Effects of cortical intermittent theta burst stimulation combined with precise root stimulation on motor function after spinal cord injury: a case series study

Activation and reconstruction of the spinal cord circuitry is important for improving motor function following spinal cord injury.We conducted a case series study to investigate motor function improvement in 14 patients with chronic spinal cord injury treated with 4 weeks of unilateral(right only)cortical intermittent theta burst stimulation combined with bilateral magnetic stimulation of L3-L4 nerve roots,five times a week.Bilateral resting motor evoked potential amplitude was increased,central motor conduction time on the side receiving cortical stimulation was significantly decreased,and lower extremity motor score,Berg balance score,spinal cord independence measure-III score,and 10 m-walking speed were all increased after treatment.Right resting motor evoked potential amplitude was positively correlated with lower extremity motor score after 4 weeks of treatment.These findings suggest that cortical intermittent theta burst stimulation combined with precise root stimulation can improve nerve conduction of the corticospinal tract and lower limb motor function recovery in patients with chronic spinal cord injury.     

Motor relearning program and Bobath method improve motor function of the upper extremities in patients with stroke

BACKGROUND: In the natural evolution of cerebrovascular disease, unconscious use of affected extremity during drug treatment and daily life can improve the function of affected upper extremity partially, but it is very slow and also accompanied by the formation of abnormal mode. Therefore, functional training should be emphasized in recovering the motor function of extremity. OBJECTIVE: To observe the effects of combination of motor relearning program and Bobath method on motor function of upper extremity of patients with stroke. DESIGN: Comparison of therapeutic effects taking stroke patients as observation subjects. SETTING: Department of Neurology, General Hospital of Beijing Jingmei Group. PARTICIPANTS: Totally 120 stroke patients, including 60 males and 60 females, averaged （59±3） years, who hospitalized in the Department of Neurology, General Hospital of Beijing Jingmei Group between January 2005 and June 2006 were recruited. The involved patients met the following criteria: Stroke attack within 2 weeks; diagnosis criteria of cerebral hemorrhage or infarction made in the 4th National Cerebrovascular Disease Conference; confirmed by skull CT or MRI; Informed consents of therapeutic regimen were obtained. The patients were assigned into 2 groups according to their wills: rehabilitation group and control group, with 30 males and 30 females in each group. Patients in rehabilitation group averaged （59±2）years old, and those in the control group averaged （58±2）years old. METHODS: ① Patients in two groups received routine treatment in the Department of Neurology. When the vital signs of patients in the rehabilitation group were stable, individualized treatment was conducted by combined application of motor relearning program and Bobath method. Meanwhile, training of activity of daily living was performed according to the disease condition changes of patients at different phases, including the nursing and instruction of body posture, the maintenance of good extremity position, bed exercise, bedside sit up and sitting position balance, sit up exercise, dynamic and static balance exercise, walking exercise, active training and passive training. The strength, time and speed of training were increased gradually according to their physical abilities. Patients were trained 45 to 60 minutes once, 5 times a week, within 2 weeks. ② Evaluation criteria of therapeutic effect: The motor function of upper extremity was evaluated by Fugl-Meyer method on the day of beginning and end of treatment. Higher points indicated better function of upper extremity. ③ t test and paired t test were used for comparing the difference of intergroup and intragroup measurement data, respectively. MAIN OUTCOME MEASURES: Changes in Fugl-Meyer scoring of two groups before and after treatment. RESULTS: Totally 120 stroke patients participated in the final analysis. Before treatment, Fugl-Meyer scoring was close between rehabilitation group and control group [（14.47±2.38）,（14.16±2.39） points, P > 0.05]; Fugl-Meyer scoring of rehabilitation group after treatment was significantly higher than that before treatment and that of control group[（37.93±2.67）,（18.36±2.43） points, t =11.053, 5.408, P < 0.01]; There were no significant differences in Fugl-Meyer scoring between before treatment in the control group and control group (P > 0.05). CONCLUSION: Combined application of motor relearning program and Bobath method can significantly improve the motor function of upper extremity of patients with stroke.     

Neuroelectrophysiological indexes and clinical characteristics of patients with peroneal muscular atrophy: Retrospective analysis of 24 cases

BACKGROUND: Peroneal muscular atrophy (PMA) is characterized by insidious onset, gradually progressive course of disease, very mild disability degree and easily subjecting to missed diagnosis and misdiagnosis. Nerve conductive velocity is helpful in the diagnosis of atypical cases. OBJECTIVE: To retrospectively analyze the characteristics of clinical manifestation, electromyogram (EMG), motor and sensory nerve conduction velocity of patients with PMA. DESIGN: Retrospective case analysis. SETTING: Department of Neurology, Guangzhou First People's Hospital. PARTICIPANTS: Twenty-four patients with PMA, including 16 males and 8 females, aged 5-68 years old, admitted to Guangzhou First People's Hospital between March 1996 and January 2006 were recruited. Informed consents were obtained from all the patients. METHODS: All the patients subjected to EMG and detection of nerve conduction velocity at distal end of four extremities with a Keypoint evoked potential/ EMG instrument (Denmark). Sensory and motor conduction velocity, EMG changes of upper and lower extremities were observed, and relationship of neuroelectrophysiological characteristics and clinical symptoms was analyzed. MAIN OUTCOME MEASURES: Changes in sensory and motor conduction velocity, EMG and clinical manifestations of 24 patients. RESULTS: ① All the patients suffered from insidious onset and gradually progressive course of PMA. Muscular atrophy of lower extremity was found in 14 patients, and that of upper extremity in 5 patients. ②Routine nerve conduction study showed that sensory and motor conduction velocity were stepped down, especially in 16 patients with typeⅠPMA (demyelinating pattern, nerve conduction velocity below normal level 50%). Motor nerve conduction velocity of median nerve, ulnar nerve, common peroneal nerve and tibial nerve averaged 34.8 m/s, 37.2 m/s, 16.5 m/s and 17.4 m/s, respectively; Sensory nerve conduction velocity of median nerve, ulnar nerve and sural nerve averaged 27.9%, 24.6 m/s and 3.1 m/s, respectively. Slowing conduction velocity and muscular strength involvement were disproportionate, i.e. myasthenia was relatively lessened, sensory and motor conduction velocities were greatly decreased. Nerve conduction velocity in distal end of two lower extremities was not detected in 8 patients, but who could still walk. CONCLUSION: ①PMA of patients is characterized by insidious onset and gradually progressive course of disease. Clinical symptom is the base to diagnose PMA. ②Neuroelectrophysiological study is a simple and easy-to-operate means with good reproducibility in diagnosing PMA. Patients with abnormal myasthenia in lower extremity can be detected in the early stage.     

Neuroelectrophysiological indexes and clinical characteristics of patients with peroneal muscular atrophy: Retrospective analysis of 24 cases

Peroneal muscular atrophy (PMA) is characterized by insidious onset, gradually progressive course of disease, very mild disability degree and easily subjecting to missed diagnosis and misdiagnosis.Nerve conductive velocity is helpful in the diagnosis of atypical cases.OBJECTIVE: To retrospectively analyze the characteristics of clinical manifestation, electromyogram (EMG),motor and sensory nerve conduction velocity of patients with PMA.DESIGN: Retrospective case analysis.SETTING: Department of Neurology, Guangzhou First People‘s Hospital.PARTICIPANTS: Twenty-four patients with PMA, including 16 males and 8 females, aged 5-68 years old,admitted to Guangzhou First People‘s Hospital between March 1996 and January 2006 were recruited.Informed consents were obtained from all the patients.METHODS: All the patients subjected to EMG and detection of nerve conduction velocity at distal end of four extremities with a Keypoint evoked potential/ EMG instrument (Denmark). Sensory and motor conduction velocity, EMG changes of upper and lower extremities were observed, and relationship of neuroelectrophysiological characteristics and clinical symptoms was analyzed.MAIN OUTCOME MEASURES: Changes in sensory and motor conduction velocity, EMG and clinical manifestations of 24 patients.RESULTS: ① All the patients suffered from insidious onset and gradually progressive course of PMA.Muscular atrophy of lower extremity was found in 14 patients, and that of upper extremity in 5 patients. ② Routine nerve conduction study showed that sensory and motor conduction velocity were stepped down,especially in 16 patients with type Ⅰ PMA (demyelinating pattern, nerve conduction velocity below normal level 50%). Motor nerve conduction velocity of median nerve, ulnar nerve, common peroneal nerve and tibial nerve averaged 34.8 m/s, 37.2 m/s, 16.5 m/s and 17.4 m/s, respectively; Sensory nerve conduction velocity of median nerve, ulnar nerve and sural nerve averaged 27.9%, 24.6 m/s and 3.1 m/s, respectively. Slowing conduction velocity and muscular strength involvement were disproportionate, I.e. Myasthenia was relatively lessened, sensory and motor conduction velocities were greatly decreased. Nerve conduction velocity in distal end of two lower extremities was not detected in 8 patients, but who could still walk.CONCLUSION: ①PMA of patients is characterized by insidious onset and gradually progressive course of disease. Clinical symptom is the base to diagnose PMA. ②Neuroelectrophysiological study is a simple and easy-to-operate means with good reproducibility in diagnosing PMA. Patients with abnormal myasthenia in lower extremity can be detected in the early stage.     

Altered protein markers related to neural plasticity and motor function following electro-acupuncture treatment in a rat model of ischemic-hypoxic brain injury *☆

BACKGROUND：Previous studies have demonstrated that acupuncture treatment could ameliorate impaired motor function,and these positive effects might be due to neural plasticity.OBJECTIVE：Myelin basic protein（MBP）,microtubule-associated protein 2（MAP2）,growth-associated protein-43（GAP-43）,and synaptophysin（SYN） were selected as markers of neural remodeling,and expression of these markers was evaluated with regard to altered motor function following brain injury and acupuncture treatment.DESIGN,TIME AND SETTING：A completely randomized experiment was performed at the Central Laboratory of Peking University First Hospital from November 2006 to May 2007.MATERIALS：Twenty-four Sprague Dawley rat pups,aged 7 days,were selected for the present experiment.The left common carotid artery was ligated to establish a rat model of ischemic-hypoxic brain injury.METHODS：All animals were randomly divided into three groups：sham operation,model,and electro-acupuncture treatment,with 8 rats in each group.Rats in the model and electro-acupuncture treatment group underwent establishment of ischemic-hypoxic brain injury.Upon model established,rats underwent hypobaric oxygen intervention for 24 hours.Only the left common carotid artery was exposed in rats of the sham operation group,without model establishment or oxygen intervention.The rats in the electro-acupuncture treatment group were treated with electro-acupuncture.One acupuncture needle electrode was inserted into the subcutaneous layer at the Baihui and Dazhui acupoint.The stimulation condition of the electro-acupuncture simulator was set to an amplitude-modulated wave of 0-100% and alternative frequency of 100 cycles/second,as well as frequency-modulated wave of 2-100 Hz and an alternative frequency of 3 cycles/second.Maximal current through the two electrodes was limited to 3-5 mA.The stimulation lasted for 30 minutes per day for 2 weeks.Rats in the sham operation and model groups were not treated with electro-acupuncture,but only fixed to the table for     

Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy： an analysis of 500 cases

Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013：221 cases showed symptoms of peripheral neuropathy （symptomatic group） and 279 cases had no symptoms of peripheral impairment （asymptomatic group）. One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases （71.6%）, among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.     

Vein transplantation using human umbilical cord blood stem cells in the treatment of stroke sequela

BACKGROUND: Transplanted mononuclear cell (MNC) of umbilical blood can survive in central nervous system (CNS) of host through blood brain barrier, differentiate into nerve cells, migrate to damaged site and integrate morphological structure and function with nerve cells of host so as to improve deficiencies of sensatory function, motor function and cognitive function and influence on stroke sequela. OBJECTIVE: To observe the vein transplantation of human umbilical cord blood stem cells (HUCBSC) for improving neurological function, limb function and activity of daily living of patients with stroke and evaluate the reliability. DESIGN: Self-controlled study. SETTING: Department of Neurosurgery, the Second People's Hospital of Zhengzhou City; Red-crossed Blood Center of Henan Province; Department of Neurosurgery, the Fist Affiliated Hospital of Zhengzhou University. PARTICIPANTS: A total of 10 patients with stroke sequela were selected from Department of Cerebral Surgery, the Second People's Hospital of Zhengzhou City from April to December 2005. There were 9 males and 1 female aged from 35 to 75 years with the mean age of 56 years. All of them were diagnosed with CT and MRI examination and coincidence with diagnostic criteria of stroke established by the Fourth National Academic Meeting for Cerebrovascular Disease. All patients provided informed consent. METHODS: 80-140 mL umbilical blood of term birth of newborn was selected hermetically and maintained in sterile plastic bag. And then, the blood was centrifugated at the speed of 1 500 r/min for 30 minutes at 22 ℃ in order to separate MNC, i.e., HUCBSC. In addition, after final diagnosis during hospitalization, stroke patients were perfused with HUCBSC through superficial vein of back of the hand. Each patient was averagely perfused with 6 portions of HUCBSC (cellular numbers ≥ 1×108/portion) and the interval between each portion was 1-7 days with the mean interval of 4 days. MAIN OUTCOME MEASURES: ① Neurological function of stroke patients was evaluated with neurological function deficiency (NFD) before treatment and at 3 months after treatment. The scale includes consciousness, level fix function, facial paralysis, language, muscle force of upper limbs, muscle force of lower limb and step function. The total scores ranged from 0 to 45; meanwhile, the lower the scores were, the better the neurological function was. ② Motor function of injured limbs was evaluated with Fugl-Meyer Assessment (FMA), including motor function of upper limbs, motor function of lower limbs, balance ability, sensory function and motion of joint. The total scores ranged from 0 to 226; meanwhile, the higher the scores were, the better the motor function of limbs was. ③ Activities of daily living (ADL) was evaluated with Barthel Index (BI), including having meals, taking a bath, dressing oneself, putting on clothes, walking in balance and stair activity. The total scores ranged from 0 to 100; meanwhile, the higher the scores were, the stronger the ADL was. RESULTS: A total of 10 patients were involved in the final analysis. After treatment, NFD of stroke patients was (10.9±5.09) points, which was lower than that before treatment [(25.4±6.09) points, t =8.213, P < 0.01]. In addition, after treatment, FMA and BI of stroke patients were (80.9±25.00) points and (81.1±15.93) points, respectively, which were higher than those before treatment [(31.9±21.85) points, (36.2±19.41) points, t =13.024, 13.670, P < 0.01]. Immuno-suppressive drugs were not used during the whole therapeutic procedure; moreover, immunological rejection and allergic reaction were not observed during the same period. CONCLUSION: Transplanting HUCBSC through superficial vein of back of the hand is regarded as a simple and safe method for the treatment of stroke sequela.     

Neurological function following intra-neural injection of fluorescent neuronal tracers in rats

Fluorescent neuronal tracers should not be toxic to the nervous system when used in long-term labeling.Previous studies have addressed tracer toxicity,but whether tracers injected into an intact nerve result in functional impairment remains to be elucidated.In the present study,we examined the functions of motor,sensory and autonomic nerves following the application of 5% Fluoro-Gold,4% True Blue and 10% Fluoro-Ruby (5μL) to rat tibial nerves via pressure injection.A set of evaluation methods including walking track analysis,plantar test and laser Doppler perfusion imaging was used to determine the action of the fluorescent neuronal tracers.Additionally,nerve pathology and ratio of muscle wet weight were also observed.Results showed that injection of Fluoro-Gold significantly resulted in loss of motor nerve function,lower plantar sensibility,increasing blood flow volume and higher neurogenic vasodilatation.Myelinated nerve fiber degeneration,unclear boundaries in nerve fibers and high retrograde labeling efficacy were observed in the Fluoro-Gold group.The True Blue group also showed obvious neurogenic vasodilatation,but less severe loss of motor function and degeneration,and fewer labeled motor neurons were found compared with the Fluoro-Gold group.No anomalies of motor and sensory nerve function and no myelinated nerve fiber degeneration were observed in the Fluoro-Ruby group.Experimental findings indicate that Fluoro-Gold tracing could lead to significant functional impairment of motor,sensory and autonomic nerves,while functional impairment was less severe following True Blue tracing.Fluoro-Ruby injection appears to have no effect on neurological function.     

Detecting the nerve function of fibril in patients with cervicalspondylotic radiculopathy using quantitative sensory testing

BACKGROUND: Pain and sensory disability are greatly affected by subjective factors, there are no quantitative indexes to evaluate cervical spondylotic radiculopathy(CSR). The judgment on clinical body examination and chief complaint always causes nonobjective results with great individual differences. Quantitative sensory testing (QST) can be used to judge the nerve function of fibril. The application of QST for the quantitative evaluation of peripheral nervous system disease needs to be further studied. OBJECTIVE: The cold-thermal sensation and pain of patients with CSR are quantitatively analyzed by using QST technology in order to evaluate the nerve function of fibril in patients with CSR. DESIGN: Case-control observation. SETTING: Pain Center of Beijing Hospital of Ministry of Health. PARTICIPANTS: Twenty patients with CSR, including 8 males and 12 females, aged from 33 to 70 years, who received treatment between January and April 2005 in Pain Center of Beijing Hospital of Ministry of Health were involved in CSR group. All the involved patients presented symptoms in unilateral upper extremity (left side 10 patients, right side 10 patients). They did not undergo physical therapy or nerve block therapy in 1 week before examination. Eight non-CSR patients who received treatment in Pain Center concurrently were involved in the control group (2 patients with trigeminal neuralgia, 4 with osteoarthrosis of knee joint and 2 with lumbar intervertebral disc protrusion), and another 12 healthy volunteers were involved. Four non-CSR patients and 12 healthy volunteers, 8 male and 12 female, were aged from 23 to 75 years. The informed consents were obtained from all the involved subjects. METHODS: The volar thresholds of cold sensation, thermal sensation, cryalgesia of thenar eminence of both upper extremities of all the subjects were examined separately by limit method with type TSA-Ⅱ temperature sensation analysator made by Medco Company (Israel). The subjects were pre-examined to be familiar with the method for sensory discrimination and affirmation. Thenar eminence vola of bilateral upper extremities were detected. The infrared detector of a semiconductor was contacted with skin. The infrared detector could be used to heat and cool skin. A group of cold-heat water circulation device was given electric current to produce temperature gradient, which was higher or lower than skin temperature. The initial temperature of infrared detector was 32 ℃, stimulation temperature was increased or decreased progressively at 1 ℃/s, and temperature change range was 0 to 50 ℃. In the first step, subjects pressed down the button to stop the stimulation when the temperature of infrared detector was decreased progressively until the subjects felt, and the threshold of cold sensation was obtained; In the second step, the threshold of thermal sensation was obtained when the temperature of infrared detector was increased progressively until the subjects felt; In the third step, the threshold of cryalgesia was obtained when the temperature of infrared detector was decreased progressively until subjects felt; and in the fourth step, the threshold of thermalgesia was obtained when the temperature of infrared detector was increased progressively until subjects felt. Each step was conducted 4 times and the mean threshold was obtained. Before each measurement, the temperature was made to rebound to the initial temperature and kept for 10 s. MAIN OUTCOME MEASURES: The thresholds of cold sensation, thermal sensation and cryalgesia, thermalgesia of thenar eminence vola of bilateral upper extremities of all the subjects. RESULTS: Twenty patients with CSR and 20 healthy subjects participated in the final results. ① In the CSR group, the threshold of cold sensation of affected side was lower than that of intact side [(29.00±1.26) ℃ vs.(30.00±1.06) ℃, P < 0.05], and the threshold of thermal sensation of affected side was higher than that of intact side [(35.04±0.87) ℃ vs. (34.14±0.99) ℃, P < 0.05]. There were no significant differences in the thresholds of cold and thermal sensation between affected side and intact side (P > 0.05). ②In the CSR group, the difference of threshold of cold sensation, thermal sensation, cryalgesia and thermalgesia between affected side and intact side was (-1.01±0.57)， (0.89±0.39), (2.49±1.10) and (-1.62±0.86) ℃, respectively , the absolute value of which was higher than that of control group, respectively [(0.04±0.28),(0.05±0.26)，(0.28±1.79)，(0.17±1.10) ℃，P < 0.01]. In the CSR group, the threshold of cold sensation and thermalgesia of affected side was lower than that of intact side, respectively; and the threshold of thermal sensation and cryalgesia of affected side was higher than that of intact side, respectively. CONCLUSION: The superficial sensation of affected extremity of patients with CSR is lessened as compared with that of intact extremity. There are dysfunctions of small myelinated fiber (Aδ fiber) and demyelinated fiber (C fiber) in the affected-side extremity. QST, as a mean for quantitatively evaluating the function of Aδ fiber and C fiber, plays an objective evaluative role in the diagnosis and therapeutic effect observation of CSR..     

Effect of post-stroke sensory disorders on the recovery processes of motor function and activity of daily living*☆ A non-randomized synchronical controlled trial

BACKGROUND: In the rehabilitation of stroke patients, clinicians usually concentrate on motor problems, such as spasm of limbs and restriction of joint motion, while sensory and perceptive problems are almost always neglected, although they are just as important. One such area is the sensory disorder. OBJECTIVE: To evaluate the motor function and activities of daily living in stroke patients with and without sensory disorders after treatment of integrated western and Chinese medicine. DESIGN: A non-randomized synchronically controlled trial. SETTING: First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine. PARTICIPANTS: Totally 500 stroke inpatients were selected from the Department of Acupuncture and Massage, the First Affiliated Hospital of Tianjin College of Traditional Chinese Medicine from January 2003 to December 2004. They all had suffered from stroke in the last 4 weeks and accompanied by sensory disorder of the ipsilateral limb to different severity. The patients were all accorded with the Diagnostic and Efficacy Evaluative Standards for Stroke (in trial) set by the Encephalopathy Emergency Assistant Group, the State Administration of Traditional Chinese Medicine in 1995, and they were diagnosed by imaging examination. The patients were stratified into sensory disorder group (n =220) and normal sense group (n =280). Informed consent for the detected items and therapeutic program was obtained from the relatives of all the participants. The study was approved by the hospital ethical committee. METHODS: All the patients were treated with acupuncture of Xing Nao Kai Qiao for restoring consciousness and inducing resuscitation, assisted by traditional Chinese medicine and western medicine specific to corresponding symptoms. The therapeutic principles were restoring consciousness and inducing resuscitation, nourishing liver and kidney, and dredging meridian. In addition, the patients were given western medical treatments for decreasing intracranial pressure, thrombolysis, reducing blood viscosity, anticoagulation, anti-arteriosclerosis, ameliorating microcirculation, also administrated with activator for nerve cells. MAIN OUTCOME MEASURES: ① The severity of motor function deficit was evaluated using clinical neurological deficit score for stroke patients set by the Fourth National Academic Meeting for Cerebrovascular Disease in 1995; ② The activities of daily living was evaluated with Barthel Index, the higher the score, the better the independence, and the less the dependence. RESULTS: All the 500 stroke patients were involved in the final analysis of results. ① The neurological deficit scores before treatment had no significant difference between the two groups (P > 0.05), but the scores after treatment were significantly decreased as compared with those before treatment in both groups (t =6.59, 12.43, P < 0.01). The neurological deficit score after treatment in the normal sense group was significantly lower than that in the sensory disorder group (t =1.63, P < 0.05). ② The scores of activities of daily living after treatment were significantly increased as compared with those before treatment in both groups (t =16.03, 25.10, P < 0.01). The scores of activities of daily living in the normal sense group were higher than those in the sensory disorder group both before and after treatment (t =6.07, 14.26, P < 0.05). CONCLUSION: Sensory disorders have obvious negative effects on the recovery of motor function and activities of daily living of stroke patients.     

针刺健康人足三里穴脑功能成像研究初步分析

目的采用磁共振脑功能成像（fMRI）技术观察针刺足三里穴引起脑内功能区的变化,并与近年来相关的研究结果比较,分析研究存在差异的原因。方法15例健康志愿者,采用改良组块设计方案,针刺左侧足三里穴进行fMRI扫描,实验数据采用AFNI软件分析处理,采用Monte Carlo模拟阈值校正方法（P〈0.05,α〈0.05）确定脑功能激活区。结果针刺左侧足三里穴引起双侧海马旁回、额中回、扣带回前部、右侧颞叶、海马、杏仁核、左侧额下回、右侧小脑及脑桥区域信号减弱,右侧中央前回及右侧顶下小叶区域信号增高。结论针刺正常人左侧足三里穴主要引起颞叶和边缘系统的脑功能变化,并且以信号减弱为主。与其他类似研究的结果有较明显的差异,这种差异可能与多种因素有关,有待进一步深入研究分析。     

加用银杏叶片对氯氮平合并心得安治疗慢性精神分裂症的疗效和安全性的影响

目的 探讨银杏叶片对氯氮平合并心得安治疗慢性精神分裂症的疗效和安全性的影响.方法 将80例慢性精神分裂症病人随机分为研究组和对照组各40例,对照组给予抗精神病药物氯氮平、心得安治疗,研究组在此基础上,加用银杏叶片治疗,治疗12周.治疗前和治疗4、8、12周末分别用阳性与阴性症状量表(PANSS)评定临床疗效,用不良反应症状量表(TESS)评定不良反应,了解药物的安全性.结果 两组PANSS各因子评分比较差异无统计学意义(P＞0.05),但是阴性症状评分(P ＝0.053),有异质性和可比性,银杏叶片还可减少氯氮平的不良反应.结论 以阴性症状为主的精神分裂症在氯氮平合并心得安治疗过程中适合加用银杏叶片以增强疗效,减少不良反应.     

西洋参茎叶皂苷对多因素诱导PC12细胞内游离钙升高的影响

BACKGROUND： Previous studies have demonstrated that intracellular Ca^2＋ （[Ca^2＋]） overload, excitotoxicity, free radical injury, and nitric oxide toxicity are involved in mechanisms of neuronal death in the ischemic brain. OBJECTIVE： To investigate the influence of Panax quinquefo/ium saponins （PQS） on multiple factors-induced Ca^2＋ overload in the rat pheochromocytoma （PC12） cell line. DESIGN, TIME AND SETTING： Intergroup comparison, in vitro study. The experiment was performed at the Heilongjiang Key Laboratory of Anti-fibrosis Biotherapy, Mudanjiang Medical University between November 2007 and April 2008. MATERIALS- In vitro cultured PC12 cells in the logarithmic phase were assigned into blank control, model, and drug treatment groups （10 μmol/L nimodipine; 40 μg/L, 100 μg/L, and 250 μg/L PQS）. Nimodipine was purchased from Jiangsu Yangtze River Pharmacy Group Co., China; PQS （purity 〉 95%, HLPC grade） was provided by School of Basic Medical Sciences, Jilin University. Caffeine, Na2S2O4, L-glutamic acid （Glu）, Fura-2/AM, and calcium ionophore A23187 were purchased from Sigma, USA. METHODS： PC12 cells in the model and drug treatment groups were separately incubated in glucose-free Hank＇s buffered saline solution ＋ Na2S2O4 （2 mmol/L） for 6 hours, Glu （200 μmot/L） plus A23187 （0.05 μmol/L） for 6 hours, KCI （50 mmol/L） for 1 hour, and caffeine （5 mmol/L） for 3 hours to establish models of intracellular Ca^2＋ overload induced by oxygen and glucose deprivation, Glu, A23187, high K＋, or caffeine. In addition, control cells were incubated in high-glucose DMEM culture medium. MAIN OUTCOME MEASURES： [Ca^2＋]i changes in PC12 cells exposed to oxygen-glucose deprivation, Glu, A23187, high K^＋, or caffeine were detected using spectrofluorometer. RESULTS： PQS blocked the [Ca^2＋]i increase induced by oxygen-glucose deprivation, Glu, A23187, high K＋, or caffeine. In particular, high-dose PQS was most effective （P 〈 0.01）. PQS significantly inhibited Glu- or caffeine-induced [Ca^2＋]i increases in the absence of extracellular Ca^2＋, but nimodipine did not. CONCLUSION： PQS blocked intracellular Ca^2＋ overload induced by oxygen-glucose deprivation, Glu, A23187, high K^＋, or caffeine. This mechanism might be involved in the attenuation of neuronal apoptosis following ischemic brain injury.     

高血压性脑出血患者急性期D-二聚体、纤维蛋白原及其降解产物的变化及意义

目的 观察高血压性脑出血患者急性期血象D-二聚体(D-D)、纤维蛋白原降解产物(FDP)及纤维蛋白原(Fib)的动态变化和临床意义.方法 免疫比浊法测定实验组与对照组的血浆D-D和Fib,采用乳胶凝聚法测定FDP.测定42例脑出血患者发病后1,3,7,14 d对空腹静脉血D-D、Fib和FDP的变化,同时与正常对照组34例相比较.结果 脑出血组第3,7,14天血浆FDP、D-D和Fib明显升高,与对照组比较差异有统计学意义(P＜0.01);脑出血组发病24 h内血浆FDP、D-D和Fib水平较对照组升高,但差异无统计学意义(P＞0.05);脑出血组血浆D-D于第3天、血浆FDP及Fib含量于第7天达到高峰.结论 脑出血急性期血浆D-D、FDP及Fib含量增加,这可能是脑出血后脑组织损伤引起外周血中纤溶活性增高的一种代偿反应.     

Protective effects of （-）-epigallocatechin-3-gallate on D-galactose-induced neuronal apoptosis in mice

BACKGROUND： The neuroprotective effects of （-）-epigallocatechin-3-gallate （EGCG）, the main polyphenolic constituent of green tea, have been widely reported. However, the action mechanisms, in particular in D-galactose-induced aging mice, remain poorly understood. OBJECTIVE： The present study investigated the protective effects of EGCG on D-galactose-induced hippocampus neuronal apoptosis in aging mice, as well as the relationship with expression of p751CD, JNK2, and p53 proteins. DESIGN, TIME AND SETTING： A randomized, controlled, molecular biological, animal experiment was performed at the Laboratory of Pharmacology, Pharmaceutical College of China Medical University, China, from September 2006 to July 2008. MATERIALS： D-galactose and EGCG （Sigma, USA）, as well as terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling （TUNEL） In Situ Cell Apoptosis Detection Kit （Promega, USA）, were used in this study. METHODS： A total of 64 mice were equally and randomly divided into D-galactose model, low-dose EGCG, high-dose EGCG, and control groups. Mice in the D-galactose model, low-dose EGCG, and high-dose EGCG groups were subcutaneously injected with 3% D-galactose （150 mg/kg）, daily for 6 weeks, to establish a mouse model of aging. Mice in the control group were treated with saline （5 mL/kg）. At 3 weeks following injection, mice in the low-dose EGCG and high-dose EGCG groups were orally administered EGCG at a dose of 2 mg/kg and 6 mg/kg, respectively, once a day, for 4 consecutive days. Mice in the control and D-galactose model groups received distilled water （5 mL/kg）. MAIN OUTCOME MEASURES： Memory function was evaluated using a step-through passive avoidance test. Neuronal apoptosis in the mouse hippocampus was detected using TUNEL staining. Expression levels of the intracellular domain of the p75 neurotrophin receptor （p75NTR）-p751CD, JNK2, and p53 proteins in the hippocampus were determined using Western blot analysis. RESULTS： The aging mouse model was induced by subcutaneous injection of D-galactose, which resulted in obvious memory impairment, increased apoptotic index, and increased protein expression levels of p751CD, JNK2, and p53 in the hippocampus, compared with control mice （P 〈 0.01）. Oral EGCG administration （2 or 6 mg/kg） for 4 weeks significantly improved levels of memory deficit in the aging mice and reduced apoptotic indices and protein expression levels of p751CD, JNK2, and p53 in the mouse hippocampus （P 〈 0.01）. CONCLUSION： Results from this study demonstrated increased protein expression levels of p751CD, JNK2, and p53, as well as increased hippocampal neuronal apoptosis in a D-galactose-induced mouse model of aging. EGCG provided protective effects against D-galactose-induced neuronal apoptosis in the hippocampus by reducing protein expression levels of p751CD, JNK2, and p53 proteins in the hippocampus of aging mice.     

Effects of tacrolimus （FK506） on sciatic nerve regeneration in rats

BACKGROUND： Tacrolimus （FK506） protects peripheral nerves located in damaged regions by inhibiting T lymphocyte proliferation and activation. OBJECTIVE： To evaluate the effect of FK506 on promoting regeneration of rat sciatic nerve. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Laboratory of the Department of Orthopedic Surgery, Dalian Medical University, China, from September 2007 to September 2008. MATERIALS： A total of 60 adult, male, Sprague-Dawley rats were equally and randomly divided into model, local administration and systemic administration groups. All rats received a neurotomy of bilateral sciatic nerves to establish models of nerve regeneration chambers. The powder and injection of FK506 were supplied by Fujisawa Pharmaceutical, Japan. METHODS： The regeneration chambers of the model group were infused with 0.2 mL saline. The systemic group were injected with 0.2 mL saline, followed by daily subcutaneous injections of FK506 （1 mg/kg）, for 14 days. The local administration group was infused with 0.2 mL FK506 （1 μg/mL）. MAIN OUTCOME MEASURES： Local immune response was observed using hematoxylin-eosin staining. Myelinated nerve fiber number, myelin sheath and nerve fiber thickness were observed using toluidine blue staining. Wet weight of gastrocnemius was evaluated. Compound muscle action potential amplitude, latency, and conduction time were recorded, and motor nerve conduction velocity was calculated using electrophysiology. RESULTS： The total number of myelinated nerve fibers in the local and systemic administration groups was significantly higher than in the model group. The density of myelinated nerve fibers, myelin sheath thickness and mean axon diameter were significantly increased in the systemic administration group compared with the model group （P 〈 0.05）. Lymphocyte infiltration was decreased in the local and systemic administration groups compared with the model group. The wet weight of rat gastrocnemius in the local and systemic administration groups were significantly greater compared with the model group （P 〈 0.05）. Motor nerve conduction velocity was the fastest in the systemic administration group, and the slowest in the model group. Compound muscle action potential amplitude was larger in the systemic administration group compared with the local administration and model groups （P 〈 0.05）. CONCLUSION： Systemic administration of FK506 can promote regeneration of rat sciatic nerve and recovery of neural function. Systemic administration produced better regeneration and recovery of function than local administration of FK506.     

Environmental factors in the development and progression of late-onset Alzheimer＇s disease

Late-onset Alzheimer＇s disease （LOAD） is an age-related neurodegenerative disorder characterized by gradual loss of synapses and neurons, but its pathogenesis remains to be clarified. Neurons live in an environment constituted by neurons themselves and glial cells. In this review, we propose that the neuronal degeneration in the AD brain is partially caused by diverse environmental factors. We first discuss various environmental stresses and the corresponding responses at different levels. Then we propose some mechanisms underlying the specific pathological changes, in particular, hypothalamic-pituitary adrenal axis dysfunction at the systemic level; cerebrovascular dysfunction, metal toxicity, glial activation, and Aβ toxicity at the intercellular level; and kinase-phosphatase imbalance and epigenetic modification at the intracellular level. Finally, we discuss the possibility of developing new strategies for the prevention and treatment of LOAD from the perspective of environmental stress. We conclude that environmental factors play a significant role in the development of LOAD through multiple pathological mechanisms.     

终丝室管膜瘤并种植1例报道

1 病例介绍 患者,女性,27岁.主因＂腰腿放射性疼痛8年,进行性加重1年余＂入院.体检：发育正常,营养良好,神志清楚,自主体位,查体合作.     

Targeting 13-secretase with RNAi in neural stem cells for Alzheimer＇s disease therapy

There are several major pathological changes in Alzheimer＇s disease, including apoptosis of cho- linergic neurons, overactivity or overexpression of 13-site amyloid precursor protein cleaving enzyme 1 （BACE1） and inflammation. In this study, we synthesized a 19-nt oligonucleotide targeting BACE1, the key enzyme in amyloid beta protein （AI3） production, and introduced it into the pSilenCircle vector to construct a short hairpin （shRNA） expression plasmid against the BACE1 gene. We transfected this vector into C17.2 neural stem cells and primary neural stem cells, resulting in downregulation of the BACE1 gene, which in turn induced a considerable reduction in reducing AI3 protein production. We anticipate that this technique combining cell transplantation and gene ther- apy will open up novel therapeutic avenues for Alzheimer＇s disease, particularly because it can be used to simultaneously target several pathogenetic changes in the disease.     

阿尔茨海默病治疗的研究进展

阿尔茨海默病（AD）是一种隐匿性起病,进行性恶化的神经退行性疾病,临床最初表现为认知功能障碍,并有可能在5～10年内完全衰退。患者往往伴随严重的记忆力丧失、精神行为异常、人格改变、言语功能障碍,无法独立生活,最终近乎于植物状态。Ferri等采用DISMOD软件在全球60岁以上人群中估计,全球的痴呆患者人数到2040年将达到8llO万左右。