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OBJECTIVE To study the effects of Yishen daluo decoction on inflammatory factors and cyclic adenosine monophosphate（cAMP）/protein kinase A （PKA）/cAMP response element binding protein （CREB） signal pathway in experimental autoimmune encephalomyelitis （EAE） model mice by inhibiting the expressions of β-arrestin1， and to explore the mechanism of Yishen daluo decoction in the treatment of EAE. METHODS Sixty mice were randomly divided into normal group， model group， TCM group （Yishen daluo decoction 20 g/kg）， positive control group （prednisone acetate 3.9 mg/kg）， β-arrestin1 siRNA adeno- associated virus （AAV-β） group， AAV-β+TCM group， with 10 mice in each group. Except for normal group， EAE model was made in other groups. AAV-β group and AAV-β+TCM group were injected with AAV-β via tail vein to interfere with the expression of β -arrestin1 protein. Starting from the 8th day of modeling， they were given corresponding drug solution/normal saline intragastrically， once a day， for consecutive 14 days. The neurological function score of mice was detected； the pathological and morphological changes were observed in the brain and spinal cord tissues of mice； the serum levels of inflammatory factors [interleukin-2 （IL-2）， IL-23， interferon-γ （IFN-γ）] in mice were determined； the expressions of β-arrestin1， cAMP， PKA and CREB in brain and spinal cord were detected. RESULTS Compared with normal group， neurological function scores， serum levels of inflammatory factors， and protein expressions of β-arrestin1 in brain and spinal cord were significantly increased （P＜0.05 or P＜ 0.01）； protein expressions of PKA， CREB and cAMP in brain and spinal cord were decreased significantly（P＜0.05 or P＜0.01）. The deep staining of cellular shrinkage and aggregation of inflammatory cells were observed in most neurons of the brain and spinal cord， with varying degrees of demyelinating. Compared with model group， the neurological function scores， pathological changes in brain and spinal cord tissues， and most indicators （except for CREB and cAMP proteins in the brain tissue of AAV-β group） were significantly reversed （P＜0.05 or P＜0.01）.Compared with AAV- β group， the neurological function scores， the levels of IFN-γ in serum and β-arrestin1 in spinal cord were significantly decreased （P＜0.05 or P＜0.01）， PKA and cAMP in brain and spinal cord tissues were significantly increased in AAV- β +TCM group （P＜0.05 or P＜0.01）. CONCLUSIONS Yishen daluo decoction can inhibit the expression of β-arrestin1 in the central nervous system thus activating the cAMP/PKA/CREB signaling pathway， relieving nervous system inflammation， and ultimately alleviates the symptoms of EAE.
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BACKGROUND: Inflammatory cells or inflammatory factors participate in the proliferation and differentiation of skeletal muscle satellite cells after denervation injury, and play an important role in the pathological process of skeletal muscle denervation. OBJECTIVE: To study the effects of passive training on skeletal muscle structure, function and expression of Actin and inflammatory factors in rats with denervated muscle atrophy. METHODS: Thirty Sprague-Dawley rats were randomly divided into sham operation group, model group and training group. In the model group and the training group, the sciatic nerve was exposed and cut off the sciatic nerve, while the sciatic nerve in the sham operation group was exposed but not cut off. Two months after modeling, rats in the training group underwent passive rehabilitation training with self-made drum for 2 months, and then the degree of muscle atrophy and motor function were evaluated by muscle wet weight ratio and Basso, Beattie and Bresnahan score. The muscle fiber fine structure and cross-sectional area were observed by hematoxylin-eosin staining, and the expression of Actin, tumor necrosis factor-α, interleukin-6 and interleukin-1β in each group was detected by immunohistochemical staining. The study protocol was approved by the Laboratory Animal Welfare Ethics Committee of Shenyang Medical College with the approval No. SYYXY2015010601. RESULTS AND CONCLUSION: The Basso, Beattie and Bresnahan score of the training group was higher than that of the model group. The wet weight ratio of the training group was higher than that of the model group; however, the cross-sectional area of the muscle fibers was lower than that of the model group (P < 0.001, P < 0.05). The expression of Actin in the training group was higher than that in the model group (P < 0.001), and the expression levels of tumor necrosis factor-α, interleukin-6 and interleukin-1β in the training group were lower than those in the model group (P < 0.001 or P < 0.05). To conclude, passive training can help to recover the muscle structure and function of denervated muscles, reduce the levels of inflammatory factors, prevent further muscle atrophy, and improve skeletal muscle strength.
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Objective To investigate the clinical diagnosis and treatment strategies for retroperitoneal paragangliomas and to enhance the diag?nostic and therapeutic levels of retroperitoneal paragangliomas. Methods The clinical data of 49 patients having retroperitoneal paragangliomas were retrospectively analyzed. We studied 21 males and 28 females between an age range 17 and 72 years(mean 45.6 years). Hypertension was observed in 19 patients,9 patients suffered from lumbago or abdominal pain,and an abdominal mass was noted in 2 cases. Physical examination re?vealed paragangliomas in 17 patients. The positive rate of localization was 77.5%(31/40),96.0%(47/49),and 100%(10/10)using B?ultra?sound,computed tomography,and MRI respectively. Serum catecholamines were measured in 19 patients,of which 16 cases(84.2%)showed ele?vated levels. Results In our study,49 patients underwent open surgery,5 patients showed multiple tumors,and 56 tumors were found during sur?gery. The most common tumor location was periaortic and pericaval(71.4%,40/56). There were 51 cases of surgery in 49 patients. 54 tumors of 49 cases were totally resected. The tumors measured 1.5?20.0 cm in diameter with a mean diameter 6.7 cm. 75%tumors had integral pelos,14.2%(8/56)invaded the surrounding organs and vessels,and 10.7%(6/56)required resection of adjacent organs. We followed up 43 patients between 6 and 138 months after surgery. Postsurgical recurrence was noted in 4 patients,and 2 patients developed metastases. One patient died from metas?tasis during the follow?up period. Conclusion Surgical resection might be the most effective method for treatment of retroperitoneal paraganglio?mas. Sufficient preoperative and perioperative management might be the key point of successful surgery. Lifelong follow?up is important as recur?rent tumors need resection.