Objective:To investigate the effect of botulinum neurotoxin type A (BoNT/A) on Nav1.3 sodium channels and the function of sodium current in neuropathic pain.Methods:Eighteen adult rats had a spared nerve injury (SNI) induced and then were randomly divided into a saline group and a BoNT/A group, each of 9. Another 9 rats formed a fake operation group, Five days after the SNI, BoNT/A (7U/kg or 15U/kg) or saline was subcutaneously administered into the plantar surface of a hindpaw. On the 3rd, 7th and 14th day after the injection, the SNI rats′ paw withdrawal threshold was measured. On the 7th and 14th day the expression of Nav1.3 protein in dorsal root ganglion (DRG) neurons was examined using western blotting, while any change in the functional tetrodotoxin-sensitive (TTX-S) current was recorded using the patch clamp technique.Results:Administration of BoNT/A at either 7U/kg or 15U/kg significantly increased the SNI-induced mechanical allodynia. The expression of Nav1.3 protein in DRG neurons increased significantly after the SNI, but had decreased significantly by the 7th and 14th day after the administration of BoNT/A. BoNT/A significantly decreased the current density in TTX-S sodium channels in DRG neurons following SNI.Conclusion:Administration of BoTN/A affects the expression of Nav1.3 protein and functional TTX-S current, relieving neuropathic pain.

Objective To explore the clinical effect of tonifying kidney and removing stasis decoction combined with the traditional treatment in the treatment of 80 cases with chronic nephritis .Methods 80 patients with chronic nephritis were randomly divided into observation group and control group according to the digital table ,40 cases in each group.The control group was given conventional western medicine treatment ,the observation group was given tonifying kidney and removing stasis decoction on the basis of the control group .The clinical effect of the two groups was compared.Results Compared with before treatment [(0.9 ±0.3) points,(0.7 ±0.3) points,(0.9 ± 0.3)points,(0.8 ±0.2)points,(1.7 ±0.8)g,(1.7 ±0.9)mmol/L,(5.7 ±1.4)mmol/L,(106.8 ±24.5)μmol/L, (8.0 ±2.6)mmol/L;(0.9 ±0.3)points,(0.7 ±0.2)points,(0.9 ±0.3)points,(0.9 ±0.3)points,(1.6 ± 0.3)g,(1.8 ±0.4)mmol/L,(5.8 ±1.3)mmol/L,(107.2 ±20.1)μmol/L,(7.9 ±2.2)mmol/L],the scores of edema,sore throat,backache and the symptoms such as dizziness anaemic and 24 h urine protein,triglyceride,total cholesterol,uric creatinine and urea nitrogen levels after treatment [(0.2 ±0.2)points,(0.3 ±0.2)points,(0.3 ± 0.2)points,(0.2 ±0.2)points,(0.9 ±0.5)g,(1.4 ±0.5)mmol/L,(4.7 ±1.2)mmol/L,(91.2 ±19.8)μmol/L, (6.0 ±1.8)mmol/L;(0.5 ±0.2) points,(0.5 ±0.2) points,(0.6 ±0.2) points,(0.5 ±0.2) points,(0.7 ± 0.2)g,(0.9 ±0.3)mmol/L,(4.2 ±0.8)mmol/L,(79.5 ±11.7)μmol/L,(4.1 ±1.2)mmol/L] were significantly decreased,the differences were statistically significant (t=6.231,6.342,6.411,6.125,5.023,5.112,3.147,1.225, 2.014,all P<0.05).And the improvements of the observation group were statistically better than those of the control group (t=5.145,4.223,5.021,4.301,6.821,6.014,2.011,0.365,1.136,all P<0.05).Conclusion Tonifying kidney and removing stasis decoction in the supplemental treatment of chronic nephritis has high efficacy ,can remove blood stasis , activate blood and greatly alleviate the symptoms , so this method can be widely used in clinical treatment.

Objective To observe the effects of dual-task motor training on motor and balance function for stroke patients. Methods From January, 2016 to June, 2017, 30 patients with stroke were assigned randomly into control group (n = 15) and treatment group (n = 15). Both groups accepted routine physical therapy, the control group accepted anti-gravity treadmill training, while the treatment group accepted dual-task training with anti-gravity treadmill, for four weeks. They were measured with balance training and evaluation system, and assessed with Fugl-Meyer Assessment-lower extremity (FMA-L), Berg Balance Scale (BBS) and modified Barthel Index (MBI), before and after treatment. Results The range of swaying on X axial (Rx) and Y axial (Ry), as well as rectangle area (RecArea) decreased after treatment in the treatment group (t > 4.719, P < 0.001), while RecArea decreased in the control group (t = 5.069, P < 0.001). Ry and RecArea were less in the treatment group than in the control group (t > 2.288, P < 0.05). The scores of FMA-L, BBS and MBI improved after treatment in both groups (t > 7.316, P < 0.001), and improved more in the treatment group than in the control group (t > 2.322, P < 0.05). Conclusion The dual-task training via anti-gravity treadmill may improve motor and balance function in stroke patients, and promote the activities of daily living.

Objective To explore the efficacy of endovascular treatment for closed articular artery injuries.Methods The clinical data of 13 patients from Jan 2010 to Dec 2014 treated for closed articular artery injuries were analyzed retrospectively.The location,severity and extent of arterial injury were confirmed by intraoperative arteriography.The diameter and length of the injured arteries were measured.The guidewire was sent to the lesion site and working wire pathway was established.When the guidewire was difficult to pass through the lesion site,femoral and posterior tibial or radial artery may be used to establish working wire pathway.The stent or stent-graft was implanted through the contralateral femoral artery or distal end of ipsilateral artery.Results Intraoperative angiography confirmed intimal injury (n =2),partial transection (n =5),complete transection (n =5) and arteriovenous fistula (n =1).Eighteen stents or stent-grafts were implanted.Treatment was successful in all patients without peiropeartive death and procedure-related complications.All were followed up for 15 to 48 months and the mean follow-up was (30 ± 11) months.Three patients with stent lumen stenosis less than 50％ as showed by angiography.There was no stent fracture,displacement,or deformation.Conclusions Endovascular treatment for closed articular artery injuries is of less invasion,shorter operative time and quick postoperative recovery.

Objective To study the effect of bilateral arm training on cortical reorganization in cerebral infarction patients using blood oxygen level-dependent functional MRI (BOLD-fMRI).Methods Fourteen cerebral infarction subjects with moderate to severe upper limb impairment participated in this randomized and single-blinded training study.Subjects in the bilateral arm training group (n =7) practiced bilateral symmetrical or opposite activities,while the control group (n =7) performed conventional,mainly unilateral,arm training.Those in both groups received fMRI scans before and after the training with passive elbow movement as the task in the imaging.Results Both groups had significant improvements in their average scores on the Fugl-Meyer upper extremity assessment and in their modified Barthel index scores after the treatment,and there were no significant differences between the two groups.Brain activation had increased in both groups after the treatment,especially in the bilateral training group.After the treatment,the first motor area (M 1),the first somatosensory area and the supplementary motor area on both sides were activated in the bilateral training group.Moreover,for patients in the bilateral training group with injuries of moderate severity,the M1 of the opposite side tended to be activated,while for those more severely injured the same side had a tendency to be activated.Conclusion Convalescing subcortical infarction patients with moderate to severe upper limb impairment benefit from bilateral arm training in terms of motor activity and performing activities in daily life.It may be related to the normalization of inhibition between the hemispheres of the bilateral cerebral cortex and the reconnection of ipsilateral corticospinal pathways.

Objective:To analyze the situation of off-label drug use in fertility clinic of one hospital to provide scientific evidence for clinical rational drug use and further standardize the behavior of off-label drug use in clinical physicians. Methods:The outpatient prescriptions in the reproductive center of the hospital during January and December in 2016 were randomly selected, the off-label drug use prescriptions were statistically analyzed according to the drug package inserts, and the rationality of the off-label drug use were e-valuated by searching the related literatures. Results:A total of 4176 off-label drug use prescriptions were collected, the primary types of off-label drug use were off-label indication, off-label dose and off-label administration. The top 3 drugs with off-label use were aspi-rin enteric-coated tablets (42. 05%), dydrogesterone tablets (27. 37%) and levocarnitine oral solution (16. 02%). The most of off-label use was supported by evidence-based medicines, while unreasonable use still existed. Conclusion: Off-label drug use is very common in the reproductive center of the hospital. The hospital should pay more attention to the phenomenon and establish relevant management system to standardize the behavior of off-label drug use in order to reduce the legal risk and promote clinical rational drug use.

Objective:To analyze the situation of off-label drug use in fertility clinic of one hospital to provide scientific evidence for clinical rational drug use and further standardize the behavior of off-label drug use in clinical physicians. Methods:The outpatient prescriptions in the reproductive center of the hospital during January and December in 2016 were randomly selected, the off-label drug use prescriptions were statistically analyzed according to the drug package inserts, and the rationality of the off-label drug use were e-valuated by searching the related literatures. Results:A total of 4176 off-label drug use prescriptions were collected, the primary types of off-label drug use were off-label indication, off-label dose and off-label administration. The top 3 drugs with off-label use were aspi-rin enteric-coated tablets (42. 05%), dydrogesterone tablets (27. 37%) and levocarnitine oral solution (16. 02%). The most of off-label use was supported by evidence-based medicines, while unreasonable use still existed. Conclusion: Off-label drug use is very common in the reproductive center of the hospital. The hospital should pay more attention to the phenomenon and establish relevant management system to standardize the behavior of off-label drug use in order to reduce the legal risk and promote clinical rational drug use.

Objective To establish a HPLC method for determination of 18β-isomer in magnesium isoglycyrrhizinate. Methods The determination was performed by Agilent Extend-C18 column ( 4. 6 mm × 250 mm, 5 μm ) . Mobile phase consisted of 0. 1 mol·L-1 potassium dihydrogen phosphate buffer solution ( adjusted to pH 7. 0 with potassium hydroxide )-acetonitrile (80︰20) at the flow rate of 1.0 mL·min-1. The column temperature was 30 ℃, and the detection wavelength was set at 250 nm. Results The resolution of magnesium isoglycyrrhizinate and 18β-isomer was greater than 2.0. The linear range of them was 0.41-2.46μg·mL-1( r=0.9998) , the detection limit was 0.21 ng, and the average recovery were 100.2%,99.1%, 110.2%,RSD were 0.9%,0.1%,0.2%(n=3). Conclusion The method is simple and accurate, and can be used for determination of 18β-isomer in magnesium isoglycyrrhizinate.

Antibody drugs often show "heterogeneity",including the related isomers differing from one another in glycosylation,charge or molecular size.Most of these isomers come from post-translational modifications,such as aggregation,degradation,glycosylation,oxidation,deamidation or disulfide misfolding,of the recombinant protein in the "cell factories".These modifications not only influence the quality,safety and efficacy of the antibodies,but also serve as an important indication of product quality throughout the whole process of antibody production.This paper reviews the relationship between glycoslation,charge and size heterogeneities of monoclonal antibodies and drug efficacy,safety,pharmacokinetics as well as immunogenicity,contributing to a better understanding of the relationship between antibody structure and function.It will provide some support and guidance for the research and development of antibody drugs,especially biosimilars.

Aim To establish the rat model of Spleen-Qi deficiency, analyse the metabolic pathways and investigate the connection between the changed urinary metabolites and Spleen-Qi deficiency, in order to explore the potential mechanisms of Spleen-Qi deficiency.Methods With the binding methods of diarrhea induced by bitter and cold, abnormal of starvation and excessive tiredness, the rat Spleen-Qi deficiency model was established.Then the activity of creatine phosphokinase(CPK) was detected.The endogenous metabolites in the urine were detected by NMR, and the data were analyzed with multivariate and statistical methods.Then the metabolites were selected that could be clearly distinct in the two groups with the fold change value(>1.2) and the P<0.05 of Student′s t-test.Both the pathway analysis and enrichment analysis were performed with Metabo Analyst 3.0.Results Compared with the normal rats, the activity of CPK decreased significantly in model rats(P<0.05).A significant separation appeared in the principal components analysis(PCA) score plot when the control group and the model group were compared, indicating that the Spleen-Qi deficiency model was successfully duplicated.The 33 differential metabolites, which mainly involved in the metabolic pathways, were distinguished from the comparision of Spleen-Qi deficiency model group and control group.The metabolic pathways was related to energy metabolism, amino acid metabolism, nucleotide metabolism and disturbance of gut microbes.Conclusions The main energy metabolic pathways (tricarboxylic acid cycle, glycolysis and liquid oxidation) may be disturbed in Spleen-Qi deficiency rats.The energy supply function is suppressed, which leads to the fatigue and weight loss in rats.