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Yan Pan, Wei Dong Chen, Lei Liu, Huijuan Yang, Baochao Chang, Caixia Cui Department of Nephrology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui Province, People’s Republic of ChinaCorrespondence: Wei Dong Chen, Email cwd2012@163.comObjective: Serum-specific antibodies as a non-invasive means to effectively diagnose idiopathic membranous nephropathy and assess clinicopathology.Methods: Immunofluorescence of anti-PLA2R and THSD7A antibodies and kidney tissue PLA2R, THSD7A and IgG4 expression in IMN and non-IMN (2020– 2021) was detected to assess the efficacy of diagnosing IMN. IMN patients were divided into two groups, anti-PLA2R antibody positive (161 cases) and negative (26 cases), and two groups, kidney tissue PLA2R (40 cases) and PLA2R+THSD7A (6 cases), to compare the clinical and pathological features, and to carry out a prognostic analysis of THSD7A-positive patients, with a focus on correlation with malignancy.Results: The positive rate of anti-PLA2R antibodies was significantly higher in IMN (P< 0.05); anti-PLA2R antibodies, kidney tissue PLA2R and IgG4 and THSD7A had some diagnostic value. Anti-PLA2R antibodies correlated with proteinuria levels in IMN patients, and their levels were negatively correlated with blood albumin (r=− 0.146, P=0.042); correlated with pathological stage and C3 and IgG4 immunodeposition; there was no significant difference in clinical pathology between kidney tissue THSD7A+PLA2R positive compared to kidney tissue PLA2R positive patients, but the probability of achieving complete remission was low and time longer, and no malignancy events were detected during follow-up.Conclusion: Anti-PLA2R antibodies, kidney tissue PLA2R, THSD7A and IgG4 have high diagnostic efficacy for IMN; anti-PLA2R antibodies can be used as diagnostic markers to assist in the assessment of clinical and pathological features; co-expression of kidney tissue PLA2R and THSD7A is not significantly different from kidney tissue PLA2R in assessing the clinical features, pathological manifestations and prognosis, but requires long-term. However, long-term follow-up is needed to monitor the potential risk, and a larger multicentre study with long-term follow-up is expected to be conducted to comprehensively assess IMN characteristics.Keywords: Idiopathic membranous nephropathy, PLA2R, THSD7A, clinical features and pathology

Xiaodong Zhu,1 Ya Huang,2 Jia Ding,1 Jianguo Liu,1 Changmeng Cui,1 Guangkui Han1 1Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, 272000, People’s Republic of China; 2College of Traditional Chinese Medicine, Shandong Polytechnic College, Jining, 272000, People’s Republic of ChinaCorrespondence: Guangkui Han, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8618266808351, Email hanguangkui1997@163.comPurpose: SN-38 (7-ethyl-10-hydroxycamptothecin), the active metabolite of irinotecan, has been extensively studied in drug delivery systems. However, its impact on neural metabolism remains unclear. This study aims to investigate the toxic effects of SN-38 on mouse brain metabolism.Methods: Male mice were divided into an SN-38 group and a control group. The SN-38 group received SN-38 (20 mg/kg/day) via intraperitoneal injection, while the control group was given an equal volume of a blank solvent mixture (DMSO and saline, ratio 1:9). Gas chromatography-mass spectrometry (GC-MS) was employed to analyze differential metabolites in the cortical and hippocampal regions of the SN-38-treated mice.Results: SN-38 induced metabolic disturbances in the central nervous system. Eighteen differential metabolites were identified in the hippocampus and twenty-four in the cortex, with six common to both regions. KEGG pathway enrichment analysis revealed statistically significant alterations in six metabolic pathways in the hippocampus and ten in the cortex (P< 0.05).Conclusion: This study is the first to demonstrate the neurotoxicity of SN-38 in male mice through metabolomics. Differential metabolites in the hippocampal and cortical regions were closely linked to purine metabolism, pyrimidine metabolism, amino acid metabolism, and glyceride metabolism, indicating disruptions in the blood-brain barrier, energy metabolism, and central signaling pathways.Keywords: SN-38 (7-ethyl-10-hydroxycamptothecin), biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

Shan Qiao,1,2,&ast; Haiyun Li,3,&ast; Caisan Cui,4 Chong Zhang,1 Aihua Wang,1 Wenjing Jiang,3 Shanchao Zhang1,5 1Department of Neurology, the First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Medical Genetics, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 3Department of Geriatric Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 4Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 5School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanchao Zhang, Email zhangshanchao2012@163.com; Wenjing Jiang, Email jiangwenjing@qiluhospital.comPurpose: CSF inflammation in subtypes of antibody-defined autoimmune encephalitis (AE) ranges in intensity from moderate to severe. In a retrospective, cross-sectional study, we characterized CSF findings in Chinese patients with anti-N-methyl-D-aspartate receptor encephalitis (NMDAR-E), anti-leucine-rich glioma-inactivated 1 encephalitis (LGI1-E), and anti-gamma aminobutyric acid-B receptor encephalitis (GABABR-E).Patients and Methods: The AE cases, including 102 NMDAR-E, 68 LGI1-E and 15 GABABR-E, were included. CSF inflammatory parameters consisted primarily of CSF leukocytes, oligoclonal bands (OCBs), and CSF/serum albumin ratios (QAlb). Ten serum cytokines were evaluated in order to classify AE subtypes.Results: 88% of NMDAR-E, 80% of GABABR-E, and 51% of LGI1-E patients had aberrant CSF features. In NMDAR-E, the CSF leukocyte count, CSF protein concentration, and age-adjusted QAlb were significantly higher than in LGI1-E, but did not differ from GABABR-E. Blood-CSF barrier dysfunction was less common in NMDAR-E patients with > 40 years old. On admission, inflammatory CSF response was more prevalent in NMDAR-E patients with a higher CASE score. With age < 60 years, CSF inflammatory changes were less frequent in LGI1-E patients, but more common in GABABR-E patients. MCP-1, IL-10, IL-1β, and IL-4 were potential classifiers for NMDAR-E, LGI1-E, and GABABR-E, and correlated substantially with CSF leukocyte count and QAlb.Conclusion: Subtype-specific patterns are formed by the various inflammatory CSF parameters in NMDAR-E, LGI1-E, and GABABR-E, and their correlation with disease severity, age, and disease duration. CSF inflammatory characteristics associated with MCP-1, IL-10, IL-1β, and IL-4 may be potential immunopathogeneses targeting markers for these AE subtypes.Keywords: autoimmune encephalitis, cytokines, neuroinflammation, cerebrospinal fluid

Benjian Gao,1,2,&ast; Fengyi Yang,1,2,&ast; Dongning Zheng,1,2 Shuai Hu,1,2 Jie Liu,1,2 Hong Liu,1,2 Yongfa Liu,1,2 LinXin Liu,1,2 Rui Wang,1,2 Yi Zhao,1,2 Cheng Cui,1,2 Cheng Fang,1,2 Jin Yang,1,2 Song Su,1,2 Yunwei Han,3 Xiaoli Yang,1,2 Bo Li1,2 1Department of General Surgery (Hepatopancreatobiliary Surgery), The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 2Academician (Expert) Workstation of Sichuan Province, Metabolic Hepatobiliary and Pancreatic Diseases Key Laboratory of Luzhou City, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaoli Yang; Bo Li, Email 344920646@qq.com; liboer2002@126.comPurpose: This study aimed to explore the clinical efficacy of transarterial chemoembolization (TACE) in combination with tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitors (ICIs) (triple therapy) compared to TACE alone (monotherapy) for advanced hepatocellular carcinoma (HCC).Material and Methods: Data of consecutive advanced HCC patients receiving triple therapy or monotherapy at our center between January 2019 and December 2022 were collected and retrospectively analyzed. Propensity score matching (PSM) and subgroup analyses were performed to reduce the bias between the two groups. The primary outcomes of the study were the overall survival (OS) and progression-free survival (PFS). The secondary outcomes were the objective response rate (ORR) and disease control rate (DCR).Results: A total of 104 patients were enrolled in this study: 41 in the triple therapy group and 63 in the monotherapy group. After PSM analysis, each group included 37 patients. The median OS and PFS were significantly longer in the triple therapy group than in the monotherapy group in the whole cohort (median OS, 18.8 vs 11.7 months, P = 0.022; median PFS, 10.5 vs 6.4 months, P = 0.012) and after PSM (median OS, 19.6 vs 12.5 months, P = 0.030; median PFS, 10.5 vs 6.7 months, P = 0.008). Furthermore, the treatment modality was an independent prognostic factor for OS (hazard ratio [HR]: 0.449, 95% confidence interval [CI]: 0.240– 0.840, P = 0.012) and PFS (HR: 0.406, 95% CI: 0.231– 0.713, P = 0.002) according to the multivariate cox regression analysis. A greater ORR was also observed in the triple therapy group (ORR: 56.7% vs 32.4%, P = 0.035). No significant difference was observed in DCR between the two groups (83.7% vs 72.9%, P = 0.259).Conclusion: The triple therapy was superior to the monotherapy regarding OS, PFS, and ORR of advanced HCC patients.Keywords: hepatocellular carcinoma, transarterial chemoembolization, tyrosine kinase inhibitors, immune checkpoint inhibitors, efficacy

Cui Cui,1 Hengyu Zhou,2 Wenjin Chen,3 Shuangzi Li,3 Xianlan Zheng1 1Department of Nursing Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of China; 2School of Nursing, Chongqing Medical University, Chongqing, People’s Republic of China; 3Neurology Department of Children’s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, People’s Republic of ChinaCorrespondence: Xianlan Zheng, Tel +8617783864677, Email zhengxianlan@vip.163.comObjective: The study aimed to describe and explore the behavioral dilemmas and support-requirement characteristics of self-management for epileptic adolescents during transition readiness.Methods: A convergent mixed-methods study was conducted. Patients (N=654) in eight hospitals in China completed a demographic and disease characteristics questionnaire and measures of epilepsy transition readiness, self-management of epilepsy, and perceived social support, and 17 patients and family care-givers were interviewed simultaneously.Results: Adolescents with epilepsy (AWEs) had low levels of self-management and transition readiness, and moderate levels of social support. Multivariate linear regression showed that age, antiepileptic drug type, comorbidities, family structure, transition readiness, and social support were statistically significant in the regression model (p< 0.05). Seven themes emerged in the qualitative analysis related to self-management behavioral dilemmas, and 11 themes emerged for support requirements. The findings from the qualitative and quantitative analyses were combined to create a conceptual model based on the SMART framework and the social cognitive theory.Conclusion: The findings indicate that the state of self-management behaviors of Chinese AWEs is not promising. The influential factors and characteristics are complex and systematic.Practice Implications: This study provides insights into the self-management practices of AWEs in China and expands previous self-management and transitional readiness strategies and models.Keywords: convergent mixed-methods, adolescence, self-management of chronic diseases, epilepsy

Chengsen Cui,1,2,&ast; Bo Lv,1,&ast; Kai Meng1,3 1School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 2China Center for Health Development Studies, Peking University, Beijing, People’s Republic of China; 3High Quality Development Research Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Meng, School of Public Health, Capital Medical University, No. 10 Xitoutiao, Youanmenwai Street, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86-10-83911577, Email mengkai@ccmu.edu.cnPurpose: Community health centers (CHCs) are an important part of the healthcare system worldwide. Based on the dual process model of organizational capabilities, this study explores the relationship between organizational capabilities and the organizational performance of CHCs, as well as the role played by the medical alliance implementation effect.Methods: In this study, whole-group sampling was used to extract CHCs. All 135 CHCs in 8 of 16 districts of Beijing were selected as subjects. The organizational capabilities of the CHCs and the medical alliance implementation effect were evaluated using a questionnaire survey of 1957 managers and 3622 medical staff, respectively. A pathway analysis of the mediating role of the organizational capabilities of CHCs and the moderating role of the medical alliance implementation effect was conducted using Mplus 8.0.Results: The development capabilities had a positive impact on basic capabilities (β = 0.878, P < 0.001), and core capabilities (β = 0.952, P < 0.001), but had no direct impact on organizational performance. Basic capabilities positively affected organizational performance (β = 1.163, P < 0.001), and core capabilities negatively affected organizational performance (β =- 0.886, P = 0.004). Both basic capabilities (β =1.022, P < 0.001) and core capabilities (β =- 0.843, P = 0.005) played a mediating role in the relationship between development capabilities and organizational performance. The moderating role of the medical alliance implementation effect was not significant.Conclusion: This study found that strengthening the organizational capabilities of CHCs can effectively improve their performance, with the development of basic capabilities being a primary concern. The medical alliance implementation effect has not had a significant impact on organizational performance, and the cooperation between CHCs and high-level hospitals should be further promoted to give full play to the medical alliance’s role and improve the organizational performance of CHCs.Keywords: community health centers, organizational capabilities, organizational performance, medical alliance implementation effect, China

Yahao Gao,1,&ast; Di Jiang,2,&ast; Changshui Wang,3 Gang An,1 Li Zhu,4 Changmeng Cui3 1Clinical Medical School, Jining Medical University, Jining, Shandong, People’s Republic of China; 2Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining, People’s Republic of China; 4Department of Clinical Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changmeng Cui, Department of Neurosurgery, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272000, People’s Republic of China, Tel +8617805378911, Email cmcuidr1989@163.comPurpose: Sodium valproate (VPA) is the most widely used broad-spectrum antiepileptic first-line drug in clinical practice and is effective against various types of epilepsy. However, VPA can induce severe cardiotoxicity, nephrotoxicity, hepatotoxicity, and neurotoxicity, which limits its use. Metabolomic studies of VPA-induced toxicity have focused primarily on changes in serum and urine metabolites but have not evaluated changes in major organs or tissues.Methods: Central target tissues (intestine, lung, liver, hippocampus, cerebral cortex, inner ear, spleen, kidney, heart, and serum) were analyzed using gas chromatography mass spectrometry to comprehensively evaluate VPA toxicity in mouse models.Results: Multivariate analyses, including orthogonal projections of the latent structure and Student’s t test, indicated that depending on the matrix used in the study (the intestine, lung, liver, hippocampus, cerebral cortex, inner ear, spleen, kidney, heart or serum) the number of metabolites differed, the lung being the poorest and the kidney the richest in number.Conclusion: These metabolites were closely related and were found to participate in 12 key pathways related to amino acid, fatty acid, and energy metabolism, revealing that the toxic mechanism of VPA may involve oxidative stress, inflammation, amino acid metabolism, lipid metabolism, and energy disorder.Keywords: sodium valproate, biomarker, gas chromatography mass spectrometry, metabolomics, toxicity mechanism

Tiannan Chen, Yuesen Lin, Chengshuo Cui, Fangfang Zhang, Tingting Su, Kaiyu Guo, Jialin Hu Department of Burn and Wound Repair, Yueqing City People’s Hospital; Wenzhou Medical College Affiliated Yueqing Hospital, Wenzhou City, Zhejiang, 325600, People’s Republic of ChinaCorrespondence: Jialin Hu, Department of Burn and Wound Repair, Yueqing City People’s Hospital; Wenzhou Medical College Affiliated Yueqing Hospital, No. 338, Qingyuan Road, Chengnan Street, Yueqing City, Wenzhou City, Zhejiang, 325600, People’s Republic of China, Tel +86 15868777770, Fax +86 577-62061788, Email hujialin_ys@163.comObjective: To explore the clinical effect of wound edge microgranular skin grafting in the treatment of various small wounds.Methods: From September 2018 to September 2021, Yueqing people’s Hospital of Wenzhou City, Zhejiang Province collected and recorded the data of 12 patients with chronic wounds and third degree burns. The method of skin grafting with particles at the edge of the wound was used to graft skin on the wound. Scar evaluation scale was used to evaluate the wound. The patients were followed up for 12 months. The preoperative and postoperative data, scar index and patient satisfaction after healing were recorded and statistically analyzed.Results: All patients in this group were followed up for 3– 12 months, and the results showed that SCAR Scale score decreased gradually over time, with patient satisfaction ranging from 80% to 96%. The patient gradually healed, scar hyperplasia gradually improved, functional activities gradually returned to normal, clinical effect is satisfactory.Conclusion: Microparticle skin grafting at the edge of wound avoids skin grafting at different skin donor sites. It has the characteristics of simple anesthesia, small trauma and convenient operation. This method can be considered when treating patients with chronic wounds and burns who need skin grafting.Keywords: wound-edge microgranular skin grafting, chronic wounds, burns, curative effect analysis

Changqing Zhang,1 Changqi Cui,1 Qi Yao2 1School of Economics and Business Administration, Chongqing University, Chongqing, 400030, People’s Republic of China; 2School of Economics and Management, Chongqing Jiaotong University, Chongqing, 400074, People’s Republic of ChinaCorrespondence: Changqi CuiSchool of Economics and Business Administration, Chongqing University, Shazheng Street, No. 174, Shapingba District, Chongqing, 400030, People’s Republic of ChinaTel +86 13752905059Email cuichangqi@cqu.edu.cnPurpose: In the big data era, many institutions (ie, hospitals) and firms use various methods to encourage people to disclose more personal information to gain competitive advantages in many businesses, such as healthcare and the Internet of Things (IoT) devices. Discussions on antecedents of individuals’ willingness to reveal private data from individual differences perspective are limited. Drawing on information boundary theory, we examine how self-construal prompts a different regulatory focus (promotion focus versus prevention focus), thus, affects individuals’ willingness to disclose private data.Methods: A mixed-method approach was used to examine our hypothesis. Study 1 (N = 93, participants in China) manipulated self-construal in lab experiments and examined participants’ actual disclosure behavior in the emerging IoT context of connected cars. Study 2 (an online survey, N = 200, participants in US) measured chronic self-construal in another disclosure context (healthcare app), replicating the preliminary effect and examined the mediating effect of the regulatory focus. Study 3 (an online experiment, N = 284, participants in US) tested the moderating effect of message framing.Results: Study 1 showed that participants primed an independent self-construal were more willing to share private information, whether it is real driving data or private identity information. Study 2 showed that independent (interdependent) self-construal individuals tend to have promotion focus (prevention focus), thus leading to higher (lower) willingness to disclose personal health information. Study 3 demonstrated that independent (interdependent) self-construal individuals are more willing to share information when presented with gain-framing (loss-framing) information.Conclusion: Independent (interdependent) self-construal positively (negatively) affects individuals’ willingness to disclose and these effects will be mediated by regulatory focus and moderated by message farming. Our study provides a theoretical paradigm that is new to the willingness to disclose literature, and offers an effective, actionable strategy on how institutions and firms can facilitate individuals’ personal information disclosure.Keywords: self-construal, willingness to disclose, regulatory focus, information boundary theory, message framing, privacy

Lingyao Qi, Hanxiong Liu, Lianchao Cheng, Caiyan Cui, Xu Chen, Siqi Yang, Lin Cai Department of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Lin CaiDepartment of Cardiology, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, People’s Republic of ChinaTel/Fax +86 28-67575956Email clin63@hotmail.comPurpose: Chronic kidney disease (CKD) is common in patients admitted with acute coronary syndrome (ACS), and it is associated with poor outcomes. However, data are limited. Hence, we examined the long-term prognostic significance of estimated glomerular filtration rate (eGFR) among Chinese patients hospitalized with ACS.Patients and Methods: This is a multicenter, observational study that included 1860 ACS patients enrolled between March 2014 and June 2019 from 11 hospitals in Chengdu. CKD-EPI equation was used to calculate the baseline eGFR. Patients were divided into three groups: eGFR ≥ 90 mL/min (normal renal function), eGFR 60 to < 90 mL/min (mild impaired renal function), and eGFR < 60 mL/min (moderate or severe renal dysfunction). The endpoint was all-cause death during follow-up.Results: At baseline, 714 patients had normal renal function, while 746 patients had mild impaired renal function, and 400 patients had moderate or severe renal dysfunction. In the follow-up of 15 months (10 months, 22 months), 261 (14.0%) patients died;, 139 (34.8%) in the moderate or severe renal dysfunction group, 94 (12.6%) in the mild impaired renal function group, and 28 (3.9%) in the normal renal function group (log-rank p-value from Kaplan–Meier analysis < 0.001). In multivariable Cox Proportional hazard analysis, age, systolic blood pressure (SBP), heart rate, eGFR, ST-elevation myocardial infarction (STEMI), and percutaneous coronary intervention (PCI) were independent predictors of all-cause death.Conclusion: In this study, among Chinese patients with ACS, renal insufficiency was associated with unfavorable long-term prognosis. Age, SBP, heart rate, eGFR, STEMI, and PCI could identify those at risk.Keywords: renal insufficiency, acute coronary syndrome, long-term prognosis, retrospective study

Xin Chen,1,2,&ast; Zhicheng Yu,1,3,&ast; Jianhua Wang,1 Wenjing Cui,1 Can Cui,1 Yajie Wang,1 Yongkang Liu,1 Hao Zhou,1 Cheng Wang,4 Zhongqiu Wang,1 Xiao Chen1 1Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210029, People’s Republic of China; 2Department of Radiology, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 3Department of Radiology, Jiading Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, 201800, People’s Republic of China; 4Department of Radiology, Nanjing Drum Tower Hospital the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongqiu Wang; Xiao ChenDepartment of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, 210029, People’s Republic of ChinaTel +86-025-86619843Email zhqwang001@126.com; chxwin@163.comPurpose: The purpose of this study was to analyze the prevalence of and risk factors for incidental pancreatic cystic lesions (PCLs) in the Chinese general population. Furthermore, the association between baseline imaging findings and PCL progression was also investigated.Patients and Methods: A total of 9826 individuals who underwent computed tomography (CT) examinations for lung cancer screening between January 1, 2018 and January 1, 2019 were included in this study. The participants’ CT imaging findings and biochemical biomarker levels were reviewed and analyzed. PCLs detected during the screening were followed up for 12 months. Associations between imaging findings and clinical factors with PCL progression were explored.Results: PCLs were observed in 172 of the 9826 participants. The crude prevalence of PCLs in total population was 1.75%. In subjects aged > 60 years, the prevalence of PCLs was 3.2% (102/3151). The occurrence of PCLs was significantly increased with an increase of age in both men and women (p < 0.001). High-risk PCLsL commonly located in pancreatic head showed extrapancreatic growth, and had high urea levels (p = 0.005, p = 0.015, p = 0.002, respectively) compared with low-risk PCLs. Location in the pancreatic head (odds ratio (OR) = 6.286, 95% confidence interval (CI): 1.842– 21.452) and extrapancreatic growth (OR = 4.049, 95% CI: 1.235– 13.333) were risk factors for PCL progression.Conclusion: PCLs are not uncommon in the Chinese general population. Location in the pancreatic head and extrapancreatic growth are the independent predictors of high-risk of PCLs and PCL progression.Keywords: pancreatic cystic lesion, computed tomography, prevalence, progression, Chinese population

Xin Yang,1– 3 Yifan Wang,1– 3 Si Chen,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1School of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, 100069, People’s Republic of China; 3Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, 100069, People’s Republic of ChinaCorrespondence: Chunying Cui; Shuang ZhangDepartment of Pharmaceutics, School of Pharmaceutical Science, Capital Medical University, No. 10 Youanmenwai Street, Fengtai, Beijing, 100069, People’s Republic of ChinaTel/Fax +86-10-8391-1668; +86-10-8391-1673Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cnBackground: Breast cancer is the most prevalent cancer among women. Doxorubicin (DOX) is a common chemotherapeutic drug used to treat many different cancers. However, multidrug resistance limits the treatment of breast cancer. MDR1 siRNA (siMDR1) combinatorial therapy has attracted significant attention as a breakthrough therapy for multidrug resistance in tumors. However, naked siRNA is easily degraded by enzymatic hydrolysis requiring an siRNA carrier for its protection. Human serum albumin (HSA) was selected as the carrier due to its excellent biocompatibility, non-toxicity, and non-immunogenicity. Cetuximab was used to modify the HSA nanoparticles in order to target the tumor tissues.Methods: This study used a central composite design response surface methodology (CCD-RSM) to investigate the optimal formula for HSA NPs preparation. Cex-HSA/DOX/MDR1 siRNA (C-H/D/M) was characterized by dynamic light scattering and transmission electron microscopy. The efficacy of C-H/D/M tumor growth inhibitory activity was investigated in vitro and in vivo using confocal imaging, MTT assay, and an MCF-7/ADR tumor-bearing mice model. RT–qPCR, ELISA analysis, and flow cytometry were used to investigate the in vitro antitumor mechanisms of C-H/D/M.Results: The diameter and PDI of the C-H/D/M were 173.57 ± 1.30 nm and 0.027 ± 0.004, respectively. C-H/D/M promoted and maintained the sustained release and the uptake of DOX significantly. After transfection, the MDR1 mRNA and P-gp expression levels were down-regulated by 44.31 ± 3.6% (P < 0.01) and 38.08 ± 2.4% (P < 0.01) in an MCF-7/ADR cell line. The fluorescent images of the treated BALB/c nude mice revealed that C-H/D/M achieved targeted delivery of siMDR1 and DOX into the tumor tissue. The in vivo tumor inhibition results demonstrated that the tumor inhibition rate of the C-H/D/M treated group was 54.05% ± 1.25%. The biosafety results indicated that C-H/D/M did not induce significant damages to the main organs in vivo.Conclusion: C-H/D/M can be used as an ideal non-viral tumor-targeting vector to overcome MDR and enhance the antitumor effect.Keywords: human serum albumin, HSA, multidrug resistance, MDR, co-delivery carrier, small interfere RNA, gene silencing

Fuqiang Liu,1– 4 Feng Han,4,5 Xiaoli Liu,4,5 Lina Yang,4,5 Caixia Jiang,4,5 Chen Cui,1– 4 Fang Yuan,1– 4 Xin Zhang,1– 4 Lei Gong,1– 4 Xinguo Hou,1– 4 Yuan Liu,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, Shandong, 250012, People’s Republic of China; 5Department of Endocrinology, Zhangqiu District People’s Hospital, Jinan, 250200, People’s Republic of ChinaCorrespondence: Yuan Liu; Li Chen Email liuyuan198735@163.com; chenli3@medmail.com.cnBackground: To investigate the correlation between serum interleukin-17A (IL-17A) levels and diabetic retinopathy (DR) in elderly individuals with type 2 diabetes mellitus (T2DM).Methods: The study included 194 elderly patients (94 males and 100 females) with T2DM. Digital retinal photography as well as fundus fluorescein angiography was employed to distinguish between nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). In addition, multiple logistic regression analysis was conducted to determine the correlation between serum IL-17A levels and DR status.Results: The average age of the study cohort was 69.14 ± 6.33 years, of which 52.08% were male. The study participants with the highest IL-17A (Q4) levels had higher TC, DBP, and low-density lipoprotein cholesterol (LDL-C) values than those the other groups. Analysis using unadjusted and adjusted linear regression revealed that the effect size of 1.09 for DR in the unadjusted model indicates that IL-17A is associated with an increase of 1.09 in DR (mmol/L) (β 1.09, 95% confidence interval (CI) 1.03, 1.16). Using the minimum-adjusted model (the model 2), as IL-17A increased, DR was higher by 1.11 (β 1.11, 95% CI 1.04, 1.18). With the fully adjusted model (the model 3), for each additional IL-17A increase, DR was higher by 1.15 (β 1.15, 95% CI 1.06, 1.24).Conclusion: Serum IL-17A levels are apparently positively correlated to DR in Chinese elderly individuals with T2DM.Keywords: interleukin-17A, diabetic retinopathy, type 2 diabetes mellitus

Yan Song, Tao Qu, Honggang Zhang, Yongkun Sun, Chengxu Cui, Yihebali Chi, Wen Zhang, Xingyuan Wang, Lin Yang Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaCorrespondence: Lin Yang; Tao QuDepartment of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of ChinaEmail linyang@cicams.ac.cn; thomasqu1972@hotmail.comBackground: In FRESCO trial, a phase III study of fruquintinib demonstrated a significant improvement on the overall survival (OS) of patients with metastatic colorectal cancer (mCRC) who failed to response to available standard treatments. The aim of the current study was to evaluate the safety and effectiveness of fruquintinib in Chinese mCRC patients in the real-world setting.Methods: Patients with mCRC treated with fruquintinib at our hospital were retrospectively reviewed. Patient demographics, treatment, adverse events and survival data were collected. OS and progression-free survival (PFS) were estimated using the Kaplan–Meier method.Results: In total, 76 patients were evaluated from December 2018 to January 2020. The median (range) age was 59.5 (34– 86) years, ECOG PS 0-1/2 was 86.8%/13.2%, and 38 (50%)/30 (39.5%) patients had experienced more than two prior therapies for mCRC. The median treatment duration was 3.6 cycles. Treatment-related adverse events (TRAEs) resulted in dose reduction were 17.1% of the patients without any treatment discontinuation. The most common grade 3 or 4 TRAEs were hypertension (9.2%), hand-foot skin reaction (7.9%), thrombocytopenia (3.9%), anaemia (2.6%), increased ALT (1.3%), oral mucositis (1.3%), proteinuria (1.3%) and neutropenia (1.3%). The median PFS was 5.1 months (95% CI 3.8– 6.4 months), and the median OS was 12.0 months (95% CI 8.0– 16.1 months). In patients with hypertension or hypothyroidism, a survival extension approximate to 6 months was observed, but the difference is not yet statistically significant. CEA decreased after fruquintinib treatment could be considered as a potential predictor for better OS.Conclusion: The outcome of this real-life study was consistent with that of the randomised controlled trial. There were no new safety concerns. Future studies of fruquintinib should be conducted to identify patients who tend to obtain more benefits from fruquintinib alone or in combination with other agents.Keywords: fruquintinib, metastatic colorectal cancer, real-world settings, toxicities

Yifan Wang,1– 3 Si Chen,1– 3 Xin Yang,1– 3 Shuang Zhang,1– 3 Chunying Cui1– 3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, People’s Republic of China; 3Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, People’s Republic of ChinaCorrespondence: Chunying Cui; Shuang ZhangDepartment of Pharmaceutics, School of Pharmaceutical Science, Capital Medical University, Number 10 Youanmenwai Street, Fengtai, Beijing, 100069, People’s Republic of ChinaTel +86-10-8391-1668; +86-10-8391-1673Fax +86-10-8391-1668; +86-10-8391-1673Email ccy@ccmu.edu.cn; zshuang@ccmu.edu.cnBackground: siRNA brings hope for cancer therapy. However, there are many obstacles for application of siRNA in clinical. Because of the excellent biocompatibility, non-toxicity and non-immunogenicity of bovine serum albumin (BSA), BSA-based nanoparticles have been widely designed as a drug carrier system.Methods: The optimal formula for BSA NPs preparation was investigated by central composite design response surface methodology (CCD-RSM), BSA-based survivin-siRNA delivery system (BSA NPs/siRNA) was characterized by dynamic light scattering, atomic force microscope, transmission electron microscope and Bradford method. The in vitro anti-tumor effect and mechanism of BSA NPs were investigated by confocal microscopic imaging, MTT assay, RT-qPCR and ELISA analysis. Moreover, the anti-tumor effect, distribution and biosafety of BSA NPs were studied in vivo.Results: The optimal formula for BSA NPs was settled to be 20 mg/mL for BSA concentration, 9 for pH value, 136% for crosslinking degree and 1.6 mL/min for speed of ethanol addition. BSA NPs/siRNA could remain stable at 4°C for 4 weeks and protect siRNA from degradation by RNase A. Besides, BSA NPs/siRNA could maintain a sustained release of siRNA and promote the uptake of siRNA significantly. The survivin-mRNA level and the survivin-protein level were decreased by 55% ± 1.6% and 54% ± 1.6% separately. The in vivo tumor inhibition results suggested that the tumor inhibition rate of BSA NPs/siRNA-treated group was 54% ± 12% and was similar with that of DOX-treated group (57% ± 9.2%, P > 0.05). The biosafety results confirmed that BSA NPs/siRNA could not induce significant damages to the main organs and blood in vivo.Conclusion: These results demonstrated that CCD-RSM was an effective tool for preparation analysis, and the BSA NPs/siRNA was a promising system for siRNA-based gene therapy.Keywords: bovine serum albumin, BSA, CCD-RSM, survivin-siRNA, nanoparticles, RNAi

Kai Liu,1,* Guo-Liang Cai,2,3 Zhe Zhuang,4,* Si-Ying Pei,1 Sheng-Nan Xu,5 Ya-Nan Wang,1 Hong Wang,1 Xin Wang,1 Cheng Cui,5 Man-Chao Sun,5 Si-Hui Guo,5 Kun-Ping Jia,1 Xiu-Zhen Wang,1 Guo-Feng Cai1 1Hanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 2Postdoctoral Research Workstation of Harbin Sport University, Harbin, 150001, People’s Republic of China; 3Department of Sport Science and Health, Harbin Sport University, Harbin, 150008, People’s Republic of China; 4Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China; 5Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-Feng CaiHanan Branch of Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, Harbin, 150001, People’s Republic of ChinaEmail cangjiong1973@163.comBackground: Interleukin-1β (IL-1)-treated mesenchymal stem cells (MSCs) and IL-1-MSCs-conditioned medium (CM) exert anti-inflammatory roles. Astrocytes are essential for the modulation of synaptic activity and neuronal homeostasis in the brain. Exosomes are the critical mediators in intercellular communication. However, the mechanism underlying the anti-inflammatory effect of IL-1-treated MSCs remains unknown.Methods: In this study, exosomes (IL-1-Exo) were isolated from IL-1-treated MSCs. In addition, lipopolysaccharide (LPS)-treated hippocampal astrocytes and status epilepticus (SE) mice were treated with IL-1-Exo. Inflammatory activity, astrogliosis, and cognitive performance were measured to determine the effect of IL-1-Exo on inflammation.Results: The results revealed that IL-1-Exo significantly inhibited LPS-induced astrogliosis and inflammatory responses of astrocytes. Also, IL-1-Exo reversed the LPS-induced effect on calcium signaling. The Nrf2 signaling pathway was associated with the effect of IL-1-Exo in LPS-treated astrocytes. Furthermore, IL-1-Exo reduced the inflammatory response and improved the cognitive performance of SE mice.Conclusion: The results suggest that IL-1-Exo inhibited LPS-induced inflammatory responses in astrocytes and SE mice and that the effect of IL-1-Exo was primarily mediated through the Nrf-2 signaling pathway. This study provides a new understanding of the molecular mechanism of inflammation-associated brain diseases and an avenue to develop nanotherapeutic agents for the treatment of inflammatory conditions in the brain.Keywords: mesenchymal stem cells, interleukin-1β, exosome, astrocyte, inflammation, Nrf-2

Ying Zhang,1 Chunying Cui,1 Lie Wang,1 Xiaosong Yu,2 Yu Wang,1 Xiaoxi Wang3 1Department of Social Medicine, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of China; 2Department of General Practice, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Medical Basic Experimental Teaching Center, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: Xiaoxi Wang Email xiaoxiwang@cmu.edu.cnPurpose: Cancer diagnosis and treatment are long-term traumatic stressors. Depression and anxiety are known to be prevalent in patients with cancer, but post-traumatic disorder (PTSD) has been overlooked frequently in this population. This study aimed to estimate the prevalence of PTSD and examined the mediating role of hope in the relationship between perceived stress and PTSD symptoms in Chinese patients with oral cancer.Methods: A total of 230 oral cancer patients were recruited to complete a questionnaire including the Posttraumatic Stress Checklist-Civilian Version (PCL-C), the Perceived Stress Scale-10 (PSS-10) and the Herth Hope Index (HHI). Analysis of variances (ANOVA)/t-test, Person’s r and hierarchical linear regression analysis methods were conducted to assess the associations among perceived stress, hope and PTSD symptoms. Asymptotic and resampling strategies were used to explore the mediating role of hope.Results: The prevalence of PTSD symptoms was 6.05% in Chinese patients with oral cancer. Perceived stress was positively related to PTSD symptoms, explaining 39.9% of the variance. In addition, hope was negatively related to PTSD symptoms, explaining 5.9% of the variance. Besides, the proportion of mediation of hope was 30.06%.Conclusion: Perceived stress was positively associated with PTSD symptoms, and hope was negatively associated with PTSD symptoms. Furthermore, hope played partial mediating role in the relationship between perceived stress and PTSD symptoms. Thus, more attention should be paid to patients’ PTSD status, and take measures is to relieve stress and increase hope.Keywords: oral cancer, hope, perceived stress, post-traumatic disorder, PTSD

Chunmei Geng,1 Yujin Guo,1 Changshui Wang,2 Changmeng Cui,3 Wenxiu Han,1 Dehua Liao,4 Pei Jiang1 1Department of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, People’s Republic of China; 2Department of Clinical Translational Medicine, Jining Life Science Center, Jining 272000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining 272000, People’s Republic of China; 4Department of Pharmacy, Hunan Cancer Hospital, Central South University, Changsha 410011, People’s Republic of ChinaCorrespondence: Pei JiangDepartment of Pharmacy, Jining First People’s Hospital, Jining Medical University, Jining 272000, People’s Republic of ChinaTel/Fax +86 537 2106208Email jiangpeicsu@sina.comPurpose: Substantial evidence indicates that lipopolysaccharide (LPS) exposure can lead to systemic inflammatory response syndrome (SIRS) and multiple organ failure. Previous metabolomic studies have mainly focused on LPS-induced depression or hepatic and renal effects. However, no comprehensive metabolomics-based analysis of the serum, liver, kidney, hippocampus, and heart following exposure to LPS has been undertaken to date.Material and Methods: Male Sprague–Dawley rats were randomly allocated to a control and a LPS-treated group (n=8). LPS for 2 weeks (0.5 mg/kg every other day) was given via intraperitoneal injection. Gas chromatography–mass spectrometry (GC–MS) was used for metabolite determination, while multivariate statistical analysis was performed to identify differentially expressed metabolites between the two groups.Results: Our study revealed that 24, 13, 12, 7, and 12 metabolites were differentially expressed between the LPS treatment group and the control group in the serum, liver, kidney, hippocampus, and heart, respectively. We further identified that these metabolic changes were mainly involved with aminoacyl-tRNA biosynthesis; glutathione metabolism; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; arginine biosynthesis; bile acid biosynthesis; and glycerolipid metabolism.Conclusion: We have systematically elucidated the metabolic changes underlying LPS-induced SIRS, thereby providing insight into the mechanisms associated with these alterations.Keywords: systemic inflammatory response syndrome, metabolites, gas chromatography–mass spectrometry, multivariate statistical analysis

Fuqiang Liu,1– 4 Lei Gong,1– 4 Weidong Qin,5 Chen Cui,1– 4 Li Chen,1– 4 Mingxiang Zhang5 1Department of Endocrinology, Qilu Hospital, Shandong University, Jinan 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases, Shandong University, Jinan 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine and Health, Jinan, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, People’s Republic of China; 5Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan Shandong 250012, People’s Republic of ChinaCorrespondence: Li ChenDepartment of Endocrinology, Qilu Hospital of Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China, Tel +86-531-8216-9255Fax +86-531-86169356Email chenli191125@126.comMingxiang ZhangKey Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, People’s Republic of China, Tel +86-531-8216-9255Fax +86-531-86169356Email zhangmingxiang2019@126.comAim: Glucagon-like peptide-1 (GLP1) is known to decrease glucagon release and may be beneficial for the reduction of elevated blood glucose. However, its role and mechanism of action in diabetes remain elusive. This study aimed to examine the function of GLP1 and analyze the mechanism of effect that GLP1exerts on inducible nitric oxide synthase (iNOS) in diabetic mice.Methods: A diabetes model was established in ApoE–/– mice fed a high-fat diet and treated with GLP1 and/or lentivirus-expressing PARP1. PARP1, iNOS, and inflammatory factors in islets were detected by Western blot and ELISA. Islet α cells and β cells and CD8+ T lymphocytes were detected by immunostaining. Islet-cell apoptosis was detected by TUNEL.Results: GLP1 inhibited the expression of PARP1 and iNOS in islets, alleviated decrease in β cells, and suppressed cell apoptosis induced by the high-fat diet. Moreover, GLP1 recovered the decline in insulin sensitivity and glucose tolerance in ApoE–/– mice fed the high-fat diet, and the effects of GLP1 were related to the inhibition of COX2 and NFκB expression.Conclusion: GLP1 significantly alleviated the decrease in β-cell numbers, suppressed β-cell apoptosis induced by the high-fat diet, inhibited the expression of iNOS, and alleviated inflammatory islet injury via inhibiting the COX2–NFκB pathway.Keywords: GLP1, islet function, PARP1

Yong Wang, Hong-wei Zhao, Cheng-fu Wang, Xiao-jiao Zhang, Jie Tao, Chun-sheng Cui, Qing-kun Meng, Yu Zhu, De-feng Luo, Ai-jie Hou, Bo Luan Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province, 110016, People’s Republic of ChinaCorrespondence: Ai-jie Hou; Bo LuanDepartment of Cardiology, The People’s Hospital of China Medical University, the People’s Hospital of Liaoning Province, No. 33, Wenyiroad, Shenhe District, Shenyang City, Liaoning Province 110016, People’s Republic of ChinaTel +86-17702488970Email 1758624242@qq.com; luanbo2016@163.comBackground: The incidence and prognosis of coronary slow-flow (CSF) and no-reflow phenomenon (NRP) in patients with coronary chronic total occlusion (CTO) who underwent percutaneous coronary intervention (PCI) remain unclear.Methods: This single-center prospective study aimed to investigate the incidence of CSF/NRP during CTO interventional therapy, determine predictors of CSF/NRP, and evaluate its effect on patient outcomes.Results: In this study, 552 patients with CTO who underwent PCI were included. CSF/NRP occurred in 16.1% of them. They had higher incidences of diabetes mellitus (53.9% vs 36.3%, p=0.002) and hypertension (50.6% vs 37.1%, p=0.018) and a lower incidence of retrograde filling grade > 2 (34.8% vs 47.1%, p=0.036). Patients with CSF/NRP had a higher neutrophil ratio (55.6± 19.4 vs 52.4± 18.3, p=0.038) and levels of low-density lipoprotein (LDL; 3.0± 0.8 vs 2.8± 0.6, p=0.029), fasting glucose (FG; 8.3± 1.3 vs 6.8± 1.1, p=0.005), uric acid (332.6± 82.9 vs 308.2± 62.8, p=0.045), and high-sensitivity C-reactive protein (Hs-CRP; 9.8± 4.8 vs 7.3± 3.9, p=0.036). A multivariate logistic regression analysis revealed that diabetes mellitus (odds ratio [OR], 1.962; 95% confidence interval [CI]: 1.198– 2.721; p=0.042), mean platelet volume (MPV; OR,1.284; 95% CI, 1.108– 1.895; p=0.046), LDL cholesterol (LDL-C; OR, 1.383; 95% CI, 1.105– 2.491; p=0.036), FG (OR, 2.095; 95% CI, 1.495– 2.899; p=0.018), Hs-CRP(OR, 2.218; 95% CI, 1.556– 3.519; p=0.029), and retrograde filling of grade > 2 (OR, 0.822; 95% CI, 0.622– 0.907; p=0.037) were independent predictors of CSF/NRP in CTO patients who underwent PCI. Kaplan-Meier analysis revealed that the patients in the CSF/NRP group had a significantly lower cumulative major cardiac and cerebrovascular events (MACCE)-free survival than those in the non-CSF/NRP group (p< 0.0001).Conclusion: Of the patients with CTO who underwent PCI, 16.1% developed CSF/NRP and had a significantly lower cumulative MACCE-free survival rate. Diabetes mellitus; higher levels of MPV, LDL-C, FG, and Hs-CRP; and a lower incidence of retrograde filling grade > 2 were independent predictors of CSF/NRP in CTO patients who underwent PCI. Thus, they can be used for risk stratification.Keywords: coronary slow-flow, no-reflow phenomenon, coronary chronic total occlusion, PCI, prognosis

Yingjian Song,1,* Huimin Liu,2,* Chunling Cui,3 Xiaonu Peng,1 Chaoyang Wang,1 Xudong Tian,4 Wenjun Li1 1Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China; 2Department of Gastroenterology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China; 3Library, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai 264000, Shandong, People’s Republic of China; 4Department of Thoracic Surgery, Liaocheng People’s Hospital, Liaocheng 252000, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong TianDepartment of Thoracic Surgery, Liaocheng People’s Hospital, No. 67, Changxi Road, Liaocheng, Shandong 252000, People’s Republic of ChinaTel +86-15653112705Email zhangding553977@126.comWenjun LiDepartment of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, No. 20 Yuhungding East Road, Zhifu District, Yantai 264000, Shandong, People’s Republic of ChinaTel +86-18653525277Email liwenjun90808@163.comObjective: To study the effect of peroxiredoxin 1 (PRDX1) on esophageal squamous carcinoma cells and determine whether it plays a role in regulating the PI3K/AKT signaling pathway.Methods: Three esophageal squamous cell carcinoma cell lines (Eca-109, EC9706, and KYSE150) and one normal cell line (human esophageal epithelial cells) were selected. The protein expression of peroxiredoxin 1 (PRDX1) and the activity of the PI3K/AKT pathway were detected via Western blotting. The proliferation ability of cells was detected through the MTT assay and cell clone formation. Apoptosis was detected using flow cytometry. Subsequently, cells were treated with a PI3K/AKT pathway inhibitor and activator, alone or in combination with silencing of PRDX1, and the above indicators were re-tested.Results: The expression of PRDX1 and activity of PI3K/AKT pathway-associated proteins were higher in esophageal cancer cells than in normal esophageal epithelial cells. Compared with normal human esophageal epithelial cells, the proliferation of the three types of esophageal cancer cells was increased, whereas their level of apoptosis was decreased (p

Jing Wang,1,2,* Jie Huang,1,3,* Shuang Yang,1,3 Chang Cui,1,3 Ling Ye,1,3 Sai-ying Wang,4 Guo-ping Yang,1,3 Qi Pei1,2 1Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Clinical Trails Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 4Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guo-ping Yang; Qi PeiThe Third Xiangya Hospital, Central South University, Yinpenling Street, Yuelu District, Changsha, Hunan 410013, People’s Republic of ChinaTel +86 131 7041 9804Fax +86 731 8861 8326Email ygp9880@126.com; peiqi1028@126.comPurpose: To assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection.Patients and methods: A randomized, open-label, parallel-controlled, Phase I study was performed with 32 patients undergoing painless gastroscopy. Patients received a single dose of esketamine (0.5 mg/kg) or racemic ketamine (1 mg/kg, esketamine:R-ketamine=1:1), injected in 10 s. Blood samples were collected for pharmacokinetic analysis. The concentrations of esketamine, R-ketamine, S-norketamine, and R-norketamine were measured with a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method.Results: After administering a single dose of esketamine and racemate ketamine, the pharmacokinetics parameters of esketamine and S-norketamine are both similar in treatment groups. The clearance of esketamine in two groups was 18.1±3.2 and 18.4±3.4 mL/min•kg, respectively. However, in the ketamine group, esketamine has a larger clearance than R-ketamine (18.4±3.4 mL/min·kg vs 15.8±3.1 mL/min·kg, P

Can Cui,1 Xiaojing Cheng,2 Liang Yan,1 Huirong Ding,3 Xiaoya Guan,1 Wenlong Zhang,4 Xiuyun Tian,1 Chunyi Hao11Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Gastrointestinal Carcinoma Translational Research Laboratory, Peking University Cancer Hospital & Institute, Beijing, People’s Republic of China; 3Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Central Laboratory, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of China; 4Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Laboratory Animal, Peking University Cancer Hospital & Institute, Beijing 100142, People’s Republic of ChinaBackground: Colorectal cancer (CRC) is one of the most prevalent gastrointestinal malignancies. The incidence of CRC has been rapidly increasing in China. Transferrin receptor 1 (TfR1) is a key regulator of cellular iron homeostasis. Several studies have demonstrated TfR1 overexpression in a variety of human tumors, but the association between TfR1 and CRC remains unclear.Methods: TfR1 expression was evaluated in six CRC cell lines and tumor tissues. A total of 201 CRC patients were included for immunohistochemistry and 19 pairs of frozen tissues were used for real-time PCR. Cell proliferation, cell cycle, cell migration and invasion, and in vivo carcinogenesis were tested after downregulation of TfR1 by lentivirus. Protein microarray and Western blot analyses were used to explore the underlying mechanisms of TfR1 in CRC.Results: TfR1 expression was higher in CRC tissues than in normal tissues (57.2% vs 22.9%, P＜0.001). TfR1 expression was obviously higher in CRC tissues with well differentiation (P＝0.008), no lymph node metastasis (P＝0.002), no distant metastasis (P＝0.006), no vascular invasion (P＜0.001) and early TNM stage (P＝0.013). CRC patients with TfR1-positive expression had a better survival than those with TfR1-negative expression (P＝0.044). Downregulation of TfR1 expression inhibited cell proliferation, promoted cells from G1 phase to S phase and facilitated cell migration and invasion. Knockdown of TfR1 also suppressed tumor growth in BALB/C-nu mice. Protein microarray and Western blot analyses showed that the Janus protein tyrosine kinase/signal transducer and activator of transcription pathway was activated along with downregulation of TfR1 expression.Conclusion: Though TfR1 was overexpressed in colorectal cancer tissues, there was evidence that downregulation of TfR1 could promote cancer progression.Keywords: colorectal cancer, transferrin receptor 1, tumor progression, JAK/STAT pathway

Yigang Wang,1 Binrong Wang,1 Junnan Liang,2 Caixia Cui,3 Chang Ying,1 Fang Huang,4 Buyun Ma,1 Xiumei Zhou,1 Liang Chu21College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, People’s Republic of China; 2Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Otorhinolaryngology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, People’s Republic of China; 4Department of Pathology, Zhejiang Provincal People’s Hospital, Hangzhou 310014, People’s Republic of ChinaBackground: Oncolytic virus can specifically replicate in and then lyse tumor cells, but seldom in normal cells. Further studies have shown the significant therapeutic effect of oncolytic virotherapy combining with other strategies, such as chemo-, radio-, and immunotherapy et al. In this study, we investigated the combinational effect of oncolytic virus ZD55-TRAIL and chemotherapy drug doxorubicin (DOX) on human laryngeal squamous cell carcinoma (LSCC).Methods: The effect of ZD55-TRAIL combined with DOX on cell growth was assessed in LSCC Hep2 cells and normal cells by MTT assay. Hochest 33342 staining was performed to observe cell morphological changes. Western blot was used to detect the expression of apoptotic activation proteins. The in vivo antitumor efficacy of combination treatment was estimated in laryngeal cancer xenograft models.Results: The combination of ZD55-TRAIL and DOX exhibited enhanced inhibitory effects on laryngocarcinoma cell growth, and had few side effects to normal cells in vitro. Chemotherapy drug increased the inducement of tumor cell apoptosis mediated by oncolytic virus. In vivo experiment confirmed that the combination treatment significantly inhibited Hep2 laryngocarcinoma xenografts growth in mice.Conclusion: The oncolytic viro-chemotherapy is a potent therapeutic approach for in vitro cytotoxicity evaluation of Hep2 cells and xenograft growth in vivo.Keywords: laryngocarcinoma, oncolytic virus, ZD55-TRAIL, doxorubicin

Jie Huang,1,2,* Cheng-xiao Fu,1,2,* Xiao-yan Yang,1,2 Chan Cui,1,2 Shuang Yang,1,2 Yun Kuang,1,2 Cheng-xian Guo,1,2 Pei Hu,3 Qi Pei,2,4 Guo-ping Yang1,2 1Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China; 2Center for Clinical Drug Evaluation, Central South University, Changsha, Hunan 410013, People’s Republic of China; 3Clinical Pharmacology Research Center, Peking Union Medical College Hospital, Beijing 100032, People’s Republic of China; 4Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People’s Republic of China *These authors contributed equally to this work Purpose: To determine the pharmacokinetic properties of the common tablet of roflumilast administered in single and multiple oral doses in Chinese subjects.Subjects and methods: Both the single- and multiple-dose studies included 12 adults (6 males and 6 females). In this single-center, open-label study, single doses of 0.25, 0.375, and 0.5 mg were administered using a randomized, three-way crossover design, and then, the 0.375 mg dose was continued for 11 days once daily. The pharmacokinetic parameters for roflumilast and roflumilast N-oxide were determined and the safety evaluation included adverse events assessed by monitoring, physical examination, vital sign tests, and clinical laboratory tests.Results: After every single dose, the time to the maximum concentration (Cmax) of roflumilast (Tmax) was 0.25–2.0 hours; thereafter, the concentration declined, with a mean half-life (t1/2) of 19.7–20.9 hours over the range of 0.25–0.50 mg. As for roflumilast N-oxide, the mean t1/2 was 23.2–26.2 hours. The area under curve from the beginning to 24 hours (AUC0–24 h), the AUC until infinity (AUCinf), and the Cmax of roflumilast and roflumilast N-oxide increased in a dose-proportional manner. After multiple doses, the accumulation index (Rac) on the 11th day of the steady state was ~1.63 for roflumilast and 3.20 for roflumilast N-oxide. No significant sex differences were observed in the pharmacokinetic parameters of roflumilast and roflumilast N-oxide. In addition, there were no serious adverse events across the trial.Conclusion: Roflumilast was safe and well-tolerated in healthy volunteers, and a linear increase in its Cmax and AUC values was observed at doses ranging from 0.25 to 0.50 mg. Keywords: pharmacokinetics, roflumilast, roflumilast N-oxide, healthy volunteer, phosphodiesterase 4 inhibitor

Xiaoli Wang,1–3 Qi Sun,1–3 Chunying Cui,1–3 Jing Li,1–3 Yifan Wang1–3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Capital Medical University, Beijing, China; 3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Capital Medical University, Beijing, China Background: The success of gene therapy is mostly dependent on the development of gene carrier. Graphene oxide (GO) possesses excellent aqueous solubility and biocompatibility, which is important for its biochemical and medical applications. Our previous work proved that GO can deliver siRNA into cells efficiently and downregulate the expression of desired protein.Methods: In this study, a novel delivery carrier, GO-R8/anti-HER2 (GRH), was developed by conjugating octaarginine (R8) and anti-HER2 antibody with GO as a tumor active-targeting vector for survivin-siRNA delivery.Results: GRH/survivin-siRNA formed nanoglobes of 195±10 nm in diameter. Real-time polymerase chain reaction analysis revealed that survivin messenger RNA expression showed a 42.4%±2.69% knockdown. The expression of survivin protein was downregulated to 50.86%±2.94% in enzyme-linked immunosorbent assay. In MTT tests, GRH exhibited no testable cytotoxicity. In vivo, GRH/survivin-siRNA showed gene silencing and inhibition of tumor growth.Conclusion: The in vitro and in vivo results consistently demonstrated that GRH/survivin-siRNA has potential to be an efficient gene silencing carrier for siRNA delivery in cancer therapy. Keywords: graphene oxide, GO, survivin-siRNA, anti-HER2 antibody, small interfering RNA, gene delivery, nanocarrier

Qi Sun,1–3 Xiaoli Wang,1–3 Chunying Cui,1–3 Jing Li,1–3 Yifan Wang1–3 1Department of Pharmaceutics, School of Pharmaceutical Sciences, Capital Medical University, Beijing, China; 2Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing, China; 3Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing, China Background: Graphene oxide (GO) has attracted intensive interest in biological and medical fields in recent years due to its unique physical, chemical, and biological properties. In our previous work, we proved that GO could deliver small interfering RNA (siRNA) into cells and downregulate the expression of the desired gene. Methods: This study investigated the potential of a modified GO nanocarrier for co-delivery of siRNA and doxorubicin (DOX) for enhanced cancer therapy. Fourier transform infrared spectroscopy, laser particle size analyzer, UV-visible spectroscopy, gel electrophoresis retardation, and in vitro release assay were studied. Results: The results of real-time polymerase chain reaction revealed that the expression of vascular endothelial growth factor (VEGF) mRNA was decreased 46.84%±3.72% (mean ± SD). Enzyme-linked immunosorbent assay indicated that the expression of VEGF protein was downregulated to 52.86%±1.10% (mean ± SD) in vitro. In vivo tumor growth assay GO-poly-L-lysine hydrobromide/folic acid (GPF)/DOX/siRNA exhibited gene silencing and tumor inhibition (66.95%±2.35%, mean ± SD) compared with naked siRNA (1.62%±1.47%, mean ± SD) and DOX (33.63%±5.85%, mean ± SD). GPF/DOX/siRNA exhibited no testable cytotoxicity. Conclusion: The results indicated that co-delivery of siRNA and DOX by GPF could be a promising application in tumor clinical therapy. Keywords: graphene oxide, siRNA delivery, co-delivery carrier, cervical carcinoma

Chunmei Cui, Hong Lu Department of Ophthalmology, Beijing Chao-Yang Hospital, Beijing, China Purpose: Conbercept is a new anti-vascular endothelial growth factor (VEGF) drug approved for the treatment of age-related macular degeneration (AMD). Although this novel drug has been widely used in clinic, unlike other anti-VEGF drugs, validation and consensus on its method of clinical application and clinical safety have not yet been achieved.Methods: Relevant literature was searched on PubMed, Web of Science, China National Knowledge Internet, and Wanfang Data. Stata 12.0 was used for data analysis. Random- and fixed-effect models were employed to evaluate heterogeneity. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were utilized to measure the improvement of AMD patients.Results: In this study, we analyzed conbercept administration and compared its application with other control clinical methods for AMD treatment. Ranibizumab, triamcinolone, and traditional transpupillary thermotherapy (TTT) were administered in the control group. No differences were found in the BCVA and CRT improvement between the groups treated with conbercept and ranibizumab. However, the conbercept group had a lower serum VEGF level. After 3 months of treatment, conbercept led to a more significant BCVA and CRT improvement than triamcinolone. A more considerable BCVA improvement was observed in the group treated with conbercept than in the group treated with TTT. Moreover, even 6 months after the treatment, the effect of conbercept on CRT improvement was still more pronounced than that of TTT.Conclusion: In AMD patients, conbercept exerts considerably more positive effects on the long-term BCVA and CRT improvement than triamcinolone and TTT. The serum VEGF level in the conbercept group was lower than that in the ranibizumab group. Keywords: AMD, VEGF, conbercept, BCVA, CRT

Bo Wu,1,2 Shu-Ting Lu,1 Kai Deng,2 Hui Yu,2 Can Cui,2 Yang Zhang,2 Ming Wu,2 Ren-Xi Zhuo,2 Hai-Bo Xu,1 Shi-Wen Huang2 1Department of Radiology, Zhongnan Hospital of Wuhan University, 2Key Laboratory of Biomedical Polymers, Ministry of Education, Department of Chemistry, Wuhan University, Wuhan, People’s Republic of China Abstract: In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo. Keywords: redox-sensitive, tumor-targeted, gadolinium, contrast agents, PLGA

Jianyu Lin,1,* Jing Wang,2,* Peng Yue,3 Xingmao Zhang,4 Ren Lang,4 Yuan Wang,4 Chen Cui,4 Qiang He4 1Integrated Department, 2Patient Service Center, The Affiliated Hospital to Capital Medical University, Beijing Chaoyang Hospital, 3School of Nursing, Department of Basic Nursing, Capital Medical University, 4Department of Hepatobiliary Surgery, The Affiliated Hospital to Capital Medical University, Beijing Chaoyang Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: Intestinal perforation is a rare complication after liver transplantation. This study was designed to calculate the incidence and investigate the outcomes of intestinal perforation in adult liver transplant patients.Materials and methods: The clinical records of liver transplant recipients between January 2014 and June 2016 were obtained. The incidence of intestinal perforation was calculated, and high risk factors were analyzed.Results: The mean operative time was 8.5 h (range: 6–11 h). The mean portal vein occlusion time was 66.5 min (range: 58–72 min), and the mean cold ischemia time was 7.9 h (range: 6.5–9.5 h). Four (2.7%) patients developed intestinal perforation from 9 to 14 days postliver transplant. All perforations were single and repaired by interrupted silk sutures. Two patients uneventfully recovered, but intestinal perforation recurred in two other patients. Simple repair was undertaken in one patient, and terminal ileum resection and ileostomy were performed in the other patient. There were no perioperative deaths.Conclusion: The incidence of intestinal perforation after liver transplantation is low. Prompt diagnosis and treatment should be carried out to reduce comorbidities and mortality. Keywords: liver transplant, intestinal perforation, incidence, treatment, nursing

Xiaojie Lv,1 Ming Zhao,1,2 Yuiji Wang,1 Xi Hu,1 Jianhui Wu,1 Xueyun Jiang,1 Shan Li,1 Chunying Cui,1 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: In the treatment of cancer patients, cisplatin (CDDP) exhibits serious cardiac and renal toxicities, while classical combinations related to CDDP are unable to solve these problems and may result in worse prognosis. Alternately, this study covalently conjugated 6-mercaptopurine (6MP) onto the surface of mercapto-modified mesoporous silica nanoparticles (MSNS) to form MSNS-6MP and loaded CDDP into the holes on the surface of MSNS-6MP to form MSNS-6MP/CDDP, a tumor-targeting nano-releasing regime for CDDP and 6MP specifically. In the S180 mouse model, the anti-tumor activity and overall survival of MSNS-6MP/CDDP (50 mg·kg-1·day-1, corresponding to 1 mg·kg-1·day-1 of 6MP and 5 mg·kg-1·day-1 of CDDP) were significantly higher than those of CDDP alone (5 mg·kg-1·day-1) or CDDP (5 mg·kg-1·day-1) plus 6MP (1 mg·kg-1·day-1). The assays of serum alanine aminotransferase, aspartate aminotransferase and creatinine, as well as the images of myocardium and kidney histology, support that MSNS-6MP/CDDP is able to completely eliminate liver, kidney and heart toxicities induced by CDDP alone or CDDP plus 6MP. Keywords: 6-mercaptopurine, cisplatin, mesoporous silica nanoparticles, cancer therapy, nanomedicine

Ciren Yangzong,1,2 Sanguan Lerkiatbundit,3 Ouzhu Luobu,4 Chaoying Cui,4 Tippawan Liabsuetrakul,2 Baima Kangzhuo,4 Deji Quzong,4 Luobu Zhandui,5 Pu Zhen,6 Virasakdi Chongsuvivatwong2 1Department of Preventive Medicine, Medical College, Tibet University, Lhasa, Tibet Autonomous Region, People’s Republic of China; 2Epidemiology Unit, Faculty of Medicine, 3Department of Pharmacy Administration, Faculty of Pharmaceutical Science, Prince of Songkla University, Songkhla, Thailand; 4High Altitude Research Centre, 5Experimental Centre, 6Department of Pharmaceutical Science, Medical College, Tibet University, Lhasa, Tibet Autonomous Region, People’s Republic of China Abstract: Parenting style experienced during childhood has profound effects on children’s futures. Scales developed in other countries have never been validated in the Tibetan context. The present study aimed to examine the construct validity and reliability of a Tibetan translation of the 23-item short form of the Egna Minnen Beträffande Uppfostran [One’s Memories of Upbringing] (s-EMBU) and to test the correlation between the parenting styles of fathers and mothers. A cross-sectional study was conducted in a sample of 847 students aged 12–21 years from Lhasa, Tibet, during September and October 2015 with a participation rate of 97.7%. The Tibetan translation of self-completed s-EMBU was administered. Confirmatory factor analysis was employed to test the scale’s validity on the first half of the sample and was then cross-validated with the second half of the sample. The final model consisted of six factors: three (rejection, emotional warmth, and overprotection) for each parent, equality constrained on factor loadings, factor correlations, and error variance between father and mother. Father–mother correlation coefficients ranged from 0.81 to 0.86, and the level of consistency ranged from 0.62 to 0.82. Thus, the slightly modified s-EMBU is suitable for use in the Tibetan culture where both the father and the mother have consistent parenting styles. Keywords: Tibetan, parenting style, s-EMBU, validity, reliability, Egna Minnen Beträffande Uppfostran

Ning Song,1 Ming Zhao,1,2 Yuji Wang,1 Xi Hu,1 Jianhui Wu,1 Xueyun Jiang,1 Shan Li,1 Chunying Cui,1 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: In spite of the usual combination form of methotrexate (MTX)/mitoxantrone (MIT) and various complex combination regimens of MTX/MIT with other anticancer drugs, the survival period, cure rate, and systemic toxicity still need to be improved. For this purpose, a nanostructured amino group-modified mesoporous silica nanoparticles (MSNN)–MTX/MIT was designed. In the preparation, the surface of mesoporous silica nanoparticles (MSNs) was modified with amino groups to form MSNN. The covalent modification of the amino groups on the surface of MSNN with MTX resulted in MSNN–MTX. The loading of MIT into the surface pores of MSNN–MTX produced nanostructured MSNN–MTX/MIT. Compared with the usual combination form (MTX/MIT), nanostructured MSNN–MTX/MIT increased the survival period greatly, heightened the cure rate to a great extent, and lowered the systemic toxicity of the treated S180 mice, significantly. These superior in vivo properties of nanostructured MSNN–MTX/MIT over the usual combination form (MTX/MIT) were correlated with the former selectively releasing MTX and MIT in tumor tissue and inside cancer cells in vitro. The chemical structure and the nanostructure of MSNN–MTX/MIT were characterized using infrared and differential scanning calorimeter spectra as well as transmission electron microscope images, respectively. Keywords: mitoxantrone, methotrexate, mesoporous silica nanoparticles, cancer therapy, nanomedicine

Laser reactive sintering, i.e., laser-induced self-propagating reaction sintering synthesis was used for the preparation of nickel aluminide intermetallic compounds. The experimental parameters controlling the ignition step such as ignition time and adiabatic temperature were calculated as a function of initial stoichiometry. Al mole ratio in initial powder mixture was varied from 25% to 50% for controlling adiabatic temperature. The increase in Al powder content resulted in the rise in adiabatic temperature and the morphology change of nickel aluminide compounds from needle-like to blocky.

Chronic hepatitis B virus (HBV) infection is caused by inadequate anti-viral immunity. Activation of plasmacytoid dendritic cells (pDC) leading to IFNα production is important for effective anti-viral immunity. Hepatitis B virus (HBV) infection lacks IFNα induction in animal models and patients and chronic HBV patients display impaired IFNα production by pDC. Therefore, HBV and HBV-derived proteins were examined for their effect on human pDC in vitro. In addition, the in vitro findings were compared to the function of pDC derived from chronic HBV patients ex vivo. In contrast to other viruses, HBV did not activate pDC. Moreover, HBV and HBsAg abrogated CpG-A/TLR9-induced, but not Loxoribine/TLR7-induced, mTOR-mediated S6 phosphorylation, subsequent IRF7 phosphorylation and IFNα gene transcription. HBV/HBsAg also diminished upregulation of co-stimulatory molecules, production of TNFα, IP-10 and IL-6 and pDC-induced NK cell function, whereas TLR7-induced pDC function was hardly affected. In line, HBsAg preferentially bound to TLR9-triggered pDC demonstrating that once pDC are able to bind HBV/HBsAg, the virus exerts its immune regulatory effect. HBV not only directly interfered with pDC function, but also indirectly by interfering with monocyte-pDC interaction. Also HBeAg diminished pDC function to a certain extent, but via another unknown mechanism. Interestingly, patients with HBeAg-positive chronic hepatitis B displayed impaired CpG-induced IFNα production by pDC without significant alterations in Loxoribine-induced pDC function compared to HBeAg-negative patients and healthy controls. The lack of activation and the active inhibition of pDC by HBV may both contribute to HBV persistence. The finding that the interaction between pDC and HBV may change upon activation may aid in the identification of a scavenging receptor supporting immunosuppressive effects of HBV and also in the design of novel treatment strategies for chronic HBV.