Objective To determine efficacy and safety of intensive lipid lowering with atorvastatin made in China in coronary artery disease(CAD)patients with high risk factors.Methods We enrolled 104 CAD patients admitted to our hospital with high risk Factors.All patients were randomized to either low dose of atorvastatin group(n=50,10 mg/daily)or large dose of atorvastatin group(n=54,40 mg/daily)for 6 months.Total cholesterol(TC),low den- sity lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),triglycerides(TG),serum glucose,hepatic function,renal function,ereatine kinase(CK)of the patients were measured before treatment and at 1 month,3 months,6 months,respectively.Results After six-month treatment,LDL-C,TC,TG levels were reduced by 38.04%,29.37%,20.74%,respectively in the low dose atorvastatin group compared with baseline; whereas reduced by 49.14%,37.69%,26.98%,respectively in the high dose atorvastatin group as compared with baseline level.As for HDL-C,it was increase of 5.98% in low dose atorvastatin group and 3.48% in high dose atorv- astatin group.Responder rates were 54.00% in low dose of atorvastatin group and 79.24% in large dose of atorvastatin group.Much more patients in the high dose atorvastatin group achieved LDL cholesterol goal compare with low dose ator- vastatin group(P

BACKGROUND:Mouse nerve growth factor can promote the repair and regeneration of injured nerves, but current experimental research shows that the effects of different treatment methods are stil controversial.
OBJECTIVE:To evaluate the effect of mouse nerve growth factor injection via different ways on the treatment of peripheral nerve injury.
METHODS:Total y 52 patients with peripheral nerve injury were randomly assigned into two groups:experimental group (local injection of mouse nerve growth factor, n=27) and control group (systemic administration of mouse nerve growth factor, n=25). The treatment was performed once a day, and lasted for 4 weeks. Then, the clinical efficacy and recovery of neurological function were compared.
RESULTS AND CONCLUSION:The good and effective rates were 85%(n=23) and 93%(n=25) in the experimental group, while 72%(n=18) and 84%(n=21) in the control group, respectively, which were significantly better in the experimental group than the control group (P<0.05). In the experimental group, 13 cases developed transient pain at injection site, including one case of remission undergoing oral analgesics;in the control group, 12 cases had transient pain at injection site, without any treatment. The results suggest that both local and total body injection of mouse nerve growth factor are safe and effective for treatment of peripheral nerve injury, but local injection is superior to systemic administration.

Objective To determine and compare the contents of astragaloside Ⅳ in different medicinal parts of Astragalus membranaceus var. mongholicus.Methods The contents of astragaloside Ⅳ in fibrous roots, root heads, taproots and whole roots of A.membranaceus var.mongholicus were determined by HPLC.Results The order of contents of astragaloside Ⅳ in A.membranaceus var.mongholicus was fibrous roots >whole roots >taproots >root heads;The content of astragaloside Ⅳ in A.membranaceus var.mongholicus from Inner Mongolia was 1.85 to 2.7 times of the standard which prescribed in 2010 edition of Chinese Pharmacopoeia.Conclusion Fibrous roots, which were discarded in traditional processing methods, can be used as raw material to extract astragaloside Ⅳ.This study may provide a reference for the harvest and produce of A.membranaceus var.mongholicus.

Objective To observe the effects of nAChR antagonistα-conotoxin Eb1.6 on ther-mal pain threshold and spinal IL-1βexpression levels and astrocytes activation in rats using L5 spinal nerve transaction (SNT)model.Methods Fifty male Sprague-Dawley rats were randomly assigned into 5 groups with each group 10 rats:sham group,different doses of α-CTX Eb1.6 (0.1 5,1.5 and 1 5 nmol/kg)groups and the saline group after SNT.Saline solution or different doses of Eb1.6 were intraperitoneally injected seven days after the surgery when the model was stable and the treatment continued for seven days.Measured the TWLs of all groups of the rats 1,2,4,7,12 hours after the in-jection on 7 d and 13 d.The rats were sacrificed and L5 spinal cord tissues were collected immediately after the behavioral tests on 13 d.The expression of GFAP and IL-1βwere assessed by Western blot assay and enzyme linked immunosorbent assay (ELISA)separately.Results Groups E1,E2,E3 and C had shorter TWL before the injection on 7 d and 13 d than group N(P <0.05).The TWLs of the rats in groups E1,E2 and E3 of 1 h,2 h and 4 h after the injection on 7 d were significantly higher than that before the injection(P <0.05)with 2 h after the injection showed the most obvious change.The TWL of 1 h,2 h,4 h and 7 h after the injection of the rats in group E1,E2 and E3 and those of 12 h after the injection of the rats in group E2 and E3 on 13 d were significantly higher than that before the injection(P <0.05 )and also higher than TWL of the respective time points on 7 d(P < 0.05 ),also with 2 h after the injection showed the most obvious change.The TWLs of 2 h after the injection a-mong group E1,E2 and E3 showed significant differences both on 7 d and 13 d (P <0.05).Rats spi-nal IL-1βand GFAP expression levels of group E1,E2,E3 and C were significantly higher than those of group N(P <0.05).Rats spinal IL-1β and GFAP expression levels of groups E1,E2,E3 signifi-cantly decreased compared with group C(P <0.05).There were significant differences among the spi-nal IL-1βand GFAP expression levels of group E1,E2 and E3(P <0.05).Conclusion Eb1.6 dose-de-pendently reduced the thermal hyperalgesia induced by L5 spinal nerve transection.Repeated treat-ment of Eb1.6 could produce better analgesic effect,which might be partly attribute to the inhibition of spinal IL-βlevels and astrocytes activation.

Objective To investigate the effect of intrathecal (IT) transplantation of different quantities of neural stem cells (NSCs) on neuropathic pain (NP) in rats.Methods Eighty-four adult pathogen-free male SD rats weighing 150-180 g were randomly divided into 7 groups ( n = 12 each) : group sham operation (S group) , NP group, NP+ NSCs 103 , 104 , 105 , 106 , 107 groups (N1-5 groups) . NP was induced by partial transection of right sciatic nerve. NSCs were transplanted into subarachnoid space in N1-5 groups. Paw withdrawal threshold to mechanical stimulation (MWT) and paw withdrawal latency to nociceptive thermal stimuli (TWL) were measured at 1 day before (baseline) and 1, 3, 7, 14 and 21 days after operation. Brain derived neurotrophic factor ( BDNF) expression in spinal dorsal horn and dorsal root ganglia (DRG) was detected by immuno-histochemistry and RT-PCR on the 7th and 21st day after operation. Results Partial transection of the sciatic nerve gradually reduced MWT and TWL after operation starting from day 1 until day 7 and 14 as compared with the baseline in group NP. IT NSC transplantation significantly increased MWT and TWL and expression of BDNF in spinal dorsal horn and DRG in a dese-dependent manner at day 7 after operation in N1-5 groups as compared with group NP. There were no significant differences in MWT and TWL and BDNF expression among N3, N4 and N5 groups at day 21 after operation.Conclusion The proper quantity of transplanted NSCs which are able to ameliorate NP induced by partial transection of sciatic nerve in rats is 105 .

Aim To explore the effect of knockdown spinal cord LCN2 by RNAi on the development of mor-phine tolerance in normal rats.Methods After suc-cessful intrathecal implantation, fourty-eight male Sprague-Dawley rats weighing 1 80 -220 grams were randomly divided into 4 groups (n =1 2):group I:control group,group II:morphine tolerance group, group Ⅲ:mismatch siRNA group,group IV:LCN2 siRNA group.The sixth day after intrathecal implanta-tion,rats were tested to ensure the position of cathe-ters,and it was recorded as d 0.On d 2 -8,rats were subcutaneously (s.c)injected of normal saline (NS) (group I)or morphine (group Ⅱ,Ⅲ,Ⅳ)1 0 μg· g -1 twice a day at 8:00 and 1 6:00.Before everyday s. c injection,rats were intrathecally injected of 1 0 μL DEPC solution (group Ⅰ,Ⅱ),1 0 μL DEPC solution containing 4 μg mismatch siRNA (group III)and 4 μg LCN2 siRNA solution (group IV).Paw withdrawal la-tencies to thermal stimuli (PWTL)were tested before morphine injection and 45 minutes after morphine in-jection on d 1 and d 9.The percentage of maximal pos-sible effect (% MPE)was calculated later.Animals were sacrificed on d 9 after the behavioral test and the lumbar enlargement segments of the spinal cord were removed for detecting the expression of phosphorylated-p38 mitogen-activated protein kinase (p-p38 MAPK) and LCN2 by Western blot and microglia marker Iba1 by immunofluorecence.Results On d 1 ,there was no significant difference in %MPE among four groups. On d 9,compared to group Ⅰ,%MPE was signifi-cantly reduced (P <0.05)while p-p38MAPK,LCN2 and Iba1 were markedly up-regulated in group Ⅱ andⅢ (P <0.05 ).On d 9,compared to group Ⅱ,%MPE was significantly increased while p-p38MAPK, LCN2 and Iba1 were markedly reduced in group IV (P<0.05).Conclusion Using LCN2 siRNA to knock-down spinal LCN2 relieves the development of mor-phine tolerance in normal rats possibly through inhibi-ting the activation of microglia and p38 MAPK in the spinal cord.

Objective To evaluate the role of expression of phosphodiesterase 4B (PDE4B) in the spinal cord in inflammatory responses in a rat model of neuropathic pain and the relationship with extracellular signal-regulated kinase (ERK).Methods Sixty healthy male Sprague-Dawley rats,weighing 180-220 g,in which intrathecal catheters were implanted at L5,6 interspace,were used.The location of catheters was confirmed 6 days later.The rats were randomly divided into 5 groups (n =12 each):sham operation group (group Sham),normal saline (NS) group,vehicle group (group Ⅴ),mismatch siRNA group (group siR-M),and PDE4B-siRNA group (group siR-B).Neuropathic pain was induced by ligation of L5 spinal nerve (SNL).In Sham group,the L5 spinal nerve was only exposed,but not ligated.Immediately after ligation and on 1,3,5,and 7 days after ligation,10 μl NS,10 μl NS,LipofectaminTM RNAiMAX,PDE4B-siRNA (2 μg/10 μl) encapsulated in mismatch siRNA and PDE4B-siRNA (2 μg/10 μl) encapsulated in LipofectaminTM RNAiMAX were injected intrathecally in Sham,NS,V,siR-M,and siR-B groups,respectively.The mechanical pain threshold was measured at 1 day before and 2,4,6 and 8 days after operation.After behavioral testing on 8th day after operation,the rats were sacrificed and the lumbar segment of the spinal cord was removed for determination of PDE4B protein,ERK and phosphor-ERK (p-ERK)expression,and TNF-α,IL-1β and IL-6 levels.Results Compared with Sham group,the mechanical pain threshold was significantly decreased at 2,4,6 and 8 days after operation in NS,V,siR-M and siR-B groups (P ＜0.05),and no significant change was found in the mechanical pain threshold at 2,4,6 and 8 days after operation (P ＞ 0.05) and the expression of p-ERK and PDE4B protein,and levels of TNF-α,IL-1β and IL-6 were increased at 2,4,6 and 8 days after operation in V and siR-M groups (P ＜ 0.05).Compared with NS group,the mechanical pain threshold was significantly increased,and the expression of p-ERK and PDE4B protein and levels of TNF-α,IL-1β and IL-6 were decreased at 2,4,6 and 8 days after operation (P ＜ 0.05),and no significant change was found in the parameters mentioned above in V and siR-M groups (P ＞ 0.05).Conclusion Up-regulation of the expression of PDE4B protein in the spinal cord is involved in the development of neuropathic pain in rats,which may be related to promoted phosphorylation of ERK in the spinal cord and enhanced inflammatory responses.

Aim Toinvestigatetheantagonisticeffect of intrathecal injection of carbenoxolone (CBX ) on neuropathic pain and its underlying mechanism.Meth-ods SixtymaleSprague-Dawleyratswererandomly divided into five groups (n =12 ):group I received sham surgery then treated with saline;group Ⅱ re-ceived SNT then treated with saline;groupⅢreceived SNT then treated with 0. 05 μg CBX;group Ⅳ re-ceived SNT then treated with 0. 5 μg CBX;group Ⅴreceived SNT then treated with 5 μg CBX.Treatment was undertaken with 10 μl volume as a single intrathe-cal injection on postoperative day 10.Mechanical with-drawl thresholds were measured 1 d before operation, 1,3,5,7 and 10 d after surgery,1 h before intrathe-cal administration,and 1 ,2,4,6 h after intrathecal administration.Lumbar spinal cord was obtained 2 h after intrathecal administration to determine the expres-sions of GFAP by immunohistology and TNF-α,IL-1βby ELISA in bilateral spinal dorsal horns.Results Comparedwiththeshamgroup,thebilateralMWTin group Ⅱ ~Ⅴ was significantly decreased.Compared with the MWT 1 h before intrathecal administration on day 10,the values at 1 ,2,4,6 h after administration of group Ⅱ and Ⅲ had no marked difference.The ip-silateral MWT in groupⅣhad no significant difference at 1,2,4 h after administration,the contralateral MWT was significantly increased,whereas GFAP and TNF-α,IL-1βwas significantly decreased in the spinal cord .In group Ⅴthe bilateral MWT was significantly improved at 1 ,2,4 h after administration,whereas GFAP and TNF-α,IL-1βwere significantly decreased inthespinalcord.Conclusions IntrathecalCBXcan inhibit the development of bilateral MWT.The analge-sic effect of CBX is implemented partly via suppressing the actation of GFAP and the realease of TNF-α,IL-1βin the spinal doral horn.

Objective To explore the effects of intrathecal injection of acetyltransferase p300 inhibitor Garcinolon on hyperalgesia in a rat model of L5 spinal nerve ligation and its underlying mechanism. Methods After lumber intrathecal catheters implanted,90 male Sprague-Dawley rats (40-50 d,weighing 180-220 g)were randomly divided into six groups (n=15 each):Naive group (group N),Sham operation group (group S),SNL group (group C)and three Garcinol treatment groups (group H:500μg/kg,group M:100μg/kg,group L:20μg/kg).Group N did not receive any operation in rats.In group S,the L5 spinal nerve was only exposed without ligation.Other four groups all received spinal nerve ligation (SNL).Group N,group S and group SNL were administrated intrathcelly with 100% DMSO (10 μl)within 3 to 6 days after SNL surgery.Other three groups were treated with Garcinol 500μg/kg (group H),100μg/kg (group M),20 μg/kg (group L)at the same points respectively.Behaviorally,thermal withdrawal latency (TWL) were measured at 1 day (T0 )before and on days 1(T1 ),3(T2 ),5(T3 ),7(T4 ),9(T5 ),11(T6 ),14(T7 )after surgery separately.On the 7th day after behavioral testing,the lumber segment of the spinal cord was removed to test the level of p300 and acetyl-p65 by western blot,while NF-κB was detected with immunofluorescence. Results Compared with group N,TWL was significantly shortened in group C,L,M and H,the levels of ace-tyl-p65 and p300 in group C,L,M and H were markedly increased,the expression of NF-κB in group C,L,M and H was markedly increased(P<0.05).Compared with group C,TWL was significantly prolonged in group M and group H,the levels of acetyl-p65 and p300 in group M and group H were dramatically decreased,the expression of NF-κB in group H was obviously decreased(P <0.05).Conclusion The acetyltransferase p300 inhibitor Garcinol imposes protective effect in SNL-induced neuropathic pain.Mechanisms are probably associ-ated with decreasing acetyl-p65 protein expression level in the NF-κB pathway.

Aim To investigate the antagonistic effect of resveratrol on neuropathic pain and its underlying mechanism. Methods Neuropathic pain was induced by ligation of L5 spinal nerve (SNL) in rats. 90 male Sprague-Dawley rats, fit with intrathecal catheters were divided randomly into six groups ( n = 15 ): naive group; sham group; SNL group; high dosage of res-veratrol group (300μg);middle dosage of resveratrol group ( 30μg ) and low dosage of resveratrol group (3μg). The naive group did not make any process. In sham group, the L5 spinal nerve was only exposed without ligation. Other groups received SNL. Different dosages of resveratrol dissolved in 10μL 100% DMSO were administered by intrathecal injections once a day for 4 days, starting on day 4 after SNL. Paw withdraw-al latency (PWL) was measured on day 1,3,5,7,9, 11,14 days after surgery separately. On day 7 after be-havioral testing, the lumbar segments of the spinal cord were removed to measure the level of SIRT1 and acety-lated-p65(Ac-p65) for western blot. The activation of NF-κB was determined through calculating the percent-age of NF-κB-immunofluorescence positive staining cells in this study. Results Compared with sham groups,the SNL group showed an obvious decrease(P< 0. 05) of PWL and SIRT1 after surgery,whereas Ac-p65 and actived NF-κB significantly increased ( P <0. 05) in the spinal cord. Administration with high and middle dosages of resveratrol markedly attenuated(P <0. 05) SNL-induced thermal hyperalgesia and down-regulation of SIRT1 and blocked (P < 0. 05) the SNL-induced up-regulation of Ac-p65 and actived NF-κB in the spinal cord. Conclusion Intrathecal resveratrol can inhibit the development of neuropathic pain and suppress the activation of NF-κB signaling in SNL rats . The analgesic effect of resveratrol is implemented partly via increasing the level of SIRT1 and deacetylat-ing p65.