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

Objective:To analyze the external root resorption of incisors caused by maxillary canine impaction, and to explore the changes of incisor external root resorption after orthodontic treatment.Methods:Twenty-four patients with impacted maxillary canines leading to external root resorption of incisors treated in Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University from July 2011 to January 2019 were selected. The age ranged from 10 to 14 years [(12.3±1.6) years], including 11 males and 14 females. The maxillary incisors with external root resorption before treatment were included in the resorption group (21 central incisors and 22 lateral incisors), and the maxillary incisors without external root resorption were used as the control group (26 central incisors and 21 lateral incisors). Cone-beam CT was taken before treatment, immediately after treatment and one year after treatment. At the one year follow-up 15 patients were collected (10 central incisors and 12 lateral incisors in the resorption group, while 16 central incisors and 12 lateral incisors in the control group). The root length and tooth volume of maxillary incisors were measured and analyzed before canine traction, after canine traction finished and at the one year follow-up.Results:After the treatment of maxillary impacted canines, the root length and volume of the central and lateral incisors in both resorption group and control group were significantly less than that before treatment ( P<0.05). At the one year follow-up, the root length and volume of the incisors (central incisors in the resorption group and the central and lateral incisors in control group) were significantly less than those immediately after impacted canine traction ( P<0.05). During the canine traction, the difference of the volume change in lateral incisors between the resorption group [(17±6) mm 3] and the control group [(12±5) mm 3] was statistically significant ( t=2.51, P<0.05). During the one year follow-up period, the difference between the changes of the root length in maxillary central incisors in the resorption group [(0.5±0.4) mm] and in the control group [(0.2±0.1) mm] was statistically significant ( t=2.35, P<0.05). Conclusions:For maxillary incisors with external root resorption caused by impacted maxillary canines, the external root resorption could not stop immediately after the treatment of impacted canines. The root resorption in maxillary lateral incisors mainly occured during the traction process, while the root resorption in maxillary central incisors existed during the orthodontic treatment and in the follow-up period.

The causes of stroke in young people are diverse, most of which are cardiogenic. However, cerebral embolism caused by cardiac myxoma is rare. Intravenous thrombolysis is given in the time window, and the therapeutic effect depends on the nature of embolus. This case is a young female patient, with acute onset, excluding bleeding on the basis of the symptoms, signs and craniocerebral CT. After diagnosed as acute ischemic stroke, the patient was performed an immediate intravenous thrombolysis, though the curative effect was poor. Excluding contraindications six hours after onset, bridging mechanical thrombectomy was performed, postoperative embolus biopsy indicating myxoma. Atrial myxoma was removed in cardiac surgery two months later, and the pathology indicated atrial myxoma. The patient recovered well during the out-of-hospital follow-up, and no further embolization occurred. Therefore, it is suggested that bridging mechanical thrombectomy may be safe and effective for acute ischemic stroke caused by atrial myxoma when intravenous thrombolysis is ineffective, and myxoma resection should be performed immediately after the disease is stable.

Objective: To explore the clinical study of different frequency repetitive transcranial magnetic stimulation in the treatment of senile schizophrenia. Methods: The 70 elderly schizophrenics admitted to Kangning Hospital Affiliated to Wenzhou Medical University from February 2018 to August 2019 were randomly divided into observation group (35 cases) and control group (35 cases). High frequency repetitive transcranial magnetic stimulation was used in the observation group and low frequency repetitive transcranial magnetic stimulation was used in the control group. Both groups were treated for 4 weeks. The changes of clinical global impression (CGI), positive and negative syndrome scale (PANSS), cognitive function rating scale for schizophrenia (SCoRS), scale of social-skills for psychiatric inpatients(SSPI) and serum sex hormone levels before and after treatment were compared between the two groups. Results: After treatment, the CGI and PANSS scores of the two groups were lower than those before treatment [observation group:(2.43 ± 0.37) scores vs. (5.61 ± 0.58) scores, (35.73 ± 6.57) scores vs. (79.95 ± 8.98) scores, t=27.346 and 23.512; control group: (3.37 ± 0.48) scores vs. (5.49 ± 0.62) scores, (40.91 ± 8.17) scores vs. (78.64 ± 9.63) scores, t=15.996 and 17.675, P<0.05]; after treatment, the CGI and PANSS scores of the observation group were lower than those of the control group (t=9.176, 2.923, P<0.05). After treatment, the SCoRS scores of the two groups was lower than those before treatment (observation group: t=12.822, control group: t=7.402, P<0.05); after treatment, the SCoRS score of the observation group was lower than that of the control group [(27.92 ± 5.41) scores vs. (34.25 ± 6.17) scores] (t=4.564, P<0.05). The SSPI scores of the two groups increased after treatment (observation group: t=9.252; control group: t=3.671, P<0.05); after treatment, the SSPI scores of the observation group were higher than those of the control group [(35.74 ± 3.27) scores vs. (30.85 ± 2.28) scores](t=7.257, P<0.05). After treatment, the serum testosterone and prolactin levels in the two groups were higher than those before treatment (observation group: t=13.853, 15.198; control group: t=10.075 and 9.225, P<0.05); after treatment, the serum testosterone and prolactin levels in the observation group were higher than those in the control group (t=5.693 and 7.202, P<0.05). Conclusions High frequency repetitive transcranial magnetic stimulation is superior to low frequency repetitive transcranial magnetic stimulation in the treatment of senile schizophrenia, and the improvement of sex hormone level is superior to low frequency repetitive transcranial magnetic stimulation, and the improvement of cognitive and social functions is superior to low frequency repetitive transcranial magnetic stimulation.

Objective: To explore the internal mechanism of short-term mindfulness intervention in reducing individual anxiety and stress perception. Methods: Totally 134 subjects were recruited and randomized into attention group (n=53), acceptance group (n=41) and control group (n=40). Attention group received observation of breathing intervention program, acceptance group received acceptance of negative emotions intervention program and the control group did not intervene mindfulness and read the social science materials of history. Before and after intervention, cancelled tasks were used to stimulate anxiety and stress perception, and self-rating anxiety scale and Chinese perceived stress scale (CPSS) were used to measure anxiety and stress perception level, and the results of cancelled tasks were recorded. Variance analysis and multiple linear regression were used for data statistics. Results: The changes of anxiety in attention group and acceptance group((-1.44±2.42)and(-1.06±2.58)) were significantly higher than that in control group(0.08±2.56)(both P<0.01). On the basis of controlling the changes of gender, age, number of cancellations and pre-test anxiety, the differences between groups had no significantly predictive effect on pre-cancellative anxiety(P>0.05). The attention group had significant predictive effect on anxiety in post-projected cancellative task compared with the control group (t=-2.84, P<0.01), while the acceptance group had no significant predictive effect on anxiety in post-projected cancellative task compared with the control group(P>0.05). Conclusion Attention and acceptance play different roles in short-term mindfulness training. Attention factor in mindfulness plays a key role in reducing anxiety level in individual tasks.

Objective To investigate the effects of inhibiting miR-29 on growth,invasion and metastasis of pancreatic cancer PANC1 cells,and explore the potential mechanism.Methods Oligonucleotides inhibiting miR-29 (anti miR-29) and control oligonucleotides (miR NC) were used to transfect PANC1 cells to establish anti miR-29 PANC1 cells and miR NC PANC1 cells.Transient transfection of PUMA siRNA,E-cadherin siRNA or NC siRNA was used to construct cotransfected anti miR29 + PUMA-siRNA-PANC1 cells and anti-miR-29 + E-cadherin-siRNA-PANC1 cells.Number of colony formations was observed,cell survival was detected by MTT,cell apoptosis was measured by flow cytometry,cell invasion was detected by transwell chamber assay,and cell migration was detected by wound healing assay.Subcutaneous injection of anti miR-29 PANC1 cells was used to establish xenograft nude mice model,and venous injection of anti miR-29 PANC1 cells was used to establish lung metastasis nude mice model,and the subcutaneous and venous injection of PANC1 cells served as control.The growth of xenograft and the number of lung metastatic nodules were observed.TUNEL method was used to detect cell apoptosis in xenograft and immunohistochemical analysis was used to detect PUMA and E-cadherin in xenograft.Results The survival rate of PANC1,miR-NC-PANC1 and anti-miR-29-PANC1 cells was 100％,(96.8 ± 2.8) ％ and (24.4 ± 3.2) ％.The number of colony formation was (213 ± 36),(196 ± 28) and (37 ± 6) per 100 high power field.The number of transmembrane cells was (56.3 ± 9.6),(49.8-± 7.3) and (11.2 ± 3.4) per 400 high power field.The distance of cell migration was (260 ± 48),(247 ± 46) and (53 ± 7) μm.Cell apoptosis rate was (1.5 +0.9) ％,(2.6 + 0.9) ％ and (22.4 + 2.8) ％.There was statistically significant difference between anti miR 29 PANC1 cells and other PANC1 cells (P ＜0.05).The survival rate,apoptosis rate,transmembrane cells and migration distance of anti-miR-29 + PUMA-siRNA-PANC1 cells was (84.7 ± 10.9) ％,(1.3 ± 0.8) ％,(49.7 ± 6.4) per 400 high power field and (182 ± 36) μm,indicating that the effects of miR 29 inhibition on PANC1 cells were abolished (all P ＜0.05).The volume of the xenograft of PANC1 and anti-miR-29-PANC1 cells was (3 800 ±270) and (1 890 ± 160)mm3,the cell apoptosis rate was 0.93 ±0.14 and 8.26 ± 1.15,the number of metastatic lung lesions was (26.4 ± 6.5) and (8.6 ± 2.7),the PUMA positivity was (7.2 ±1.6) ％ and (43.8 ± 7.6) ％,E-cadherin positivity was (8.3 ± 3.6) ％ and (47.4 ± 5.7) ％,respectively.The xenograft volume and the number of metastatic lung nodules of anti miR29 PANC1 cells was obviously decreased or decreased,but cell apoptosis rate,PUMA positivity and E cadherin positivity were obviously increased,and the differences were all statistically significant (P ＜ 0.05).Conclusions Inhibiting miR-29 expression can decrease cell proliferation,migration and metastasis of PANC1 cells,and the potential mechanism may be associated with the upregulation of PUMA and E-cadherin.

Aim To investigate the effects of high glu-cose on cholesterol metabolism in renal tubular cells and the intervention of the anthocyanins. Methods HK-2 cells were grown in the DMEM medium supple-mented with 10% FBS and were divided into 5 groups:normal glucose group, high glucose group, mannitol group, C3G group and Cy group. Effect of anthocya-nins on cell viability was detected with MTT, and cho-lesterol accumulation was detected with Amplex Red Cholesterol Assay kit and Filipin staining. Expression of ABCA1 was detected with RT-qPCR and Western Blot. Results In compared with control groups, HG significantly promoted cholesterol mass inside the cell and decreased the cholesterol concentration in the me-dium after treatment for 24 h or 48 h. The levels of mRNA and protein of ABCA1 were detected with RT-qPCR and Western blot, and both were decreased in the presence of HG. Whereas treatment with C3G and Cy markedly attenuated HG-induced cholesterol mass inside the cell by up-regulating the expression of AB-CA1. Conclusions High glucose can reduce the ex-pressions of the ABCA1, and then decrease cholesterol efflux and increase the cholesterol accumulation in HK-2 cells. Anthocyanins can decrease cholesterol accu-mulation by up-regulating the expression of ABCA1.

Objective To identify the arteriographic manifestations of emergency uterine artery angiography and the efficacy of embolization treatment of postcesarean massive hemorrhage caused by placenta previa.Methods Emergency uterine artery angiogra-phy was performed in 35 patients with massive hemorrhage after cesarean section due to placenta previa.Emergency uterine arterial embolization (EUAE)was conducted using embolic agents such as tricacryl gelatin microsphere (TAGM)and gelatin sponge.Arte-riographic manifestations and effect of the emolotherapy were analyzed retrospectively.Results Contrast extravasations were con-firmed in 27 patients,and uterine artery pseudoaneurysms were in 8.The hemorrhage completely stopped after embolotherapy in all patients.A 12 month follow-up showed no recurrence hemorrhage and any severe complications were observed in all patients,such as necrosis of the uterus and ovary.Conclusion EUAE can be used as a safe,effective and minimally invasive therapeutic option for postcesarean massive hemorrhage caused by placenta previa.It is the key for the success of embolotherapy to choice and use reasona-ble embolic agents.

AIM:To explore the change of antithrombin Ⅲ( AT-Ⅲ) in the patients with atherosclerotic cere-bral infarction .METHODS:Chromogenic substrate assay was used to measure the activity of AT-Ⅲ in 55 patients with atherosclerotic cerebral infarction and 55 healthy controls , and the correlation analysis was applied to determine the AT-Ⅲactivity with the severity of damage in central nervous system and general biochemical parameters .The levels of TNF-αand IL-6 in the plasma were detected by ELISA .Immunocomplex in the plasma was measured by enzyme immunoassay (EIA). The number and phenotype of the monocytes in peripheral blood were analyzed by flow cytometry .ELISA was also applied to determine the secretion of TNF-αand IL-6 from the monocytes after the stimulation of immunocomplex .The expression of AT-Ⅲin human brain vascular endothelial cells after the stimulation of TNF-αand IL-6 was observed by Western blotting . RESULTS:The activity of AT-Ⅲsignificantly decreased in the patients with atherosclerotic cerebral infarction , and nega-tively correlated with the damage degree of nervous system function , systolic pressure , diastolic pressure , glucose , choles-terol, triglyceride, low-density lipoprotein cholesterol and homocysteine , while positively correlated with high-density lipo-protein.In addition, the plasma levels of TNF-αand IL-6 increased significantly , accompanied with the enhancement of immunocomplex level .The numbers of CD14 + CD16 + and CD14 + CD32 + monocytes in peripheral blood were not changed , while CD14 +CD64 +monocytes increased obviously .The secretion of TNF-αand IL-6 by monocytes were signifi-cantly enhanced after stimulated with immunocomplex , while the protein expression of AT-Ⅲ in the human brain vascular endothelial cells was down-regulated after co-incubated with TNF-αor IL-6.CONCLUSION:Decreased AT-Ⅲactivity in the patients with atherosclerotic cerebral infarction is one of the risk factors of cerebral infarction , and related with the dis-ease severity .The production of pro-inflammatory cytokines through immunocomplex from CD 14 +CD64 +monocytes may be involved in the mechanism .Improvement of AT-Ⅲactivity may protect against cerebral ischemia .

Objective To investigate correlations between nursing students’discrimination on psychopaths and exposure to them.Method One hundred and twenty-one nursing students were involved in the investigation by a general information questionnaire,a discrimination against mental patients scale(DAMPS)and an exposure to mental patients scale(FLS).Results The total mean score on discrimination,scores on isolation dimension and scores on capability were all significantly lower than the norms(all P<0.01).Negative correlation was observed between nursing students’discrimination against patients and exposure to patients(r=-0.31,P<0.05). Conclusion Measures should be taken to encourage nurses to understand patients so as to alleviate their discrimination.