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Background Apathy is common in Alzheimer's disease (AD) patients. However, its relation with other clinical symptoms in AD and brain structural changes in magnetic resonance imaging is unclear. Results Compared with AD with no apathy group, cognitive function and activities of daily living were significantly impaired and neuropsychiatric symptoms were obviously presented in AD with apathy group (P 0.05). Correlation analyses and multiple linear analyses revealed that thickness of left temporal pole and volume of posterior corpus callosum were significantly and negatively correlated with Modified Apathy Estimation Scale score in AD patients (P Conclusions Apathy with AD is positively correlated with cognitive impairment, neuropsychiatric symptoms and poor activities of daily living. Atrophy of left temporal pole and posterior corpus callosum presented by MRI is positively related with apathy of AD. Methods In this study, 137 AD patients were recruited and divided into AD with apathy group and AD with no apathy group according to Modified Apathy Estimation Scale score. We evaluated patients' cognitive function, neuropsychiatric symptoms and activities of daily living, detected the frequency of Apolipoprotein E genotypes and measured cortical thickness and volume by magnetic resonance imaging (MRI).

Background and Purpose: Symptomatic hemorrhage contributes to an increased risk of repeated bleeding and morbidity in cerebral cavernous malformation (CCM). A better understanding of morbidity after CCM hemorrhage would be helpful to identify patients of higher risk for unfavorable outcome and tailor individualized management. Methods: We identified 282 consecutive patients who referred to our institute from 2014 to 2018 for CCM with symptomatic hemorrhage and had an untreated follow-up period over 6 months after the first hemorrhage. The morbidity after hemorrhage was described in CCM of different features. Nomogram to predict morbidity was formulated based on the multivariable model of risk factors. The predictive accuracy and discriminative ability of nomogram were determined with concordance index (C-index) and calibration curve, and further validated in an independent CCM cohort of a prospective multicenter study from 2019 to 2020. Results: The overall morbidity of CCM was 26.2% after a mean follow-up of 1.9 years (range 0.5–3.5 years) since the first hemorrhage. The morbidity during untreated follow-up was associated with hemorrhage ictus (adjusted odds ratio per ictus increase, 4.17 [95% CI, 1.86–9.33]), modified Rankin Scale score at initial hemorrhage (adjusted odds ratio per point increase, 2.57 [95% CI, 1.82–3.63]), brainstem location (adjusted odds ratio, 2.93 [95% CI, 1.28–6.68]), and associated developmental venous anomaly (adjusted odds ratio, 2.21 [95% CI, 1.01–4.83]). Subgroup analysis revealed similar findings in brainstem and non-brainstem CCM. Nomogram was contracted based on these features. The calibration curve showed good agreement between nomogram prediction and actual observation. The C-index of nomogram predicting morbidity was 0.83 (95% CI, 0.77–0.88). In validation cohort, the nomogram maintained the discriminative ability (C-index, 0.87 [95% CI, 0.78–0.96]). Conclusions: Multiple symptomatic hemorrhages, initial neurological function after hemorrhage, brainstem location, and associated developmental venous anomaly were associated with morbidity of CCM hemorrhage. The nomogram represented a practical approach to provide individualized risk assessment for CCM patients. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04076449.

ObjectiveThe brain compensation mechanism in postoperative delirium (POD) has not been reported. We uncovered the mechanism by exploring the association between POD and glioma grades, and the relationship between preoperative brain structural and functional compensation with POD in patients with frontal glioma.MethodsA total of 335 adult patients with glioma were included. The multivariable analysis examined the association between tumor grade and POD. Then, 20 patients with left frontal lobe glioma who had presurgical structural and functional MRI data and Montreal Cognitive Assessment (MoCA) in this cohort were analyzed. We measured the gray matter volume (GMV) and functional connectivity (FC) in patients with (n = 8) and without (n = 12) POD and healthy controls (HCs, n = 29) to detect the correlation between the structural and functional alteration and POD.ResultsThe incidence of POD was 37.3%. Multivariable regression revealed that high-grade glioma had approximately six times the odds of POD. Neuroimaging data showed that compared with HC, the patients with left frontal lobe glioma showed significantly increased GMV of the right dorsal lateral prefrontal cortex (DLPFC) in the non-POD group and decreased GMV of right DLPFC in the POD group, and the POD group exhibited significantly decreased FC of right DLPFC, and the non-POD group showed the increasing tendency. Partial correlation analysis showed that GMV in contralesional DLPFC were positively correlated with preoperative neurocognition, and the GMV and FC in contralesional DLPFC were negatively correlated with POD.ConclusionsOur findings suggested that insufficient compensation for injured brain regions involving cognition might be more vulnerable to suffering from POD.

Objective To investigate the prognostic value of dynamic susceptibility contrast⁃enhanced MRI (DSC⁃MRI), 3D⁃arterial spin labeling (3D⁃ASL) and intravoxel incoherentmotion (IVIM) in glioblastoma. Methods From August 2016 to October 2017, a total of 34 patients with glioblastoma were enrolled. According to the overall survival (OS), they were divided into < 14 months group (17 cases) and ≥ 14 months group (17 cases). MRI conventional sequences, DSC⁃MRI, 3D⁃ASL, IVIM were acquired before operation. Multiple regions of interest (ROIs) were placed in the tumor⁃enhanced region and the peritumoral region, and recorded the values of DSC⁃maximum relative cerebral blood volume (DSC⁃rCBV max ) and relative cerebral blood flow (DSC⁃rCBF), ASL⁃cerebral blood flow (ASL⁃CBF), IVIM⁃perfusion fraction (PF). Receiver operating characteristic (ROC) curve was used to evaluated the prognostic value of the imaging indicators. Results There were no significant differences in ASL⁃CBF, IVIM⁃PF, DSC⁃rCBF and DSC⁃rCBV max between the OS < 14 months group and the OS ≥ 14 months group in tumor⁃enhanced region (P > 0.05, for all). In the peritumoral region, the IVIM⁃PF of the patients in OS < 14 months was lower (P = 0.011) while DSC⁃rCBF (P = 0.009) and DSC⁃rCBV max (P = 0.012) were higher than OS ≥ 14 months group. The area under the ROC curve was 0.579 (95%CI: 0.372-0.787, P = 0.453), 0.763 (95%CI: 0.588-0.937, P = 0.013) and 0.746 (95%CI: 0.565-0.926, P = 0.020) respectively, suggesting that DSC⁃rCBF and DSC⁃ rCBV max have better reference value for prognosis. Conclusions The imaging indicators of DSC⁃MRI have an effect on the OS of glioblastoma, while IVIM and ASL have not shown an effect on overall survival. DOI：10.3969/j.issn.1672⁃6731.2019.11.008

Voriconazole is widely recommended for the prevention and treatment of invasive fungal infections in hematopoietic stem cell transplantation patients. However, its use is limited by a narrow therapeutic range and large inter-individual variability. This study aimed to characterize the pharmacokinetics of voriconazole in Chinese hematopoietic stem cell transplantation patients, to explore factors affecting its pharmacokinetic parameters, and to provide recommendations for its optimal dosing regimens. A total of 121 serum concentration samples from 23 patients were retrospectively included. Voriconazole concentrations were detected, and patient clinical data were recorded. Population pharmacokinetic analysis was performed by a non-linear, mixed-effect modeling approach. Goodness-of-fit plots, bootstrap method, prediction-corrected visual predictive check and external validation by an independent group of seven patients were performed to evaluate the final model. A one-compartment model with first-order elimination successfully described the data. The absorption rate constant was fixed at 1.1 h−1 and bioavailability was fixed at 0.895. The typical values for voriconazole clearance and distribution volume were 9.52 L/h and 155 L, respectively. CYP2C19*2 genotype and mycophenolate mofetil combination presented a significant impact on the clearance. Compared with CYP2C19*2 carriers, voriconazole clearance was proven to be higher in CYP2C19*1/*1 patients. A population pharmacokinetic model of voriconazole was successfully established in Chinese hematopoietic stem cell transplantation patients. Based on the final model, CYP2C19*2 genotyping coupled with therapeutic drug monitoring seems to be useful to guide voriconazole dosing and to explain subtherapeutic concentrations in clinical practice.

Background Olfactory dysfunction (OD) is reported as a useful predictor for Alzheimer’s disease (AD). There are three sub-domains of olfaction: olfactory threshold, discrimination and identification. In AD patients, whether the performance of three sub-domains has different influential factors or relates to specific brain magnetic resonance imaging (MRI) change is not clear. Methods We recruited 105 typical AD patients, assessed patients’ cognitive function, neuropsychiatric symptoms and activity of daily living by related scales, evaluated patients’ olfactory function by Sniffin’ Sticks test and measured patients’ cortical thicknesses by MRI. Results Olfactory threshold negatively correlated with AD patients’ age and positively related to cognitive function; olfactory discrimination positively related to patients’ cognitive function and cortical thickness of left lateral orbitofrontal gyrus; olfactory identification positively related to patients’ cognitive function and cortical thicknesses of left medial orbitofrontal gyrus, left middle temporal gyrus and bilateral superior temporal gyrus. Conclusions The three sub-domains of olfaction in AD patients have different influential factors: age influences olfactory threshold and cognitive function influences all three olfactory sub-domains. The performance of olfactory discrimination and identification in AD patients was associated with the cortical thickness of orbitofrontal gyrus and temporal lobe.

Purpose: The conventional examination of molecular characteristics for glioma requires surgical removal and could not be used in the surgery planning. The aim is to develop a method previewing glioma malignancy with regular structural MRI images. Methods: 52 glioma patients in frontal lobe (mean age 43.2±9.3 years, 34 male) and 117 healthy controls (mean age 32.6±9.8 years, 83 male) participated in the study. All patients underwent neurocognitive test and molecular examinations, including 1p/19q co-deletion, isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation. A series of individual structural abnormality indexes based on preoperative structural MRI were proposed and explored the associations with these clinical indicators.Results: Individual structural abnormality maps displayed that bilateral hippocampus, parahippocampus, insula, putamen and thalamus were constantly affected by glioma regardless of the histological grade, tumor hemisphere and molecular status. Higher grade glioma patients suffered more structural abnormalities, especially in the contralateral hemisphere and non-tumor regions. The molecular indicators, including IDH1 mutation, 1p/19q co-deletion, TERT promoter mutations and MGMT promoter methylation, as well as neurocognitive performance were all significantly correlated to individual structural abnormality indexes.Conclusion: Our proposed individual structural abnormality indexes show great potentials to access the glioma pathological, neurocognitive and molecular indicators, which is very helpful for neurosurgeons to determine the personalized treatment strategies.

Although every glioma patient varies in tumor size, location, histological grade and molecular biomarkers, structural abnormalities are commonly conducted in a group-level, leading to the miss of individual structural atrophy. In this study, we introduced an individual-level structural abnormality detection method for glioma patients and proposed several novel abnormality indexes to depict the individual atrophy pattern. Forty-five glioma patients in frontal lobe and fifty-two age-matched healthy controls participated in the study. All patients underwent neurocognitive test and molecular examinations, including 1p/19q co-deletion, isocitrate dehydrogenase (IDH) mutation, telomerase reverse transcriptase (TERT) promoter mutation and O6-methylguanine-DNA methyltransferase (MGMT) promotor methylation. Individual structural abnormality maps for every glioma patient were calculated from the preoperative T1 images, and the individual abnormality index were further computed and explored the associations with clinical indicators. The results manifested that: 1. Every glioma patient show unique atrophy pattern; 2. Glioma patients also share consistent atrophy regions; 3. The atrophy pattern is influenced by some molecular biomarkers. Our study provides an effective way to access the individual structural abnormalities in glioma patients, and displays great potentials in individualized precision medicine for glioma patients.

Background: Previous studies reported that gender and age could influence urine metabolomics, which should be considered in biomarker discovery. As a consequence, for the baseline of urine metabolomics characteristics, it becomes critical to avoid confounding effects in clinical cohort studies. Results: In this study, we provided a comprehensive lifespan characterization of urine metabolomics in a cohort of 348 healthy children and 315 adults aged 1 to 70 years using liquid chromatography coupled with high resolution mass spectrometry. Our results suggested that gender-dependent urine metabolites are much greater in adults than in children. The pantothenate and CoA biosynthesis and alanine metabolism pathways were enriched in early life. Androgen and estrogen metabolism showed high activity during adolescence and youth stages. Pyrimidine metabolism was enriched in the old stage. Conclusion: Based on the above analysis, metabolomic characteristics of each age stage were provided. This work could help us understand the baseline of urine metabolism characteristics and contribute to further studies of clinical disease biomarker discovery.

Background: Cardiovascular disease has one of the highest mortality rates among all the diseases. Platelets play an important role in the pathogenesis of cardiovascular diseases. Platelet membrane glycoprotein GPIIb/IIIa antagonists are the most effective antiplatelet drugs, and pulaimab is one of these. The study aims to promote individual medication of pulaimab [anti-GPIIb/IIIa F(ab)2 injection] by discovering the pharmacological relationship among the dose, concentration, and effects. The goal of this study is to establish a population pharmacokineticpharmacodynamic model to evaluate the antiplatelet effect of intravenous pulaimab injection. Methods: Data were collected from 59 healthy subjects who participated in a Phase-I clinical trial. Plasma concentration was used as the pharmacokinetic index, and platelet aggregation inhibition rate was used as the pharmacodynamic index. The basic pharmacokinetics model was a two-compartment model, whereas the basic pharmacodynamics model was a sigmoid-EMAX model with a direct effect. The covariable model was established by a stepwise method. The final model was verified by a goodness-of-fit method, and predictive performance was assessed by a Bootstrap (BS) method. Results: In the final model, typical population values of the parameters were as follows: central distribution Volume (V1), 183 L; peripheral distribution Volume (V2), 349 L; Central Clearance (CL), 31 L/h; peripheral clearance(Q), 204 L/h; effect compartment concentration reaching half of the maximum effect (EC50), 0.252 mg/L; maximum effect value (EMAX), 54.0%; and shape factor (γ), 0.42. In the covariable model, thrombin time had significant effects on CL and EMAX. Verification by the goodness-of-fit and BS methods showed that the final model was stable and reliable. Conclusion: A model was successfully established to evaluate the antiplatelet effect of intravenous pulaimab injection that could provide support for the clinical therapeutic regimen.

Methotrexate (MTX) pharmacokinetics has substantial inter-individual variability and toxicity. In children with medulloblastoma treated with high-dose methotrexate (HD-MTX), the pharmacokinetic properties of methotrexate have not been established. A total of 660 serum samples from 105 pediatric patients with medulloblastoma were included in a population pharmacokinetic (PPK) analysis of methotrexate by using the nonlinear mixed-effects modeling method. The basic one-compartment population pharmacokinetic model was established by NONMEM software and the first-order conditional estimation (FOCE) method, and the final covariate model was obtained by the stepwise regression method. Weight (WT), creatinine clearance (CrCL), and whether the treatment was combined with dexamethasone (DEX) were covariates that had significant effects on the clearance rate (CL) of the model. The pharmacokinetic equation of CL in the final covariate model was as follows: CLi = 9.23× (1 + 0.0005× (θCrCL -105.78)) × (1 + 0.0017× (θWT -16)) × eηcl,i (L/h), IF (θDEX ) CLi = 1.19× CLi (L/h). The estimation accuracy of all pharmacokinetic parameters were acceptable (relative standard error < 14.74%). The goodness-of-fit diagram and bootstrap tests indicated that the final PPK model was stable with acceptable predictive ability. The PPK model may be useful for determining personalized medication levels in pediatric medulloblastoma patients undergoing HD-MTX therapy.

We explored changes in clinical features and neuropathological mechanisms underlying olfactory dysfunction (OD) in 60 patients with Alzheimer's disease (AD). Olfactory function was evaluated using the Sniffin' Sticks test and a threshold discrimination identification (TDI) score. Based on the TDI score, we divided patients according to the presence or absence of OD (AD-OD and AD-NOD, respectively). Cognitive and neuropsychiatric symptoms were evaluated by a series of rating scales. The volumes and cortical thickness of the thalamus, hippocampus, and amygdala were measured using structural magnetic resonance imaging. Neuropathological protein levels in cerebrospinal fluid were measured. The frequency of OD was 50%. TDI scores were lower in the AD-OD group than in the AD-NOD group (p < 0.001). Compared with the AD-NOD group, the AD-OD group showed greater cognitive function impairments (p < 0.001), and daily living activities were more severely compromised (p = 0.019). The AD-OD group had lower hippocampal and amygdala volumes (p = 0.025, p = 0.030, respectively) and a more pronounced reduction in cortical thickness (p = 0.010). The total tau level was lower in the AD-OD group than the AD-NOD group (p = 0.040). Lower Mini-Mental State Examination scores and thinner AD-signature cortices were associated with lower TDI scores (OR = 0.826, p < 0.001; OR = 1.433, p = 0.008). Overall, in AD patients, the impairments in olfactory discrimination and identification seem to be more correlated with cognitive levels. OD in AD may be an indicator of pathological cognitive decline and structural changes.

Objective To investigate the distribution of abnormal neurological activity of patients with recurrent optic neuritis (ON) by resting-state functional magnetic resonance imaging (fMRI), and to explore the relationship between baseline neurological function and clinic. Methods Resting-state fMRI were collected from 35 patients with recurrent ON and 50 normal controls who were matched in sex, age and education with patients. The amplitude of low-frequency fluctuation (ALFF) difference was investigated and compared between 2 groups. The correlation of brain regions with significantly different mALFF with duration, Paced Auditory Serial Addition Test (PASAT) and vision was further explored. Results Compared to normal controls, patients with recurrent ON showed significantly decreased mALFF in left cuneus/precuneus, left superior temporal gyrus, bilateral inferior temporal gyri, bilateral lingual gyri, right middle occipital gyrus (P < 0.01), and significantly increased mALFF in bilateral inferior frontal gyri and left medial frontal gyrus (P < 0.01). The positive correlation between duration and mALFF in left superior temporal gyrus (r = 0.403, P < 0.05) and right lingual gyrus (r = 0.472, P < 0.05) was observed in recurrent ON patients. Conclusions Resting-state fMRI can detect decreased neurological function in the temporal and occipital lobes which are involved in visual processing and increased neurological function in the frontal lobe which is involved in default mode network (DMN) in recurrent ON. It will provide evidence for evaluating neurological function and predicting the prognosis of ON in the early stage. DOI: 10.3969/j.issn.1672-6731.2016.06.007

Objective To determine the pharmacokinetics (PK) of vancomycin in Chinese infant patients using a population pharmacokinetic (PKK) approach in order to provide support for individualized vancomycin therapy. Method The data included 72 sets of steady-state peak and trough serum concentrations from 61 infants (0 - 1 years). PPK analysis was performed using the nonlinear mixed-effects modeling software. Inter- and intraindividual variability was estimated for the clearance and distribution volume of vancomycin. The potential effects of patient sex, postnatal age, postconceptional age, height, weight, body surface area, body mass index, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, white blood cell count, serum creatinine, and concomitant medications on vancomycin PKs were explored. Results A one-compartment linear model with first-order elimination was used to describe the data. Weight and postnatal age had a significant influence on vancomycin clearance. The typical population parameter estimates of clearance and distribution volume were 0.46 L/h and 4.45 L, respectively. Goodness-of-fit plots and bootstrap outcomes confirmed the relatively good stability and prediction capability of the model. Conclusion This study initially established a vancomycin PPK model to estimate individual PK parameters in Chinese infant patients. .

Objective To assess the diffusion changes of normal appearing spinal cord (NASC) in MRI examination in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). Methods Axial diffusion tensor imaging (DTI) of cervical cord was performed in 10 patients with NMO, 14 patients with MS and 13 sex- and age-matched healthy controls. Mean diffusivity (MD) and fractional anisotropy (FA) were measured in the C2-5 level of spinal cord. Regions of interest (ROIs) were placed in the anterior, lateral, posterior funiculi of spinal cord, and the central gray matter of spinal cord. Results Compared with healthy controls, the values of FA in anterior, lateral and posterior funiculi of spinal cord were significantly decreased (P < 0.05, for all) and MD in left lateral funiculus, posterior funiculus and gray matter were significantly increased (P ≤ 0.05, for all) in NMO group, and the FA values of right lateral and posterior funiculi in MS group were significantly decreased (P < 0.05, for all). Compared with MS group, FA value in patients with NMO was significantly decreased in lateral funiculus, and MD value in left lateral and right posterior funiculi were significantly increased (P < 0.05, for all). Conclusions NASC diffusion abnormalities were found both in patients with NMO and MS. The difference of DTI indicators between NMO and MS patients may offer important information in the early diagnosis and differential diagnosis of NMO and MS. doi: 10.3969/j.issn.1672-6731.2014.10.007

Objective To assess the diffusion changes of normal⁃appearing spinal cord (NASC) in patients with multiple sclerosis (MS). Methods Axial diffusion tensor imaging (DTI) of the cervical spinal cord was performed in 13 patients with MS and 13 sex ⁃ and age ⁃ matched healthy controls. Fractional anisotropy (FA) and mean diffusivity (MD) measurements were made in the spinal cord at the C2-5 level. Regions of interest (ROIs) were placed in the anterior, lateral, posterior spinal cord, and the central spinal cord. Expanded Disability Status Scale (EDSS) scores were investigated. Study t ⁃ test and Pearman correlation were performed. Results Compared with healthy controls, FA in NASC of patients with MS was significantly decreased in several regions including the left anterior (mean ± SD of 0.44 ± 0.06 versus 0.48 ± 0.04 in control subjects, P = 0.000), right anterior (0.42 ± 0.06 versus 0.48 ± 0.04, P = 0.000), left lateral (0.48 ± 0.06 versus 0.51 ± 0.01, P = 0.001), right lateral (0.49 ± 0.06 versus 0.51 ± 0.03, P = 0.007), and left posterior (0.48 ± 0.06 versus 0.51 ± 0.03, P = 0.002), right posterior (0.48±0.06 versus 0.50 ± 0.03, P = 0.007). Negative correlation was observed between FA reduction with EDSS scores (r = ⁃ 0.328-⁃ 0.207, P = 0.001-0.035). Positive correlation was seen between MD with EDSS scores in ROIs (r = 0.234-0.409, P = 0.000-0.018). Conclusion NASC diffusion abnormalities were found in patients with MS. The association between FA in NASC and EDSS suggests FA may be a potentially quantitative biomarker for monitoring clinical severity of MS with latent lesion. DOI：10.3969/j.issn.1672⁃6731.2012.04.007

Objective To investigate the presence of damage to the normal⁃appearing thalamus in relapsing⁃remitting multiple sclerosis (RRMS) and the relationship of diffusion tensor imaging (DTI) with the degree of disability of patients with RRMS. Methods Conventional MRI and DTI were acquired in 24 patients with relapsing ⁃remitting MS and 24 age ⁃ and sex ⁃ matched healthy volunteers. DTI parameters including fractional anisotropy (FA) and mean diffusivity (MD) were measured in normal⁃appearing thalamus by application areas of interest method. Group differences in MD and FA were examined and correlations between DTI parameters and clinical score of patients or lesion volume were investigated. Results Patients with RRMS had lower thalamic MD [(85.34 ± 14.68) × 10⁃3 mm2/s] than volunteers [(98.42 ± 13.10) × 10⁃3 mm2/s, t = ⁃ 3.257, P = 0.002], and higher FA (0.40 ± 0.04) than volunteers (0.36 ± 0.05, t = 3.163, P = 0.003). In patients with RRMS, MD values correlated with the Paced Auditory Serial Addition Test (PASAT) scores (r = 0.711, P = 0.000). Conclusion DTI was sensitive to detect abnormalities in normal⁃appearing thalamus of patients with RRMS. The association between thalamic DTI indexes and functional impairment suggests DTI is a promising marker of the RRMS for future studies. DOI：10.3969/j.issn.1672⁃6731.2012.02.010

Sorafenib is slightly absorbed in the gastrointestinal tract due to its poor solubility in water. To improve its absorption, a novel nanoparticulate formulation-nanomatrix was used in the study. The nanomatrix was a system prepared from a porous material Sylysia(®) 350 and a pH sensitive polymer Eudragit(®). The formulations were optimized by orthogonal design (L(9)(3(4))) and their bioavailability were evaluated in rat, comparing to pH-sensitive Eudragit nanoparticles and suspension of sorafenib. In the formulations, the ratio of sorafenib to Eudragit(®) S100 was found to be more important determinant of the sorafenib bioavailability than the ratio of sorafenib to Sylysia(®) 350. As for the bioavailability, the AUC(0-36 h) of sorafenib nanomatrix was 13-33 times to that of sorafenib suspension, but only 16.8% to 40.8% that of Eudragit(®) S100 nanoparticles. This may be resulted from the different drug dispersion degree, release character and bioadhension activity. However, because all the materials used in the nanomatrix formulation are commonly adjuvant, safe, easy to get and cheap, above all, the nanomatrix formulation can solve the stability and scaling up problems in the nanoparticles, it had potential to develop into a product in the future.

To investigate the feature brain damage and clinical manifestations in neuromyelitis optica (NMO) patients; To investigate the relationship between serum NMO-IgG antibody and NMO brain damage.Clinical data of 37 NMO patients and their head and spinal cord MRI by 1.5T superconducting MR scanner, were analyzed; serum NMO-IgG antibody were measured by immunofluorescence.17 cases were found to have abnormal signals on MRI, which were mainly in the white matter, pons, medulla, ventricle, aqueduct, and around the corpus callosum; According to pathological changes, brain damage can be divided into scattered irregularity (13 cases), fusion (3 cases), multiple sclerosis-like (1 case), with scattered irregularity more common, 5 cases had clinical manifestations of brain damage: somnolence, vomiting, diplopia, visual rotation, 11 cases patients with brainstem damage show positive serum NMO-IgG antibodies.Brain damage can be seen in half of NMO patients, they often located in the high expression area of AQP4: brain white matter, periventricular, brainstem and so on. Clinical symptoms has nothing to do with the size of lesions but the location, they often occur when brainstem was involved. Serum NMO-IgG is helpful in differentiating NMO with brain damage and MS.

To study the using of the method in vitro and in vivo of lasting time of ciliary movement in ligustrazine, synthetic borneol.(1) Method in vitro-The lasting time of ciliary movement was observed with forty-fold optical microscope after dropping liquid medicine on exteacorporeal frog palate mucosa. Then mucosa was cleared. It was observed whether the ciliary movement was recovered and the lasting time was recorded from recovering to stopping once again. (2) Method in vivo-Liquid medicine or normal saline was dropped on frog palate mucosa by contacting thirty minutes. Then mucosa was cleared. The lasting time of ciliary movement was observed with forty-fold optical microscope by separating palate mucosa.Relatively percentage of lasting time of ciliary movement of ligustrazine in vitro and in vivo was 9.8%, 87.3%; The relatively percentage of synthetic borneol in vitro and in vivo was 9.3%, 89.5%.The method in vitro and in vivo of lasting time of ciliary movement can be the one of the selecting ways of Chinese drug's toxicity of nasal mucosa, and it have virtues and defects respectively. Ligustrazine, synthetic borneol have significantly toxical effect on exteacorporeal lasting time of ciliary movement.