Objective To establish the mouse model of sclerotic skin. Methods The sclerotic skin was induced by local injections of bleomycin (BLM) in C3H and BALB/c mice. The injection solution was prepared with BLM at the concentration of 200?g/mL in PBS. In the test group 0.1 mL BLM solution was injected daily into the back of the mice for 3 weeks. For the control mice same amount of PBS was injected daily for 3 weeks. After 3 weeks, the histology of the skin and lungs was compared between the different groups, also the changes of skin thickness and quantity of collagen. Results After the treatment of BLM sclerotic skin was observed in both C3H and BALB/c mice, in which the thickness of skin and the quantity of collagen (6 mm ? 6 mm) were higher than those in the control mice (P

Objective To find out the change of bone density in premenopausal women with systemic scleroderma (SSc) and its association with gluecorticosteroid.Methods Using a clinical bone densitometer manufactured by British McCue CuBA Cobroadband ultrasound attenuation (BUA) and velocity of sound (VOS) were measured at the left heel bone in 58 premenopausal patients with systemic scleroderma.Among them,35 patients had taken gluecorticosteroid,and the other 23 had not.Levels of serum estradiol (E 2) in 19 out of 58 patients with systemic scleroderma were determined and compared with healthy controls.Results Levels of broadband ultrasound attenuation and velocity of sound measured in permenopausal patients with systemic scleroderma who had taken gluecorticosteroid were significantly lower than those in ones who had not taken gluecorticoseroid ( P 0 05).Conclusion The bone mineral density and the level of BUA and VOS in premenopausal patients with systemic scleroderma,who had taken gluecorticosteroid,are obviously decreased,but there is no significant difference between patients without taking gluecorticosteroid and healthy controls.It indicates that systemic scleroderma is no dangerous factor of osteoporosis.And bone density in premenopausal patients with systemic scleroderma is related with the patients who have taken gluecorticosteroid for a long time.

Objective To establish a mouse model for scleroderma.Methods Forteen BALB C and 14 C3H female mice were averagely divided into model 1 and controls.Daily 0 1 ml BLM at a concentration of 200 ?g/ml was injected intracutaneusly into the backs of model 1 mice for 3 weeks,and 0 1 ml solution of PBS were injected intracutaneusly into the backs of control mice for 3 weeks.Observing the histological change of skin and lungs was made and measuring the thickness of dermis was performed with a medical analysis system of the color picture,determined the collagenic quantity was done with photoelectric colorimetry,and calculating the immunohistochemical index of collagen type Ⅰ and Ⅲ and transforming growth factor ? 1 (TGF ? 1) in the skin lesions from the mouse model and control was done.SPSS was used to finish the statistical analysis of the detective value from model 1 and controls.Results In the skin of model mice,the thickness of dermis markedly thickened ( P

Objective To evaluate the relationship of peripheral blood Th17 and regulatory T (Treg) cells with disease activity in patients with systemic sclerosis (SSc).Methods This study recruited 21 patients with active SSc,24 patients with inactive SSc and 24 normal human controls with informed consent.Peripheral blood samples were obtained from these subjects.Flow cytometry was used to detect the percentages of Th17 and Treg cells in peripheral blood CD4+ cells,a fluorescence-based quantitative PCR to determine the levels of interleukin (IL)-17A,retinoid-related orphan receptor gamma t (RoRγt),forkhead box P3 (FoxP3) mRNA in peripheral blood mononuclear cells (PMBCs),and enzyme linked immunosorbent assay to measure the serum level of IL-17.Results Increased percentage of Th17 cells in peripheral blood CD4+ cells was observed in patients with active SSc compared with those with inactive SSc and normal human controls (2.34％ ± 1.19％vs.0.68％ ± 0.39％ and 0.57％ ± 0.49％,respectively,both P ＜ 0.05).No statistical difference was noted in the percentage of Treg cells in CD4+ cells or the mRNA expression levels of FoxP3 between the patients with active SSc,inactive SSc and normal human controls (all P ＞ 0.05).There was a significant increase in the mRNA expression of IL-17A,RoRγt in PBMCs and serum levels of IL-17 in patients with active SSc compared with patients with inactive SSc and normal human controls ( 11.73 ± 0.80 vs.9.77 ± 1.30 and 10.79 ± 0.74,respectively,both P ＜ 0.05; 18.48 ± 1.09 vs.15.89 ± 1.48 and 17.77 ± 1.64,respectively,both P ＜ 0.05; 53.60± 9.90 pg/ml vs.15.18 ± 3.24 pg/ml and 15.53 ± 4.12 pg/ml,respectively,both P ＜ 0.05).The percentage of Th17 cells in CD4+ cells and serum IL-17 levels were both positively correlated with disease activity in patients with active SSc (r =0.675,0.644,respectively,both P ＜ 0.05).Conclusions Th17 cells are highly proliferative in patients with active SSc,which may be closely correlated with the activity of SSc.

OBJECTIVE Toinvestigatetheantidepressantandantianxietyeffectofproanthocyani-dins(OPC)inchronicallystressedratsanditsunderlyingmechanism.METHODS Onemethodwas selected from 8 different stress methods each day,and the rats were treated with OPC (25,50 and 1 00 mg·kg -1 )1 h before the stress method.The chronically stressed model was established.After 21 d stress experi ment,the i mmobility ti me in force swi mming test,sucrose consu mption and the nu mber of marbles buried in the marble burying test were observed respectively each day.OPC (25,50 and 1 00 mg·kg -1 )was given 1 h before each test.In addition,Western blotting was used to analyze the expression of brain derived neurotrophic factor (BDNF) and phosphorylated cyclic AMP response element-bindingprotein(p-CREB)inthehippocampusandfrontalcortex.RESULTS Comparedwith the control group,the chronically stressed group showed obvious depressive-like and anxiety-like behav-ior,while the immobility time decreased from (90.57 ±4.27)s in chronically stressed group to (78.25 ± 2.53)s (P<0.05),(72.12 ±3.21 )s(P<0.05)and (60.77 ±3.41 )s (P<0.05)when ig given OPC 25,50 and 100 mg·kg -1 respectively,the ratio of sucrose preference increased from (42.80 ±4.92)%to (67.54 ±4.32)%(P<0.05)and (72.21 ±7.99)%(P<0.05)when ig given OPC 50 and 1 00 mg· kg -1 respectively,the number of buried marbles decreased from 1 .57 ±0.21 in chronically stressed group to 0.63 ±0.26 (P<0.05)and 0.44 ±0.1 8 (P<0.05)when ig given OPC 50 and 1 00 mg·kg -1 respectively.The expression of p-CREB in the hippocampus and frontal cortex distinctively increased in OPC group (25,50 and 100 mg·kg -1 )(P<0.05),so did the expression of BDNF in the hippocampus andfrontalcortexinOPCgroup(50and100mg·kg-1)(P<0.05).CONCLUSION OPCcanreverse the depressive-like and anxiety-like behavior in chronically stressed rats,which may be related to the cAMP-CREB-BDNF signal transduction cascades.

Objective To investigate features of skin lesions of patients with systemic sclerosis (SSc),and to analyze the relationship of skin manifestations with clinical classification,autoantibodies and internal organ involvement.Methods Clinical data were collected from 120 patients with SSc in Department of Dermatology of Zhongshan Hospital Affiliated to Fudan University and Department of Scleroderma of Shanghai TCM-integrated Hospital between 2012 and 2014,and analyzed retrospectively.Results Among the 120 patients with SSc,118 (98.3％) had Raynaud's phenomenon,116 (96.7％) had skin sclerosis,including 101 (84.2％) with sclerosis of skin over the dorsum of fingers,90 (75％) had swollen skin,including 84 (70％)with swollen fingers,77 (64.2％) had poikiloderma,75 (62.5％) had thinned lip,74 (61.7％) had telangiectasia,63 (52.5％) had radial furrowing around the mouth,57 (47.5％) had mask-like face,49 (40.8％) had hyperplasia of nail cuticle,35 (29.2％) had petechiae of the nailfolds,25 (20.8％) had depressed fingertip,24 (20.0％) had atrophy of the finger pulp,24 (20.0％) had distal finger shortening,and 15 (12.5％) had fingertip ulcer.Anti-Scl-70 antibody and anti-centromere antibody (ACA) were positive in 42 (35.0％) and 31 (25.8％) patients respectively.The incidence of swollen fingers,fingertip ulcer,atrophy of the finger pulp was significantly higher in the anti-Scl-70 antibodypositive group than in the-negative group(P ＜ 0.05),and the incidence of sclerosis of skin over the dorsum of fingers,poikiloderma,fingertip ulcer and atrophy of the finger pulp was all significantly higher in the antiScl-70 antibody-positive group than in the ACA-positive group (P ＜ 0.05).The main internal organ involvement included interstitial lung disease (50％,44/88),cardiac involvement (47.8％,55/115),pulmonary arterial hypertension (35.7％,41/115),esophageal involvement (28.3％,34/120) and kidney involvement (9.2％,11/120).Patients with diffuse cutaneous systemic sclerosis (dcSSc) showed significantly higher incidence of cardiac involvement and poikiloderma compared with those with limited cutaneous systemic sclerosis (lcSSc) (P ＜ 0.01).Swollen fingers,sclerosis of skin over the dorsum of fingers,poikiloderma,telangiectasia,lip thinning,and radial furrowing around the mouth most commonly occurred in patients with early SSc,and swollen fingers and sclerosis of skin over the dorsum of fingers were highly correlated with the occurrence of pulmonary arterial hypertension.Telangiectasia,depressed fingertip and fingertip ulcer were significantly correlated with the occurrence of interstitial lung disease,and atrophy of the finger pulp was significantly correlated with the occurrence of cardiac involvement (both P ＜ 0.05).Conclusions Raynaud's phenomenon,swollen fingers,sclerosis of skin over the dorsum of fingers,poikiloderma,telangiectasia,lip thinning and radial furrowing around the mouth can be helpful for the early diagnosis of SSc.Pulmonary arterial hypertension commonly occurs in the early stage of SSc.Depressed fingertip and fingertip ulcer indicate the occurrence of interstitial lung disease,and the atrophy of the finger pulp indicates cardiac involvement.

Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the negative symptoms of chronic schizophrenia and on the P300 component of schizophrenics' event-related potentials (ERPs).Methods Ninety convalescing schizophrenia patients were randomly divided into a 5 Hz group,a 10 Hz group and a 15 Hz group,each of 30.The three groups were treated with the corresponding 5 Hz,10 Hz or 15 Hz rTMS once a day,five times a week for five consecutive weeks.The P300 ERPs of all three groups were tested before and after the treatment.Any curative effect was evaluated using the scale for the assessment of negative symptoms (SANS).Results After the treatment,the average SANS score of the 10 Hz group was significantly different from that before the treatment and also from those of the other two groups after the treatment.After the treatment,significant improvement was also observed in the amplitude of P300 in the 10 Hz group.The treatment's effectiveness was negatively correlated with age and longer course of the disease.Conelusion rTMS at 10 Hz is the most effective of the protocols tested for improving the negative symptoms of schizophrenia and improving cognitive functioning.

Uncontrolled fibrosis of skin and internal organs is the main characteristic of scleroderma, and collagen is a major extracellular matrix protein that deposits in the fibrotic organs. As the chaperone of collagen, heat shock protein 47 (HSP47) is closely related with the development of fibrosis. To explore the potential function of HSP47 in the pathogenesis of scleroderma, the clinical, in vivo and in vitro studies were performed. In clinical, the increased mRNA level of HSP47 was observed in the skin fibroblasts and PBMC from scleroderma patients, and the enhanced protein level of HSP47 was also detected in the skin biopsy and plasma of the above patients. Unexpectedly, the enhanced levels of HSP47 were positively correlated with the presence of anti-centromere antibody in scleroderma patients. Moreover, a high expression of HSP47 was found in the skin lesion of BLM-induced scleroderma mouse model. Further in vitro studies demonstrated that HSP47 knockdown could block the intracellular and extracellular collagen over-productions induced by exogenous TGF-β. Therefore, the results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma. The high expression of HSP47 can be detected in the circulatory system of scleroderma patients, indicating that HSP47 may become a pathological marker to assess the progression of scleroderma, and also explain the systemic fibrosis of scleroderma. Meanwhile, collagen over-expression is blocked by HSP47 knockdown, suggesting the possibility that HSP47 can be a potential therapeutic target for scleroderma.
Adolescent ; Adult ; Animals ; Biopsy ; Blotting, Western ; Cells, Cultured ; Collagen ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; Fibrosis ; HSP47 Heat-Shock Proteins ; blood ; genetics ; metabolism ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Mice ; Mice, Inbred C3H ; Middle Aged ; NIH 3T3 Cells ; Protein Binding ; RNA Interference ; Reverse Transcriptase Polymerase Chain Reaction ; Scleroderma, Systemic ; blood ; genetics ; metabolism ; Skin ; metabolism ; pathology ; Transforming Growth Factor beta ; pharmacology ; Young Adult