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

Zhi-Feng Liu,* Yang Zhang,* Jing Liu, Yu-Yan Wang, Mo Chen, Er-Yang Liu, Jun-Ming Guo, Yan-Hua Wang, Zhi-Wen Weng, Chang-Xin Liu, Chang-He Yu, Xi-You Wang Tuina and Pain Management Department, Beijing University of Chinese Medicine Affilliated Dongzhimen Hospital, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chang-He Yu; Xi-You Wang, Email yakno2@163.com; dwxy658@163.comAbstract: Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.Keywords: knee osteoarthritis, traditional Chinese non-pharmacological therapy, mechanism, acupuncture, tuina, acupotomy

Shao-Li Huang,1– 3,* Hong-Yi Xin,4,5,* Xiao-Yan Wang,4,5,* Guang-Gui Feng,3 Fu-Qing Wu,3 Zhi-Peng Feng,6 Zhou Xing,2 Xi-He Zhang,4,5 Hong-Wu Xin,4,7,8 Wen-Ying Luo1 1Medical Laboratory Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524400, People’s Republic of China; 2First Clinical College, Guangdong Medical University, Guangdong, 524400, People’s Republic of China; 3Clinical laboratory, Lianjiang People’s Hospital, Guangdong, 524400, People’s Republic of China; 4Doctoral Scientific Research Center, Lianjiang People’s Hospital, Guangdong, 524400, People’s Republic of China; 5Guangdong Medical University Affiliated Lianjiang People’s Hospital, Guangdong, 524400, People’s Republic of China; 6Department of Gastroenterology, Yueyang Hospital Affiliated to Hunan Normal University, Yueyang, Hunan, 414000, People’s Republic of China; 7Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Faculty of Medicine, Yangtze University, Jingzhou, Hubei, 434023, People’s Republic of China; 8Research Centre of Molecular Medicine, Medical College of Chifeng University, Chifeng, Inner Mongolian Autonomous Region, 024000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wen-Ying Luo, Medical laboratory Center, Affiliated Hospital of Guangdong Medical University, 57th South Renmin Road, Zhanjiang, 524001, People’s Republic of China, Tel +86 18312728748, Email luo_wenying@126.com Xi-He Zhang, Doctoral Scientific Research Center, Lianjiang People’s Hospital, Guangdong, 524400, People’s Republic of China, Tel +86 19126491230, Email hljsnjx@163.comAbstract: Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.Keywords: venous thromboembolism, miRNA, neutrophil extracellular traps, plasminogen activator inhibitor-1, EVs, inflammatory factor

Xiao-Yu Wang,1– 3,* San-Hua Xu,3,* Hong Wei,3,* Min Kang,3 Jie Zou,3 Qian Ling,3 Hui Huang,3 Xu Chen,4 Yi-Xin Wang,5 Yi Shao,3 Yao Yu1 1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Jiangxi Clinical Research Center for Endocrine and Metabolic Disease, Jiangxi Branch of National Clinical Research Center for Metabolic Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 2The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Jiangxi Branch of National Clinical Research Center for Ocular Disease, Nanchang, Jiangxi, 330006, People’s Republic of China; 4Department of Ophthalmology and Visual Sciences, Maastricht University, Maastricht, Limburg Province, 6200MA, Netherlands; 5School of Optometry and Vision Sciences, Cardiff University, Cardiff, CF244HQ, UK*These authors contributed equally to this workCorrespondence: Yi Shao, Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email freebee99@163.com Yao Yu, Department of Endocrinology and Metabolism, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China, Email yuyao1234562023@163.comPurpose: This study aimed to explore the spontaneous brain activity in patients with diabetic optic neuropathy (DON) by using the amplitude of low-frequency fluctuation (ALFF) technique.Methods: Sixteen DON patients and 16 age- and sex-matched healthy controls (HCs) were recruited. ALFF along with functional MRI method was used to detect the intrinsic brain activity alterations. The mean values of ALFF in DON patients and HCs were analyzed by receiver operating characteristic (ROC) curves. Pearson’s correlation analysis was used to determine the correlation between Hospital Anxiety and Depression Scale (HADS) and ALFF values of DONs.Results: The DON group showed significantly increased ALFF values in the fusiform gyrus, and decreased ALFF values in the medial frontal gyrus/left frontal superior orbit/right frontal medial orbit, and left frontal inferior triangle. ROC curve analysis indicated that the accuracy of AUC was good. The anxiety scale and depression scale of the DON group were negatively correlated with the ALFF values of the medial frontal gyrus.Conclusion: DON is a neurodegenerative disease involving multiple brain regions. The abnormal activity of neurons in these brain regions helps to reveal the underlying neural mechanisms of brain activity related to DON.Keywords: ALFF, fMRI, diabetic optic neuropathy, spontaneous brain activity

Xiao-Yan Wang,1 Xiao-Jing Zhang,2 Xiao Xia,3 Shu-Zhen Chang,4 An-Zhao Wu4 1Infectious Diseases Department II, Shandong Public Health Clinical Center, Jinan, 250000, People’s Republic of China; 2Public Health Department, Shandong Public Health Clinical Center, Jinan, 250000, People’s Republic of China; 3Medical Insurance Office, Shandong Public Health Clinical Center, Jinan, 250000, People’s Republic of China; 4TCM & Western Medicine Department, Shandong Public Health Clinical Center, Jinan, 250000, People’s Republic of ChinaCorrespondence: An-Zhao Wu, TCM & Western Medicine Department, Shandong Public Health Clinical Center, 2999 Gangxing West Road, High Tech District, Jinan, 250000, People’s Republic of China, Tel +86 531-86568184, Email anzhaowu564@outlook.comObjective: This study aimed to analyze the epidemiological and clinical characteristics of measles in Jinan, Shandong, China, over a 32-year stage to facilitate measles prevention in the future.Methods: Data on measles cases from 1991 to 2022 were obtained from the public health department and medical records of patients at Shandong Public Health Clinical Center. Retrospective analysis was conducted on the distribution of measles cases in different years, months, and age groups, and observation of the differences in clinical manifestations and complications among different age groups.Results: From January 1991 to December 2022, 7531 measles cases were recorded at Shandong Public Health Clinical Center. During the 32-year period, there were two outbreaks of measles in 2008 and 2016, respectively. During the COVID-19 pandemic period from 2020 to 2022, the number of cases reached the lowest point in the past 30 years. The number and percentage of cases in the 0– 1y groups was significantly higher than in other age groups, and 97.75% patients in this group did not receive measles vaccine. Complications such as pneumonia and myocarditis appeared more frequent in patients under 12 years of age, but liver function damage is more common in adult patients.Conclusion: Although the measles epidemic has been greatly controlled since the use of measles vaccine, intermittent outbreaks still exist, so there is still a long way to go to eliminate measles. The proportion of infants under the age of 1 without measles vaccine and adults over 24 years old accounts for nearly 80% of the total. This group of people should be of concern, and feasible measures should be designated to protect these susceptible populations.Keywords: measles, epidemiology, clinical characteristics, vaccination, China

Xin-Qi He,1,* Hui-Qing Qiu,2,* Meng Wang,3,* Ya-Fei Mao,4 Xin-Yuan Li,4 Xian-Yun Wang,5 Yu-Lan Geng,4 Le Wang6 1Department of Vascular Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 2Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 3Department of Radiology and Nuclear Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Department of Laboratory Medicine, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Scientific Research Data Center, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 6Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu-Lan Geng, Department of Laboratory Medicine, The First Hospital of Hebei Medical University, No. 89 of Donggang Road, Yuhua District, Shijiazhuang, 050031, People’s Republic of China, Tel +86 311 87156567, Fax +86 311 85917029, Email ylgeng123@163.com Le Wang, Department of Cardiology, The First Hospital of Hebei Medical University, No. 89 of Donggang Road, Yuhua District, Shijiazhuang, 050031, People’s Republic of China, Tel +86 311 87155263, Fax +86 311 85917029, Email coronary2012@163.comBackground: A thoracic aortic aneurysm (TAA) is a known condition seen in cardiovascular practice. A TAA rupture and postoperative infection may result in death. Preoperative infections leading to death are extremely rare.Case Study: A 62-year-old Chinese female was admitted to The First Hospital of Hebei Medical University with a two-day history of abdominal pain. She was diagnosed with a TAA rupture and underwent immediate surgery. The preoperative urine analysis indicated that the positive bacteria and white blood cell count suggested a urinary tract bacterial infection. The patient was administered the empiric antibiotics, cefazolin; however, her blood pressure continued to drop during the perioperative period and she died of uncorrectable acidosis 8 h after the operation. On the second day after death, both the blood and urine cultures were positive for Pseudomonas aeruginosa.Conclusion: Given that this patient with a TAA rupture died of uncorrected acidosis caused by preoperative infection, it is important to evoke the diagnosis in the context of TAA. Routine laboratory indicators are valuable factors for surgeons and physicians in assessing a patient’s condition and improving their prognosis.Keywords: thoracic aortic aneurysm, infection, sepsis, acidosis, urine routine, emergency surgery, empirical medication, Pseudomonas aeruginosa

Ma-Chao Li,1,* Xiao-Yue Wang,1,* Tong-Yang Xiao,2,* Shi-Qiang Lin,3 Hai-Can Liu,1 Cheng Qian,4 Da Xu,1 Gui-Lian Li,1 Xiu-Qin Zhao,1 Zhi-Guang Liu,1 Li-Li Zhao,1 Kang-Lin Wan1 1State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Bioinformatics, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, People’s Republic of China; 4Beijing Center for Disease Control and Prevention, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Li Zhao; Kang-Lin Wan, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, P.O. Box 5, Changping, Beijing, 102206, People’s Republic of China, Tel/Fax +86 10 58900779, Email zhaolili@icdc.cn; wankanglin@icdc.cnObjective: To assess the relationship between the variant rpoB mutations and the degree of rifampin (RIF)/rifabutin (RFB) resistance in Mycobacterium tuberculosis (M. tuberculosis).Methods: We analyzed the whole rpoB gene in 177 M. tuberculosis clinical isolates and quantified their minimum inhibitory concentrations (MICs) using microplate-based assays.Results: The results revealed that of the 177 isolates, 116 were resistant to both RIF and RFB. There were 38 mutated patterns within the sequenced whole rpoB gene of the 120 isolates. Statistical analysis indicated that mutations, S450L, H445D, H445Y, and H445R, were associated with RIF and RFB resistance. Of these mutations, S450L, H445D, and H445Y were associated with high-level RIF and RFB MIC. H445R was associated with high-level RIF MIC, but not high-level RFB MIC. D435V and L452P were associated with only RIF, but not RFB resistance. Q432K and Q432L were associated with high-level RFB MIC. Several single mutations without statistical association with rifamycin resistance, such as V170F, occurred exclusively in low-level RIF but high-level RFB resistant isolates. Additionally, although cross-resistance to RIF and RFB is common, 21 RIF-resistant/RFB-susceptible isolates were identified.Conclusion: This study highlighted the complexity of rifamycin resistance. Identification of the rpoB polymorphism will be helpful to diagnose the RIF-resistant tuberculosis that has the potential to benefit from a treatment regimen including RFB.Keywords: Mycobacterium tuberculosis, rifampin resistance, rifabutin resistance, mutation

Hong-Peng Chen,1,2,* Xiao-Yan Wang,1,* Xiao-Yan Pan,1 Wang-Wang Hu,1 Shu-Ting Cai,1 Kiran Joshi,3 Lie-Hua Deng,1,2 Daqing Ma3 1Department of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, People’s Republic of China; 2Zhanjiang Key Laboratory of Organ Injury and Protection and Translational Medicine, Zhanjiang, Guangdong, People’s Republic of China; 3Division of Anesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK*These authors contributed equally to this workCorrespondence: Lie-Hua Deng; Daqing MaDepartment of Critical Care Medicine, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, ChinaEmail glinson@126.com; d.ma@imperial.ac.ukIntroduction: Because of its high morbidity and mortality, sepsis remains the leading cause of death in the ICU. Microparticles (MP) have been largely studied as potential diagnostic or prognostic markers in various diseases including sepsis.Objective: The biological and clinical relevance of neutrophil-derived microparticles (NDMPs) within the MP population remains unclear. The objective of this study was to elucidate the relationship between plasma NDMPs and the prognosis of patients with sepsis and/or septic shock.Methods: The study was designed as an observational, noninterventional clinical study. The cohort for this study included 40 sepsis and 40 septic shock patients together with 10 healthy controls admitted to the Intensive Care Unit (ICU) and the Health Surveillance Center in the Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China, from January to November 2018, respectively. The degree of critical disease for sepsis and septic shock was evaluated, with data analyses conducted from 2018 to 2019.Results: On days 1, 3 and 5 post-admission a series of data including plasma NDMP levels, patient demographics, TNF-α levels, IL-6 levels, sTREM-1 levels, and the sepsis severity score measurements were collected. A survival curve was plotted against levels of plasma NDMPs. Levels of NDMPs were observed to be higher in the septic shock patients than in the sepsis patients on days 1, 3, and 5 post-ICU admission (p < 0.05). NDMP levels were significantly increased in sepsis and septic shock patients with a parallel increase in pro-inflammatory mediators and sepsis severity score (p < 0.05) as well as mortality.Conclusion: Our data suggest that NDMPs may be a biomarker of sepsis severity and mortality although its implications on sepsis prognosis warrant further study.Keywords: sepsis, septic shock, cell-derived microparticles, biomarker, prognosis

Lu Ding, Yu-Hang Gao, Ye-Ran Li, Yi-Fan Huang, Xin-Yu Wang, Xin Qi Department of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin University, Chang Chun, People’s Republic of ChinaCorrespondence: Xin QiDepartment of Orthopaedic Surgery, The First Hospital of Jilin University, Jilin University, Xinmin St 71, Chang Chun, People’s Republic of ChinaTel +8615843073202Fax +86043181875600Email qixindoc@163.comPurpose: This study was to evaluate the metabolic score for insulin resistance (METS-IR) in female knee osteoarthritis (KOA) patients in a Chinese population. The associations between METS-IR and adipokines, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were investigated.Patients and Methods: This study included 4686 women from the 2011 China Health and Retirement Longitudinal Study (CHARLS) and 108 women who underwent arthroplasty of KOA at a university hospital. The clinical data were collected, and adipokines were evaluated. METS-IR was calculated in the KOA patients and compared with the national baseline. Logistic regression analyses were applied to explore the associations of METS-IR with adipokines, ESR, and CRP.Results: Receiver operating characteristic curve analysis of METS-IR and metabolic syndrome (MetS) in national baseline showed an area under the curve value of 0.851, with sensitivity of 0.777 and specificity of 0.772. The METS-IR of KOA was higher than the national baseline level (40.29 ± 6.98 vs 36.20 ± 8.50, P < 0.01), even after adjusting age. In addition, the METS-IR was higher in patients with KOA who had MetS than in those without metabolic syndrome (nMetS), even after adjusting body mass index (BMI). After adjusting for age and BMI, METS-IR was associated with CRP (OR 1.238, 95% confidence interval (CI) 1.088, 1.409, P < 0.01), ESR (OR 1.124, 95% CI 1.008, 1.254, P = 0.036), plasma leptin (OR 1.123, 95% CI 1.052, 1.199, P < 0.01), plasma resistin (OR 1.134, 95% CI 1.011, 1.271, P = 0.031), and plasma adiponectin (OR 0.865, 95% CI 0.771, 0.971, P = 0.014).Conclusion: METS-IR in female KOA was higher than that of the national baseline. The METS-IR was related to adipokine disorder and inflammatory activity. These findings suggest that METS-IR can be used to evaluate the degree of involvement of MetS in KOA.Keywords: knee osteoarthritis, metabolic syndrome, insulin resistance, metabolic score for insulin resistance

Xiang-Zhi Zhao,1,2 Wei Zhang,1 Yang Cao,1,3 Shuai-Shuai Huang,4 Yi-Zhen Li,5 Dan Guo,1 Xing-Yue Wang,1 Hai-Tao Ran1,3 1Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing 400016, People’s Republic of China; 2Department of Cardiovascular Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People’s Republic of China; 3Ultrasound Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 4Department of Renal Disease, Urology and Nephrology Hospital of Ningbo University, Ningbo 315100, Zhejiang, People’s Republic of China; 5Department of Cardiovascular Ultrasound and Noninvasive Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, People’s Republic of ChinaCorrespondence: Hai-Tao RanUltrasound Department of the Second Affiliated Hospital of Chongqing Medical University, No. 76, Linjiang Road, Chongqing, Yuzhong District 400010, People’s Republic of ChinaEmail ranhaitao@cqmu.edu.cnObjective: To construct an ideal theranostic nanoplatform (LIP3); to clarify its physicochemical properties; to confirm its characteristics of dual-modality imaging, active-targeting, and cascade amplification therapy for mammary carcinoma; and to perform a preliminary exploration of the cytotoxicity mechanism.Design: A self-prepared liposome nanosystem, LIP3, can actively target 4T1 cells because the surface is linked with C-RGD. Haematoporphyrin monomethyl ether (HMME), an excellent sonosensitizer entrapped in the lipid bilayer, can function in photoacoustic imaging. Low-intensity focused ultrasound (LIFU) of ultrasound-targeted microbubble destruction (UTMD) promotes localized drug delivery into tumours because PFH, a phase-change substance, is loaded in the LIP3 core, achieving visualization of targeted drug release, and sonodynamic therapy (SDT) can kill tumour cells. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging and precise treatment.Results: The self-prepared lipid nanosystem, LIP3, meets the above expectations and has ideal physicochemical properties, with a regular sphere with uniform distribution. Contrast-enhanced ultrasound (CEUS), photoacoustic imaging, and bimodal imaging were effective in vitro. In 4T1 cell experiments, the cell capacity was as high as 42.9%, and the cytotoxicity to 4T1 was more than 5 times that of LIP1 (containing AQ4N only) and more than 2 times that of LIP2 (containing only HMME), achieving comparable results as cascade therapy for mammary cancer.Conclusion: LIP3, a theranostic nanoplatform, was successfully constructed and conformed to the physicochemical characterization of ideal nanoparticles, with active-targeting, dual-modality imaging, visualized drug release, and precise treatment under the action of LIFU. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.Keywords: LIFU, SDT, HMME, AQ4N

Xiao-Dong Zhang,1,2 Guang-Xue Liu,3 Xiao-Yue Wang,2 Xiao-Jie Huang,4 Jing-Li Li,1 Rui-Li Li,2 Hong-Jun Li2 1Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, People’s Republic of China; 2Department of Radiology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of China; 3Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 4Center for Infectious Diseases, Beijing Youan Hospital, Capital Medical University, Beijing 100069, People’s Republic of ChinaCorrespondence: Rui-Li Li; Hong-Jun LiDepartment of Radiology, Beijing Youan Hospital, Capital Medical University, No. 8, Xi Tou Tiao, Youanmen Wai, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 010 83997337Fax +86 010 63051182Email 1985lrli@sina.com; lihongjun00113@sina.comObjective: This study assessed the possible effect of syphilis co-infection in the brain function in young HIV patients by using voxel-wise degree centrality (DC) analysis.Methods: Forty-four syphilis-co-infected HIV patients (HIV+/syphilis+), 45 HIV patients without syphilis history (HIV+/syphilis-) and 43 matched healthy controls (HC) underwent resting-state fMRI examinations. Laboratory tests and a battery of neuropsychological tests were performed before each MRI examination. One-way ANOVA was used to compare the differences of DC among the three groups. The correlations between MRI metrics and laboratory/neuropsychological tests in each patient’s group were performed by Pearson correlation analysis.Results: Compared with HIV+/syphilis-, worse performance in complex motor skills was found in HIV+/syphilis+. Compared with HC, HIV+/syphilis+ and HIV+/syphilis- groups showed attenuated DC in the right orbital frontal cortex and increased DC in the left parietal/temporal cortex. Besides, we also found increased DC in the left inferior frontal cortex and bilateral posterior cingulated cortex/precuneus in HIV+/syphilis+ compared with HC. Moreover, compared with HIV+/syphilis-, HIV+/syphilis+ displayed decreased DC in the left middle occipital cortex. Additionally, in HIV+/syphilis+ group, the mean z value of DC was correlated to the CD4+ cell counts and the learning and delayed recall score.Conclusion: Syphilis co-infection might be related to more brain functional reorganization in young HIV patients which could be reflected by DC value.Keywords: syphilis, HIV, functional connectivity, fMRI, brain

Fei Ye1,*, Qiong Lan Tang2,*, Fang Ma1,*, Lei Cai,1 Ming Chen,1 Xiao Xia Ran,1 Xiao Yu Wang,1 Xue Feng Jiang11Department of Obstetrics and Gynecology, The First Affiliated Hospital, Jinan University, Guangzhou 510630, People’s Republic of China; 2Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People’s Republic of China*These authors contributed equally to this workBackground/aims: Circular RNAs (circRNAs), a class of newly discovered endogenous noncoding RNAs, have shown large capabilities in gene regulation. Patients with the grade 3 endometrial cancer (EC) have a generally poor prognosis, and the specific role of circRNAs in the grade 3 EC remains unclear. This study aims to investigate the roles of circRNAs in the grade 3 EC.Methods: In the current study, we screened the expression profiles of circRNAs taken from two women with the grade 3 EC and adjacent non-cancerous endometrial tissue using circRNAs sequencing. Bioinformatic analyses were applied to study these differentially expressed circRNAs. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) of six dysregulated circRNAs was performed to validate the sequencing results. Bioinformatic analyses, including the negative correlation network analyses of circRNAs–microRNAs (miRNAs)–messenger RNAs (mRNAs) and the Cytoscape, were used to delineate the interaction of circRNAs/miRNAs of the entire network.Results: Data of circRNA sequencing showed a significant change in 75,928 unique circRNAs (P

Yan Lei Chen,1 Weirong Joshua Sng,2 De Yun Wang,2 Xue Yan Wang11Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Otolaryngology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, SingaporeBackground: Several studies have shown that the use of antibiotics early in life significantly increases the risk of asthma in children. It is unclear whether antibiotics are more commonly used in patients with allergy-related diseases.Methods: A multistage, clustered and random sampling with a field-interviewer-administrated survey study was performed to investigate if there was multiple use of antibiotics (MUA) in patients with allergic rhinitis (AR), conjunctivitis, chronic urticaria (CU), and asthma in the grasslands of northern China. MUA was defined as antibiotic usage for at least 3 days and for more than 3 times a year in the past 2 years.Results: A total of 5,787 subjects completed the study, with 1,079 subjects (18.6%) identified as MUA. MUA was more common in patients with AR (23.7% vs 16.2%, P

Hong-Yi Yang, Dai-Hong Guo, Wang-Ping Jia, Man Zhu, Yuan-Jie Xu, Xiao-Yu Wang Department of Pharmaceutical Care, General Hospital of People’s Liberation Army, Beijing 100853, China Background: Fluoroquinolone-related hepatotoxicity is rare but serious and is attracting increasing attention. We explored the incidence, clinical features and risk factors of acute liver injury associated with fluoroquinolone use.Materials and methods: Based on the Adverse Drug Events Active Surveillance and Assessment System that we developed, we carried out a case-control study by enrolling patients who were hospitalized and received fluoroquinolones to treat or prevent infections at the Chinese People’s Liberation Army General Hospital from Jan 2016 to Dec 2017. The incidence of fluoroquinolone-induced acute liver injury was estimated, and logistic regression was used to reveal the risk factors of this adverse reaction.Results: We found that 17,822 patients received fluoroquinolones, and 13,678 of them met the inclusion criteria. A total of 91 patients developed acute liver injury after receiving the medication, and 369 controls were matched to these patients. The overall incidence of fluoroquinolone-induced acute liver injury in the Chinese population is approximately 6–7 cases per 1,000 individuals annually. Multivariate logistic regression analysis showed that older age slightly decreased the risk of hepatotoxicity (OR, 0.98; 95% CI, 0.96–0.99). The male sex (OR, 2.19; 95% CI, 1.07–4.48), alcohol abuse (OR, 2.91; 95% CI, 1.39–6.11) and hepatitis B carrier status (OR, 2.38; 95% CI, 1.04–5.48) increased the risk of liver injury. Concurrent use of cephalosporins or carbapenems was also associated with an increased risk.Conclusion: Increased risk of fluoroquinolone-related hepatotoxicity may be associated with youth, the male sex, alcohol abuse, hepatitis B carrier status and the concurrent use of cephalosporins or carbapenems. Keywords: fluoroquinolones, drug-induced liver injury, incidence, risk factors, pharmacovigilance

Ying Zhu,1,2,* Xiang-Yu Wang,1,2,* Yu Zhang,1,2,* Da Xu,1,2,* Jian Dong,3,4 Ze Zhang,1,2 Chen-He Yi,1,2 Hu-Liang Jia,1,2 Xin Yang1,2 1Department of General Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China; 2Institutes of Cancer Metastasis, Fudan University, Shanghai 200040, China; 3Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China; 4Institute of Advanced Surgical Technology and Engineering, First Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710061, China *These authors contributed equally to this work Background: Agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 immune checkpoint exhibited promising clinical outcomes in a variety of malignant tumors, including intrahepatic cholangiocarcinoma (ICC). However, the relationship between PD-L1 expression and CD8+ T-cell immune responses is not well defined in ICC.Patients and methods: We investigated PD-L1 expression immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 192 ICC patients undergoing curative resection and correlated our results with the clinicopathologic features and prognosis. We also quantified CD8+ T-cell infiltration in ICC specimens and evaluated the relationship between PD-L1 expression and CD8+ T-cell infiltration. After incubating human ICC cell lines (HCCC9810 and RBE) with interferon (IFN)-γ, we measured the PD-L1 expression of these ICC cells by Western blot and flow cytometry.Results: Only 34 patients (17.7%) showed ≥5% membranous PD-L1 expression on tumor cells, and tumoral PD-L1 overexpression (≥5%) was significantly associated with superior overall survival (P=0.012) and disease-free survival (P=0.018). A significant positive association was found between PD-L1 expression and the presence of CD8+ T-cells. In fresh frozen ICC specimens, IFN-γ was found to be significantly correlated with PD-L1 and CD8A gene expression, as evaluated by reverse transcription-polymerase chain reaction. Moreover, stimulation of the HCCC9810 and RBE cells with recombinant IFN-γ, secreted by CD8+ T-cells rapidly induced PD-L1 upregulation in these cell lines in vitro.Conclusion: Tumor PD-L1 overexpression is mainly stimulated by activated CD8+ T-cells pre-existing in the ICC microenvironment, and PD-L1 is a favorable prognostic factor for the patients. These observations suggest that anti-PD-L1/programmed death receptor 1 therapy may benefit ICC patients with tumor cell PD-L1 expression and the presence of CD8+ T-cells. Keywords: tumor microenvironment, adaptive immune resistance, PD-L1, CD8+ T-cell, IFN-γ

Yan-zhi Liu,1,2 Mohammed P Akhter,3 Xiang Gao,4 Xiao-yan Wang,2 Xiao-bei Wang,2 Gang Zhao,2 Xin Wei,2 Hao-jun Wu,4 Hang Chen,4 Dong Wang,2 Liao Cui1 1Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; 3Osteoporosis Research Center, Department of Medicine, Creighton University, Omaha, NE, USA; 4Stem Cell Research and Cellular Therapy Center, Department of Orthopaedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China Background: The objective of the study was to investigate the effects of glucocorticoid (GC) on the fracture healing process in a closed femur fracture mice model.Materials and methods: Forty 12-week-old female CD-1 mice were randomly allocated into four groups: healthy control and mice with prednisone exposure (oral gavage), 6 mg/kg/day (GC-L), 9 mg/kg/day (GC-M) and 12 mg/kg/day (GC-H). Three weeks after the initiation of prednisone dosing, closed femur fractures were created on prednisone-exposed mice and the healthy control. Prednisone administration was continued for 9 weeks post-fracture, and X-ray imaging was performed weekly to monitor the fracture healing process until the mice were euthanized. Necropsy was performed after 9 weeks and the fractured femurs were isolated and processed at necropsy for micro-CT and biomechanical property analysis. Another 20 mice (control and GC-H, 10 mice/group) were used for histology and micro-CT analysis at early time point (2-week post fracture) with continued prednisone exposure.Results: The results showed that oral administration of prednisone for 3 months in this strain of mice could inhibit endochondral ossification and delay the healing process, especially hard callus formation (woven bone) and bone remodeling during healing. It also could significantly decrease bone biomechanical properties.Conclusion: Long-term GC administration leads to significantly delayed fracture healing and impaired bone biomechanical properties. This mouse model may be used to systematically study the cellular and molecular mechanisms underlying fracture healing with GC treatment background and may also be used to study the influence of different therapeutic interventions for bone fracture healing. Keywords: delayed healing, non-union, fracture, glucocorticoid, mouse, stiffness, toughness

Liju Zong, Junjun Yang, Xiaoyu Wang, Yujia Kong, Tong Ren, Jun Zhao, Fengzhi Feng, Xirun Wan, Yang Xiang Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China Purpose: The aims of this study were to analyze the clinical features, identify prognostic factors, and evaluate the survival outcomes of gestational trophoblastic neoplasia (GTN) patients with liver metastases. Patients and methods: Forty patients with liver metastases arising from GTNs, who were treated at the Peking Union Medical College Hospital (Beijing, People’s Republic of China) between January 1999 and December 2015, were recruited from the institutional database, and their medical records were reviewed. Univariate and multivariate analyses were performed to identify independent risk factors for survival. Results: Twenty-seven patients (67.5%) achieved complete remission after multidrug chemotherapy treatment. The remaining 13 patients (32.5%) had disease progression. Eighteen patients (45.0%) died during treatment or follow-up. A history of failed multidrug chemotherapy was an independent risk factor for survival (OR: 5.57, 95% CI: 1.42–21.86, P=0.014). Moreover, patients with an International Federation of Gynecology and Obstetrics (FIGO) score of >16 had a significantly poorer survival than those with a score of ≤16 (P16 have poorer survival outcomes. Multidrug chemotherapy is the key to the management of GTN patients with liver metastases. Keywords: multidrug chemotherapy failure, FIGO score, multidrug chemotherapy, hepatic metastasis

Ting Ting Ma,1–3 Yan Zhuang,1 Hai Ying Gong,4 Anthony Chauang Yii,5 Xue Yan Wang,1 Huan Zhong Shi2,3 1Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, 2Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, 3Center of Medical Research, Beijing Institute of Respiratory Diseases, 4Fangshan District Center for Disease Control and Prevention, Beijing, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore Background: The diagnosis of asthma is made on the basis of variable respiratory symptoms and supported by objective evidence of variable airflow limitation. However, spirometry and bronchoprovocation tests may not be routinely available in resource-scarce settings or in the context of large-scale epidemiological studies. There is a gap in knowledge about the predictive value of respiratory symptoms for the diagnosis of pollen-induced asthma.Objective: The aim of this study was to investigate the predictive value of self-reported respiratory symptoms for diagnosing pollen-induced asthma.Patients and methods: We recruited 1,161 patients with respiratory symptoms who presented to the respiratory medicine outpatient clinic of two central hospitals in Inner Mongolia during the pollen season of July–September 2015. All patients were interviewed by a respiratory physician and completed a questionnaire survey, lung function tests and skin prick tests for common inhaled allergens.Results: A total of 392 patients (33.8%) were diagnosed with asthma and 292 (25.2%, 160 adults, 132 children) with pollen-induced asthma. Respiratory symptoms of cough, wheezing, dyspnea, chest pain and nocturnal awakenings due to breathlessness were all associated with increased odds of being diagnosed with pollen-induced asthma, with cough being the most common symptom in both adults and children, giving a sensitivity of 90.6% in adults and 88.6% in children. Wheezing was the most specific symptom (78% and 89.5% in adults and children, respectively) compared to other symptoms. Overall, the positive predictive value of respiratory symptoms was poor for diagnosing pollen-induced asthma, with the exception of wheezing in children which had a high positive predictive value of 72.7%.Conclusion: Cough was the predominant symptom in adults and children with pollen-induced asthma. Wheezing was a reliable predictor of pollen-induced asthma in children. In adults, respiratory symptoms were not sufficiently reliable for diagnosing pollen-induced asthma. Keywords: pollen-induced asthma, asthma symptoms, wheezing, cough, shortness of breath

Yu-Dan Liang,1,* Ying Li,1,* Jian Zhao,2 Xiao-Yin Wang,3 Hui-Zheng Zhu,1 Xiu-Hua Chen1 1The Second Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, 2Longgang District People’s Hospital of Shenzhen, Shenzhen, 3Guangdong Second Traditional Chinese Medicine Hospital, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Acupuncture has been applied to relieve low back pain (LBP) in many countries. However, a bibliometric analysis of the global use of acupuncture for LBP is rare.Objective: The aim of this study was to demonstrate the state of the art and trends concerning the global use of acupuncture for LBP in recent 20 years.Methods: Literature relating to acupuncture for LBP from 1997 to 2016 was retrieved from Web of Science. CiteSpace was used to analyze country/institution, cited journals, authors/cited authors, cited references, and keywords. An analysis of counts and centrality was used to reveal publication outputs, countries/institutions, core journals, active authors, foundation references, hot topics, and frontiers.Results: A total of 958 references were obtained, and the total number of publications continually increased over the investigated period. Journal articles (662) were the most frequently occurring document type. The most productive country and institution in this field was the USA (342) and Harvard University (47), respectively. The J Altern Complem Med (69) was the most productive journal, and Pain (636) was the most cocited journal, which reflected the nature of the research. The Haake’s (2007) article (cocitation counts: 130) and the Cherkin’s (2001) article (centrality: 0.59) were the most representative and symbolic references, with the highest cocitation number and centrality, respectively. Cherkin was the most influential author, with the highest number of publications of 25 and a cocitation number of 226. The four hot topics in acupuncture for LBP were research method, evaluation, economy, and comprehensive therapy. The three frontier topics were intervention, test reliability, and prevalence.Conclusion: This study provides an insight into acupuncture for LBP and valuable information for acupuncture researchers to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers. Keywords: acupuncture, low back pain, bibliometric analysis, CiteSpace, cocitation

Kaida Jiang,1 Lingjiang Li,2 Xueyi Wang,3 Maosheng Fang,4 Jianfei Shi,5 Qiuyun Cao,6 Jincai He,7 Jinan Wang,8 Weihao Tan,8 Cuili Hu8 1Psychiatry Department, Shanghai Mental Health Center, Shanghai, 2Psychiatry Department,The Second Xiangya Hospital, Central South University, Changsha, 3Psychiatry Department, First affiliated Hospital of Hebei Medical University, Shijiazhuang, 4Psychiatry Department, Wuhan Mental Health Center, Wuhan, 5Psychiatry Department, Hangzhou the 7th Hospital, Hangzhou, 6Psychology Department, Nanjing Drum Tower Hospital, Nanjing, 7Neurology Department, First affiliated Hospital of Wenzhou Medical University, Wenzhou, 8Medical Affairs Department, Xi’an Janssen Pharmaceutical Ltd., Beijing, People’s Republic of China Background: Significant anxiety symptoms are associated with poor clinical course and outcome in major depressive disorder (MDD). This single-arm, open-label study aimed to evaluate the efficacy and tolerability of escitalopram treatment in patients with MDD and anxiety symptoms. Methods: Adult patients with MDD and anxiety symptoms (Montgomery–Asberg Depression Rating Scale [MADRS] ≥22 and Hamilton Anxiety Rating Scale [HAM-A] ≥14) were enrolled and received escitalopram (10–20 mg/day) treatment for 24 weeks. Symptom status was assessed by MADRS, 17-item-Hamilton Depression Rating Scale, HAM-A, and Clinical Global Impression Scale at baseline and the following visits. Quality of life was assessed by Short Form-12, and safety was evaluated by adverse events, laboratory investigations, vital signs, and physical findings. Results: Overall, 200 of 318 (66.2%) enrolled patients completed the 24-week treatment. The remission (MADRS ≤10 and HAM-A ≤7) rate in the full analysis set (N=285) was 73.3% (95% confidence interval: 67.80, 78.38) at week 24. Mean (± standard deviation) MADRS total score was 33.4 (±7.13) and HAM-A score was 27.6 (±7.26) at baseline, which reduced to 6.6 (±10.18) and 6.0 (±8.39), respectively, at week 24. Patients with higher baseline depression and anxiety level took longer to achieve similar remission rates. Overall, 80 of the 302 (26.5%) patients included in the safety set reported at least 1 treatment-emergent adverse event (TEAE). Most frequently reported TEAEs (>2%) were headache (4.0%), nasopharyngitis (3.6%), nausea (3.0%), and dizziness (2.6%). Serious TEAEs were reported by 1.3% patients; no deaths were reported. Conclusion: Escitalopram 10–20 mg/day was effective and well-tolerated in the long-term treatment of MDD with anxiety symptoms in adult Chinese population. Keywords: anxiety, Chinese, escitalopram, long term, major depressive disorder

Zhen-Yu Peng,1,2 Rui Chen,3 Zuo-Zhong Fang,2 Bin Chen,2 Zhi-Hua Wang,4 Xi-Yang Wang1 1Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, 2Department of Spine Surgery, Chenzhou No.1 People’s Hospital, Chenzhou, 3Department of Neurosurgery, Nanhua Hospital Affiliated to Nanhua University, Hengyang, 4Department of Orthopedics, Chenzhou No.1 People’s Hospital, Chenzhou, Hunan, People’s Republic of China Background: Chemokines have been identified to be involved in the modulation of pain through both peripheral and central mechanisms. However, the role of chemokines in lumbar disk herniation (LDH) with sciatic pain remains unknown. Objective: The current study was performed to explore the expression of two most commonly studied chemokines CX3CL1 and CCL2 and assess their associations with clinical severity in LDH patients with sciatic pain. Methods: The soft tissues around nerve root (STANR), annulus fibrosus (AF), and nucleus pulposus (NP) biopsies were obtained from 36 LDH patients with chronic sciatic pain and 10 scoliosis patients (painless controls). The serum and local expressions of CX3CL1 and CCL2 were determined using enzyme-linked immunosorbent assay and Western blot analysis, respectively. The visual analog scale (VAS) scores for low back pain and lower extremity pain and Japanese Orthopaedic Association (JOA) scores were recorded on the day of hospital admission to evaluate the clinical severity. LDH patients with sciatic pain were divided into severe pain (SP) group (VAS ≥7; n=18) and mild-to-moderate pain (M-MP) group (VAS

Xiao-yan Wang, Huan-tao Zong, Yong Zhang Department of Urology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China Background: Prostate artery embolization (PAE) is emerging and is a promising minimally invasive therapy that improves lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH). The purpose of this article was to evaluate the efficacy and safety of PAE on LUTS related to BPH. Materials and methods: A literature review was performed to identify all published articles of PAE for BPH. The sources included MEDLINE, EMBASE and Cochrane Library from 1980 to 2016. A systematic review and meta-analysis was conducted. The outcome measurements were combined by calculating the mean difference with 95% confidence interval. Statistical analysis was carried out using Review Manager 5.3.0. Results: Twelve studies involving 840 participants were included. Compared with baseline, the International Index of Erectile Function (IIEF-5; International Prostate Symptom Score) scores, the quality of life scores, peak urinary flow rate (Qmax) and postvoid residual volume all had significant improvements during the 24-month follow-up (all P

Xiaoyi Wang, Ying Wang, Xiaoyuan Feng, Ying Lu, Yu Zhang, Wenwen Wang, Wentao Zhu School of Management, Beijing University of Chinese Medicine, Beijing, People’s Republic of China Objective: The aim of the study was to evaluate the effectiveness, safety, and cost associated with Wenxin keli in the treatment of cardiovascular diseases based on meta-analysis. Methods: The terms “Wenxin keli” and “Wenxin” were used as the search terms in the PubMed, ProQuest, Springer, the Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP (Chinese Scientific Journals Database), and Wan fang electronic databases (from January 2000 to October 2015). Relevant print journals and conference papers were also searched. Studies on randomized controlled trials (RCTs) of Wenxin keli used in the treatment of cardiovascular diseases were screened, and its indications were classified. Meta-analysis of these studies was conducted using the RevMan 5.2 software. Results: A total of 49 RCTs (n=4,610) were included, 29 of which focused on arrhythmia, seven on angina, seven on heart failure, two on viral myocarditis, and four on menopausal syndrome. Analysis of the therapeutic indications of Wenxin keli showed that it was comparatively more curative and effective than other available treatments for cardiovascular diseases. Conclusion: Wenxin keli showed better clinical efficacy in the treatment of arrhythmia, angina, and heart failure; however, more high-quality evidence is needed to support its use in the clinical setting. Keywords: Wenxin keli, cardiovascular disease, meta-analysis, systematic review

Pu Yan,* Xiao-yan Wang,* Wei Huang, Yong Zhang Beijing Tian Tan Hospital, Capital Medical University, Neurology Research Division, China National Clinical Research Center for Neurological Disease, Beijing, People’s Republic of China *These authors contributed equally to this work. Background: A meta-analysis was performed to evaluate the efficacy and safety of intrarectal local anesthestic (IRLA), periprostatic nerve block (PPNB), and the combined modalities in alleviating the pain during transrectal ultrasound (TRUS)-guided prostate biopsy.Materials and methods: A literature review was performed to identify all published randomized controlled trials (RCTs) about IRLA vs no anesthesia or placebo gel; PPNB vs no injection, periprostatic placebo injection, or IRLA; combined PPNB and IRLA vs PPNB alone; and combined PPNB and intraprostatic nerve block (IPNB) vs PPNB alone before TRUS-guided biopsy. Sources included MEDILINE, EMBASE, and Cochrane Library from 1980 to 2016. The main outcomes were biopsy pain score, probe manipulation pain score, and anesthetic infiltration pain score assessed by the visual pain scale.Results: A total of 26 articles involving 36 RCTs were used in this analysis: Although IRLA can lead to pain reduction, the result was not statistically significant when compared with no anesthesia or placebo gel (weighted mean difference [WMD]: -0.22, 95% CI: -0.45 to 0, P=0.06). PPNB can lead to significantly lower biopsy pain scores when compared with no analgesia (WMD: -1.32, 95% CI: -1.68 to -0.95, P

Xue Yan Wang,1 Margaret Lim-Jurado,2 Narayanan Prepageran,3 Pongsakorn Tantilipikorn,4 De Yun Wang5 1Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2St Luke’s Medical Center, Quezon City, Manila, Philippines; 3Department of Otorhinolaryngology, Head & Neck Surgery, University Malaya Faculty of Medicine, Kuala Lumpur, Malaysia; 4Rhinology and Allergy Division, Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 5Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Abstract: Allergic rhinitis and urticaria are common allergic diseases that may have a major negative impact on patients’ quality of life. Bilastine, a novel new-generation antihistamine that is highly selective for the H1 histamine receptor, has a rapid onset and prolonged duration of action. This agent does not interact with the cytochrome P450 system and does not undergo significant metabolism in humans, suggesting that it has very low potential for drug–drug interactions, and does not require dose adjustment in renal impairment. As bilastine is not metabolized and is excreted largely unchanged, hepatic impairment is not expected to increase systemic exposure above the drug’s safety margin. Bilastine has demonstrated similar efficacy to cetirizine and desloratadine in patients with seasonal allergic rhinitis and, in a Vienna Chamber study, a potentially longer duration of action than fexofenadine in patients with asymptomatic seasonal allergic rhinitis. It has also shown significant efficacy (similar to that of cetirizine) and safety in the long-term treatment of perennial allergic rhinitis. Bilastine showed similar efficacy to levocetirizine in patients with chronic spontaneous urticaria and can be safely used at doses of up to fourfold higher than standard dosage (80 mg once daily). The fourfold higher than standard dose is specified as an acceptable second-line treatment option for urticaria in international guidelines. Bilastine is generally well tolerated, both at standard and at supratherapeutic doses, appears to have less sedative potential than other second-generation antihistamines, and has no cardiotoxicity. Based on its pharmacokinetic properties, efficacy, and tolerability profile, bilastine will be valuable in the management of allergic rhinitis and urticaria. Keywords: bilastine, second-generation antihistamines, allergic rhinitis, urticaria

Dandan Liu,1 Hao Pan,2 Fengwei He,1 Xiaoyu Wang,3 Jinyu Li,3 Xinggang Yang,3 Weisan Pan31Department of Pharmaceutical Engineering, School of Biomedical and Chemical Engineering, Liaoning Institute of Science and Technology, Benxi, People’s Republic of China; 2School of Pharmacy, Queen’s University Belfast, Belfast, Northern Ireland, UK; 3Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China Abstract: The purpose of this work was to explore the particle size reduction effect of carvedilol on dissolution and absorption. Three suspensions containing different sized particles were prepared by antisolvent precipitation method or in combination with an ultrasonication process. The suspensions were characterized for particle size, surface morphology, and crystalline state. The crystalline form of carvedilol was changed into amorphous form after antisolvent precipitation. The dissolution rate of carvedilol was significantly accelerated by a reduction in particle size. The intestinal absorption of carvedilol nanosuspensions was greatly improved in comparison with microsuspensions and solution in the in situ single-pass perfusion experiment. The in vivo evaluation demonstrated that carvedilol nanosuspensions and microsuspensions exhibited markedly increased Cmax (2.09- and 1.48-fold) and AUC0–t (2.11- and 1.51-fold), and decreased Tmax (0.34- and 0.48-fold) in contrast with carvedilol coarse suspensions. Moreover, carvedilol nanosuspensions showed good biocompatibility with the rat gastric mucosa in in vivo gastrointestinal irritation test. The entire results implicated that the dissolution rate and the oral absorption of carvedilol were significantly affected by the particle size. Particle size reduction to form nanosized particles was found to be an efficient method for improving the oral bioavailability of carvedilol. Keywords: carvedilol, nanosuspensions, intestinal absorption, oral bioavailability, gastrointestinal irritation

Pei-Li Zhu,1 Si-Yuan Pan,1 Shu-Feng Zhou,2 Yi Zhang,1 Xiao-Yan Wang,1 Nan Sun,1 Zhu-Sheng Chu,1 Zhi-Ling Yu,3 Kam-Ming Ko41Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People’s Republic of China; 4Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People’s Republic of ChinaBackground: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF), a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb) pulp (AqSF-P) or an SF-related synthetic analog, bicyclol (BY), on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL) mice.Methods: Male mice obtained from the Institute of Cancer Research (ICR) were fed on a normal diet (ND) or high cholesterol/bile salt (0.5%/0.15%, w/w) diet (HCBD) containing FF (0.03% or 0.1%, w/w) with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w) or BY (0.025%, w/w) for 10 days. Then serum lipid levels and alanine aminotransferase (ALT) activity, as well as hepatic triglyceride (TG), total cholesterol (TC), and glucose levels, were measured.Results: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79%) in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67%) and in HCBD-fed mice (up to 54%), when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was enhanced (up to 19%) by AqSF-P cosupplementation in both normal and HCL mice. FF supplementation enhanced the excretion of fecal TC (by 75%) in mice fed with HCBD. Fecal TC contents were increased by 14%/9% in the combination therapy with FF and AqSF-P in ND-/HCBD-fed mice. Serum ALT activity was elevated by 45% in HCBD-fed mice. FF caused a significant increase in ALT activity by 198% and 120% in normal and HCL mice, respectively. BY markedly attenuated the ALT activity by 54% in mice fed with ND supplemented with 0.1% FF and by 42% in mice fed with HCBD supplemented with 0.03% FF.Conclusion: AqSF-P cosupplementation augmented the hepatic lipid-/glucose-lowering effects of FF. BY ameliorated FF-induced liver injury in normal and HCL mice.Keywords: bicyclol, hepatotoxicity, synergist, fatty liver disease, fat index, interaction

Yi Zhang,1 Si-Yuan Pan,1 Shu-Feng Zhou,2 Xiao-Yan Wang,1 Nan Sun,1 Pei-Li Zhu,1 Zhu-Sheng Chu,1 Zhi-Ling Yu,3 Kam-Ming Ko4 1Department of Pharmacology, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, People's Republic of China; 2Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 3School of Chinese Medicine, Hong Kong Baptist University, 4Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China Background: Schisandrin B (Sch B), a dibenzocyclooctadiene compound, is isolated from schisandrae fructus (SF). This study was conducted to compare the time- and dose-response between Sch B- and SF oil (SFO)-induced changes in hepatic and serum parameters in mice. Methods: Institute of Cancer Research (ICR) mice were given a single oral dose of Sch B (0.125–2 g/kg) or SFO (0.3–5 g/kg). Serum alanine aminotransferase (ALT) activity, hepatic malondialdehyde, and triglyceride (TG) levels were measured at increasing time intervals within 6–120 hours postdosing. Results: Serum ALT activity was elevated by 60%, with maximum effect (Emax) =45.77 U/L and affinity (KD) =1.25 g/kg at 48–96 hours following Sch B, but not SFO, treatment. Sch B and SFO treatments increased hepatic malondialdehyde level by 70% (Emax =2.30 nmol/mg protein and KD =0.41 g/kg) and 22% (Emax =1.42 nmol/mg protein and KD =2.56 g/kg) at 72 hours postdosing, respectively. Hepatic index was increased by 16%–60% (Emax =11.01, KD =0.68 g/kg) and 8%–32% (Emax =9.88, KD =4.47 g/kg) at 12–120 hours and 24–120 hours after the administration of Sch B and SFO, respectively. Hepatic TG level was increased by 40%–158% and 35%–85%, respectively, at 12–96 hours and 6–48 hours after Sch B and SFO treatment, respectively. The values of Emax and KD for Sch B/SFO-induced increase in hepatic TG were estimated to be 22.94/15.02 µmol/g and 0.78/3.03 g/kg, respectively. Both Sch B and SFO increased serum TG (up to 427% and 123%, respectively), with the values of Emax =5.50/4.60 mmol/L and KD =0.43/2.84 g/kg, respectively. Conclusion: The findings indicated that Sch B/SFO-induced increases in serum/hepatic parameters occurred in a time-dependent manner, with the time of onset being serum TG level < hepatic TG level < hepatic index < serum ALT activity. However, the time of recovery of these parameters to normal values varied as follow: serum TG level < hepatic TG level and liver injury < hepatic index. The Emax and affinity of Sch B on tissue/enzyme/receptor were larger than those of SFO. Keywords: pharmacodynamics, hepatomegaly, alanine aminotransaminase, affinity, maximum effect

Chengchu Liu,1,2,* Qing Zhu,1,* Wenhui Wu,1 Xiaolin Xu,1 Xiaoyu Wang,3 Shen Gao,3 Kehai Liu11Department of Biopharmaceutics, College of Food Science and Technology, Shanghai Ocean University, Shanghai, China; 2Shanghai Engineering Research Center of Aquatic-Product Processing and Preservation, Shanghai, China; 3Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai China*The first two authors contributed equally to this workBackground: Chitosan shows particularly high biocompatibility and fairly low cytotoxicity. However, chitosan is insoluble at physiological pH. Moreover, it lacks charge, so shows poor transfection. In order to develop a new type of gene vector with high transfection efficiency and low cytotoxicity, amphiphilic chitosan was synthesized and linked with low-molecular weight polyethylenimine (PEI).Methods: We first synthesized amphiphilic chitosan – N-octyl-N-quatenary chitosan (OTMCS), then prepared degradable PEI derivates by cross-linking low-molecular weight PEI with amphiphilic chitosan to produce a new polymeric gene vector (OTMCS–PEI). The new gene vector was characterized by various physicochemical methods. We also determined its cytotoxicity and gene transfecton efficiency in vitro and in vivo.Results: The vector showed controlled degradation. It was very stable and showed excellent buffering capacity. The particle sizes of the OTMCS–PEI/DNA complexes were around 150–200 nm with proper zeta potentials from 10 mV to 30 mV. The polymer could protect plasmid DNA from being digested by DNase I at a concentration of 2.25 U DNase I/µg DNA. Furthermore, they were resistant to dissociation induced by 50% fetal bovine serum and 1100 µg/mL sodium heparin. OTMCS–PEI revealed lower cytotoxicity, even at higher doses. Compared with PEI 25 KDa, the OTMCS–PEI/DNA complexes also showed higher transfection efficiency in vitro and in vivo.Conclusion: OTMCS–PEI was a potential candidate as a safe and efficient gene vector for gene therapy.Keywords: nonviral gene vector, polyethylenimine, transfection efficiency, cytotoxicity

The endogenous electric fields at the wound site had been found since 18th century, while its biological significance in wound healing, organ regeneration and development was unveiled until recent year. Here we summarized the mechanisms of the generation of endogenous electric fields and its significance in different biological events. Moreover, the ion flux behind the endogenous electric fields was introduced as well.