Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective: To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital-cervical fusion system in single stage. Methods: Thirty-seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital, Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3±12.3) years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital-cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, clivus-canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired t-test. Results: The mean JOA score of the patients increased from 10.5 to 14.4 at the one-year follow-up(t=14.3, P=0.00). Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus-canal angle improved from (118.0±6.5) degrees preoperative to (143.7±5.0) degrees postoperative(t=6.2, P=0.00). Shrinkage of the syrinx was observed 1 week after surgery in 24 patients, and 6 months in 31 patients.Twenty-eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One-side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness, and relieved in 2 weeks.Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions The treatment of AAD associated with BI using Xuanwu occipital-cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.

Objective To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital?cervical fusion system in single stage. Methods Thirty?seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital,Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3 ± 12.3)years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital?cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI),the distance of odontoid tip above Chamberlain line,clivus?canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired t?test. Results The mean JOA score of the patients increased from 10.5 to 14.4 at the one?year follow?up(t=14.3,P=0.00).Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus?canal angle improved from (118.0±6.5)degrees preoperative to (143.7±5.0)degrees postoperative(t=6.2,P=0.00).Shrinkage of the syrinx was observed 1 week after surgery in 24 patients,and 6 months in 31 patients.Twenty?eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One?side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness,and relieved in 2 weeks.Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions The treatment of AAD associated with BI using Xuanwu occipital?cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.

Objective To examine the effect of posterior reduction in atlantoaxial dislocation (AAD) associated with basilar invagination(BI) using Xuanwu occipital?cervical fusion system in single stage. Methods Thirty?seven AAD accompanied with BI cases treated at Department of Neurosurgery, Xuanwu Hospital,Capital Medical Universiy and the Second Hospital of Hebei Medical University were retrospective analyzed. There were 15 males and 22 females with age of (42.3 ± 12.3)years (range: 18-69 years). All the cases had congenital osseous abnormalities, such as assimilation of atlas and abnormal cervical fusion. Anterior tissue was released through posterior route followed by cage implantation into facet joint and occipital?cervical fixation with cantilever technique. The clinical results were evaluated using Japanese Orthopedic Association scale(JOA) and the main radiological measurements including anterior atlantodental interval (ADI),the distance of odontoid tip above Chamberlain line,clivus?canal angle(CCA) and the length of syrinx were collected. The preoperative and postoperative JOA score and radiological measurements were compared by paired t?test. Results The mean JOA score of the patients increased from 10.5 to 14.4 at the one?year follow?up(t=14.3,P=0.00).Complete reduction of AAD and BI was achieved in 34 patients.The mean clivus?canal angle improved from (118.0±6.5)degrees preoperative to (143.7±5.0)degrees postoperative(t=6.2,P=0.00).Shrinkage of the syrinx was observed 1 week after surgery in 24 patients,and 6 months in 31 patients.Twenty?eight patients achieved bone fusion 6 months after surgery. All the patients achieved bone fusion 12 months after surgery. One?side vertebral artery occlusion was diagnosed in 1 case postoperatively for transient dizziness,and relieved in 2 weeks.Two patients developed moderate neck pain after surgery, and relieved in 1 month. No implant failure, spacer subsidence or infection was observed. Conclusions The treatment of AAD associated with BI using Xuanwu occipital?cervical fusion system from posterior approach in single stage is effective and safe. Cage implantation intraarticularly and fixation with cantilever technique achieve complete reduction in most cases.

Objective To investigate the effects of bone marrow mesenchymal stem cells (BMSC) on the expression of inflammatory factors in rats with multiple organ dysfunction syndrome (MODS). Methods BMSC extracted from the 4-week-old Sprague-Dawley (SD) rats was cultivated and identified in vitro, then the 4th passage of which was used in the experimental study. Sixty SD rats were randomly(random number) divided into three groups (n=20 in each group): Sham group (SG), MODS group (MG) and BMSC group (BG). Rats in the MG was injected by 1 mg/kg lipopolysaccaride (LPS) via great saphenous vein, rats in the SG injected with the same volume sterile phosphate buffer saline and rats in the BG infused by 1×106/cells BMSCs through the tail vein at 2 h after LPS injection. The survival rate, tissue pathological changes of the lung, liver and heart by hematoxylin and eosin (HE) staining, organ dysfunction measurement by blood gas analysis and biochemical indicators as well as the related inflammatory factors by protein microarray and enzyme linked immunosorbent assay (ELISA), were detected 72 h post operation. Multi-group quantitative data was analyzed by one way ANOVA, paired-comparisons by LSD-t test and the comparisons of survival curves in the three groups by Log-rank test. The value of P<0.05 was considered statistically significant. Results The survival rate in SG, MG and BG was 100％, 60％ and 80％, respectively. The survival curves showed that the survival rate of SG was higher than the MG and BG (SG vs. MG, χ2=9.798, P=0.0017; SG vs. BG, χ2=4.333, P=0.0374), but there was no significant difference comparing the BG to the MG (χ2=2.408, P=0.1207). The tissue congestion and edema, and inflammatory cells infiltration in the lung, liver, and heart of the MG were observed by HE staining, while these changes reduced in the BG. Compared with the SG, the levels of pH and PaCO2 and lactic acid (Lac) increased significantly (all P<0.01), the level of total bilirubin (TB) significantly increased [(0.801±0.501)U/L vs. (2.533±0.382)U/L, P=0.003], while the albumin(ALB) level decreased significantly[(35.471±4.015)U/L vs. (23.202±4.872)U/L, P<0.01], and creatine kinase (CK) level increased significantly in MG [(315.670±41.402) vs. (708.250±219.201), P=0.042]. After BMSC treatment, the organ function improved significantly (all P<0.05). Gamma interferon (IFN-γ) and monocyte chemotactic protein 1 (MCP-1) were the differential expression factors in protein chips. The results of ELISA were similar to the protein chips: compared with the SG, IFN-γ and MCP-1 expressions in the MG increased significantly (P<0.01). Compared with MG, the expressions of IFN-γ and MCP-1 decreased significantly in the BG (P<0.01). Conclusion BMSC administration could modulate the inflammatory response of MODS rats by inhibiting the levels of IFN-γ and MCP-1, and improve the organ function and the survival rate.

Objective To investigate the underlying mechanism of bone marrow mesenchymal stem cells (BMSC) modulating the inflammatory response during the multiple organ dysfunction syndrome (MODS), especially the expression of inflammatory cytokines, which will provide new theoretical and experimental basis of MODS in clinic. Methods BMSC of Sprague-Dawley (SD) rat (female, 4 weeks) was extracted and cultivated, and the 4th passage were used in experimental study. According to the random number table, 60 female SD rats were divided into three groups (n = 20 per group): sham group, MODS group, BMSC group. MODS model in rats was induced by lipopolysaccaride (LPS, 1 mg/kg) via femoral vein injection. Sham group was injected with the sterile phosphate buffer saline (PBS) in the same volume. BMSC group, in which BMSC infusion was started at 2 hours after 0.5 mL LPS stimulation (1×106/cells) through the tail vein. The survival rate was observed after 72 hours in each group. Abdominal aortic blood was collected for routine blood and biochemical examination at 72 hours after operation. Protein microarray was used to detect the related 34 inflammatory cytokines. Signal ratio was defined as the differentially expressed factors when it was more than 2.0 or less than 0.5. And enzyme linked immunosorbent assay (ELISA) was be applied to validate the significant inflammation factor. Meanwhile, the heart, kidney, intestine tissue was harvested, then their pathological changes were observed by hematoxylin eosin (HE) staining.Results 20, 12, 16 rats lived in sham group, MODS group and BMSC group respectively at 72 hours after operation. Compared with the sham group, the indicators (routine blood, liver and kidney function, myocardial enzyme) were apparently unusual, and the heart, kidney, intestine tissue were injured obviously in the MODS group. After BMSC administration, the organ function was improved and tissue damaged was alleviated significantly. Protein microarray showed that interleukin-4 (IL-4) and receptor for advanced glycation end products (RAGE) were significantly different in 34 goal cytokines. The signal ratio change of IL-4 was 0.397, 1.124, 2.826 respectively, and the signal ratio of RAGE was 6.197, 1.552, 0.250, respectively in MODS/sham group, BMSC/sham group, BMSC/MODS group. ELISA validated the result that the expression level of IL-4 decreased significantly (ng/L:3.59±1.21 vs. 29.10±5.78) and the expression level of RAGE increased significantly (ng/L: 1.09±0.04 vs. 0.11±0.03) in MODS group as compared with sham group (bothP < 0.05). Compared with the MODS group, the level of IL-4 was obviously higher than that in BMSC group (ng/L: 9.59±2.21 vs. 3.59±1.21,P < 0.01), and RAGE decreased significantly (ng/L: 0.29±0.07 vs. 1.09±0.04,P < 0.05).Conclusions BMSC administration can regulate the expression of IL-4 and RAGE in the rats subjected to MODS. Moreover, BMSC can promote the restoration of tissue and organ function, thus improve the survival rate. BMSC may be the target in cell therapy for the inflammatory disease.

The culture of umbilical cord-derived mesenchymal stem cells is extremely important for studies on umbilical cord mesenchymal stem cells. Optimization of cellculture technology is crucial for clinical application of mesenchymal stem cells and even celltherapy. Meanwhile, the labeling and tracer technique of umbilical cord-derived mesenchymal stem cells is a hotspot in stem celltransplantation. OBJECTIVE:To review the research and development of the cellmarkers and tracer methods of umbilical cord-derived mesenchymal stem cells. METHODS:A computer-based search of VIP, CNKI, Medline, Highwire and Foreign Journals Integration System databases was performed for articles concerning culture and labeling of umbilical cord-derived mesenchymal stem cells published from January 2001 to October 2013. The keywords were“stem cells, mesenchymal stem cells, umbilical cord-derived mesenchymalstem cells, cellculture, labeling methods”in Chinese and English, respectively. Final y, 35 articles were included in result analysis. RESULTS AND CONCLUSION:Umbilical cord-derived mesenchymal stem cells have not yet been widely used, mainly because of the immature isolation, culture and staining techniques of umbilical cord-derived mesenchymal stem cells. These techniques are worthy of further optimization studies. Although in recent years, cellmarkers and tracer technology of umbilical cord-derived mesenchymal stem cell s have made great progress, there are stil many problems need to be solved.

Objective To investigate the effects of angiotensin1-7 (Ang1-7) on renal tubulointerstitial fibrosis of diabetic rats.Methods Thirty-two male Wistar rats were randomly divided into four groups: normal control group,diabetic group,telmisartan group,Ang1-7-treated group.For 9 weeks after diabetes mellitus model established,24 h proteinuria,urine NAG/Cr,glucose,insulin,TG,TC,BUN,Scr,Na+ and K+ were assessed.Renal pathological changes were evaluated by PAS staining; Expression of TGF-β1,PPARγ and α-SMA mRNA was deteeted by real-time PCR; Protein levels of PPARγ,α-SMA and TGF-β1 were detected by Western blotting.Results (1)At the end of the ninth week,the blood pressure,proteinuria,renal weight/body weight in group DM were significantly higher than those in group NC (P＜0.05).(2)Renal interstitial fibrosis in group DM was obviously severe as compared to group NC (P＜0.05),but was improved in group TM and group T(P＜0.05).(3)TGF-β1 and α-SMA mRNA in group DM were significantly increased,and PPARγ mRNA was significantly decreased.Compared with group DM,TGF-β1 and α-SMA mRNA were significantly decreased,and PPARγ mRNA was significantly increased in group TM and group T,especially in group T.(4)TGF-β1 and α-SMA in group DM were significantly increased,and PPARγ decreased significantly.Compared with group DM,TGF-β1 and α-SMA decreased significantly,PPARγ increased significantly in group TM and group T,especially in group T.Conclusion Ang1-7 inhibits high glucose-induced α-SMA expression in vivo through up-regulating the PPAR expression and may inhibit renal tubulointerstitial fibrosis of diabetic rats.