BACKGROUND: Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. METHODS: We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. RESULTS: The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P < 0.05) and placebo (13.9%, P < 0.05) groups. The proportion of patients achieving an sPGA score 0 or 1 was 66.3% in the benvitimod group and 63.9% in the calcipotriol group, which were both significantly higher than that in the placebo group (34%, P < 0.05). In the long-term follow-up study, 50.8% of patients experienced recurrence. After retreatment with 1% benvitimod, 73.3% of patients achieved an sPGA score of 0 or 1 again at week 52. Adverse events included application site irritation, follicular papules, and contact dermatitis. No systemic adverse reactions were reported. CONCLUSION: During this 12-week study, benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. TRIAL REGISTRATION Chinese Clinical Trial Registry (ChiCTR), ChiCTR-TRC-13003259; http://www.chictr.org.cn/showprojen.aspx?proj=6300.
Double-Blind Method ; Follow-Up Studies ; Humans ; Ointments ; Psoriasis/drug therapy* ; Resorcinols ; Severity of Illness Index ; Stilbenes ; Treatment Outcome

Adult ; China ; Databases, Factual ; Female ; Humans ; Male ; Middle Aged ; Pituitary Diseases ; classification ; epidemiology ; Registries ; Software

This paper aimed to investigate the anti-influenza virus activity of the genus Paeonia, screen potential anti-influenza virus compounds and predict targets of anti-influenza virus to explore the mechanism of anti-influenza virus activity. First of all, a total of 301 compounds of the genus Paeonia were summarized from the literatures in recent ten years. The candidate active ingredients from the genus Paeonia were identified by database such as PubChem and Chemical Book. The ligands were constructed by ChemDraw, Avogadro and Discovery Studio Visualizer. Secondly, 23 potential anti-influenza virus targets were developed by combining the target database and the literatures. Uniprot database was used to find the anti-influenza virus targets, and RCSB was used to identify targets associated with anti-influenza virus activity as docked receptor proteins. QuickVina 2.0 software was used for molecular docking. Finally, the Cytoscape 3.5.1 software was used to map the potential activity compounds of the genus Paeonia against influenza virus and the anti-influenza virus target network. Uniprot online database was used to analyze the target GO enrichment and KEGG metabolic pathways. The results showed that 74 compounds of the genus Paeonia had anti-influenza virus effect and 18 potential anti-influenza virus targets were screened. GO analysis concluded that the mechanism of the genus Paeonia anti-influenza virus is consistent with the mechanism of NA anti-influenza virus in order to stop the sprouting, dispersion and diffusion of virus and reduce the ability of virus to infect, so that the infection can be restricted so as to achieve the anti-influenza virus effect.

Objective we assessed our institutional outcomes of hybrid treatment for aortic arch disease with supra-aortic debranching and endovascular stent graft repair.Methods From March 2016 to November 2016,6 patients underwent Hybrid total aortic arch repair:1 had aortic arch pseudoaneurysm;1 had type Ⅲ aortic dissection;4 had aortic arch aneurysm because of hypotension,of whom 1 with aneurysm prerupture and 1 with Aortic intramural hematoma.Supra-aortic vessels were involved and high-risk for traditional operations in all patients.Bifurcated artificial vessels were used,main vessel was end-to-side anastomosed with ascending aorta.Branching vessel were end-to-end anastomosed with right innominate artery and left subclavian artery,end-to-side anastomosed with left common carotid artery.Then,stent graft was implanted into ascending aorta and aortic arch.All patients were followed postoperatively,with regularly contrast computed tomography angiogram (CTA) and echocardiography(discharge,three months,six months,and yearly).Results Hybrid procedure with supra-aortic debranching and endovascular stent graft repair were completed in all patients,technical success rate was 100％.There were no perioperative obvious morbidity and mortality,follow-up period were 2-9 months.1 patients had stroke during follow-up period,condition improved after treatment.Supra-aortic vessels were patency and there were no endoleak in all patients.There were no recurrent aortic disease during follow-up period.Conclusion Hybrid aortic arch replacement can be performed with good postoperative and early results in high-risk patients for traditional open repair.

BACKGROUND:Mesenchymal stem cells have unique homing,immunoregulation and anti-inflammatory properties.After intravenous injection,mesenchymal stem cells can home to the damaged target organs and tissues,and function to repair damaged tissues.OBJECTIVE:To observe the pathological changes of lung tissues in rats with emphysema after mesenchymal stem cells transplantation.METHODS:Twenty-four female Wistar rats were randomly divided into experimental group,control group and healthy control group.In the first two groups,the model of pulmonary emphysema was established by the method of dropping porcine pancreatic elastase.BrdU-labeled mesenchymal stem cells were injected into the tail vein of the rats in the experimental group,and PBS was injected in the control group.After 14 days,the pathological changes of lung tissues were observed.Tumor necrosis factor-α level,alveolar wall apoptotic index,anti-CD34 and anti-BrdU immunohistochemical changes in the bronchoalveolar lavage fluid were detected.RESULTS AND CONCLUSION:Compared with the healthy control group,the tumor necrosis factor-α level and apoptotic index of alveolar wall cells increased (P ＜ 0.01),and the relative areas of anti-Brdu and anti-CD34 decreased (P ＜ 0.01) in the control group.Compared with the control group,the level of tumor necrosis factor-α and apoptotic index of alveolar wall cells decreased (P ＜ 0.01),and the relative area of anti-Brdu and anti-CD34 increased (P ＜ 0.01) in the experimental group.The histopathological findings showed that both the control group and the experimental group showed emphysema-like changes,but these changes were milder in the experimental group than the control group.To conclude,mesenchymal stem cells can inhibit inflammatory response and apoptosis in experimental emphysema,improve the pathological changes of the lung,and moreover,bone marrow mesenchymal stem cells can differentiate into lung vascular endothelial cells.

Background:Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course,and available treatments for delaying the progression to end-stage renal disease are limited.This study aimed to assess the efficacy and safety of the traditional Chinese medicine,Niaoduqing particles,for delaying renal dysfunction in patients with stage 3b-4 CKD.Methods:The present study was a prospective,randomized,double-blind,placebo-controlled,multicenter clinical trial.From May 2013 to December 2013,300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml,min-1· 1.73 m-2,aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces.Patients were randomized in a 1∶1 ratio to either a test group,which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks,or a control group,which was administered a placebo using the same methods.The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment.The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test.The present study reported results based on an intention-to-treat (ITT) analysis.Results:A total of 292 participants underwent the ITT analysis.At 24 weeks,the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) μmol/L for the test and control groups,respectively (Z =2.642,P =0.008),and the median change in eGFR was-0.2 (-4.3-2.7) and-2.2 (-5.7-0.8) ml·min-1.1.73 m-2,respectively (Z =-2.408,P =0.016).There were no significant differences in adverse events between the groups.Conclusions:Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD.This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction.

OBJECTIVE To observe the influence of fire-needle therapy on JNK and p38MAPK in ankle-joint of rheumatoid arthritis(RA) rats to explore its underlying mechanism in RA treatment.METHODS 40 male SD rats were randomly divided into normal group,model group,fire-needle group and medication(methotrexate,MTX)group,with 10 cases in each group. Fire-needle was applied to Jiaji(EX-B2) and Ashi point every other day,twice altogether.The right hindpaw swelling volume of rats were detected on the 1st,2nd,4th,6th and 8th day,respectively.The pathological changes in synovial tissue of the right ankle joint were observed by optical microscope.The expression of JNK and p38 was detected by immunohistochemical method and Western blot.RESULTS In comparison with the control group,the swelling paw volumes at the 2nd day signifi-cantly increased of the rest 3 groups(P <0.01).Compared to the model group,the swelling paw volumes on the 8th day in fire-needle group decreased significantly(P <0.05).Serum TNF-αand IL-1β(P <0.05)contents increased in model group compa-ring with normal group,while decreased in fire-needle group and medication group comparing with model group.The patho-logical states of synovial tissue of the right ankle joint in both fire-needle and medication groups were relatively lighter than those of the model group.In comparison with normal group,the expression of JNK and p38 in local synovial tissue of the right ankle joint increased significantly in model group(P <0.05~0.01).Compared with model group,the expression of JNK and p38 of fire-needle and medication group both decreased significantly(P <0.05).These changes were also found in photographs made by immunohistochemical method.CONCLUSION Fire-needle therapy can dowm-regulate the expression of JNK and p38 in local synovial tissue of the right ankle join in MAPK signal transduction pathways,which is the possible mechanism of fire-needle therapy for RA treatment.

OBJECTIVETo study the relationship between fibrotic focus (FF) and carbonic anhydrase (CA) IX in invasive ductal carcinomas (IDC) of the breast.

METHODSIn 167 cases of IDC, the FF was assessed morphologically, and expression of ER, PR and CA IX was evaluated using MaxVision immunohistochemistry.

RESULTSThe expression of CA IX in IDC with and without FF was 56.3% (45/80) and 28.7% (25/87) respectively, with significant difference (P=0.001). In IDC with FF, the CA IX expression of tumor cells in tumors with CA IX-positive fibroblasts (35/40, 87.5%) was significantly (P<0.001) higher than that in tumors with CA IX-negative fibroblasts (10/40, 25.0%). In IDC with FF, the CA IX expression of fibroblasts of FF in grade 3 IDC (23/33, 69.7%) was significantly (P=0.006) higher than that in grade 1+2 tumors (17/47, 36.2%). The ER and PR expression of tumor cells in tumors containing CA IX-negative fibroblasts was 72.5% (29/40) and 65.0% (26/40) respectively, whereas the ER and PR expression of tumor cells in tumors containing CA IX-positive fibroblasts was 50.0% (20/40) and 42.5% (17/40) respectively; the difference was statistically significant (for both ER and PR, P=0.04). The age of patients with tumors containing CA IX-negative fibroblasts was significantly (P=0.002) older than those containing CA IX-positive fibroblasts. The FF diameter/tumor diameter in tumors containing CA IX-positive fibroblasts was significantly larger than those containing CA IX-negative fibroblasts. (3) For the groups of tumor size≤2 cm and tumor size between 2 cm to 5 cm, the diameter of the fibrotic focus was significantly (P<0.01) smaller than the fibrotic focus size of tumors>5 cm in size.

CONCLUSIONSCA IX expression is correlated with FF, and that in fibroblasts of FF correlated with patients' age, tumor grade, hormone receptors and FF diameter/tumor diameter. CA IX expression in FF might be a marker for poor prognosis in patients with breast cancer.

Age Factors ; Antigens, Neoplasm ; Breast Neoplasms ; metabolism ; pathology ; Carbonic Anhydrase IX ; Carbonic Anhydrases ; Carcinoma, Ductal, Breast ; enzymology ; pathology ; Female ; Fibroblasts ; metabolism ; Humans ; Immunohistochemistry ; Neoplasm Grading ; Neoplasm Proteins ; Receptors, Estrogen ; metabolism ; Receptors, Progesterone ; metabolism

Objective To study the relationship between fibrotic focus ( FF ) and carbonic anhydrase ( CA) Ⅸin invasive ductal carcinomas ( IDC) of the breast.Methods In 167 cases of IDC, the FF was assessed morphologically, and expression of ER, PR and CA Ⅸ was evaluated using MaxVision immunohistochemistry.Results The expression of CAⅨin IDC with and without FF was 56.3%(45/80) and 28.7%(25/87) respectively, with significant difference (P=0.001).In IDC with FF, the CA Ⅸexpression of tumor cells in tumors with CAⅨ-positive fibroblasts (35/40, 87.5%) was significantly (P<0.001) higher than that in tumors with CAⅨ-negative fibroblasts (10/40, 25.0%).In IDC with FF, the CAⅨexpression of fibroblasts of FF in grade 3 IDC ( 23/33, 69.7%) was significantly ( P =0.006 ) higher than that in grade 1 +2 tumors (17/47, 36.2%).The ER and PR expression of tumor cells in tumors containing CA Ⅸ-negative fibroblasts was 72.5% ( 29/40 ) and 65.0% ( 26/40 ) respectively, whereas the ER and PR expression of tumor cells in tumors containing CAⅨ-positive fibroblasts was 50.0%(20/40) and 42.5% (17/40) respectively; the difference was statistically significant (for both ER and PR, P=0.04 ) .The age of patients with tumors containing CA Ⅸ-negative fibroblasts was significantly ( P=0.002) older than those containing CA Ⅸ-positive fibroblasts.The FF diameter/tumor diameter in tumors containing CA Ⅸ-positive fibroblasts was significantly larger than those containing CA Ⅸ-negative fibroblasts.(3) For the groups of tumor size≤2 cm and tumor size between 2 cm to 5 cm, the diameter of the fibrotic focus was significantly (P<0.01) smaller than the fibrotic focus size of tumors >5 cm in size. Conclusions CA IX expression is correlated with FF, and that in fibroblasts of FF correlated with patients′age, tumor grade, hormone receptors and FF diameter/tumor diameter.CAⅨexpression in FF might be a marker for poor prognosis in patients with breast cancer.

Objective To evaluate the schistosomiasis control effect of the measures of replacing cattle with machine for cul?tivation and forbidding depasturage of livestock on marshlands in marshland and lake regions. Methods The retrospective re?view and field survey were implemented in the Jiangling and Gongan counties of Hubei Province where were implemented with the measure of replacing cattle with machine for cultivation,and Yuanjiang and Huarong counties of Hunan Province where were implemented with the measure of forbidding the depasturage of livestock on marshlands. The schistosome infection status of hu?man,cattle,and Oncomelania hupensis snails,and schistosome?infested field excreta were surveyed from 2007 to 2013. The ef?fects of the interventions were compared before and after their implementations. Results The 6 villages of Hubei Province were implemented with the measure of replacing cattle with machine for cultivation,and 7 villages of Hunan Province were imple? mented with the measure of forbidding the depasturage of livestock on marshlands. From 2007 to 2013,the schistosome infection rates of residents declined from 3.95%to 0.70%(χ2 =128.376,P<0.05),with the descend range of 82.53%. The descend ranges of the measures of replacing cattle with machine for cultivation and forbidding the depasturage of livestock on marshlands were 83.081%and 81.62%respectively,and there was no significant difference between the two measures(χ2 =0.132,P>0.05). The infection rate of cattle decreased from 3.66%in 2007 to 0.65%in 2013,and the descend range was 82.24%(χ2=13.692,P<0.05). The field excreta was surveyed in the snail breeding place in 2013. The investigated area was 157.435 hm2, and 625 samples of field feces of cattle were collected with the density of field excreta of 3.97/hm2,and the positive rate was 1.12%(7/625). The schistosome infection rate of snails and the density of infected snails decreased successively from 2007, and no infected snails were detected from 2011 to 2013. Conclusions The schistosomiasis endemic situation are decreased sig?nificantly after the interventions of replacing cattle with machine for cultivation and forbidding the depasturage of livestock on marshlands. Therefore,schistosomiasis control effect of these measures is notable in the marshland and lake regions.