Search

Xulin Liu,1,&ast; Zhancheng Qiu,2,&ast; Elijah Ndhlovu,1,&ast; Yunyan Wan,3 Huapeng Sun,4 Shuai Wang,5 Yugang Cao,6 Peng Zhu1 1Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 3Department of Hepatobiliary Pancreatic Surgery, Taihe Hospital, Shiyan City, Hubei Province, People’s Republic of China; 4Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, People’s Republic of China; 5Department of Hepatobiliary Surgery, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 6Department of Hepatobiliary and Pancreatic Surgery, Huangshi Central Hospital of Edong Healthcare Group, Huangshi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng Zhu, Department of Hepatic Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China, Tel +86 13907170712, Email zhupeng@tjh.tjmu.edu.cnPurpose: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection.Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis.Results: Multivariate COX regression showed that HBV DNA ≥ 10,000 IU/mL (P < 0.001), HALP score ≤ 38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III–IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001).Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.Keywords: early recurrence, hepatocellular carcinoma, HALP score, nomogram, Barcelona Clinic of Liver Cancer staging system, disease-free survival

Hao Du,1 Wentao Li,1 Xueyi Li,2 Zhiyuan Qiu,1 Jie Ding,2 Yi Zhang1 1Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Cultivation and Construction Site of the State Key Laboratory of Intelligent Imaging and Interventional Medicine, Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of China; 2Department of Biochemistry and Molecular Biology, Medical School, Southeast University, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Jie Ding; Yi Zhang, Email dingjie711@seu.edu.cn; yizhangcir@126.comBackground: Poly-L-lactic acid (PLLA) stents have broad application prospects in the treatment of cardiovascular diseases due to their excellent mechanical properties and biodegradability. However, foreign body reactions caused by stent implantation remain a bottleneck that limits the clinical application of PLLA stents. To solve this problem, the biocompatibility of PLLA stents must be urgently improved. Albumin, the most abundant inert protein in the blood, possesses the ability to modify the surface of biomaterials, mitigating foreign body reactions—a phenomenon described as the “stealth effect”. In recent years, a strategy based on albumin camouflage has become a focal point in nanomedicine delivery and tissue engineering research. Therefore, albumin surface modification is anticipated to enhance the surface biological characteristics required for vascular stents. However, the therapeutic applicability of this modification has not been fully explored.Methods: Herein, a bionic albumin (PDA-BSA) coating was constructed on the surface of PLLA by a mussel-inspired surface modification technique using polydopamine (PDA) to enhance the immobilization of bovine serum albumin (BSA).Results: Surface characterization revealed that the PDA-BSA coating was successfully constructed on the surface of PLLA materials, significantly improving their hydrophilicity. Furthermore, in vivo and in vitro studies demonstrated that this PDA-BSA coating enhanced the anticoagulant properties and pro-endothelialization effects of the PLLA material surface while inhibiting the inflammatory response and neointimal hyperplasia at the implantation site.Conclusion: These findings suggest that the PDA-BSA coating provides a multifunctional biointerface for PLLA stent materials, markedly improving their biocompatibility. Further research into the diverse applications of this coating in vascular implants is warranted. Keywords: vascular stent, Poly-L-lactic acid, albumin, biomimetic coating, stealth effect

Yuting Kang,1,&ast; Qiujie Li,2,&ast; Yao Yao,3 Chao Xu,2 Zhuoran Qiu,2 Wei Jia,1,3 Gang Li,1,3 Pengtao Wang1 1Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2College of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gang Li; Pengtao Wang, General Hospital of Ningxia Medical University, Technology Building 601, 804 Shengli Road, Yinchuan, People’s Republic of China, Tel +86-0951-6744462 ; +86-0951-6743330, Email gone.lee@163.com; wangpengtao2021@163.comPurpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023.Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms.Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region.Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.Keywords: Aspergillus fumigatus, azole resistance, cyp51A mutation, tandem repeat sequences

Chujun Chen, Zerui Yang, Zhikun Qiu Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of ChinaCorrespondence: Zhikun Qiu, Email tougaoqzk@126.comPurpose: Gestational diabetes mellitus (GDM) is a common metabolic disorder during pregnancy that is associated with placental inflammation and adverse pregnancy outcomes. However, the mechanisms of inflammation in GDM are still unclear.Methods: Bulk transcriptome, single-cell transcriptome, clinical information, and samples were collected from GSE154414, GSE70493, GSE173193 and a retrospective cohort. Bioinformatics prediction was used to explore the mechanisms of placental inflammation, and multiplex immunofluorescence was used to validate the results.Results: First, we found that GDM is characterized by low-grade inflammation and is linked to several adverse pregnancy outcomes, as supported by our collected clinical data. Additionally, we identified ten hub genes (FCGR3B, CXCR1, MMP9, ITGAX, CCL5, GZMB, S100A8, LCN2, TGFB1, and LTF) as potential therapy targets and confirmed the binding of corresponding predictive therapeutic agents by molecular docking. Transcriptome sequencing analysis has shown that macrophages are primarily responsible for the emergence of placental inflammation, and that M1 macrophage polarization increased while M2 macrophage polarization decreased in GDM when compared to the control sample. Multiplex immunofluorescence staining of CD68, CD80, and ACSL4 was performed and suggested that ferroptosis of macrophages may contribute to placental inflammation in GDM.Conclusion: In conclusion, our findings provide a better understanding of the mechanisms of inflammation in GDM and suggest potential therapeutic targets for this condition. Keywords: gestational diabetes mellitus, placental inflammation, macrophage, therapy targets, ferroptosis

Chenkai Yang,1,&ast; Xiangqian Cao,1,&ast; Lei He,2,3,&ast; Cong Wu,2,&ast; Mengxin Zhao,2 Fei Duan,2 Zhiwen Qiu,2 Xiaodong Zhu,2 Yilin Yan,1 Shengzhou Li,1 Wei Li,2 Bing Shen1 1Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, Shanghai, People’s Republic of China; 3School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li, Department of Nanomedicine & Shanghai Key Laboratory of Cell Engineering, Naval Medical University, 800 Xiangyin Road, Yangpu District, Shanghai, 200433, People’s Republic of China, Tel +86 21 81871644, Fax +86 21 81870801, Email liwei_dds@163.com Bing Shen, Department of Urology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 85 Wujin Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel/Fax +86 18017181979, Email urodrshenbing@shsmu.edu.cnIntroduction: Insufficient tumor permeability and inadequate nanoparticle retention continue to be significant limitations in the efficacy of anti-tumor drug therapy. Numerous studies have focused on enhancing tumor perfusion by improvement of tumor-induced endothelial leakage, often known as the enhanced permeability and retention (EPR) effect. However, these approaches have produced suboptimal therapeutic outcomes and have been associated with significant side effects. Therefore, in this study, we prepared tumor cell membrane-coated gold nanorods (GNR@TM) to enhance drug delivery in tumors through homogeneous targeting of tumor cell membranes and in situ real-time photo-controlled therapy.Methods: Here, we fabricated GNR@TM, and characterized it using various techniques including Ultraviolet-Visible (UV-Vis) spectrophotometer, particle size analysis, potential measurement, and transmission electron microscopy (TEM). The cellular uptake and cytotoxicity of GNR@TM were analyzed by flow cytometry, confocal laser scanning microscopy (CLSM), TEM, CCK8 assay and live/dead staining. Tissue drug distribution was determined by inductively coupled plasma mass spectrometry (ICP-MS) and immunofluorescence staining. Furthermore, to evaluate the therapeutic effect, mice bearing MB49 tumors were intravenously administered with GNR@TM. Subsequently, near-infrared (NIR) laser therapy was performed, and the mice’s tumor growth and body weight were monitored.Results: The tumor cell membrane coating endowed GNR@TM with extended circulation time in vivo and homotypic targeting to tumor, thereby enhancing the accumulation of GNR@TM within tumors. Upon 780 nm laser, GNR@TM exhibited excellent photothermal conversion capability, leading to increased tumor vascular leakage. This magnification of the EPR effect induced by NIR laser further increased the accumulation of GNR@TM at the tumor site, demonstrating strong antitumor effects in vivo.Conclusion: In this study, we successfully developed a NIR-triggered nanomedicine that increased drug accumulation in tumor through photo-controlled therapy and homotypic targeting of the tumor cell membrane. GNR@TM has been demonstrated effective suppression of tumor growth, excellent biocompatibility, and significant potential for clinical applications. Keywords: intratumor drug accumulation, photo-controlled therapy, homotypic targeting, tumor cell membrane, gold nanorods

Jianfen Liang,1,&ast; Jun Liu,1,&ast; Zhuolin Qiu,1 Guoliang Sun,1 Ping Xiang,2 Ziqing Hei,1 Xiang Li1 1Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510630, People’s Republic of China; 2Department of Medical Quality Management, Nanfang Hospital, Southern Medical University, Guangzhou, 510630, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Li, Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-Sen University, Number 600, Tianhe Road, Guangzhou, 510630, Guangdong province, People’s Republic of China, Tel +86-20-85253132, Fax +86-20-85252297, Email lixiang27@mail.sysu.edu.cnBackground: Postoperative sore throat is a frequent adverse event after double-lumen endobronchial tube (DLT) intubation. The aim of this study was to investigate whether esketamine gargle has a preventive effect on the incidence of postoperative sore throat in patients undergoing DLT intubation.Methods: This trial included 140 patients undergoing elective thoracic surgery at the third affiliated hospital of Sun Yat-Sen University. Patients were randomly allocated into the following two groups of 70 patients each: the control group, gargling with saline of 30 mL, and the esketamine group, gargling with an esketamine solution of 30 mL (2 mL/50 mg esketamine in 28 mL saline), 5 min prior to anaesthesia induction. The primary outcome was the incidence of sore throat 24 h after surgery. The main secondary outcomes included the incidence of sore throat and hoarseness at 1 h and 48 h after surgery, as well as the intraoperative haemodynamic responses.Results: The incidence of sore throat was significantly higher in the control group (47.1%, 33/70 patients) compared with the esketamine group (12.9%, 9/70 patients) at 24 h after surgery (RD, 0.41; 95% confidence interval, 0.26– 0.57; p < 0.001). Furthermore, the incidence of sore throat at 1 h (p = 0.027), 24 h (p = 0.019), and seventh day (p = 0.031) as well as hoarseness at 1 h (p = 0.027), 24 h (p = 0.019), and 48 h (p = 0.031) after surgery were reduced in the esketamine group. Significant differences were seen in the peak levels of systolic blood pressure, mean arterial blood pressure, and heart rate between the groups during the intubation (p < 0.05). Besides, no patient developed an adverse reaction to esketamine.Conclusion: Preoperative gargling of esketamine can provide an effect against sore throat after DLT intubation without adverse side effects and effectively inhibit sharp elevations in heart rate and blood pressure during double-lumen intubation procedures.Keywords: esketamine, topical application, postoperative sore throat, double-lumen endobronchial tubes, intubation

Jian Peng,1– 3,&ast; Yue Wang,3,&ast; Zhaoyin Wu,3 Chengju Mao,3 Lu Li,1,2 Huijun Cao,4 Zhilang Qiu,3 Guo Guo,3,5 Guiyou Liang,4,5 Feng Shen1,2 1Department of Intensive Care Unit, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People’s Republic of China; 2Guizhou Institute of Precision Medicine, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People’s Republic of China; 3Key Laboratory of Infectious Immune and Antibody Engineering of Guizhou Province, Cellular Immunotherapy Engineering Research Center of Guizhou Province, School of Biology and Engineering/School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 550025, People’s Republic of China; 4Department of Cardiac Surgery, the affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550009, People’s Republic of China; 5Translational Medicine Research Center, Guizhou Medical University, Guiyang, Guizhou, 550025, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Shen; Guiyou Liang, Email doctorshenfeng@163.com; guiyou515@163.comIntroduction: Acinetobacter baumannii has become a major difficulty in the treatment of bacteria-associated infection. The previously reported antimicrobial peptide Cec4 exhibited good and stable activity against A. baumannii in vitro, but the mechanisms and effects in vivo are elusive.Methods: The effects of Cec4 on bacterial membrane permeability, membrane potential and bacterial reactive oxygen species were measured. The cell membrane localization of antimicrobial peptides was studied by fluorescence labelling. The ability of bacteria to develop resistance to antimicrobial peptides was studied by continuous induction, and transcriptome difference was analysed. The in vivo toxicity of Cec4 against nematodes and mice was studied, and the in vivo therapeutic potential of Cec4 against A. baumannii was assessed.Results: Cec4 effectively cleared multidrug-resistant A. baumannii by altering bacterial cell membrane permeability, changing bacterial cell membrane polarity, and increasing bacterial intracellular reactive oxygen species. Cec4 affected the expression of the secretion system, outer membrane, and efflux pump genes of A. baumannii. In addition, the bacteria did not acquire stable drug-resistant ability. Cec4 at 1.024 mg/mL did not affect the proliferation of HeLa and HepG2 cells, and Cec4 at 45 mg/kg had little effect on the mortality of Caenorhabditis elegans, even the liver and kidney tissues of mouse. Most importantly, Cec4 could effectively improve the survival rates and reduce the bacterial load of various tissues in the mouse model of infection.Conclusion: In conclusion, Cec4 can damage the cell membrane of bacteria, and the bacteria is not easy to produce resistance to Cec4. Besides, Cec4 has good potential for the treatment of multidrug-resistant A. baumannii infections.Keywords: antimicrobial peptide, A. baumannii, sepsis, skin infection, drug safety

Zhuoyin Qiu,1,2,&ast; Tingting Guo,1,2,&ast; Xihua Sheng,1,2 Ying Tang,1,2 Huaping Du1,2 1Department of Neurology, Suzhou Ninth People’s Hospital, Suzhou, People’s Republic of China; 2Department of Neurology, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaping Du, Department of Neurology, Suzhou Ninth People’s Hospital, No. 2666, Ludang Road, Wujiang District, Suzhou, Jiangsu, 215000, People’s Republic of China, Tel +86 512-82885052, Email duhuaping226@126.comPurpose: This study aims to investigate the prognostic value of the peripheral neutrophil-to-lymphocyte ratio (NLR) in patients with chronic internal carotid artery occlusion (CICAO) complicated by cerebral infarction.Patients and Methods: The clinical data of 99 CICAO patients complicated by cerebral infarction were retrospectively analyzed. The modified Rankin Scale (mRS) was used to assess their 3-month prognosis, and a multivariate logistic regression model was established to explore risk factors for poor prognosis.Results: Multivariate logistic regression analysis demonstrated that NLR (OR=2.114; 95% CI: 1.129– 3.959) and baseline National Institute of Health Stroke Scale (NIHSS; OR=1.288, 95% CI: 1.053– 1.574) score were risk factors of poor prognosis. The area under the receiver operator characteristic (ROC) curve of NLR in predicting the 3-month outcome after onset was 0.717 (95% CI: 0.606– 0.828, P< 0.000). The optimal cut-off value was 3.22, with a sensitivity of 0.743 and a specificity of 0.791.Conclusion: NLR is an independent risk factor for the poor prognosis of CICAO patients complicated by cerebral infarction and can serve as an indicator for clinical prognosis.Keywords: chronic internal carotid artery occlusion, cerebral infarction, neutrophil-to-lymphocyte ratio, prognosis, predictive factors

Zhishen Ruan,1,&ast; Dan Li,1,&ast; Yuanlong Hu,1 Zhanjun Qiu,1,2 Xianhai Chen1,2 1The First Clinical College, Shandong Chinese Medical University, Ji Nan, People’s Republic of China; 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji Nan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanjun Qiu; Xianhai Chen, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Ji Nan, People’s Republic of China, Tel/Fax +86 0531 18660199889, Email qiuzhj227@163.com; chenxianhai18@163.comBackground: Acute respiratory failure (ARF) is a common cause of admission to the intensive care unit (ICU) for patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). There is still a lack of effective interventions and treatments. ACE inhibitors (ACEI)/ angiotensin II receptor blockers (ARB) were effective in COPD patients. We aimed to study the effect of ACEI/ARB use on AECOPD combined with ARF and evaluate the effect of in-hospital continuation of medication.Methods: We included patients with AECOPD and ARF from the Medical Information Bank for Intensive Care (MIMIC-III) database. MIMIC III is a large cohort database from Boston, USA. Patients were divided into two groups according to the use of ACEI/ARB before admission. Propensity score matching (PSM) was used to reduce potential bias between the two groups. Cox regression and Kaplan-Meier curves compared 30-day mortality in ACEI/ARB users and non-users. We also defined and analyzed the use of in-hospital ACEI/ARB. Multiple models were used to ensure the robustness of the findings. Subgroup analysis was used to analyze the variability between groups.Results: A total of 544 patients were included in the original study. After PSM, 256 patients were included in the matched cohort. Multivariate Cox regression showed 30-day mortality was significantly lower in ACEI/ARB users compared with controls (HR = 0.50, 95% CI: 0.29– 0.86, p= 0.013). In PSM and inverse probability-weighted models, the results are stable Continued in-hospital use of ACEI/ARB remains effective (HR 0.40, 95% CI 0.22– 0.74, p = 0.003). Kaplan-Meier showed a significant difference in survival between the two groups.Conclusion: This study found that pre-hospital ACEI/ARB use was associated with reduced mortality in patients with AECOPD and ARF.Keywords: chronic obstructive pulmonary disease, acute respiratory failure, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, mortality

Chunhui Tian,1,2,&ast; Renwu Zhao,2,&ast; Zengyu Qiu,1 Yehai Liu2 1Department of Otolaryngology-Head and Neck Surgery, Suzhou Hospital of Anhui Medical University, Suzhou, People’s Republic of China; 2Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yehai LiuDepartment of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Anhui Medical University, 218 Ji-xi road, Hefei, People’s Republic of ChinaTel +8613856906986Email liuyehai@ahmu.edu.cnObjective: To determine the effectiveness of pyogenic cavity aerobic therapy with negative pressure drainage in the treatment of deep neck space infections (DNSI).Methods: The study was a prospective, observational analysis of 36 cases of DNSI at a tertiary care center. The patients were divided into two groups according to the treatment method. Group A was treated with pyogenic cavity aerobic therapy with negative pressure drainage and included 13 patients (6 males and 7 females), while group B was treated with traditional incision debridement drainage and included 23 patients (12 males and 11 females). The average hospitalization days and doctors’ workload (ie, average days of postoperative dressing changes) were analyzed and compared between the two groups.Results: The mean hospitalization days in the traditional dressing group were 26.74 ± 3.39 days, while the average days of postoperative dressing change were 25.91 ± 3.43 days. In contrast, the averages for hospitalization days and days of postoperative dressing changes in the pyogenic cavity aerobic therapy plus negative pressure drainage were 11.08 ± 2.11 and 3.69 ± 0.21 days, respectively. All 36 patients were cured. Compared with the group B, group A had a shorter hospital stays and lower doctor workloads (P < 0.001).Conclusion: Pyogenic cavity aerobic therapy is an effective and simple method for changing dressings after DNSI. This therapy, when combined with negative pressure drainage, shortens hospitalization days and days that require a dressing change. This has reduced the workload of clinical doctors and pain experienced by patients. This therapy also has a high degree of safety and a very satisfactory curative effect.Keywords: deep neck infections, neck abscess, therapy, drainage

Yuanlong Hu,1,&ast; Xiaomeng Cheng,1,&ast; Zhanjun Qiu,2 Xianhai Chen2 1Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China; 2The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhanjun Qiu; Xianhai Chen Email qiuzhj227@163.com; chenxianhai18@163.comPurpose: This study aimed to identify the COPD molecular subtypes reflecting pulmonary function damage on the basis of metabolism-related gene expression, which provided the opportunity to study the metabolic heterogeneity and the association of metabolic pathways with pulmonary function damage.Methods: Univariate linear regression and the Boruta algorithm were used to select metabolism-related genes associated with forced expiratory volume in the first second (FEV1) and FEV1/forced vital capacity (FVC) in the Evaluation of COPD to Longitudinally Identify Predictive Surrogate Endpoints (ECLIPSE) cohort. COPD subtypes were further identified by consensus clustering with best-fit. Then, we analyzed the differences in the clinical characteristics, metabolic pathways, immune cell characteristics, and transcription features among the subtypes.Results: This study identified two subtypes (C1 and C2). C1 exhibited higher levels of lower pulmonary function and innate immunity than C2. Ten metabolic pathways were confirmed as key metabolic pathways. The pathways related to N-glycan, hexosamine, purine, alanine, aspartate and glutamate tended to be positively associated with the abundance of adaptive immune cells and negatively associated with the abundance of innate immune cells. In addition, other pathways had opposite trends. All results were verified in Genetic Epidemiology of COPD (COPDGene) datasets.Conclusion: The two subtypes reflect the pulmonary function damage and help to further understand the metabolic mechanism of pulmonary function in COPD. Further studies are needed to prove the prognostic and therapeutic value of the subtypes.Keywords: chronic obstructive pulmonary disease, molecular subtype, metabolic pathway, pulmonary function

Aftab Ullah,1 Gang Chen,2 Abid Hussain,3,4 Hanif Khan,1 Azar Abbas,5 Zhanwei Zhou,5 Muhammad Shafiq,6 Saleem Ahmad,7 Usman Ali,8 Muhammad Usman,6 Faisal Raza,8 Abrar Ahmed,8 Zijie Qiu,5 Maochao Zheng,1 Daojun Liu1 1Department of Pharmacy, Shantou University Medical College, Shantou, 515041, Guangdong, People’s Republic of China; 2Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China; 3School of Life Science, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, 100081, People’s Republic of China; 4Chinese Academy of Sciences (CAS) Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing, 100190, People’s Republic of China; 5School of Pharmacy, China Pharmaceutical University, Nanjing, 210028, Jiangsu, People’s Republic of China; 6Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong, 515041, people’s Republic of China; 7Department of Medicine, Shantou University Medical College Cancer Hospital, Shantou, People’s Republic of China; 8School of Pharmacy, Shanghai Jiaotong University, Shanghai, 200240, Shanghai, People’s Republic of ChinaCorrespondence: Aftab Ullah; Daojun Liu Email aftab@stu.edu.cn; liudj@stu.edu.cnBackground: Liver fibrosis is a chronic liver disease with excessive production of extracellular matrix proteins, leading to cirrhosis, hepatocellular carcinoma, and death.Purpose: This study aimed at the development of a novel derivative of polyethyleneimine (PEI) that can effectively deliver transforming growth factor β (TGFβ) siRNA and inhibit chemokine receptor 4 (CXCR4) for TGFβ silencing and CXCR4 Inhibition, respectively, to treat CCl4-induced liver fibrosis in a mouse model.Methods: Cyclam-modified PEI (PEI-Cyclam) was synthesized by incorporating cyclam moiety into PEI by nucleophilic substitution reaction. Gel electrophoresis confirmed the PEI-Cyclam polyplex formation and stability against RNAase and serum degradation. Transmission electron microscopy and zeta sizer were employed for the morphology, particle size, and zeta potential, respectively. The gene silencing and CXCR4 targeting abilities of PEI-Cyclam polyplex were evaluated by luciferase and CXCR4 redistribution assays, respectively. The histological and immunohistochemical staining determined the anti-fibrotic activity of PEI-Cyclam polyplex. The TGFβ silencing of PEI-Cyclam polyplex was authenticated by Western blotting.Results: The 1H NMR of PEI-Cyclam exhibited successful incorporation of cyclam content onto PEI. The PEI-Cyclam polyplex displayed spherical morphology, positive surface charge, and stability against RNAse and serum degradation. Cyclam modification decreased the cytotoxicity and demonstrated CXCR4 antagonistic and luciferase gene silencing efficiency. PEI-Cyclam/siTGFβ polyplexes decreased inflammation, collagen deposition, apoptosis, and cell proliferation, thus ameliorating liver fibrosis. Also, PEI-Cyclam/siTGFβ polyplex significantly downregulated α-smooth muscle actin, TGFβ, and collagen type III.Conclusion: Our findings validate the feasibility of using PEI-Cyclam as a siRNA delivery vector for simultaneous TGFβ siRNA delivery and CXCR4 inhibition for the combined anti-fibrotic effects in a setting of CCl4-induced liver fibrosis.Keywords: polyethyleneimine, cyclam, gene delivery, liver fibrosis, CXCR4

Jiuzhou Liu,1,* Shasha Ren,2,* Xiangyu Zhang,3 Yun Feng,2 Zhenglun Qiu,2 Li Ma,4 Jingwen Huang4 1Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, 471003, People’s Republic of China; 2Department of Breast and Thyroid Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, 471009, People’s Republic of China; 3Department of Pathology, Jining First People’s Hospital, Jining Medical University, Jining, 272000, People’s Republic of China; 4The First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jingwen Huang; Jiuzhou Liu Email byyfyhjw1988@163.com; Liu_JiuzhouBC@163.comBackground: Breast cancer (BC) is the most common type of cancer among women worldwide, and about 30% of males will have recurrent disease.Methods: In order to treat recurrent BC, we designed a type of silica nanodelivery system loaded with epirubicin and curcumin (composite nanoparticles, CNPs). To promote CNPs clinical application, the stability, the blood, immune and cell compatibility, skin stimulation experiments, anti-tumor activity in vivo and in vitro were studied.Results: In our study, the CNPs had a particle size of 73.9 nm and a uniform size and morphology; moreover, they maintained physical and chemical stability in the blood protein environment. Additionally, results showed that nanoparticles had good blood and immune compatibility, and they did not affect intracellular superoxide dismutase (SOD) and intracellular catalase (CAT). Skin stimulation experiments showed that CNPs did not cause any obvious irritative damage to the intact skin of rabbits. In the cytotoxicity study, CNPs showed strongest antitumor activity. The results of cell cycle and apoptosis studies showed that CNPs could mainly induce apoptosis of S and G2/M phase cells. In vivo, CNPs showed strongest aggregation in the tumor after 6 h of tail vein administration, and a large amount of CNPs continued to accumulate in the blood after 12 h of administration, indicating that CNPs had long circulation ability. The in vivo antitumor activities showed that CNPs had the strongest antitumor activity and tumor targeting ability, and hematoxylin-eosin staining of internal organs showed no obvious difference between treatment groups and negative control.Conclusion: CNPs have an ideal biosafety and therapeutic effect for recurrent BC, and they have potential clinical application value.Keywords: nanoparticles, breast cancer, chemotherapy, targeting, biocompatibility

Jingyi Du,* Yifan Deng,* Zhuolin Qiu, Guoliang Sun, Yue Guo, Ziqing Hei, Xiang Li Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Number 600, Tianhe Road, Guangzhou, 510630, People’s Republic of ChinaTel/ Fax +86 20 8525 3132Email lixiang27@mail.sysu.edu.cnPurpose: Cognitive impairment is a complication that most frequently happens in patients with chronic neuropathic pain and has limited effective therapy. The aim of this study was to explore the effects of curcumin on the cognitive deficit in rats with peripheral nerve injury induced-neuropathic pain.Methods: The neuropathic pain rat model was constructed using chronic constriction injury (CCI). The curcumin (60 mg/kg) or vehicle was intraperitoneally administered once a day, beginning at 14th day after surgery and continued for 14 consecutive days. The nociceptive threshold tests were measured by paw mechanical withdraw threshold (PMWT) and paw thermal withdrawal latency (PTWL), while the spatial memory abilities were evaluated by the Morris water maze test. The mean counts of bromodeoxyuridine (Brdu)/neuronal nuclei (NeuN) as well as Brdu/doublecortin (DCX) co-labeled cells were used to evaluate neurogenesis in the dentate gyrus of hippocampus. The ultrastructure of the synapse in hippocampal region was visualized using transmission electron microscopy (TEM).Results: Increased PMWT and PTWL, as well as relieved memory deficits, were found in CCI rats under curcumin administration. Moreover, curcumin treatment increased the number of newly born immature (BrdU/NeuN) and newly generated mature neurons (BrdU/DCX). The TEM examination revealed increased PSD thickness and shorter active zone length as well as narrowed synaptic cleft width in the hippocampal region of CCI rats after curcumin injection.Conclusion: Curcumin can alleviate CCI induced nociceptive behaviors and memory deficit. This effect might be associated with hippocampal neurogenesis and synaptic plasticity improvements, which indicated curcumin as a potential strategy for the cognitive impairment restoration under prolonged neuropathic pain condition.Keywords: curcumin, peripheral nerve injury, cognitive impairment, hippocampus neurogenesis

Zhendong Qiu,* Wenhong Deng,* Yupu Hong, Liang Zhao, Man Li, Yongjun Guan, Yingru Su, Chen Chen, Qiao Shi, Jia Yu, Weixing Wang Department of General Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weixing Wang; Jia YuDepartment of General Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, People’s Republic of ChinaEmail sate.llite@163.com; yogaqq116@163.comPurpose: To research the effects of ATP citrate lyase (ACLY) and Sterol-regulatory element binding protein 1 (SREBP1) on the biology and lipid metabolism of colorectal cancer cells.Methods: Colorectal cancer cells Caco-2 and Lovo were transfected with ACLY or SREBP1 gene knockdown lentiviruses. Four groups were set: ACLY knockdown, SREBP1 knockdown group, empty vector-transfected (negative control), and untreated cells (blank control). Cell proliferation was measured using CCK-8, colony formation, and EdU labeling assays. Apoptosis was detected using Annexin V-APC/7- AAD and JC-1 assay. Transwell migration and wound healing assays analyzed cell migration and invasion. A triglyceride test kit and oil red O stain assessed cell lipid production. Key factors related to lipid metabolism were detected.Results: ACLY and SREBP1 promoted cell proliferation at 48 and 120 h, but there was no significant difference in Caco-2 cells at 24 h, at which point the effect of SREBP1 was more important. ACLY’s effect on cell proliferation was more obvious at 120 h. Colony formation assays in Caco-2 showed similar results to the CCK-8 assay at 120 h, but ACLY knockdown had no effect in Lovo cells. EDU assays showed that ACLY or SREBP1 facilitated DNA reproduction in the two cell lines, in which SREBP1 was more significant. Knockdown of the two genes showed significant differences in Lovo cells. However, ALCY knockdown promoted apoptosis to a greater extent than SREBP1 knockdown in Caco-2 cells. In addition, ACLY and SREBP1 enhanced migration, invasion, and lipid production in both cell lines. Knockdown of ACLY or SREBP1 reduced lipid metabolism pathway gene expression in the two cell lines.Conclusion: Knockdown of ACLY and SREBP1 genes inhibit the proliferation, migration, and invasion of colorectal cancer cells, while promoting their apoptosis. Our results identified potential new targets to treat colorectal cancer via lipid synthesis modulation in cancer cells.Keywords: ATP-citrate lyase, colorectal cancer, lipid metabolism, sterol-regulatory element binding protein 1

Zhengguo Qiu,1 Qianhe Shen,2 Chao Jiang,3 Li Yao,4 Xiaopeng Sun,5 Jing Li,6 Chongzhen Duan,1 Rui Li,1 Xiuli Li,1 Subash CB Gopinath,7,8 Periasamy Anbu,9 Thangavel Lakshmipriya,8 Xu Li10 1Department of Anesthesiology, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, 712000, People’s Republic of China; 2Department of Anesthesiology, Xi’an GemFlower Changqing Hospital, Xi’an, Shaanxi, 710200, People’s Republic of China; 3The Third Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 4Department of Neurology, The Hospital of Xidian Group, Xi’an, Shaanxi, 710077, People’s Republic of China; 5Department of Otolaryngology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 6Department of Anesthesiology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, 710038, People’s Republic of China; 7Faculty of Chemical Engineering Technology, Universiti Malaysia Perlis (UniMAP), Arau, Perlis, 02600, Malaysia; 8Institute of Nano Electronic Engineering, Universiti Malaysia Perlis (UniMAP), Kangar, 01000, Malaysia; 9Department of Biological Engineering, College of Engineering, Inha University, Incheon, 402-751, Republic of Korea; 10Department of Surgery and Anesthesiology, Xi’an Hospital of Traditional Chinese Medicine, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Xu Li Email qzg2020@sina.comBackground: Alzheimer’s disease (AD) is a neurodegenerative chronic disorder that causes dementia and problems in thinking, cognitive impairment and behavioral changes. Amyloid-beta (Aβ) is a peptide involved in AD progression, and a high level of Aβ is highly correlated with severe AD. Identifying and quantifying Aβ levels helps in the early treatment of AD and reduces the factors associated with AD.Materials and Methods: This research introduced a dual probe detection system involving aptamers and antibodies to identify Aβ. Aptamers and antibodies were attached to the gold (Au) urchin and hybrid on the carbon nanohorn-modified surface. The nanohorn was immobilized on the sensor surface by using an amine linker, and then a Au urchin dual probe was immobilized.Results: This dual probe-modified surface enhanced the current flow during Aβ detection compared with the surface with antibody as the probe. This dual probe interacted with higher numbers of Aβ peptides and reached the detection limit at 10 fM with R2=0.992. Furthermore, control experiments with nonimmune antibodies, complementary aptamer sequences and control proteins did not display the current responses, indicating the specific detection of Aβ.Conclusion: Aβ-spiked artificial cerebrospinal fluid showed a similar response to current changes, confirming the selective identification of Aβ.Keywords: amyloid-beta, biomarker, nanomaterial, aptamer, antibody

Ruixin Jia,1,* Lesheng Teng,2,* Lingyu Gao,1 Ting Su,1 Lu Fu,3 Zhidong Qiu,1 Ye Bi1,4 1College of Pharmacy, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China; 2School of Life Science, Jilin University, Changchun, Jilin, People’s Republic of China; 3College of Life Science, Jilin Agricultural University, Changchun, Jilin, People’s Republic of China; 4Practice Training Center, Changchun University of Chinese Medicine, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ye BiPractice Training Center, Changchun University of Chinese Medicine, 1035 Boshuo Road, Changchun, Jilin, People’s Republic of ChinaTel/Fax +86-431-86763979Email biye88@outlook.comZhidong QiuCollege of Pharmacy, Changchun University of Chinese Medicine, 1035 Boshuo Road, Changchun, Jilin, People’s Republic of ChinaTel/Fax +86-431-86763979Email qzdcczy@163.comAbstract: Nanomedicines afford unique advantages in therapeutic intervention against tumors. However, conventional nanomedicines have failed to achieve the desired effect against cancers because of the presence of complicated physiological fluids and the tumor microenvironment. Stimuli-responsive drug-delivery systems have emerged as potential tools for advanced treatment of cancers. Versatile nano-carriers co-triggered by multiple stimuli in different levels of organisms (eg, extracorporeal, tumor tissue, cell, subcellular organelles) have aroused widespread interest because they can overcome sequential physiological and pathological barriers to deliver diverse therapeutic “payloads” to the desired targets. Furthermore, multiple stimuli-responsive drug-delivery systems (MSR-DDSs) offer a good platform for co-delivery of agents and reversing multidrug resistance. This review affords a comprehensive overview on the “landscape” of MSR-DDSs against tumors, highlights the design strategies of MSR-DDSs in recent years, discusses the putative advantage of oncotherapy or the obstacles that so far have hindered the clinical translation of MSR-DDSs.Keywords: multi-stimuli responsive nanoparticles, drug delivery, tumor microenvironment, oncotherapy

Jia Yang,1 Zhandong Qiu,1,2 Yu Fang3 1Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, People’s Republic of China; 2Department of Neurology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of China; 3Department of Emergency Medicine, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of ChinaCorrespondence: Zhandong Qiu Email 003qiu86@163.comObjective: To compare the differences in neuropsychological and personality characteristics between male patients with lacunar infarction with hazardous drinking and non-hazardous drinking.Methods: From May to October 2016, a total of 124 male outpatients and inpatients with lacunar infarction were selected in the Department of Neurology, Tongji Hospital, and they were divided into a hazardous drinking group (HD group, n=52) and a non-hazardous drinking group (NHD group, n=72) according to alcohol consumption habits. General information, MoCA score, EPQ score and SCL-90 score were compared between the two groups.Results: Incidence of cognitive disorder in the HD group and NHD group was 59.6% and 56.9% respectively, showing no significant difference (P> 0.05). Scores of visuospatial and executive function, memory, attention and total MoCA score in the HD group were significantly lower than those in the NHD group (P< 0.05), while no significant difference in naming, language, abstract thinking or orientation was found between the two groups (P> 0.05). Scores of extroversion and introversion, neuroticism and psychoticism in the HD group were significantly higher than those in the NHD group (P< 0.05), while no significant difference in lie or feint score was found between the two groups (P> 0.05). Scores of somatization, interpersonal sensitivity, anxiety, hostility, bigotry and psychoticism factors, and total SCL-90 score in the HD group were significantly higher than those in the NHD group (P< 0.05), while no significant difference in scores of obsessive-compulsive, depression and terror factors were found between the two groups (P> 0.05).Conclusion: Compared with male patients with lacunar infarction with non-hazardous drinking, male lacunar infarction patients with hazardous drinking showed worse visuospatial and executive function, memory, attentiveness, cognitive function and mental health status, with more obvious change of personality, thus extra attention is needed for male lacunar infarction patients with hazardous drinking.Keywords: male, lacunar infarction, hazardous drinking, neuropsychology, personality

Limin Zhou,1,* Haojun Wu,2,* Xiang Gao,2,* Xiaoyan Zheng,1 Hang Chen,2 Hailong Li,1 Jun Peng,1 Weichong Liang,1 Wenxing Wang,1 Zuocheng Qiu,3 Anjaneyulu Udduttula,3 Kefeng Wu,1 Lin Li,4 Yuyu Liu,1 Yanzhi Liu1,3 1Guangdong Key Laboratory for Research and Development of Natural Drugs, Department of Pharmacology, Guangdong Medical University, Zhanjiang, Guangdong 524023, People’s Republic of China; 2Department of Orthopaedics, Stem Cell Research and Cellular Therapy Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, People’s Republic of China; 3Translational Medicine R&D Center, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, People’s Republic of China; 4School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, Guangdong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence : Yanzhi Liu Email liuyanzhi02@163.comYuyu Liu Email liuyuyu77@163.comAim: Nonunion is a major complication in fracture repair and remains a challenge in orthopaedics and trauma surgery. In this study, we aimed to evaluate the effectiveness of treatment of nonunion with a large radial defect using a bone-targeting liposome-encapsulated salvianic acid A (SAA-BTL)-incorporated collagen sponge and further elucidate whether the effects were closely related to histone deacetylase 3 (HDAC 3)-mediated endochondral ossification in nonunion healing process.Methods: Fifteen New Zealand female rabbits were randomly divided into three groups. Segmental radius critical size defects (15 mm) were created via surgery on both the forelimbs of the rabbits. The SAA-BTL/SAA/saline-incorporated collagen sponges were implanted into the defects in the three groups, respectively, for four weeks of treatment. X-ray imaging, micro-computed tomography (CT) analysis, histology, and immunofluorescence analysis (HDAC3, collagen II, VEGFA, and osteocalcin) were performed to determine the effects of the treatments. In addition, a short interfering RNA was applied to induce HDAC3 knockdown in the chondrogenic cell line ATDC5 to investigate the roles of HDAC3 and SAA intervention in endochondral ossification in nonunion healing.Results: X-ray imaging and micro-CT results revealed that SAA-BTL-incorporated collagen sponges significantly stimulated bone formation in the nonunion defect rabbit model. Furthermore, immunofluorescence double staining and histology analysis confirmed that SAA-BTL significantly increased the expression of P-HDAC3, collagen II, RUNX2, VEGFA, and osteocalcin in vivo; accelerated endochondral ossification turnover from cartilage to bone; and promoted long bone healing of nonunion defects. ATDC5 cells knocked down for HDAC3 showed significantly decreased expression of HDAC3, which resulted in reduced expression of chondrogenesis, osteogenesis, and angiogenesis biomarker genes (Sox9, Col10a1, VEGFA, RUNX2, and Col1a1), and increased expression of extracellular matrix degradation marker (MMP13). SAA treatment reversed these effects in the HDAC3 knockdown cell model.Conclusion: SAA-BTL can improve nonunion healing through the regulation of HDAC3-mediated endochondral ossification.Keywords: nonunion, fracture, HDAC3, endochondral ossification, bone-targeting liposome, salvianic acid A

Xinyue Zhu,1,2 Zuyun Qiu,1,3 Zixiang Liu,1 Yifeng Shen,4 Qiaoyin Zhou,5 Yan Jia,1,3 Xiaojie Sun,1,3 Shiliang Li1 1Department of Acupuncture and Moxibustion, China–Japan Friendship Hospital, Beijing, People’s Republic of China; 2Department of Rehabilitation Medicine, Beijing First Hospital of Integrated Chinese and Western Medicine, Beijing, People’s Republic of China; 3Graduate School, Beijing University of Traditional Chinese Medicine, Beijing, People’s Republic of China; 4Department of Traditional Chinese Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 5Chinese Medicine College, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Shiliang Li Department of Acupuncture and Moxibustion, China–Japan Friendship Hospital, 4 Sakura Garden Road, Beijing 100029, People’s Republic of ChinaTel +86-135-8177-6268Email zrlishiliang@163.comCase: The patient was a 62-year-old woman presenting with low-back pain of 3 years’ duration and numbness in the right leg.Diagnosis: She was diagnosed with lumbar spinal stenosis based on combined magnetic resonance imaging, physical examination, and symptoms.Interventions: Treatment with computed tomography–guided percutaneous release of the ligamentum flavum was delivered.Outcomes: Relief of symptoms immediately after treatment and complete resolution of symptoms after 1 month were achieved. At follow-up, there was no recurrence of symptoms after 2, 4, 6, and 12 months.Conclusion: Lumbar ligamentum flavum hypertrophy is an important cause of degenerative lumbar spinal stenosis. The hypertrophic ligamentum flavum can directly compress the spinal canal, squeeze the cauda equina, and simultaneously lead to a reduction in the anteroposterior diameter of the intervertebral foramen, which compresses the nerve roots and causes numbness and other symptoms of lower extremities. In clinical practice, doctors should combine imaging findings with patient symptoms for diagnosis and an individualized treatment plan for each patient with lumbar spinal stenosis, and conduct gradual stepwise treatment using conservative minimally invasive surgery to prevent excessive surgery.Keywords: CT guidance, ligamentum flavum, lumbar spinal stenosis, minimally invasive surgery, needle knife

Zhiyu Qiu,1,2,* Lujun Shen,1,3,* Shuanggang Chen,1,3,* Han Qi,1,3 Fei Cao,1,3 Lin Xie,1,3 Weijun Fan1,3 1Department of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Zhong Shan Medical School, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 3State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weijun FanDepartment of Minimally Invasive Interventional Therapy, Sun Yat-sen University Cancer Center, No. 651 Dongfeng East Road, Guangzhou, Guangdong 510060, People’s Republic of ChinaTel/fax +86 20 8734 3272Email fanwj@sysucc.org.cnPurpose: This research aimed to compare the efficacy of combination treatment of transcatheter arterial chemoembolization (TACE) with apatinib versus TACE-alone for intermediate and advanced-stage hepatocellular carcinoma (HCC) cases refractory to TACE.Patients and methods: A total of 125 patients with TACE refractory intermediate or advanced-stage HCC were enrolled and classified as TACE-apatinib group and TACE-alone group. One-to-one matched pairs between two groups were generated using propensity score matching (PSM). Associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Adverse effects (AEs) were compared between two treatment groups to assess the safety of apatinib.Results: Before PSM analysis, the median OS and PFS were 17.0 and 7.0 months in the TACE-apatinib group, while 8.5 and 2.5 months in the TACE-alone group (P

He-Ying Zhong, Zhou Yang, Zhen Qiu, Shao-Qing Lei, Zhong-Yuan XiaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of ChinaCorrespondence: Zhong-Yuan XiaDepartment of Anesthesiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan 430060, Hubei Province, People’s Republic of ChinaTel +86 1 380 862 8560Email xiazhongyuan2005@aliyun.comObjective: In this study, the neuroprotective mechanism of 2-arachidonoylglycerol 2-AG against non-caspase-dependent apoptosis in mice hippocampal neurons following MCAO was investigated.Method: One hundred and fifty healthy clean male C57BL/6 mice were randomly divided into 3 groups: sham group, model group and 2-AG treatment group, 50 mice in each group. A modified Zea Longa method was used to establish a model of middle cerebral artery occlusion (MCAO) in mice. The apoptosis rate and mitochondrial membrane potential of hippocampal nerve cells were measured by flow cytometry. The mRNA expressions of AIF, Endo G and BNIP3 in hippocampal tissues were determined by qPCR. Western blot was used to determine the protein expressions of AIF, Endo G and BNIP3 in the mitochondria of hippocampal tissue.Results: The apoptosis rate of hippocampal neurons in the group treated with 2-AG was significantly lower than that of the model (P

Zhengang Qiu,1,2,* Anqi Lin,1,* Kun Li,1,* Weiyin Lin,1,* Qiongyao Wang,1 Ting Wei,1 Weiliang Zhu,1 Peng Luo,1 Jian Zhang11Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, People’s Republic of China; 2Department of Oncology, First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, People’s Republic of China*These authors contributed equally to this work Purpose: Platinum-based chemotherapy, consisting of etoposide and cisplatin (EP), has been the cornerstone of therapy for extensive-stage small-cell lung cancer (ES-SCLC) for decades. Despite the marked initial sensitivity of SCLC to chemotherapy, EP regimens cannot avoid the emergence of drug resistance in clinical practice. With the rise of new chemotherapy regimens in recent years and the primary resistance or insensitivity of ES-SCLC to EP regimens, it is desirable to be able to identify patients with resistant or insensitive ES-SCLC.Methods: The sequencing and drug sensitivity data of SCLC cell lines were provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). The data regarding sensitivity to etoposide of 54 SCLC cell lines were analyzed, and etoposide-sensitive cell lines and etoposide-resistant cell lines were differentiated according to the IC50 values defined by the GDSC. ROC curve analysis was performed on all mutations and combinations of mutations to select the optimal panel to predict resistance to etoposide.Results: ROC analysis of etoposide resistance revealed that the most significant single gene mutation indicating resistance to etoposide was CSMD3, and the accuracy of predicting resistance to etoposide proved to be the highest when there was any mutation in CSMD3/PCLO/RYR1/EPB41L3, area under the curve =0.804 (95% confidence interval: 0.679–0.930,P

Fan Xu,1 Wenbin Ma,2 Yongmin Huang,1 Zhihai Qiu,1 Lei Sun11Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hung Hom, Hong Kong SAR, People’s Republic of China; 2Department of Neurology, Binzhou Medical University Hospital, Binzhou, Shandong, People’s Republic of ChinaBackground: Parkinson's disease (PD) is a common neurodegenerative disorder that affects many people every year. Deep brain stimulation (DBS) is an effective nonpharmacological method to treat PD motor symptoms. This meta-analysis was conducted to evaluate the efficacy of subthalamic nucleus (STN)-DBS versus globus pallidus internus (GPi)-DBS in treating advanced PD.Methods: Controlled clinical trials that compared STN-DBS to GPi-DBS for short-term treatment of PD in adults were researched up to November 2015. The primary outcomes were the Unified Parkinson’s Disease Rating Scale Section (UPDRS) III score and the levodopa-equivalent dosage (LED) after DBS. The secondary outcomes were the UPDRS II score and the Beck Depression Inventory (BDI) score.Results: Totally, 13 studies containing 1,148 PD patients were included in this meta-analysis to compare STN-DBS versus GPi-DBS. During the off-medication state, the pooled weighted mean difference (WMD) of UPDRS III and II scores were −2.18 (95% CI =−5.11 to 0.74) and −1.96 (95% CI =−3.84 to −0.08), respectively. During the on-medication state, the pooled WMD of UPDRS III and II scores were 0.15 (95% CI =−1.14 to 1.44) and 1.01 (95% CI =0.12 to 1.89), respectively. After DBS, the pooled WMD of LED and BDI were −254.48 (95% CI =−341.66) and 2.29 (95% CI =0.83 to 3.75), respectively.Conclusion: These results indicate that during the off-medication state, the STN-DBS might be superior to GPi-DBS in improving the motor function and activities of daily living for PD patients; but during the on-medication state, the opposite result is observed. Meanwhile, the STN-DBS is superior at reducing the LED, whereas the GPi-DBS shows a significantly greater reduction in BDI score after DBS. Keywords: Parkinson disease, deep brain stimulation, subthalamic nucleus, globus pallidus internus

Mei R Fu,1 Deborah Axelrod,2,3 Charles M Cleland,1 Zeyuan Qiu,4 Amber A Guth,2,3 Robin Kleinman,2 Joan Scagliola,2 Judith Haber1 1College of Nursing, New York University, 2Department of Surgery, NYU School of Medicine, 3NYU Clinical Cancer Center, New York, NY, 4Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA Abstract: Breast cancer-related lymphedema is a syndrome of abnormal swelling coupled with multiple symptoms resulting from obstruction or disruption of the lymphatic system associated with cancer treatment. Research has demonstrated that with increased number of symptoms reported, breast cancer survivors' limb volume increased. Lymphedema symptoms in the affected limb may indicate a latent stage of lymphedema in which changes cannot be detected by objective measures. The latent stage of lymphedema may exist months or years before overt swelling occurs. Symptom report may play an important role in detecting lymphedema in clinical practice. The purposes of this study were to: 1) examine the validity, sensitivity, and specificity of symptoms for detecting breast cancer-related lymphedema and 2) determine the best clinical cutoff point for the count of symptoms that maximized the sum of sensitivity and specificity. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Lymphedema symptoms were assessed using a reliable and valid instrument. Validity, sensitivity, and specificity were evaluated using logistic regression, analysis of variance, and areas under receiver operating characteristic curves. Count of lymphedema symptoms was able to differentiate healthy adults from breast cancer survivors with lymphedema and those at risk for lymphedema. A diagnostic cutoff of three symptoms discriminated breast cancer survivors with lymphedema from healthy women with a sensitivity of 94% and a specificity of 97% (area under the curve =0.98). A diagnostic cutoff of nine symptoms discriminated at-risk survivors from survivors with lymphedema with a sensitivity of 64% and a specificity of 80% (area under the curve =0.72). In the absence of objective measurements capable of detecting latent stages of lymphedema, count of symptoms may be a cost-effective initial screening tool for detecting lymphedema. Keywords: screening, risk, swelling, pain, heaviness, sensitivity

The post-installation consolidation settlement of spudcan foundations is an issue of concern for the offshore jack-up industry, especially when jack-up rigs operate for a long period such as those serving as production units. Although many centrifuge tests or numerical calculations have been conducted for spudcan behaviour after consolidation, there are no guidelines available to predict the consolidation settlement development. This paper reports a study dedicated to this subject. The spudcan installation and consolidation under operational load was continually simulated through the dual-stage Eulerian-Lagrangian analyses incorporating the modified Cam-clay model. Its feasibility and reliability were verified by comparison with other experimental results in literature. Parametric studies were carried out for spudcans under various soil parameters and geometrical conditions. A suitable method, Hyperbolic method, is proposed to predict spudcan settlement during consolidation with observed data.

Zhifang Qiu,1,2 Steven L Farnsworth,2 Anuja Mishra,1,2 Peter J Hornsby1,21Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, TX, USA; 2Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, San Antonio, TX, USAAbstract: The development of the technology for derivation of induced pluripotent stem (iPS) cells from human patients and animal models has opened up new pathways to the better understanding of many human diseases, and has created new opportunities for therapeutic approaches. Here, we consider one important neurological disease, Parkinson's, the development of relevant neural cell lines for studying this disease, and the animal models that are available for testing the survival and function of the cells, following transplantation into the central nervous system. Rapid progress has been made recently in the application of protocols for neuroectoderm differentiation and neural patterning of pluripotent stem cells. These developments have resulted in the ability to produce large numbers of dopaminergic neurons with midbrain characteristics for further study. These cells have been shown to be functional in both rodent and nonhuman primate (NHP) models of Parkinson's disease. Patient-specific iPS cells and derived dopaminergic neurons have been developed, in particular from patients with genetic causes of Parkinson's disease. For complete modeling of the disease, it is proposed that the introduction of genetic changes into NHP iPS cells, followed by studying the phenotype of the genetic change in cells transplanted into the NHP as host animal, will yield new insights into disease processes not possible with rodent models alone.Keywords: Parkinson's disease, pluripotent cell differentiation, neural cell lines, dopaminergic neurons, cell transplantation, animal models

A method for detecting dc spin current propagation through an epitaxial antiferromagnetic (AFM) NiO layer is presented. Spin current is generated by spin pumping from an adjoining ferromagnetic (FM) layer and detected in a non-magnetic metallic layer by the inverse spin Hall effect. Comparison is made with a YIG/Pt bilayer, where only the Pt layer is electrically conducting, but for which spin Hall magnetoresistance makes an additional contribution to the measured signal. The signal obtained from the multilayered stack containing the AFM NiO layer is found to contain additional contributions due to anisotropic magnetoresistance. By exciting the sample with out-of-plane rf magnetic field and making measurements with a static field applied at different orientations within the plane of the sample, a signal associated with the dc spin current may be identified.

Néel-type magnetic skyrmions in multilayers are promising candidates for ultra-low power spintronic devices. To image the Néel-type skyrmions using Lorentz transmission electron microscopy (L-TEM), the samples must be tilted. Thus, the external magnetic field consists of both in-plane and out-of-plane components. To date, it is still not well known on the effect of the in-plane magnetic field on the L-TEM images, leading to ambiguities in retrieving the structure of Néel-type skyrmions. Here, Néel-type skyrmions in three [Pt/Co/Ta]20 multilayer samples, with the easy magnetization axis being tuned from the out-of-plane to the in-plane direction by increasing the Co thickness from 1.8 to 2.2 nm, are imaged. When using a smaller defocus value (-2 mm) and a higher magnification (×9100) of L-TEM, a surprising dark-bright-dark-bright double contrasted pattern, instead of the previously reported dark-bright contrasted pattern, is observed. The additional dark-bright contrasted pattern becomes more evident for thicker Co layer samples in which the magnetization axis tilts more toward the in-plane direction. Further analysis, via a combination of magnetic force microscopy experiments, micromagnetic simulations, and micromagnetic analysis to Lorentz TEM simulation, shows that the additional dark-bright features originate from the deformation of the Néel-type skyrmions within an in-plane magnetic field.

Among many efforts in the research of van der Waals (vdW) magnetic materials, increasing the Curie temperature above room temperature has been at the center of research in developing spintronics technology using vdW materials. Here an effective and reliable method of increasing the Curie temperature of ferromagnetic Fe3GeTe2 vdW materials by Ga implantation is reported. It is found that implanting Ga into Fe3GeTe2 by the amount of 10−3 Ga Å−3 could greatly enhance the Fe3GeTe2 Curie temperature by almost 100%. Spatially resolved microdiffraction and element-resolved X-ray absorption spectroscopy show little changes in the Fe3GeTe2 crystal structure and Fe valence state. In addition, the Ga implantation changes the Fe3GeTe2 magnetization from out-of-plane direction at low temperature to in-plane direction at high temperature. The result opens a new opportunity for tailoring the magnetic properties of vdW materials beyond room temperature.