Differences in the uptake and translocation of differentially charged microplastics by the taproot and lateral root of mangroves.

The interception of microplastics (MPs) by mangrove roots plays an indispensable role in reducing the environmental risks of MPs. However, there remains limited research on the fate of the intercepted MPs. Hereby, the uptake and subsequent translocation of 0.2 µm and 2 µm PS MPs with different coating charge by the typical salt-secreting mangrove plants (Aegiceras corniculatum) were investigated. Compared to amino-functionalized PS with positive charge (PS-NH2), the visualized results indicated that the efficient uptake of carboxy-functionalized PS with negative charge (PS-COOH) was more dependent on taproots. But for the lateral roots, it only allowed the entry of PS-NH2 instead of PS-COOH. The specific uptake pathways of PS-NH2 on the lateral roots could attribute to the release of H+ and organic acids by root hairs, as well as the relative higher Zeta potential. After entering the Aegiceras corniculatum roots, the translocation of PS MPs was restricted by their particle sizes. Furthermore, the release of PS MPs from Aegiceras corniculatum leaf surfaces through the salt glands and stomata was observed. And the decline in the photochemical efficiency of leaves under PS MPs exposure also indirectly proved the foliar emission of PS MPs. Our study improved the understanding of the environmental behaviors and risks of the retained MPs in mangroves.

Case report: Successful treatment with contezolid in a patient with tuberculous meningitis who was intolerant to linezolid.

Tuberculous meningitis (TBM) is the most common form of central nervous system tuberculosis (TB) and the most severe form of extrapulmonary TB. It often presents with non-specific symptoms initially and has a high mortality and disability rate. With good central nervous system penetration, linezolid is recommended for treating drug-resistant, severe, or refractory tuberculous meningitis in China. Despite the benefits of linezolid on TBM treatment, the adverse effects of long-term therapy, such as myelosuppression, peripheral neuritis, and optic neuritis, are notable and can be severe and even life-threatening, leading to discontinuation and compromising treatment expectations. Contezolid is a novel oxazolidinone antibacterial agent approved by the National Medical Products Administration of China in 2021, which has a more favorable safety profile than linezolid in terms of myelosuppression and monoamine oxidase inhibition. Here we first report a case of TBM in a patient who was intolerant to antituberculosis treatment with linezolid and achieved good efficacy and safety results after the compassionate use of contezolid. Given the widespread use of linezolid in TB treatment and the potential risks for long-term use, multi-center prospective controlled clinical trials in TB and TBM patients are needed to investigate the appropriate use of contezolid further.

Self-Adhesive Self-Healing Thermochromic Ionogels for Smart Windows with Excellent Environmental and Mechanical Stability, Solar Modulation, and Antifogging Capabilities.

Current thermochromic materials used in smart windows still face challenges, such as poor mechanical and environmental stability, unsatisfactory solar modulation capacity, and low transparency. Herein, the first self-adhesive self-healing thermochromic ionogels with excellent mechanical and environmental stability, antifogging capability, transparency, and solar modulation capability by loading binary ionic liquids (ILs) into rational-designed self-healing poly(urethaneurea) with acylsemicarbazide (ASCZ) moieties that have reversible and multiple hydrogen bonds are reported and their feasibility as smart windows with reliability and long service life is demonstrated. The self-healing thermochromic ionogels can switch between transparent and opaque without leakage or shrinkage, by the constrained reversible phase separation of ILs within the ionogels. The ionogels have the highest transparency and solar modulation capability among reported thermochromic materials and such excellent solar modulation capability can be well maintained after undergoing 1000 transitions, stretches, and bends, and storage at -30 °C, 60 °C, 90% RH, and vacuum environment for 2 months. The formation of high-density hydrogen bonds among the ASCZ moieties contributes to the excellent mechanical strength of the ionogels and allows the thermochromic ionogels to spontaneously heal their damages and be fully recycled at room temperature without the loss of thermochromic capabilities.

Takotsubo syndrome triggered by change in position in a patient with thoracic vertebral fracture: A case report.

RATIONALE: Takotsubo syndrome (TTS) is characterized by recovery of wall motion abnormalities and acute left ventricular dysfunction, which are often caused by acute physical or emotional stressors. It is rarely reported that TTS can be precipitated by change in position in the patient in the operating room. We report a case of a patient with a thoracic vertebral fracture who presented with TTS precipitated by changing from a supine to a prone position before percutaneous kyphoplasty (PKP) under local anesthesia. PATIENT CONCERNS: A 76-year-old man who was diagnosed with a fracture in a thoracic vertebra was sent to the operating room to undergo PKP under local anesthesia. Approximately 5 minutes after changing from a supine to a prone position, which is necessary for PKP, the patient experienced chest pain, headache, and sweating. DIAGNOSIS: A fracture in a thoracic vertebra; TTS. INTERVENTIONS: As a result of 12-lead electrocardiography, echocardiography, left ventriculogram, and cardiac catheterization, the diagnosis of TTS was retained, and supportive therapy was initiated. OUTCOMES: Two hours later, the patient's symptoms mitigated significantly and the ST segment returned to baseline. Four days later, echocardiography showed normal systolic function without wall motion abnormalities and the patient returned to the orthopedics ward for further treatment. LESSONS: It is necessary for anesthetists to recognize TTS which is life-threatening during monitored anesthetic care (MAC). We highlight the importance of being alerted to the possibility of TTS when managing patients with thoracic vertebral fractures undergoing surgery under local anesthesia.

Prognostic value of magnetic resonance imaging performed during the subacute phase in adult patients with hypoxic-ischemic encephalopathy for long-term neurological outcomes.

OBJECTIVE: To investigate the value of a model based on brain magnetic resonance imaging (MRI) performed in the subacute phase (between the 1st and 30th day) in predicting long-term neurological outcomes of adult hypoxic-ischemic encephalopathy (HIE) patients. METHODS: Ninety-six adult HIE patients who underwent conventional MRI and diffusion-weighted imaging (DWI) during the subacute phase were retrospectively analyzed. Favorable (Cerebral Performance Categories (CPC) 1-2) and unfavorable outcome (CPC 3-5) groups were created based on patient neurological status approximately three months after the onset of hypoxic-ischemic events. A multivariate stepwise regression model was applied after univariate analysis of MRI findings, and then the overall MRI score, Alberta Stroke Program Early Computed Tomography Score (ASPECTS), Bilateral ASPECTS (Bi-ASPECTS), modified ASPECTS (mASPECTS) and Bi-ASPECTS combined with posterior circulation ASPECTS (PC-ASPECTS) were calculated based on MRI findings. Receiver operating characteristic (ROC) curves were used to assess prognostic accuracy. RESULTS: Both univariate and multivariate analyses showed the cerebral cortex and cerebellum, neostriatum, hippocampus, brainstem and postanoxic leukoencephalopathy were independent prognostic factors for unfavorable outcomes. The multivariate regression analysis resulted in an overall classification accuracy of 84.4%, a sensitivity of 84.2% (95% CI, 71.6-92.1%), and a specificity of 92.3% (95% CI, 78.0-98.0%) for unfavorable outcomes. The model had an areas under the ROC curves (AUC) of 0.944 (95% CI, 0.901-0.987); the MRI overall scores were 0.918 (95% CI, 0.866, 0.971), ASPECTS 0.839 (95% CI, 0.755, 0.923), Bi-ASPECTS 0.837 (95% CI, 0.753, 0.922), mASPECTS 0.851(95% CI, 0.771, 0.931) and Bi-ASPECTS+PC-ASPECTS 0.876 (95% CI, 0.806, 0.946). CONCLUSIONS: The multivariate model based on conventional MRI combined with DWI performed in the subacute phase could help predict the prognosis of adult HIE with high performance.

A sensitive and rapid "off-on" fluorescent probe for the detection of esterase and its application in evaluating cell status and discrimination of living cells and dead cells.

The discrimination of living and dead cells shows great importance in the development of biology, pathology, medicine, and pharmacology research. Herein, we synthesized a simple benzothiazole-based probe, EP, which was characterized via1H NMR (hydrogen nuclear magnetic resonance) spectroscopy, 13C NMR (carbon nuclear magnetic resonance) spectroscopy and HRMS (high-resolution mass spectroscopy). The fluorescence changes in response to esterase were characterized via fluorescence spectroscopy. EP exhibited a 70-fold fluorescence enhancement in the presence of esterase and possessed a very low limit of detection (4.73 × 10-5 U mL-1). EP also showed high selectivity to esterase compared to other biological species. Bright fluorescence appeared in living cells, which was activated by esterase when incubated with EP. In paraformaldehyde or H2O2 pretreated cells, the fluorescence became very weak since esterase became inactive in these cells. In summary, the EP probe can monitor esterase activity both in vitro and in living cells and can be used to evaluate the health status of cells and discriminate living and dead cells effectively.

[Magnetic resonance imaging features of glioma with Brg/Brm associated factor 53a expression].

OBJECTIVE: To explore the magnetic resonance imaging (MRI) characteristics of glioma with Brg/Brm-associated factor 53a (BAF53a) expression.
 Methods: A total of 121 patients with glioma was divided into a BAF53a high expression group (n=79) and a low expression group (n=42) according to the results of immunohistochemistry. Then the MRI characteristics, including lesion location, number, boundary, maximum diameter, peripheral edema, midline structure shift, homogeneity, cystic necrosis, hemorrhage, strengthening degree, ependymal strengthening, pia mater enhancement, deep white matter invasion and lesion across the midline (total 14 items), were analyzed.
 Results: The results showed that there were significance difference in lesion border, lesion edema, enhancement of the lesion, and deep white matter invasion between the 2 groups (all P<0.05).
 Conclusion: The MRI characteristics, such as lesion border, lesion edema degree, enhancement degree of the lesion and deep white matter invasion, might be associated with BAF53a expression in gliomas.

Durable, Highly Electrically Conductive Cotton Fabrics with Healable Superamphiphobicity.

Electrically conductive fabrics with liquid repellency and corrosive resistance are strongly desirable for wearable displays, biomedical sensors, and so forth. In the present work, highly electrically conductive and healable superamphiphobic cotton fabrics are fabricated by a solution-dipping method that involves (NH4)2PdCl4-catalyzed electroless deposition of Cu and the subsequent deposition of a mixture of fluorinated-decyl polyhedral oligomeric silsesquioxane (F-POSS) and 1 H,1 H,2 H,2 H-perfluorooctyltriethoxysilane (POTS) on cotton fabrics. Because of their superamphiphobicity, the resulting fabrics are self-cleaning and exhibit excellent resistance against corrosive acidic and basic solutions. The as-prepared fabrics have a sheet resistance of ∼0.33 Ω·sq-1 and show excellent electromagnetic interference shielding and electrothermal heating ability. Because of the preserved F-POSS and POTS molecules, the fabrics can conveniently and repeatedly restore the loss of superamphiphobicity by applying a low voltage of 1.0 V or heating the fabrics at 135 °C to facilitate the migration of the preserved F-POSS and POTS to the surface of cotton fabrics. The integration of healable superamphiphobicity into the Cu-coated fabrics generates multiple functional cotton fabrics with excellent conductivity, electromagnetic interference shielding, self-cleaning ability, and significantly enhanced durability.

Resting-state fMRI in primary Sjögren syndrome.

Background The involvement of the central nervous system in primary Sjögren syndrome (pSS) remains controversial. Functional magnetic resonance imaging (fMRI) is a relatively new method that can be applied to investigate the heterogeneity of central nervous system (CNS) involvement in pSS patients through regional homogeneity (ReHo) analysis. Purpose To collect data from pSS patients and healthy controls, and use ReHo analysis to elucidate the neurobiological mechanism of CNS involvement in pSS. Material and Methods Fourteen clinically diagnosed pSS patients and 14 age- and gender-matched healthy controls underwent resting-state fMRI. The data were processed by ReHo analysis. The double sample t-test was used to compare ReHo data between groups. Results Compared to controls, pSS patients had significantly increased ReHo values in the right cerebrum, left limbic lobe, right middle temporal gyrus, and the inferior parietal lobe. However, ReHo values significantly decreased in the right lingual gyrus, left cuneiform lobe, left superior occipital gyrus, bilateral middle occipital gyrus, and the fronto-parietal junction area ( P < 0.01, clusters ≥ 50 voxels). Conclusion This study demonstrates the abnormal brain activity in the visual cortex and fronto-parietal junction area in pSS patients, suggesting pathological neuronal dysfunction in these regions.

[Value of 1H-MRS on SCA3/MJD diagnosis and clinical course].

OBJECTIVE: To investigate the value of proton magnetic resonance spectroscopy (1H-MRS) on the diagnosis of SCA3/MJD, and to calculate the correlation between 1H-MRS ratio and the clinical score.
 Methods: Sixteen patients with SCA3/MJD and 19 healthy volunteers were scanned with 1H-MRS. The data of N-acetyl aspartate, creatine, choline-containing compounds, myoinositol, NAA/Cr, Cho/Cr, and mI/Cr ratio were collected, which were grouped for comparative study. The onset patients with SCA3/MJD were evaluated with the International Cooperative Ataxia Rating Scale and Scale for the Assessment and Rating of Ataxia, the correlation between NAA/Cr, Cho/Cr or mI/Cr ratio and the clinical score was calculated.
 Results: The NAA/Cr in the pons and cerebellar dentate nucleus from the onset patients with SCA3/MJD was significantly reduced compared to that in the normal control group. The NAA/Cr in the cerebellar dentate nucleus of onset patients with SCA3/MJD was obviously correlated with ICARS.
 Conclusion: SCA3/MJD lesions are mainly located in the cerebellum and brainstem, where gray and white mater are also involved. The cerebellar dentate nucleus may be the earliest involved area. There is a correlation between the ICARS and the cerebellar lesion degree. The ICARS reflects the severity of clinical manifestations. 1H-MRS is useful in the diagnosis of SCA3/MJD.

Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.

NS1619 regulates the expression of caveolin-1 protein in a time-dependent manner via ROS/PI3K/PKB/FoxO1 signaling pathway in brain tumor microvascular endothelial cells.

NS1619, a calcium-activated potassium channel (Kca channel) activator, can selectively and time-dependently accelerate the formation of transport vesicles in both the brain tumor capillary endothelium and tumor cells within 15min of treatment and then increase the permeability of the blood-brain tumor barrier (BTB). However, the mechanism involved is still under investigation. Using a rat brain glioma (C6) model, the expression of caveolin-1, FoxO1 and p-FoxO1 protein were examined at different time points after intracarotid infusion of NS1619 at a dose of 30µg/kg/min. Internalization of Cholera toxin subunit (CTB) labeled fluorescently was monitored by flow cytometry. The expression of caveolin-1 and FoxO1 protein at tumor microvessels was enhanced and caveolae-mediated CTB endocytosis was increased by NS1619 infusion for 15min. Compared with the 15min group, the expression of caveolin-1 protein was significantly decreased and the level of phosphorylation of FoxO1 was significantly increased in the NS1619 2h group. In addition, inhibitors of reactive oxygen species (ROS) or PI3K or PKB significantly attenuated the level of FoxO1 phosphorylation and also increased the expression of caveolin-1 protein in Human Brain Microvascular Endothelial Cells (HBMECs) cocultured with human glioma cells (U87) 2h after NS1619 treatment. This led to the conclusion that NS1619-mediated transport vesicle increase is, at least partly, related to the ROS/PI3K/PKB/FoxO1 signaling pathway.

Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.

Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon-telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.

Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis.

Recently, traditional Chinese medicine has gained attention for its potential use as a chemotherapeutic agent. Pseudolaric acid B (PAB) is a diterpene acid isolated from Pseudolarix kaempferi and possesses antifungal, antimicrobial, antifertility and antiangiogenic properties. It was also reported that PAB may inhibit proliferation and induce apoptosis in various types of cancer. However, its effects on A549 lung cancer cells remain to be determined. The present study aimed to determine the potential roles of PAB in the proliferation and apoptosis of A549 cells. The results showed that PAB inhibited A549 cell proliferation in a time­ and dose­dependent manner. Fluorescence microscopy results showed that cells treated with 20 µmol/l PAB for 24 h exhibited karyorrhexis and apoptotic body formation. In addition, A549 cells were treated with 5, 10, 20, 40 or 80 µmol/l PAB for 24 h and apoptosis was analyzed using Annexin­V/propidium iodide kit. The apoptosis rates were 8.95, 18.71, 24.66, 35.02 and 43.64%, respectively, in PAB­treated cells and 0.80% in the control group. Furthermore, western blot analysis showed that PAB treatment upregulated the protein levels of Bax, Bad and downregulated Bcl­2 and Bcl­xl expression. In conclusion, PAB may serve as a potent chemotherapeutic agent against human lung cancer.

Injectable nimodipine-loaded nanoliposomes: preparation, lyophilization and characteristics.

The main purpose of this study was to prepare nimodipine-loaded nanoliposomes for injection and evaluate their characteristics after lyophilization. Nimodipine-loaded nanoliposomes were prepared by the emulsion-ultrasonic method with sodium cholesterol sulfate (SCS) as the regulator and then lyophilized by adding different cryoprotectants. SCS was used as a blender of regulator and surfactant and helped to prepare smaller liposomes due to the steric hindrance of the sulfate group. The results showed that nimodipine-loaded nanoliposomes with a 20:1 of egg yolk lecithin PL-100M vs. SCS ratio had a particle size of 86.8±42.007 nm, a zeta potential of -13.94 mV and an entrapment efficiency (EE) of 94.34% and could be stored for 12 days at 25°C. Because of the good bulking effect of mannitol and the preservative effect of trehalose, they were used to obtain suitable lyophilized nanoliposomes. The lyophiles containing 10% mannitol and 20% trehalose had a good appearance and a slightly altered particle size after rehydration. In addition, the lyophilized products were characterized by differential scanning calorimetry, X-ray diffraction and scanning electron microscopy, which confirmed the morphous state of trehalose, mannitol and the mixture. Trehalose could inhibit mannitol crystallization to some extent. The drug release from nanoliposomes before and after lyophilization in pH 7.4 phosphate buffer containing 30% ethanol was also examined and both profiles were found to fit the Viswanathan equation. This means that the drug release was controlled by the pore diffusion resistance.

Ultrasound-assisted extraction of phillyrin from Forsythia suspensa.

Forsythia suspensa (Thunb.) Vahl is one of the most widely used traditional Chinese medicines, and possesses important biological activities, such as antibacterial, antiviral, anti-inflammatory and antioxidant activities. Phillyrin is the main bioactive component of Forsythia suspensa. In this paper, ultrasound-assisted extraction of phillyrin from Forsythia suspensa was studied with HPLC-photodiode array detection. Effects of several experimental parameters, such as type and concentration of extracting solvent, ratio of liquid to material, extraction temperature, and time of sonication on extraction efficiencies of phillyrin from Forsythia suspensa were evaluated. The optimal extraction conditions were 1g plant sample with 10 ml of 20% methanol and the extraction for 60 min at 60°C under ultrasonic irradiation. Under the optimum conditions, the yield of phillyrin was 0.713±0.009 mg/g. The results indicated that the ultrasound-assisted extraction is a very useful method for the extraction of important phytochemicals from plant materials.

Comparative study of the stability of venlafaxine hydrochloride sustained-release pellets prepared by double-polymer coatings and hot-melt subcoating combined with Eudragit(®) NE30D outercoating.

The aim of this paper was to study the comparative stability of venlafaxine hydrochloride (VEN) sustained-release pellets prepared by double-polymer coatings and hot-melt subcoating combined Eudragit(®) NE30D outercoating. The uncoated VEN pellets, containing 45% (w/w) VEN, 45% (w/w) MCC (PH101), 10% (w/w) stearic acid and 0.5% (w/w) Carbopol974, were prepared by extrusion-spheronization. Satisfactory release profiles were obtained when VEN pellets were prepared by 4% EC subcoating combined with 4% Eudragit(®) NE30D outercoating and 8% hot-melt subcoating combined with 6% Eudragit(®) NE30D outercoating, respectively. The storage stability was monitored by measuring the drug release over six months storage at 40°C/75% RH and at room temperature (25 ± 2°C/60% RH). The release of pellets with double-polymer coatings increased markedly, while drug release of pellets prepared by hot-melt subcoating combined with polymer coating gradually decreased. Basically, the former may be attributed to the main role of drug migration into the EC subcoating, and the latter may be caused by the fusion and resolidification of stearic acid particles and the further aging of the Eudragit(®) NE30D outercoating. In summary, regardless of the change in release, drug dissolution met the standard requirement and the stability was acceptable during the storage period.

Isosorbide-5-mononitrate (5-ISMN) sustained-release pellets prepared by double layer coating for reducing 5-ISMN migration and sublimation.

The major aim of this study was to prepare isosorbide-5-mononitrate (5-ISMN) sustained-release pellets and evaluate their stability. The pellets were prepared by extrusion/spheronization, and then the core pellets were coated with ethylcellulose (EC 10cp) and Eudragit(®)NE30D. Here, EC was used as the subcoating agent while Eudragit(®)NE30D acted as the outer-coating agent. 5-ISMN sustained-release pellets as a novel drug delivery system contained the immediate-release portion in the outer-coating layer. Unexpectedly, 5-ISMN was found to migrate from the interior of the pellets to the surface forming needle crystals and exhibited the phenomenon of sublimation, which resulted in a tremendous increase in the release rate. Our research showed that the migration and sublimation of the active ingredient was related to the temperature and humidity. Polyvinylpyrrolidone (PVP K30) can affect the precipitation of 5-ISMN by forming a charge transfer complex between the drug and PVP, while hydroxypropyl methyl cellulose (HPMC E5) had no effect, and confirmed the correctness of this view through photographs and IR spectra. In the investigation of the stability, the results showed that there was no sublimation and migration while the pellets stored at 25°C/60%RH (ambient conditions) and 40°C/75% RH (stress conditions) during a 6-month period.

Preparation and evaluation of nicotinic acid sustained-release pellets combined with immediate release simvastatin.

This study was performed to prepare high-dose nicotinic acid (NA) loaded sustained-release pellets coated with double polymer and simvastatin (SIM). The uncoated pellets were prepared by extrusion-spheronization and the double ethylcellucose (EC) films were coated in a bottom-spray fluidized bed coater. SIM was milled by wet grinding and then the milled suspension was layered on the coated pellets. Results showed that coated with 1.5% subcoating and 1% outer coating composed of EC and polyvinyl pyrrolidone K30 (PVP(K30)) in ratios of 5:1 and 2:1, NA release behavior was very similar to the reference (NER/S; SIMCOR, Abbott) in different media. And SIM was delivered more rapidly than that of the reference, while the SIM layer had no influence on NA release. During 6-month storage at 40°C/75% RH, the two drugs exhibited stable dissolution behavior. It was observed that the content uniformity of SIM was provided by the present preparation and SIM was stable if adding light magnesium oxide in the grinding procedure. Results indicated it was possible to prepare high-dose sustained-release NA pellets combined with little-dose immediate release SIM by spraying double EC polymer and SIM milled suspension on NA pellets in a bottom-spray fluidized bed coater, respectively.

A new rapid ultra-performance liquid chromatography method for the pharmacokinetic and bioavailability study of diclofenac sodium aqueous injection and lipid microsphere injection in rats.

A novel, rapid and selective ultra performance liquid chromatography mass spectrometric method had been developed for the pharmacokinetic study of diclofenac sodium (DS) after single intravenous injection of DS aqueous injection and DS lipid microsphere (LM) injection in rats. Ketoprofen (KP) was used as internal standard. Samples were treated by a one-step liquid liquid extraction. Separation was performed on an Acquity UPLC BEH C(18) column (50 x 2.1 mm i.d., 1.7 mum). The mobile phase consisted of acetonitrile-0.1% ammonium hydroxide aqueous solution (20 : 80, v/v) initially in the gradient mode. The detection was carried out by means of electrospray ionization mass spectrometry in negative ion mode with multiple-reaction monitoring mode. Standard curves showed good linearity (r > 0.99) from the plasma concentration of 0.1-50 microg/mL. The lower limit of quantification was 0.1 microg/mL. The intra- and inter-day precisions and the accuracy all satisfied the acceptance criteria. The developed method was validated and successfully applied to the pharmacokinetics study of DS aqueous injection and LM injection. The results showed that the two preparations were bioequivalent in rats.