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Context: Cepharanthine (CPA) has been reported to possess a wide range of pharmacological activities.Objective: This study investigates the pharmacokinetic characteristics after oral or intravenous administration of CPA by using a sensitive and rapid LC–MS/MS method.Materials and methods: A sensitive and rapid LC–MS/MS method was developed for the determination of CPA in Sprague–Dawley rat plasma. Twelve rats were equally randomized into two groups, including the intravenous group (1 mg/kg) and the oral group (10 mg/kg). Blood samples (250 μL) were collected at designated time points and determined using this method. The pharmacokinetic parameters were calculated.Results: The calibration curve was linear within the range of 0.1–200 ng/mL (r = 0.999) with the lower limit of quantification at 0.1 ng/mL. After 1 mg/kg intravenous injection, the concentration of CPA reached a maximum of 153.17 ± 16.18 ng/mL and the t1/2 was 6.76 ± 1.21 h. After oral administration of 10 mg/kg of CPA, CPA was not readily absorbed and reached Cmax 46.89 ± 5.25 ng/mL at approximately 2.67 h. The t1/2 was 11.02 ± 1.32 h. The absolute bioavailability of CPA by oral route was 5.65 ± 0.35%, and the bioavailability was poor.Discussion and conclusions: The results indicate that the bioavailability of CPA was poor in rats, and further research should be conducted to investigate the reason for its poor bioavailability and address this problem.

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Background: This study aimed to examine the expression level and prognostic value of microRNA-29a (miR-29a) in human cholangiocarcinoma (CCA). Patients and Methods: The expression of miR-29a was measured in tissues collected from 125 CCA patients using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Survival analysis was carried out using the Kaplan-Meier method and log-rank test. The prognostic value of miR-29a was examined with Cox regression analysis. Results: The results of qRT-PCR demonstrated that miR-29a expression was significantly upregulated in CCA tissue samples compared with matched noncancerous samples. Overexpression of miR-29a was found to be correlated with lymph node metastasis, clinical stage, and differentiation of CCA. The Kaplan-Meier survival curves suggested that patients with high miR-29a levels had poor overall survival compared to those with low miR-29a expression. From the results of the Cox regression analysis, we considered increased miR-29a expression to be an independent prognostic factor for patients with CCA. Conclusion: Our study data demonstrated that upregulated miR-29a expression is associated with progression of CCA and might act as a prognostic biomarker in CCA patients.

Recent evidence has shown that demyelination occurs along with axonal degeneration in spinal cord injury (SCI) during the secondary injury phase. Oligodendrocyte precursor cells (OPC) are present in the lesions but fail to differentiate into mature oligodendrocytes and form new myelin. Given the limited recovery of neuronal functions after SCI in adults without effective treatment available so far, it remains unknown whether enhancing OPC differentiation and myelination could benefit the recovery of SCI. To show the significance of myelin regeneration after SCI, the injury was treated with clemastine in the rat model. Clemastine is an FDA-approved drug that is potent in promoting oligodendrocyte differentiation and myelination in vivo, for four weeks following SCI. Motor function was assessed using sloping boards and grid walking tests and scored according to the Basso, Beattie, and Bresnahan protocol. The myelin integrity and protein expression were evaluated using transmission electron microscopy and immunofluorescence, respectively. The results indicated that clemastine treatment preserves myelin integrity, decreases loss of axons and improves functional recovery in the rat SCI model. The presented data suggest that myelination-enhancing strategies may serve as a potential therapeutic approach for the functional recovery in SCI.

The study was supported by the Foundation of the Program of Technology of Education Committee of Chongqing (No. KJQN201800122) and the Program of Technology of Science and Technology Committee of Yuzhong District in Chongqing (No. 20180131) Background: Disruption of the blood-brain barrier (BBB) is a mechanism in the pathogenesis of traumatic brain injury. Basic fibroblast growth factor (bFGF) is expressed in angiogenesis, neurogenesis, and neuronal survival. This study aimed to investigate the role of bFGF in vitro in human brain microvascular endothelial cells (HBMECs) challenged by oxygen-glucose deprivation/reperfusion (OGD/R). Material/Methods: HBMECs were cultured in glucose-free medium and an environment with <0.5% oxygen in an anaerobic chamber. Immunocytochemistry, Western blot, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to measure the protein and mRNA expression levels of bFGF, tight junction, adherens junction, apoptotic proteins, and matrix metalloproteinases (MMPs). The effects of bFGF on the viability of HBMECs was evaluated using the cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated using the TUNEL assay, and endothelial permeability was quantified using a transwell migration assay with fluorescein isothiocyanate (FITC) conjugated with dextran. The effects of bFGF were evaluated following inhibition of fibroblast growth factor receptor 1 (FGFR1) with PD173074 and inhibition of ERK with PD98059. Results: Following OGD/R of HBMECs, bFGF significantly reduced cell permeability and apoptosis and significantly inhibited the down-regulation of the expressions of proteins associated with tight junctions, adherens junctions, apoptosis and matrix metalloproteinases (MMPs). The effects of bFGF were mediated by the activation of FGFR1 and ERK, as they were blocked by FGFR1 and ERK inhibitors. Conclusions: Permeability and apoptosis of HBMECs challenged by OGD/R were reduced by bFGF by activation of the FGFR1 and the ERK pathway.

ObjectiveMinimally invasive puncture and drainage (MIPD) of hematomas was the preferred option for appropriate patients with hypertensive intracerebral hemorrhage (HICH). The goal of our research was to introduce the MIPD surgery using mixed reality holographic navigation technology (MRHNT).MethodWe provided the complete workflow for hematoma puncture using MRHNT included three-dimensional model reconstruction by preoperative CT examination, puncture trajectory design, immersive presentation of model, and real environment and hematoma puncture using dual-plane navigation by wearing special equipment. We collected clinical data on eight patients with HICH who underwent MIPD using MRHNT from March 2021 to August 2021, including the hematoma evacuation rate, operation time, deviation in drainage tube target, postoperative complications, and 2-week postoperative GCS.ResultThe workflow for hematoma puncture using MRHNT were performed in all eight cases, in which the average hematoma evacuation rate was 47.36±9.16%, the average operation time was 82.14±15.74 min, and the average deviation of the drainage tube target was 5.76±0.80 mm. There was no delayed bleeding, acute ischemic stroke, intracranial infection, or epilepsy 2 weeks after surgery. The 2-week postoperative GCS was improved compared with the preoperative GCS.ConclusionThe research concluded it was feasible to perform the MIPD by MRHNT on patients with HICH. The risk of general anesthesia and highly professional holographic information processing restricted the promotion of the technology, it was necessary for technical innovation and the accumulation of more case experience and verification of its superiority.