Objective To investigate the protective effect of Dexmedetomidine（Dex） on the colon and spinal cord of irritable bowel syndrome（IBS） rats with chronic functional visceral pain, and its underlying mechanism of its effects on phosphorylation of extraeellular signal regulated kinase 1（ERK1） and cyclic adenosine monophosphate response element binding protein（CREB）. Methods Forty SPF-grade male SD rats（6～8 g） were inflicted with colorectal dilatation（CRD） stimulation to establish a rat model of irritable bowel syndrome（IBS）. Then the animals were divided into normal group, model group, Dex group and Dex+pc group. The rats from the normal group do not do any treatment, and those of the model group, Dex group and Dex+pc group received CRD stimulation. After successful modeling, the rats in the Dex group were injected intraperitoneally with 5 μg/kg Dex hydrochloride injection daily, and those in the Dextpc group were injected intraperitoneally with 5 μg/kg Dex hydrochloride daily, as well as pc DNA3.1-CREB. The rats in the control group and model group were injected intraperitoneally with the same dose of normal saline and 100 nmol/L of pc DNA3.1-CREB-NC. TUNEL assay was used to detect cell apoptosis, real-time quantitative polymerase chain reaction（RT-qPCR） was employed to detect the mRNA expression of ERK1 and CREB, and Western blotting was used to detect the expression of p-ERK1 and p-CREB in rat spinal cord tissues. Results Compared with the normal group, the cell apoptotic rate, mRNA levels of ERK1 and CREB, and expression of p-ERK1 and p-CREB in spinal cord tissues were significantly increased in the model, Dex and Dex+pc groups（P＜0.05）. The Dex group and Dex+pc group had obviously lower apoptotic rate, decreased ERK1 and CREB expression at mRNA level, and reduced expression of p-ERK1 and p-CREB than the model group（P＜0.05）. What’s more, apoptotic rate, mRNA expression of ERK1 and CREB, and protein expression of p-ERK1 and p-CREB were notably higher in the Dex+pc group than the Dex group（P＜0.05）. Conclusion Dex can significantly inhibits the apoptosis in spinal cord tissue of rats with chronic functional visceral pain. It may play a protective role in colon and spinal cord tissues by inhibiting the phosphorylation of ERK1 and CREB.

目的 探究血塞通联合盐酸文拉法辛治疗短暂性脑缺血发作(TIA)和轻型卒中患者卒中后躯体化症状的临床疗效.方法 将84例TIA和轻型卒中患者随机分为对照组和研究组,每组各42例.对照组给予盐酸文拉法辛缓释胶囊治疗,研究组给予血塞通软胶囊联合盐酸文拉法辛缓释胶囊治疗.比较两组治疗前后健康问卷躯体症状群量表(PHQ-15)、汉米尔顿抑郁量表(HAMD)、汉米尔顿焦虑量表(HA-MA)评分及治疗期间不良反应发生情况.结果 治疗前两组患者PHQ-15、HAMD、HAMA量表评分差异无统计学意义(P>0.05);治疗2、4、6周,研究组患者PHQ-15、HAMD、HAMA量表评分均低于对照组(P<0.05).两组患者不良反应发生率比较差异无统计学意义(P>0.05).结论 血塞通软胶囊联合盐酸文拉法辛缓释胶囊治疗TIA和轻型卒中患者卒中后躯体化症状的疗效肯定,无明显不良反应.

目的 探讨舒芬太尼局部用药对超声引导下胸椎旁阻滞罗哌卡因半数有效浓度(EC50)的影响.方法 择期行胸腔镜下肺叶切除术的患者42例,男23例,女19例,年龄30～65岁,BMI 18～28 kg/m2,ASAⅠ—Ⅲ级,在T4-5水平行超声引导下椎旁神经阻滞.采用随机数字表法将患者分为两组:对照组(C组)和观察组(T组).C组神经阻滞用药为罗哌卡因20 ml;T组神经阻滞用药为罗哌卡因复合舒芬太尼0.6 ug/ml的混合液20 ml.罗哌卡因浓度由上下序贯法确定,起始浓度为0.5％,间隔浓度比值为1.2.若阻滞效果评定为优良,则下一例采用低一级浓度;若阻滞效果评定为差,则下一例采用高一级浓度.研究终点为达到7个上下周期,或者罗哌卡因浓度≤0.1％或≥1％并持续7例.按照Dixion-Massey EC50序贯法计算公式计算罗哌卡因EC50及其95％CI.结果 C组罗哌卡因EC50为0.41％,95％CI为0.39％～0.43％;T组罗哌卡因EC50为0.33％,95％CI为0.31％～0.35％.结论 复合舒芬太尼0.6μg/ml局部用药可降低罗哌卡因胸椎旁阻滞的EC50.

Objective:To evaluate the effect of astaxanthin on neuropathic pain in rats and the role of spinal heme oxygenase-1 (HO-1).Methods:Seventy-two SPF-grade healthy adult male Sprague-Dawley rats, weighing 200-250 g, in which intrathecal catheters were successfully implanted, were divided into 6 groups ( n=12 each) by a random number table method: blank control group (group C), sham operation group (Sham group), neuropathic pain (NP) group, NP plus dimethyl sulfoxide (DMSO) group (NP + DMSO group), NP plus astaxanthin group (NP + AST group) and NP plus zinc protoporphyrin plus astaxanthin group (NP+ ZnPP+ AST group). NP was induced by chronic constriction injury in anesthetized rats.In Sham group, the sciatic nerve was only isolated without ligation.At 5 days after establishing the model, 0.5% DMSO 10 μl was intrathecally injected in NP+ DMSO group, astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ AST group, HO-1 inhibitor zinc protoporphyrin 24 μg (dissolved in 10 μl DMSO) was intrathecally injected, and 3 h later astaxanthin 1 μg (dissolved in 10 μl DMSO) was intrathecally injected in NP+ ZnPP+ AST group.Injection was given once a day for 10 consecutive days in the 3 groups mentioned above.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before establishing the model and 3, 7 and 14 days after establishing the model.The rats were sacrificed at 14 days after establishing the model, and the L 4-6 lumbar segments of the spinal cord were removed for determination of the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), superoxide dismutase (SOD) and glutathione peroxidase (GHS-PX)(by enzyme-linked immunosorbent assay) and expression of HO-1 (by Western blot). Results:Compared with group C and group Sham, the MWT was significantly decreased and TWL was shortened at each time point after establishing the model, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was up-regulated in the other four groups, the SOD and GSH-PX contents were significantly decreased in NP group, NP+ DMSO group and NP+ ZnPP+ AST group, and the SOD and GSH-PX contents were significantly increased in NP+ AST group ( P<0.05). Compared with NP group, the MWT was significantly increased and TWL was prolonged at 7 and 14 days after establishing the model, the contents of TNF-α and IL-1β were decreased, and the expression of HO-1 was up-regulated in NP+ AST group, the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05), and no significant change was found in the parameters mentioned above in NP+ DMSO group ( P>0.05). Compared with NP+ AST group, the MWT was significantly decreased and TWL was shortened at 7 and 14 days after establishing the model, the contents of SOD and GSH-PX were decreased, the contents of TNF-α and IL-1β were increased, and the expression of HO-1 was down-regulated in NP+ ZnPP+ AST group ( P<0.05). Conclusion:Astaxanthin can reduce NP in rats, and the mechanism is related to up-regulating the expression of HO-1 in the spinal cord and inhibiting oxidative stress and inflammatory responses.

神经病理性疼痛是指由影响躯体感觉系统的病变或疾病引起的疼痛,是最难治疗的神经系统疾病之一,同时也是全世界主要的公共卫生问题.近年来的研究表明,炎性小体作为一种先天免疫复合物,通过开启炎症反应过程参与神经病理性疼痛的发生及发展过程.本文通过查阅经典以及最新的相关文献,总结了炎性小体结构特点及在多种神经病理性疼痛相关疾病中的作用和相关机制,以及靶向炎性小体活性在神经病理性疼痛中的治疗,为神经病理性疼痛的发生机制及治疗前景提供新的思路.

AMP激活的蛋白激酶(AMPK)是一种进化保守的丝氨酸/苏氨酸激酶,在调节全身细胞能量代谢的稳态中起着至关重要的作用.在正常生理情况下,AMPK能够促进大脑发育和调节神经元极化.在缺血性脑卒中中,AMPK的上调可以减弱氧化应激,抑制神经炎症,调节神经元自噬和凋亡,改善线粒体功能,抑制谷氨酸兴奋性毒性和促进新生血管形成等.AMPK在缺血性脑卒中的治疗中具有促进功能恢复的作用,主要形式包括药物治疗、物理疗法和受体靶向治疗.但靶向AMPK的应用在临床中的证据和机制依然不是很充足,有待进一步研究.

Thoracic paravertebral block (TPVB) can provide effective analgesia in the early postoperative period. Recent studies have shown that the use of local anesthetics combined with adjuvant drugs prolongs sensory or motor block time and improves post-operative pain scores. This article summarizes the clinical effects, dosages, mechanism of action, safety and effectiveness of different local anesthetic adjuvants when used in TPVB, which helps to clarify the clinical significance of adjuvant drugs used in TPVB. In the meantime, it is also helpful to find a reasonable drug compatibility and dosage, enhance the analgesic effect of TPVB, extend the duration of analgesia, and accelerate the rapid recovery of patients after surgery, providing a new reference for clinical anesthesia analgesia.

目的 评价乌灵胶囊联合盐酸文拉法辛缓释胶囊治疗脑梗死后患者躯体化症状的临床疗效.方法将68例脑梗死后患者随机分为对照组和研究组,每组各34例.对照组给予盐酸文拉法辛缓释胶囊治疗,研究组给予乌灵胶囊联合盐酸文拉法辛缓释胶囊治疗.比较两组治疗前及治疗后第2、4及6周汉米尔顿抑郁量表(HAMD)、汉米尔顿焦虑量表(HAMA)、健康问卷躯体症状群量表(PHQ-15)评分及治疗期间不良反应发生情况.结果治疗前两组HAMD、HAMA、PHQ-15评分比较,差异无统计学意义(P>0.05);治疗后第2、4及6周研究组HAMD、HAMA及PHQ-15评分低于对照组(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05).结论乌灵胶囊联合盐酸文拉法辛缓释胶囊治疗脑梗死后患者躯体化症状的临床疗效肯定,安全可靠.

Objective:To observe the effects of catalpol through intraperitoneal injection on the neuropathic pain of the rats with chronic constriction injury (CCI).Methods:Fifty-six male SD rats were established into CCI models,and randomly divided into seven groups at the forth day after the surgery: sham operation group, solvent group(physiological saline),positive medicine group(gabapentin 50 mg/kg);catalpol groups(1,5,25 and 125 mg/kg), by intraperitoneal injection.MWT value and MPE value were measured to analyze the effects of catalpol.Results:Compared with before operation and sham operation group,administration of catalpol each day could reverse acute mechanical pain of the rats.After intraperitoneal injection of positive medicine and catalpol,MPE of the rats raised (P<0.05),after consecutive administration of catalpol(1,5,25 and 125 mg//kg)and positive medicine(gabapentin 50 mg/kg)for seven days consecutively,MPE reached(31.94±5.64)%,(38.06± 5.78)%,(61.94±5.14)%,(69.13±5.12)% and(61.19± 6.18)% respectively.Conclusion:Intraperitoneal injection of catalpol could notably decrease neuropathic pain of CCI rats,which shows dose-dependent relation.

目的 对PBL结合CBL教学法在诊断学神经系统查体见习中的应用进行评价.方法 将兰州大学进行诊断学神经系统查体见习的2014级临床医学专业五年制学生50例随机分为PBL结合CBL教学组(25例)和传统教学组(25例),对两组学生分别采用PBL结合CBL教学法和传统教学法进行授课,对两组学生查体和理论考核成绩比较,教学完成后进行教学反馈问卷调查.结果 PBL结合CBL教学组理论考试和实践技能考核成绩好于传统教学组(P<0.05);PBL结合CBL教学组在激发学习兴趣、提高自学能力、提高沟通合作能力、提高解决问题能力、加深知识掌握理解、利于临床思维建立6个方面的问卷调查结果好于传统教学组(P<0.05).结论 PBL结合CBL教学法应用于诊断学神经系统查体见习教学中有助于提高教学质量.

迟发性性腺功能减退（late-onset hypogonadism， LOH）是一种与年龄增长相关的临床和生物化学综合征，又称为年龄相关的睾酮缺乏综合征，是指老年男性血睾酮水平低于正常年轻男性参考值，伴随有体能下降、性功能障碍及心理障碍等睾酮不足的临床表现，并逐渐导致生活质量下降和多器官的损害[1]。随着我国步入老龄化社会，作为严重影响中老年男性生活质量和健康的重要疾病之一，LOH已成为研究的热点和难点，近年来LOH的相关研究取得许多进展。

目的 探讨托吡酯预防性治疗偏头痛的临床疗效.方法 将150例偏头痛患者随机分为对照组和研究组各75例,对照组给予丙戊酸钠400 mgd,最高可增加到600 mg/d;研究组口服托吡酯25 mg/d,剂量每周递增25 mg,最高到100 mg/d,3个月为一个疗程,比较两组临床疗效.结果 研究组总有效率62.7％,显著高于对照组的46.7％(P＜0.05),研究组从干预的第4周开始,头痛发作频率、每月发作天数以及严重程度均显著低于对照组(P＜0.05).研究组α波频率变慢、δ波增多及θ波增多的病例显著多于对照组(P＜0.05).研究组共发生不良反应19例,对照组25例,两组间比较,差异无统计学意义(P＞0.05).结论 托吡酯预防性治疗偏头痛具有较好的临床疗效,且不良反应发生率低,可以有效减轻头痛发作程度,降低发作频率,缩短发作时间,值得临床推广.

观察局部亚低温对脑再灌注治疗时间窗的影响并研究其机制.将120只Wistar大鼠随机分为假手术组10只;大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)24 h组10只;常温再灌注组50只;亚低温再灌注组50只.动物均在再灌注24 h后处死,但MCAO24 h组大脑中动脉闭塞24 h后直接处死.采用TTC染色观察梗死体积,用干-湿质量法测定脑含水量,用原位末端标记(TUNEL)观察神经细胞凋亡的变化,采用免疫组化法检测基质金属蛋白酶9(MMP-9)的表达.与脑梗死的近期结局MCAO24 h组的梗死体积、脑含水量、TUNEL阳性细胞数MMP-9的表达相比较:常温组MCAO2h3 h再灌注24 h有统计学差异(P＜0.01),MCAO 4～6 h再灌注24h没有统计学差异(P＞0.05);亚低温组MCAO 2～4h再灌注24h各组有统计学差异(P＜ 0.01);MCAO 5～6h再灌注24 h没有统计学差异(P＞0.05).亚低温再灌注组各时相点的梗死体积、脑含水量、TUNEL阳性细胞数的表达均显著低于相应常温组(P＜0.01,P＜0.05).再灌注期间实施局部亚低温可延长再灌注治疗时间窗,其机制可能与抑制神经细胞凋亡及抑制MMP-9的表达有关.

Objective To observe the short-term therapeutic effect of local mild hypothermia on intracranial infection and mechanisms.Methods Forty patients with encephalic infections(12 viral encephalitis,16 tuberculous meningitis,12 purulent meningitis)were classified into two groups,i.e.,normal temperature subgroup and mild hypothermia subgroup.The mild hypothermia subgroup was used mild hypothermia therapy.RIA was rented for concentration of serum and CSF NSE,enzyme-linked immunosorbent assay(ELISA)was used to detect concentration of serum and CSF MMP-9.Routine and biochemical test were made on cerebral spinal fluid(CSF).Results After local mild hypothermia therapy for seven days,WBC,protein,intracranial pressure(ICP)in mild hypothermia group were declined more sharply,but the glucose raised more compared with normal temperature group(P <0.01);The concentration of NSE and MMP-9 of mild hypothermia group were declined more sharply than those of normal temperature group.Conclusion Blood brain barrier damage and the encephalic damage exist in the intracranial infection.Local mild hypothermia can decrease the damage of nerve cell,and benefit microcirculation.