1.Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study.
Wei QIU ; De-Hui HUANG ; Shi-Fang HOU ; Mei-Ni ZHANG ; Tao JIN ; Hui-Qing DONG ; Hua PENG ; Chao-Dong ZHANG ; Gang ZHAO ; Yi-Ning HUANG ; Dong ZHOU ; Wei-Ping WU ; Bao-Jun WANG ; Ji-Mei LI ; Xing-Hu ZHANG ; Yan CHENG ; Hai-Feng LI ; Ling LI ; Chuan-Zhen LU ; Xu ZHANG ; Bi-Tao BU ; Wan-Li DONG ; Dong-Sheng FAN ; Xue-Qiang HU ; Xian-Hao XU ; TOWER Trial Chinese Group
Chinese Medical Journal 2018;131(23):2776-2784
Background:
Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.
Methods:
TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).
Results:
Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.
Conclusions:
Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.
Trial Registration
ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.
China
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Crotonates
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administration & dosage
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adverse effects
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therapeutic use
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Double-Blind Method
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Drug Administration Schedule
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Humans
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Immunosuppressive Agents
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administration & dosage
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adverse effects
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therapeutic use
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Multicenter Studies as Topic
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Multiple Sclerosis
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drug therapy
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metabolism
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Proportional Hazards Models
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Toluidines
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administration & dosage
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adverse effects
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therapeutic use
2.The therapeutic effect between metal augment and impacted bone grafting in the hip revision of acetabular bone defect
Zhan-Jie CHEN ; Lei ZHANG ; Chang-Nian DING ; Li-Wu ZHOU ; Ting GUO ; Ni-Rong BAO ; Bei-Yue WANG ; Jian-Ning ZHAO
Journal of Medical Postgraduates 2018;31(4):373-376
Objective The application of metal augments in the revision of total hip arthroplasty(THA)has achieved re-markable results in the treatment of bone defects.However,there are limited studies compared this effective method with the traditional treatment.The purpose of this article is to investigate the curative effect of both metal augmentation and impacted bone grafting in the revision of acetabular bone defect. Methods We retrospectively analyzed 20 patients(20 hips)with bone defects after THA in Au-thority of Nanjing General Hospital of Nanjing Military Region from August 2010 to February 2017.These 20 patients were allocated into 2 groups:impacted bone grafting group(n=11,filling acetabular bone defect with autogenous iliac bone and artificial bone)and metal aug-mentation group(n=9,filling acetabular bone defect with metal aug-ment).The duration of surgery,blood loss and the hospital for special surgery knee score(HSS)were compared between these two groups and the Harris score was applied to evaluate the hip function and full weight bearing. Results The surgery duration and blood loss of impacted bone grafting group were significantly increased when compared with the metal augmentation group(44.5±7.82 min vs 36.22±5.19 min and 431.82±57.76 mL vs 333.33±72.80 mL respec-tively).there were 3 cases showed mild bone resorption in the I regions in the impacted bone grafting group, while only one case showed mild bone resorption in the II region in the metal augmentation group.The HSS scores in the metal augmentation group were higher than those in the impacted bone grafting group at the time of postoperative 2 weeks(43.89±2.76 vs 40.82±4.42), 3 months (49.89±2.03 vs 45.27±3.90)and 6 months(53.44±2.46 vs 50.55±3.67), the differences were statistically significant(P<0.001). The Harris scores in the metal augmentation group were higher than those in the impacted bone grafting group(P<0.01).The metal augmentation group had a shorter time of getting out of bed compared with the impacted bone grafting group(P<0.01). Conclusion For those patients with upper acetabular bone defect,revision surgery using metal augments can save the operation time.Meanwhile, it is also superior to the impacted bone grafting in the early prosthesis stability and bone ingrowth,and thus enables to shorten the time on getting out of bed and promote functional.
3.Impact of the Action Time of Inducers on Differentiation of 3T3-L1 Cells.
Xin-nong LIU ; Xiu LIU ; Tian-jia LI ; Zhan-qi WANG ; Leng NI ; Bao LIU ; Chang-wei LIU
Acta Academiae Medicinae Sinicae 2016;38(3):271-274
Objective To explore the effect of the action time of inducers on the differentiation of 3T3-L1 cells to adipocytes. Methods According to the "Cocktail" method,3T3-L1 cells were divided into three groups according to the action time of inducers,with the action time being 2,3 or 4 days,respectively. Cell morphology was observed using inverted microscope and adipose content were detected by Oil red "O" staining and detection of triglyceride. The cell viability was identified by trypan blue staining method. Results The proportion of samples (n=12) with differentiation rate above 80% in group A was 66% (12/18),while the differentiation rate of all the samples (n=18)in group B and group C were above 80%. For the Oil red "O",the OD value at 510 nm in group C was 2.59±0.17,which was significantly higher than that in group A (2.12±0.47;F=6.62,P=0.0001)and group B (2.20±0.17;F=5.15,P=0.0001),while no significant difference was found between group A and group B (F=1.14,P=0.74). As for the triglyceride,the value in group C was (1351.04±119.01)ng/ml,which was significantly higher than that in group A[ (1077.88±272.75)ng/ml;F=6.73,P=0.001] and group B [(1089.38±115.39)ng/ml;F=5.78,P=0.001],while no difference was found between group A and group B (F=0.27,P=0.64). The cell viability in group A,B,and C was (98.3±1.2)%,(98.5±1.8)%,and (98.9±2.1)%,respectively,showing no significant difference (F=0.18,P=0.83). Conclusions The modified procedure for the differentiation of 3T3-L1 cells to adipocytes can increase the differentiation rate and thus may be applied for establishing adipocyte models. The recommended action time is three days.
3T3-L1 Cells
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Adipocytes
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cytology
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drug effects
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Animals
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Cell Culture Techniques
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Cell Differentiation
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drug effects
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Mice
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Time Factors
4.Chemical profiling of Qixue Shuangbu Tincture by ultra-performance liquid chromatography with electrospray ionization quadrupole-time-of-flight high-definition mass spectrometry (UPLC-QTOF/MS).
Lin-Wei CHEN ; Qin WANG ; Kun-Ming QIN ; Xiao-Li WANG ; Bin WANG ; Dan-Ni CHEN ; Bao-Chang CAI ; Ting CAI
Chinese Journal of Natural Medicines (English Ed.) 2016;14(2):141-146
The present study was designed to develop and validate a sensitive and reliable ultra high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) method to separate and identify the chemical constituents of Qixue Shuangbu Tincture (QXSBT), a classic traditional Chinese medicine (TCM) prescription. Under the optimized UPLC and QTOF/MS conditions, 56 components in QXSBT, including chalcones, triterpenoids, protopanaxatriol, flavones and flavanones were identified and tentatively characterized within a running time of 42 min. The components were identified by comparing the retention times, accurate mass, and mass spectrometric fragmentation characteristic ions, and matching empirical molecular formula with that of the published compounds. In conclusion, the established UPLC-QTOF/MS method was reliable for a rapid identification of complicated components in the TCM prescriptions.
Chromatography, High Pressure Liquid
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methods
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Drugs, Chinese Herbal
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chemistry
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Spectrometry, Mass, Electrospray Ionization
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methods
5.Comparison of the characteristics of the medical humanities education between Chinese and American medical colleges and its enlightenment
Fang TIAN ; Xiaowei NI ; Ziming ZHOU ; Hong BAO ; Shixin CHANG
Chinese Journal of Medical Education Research 2015;14(4):337-341
American medical colleges attach great importance to the humanistic education.The rich humanities curriculum is fully integrated into the teaching practice thus the mutual penetration of medicine and the humanities is achieved.They have specific and detailed examination evaluation system and the teaching method was more practical and participatory.By contrast,nost of the medical colleges in our country neglect the humanities construction and the cultivation of medical students' humanistic spirit.The coverage of the humanities curriculum is relatively narrow and the faculty is insufficient.We should promote the development of humanistic cducation,attach importance to the construction of medical humanities,set up appropriate curriculum system,increase the investment in faculty and reform the teaching method and examination method.
6.Prediction of Cerebral Hyperperfusion Syndrome with Velocity Blood Pressure Index.
Zhi-Chao LAI ; Bao LIU ; Yu CHEN ; Leng NI ; Chang-Wei LIU
Chinese Medical Journal 2015;128(12):1611-1617
BACKGROUNDCerebral hyperperfusion syndrome is an important complication of carotid endarterectomy (CEA). An >100% increase in middle cerebral artery velocity (MCAV) after CEA is used to predict the cerebral hyperperfusion syndrome (CHS) development, but the accuracy is limited. The increase in blood pressure (BP) after surgery is a risk factor of CHS, but no study uses it to predict CHS. This study was to create a more precise parameter for prediction of CHS by combined the increase of MCAV and BP after CEA.
METHODSSystolic MCAV measured by transcranial Doppler and systematic BP were recorded preoperatively; 30 min postoperatively. The new parameter velocity BP index (VBI) was calculated from the postoperative increase ratios of MCAV and BP. The prediction powers of VBI and the increase ratio of MCAV (velocity ratio [VR]) were compared for predicting CHS occurrence.
RESULTSTotally, 6/185 cases suffered CHS. The best-fit cut-off point of 2.0 for VBI was identified, which had 83.3% sensitivity, 98.3% specificity, 62.5% positive predictive value and 99.4% negative predictive value for CHS development. This result is significantly better than VR (33.3%, 97.2%, 28.6% and 97.8%). The area under the curve (AUC) of receiver operating characteristic: AUC(VBI) = 0.981, 95% confidence interval [CI] 0.949-0.995; AUC(VR) = 0.935, 95% CI 0.890-0.966, P = 0.02.
CONCLUSIONSThe new parameter VBI can more accurately predict patients at risk of CHS after CEA. This observation needs to be validated by larger studies.
Aged ; Blood Pressure ; physiology ; Cerebrovascular Circulation ; physiology ; Cerebrovascular Disorders ; physiopathology ; Endarterectomy, Carotid ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Prospective Studies
7.Research advances in endotension after endovascular abdominal aneurysm repair.
Gen-huan YANG ; Bao LIU ; Rong ZENG ; Leng NI ; Chang-wei LIU
Acta Academiae Medicinae Sinicae 2014;36(5):556-559
When more abdominal aortic aneurysms are repaired by endovascular approaches, the post-operative endotension without endoleak increase along with the extended follow-up. An early detection of such endotension and a proper differentiation from endoleaks are particularly important for the treatment decision-making. This article reviews the mechanism, diagnosis, and management of endotension.
Aortic Aneurysm, Abdominal
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surgery
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Blood Vessel Prosthesis Implantation
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Humans
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Postoperative Complications
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Stents
8.Expressions of p-c-jun and cyclinD1 between vascular smooth muscle cells and endothelial cells exposured to cigarette smoke extract.
Tian-jia LI ; Chang-wei LIU ; Ze-bin HUANG ; Leng NI ; Zhi-chao LAI ; Li-fei WU ; Bao LIU
Acta Academiae Medicinae Sinicae 2013;35(2):185-189
OBJECTIVETo investigate the cell viabilities of vascular smooth muscle cells and vascular endothelial cells stimulated by cigarette smoke extract(CSE) .
METHODSThe CSE was prepared by smoke-bubbled phosphate buffered saline(PBS) generation.After culturing cells with different concentrations of CSE, we used the cell counting kit-8 to determine the cell viability.The expression levels of c-jun and cyclinD1 were analyzed through Western blot.The c-jun plasmid was transfected to detect the change of cyclinD1 expression.
RESULTSThe smooth muscle cell viability increased when the CSE concentration ranged 0.625%-10%, whereas the endothelial cells viability decreased when exposed to the CSE concentration. After exposure to CSE for 48 hours, there was no difference in c-jun expression between toxin group and PBS group;however, the expression of p-c-jun in the smooth muscle cells significantly increased in the toxin groups than in the PBS group(P<0.05) and the expression of p-c-jun in the vascular endothelial cells significantly decreased(P<0.05) . The level of cyclinD1 significantly increased after exposed to CSE, and its expression level also increased in respond to the c-jun overexpression.
CONCLUSIONCSE can enhance the proliferation of vascular smooth muscle cells and decrease in the activity of endothelial cells proliferation, which may be explained by the phosphorylation of c-jun and the expression of cyclinD1.
Cell Proliferation ; drug effects ; Cell Survival ; Cells, Cultured ; Cyclin D1 ; metabolism ; Endothelial Cells ; drug effects ; metabolism ; Humans ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Proto-Oncogene Proteins c-jun ; metabolism ; Tobacco ; adverse effects
9.Risk analysis for cerebral hyperperfusion syndrome after carotid endarterectomy.
Leng NI ; Chang-Wei LIU ; Li-Ying CUI ; Bao LIU ; Wei YE ; Shan GAO ; Ying-Huan HU ; Zhi-Chao LAI
Chinese Journal of Surgery 2013;51(9):800-803
OBJECTIVETo analyze risk factors for cerebral hyperperfusion syndrome (CHS) after carotid endarterectomy (CEA).
METHODSFrom September 2010 to September 2012, 183 consecutive patients with carotid artery stenosis who had indications for CEA entered the study. There were 149 male and 34 female patients, aged from 38 to 83 years with an average of (66 ± 9) years. Intracranial blood flow changes were monitored through transcranial Doppler routinely. Pre- and post-operative middle cerebral artery velocity (VMCA) were recorded. CHS was diagnosed by the combination of hyperperfusion syndrome and 100% increase of VMCA after operation compared with pre-operative baseline values. The patients who had CHS during hospitalization were recorded. Pre-operative and operative related factors were analyzed by univariate analysis, followed by Logistic regression model, to identify the risk factors of CHS.
RESULTSOverall, CHS occurred in 15 patients (8.2%) after CEA. The average onset time was (2.6 ± 0.2) days after surgery. By decreasing blood pressure and using dehydration medicine, all the patients with CHS recovered before discharge. None of them developed to intracranial hemorrhage. On univariate analysis, significant risk factors for CHS were history of stoke, symptomatic carotid artery stenosis and shunting during operation. On Logistic regression model, independent risk factor was symptomatic carotid artery stenosis (OR = 6.733, 95%CI: 1.455-31.155, P = 0.015), while shunting during operation (OR = 0.252, 95%CI: 0.067-0.945, P = 0.041) was a protective factor.
CONCLUSIONSSymptomatic carotid artery stenosis is an independent risk factor for CHS after CEA and shunting during operation is a protective factor. Using shunt may be an effective method of preventing CHS after CEA.
Carotid Stenosis ; surgery ; Endarterectomy, Carotid ; Humans ; Middle Cerebral Artery ; Risk Assessment ; Risk Factors
10.New method to predict cerebral hyperperfusion syndrome after carotid endarterectomy by transcranial Doppler.
Bao LIU ; Zhi-Chao LAI ; Leng NI ; Yong-Jun LI ; Yue-Hong ZHENG ; Wei-Wei WU ; Wei YE ; Rong ZENG ; Yu CHEN ; Jiang SHAO ; Chang-Wei LIU
Chinese Journal of Surgery 2013;51(6):504-507
OBJECTIVETo determine the diagnostic value for predicting cerebral hyperperfusion syndrome (CHS) by adding a transcranial Doppler (TCD) measurement at the end of the carotid endarterectomy (CEA) at the operating room.
METHODSPatients who underwent CEA between August 2009 and December 2011 of the prospective clinical trial in whom both intra- and post-operative TCD monitoring were performed were included. The middle cerebral artery velocities pre-clamping, post-declamping and post-operatively were measured by TCD. The intra-operative velocity increase ratio (VR1) was compared to the postoperative velocity increase ratio(VR2) in relation to CHS by calculating the sensitivity,specificity, positive predictive value, negative predictive value. The receiver operating characteristic curve (ROC) were also performed. The area under the curve (AUC) of ROC of VR1 and VR2 were compared.All the data were analyzed using SPSS 20.0 software.
RESULTSVR1 > 100% was identified in 6 patients, while VR2 > 100% was identified in 18 patients, respectively. Ten patients were diagnosed with CHS. The AUC of VR2 (0.728) was higher than AUC of VR1 (0.636). The best fit cutoff point of VR2 was 100%. The sensitivity, specificity, positive predictive value, negative predictive value were 70%, 83%, 39%, 95%, respectively, which demonstrates a better predictive power than VR1.
CONCLUSIONBesides the commonly used intra-operative TCD monitoring, additional TCD measurement at the end of the carotid endarterectomy at the operating room is more useful to more accurately predict CHS.
Adult ; Aged ; Aged, 80 and over ; Cerebrovascular Circulation ; Endarterectomy, Carotid ; Female ; Humans ; Intraoperative Complications ; diagnostic imaging ; Male ; Middle Aged ; Middle Cerebral Artery ; ultrastructure ; Monitoring, Intraoperative ; Predictive Value of Tests ; Prospective Studies ; Sensitivity and Specificity ; Ultrasonography, Doppler, Transcranial

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