Morbidity After Symptomatic Hemorrhage of Cerebral Cavernous Malformation: A Nomogram Approach to Risk Assessment.

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.

Population pharmacokinetics of cyclosporine A in Chinese patients with nephrotic syndrome in individualized drug administration
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OBJECTIVE: To establish a population pharmacokinetic (PopPK) model of cyclosporine A (CsA) in Chinese patients with nephrotic syndrome (NS) and to use the model to guide the adjustment of individualized dosage regimens. MATERIALS AND METHODS: 216 CsA therapeutic drug monitoring (TDM) concentration observations were collected from 127 Chinese patients with NS. The basic model was developed as a one-compartment PK model with first-order absorption and linear elimination. The first-order conditional estimation (FOCE) method was applied to establish the final model with covariates using NONMEM software. The final model was evaluated through internal validation including goodness-of-fit analysis and bootstrap method as well as external validation using 39 additional PK observations from 35 patients with NS. RESULTS: A PopPK model of CsA was established in Chinese NS patients with influence of body weight on clearance. The internal and external validation results showed that the final model was stable. CONCLUSION: The established population model adequately characterized the PK of CsA in Chinese patients and could support individualized medication during treatment of NS with CsA.

Population pharmacokinetics of high-dose methotrexate in Chinese pediatric patients with medulloblastoma.

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.

Population pharmacokinetics of vancomycin in Chinese infants
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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.
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White Matter Microstructure Changes Revealed by Diffusion Kurtosis and Diffusion Tensor Imaging in Mutant Huntingtin Gene Carriers.

Background: Diffusion magnetic resonance imaging (dMRI) has revealed microstructural changes in white matter (WM) in Huntington's disease (HD). Objective: To compare the validities of different dMRI, i.e., diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in HD. Methods: 22 mutant huntingtin (mHTT) carriers and 14 controls were enrolled. Clinical assessments and dMRI were conducted. Based on CAG-Age Product (CAP) score, mHTT carriers were categorized into high CAP (hCAP) and medium and low CAP (m& lCAP) groups. Spearman analyses were used to explore correlations between imaging parameters in brain regions and clinical assessments. Receiver operating characteristic (ROC) was used to distinguish mHTT carriers from control, and define the HD patients at advanced stage. Results: Compared to controls, mHTT carriers exhibited WM changes in DKI and DTI. There were 22 more regions showing significant differences in HD detected by MK than FA. Only MK in five brain regions showed significantly difference between any two group, and negatively correlated with the disease burden (r = -0.80 to -0.71). ROC analysis revealed that MK was more sensitive and FA was more specific, while Youden index showed that the integration of FA and MK gave rise to higher authenticities, in distinguishing m& lCAP from controls (Youden Index = 0.786), and discerning different phase of HD (Youden Index = 0.804). Conclusions: Microstructural changes in WM occur at early stage of HD and deteriorate over the disease progression. Integrating DKI and DTI would provide the best accuracies for differentiating early HD from control and identifying advanced HD.

Independent and reproducible hippocampal radiomics biomarkers for multisite multiple sclerosis and neuromyelitis optica spectrum disorders.

OBJECTIVE: To investigate the abnormal radiomics features of the hippocampus in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and to explore the clinical implications of these features. METHODS: 752 participants were recruited in this retrospective multicenter study (7 centers), which included 236 MS, 236 NMOSD, and 280 normal controls (NC). Radiomics features of each side of the hippocampus were extracted, including intensity, shape, texture, and wavelet features (N = 431). To identify the variations in these features, two-sample t-tests were performed between the NMOSD vs. NC, MS vs. NC, and NMOSD vs. MS groups at each site. The statistical results from each site were then integrated through meta-analysis. To investigate the clinical significance of the hippocampal radiomics features, we conducted further analysis to examine the correlations between these features and clinical measures such as Expanded Disability Status Scale (EDSS), Brief Visuospatial Memory Test (BVMT), California Verbal Learning Test (CVLT), and Paced Auditory Serial Addition Task (PASAT). RESULTS: Compared with NC, patients with MS exhibited significant differences in 78 radiomics features (P < 0.05/862), with the majority of these being texture features. Patients with NMOSD showed significant differences in 137 radiomics features (P < 0.05/862), most of which were intensity features. The difference between MS and NMOSD patients was observed in 47 radiomics features (P < 0.05/862), mainly texture features. In patients with MS and NMOSD, the most significant features related to the EDSS were intensity and textural features, and the most significant features related to the PASAT were intensity features. Meanwhile, both disease groups observed a weak correlation between radiomics data and BVMT. CONCLUSION: Variations in the microstructure of the hippocampus can be detected through radiomics, offering a new approach to investigating the abnormal pattern of the hippocampus in MS and NMOSD.

Clinical, pathological, and radiological features of 80 pediatric diffuse intrinsic pontine gliomas: A single-institute study.

Objective: Diffuse intrinsic pontine gliomas (DIPGs) are rare but devastating diseases. This retrospective cross-sectional study aimed to investigate the clinical, radiological, and pathological features of DIPGs. Materials and methods: The clinical data of 80 pediatric DIPGs under clinical treatment in Beijing Tiantan Hospital from July 2013 to July 2019 were retrospectively collected and studied. A follow-up evaluation was performed. Results: This study included 48 men and 32 women. The most common symptoms were cranial nerve palsy (50.0%, 40/80 patients) and limb weakness (41.2%, 33/80 patients). Among the 80 patients, 24 cases were clinically diagnosed, 56 cases were pathologically verified, and 45 cases were tested for H3K27 alteration status, with 34 H3K27 alteration cases confirmed. Radiological results indicated that enhancement was common (65.0%, 52/80 patients). Cho/Cr was of predictive value for H3K27 alteration status (P = 0.012, cutoff value = 2.38, AUC = 0.801). Open cranial surgery followed by further chemotherapy and radiotherapy was beneficial for patients' overall survival. Cox regression analysis indicated H3K27 alteration to be the independent prognostic influencing factor for DIPGs in this series (P = 0.002). Conclusion: DIPGs displayed a wide spectrum of clinical and imaging features. Surgery-suitable patients could benefit from postoperative comprehensive therapy for a better overall survival. H3K27 alteration was the independent prognostic influencing factor for DIPGs.

Higher Grade Glioma Increases the Risk of Postoperative Delirium: Deficient Brain Compensation Might Be a Potential Mechanism of Postoperative Delirium.

Objective: The 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. Methods: A 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. Results: The 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. Conclusions: Our findings suggested that insufficient compensation for injured brain regions involving cognition might be more vulnerable to suffering from POD.

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.

Clinical outcome of autologous peripheral blood stem cell transplantation in opticospinal and conventional forms of secondary progressive multiple sclerosis in a Chinese population.

To evaluate clinical outcomes of autologous peripheral blood stem cell transplantation (APBCST) between opticospinal multiple sclerosis (OSMS) and conventional multiple sclerosis (CMS) during disease progressive stage in a Chinese population. Thirty-six secondary progressive MS patients, among whom 21 were with OSMS and 15 with CMS, underwent APBSCT and were followed up for an average of 48.92 months (range, 10-91 months). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. Modified BEAM conditioning regimen (Tiniposide, melphalan, carmustin, and cytosine arabinoside) were administered. Outcomes were evaluated using the expanded disability status scale (EDSS). No maintenance treatment was administered if there was no disease progression. No treatment-related mortality occurred. Among the 36 patients, one OSMS patient dropped during the follow-up. Among the 22 relapse-free patients, 20 were with continuous neurological improvement without any relapse events, and two remained in neurologically stable states. Among the 13 relapse patients, seven had experienced of neurological relapse, but with no progression during the follow-up period; and six experienced neurological deterioration after transplantation and needed further immunosuppressant treatment. The confirmed relapse-free survival rate was 62.9% and progression-free survival rate was 83.3% after 91 months according to Kaplan and Meier survival curves. Eleven of the 20 OSMS patients (55%) and two of the 15 CMS patients (13.3%) stayed in disease active group (P = 0.014). For the 20 OSMS patients, the overall EDSS score decreased significantly after transplantation (P = 0.016), while visual functions had no significant improvement (P = 0.716). Progressive OSMS has a higher relapse rate than CMS following APBSCT.

[The clinical and magnetic resonance imaging studies of brain damages in neuromyelitis optica].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Clinical features and brain structural changes in magnetic resonance imaging in Alzheimer's disease patients with apathy.

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). The frequency of Apolipoprotein E genotypes was not significantly different (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<0.05). 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).

Antiplatelet Effect of a Pulaimab [Anti-GPIIb/IIIa F(ab)2 Injection] Evaluated by a Population Pharmacokinetic-pharmacodynamic Model.

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.

Clinical, Structural, and Neuropathological Features of Olfactory Dysfunction in Patients with Alzheimer's Disease.

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.

[Effect of ligustrazine, synthetic borneol on lasting time of ciliary movement].

OBJECTIVE: To study the using of the method in vitro and in vivo of lasting time of ciliary movement in ligustrazine, synthetic borneol. METHODS: (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. RESULTS: 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%. CONCLUSION: 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.

Clinical Features of Patients with Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) was long believed to be an aggressive form of multiple sclerosis (MS). This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. METHODS: Data including the patients' serum and cerebrospinal fluid (CSF) tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein (MOG) autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody (AQP4-Ab). The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was performed to analyze the continuous variables. RESULTS: Totally 85 MS patients (49%) and 90 NMOSD patients (51%) were enrolled, including 124 (71%) women and 51 (29%) men. Fewer MS patients (6%) had autoimmune diseases compared to NMOSD (19%) (Δ2 = 6.9, P < 0.01). Patients with NMOSD had higher Expanded Disability Status Scale scores (3.5 [3]) than MS group (2 [2]) (Z = -3.69, P < 0.01). The CSF levels of white cell count and protein in both two groups were slightly elevated than the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients (MS: 0, NMOSD: 67%; Δ2 = 63.9, P < 0.01). Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS (MS: 59%, NMOSD: 20%; Δ2 = 25.7, P < 0.01). No significant difference of MOG autoantibodies was found between the two groups. CONCLUSION: The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

Bioavailability and pharmacokinetics of sorafenib suspension, nanoparticles and nanomatrix for oral administration to rat.

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.