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 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.

Objective To explore the clinical effect of two-points approach vascular stenting technique (via both the femoral artery and posterior tibial artery of the affected side) in repairing blunt popliteal artery injuries.Methods The clinical data of eleven patients with blunt popliteal arterial injuries,who were treated with two-points approach vascular stenting technique during the period from March 2011 to March 2015 as single-approach stenting repair failed,were retrospectively analyzed.First,antegrade puncture of the femoral artery on the affected side with subsequent angiography was performed to evaluate the arterial injury,when the attempt to push the guide-wire to pass the injured arterial segment by twisting manipulation failed the puncture of posterior tibial artery was immediately carried out,then,a 4-French single-bend catheter together with a goose neck snare was inserted.Guide-wire capture technique was used to gasp the guide-wire in the injured artery segment,and then the guide-wire was pulled to pass through the injured artery segment.In this way,the guide-wire working circle was reliably established,and along the guide-wire the vascular stent was inserted and delivered to the right site to repair the injured artery.A 6-French guiding catheter was inserted to perform thrombus aspiration for eliminating the distal outflow obstruction caused by thrombus.Thrombolytic therapy with small dose of urokinase through a indwelling catheter was employed for the treatment of peripheral arterial thrombosis.Results The technical success rate was 100％.Angiography revealed that partial transection of artery was detected in 7 patients,and complete transection of artery in 4 patients.A total of 16 stents were implanted.No perioperative mortality or procedure-related complication occurred.All patients were followed up for 13-24 months,with a mean of (18.7±3.8) months.In-stent thrombosis occurred in 2 patients,which was treated with thrombolytic therapy and the blood flow recovered;severe in-stent stenosis (＞70％) was seen in 3 patients,in whom the blood flow returned to normal after balloon dilation therapy;mild in-stent stenosis (＜30％) was found in 6 patients,and no special treatment was given.During the follow-up period,no stent fracture,deformation,or displacement was seen,and no patient needed to have an amputation surgery.Conclusion In treating blunt popliteal artery injuries,two-points approach vascular stenting technique can effectively reduce the operation time,rapidly recover the blood flow of the injured popliteal artery,and shorten the time of limb ischemia.This technique has very satisfactory clinical shortterm effect.

Objective To evaluate the efficacy of endovascular interventional minimally invasive techniques in treatment of acute brachial artery injury.Methods A retrospective case series study was designed to analyzed data of 16 cases (11 males and 5 females) sustaining acute brachial artery injury treated from March 2011 to August 2016.Mean age was 47.9 years (range,27-66 years).Left upper extremity vascular injury occurred in 7 cases and right upper extremity vascular injury occurred in 9.There were 13 cases of arterial intima injury and 3 of arterial pseudoaneurysm.All patients underwent endovascular therapy including stent implantation and balloon dilatation.Angiography was used to evaluate the repair of brachial artery and the operation time was recorded.Improvements of distal limb arterial pulse and limb ischemic symptoms were observed,and the patients who were followed up with stent lumen stenosis more than 50％ received endovascular treatment again.Results The procedures was successful in all patients,with operation time of 30-75 minutes (mean,45 minutes).After the insertion of a stent,recovered brachial artery blood flow and disappeared pseudoaneurysm were observed on angiography,without occurrence of stent stenosis or contrast extravasation.Symptoms of local pain and numbness were alleviated,and blood supply of the distal brachial artery was improved after operation.All patients were followed up for 3-36 months(mean,16.7 months).The false aneurysm did not recur.Two cases of stent stenosis more than 50％ had a second balloon dilation procedure and the blood flow returned to normal.Stent patency was found in 14 cases with stent stenosis of less than 50％.During the follow-up period,no ischemic necrosis,displacement of the stent or stent fracture were found.Conclusion For acute brachial artery injury,endovascular management exhibits higher technical success rate and good clinical outcome with a low incidence of complications.

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.

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.