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Ya-Jun Yang,1,* Yu-Mei Feng,1,* Tong-Xuan Wang,1 Jing-Yun Wang,2 Qian-Yun Pang,1 Hong-Liang Liu1 1Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China; 2School of Medicine, Chongqing University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong-Liang Liu; Qian-Yun Pang, Department of Anesthesiology, Chongqing University Cancer Hospital, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel +86 13883686721, Email liuhl75@163.comBackground: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes.Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications.Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016– 0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999– 0.999), blood loss (OR: 0.998, 95% CI: 0.998– 0.999), transfusion (OR:0.327, 95% CI: 0.218– 0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051– 1.744), and hospital stay (OR:1.019, 95% CI:1.008– 1.029).Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.Keywords: noradrenaline, outcome, older adult, non-cardiac surgery

Miao Zhang, Jing Liu, Yu-Chen Pan, Hui-Li Liu, Jing Shu, Xiao-Ming Wu, Yang Yang Department of Pediatric Gynecology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, ChinaCorrespondence: Jing Liu, Department of Pediatric Gynecology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, 100045, People’s Republic of China, Tel +86 010 59616889, Email liujing2893@126.comObjective: The aim of this study was to analyze the prevalence of vaginal flora and drug resistance in bacterial vaginitis among girls.Methods: A total of 3099 girls (0– 10 years old) with vaginitis who visited the Beijing Children’s Hospital from January 2020 to December 2021 were included in the present study. The clinical data, results of bacterial culture of vaginal secretions, and drug sensitivity reports of the subjects were collected and analyzed.Results: Of the 3099 girls with vaginitis, 399 girls had a positive bacterial culture of vaginal secretions. Nineteen types of bacteria were cultured from the vaginal secretions of these 399 girls, with a total of 419 strains. The top three infective bacteria were Haemophilus influenzae (127 strains, 30.31%), Staphylococcus aureus (66 strains, 15.75%), and Streptococcus agalactiae (32 strains, 7.64%). Additionally, 20 girls were simultaneously infected with two types of bacteria. Staphylococcus aureus, Group G Streptococcus, Haemophilus parainfluenzae, and Pseudomonas aeruginosa more frequently occurred in mixed infections. The number and bacterial detection rate among school-age girls were higher than those of preschool-age girls. We found seasonal variation in infection rates, and vaginitis among girls was higher in summer. Recurrence of vaginitis in girls was not related to the type of pathogenic bacteria in the infection. Drug sensitivity analyses showed that the resistance rates of clindamycin and erythromycin were generally high, 70– 100%. After the coronavirus disease 2019 outbreak, the resistance rates of some antibiotics had decreased to varying degrees.Conclusion: Improving the understanding of vaginal flora and drug resistance in girls with vaginitis will facilitate the selection of highly effective and sensitive antibacterial drugs and reduce the production of drug-resistant strains.Keywords: drug sensitivity analysis, girls, pathogenic bacteria, vaginitis

Liang Chen, Xiao-Hang Ding, Kang-Jun Fan, Ming-Xin Gao, Wen-Yuan Yu, Hong-Li Liu, Yang Yu Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Yang Yu, Email heartyuyang@hotmail.comBackground: Data on the relationship between the triglyceride glucose (TyG) index and prognosis after off-pump coronary artery bypass grafting (OPCABG) are limited. This retrospective observational cohort study evaluated the association of the TyG index with prognosis in patients with diabetes mellitus who underwent OPCABG.Methods: The TyG index was calculated using the following equation: TyG index = ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2). The primary outcomes included the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which were defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke and symptomatic graft failure. The association between the TyG index and MACCEs was assessed by Cox proportional hazards regression analysis.Results: A total of 1578 patients with diabetes who underwent OPCABG (mean age, 62.9 ± 8.0 years; men, 72.7%) were enrolled in this study. Over the follow-up of 2 years, 176 patients (11.2%) had at least 1 primary endpoint event. The follow-up incidence of the primary endpoint rose with increasing TyG index tertiles. The multivariate Cox proportional hazards regression analysis adjusted for multiple confounders revealed a hazard ratio for the primary endpoint of 2.133 (95% CI 1.347– 3.377; P for trend = 0.001) when the highest and lowest TyG index tertiles were compared.Conclusion: The TyG index was significantly and positively associated with MACCEs, suggesting that the TyG index may be a valuable predictor of adverse cardiovascular and cerebrovascular outcomes after OPCABG in patients with T2DM.Keywords: triglyceride-glucose index, off-pump coronary artery bypass grafting, major adverse cardiovascular and cerebrovascular events, type 2 diabetes mellitus

Qian-Yun Pang, Li-Ping Duan, Yan Jiang, Hong-Liang Liu Department of Anesthesiology, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People’s Republic of ChinaCorrespondence: Hong-Liang LiuDepartment of Anesthesiology, Chongqing University Cancer Hospital, Chongqing University, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of ChinaTel +86 13883686721Email liuhl75@163.comBackground: General anaesthesia is the commonly provided for breast cancer surgery, but the effects of inhalational anaesthesia and propofol-based intravenous anaesthesia on short- and long-term outcomes after breast cancer surgery are not clear. In this study, we conduct a meta-analysis of randomized controlled trials (RCTs) to explore the superior anaesthetic for breast cancer surgery patients.Methods: We searched the Embase, Medline, Cochrane Library, Web of Science, CNKI, and Wanfang databases (up to January, 2021) for RCTs in which inhalational anaesthesia and propofol-based intravenous anaesthesia were compared and short- and long-term outcomes were assessed in breast cancer surgical patients. The meta-analysis was performed by Stata 12.0.Results: Twenty RCTs with a total of 2201 patients were included. Compared with inhalational anaesthesia, propofol-based intravenous anaesthesia was associated with more postoperative rescue analgesia (I2=0%, RR: 1.18, 95% CI: 1.07– 1.30, P=0.001) but a lower incidence of postoperative nausea and vomiting (PONV) (I2=25.5%, RR: 0.71, 95% CI: 0.62– 0.81, P< 0.001) and postoperative rescue antiemetics (I2=0%, RR: 0.69, 95% CI: 0.58– 0.82, P< 0.001). Propofol-based intravenous anaesthesia preserved nature killer cell cytotoxicity (I2=86.2%, SMD: 0.76, 95% CI: 0.13– 1.39, P=0.018), decreased IL-6 level (I2=98.0%, SMD: − 3.09, 95% CI: − 5.70– − 0.48, P=0.021) and neutrophil-to-lymphocyte ratio (I2=0%, SMD: − 0.28, 95% CI: − 0.53– − 0.03, P=0.030), and increased 2-year recurrence-free survival rate (I2=0%, RR: 1.10, 95% CI: 1.00– 1.20, P=0.043) but did not affect recurrence or the overall survival rate (P> 0.05).Conclusion: Propofol-based intravenous anaesthesia increases postoperative rescue analgesia but reduces PONV compared with inhalational anaesthesia in breast cancer surgery. The benefit of propofol over inhalational anaesthetics in the preservation of anti-cancer immunity is obvious, but it is difficult to conclude that propofol can exert long-term benefits due to the small sample size.Keywords: inhalational anaesthesia, propofol, breast cancer, surgery, outcome, analgesia

Hai-bo Wu,1,&ast; Chen-si Yang,1,2,&ast; Yun-can Wang,3 Yue-tao Xie,1 Xue-chao Wang,1 Hui-liang Liu,1 Rong-pin Du1 1Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Hebei Northen University Graduate School, Zhangjiakou, Hebei, People’s Republic of China; 3Department of Ultrasound, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rong-pin DuDepartment of Cardiology, Hebei General Hospital, No. 348, Peace West Road, Shijiazhuang, 050000, Hebei, People’s Republic of ChinaTel +86 15128138630Fax +86 0311 85989696Email durp_as11@163.comObjective: The present study aims to investigate micro ribonucleic acid-365 (miR-365) serum expression and its correlation with left ventricular hypertrophy (LVH) in patients with hypertension (HT).Methods: Eighty-four patients were selected as study subjects and divided into three groups: the experimental group (n = 28), the observation group (n = 29), and the control group (n = 27). The experimental group included patients with LVH-accompanied HT who were treated in the People’s Hospital of Hebei Province between November 2019 and November 2020, the observation group included patients with HT unaccompanied by LVH, and the control group included healthy age and gender-matched subjects who underwent health examinations in our physical examination center. The cardiac echocardiography, 24-h Holter electrocardiogram, and circulating miR-365 levels in all subjects were measured. The differences in circulating miR-365 expression levels among the three groups were compared, and the correlations between the miR-365 expression levels and the blood pressure parameters (24-h mean systolic blood pressure [SBP] and 24-h mean diastolic blood pressure [DBP]), inter-ventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular internal diameter (LVID), left ventricular mass (LVM), LVM index (LVMI), and LVH-related indicators were analyzed.Results: The relative miR-365 expressions in the experimental, observation, and control groups were 2.08 (1.60, 2.34), 0.62 (0.44, 0.83), and 0.66 (0.35, 0.86), respectively. Patient miR-365 expression was significantly higher in the experimental group than in the observation group and the control group; the differences were statistically significant (p < 0.000). Furthermore, miR-365 expression was significantly correlated with SBP, DBP, IVST, LVPWT, LVID, LVM, and LVMI; the greatest correlation was with LVMI. Further univariate linear regression analysis revealed that miR-365 expression was linearly and positively correlated with LVMI and that miRNA-365 expression increased with the LVMI value.Conclusion: The miR-365 serum expression in patients with LVH-accompanied HT was increased compared with the observation group and the control group and positively correlated with the LVH degree.Keywords: essential hypertension, left ventricular hypertrophy, RT-PCR, microRNA

Xiao-Long Liang, Ran An, Qi Chen, Hong-Liang Liu Chongqing University Cancer Hospital, School of Medicine, Chongqing University, Chongqing, 400030, People’s Republic of ChinaCorrespondence: Hong-Liang LiuChongqing University Cancer Hospital, School of Medicine, Chongqing University, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of ChinaTel +86 13883686721Email liuhl75@163.comBackground: To date, there is no definitive evidence for the analgesic effects and side effects of thoracic epidural anesthesia (TEA) versus thoracic paravertebral block (TPVB) after thoracoscopic surgery. In this study, we conducted a meta-analysis of published randomized clinical trials (RCTs) to analyze the analgesic effects of TEA versus TPVB after thoracoscopic surgery.Methods: We systematically searched RCTs published by October 26, 2020, in PubMed, EMBASE, and Cochrane library and conducted a meta-analysis to analyze the analgesic effects of TEA versus TPVB after thoracoscopic surgery. The primary measure was postoperative pain score, and the secondary measures were postoperative 24-hour usage of opioids, hypotension, postoperative nausea, and vomiting.Results: A total of 458 patients from five RCTs were included in this study. After thoracoscopic surgery, the numerical rating scale (NRS) score for resting pain was higher in the TPVB group than in the TEA group at 1– 2 hours and 4– 6 hours after surgery (MD = 0.44, 95% CI = 0.24 to 0.64, P < 0.0001, I2 = 0%; MD = 0.47, 95% CI = 0.23 to 0.70, P < 0.0001, I2 = 0%). The postoperative 24-hour usage of morphine was higher in the TPVB group than in the TEA group (SMD = 0.67; 95% CI = 0.03 to 1.31; P = 0.04; I2 = 84%). The incidence of hypotension was significantly lower in the TPVB group than in the TEA group (OR = 4.52; 95% CI = 2.03 to 10.10; P = 0.0002; I2 = 0%). No significant between-group difference was observed in postoperative nausea and vomiting (PONV).Conclusion: Compared with TPVB, TEA provides statistically significant but clinically unimportant short-term benefits following thoracoscopic surgery.Keywords: thoracic paravertebral block, thoracic epidural anesthesia, thoracoscopic surgery, meta-analysis

Hai-Lin Liu,1,* Rui-Hao Zhou,2,* Li-Li Luo,1 Xue Yuan,1 Ling Ye,2 He-Guo Luo1 1Department of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of China; 2Department of Pain Management, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: He-Guo LuoDepartment of Anesthesiology, The Third Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330008, People’s Republic of ChinaEmail 542534631@qq.comBackground: Although ultrasound-guided transversus abdominis plane block (TAPB) is widely used in multimodal analgesia after cesarean delivery (CD), the complications of TAPB during analgesia after CD have rarely been reported.Methods: A total of 84 cases of CD were randomly assigned to either a ropivacaine group (R group) or ropivacaine + dexamethasone group (RD group) in this double-blind trial. The pain site and pain degree at rest and during activity at 2 h, 6 h, 10 h, 12 h, 14 h, 16 h, 20 h, and 24 h after maternal surgery were recorded. The consumption of opioids at 24h, postoperative nausea, vomiting, exhaustion, and other adverse reactions were recorded.Results: A total of 80 patients were included in the analysis of results. A total of 19 patients developed ISP, 14 in the R group and 5 in the RD group. The incidence of ISP in the R and RD groups was 35% and 12.5%, respectively. The results described above showed that combining dexamethasone with ropivacaine reduced the incidence of ISP, and the difference was statistically significant (P< 0.05). Two groups of women with positive ISP had higher values of opioid consumption than women with negative ISP, but the difference was not significant.Conclusion: Dexamethasone as an adjuvant for ropivacaine can effectively relieve the ISP of ultrasound-guided TAPB after CD, and can enhance the analgesic effect of ropivacaine.Keywords: dexamethasone, ropivacaine, cesarean delivery, transversus abdominis plane block, postoperative analgesia, injection site pain

Man-Yu Dong, Bao-Lin Tang, Xiao-Yu Zhu, Si-Qi Cheng, Xin-Chen Fang, Juan Tong, Xiang Wan, Chang-Cheng Zheng, Hui-Lan Liu, Zi-Min Sun Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, People’s Republic of ChinaCorrespondence: Zi-Min SunDepartment of Hematology, The First Affiliated Hospital of University of Science and Technology of China, No. 17, Lujiang Road, Hefei, Anhui 230001, People’s Republic of ChinaTel +86 551 6228 2992Fax +86 551 6228 2121Email zmsun_vip@163.comIntroduction: Current consensus recommends a protective effect of cytomegalovirus (CMV) infection on relapse after peripheral blood or bone marrow hematopoietic stem cell transplantation. However, in cord blood transplantation (CBT), studies of CMV infection, especially CMV viral load, on relapse are limited.Patients and Methods: Wct e retrospectively analyzed the effect of CMV infection on 3-year outcomes in 249 AML patients according to CMV DNA load (DNA copies < 1000/mL and DNA copies ≧1000/mL) within 100 days after CBT. Furthermore, eight-colour flow cytometry was used to detect peripheral blood lymphocyte subsets in 38 patients who received CBT in the last year, and 10 healthy volunteers were included as controls.Results: The results showed that CMV DNA load did not affect the cumulative incidence of relapse in the whole study population. However, in patients with complete remission status before transplantation, the high CMV DNA load group showed a significantly reduction of relapse than the low CMV DNA load group (3.9% vs 14.6%, p=0.012, respectively), which was confirmed by multivariate analysis (HR 0.23; 95% CI, 0.07– 0.73, p = 0.012). Surprisingly, high or low CMV DNA load did not significantly affect non-relapse mortality or overall survival (18.0% vs 17.0%, p=0.777 and 79.0% vs 74.6%, p=0.781, respectively). Besides, the absolute number of CD8+ T cells were increased in the high CMV DNA load group compared with the low DNA load group 1 month after CBT (0.20× 10 9/L vs 0.10× 10 9/L, p=0.021, respectively).Conclusion: DNA copies ≧1000/mL for AML patients in complete remission was associated with a lower incidence of relapse after CBT, which might partly result from the expansion of CMV-related CD8+ T cells.Keywords: cord blood transplantation, cytomegalovirus, DNA load, relapse, acute myeloid leukemia, complete remission

Hong-Li Liu,1,* Min Zong,1,* Han Wei,1 Cong Wang,2 Jian-Juan Lou,1 Si-Qi Wang,1 Qi-Gui Zou,1 Yan-Ni Jiang1 1Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan-Ni JiangDepartment of Radiology, The First Affiliated Hospital of Nanjing Medical University, No. 300, Guangzhou Road, Nanjing 210029, People’s Republic of ChinaTel +86 1 377 665 2465Fax +86 258 372 4440Email jyn_njmu@163.comBackground: Triple-negative breast cancers generally occur in young women with remarkable potential to be aggressive. It will be of great help to detect this subtype of tumor early. To retrospectively evaluate the performance of histogram analysis of apparent diffusion coefficient (ADC) maps in distinguishing triple-negative breast cancer (TNBC) from other subtypes of breast cancer (non-TNBC), when combined with magnetic resonance imaging (MRI) features.Materials and methods: From February 2014 to December 2018, 192 patients were included in this study taking preoperative standard MRI (s-MRI) and DWI. Seventy-six of them were pathologically confirmed with TNBC and rest 116 with other subtypes. First, their clinical-pathological features and morphological characteristics on MRI were assessed, including tumor size, foci quantity, tumor shape, margin, internal enhancement, and time-signal intensity curve types, in addition to the signal intensity on T2-weighted images. Second, whole-lesion apparent diffusion coefficient (ADC) histogram analysis was executed. Finally, both univariate and multivariate regression analyses were applied to identify the most useful variables in separating TNBCs from non-TNBCs, and then their effects were evaluated following receiver operating characteristic curve analysis.Result: Multivariate regression analysis indicated that circumscribed margin, rim enhancement, and ADC90 were important predictors for TNBC. Increased area under curve (AUC) and improved specificity can be obtained when combined s-MRI and DWI (circumscribed margin+rim enhancement+ADC90>1.47×10−3 mm2/s) is taken as the criterion, other than s-MRI (circumscribed margin+rim enhancement) alone (s-MRI+DWI vs s-MRI; AUC, 0.833 vs 0.797; specificity, 98.3% vs 89.7%; sensitivity, 68.4% vs 69.7%).Conclusion: Circumscribed margin and rim enhancement on s-MRI and ADC90 are three important elements in detecting TNBC, while ADC histogram analysis can provide additional value in this detection.Keywords: triple-negative breast cancer, magnetic resonance imaging, morphological features, diffusion-weighted imaging, histogram analysis

Huilan Liu,* Huijuan Huang,* Boheng Li, Dong Wu, Fengmei Wang, Xiao hua Zheng, Qingxia Chen, Bifang Wu, Xiaojie FanDepartment of Obstetrics and Gynecology, East Hospital, Xiamen University, Fuzhou, Fujian, People’s Republic of China*These authors contributed equally to this workPurpose: The goal of this study was to investigate the anti-osteoporosis effect of extra virgin olive oil (EVOO) in vivo, and explore its antioxidant, anti-inflammatory properties in Sprague Dawley rats and its anticancer properties in patients.Materials and methods: A total of 120 healthy female Sprague Dawley rats aged 6 months were divided into four groups: 1) sham-operated control (Sham group, n=30); 2) ovariectomized (OVX group, n=30); 3) ovariectomized rats supplemented with EVOO (OVX + Olive, n=30); 4) ovariectomized rats supplemented with estrogen (OVX + E2, n=30). EVOO and estrogen were administered by oral gavage at a dose of 1 mL/100 g weight on a daily basis for 12 consecutive weeks. Twelve weeks later blood samples were obtained to detect the levels of calcium, alkaline phosphatase, phosphorus, interleukin-6 (IL-6), malonyldialdehyde (MDA), and nitrate content. Dual energy X-ray absorptiometer measured bone mineral density (BMD) of ovariectomized Sprague Dawley rats that had been fed olive oil for 3 months. Blood samples from patients, who regularly consumed olive oil over a 1 year period were also used to measure carbohydrate antigen 125, carcino-embryonic antigen, α-fetoprotein, and carbohydrate antigen 19-9 levels. BMD of lumbar spine and left femur was also evaluated by dual energy X-ray absorptiometry.Results: Animal experiments showed that EVOO significantly increased BMD and decreased phosphatase, alkaline phosphatase, IL-6, MDA, and nitrate levels. However, it had no significant effect on the Ca2+ level. In clinical follow-up, EVOO also improved patient BMD levels on L3, L4, and left femoral neck, and reduced carbohydrate antigen 125, α-fetoprotein, and carcino-embryonic antigen levels. But it had no significant effect on the carbohydrate antigen 19-9 level.Conclusion: EVOO illustrated significant anti-osteoporosis, antioxidant, anti-inflammatory, and anticancer properties in vivo. However, further studies are required to determine the active component(s) responsible for these effects.Keywords: olive oil, prevention, treatment, osteoporosis, artificial menopause

Hung-Wei Yang,1,* Mu-Yi Hua,1,* Kun-Ju Lin,2,* Shiaw-Pyng Wey,3 Rung-Ywan Tsai,4 Siao-Yun Wu,5 Yi-Ching Lu,5 Hao-Li Liu,6 Tony Wu,7 Yunn-Hwa Ma5 1Chang Gung Molecular Medicine Research Center, Department of Chemical and Materials Engineering, 2Molecular Imaging Center, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 3Department of Medical Imaging and Radiological Sciences, 4Electronics and Optoelectronics Research Laboratories, Industrial Technology Research Institute, Hsin-chu, Taiwan, Republic of China; 5Department of Physiology and Pharmacology and Healthy Aging Research Center, 6Department of Electrical Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, Republic of China; 7Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, Tao-Yuan, Taiwan, Republic of China*These authors contributed equally to this workAbstract: Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 µg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15–25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.Keywords: thrombolysis, recombinant tissue plasminogen activator, magnetic nanocarriers, magnetic targeting, targeting therapy

Hung-Wei Yang,1,2 Mu-Yi Hua,1 Hao-Li Liu,3 Chiung-Yin Huang,2 Kuo-Chen Wei21Molecular Medicine Research Center, Department of Chemical and Materials Engineering, Chang Gung University, 2Department of Neurosurgery, Chang Gung University and Memorial Hospital, 3Department of Electrical Engineering, Chang Gung University, Taoyuan, TaiwanAbstract: Nanoparticles (NPs) play an important role in the molecular diagnosis, treatment, and monitoring of therapeutic outcomes in various diseases. Their nanoscale size, large surface area, unique capabilities, and negligible side effects make NPs highly effective for biomedical applications such as cancer therapy, thrombolysis, and molecular imaging. In particular, nontoxic superparamagnetic magnetic NPs (MNPs) with functionalized surface coatings can conjugate chemotherapeutic drugs or be used to target ligands/proteins, making them useful for drug delivery, targeted therapy, magnetic resonance imaging, transfection, and cell/protein/DNA separation. To optimize the therapeutic efficacy of MNPs for a specific application, three issues must be addressed. First, the efficacy of magnetic targeting/guidance is dependent on particle magnetization, which can be controlled by adjusting the reaction conditions during synthesis. Second, the tendency of MNPs to aggregate limits their therapeutic use in vivo; surface modifications to produce high positive or negative charges can reduce this tendency. Finally, the surface of MNPs can be coated with drugs which can be rapidly released after injection, resulting in targeting of low doses of the drug. Drugs therefore need to be conjugated to MNPs such that their release is delayed and their thermal stability enhanced. This chapter describes the creation of nanocarriers with a high drug-loading capacity comprised of a high-magnetization MNP core and a shell of aqueous, stable, conducting polyaniline derivatives and their applications in cancer therapy. It further summarizes some newly developed methods to synthesize and modify the surfaces of MNPs and their biomedical applications.Keywords: magnetic nanoparticles, drug delivery, biomedical applications, cancer therapy

Yunn-Hwa Ma,1 Si-Yi Chen,1 Shu-Ju Tu,2 Hung-Wei Yang,3 Hao-Li Liu41Department of Physiology and Pharmacology and Healthy Aging Research Center, 2Department of Medical Image and Radiological Sciences, 3Department of Chemical and Material Engineering, 4Department of Electrical Engineering, College of Medicine and College of Engineering, Chang Gung University, Kuei-Shan, Tao-Yuan, Taiwan, ROCAbstract: Magnetic nanoparticles (MNPs) have been proposed for targeted or embolization therapeutics. How MNP retention occurs in circulation may critically determine local hemodynamics, tissue distribution of MNPs, and the therapeutic effects. We attempted to establish a microcirculation model to study the magnetic capture of MNPs in small vessels and to determine the factors affecting MNP retention. Two-dimensional hemodynamic changes in response to magnet-induced MNP retention in the microvessels of the cremaster muscle in vivo were observed in a real-time manner using a laser speckle imaging technique. Changes in tissue perfusion of the cremaster muscle appeared to be closely correlated with the location of the magnet placement underneath the muscle in response to intra-arterial administration of dextran-coated MNPs. Magnet-related retention was observed along the edge of the magnet, as corroborated by the results of histology analysis and microcomputed tomography. In these preparations, tissue iron content almost doubled, as revealed by inductively coupled plasma optical emission spectroscopy. In addition, MNP retention was associated with reduced downstream flow in a dose-dependent manner. Dissipation of MNPs (5 mg/kg) occurred shortly after removal of the magnet, which was associated with significant recovery of tissue flow. However, MNP dissipation did not easily occur after administration of a higher MNP dose (10 mg/kg) or prolonged exposure to the magnetic field. An ultrasound after removal of the magnet may induce the partial dispersion of MNPs and thus partially improve hemodynamics. In conclusion, our results revealed the important correlation of local MNP retention and hemodynamic changes in microcirculation, which can be crucial in the application of MNPs for effective targeted therapeutics.Keywords: targeted delivery, magnetic nanoparticles, hemodynamics, microcirculation