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Huiqin Sun,1,* Lu Zhou,2,* Yihan Lu,2 Yingchuan Li,3 Yan Huo,4 Weifeng Huang5 1Department of Anesthesiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3Department of Critical Care Medicine, Tongji University Affiliated Shanghai Tenth People’s Hospital, Shanghai, People’s Republic of China; 4Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090 People’s Republic of China; 5Department of Critical Care Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Fudan, 200031, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weifeng Huang, Department of Critical Care Medicine, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, 366 NorthLongchuan Rd, Xuhui District, Shanghai, 200031, People’s Republic of China, Email breeze-huang@hotmail.com Yan Huo, Department of Pharmacy, Yangpu Hospital, School of Medicine, Tongji University, Shanghai, 200090, People’s Republic of China, Email huoyan@sjtu.edu.cnIntroduction: Pulmonary embolism (PE), the most serious presentation of venous thromboembolism (VTE), is associated with a high rate of mortality and expense. Clinical studies on pregnant women with PE are scarce. The aim of this study was to analyze the clinical impact of fibrinolytic enzyme activation inhibitor-1 (PAI-1) 4G/5G genetic polymorphisms, methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298C) and rs1801133 (C677T) genetic polymorphisms, and establish a predictive model for pregnant women.Material and Methods: Between September 2022 and August 2023, 53 pregnant women with PE were enrolled. Using the propensity score matching method, 106 consecutive pregnant women without VTE were 1:2 matched. The relevant patient data were collected, and the susceptibility genes for PE were detected to determine genetic polymorphisms, and PE susceptibility in pregnant women, as well as to develop predictive models.Results: Our study showed that 4G/4G homozygous mutations increased the risk of pregnant PE fourfold (OR = 4.46, 95% CI = 1.59– 12.50, P = 0.004), whereas the 4G allele mutation increased the risk twofold (OR = 2.33, 95% CI = 1.35– 4.04, P = 0.002). A nomogram was established to predict the risk of pregnant women with PE by four predictive features including PAI-1 genetic polymorphisms, international normalized ratio (INR), antithrombin-III (AT-III) activity, and platelet count (PLT). The area under the curve (AUC) of the nomogram was 0.821 (0.744– 0.898). The AUC of the internal validation group was 0.822 (0.674– 0.971). Decision curve analysis revealed that the nomogram has a higher net benefit in the following threshold: probability interval of ≥ 15%.Conclusion: The PAI-1 4G/4G genotype is an independent risk factor for pregnant women with PE; furthermore, the presence of the 4G allele can increase the risk of PE. The study established a nomogram to predict the risk of PE in pregnant women.Keywords: pulmonary embolism, pregnant women, genetic polymorphisms, PAI-1, nomogram model

Simin Liu,1,* Zhiyuan Tian,2 Taiming Zhang,3 Jirong Zhang,3 Yanlei Huo,1,* Chao Ma1 1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nuclear Medicine, Zibo Ninth People’s Hospital, Zibo, Shandong, People’s Republic of China; 3Department of Medical Imaging, People’s Hospital of Shuangjiang Autonomous Country, Lincang, Yunnan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chao Ma, Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University, Yanchangzhong Road 301, Shanghai, 200072, People’s Republic of China, Tel +86 21-66302075, Email mc_7419@hotmail.comObjective: To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, brand name, Yunke) on bone metastases (BM).Procedures: In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, 99Tc+SnCl2 and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed.Results: In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38.Conclusion: Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.Keywords: 99Tc-MDP, bone metastases, molecular mechanisms, RM-1, prostate cancer

Qian Zhang,1 Xiaomei Wang,1 Mingzhe Liu,1 Bin Li,1 Kun Zhang,1 Yaqi Han,1 Jiali Li,2 Yan Xin,3 Yan Huo,1 Zhenjie Hu1 1Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 2Department of Intensive Care Unit, The Sixth People’s Hospital of Hengshui, Hengshui, Hebei Province, 053000, People’s Republic of China; 3Department of Intensive Care Unit, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaCorrespondence: Yan Huo; Zhenjie Hu, Department of Intensive Care Unit, The Fourth Hospital of Hebei Medical University, No. 12 of Jiankang Road, Changan District, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095367, Email huoyan523@hebmu.edu.cn; 46400533.hebmu.edu.cnObjective: The aim of this study is to examine the diagnostic significance of using handgrip dynamometry and diaphragmatic ultrasound in intensive care unit-acquired weakness (ICU-AW).Methods: This study included patients who received mechanical ventilation in the ICU at the Fourth Hospital of Hebei Medical University from July to December 2020. We collected comprehensive demographic data and selected conscious patients for muscle strength and ICU-AW assessments. The evaluation comprised grip strength measurement and bedside ultrasound for diaphragmatic excursion (DE) and thickening fraction (DTF). Results were documented for comparative analysis between patient groups, focusing on the diagnostic efficacy of grip strength, DE, DTF, and their combined application in diagnosing ICU-AW.Results: A total of 95 patients were initially considered for inclusion in this study. Following the exclusion of 20 patients, a final cohort of 75 patients were enrolled, comprising of 32 patients (42.6%) diagnosed with ICU-AW and 43 patients (57.4%) classified as non-ICU-AW. Comparative analysis revealed that grip strength, DE, and DTF were significantly lower in the ICU-AW group (P < 0.05). Subgroup analysis specific to male patients demonstrated a noteworthy decrease in grip strength, DE, and DTF within the ICU-AW group (P < 0.05). Receiver operating characteristic curve analysis indicated statistically significant diagnostic value for ICU-AW with grip strength, DE, DTF, and grip strength and diaphragmatic ultrasound (P < 0.01). Furthermore, it was observed that the amalgamation of grip strength and diaphragmatic ultrasound significantly enhanced the diagnostic accuracy of ICU-AW in patients who are critically ill.Conclusion: Grip strength, DE, DTF, and the combined use of grip strength with diaphragm ultrasound demonstrated diagnostic efficacy in ICU-AW. Notably, the integration of grip strength with diaphragm ultrasound exhibited a heightened capacity to enhance the diagnostic value specifically in patients diagnosed who are critically ill with ICU-AW.Keywords: diaphragmatic excursion, diaphragm thickening fraction, handgrip dynamometer, ICU acquired weakness

Huiqiong Liu,1 Dao Wang,1 Miaomiao Tang,1 Peisheng Jia,1 Yufeng Huo,1 Erhu Wei,1 Hao Xu,2 Xiaohui Chi,2 Huaili Wang1 1Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Huaili Wang, Department of Pediatric Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, No. 1 Longhu East Zhonghuan Road, Zhengzhou, 450052, People’s Republic of China, Tel +86-371-66271057, Email whlek6527@126.comPurpose: With the spread of multiple drug-resistant bacteria, blaNDM-1 and mcr-9 have been detected in various bacteria worldwide. However, the simultaneous detection of blaNDM-1 and mcr-9 in Enterobacter hormaechei has been rarely reported. This study identified an E. hormaechei strain carrying both blaNDM-1 and mcr-9. We investigated the genetic characteristics of these two resistance genes in detail, elucidating various potential mechanisms by which they may be transmitted.Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) with Illumina and PacBio platforms and phylogenetic analysis. Subsequent investigations were performed, including antimicrobial susceptibility testing and multilocus sequence typing (MLST).Results: We isolated an E. hormaechei strain DY1901 carrying both blaNDM-1 and mcr-9 from the sputum sample. Susceptibility testing showed that the isolate was multidrug-resistant. Multiple antibiotic resistance genes and virulence genes are widely distributed in DY1901. S1-PFGE, Southern blotting, and plasmid replicon typing showed that DY1901 carried four plasmids. The plasmid carrying mcr-9 was 259Kb in size and belonged to IncHI2, while the plasmid carrying blaNDM-1 was 45Kb in length and belonged to IncX3.Conclusion: The E. hormaechei strain isolated in this study has a broad antibiotic resistance spectrum, posing a challenge to clinical treatment. Plasmids carrying mcr-9 are fusion plasmids, and those taking NDM are widely disseminated in China, suggesting that we should conduct routine genomic surveillance on such plasmids to curb the spread of drug-resistant bacteria in the region.Keywords: E. hormaechei, New Delhi metallo-β-lactamase, mcr-9, whole-genome sequencing, phylogenetic analysis

In order to attenuate the various low-frequency vibrations that may cause structural fatigue and damage, impact human health and affect work efficiency, this paper presents a novel local resonance metamaterial sandwich meta-plate structure containing a cantilever spiral beam-mass resonator, and investigates vibration reduction effects of it within the obtained low-frequency bandgap range. For this purpose, a theoretical model of the low-frequency resonator being composed by a cantilever Archimedean spiral beam and cylindrical mass is established. The natural frequency of it is calculated by solving the Euler-Lagrange equation of the resonator. The accuracy and reliability of the theoretical model are verified through COMSOL simulation. The stress distribution of five types of cantilever spiral beam mass resonators (i.e. Archimedes spiral, triangle spiral, square spiral, pentagon spiral and hexagon spiral) and different cross-sectional shapes (rectangular, square, circular, diamond and triangular) are analyzed. Then, a unit cell model of a sandwich meta-plate with a cantilever Archimedean spiral beam resonator is selected. Hamilton’s principle is used to deduce the bandgap range under infinite periods, and the theoretical solutions are also verified. The parameter optimization of the substrate plate and resonator are also studied. Moreover, the effects of the various structural variables on the bandgap range are systematically explored. Finally, the dynamic responses of the sandwich meta-plate composed of 5 × 8-unit cells under different excitation frequencies, boundary conditions and structural damping are analyzed. [ABSTRACT FROM AUTHOR]

Wenbin Qiao,1,&ast; Jiahui Fan,1,&ast; Xiaoqian Shang,1,&ast; Liang Wang,2 Bahetibieke Tuohetaerbaike,2 Ying Li,2 Li Zhang,2 YiShan Huo,1 Jing Wang,3 Xiumin Ma1,2 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, 830000, People’s Republic of China; 2First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3Respiratory Department of the Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiumin MaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, No. 789 Suzhou Road, Urumqi, 830011, Xinjiang Uygur Autonomous Region, People’s Republic of ChinaTel +86-13369649029Email maxiumin1210@sohu.comJing WangRespiratory Department of the Second Affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570000, People’s Republic of ChinaTel +86-13629925886Email tlfwj@163.comObjective: Central nervous system tuberculosis is the most serious form of extrapulmonary tuberculosis. We aim to discover potential biomarkers involved in the development of the disease.Methods: Through gene difference analysis, construction of a protein interaction network and tissue specific analysis and other bioinformatics analysis methods, we found out the relatively high expression of important substances in the central nervous system, interferon induced protein with tetratricopeptide repeats 1. Subsequently, the lesion tissue and the resection margin tissue away from the lesion were collected from the 6 cases of central nervous system tuberculosis patients diagnosed from 2019 to 2020, and the pathological manifestations were observed by Hematoxylin and Eosin (H&E) staining, and the expression of IFIT1 was verified by immunohistochemistry.Results: A total of 101 differential genes were analyzed between extrapulmonary tuberculosis patients and normal people, and they were mainly enriched in the interferon pathway. The protein interaction network unearthed 34 key genes. Through tissue specific analysis, it was found that IFIT1 is relatively high in the central nervous system. H&E staining showed the expression of multinucleated macrophages, and immunohistochemistry showed that IFIT1 was significantly positively expressed in the lesion tissue.Conclusion: IFIT1 is an important substance involved in central nervous system tuberculosis.Keywords: central nervous system tuberculosis, biomarkers, interferon induced protein with tetratricopeptide repeats 1, hematoxylin and eosin staining, immunohistochemistry staining

BackgroundPregnancy outcomes of perinatally human immunodeficiency virus-infected women (PHIV) are poorly defined.MethodsWe compared preterm delivery and birth weight (BW) outcomes (low BW [LBW],

Yue Zhang,1 Jingyi Li,2 Chengzhang Liu,3 Hongxiang Yu,1 Chen Chen,1 Chonglei Bi,4 Chongqian Fang,4 Hai Ma,5 Aimin Li,6 Qing Dong,7 Lishun Liu,8 Binyan Wang,3 Xiao Huang,9 Xiaoshu Cheng,9 Pierre Zalloua,10 Xiping Xu,11 Yong Huo,12 Gang Li1 1Department of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 3Shenzhen Evergreen Medical Institute, Guangzhou, People’s Republic of China; 4People’s Hospital of Rongcheng, Rongcheng, Shandong, People’s Republic of China; 5Health and Family Planning Commission, Rongcheng, Shandong, People’s Republic of China; 6Department of Neurosurgery, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, People’s Republic of China; 7Lianyungang Health Committee, Lianyungang, Jiangsu, People’s Republic of China; 8Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, People’s Republic of China; 9Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 10School of Medicine, Lebanese American University, Beirut, Lebanon; 11Division of Nephrology, Nanfang Hospital, Southern Medical University; National Clinical Research Center for Kidney Disease; State Key Laboratory of Organ Failure Research; Guangdong Provincial Institute of Nephrology, Guangzhou, People’s Republic of China; 12Department of Cardiology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Gang Li 1800 Yuntai Road, Shanghai, 200123, People’s Republic of ChinaTel +86-21-38804518-22107Fax +86-21-58798999Email ligang@tongji.edu.cnBackground and Purpose: Elevated high-density lipoprotein cholesterol (HDL-C) levels have displayed protection against cardiovascular disease. However, the association between specific lipoprotein classes and first ischemic stroke (IS) has not been well defined, particularly in higher-risk hypertensive populations. Our study evaluated the associations of HDL-C with first IS in a Chinese hypertensive population.Methods: The study population was obtained from a community-based cohort study of hypertension in Lianyungang and Rongcheng, China. A nested case-control design was used that included 2463 identified first IS cases and 2463 controls matched by age ± 1 year, sex, and region.Results: After adjusting for potential confounders, HDL-C was inversely associated with first IS (adjusted odds ratio [aOR]: 0.91; 95% confidence interval [CI]: 0.85– 0.98). HDL-C levels of at least 65.4 mg/dL displayed a significant protective effect for first IS (aOR: 0.82; 95% CI: 0.69– 0.98). Conversely, adverse effects of first IS were observed for low-density lipoprotein cholesterol (LDL-C) levels ≥ 138.1 mg/dL (aOR: 1.20; 95% CI: 1.02– 1.42) and triglyceride (TG) levels ≥ 140.8 mg/dL (aOR: 1.27; 95% CI: 1.09– 1.49). The risk associations of LDL-C and TG with first IS were attenuated in the presence of high HDL-C (≥ 53.0 mg/dL); an increased risk of first IS was only found in the presence of low HDL-C (< 53.0 mg/dL) when LDL-C (aOR: 1.66; 95% CI: 1.19– 2.31) and TG (aOR: 1.47; 95% CI: 1.17– 1.84) were combined with HDL-C for analysis.Conclusion: In this community-based Chinese hypertensive population, higher HDL-C was a significant protective factor of first IS. These data add to the evidence describing the relationship between lipids and IS and suggest that HDL-C maybe is a marker of IS risk in Chinses hypertensive population.Keywords: high-density lipoprotein cholesterol, lipids, ischemic stroke, epidemiology

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

© The Author(s) 2016. Hydrogen production via electrochemical water splitting is a promising approach for storing solar energy. For this technology to be economically competitive, it is critical to develop water splitting systems with high solar-to-hydrogen (STH) efficiencies. Here we report a photovoltaic-electrolysis system with the highest STH efficiency for any water splitting technology to date, to the best of our knowledge. Our system consists of two polymer electrolyte membrane electrolysers in series with one InGaP/GaAs/GaInNAsSb triple-junction solar cell, which produces a large-enough voltage to drive both electrolysers with no additional energy input. The solar concentration is adjusted such that the maximum power point of the photovoltaic is well matched to the operating capacity of the electrolysers to optimize the system efficiency. The system achieves a 48-h average STH efficiency of 30%. These results demonstrate the potential of photovoltaic-electrolysis systems for cost-effective solar energy storage.

Silver solid solution phase with indium has been discovered to have great mechanical properties and anti-tarnishing property, as shown in the results of our previous study. It is important to know the stress vs. strain curve before adopting this material in industrial applications. The growth of the homogeneous silver solid solution phase with indium is first described. The X-ray diffraction (XRD) patterns and scanning electron microscope/energy dispersive X-ray spectroscopy (SEM/EDX) results are reported to verify the chemical composition of silver solid solution phase with indium samples. Based on the results, one could reversely determine the indium element composition in (Ag)-xxIn solid solution by examining the lattice constant value using XRD for unknown compositions. The preparation of ASTM tensile test samples and tensile test experimental setting are explained in details. The intrinsic mechanical material properties of silver solid solution phase with indium, i.e., characteristic stress vs. strain curves, are presented and analyzed, with pure silver stress vs. strain curve in comparison. According to the experimental results, silver solid solution phase with indium exhibits low yield strength, high ultimate tensile strength, and large elongation value before fracture, compared to pure silver. In addition, fractography of the fracture surface of the tested sample has been studied to confirm the superior ductility of silver solid solution phase with indium. These superior mechanical properties may bring silver solid solution phase with indium new applications in various industries such as electronics and brazing.

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

Kongying Lin,1,* Qizhen Huang,2,* Yuting Huo,3,* Jianxing Zeng,1 Zongren Ding,1 Pengfei Guo,4 Zhenwei Chen,4 Yongyi Zeng,1 Jingfeng Liu1,4 1Department of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China; 2Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China; 3Department of Otolaryngology, Fujian Medical Maternity and Child Care Hospital, Fuzhou 350014, People’s Republic of China; 4The Big Data Institute of Southeast Hepatobiliary Health Information, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingfeng Liu; Yongyi ZengDepartment of Hepatopancreatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Xihong Road 312, Fuzhou 350025, People’s Republic of ChinaTel/ Fax +86 591 8370 5927Email drjingfeng@126.com; lamp197311@126.comPurpose: To develop and validate a nomogram for individualized prediction of the long-term prognosis of patients with non-B, non-C hepatocellular carcinoma (NBNC-HCC) who underwent hepatectomy.Materials and Methods: Five hundred ninety-four patients who met the criteria were included in the research and randomly categorized into the training or validation cohort. The nomogram was constructed on the basis of the independent risk variables that were acquired via multivariate Cox proportional hazard regression analysis. Several complementary methods included the Harrell c-index, time-dependent areas under the receiver operating characteristic curve (tdAUC), and calibration plot, and the Kaplan–Meier curve with Log rank test were used to test predictive performance of the model. The clinical utility of the model was tested by the decision cure analysis (DCA).Results: Tumor diameter, tumor number, elevated serum gamma-glutamyl transpeptidase (GGT) level, microvascular invasion (MVI), and macrovascular invasion were independent risk factors of prognosis of NBNC-HCC. C-indexes of the nomogram were 0.702 (95% confidence interval [CI], 0.662– 0.741) in the training cohort and 0.700 (95% CI, 0.643– 0.758) in the validation cohort, and median tdAUC values of the nomogram were 0.743 (range, 0.736– 0.775) in the training cohort and 0.751 (range, 0.686– 0.793) in the validation cohort, which were both higher than those in the conventionally used Barcelona Clinic Liver Cancer staging system, American Joint Committee on Cancer, and eighth edition and the model of Zhang et al. The calibration plot depicted a good consistency between prediction of the model and observed outcome. The Kaplan–Meier curve analysis showed that the model was able to separate patients into three distinct risk subgroups. The DCA analysis also demonstrated that the nomogram was clinically useful.Conclusion: We developed and validated a nomogram that was accurate and clinically useful in patients with NBNC-HCC who underwent hepatectomy.Keywords: non-B non-C hepatocellular carcinoma, resection, prognosis, nomogram, survival

In contrast to the extensive study of domain reversal in ferromagnetic materials, the domain switching process in antiferromagnets is much less studied due to the difficulty of probing antiferromagnetic spins. Using a combination of hysteresis loop, Kerr microscope, and x-ray magnetic linear dichroism measurements, we investigated the antiferromagnetic (AFM) domain switching process in single crystalline Fe/CoO bilayers on MgO(001). We demonstrate that the CoO AFM switching is a Kolmogorov-Avrami process in which the thermal activation energy creates AFM domain nucleation centers which further expand by domain wall propagation. From the temperature- and thickness-dependent measurements, we are able to retrieve quantitatively the important parameter of the CoO AFM activation energy, which is shown to increase linearly with CoO thickness.

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

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

Jie Jiang,1 Yu-Jie Zhou,2 Jian-Jun Li,3 Jun-Bo Ge,4 Ying-Qing Feng,5 Yong Huo1 On behalf of ASAP Study Investigators 1Department of Cardiology, Peking University First Hospital, Xicheng District, Beijing 100034, China; 2Department of Cardiology, Beijing Anzhen Hospital, Chaoyang District, Beijing 100029, China; 3Department of Cardiology, Fuwai Hospital, Xicheng District, Beijing 100037, China; 4Department of Cardiology, Fudan University Zhongshan Hospital, Xuhui District, Shanghai 200032, China; 5Department of Cardiology, Guangdong General Hospital, Yuexiu District, Guangzhou, Guangdong Province 510080, China Objective: Despite current standard of care, the overall lipid goal attainment rate for hyperlipidemia patients, especially those who have experienced acute coronary syndrome (ACS), is suboptimal, which predisposes them to a higher residual risk of atherothrombotic events. This study aimed to describe characteristics of Chinese patients who recently experienced an ACS event and were on lipid-lowering treatment, yet failing to reach targeted goal. Methods: A multicenter, cross-sectional study was conducted to recruit 2,034 Chinese patients who experienced an ACS (ST segment elevation myocardial infarction [STEMI], non-STEMI, or unstable angina) event within the past 4–40 weeks and were on statin treatment (>2 weeks) from March 2015 to December 2016. All eligible patients underwent a fasting lipid test after enrollment and data on medical history were collected. Results: The mean age of 1,994 eligible patients was 61.0±9.84 years. Among them, 1,493 (74.9%) patients received intensive statin therapy (defined as atorvastatin 40 or 80 mg, or rosuvastatin 20 mg per protocol) and 499 (25.0%) patients were on maximum tolerated dose statin. Of the 1,994 eligible subjects, 1,273 (63.8%) patients did not achieve the lipid goal at the time of enrollment. Among the not-at-goal patients, 910 (71.5%) received intensive statin therapy; the majority (73.4%) of them were male; the mean age was 61.2±10.1 years old; 699 (54.9%) patients had a history of hypertension; 25.3% had diabetes mellitus; and 29.5% were current smokers. The mean low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and ApoB levels at enrollment of this group of patients were 2.460±0.7139 mmol/L, 3.094±0.8861 mmol/L, and 0.840±0.3015 g/L, respectively. Conclusion: The study result demonstrates that overall more than half of the patients who recently (4–40 weeks) experienced ACS who were treated did not reach the guideline-recommended LDL-C and non-HDL-C goal. These results highlight the potential necessity for a new drug beyond statins to further reduce disease burden in the future. Keywords: acute coronary syndrome, intensive statin treatment, lipid goal attainment, lipid-lowering treatment

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

Yating Huo, Lili Guan, Jiawen Xu, Luqian Zhou, Rongchang Chen State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China Background: Airway remodeling is an important feature of chronic obstructive pulmonary disease (COPD) that is associated with disease severity and irreversible airflow limitation. An extensive alteration of the extracellular matrix (ECM) surrounding the airway smooth muscle (ASM) bundle is one of the pathological manifestations of airway remodeling, which contributes to the decline in lung function. Tiotropium, a long-acting inhaled muscarinic receptor antagonist, has been confirmed to play a role in preventing airway remodeling including ECM deposition beyond bronchodilation in vivo, but the relationship between ASM cell (ASMC) relaxation and ECM production remains unclear. Purpose: In this study, we attempted to investigate the influence of tiotropium on ECM production by ASMCs and the underlying mechanism. Methods: Tiotropium was added 30 minutes before the addition of methacholine to primary cultured human ASMCs. Protein expression was analylized by Western Blot and mRNA abundance was determined by real-time PCR. Results: We found that tiotropium reduced collagen I protein expression, and the mRNA abundance of collagen I, fibronectin, and versican. β-catenin signaling was inactivated by inhibiting glycogen synthase kinase 3β (GSK3β) phosphorylation in this process. Tiotropum inhibited the amount of active β-catenin and its transcription activity. Furthermore, overexpression of active β-catenin by adenoviruses carrying the S33Y mutant resisted the suppressive effect of tiotropium on collagen I protein expression. However, silencing β-catenin by specific small interfering RNA enhanced the negative effect of tiotropium. Conclusion: These findings suggest that relaxation of ASMCs by tiotropium can prevent ECM production through β-catenin signaling. Keywords: tiotropium, collagen I, β-catenin, airway smooth muscle cell

Jiancheng Wang,1,* Binyan Wang,1,2,* Min Liang,1 Guobao Wang,1 Jianping Li,3 Yan Zhang,3 Yong Huo,3 Yimin Cui,4 Xiping Xu,1,5 Xianhui Qin1 1National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Renal Division, Nanfang Hospital, Southern Medical University, Guangzhou, 2Institute for Biomedicine, Anhui Medical University, Hefei, 3Department of Cardiology, 4Department of Pharmacy, Peking University First Hospital, Beijing, 5Beijing Advanced Innovation Center for Food Nutrition and Human Health, Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China *These authors contributed equally to this work Objective: Whether serum bilirubin and cigarette smoking affect the risk of renal function decline remains inconclusive. We aimed to test the independent and combined effects of bilirubin and cigarette smoking on the progression of chronic kidney disease (CKD) in hypertensive adults. Methods: The study population consisted of 12,633 patients in the renal sub-study of the China Stroke Primary Prevention Trial. The primary outcome was progression of CKD, defined as a decrease in estimated glomerular filtration rate (eGFR) of ≥30% and to a level of