BACKGROUNDS The cyclic AMP response element-binding protein (CREB) plays an important role in neuropathic pain. Kinesin superfamily motor protein 17 (KIF17) is involved in long-term memory formation. CREB could increase the level of KIF17 when activated by synaptic input. This study is to investigate the role and mechanism of CREB antisense oligonucleotide (ODN) in neuropathic pain induced by chronic constriction injury (CCI) in mice. RESULTS CCI surgery decreased thresholds of mechanical allodynia and thermal hyperalgesia whereas CREB antisense oligonucleotide ODN significantly attenuated these pain behaviors (P < 0.05). CCI significantly induced the protein expression of phosphorylated CREB (pCREB) and KIF17, but not KIF5B, in the spinal cord of CCI mice (P < 0.05). Additionally, the mRNA expression of CREB and KIF17 was significantly increased by CCI (P < 0.05). However, CREB antisense ODN significantly decreased the protein expression of pCREB and KIF17 (but not KIF5B), and the mRNA expression of CREB and KIF17 (P < 0.05). CONCLUSIONS CREB antisense oligonucleotide ODN may reduce neuropathic pain through targeting CREB and decreasing the expression of pCREB and KIF17.

Outreach service of academic library is one of the proactive ways for academic librarians to provide services outside the walls of library buildings.By the method of case analysis,the paper introduces the outreach services of academic library in the United States for various user communities,including freshmen,minority students,students in university residence,and faculties and students at different schools.The innovation of outreach service of academic library in the United States has positive implications for academic libraries in China.It also suggests that academic libraries should broaden the scope of service outreach,consider better arrangement of time and space,take flexible measures of publicity,and cooperate with various administrative departments within universities.

Background: The mammalian target of rapamycin (mTOR) is known to regulate cell growth, and it also participates in pain transmission as has been recently verified in inflammatory and neuropathic pain models. The targeting of mTOR represents a new strategy for the control of chronic pain. In the present study, we investigated the effect of mTOR in the expression of PSD95 and NR2B-PSD95 or GluA2-PSD95 interaction ratio in a chronic constriction injury (CCI) mice model.Methods: Paw mechanical withdrawal threshold (PMWT) and paw withdrawal thermal latency (PWTL) were respectively used to assess mechanical allodynia and thermal hyperalgesia after CCI operation and intrathecal injection of rapamycin. Western blot and co-immunoprecipitation were used to investigate the effects of rapamycin on the expression of PSD95 and interaction ratio of NR2B-PSD95 or GluA2-PSD95 in the spinal dorsal horn of mice.Results: Our study demonstrated that the inhibition of spinal mTOR with intrathecal injections of rapamycin (1 mu g/5 mu L) for days 1-6 after CCI surgery led to an obvious decrease in CCI-induced neuropathic pain. Rapamycin significantly reduced the PMWT of CCI mice, whereas there was no significant effect on PWTL. The active form of the mTOR signaling pathway (p-mTOR, p-4EBP1 and p-p70S6k) at the spinal level remarkably increased in CCI mice, and rapamycin could inhibit this up-regulation. The increased expression of PSD95 and the interaction ratio of GluA2-PSD95 or NR2B-PSD95 could also be inhibited by intrathecal injection of rapamycin.Conclusion: These data suggest that the mTOR pathway is activated in the spinal dorsal horn in CCI-induced neuropathic pain, and the intrathecal injection of rapamycin can reduce mechanical allodynia. Our findings indicate that spinal mTOR is an important component of CCI-induced neuropathic pain, and mTOR may be a potential target for chronic pain therapy. (C) 2013 Published by Elsevier Inc.

The aim of the present study was to determine whether the cAMP response element binding protein (CREB) contributes to neuropathic pain during development stage. Adult (7-8 weeks old) male C57BL/6 mice weighing 20-25 g were used. Intrathecal catheter implantation and chronic constriction of the sciatic nerve of the animals were performed. Western blotting and reverse transcription PCR experiments were carried out. Our study demonstrated that the expression of spinal NMDAR after peripheral nerve injury was modulated by central CREB. Chronic constriction nerve injury (CCI) in mice induced thermal hyperalgesia and mechanical allodynia. The increase of NR1 and NR2B subunits of the NMDAR was significantly diminished by intrathecal administration of the CREB antisense oligonucleotide against CREB and pCREB. Additionally, nociceptive behavior induced by CCI was attenuated by intrathecal administration of the CREB antisense oligonucleotide during the period of injection, and the above effects of relieving pain lasted at least 12 days following the last injection. Our results suggested that central functional pCREB may contribute to the development of neuropathic pain and regulate the expression of the NR1 and NR2B subunits of the NMDAR in the process.

With the current state of high-intensity tasks, denso center’s capacity is constrained by many factors. The main contradiction of restricting production is the problem of workshop production scheduling bottlenecks under the multi-model task. In this paper, shop scheduling algorithm based on particle swarm optimization (PSO) is proposed, taking a monthly production task of denso center for example, with simulation and practical application of the algorithm flow. The results show that shop scheduling plan can be formed by this method quickly and efficiently, especially for multi-tasking systems, which can really give the macro optimal solution by PSO algorithm, giving the minimum time to guarantee all the tasks are completed.

Objective To investigate the effects of repeated intrathecal cyclic AMP response elementbinding protein (CREB) antisense oligodeoxynucleotide (ODN) on the expression of NR2A in spinal cord in mice with neuropathic pain produced by chronic constrictive injury of the sciatic nerve (CCI).Methods Forty C57BL/6 male mice in which intrathecal catheter was successfully implanted were randomly divided into 4 groups ( n =10 each):normal saline group (group NS),CREB sense ODN group (group S),CREB missense ODN group (group M),and CREB antisense ODN group (group A).In groups NS,S,M and A,normal saline 5μl,sense ODN 5 μg/5 μl,missense ODN 5 μg/5 μl and antisense ODN 5 μg/5 μl were injected intrathecally once a day for 6 days,starting from the 1st day after CCI,respectively.Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured on day 1 before CCI and on day 1,3,5 and 7 after CCI.Five mice from each group were sacrificed on day 7 and 14 after CCI and the lumbar segment of the spinal cord (L3-5 )was removed for determination of NR2A expression using Western blot and RT-PCR.Results Compared with the baseline value,no significant change was found in PWMT and PWTL on day 1-7 after CCI in group A ( P ＞0.05),while PWMT and PWTL were significantly decreased on day 1-7 after CCI in groups NS,S and M (P ＜0.05).Compared with groups NS,S and M,the expression of NR2A mRNA and protein was significantly downregulated on day 7 and 14 after CCI in group A ( P ＜ 0.05).The expression of NR2A mRNA and protein was significantly up-regulated on day 14 after CCI compared with that on day 7 after CCI in all the groups.Conclusion Intrathecal CREB antisense ODN during the development of neuropathic pain can attenuate neuropathic pain and inhibition of the expression of NR2A in mouse spinal cord may be involved in the mechanism.

Second Life is a virtual world,which utilizes the 3D technology and highly simulates the real word.This paper briefly describes the Second Life,expounds the use of Second Life in reference service of libraries.Meanwhile,it proposes correlated suggestions about how to offer reference service by fully using Second Life.

The code of ethics for librarians contributes to restrict the behavior of librarians in their profession,and is beneficial to maintaining intellectual freedom in library and guarantees users' rights.Based on the connotation of the code of ethics for librarians,the paper introduces the significance and content of librarians' occupation ethics,which is made by IFLA/FAFI.And some opinions about the code of ethics for librarians are also expressed,such as the special construction,the implementation,the role of library association,which are based on the analysis about cases that include the code of ethics for librarians that is made by the Thai Library Association(TLA) and the Colegio de Bibliotecarios de Chile.

Objective To investigate the role of Akt/glycogen synthase kinase-3β (GSK-3β) signaling pathway in neuropathic pain in mice.Methods Thirty-six male C57BL/6 mice,aged 7-8 months,weighing 20-25 g,were randomly divided into 2 groups:sham operation group (group.S,n =9) and chronic constrictive injury (CCI) group (n =27).CCI was produced by placing loosely constrictive ligatures around the common sciatic nerve.Six animals were taken from each group and paw withdrawal threshold to mechanical stimulation (PWMT)and paw withdrawal latency to thermal stimuli (PWTL) were measured on day 1 before operation and on day 1,3,5,7,10,14,17 and 21 after CCI.Three mice were sacrificed on day 3 after CCI in group S and on day 1,3,5,7,10,14 and 21 after CCI in group CCI.The L3-5 segment of the spinal cord was removed for determination of the expression of Akt,phospho-Akt and phospho-GSK-3β by Western blot.Results Compared with group S,PWMT was significantly decreased and PWTL was significantly shortened on day 1-21 after CCI,the expression of Akt was significantly up-regulated on day 7-21 after CCI,and the expression of phospho-Akt and phospho-GSK-3βwas significantly up-regulated on day 1-21 after CCI in group CCI ( P ＜ 0.05).Conclusion Akt/GSK-3β signaling pathway is involved in the development and maintenance of neuropathic pain in mice.

Background Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation. Results Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn’t affected. Conclusion These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects.

Objective To investigate the effects of repeated injection of flurbiprofen axetil on pain behaviors and side effects in a rat model of bone cancer pain.Methods 24 female SD rats were randomly divided into 3 groups(n=8) as follows.Sham group (S group): intra-tibial injection of 10 μl Hank's solution.Tumor group (T group): intra-tibial injection of 10 μl 4×105 Walker 256 mammary gland carcinoma cells.Flurbiprofen axetil group (Fa group): intraperitoneal injection of flurbiprofen axetil on day 15 to 21 after tumor model.Paw withdrawal mechanical threshold (PWMT) was tested on day 1 before surgery and days 1,3,5,7,10,14,15,17,19,21,24 after surgery.The blood,liver,kidney and ipsilateral tibial bone of all rats were obtained on day 24 to examine the pathological changes.Results ① Compared to S group,the PWMT in T group decreased significantly at day 5 after tumor surgery [(10.92±1.04) g vs (9.01±1.49) g,P＜0.05],and peaked at day 14 after surgery.Compared to T group,the PWMT in Fa group increased obviously at day 17[(6.64±1.70) g vs (4.06±1.69) g,P＜0.05].At day 21,the PWMT in Fa group was lower than that in S group [(8.04±0.81) g vs (10.31±1.35) g,P＜0.05].② The results of bleeding and clotting tests [prothrombin time(PT),activated partial prothrombin time (APTT),thrombin time (TT),fibrinogen (FIB),platelet (PLT)],hepatic and renal functional tests [glutamic-pyruvic transaminase (ALT),aspartate amino-transaminase (AST),total protein (TP),urea (UREA),creatinine (CREA)]had no significant difference among S group,T group and Fa group.③ HE staining revealed that there were no significant pathological changes in liver and renal tissue after repeated intraperitoneal injection of flurbiprofen axetil.Live tumor cells were found in tibia marrow cavities in both T and Fa groups.Conclusions Repeated intraperitoneal injection of flurbiprofen axetil could significantly attenuate bone cancer pain in rats while having no influence on hepatic and renal functions as well as hemostatic function.

Objective To investigate the effects of Akt3 gene knockout on neuropathic pain behaviors induced by chronic constriction injury of sciatic nerve (CCI).Methods Experiment was divided into two groups:Akt3 knockout group (Akt3-/-,n =12),wild type group (WT,n =12 ).Randomly numbered,the right sciatic nerve of mice were received the operation of chronic constriction injury.Paw withdrawal mechanical threshold (PWMT)and paw withdrawal thermal latency (PWTL) were tested on day 1 before operation and day 1,3,5,7,10,14,17,21 afterCCI.Results The basic values of PWMT(right:(1.09±0.20)g,(1.17±0.22)g;left:(1.17±0.15)g,(1.22±0.23)g,P＞0.05) andPWTL(right:(6.18±1.11)s,(6.20±1.25)s;left:(5.82±0.91)s,(5.92± 1.71 ) s,P ＞ 0.05 ) had no statistically significant differences between two groups.On day 1 after operation,compared with basic values,the PWMT and PWTL of the right paw in both Akt3-/- group and WT group decreased significantly (P ＜ 0.05 ),and at least lasted up to day 21.The PWMT( 3d:(0.42 ± 0.22 ) g,(0.72 ± 0.36) g ; 17d:(0.29 ±0.15)g,(0.49 ±0.19) g;21d:(0.27 ±0.18)g,(0.56 ±0.15)g,P＜0.05) and PWTL(5d:(2.43 ±0.68)s,(3.13±0.52)s;17d:(2.43±1.26)s,(3.84±1.29)s ;21d:(2.14±1.23)s,(4.07±1.26)s,P＜0.05 ) of the right paw in Akt3-/- group was significantly lower than those in WT group.The PWMT and PWTL of the left paw in Akt3-/- group and WT group had no obvious differences (P ＞ 0.05 ). However.compared to left paw,the PWMT and PWTL of the right paw of the two groups were obviously lower (P ＜ 0.05 ).Conclusion The neuropathic pain induced by CCI increased in Akt3 gene knockout mice.

Objective To investigate the effects of intrathecally cyclic AMP response element-binding protein(CREB) antisense oligodeoxynucleotide (ODN) on neuropathic pain behaviors.Methods Using mouse model of neuropathic pain induced by chronic constriction injury of sciatic nerve (CCI),24 male C57BL/6 mice successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into 4groups(n=6):Saline group(NS),CREB sense ODN group(S),CREB missense ODN group(M),CREB antisense ODN group(A).Mice in NS,S,M and A were intrathecally treated with Saline 5μ l,Sense ODN 5μg/5μl,Missense ODN 5μg/5μl and Antisense ODN 5μg/Sμl once daily on day 1 ～6 after CCI respectively.Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency(PWTL) were tested on day 1 before CCI and day 1,3,5,7,10,14,17,21 after CC(I).Results Mice in A group maintained the pain thresholds in the baseline and lasted at least 7 days after CCI ( 7 d,PWMT:( 0.81 ± 0.20 ) g vs ( 1.00 ± 0.19 ) g,P ＞ 0.05 ;PWTL:(5.96 ± 0.69) s vs (6.93 ± 1.08 ) s,P ＞ 0.05 ).The withdrawal thresholds in the ipsilateral hind paws of the mouse were significantly lower than baseline in A group on day 10 after CCI( 10 d,PWMT:(0.56 ±0.19)g vs (1.00±0.19)g,P＜0.05; PWTL:(3.93 ±0.28)s vs (6.93 ± 1.08)s,P＜0.05).Compared with NS group ( 10 d,PWMT:(0.56 ±0.19)g vs (0.37 ±0.08)g,P＜0.05; PWTL:(3.93 ±0.28)s vs (3.14 ±0.45)s,P＜0.05),S group,M group,the withdrawal thresholds of A group was significantly elevated on day 10 after CCI.These effects lasted up to at least day 21 after CCI.Conclusion Intrathecally treated with CREB antisense ODN in the development of neuropathic pain induced by CCI completely improved pain behaviors during the course of injection,and the effects of relief pain lasted at least 15d after no injection.

Objective To investigate the analgesic effects of intraperitoneal lithium chloride injection on radicular pain behaviors in rats.Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion(CCD) ,40 male SD rats were randomly divided into model group and Sham-operation group (group S, n= 12) of radicular pain were established.The rats in the model group were subdivided randomly into Control group(group C, n= 12) ,Early treatment group(group E, n=8) and Later treatment group(group L, n= 8 ).Rats in group E were intraperitoneal injected with lithium chloride once daily on day 2 ～ 4 after CCD respectively,while rats in L,group C and S treated with Vehicle(0.9% NaCl).Rats in L group were intraperitoneal treated with lithium chloride on day 12 ～ 14 after CCD respectively,while rats in E,group C and S received Vehicle.The pain ethology indexes such as paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were tested on day 1 before operation and day 1,4,7,10, 14, 17 and 21 after operation.Results Compared to S group and preoperative level, PWMT and PWTL decreased at Day 1 postoperative in group C (P＜0.05).At day 4 after the operation,compared with group C(7.712 ±0.237)g and (8.190 ±0.382) s,PWMT and PWTL of E group increased to ( 14.607 ± 0,280) g and ( 19.940 ± 0.933 ) s (P ＜ 0.05 ) after intraperitoneal injected lithium chloride.At day 14, compared with group C ( 6.788 ± 0.331 ) g and ( 7.301 ± 0.481 ) s, PWMT and PWTL of group L increased to ( 11.700 ± 0.379) 8 and ( 18.524 ± 1.060) s (P ＜ 0.05 ).This analgesic effect of lithium chloride continued to exist at day 21.However, there was still a significant difference between S group and E,group L(P＜0.05).Conclusion Intraperitoneal lithium chloride injection alleviates pain behavior on radicular pain in rats.

Objective To investigate the effects of intrathecally coadministered dexamethasone and spironolactone in trathecally on radicular pain behaviors.Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion (CCD) ,48 male SD rats successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into Sham-operation group (Sham group, n= 12),Control group ( C group, n = 12 ), Dexamethasone group ( D group, n = 8 ), Spironolactone group ( S group, n = 8 )and Dexamethasone plus spironolactone group (DS group, n=8).Rats in D group,S group or DS group were intrathecally treated with dexamethasone 4 μg, spironolactone 3 μg or dexamethasone 4 μg plus spironolactone 3 μg twice daily on day 2 ～4 after CCD respectively,while rats in C and Sham group received 10μl 10% alcohol.Paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency (PWTL) were tested on day 1 before CCD and day 1,4,7,10,14,17 and 21 after CCD.Results Compared with Sham group, both PWMT and PWTL were significantly decreased after CCD surgery on the ipsilateral side(P＜0.01 ＝.Intrathecally administrated with dexamethasone significantly improved pain behaviors (P＜0.01 ＝ and these therapeutic effects lasted up to 10 days after CCD surgery.As with dexamethasone,intrathecal spironolactone also significantly attenuated PWMT (P＜0.01 ＝ and PWTL (P＜0.01 ＝ and the change lasted up to 7 days after CCD surgery.Coadministration spironolactone and dexamethasone exhibited significant synergies( PWMT: ( 13.52 ± 0.72) g vs ( 11.58 ± 1.38 ) g, P ＜0.01; PWTL: ( 19.63 ± 1.68) s vs ( 14.14 ± 1.52) s, P ＜ 0.01 ＝.These effects lasted up to at least 10 days.Conclusion Both dexamethasone and spironolactone intrathecally have therapeutic effects on radicular pain behaviors, combination injection of these two drugs could generate significant synergies.

Aim To investigate the effects of intrathecal delivery of spironolactone on radicular pain behaviors and the underlying mechanisms.Methods Using rat model of radicular pain induced by chronic compression of dorsal root ganglion(CCD),77 male SD rats successfully received intrathecal catheter implantation and without motor dysfunction were randomly divided into 3 groups:sham-operation group(Sham group,n=27),chronic compression of dorsal root gan-glion group(CCD group,n=27) and spironolactone group(Spir group,n=23).Rats in Spir group were intrathecally treated with spironolactone 3 μg/10 μl twice daily on day 2～4 after CCD,while rats in CCD and Sham group received 10 μl 10% alcohol.Paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)were tested on day 1 before CCD and day 1,4,7,10,14 after CCD(n=12 in CCD and Sham group,n=8 in Spir group).The expression of phosphorylated p65(p-p65)among 3 groups on day 4,7,10 after CCD was revealed by Western blot(n=5 in each group).Results Compared with Sham group,both PWMT(P0.01)and PWTL(P0.01)were significantly decreased after CCD on the ipsilateral side,so were the expression of p-p65(P0.01).No significant difference was found in sham group(P0.05)and on the contralateral side(P0.05).Intrathecal spironolactone significantly reduced mechanical allodynia(11.58±1.38 vs 7.71±0.82 on Day 4,P0.01;10.89±1.46 vs 7.49±1.11 on Day 7,P0.01)and thermal hyperalgesia(14.14±1.52 vs 8.19±1.32 on Day 4,P0.01;13.56±1.63 vs 8.56±1.56 on Day 7,P0.01)in comparison to vehicle-treated CCD rats.Consistently,the expression of p-p65 also significantly decreased(P0.01).Conclusions Intrathecal spironolactone had therapeutic effects on radicular pain induced by chronic compression of dorsal root ganglion in rats.The inhibition of MR-NF-κB pathway was one of the main underlying mechanisms.

High levels of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are colocalized in the substantia gelatinosa. This indicates that the pain pathways appear to be under a strong regulation of these receptors. However, their respective effects on pain behaviors and their interaction remain unclear. Here we show that the nociceptive behaviors induced by chronic compression of the lumbar dorsal root ganglion (CCD) are attenuated by either GR agonist dexamethasone (4 = 2 μg > vehicle) or MR antagonist spironolactone (3 μg) administered intrathecally twice daily for postoperative days 2–4, whereas the GR antagonist mifepristone (2 μg) significantly exacerbated both mechanical hyperalgesia and thermal allodynia. Co-administration of spironolactone (3 μg) with dexamethasone (2 μg or 4 μg) twice daily on days 2–4 after CCD surgery produced positive synergistic effects. Moreover, different from intrathecally administered dexamethasone alone [no difference was found between two dose levels of dexamethasone (4 μg = 2 μg)], dexamethasone suppresses mechanical allodynia and thermal hyperalgesia in a dose-dependent manner (4 μg > 2 μg > vehicle) when combined with spironolactone (3 μg). These findings indicate that both central GRs and MRs play an important role in the regulation of pain behaviors and they have a perplexing interaction with each other. Spironolactone can enhance the analgesic effects of dexamethasone via complex mechanisms.

Electrochemical atomic force microscope(EC-AFM) is an analytical instrument that combines electrochemical analysis with atomic force microscope.It can perform in-situ electrochemical scanning probe micro analysis for scientific researches on biosensors,new types of batteries,electrochemical corrosion,and so on.In order to integrate the electrochemical scannng with AFM functions,the field programmable gate array(FPGA) is chosen in the design of control circuit to increase the reliability of the system.The electrochemical workstation is closely integrated with the head of AFM to ensure that the weak signal is not interfered,and it has a variety of electrochemical working modes.The system is stable,and has high repeatability and strong anti-interference capability.