Objective To explore the efficacy and safety of tocilizumab in combination with disease-modifying anti-rheumatoid drugs (DMARDs) for the treatment of rheumatoid arthritis (RA) patients with moderate to severe activity and inadequate response to DMARDs. Methods Thirty-two RA patients with inadequate response to DMARDs were treated with tocilizumab along with stable dose of DMARDs for 12 weeks, adverse reactions were recorded, clinical laboratory and physiological indices were recorded 4, 8, and 12 weeks after treatment. The routine blood, liver and kidney function tests, morning stiffness, rest pain, tender joint count, swollen joint count, overall evaluation of the patient and physician to disease and health assessment questionnaire, blood sedimentation, C-reactive protein (CRP), Disease activity score 28 (DAS28), simplified disease activity index (SDAI) score, clinical disease activity index (CDAI). Repetitive measure analysis of variance wase used for statistical analysis. Results The clinical laboratory indices and DAS28, SDAI, CDAI scores observed in all of the patients were significantly improved (P<0.05). After 8 and 12 weeks of treatment, disease activity was further improved with statistical significance (P<0.05). The levels of IL-6 were downregulated obvious compared with before [(26±14) pg/ml vs (76±39) pg/ml, t=-6.925, P<0.01], and no obvious adverse reactions were observed. Conclusion Tocilizumab can quickly improve the symptoms and the control disease activity of refractory active RA within a few weeks.

Objective To investigate the feasibility of non-contrast-enhanced renal MR angiography (NCE-MRA) using time spatial labeling inversion pulse (Time-SLIP) technique,and to discuss the optimized inversion time (TI) and its relationship with age.Methods A total of 61 healthy volunteers were divided into two groups by age,22-50 years (n=32)and 51 80 years (n=29).All volunteers underwent 3.0T MRI examination with 6 different TIs sequences (1 200,1 300,1 400,1 600,1 600,1 700 ms).The vessel to-kidney signal ratio (VKR),grade of renal artery branches,grade of renal artery imaging quality were measured and analyzed.Results The VKR values were the highest at TI=1 500 ms in both sides ot kidneys.The scores of renal artery branches were gradually rising up but tending to be steady higher than 1 400 ms.Among all the subjects,the highest score of renal artery imaging quality was at TI=1 500 ms.In 22-50 years group,the highest score of renal artery imaging quality was at TI=1 500 ms.Meanwhile,the highest score was found at TI=1 600 ms in 51 80 years group.Moreover,the grade of renal artery imaging in the 22-50 years group acquired better scores compared to the 51 80 years group (all P＜0.05).Conclusion Time-SLIP technique is helpful to obtain renal MRA without contrast medium.The optimized TI value is 1 500 ms.Moreover,age can affect the optimized TI value.

MicroRNA (miRNA) negatively regulates gene expression at the post-transcriptional level.Studies find that the abnormal expression of miR-151-5p in various human tumors may play an important role in the development of human tumors,especially in the invasion and metastasis.Further studies of miR-151-5p contribute to a more in-depth understanding of tumor invasion and metastasis,which have potential value in tumor diagnosis,treatment and prognosis.

Blood Circulation ; drug effects ; physiology ; Diabetic Angiopathies ; therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional

Objective To evaluate therapeutic effects of simvastatin on serum expressions of cytokines and synovial tissue aspartic protease-3 (Caspase-3) in collagen induced arthritis (CIA) in rats, and the mechanism thereof. Methods The rat model of CIA was established by injecting bovine Ⅱ collagen. Sixteen model rats were randomly divided into two groups:CIA model group (sterile water 5 mL·kg-1·d-1 by gavage) and simvastatin group (2.0 mg·kg-1·d-1 by gavage). Seven normal rats were included in control group (sterile water 5 mL·kg-1·d-1 by gavage). The arthritis index (AI) and hind paw vol-umes were recorded once a week. The serum levels of cytokine, tumor necrosis factor (TNF)-αand interleukin (IL)-6 were measured by ELISA 42 days after the initial immunization. The expression of Caspase-3 in ankle synovial tissue was detect-ed by immunohistochemical method, and pathological results of HE staining in rat ankle were compared between three groups. Results Values of AI were decreased on the 24-d of the initial immunization in simvastatin group and CIA model group, which was significantly decreased on the 35-d of the initial immunization in simvastatin group than that of CIA model group (P＜0.05). The values of hind paw volumes were decreased on the 14-d of the initial immunization in simvastatin group and CIA model group, which was still significantly higher than those of control group (P＜0.05). The values of hind paw volumes were decreased on the 35-d and 42-d of the initial immunization in simvastatin group than those of CIA model group (P＜0.05). The serum levels of TNF-αand IL-6 on the 42-d of the initial immunization were significantly lower in simvastatin group than those of CIA model group, but which were significantly higher than those of control group ( P＜0.05). There were more synovial hyperplasia in simvastatin group than those of CIA model group. Only a small amount of inflamma-tory cell infiltration was found in simvastatin group. The expression of Caspase-3 was significantly higher in simvastatin group than that of CIA model group. Conclusion Simvastatin can significantly inhibit the serum levels of TNF-αand IL-6 in CIA model rats, and can up-regulate the expression of Caspase-3 in ankle of model rats.

Objective To evaluate the role of chemokine CXC ligand 13 (CXCL13) in spinal cord in neuropathic pain (NP) in rats.Methods One hundred and eight male Sprague-Dawley rats,weighing 150-200 g,were randomly divided into 4 groups (n =27 each):sham operation group (group S),group NP,small interference RNA (siRNA) negative control group (group NS) and CXCL13-siRNA group (group CS).The animals were anesthetized with intraperitoneal ketamine 50 mg/kg.NP was induced by ligation of L5 spinal nerve (SNL) in groups NP,NS and CS.L5 spinal nerve was only exposed but not occluded in group S.CXCL13-siRNA lentivirus and siRNA negative control lentivirus were injected intrathecally in groups CS and NS,respectively.Mechanical pain threshold was measured at 3,7 and 14 days after SNL.Then the rats were sacrificed and L4-6 segments of the spinal cord were obtained for determination of coexpression of CXCL13 and Neun (by immunofluorescence),activation of astrocytes,and expression of CXCL13 and glial fibrillary acidic protein (GFAP) protein (by Western blot) and mRNA (by RT-PCR) in spinal cord tissues.Results Compared with group S,mechanical pain threshold was significantly decreased and the expression of CXCL13 and GFAP protein and mRNA was up-regulated at each time point after operation in groups NP,NS and CS (P ＜ 0.05).Compared with group NP,mechanical pain threshold was significantly increased and the expression of CXCL13 and GFAP protein and mRNA was down-regulated at each time point after operation in group CS (P ＜ 0.05).There was no significant difference in the indexes mentioned above at each time point after operation between groups NP and NS (P ＞ 0.05).Conclusion CXCL13 is involved in the development and maintenance of NP in rats via activation of astrocytes.

AIM: To investigate the effects of Scutellaria barbata flavonoids (SBF) on neurofibrillary tangle (NFT) aggregation, tau protein phosphorylation and the regulated mechanism of glycogen synthase kinase (GSK) 3βand protein phosphatase (PP) 2A in the rats induced by amyloid βprotein 25-35 (Aβ25-35) in combination with AlCl3 and re-combinant human transforming growth factor ( RHTGF)-β1( composited Aβ) .METHODS:The male SD rats were used to establish the simulated Alzheimer disease ( AD) model by intracerebroventricular injection of composited Aβ.The Morris water maze was applied for screening the successful model rats with learning and memory deficits .The successful model rats were daily and orally administrated with SBF at doses of 35, 70 and 140 mg/kg or positive control drug Ginkgo biloba leaves flavonoids ( GLF) at 140 mg/kg for 37 d.The silver nitrate staining was used to determine the cortical NFT .The protein levels of total tau, phosphorylated protein of tau at Ser199 and Ser214 sites, GSK3βand PP2A in hippocampus and cortex were determined by Western blot .The mRNA expression of GSK3βand PP2A in the hippocampus and cortex was detected by RT-PCR.RESULTS:Compared with sham group , the cell number of positive NFT with silver nitrate staining in model rat cerebral cortex was significantly increased .The protein levels of phosphorylated tau protein at Ser 199 and Ser214 sites, GSK3βin the hippocampus and cerebral cortex in the model rats dramatically elevated , and PP2A was marked decreased as compared with the sham group rats.Meanwhile, the mRNA expression of GSK-3βsignificantly increased but PP2A was de-creased.However, these above abnormalities were differently attenuated by treating with SBF at different doses or GLF at 140 mg/kg for 37 d.CONCLUSION: SBF suppresses the NFT aggregation by inhibition of the regulatory functions of GSK-3βand PP2A, thus reducing the phosphorylation of tau protein .

In order to test the equilibrium solubility of puerarin in different solvents and solubilizer,cilia toxicity and irritation of these excipient, the balance method, toad in the ciliary body toxicity and rat nasal mucosa irritation were used respectively. Results showed that puerarin solubility was 56.44 g x L(-1) in combined solvent of 30% PEG200 and 10% Kolliphor HS 15. With normal saline solution as negative control and sodium deoxycholate as positive control, the effects of 30% PEG200, 30% PEG 400, 10% Kolliphor HS 15 and combination of 30% of PEG200 and 10% Kolliphor HS 15 on toad palate cilium were observed and cilia movement duration was recorded. The results indicated that there was no significant difference in cilia movement duration among 30% PEG200, 10% Kolliphor HS 15 and normal saline group. The rats long-term nasal mucous membrane irritation of 30% PEG 400, 10% Kolliphor HS 15, which had no cilia toxicity, was studied, with normal saline solution as negative control. There were no significant difference revealed on rat nasal mucosa epithelial thickness among 30% PEG 400, 10% Kolliphor HS 15 and normal saline. Above researches showed 30% PEG 400, 10% Kolliphor HS 15 was ideal for solubility of puerarin nasal drops and showed a lower cilia toxicity and irritation, and can be used as the solvent and solubilizer of puerarin nasal drops.
Administration, Intranasal ; methods ; Animals ; Anura ; Cilia ; chemistry ; Female ; Isoflavones ; chemistry ; Male ; Nasal Mucosa ; Polyethylene Glycols ; chemistry ; Rats ; Rats, Sprague-Dawley ; Solubility ; Solvents ; chemistry

The stability of melittin in different solvents (water, deoxygenated water, physiological saline, PBS, 50% ethanol, ethanol, glycerol)was studied and the results showed that the stability of melittin is not influenced by light, temperature and pH in 50% ethanol, which melittin can be completed dissolved when compared with ethanol and glycerol, in such, 50% ethanol was chosen as solvent storage when measured content of melittin. Then the effect of different concentrations of PBS, the pH of PBS and rat skin ho- mogenates were tested, and the results showed that melittin was degraded rapidly at low concentration solution and low ionic strength. Increasing pH of PBS and rat skin homogenate can accelerate the degradation of melittin. These researches provide an experimental ba- sis for further study of melittin.
Animals ; Drug Stability ; Ethanol ; chemistry ; Hydrogen-Ion Concentration ; Melitten ; chemistry ; Rats ; Skin ; drug effects ; Solvents ; chemistry ; Temperature

Air Pollutants ; toxicity ; China ; epidemiology ; Hospitals, Public ; Humans ; Patient Admission ; Respiratory Tract Diseases ; etiology ; physiopathology ; Temperature ; Weather