[Effect of triptolide in improving platelet activation in patients with ankylosing spondylitis by regulating VEGFA,SDF-1,CXCR4 pathway].

The effect of triptolide( TP) on VEGFA,SDF-1,CXCR4 pathway were investigated in vitro to explore the mechanism in improving platelet activation in patients with ankylosing spondylitis( AS). Peripheral blood mononuclear cells( PBMC) were used for the experiment and divided into 4 groups: normal group( NC),model group( MC),triptolide group( TP),and AMD3100 group. The optimal concentration of TP was measured by the MTT method. The expressions of TNF-α,IL-1ß,IL-4,IL-10,VEGFA and VEGFR were detected by ELISA. The expressions of SDF-1,CXCR4 and VEGFA were detected by real-time quantitative PCR( RT-qPCR).The expressions of SDF-1,CXCR4,VEGFA and VEGFR were detected by Western blot. The expression levels of CD62 p,CD40 L and PDGFA were detected by immunofluorescence. MTT results showed that medium-dose TP had the strongest inhibitory effect on cells at24 h. The results of ELISA and PCR showed that TP inhibited mRNA expressions of IL-1ß,TNF-α,VEGFA,VEGFR and SDF-1,CXCR4 and VEGFA. The results of Western blot indicated that TP inhibited SDF-1,CXCR4 and VEGFA,VEGFR protein expressions; immunofluorescence results indicate that TP can inhibit the expressions of CD62 p,CD40 L,PDGFA. TP may regulate platelet activation by down-regulating SDF-1,CXCR4,VEGFA and VEGFR mRNA expressions,thereby down-regulating IL-1ß and TNF-αexpressions,and up-regulating the expressions of IL-4 and IL-10 cytokines.

[Effect of Tripterygium Glycosides Tablets on immune-induced liver and kidney function in patients with rheumatoid arthritis based on data mining].

This paper aims to investigate the effect of oral administration of Tripterygium Glycosides Tablets combined with traditional Chinese medicine on immune inflammatory index in patients with rheumatoid arthritis,in order to explore the compatibility mode of traditional Chinese medicine in the treatment of rheumatoid arthritis. Medical records of hospitalized patients with rheumatology at the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine from June 2012 to December 2017 were collected. The combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine was adopted for the experimental group,while the simply administration of Tripterygium Glycosides Tablets were adopted for the control group. SPSS 21. 0 was used to analyze the changes of general conditions and immune inflammatory metabolic indexes in the two groups of RA patients. The association rules were analyzed by SPSS Clementine 14. 2 software Apriori module,and the random walk model was evaluated by ORACLE 10 g tool. The results showed that a total of 1 220 patients with rheumatoid arthritis met the requirements of this study,including 322 in the experimental group and 898 in the control group. Before treatment,there was no significant difference in age and duration between the two groups. The difference value of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR in the two groups of RA patients decreased before and after treatment,and the experimental group was superior to the control group in reduction of Ig A,Ig G,RF,CCP-AB,hs-CRP and ESR.The control group was superior to the experimental group in reduction of Ig M( P<0. 01 or P<0. 05). Compared with before treatment,ALT,AST,ALP,GGT,CREA,BUN,b-MG,MA,TRU and Ig U all increased,with statistically significant differences( P<0. 01).The UA of the two groups of RA patients decreased after treatment,with statistically significant differences( P<0. 01). The experimental group was superior to the control group in reduction of UA,with statistically significant differences( P < 0. 05 or P < 0. 01). The herbs adopted in the prescriptions of 1 220 patients were mainly classified into four categories,namely spleen-sweating herbs,blood-activating and stasis-relieving herbs,phlegm and phlegm-relieving herbs,and heat-clearing and antidote herbs. The results of association rule analysis indicated a significant correlation between the single-flavored Tripterygium Glycosides Tablets,oral Chinese medicine and immune inflammation,and improvement of liver and kidney function indexes. The results of the random walk model analysis indicated that the experimental group's Ig M and hs-CRP were superior to those of the control group in terms of random fluctuation maximum,walking positive growth rate,comprehensive evaluation index increasing rate,comprehensive improvement rate,comprehensive evaluation index recording times,and expected improvement value. The results of this study showed that the single administration of Tripterygium Glycosides Tablets can effectively improve the immune inflammatory metabolic index of patients with rheumatoid arthritis,and the combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine could alleviate the immune inflammatory index of RA patients and reduce liver and kidney dysfunction compared with simple oral administration. The comprehensive evaluation Ig M and hs-CRP in the group of combined administration of Tripterygium Glycosides Tablets and traditional Chinese medicine were better than those in the group of the Tripterygium Glycosides Tablets. There was a long-term correlation between the comprehensive evaluation index and the intervention measures of the two groups of patients.

[Effect of traditional Chinese medicine invigorating spleen unit therapy on inflammatory markers in patients with osteoarthritis based on random walk model].

To evaluate the effect of traditional Chinese medicine(TCM) invigorating spleen unit therapy on inflammatory markers of osteoarthritis(OA) patients by random walk model. The patient information was collected by the data processing system of medical records of the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. In-patient information of the department of rheumatology of the hospital between June 2012 and December 2016 was collected and summarized. Based on the use of traditional Chinese medicine decoction and hospital-prepared compound Qiyi Capsules(Xinfeng Capsules),the patients were divided into the unit therapy group and the simple endotherapy group. The random walk model was used to evaluate the effect of traditional Chinese medicine invigorating spleen unit therapy on TCM spleen therapy unit(ESR) and high sensitive C reactive protein(hs-CRP). A total of 3 517 cases of OA patients met the study requirements. The simple endotherapy group had 1 771 cases(50. 36%),while the unit therapy group had 1 746 cases(49. 64%). The baseline data analysis showed that the general information of the cases,the TCM oral intake frequency and the core prescription information had no statistically significant difference,with comparability. The unit therapy group showed the maximum ESR stochastic volatility at 924,walking step number of 1 771,forward walking growth rate at 0. 264 5,ratio at3. 78,random fluctuation power law at 0. 306 5± 0. 076 8,positive increase rate of comprehensive evaluation index at 0. 264 5,and comprehensive evaluation index record number of 1 771; whereas the simple endotherapy group showed the maximum ESR random fluctuation value at 478,walking step number of 1 399,forward walking growth rate at 0. 152 4,ratio at 6. 56,random fluctuation power law at 0. 347 4±0. 101 7,positive increase rate of comprehensive evaluation index at 0. 152 4,and comprehensive evaluation index record number of 1 399. The unit therapy group showed the maximum hs-CRP random fluctuation value at 391,walking step number of1 081,forward walking growth rate at 0. 178 1,ratio at 5. 62,random fluctuation power law at 0. 343 6±0. 094 7,positive increase rate of comprehensive evaluation index at 0. 178 1,and comprehensive evaluation index record number of 1 081; while the simple endotherapy groups showed the maximum hs-CRP random fluctuation value at 210,walking step number of 797,forward walking growth rate at0. 113 2,ratio at 8. 83,random fluctuation power law at 0. 382 6±0. 109,positive increase rate of comprehensive evaluation index at0. 113 2,and comprehensive evaluation index record number of 797. According to our department of rheumatism,there was a longrange correlation between the two groups in the comprehensive evaluation index and the intervention measures. TCM spleen strengthening unit therapy has a better effect in alleviating the inflammatory index of OA than traditional Chinese medicine.

Synergism of amlodipine and candesartan on blood pressure reduction and organ protection in hypertensive rats.

This study was designed to investigate the possible synergism of amlodipine and candesartan on the reduction of blood pressure (BP) in hypertensive rats. The end organ protection was also observed. In acute experiment, spontaneously hypertensive rats (SHRs) were treated with intragastric administration of amlodipine (0.5, 1, 2, 3 mg/kg), candesartan (1, 2, 3, 4, 6, 8 mg/kg), and 14 different combinations to find the possible ratio of synergistic interaction. In two kidneys, one clip (2K1C) rats, the effects of amlodipine (1 mg/kg), canderastan (2 mg/kg) and their combination on BP reduction were also observed. In chronic study, SHRs were treated with amlodipine (1 mg/kg), candesartan (2 mg/kg), and their combination for 5 months. Organ damage evaluation was performed after BP recording. The probability sum test (q test) was used to evaluate the synergistic action. There is a synergistic interaction between amlodipine and candesartan on BP reduction. The optimal dose ratio is 1:2. The synergistic effect was also confirmed by 2K1C hypertensive rats. In chronic study, this combination (1:2) possessed an obvious synergism on the reduction of BP and BP variability (BPV) and protection on end organs. Multiple regression analysis showed that heart and aortic hypertrophy indexes and glomerular damage parameters were positively related to BP and BPV. In conclusion, combination of amlodipine and candesartan exhibited a potent antihypertensive effect and possessed an obvious synergism on BP reduction and organ protection in hypertension. The optimal proportion was 1:2. BP and BPV reduction may both importantly contribute to end organ protection.

A combination of neostigmine and anisodamine protects against ischemic stroke by activating α7nAChR.

BACKGROUND: Increasing endogenous acetylcholine by neostigmine decreased the ischemic cerebral injury. The off-target action on muscarinic receptor produced a variety of adverse effects and limited the clinical application on stroke. AIM: We combined neostigmine with anisodamine and investigated the neuroprotection and mechanism. METHODS: Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion. Neuroprotective action of neostigmine in combination with anisodamine at varying ratios was examined to determine the optimal combination as well as ideal therapeutic window. Potential involvement of α7 nicotinic acetylcholine receptor was examined by measuring the infarct size, the expression of proinflammatory cytokines, and the biomarkers of apoptosis in α7 nicotinic acetylcholine receptor knockout mice. A set of in vitro experiments was conducted in RAW264.7 cells to probe into potential molecular mechanisms. RESULTS: The neostigmine/anisodamine combination conferred neuroprotection. The protection was most potent at a ratio of 1:500. At such a ratio, the combination increased the binding of acetylcholine to α7 nicotinic acetylcholine receptor and reduced proinflammatory cytokines. The neuroprotection was evident only in wild-type and not in α7 nicotinic acetylcholine receptor knockout mice. The combination significantly decreased the expression of Bad and Bax, and increased Bcl-2 and Bcl-xl in α7 nicotinic acetylcholine receptor wild-type mice but not in knockout mice. The combination did not affect caspase-8, cleaved caspase-8, or caspase-12. CONCLUSIONS: Current study identified the optimal combination of neostigmine and anisodamine against ischemic stroke, and indicated that the acetylcholine-α7 nicotinic acetylcholine receptor is involved in the protective effects.

ALDH2 protects against stroke by clearing 4-HNE.

Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that metabolizes ethanol and toxic aldehydes such as 4-hydroxy-2-nonenal (4-HNE). Using an unbiased proteomic search, we identified ALDH2 deficiency in stroke-prone spontaneously hypertensive rats (SHR-SP) as compared with spontaneously hypertensive rats (SHR). We concluded the causative role of ALDH2 deficiency in neuronal injury as overexpression or activation of ALDH2 conferred neuroprotection by clearing 4-HNE in in vitro studies. Further, ALDH2-knockdown rats revealed the absence of neuroprotective effects of PKCε. Moderate ethanol administration that is known to exert protection against stroke was shown to enhance the detoxification of 4-HNE, and to protect against ischemic cerebral injury through the PKCε-ALDH2 pathway. In SHR-SP, serum 4-HNE level was persistently elevated and correlated inversely with the lifespan. The role of 4-HNE in stroke in humans was also suggested by persistent elevation of its plasma levels for at least 6 months after stroke. Lastly, we observed that 21 of 1 242 subjects followed for 8 years who developed stroke had higher initial plasma 4-HNE levels than those who did not develop stroke. These findings suggest that activation of the ALDH2 pathway may serve as a useful index in the identification of stroke-prone subjects, and the ALDH2 pathway may be a potential target of therapeutic intervention in stroke.

Involvement of acetylcholine-α7nAChR in the protective effects of arterial baroreflex against ischemic stroke.

AIMS: Decreased baroreflex sensitivity is associated with poor outcome in many cardiovascular diseases including stroke, but the molecular mechanism underlying this relationship is unclear. This work was designed to test the hypothesis that acetylcholine (ACh) and α7 nicotinic ACh receptor (α7nAChR) mediate the protection of arterial baroreflex against stroke. METHODS: Sinoaortic denervation (SAD) was used to impair the function of arterial baroreflex, and anticholinesterase agents were used to activate the cholinergic system and increase endogenous ACh. Middle cerebral artery occlusion (MCAO) was performed in the α7nAChR knockout (KO) mice and Sprague-Dawley rats. RESULTS: We found decreased expression of vesicular ACh transporter (VAChT) and α7nAChR in rat brain after SAD. In rats subjected to MCAO, neostigmine significantly reduced the infarct size. The protective effects of neostigmine were abolished by selective nAChR antagonist vecuronium but not by mAChR antagonist anisodamine. In addition, the effect of neostigmine disappeared in α7nAChR KO mice. In cultured neurons, ACh inhibited cell death induced by H(2) O(2) . In cultured microglial cells, ACh decreased the release of proinflammatory cytokines induced by lipopolysaccharide. These in vitro effects were blocked by selective α7nAChR antagonists. CONCLUSION: Taken together, these findings indicate that the ACh-α7nAChR involved in the protective effects of arterial baroreflex against ischemic stroke.