Objective To investigate the effects of mirabegron combined with electroacupuncture on urodynamic parameters in rats with overactive bladder(OAB)by regulating the insulin receptor substrate(IRS)/phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(AKT)/endothelial nitric oxide synthase(eNOS)signaling pathway.Methods Sixty female SD rats were selected as the study subjects and randomly divided into control group,model group,mirabegron group,electroacupunc-ture group,and mirabegron+electroacupuncture group using a random number table method,with 12 rats in each group.Except for the control group,the other groups were used to establish OAB rat models by the bladder outlet obstruction method.The mirabegron group received intragastric administra-tion of 8 mg/kg mirabegron suspension.The electroacupuncture group received electroacupuncture stimu-lation for 5 min each time.The mirabegron+electroacupuncture group received intragastric administration of mirabegron suspension while undergoing electroacupuncture stimulation.The control group,the model group,and the electroacupuncture group received an equal volume of normal saline intragastrically once a day for 7 consecutive days.Urodynamic parameters(basal micturition pressure,peak mictu-rition pressure,micturition interval,and residual urine volume)were measured in each group.After measuring bladder blood flow using a laser speckle imaging instrument,the wet weight of the rat bladder tissue was weighed,and the bladder index was calculated.Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of urinary nerve growth factor(NGF),and interleu-kin-1[3(IL-1β),malondialdehyde(MDA),and superoxide dismutase(SOD)in bladder tissue.Western blot was used to detect the expression levels of phosphorylated(p)-IRS1,p-PI3K,p-AKT and p-eNOS in bladder tissue.Results Compared with the model group,the basal micturition pressure,peak micturition pressure,and bladder index were all decreased,the residual urine vol-ume was reduced,the micturition interval was prolonged,the bladder blood flow was increased,the SOD content in bladder tissue was increased,the NGF content in urine and the IL-1 β and MDA contents in bladder tissue were decreased,and the expression levels of p-IRS1,p-PI3K,p-AKT and p-eNOS were increased in the mirabegron group,the electroacupuncture group,and the mirabegron+electroacupuncture group,with statistically significant differences(P＜0.05 or P＜0.01).The results of the above indicators in the mirabegron+electroacupuncture group were all better than those in the mirabegron group and the electroacupuncture group,with statistically significant differ-ences(P＜0.05 or P＜0.01).Conclusion Mirabegron combined with electroacupuncture can improve urodynamic parameters in OAB rats than used alone,and its mechanism may be related to the activation of the IRS/PI3K/AKT/eNOS signaling pathway.

Neuronal intranuclear inclusion disease（NIID）is a rare hereditary neurodegenerative disorder that can affect multiple systems. However，it is uncommon for urinary dysfunction to be the initial symptom. This article reports five cases. The five patients began to experience voiding dysfunction such as frequent urination，weak urination，and incomplete urination at the mean ages of 55.4（47 - 65）years old. Four months to twelve years after urinary onset，neurological symptoms such as headache，memory decline，transient loss of consciousness，and unsteady gait began to appear. Four of the five cases had a family history. Brain MRI revealed the “ribbon sign” or “crest sign” in all cases. Skin biopsy revealed eosinophilic inclusions in the cell nuclei，and NOTCH2NLC gene testing identified abnormal GGC mutations. Three of the five patients underwent cystostomy due to secondary hydronephrosis，while the other two received no special treatment. After a follow-up of 18 to 35 months since diagnosis，the patients who underwent cystostomy had normal renal function. Neurological symptoms in all five patients worsened to varying degrees.

Neuronal intranuclear inclusion disease（NIID）is a rare hereditary neurodegenerative disorder that can affect multiple systems. However，it is uncommon for urinary dysfunction to be the initial symptom. This article reports five cases. The five patients began to experience voiding dysfunction such as frequent urination，weak urination，and incomplete urination at the mean ages of 55.4（47 - 65）years old. Four months to twelve years after urinary onset，neurological symptoms such as headache，memory decline，transient loss of consciousness，and unsteady gait began to appear. Four of the five cases had a family history. Brain MRI revealed the “ribbon sign” or “crest sign” in all cases. Skin biopsy revealed eosinophilic inclusions in the cell nuclei，and NOTCH2NLC gene testing identified abnormal GGC mutations. Three of the five patients underwent cystostomy due to secondary hydronephrosis，while the other two received no special treatment. After a follow-up of 18 to 35 months since diagnosis，the patients who underwent cystostomy had normal renal function. Neurological symptoms in all five patients worsened to varying degrees.

Objective In this study,we investigated the active ingredients,targets and molecular mechanisms of Bai zhi based on network pharmacology and mRNA transcriptome sequencing technology for the treatment of microgravity induced bone loss,with a view to providing new therapeutic strategies for microgravity induced bone loss diseases.Methods Investigating the antagonistic effect of the traditional Chinese medicine Bai zhi on microgravity induced bone loss by constructing a hindlimb unloading mice model.18 healthy male mice were randomly divided into Control,HLU and HLU+BZ groups,6 mice in each group,and the effects of Bai zhi on the bone mineral density of the model mice were evaluated after 28 d of continuous gavage.Screening the active ingredients and targets of Bai zhi through TCMSP,Genecards,OMIM,TTD,DisGeNET and other network pharmacology databases.A hindlimb tail suspension unloading animal(HLU)model was established,and the differentially expressed genes(DEGs)responding to mechanical unloading were analyzed using transcriptome sequencing methods,and the targets of Bai zhi active ingredients intersected with the targets of the differentially expressed genes responding to mechanical unloading,so that the core gene targets of Bai zhi for intervening in weightlessness bone loss could be obtained;Construction of Bai zhi component-target protein interaction network(PPI)using String database and Cytoscape software,and enrichment and analysis of key signaling pathways of Bai zhi for treating microgravity induced bone loss using R Studio software.Results Bai zhi effectively restored bone loss in hindlimb tail suspension mice.By quantitative analysis of bone mineral density scanning of hindlimb tail suspension mice,the results showed that Bai zhi significantly restored the loss of bone mineral density in the model mice(P?

Objective:To investigate the protective effect of calycosin on microgravity-induced muscle atrophy by using real-time shear wave elastography (RT-SWE).Methods:The potential key active compound calycosin of anti-muscular atrophy in Astragali Radix was screened by systematic pharmacology. Eighteen healthy male Sprague-Dawley rats were divided into the control group [0.5% carboxymethyl cellulose-Na (CMC-Na) gavage], the hind limb unloading (HLU)+CMC-Na group (HLU+0.5% CMC-Na gavage), and the HLU+calycosin group (HLU+calycosin gavage) according to the method of random number table, with 6 rats in each group. After 28 d of continuous administration, the organ index, the toxicity of liver and kidney, the wet weight of soleus muscle and the ratio of muscle weight to body weight was measured, respectively. The non-invasive RT-SWE was used to evaluate the thickness and elastic modulus of rectus femoris in each group and the one-way analysis of variance was used to compare the differences among groups.Results:There was no significant difference in organ index, liver and kidney toxicity among different groups of rats (all P>0.05). There were significant differences in the weight of soleus muscle and the ratio of muscle weight to body weight among different groups of rats ( F=60.66, 56.44, both P<0.001). Compared with the HLU+CMC-Na group, the weight of soleus muscle and the ratio of muscle weight to body weight in the HLU+calycosin group increased, and the differences were significant (both P<0.01). The thickness and elastic modulus of rectus femoris of rats in different groups were significantly different ( F=35.47, 14.68, both P<0.001). Compared with the HLU+CMC-Na group, the muscle thickness and elastic modulus of rats in HLU+calycosin group were increased, and the differences were significant (both P<0.01). Conclusions:The treatment of calycosin has no side effects on rats. It can improve the thickness and elastic modulus of rectus femoris, and effectively prevent microgravity-induced muscle atrophy, which may provide a new candidate drug for astronaut muscular atrophy.

Objective:To investigate the protective effect of calycosin on microgravity-induced muscle atrophy by using real-time shear wave elastography (RT-SWE).Methods:The potential key active compound calycosin of anti-muscular atrophy in Astragali Radix was screened by systematic pharmacology. Eighteen healthy male Sprague-Dawley rats were divided into the control group [0.5% carboxymethyl cellulose-Na (CMC-Na) gavage], the hind limb unloading (HLU)+CMC-Na group (HLU+0.5% CMC-Na gavage), and the HLU+calycosin group (HLU+calycosin gavage) according to the method of random number table, with 6 rats in each group. After 28 d of continuous administration, the organ index, the toxicity of liver and kidney, the wet weight of soleus muscle and the ratio of muscle weight to body weight was measured, respectively. The non-invasive RT-SWE was used to evaluate the thickness and elastic modulus of rectus femoris in each group and the one-way analysis of variance was used to compare the differences among groups.Results:There was no significant difference in organ index, liver and kidney toxicity among different groups of rats (all P>0.05). There were significant differences in the weight of soleus muscle and the ratio of muscle weight to body weight among different groups of rats ( F=60.66, 56.44, both P<0.001). Compared with the HLU+CMC-Na group, the weight of soleus muscle and the ratio of muscle weight to body weight in the HLU+calycosin group increased, and the differences were significant (both P<0.01). The thickness and elastic modulus of rectus femoris of rats in different groups were significantly different ( F=35.47, 14.68, both P<0.001). Compared with the HLU+CMC-Na group, the muscle thickness and elastic modulus of rats in HLU+calycosin group were increased, and the differences were significant (both P<0.01). Conclusions:The treatment of calycosin has no side effects on rats. It can improve the thickness and elastic modulus of rectus femoris, and effectively prevent microgravity-induced muscle atrophy, which may provide a new candidate drug for astronaut muscular atrophy.

Objective To explore the effect of salmon calcitonin on osteoporosis induced by spinal cord injury. Methods 100 patients with osteoporosis induced by spinal cord injury from September 2011 to September 2014 in our department were included. They were randomly divided into control group (n=50) and observation group (n=50). The control group received vitamin D3 only, while the observation group received vitamin D3 combined with salmon calcitonin on the basis of rehabilitation physiotherapy, for 6 months. Visual Analogue Scale (VAS) of pain was evaluated in different periods. The bone mineral density (BMD) of lumbar spine and femoral neck, the parathyroid hormone (PTH), bone gla protein (BGP) and 1,25- dihydroxy vitamin D3 (1,25-(OH)2D3) were tested and recorded. Results The VAS score was lower in the observation group than in the control group 1, 2, 3 and 6 months after treatment (P<0.001). The BMD of lumbar spine and femoral neck was significantly higher, the PTH and BGP were significantly lower and the 1,25-(OH)2D3 was significantly higher in the observation group than in the control group after treatment (P<0.001). Conclusion Combination of salmon calcitonin can effectively reduce the bone pain and improve the BMD in patients with osteoporosis induced by spinal cord injury.

Objective To evaluate the effects of exendin-4 on glial brillary acidic protein (GFAP ) and interleukin-1β(IL-1β) expression in hippocampi of aged rats .Methods Forty-eight healthy male Sprague-Dawley rats ,aged 22-24 weeks ,weighing 500-700 g ,were randomly divided into 4 groups (n=12 each) using a random number table:control group (group C ) ,exendin-4 group (group E ) ,operation group (group O ) and exendin-4 plus operation group (group OE) .The rats were anesthetized with intraperitoneal fentanyl and droperidol .Groups C and E did not receive anesthesia or splenectomy .In O and OE groups ,splenectomy was carried out .In E and OE groups , exendin-4 5 μg/kg was injected intraperitoneally at 30 min before skin incision and 12 h after operation .C and O groups received the equal volume of normal saline instead of exendin-4 .Learning and memory function was assessed using Morris water maze test (escape latency (EL) and total swimming distance (TSD) at 1 day before operation (T0 ) .The fasting blood glucose was measured after anesthesia (T1 ) ,at the end of operation (T2 ) and on postoperative day 1 (T3 ) .The rats were sacrificed after assessment of the cognitive function at T 3 and the hippocampi were removed for determination of the expression of GFAP (by immuno-histochemistry ) and IL-1β(by Western blot ) .Results There was no significant difference in the EL and TSD at T0 between the four groups ( P>0.05) .Compared with group C ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was increased at T2 ,3 ,and the expression of IL-1βand GFAP was up-regulated at T3 in O and OE groups ( P<0.05) .Compared with group O ,the EL and TSD were significantly prolonged at T3 and fasting blood glucose was decreased at T2 ,3 ,and the expression of IL-1βand GFAP was down-regulated at T3 in group OE ( P<0.05) . Conclusion Exendin-4 can improve the postoperative cognitive function of aged rats by inhibiting inflammatory responses in hippocampi and maintaining stable perioperative blood glucose .