between clinical demand and antimicrobial treatment innovation, as well as the membrane permeability obstacle especially in gram-negative bacteria fearfully restrict the reformation of antibacterial strategy. Metal-organic frameworks (MOFs) have the advantages of adjustable apertures, high drug-loading rates, tailorable structures, and superior biocompatibilities, enabling their utilization as drug delivery carriers in biotherapy applications. Additionally, the metal elements in MOFs are usually bactericidal. This article provides a review of the state-of-The-art design, the underlying antibacterial mechanisms and antibacterial applications of MOF- and MOF-based drug-loading materials. In addition, the existing problems and future perspectives of MOF- and MOF-based drug-loading materials are also discussed.Keywords: MOF, nanomaterial, antibacterial, mechanism, application

Jianwei Liu,1,&ast; Minmin Sun,2,&ast; Kunpeng Fang,3,&ast; Jie Wang,1,&ast; Bowen Ma,1 Li Song,1 Ting Liu,1 Ming Tang,4 Kui Wang,1 Yong Xia4 1Department of Hepatic Surgery II, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 2Department of Hepatic Surgery I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 3Department of Special Treatment I, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China; 4Department of Hepatic Surgery IV, Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), Shanghai, 200438, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Xia, Department of Hepatic Surgery (IV), Third Affiliated Hospital of Naval Medical University (Eastern Hepatobiliary Surgery Hospital), &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel +86-2181875005, Fax +86-2165562400, Email xia.yong@126.com Kui Wang, Department of Hepatic Surgery (II), Eastern Hepatobiliary Surgery Hospital, Navy Medical University, &num;225 Changhai Road, Shanghai, 200438, People’s Republic of China, Tel\Fax +86-2181875514, Email wangkuiykl@163.com

Yao Liu,1– 3 Jinqing Liu,1– 3 Lei Fu,1– 3 Chuan Jiang,1– 3 Shifang Peng1– 3 1Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Viral Hepatitis of Hunan Province, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Shifang Peng, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Email sfp1988@csu.edu.cnObjective: Despite its high case-fatality risk, pyogenic liver abscess (PLA) lacks clear management guidelines in patients with negative microbial cultures. Our aim was to evaluate differences in clinical characteristics between patients with culture-negative liver abscess (CNLA) and those with culture-positive liver abscess (CPLA), and identify differences in the main causative pathogen.Methods: In this study, we retrospectively collected medical records of PLA patients admitted to a teaching hospital from January 2010 to December 2019.Results: In total, 324 PLA patients were enrolled in this study. Of these, 202 (62.3%) cases were confirmed cultural positive, including 109 patients (54%) and 20 (9.9%) patients infected with Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E.coli), respectively. Patients in the CPLA group were older (p=0.029) and had higher prevalence of abscesses larger than 5 cm in diameter (p = 0.003), gas-forming rate (p = 0.016), and percutaneous drainage (p < 0.001) compared with CNLA group. Patients with CPLA had significantly longer hospitalizations than those with CNLA (p = 0.010). Nevertheless, there was no significant difference in in-hospital mortality between the two groups (p = 0.415). Compared with patients with E. coli, those with K. pneumoniae had higher incidence of diabetes mellitus (p = 0.041), solitary abscess (p < 0.001), localization in the right hepatic lobe (p = 0.033), abscess size larger than 5 cm (p < 0.001) and percutaneous drainage (p = 0.002), but mortality was not significantly different (p = 1.000).Conclusion: No significant difference in in-hospital mortality was found between patients with CNLA and those with CPLA group. However, clinical characteristics and management were different between the main causative pathogens, including K. pneumoniae and E. coli.Keywords: PLA, culture negative, culture positive, Klebsiella pneumoniae, Escherichia coli

Yuhao Zeng,1,&ast; Sha Zhu,1,&ast; Zilin Wang,1 Junru Chen,1 Jindong Dai,1 Zhenhua Liu,1 Guangxi Sun,1 Jiayu Liang,1 Xingming Zhang,1 Zhipeng Wang,1 Jinge Zhao,1 Yuchao Ni,1 Jiyu Yang,1 Minghao Wang,1 Qiang Wei,1 Xiang Li,1 Ni Chen,2 Zhiping Li,3 Xin Wang,3 Yali Shen,3 Jin Yao,4 Rui Huang,5 Jiyan Liu,6 Diming Cai,7 Hao Zeng,1 Pengfei Shen1 1Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 5Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 6Department of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 7Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pengfei Shen; Hao Zeng, Department of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China, Email cdhx510@163.com; kucaizeng@163.comPurpose: Multidisciplinary team (MDT) discussion is a widely used model to manage patients diagnosed with cancer. However, there has been no direct evidence to prove its effect on the prognosis of metastatic renal cell carcinoma (mRCC) patients, so this study explored the impact of MDT discussion on mRCC patient survival.Methods: The clinical data of 269 mRCC patients were retrospectively collected from 2012 to 2021. The cases were grouped into the MDT and non-MDT groups, then subgroup analysis was performed according to different histology types, as well as exploring the role of MDT in patients who have undergone multiple-line therapy. Overall survival (OS) and progression free survival (PFS) were set as the study endpoint.Results: Approximately half (48.0%, 129/269) of the patients were in the MDT group, with univariable survival analyses showing these patients had remarkably longer median OS (MDT group: 73.7 months; non-MDT group: 33.2 months, hazard ratio (HR): 0.423 (0.288, 0.622), p< 0.001) and longer median PFS (MDT group: 16.9 months, non-MDT group: 12.7 months, HR: 0.722 (0.542, 0.962), p=0.026). Furthermore, MDT management resulted in longer survival for both ccRCC and non-ccRCC subgroups. Patients in the MDT group were more likely to receive multi-line therapy (MDT group: 79/129, 61.2% vs non-MDT group: 56/140, 40.0%, p< 0.001), and within this patient group, MDT management still resulted in longer OS (MDT group: 94.0 months; non-MDT group: 43.5 months, p=0.009).Conclusion: MDT is associated with prolonged overall survival in mRCC independent of histology, ensuring that patients receive better management and precise treatment.Keywords: mRCC, MDT, overall survival, prognosis, ccRCC, non-ccRCC, multi-line treatment

Yongli Liu,1 Jing Liu,2 Wei Wang3 1Department of Education, Shanxi Datong University, Datong, People’s Republic of China; 2School of Journalism, Shanxi Datong University, Datong, People’s Republic of China; 3Department of Psychology, Shanxi Datong University, Datong, People’s Republic of ChinaCorrespondence: Wei Wang, Professor of Department of Psychology, Shanxi Datong University, Datong, People’s Republic of China, Email wangwei05028@163.comPurpose: Social isolation during the COVID-19 pandemic has greatly increased the probability of Internet dependence. This study sought to examine the relation between future time perspective and college students’ Internet dependence, as well as the mediating role of boredom proneness and the moderating effect of self-control in the link between boredom proneness and Internet dependence.Materials and Methods: A questionnaire survey was carried out among college students from two universities in China. A sample of 448 participants varying from freshmen to seniors completed questionnaires on future time perspective, Internet dependence, boredom proneness and self-control.Results: Results indicated that college students with high future time perspective were less likely to fall into Internet dependence and boredom proneness mediated this relationship. The relation between boredom proneness and Internet dependence was moderated by self-control. Boredom proneness had a greater impact on Internet dependence for students with low self-control.Conclusion: Future time perspective could influence Internet dependence through the mediating role of boredom proneness, which is moderated by self-control. The results advanced our understanding of how future time perspective affected college students’ Internet dependence, revealing that intervention strategies which could improve students’ self-control would be instrumental in reducing Internet dependence.Keywords: future time perspective, Internet dependence, boredom proneness, self-control

Jingjing Hao, Jingyuan Liu, Lin Pu, Chuansheng Li, Ningning Yin, Ang Li Department of Critical Care Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Ang Li, Email liang@ccmu.edu.cnBackground: Respiratory failure in acquired immunodeficiency syndrome (AIDS) patients was the leading cause of intensive care unit (ICU) admission in our center. We aimed to describe the pulmonary infections and outcomes for respiratory failure in AIDS patients.Methods: A retrospective study was conducted on AIDS adult patients with respiratory failure who were admitted to the ICU in Beijing Ditan hospital, China, from January 2012 to December 2021. We investigated pulmonary infections complicated by respiratory failure in AIDS patients. The primary outcome was ICU mortality, and a comparison between survivors and nonsurvivors was performed. Multiple logistic regression analysis was used to identify predictors of ICU mortality. The Kaplan-Meier curve and Log rank test were used for survival analysis.Results: A total of 231 AIDS patients were admitted to ICU with respiratory failure over a 10-year period with a male predominance (95.7%). Pneumocystis jirovecii pneumonia was the main etiology of pulmonary infections (80.1%). The ICU mortality was 32.9%. In multivariate analysis, ICU mortality was independently associated with invasive mechanical ventilation (IMV) [odds ratio (OR), 27.910; 95% confidence interval (CI, 8.392– 92.818; p = 0.000) and the time before ICU admission (OR, 0.959; 95% CI, 0.920– 0.999; p = 0.046). In the survival analysis, patients with IMV and later admission to ICU had a higher probability of mortality.Conclusion: Pneumocystis jirovecii pneumonia was the primary etiology for respiratory failure in AIDS patients admitted to the ICU. Respiratory failure remains a severe illness with high mortality, and ICU mortality was negatively associated with IMV and later admission to ICU.Keywords: acquired immunodeficiency syndrome, AIDS, respiratory failure, pulmonary infections, ICU mortality

Jichao Liu,1 Nan Zhao,2 Shi-Han Su,3 Yun Gao,2 Bo Qi4 1Department of Hand and Foot Micro Burn Plastic Surgery, 3201 Hospital, Hanzhong, People’s Republic of China; 2Department of Neurosurgery, The First Hospital of Kunming, Kunming, People’s Republic of China; 3Department of Internal Medicine-Neurology, 920th Hospital of Joint Logistics Support Force, Kunming, People’s Republic of China; 4Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming, People’s Republic of ChinaCorrespondence: Bo Qi, Department of Orthopaedics, 920th Hospital of Joint Logistics Support Force, Kunming, 650000, People’s Republic of China, Email kmqb66@sina.comBackground: Bone dysfunction is a crucial problem that occurs during rheumatoid arthritis (RA) disease. Osteoclast plays a significant role in bone resorption and osteoclast differentiation and its enhancement of bone destruction. Edaravone remarkably exhibited free radical scavenging and anti-inflammatory effects. The objective of the current investigation is to comfort the inhibitory effect of Edaravone (ED) against complete Freund adjuvant (CFA) rat model via inhibition of angiogenesis and inflammation.Methods: Subcutaneous injection of CFA (1%) was used to induce arthritis; the rats were divided into different groups and received the oral administration of ED. Paw edema, body weight, and arthritis score were regularly estimated. Biochemical parameters were estimated, respectively. We also estimate the level of hypoxia-inducible factor-1α (HIF-1α), angiopoietin 1 (ANG-1), and vascular endothelial growth factor (VEGF). We also checked into how ED affected the differentiation of osteoclasts utilising a co-culture system with monocytes and synovial fibroblasts in arthritis rats.Results: ED treatment significantly (P< 0.001) suppressed the arthritis score and paw edema and improved the body weight. ED treatment significantly (P< 0.001) altered the antioxidant parameters and pro-inflammatory cytokines: inflammatory mediator nuclear kappa B factor (NF-κB), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2), respectively. Furthermore, ED treatment significantly (P< 0.001) suppressed the level of ANG-1, HIF-1α, and VEGF, respectively. The results suggest that ED suppressed osteoclast differentiation and also decreased the level of cytokines and osteopontin (OPN), receptor activator for nuclear factor-κ B Ligand (RANKL) and macrophage colony stimulating factor (M-CSF) in the co-culture supernatant of monocytes and synovial fibroblasts.Conclusion: Edaravone could mitigate CFA via inhibiting angiogenesis and inflammatory reactions, which may be linked with the HIF-1α–VEGF–ANG-1 axis and also enhance the bone destruction of murine arthritis via suppression of osteoclast differentiation and inflammatory reaction.Keywords: Edaravone, oxidative stress, arthritis, inflammation, angiogenesis, osteoclast differentiation

Guangming Li,1,2 Juan Liu,2 Haiying Wen,3 Qiyun Shen4 1Key Laboratory of Brain, Cognition and Education Sciences, Ministry of Education, South China Normal University, Guangzhou, 510631, People’s Republic of China; 2School of Psychology, Center for Studies of Psychological Application, and Guangdong Key Laboratory of Mental Health and Cognitive Science, South China Normal University, Guangzhou, 510631, People’s Republic of China; 3Department of Fashion Design, Guangdong Province Technician College of Light Industry, Guangzhou, 510315, People’s Republic of China; 4Zhongshan Polytechnic, Zhongshan, 528404, People’s Republic of ChinaCorrespondence: Guangming Li, Email Lgm2004100@m.scnu.edu.cnBackground: Depression of adolescents is an important public health problem. Persistent depression will become a huge hidden danger of individual mental health development. It is important to study the change mechanism of adolescents’ depression.Methods: A total of 563 males and 739 females aged 11– 19 years reported their depression. 1302 adolescents participated in a short-term 6-month longitudinal study. They were contacted every three months for two follow-up tests (T2 and T3). Participants completed internet addiction test, self-rating anxiety scale and self-rating depression scale. Multiple-group latent profile transition analysis (MLPTA) was used to identify meaningful subgroups and transitions between groups across time. Covariates (anxiety and internet addiction) were used to analyze the influencing factors.Results: The results showed that: (1) There are three categories of adolescents’ depression, namely no-depression group, low-depression-mountain group and low-depression-hill group. (2) The depression of the subjects showed a trend of improvement, but the proportion of low-depression-mountain group is relatively high at three time points (0.44, 0.59, and 0.30). (3) The transition probability between the low-depression-mountain group and the no-depression group is large, which suggests the low-depression-mountain group can easily convert into the no-depression group, but the transition probability from low-depression-hill group to other groups is relatively low and stable, which suggests the low-depression-hill group is not easily converted into the no-depression group. (4) Both anxiety and internet addiction affect the development of adolescents’ depression across three time points. Anxiety played a significant role in affecting female adolescents’ depression, while internet addiction played a significant role in affecting male adolescents’ depression.Conclusion: This study demonstrated a transition pattern in adolescents’ depression. We should pay more attention to the low-depression-mountain group and try to do their mental health well. Adolescents’ Depression changes rapidly with anxiety and internet addiction for different genders, which suggests that some interventions are needed.Keywords: adolescents, depression, multiple-group latent profile transition analysis, anxiety, internet addiction

Mengqi Zhang,1,&ast; Shengxian Bao,2,&ast; Guanhua Qiu,2,&ast; Jingchen Liang,2 Qin Wang,2 Xiaoqi Zhu,2 Guchun Qin,1 Junjie Liu,2 Chang Zhao1 1Department of Interventional Therapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Ultrasound and Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junjie Liu; Chang Zhao, Email liujunjie197806@163.com; 710519137@qq.comPurpose: In this experiment, we constructed a magnetic targeting nano-diagnosis and treatment platform of doxorubicin (DOX) combined with iron nanoparticles, and explored their application value and mechanism in the treatment of Triple Negative Breast Cancer (TNBC), as well as its new diagnosis and treatment mode in Magnetic Resonance Imaging (MRI).Patients and Methods: Hollow mesoporous nanoparticles (HFON) were synthesized by solvothermal method, and loaded the drug DOX (DOX@HFON) to treat TNBC. The experiments in vivo and in vitro were carried out according to the characteristics of the materials. In vitro experiments, the killing effect of the drug on cells was verified by cell viability CCK8, ROS generation level, LPO evaluation and flow cytometry; the MRI effect and targeted anti-tumor therapy effect were studied by in vivo experiments; then the tumor tissue sections were detected by Ki-67, CD31, ROS, LPO and TUNEL immunofluorescence detection; H&E staining and blood biochemical tests were used to evaluate the biosafety of the materials.Results: Through a series of characterization tests, it is confirmed that the nano-materials prepared in this experiment have positive drug loading properties. MDA-MB-231 cells had great phagocytic ability to DOX@HFON under Confocal Laser Scanning Microscope (CLSM). Experiments in vitro confirmed that DOX and Fe were released and concentrated in cells, and a large number of ROS production and induction of LPO were detected by DCFH-DA and C11-BODIPY probes in cells. Apoptosis experiments further confirmed that DOX@HFON induced apoptosis, autophagy and ferroptosis. In the vivo experiment, the anti-tumor therapy effect of MAGNET@DOX@HFON group was the most significant, and in MRI also proved that the drug had great tendency and imaging ability in tumor tissue.Conclusion: The new magnetic targeting nano-diagnosis and treatment platform prepared in this experiment is expected to become a new treatment model for TNBC.Keywords: nanoparticles, DOX, Fenton, ROS

Mingpeng Li,1,2,&ast; Xiaorui Cui,3,&ast; Yanbin Meng,4 Mengli Cheng,4 Jinsong He,3 Wei Yuan,3 Jing Ni,5 Jianping Liu6 1Department of Cardiovascular, Chenzhou No. 1 People’s Hospital, Chenzhou, People’s Republic of China; 2The First Affiliated Hospital of Xiangnan University, Chenzhou, People’s Republic of China; 3Department of Neurology, Affiliated Hospital of Xiangnan University, Chenzhou, People’s Republic of China; 4Xiangnan University, Chenzhou, People’s Republic of China; 5Hunan University of Science and Technology, Xiangtan, People’s Republic of China; 6Institute of Cardiovascular and Cerebrovascular Diseases, Xiangnan University, Chenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Liu, No. 25 Renmin West Road, Chenzhou, 423000, People’s Republic of China, Email xxgyjs@163.comBackground: Although the prevalence of hypertension has been well studied in middle age and elderly populations, few studies have systematically investigated the prevalence of hypertension and its association with cardiovascular and cerebrovascular risk factors in young populations.Objective: This study examined the prevalence of hypertension in college students and its correlation with cardiovascular and cerebrovascular risk factors, such as neck circumference and body mass index (BMI).Methods: This population-based study recruited a total of 1719 students (723 were junior, 502 were sophomore, and 494 were freshman), including 996 males (average age: 20.8 years) and 723 females (average age: 20.4 years). Hypertension was defined by the 2018 revised edition of the Chinese Guidelines for Prevention and Treatment of Hypertension. Blood and pulse pressure were measured using standard protocols. Circulating levels of lipids, glucose, glycosylated hemoglobin (GHb), leptin, and adiponectin were determined using standard methods. The Chi-squared (χ2) test was used for comparison of significant differences between groups. Linear and logistic regression analyses were used to explore risk factors that significantly influence hypertension.Findings: The prevalence of hypertension was 10.59% in the total cohort, and sophomores had a higher prevalence of hypertension than freshmen and juniors (χ2 = 19.372; P < 0.001). In addition, male students had a significantly higher prevalence of hypertension (10.24%) and abnormal pulse pressure (8.13%) than female students (1.4% and 0.83%) (χ2 = 327.424, P < 0.001 for high SBP and χ2 = 60.49, P < 0.001 for high DBP, respectively). Correlation analysis revealed that hypertension was significantly correlated with neck circumference and BMI (r = 0.509, P < 0.001; r = 0.474, P < 0.001), but not significantly correlated with the other parameters examined.Conclusion: The prevalence of hypertension in college students is closely correlated with two obesity indicators, neck circumference and BMI.Keywords: cardiovascular and cerebrovascular events, college students, correlation, hypertension, risk factors

Yuyan Cao,1,&ast; Xinhua Ye,1,&ast; Xiaoqing Yuan,1 Juan Liu,1 Qing Zhang2 1Department of Endocrinology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China; 2Changzhou Medical Center, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Juan Liu; Qing Zhang, Email liujuan_work@163.com; 1034173982@qq.comAim: The purpose of this paper is to investigate the relationship between serum pentosidine levels and cardiac function and vascular disease in diabetic patients, and to provide a new reference indicator for the early detection of diabetic cardiovascular complications.Materials and Methods: This was a cross-sectional study. One hundred and twenty-two patients with type 2 diabetes were grouped by LVEF quartiles to compare the differences between their clinical data and serum pentosidine levels. Also, the correlation between serum pentosidine and clinical indicators was assessed. The effect of serum pentosidine on cardiac function and vascular stiffness was analyzed by multiple stepwise regression.Results: Serum pentosidine levels were higher in patients with LVEF ≤ 57%. Serum pentosidine levels were positively correlated with waist-to-hip ratio, hemoglobin, AIP, baPWV, LVESD, and ARD, and negatively correlated with LVEF. Low serum pentosidine was associated with increased LVESD; high pentosidine was significantly associated with increased ARD, high AIP and high baPWV.Conclusion: The results suggest that serum pentosidine, a member of AGEs, may reflect cardiac remodeling and dysfunction as well as atherosclerosis.Keywords: pentosidine, T2DM, cardiac dysfunction, atherosclerosis

Fei Tian,1,&ast; Zuyang Xi,1,&ast; Ling Ai,2 Xiaojing Zhou,1 Zhaohui Zhang,1,&ast; Jinglan Liu,1 Yuanyuan Mi,3 Shengmin Gui,1 Chaxiang Li,1 Min Liu1 1The First College of Clinical Medical Science, China Three Gorges University, Teaching and Research Section of Clinical Nursing, Yichang, People’s Republic of China; 2Nursing Department, China Xingshan County People’s Hospital, Xingshan, People’s Republic of China; 3Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei Tian, The First College of Clinical Medical Science, China Three Gorges University, Teaching and Research Section of Clinical Nursing, Yichang, 433000, People’s Republic of China, Tel +86 13687271927, Email 980347043@qq.comObjective: To investigate the willingness of nurses in Yichang to participate in “Internet plus nursing services” and analyze the influencing factors in order to provide reference for the implementation of “Internet plus nursing services”.Methods: Using the “Internet plus Nursing Service” questionnaire, a cross-sectional survey was conducted among 1447 nurses in Yichang by convenience sampling from July to September in 2022, and the related influencing factors were analyzed. The questionnaire was composed of two parts: the demographic characteristics and the questionnaire of nurses’ willingness to participate in “Internet plus nursing service”, including 4 dimensions: awareness, promoting factors, concern factors and training needs. Likert 5-point scoring method was used for scoring. Binary logistic regression was used to screen the variables, and the ROC curve and Nomogram risk prediction model were drawn.Results: A total of 1233 valid questionnaires were collected. It shows that 76.07% of nurses in Yichang are willing to participate in “Internet plus nursing services”. Among them, education background, specialist nurses, awareness, promotion factors, concerns and training needs are the independent influencing factors (all P < 0.05). The area under the ROC curve (AUC) of the prediction model is 0.802, and the consistency index (c-index) of nomogram is 0.800. The average absolute error of internal calibration is 0.014, and the model has good accuracy and discrimination.Conclusion: Nurses in Yichang have a high willingness to participate in “Internet plus nursing services”, a low awareness of the program and a high demand for relevant professional training. It is suggested that the government and hospitals should strengthen the publicity of “Internet plus nursing services”, improve relevant laws and regulations and strengthen the construction of specialist nurses’ team, so as to provide a good practice environment for nurses’ door-to-door service.Keywords: internet plus nursing services, willingness, influencing factors

Fei Wang,1– 3,&ast; Jitao Liu,1– 3 Quan An,1– 4,&ast; Yiming Wang,1– 3 Yang Yang,1– 3 Tong Huo,1– 3 Simin Yang,5 Ruijun Ju,5 Qianghua Quan1– 4 1Research and Development Department, Yunnan Baiyao Group Health Products Co., Ltd., Kunming, People’s Republic of China; 2East Asia Skin Health Research Center, Beijing, People’s Republic of China; 3Research and Development Department, REAL DermaSci & Biotech Co., Ltd., Beijing, People’s Republic of China; 4Research and Development Department, Yunnan Baiyao Group Shanghai Science & Technology Co., Ltd., Shanghai, People’s Republic of China; 5Beijing Key Laboratory of Enze Biomass Fine Chemicals, Department of Pharmaceutical Engineering, Beijing Institute of Petrochemical Technology, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianghua Quan, Yunnan Baiyao Group Health Products Co., Ltd, Kunming, People’s Republic of China, Email 18811781508@163.comIntroduction: Inflammation generally refers to the body’s defensive response to stimuli, and skin inflammation is still one of the major problems that affect human physical and mental health. While current pharmacological treatments are reported to have cytotoxicity and various side effects, herbal medicines with few side effects and low cytotoxicity are considered as alternative therapeutic approaches.Methods: In order to investigate anti-inflammatory effects and mechanisms of ALOE, the potential cytotoxicity of A. vera extracts (ALOE) was determined in vitro at first. The production of the pro-inflammatory proteins (ie, IL-6, TNF-α) in lipopolysaccharides (LPS) and ultraviolet A (UVA)-stimulated HaCaT and RAW264.7 cells were then treated with ALOE to test its inhibitory effects using enzyme-linked immunosorbent assay (ELISA). To further explore the anti-inflammatory mechanisms of ALOE, quantitative Polymerase Chain Reaction (qPCR) was used to analyze the mRNA expression of inflammatory genes iNOS, COX-2 and NO production. For NF-κB and MAPK signaling pathways analysis, Western blotting and nuclear fluorescence staining were used to evaluate the expression of key factors.Results: ALOE did not exhibit obvious cytotoxicity (0– 3 mg/mL) in vitro. ALOE was able to inhibit the expression of pro-inflammatory cytokines IL-6, TNF-α and functioned more prominently in LPS-induced model. ALOE could also suppress the mRNA expression of LPS-induced iNOS and COX-2 and further down-regulate NO level. Furthermore, ALOE reduced the protein expression of P65 in NF-κB signaling pathway and suppressed LPS-induced activation of ERK and JNK, instead of p38 MAPK pathway.Conclusion: Taken together, these results demonstrated that ALOE is a potential treatment in suppressing LPS-stimulated inflammation reactions targeting NF-κB, JNK and ERK signaling pathways. The anti-inflammatory effects of ALOE indicated that it has the potential to become an effective cosmetic ingredient.Keywords: Aloe vera extracts, anti-inflammation, LPS, iNOS, COX-2, NO, P65, MAPK, NF-κB

Guangda He,1 Runqing Ji,1 Xiqian Huo,1 Xiaoming Su,1 Jinzhuo Ge,1 Wei Li,1 Lubi Lei,1 Boxuan Pu,1 Aoxi Tian,1 Jiamin Liu,1 Lihua Zhang,1 Yongjian Wu2 On behalf of the China PEACE Collaborative Group1National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, People’s Republic of China; 2Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lihua Zhang, National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, 167 Beilishi Road, Beijing, 100037, People’s Republic of China, Email zhanglihua@fuwai.com Yongjian Wu, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People’s Republic of China, Email wuyongjian@fuwai.comBackground: Inflammation contributes to the progression of heart failure (HF). However, long-term inflammatory trajectories and their associations with outcomes in patients with acute HF remain unclear.Methods: Data was obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Prospective Heart Failure Study, and high-sensitivity C-reactive protein (hsCRP) was used to reflect the inflammatory level. Only patients who survived over 12-month and had hsCRP data at admission, 1-, and 12-month after discharge were included. The latent class trajectory modeling was used to characterize hsCRP trajectories. Multivariable Cox regression models were used to explore the association between hsCRP trajectories and following mortality.Results: Totally, 1281 patients with a median 4.77 (interquartile range [IQR]: 4.24– 5.07) years follow-up were included. The median age was 64 years (IQR: 54– 73 years); 453 (35.4%) were female. Four distinct inflammatory trajectories were characterized: persistently low (n = 419, 32.7%), very high-marked decrease (n = 99, 7.7%), persistently high (n = 649, 50.7%), and persistently very high (n = 114, 8.9%). Compared with the persistently low trajectory, the all-cause mortality was increased in a graded pattern in the persistently high (hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.23– 2.07) and persistently very high (HR: 2.56, 95% CI: 1.83– 3.70) trajectories; nevertheless, the mortality was not significantly increased in very high-marked decrease trajectory (HR: 0.94, 95% CI: 0.57– 1.54).Conclusion: Four distinct inflammatory trajectories were identified among patients with acute HF who survived over 12-month. Patients with persistently high and very high trajectories had significantly higher mortality than those with the persistently low trajectory.Keywords: heart failure, high-sensitivity C-reactive protein, trajectory, latent class trajectory modeling, mortality

Yiwen Dong,1– 3 Litao Yao,2– 4,&ast; Lei Cai,1 Mi Jin,1 Tymour Forouzanfar,2,3 Lianjun Wu,1 Jinsong Liu,1,&ast; Gang Wu2,3 1School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery/Pathology, Amsterdam UMC and Academic Center for Dentistry Amsterdam (ACTA), Vrije Universiteit Amsterdam, Amsterdam Movement Science, Amsterdam, Amsterdam, the Netherlands; 3Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam (UvA) and Vrije Universiteit Amsterdam (VU), Amsterdam, the Netherlands; 4Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Litao Yao, Department of Dentistry, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Zhejiang, Email yaolt@srrsh.com Jinsong Liu, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, 325027, People’s Republic of China, Email jinsong0719@wmu.edu.cnIntroduction: An antibacterial and pro-osteogenic coaxially electrospun nanofiber guided bone regeneration (GBR) membrane was fabricated to satisfy the complicated and phased requirements of GBR process.Methods: In this study, we synthesize dual-functional coaxially electrospun nanofiber GBR membranes by encapsulating parathyroid hormone (PTH) in the core layer and magnesium oxide nanoparticles (MgONPs) in the shell layer (MgONPs-PCL/PTH-PCL). Herein, the physicochemical characterization of MgONPs-PCL/PTH-PCL, the release rates of MgONPs and PTH, and antibacterial efficiency of the new membrane were evaluated. Furthermore, the pro-osteogenicity of the membranes was assessed both in-vitro and in-vivo.Results: We successfully fabricated a coaxially electrospun nanofiber MgONPs-PCL/PTH-PCL membrane with the majority of nanofibers (> 65%) ranged from 0.40~0.60μm in diameter. MgONPs-PCL/PTH-PCL showed outstanding antibacterial potential against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) through the release of MgONPs. We also discovered that the incorporation of MgONPs significantly prolonged the release of PTH. Furthermore, both the in-vivo and in-vitro studies demonstrated that high dosage of PTH promoted pro-osteogenicity of the membrane to improve bone regeneration efficacy with the presence of MgONPs.Conclusion: The new composite membrane is a promising approach to enhance bone regeneration in periodontitis or peri-implantitis patients with large-volume bone defects.Keywords: antibacterial property, pro-osteogenicity, coaxially electrospun, barrier membrane, guided bone regeneration

Jing Liu,1,2 Jianli Li,1 Dongyan Gao,1 Jing Wang,1 Meinv Liu,1 Dongdong Yu1 1Department of Anesthesiology, Hebei General Hospital, Shijiazhuang City, People’s Republic of China; 2Graduate Faculty, Hebei North University, Zhangjiakou City, People’s Republic of ChinaCorrespondence: Jianli Li, Department of Anesthesiology, Hebei General Hospital, Shijiazhuang city, Hebei Province, 050051, People’s Republic of China, Tel +81 85988447, Email hblijianli@163.comPurpose: This study was to investigate the incidence and potential predictive factors for postoperative delirium (POD) in older people following urinary calculi surgery, and to establish the corresponding risk stratification score by the significant factors to predict the risk of POD.Patients and Methods: We retrospectively analyzed the perioperative data of 195 patients aged 65 or older who underwent elective urinary calculi surgery between September 2020 and September 2022. POD was defined by chart-based method, and the serum uric acid to creatinine (SUA/Cr) ratio as well as neutrophil-to-lymphocyte ratio (NLR) were calculated, respectively. Identification of the risk factors for POD was performed by univariate and multivariate logistic regression analysis. Moreover, the risk stratification score was developed based on the regression coefficients of the associated variables.Results: In 195 eligible patients following urinary calculi surgery, the median age was 69 (66– 72) and 19 patients ultimately developed POD (9.7%). The results by univariate analysis showed that patients with advanced age, high American Society of Anesthesiologists (ASA) physical status (≥ 3) and low SUA/Cr ratio (≤ 3.3) were more likely to develop POD, but dexmedetomidine can significantly decrease the risk of the occurrence of POD. The multivariate analysis further indicated that high ASA physical status (≥ 3) and low SUA/Cr ratio (≤ 3.3) were independently associated with POD, and the POD incidence could obviously be elevated with the increase of risk stratification score. Moreover, patients with delirium had longer hospital stays.Conclusion: POD is frequent in geriatric patients following urinary calculi surgery (9.7%). The high ASA physical status (≥ 3) and low SUA/Cr ratio (≤ 3.3) were effective predictors of POD. The corresponding risk stratification based on these factors could be beneficial to determining patients who are susceptible to POD, and thus better preventing and reducing the occurrence of POD. However, large prospective studies are needed to confirm this finding.Graphical Abstract: Keywords: postoperative delirium, serum uric acid to creatinine ratio, ASA physical status, risk stratification score, urinary calculi surgery, older adults

Chengkai Yang,1 Xiaoya Wu,2 Jianyong Liu,3 Huaxiang Wang,1 Yi Jiang,3 Zhihong Wei,3 Qiucheng Cai3 1The Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 2Eastern Hospital Affiliated to Xiamen University, Fuzhou, 350025, People’s Republic of China; 3Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, Fuzhou, 350025, People’s Republic of ChinaCorrespondence: Qiucheng Cai; Zhihong Wei, Department of Hepatobiliary Surgery, 900 Hospital of The Joint Logistics Team, No. 156 The Second West Ring Road, Fuzhou, Fujian, 350025, People’s Republic of China, Tel +86 13514072408 ; +86 18059055977, Email caiqiucheng2211@163.com; 779349357@qq.comPurpose: In this study, we developed a nomogram based on the platelet–albumin–bilirubin (PALBI) score to predict recurrence-free survival (RFS) after curative resection in alpha-fetoprotein (AFP)-negative (≤ 20 ng/mL) hepatocellular carcinoma (HCC) patients.Patients and Methods: A total of 194 pathologically confirmed AFP-negative HCC patients were retrospectively analyzed. Univariate and multivariate Cox regression analyses were performed to screen the independent risk factors associated with RFS, and a nomogram prediction model for RFS was established according to the independent risk factors. The receiver operating characteristic (ROC) curve and the C-index were used to evaluate the accuracy and the efficacy of the model prediction. The correction curve was used to assess the calibration of the prediction model, and decision curve analysis was performed to evaluate the clinical application value of the prediction model.Results: PALBI score, MVI, and tumor size were independent risk factors for postoperative tumor recurrence (P < 0.05). A nomogram prediction model based on the independent predictive factors was developed to predict RFS, and it achieved a good C-index of 0.704 with an area under the ROC curve of 0.661 and the sensitivity was 73.2%. Patients with AFP-negative HCC could be divided into the high-risk group or the low-risk group by the risk score calculated by the nomogram, and there was a significant difference in RFS between the two groups (P < 0.05). Decision curve analysis (DCA) showed that the nomogram increased the net benefit in predicting the recurrence of AFP-negative HCC and exhibited a wider range of threshold probabilities than the independent risk factors (PALBI score, MVI, and tumor size) by risk stratification.Conclusion: The nomogram based on the PALBI score can predict RFS after curative resection in AFP-negative HCC patients and can help clinicians to screen out high-risk patients for early intervention.Keywords: hepatocellular carcinoma, platelet–albumin–bilirubin score, alpha-fetoprotein-negative, recurrence-free survival, nomogram