Search

Wentao Ge,1,2 Wei Bian,2 Lu Wang,2 Lizhen Duan,1 Jiaying Guo,1 Lihua Wang2 1Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, People’s Republic of China; 2Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of ChinaCorrespondence: Lihua Wang, Hospital Administration Office, Southwest Hospital, Third Military Medical University (Army Medical University), 29 Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email yiwa@tmmu.edu.cnObjective: To develop a medication literacy intervention program for glaucoma and test its effects on medication literacy, medication self-efficacy and medication adherence.Methods: The intervention was constructed according to the Information-Motivation-Behavioral skills Model and the Health Belief Model. Preliminary protocols were revised through expert group meetings and pre-experiments to form a formal intervention plan. Subsequently, 66 patients with glaucoma were enrolled and randomly assigned to the control and intervention groups. The control group was received with routine follow-up and education for glaucoma patients, while the intervention group was given an 8-weeks medication literacy intervention for glaucoma patients. Before the implementation of the intervention and at the end of the 8th week of the intervention, the Chinese Version of the Medication Literacy Scale, the Short Version of the Glaucoma Medication Self-Efficacy Questionnaire and the Chinese version of the Morisky Medication Adherence Scale-8 were used to evaluate the medication literacy level, medication self-efficacy and medication adherence of glaucoma patients in the intervention group and the control group.Results: We developed an 8-weeks multi-component medication literacy intervention for glaucoma. Before the start of the intervention, there were no statistically significant differences in the scores of medication literacy, medication self-efficacy and medication adherence between the control group and the intervention group. After the intervention, the medication literacy, medication self-efficacy, and medication adherence of the intervention patients were significantly better than those of the control group (P< 0.05).Conclusion: The 8-weeks multi-component intervention for glaucoma patients can improve their medication literacy, medication self-efficacy, and medication adherence.Keywords: glaucoma, medication adherence, medication literacy, nursing evaluation research, self-efficacy

Jing Sun,1,2,&ast; Wengang Li,3,&ast; Weiping He,3,&ast; Yanping Yang,4,&ast; Lewei Duan,5 Tingshi Su,6 Aimin Zhang,3 Tao Zhang,3 Xiaofang Zhao,7 Xiaoyun Chang,3 Xuezhang Duan1– 3 1 307 Clinical College of PLA, ANHUI Medical University, Beijing, People’s Republic of China; 2The Fifth Clinical College, ANHUI Medical University, Hefei, Anhui, People’s Republic of China; 3Department of Radiation Oncology, Senior Department of Oncology, The Fifth Medical Center of PLA General Hospital, Beijing, People’s Republic of China; 4Department of Oncology, Kaifeng People’s Hospital, Kaifeng, Henan, People’s Republic of China; 5Laboratory of Epigenetics at Institutes of Biomedical Sciences, and Intelligent Medicine Institute, Fudan University, Shanghai, People’s Republic of China; 6Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of China; 7Graduate School of PLA Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuezhang Duan, 307 Clinical College of PLA, ANHUI Medical University, No. 8 East Street, Fengtai District, Beijing, People’s Republic of China, Email duanxuezhang2006@163.comPurpose: Radiofrequency ablation (RFA) is a micro-invasive treatment for early-stage HCC patients. Stereotactic body radiation therapy (SBRT) has also been proven an effective and safe treatment for HCC patients. This multi-center study is to compare the efficacy of computed tomography (CT)-guided RFA and CT-based SBRT in naïve HCC patients with tumor diameters ≤ 5 cm.Patients and Methods: This retrospective cohort study included 1001 treatment-naïve HCC patients from three hospitals or medical centers. The patients received RFA (n = 481) or SBRT (n = 520) treatment between December 2011 and May 2019. Furthermore, subgroup analyses of all patients were conducted based on Couinaud’s classification of liver segments.Results: After matching, the local control (LC) rates of the SBRT group were better than those of the RFA group (p=0.024&ast;), which mainly referred to the patients whose tumors were located in the S7/S8 (p=0.006&ast;). Among patients with tumors located in S1, nineteen patients (19/21) underwent SBRT. The 1-, 3- and 5-year LC rates were 100%, 87.8% and 87.8% in the SBRT group, and the 1-, 3- and 5-year OS rates were 100%, 69.8% and 69.8%, respectively. Moreover, the OS rates in S5/S6 group in RFA were higher than those in SBRT group.Conclusion: The LC rates were better in the SBRT group than in the RFA group for the patients with lesions localized in S7/S8, and SBRT could also be a therapeutic option for patients with lesions in S1. Moreover, patients with tumors located in S5/S6 were better candidates for RFA treatment than SBRT.Keywords: Stereotactic body radiation therapy, Computed tomography-guided radiofrequency, Naive hepatocellular carcinoma, Couinaud’s segmentation

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

Qingbao Guo,1,2,&ast; Manli Xie,3,&ast; Qian-Nan Wang,4,&ast; Jingjie Li,1,2 Simeng Liu,1,2 Xiaopeng Wang,1,2 Dan Yu,5 Zhengxing Zou,5 Gan Gao,1,2 Qian Zhang,5 Fangbin Hao,1,2 Jie Feng,5 Rimiao Yang,5 Minjie Wang,1,2 Heguan Fu,5 Xiangyang Bao,5 Lian Duan2 1Medical School of Chinese PLA, Beijing, People’s Republic of China; 2Department of Neurosurgery, First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Occupational Diseases, Xi’an Central Hospital, Xi’an, Shanxi, People’s Republic of China; 4Department of Neurosurgery, Eighth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 5Department of Neurosurgery, Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangyang Bao; Lian Duan, Email bzy123@163.com; duanlian307@sina.comBackground: Moyamoya disease (MMD) signifies a cerebrovascular disorder with obscure origin and a more rapid and severe progression in children than adults. This investigation aims to uncover age-associated distinctions through proteomic and metabolomic profiling to gain insights into the underlying mechanisms of MMD.Methods: Twelve MMD patients—six children and six adults—along with six healthy controls (HC), participated, each providing a 10 mL blood sample. Serum proteomic and metabolomic analyses were conducted using ultra-performance liquid chromatography and high-resolution mass spectrometry, complemented by bioinformatics to identify differential biomolecules and their interactions. Pathway implications were ascertained using GO and KEGG enrichment analysis.Results: Notable proteomic and metabolomic discrepancies were observed between pediatric and adult MMD subjects. A total of 235 and 216 proteins varied in adult and pediatric cases compared to HCs, with 73 proteins shared. In addition, 129 and 74 anionic, plus 96 and 104 cationic metabolites, were differentially expressed in the pediatric and adult groups, respectively, with 34 anionic and 28 cationic metabolites in common. Age-specific biomolecules further characterized these distinctions. Enrichment analysis pinpointed immunity and inflammation pathways, with vitamin digestion and absorption highlighted as pivotal in pediatric MMD.Conclusion: This study unveils distinct metabolic and proteomic patterns within pediatric and adult MMD patients. The critical role of the vitamin digestion and absorption pathway in the pathogenesis of pediatric MMD offers novel insight into disease mechanisms. Keywords: proteomics, metabolomics, pediatric patients, moyamoya disease, integration analysis

Ling Duan,1 Wenhui Guo,1 Shuo Yin,1 Shoubo Yang,1 Jie Liu,2 Yunyun Duan,3 Gehong Dong,4 Wenbin Li,1 Feng Chen1 1Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 2Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 3Department of Radiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of China; 4Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, People’s Republic of ChinaCorrespondence: Wenbin Li; Feng Chen, Department of Neuro-Oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, No. 119 West Nansihuan Road, Beijing, 100070, People’s Republic of China, Tel +86-10-59975034, Email liwenbin@ccmu.edu.cn; chenfeng406@sina.comPurpose: To investigate the prognostic significance of pan-immune-inflammation value (PIV) and PILE score (based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)) in patients with primary central nervous system lymphoma (PCNSL).Patients and Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was incorporated based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier curves and Cox hazards regression models were applied for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined.Results: Baseline high PIV was significantly associated with worse overall survival (OS) in univariate (HR 3.990, 95% CI 1.778– 8.954, p < 0.001) and multivariate (HR 3.047, 95% CI 1.175– 7.897, p = 0.022) analyses. High PIV was also associated with worse progression-free survival (PFS) in univariate (HR 2.121, 95% CI 1.075– 4.186, p = 0.030) but not significant in multivariate analyses. PIV outperformed other systemic inflammation parameters. The patients in the high PILE group (PILE score 2– 3) had worse OS (p = 0.008) and PFS (p < 0.001) compared to the low PILE group (PILE score 0– 1). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05– 0.46; p < 0.001).Conclusion: High PIV and PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for therapeutic response in PCNSL.Keywords: primary central nervous system lymphoma, pan-immune inflammation value, PILE score, prognosis

Li Ren, Zhaoling Li, Ji Wu, Lian Duan, Jialiang Gao Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Li Ren, Cardiovascular Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Address: No. 5, Beixiange, Xicheng District, Beijing, 100053, People’s Republic of China, Tel +86 18600697916, Email renlirl7961@hotmail.comObjective: This study aimed to assess the knowledge, attitudes and practices (KAP) among elderly coronary heart disease (CHD) patients toward self-perceived health abilities.Methods: This web-based study was carried out between April 2023 and September 2023 at Guang’anmen Hospital, China Academy of Chinese Medical Sciences. A self-developed questionnaire was utilized to collect demographic information from elderly CHD patients, and evaluate their KAP towards self-perceived health abilities.Results: A total of 568 valid questionnaires were collected. Among the participants, the average age was 65.97± 5.50 years, and 298 (52.46%) were female, and the mean scores for knowledge, attitudes, and practices were 6.34± 2.29 (possible range: 0– 9), 35.24± 4.99 (possible range: 9– 45), and 27.79± 10.09 (possible range: 9– 45), respectively. The structural equation model demonstrated that elderly CHD patients’ knowledge directly affects attitudes and practices, with path coefficient of 0.93 (P< 0.001) and 0.39 (P=0.033), respectively. Moreover, attitudes play an intermediary role between knowledge and practice with path coefficient of 0.75 (P< 0.001). Furthermore, residence directly affects knowledge with path coefficient of 0.67 (P< 0.001), cardiac function directly affects knowledge with path coefficient of − 0.97 (P< 0.001) and history of interventional therapy directly affects practice with path coefficient of 4.23 (P< 0.001).Conclusion: Elderly CHD patients demonstrated sufficient knowledge, positive attitudes, and proactive practices towards self-perceived health abilities. However, educational programs and behavior modification are recommended, particularly for elderly with lower age and education, living in rural areas, lacking interventional therapy, obese, or taking multiple CHD medications.Keywords: knowledge, attitudes, practices, cross-dimensional study, coronary heart disease, self-perceived health abilities

Min-Jie Wang,1– 3 Jiayu Wang,4 Houdi Zhang,2,3 Fang-Bin Hao,1– 3 Gan Gao,1– 3 Si-Meng Liu,1– 3 Xiao-Peng Wang,1– 3 Jing-Jie Li,1– 3 Zheng-Xing Zou,2,3 Qing-Bao Guo,1– 3 He-Guan Fu,2,3 Yi-Qin Han,2,3 Cong Han,2,3 Lian Duan2,3 1Chinese PLA Medical School, Beijing, People’s Republic of China; 2Department of Neurosurgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Neurosurgery, the Fifth Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Immunology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lian Duan; Cong Han, Department of Neurosurgery, Department of Neurosurgery, the Fifth Medical Centre (South Campus), Chinese PLA General Hospital, No. 8 Dong-Da Street, Fengtai District, Beijing, 100071, People’s Republic of China, Tel +86-10-66947389 ; +86-13466346163 ; +86-10-66947388, Fax +86-10-62177976, Email duanlian307@sina.com; hc82225@126.comBackground: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD.Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression.Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003&ast;). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001&ast;). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006&ast;), diastolic blood pressure (P=0.004&ast;) and serum complement C3 expression (P=0.015&ast;) were associated with vasculopathy progression after adjusting different covariables.Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late–Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.Keywords: moyamoya disease, complement, Suzuki stage, nomogram

Yuanyuan Xie,1,&ast; Shifang Li,1,&ast; Dinan Wu,2 Yining Wang,2 Jiepeng Chen,3 Lili Duan,3 Shuzhuang Li,4 Yuyuan Li2 1The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China; 2Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, People’s Republic of China; 3Sungen Bioscience Co., Ltd, Guangdong, People’s Republic of China; 4College of Basic Medical Science, Dalian Medical University, Dalian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuyuan Li; Shuzhuang Li, Tel +86 411 86118983, Email liyuyuan831221@163.com; shuzhuangli@126.comAbstract: Vitamin K (VK) comprises a group of substances with chlorophyll quinone bioactivity and exists in nature in the form of VK1 and VK2. As its initial recognition originated from the ability to promote blood coagulation, it is known as the coagulation vitamin. However, based on extensive research, VK has shown potential for the prevention and treatment of various diseases. Studies demonstrating the beneficial effects of VK on immunity, antioxidant capacity, intestinal microbiota regulation, epithelial development, and bone protection have drawn growing interest in recent years. This review article focuses on the mechanism of action of VK and its potential preventive and therapeutic effects on infections (eg, asthma, COVID-19), inflammation (eg, in type 2 diabetes mellitus, Alzheimer’s disease, Parkinson’s disease, cancer, aging, atherosclerosis) and autoimmune disorders (eg, inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis). In addition, VK-dependent proteins (VKDPs) are another crucial mechanism by which VK exerts anti-inflammatory and immunomodulatory effects. This review explores the potential role of VK in preventing aging, combating neurological abnormalities, and treating diseases such as cancer and diabetes. Although current research appoints VK as a therapeutic tool for practical clinical applications in infections, inflammation, and autoimmune diseases, future research is necessary to elucidate the mechanism of action in more detail and overcome current limitations.Keywords: vitamin K, VK-dependent proteins, infection, inflammation, auto-immune disease

Han-Ze Du,1,&ast; Kang Chen,1,&ast; Li-Yuan Zhang,1,&ast; Yue-Lun Zhang,2 Dan-Ning Wu,1 Xiao-Yuan Guo,1 Lian Duan,1 Lin-Jie Wang,1 Hong-Bo Yang,1 Shi Chen,1 Hui Pan,1 Hui-Juan Zhu1 1Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 2Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Pan; Hui-Juan Zhu, Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Email panhui20111111@163.com; shengxin2004@163.comContext: The high prevalence of hypothalamic obesity (HO) and dyslipidemia in individuals with craniopharyngioma (CP) following surgery is a cause for increasing concern. However, few studies have explored the lipid profile in pediatric CP patients, with inconsistent findings. In addition, the role of recombinant human growth hormone (rhGH) replacement remains unclear in these patients.Objective: To compare the blood lipid profile among post-operative craniopharyngioma children and adolescents with that among healthy controls and to reveal the effects of rhGH replacement.Methods: Data of 79 post-operative craniopharyngioma children and adolescents in our center were retrospectively collected. Sixty patients underwent rhGH replacement during the follow-ups. We selected 36 patients who received rhGH replacement therapy, while 20 patients received rhGH replacement for at least 1 year and had complete lipid data before and after treatment and compared them with 19 patients who did not receive rhGH replacement therapy.Results: Craniopharyngioma patients had higher total cholesterol (TC) (5.17 vs 3.77 mmol/L), triglyceride (TG) (1.51 vs 0.73 mmol/L), and low-density lipoprotein cholesterol (LDL-C) (3.14 vs 2.10 mmol/L), and lower high-density lipoprotein cholesterol (HDL-C) (1.06 vs 1.39 mmol/L) than controls (all p < 0.001). The lipid profile of obese and non-obese patients was not significantly different. After rhGH replacement, TC was 0.90 mmol/L lower (p = 0.002) and LDL-C was 0.73 mmol/L lower (p = 0.010) than baseline. Although the baseline LDL-C was higher, patients with rhGH replacement had lower LDL-C (− 0.73 mmol/L adjusted for age and sex, p = 0.045) after the initiation of replacement compared with patients without rhGH replacement.Conclusion: The lipid profile of obese and non-obese children and adolescents with craniopharyngioma was unfavorable, and rhGH replacement could improve their lipid profile.Keywords: craniopharyngioma, dyslipidemias, obesity, human growth hormone, hypothalamic obesity

Rongfeng Han, Lijun Duan, Yang Zhang, Xia Jiang Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, People’s Republic of ChinaCorrespondence: Rongfeng Han, Department of Endocrinology, Tianjin First Center Hospital, Tianjin, 300192, People’s Republic of China, Email hanmenghappy@126.comBackground: Type 2 diabetes mellitus (T2DM) patients are likely to develop kidney disease. Early diagnosis, finding predictors and controlling risk factors are of great significance for T2DM patients. This study investigated the ability of uric acid (UA), the uric acid to creatinine (CR) ratio (UA/CR) and the uric acid to high-density lipoprotein cholesterol ratio (UHR) to assess the kidney function of T2DM patients and determined the relationship between the three indicators and the estimated glomerular filtration rate (eGFR).Methods: A total of 1326 adult T2DM patients were enrolled in the current study. Patients were stratified into three groups according to their eGFRs. Spearman correlation was used to analyze the correlation between three indicators and the clinical variables. Logistic regression analysis was used to assess the association between the three indicators and diabetic kidney disease (DKD) and kidney impairment (eGFR < 60 mL/min/1.73 m2). Receiver operating characteristic (ROC) analyses and the area under the ROC curve (AUC) were then used to assess the ability of UA, UA/CR, and UHR to discriminate kidney impairment in T2DM.Results: UA and UHR demonstrated a positive association with DKD risk (P < 0.05). The odds ratios (ORs) were 1.005 (95% CI, 1.004– 1.007) and 1.057 (95% CI, 1.039– 1.076), respectively. UA/CR was negatively correlated with DKD risk (OR, 0.922 (95% CI, 0.876, 0.970), P < 0.05). Furthermore, UA and UHR demonstrated a strong positive association with kidney impairment risk, while UA/CR was negatively correlated with kidney impairment risk in T2DM patients (P < 0.05 for all) after adjusting for confounding factors. UA had the highest AUC (0.762) among the three indicators. UHR had a greater AUC (0.713) than UA/CR, which had an AUC value of 0.148 (p < 0.001).Conclusion: UA is the best indicator of renal impairment (eGFR < 60 mL/min/1.73 m2) among the three indicators, and UHR is a better indicator than UA/CR.Keywords: type 2 diabetes mellitus, T2DM, uric acid, UA, uric acid to creatinine ratio, UA/CR, uric acid to high-density lipoprotein cholesterol ratio, UHR, estimated glomerular filtration rate, eGFR

Jun Li,1,&ast; Yangyang Yang,2,&ast; Xiumin Han,3,&ast; Jing Li,2 Mengxiao Tian,1 Wenjing Qi,1 Huniu An,3 Chuanchuan Wu,1 Yao Zhang,1 Shuai Han,4 Liping Duan,4 Weisi Wang,4 Wenbao Zhang1 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai, People’s Republic of China; 3Qinghai Provincial People’s Hospital, Xining, Qinghai, People’s Republic of China; 4NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbao Zhang; Weisi Wang, Tel +86 991 4366319 ; +86 21 64377008, Email wenbaozhang2013@163.com; wangws@nipd.chinacdc.cnBackground: Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment.Methods: Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE.Results: H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole- and free H1402-treated individuals.Conclusion: Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.Graphical Abstract: Keywords: alveolar echinococcosis, Echinococcus multilocularis, PLGA, nanoparticles, liver targeting, oral administration

Shangwen Jing,1,&ast; Yantong Lu,1,2,&ast; Jing Zhang,1 Yan Ren,1,2 Yousheng Mo,3 Dongdong Liu,3 Lining Duan,4 Zhongyu Yuan,5 Changjun Wang,2 Qi Wang1 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatric Institute, Guangzhou, People’s Republic of China; 3The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 5Department of Medical Oncology, Sun Yat-Sen University Cancer Center, the State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjun Wang; Qi Wang, Email gzwchj@126.com; wangqi@gzucm.edu.cnIntroduction: Breast cancer (BC) is the leading female malignancy, with one million new cases diagnosed worldwide per year. However, the current treatment options for BC patients have difficulty achieving satisfactory efficacy. Ferroptosis is a new mode of regulated cell death that plays a key role in the inhibition of tumorigenesis. Levistilide A (LA), as an active compound extracted from Chuanxiong Rhizoma, might prevent the development of tumors by regulating the critical cellular processes of ferroptosis.Methods: In this study, the underlying mechanisms of LA on ferroptosis in BC were explored in vitro. The effect of LA on the viability and mitochondrial function of BC cells was determined. Moreover, the effect of LA on the expression levels of key molecules involved in ferroptosis and the nuclear factor erythroid-2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) signaling pathway was evaluated.Results: LA significantly reduced cell viability and damaged the mitochondrial structure and function of BC cells in a dose-dependent manner. Furthermore, LA treatment markedly enhanced reactive oxygen species (ROS)-induced ferroptosis by activating the Nrf2/HO-1 signaling pathway.Conclusion: These findings suggest that LA may be a potential lead compound for breast cancer therapy by inducing ferroptosis in tumor cells.Keywords: breast cancer, levistilide A, ferroptosis, Nrf2/HO-1 signaling pathway

Chunsheng Tian,1,2 Li Duan,1,3 Chunfeng Fu,1 Juan He,1 Jiali Dai,1 Gang Zhu1 1Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China; 2Shenyang Mental Health Center, Shenyang, 110168, People’s Republic of China; 3School of Nursing, Chengde Medical University, Chengde, 067000, People’s Republic of ChinaCorrespondence: Gang Zhu, Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People’s Republic of China, Tel/Fax +86-24-83282184, Email gzhu@cmu.edu.cnBackground: Recently, researchers have conducted many studies on the potential contribution of the retina and other eye structures on schizophrenia. This study aimed to evaluate differences in iris characteristics between patients with schizophrenia and healthy individuals so as to find more easily accessible and easily measurable biomarkers with a view to improving clinical assessments and furthering our understanding of the disease.Methods: Overall, 80 patients with schizophrenia and 52 healthy individuals were included in the case group and the control group, respectively. Iris images were collected from all subjects to compare differences in the structure and color of the iris. The Positive and Negative Symptom Scale (PANSS) and the Modified Overt Aggression Scale (MOAS) were used to evaluate the clinical symptoms and characteristics of 45 first-episode untreated schizophrenics, and analyzed correlations between iris characteristics and schizophrenia symptoms.Results: There were significant differences in iris crypts (P< 0.05) and pigment spots (P< 0.01) between the case and control group, but no significant difference was found in iris wrinkles (P< 0.05). The logistic regression analysis demonstrated that the total iris crypts [odds ratio (OR) 1.166, 95% confidence interval (CI) 1.022– 1.330] and total iris pigment spots (OR 1.815, 95% CI 1.186– 2.775) increased the risk of suffering from schizophrenia. Furthermore, it was demonstrated that the number of iris crypts was positively associated with the MOAS score (r=0.474, P< 0.01). Moreover, the number of the iris pigment spots (r=0.395, P< 0.01) and wrinkles (r=0.309, P< 0.05) were positively correlated with the subjects’ negative symptom scores, respectively.Conclusion: Iris crypts and pigment spots were identified as potential biomarkers for detecting schizophrenia. In patients with first-episode untreated schizophrenia, iris characteristics may help psychiatrists to identify the illness and its severity, and to detect characteristic clinical symptoms.Keywords: schizophrenia, biomarker, iris, crypt, pigment spot

Jiao Peng,1– 3,&ast; Xi Li,4,&ast; Lin Zheng,3,5 Lifang Duan,1 Zhengxian Gao,2,5 Die Hu,1 Jie Li,6 Xiaofeng Li,6 Xiangchun Shen,5 Haitao Xiao2 1Department of Pharmacy, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 2School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, People’s Republic of China; 3Engineering Research Center for the Development and Application of Ethnic Medicine and TCM, Ministry of Education, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, People’s Republic of China; 4Department of Gastroenterology, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China; 5School of Pharmacy, State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, People’s Republic of China; 6Department of Laboratory Medicine, Peking University Shenzhen Hospital, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haitao Xiao, School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, 518060, People’s Republic of China, Email xhaitao@szu.edu.cn Xiangchun Shen, School of Pharmacy, Guizhou Medical University, Guizhou, 550004, People’s Republic of China, Email shenxiangchun@126.comPurpose: GLP-1 based therapy represents a new treatment option for inflammatory bowel disease. Ban-Lan-Gen (BLG) granule, a known anti-viral TCM formulation, exhibits potential anti-inflammatory activities in treating various kinds of inflammation. However, its anti-inflammatory effect on colitis and the underlying mechanisms remain unknown.Methods: Dextran sulfate sodium (DSS)-induced chronic relapsing colitis in mice was established. The disease activity index, histological sign of damage, and levels of proinflammatory cytokines were performed to assess the protective effects of BLG. Serum GLP-1 level and colonic Gcg, GPR41 and GRP43 expression, the community compositions of gut microbiota, the levels of SCFAs in the feces and GLP-1 release from primary murine colon epithelial cells were performed to characterize the effects of BLG on gut microbiota and gut SCFA derived-GLP-1 production.Results: BLG treatment significantly alleviated body weight loss, DAI, colon shortening, colon tissue damage, and pro-inflammatory cytokine levels of TNF-α, IL-1β and IL-6 in the colon tissues. Moreover, BLG treatment could observably restore colonic Gcg, GPR41 and GRP43 expression and serum GLP-1 level of colitic mice, as well as correct the alteration of gut microbiota in colitic mice by increasing the abundances of SCFA-producing bacteria, eg, Akkermansia and Prevotellaceae_UCG-001, and decreasing the abundances of bacteria, eg, Eubacterium_xylanophilum_group, Ruminococcaceae_UCG-014, Intestinimonas, and Oscillibacter. Furthermore, BLG treatment could markedly increase the levels of SCFAs in feces of colitic mice. In parallel, ex vivo assay also showed that and the extract of feces from BLG-treatment mice could greatly stimulate the secretion of GLP-1 from primary murine colon epithelial cells.Conclusion: These findings suggest that the anti-colitis effects of BLG are achieved at least partly by regulating gut microbiota and restoring gut SCFA derived-GLP-1 production, and BLG has the potential to be developed as a promising agent for the treatment of chronic relapsing colitis.Keywords: colitis, Ban-Lan-Gen granule, gut microbiota, short-chain fatty acids, GLP-1

Qi Tan,&ast; Limin Duan,&ast; Qi Huang,&ast; Wenjuan Chen,&ast; Zimo Yang, Jiangbin Chen, Yang Jin Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yang JinDepartment of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases of Health Ministry, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, People’s Republic of ChinaTel +86-135-5436-1146Fax +86-27-85755457Email whuhjy@126.comBackground: There is a close relationship among inflammation, glycolysis, and tumors. The IL-1 family includes important inflammatory cytokines, among which IL-1β has been widely studied. In this study, we focused on the effect of IL-1β on glycolysis of lung adenocarcinoma (LUAD) cells in vivo and in vitro and explored its possible mechanisms.Methods: A bioinformatic database and quantitative real-time PCR were used to analyze the expression of glycolysis-related enzyme genes and their correlations with IL1β in human LUAD samples. The human LUAD cell line A549 and Lewis lung carcinoma LLC cell line were stimulated with IL-1β. In vitro treatment effects, including glycolysis level, migration, and invasion were evaluated with a glucose assay kit, lactate assay kit, Western blotting, wound healing, and the transwell method. We established a mouse model of subcutaneous tumors using LLC cells pretreated with IL-1β and analyzed in vivo treatment effects through positron-emission tomography-computed tomography and staining. Virtual screening and molecular dynamic simulation were used to screen potential inhibitors of IL-1β.Results: Our results showed that IL1β was positively correlated with the expression of glycolysis-related enzyme genes in LUAD. Glycolysis, migration, and invasion significantly increased in A549 and LLC stimulated with IL-1β. In vivo, IL-1β increased growth, mean standard uptake value, and pulmonary tumor metastasis, which were inhibited by the glycolysis inhibitor 2-deoxy-D-glucose and p38-pathway inhibitors. Small molecular compound ZINC14610053 was suggested being a potential inhibitor of IL-1β.Conclusion: IL-1β promotes glycolysis of LUAD cells through p38 signaling, further enhancing tumor-cell migration and invasion. These results show that IL-1β links inflammation to glycolysis in LUAD, and targeting IL-1β and the glycolysis pathway may be a potential therapeutic strategy for lung cancer.Keywords: interleukin 1β, glycolysis, lung adenocarcinoma, p38 signaling

Cong Yang,1,&ast; Mengmeng Han,1,2,&ast; Ruoyu Li,1,&ast; Ligui Zhou,1,3 Ying Zhang,1,2 Lining Duan,1,4 Shiyu Su,1,4 Min Li,1,4 Qi Wang,1 Tongkai Chen,1,&ast; Yousheng Mo5,&ast; 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 2The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 4Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tongkai Chen; Yousheng Mo Email chentongkai@gzucm.edu.cn; 378480308@qq.comBackground: Intracerebral hemorrhage (ICH) is a form of severe stroke, the pathology of which is tied closely to a recently discovered form of programmed cell death known as ferroptosis. Curcumin (Cur) is a common phenolic compound extracted from the rhizome of Curcuma longa capable of hematoma volume and associated neurological damage in the context of ICH. Despite exhibiting therapeutic promise, the efficacy of Cur is challenged by its poor water solubility, limited oral bioavailability and inability to efficiently transit across the physiological barriers. Polymer-based nanoparticles (NPs) have widely been employed to aid in drug delivery efforts owing to their ideal biocompatibility and their ability to improve the bioavailability and pharmacokinetics of specific drugs of interest.Methods: In this study, we encapsulated Cur in NPs (Cur-NPs) and explored the effect of these Cur-NPs to enhance Cur delivery both in vitro and in vivo. Furthermore, we evaluated the anti-ferroptosis effect of Cur-NPs in ICH model mice and erastin-treated HT22 murine hippocampal cells.Results: The resultant Cur-NPs were spherical and exhibited a particle size of 127.31± 2.73 nm, a PDI of 0.21± 0.01 and a zeta potential of − 0.25± 0.02 mV. When applied to Madin Darby canine kidney (MDCK) cells in vitro, these Cur-NPs were nonspecifically internalized via multiple endocytic pathways, with plasma membrane microcapsules and clathrin-mediated uptake being the dominant mechanisms. Within cells, these NPs accumulated in lysosomes, endoplasmic reticulum and mitochondria. Cur-NPs were capable of passing through physiological barriers in a zebrafish model system. When administrated to C57BL/6 mice, they significantly improved Cur delivery to the brain. Most notably, when administered to ICH model mice, Cur-NPs achieved superior therapeutic outcomes relative to other treatments. In a final series of experiments, these Cur-NPs were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells.Conclusion: These Cur-NPs represent a promising means of improving Cur delivery to the brain and thereby better treating ICH.Keywords: Intracerebral hemorrhage, nanoparticles, curcumin, brain delivery, blood-brain barrier, ferroptosis

Yun Zhang,1 Jie Wang,2 Yong-Mei Liu,2 Yin-Ying Chen,3 Xiao-Chen Yang,4 Lian Duan2 1Department of Immunology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 2Department of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3Department of the Scientific Research Office, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 4Department of Cardiology & Health Care, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaCorrespondence: Jie WangDepartment of Cardiology, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of ChinaTel +86 010-88001148Email wangjiedoctor2015@163.comBackground and Purpose: Two Chinese herbal medicines Huang Qi (HQ, Astragalus mongholicus) and Dan Shen (DS, Salvia miltiorrhiza) are often combined to treat coronary heart disease (CHD). The purpose of this study was to identify the underlying synergistic effects and mechanisms of HQ and DS against CHD.Methods: The active components and targets of HQ and DS, CHD-related genes, and the biological progression were analysed by network pharmacology. The myocardial infarction (MI) rat model was established by ligating the left anterior descending coronary artery. Cardiac function was detected by ultrasonic electrocardiography. The MI size, fibrosis, cardiac hypertrophy, lipid metabolism, blood viscosity, and coagulation indexes were analysed by histological staining or chemical methods, respectively.Results: A total of 170 shared and specific seed genes of HQ and DS against CHD were identified. The shared and specific biological processes of HQ and DS against CHD were obtained. The LVEF and LVFS values significantly increased, the myocardium infarct size and fibrosis significantly decreased, the values of lipid metabolism indexes and blood viscosity indexes significantly reduced in the HQ + DS treatment group vs HQ or DS single treatment (P < 0.05); the LVEDd, LVEDs, and the CSA values significantly reduced in HQ single and HQ + DS treatment groups vs MI group (P < 0.05); the coagulation index (APTT, PT, TT, and FIB) values decreased significantly in the DS single and HQ + DS treatment groups vs MI group (P < 0.05).Conclusion: In MI rats, HQ and DS exhibited synergistic effects on improving cardiac function, reducing MI size, fibrosis, regulating hyperlipidaemia, and maintaining circulatory system homeostasis; HQ had the specific advantage of alleviating cardiac remodelling; DS had the specific advantage of regulating hypercoagulability. This study revealed that HQ and DS not only exerted synergistic effects but also exhibited complementary effects on CHD.Keywords: coronary heart disease, Astragalus mongholicus, Salvia miltiorrhiza, synergistic effects, network pharmacology, myocardial infarction

LianLi Duan,1,&ast; Jinyong Zhang,1,&ast; Zhifu Chen,1 Qiang Gou,1 Qingshan Xiong,1 Yue Yuan,1 Haiming Jing,1 Jiang Zhu,2 Li Ni,3 Yuling Zheng,4 Zhiyong Liu,5 Xiaokai Zhang,1 Hao Zeng,1 Quanming Zou,1 Zhuo Zhao1 1National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, 400038, People’s Republic of China; 2Department of Pathology, Southwest Hospital, Army Medical University, Chongqing, 400038, People’s Republic of China; 3Obstetrics and Gynecology, The First People’s Hospital of Jiulongpo District, Chongqing, 400050, People’s Republic of China; 4State Key Laboratory of Pathogens and Biosecurity, Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China; 5Department of Laboratory Medicine, Southwest Hospital, Army Medical University, Chongqing, 400038, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuo Zhao; Quanming Zou Email zhaozhuo198309@163.com; qmzou2007@163.comPurpose: We previously reported that monoclonal antibody (mAb) cocktail improves survival in Staphylococcus aureus infection. In this study, we used acute pneumonia model and lethal sepsis model to investigate the efficacy of antibiotic combined with epitope-specific mAb cocktail in treating MRSA252 infection.Methods: MRSA252 was challenged by tail vein injection or tracheal intubation to establish sepsis model or pneumonia model. One hour after infection, the mice received a single intravenous injection of normal saline, vancomycin, and vancomycin combined monoclonal antibody, linezolid alone or linezolid combined monoclonal antibody. Daily record survival rate (total 7 days), bacterial load, histology, cytokine analysis of serum and alveolar lavage fluid, and in vitro determination of the neutralizing ability of antibodies to SEB toxin and Hla toxin explained the mechanism of antibody action.Results: The mAb cocktail combined with low doses of vancomycin or linezolid improved survival rates in acute pneumonia model (70%, 80%) and lethal sepsis model (80%, 80%). Epitope-specific monoclonal antibodies reduced bacterial colonization in the kidneys and lungs of mice and inhibited the biological functions of the toxins Hla and SEB in vitro. Compared to the antibiotic alone or PBS groups, the combination group had higher levels of IL-1α, IL-1β and IFN-γ and lower levels of IL-6, IL-10, TNF-α. Further, the combination of antibiotic and mAb cocktail improved infection survival against the clinical MRSA isolates in a lethal sepsis model.Conclusion: This study demonstrates a novel method to treat people with low immunity against drug-resistant S. aureus infections.Keywords: methicillin-resistant Staphylococcus aureus, immunodominant epitope, monoclonal antibody, lethal sepsis, pneumonia

Ding Wang,1,&ast; Xi Zhan,1,&ast; Rui Wu,2 Yan You,3 Weixian Chen,1 Liang Duan1 1Department of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Duan; Weixian ChenDepartment of Laboratory Medicine, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjiang Road, Yu Zhong District, Chongqing, People’s Republic of ChinaTel/Fax +86-023-63693193; +86-023-63693701Email duanliang@cqmu.edu.cn; chenweixian75@163.comPurpose: The diagnosis and management of liver cirrhosis remain challenging due to its diverse clinical manifestations and elusive severity evaluation. Pyroptosis, an identified inflammatory form of cell death, has recently been reported to participate in cirrhosis development. Nonetheless, the clinical significance of pyroptosis in liver cirrhosis remains largely unexplored.Patients and Methods: One hundred and fifty-one liver cirrhosis patients either alone or in combination with various complications and twenty-nine gender- and age-matched healthy controls (HCs) were enrolled in this study. Pyroptosis-related indicators gasdermin D (GSDMD), IL-1ß and IL-18 were measured by IHC in tissue section and by ELISA in serum, respectively, and correlations of their circulating levels with disease severity as well as their potential as biomarkers for monitoring cirrhosis progression were evaluated.Results: Increased levels of the circulating pyroptosis-related indicators GSDMD, IL-1ß and IL-18 were observed in liver cirrhosis patients, especially those with an etiology of viral infection. In addition, all three indicators were positively correlated with disease severity parameters, including Child-Pugh classification, APRI scores and compensated status. Furthermore, receiver operating characteristic (ROC) analysis showed that circulating IL-1ß exerted potential discriminating power for SBP occurrence in liver cirrhosis, but GSDMD possessed differentiating power for SBP in liver cirrhosis with ascites, which yielded area under the ROC curve (AUC) of 0.81 and 0.80, respectively.Conclusion: Liver cirrhosis patients exhibited increased levels of circulating GSDMD, IL-1ß and IL-18, all of which were positively correlated with disease severity. More importantly, the identified circulating IL-1ß and GSDMD exhibited potentials as novel biomarkers for liver cirrhosis patients presenting with SBP.Keywords: GSDMD, IL-1ß, IL-18, liver cirrhosis, severity, complication

Duan L, Zuo J, Zhang F, et al. Int J Nanomedicine. 2020;15:3605–3620. The authors have advised Figure 9 on page 3618 is incorrect. An error was made during the preparation of images for part 9C. The correct Figure 9 is shown in Download Article. The authors apologise for this error. Read the original article

Meng Zhang, Fuqiang Zhang, Te Liu, Pu Shao, Lian Duan, Jun Yan, Xupeng Mu,* Jinlan Jiang* Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinlan Jiang; Xupeng MuScientific Research Center, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, Jilin, People’s Republic of ChinaEmail jiangjinlan@jlu.edu.cn; muxupeng@jlu.edu.cnPurpose: Nanoparticle (NP)-based chemo-photothermal therapy (CPT) has been shown to be a promising non-invasive approach for antitumor treatment. However, NPs must overcome the limitations of opsonization, clearance of the reticuloendothelial system, and ineffective targeting of tumor tissue sites. To solve these problems, stem cell membrane (SCM)-camouflaged polydopamine nanoparticles (PDA@SCM NPs) carrying the hydrophobic anticancer drug 7-ethyl-10-hydroxycamptothecin (SN38) were constructed for CPT of malignant bone tumors.Methods: We developed umbilical-cord mesenchymal stem cell membrane-coated polydopamine nanoparticles encapsulating SN38 (PDA-SN38@SCM NPs) as an efficient tumor-targeting drug-delivery platform for CPT of malignant bone tumors. We characterized PDA@SCM NPs and evaluated the biocompatibility and anti-phagocytosis properties of PDA@SCM NPs. The antitumor activity of PDA-SN38@SCM NPs was evaluated in MG63 lines and an MG63 xenograft model in mice.Results: Synthesized PDA-SN38@SCM NPs retained an excellent photothermal effect after SN38 loading. The drug release of PDA-SN38@SCM NPs could be triggered by near-infrared irradiation and an acidic stimulus. PDA@SCM NPs exhibited lower nonspecific macrophage uptake, longer retention in blood, and more effective accumulation at tumor sites than that shown by PDA NPs. Confocal laser scanning microscopy (CLSM) and flow cytometry showed that MG63 cells took up more PDA-SN38@SCM NPs than PDA-SN38 NPs. In vitro and in vivo antitumor studies demonstrated the outstanding performance of PDA-SN38@SCM NPs in synergistic CPT for bone tumors.Conclusion: PDA-SN38@SCM NPs demonstrated an extraordinary synergistic CPT effect and could be a promising strategy for the treatment of malignant bone tumors.Keywords: stem cell membrane, polydopamine nanoparticles, chemo-photothermal therapy

Xiaojun Shao1 *,* Ci Yan1 *,* Dongxue Sun,1 Chunfeng Fu,1 Chunsheng Tian,1 Li Duan,1 Gang Zhu1,2 1Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gang ZhuDepartment of Psychiatry, Tthe First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaTel/ Fax +86-24-83282184Email gzhu@cmu.edu.cnObjective: The dopamine and oxidative stress hypotheses are leading theories of the pathoetiology of schizophrenia (SCZ). Glutathione Peroxidase 1 (GPx-1), a major antioxidant enzyme, and the most abundantly expressed member of the GPx family, plays an important role in metabolic dopamine changes, which are closely related to neurological and psychiatric disorders. The impact of GPx-1 polymorphisms has rarely been explored in the field of SCZ. Here, we explored the possible relationship between GPx-1 gene polymorphisms and SCZ in Chinese Han subjects by using the polymerase chain reaction-restriction fragment length polymorphism method.Methods: DNA from 786 patients (360 patients with schizophrenia and 426 healthy controls) was genotyped for the single-nucleotide polymorphisms rs1800668 C/T and rs1050450 C/T in GPx-1 using polymerase chain reaction-restriction fragment length polymorphism analysis. Analysis of the association between GPx-1 and SCZ was performed using SPSS 22.0, while Haploview 4.2 software and SHEsis software were used to perform linkage disequilibrium analysis and haplotype analysis.Results: The results indicated that the GPx-1 polymorphisms rs1050450 and rs1800668 were associated with SCZ. We found that the C-allele of rs1800668 C/T may be a protection factor against SCZ in general, but in particular, for males. Furthermore, the CT and TC (GPx-1 rs1800668 C/T and rs1050450 C/T) haplotypes may be susceptible to SCZ in the population. Finally, no significant differences in allelic or genotypic frequencies of rs1050450 were detected between cases and controls from whole or stratification analyses by gender.Conclusion: GPx-1 polymorphisms are related to SCZ in Chinese Han subjects. Our results suggested that GPx-1 may be a potential gene that influences SCZ.Keywords: case-control study, Chinese Han population, GPx1, polymorphism, schizophrenia

Lei Duan, Man Li, Fan Wang, Yulun Cai, Huiying Li, Wenli Zhou, Yuerui Li, Qiang Chen, Jing Bai, Hongbin Liu Department of Geriatric Cardiology, National Clinical Research Center for Geriatric Diseases, The Second Medical Center of PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Hongbin Liu Department of Geriatric CardiologyNational Clinical Research Center for Geriatric Diseases, The Second Medical Center of PLA General Hospital, 28 Fuxing Road, Beijing 100853, People’s Republic of ChinaTel +86 010 66876349Email liuhb301@sina.comBackground: It is uncertain whether long-term use of clopidogrel alone can cause gastric mucosal injury. This study aimed to evaluate the relationship between ABCB1 C3435T polymorphisms, which could affect the intestinal absorption of clopidogrel, and gastric mucosal erosion in elderly Chinese men who used clopidogrel alone.Methods: We selected 298 male patients (aged between 68.2 and 89.5 years, average age 78); 201 of them constituted the control group, and 97 constituted the case group. Patients taking clopidogrel alone who had undergone endoscopic screening for gastric erosion were analyzed for ABCB1 C3435T polymorphisms by a TaqMan assay.Results: The proportion of people carrying the ABCB1 3435T allele (n = 63, 64.9% vs n = 97, 48.3%, p = 0.007) was significantly higher in the case group than in the control group. After adjustments for significant factors were made, ABCB1 3435T allele carrier (OR 2.14, 95% CI 1.43– 3.84, p < 0.01) was found to be associated with gastric mucosal erosion in people who used clopidogrel alone.Conclusion: Carrying the ABCB1 3435T allele may be a useful genetic predictor for clopidogrel-induced gastric mucosal erosion in elderly Chinese men.Keywords: clopidogrel, polymorphism, single nucleotide, ABCB1 C3435T, gastric mucosa, risk factor

Lian Duan,1 Jianlin Zuo,2 Fuqiang Zhang,1 Binxi Li,3 Zhonghang Xu,4 Hao Zhang,3 Bai Yang,3 Wenzhi Song,5 Jinlan Jiang1 1Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Orthopaedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 3State Key Laboratory of Supramolecular Structure and Material, College of Chemistry, Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, People’s Republic of China; 5Department of Stomatology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, People’s Republic of ChinaCorrespondence: Jinlan Jiang; Wenzhi SongChina-Japan Union Hospital of Jilin University, No. 126 Xian Tai Street, Changchun, Jilin, People’s Republic of ChinaTel|Fax +86 431-84995432Email jiangjinlan@jlu.edu.cn; songwz@jlu.edu.cnPurpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field.Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections.Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head.Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.Keywords: SPION@PDA NPs, HU-MSCs, GC-ONFH, apoptosis

Ci Yan,1 Li Duan,1 Chunfeng Fu,1 Chunsheng Tian,1 Bihui Zhang,1 Xiaojun Shao,1 Gang Zhu1,2 1Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Central Laboratory, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaCorrespondence: Gang ZhuDepartment of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of ChinaTel/Fax +86 248 328 2184Email gzhu@cmu.edu.cnBackground: Glutathione S-transferase (GST) is an important antioxidant enzyme in the body. The weakening of the antioxidant system causes damage to the cells and tissues that make up the organism, adversely affects the function of the nervous system, and ultimately leads to schizophrenia (SCZ). Previous studies have yielded inconsistent results across different ethnic populations.Purpose: This case–control study was carried out to investigate whether genetic polymorphisms in GST could be associated with SCZ in the Chinese Han population.Patients and Methods: A total of 794 participants, including 379 SCZ patients (case group) and 415 healthy individuals (control group), were genotyped by polymerase chain reaction-restriction fragment length for polymorphisms in GST genes.Results: The study found that the frequency of the GSTM1 null genotype was higher in case group than control group (p=0.003). The frequency of the GSTM1 and GSTT1 double null genotype was also higher in case group than control group (p=0.008).Conclusion: We conclude that the GSTM1 null genotype and the GSTM1 and GSTT1 double null genotype may be related to the onset of SCZ in Chinese Han population.Keywords: glutathione transferase, gene polymorphisms, schizophrenia

PengYu Yang, Wei Kang, YaWen Pan, XianJun Zhao, Lei Duan Department of Neurosurgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of ChinaCorrespondence: Lei DuanDepartment of Neurosurgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou University, 82 Cuiyingmen, Chengguan District, Lanzhou 730030, People’s Republic of ChinaEmail ldeydl@163.comBackground: Homeobox (HOX) genes encode transcription factors that are critical to morphogenesis and cell differentiation. Although the dysregulation of several HOX genes in glioblastoma (GBM) has been reported, little is known about HOXC6 expression in GBM. Therefore, in this study, we investigated the expression levels of the HOXC6 in GBM and explored the regulatory mechanism underlying the role of HOXC6 in GBM progression.Methods: The ONCOMINE and Oncolnc databases were used to predict the expression level of HOXC6 mRNA and its prognostic value in GBM. The expressions of HOXC6 mRNA in GBM tissues and adjacent brain tissues were detected using qRT-PCR and Western blot. Immunohistochemistry was performed to verify the HOXC6 protein expression in 107 GBM tissues. Kaplan–Meier and Cox analyses were performed to validate the correlation between HOXC6 expression and GBM prognosis. Lentivirus-mediated HOXC6 mRNA overexpression and interference system were established and transfected into U251 and U87 cell lines. CCK-8, colony formation, wound healing and transwell assay were utilized to evaluate the effects of HOXC6 on proliferation and migration of human GBM cells.Results: High expression of HOXC6 was observed in GBM tissues and GBM cells lines, and it correlated with a decreased overall survival and disease-free survival. Overexpression of HOXC6 promoted the GBM cell proliferation and migration, whereas depletion of HOXC6 reduced GBM cell proliferation and migration. Mechanistic study showed that upregulation of HOXC6 significantly increased the phosphorylation of Jun amino-terminal kinase, ERK and P38, as well as the expression of mitogen-activated protein kinase (MAPK) signaling–related genes, including c-myc, c-jun and p53. Inversely, silencing HOXC6 showed the opposite results.Conclusion: HOXC6 promoted proliferation and migration of GBM cells via the activation of MAPK pathway.Keywords: HOXC6, glioblastoma, proliferation, migration, MAPK pathway

Bin Yang,1,* Lili Guo,2,* Guangming Lu,1,* Wenli Shan,2 Lizhen Duan,2 Shaofeng Duan31Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, People’s Republic of China; 2Department of Radiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of China; 3GE Healthcare China, Shanghai 210000, People’s Republic of ChinaCorrespondence: Lili GuoDepartment of Radiology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of ChinaEmail guolili163@163.comGuangming LuDepartment of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, People’s Republic of ChinaTel +86 13 95 160 8346Fax +86 2 58 480 4659Email cjr.luguangming@vip.163.com*These authors contributed equally to this workPurpose: We aimed to assess the classification performance of a computed tomography (CT)-based radiomic signature for discriminating invasive and non-invasive lung adenocarcinoma.Patients and Methods: A total of 192 patients (training cohort, n=116; validation cohort, n=76) with pathologically confirmed lung adenocarcinoma were retrospectively enrolled in the present study. Radiomic features were extracted from preoperative unenhanced chest CT images to build a radiomic signature. Predictive performance of the radiomic signature were evaluated using an intra-cross validation cohort. Diagnostic performance of the radiomic signature was assessed via receiver operating characteristic (ROC) analysis.Results: The radiomic signature consisted of 14 selected features and demonstrated good discrimination performance between invasive and non-invasive adenocarcinoma. The area under the ROC curve (AUC) for the training cohort was 0.83 (sensitivity, 0.84 ; specificity, 0.78; accuracy, 0.82), while that for the validation cohort was 0.77 (sensitivity, 0.94; specificity, 0.52 ; accuracy, 0.82).Conclusion: The CT-based radiomic signature exhibited good classification performance for discriminating invasive and non-invasive lung adenocarcinoma, and may represent a valuable biomarker for determining therapeutic strategies in this patient population.Keywords: lung adenocarcinoma, radiomics, biomarker, computed tomography

Shouliang Wang,1 Bin Xia,1 Zonglei Qiao,2 Lian Duan,3 Gongming Wang,1 Wenjun Meng,1 Zhifei Liu,1 Yu Wang,1 Mengyuan Zhang11Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People’s Republic of China; 2Department of Anesthesiology, Qingyun County People’s Hospital, Dezhou 253700, Shandong Province, People’s Republic of China; 3Department of Ophthalmology, Qianfoshan Hospital Affiliated to Medical School of Shandong University, Jinan 250014, Shandong Province, People’s Republic of ChinaBackground: Bupivacaine (BUP) acts as a local anesthetic, which is extensively used for clinical patients but could generate neurotoxicity in neurons. Tetramethylpyrazine (TET) exhibits strong neuron protective effects against neurotoxicity. Hence, we investigate the effect of TET on BUP-induced neurotoxicity in SH-SY5Y cells.Methods: CCK-8 assay was used to detect cell proliferation in SH-SY5Y cells. In addition, Western blotting was used to examine Bax, Bcl-2, active caspase 3, LC3II, Beclin 1 and p-62 protein levels in cells. Moreover, ELISA assay was used to detect the levels of total glutathione (GS), superoxide dismutase (SOD) and malondialdehyde (MDA) in cells.Results: In this study, we found that TET attenuated the neurotoxicity of BUP on SH-SY5Y cells. Meanwhile, TET alleviated BUP-induced apoptosis in SH-SY5Y cell via decreasing the expressions of active caspase-3 and Bax and increasing the expression of Bcl-2. In addition, monodansylcadaverine staining assay and Western blotting results confirmed that TET induced autophagy in SH-SY5Y cells via increasing the LC3II/I and Beclin 1 levels. Furthermore, TET attenuated BUP-induced oxidative damage in SH-SY5Y cells via upregulation of the levels of total GS and SOD and downregulation of the level of MDA. Interesting, the protective effects of TET against BUP-induced neurotoxicity in SH-SY5Y cells were reversed by autophagy inhibitor 3-methyladenine (3MA).Conclusion: These data indicated that TET may play a neuroprotective role via inhibiting apoptosis and inducing autophagy in SH-SY5Y cells. Therefore, TET may be a potential agent for the treatment of human neurotoxicity induced by BUP.Keywords: tetramethylpyrazine, bupivacaine, neurotoxicity, human neuroblastoma cell

Yinian Zhang,1,2,* Hua-Teng Dong,3,* Lei Duan,1,2 Liang Niu,1,2 Guo-Qiang Yuan,1,2 Jun-Qiang Dai,1,2 Bo-Ru Hou,1,2 Ya-Wen Pan1,2 1Department of Neurosurgery and Laboratory of Neurosurgery, Lanzhou University Second Hospital, Lanzhou 730030, People’s Republic of China; 2Institute of Neurology, Lanzhou University, Lanzhou 730030, People’s Republic of China; 3Department of Pediatric Neurology, Gansu Provincial Maternity and Child-Care Hospital, Lanzhou 730050, People’s Republic of China *These authors contributed equally to this work Objectives: Despite the availability of effective antiepileptic drugs, epileptic patients still suffer from intractable seizures and adverse events. Better control of both seizures and fewer side effects is needed in order to enhance the patient’s quality of life. We performed the present study with an attempt to explore the effect that HDAC4 gene silencing would have on epilepsy simulated by model rats. Furthermore, the study made additional analysis on the relativity of the HDAC4 gene in regard to its relationship with the gamma-aminobutyric acid (GABA) signaling pathway. Materials and methods: Tremor rats were prepared in order to establish the epilepsy model. The rats would go on to be treated with si-HDAC4 in order to identify roles of the HDAC4 in levels of GABAARα1, GABAARα4, GAD65, GAT-1, and GAT-3. Finally, both electroencephalogram behavior and cognitive function of the rats following the treatment of si-HDAC4 were observed. Results: Levels of the GABAARα1 and GABAARα4 showed an evident increase, while GAD65, GAT-1, and GAT-3 displayed a decline in the epilepsy rats treated with the aforementioned si-HDAC4 when compared with the epilepsy rats. After injection of si-HDAC4, the epilepsy rats presented with a reduction in seizure degree, latency and duration of seizure, amount of scattered epileptic waves, and occurrence of epilepsy, with an improvement in their cognitive function. Conclusion: The study highlighted the role that HDAC4 gene silencing played in easing the cases of epilepsy found in the model rats. This was shown to have occurred through the upregulation of both GABAARα1 and GABAARα4 levels, as well as in the downregulation of GAD65, GAT-1, and GAT-3 levels. The evidence provided shows that the HDAC4 gene is likely to present as a new objective in further experimentation in the treatment of epilepsy. Keywords: epilepsy, HDAC4, gene silencing, GABA receptor, GABA transporter, seizures