Silencing of SMAD family member 3 promotes M2 polarization of macrophages and the expression of SMAD7 in rheumatoid arthritis / 细胞与分子免疫学杂志

Objective To investigate the effect of SMAD family member 3(SMAD3) silenced by small interfering RNA (siRNA) on macrophage polarization and transforming growth factor β1 (TGF-β1)/ SMAD family signaling pathway in rheumatoid arthritis (RA). Methods RA macrophages co-cultured with rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were used as a cell model. TGF-β1 was used to stimulate macrophages, and SMAD3-specific siRNA (si-SMAD3) and negative control siRNA (si-NC) were transfected into human RA macrophages co-cultured in TranswellTM chamber. The expression of SMAD3 mRNA was detected by real-time fluorescence quantitative PCR, and the expression of TGF-β1, SMAD3 and SMAD7 protein was detected by Western blot analysis. The contents of TGF-β1 and IL-23 in cell culture supernatant were determined by ELISA. Cell proliferation was detected by CCK-8 assay. TranswellTM chamber was used to measure cell migration. Results Compared with the model group and the si-NC group, the expression of TGF-β1, SMAD3 mRNA and protein in RA macrophages decreased significantly after silencing SMAD3. In addition, the secretion of IL-23 decreased significantly, and the cell proliferation activity and cell migration were inhibited, with high expression of SMAD7. Conclusion Knockdown of SMAD3 can promote M2 polarization and SMAD7 expression in RA macrophages.

Synovial and pulmonary dysfunctions are induced by crosstalk of Smad and Erk pathways in an arthritis model.

In the current experiment, the effects of transforming growth factor (TGF)-ß1/Smad and ERK pathway crosstalk on synovial and pulmonary systems during rheumatoid arthritis have been investigated. For this purpose, rats were divided into normal control (NC) and model control (MC) groups. In the MC group, 0.1 ml Freund's complete adjuvant was injected intradermally into the right hind paw, and the resulting inflammation represented a rheumatoid arthritis model. Joint swelling and changes in lung functions were observed in arthritic rats. Synovial and lung were observed by light and electron microscopies. Enzyme-linked immunosorbent assays were used to detect TGF-ß1, interleukin (IL)-1ß, IL-4, IL-10, interferon-γ (IFN-γ), connective tissue growth factor (CTGF), and fibroblast growth factor (FGF). PCR, immunohistochemistry, and immunoblotting were used to detect changes in Smad and ERK pathways of synovial and lung tissues. Compared with the NC group, toe swelling was elevated in the MC group. Pulmonary functions FEV1, FEF50, FEF75, MMF, and PEF were decreased (P< 0.01). Serum cytokines IL-1ß, IL-4, TGF-ß1, and CTGF were increased, while IFN-γ, IL-10, Th1/Th2 cell ratio, and FGF were decreased (P< 0.01 or P< 0.05). Expression of TGF-ß1 and Smad2/3/4 mRNAs and TGF-ß1, TßRI, TßRII, Smad2/3, p-Smad2/3, and Smad4 proteins in the synovial membrane and lung tissue were increased, and expression of Smad7 mRNA and protein was decreased (P<0.01) or P<0.05). Expression of ERK2 mRNA and p-ERK1/2 protein was increased in the synovial membrane and lung tissue, and expression of ERK1/2 mRNAs and ERK1/2 and p-ERK1/2 proteins was increased in lung tissue (P< 0.01 or P< 0.05). Correlation analysis showed that FEV1 was negatively correlated with TGF-ß1 mRNA and protein in arthritic rats, FEF25 was negatively correlated with Smad4 protein, and FEF50 was negatively correlated with the TßRII protein, and FEF75, TGF-ß1 and Smad3 mRNAs. There was a negative correlation between Smad2/3 protein and a negative correlation between PEF and TGF-ß1 protein (P< 0.05). FEF50 and MMF were positively correlated with Smad7 mRNA (P< 0.05). FEV1 was negatively correlated with ERK2 mRNA, and FEF25 was negatively correlated with p-ERK1/2 protein. FEF75 and MMF were negatively correlated with ERK1/2 and p-ERK1/2, respectively (P< 0.05). ERK1 mRNA was positively correlated with Smad3 mRNA and TßRII protein, ERK2 mRNA was positively correlated with p-Smad2/3, and ERK1/2 protein was positively correlated with Smad2 mRNA, Smad4 protein, p-ERK1/2 protein, Smad4 mRNA, and p-Smad2/3 protein (P< 0.05). p-ERK1/2 protein was negatively correlated with Smad7 protein (P< 0.05). It is concluded that arthritic rats have synovial and systemic pulmonary damage. Smad and ERK pathway crosstalk leads to systemic lesions. Smad and ERK pathways are gradually activated by phosphorylation under the induction of the TGF-ß1 promoter, and then participate in transcriptional activities, leading to the increase in synovial inflammation of arthritis, pulmonary lesions, and decreases in lung functions.

Research advances on mechanism and lesion location of vertical nystagmus / 临床耳鼻咽喉头颈外科杂志

Summary@#Vertical nystagmus is a vertical nystagmus caused by structural abnormalities and/or dysfunction of the central vestibular system and observed in situ in the center of the eyeball. There are two kinds of nystagmus （UBN） and downbeat nystagmus （DBN） according to the direction of nystagmus. The diagnosis of UBN is mainly made by naked eye or electronystagmography/viewer. It is a common neuro-ophthalmologic sign in the field of vestibular medicine. In this paper, the mechanism of vertical nystagmus formation and the location of lesions were briefly introduced, in order to provide help for the diagnosis and treatment of Vertigo.

Research advances on mechanism and lesion location of vertical nystagmus / 临床耳鼻咽喉头颈外科杂志

Vertical nystagmus is a vertical nystagmus caused by structural abnormalities and/or dysfunction of the central vestibular system and observed in situ in the center of the eyeball. There are two kinds of nystagmus （UBN） and downbeat nystagmus （DBN） according to the direction of nystagmus. The diagnosis of UBN is mainly made by naked eye or electronystagmography/viewer. It is a common neuro-ophthalmologic sign in the field of vestibular medicine. In this paper, the mechanism of vertical nystagmus formation and the location of lesions were briefly introduced, in order to provide help for the diagnosis and treatment of Vertigo.

Model test to improve self-management behavior of middle-aged stroke patients: based on the integration of health belief model and planned behavior theory / 中国实用护理杂志

Objective@#To examine the integrated model of self-management behavior in middle-aged stroke patients based on health belief model and planned behavior theory.@*Methods@#A self-designed general information questionnaire, self-management behavior cognition and attitude questionnaire and self-management behavior scale, were used to investigate 654 cases of first middle-aged stroke patients in the neurology department of 3 grade a hospitals in Qingdao.@*Results@#The standardization factor load of each theoretical dimension in the theoretical integration model was 0.51-0.91 (0.72±0.11). Behavioral intention had a direct positive predictive effect on self-management behavior, with an effect value of 0.49 (t = 7.41, P < 0.01). Perceived behavior control not only had a direct positive prediction effect on self-management behavior, but also indirectly influenced self-management behavior through behavioral intention. The effect values are 0.12 (t = 2.75, P < 0.05) and 0.04 (t = 2.18, P < 0.05), respectively. Behavioral attitude exerts influence on self-management behavior through behavioral intention, and the effect value is 0.40 (t = 14.71, P < 0.01). Subjective norms not only influenced self-management behavior through behavioral intention, but also indirectly influenced behavioral intention and self-management behavior through behavioral attitude, with the effect value of 0.25. The effects of perceived benefits and perceived severity on self-management behaviors were 0.21 and 0.04, respectively. The theoretical integration model can explain 62% variance variation of self-management behavior.@*Conclusion@#The theoretical integration model of self-management behavior of middle-aged stroke patients based on the health belief model and planned behavior theory can better explain the behavior. This model can be applied to stroke patients in an attempt to provide theoretical basis for the formulation of personalized nursing measures for stroke patients.

Model test to improve self-management behavior of middle-aged stroke patients: based on the integration of health belief model and planned behavior theory / 中国实用护理杂志

Objective To examine the integrated model of self-management behavior in middle-aged stroke patients based on health belief model and planned behavior theory. Methods A self- designed general information questionnaire, self- management behavior cognition and attitude questionnaire and self-management behavior scale, were used to investigate 654 cases of first middle-aged stroke patients in the neurology department of 3 grade a hospitals in Qingdao. Results The standardization factor load of each theoretical dimension in the theoretical integration model was 0.51-0.91 (0.72±0.11). Behavioral intention had a direct positive predictive effect on self-management behavior, with an effect value of 0.49 (t=7.41, P<0.01). Perceived behavior control not only had a direct positive prediction effect on self-management behavior, but also indirectly influenced self-management behavior through behavioral intention. The effect values are 0.12 (t=2.75, P<0.05) and 0.04 (t=2.18, P<0.05), respectively. Behavioral attitude exerts influence on self- management behavior through behavioral intention, and the effect value is 0.40 (t = 14.71, P < 0.01). Subjective norms not only influenced self-management behavior through behavioral intention, but also indirectly influenced behavioral intention and self-management behavior through behavioral attitude, with the effect value of 0.25. The effects of perceived benefits and perceived severity on self-management behaviors were 0.21 and 0.04, respectively. The theoretical integration model can explain 62% variance variation of self-management behavior. Conclusion The theoretical integration model of self-management behavior of middle-aged stroke patients based on the health belief model and planned behavior theory can better explain the behavior. This model can be applied to stroke patients in an attempt to provide theoretical basis for the formulation of personalized nursing measures for stroke patients.

Effect of Xinfeng Capsule on lung function in rats with adjuvant-induced arthritis and its mechanism / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of Xinfeng Capsule (XFC) on pulmonary function and related mechanism in adjuvant-induced arthritis (AA) rats.</p><p><b>METHODS</b>The rats were randomly divided into five groups: normal control (NC), model control (MC) groups, methotrexate (MTX), tripterygium glycosides tablet (TPT) and Xinfeng capsule (XFC) treatment groups. The adjuvant-induced arthritis model was established by intracutaneous injection of 0.1 mL Freund ' s complete adjuvant in the right paw of rats; the drugs were given 19 d after model establishment. The toe swelling degree (E), arthritis index (AI), pulmonary function, peripheral blood Treg levels, pathological changes of lung tissue and expression of Foxp3, TGF-β1, Smad3, Smad7 proteins in lung tissue were measured 30 d after drug administration.</p><p><b>RESULTS</b>Compared to NC group, the levels of E, AI, alveolitis score, TGF-β1 and Smad3 were significantly increased (P <0.05 or P <0.01); maximum expiratory flow 25% of vital capacity (FEF25),50% maximal expiratory vital capacity flow (FEF50), maximum expiratory flow at 75% of vital capacity (FEF75), maximum mid-expiratory flow (MMF), force peak expiratory flow (PEF), CD4+ CD25+ Treg, Foxp3 and Smad7 were significantly decreased in MC group (P <0.05 or P < 0.01). Compared to MC group,the expression of E, AI, TGF-β1 and Smad3 were reduced, while FEF50, FEF75, MMF, PEF, Treg, Foxp3 and Smad7 were elevated in XFC group (P <0.05 or P <0.01). Compared to XFC group, the level of body mass,FEF25,FEF50, FEF75, MMF and Treg were lower in MTX and TPT groups (P <0.05 or P <0.01).</p><p><b>CONCLUSION</b>There are inflamed joints and reduced pulmonary function in rats of adjuvant-induced arthritis. XFC can inhibit paw edema degrees, reduce arthritis response, and improve pulmonary function, which is associated with up-regulating expression of Treg and Foxp3, down-regulating the expression of TGF-β1 and adjusting TGF-β1/Smads signal pathway.</p>

Effects of Xinfeng Capsule on Depressive Mood and Serum Cortisol in Patients with Rheumatoid Arthritis / 中国中医药信息杂志

Objective To observe effects of Xinfeng capsule(XFC)on depressive mood and serum cortisol in patients with rheumatoid arthritis and study its mechanism.Methods 76 RA patients were randomly divided into two groups.The treatment group(n=40)was treated with XFC,and the control group(n=36)with Zhengqing Fengtongning.The targets included clinical effects,symptom and sign,integral of quality of life,self-rating depression scale(SDS)and serum cortisol.Results The effects of XFC were similar to that of Zhengqing Fengtongning in the total effective rate,improving symptoms and sign,active index,etc.XFC was superior to Zhengqing Fengtongning in improving SDS standard score,the symptoms of splenic asthenia and quality of life(P

The influence of Xinfeng capsule on pulmanory HRCT images and cytokines in blood serum of adjuvant arthritis rats / 中国免疫学杂志

Objective:To observe the influence of Xinfeng capsule(XFC) on pulmonary HRCT images and cytokines(TNF-?,IL-10) in blood serum adjuvant arthritis rats.Methods:60 rats were averagely divided into normal control group,model control group,methotrexate(MTX) treated group,tripterygium wilfordii polycoride tablet(TPT) treated group, XFC treated group,12 in each.Except for the rats of normal group,the others were intracutaneously injected with 0.1 ml of Freund’s complete adjuvant in the right hindlimb.After 19 days,different drugs were given to all rats. Pulmonary HRCT images were obtained and the blood samples were reserved for assaying cytokines.Results:In model control group ,the lungs’ outlines weren’t clear and the blood vessels expanded with the edges of them being obscure and unregular. There were high density images shaped as rope and slip in lungs of model control group rats and the pleura near the images were a little thickening. In MTX treated group, there were high density images shaped as slice along pulmonary veins. The veins of the blood vessels were obscure and the edges were unclear. In TPT treated group,there were multiple high density images shaped as tubercle and slice and the boundary were not clear. In XFC treated group, the lungs’ outlines were clear and the veins were well-distributed. High density images shaped as spot were found in part lungs. Compared with normal control group,tumor necrosis factor-?(TNF-?) in blood serum ascended obviously in model control group(P0.05).Conclusion:XFC eliminates swelling by down-regulating the levels of TNF-?, up-regulating the levels of IL-10, restraining the inflammatory reaction.In adittion,cytokines participated in forming pulmanory fibrofication.So the changes of pulmanory HRCT images were also improved at the same time.