Objective:Through reading a lot of literature on the critical path planning of FDA, analyzed the contribution and shortage of the critical path plan to China's medical device market access system.Methods: To analyze the critical path planning of FDA by using the method of literature review.Results: China should reference the critical path plan, reform the existing medical instrument market access system, improve the efficiency, simplify the procedure and promote the safety and development of the product.Conclusion: The research on the critical path planning of FDA is very important for the construction of China's modern medical device market access path.

BACKGROUND:So far steroid pulse therapy andsurgical decompressionarethe main accepted therapiesfor spinal cord injury, but these methods make no effects on injured neurons. Nerve growth factors and endogenous neural stem cels play a role in theneuronalregeneration and remyelination, which provides a newidea for spinal cord injury treatment.
OBJECTIVE:To explore the effect of the basic fibroblast growth factor on proliferation of endogenous neural stem cels after spinal cord injury and to analyze its relationship with the increased fluoro-gold labeled neurons.
METHODS:Totaly 48 Kunming mice were randomly divided into four groups including normal, spinal cord injury, treatment and sham operation groups. Acute spinal cord injury models were establishedin the spinal cord injury and treatment groups, andthe normal group was subjected to operationthat did not damage the spinal cord. At 2hoursafter regaining consciousness, the treatment group was givendailyinjection of MTPBS containing 25 μg/kg basic fibroblast growth factors and 1% album. And at 7 days, laminectomy was carried out again at the L1segment in the former three groups and a smal piece of sterile gelfoam soaked with fluoro-gold was inserted into the incision. The sham operation group was given no processing. Afterwards, mouse motor behavior was assessed using Rotarod and Platform Hang tests; neurons in the corticospinal and rubrospinal tracts were labeled with fluoro-gold; the number of endogenous neural stem cels positive for nestin was detected by immunohistochemistry method. Besides, the correlation betweenthe number offluoro-gold labeled neurons andthe number ofendogenous neural stem cels was assessed.
RESULTS AND CONCLUSION:The basic fibroblast growth factor could significantly improve the mouse motor behavior after spinal cordinjury. And the number of endogenous neural stem cels was significantly increased after the basic fibroblast growth factor injection, which was related to the increased fluoro-gold labeled neurons.In conclusion, basic fibroblast growth factors play an important role in the proliferation of endogenous neural stem cels after spinal cord injury. Furthermore, endogenous neural stem cels improve locomotive behaviors by encouraging the neuronalproliferation.

By using three-dimensional finite element analysis method, the necessity of tail joints in the establishment of finite model specifically for the widely used tail-suspended rat experiments in weightlessness simulation was explored. A weightlessness tail-suspended three-dimensional finite element rat model was established using CT scan and Abaqus software, and the computation and analysis were conducted using the same model. The stress distribution and displacement in tail, lumbar spine, pelvis and femur of a tail-suspended rat both with and without cartilage were simulated and calculated.The results showed that stress distribution and displacement of tail-suspended rat were quite different between rats with cartilage and without cartilage, which affected the calculation precision of the model. Accordingly the consideration of articular cartilage in establishing the tail-suspended three-dimension finite element rat model is quite necessary,In addition, the asymmetry of pelvis stress distribution of tail-suspended rat suggests that the degree of balance of tail-suspended rat will affect the stress distribution in rats.

Objective To study the effect of long‐acting nitrate on cardiac function and expression of AngⅡreceptor (ATR)subtypes in kidneys of chronic heart failure (CHF)rats after myocardial infarction .Methods Ninety male Wistar rats aged 10 weeks were randomly divided into control group (group A ,n=9) ,sham operation group (group B ,n=8) ,HF model group (group C ,n=9) , low Elantan dose group (group D ,n=9) ,high Elantan dose group (group E ,n=9) ,olmesartan group (group F ,n=9) ,and combined high Elantan dose and olmesartan group (group G ,n=8) .A HF model was established by ligating the left anterior descending artery .The animals received gastric drugs for 6 weeks .Their cardiac function was assyed by ultrasound echocardiography and expressions of AT1 R and AT2 R were detected by RT‐PCR and Western blot ,respectively .Results The PRA and AngⅡexpression levels were significantly higher ,the AT1 R expression level was significantly higher and the AT2 R expression level was significantly lower in group C than in group B (P<0 .01 ,P<0 .05) .The PRA and AngⅡexpression levels were significantly lower ,the AT1 R expression level was significantly lower and the AT2 R expression level was significantly higher in groups E‐G than in group C (P<0 .05 ,P<0 .01) .The receptor expression levels were much higher in group G than in group F (P<0 .05) .Conclusion Long‐term use of long‐acting nitrate can effectively improve cardiac function and protect renal function .

Objective To investigate the influence of blood pressure level on carotid intima‐media thickness (CIM T ) and plaque in elderly patients with coronary heart disease(CHD) .Methods 100 elderly CHD patients with hypertension admitted in our hospital from Jan .to Dec .2012 was collected .an epidemiological investigation was applied ,and blood pressure was measured .carotid CIMT and plaque were determined by colored Doppler ultrasound .multivariate linear regression model or Logistic regression model was used to analyze the effect of blood pressure on CIMT and plaque .Results A total of 100 subjects were enrolled .CIMT and plaque prevalence were (0 .7 ± 0 .1)mm ,45 .8% in 48 males and (0 .7 ± 0 .1)mm ,34 .6% in 52 females .the difference was statisti‐cally significant(χ2 =5 .609 ,P=0 .018) .multiple regression models showed that ,after adjusting relevant factors ,CIMT increased 0 .001 14 mm with SBP 1 mm Hg increase and CIMT increased 0 .001 18 mm with pulse pressure 1 mm Hg increase in males .Lo‐gistic regression model showed that the risk of plaque number >1 was higher in grade Ⅲhypertension compared to grade 1 hyper‐tension(OR= 2 .115 ,95% CI= 1 .128~ 3 .966 ,P= 0 .020) .Conclusion Elderly CHD patients with hypertension ,especially in males ,carotid CIMT increase while systolic BP and high pulse are high ,which cause the high risk of carotid artery plaque;hyperten‐sion is a independent risk factor for atherosclerosis in elderly CHD patients .

[Objective]To examine the effects of TGF-?1 on the production of ?-SMA and extracellular matrix in flexor tendon sheath fibroblasts. [Methods]Sheath fibroblasts were obtained from rabbit flexor tendons.Cell culture was supplemented with 5ng/ml of TGF-?1.After 48 hours incubation,the production of a-SMA was assayed by Western-Blot.The productions of collagen I and fibronectin in supernatants culture were examined using ELISA.[Results]Treatment with TGF-?1 significantly stimulated a-SMA production in flexor tendon sheath fibroblasts (P

Objective To study the force and pressure transmission through normal wrist,and the effect of transverse carpal ligament release on the biomechanics of carpal tunnel.Methods A 3-D finite element model of the wrist based on CT scan images was established.The load transmission of carpus and the distribution of contact stress on radiocarpal joint under axial compressive force on metacarpals as well as the effect of transverse carpal ligament(TCL)release on the displacement of carpal bones were computed and analyzed.Results The computational results of force and pressure transmission through normal carpus matched well with previous studies.The release of TCL resulted in radial and palmar displacement of the scaphoid,flexion and radial rotation of radiocarpal joint as well as a further radial deviation of the whole carpal tunnel.Conclusion A 3-D finite element model of the wrist that includes the carpal tunnel,distal radius and ulna and proximal metacarpals is developed.This model may simulate the load transmission better and contact stress distribution of carpal tunnel and radiocarpal joint,as well as provide an operational plateform for further deeply studing on biomechanical behavior of carpal structure.The computed and analyzed results of the effect of TCL release on the displacements of carpal bones can be served as related theoratic base on carpal tunnel syndrome,carpal tunnel release surgery and recovery after operation.

[Objective]To examine the difference of proliferation and ?-smooth muscle actin(?-SMA) expression between healing and normal medial collateral ligament(MCL) fibroblasts.[Method]Ten adult,male,Sprague-Dawley rats weighing between 350 and 375 g were used in this study.Normal and healing MCL were cut into small pieces in aseptic conditions,and then placed and cultured in culture chamber.Fibroblasts were passaged with 0.25% trypsin.After 24 and 48 hours incubation,MTT was used to measure the cell proliferation.The production of ?-SMA was measured by Western Blot.[Result]After 24 and 48 hours incubation,healing fib roblasts showed absorbency values of 0.49?0.080 and 0.53?0.07 respectively.II was found that healing fibroblasts proliferated faster than normal fibroblasts(P

Objective To investigate the effects of different doses of propofol anesthesia on the long-term cognitive function in neonatal rats.Methods One hundred 7-day-old male Sprague-Dawley rats,weighing 9-18 g,were randomly divided into 5 groups (n =20 each) ∶ control group (C group) and propofol 25,50,100 and 200mg/kg groups (groups P1-4,respectively).Groups P1 and P2 received intraperitoneal propofol 25 and 50 mg/kg,respectively.Groups P3 and P4 received intraperitoneal propofol 100 and 200 mg/kg,respectively,and after righting reflex completely recovered,an increment of propofol 50 mg/kg was given until the total amount was finished.Five animals in each were chosen and arterial blood samples were obtained immediately after the animals were fully awake for blood gas analysis.The rats were then continuously fed.When the rats were 9 weeks old,the spatial learning and memory function was tested by Morris water maze.The animals were then sacrificed and their brains were removed for detection of the expression of nerve growth factor (NGF) and Caspase-9 protein and mRNA in hippocampal tissues (by Western blot analysis and RT-PCR) and for microscopic examination of the ultrastructure of hippocampal neurons.Results There was no significant difference in blood gas analysis index between the 5 groups (P ＞ 0.05).Compared with group C,no significant change was found in the escape latency and frequency of crossing the original platform in group P1,the escape latency was prolonged and the frequency of crossing the original platform was decreased in groups P2-4,the expression of NGF protein and mRNA was down-regulated and the expression of Caspase-9 protein and mRNA was up-regulated in groups P1-4 (P ＜ 0.05).The escape latency was gradually prolonged,the expression of NGF protein and mRNA was gradually down-regulated and the expression of Caspase-9 protein and mRNA was gradually up-regulated in groups P1-4.The frequency of crossing the original platform was decreased in groups P2-4 compared with group P1 (P ＜ 0.05).There was no significant difference in the frequency of crossing the original platform between groups P2-4 (P ＞ 0.05).Nucleus condensation,chromatin condensation,nuclear fragmentation and apoptotic bodies were observed in groups P2-4.Conclusion Propofol anesthesia can impair the long-term cognitive function in neonatal rats,the effect is related to the dose,and inhibition of NGF expression and increase in the activity of Caspase-9 may be involved in the mechanism.

Objective To evaluate the effects of propofol on apoptosis in the hippocampal neurons of fetal rats in vitro.Methods The isolated hippocampal neurons were seeded into 96-well plates or 24-well plates at a density of 5 × 104 cells/ml.The cells were randomly divided into 5 groups (n =18 each) using a random number table:control group (group C),in tralipid group (group Ⅰ) and propofol 1,10,100 μmol/L groups (P1-3 groups).In group Ⅰ,10％ intralipid was added to the culture media until the final concentration reached 100 μmol/L.In groups P1-3,propofol was added to the culture media until the final concentration reached 1,10 and 100 μmol/L,respectively,and the cells were then incubated for 3 h.The cell apoptosis was assessed by flow cytometry.The expression of Bcl-2 mRNA and caspase-3 mRNA was detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).The expression of Bcl-2 and actived-caspase-3 protein was determined by Western blot analysis.The apoptosis rate was calculated.Results Compared with group C,the apoptosis rate was significantly increased,the expression of Bcl-2 mRNA and protein was down-regulated,and the expression of caspase-3 mRNA and actived-caspase-3 protein was up-regulated in P1-3 groups (P ＜ 0.05).There was no significant difference in the parameters mentioned above between group Ⅰ and group C (P ＞ 0.05).Conclusion Propofol induces apoptosis in isolated hippocampal neurons by inhibiting Bcl-2 expression and enhancing caspase-3 activity in fetal rats.