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Jiahuan Guo,1 Dandan Wang,1 Jiaokun Jia,1 Jia Zhang,1 Yanfang Liu,1 Jingjing Lu,1,2 Xingquan Zhao,1– 4,&ast; Jing Yan1,&ast; 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Center of Stroke, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao; Jing Yan, Email zxq@vip.163.com; joyce_yj@163.comPurpose: Inflammatory response plays essential roles in the pathophysiology of both ischemic stroke and atrial fibrillation (AF). We aimed to investigate whether composite inflammatory markers, including neutrophil to lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR), can serve as early predictors of short- and long-term outcomes in ischemic stroke patients with AF.Patients and Methods: Ischemic stroke patients with AF were enrolled in this cohort study. The primary outcome was 1-year functional dependence or death (modified Rankin scale (mRS) score 3– 6). Secondary outcomes included hemorrhagic transformation (HT) and early neurological deterioration (END, increase in the National Institutes of Health Stroke Scale (NIHSS) ≥ 4 within 7 days). Partial correlations were performed to assess the correlation between systemic inflammation markers and admission NIHSS scores. Univariate and multivariate logistic analyses were performed to investigate whether systemic inflammatory markers were independent predictors of adverse outcomes.Results: A total of 408 patients were included. Partial correlation analysis revealed statistically significant but weak correlations between the NLR (r = 0.287; P < 0.001), PLR (r = 0.158; P = 0.001) and admission NIHSS score. Compared with patients without HT or END, patients who developed HT or END had higher NLR and PLR, and lower LMR. Patients in the functional dependence or death group had significantly higher NLR and PLR, and lower LMR than those in the functional independence group (all P < 0.001). Multivariate logistic analysis indicated that NLR, LMR and PLR were independent predictors of HT (OR = 1.069, 0.814 and 1.003, respectively), END (OR = 1.100, 0.768 and 1.006, respectively) and adverse 1-year functional outcome (OR = 1.139, 0.760 and 1.005, respectively).Conclusion: NLR, LMR and PLR were independent predictors for in-hospital HT, END and long-term functional outcome in ischemic stroke patients with AF. Close monitoring of these inflammatory markers may help guide risk stratification and clinical treatment strategies.Keywords: inflammation, ischemic stroke, atrial fibrillation, hemorrhagic transformation, early neurological deterioration, functional outcome

Jie Jia,1,&ast; Tao Sun,1,&ast; Jiamin Tang,1 Kaidi Sun,1 Zhengnan Meng,1 Hailong Zhu,2 Xianhong Huang1 1Department of Health Policy and Management, School of Public Health, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China; 2Department of Sociology, School of Public Administration, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xianhong Huang, Department of Health Policy and Management, School of Public Health, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China, Tel/Fax +86-571-2886-5627, Email hxh974291@163.comPurpose: Healthcare professionals’ participation is crucial for the efficient implementation of multidisciplinary team (MDT) collaboration models. We identified the key factors influencing healthcare professionals’ preference to participate in MDTs in tertiary hospitals.Methods: To clarify the attributes and levels of the discrete choice experiment (DCE), we conducted a targeted literature review and conducted in-depth interviews with MDT service providers. Following this, a DCE was designed to evaluate healthcare professionals’ preferences for MDT participation, and the influence of factors such as salary subsidies, leadership attention, patient participation, quality assessment, working intensity, and case complexity. A conditional logit model estimated the utility of each attribute. Willingness-to-pay estimates were derived by taking the negative ratio of the coefficients of non-economic and economic attributes. A series of policy simulation analyses were conducted.Results: Two hundred healthcare professionals completed the questionnaire, with 180 valid responses used for analysis. All attributes were statistically significant. Leadership attention and working intensity were the primary factors influencing staff willingness to participate in MDTs, followed by quality assessment and salary subsidies. Significant preference differences were observed between respondents; compared with mid-level staff, senior-level healthcare professionals believed patient engagement would be more helpful in boosting participation. The policy simulation showed that changing leadership attention from “neglect” to “emphasis” would increase the probability of staff choosing to participate in MDTs from 24.4% to 66.98%.Conclusion: Leadership attention was the primary concern for healthcare professionals in MDTs. To effectively motivate staff participation in MDTs, policymakers should adopt a holistic approach that considers work motivation and individual backgrounds, including competitive salary packages and a positive work environment. They should concurrently introduce MDT case complexity measurement tools to optimize resource allocation. Addressing staff members’ unique needs and career aspirations by creating targeted training programs, pathways for advancement, and personalized career development plans are also crucial.Keywords: multidisciplinary medical services, participation motivation, health services research, discrete choice experiment

Abstract Background Epimedin A (EA) has been shown to suppress extensive osteoclastogenesis and bone resorption, but the effects of EA remain incompletely understood. The aim of our study was to investigate the effects of EA on osteoclastogenesis and bone resorption to explore the corresponding signalling pathways. Methods Rats were randomly assigned to the sham operation or ovariectomy group, and alendronate was used for the positive control group. The therapeutic effect of EA on osteoporosis was systematically analysed by measuring bone mineral density and bone biomechanical properties. In vitro, RAW264.7 cells were treated with receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) to induce osteoclast differentiation. Cell viability assays, tartrate-resistant acid phosphatase (TRAP) staining, and immunofluorescence were used to elucidate the effects of EA on osteoclastogenesis. In addition, the expression of bone differentiation-related proteins or genes was evaluated using Western blot analysis or quantitative polymerase chain reaction (PCR), respectively. Results After 3 months of oral EA intervention, ovariectomized rats exhibited increased bone density, relative bone volume, trabecular thickness, and trabecular number, as well as reduced trabecular separation. EA dose-dependently normalized bone density and trabecular microarchitecture in the ovariectomized rats. Additionally, EA inhibited the expression of TRAP and NFATc1 in the ovariectomized rats. Moreover, the in vitro results indicated that EA inhibits osteoclast differentiation by suppressing the TRAF6/PI3K/AKT/NF-κB pathway. Further studies revealed that the effect on osteoclast differentiation, which was originally inhibited by EA, was reversed when the TRAF6 gene was overexpressed. Conclusions The findings indicated that EA can negatively regulate osteoclastogenesis by inhibiting the TRAF6/PI3K/AKT/NF-κB axis and that ameliorating ovariectomy-induced osteoporosis in rats with EA may be a promising potential therapeutic strategy for the treatment of osteoporosis.

Man Yang,1– 3,&ast; Xiang Xu,4,5,&ast; Xing-an Zhao,1,2 Yun-na Ge,1,2 Juan Qin,1 Xi-ya Wang,1,2 Hua-lei Dai,1 Ji Jia,1 Si-ming Tao1 1Department of Cardiology, The Affiliated Hospital of Yunnan University, Kunming City, Yunnan Province, People’s Republic of China; 2School of Medicine, Dali University, Dali City, Yunnan Province, People’s Republic of China; 3Department of Cardiology, The First People’s Hospital of Dali, Dali City, Yunnan Province, People’s Republic of China; 4School of Medicine, Yunnan University, Kunming City, Yunnan Province, People’s Republic of China; 5Department of Cardiology, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Si-ming Tao, Department of Cardiology, The Affiliated Hospital of Yunnan University, No. 176, Youth Road, Kunming, Yunnan Province, 650021, People’s Republic of China, Email taosm6450@ynu.edu.cnBackground: Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF.Methods: This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses.Results: Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism.Conclusion: Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.Keywords: atrial fibrillation, M2 macrophage, cardiac fibrosis, inflammation, single-cell RNA-sequencing, bulk RNA-sequencing

Fangfang Fan,1,2,&ast; Zhe Liang,1,2,&ast; Zhihao Liu,1 Pengfei Sun,1 Lihua Hu,1 Jia Jia,1,2 Yan Zhang,1,2 Jianping Li1,2 1Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China; 2Institute of Cardiovascular Disease, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianping Li, Department of Cardiology & Institute of Cardiovascular Disease, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Email lijianping03455@pkufh.comPurpose: Early identification of new residual risk factors for coronary heart disease (CHD) is warranted. In this study, we aim to investigate the association between the serine concentration, an important amino acid in one-carbon metabolism, and CHD in Chinese hospitalized patients.Patients and Methods: This case–control study included 428 case–control pairs comprising patients with CHD with a maximum coronary artery stenosis degree of > 70% and controls with stenosis of < 30%. The individuals were matched by age, sex, and date of coronary angiography at Peking University First Hospital from January 1, 2016, to December 31, 2019. Conditional logistic regression was used to investigate the associations between the serine concentration and CHD.Results: Patients with CHD were aged 63.48 ± 10.38 years, and 43.73% were male. Compared with controls, patients with CHD had a slightly lower serine concentration (13.35 ± 4.20 vs 13.77 ± 4.08 μg/mL), but the difference was not significant. In the multivariable conditional logistic regression analysis, for every 1 μg/mL increase in serine concentration, the odds of CHD decreased by 6% (95% confidence interval [CI] 0.90– 0.99; P = 0.010). Patients with a serine concentration of ≥ 13.41 μg/mL had a lower CHD risk than those with a serine concentration of < 13.41 μg/mL (odds ratio [OR] 0.57, 95% CI 0.39– 0.84; P = 0.004). Subgroup analyses showed that sex interacted with the relationship between serine concentration and CHD (Pinteraction = 0.039), which was more significant in males (OR 0.93, 95% CI 0.87– 0.98; P = 0.013) than in females.Conclusion: This study observed an inverse association between the serine concentration and CHD prevalence in Chinese hospitalized patients, which revealed that serine might play a protective role in CHD.Keywords: serine, coronary heart disease, case–control, one-carbon metabolism

Hongmei Sun,1,2 Chao Lv,2,3 Xiaoxue Zhang,1,2 Xuan Sun,1,3,4 Siyu Chen,1,3,4 Ke Li,3,4 Yazhuo Hu,2,3 Yuxin Feng,1,2 Tong Yin,2,3 Jianjun Jia2,3 1Medical School, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Institute of Geriatrics, Chinese PLA General Hospital, Beijing, People’s Republic of China; 3National Clinical Research Center of Geriatric Diseases, Chinese PLA General Hospital, Beijing, People’s Republic of China; 4Department of Geriatric Neurology, the Second Medical Centre, Chinese PLA General Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jianjun Jia; Tong Yin, Institute of Geriatrics, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, Haidian District, 100853, People’s Republic of China, Email jiajianjun301@126.com; yintong301@163.comBackground: Genetic variation plays an important role in drug response, there are few relevant studies on patients with Alzheimer’s disease continuum (ADC).Objective: This study focused on the associations between two single nucleotide polymorphisms (SNPs) (rs3793790 and rs2177370) located in the CHAT gene and donepezil response in ADC patients, and further evaluated the associations between the two SNPs and ADC.Material and Methods: According to 2018 National Institute on Aging and Alzheimer’s Association (NIA-AA) standard, amyloid β-protein positive (Aβ+) and negative (Aβ-) patients were recruited according to the Aβ-PET/CT standard. rs3793790 and rs2177370 were genotyped in buccal swab samples by using the MassARRAY system. We used the Mini Mental State Examination (MMSE) in Chinese version, caregiver evaluation, and prescribing behavior to assess therapeutic response during the 9-month period. Using logistic regression models, we analyzed the relationship between the two SNPs and donepezil response in 58 Aβ+ patients treated with donepezil alone at the initial diagnosis of ADC. We also explored a probable link between the two SNPs and ADC in 147 Aβ+ and 73 Aβ– patients using a logistic regression analysis.Results: The chance of donepezil response was higher in patients with the G allele of rs3793790 and/or the A allele of rs2177370 than in those without (odds ratio (OR) 6.83, 95% confidence interval (CI): 1.64– 28.49). Additionally, the rs3793790 variant was not associated with ADC, whereas the A allele in rs2177370 increased 1.51-fold the ADC risk (OR 2.51, 95% CI: 1.28– 4.95).Conclusion: The genetic variants of rs3793790 and rs2177370 were associated with the donepezil response, and rs2177370 may have a moderate relationship with the risk of ADC.Keywords: Alzheimer’s disease, pharmacogenomics, variant, gene, donepezil

Qian Chen,1,2 Chengyin Yu,1,2 Qingqing Wu,1,2 Rong Song,1,2 Ye Liu,1,2 Sheng Feng,3 Chen Yu,1,2 Jingying Jia1,2 1Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, People’s Republic of China; 3Jiangsu Hengrui Pharmaceuticals Co., Ltd, Lianyungang, Jiangsu, People’s Republic of ChinaCorrespondence: Jingying Jia, Center Laboratory, Shanghai Xuhui Central Hospital, No. 966, Huaihai Road (M), Shanghai, People’s Republic of China, Tel/Fax +86-21-54030254, Email jyjia@shxh-centerlab.comPurpose: Henagliflozin is an original, selective sodium-glucose cotransporter 2 (SGLT2) inhibitor. Hydrochlorothiazide (HCTZ) is a common anti-hypertensive drug. This study aimed to evaluate the potential interaction between henagliflozin and HCTZ.Methods: This was a single-arm, open-label, multi-dose, three-period study that was conducted in healthy Chinese volunteers. Twelve subjects were treated in three periods, period 1: 25 mg HCTZ for four days, period 2: 10 mg henagliflozin for four days and period 3: 25 mg HCTZ + 10 mg henagliflozin for four days. Blood samples and urine samples were collected before and up to 24 hours after drug administrations on day 4, day 10 and day 14. The plasma concentrations of henagliflozin and HCTZ were analyzed using LC-MS/MS. The urine samples were collected for pharmacodynamic glucose and electrolyte analyses. Tolerability was also evaluated.Results: The 90% CI of the ratio of geometric means (combination: monotherapy) for AUCτ,ss of henagliflozin and HCTZ was within the bioequivalence interval of 0.80– 1.25. For henagliflozin, co-administration increased Css, max by 24.32% and the 90% CI of the GMR was (108.34%, 142.65%), and the 24-hour urine volume and glucose excretion decreased by 0.43% and 19.6%, respectively. For HCTZ, co-administration decreased Css, max by 19.41% and the 90% CI of the GMR was (71.60%, 90.72%), and the 24-hour urine volume and urinary calcium, potassium, phosphorus, chloride, and sodium excretion decreased by 11.7%, 20.8%, 11.8%, 11.9%, 22.0% and 15.5%, respectively. All subjects (12/12) reported adverse events (AEs), but the majority of theses AEs were mild and no serious AEs were reported.Conclusion: Although Css,max was affected by the combination of henagliflozin and HCTZ, there was no clinically meaningful safety interaction between them. Given these results, coadministration of HCTZ should not require any adaptation of henagliflozin dosing.Trial Registration: ClinicalTrials.gov NCT06083116.Keywords: henagliflozin, drug-drug interaction, hydrochlorothiazide, pharmacokinetics, tolerability, pharmacodynamics, selective sodium-glucose cotransporter 2

Jingchao Jia,1,2,&ast; Jing Yang,3,&ast; Leimin Qian,2 Biao Zhou,2 Xiaodong Tang,2 Shuanghai Liu,2 Li Wu,4 Jifeng Chen,5 Yuting Kuang1 1Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2Department of General Surgery, Jiangyin Hospital Affiliated to Nantong University, Wuxi, People’s Republic of China; 3Jiangnan University Medical Center, Wuxi, People’s Republic of China; 4Department of Pharmaceutics, People’s Hospital of Shanggao, Yichun, People’s Republic of China; 5The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuting Kuang, Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China, Email yuting_kuang@163.com Jifeng Chen, The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, People’s Republic of China, Email chenjifeng-1987@163.comIntroduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range.Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2’-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy.Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth.Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.Keywords: NIR-controlled siRNA release, nanopolyplex, UCNPs, anti-tumor therapy

BackgroundAdjuvants are widely used to enhance and/or direct vaccine-induced immune responses yet rarely evaluated head-to-head. Our trial directly compared immune responses elicited by MF59 versus alum adjuvants in the RV144-like HIV vaccine regimen modified for the Southern African region. The RV144 trial of a recombinant canarypox vaccine vector expressing HIV env subtype B (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost adjuvanted with alum is the only trial to have shown modest HIV vaccine efficacy. Data generated after RV144 suggested that use of MF59 adjuvant might allow lower protein doses to be used while maintaining robust immune responses. We evaluated safety and immunogenicity of an HIV recombinant canarypox vaccine vector expressing HIV env subtype C (ALVAC-HIV) prime followed by ALVAC-HIV plus a bivalent gp120 protein vaccine boost (gp120) adjuvanted with alum (ALVAC-HIV+gp120/alum) or MF59 (ALVAC-HIV+gp120/MF59) or unadjuvanted (ALVAC-HIV+gp120/no-adjuvant) and a regimen where ALVAC-HIV+gp120 adjuvanted with MF59 was used for the prime and boost (ALVAC-HIV+gp120/MF59 coadministration).Methods and findingsBetween June 19, 2017 and June 14, 2018, 132 healthy adults without HIV in South Africa, Zimbabwe, and Mozambique were randomized to receive intramuscularly: (1) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/MF59 (months 3, 6, and 12), n = 36; (2) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/alum (months 3, 6, and 12), n = 36; (3) 4 doses of ALVAC-HIV+gp120/MF59 coadministered (months 0, 1, 6, and 12), n = 36; or (4) 2 priming doses of ALVAC-HIV (months 0 and 1) followed by 3 booster doses of ALVAC-HIV+gp120/no adjuvant (months 3, 6, and 12), n = 24. Primary outcomes were safety and occurrence and mean fluorescence intensity (MFI) of vaccine-induced gp120-specific IgG and IgA binding antibodies at month 6.5. All vaccinations were safe and well-tolerated; increased alanine aminotransferase was the most frequent related adverse event, occurring in 2 (1.5%) participants (1 severe, 1 mild). At month 6.5, vaccine-specific gp120 IgG binding antibodies were detected in 100% of vaccinees for all 4 vaccine groups. No significant differences were seen in the occurrence and net MFI of vaccine-specific IgA responses between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/alum-prime-boost groups or between the ALVAC-HIV+gp120/MF59-prime-boost and ALVAC-HIV+gp120/MF59 coadministration groups. Limitations were the relatively small sample size per group and lack of evaluation of higher gp120 doses.ConclusionsAlthough MF59 was expected to enhance immune responses, alum induced similar responses to MF59, suggesting that the choice between these adjuvants may not be critical for the ALVAC+gp120 regimen.Trial registrationHVTN 107 was registered with the South African National Clinical Trials Registry (DOH-27-0715-4894) and ClinicalTrials.gov (NCT03284710).

Jicheng Jia,1,2 Yongchao Ma,3 Shengnan Xu,1 Jiaqi Zheng,2 Xinli Ma,2 Yuzhen Zhang,2 Weijuan Sun,2 Lizhi Liu2 1Department of Education, The National University of Malaysia, Kuala Lumpur, Malaysia; 2Department of Talent Development and Continuing Education, Shandong Shengli Vocational College, Dongying, Shandong, People’s Republic of China; 3Computer Science, North Dakota State University, Fargo, ND, USACorrespondence: Jicheng Jia, Tel +86 15689138097, Email wabajjc@163.comObjective: This study aimed to investigate the impact of academic self-efficacy on test anxiety among higher vocational students, as well as the role of sense of life meaning, fear of failure, and gender difference in mediating this relationship.Methods: A total of 2231 higher vocational students from Shandong Province were surveyed by means of Academic Self-efficacy Questionnaire, Meaning in Life Questionnaire, and Test Anxiety Scale.Results: There were significant negative correlations among academic self-efficacy, sense of life meaning, and test anxiety. Fear of failure was positively correlated with test anxiety. Sense of life meaning and fear of failure played a mediating role in the relationship between academic self-efficacy and test anxiety. The chain mediating effect was significant only in the female group, not in the male group. In contrast, academic self-efficacy indirectly predicted test anxiety by the independent mediating effect of sense of life meaning or fear of failure in the male group.Conclusion: Academic self-efficacy may influence test anxiety through the independent mediating effect of sense of life meaning, fear of failure, and the chain mediating effect, and there is a gender difference in these effects.Keywords: higher vocational students, academic self-efficacy, sense of life meaning, fear of failure, test anxiety

Ge Ban,1 Yingze Hou,2 Zhean Shen,3 Jingjing Jia,1 Lei Chai,1 Chongyang Ma1 1School of Intelligent Medical Engineering, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 2Clinical Medical College, Sanquan College of Xinxiang Medical University, Xinxiang, 453003, People’s Republic of China; 3Department of Biomedical Research, Research and Innovation Center, Xinjiang Institute of Technology, Xinjiang, 843100, People’s Republic of ChinaCorrespondence: Ge Ban, Email bange119@qq.comAbstract: Graphene-family nanomaterials (GFNs) possess mechanical stiffness, optical properties, and biocompatibility making them promising materials for biomedical applications. However, to realize the potential of graphene in biomedicine, it must overcome several challenges that arise when it enters the body’s circulatory system. Current research focuses on the development of tumor-targeting devices using graphene, but GFNs accumulated in different tissues and cells through different pathways, which can cause toxic reactions leading to cell apoptosis and body dysfunction when the accumulated amount exceeds a certain limit. In addition, as a foreign substance, graphene can induce complex inflammatory reactions with immune cells and inflammatory factors, potentially enhancing or impairing the body’s immune function. This review discusses the biomedical applications of graphene, the effects of graphene materials on human immune function, and the biotoxicity of graphene materials.Keywords: graphene family nanomaterials, biomedical, biocompatibility, biomedical limitation, immune system

Jingnan Jia, Chaoqun Yan, Xiancheng Zheng, Anqi Shi, Zhijun Li, Lufan Xu, Zhiyuan Hui, Yichao Chen, Zimin Cao, Jun Wang Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of ChinaCorrespondence: Chaoqun Yan; Jun Wang, Department of Acupuncture and Moxibustion, Dongzhimen Hospital, Beijing University of Chinese Medicine, Hai Yun Cang on the 5th Zip, Dongcheng District, Beijing, 100700, People’s Republic of China, Tel +86-10-84013161, Email yanchaoqun857@126.com; wangjunee@yeah.netPurpose: Acupuncture has been recognized as an effective and safe alternative therapy for migraine, but its central mechanism has not yet been adequately explained. Meanwhile, research into the clinical efficacy and central mechanism of true acupuncture (TA) and sham acupuncture (SA) is lacking. It is necessary to investigate whether TA has better efficacy than SA, and how they achieve different effects. This study aims to evaluate the efficacy of TA and SA, observe the brain response caused by TA and SA, and further investigate the central nervous mechanism of TA and SA treatment for patients with migraine.Patients and Methods: This is a randomized controlled neuroimaging trial combining acupuncture treatment with functional magnetic resonance imaging, with patients and outcome assessors blinded. A total of 60 patients with migraine will be randomly allocated to receive 12 sessions of either TA or SA treatments (three sessions per week for 4 weeks), and 30 healthy participants will be recruited as the healthy control (HC) group. Outcome assessment and neuroimaging will be conducted before and after the entire intervention. A headache diary and questionnaires of life quality and psychological properties will be used to evaluate clinical efficacy. Multimodal magnetic resonance imagining data analysis will be used to investigate the central mechanism of TA or SA in treating migraine. Pearson’s correlation analysis will be used to reveal the relationship between the brain response and clinical improvements.Conclusion: The results of this study will reveal the brain response to TA and SA in patients with migraine and contribute to further expanding the knowledge of their central mechanism.Study Registration: This trial has been approved by the ethics committee of Dongzhimen Hospital affiliated to Beijing University of Chinese Medicine (DZMEC-KY-2020-38) and registered in the Chinese Clinical Trial Registry (registration number ChiCTR2000033995).Keywords: migraine, acupuncture, functional magnetic resonance imaging, protocol

Yanfang Liu,1– 3,&ast; Xinmin Liu,1,2,&ast; Jiaokun Jia,1– 3 Jiahuan Guo,1,2 Guangshuo Li,1,2 Xingquan Zhao1– 4 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao, Email zxq@vip.163.comBackground and Purpose: There is limited available evidence for the relationship between uric acid (UA) levels and ischemic stroke in young adults. We aimed to explore the association between UA levels and acute ischemic stroke (AIS) in young patients.Materials and Methods: This was a prospective and observational study. We recruited young patients aged 18– 45 years with AIS at our tertiary hospital. Patients were categorized into four groups according to quartiles of UA levels. The primary outcome was functional outcome at 3 months. The secondary outcomes included stroke severity, in-hospital complications, and functional outcome at discharge. Modified Rankin Scale (mRS) scores were used to assess functional outcome as poor (mRS=2-6) or favorable(mRS=0-1).Results: A total of 636 patients were enrolled in the current analysis. The four groups were defined as follows: Q1≤ 289.8 μmol/L, 289.8 μmol/ L

Qu-Zhen Tashi,1 Sang-Bu Tsering,1 Na-Ni Zhou,2 Yi Zhang,2 Yu-Juan Huang,3 Jia Jia,2 Ting-Jun Li3 1Department of Pediatrics, Shigatse Peopel’s Hospital, Shigatse, Tibet, 857000, People’s Republic of China; 2Fujungenetics Technologies Inc. Shanghai, Shanghai, 200333, People’s Republic of China; 3Department of Emergency, Children’s Hospital of Shanghai, Shanghai, 200062, People’s Republic of ChinaCorrespondence: Ting-Jun Li, Department of Emergency, Children’s Hospital of Shanghai, No. 355 of Huding Road, Putuo District, Shanghai, 200062, People’s Republic of China, Tel +86 18930590701, Email lijuntingta@126.com Jia Jia, Fulgent Technologies Inc, No. 70 of Tongchuan Road, Putuo District, Shanghai, 200333, People’s Republic of China, Tel +86 18658176000, Email jiajiajjyat@126.comObjective: High altitude heart disease (HAHD) is a common pediatric disease in high altitude areas. It usually occurs in people who have lived for a long time or have lived for more than 2500m above sea level. Its common inducement is respiratory tract infection. The clinical differential diagnosis is difficult because the symptoms of HAHD are similar to those of congenital heart disease; Due to the limitation of medical conditions, many patients are in the state of losing follow-up or not seeking medical treatment, resulting in poor prognosis of HAHD and becoming a high-altitude disease with high mortality. Clarifying the molecular mechanism of HAHD, developing early molecular screening technology and accurate treatment methods of HAHD are the key to improve the ability of prevention and treatment of HAHD.Methods: First, the literature in the PubMed and CNKI databases were screened based on keywords and abstracts. Then, the literature for the study was identified based on the fitness between the content of the literature, the research objectives, and the timeliness of the literature. Finally, a systematic molecular mechanism of HAHD was established by investigating the literature and sorting out the genetic adaptations of Tibetan populations compared with low-altitude populations that migrated to the plateau.Results: With the investigation of the 48 papers screened, it was found that genes capable of enhancing the hypoxic ventilatory response and resistance to pulmonary hypertension were all correlated with the hypoxia-inducible factor (HIF) pathway, consisting mainly of three pathways, HIF-1α, HIF-2α, and NO.Conclusion: The low prevalence of HAHD in Tibetan aboriginal children was mainly due to the genetic adaptation of the Tibetan population to the high altitude environment, which coordinated the cellular response to hypoxia by regulating the downstream hypoxia control genes in the HIF pathway.Keywords: altitude sickness, pediatric, high altitude heart disease, HAHD, molecular mechanism

Huan Tang, Yizhuo Xie, Ming Zhu, Juan Jia, Rui Liu, Yujia Shen, Yucui Zheng, Xin Guo, Dongfanghui Miao, Jin Pei Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Jin Pei, Department of Biopharmacy, School of Pharmaceutical Sciences, Jilin University, 1163 Xinmin Street, Changchun, 130021, People’s Republic of China, Tel +86 431 85619725, Email peijin@jlu.edu.cnPurpose: Ovarian cancer is the most lethal gynecologic malignancy. The combination of paclitaxel (PTX) and carboplatin (CBP) is the first-line remedy for clinical ovarian cancer. However, due to the limitations of adverse reaction and lacking of targeting ability, the chemotherapy of ovarian cancer is still poorly effective. Here, a novel estrone (ES)-conjugated PEGylated liposome co-loaded PTX and CBP (ES-PEG-Lip-PTX/CBP) was designed for overcoming the above disadvantages.Methods: ES-PEG-Lip-PTX/CBP was prepared by film hydration method and could recognize estrogen receptor (ER) over-expressing on the surface of SKOV-3 cells. The characterizations, stability and in vitro release of ES-PEG-Lip-PTX/CBP were studied. In vitro cellular uptake and its mechanism were observed by fluorescence microscope. In vivo targeting effect in tumor-bearing mice was determined. Pharmacokinetics and biodistribution were studied in ICR mice. In vitro cytotoxicity and in vivo anti-tumor efficacy were evaluated on SKOV-3 cells and tumor-bearing mice, respectively. Finally, the acute toxicity in ICR mice was explored for assessing the preliminary safety of ES-PEG-Lip-PTX/CBP.Results: Our results showed that ES-PEG-Lip-PTX/CBP was spherical shape without aggregation. ES-PEG-Lip-PTX/CBP exhibited the optimum targeting effect on uptake in vitro and in vivo. The pharmacokinetics demonstrated ES-PEG-Lip-PTX/CBP had improved the pharmacokinetic behavior. In vitro cytotoxicity showed that ES-PEG-Lip-PTX/CBP maximally inhibited SKOV-3 cell proliferation and its IC50 values was 1.6 times lower than that of non-ES conjugated liposomes at 72 h. The in vivo anti-tumor efficacy study demonstrated that ES-PEG-Lip-PTX/CBP could lead strong SKOV-3 tumor growth suppression with a tumor volume inhibitory rate of 81.8%. Meanwhile, acute toxicity studies confirmed that ES-PEG-Lip-PTX/CBP significantly reduced the toxicity of the chemo drugs.Conclusion: ES-PEG-Lip-PTX/CBP was successfully prepared with an optimal physicochemical and ER targeting property. The data of pharmacokinetics, anti-tumor efficacy and safety study indicated that ES-PEG-Lip-PTX/CBP could become a promising therapeutic formulation for human ovarian cancer in the future clinic.Graphical Abstract: Keywords: ovarian cancer, combination therapy, drug delivery system, liposome, estrogen receptor

Jie Jia,1,2 Ji-Qun Yang,3 Ying-Rong Du,3 Yu Xu,2 Deshenyue Kong,1,2 Xiu-Ling Zhang,3 Jun-Hong Mao,1,2 Gui-Fang Hu,3 Kun-Hua Wang,1,2,4 Yi-Qun Kuang1,2 1NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 3Third People’s Hospital of Kunming City/Drug Rehabilitation Hospital of Kunming City, Kunming, 650041, People’s Republic of China; 4School of Medicine, Yunnan University, Kunming, 650500, People’s Republic of ChinaCorrespondence: Yi-Qun Kuang; Kun-Hua Wang, NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People’s Republic of China, Email yq610433@hotmail.com; wangkunhua1964@126.comBackground: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown.Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS).Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR.Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.Keywords: drug use, hypertension, treatment-resistant, transcriptome, immunoregulation

Suting Chen,&ast; Fen Wang,&ast; Yi Xue, Fengmin Huo, Junnan Jia, Lingling Dong, Liping Zhao, Guanglu Jiang, Hairong Huang National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, China&ast;These authors contributed equally to this workCorrespondence: Hairong Huang, Email huanghairong@tb123.org; Guanglu Jiang, guanglu0725@126.comBackground: Nontuberculous mycobacteria (NTM) and their associated diseases remain neglected. Through minor modifications in our diagnostic algorithm, we observed an unexpected higher number of cultivable NTM isolates. Therefore, a retrospective study was performed thoroughly to investigate the effect of changed laboratory procedures on NTM isolation in a specialized tuberculosis hospital.Methods: NTM isolation rates and composition of NTM species were compared for the two diagnostic algorithms: (1) by using traditional p-nitrobenzoic acid (PNB) selective medium as a preliminary test to identify NTM isolates among the positive cultures (procedure I) and (2) by using the MPT64 antigen detection method to distinguish between Mycobacterium tuberculosis complex (MTBC) isolates and possible NTM isolates after a positive MGIT960 liquid culture (procedure II).Results: The NTM isolation rate in procedure II was significantly higher than the procedure I (18.08% vs 9.71%; P< 0.001). A noticeable increase in the ratio of NTM isolates among the identified mycobacteria was observed over the studied years (ie, from 58.18% in 2019 to 72.93% in 2021), which indicated a more precise prescription of species identification test after prompt information was provided in procedure II. In addition, the consistency of the identified species using multiple specimens from the same patient did not present a significant difference between the procedures.Conclusion: According to our study, NTM infection might be far more underestimated than it is. A diagnostic procedure combining MGIT960 culture and MPT64 antigen detection could timely and easily identify clues of NTM isolates and improve the diagnosis of NTM infections.Keywords: tuberculosis, nontuberculous mycobacteria, p-nitrobenzoic acid, MPT64 antigen, species

Abstract Background The high prevalence of falling among older adults constitutes a major public and clinical health concern. Many elderly persons may develop activities-specific restriction due to the risk of falling. This highlights the need for relevant evaluative tools. Methods This cross-sectional study used activities-specific performance frequency indicators to quantify activity restrictions in elderly participants, with all measures based on items from the Activities-Specific Balance Confidence (ABC) scale. Specifically, we tested for correlations between activities-specific performance frequency and balance confidence, functional balance/mobility, and fall history. There were 88 elderly participants, including 28 with stroke, 30 with Parkinson’s disease, and 30 with no neurological diseases. In addition to their activities-specific performance frequency measures, we collected a series of demographic and health-related characteristics from each participant. We analyzed between-group differences in activities-specific performance frequency and other demographic and health-related characteristics via the one-way analysis of variance and Kruskal-Wallis test. Next, we used the Spearman’s rank correlation test and binary logistic regression to investigate the correlations between activities-specific performance frequency and demographic/other health-related characteristics. Results There were significant group differences in performance frequency for all ABC activity items except for walking around the house, average ABC scores, and functional balance/mobility among normal older adults, participants with strokes and those with Parkinson's disease. Activities-specific performance frequency showed stronger correlations with activities-relevant functional mobility (r=0.250-0.713 for 15 items with significant correlations, 13 activity items with r≧0.4) than with balance confidence (r=0.279-0.668 for 13 items with significant correlations, 10 activity items with r≧0.4). The performance frequency of walking in crowds/bumped was the most sensitive measure for predicting fallers (odd ratio=3.310, p

Xuechun Wang,1,&ast; Jia Jia,2,&ast; Xuehong Gu,3 Wei-wei Zhao,4 Caiping Chen,5 Wanxin Wu,6 Jiayuan Wang,1 Midie Xu7 1Department of Laboratory, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 2Shanghai Center for Bioinformation Technology, Shanghai, 201202, People’s Republic of China; 3Department of Nursing, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 4Department of Rehabilitation Medicine, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 5Department of Breast Surgery, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 6Department of Pathology, Jiaxing First Hospital, Jiaxing, 314000, People’s Republic of China; 7Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuehong GuDepartment of Nursing, Jiaxing First Hospital, No. 1882 of Central South Road, Jiaxing, 314000, People’s Republic of ChinaTel +86 13957368443Fax +86 573-83599079Email guxuehong145@163.comObjective: Breast cancer has become a fatal disease for women world-wide. Its incidence in China has been increasing yearly, and the identification of early-stage biomarkers is urgently required.Methods: ANOVA was carried out in the case of a primary tumor, adjacent normal tissue, and tumor metastasis of breast cancer, and on pan-cancer samples using the genome-wide methylation data of 31 solid tumor Illumina Methylation 450K chips downloaded from The Cancer Genome Atlas (TCGA) website in September 2018. Methylation sites showing a significant difference (P ≤ 0.05) were screened and compared with the whole-genome methylation data of 31 other solid tumor species in the TCGA database using t-tests in order to screen the methylation sites of breast cancer-specific expression. The expression of the screened methylation sites was confirmed through pyrosequencing in 45 cases of breast cancer, lung cancer, gastric cancer, and colorectal cancer.Results: A total of 10 specific breast cancer methylation sites (cg13683194, cg07996594, cg21646032, cg07671949, cg21185686, cg03625109, cg16429070, cg23601468, cg24818566, and cg01240931) were analyzed; nine genes (C9orf125, RARB, ESR1, RUNX3, PCDHGB7, DBC1, PDGFRB, TIMP3, and APC) were involved. The overall effect was excellent; a total of 4 methylation sites (2 in the DBC1 gene [cg03625109 and cg24818566], 1 in the C9orf125 gene [cg13683194], and 1 in the PDGFRB gene [cg16429070]) could effectively distinguish breast cancer from 31 other cancer species. The pyrosequencing results revealed that 7 screened methylation sites could significantly distinguish between breast cancer, lung cancer, gastric cancer, and colorectal cancer samples; these sites could also specifically distinguish between luminal A, luminal B, HER2, and Basal-like types of breast cancer.Conclusion: The 10 breast cancer methylation sites screened in the present study can effectively distinguish breast cancer from 31 other solid tumors, and they are expected to be used as biomarkers for early screening of breast cancer.Keywords: breast cancer, Basal-like breast cancer, methylation, biomarker, TCGA, ANOVA

Jie Cheng,1,&ast; Siyang Wang,2,&ast; Jingying Jia,3 Qian Chen,3 Yunxiao Song,4 Junsheng Li1 1Department of Urinary Surgery, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Department of Geratology, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 3Department of Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 4Department of Clinical Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junsheng LiDepartment of Urinary Surgery, Shanghai Xuhui Central Hospital, No. 966 Huaihai Road, Shanghai, 200031, People’s Republic of ChinaTel +86-21 31270810Email lijunshengdy@163.comPurpose: Red cell distribution width (RDW), an inflammation biomarker, has been linked to poor outcomes in patients with different types of cancers. The present study aimed to investigate the relationship between pre-/post-treatment 3-month RDW levels and changes in RDW with 3-year prognosis of prostate cancer.Patients and Methods: A total of 348 patients with prostate cancer were recruited between June 1, 2012 and June 1, 2017 and were followed up for at least 3 years. RDW was measured with the Mindray BC-6800Plus automatic blood counting system at pre- and post-treatment 3-month. Demographic and clinical information of the participants were also collected. The overall survival (OS) and cancer-specific survival (CSS) were analyzed using the Kaplan–Meier method. Cox regression and competing risk regression analyses were performed.Results: During the follow-up period, 51 (14.66%) deaths occurred. The levels of pre- and post-treatment RDW levels were significantly higher in the death group than in the survival group (p< 0.001). In the death group, the level of RDW continued to rise in most subjects, and the mean level of RDW was significantly higher at post-treatment than pre-treatment, contrary to the results observed in the survival group. Multivariate Cox regression analysis revealed that high pre-treatment RDW, high post-treatment RDW, and persistently higher RDW were independently associated with OS and CSS (p< 0.001). Similar results were observed in the competing risk regression analysis. Kaplan–Meier analysis revealed that patients with higher pre-treatment RDW levels, higher post-treatment RDW levels, and persistently higher RDW levels had poorer 3-year OS and CSS rates (p< 0.05).Conclusion: The levels of and changes in RDW before and after treatment were associated with the 3-year prognosis of prostate cancer, suggesting that RDW might be an efficient prognostic predictor in patients with prostate cancer.Keywords: red cell distribution width, prostate cancer, prognostic, overall survival, cohort study

Danyun Jia,1 Jinyu Zheng,2 Yiyang Zhou,2 Jinqiu Jia,3 Xiaoxiao Ye,4 Bingbing Zhou,4 Xingxing Chen,4 Yunchang Mo,1 Junlu Wang1 1Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China; 2Department of Clinical Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of China; 3Department of Pediatric, Taizhou Women and Children’s Hospital of Wenzhou Medical University, Taizhou, 317599, Zhejiang, People’s Republic of China; 4Department of Nursing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People’s Republic of ChinaCorrespondence: Yunchang Mo; Junlu Wang Email myc1104@163.com; wjlprof2020@163.comPurpose: To evaluate whether ferroptosis is involved in hyperoxic acute lung injury (HALI) and its mechanisms through the HALI model.Methods: HE staining was used to assess lung injury pathology after the establishment of neonatal rat HALI model. ELISA was used to detect ROS, GPX4, and GSH expression. Prussian blue staining and Western Blot were used to detect iron deposition and the expression of ferroptosis-related proteins, respectively.Results: The HALI group showed pathological changes with larger and fewer alveoli and thicker alveolar septa after HE staining. Prussian blue staining detected significant iron deposition in the lung tissue of the HALI group. GPX4, GSH, GSS, and SLC7A11 expressions were significantly decreased in the HALI group than in the normal control group. In contrast, ROS, TFRC, FHC, and FLC expressions showed opposite results (p< 0.05).Conclusion: Ferroptosis may be involved in the pathological process of hyperoxic lung injury in neonatal rats.Keywords: ferroptosis, hyperoxic lung injury, neonatal rats

Hongjie Qian,1,2 Qian Chen,1,2 Liyu Liang,1,2 Yang Zou,1,2 Huahua Pu,1,2 Liang Xin,1,2 Rong Song,1,2 Tingting Li,1,2 Huijuan Zhu,1,2 Yu Wang,3 Guanghui Tian,4 Jingshan Shen,2,3 Hualiang Jiang,2,3 Chen Yu,1,2 Zhen Wang,2,3 Jingying Jia1,2 1Central Laboratory, Shanghai Xuhui Central Hospital, Shanghai, 200031, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, 200031, People’s Republic of China; 3CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People’s Republic of China; 4Vigonvita Life Science Co., Ltd., Suzhou, 215123, People’s Republic of ChinaCorrespondence: Jingying JiaShanghai Xuhui Central Hospital, No. 966, Huaihai Road(M), Shanghai, 200031, People’s Republic of ChinaTel/Fax +86 21 54030254Email jyjia@shxh-centerlab.comZhen WangShanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555 Zu Chong Zhi Road, Pudong, Shanghai, 201203, People’s Republic of ChinaTel +86 21 20231000Fax +86 21 20231962Email wangzhen@simm.ac.cnPurpose: TPN171H is a novel, potent and selective phosphodiesterase type 5 (PDE5) inhibitor for the treatment of pulmonary arterial hypertension (PAH). The objective of this study was to evaluate the safety, tolerability, and pharmacokinetics of TPN171H in healthy subjects after single and multiple dosing, in addition, to investigate the food effect on pharmacokinetics and safety of TPN171H.Methods: The entire study was comprised of three parts: Part I (single ascending-dose study), Part II (food effect study), and Part III (multiple ascending-dose study). A total of 63 healthy subjects were enrolled in the study. TPN171H tablet or placebo was administered per protocol requirements. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety was assessed by clinical examinations and adverse events.Results: In Part I, AUC and Cmax were proved to be linear within the 5– 30 mg dose range. T1/2 of TPN171H was 8.02– 10.88 h. In Part II, we figured out that TPN171H administration under fed condition could decrease Cmax, prolong Tmax, but had no effect on AUC. In Part III, the accumulation ratio at steady-state for AUC and Cmax indicated that TPN171H has a slight accumulation upon repeated dosing. Subjects were generally tolerable after TPN171H administration. Compared with other PDE5 inhibitors, TPN171H was found to have no impact on blood pressure and color discrimination.Conclusion: TPN171H was safe and generally tolerated in healthy subjects. Based on the half-life, food effect, and safety profile of TPN171H, we recommend a once-daily, post-meal administration of TPN171H in subsequent clinical studies in healthy subjects and patients with PAH.Keywords: TPN171H, PDE5 inhibitor, safety, pharmacokinetics, food effect, healthy subjects

Che X, Lu R, Fu Z, et al. Drug Des Devel Ther. 2018;12:3357–3368. At the authors request, the Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. The authors became aware of concerns relating to the alleged duplication of images in Figure 7. Specifically, Figure 7B, Medium (100x), appears to have been duplicated with the same image for Figure 7E, YSL 0.4 mg/ml (100x), which has been flipped. While some original data was still available, the authors were unable to retrieve all of it in a satisfactory manner. In addition, some to the key cellular extraction material had not been well preserved. While the authors were still confident in the overall findings described in the article, to maintain the integrity of the scientific publication record, they decided it appropriate to request a retraction rather than pursue a corrigendum. The editor agreed with decision and approved the authors retraction request. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Suting Chen,1,* Tianlu Teng,1,2,* Zhuman Zhang,1 Yuanyuan Shang,1,2 Hua Xiao,1 Guanglu Jiang,1 Fen Wang,1 Junnan Jia,1 Lingling Dong,1 Liping Zhao,1 Naihui Chu,2 Hairong Huang1 1National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China; 2Department of Tuberculosis; Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hairong Huang; Naihui Chu Tel +86-10-89509159; +86-10-89509301Email nclhuang@ccmu.edu.cn; dongchu1994@sina.comObjective: Treatment choices for Mycobacterium abscessus (M. abscessus) infections are very limited, and the prognosis is generally poor. Effective new antibiotics or repurposing existing antibiotics against M. abscessus infection are urgently needed. Carbonyl cyanide 3-chlorophenylhydrazone (CCCP), a member of the lipophilic weak acid class, is known as an efflux pump inhibitor for Mycobacterium tuberculosis. The aim of this study was to determine the inhibitory activity of CCCP as a potential novel antibiotic against M. abscessus.Methods: A total of 47 reference strains of different mycobacterial species and 60 clinical isolates of M. abscessus were enrolled. In vitro inhibitory activity of CCCP was accessed using microplates alamar blue method with the reference and clinical isolates. The activity of CCCP against intracellular M. abscessus residing within macrophage was also evaluated by intracellular colony numerating assay.Results: CCCP exhibited good activity against M. abscessus clinical isolates in vitro, the minimum inhibitory concentration (MIC) ranged from 0.47 μg/mL to 3.75 μg/mL, with a MIC50 of 1.875 μg/mL and MIC90 of 3.75 μg/mL. At concentrations safe for the cells, CCCP exhibited highly intracellular bactericidal activities against M. abscessus and M. massiliense reference strains, with inhibitory rates of 84.8%± 8.8% and 72.5%± 13.7%, respectively. CCCP demonstrated bactericidal activity against intracellular M. abscessus that was comparable to clarithromycin, and concentration-dependent antimicrobial activity against M. abscessus in macrophages was observed. In addition, CCCP also exhibited good activities against most reference strains of rapidly growing mycobacterial species.Conclusion: CCCP could be a potential candidate of novel antimicrobiological agent to treat M. abscessus infection.Keywords: Mycobacterium abscessus, carbonyl cyanide 3-chlorophenylhydrazone, minimum inhibitory concentration, intracellular bactericidal activity

Yusi Gao, Fangfang Fan, Jia Jia, Yimeng Jiang, Danmei He, Zhongli Wu, Yong Huo, Jing Zhou, Yan Zhang Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Jing ZhouDepartment of Cardiology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of ChinaTel +86-10-83575728Fax +86-10-66551383Email zhoujing123@yahoo.comIntroduction: Elevated heart rate is linked with poor prognosis and has been shown to accelerate the progress of atherosclerosis. However, the association between heart rate and new-onset PAD is unknown.Methods: A total of 3463 participants without PAD at baseline from a community-based cohort in Beijing were included and followed up for 2.3 years. PAD was defined as ankle–brachial index (ABI) ≤ 0.9. We used multivariate logistic regression models to investigate the association of heart rate and the risk of new-onset PAD.Results: Participants were 56.67 ± 8.54 years old, and 36.12% were men. The baseline ABI was 1.11 ± 0.08, and the incidence of new-onset PAD was 2.97%. Multivariate regression models, adjusted for sex, age, risk factor of atherosclerosis, medications, and baseline ABI, showed that heart rate was significantly associated with incidence of PAD (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.03– 1.43, P = 0.020); every increase of 10 heart beats per minute (bpm) was associated with a 22% increase in the odds of developing new-onset PAD. Respondents in the higher-heart rate group (≥ 80 bpm) had an increased risk of new-onset PAD, compared with those in the lower-heart rate group (< 80 bpm) (OR = 1.73, 95% CI: 1.14– 2.63, P = 0.010). Subgroup analyses revealed no significant heterogeneity among the analyzed subgroups.Conclusion: Elevated heart rate was independently associated with the risk of new-onset PAD in a community-based population in Beijing. Heart rate management should be considered for the purpose of PAD prevention.Keywords: cohort studies, heart rate, peripheral arterial disease, ankle–brachial index

IntroductionThe newly developed Composite Activity-related Risk of Falls Scale (CARFS) is designed to measure composite activity-related risk of falls (CARF) in relation to the activity-specific fear of falling and physical behavior. This study tested the reliability and validity of the CARFS in older people with various health statuses and persons with stroke or spinal cord injury.MethodsParticipants included 70 older adults, 38 persons with stroke, and 18 with spinal cord injury. They were first surveyed using a combined questionnaire including the CARFS and activity-specific balance confidence (ABC) scale in addition to items asking for personal and disease-related information, fall history, walking independence levels for examining internal consistency, ceiling and floor effects, and convergent validity in each participant group. One week after the initial survey, 33 older participants were reexamined using the CARFS to analyze test-retest reliability, where a minimal detectable change was found. Significance was set at α = 0.05 for all analyses.ResultsThe CARFS showed excellent test-retest reliability in the dimensions of fear of falling, physical behavior, and CARF [ICC (3,1) = 0.972, 0.994, and 0.994, respectively for their overall score], with a minimal detectable change of 3.944 in the older population. The internal consistency of CARFS items was excellent in the older participants, good in participants with stroke or spinal cord injury (Cronbach's alpha = 0.945, 0.843, 0.831 in each participant group, respectively). No ceiling and floor effects were demonstrated in the wide range of people. For the convergent validity, overall CARF score was significantly correlated with the average ABC score in each participant group (rho = −0.824, −0.761, and −0.601, respectively; p < 0.01), and was significantly correlated with walking independence levels in each participant group (rho = −0.636, −0.423, and −0.522, respectively; p < 0.01). It showed weak correlation with the number of previous falls only in participants with stroke (rho = 0.291, p = 0.076).ConclusionThe CARFS is a reliable and valid tool for measuring fall risk in older people and persons with stroke or spinal cord injury.

Jidi Zhao,1 Jianguo Jia,2 Ying Qian,3 Lumin Zhong,4 Jiancong Wang,5 Yuyang Cai4,6 1Faculty of Economics and Management, East China Normal University, Shanghai, People’s Republic of China; 2System Dynamics Chapter, Systems Engineering Society of China, Beijing, People’s Republic of China; 3School of Management, Shanghai University, Shanghai, People’s Republic of China; 4School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 5Institute of Global Health, University of Geneva, Geneva, Switzerland; 6China Institute for Urban Governance, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaCorrespondence: Yuyang Cai; Ying Qian Email caiyuyang@sjtu.edu.cn; qian.ying@t.shu.edu.cnPurpose: It is unclear how and to what extent various infection prevention and control (IPC) policies affect the spread of an epidemic during work resumption. In order to assess the impact of IPC policies, this research addresses the results of a policy simulation in Shanghai, China, which estimates the transmission dynamics of COVID-19 under various IPC policies and offers evidence-based outcomes of work resumption policies for the world.Materials and Methods: This simulation research is based on a system dynamics (SD) model that integrates IPC work resumption policies implemented in Shanghai into the classical susceptible-exposed-infected-removed (SEIR) epidemiological model. Input data were obtained from official websites, the Baidu migration index and published literature. The SD model was validated by comparing results with real-world data.Results: The simulations show that a non-quarantined and non-staged approach to work resumption (Policy 1) would bring a small secondary outbreak of COVID-19. The quarantined but non-staged approach (Policy 2) and the non-quarantined but staged approach (Policy 3) would not bring a secondary outbreak of COVID-19. However, they both would generate more newly confirmed cases than the staged and quarantined approach (Policy 4). Moreover, the 14-day quarantine policy alone appears to be more effective in reducing transmission risk than the staged work resumption policy alone. The combined staged and quarantined IPC policy led to the fewest confirmed cases caused by work resumption in Shanghai, and the spread of COVID-19 stopped (ie, the number of newly confirmed cases reduced to zero) at the earliest date.Conclusion: Conservative IPC policies can prevent a second outbreak of COVID-19 during work resumption. The dynamic systems model designed in this study can serve as a tool to test various IPC work resumption policies, facilitating decision-making in responses to combating the COVID-19 pandemic.Keywords: IPC policies, work resumption, COVID-19, system dynamics, SEIR

Qingqing Wu,1,2 Xiaodong Wang,3 Qian Chen,1,2 Yang Zou,1,2 Xiaoyan Xu,1,2 Tingting Li,1,2 Chen Yu,1,2 Fu Zhu,1,2 Kanyin E Zhang,4 Jingying Jia,1,2 Yanmei Liu1,2 1Center Laboratory, Shanghai Xuhui Central Hospital, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Phase I Clinical Research & Quality Consistency Evaluation for Drugs, Shanghai, People’s Republic of China; 3Changzhou Siyao Pharmaceuticals Co., Ltd, Jiangsu, People’s Republic of China; 4ViaClinical Ltd, Shanghai, People’s Republic of ChinaCorrespondence: Yanmei LiuCenter Laboratory, Shanghai Xuhui Central Hospital, No. 966, Huaihai Road(M), Shanghai, People’s Republic of ChinaTel/Fax +86-21-54030254Email ymliu@shxh-centerlab.comPurpose: To compare the bioequivalence of two formulations of valsartan (80 mg capsules) under fasting and fed conditions in healthy Chinese volunteers using a full-replicate study design.Methods: A total of 78 Subjects were randomly assigned to fasting cohort (n = 48) or fed cohort (n = 30). Each cohort includes 4 single-dose observation periods and 3-day washout periods. Blood samples were collected at designed time point. Plasma concentration of valsartan was analyzed by a validated LC-MS/MS method. Noncompartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the within-subject standard deviation (SWR) of the reference formulation, either reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) method was used to evaluate the bioequivalence of the two formulations.Results: Under fasting conditions, the RSABE method was used to evaluate the bioequivalence of Cmax (SWR> 0.294), while ABE method was used to evaluate the bioequivalence of AUC0-t and AUC0-∞. The geometric mean ratio (GMR) of the test/reference for Cmax was 99.52%, and the 95% upper confidence bound was < 0. For AUC0-t and AUC0-∞ comparisons, GMRs were 102.07% and 101.92%, and the 90% CIs of the test/reference were 96.28%– 108.21%, 96.28%– 107.88%, respectively. Under fed conditions, the SWR value of Cmax, AUC0-t and AUC0-∞ all exceeded the cutoff value of 0.294 and therefore, the RSABE method was used. The GMRs for Cmax, AUC0-t and AUC0-∞ were 98.78%, 103.33% and 103.08%, respectively, while the 95% upper confidence bound values were all < 0. These results all met the bioequivalence criteria for highly variable drugs. All adverse events were mild and transient.Conclusion: In this study, the generic formulation of valsartan 80 mg capsule was considered to be bioequivalent to the reference product under both fasting and fed conditions, and satisfied the requirements for marketing in China.NMPA Registration No: CTR20181422.Keywords: valsartan, bioequivalence, replicate, pharmacokinetics, safety

Mengyuan Liu,1,2 Fangfang Fan,1,2 Bo Liu,1,2 Jia Jia,1,2 Yimeng Jiang,1,2 Pengfei Sun,1,2 Danmei He,1,2 Jiahui Liu,1,2 Yuxi Li,1,2 Yong Huo,1,2 Jianping Li,1,2 Yan Zhang1,2 1Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of China; 2Institute of Cardiovascular Disease, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yan Zhang; Jianping Li Tel +86 10 83575262; +86 10 83575728Fax +86 10 66551383Email drzhy1108@163.com; lijianping03455@pkufh.comPurpose: Hyperhomocysteinemia is an independent risk factor for cardio- and cerebrovascular diseases. However, the relationship between plasma homocysteine (Hcy) concentration and peripheral arterial disease (PAD) has not been completely characterized. The aim of the present study was to determine the relationship between plasma Hcy concentration and new-onset PAD and to assess the effects of combinations of Hcy and traditional cardiovascular risk factors.Patients and Methods: We conducted a prospective community-based cohort study of 3119 Chinese participants who did not have PAD at baseline, with a median follow-up period of 2.30 years. We used multivariate logistic regression models to evaluate the relationship between high Hcy (≥ 10μmol/L) and new-onset PAD. The effects of combinations of high Hcy and traditional cardiovascular risk factors were assessed using logistic regression analysis.Results: After adjustment for 14 covariates, high Hcy concentration was significantly associated with new-onset PAD (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.08– 4.03, P=0.030). Smokers with high Hcy concentration were substantially more likely to have new-onset PAD than non-smokers with normal Hcy concentration (OR=4.44, 95% CI: 1.77– 11.12, P=0.001). The effect of diabetes on PAD became significant when present in combination with high Hcy concentration (OR=3.67, 95% CI: 1.25– 10.80, P=0.018). Participants with both elevated Hcy levels and older age had the highest risk of new-onset PAD (OR=4.28, 95% CI: 1.83– 10.01, P< 0.001). With regard to the joint effect of Hcy and hypertension, dyslipidemia or sex, there was also a trend towards increased risk across four different groups (P for trend=0.026, 0.035, 0.016, respectively).Conclusion: High plasma Hcy concentration independently predicts the incidence of PAD. Furthermore, there is a joint effect of high Hcy concentration and traditional cardiovascular risk factors such as smoking, diabetes and aging on the incidence of PAD.Keywords: peripheral arterial disease, atherosclerosis, hyperhomocysteinemia, cohort study, community-based population

Lin Wang,1,* Jun Xiao,2,* Min-Zhe Li,3 Wen-Hao Teng,2 Jing Jia,1 Lu Lin,1 Sheng Liu,2 Xing-ming Ye,1 Wei-Dong Zang,2 Ying Chen1 1Central Laboratory, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350000, People’s Republic of China; 2Department of Gastrointestinal Surgery, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350000, People’s Republic of China; 3General Surgery Department, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Dong ZangDepartment of Gastrointestinal Surgery, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350000, People’s Republic of ChinaEmail zwddoctor@126.comYing ChenCentral Laboratory, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou 350000, People’s Republic of ChinaEmail fjbccy@fjmu.edu.cnIntroduction: The aim of the present study was to evaluate a nomogram model for predicting the 5-year overall survival (OS) in lymph node-metastatic colorectal cancer (CRC) patients by combining inflammation markers with some traditional prognostic factors.Methods: A total of 399 patients with stage III (pTXN1-3M0) CRC operated from January 2007 to December 2012 were enrolled in this retrospective study. All patients underwent D2 lymphadenectomy in the hospital. A prognostic nomogram based on the integration of traditional prognostic factors and NLR (neutrophil-to-lymphocyte ratio) and PLR (platelet-to-lymphocyte ratio) was established and compared with the nomogram based on the traditional prognostic factors alone. ROC curves were further applied to verify the predictive accuracy of the established model.Results: Both NLR (P=0.00) and PLR (P=0.01) predicted the 5-year OS. In multivariate analysis, age, T3 category, T4 category, N2 category, N3 category, Pgp (P-glycoprotein), NLR and PLR are proven to be independent (all P≤ 0.05). The established nomogram showed better predictive power than that of traditional profile (c-index: 0.66 versus 0.63) in both training and validation cohorts. External assessment by ROC curve analysis demonstrated that the established model had a good prediction accuracy of 5-year OS in stage III CRC patients, with area under curve values of 0.657 and 0.629 in training and validating sets, respectively.Conclusion: A nomogram based on the integration of traditional prognostic factors and inflammatory markers (NLR and PLR) could provide more precise long-term prognosis information for lymph node-metastatic CRC patients than the model based on traditional profile alone. This model might be useful for clinical application in personalized evaluation.Keywords: nomogram, TNM staging system, lymph node metastasis, colorectal cancer, prognosis

Jiaoying Jia, Yan Cui, Zhigang Tan, Wenjia Ma, Yugang Jiang Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha City, Hunan Province 410011, People’s Republic of ChinaCorrespondence: Yugang JiangDepartment of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha City, Hunan Province 410011, People’s Republic of ChinaTel +8673185295880Email jiangyugang123@csu.edu.cnBackground/Aims: Multiple studies have found that microRNAs (miRNAs) are involved in the development of cerebral ischemia. MiR-579-3p can inhibit inflammatory responses and apoptosis, leading to ischemia/reperfusion (I/R) damage. However, the mechanism of how miR-579-3p actions in brain I/R injury remains unclear. This study aimed to investigate the mechanism of the role of miR-579-3p in brain I/R injury.Methods: A rat model of cerebral ischemia–reperfusion injury was established by suture method. The effects of miR-579-3p on cerebral infarction size, brain water content, and neurological symptoms were evaluated. Flow cytometry was used to detect apoptosis. ELISA was used to detect the level of inflammatory factors. Western blot was used to detect the expression of P65, NCOA1, Bcl-2 and Bax. The relationship between miR-579-3p and NCOA1 was analyzed by bioinformatics analysis and luciferase assay.Results: Overexpression of miR-579-3p reduced infarct volume, brain water content and neurological deficits. Overexpression of miR-579-3p inhibited the expression level of the inflammatory cytokines, such as TNF-α, IL-6, COX-2 and iNOS, and increased the expression level of IL-10. MiR-579-3p overexpression inhibited NF-кB activity by reducing NRIP1. In addition, miR-579-3p could reduce the apoptotic rate of cortical neurons. Overexpression of miR-579-3p inhibited the activity of caspase-3, increased the expression level of anti-apoptotic gene Bcl-2 in neurons, and decreased the expression level of apoptotic gene Bax.Conclusion: miR-579-3p can be used to treat brain I/R injury, and its neuroprotective effect may be ascribed to the reduction of inflammation and apoptosis.Keywords: ischemia/reperfusion, miR-579-3p, inflammation, apoptosis

Hui Shi,1,2,* Shuo Sun,1,* Haoyue Xu,3,* Zongren Zhao,3 Zhengzhong Han,3 Jun Jia,3 Dongmei Wu,4 Jun Lu,4 Hongmei Liu,3,5 Rutong Yu1,3,5 1Clinical Medical College, Nanjing Medical University, Nanjing, People’s Republic of China; 2The Second People’s Hospital of Lianyungang, Lianyungang, People’s Republic of China; 3Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, People’s Republic of China; 4Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu, People’s Republic of China; 5Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Rutong Yu; Hongmei Liu Tel +86 13182310079; +86 17716228111Email yu.rutong@163.com; liuhongmei816@sina.comIntroduction: Temozolomide (TMZ) is the first-line chemotherapeutic option to treat glioma; however, its efficacy and clinical application are limited by its drug resistance properties. Polo-like kinase 1 (PLK1)-targeted therapy causes G2/M arrest and increases the sensitivity of glioma to TMZ. Therefore, to limit TMZ resistance in glioma, an angiopep-2 (A2)-modified polymeric micelle (A2PEC) embedded with TMZ and a small interfering RNA (siRNA) targeting PLK1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Materials and Methods: TMZ was encapsulated by A2-PEG-PEI-PCL (A2PEC) through the hydrophobic interaction, and siPLK1 was complexed with the TMZ-A2PEC through electrostatic interaction. Then, an angiopep-2 (A2) modified polymeric micelle (A2PEC) embedding TMZ and siRNA targeting polo-like kinase 1 (siPLK1) was developed (TMZ-A2PEC/siPLK).Results: In vitro experiments indicated that TMZ-A2PEC/siPLK effectively enhanced the cellular uptake of TMZ and siPLK1 and resulted in significant cell apoptosis and cytotoxicity of glioma cells. In vivo experiments showed that glioma growth was inhibited, and the survival time of the animals was prolonged remarkably after TMZ-A2PEC/siPLK1 was injected via their tail vein.Discussion: The results demonstrate that the combination of TMZ and siPLK1 in A2PEC could enhance the efficacy of TMZ in treating glioma.Keywords: co-delivery, polymeric micelle, siPLK1, TMZ, drug resistance, glioma

Jianjun Jia,1 Xiaomao Li,2 Suiqun Guo,3 Xingmei Xie1 1Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of China; 2Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510632, People’s Republic of China; 3Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510632, People’s Republic of ChinaCorrespondence: Jianjun JiaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, People’s Republic of ChinaTel/ Fax +86-020-38688359Email jiajianjun615@sohu.comBackground: Dendritic cells (DCs) are reported to play an important role in activating the anti-tumor immune responses. p38 MAPK14 signaling plays an important role in controlling their activity. Here, we identified that miR-155 suppressed the translation of p38 and impaired the functioning of dendritic cells in endometrial cancer.Methods: HEC1A endometrial cancer cell lines were used for the study which was transfected in the C57BL/6 mice. Murine bone marrow-derived dendritic cells (BMDCs) were isolated from the mice. Target prediction was done by TargetScan which was confirmed by RT-PCR analysis. The protein expression was carried by Western blot analysis. Levels of IL-12 were evaluated by ELISA. Mice injected with HEC1A cells were subjected to tumor challenge study.Results: On screening the binding sites of p38 MAPK14 gene, miR-155 was found to bind the 3ʹUTR directly and blocked its translation. The levels of miR-155 were upregulated in dendritic cells and RAW264.7 cells, miR-155 showed inhibitory effect on expression levels of p38. In dendritic cells, miR-155 was found to regulate the expression of IL-12, also miR-155 inhibitor stimulated the differentiation of Th1 cells in mice induced with endometrial cancer. In dendritic cells, miR-155 inhibited the expression of p38 gene and decreased their ability to interfere in tumor growth.Conclusion: The study concludes suppressive role of miR-155 in the process of dendritic cells mediated anti-tumor immunity, also inhibiting miR-155 provides a novel strategy for countering endometrial cancer.Keywords: miR-155, dendritic cells, p38, IL-12, RAW264.7 cells

Ying Yang, Jun Jia, Zhiwei Sun, Chuanling Liu, Yanjie Xiao, Jing Yu, Feng Du, Xiaodong Zhang Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), The VIP-II Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital & Institute, Beijing, ChinaCorrespondence: Xiaodong ZhangKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education, China), The VIP-II Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital & Institute, Beijing, ChinaEmail zhangxd0829@163.comPurpose: Esophageal squamous cell carcinoma (ESCC) is a critical threat to health and life. More than half of ESCC patients have recurrent or metastatic disease. Most late-stage patients undergo first-line treatment but experience further progression. Many of these patients have good performance status and are able to receive second-line therapy and even further treatments rather than best supportive care. Our analysis aimed to explore whether multiple lines of active treatment are beneficial in ESCC patients.Methods: We conducted a retrospective cohort study. Univariate and multivariate survival analyses were used to identify whether the number of active treatment lines was related to prognosis. All analyses and the corresponding survival curves were based on the Cox proportional hazard regression model and the Kaplan–Meier method. Comparisons between groups were conducted using the t-test, chi-square test, and Fisher’s exact test, as applicable.Results: Of a total of 138 patients with recurrent or metastatic disease, 66 (61.1%) received one line of active treatment, and 42 (38.9%) patients received two and more lines. Multiple lines of active therapy were statistically significantly associated with better prognosis (crude hazard ratio (HR) (95% confidence interval (CI))=0.21 (0.06– 0.73)), even after adjusting for relevant confounders (adjusted HR (95% CI)=0.19 (0.04– 0.86)). More grade 3– 4 hepatotoxicity patients were observed in the multiple-line treatment group (p=0.033). A small number of patients were cured by palliative management; these patients were more likely to have received both systematic and local treatment than other patients with repeated progression (9/15 versus 40/117, p=0.051).Conclusion: Multiple lines of active treatment are related to prolonged survival in recurrent and metastatic ESCC patients, and adverse effects are acceptable. Comprehensive therapy modalities are recommended.Keywords: multiple lines of active treatment, esophageal squamous cell carcinoma, prognosis

Li Ke, 1, 2,* Jingshu Chen, 3,* Jia Jia, 1,* Pan Ke, 4 Xueqin Chen, 4 Zongfu Mao, 2 Bing Liu 3, 4 1School of Nursing, Hubei University of Medicine, Shiyan, People’s Republic of China; 2Global Health Institute, Wuhan University, Wuhan, People’s Republic of China; 3School of Public Health and Management, Hubei University of Medicine, Shiyan, People’s Republic of China; 4Center of Health Administration and Development Studies, Hubei University of Medicine, Shiyan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bing LiuCenter of Health Administration and Development Studies, Hubei University of Medicine, 30 South Renmin Road, Shiyan 442000, People’s Republic of ChinaTel +86 138 7277 1527Fax +86 0719 889 2203Email sy-lb@126.comPurpose: This study aimed to evaluate outpatient satisfaction in tertiary hospitals in Shiyan, China, to predict which items had highest priorities for outpatient satisfaction, and to identify population groups on which the medical institutions should focus.Patients and Methods: A cross-sectional survey was conducted at three tertiary hospitals in Shiyan city of China, from March to June 2018. An 18-item outpatient satisfaction questionnaire was applied. We conducted matrix analysis to describe the distribution of satisfaction score and the degree of influence of the items. Outpatient satisfaction was classified into the lowest and highest groups according to the 80/20 rule. Logistic regression model was used to identify demographic factors which might influence outpatient satisfaction.Results: A total of 2109 valid questionnaires were completed. The “waiting time”, “diagnosis and treatment time” and “medical charges” items showed relatively higher degrees of influence but earned lower levels of satisfaction. Outpatients with a college level or above educational background (AOR=1.36, 95% CI=1.03– 1.79) and with a family per-capita monthly income (FPMI)> 7000 CNY (AOR=3.30, 95% CI=1.60– 6.81) were more prevalent in the lowest satisfaction group. Outpatients with college level or above education background (COR=0.77, 95% CI=0.60– 0.99), FPMI of 3001– 5000 CNY (AOR=0.76, 95% CI=0.60– 0.96), non-local residents (AOR=1.48, 95% CI=1.07– 2.04), and urban workers with medical insurance (AOR=1.74, 95% CI=1.27– 2.39) were more prevalent in the highest satisfaction group.Conclusion: The survey indicated that “long time to wait for treatment”, “short treatment time”, and “medical charges too expensive” were the top three aspects that need to be improved with priority by medical institutions. Education level, income level, residence and type of health insurance were the sociodemographic characteristics that significantly affect the outpatient satisfaction in tertiary hospitals. These factors need to be paid more attention by healthcare professionals to improve the patients’ satisfaction.Keywords: outpatients’ satisfaction, tertiary hospitals, importance matrix analysis, the 80/20 rule

Jiaxin Jia, Shudi Zhang, Kai Wen, Quanshun Li Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun 130012, People’s Republic of ChinaCorrespondence: Quanshun Li Tel +86-431-85155201Fax +86-431-85155200Email quanshun@jlu.edu.cnBackground: Zeolitic imidazole framework-8 (ZIF-8) as an emerging platform has exhibited great potential in the protein delivery owing to its tunable chemical functionality.Materials and methods: ZIF-8 was employed as a carrier for the encapsulation and intracellular delivery of RNase A, aimed to achieve a rapid release of proteins in an acidic environment. The intracellular uptake of RNase A was studied by confocal laser scanning microscopy (CLSM), and the inhibition of cell proliferation after the delivery of RNase A was evaluated by MTT assay, Live/Dead staining, and TUNEL cell apoptosis analysis, using human lung adenocarcinoma cell line A549 as a model. The biocompatibility of RNase A@ZIF-8 nanoparticles was systematically detected through the hemolysis and cytotoxicity assay.Results: The RNase A@ZIF-8 nanoparticles constructed by biomimetic mineralization could not only facilitate the encapsulation of protein molecules (protein loading: 13.4%) but also maintain the enzymatic activity and stability of RNase A. The CLSM images showed that RNase A@ZIF-8 nanoparticles could efficiently improve the intracellular uptake of RNase A. Moreover, RNase A@ZIF-8 nanoparticles could obviously inhibit the cell proliferation through the induction of cell apoptosis, with 31.3% of cell death at an RNase A concentration of 10 μg/mL. Finally, RNase A@ZIF-8 nanoparticles were elucidated to possess excellent biocompatibility, with hemolysis of

Zhongli Wu, Yimeng Jiang, Jia Jia, Danmei He, Pengfei Sun, Jianping Li, Yong Huo, Fangfang Fan, Yan Zhang Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Fangfang Fan; Yan ZhangDepartment of Cardiology, Peking University First Hospital, Beijing 100034, People’s Republic of ChinaTel +86 10 8357 5262; +86 10 8357 5728Fax +86 10 6655 1383Email fang9020@126.com; drzhy1108@163.comPurpose: This study aimed to determine the relationship between the metabolic syndrome (MetS) and rapid estimated glomerular filtration rate (eGFR) decline in a Chinese community-based population.Patients and methods: A total of 3108 participants were recruited between December 2011 and July 2014 from an observational study cohort designed for the study of atherosclerotic diseases in Beijing, China. The outcome was a rapid eGFR decline. Subgroup and interaction analyses were performed with respect to a number of covariates.Results: Over a median follow-up period of 2.34 (IQR: 2.29–2.41) years, the overall incidence of rapid eGFR decline was 7.24%. We found that the MetS was significantly associated with the risk of rapid eGFR decline (odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.28–2.23, p

Yanglong Zhu,1 Kuan Liu,2 Jianjian Deng,1 Jing Ye,1 Fanrong Ai,3 Huan Ouyang,4 Tianlong Wu,1 Jingyu Jia,1 Xigao Cheng,1 Xiaolei Wang21Department of Orthopedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of China; 2Institute of Translational Medicine, Nanchang University, Nanchang 330088, People’s Republic of China; 3School of Mechanical & Electronic Engineering, Nanchang University, Nanchang 330031, People’s Republic of China; 4Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, People’s Republic of ChinaBackground: Nowadays, zirconia ceramic implants are widely used as a kind of hip prosthesis material because of their excellent biocompatibility and long-term wear resistance. However, the hip joint is one of the major joints with complex 3D morphological structure and greatly individual differences, which usually causes great material waste during the process of surgical selection of prosthesis.Methods: In this paper, by combining ceramic 3D printing technology with antibacterial nano-modification, zirconia ceramic implant material was obtained with precise 3D structure and effective antibacterial properties. Among which, two technical problems (fragile and sintering induced irregular shrinkage) of 3D printed ceramics were effectively minimized by optimizing the reaction conditions and selective area inversing compensation. Through in vivo and in vitro experiments, it was confirmed that the as prepared hip prosthesis could precisely matched the corresponding parts, which also exhibited good biocompatibility and impressive antibacterial activities.Results: 1) Two inherent technical problems (fragile and sintering induced irregular shrinkage) of 3D printed ceramics were effectively minimized by optimizing the reaction conditions and selective area inversing compensation. 2) It could be seen that the surface of the ZrO2 material was covered with a layer of ZnO nano-particles. A universal testing machine was used to measure the tensile, bending and compression experiments of ceramic samples. It could be found that the proposed ZnO modification had no significant effect on the mechanical properties of ZrO2 ceramics. 3) According to the plate counting results, ceramics modified with ZnO exhibited significantly higher antibacterial efficiency than pure ZrO2 ceramics, the ZrO2-ZnO ceramics had a significant killing effect 8 hours. 4) The removed implants and the tissue surrounding the implant were subjected to HE staining. For ZrO2-ZnO ceramics, inflammation was slight, while for pure ZrO2 ceramics, the inflammatory response could be seen that the antibacterial rate of the ZrO2-ZnO ceramics was significantly better than that of the pure ZrO2 ceramics group. 5) It could be seen that the cytotoxicity did not increase proportionally with the increase of concentration, all of viability were still above 80%. This suggested that our materials were safe and could be applied as a type of potential biomaterial in the future. 6) Further animal studies demonstrated that the implant was in good position without dislocation. This resulted implied that the proposed method can achieve accurate 3D printing preparation of ceramic joints. In addition, the femurs and surrounding muscles around the implant were then sectioned and HE stained. Results of muscle tissue sections further showed no significant tissue abnormalities, and the growth of new bone tissue was observed in the sections of bone tissue.Conclusion: 1) The ceramic 3D printing technology combined with antibacterial nano-modification can quickly customize the ideal implant material with precise structure, wear-resistant and effective antibacterial properties. 2) Two inherent technical problems (fragile and sintering induced irregular shrinkage) of 3D printed ceramics were effectively minimized by optimizing the reaction conditions and selective area inversing compensation. 3) ZnO nano-materials were modified on the ceramic surface, which could effectively killing pathogenic bacteria.Keywords: zirconia, 3D printing, antibacterial, surface modification, implant material

Qianzi Che,1 Ying Yang,2 Guanliang Cheng,2 Jia Jia,2 Fangfang Fan,2 Jianping Li,2 Yong Huo,2 Dafang Chen,1 Yan Zhang21Department of Epidemiology & Biostatistics, Peking University Health Science Center, Beijing, People’s Republic of China; 2Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaBackground: Type 2 diabetes (T2DM), hypertension and kidney dysfunction are known risk factors for cardiovascular disease, but their combined effect on carotid plaque remains uncertain. This study aims to assess the associations between T2DM, hypertension, kidney dysfunction and carotid plaque, and further explore the combined effect of three diseases.Patients and methods: We conducted a cross-sectional analysis among 3,815 community-dwelling adults in a Chinese atherosclerosis cohort. Estimated glomerular filtration rate (eGFR), hypertension and T2DM were evaluated as risk factors for carotid plaque. The presence, number and total area of carotid plaques were also assessed. Using logistic model, mutinomial logistic model and generalized linear regression model, the relationship between risk factors and carotid plaque was examined.Results: T2DM, hypertension, decreased GFR, and, inversely, eGFR, were independently associated with the presence, number and total area of carotid plaque. Stratified analysis by T2DM and hypertension showed T2DM attenuated the association between eGFR change and carotid plaque. There was a cumulative relationship between three risk factors and carotid plaque burden. The OR for the number of plaques was 1.0 (reference), 1.55 to 2.03, 1.94 to 3.14, and 3.69 (all P

Xiaotong Dai,1 Ying Yang,2 Guan-Liang Cheng,2 Jia Jia,2 Fang-Fang Fan,2 Jian-Ping Li,2 Yong Huo,2 Zhike Liu,1 Dafang Chen,1 Yan Zhang21Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, People’s Republic of China; 2Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaBackground: Increased arterial stiffness measured by brachial-ankle pulse wave velocity is associated with cardiovascular disease. However, the rates at which brachial-ankle pulse wave velocity and blood glucose accelerate within individuals who differ in blood pressure levels are largely unknown.Methods: This study was based on the baseline data of a Chinese community-based atherosclerosis cohort which included 7402 individuals. Using generalized linear regression models, the relationship between blood glucose levels and brachial-ankle pulse wave velocity, and the relationship between blood pressure levels and brachial-ankle pulse wave velocity were examined.Results: A marked interaction between hypertensive state and diabetic state was seen for brachial-ankle pulse wave velocity (P for interaction

Lijun Yang,* Yafei Ye,* Jie Chu, Jinlin Jia, Yunhui Qu, Ting Sun, Huiqing Yin, Liang Ming, Junhu Wan, Fucheng HeDepartment of Medical Laboratory, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan Province, People’s Republic of China*These authors contributed equally to this workBackground: Long noncoding RNAs (lncRNAs), a class of noncoding RNA nucleotides >200 bp, has been demonstrated to play vital role in the development of cancer. FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) has been reported as an lncRNA which acts as a tumor-promoting effect in some cancers. However, the role of it in esophageal squamous cell carcinoma (ESCC) and its potential regulatory mechanism was unclear now.Methods: qRT-PCR was used to detect the levels of FEZF1-AS1 and mRNA CTNNB1 (β-catenin) in ESCC tissues and cells. Cell transfection experiments were used to knock down or overexpress the level of FEZF1-AS1 in EC1 and EC9706 cell lines. WST-1 assays, cell cycle assays, scratch wound assays, migration, and invasion assays were used to evaluate the function of FEZF1-AS1 in ESCC progression.Results: FEZF1-AS1 was remarkably upregulated in ESCC tissues and cell lines. Silencing of FEZF1-AS1 significantly inhibited the migration and invasion of ESCC cells, while overexpression of FEZF1-AS1 notably accelerated ESCC migration and invasion. Meanwhile, the levels of FEZF1-AS1 had no effect on ESCC cell proliferation and cell cycle. We also found that β-catenin was upregulated in ESCC tissues, and the level of it was positively correlated with the expression of FEZF1-AS1. Silencing of FEZF1-AS1 could decrease the mRNA and protein level of β-catenin, while overexpression FEZF1-AS1 could lead to the contrary.Conclusion: Our results suggested that the expression of lncRNA FEZF1-AS1 played an important role in ESCC progression, especially the motility of the tumor. FEZF1-AS1 may provide us with a new sight for ESCC treatment.Keywords: esophageal squamous cell carcinoma, lncRNA, FEZF1-AS1, biological function, β-catenin

Qi Xue, Ming-zhao Qin, Jing Jia, Jin-ping Liu, Yun Wang Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China Purpose: Frailty and atherosclerotic diseases are prevalent among the older people and usually present the same pathogenesis and risk factors. Therefore, the aim of this study was to determine the association between frailty and atherosclerosis.Patients and methods: The enrolled participants were 171 patients aged 60–96 years in Beijing Tongren Hospital. Data that were collected included sex, age, height, weight, calculated body mass index (BMI), past medical history, comorbidities (including hypertension, coronary heart disease [CHD], and diabetes), ability to perform activities of daily living (ADL) as measured using the Barthel index, handgrip strength, 15-feet (4.57 m) walking speed, body composition features determined by bioelectrical impedance analysis, the ankle–brachial index (ABI), and atherosclerosis determined by the cardio-ankle vascular index (CAVI). Patients were divided into frail, pre-frail, and non-frail groups using Fried’s frailty index. ANOVA was used to assess the differences among these groups. Linear correlation analysis was used to examine the relationship between the CAVI and frailty phenotype. Ordinal multivariate logistic regression analysis was used to examine the factors affecting frailty and the relationship between frailty and atherosclerosis.Results: The population was categorized as 21.3% frail, 38.4% pre-frail, and 40.3% non-frail. Patients in the frail group were older, had lower handgrip strength, slower walking speed, and a lower ABI and a higher proportion of carotid intima-media thickening with values of at least 1 mm compared with those in the pre-frail and non-frail groups. The CAVI score was higher in the frail group than that in the other two groups. There were significant inverse linear correlations between grip strength, walking speed, and the CAVI. CAVI showed an independent risk factor for frailty (OR: 2.013, 95% CI 1.498–2.703, p

Xiaoning Wu,1–3,* Jialing Zhou,1–3,* Wen Xie,4 Huiguo Ding,5 Xiaojuan Ou,1–3 Guofeng Chen,6 Anlin Ma,7 Xiaoyuan Xu,8 Hui Ma,9 Youqing Xu,10 Xiaoqing Liu,11 Tongtong Meng,1–3 Lin Wang,1–3 Yameng Sun,1–3 Bingqiong Wang,1–3 Yuanyuan Kong,1–3 Hong Ma,1–3 Hong You,1–3 Jidong Jia1–3 1Liver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China; 2Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing, China; 3National Clinical Research Center of Digestive Diseases, Beijing, China; 4Liver Fibrosis Centre, Beijing Ditan Hospital, Capital Medical University, Beijing, China; 5Department of Digestive Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, China; 6Liver Fibrosis Centre, Beijing 302 Hospital, Beijing, China; 7Department of Infectious Diseases, China-Japan Friendship Hospital, Beijing, China; 8Department of Infectious Diseases, Peking University First Hospital, Beijing, China; 9Liver Research Centre, Peking University People’s Hospital, Beijing, China; 10Department of Digestive Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; 11Department of Infectious Diseases, Peking Union Medical College Hospital, Beijing, China *These authors contributed equally to this work Background: De novo combination of lamivudine (Lam) and adefovir (Adv) was not rarely used in clinical practice. However, head-to-head comparisons of entecavir (Etv) monotherapy with this combination in hepatitis B virus (HBV)-related compensated cirrhosis patients are unavailable. This study aimed to compare the efficacy and safety of Etv monotherapy with combination therapy in patients with HBV-related compensated liver cirrhosis.Methods: Treatment-naïve patients with HBV-related compensated liver cirrhosis were recruited to receive either Etv monotherapy or a de novo combination of Lam and Adv. Data were collected at baseline and every 6 months thereafter.Results: A total of 578 patients (485 in Etv group, 93 in combination group) were included. Baseline characteristics were comparable between the two groups. At the end of 1, 2, and 3 years, HBV DNA was undetectable in 82.7%, 96.2%, and 94.3% of patients in the Etv group and 88.9%, 81.7%, and 84.6% in the combination group, respectively (all P>0.05). The cumulative virological breakthrough rate at 1, 2, and 3 years was 2.7%, 6.7%, and 9.8% in the Etv group and 2.9%, 13.3%, and 32.2% in the combination group, respectively (P=0.003). After propensity-score adjustment for age, sex, and baseline HBeAg, ALT, and total bilirubin, virological breakthrough was higher in the de novo combination of Lam and Adv (HR 2.83, 95% CI 1.37–5.86; P

Pan Ke,1,* Fengbo Jiang,2,* Dongmei Wu,3,* Li Ke,2 Zi Lin,2 Jia Jia,2 Baoxia Ye,3 Bing Liu1 1Health Management and Health Development Research Center of Hubei University of Medicine, Shiyan, People’s Republic of China; 2Postgraduate Training Base of Hubei University of Medicine, Jinzhou Medical University, Jinzhou, People’s Republic of China; 3Department of Cardiology Three Wards, Shiyan Taihe Hospital (The Affiliated Hospital of Hubei University of Medicine), Shiyan, People’s Republic of China *These authors contributed equally to this work Background: Conflicts between doctors and patients occur in People’s Republic of China each year. Serious negative relationships between doctors and patients are a significant social problem. This study aims to evaluate the satisfaction of inpatients in a tertiary hospital through a third party and analyze the relationship between sociodemographic characteristics and overall satisfaction. Patients and methods: A cross-sectional investigation was conducted to obtain the demographic information and results for 20 items in an inpatient satisfaction questionnaire. A total of 872 inpatients were studied. Descriptive analysis was conducted using SPSS version 22.0 software. Independent sample t-tests and one-way ANOVA were used to compare the mean differences between groups. Multiple linear regression analysis was conducted to study the relationship between different demographic characteristics and overall satisfaction. P-values of 0.05). Multiple linear regression analysis results showed that residence, age, occupation and education status were the factors affecting inpatient satisfaction. In further analyses, diet management, medical expenses, complaint management and hospital environment were in urgent need of improvement. Conclusion: The overall level of inpatient satisfaction with this hospital seems to be acceptable, although areas for improvement remain. Keywords: satisfaction, sociodemographic characteristics, importance matrix analysis, influencing factors

Xuchun Che,1,* Rong Lu,1,2,* Zheng Fu,2 Yajun Sun,3 Zhi-feng Zhu,2 Jin-ping Li,2 Song Wang,2 Jing Jia,2 Qing Wang,4 Zhi Yao1 1Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Educational Ministry of China, School of Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Drug Development, Tianjin Kangzhe Pharmaceutical Company, Ltd., Tianjin, People’s Republic of China; 3Department of Blood Transfusion, General Hospital, Tianjin Medical University, Tianjin, People’s Republic of China; 4Department of Clinical Laboratory, General Hospital, Tianjin Medical University, Tianjin, People’s Republic of China *These authors contributed equally to this work Background: Tyroserleutide (YSL) inhibits the growth and metastasis of human hepatocellular carcinoma (HCC). This paper studied the effect of YSL on metastasis of human HCC and investigated its mechanisms. Methods: In vivo, experimental lung metastasis models of human HCC SK-HEP-1 cells in nude mice were established, and In vitro, the proliferation, adhesion and invasion of SK-HEP-1 cells were detected. Results: In vivo, YSL significantly inhibited the metastasis of human HCC. In vitro, YSL significantly inhibited the proliferation, adhesion and invasion of SK-HEP-1 cells. Through analyses with reverse transcription PCR (RT-PCR) and Western blot, we observed that YSL significantly inhibited the expressions of ICAM-1 in SK-HEP-1 cells. Through RT-PCR, Western blot and zymography methods, YSL was discovered to decrease the mRNA level, protein expression and activity of MMP-2 and -9 in SK-HEP-1 cells. Conclusion: We concluded that YSL could inhibit tumor growth and metastasis of human HCC SK-HEP-1 cells. Keywords: proliferation, adhesion, invasion, ICAM-1, MMP-2, MMP-9

Xingang Wang,1 Fangfang Fan,1 Jia Jia,1 Xin Xu,2 Xianhui Qin,2 Bo Zheng,1 Haixia Li,3 Liguang Dong,4 Shuyu Wang,5 Jianping Li,1 Yong Huo,1 Jingtao Dou,6 Yan Zhang1 1Department of Cardiology, Peking University First Hospital, Beijing, China; 2National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, China; 3Clinical Laboratory, Peking University First Hospital, Beijing, China; 4Peking University Shougang Hospital, Beijing, China; 5Beijing Hypertension League Institute, Beijing, China; 6Department of Endocrinology, Chinese PLA General Hospital, Beijing, China Background: Chronic kidney disease (CKD) has become a major issue worldwide and hyperglycemia is known as an important risk factor responsible for CKD progression. Few studies have investigated whether fasting plasma glucose (FPG) could predict kidney function decline (KFD) risk better than postprandial plasma glucose, and vice versa. In this study, we investigated the roles of FPG and 2-hour plasma glucose (2 h-PG) in predicting KFD risk in a Chinese community-based population without baseline deterioration of kidney functions. Methods: Subjects with normal kidney function from an atherosclerosis cohort in Beijing, China were followed up for 2.3 years. The outcome was KFD (a drop in glomerular filtration rate category accompanied by 25% or greater decline of estimated glomerular filtration rate from the baseline or a sustained decline of more than 5 mL/min/1.73 m2/year rate). Results: A total of 3,738 subjects were included of which, 7.7% of the subjects suffered from KFD. After covariates adjustments, both FPG (OR =1.23, P7.0 mmol/L had 1.83 times and 2.51 times KFD risk respectively, compared to subjects with FPG level