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The treatment of huge hepatocellular carcinoma (HCC) is still challengeable due to its deteriorative heterogeneity, for which conventional transarterial chemoembolization (TACE) is proposed as an efficient therapy; however, drug-eluting beads TACE (DEB-TACE) is rarely reported in these patients. Thus, the current study aimed to explore the efficacy, prognostic factors, and safety of DEB-TACE using CalliSpheres in huge HCC patients.Ninety-nine huge HCC patients treated by DEB-TACE using CalliSpheres were retrospectively reviewed. Treatment response, change of tumor markers, liver function indexes, progression-free survival (PFS), and adverse events were retrieved.Objective response rate (ORR) was 66.1%, 48.6%, and 23.8%, then disease control rate (DCR) was 85.5%, 67.6%, and 33.3% at month (M) 1, M3, and M6, respectively; furthermore, carcinoembryonic antigen (CEA) (p = 0.037), alpha fetoprotein (AFP) (p 0.001), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) (p 0.001) were all declined at 1 month after DEB-TACE. The median PFS was 8.3 (95% confidence interval: 6.0-10.6) months with 1-year and 2-year PFS rates of 38.5% and 15.5%, accordingly. Moreover, elevated China liver cancer (CNLC) stage (p = 0.036, hazard ratio (HR): 1.937) and abnormal cancer antigen 199 (p = 0.019, HR: 2.465) were correlated with unfavorable PFS. Besides, liver function indexes were not deteriorated after DEB-TACE. Lastly, main adverse events included pain (20.2%), fever (17.2%), nausea (14.1%), and vomit (9.1%), which were mild and manageable.DEB-TACE using CalliSpheres presents satisfying efficacy and tolerable safety in huge HCC patients, suggesting that it might be a good treatment option for these patients.

To determine the prevalence and the associated factors of self-perceived medical errors among Chinese emergency department nurses.The emergency department is a place with a high incidence of medical errors. Studies about the occurrence and related influencing factors of medical errors among emergency nurses in China are very insufficient.A nationwide cross-sectional study.A nationwide cross-sectional study was conducted from July 2018-August 2018. A total of 17,582 emergency department nurses from 31 provinces across China were eventually included in the analysis. Logistic regression is applied to examine the association of the independent variables with the perceived medical errors. The reporting of this study was compliant with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies.Of 17,582 participating nurses, 4445 (25.28%) reported self-perceived medical errors in the past 3 months. Nurses who were serving as nurses-in-charge; who reported fair or bad physical health; who reported staff shortage; who were exposed to more verbal abuse at work; who experienced effort-reward imbalance; who reported more over-commitment; or who had depressive symptoms were more likely to report medical errors. Older age and female gender were protective factors.In this study, a quarter of the emergency nurses reported that they had made medical errors in the past 3 months. Self-perceived medical errors are associated with multiple domains of work-related factors and personal distress. Feasible measures should be taken to reduce nurses' workload, improve their working environment, monitor and minimise the occurrence of medical errors among emergency department nurses.Emergency nurses, who are the most frequently in contact with patients, play an important role in identifying risk factors and preventing medical errors. Identifying risk factors that may lead to medical errors in the medical environment from both internal and external aspects will help nursing practitioners, hospital administrators and policy makers to take timely preventive measures to reduce the occurrence of medical errors and reduce harm to patients.

Patients with unresectable intrahepatic cholangiocarcinoma (ICC) have poor survival. Conventional transarterial chemoembolization (c-TACE) and drug-eluting beads transarterial chemoembolization (DEB-TACE) are two treatment options for ICC, and this systematic review describes the efficacy of each of these modalities for unresectable ICC to guide clinical practice.A literature search was performed in PubMed, Web of Science, and Embase databases regarding transhepatic arterial chemoembolization for intrahepatic cholangiocarcinoma. The Newcastle-Ottawa quality assessment Scale (NOS) was used to assess the risk of bias. Tumor response, disease control, and 1-, 2-, 3-year overall survival rate were pooled for estimation.The number of initial search results was 1035, and 19 articles met the inclusion criteria for this study after the screening. A total of 23 study cohorts and 1091 patients were provided. The pooled objective response rate (ORR) for c-TACE and DEB-TACE treating ICC was 29.4% (95% CI 11.6-50.8%) and 51.2% (95% CI 30.6-71.7%), respectively; disease control rate (DCR) was 72.8% (95% CI 55.6-87.3%) and 88.7% (95% CI 78.8-96.2%), respectively. The pooled survival rate at 1 year, 2 year, and 3 year was 49.7% (95% CI 39.1-60.3%), 24.0% (95% CI 12.6-37.3%), and 23.5% (95% CI 11.1-38.7%) for c-TACE; 58.6% (95% CI 44.2-72.3%), 26.7% (95% CI 18.1-36.3%), and 16.2% (95% CI 6.0-29.4%) for DEB-TACE.The descriptive analysis suggested that DEB-TACE treatment for ICC may have better tumor response and disease control rates than c-TACE treatment, but the impact on overall survival was not demonstrated significantly by DEB-TACE treatment.

Brain infiltration of the natural killer (NK) cells has been observed in several neurodegenerative disorders, including Parkinson's disease (PD). In a mouse model of α-synucleinopathy, it has been shown that NK cells help in clearing α-synuclein (α-syn) aggregates. This study aimed to investigate the molecular mechanisms underlying the brain infiltration of NK cells in PD. Immunofluorescence assay was performed using the anti-NKp46 antibody to detect NK cells in the brain of PD model mice. Next, we analyzed the publicly available single-cell RNA sequencing (scRNA-seq) data (GSE141578) of the cerebrospinal fluid (CSF) from patients with PD to characterize the CSF immune landscape in PD. Results showed that NK cells infiltrate the substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice and colocalize with dopaminergic neurons and α-syn. Moreover, the ratio of NK cells was found to be increased in the CSF of PD patients. Analysis of the scRNA-seq data revealed that Rac family small GTPase 1 (RAC1) was the most significantly upregulated gene in NK cells from PD patients. Furthermore, genes involved in regulating SN development were enriched in RAC1

Background: Self-medication behavior has great adverse effects on children. The aims of this study were to assess the prevalence of self-medication with antibiotics (SMA) among children aged 0–5 ye...

The tumor microenvironment with overexpressed hydrogen peroxide (H2O2) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with in situ generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with H2O2 to produce •OH and release Cu2+. Then, the Cu2+ further depletes GSH to generate Cu+ for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.

PurposeMedical errors are a global concern, and specifically, EDs are at considerable risk for medical errors. Few studies focus on the healthcare provider’s self-perceived medical errors in hospitals, let alone the ED. Hence, this study explored perceived medical errors and their correlation with work-related factors and personal distress among physicians in EDs in China.MethodsFrom July 2018 to August 2018, a national web-based cross-sectional study was conducted. The link to the web-based questionnaire was posted on the emergency physicians’ working platform, inviting Chinese licensed emergency physicians to participate anonymously in this survey. Our outcome of interest, medical errors, was investigated using self-reporting methods. Occupational stress was assessed using the Chinese version of the Effort-Reward Imbalance scale. The Patient Health Questionnaire, the subscale of the 10-item Positive and Negative Affect Schedule, the subscale of the validated Leiden Quality of Work Questionnaire and the 10-item Generalised Self-efficacy Scale were used to assess personal distress. Logistic regression analysis was used to determine factors significantly associated with perceived medical errors.ResultsA sample of 10 457 emergency physicians completed the survey. Almost half (43.63%) of physicians reported self-perceived medical errors during the previous 3 months. The rate of workplace verbal aggression, effort-reward imbalance and depressive symptoms were 81.81%, 78.39% and 35.71%, respectively. Medical errors were more likely to be reported among chief physicians, and those who reported the department was short-staffed for physicians, and who experienced workplace verbal aggression and intense work stress. Medical errors were significantly associated with negative affect and lower self-efficacy.ConclusionSelf-perceived medical errors are prevalent among physicians working in EDs and are associated with their workplace environment and personal distress. Targeted interventions are required to reduce physicians’ workload and improve their working environment. Accounting for healthcare providers’ distress is imperative for reducing the incidence of medical errors and improving their health.

Background Self-medication is one of the most common forms of inappropriate use of antibiotics. This study aimed to assess the prevalence of self-medication with antibiotics (SMA) in China and evaluate the related factors. Methods A cross-sectional survey was conducted in Wuhan, Hubei, China from July 1, 2019 to July 31, 2019. Participants were recruited in public places to answer a structured questionnaire. The information of participants’ social demographic characteristics, antibiotic knowledge and health beliefs were collected. Binary Logistics regression analysis was used to examine the associated factors of SMA. Results Of the 3206 participants, 10.32% reported SMA in the past 6 months. Participants who with middle or high perceived barriers to seek health care services showed a higher likelihood of SMA (P P Conclusions Compared with developed countries, the prevalence of SMA in China is still higher. Measures to conduct public health education and improve the accessibility of health services are crucial to decrease the overall self-medication rate in China.

Polymer porous microspheres with large specific surface areas and good fluidity have promising important applications in the biomedical field. However, controllable fabrication of porous microspheres with precise size, morphology, and pore structure is still a challenge, and phase separation caused by the instability of the emulsion is the main factor affecting the precise preparation of porous microspheres. Herein, a method combining the iso-density emulsion (IDE) template and microfluidics was proposed to realize the controllable preparation of polymer porous microspheres. The IDE exhibited excellent stability with minimal phase separation within 4 h, thus showing potential advantages in the large-scale preparation of porous microspheres. With the IDE template combined microfluidics technique and the use of a customized amphoteric copolymer, PEG-b-polycaprolactone, polycaprolactone (PCL) porous microspheres with porosity higher than 90% were successfully prepared. Afterwards, the main factors, including polymer concentration, water–oil ratio and homogenization time were investigated to regulate the pore structure of microspheres, and microspheres with different pore sizes (1–30 μm) were obtained. PCL porous microspheres exhibited comparable cell viability relative to the control group and good potential as cell microcarriers after surface modification with polydopamine. The modified PCL porous microspheres implanted subcutaneously in rats underwent rapid in vivo degradation and tissue ingrowth. Overall, this study demonstrated an efficient strategy for the precise preparation of porous microspheres and investigated the potential of the as-prepared PCL porous microspheres as cell microcarriers and micro-scaffolds.

Background Effort-reward imbalance is an adverse psychological response to working conditions that has several negative effects on nurses. However, there is little research on effort-reward imbalance and its influencing factors among nurses in emergency departments. This study aimed to understand the current situation of effort-reward imbalance and explore its influencing factors among emergency department nurses in China. Methods From July to August 2018, a structured online questionnaire survey was conducted among emergency department nurses in China. Data were collected from emergency department nurses employed in hospitals providing pre-hospital care in China. The questionnaire consisted of sociodemographic characteristics, work-related factors and effort-reward imbalance. A descriptive analysis and a binary logistic regression were conducted to explore the effort-reward imbalance and its influencing factors among emergency department nurses. Results The study involved 17,582 emergency department nurses; notably, the prevalence of effort-reward imbalance was 59.66%. The participating nurses who were males, aged 25 to 34 years, whose educational level was a bachelor degree or above, who had a junior or above title, who had longer years of service, and who had suffered verbal or physical violence in the past year had a higher risk of effort-reward imbalance. Furthermore, the nurses with a high monthly income, who believed that the number of nurses met the department’s demand had a lower risk of effort-reward imbalance. Conclusions Effort-reward imbalance was prevalent among emergency department nurses in China. Measures such as adjusting the night shift frequency, increasing the number of nurses, raising salaries and reducing workplace violence should be considered to reduce the level of effort-reward imbalance.

Background To evaluate the clinical characteristics and angiographic features of transcatheter angiographic embolization (TAE) in patients with active bleeding after percutaneous nephrolithotomy (PCNL).Methods Between October 2009 and April 2018, 45 patients who underwent TAE for hemorrhage control after PCNL were reviewed retrospectively. Patient clinical characteristics and angiographic features of TAE were analyzed.Results Of the 3148 patients, 45 (1.4%), including 35 men (77.78%) and 10 women (22.22%), were treated with TAE after PCNL. Ten patients (22.22%) had a history of kidney surgery. The interval from the bleeding episode to TAE was 3 days (range, 1–6 days). In addition, 27 (60.0%) and 18 patients (40.0%) experienced sudden onset of bleeding and delayed bleeding, respectively. Arterial laceration, arteriovenous fistula, and negative angiographic finding was found in 28 (62.2%), 7 (15.6%), and 10 patients (22.2%), respectively. Thirty-five patients (92.1%) achieved primary clinical success. The median corrected hemoglobin decrease from bleeding episode to TAE was 52 g/L (25.25, 71.00). The median corrected hemoglobin decrease rate from bleeding episode to TAE was 13.11 g/L d (5.60, 26.12). The hemoglobin decrease from bleeding episode to TAE was lesser in negative angiographic patients (28.50 (10.75,51.25) g/L VS 53.7 (35.0,73.13) g/L) than in positive angiographic patients (PConclusion TAE is a safe and effective treatment for patients with post-PCNL bleeding. TAE should be performed for post-PCNL bleeding in patients with hemoglobin decrease of >25 g/L or hemoglobin decrease rate of >5.5 g/L·d following conservative management.

To discuss postoperative thrombocytopenia in the treatment of hepatocellular carcinoma (HCC) through transcatheter arterial chemoembolization (TACE) with single application of Lobaplatin as chemotherapy drug.The study retrospectively analyzed 1,945 HCC patients treated with TACE in our hospital from May 2013 to May 2018. The number of first-time users of lobaplatin reached 128, the second-time users reached 417, the third-time and above users 239. The analysis examined various items of patients, including gender, age, multiple preoperative examination indicators (platelet level, liver function tests, AFP level), ascites, preoperative presence of peptic ulcer at the initial (3-7 days) and long-term (21-90 days) postoperative stages. Platelet levels were evaluated according to the WHO Grading System for Hematologic Toxicity for side effects of anticancer drugs.For HCC patients with normal pre-intervention platelet level, the incidences of mild decrease, moderate decrease and severe decrease after intervention were 16.50%, 10.47% and 4.88% respectively, the incidences of long-term platelet reduction after intervention were 13.25%, 4.73% and 1.65% respectively. The level of post-intervention thrombocytopenia was not correlated with the cycles of lobaplatin use. The initial thrombocytopenia was more obvious in female patients after intervention. The presence or absence of peptic ulcer and ascites before the intervention had an effect on the initial thrombocytopenia after the intervention. Platelet level before intervention was correlated with that after intervention. The liver function grading before intervention had no effect on the two levels of thrombocytopenia after intervention. There was a correlation between AFP level grouping before intervention and initial thrombocytopenia after intervention.The long-term incidence of thrombocytopenia after interventional therapy was not high in TACE patients with HCC treated with LPT alone, which was relatively safe. Besides, the occurrence of thrombocytopenia after intervention had certain characteristics, which can be used to guide clinical practice, so as to reduce the incidence of thrombocytopenia or provide targeted symptomatic support treatment.

Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness. Magnetic resonance imaging (MRI) studies report an association between POAG and nonvisual pathway alterations. Locus coeruleus (LC) is a major source of norepinephrine released in the brain, and norepinephrine can reduce intraocular pressure via increasing aqueous outflow. This study aimed to investigate the relationship between glaucoma and the LC in patients with POAG and animal models. Resting-state functional MRI was performed using a 3-Tesla MR scanner with an eight-channel phased-array head coil, and MRI data were analyzed. A rat model of chronic glaucoma was generated by episcleral vein ligation and cauterization. DBA/2J mice that develop glaucoma with age were also acquired. Immunohistochemistry and immunofluorescence staining were used to investigate LC tyrosine hydroxylase (TH) and dopamine β-hydroxylase (DβH) expression, as well as cell apoptosis by terminal deoxynucleotidyl transferase dUTP Nick-End Labeling staining. Patients with POAG showed significantly increased amplitude of low-frequency fluctuation (ALFF) in the LC compared with controls. LC ALFF values showed significant correlations with cup-to-disk ratio, retinal nerve fiber layer thickness, and visual function (P 0.05). Functional connectivity (FC) between the LC and frontal and insular lobes was reduced, but elevated between the LC and parahippocampal gyrus, compared with controls. Glaucoma animal models revealed reduced expression of TH and DβH in the LC, and increased cell apoptosis. In this study, we provide novel evidence for the relationship between the LC and glaucoma. The LC may act as a network in POAG pathogenesis and intraocular pressure regulation.

The aim of the present study was to investigate the utility of diffusion tensor imaging (DTI) parameters of the central visual pathway and the size of the lateral geniculate nucleus (LGN) in the diagnosis of primary open-angle glaucoma (POAG). To test this, 24 POAG patients and 24 age- and gender-matched controls underwent 3.0 Tesla magnetic resonance imaging examinations, including DTI and LGN structural imaging. Receiver operating characteristic (ROC) curves were generated and Spearman's correlation coefficients were also determined. The results indicated that regarding the discrimination of POAG patients from healthy controls, the fractional anisotropy (FA) values of the optic tract, at a cutoff of ≤0.412, with an area under the ROC curve of 0.931, exhibited the highest sensitivity (79.2%) and specificity (89.6%). The FA values of the optic tract and the optic radiation were significantly correlated with LGN size, while the mean diffusivity values were not. In conclusion, the FA value of the optic tract may be a sensitive and reliable biomarker for glaucoma evaluation.

The purpose of this study was to explore the central mechanism of transauricular vagus nerve stimulation (taVNS) to human by fMRI and to find a suitable taVNS site for potential tinnitus treatment. 24 healthy subjects aged between 28 and 38 years were enrolled in the experiment. 8 subjects were stimulated in the auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) in the left ear, 8 subjects were stimulated at the anterior wall of the auditory canal and left lower limb as an anterior stimulation group; 8 persons who were arranged in a sham group received taVNS at the left ear lobe and tail of the helix. Functional magnetic resonance imaging (fMRI) data from the cortices was collected and an Alphasim analysis was performed. We found that taVNS at auricular acupoints CO10-12, TF4 can instantly and effectively generate blood oxygenation level dependent (BOLD) signal changes in the prefrontal, auditory and limbic cortices of healthy subjects by fMRI. When comparing the acupoints group and the sham group in the left brain, the signals from the prefrontal cortex, the auditory ascending pathway including superior temporal gyrus, middle temporal gyrus, thalamus and limbic system regions such as putamen, caudate, posterior cingulate cortex, amygdala and parahippocampal gyrus were increased under our stimulation. The difference of the BOLD signal in the left brain between acupoints group and anterior group was in the superior temporal gyrus. We could also find signal differences in several regions of right brain among the groups. In conclusion, taVNS at acupoints CO10-12, TF4 could activate the prefrontal, auditory and limbic cortices of healthy brain and this scheme could be a promising tool for tinnitus treatment.

The purpose of this study is to evaluate the magnetic susceptibility of normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) using quantitative susceptibility mapping.Ninety-four patients with relapse-remitting MS (RRMS) (37 with gadolinium-enhancing lesions and 57 with only gadolinium-nonenhancing lesions) and 55 healthy control subjects were included in this retrospective study. The susceptibility values of NAWM relative to CSF in patients with MS were compared with those of white matter (WM) in healthy control subjects and were correlated with the patient status of gadolinium-enhancing lesions, disease duration, and expanded disability status scale scores.All 37 patients with RRMS and gadolinium-enhancing lesions also had gadolinium-nonenhancing lesions. Susceptibility values of NAWM in patients with MS and only gadolinium-nonenhancing lesions (-18.29 ± 8.03 parts per billion [ppb]) were higher than those for WM in healthy control subjects (-25.81 ± 6.02 ppb; p0.001) and NAWM in patients with gadolinium-enhancing lesions (-25.64 ± 6.55 ppb; p0.001). Susceptibility values of NAWM in patients with MS with gadolinium-enhancing lesions were similar to those for WM in healthy control subjects (p = 0.91). This trend was dependent on neither NAWM region nor disease duration when the data were controlled for age. NAWM susceptibility was not correlated with either disease duration or expanded disability status scale (p0.05).In patients with RRMS and gadolinium-nonenhancing lesions, the susceptibility values of NAWM decrease when gadolinium-enhancing lesions appear, approaching values similar to those of WM in healthy control subjects, suggesting that NAWM may contribute to the iron accumulation observed in early active MS lesions.

The intravenous methylprednisolone (iv MP) strategy for Graves' ophthalmopathy (GO) and evaluation of its activity against the disease warrants further exploration. A prospective randomized controlled trial for 3 months was performed in a tertiary referral teaching hospital to compare the efficacy and safety of two different regimens of iv MP, and determine the value of clinical activity score (CAS) and T2 relaxation time (T2RTs) and areas of extraocular muscles (EOMs) by magnetic resonance imaging for diagnosis of active GO. Forty patients with moderate to severe GO and CAS ≥ 3 or 1 ≤ CAS3 with prolonged T2RTs on EOMs were randomly assigned to a monthly (MR: 1.5 g iv MP monthly for 3 months) or weekly (WR: 0.5 g iv MP weekly for 6 weeks, followed by 0.25 g weekly for 6 weeks) regimen. Overall response based on ophthalmic symptoms, T2RTs, areas of EOMs and adverse effects were recorded at each visit. The total rate of response was 71.9%. Rates of improved, unchanged, deteriorated were similar between the MR and WR groups (p0.05). The maximum T2RTs and areas significantly decreased at the end of intervention in both groups (p0.05). Results show that both MR and WR are effective and safe in treatment of GO. T2RTs combined with CAS can sensitively detect active GO and predict the response to iv MP.

To investigate the relationship between morphological changes in the lateral geniculate nucleus (LGN), as measured by magnetic resonance imaging (MRI), and damage to the optic disc in primary open-angle glaucoma (POAG) patients.A total of 23 patients with POAG and 23 age- and gender-matched non-glaucomatous subjects were enrolled. Every patient had structural damage to the optic disc. Cup-to-disc ratio (CDR) and retinal nerve fiber layer thickness (RNFLT) were measured, and 3.0-Tesla MRI examinations performed. Bilateral LGNs were identified and manually extracted, and their maximum heights and volumes compared with the clinical damage to the optic disc.In POAG patients, morphological changes in LGNs and RNFLT were consistently varied (P0.05), while a negative correlation between LGN measurements and CDR was observed (P0.05). LGN height was more significantly correlated with damage to the optic disc than was LGN volume. In contrast, no significant correlation was found between morphological changes in LGNs and age or optic disc parameters in the non-glaucomatous controls (P0.05).LGN atrophy in POAG patients was altered in a manner consistent with damage to the optic disc. Morphological changes in LGNs as measured by MRI and especially LGN maximum height may be useful ways to detect optic nerve neuropathy in glaucoma.

A high-performance imaging probe with NIR luminescence and synergistically enhanced T1−T2 relaxivity was synthesized. This nanoprobe exhibits a relatively high tumor-targeting efficacy and enables NIR optical and T1-/T2-weighted MR imaging of hepatic tumor cells in vivo.

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody–conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t -test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T 2 relaxivity was 92.73 s −1 mM −1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T 2 -weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R 2 value increased by 30% compared to baseline. However, T 2 -weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.

Qing Zhou,1,* Ketao Mu,2,* Lingyu Jiang,1 Hui Xie,3 Wei Liu,1 Zhengzheng Li,1 Hui Qi,1 Shuyan Liang,1 Huibi Xu,1 Yanhong Zhu,1 Wenzhen Zhu,2 Xiangliang Yang11National Engineering Research Center for Nanomedicine, College of Life Science and Technology, 2Radiology Department, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 3Department of Information Processing, China Patent Information Center, Wuhan, People’s Republic of China*These authors contributed equally tothis workAbstract: Surgical resection is the primary mode for glioma treatment, while gross total resection is difficult to achieve, due to the invasiveness of the gliomas. Meanwhile, the tumor-resection region is closely related to survival rate and life quality. Therefore, we developed optical/magnetic resonance imaging (MRI) bifunctional targeted micelles for glioma so as to delineate the glioma location before and during operation. The micelles were constructed through encapsulation of hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) with polyethylene glycol-block-polycaprolactone (PEG-b-PCL) by using a solvent-evaporation method, and modified with a near-infrared fluorescent probe, Cy5.5, in addition to the glioma-targeting ligand lactoferrin (Lf). Being encapsulated by PEG-b-PCL, the hydrophobic SPIONs dispersed well in phosphate-buffered saline over 4 weeks, and the relaxivity (r2) of micelles was 215.4 mM–1·s–1, with sustained satisfactory fluorescent imaging ability, which might have been due to the interval formed by PEG-b-PCL for avoiding the fluorescence quenching caused by SPIONs. The in vivo results indicated that the nanoparticles with Lf accumulated efficiently in glioma cells and prolonged the duration of hypointensity at the tumor site over 48 hours in the MR image compared to the nontarget group. Corresponding with the MRI results, the margin of the glioma was clearly demarcated in the fluorescence image, wherein the average fluorescence intensity of the tumor was about fourfold higher than that of normal brain tissue. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay results showed that the micelles were biocompatible at Fe concentrations of 0–100 µg/mL. In general, these optical/MRI bifunctional micelles can specifically target the glioma and provide guidance for surgical resection of the glioma before and during operation.Keywords: MRI, fluorescence image, micelles, lactoferrin, glioma

In order to delineate the location of the tumor both before and during operation, we developed targeted bi-functional polymeric micelles for magnetic resonance (MR) and fluorescence imaging in liver tumors. Hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs) were loaded into the polymeric micelles through self-assembly of an amphiphilic block copolymer poly(ethylene glycol)-poly(ϵ-caprolactone). After, transferrin (Tf) and near-infrared fluorescence molecule Cy5.5 were conjugated onto the surface of the polymeric micelles to obtain the nanosized probe SPIO@PEG-b-PCL-Tf/Cy5.5 (SPPTC). Imaging capabilities of this nanoprobe were evaluated both in vitro and in vivo. The accumulation of SPPTC in HepG2 cells increased over SPIO@PEG-b-PCL-Cy5.5 (SPPC) by confocal microscopy. The targeted nanoprobe SPPTC possessed favorable properties on the MR and fluorescence imaging both in vitro and in vivo. The MTT results showed that the nanoprobes were well tolerated. SPPTC had the potential for pre-operation evaluation and intra-operation navigation of tumors in clinic.

To investigate nerve fibre damage of the visual pathway in patients with primary open-angle glaucoma using tract-based spatial statistical analysis of diffusion tensor imaging and correlate these measures with the clinical severity of glaucoma.Cross-sectional study.Twenty-five individuals with primary open-angle glaucoma and 24 healthy controls were recruited.All subjects underwent detailed ophthalmological examinations, including the cup-to-disc ratio, retinal nerve fibre layer thickness and visual fields test. Diffusion tensor imaging of the visual pathway was performed using a 3.0-T magnetic resonance scanner.Diffusivity changes of the nerve fibres in the visual pathway were calculated through tract-based spatial statistical analysis. The mean diffusivity and fractional anisotropy were assessed and compared with ophthalmological measurements.Compared with controls, bilateral optic tracts and optic radiations in primary open-angle glaucoma patients showed significantly decreased fractional anisotropy and increased mean diffusivity (P0.05). In the glaucoma group, the fractional anisotropy of the optic tracts and optic radiations varied consistently with the cup-to-disc ratio, retinal nerve fibre layer thickness and visual function analysis, respectively (P0.05). The mean diffusivity of the optic tracts correlated with these ophthalmological measurements (P0.05). However, no significant correlation was observed between the mean diffusivity of the optic radiations and the ophthalmological measurements (P0.05).The optic tracts and optic radiations of primary open-angle glaucoma patients demonstrated radiological evidence of neurodegeneration. This varied with damage to the optic disc and with the loss of visual function. Tract-based spatial statistical analysis of diffusion tensor imaging is an objective and effective tool for detecting the loss of cortical nerve fibres in primary open-angle glaucoma.