BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

AIM:To explore the synergistic sensitization effect of human umbilical cord mesenchymal stem cell culture supernatant(hUMSC-CM)combined with temozolomide(TMZ)on various glioma cell lines,and to elucidate the underlying mechanisms.METHODS:The hUMSC-CM was harvested using two different serum deprivation tech-niques at 24 and 48 h,and was converted into freeze-dried powder,which was then given to rat malignant glioma cell line RG-2,human astrocytoma cell line U251 and human glioblastoma cell line LN-428 at 5 concentrations(0,1,3,6 and 9 g/L).The effectiveness and sensitivity of hUMSC-CM for inhibiting growth of glioma cells at 24,48 and 72 h were as-sessed using CCK-8 assay.Hematoxylin-eosin(HE)staining combined with CCK-8 assay was employed to evaluate the chemotherapy sensitivity of glioma cells after 48 h of treatment with TMZ at 6 concentrations(0,25,50,100,200 and 400 μmol/L).Two concentrations(3 and 9 g/L)of hUMSC-CM and 3 concentrations(50,100 and 200 μmol/L)of TMZ were chosen for concurrent treatment of glioma cells to assess the proliferation and pathological alterations.TUNEL staining was utilized to detect apoptosis.Flow cytometry was utilized to analyze cell cycle modifications.The expression alterations of apoptosis-inducing proteins,cleaved caspase-3,cleaved caspase-8 and cleaved PARP1,as well as autophagy-inducing proteins beclin-1 and LC3,were examined using Western blot to investigate the synergistic sensitization mechanism of hUMSC-CM combined with TMZ in vitro.RESULTS:The susceptibility of glioma cell lines to hUMSC-CM and TMZ varied,with RG-2 showing the highest sensitivity,followed by U251,and then LN-428.The inhibitory effect of hUMSC-CM(3 and 9 g/L)and TMZ(50,100 and 200 μmol/L)combined treatment on glioma cells was significantly greater than that that of single-agent treatments(P＜0.05),demonstrating a dose-and concentration-dependent enhancement.Notably,the combination of 9 g/L hUMSC-CM(C9)with 50 μmol/L TMZ(T50)effectively suppressed glioma cell growth.CCK-8 as-say indicated a significant reduction of cell viability in C9+T50 group compared with either C9 or T50 alone(P＜0.05).HE staining and TUNEL staining revealed pronounced morphological changes and significant apoptotic features in glioma cells treated with C9+T50.Flow cytometric analysis confirmed that C9+T50 induced cell cycle arrest in glioma cells.Fur-thermore,compared with control group,the levels of cleaved caspase-3,cleaved caspase-8,cleaved PARP1,beclin-1,and LC3-Ⅱ/LC3-Ⅰ were significantly elevated in the C9+T50-treated glioma cells(P＜0.01).CONCLUSION:(1)The concomitant administration of hUMSC-CM and TMZ exerts a broad inhibitory effect on glioma cells,with a synergistic sen-sitization observed across different cell lines.(2)The enhancement of glioma cell sensitivity to TMZ by hUMSC-CM may be attributed to the modulation of caspase-8/caspase-3/PARP1 signaling pathway and the induction of both apoptosis and autophagy in glioma cells.

To develop a framework for clinical teaching management (CTM) position competencies, and to initiate the preliminary application of this framework.

Polycyclic aromatic hydrocarbons (PAHs) are a class of common environmental pollutants that pose threats to human health. In this study, a mesophilic bacterial strain CFP312 (grown at 15-37 °C, optimal at 30 °C) was isolated from PAHs-contaminated soil samples. It was identified as Moraxella sp. by morphological observation, physiological and biochemical test, and 16S rRNA gene phylogeny analysis. This is the first reported PAHs degrading strains in Moraxella. Degradation analysis showed that 84% and 90% of the loaded phenanthrene (400 mg/L) were degraded within 48 h and 60 h, and the degradation rates reached 1.21 and 1.29 mg/(L·h), respectively. During the degradation of phenanthrene, phenanthrene-3,4-dihydrodiol was detected as an intermediate. Based on this, it was proposed that double oxygenation at the positions 3 and 4 of phenanthrene was the first step of biodegradation. Adaptability of strain CFP312 to different enhanced phenanthrene-degradation systems was tested in aqueous-organic system, micellar aqueous system, and cloud point system. Strain CFP312 showed good adaptability to different systems. In addition, the bacterium can rapidly degrade the phenanthrene in contaminated soil in slurry-aqueous system, indicating great potential in environmental remediation.
Biodegradation, Environmental ; Humans ; Phenanthrenes ; Polycyclic Aromatic Hydrocarbons ; RNA, Ribosomal, 16S/genetics* ; Soil Microbiology ; Soil Pollutants

Objective:To explore the value of multi-parametric MRI for thyroid gland in differentiating benign and malignant thyroid nodules.Methods:From December 2018 to May 2020, 78 patients with 91 post-surgically pathologically confirmed thyroid nodules were enrolled in Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. For each patient, the following MRI findings were obtained including the nodules′ location, size, shape, margin, signal intensity, cystic change, degree and pattern of contrast enhancement, involvement of surrounding structure, and ADC values. The time-intensity curve (TIC) were plotted and subtyped based on dynamic contrast enhancement MRI. The MRI findings between the benign and malignant thyroid nodules were compared using Mann-Whitney U test, χ 2 test or Fisher exact test. Multiple logistic regression analysis was used to select independent predictive variables and build a combined model, and the ROC curve was used to evaluate the diagnostic performance of each MRI finding and the combined model. Results:Between the benign and malignant thyroid nodules, the significant differences were found in size, shape, margin, presence of cystic changes, T 1WI signal intensity, ADC value, enhancement homogeneity, TIC subtypes and presence of thyroid capsule involvement ( P<0.05). Multivariate logistic analysis showed that ill-defined margin (OR=77.61), no presence of cystic changes (OR=36.11) and difference between TIC subtypes (OR=83.41) were independent predictive variables, and the area under the ROC curve (AUC) was 0.879, 0.788, and 0.751, respectively. The AUC, sensitivity and specificity of the combined model were 0.977, 0.986, and 0.904, respectively. Conclusions:Thyroid multi-parametric MRI derived findings can be used for the differential diagnosis of benign and malignant nodules. Combined with the independent risk factors with ill-defined margin, no presence of cystic changes, TIC of type plateau or washout, the diagnostic model has a higher diagnostic efficiency.

Objective:To explore the teaching effect of high-fidelity simulation teaching in emergency and critical care nursing course.Methods:From March to June 2019, 56 four-year nursing undergraduates from Xiamen Medical College in 2016 were selected as research subjects by convenient sampling. The high-fidelity simulation teaching was carried out in the emergency and critical care nursing course. The Jeffries Simulation Design Scale (SDS) and open-group interviews were used to evaluate the learning effect.Results:Among 56 students, scores of simulation teaching confidence and satisfaction were (3.80±0.80) and (4.00±0.62) respectively. Group interviews showed that students directly applied the theoretical knowledge they had learned to work situations, and students enhanced their self-learning ability and reflected on operational errors in simulation so as to provoke thinking and enhance learning confidence and personal learning ability.Conclusions:The application of high-fidelity simulation teaching in emergency and critical care nursing course can improve the self-confidence, teamwork ability and comprehensive quality of nursing undergraduates, and increase teaching satisfaction, which is feasible.

Objective:To observe dynamic change of phosphorylated tau protein and non phosphorylated tau protein in axon and explore whether GSK3 in serum were related with phosphorylated tau protein in brain of EAE mice.Methods: Mice were randomly divided into six groups:EAE group of acute stage,EAE group of paralytic stage,EAE group of remission stage,control group of acute stage,control group of paralytic stage,control group of remission stage,each group had twelve mice.EAE model were constructed by MOG35-55 peptides in EAE group, the saline was used in control group.The nerve function scores and incidence were observed and compared.We observed degree of brain inflammation by HE staining and measured axons which contained two kinds of tau protein by immunohistochemistry.GSK3 in serum was tested to find correlation with phosphorylated tau protein in brain by ELISA method.Results:Nerve function scores in EAE group were higher than control group.The degree of inflammation damage was more serious in EAE group than control group,gradually enhancing with time.Phosphorylated tau protein in brain gradually increased before mice paralyzing(P<0.01),but it decreased when symptom relieved(P<0.01).GSK3 in serum were correlated with phosphorylated tau protein in brain(r=0.9326,P<0.01),linear regression equation:Y=2.950+0.418X.Conclusion:Phosphorylated tau protein in brain are correlated with axon damage and GSK3 in serum could indirectly reflect axon damage in brain.

Objective The researchers aimed to investigate the feasibility and efficiency of cultivating ICU talents in nursing profession of higher vocational college.Methods On the basis of the nursing profession in college,the ICU direction was established in the talent cultivation mode of higher vocational college in 2007,2008 and 2009.And the students majored in ICU specialty were cultivated by the joint effort of college and the affiliated hospitals,and cultivate more professional talents of narrower direction.The feedback of teaching,the rate of employment,and the comprehensive evaluation of the graduates' quality from employers were informed by using the self-developed questionnaire.Results The rate of passing Chinese Licensure Examination for Nurse and the rate of employment were 100 percent.The students were satisfied in studying in this specialty,the graduates majored in ICU specialty were employed by the tertiary hospitals,and much higher evaluation were given by the employers.Conclusions To establish the ICU specialty in nursing profession of higher vocational college has benefits for the professionalization and specialization of nursing,which builds a solid ground for cultivating specialized ICU nurses in the hospital.

To investigate the correlation between LCN 2 or CXCL10 and experimental autoimmune encephalomyelitis(EAE),and the effect of Fluoxetine in EAE mice.Methods: Mice were randomly divided into four groups: control group, EAE group, intervention group and fluoxetine group , each group included twenty mice.EAE model were constructed with MOG35-55 in the intervention group and fluoxetine group ,following ultraviolet (UV) (280-320 nm) irradiation.Mice in fluoxetine group were given fluoxetine (10 mg/kg) by daily gavage since immunized ,and the saline was used in the control group ,intervention group and EAE group in the same way and same time.The drug/saline was continuously administered from the immunization to the day mice were sacrificed.The mean attacked time ,the nerve function grades and the incidence were observed and compared.We observed brain pathological changes by HE staining and immunohistochemistry;CXCL10 were tested by ELISA method ,and compared among the four groups.Results:The mean attacked time ,the nerve function grades and the incidence in the fluoxetine group were lower than those in the intervention group and EAE group ,there were significant differences between two groups (P<0.05),in the intervention group were lower than those in the EAE group ,there were significant differences between two groups ( P<0.05 ).Fluoxetine treated EAE mice showed decreased degree of inflammatory infiltration;the mean rank of positive cells lower in the fluoxetine group than those in the EAE group,the differences were significant between two groups ( P<0.05 ).The expression of CXCL10 in the peripheral blood plasma of fluoxetine group were lower than those in the EAE group ,there were significant differences between two groups ( P<0.05 ).Levels of LCN2 expression were correlated with those of CXCL 10 in the EAE group.Conclusion: LCN2, CXCL10 are correlated with the pathogenesis of EAE.Fluoxetine could alleviate clinical symptoms of EAE and alleviate the morbidity of EAE.

Reversible cerebral vasoconstriction syndrome (RCVS) usually occurs during normal pregnancy or a few days after delivery. The gold standard of diagnosis is the reversibility of cerebral vascular constriction confirmed by digital subtraction angiography (DSA). In this article, we descried the clinical and imaging features of one RCVS case proved by repeating DSA, and discussed the probably pathophysiological mechanisms.