Diagnostic value of F wave changes in patients with Charcot-Marie-Tooth1A and chronic inflammatory demyelinating polyneuropathy / 北京大学学报(医学版)

OBJECTIVE@#To analyze and compare the characteristics and causes of F wave changes in patients with Charcot-Marie-Tooth1A (CMT1A) and chronic inflammatory demyelinating polyneuropathy (CIDP).@*METHODS@#Thirty patients with CMT1A and 30 patients with CIDP were enrolled in Peking University Third Hospital from January 2012 to December 2018. Their clinical data, electrophysiological data(nerve conduction velocity, F wave and H reflex) and neurological function scores were recorded. Some patients underwent magnetic resonance imaging of brachial plexus and lumbar plexus, and the results were analyzed and compared.@*RESULTS@#The average motor conduction velocity (MCV) of median nerve was (21.10±10.60) m/s in CMT1A and (31.52±12.46) m/s in CIDP. There was a significant difference between the two groups (t=-6.75, P < 0.001). About 43.3% (13/30) of the patients with CMT1A did not elicit F wave in ulnar nerve, which was significantly higher than that of the patients with CIDP (4/30, 13.3%), χ2=6.65, P=0.010. Among the patients who could elicit F wave, the latency of F wave in CMT1A group was (52.40±17.56) ms and that in CIDP group was (42.20±12.73) ms. There was a significant difference between the two groups (t=2.96, P=0.006). The occurrence rate of F wave in CMT1A group was 34.6%±39%, and that in CIDP group was 70.7%±15.2%. There was a significant difference between the two groups (t=-5.13, P < 0.001). The MCV of median nerve in a patient with anti neurofascin 155 (NF155) was 23.22 m/s, the latency of F wave was 62.9-70.7 ms, and the occurrence rate was 85%-95%. The proportion of brachial plexus and lumbar plexus thickening in CMT1A was 83.3% (5/6) and 85.7% (6/7), respectively. The proportion of brachial plexus and lumbar plexus thickening in the CIDP patients was only 25.0% (1/4, 2/8). The nerve roots of brachial plexus and lumbar plexus were significantly thickened in a patient with anti NF155 antibody.@*CONCLUSION@#The prolonged latency of F wave in patients with CMT1A reflects the homogenous changes in both proximal and distal peripheral nerves, which can be used as a method to differentiate the CIDP patients characterized by focal demyelinating pathology. Moreover, attention should be paid to differentiate it from the peripheral neuropathy caused by anti NF155 CIDP. Although F wave is often used as an indicator of proximal nerve injury, motor neuron excitability, anterior horn cells, and motor nerve myelin sheath lesions can affect its latency and occurrence rate. F wave abnormalities need to be comprehensively analyzed in combination with the etiology, other electrophysiological results, and MRI imaging.

Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Calculation of the prevalence of progressive muscular atrophy among adults in China based on urban medical insurance data from 15 provinces / 北京大学学报(医学版)

OBJECTIVE@#To analyze the characteristics of patients with progressive muscular atrophy (PMA) and calculate the prevalence of PMA in China in 2016.@*METHODS@#A retrospective analysis based on China's urban employee basic medical insurance data and the urban residence basic medical insu-rance data from January 1, 2016 to December 31, 2016 was carried out. Children under 18 years old were excluded. Patients with progressive muscular atrophy were identified by disease names and codes. Subgroup analyses by gender, region and age were carried out to calculate the gender-specific, region-specific and age-specific prevalences. Age-adjusted national prevalence was estimated based on 2010 Chinese census data. Sensitivity analyses were done by only considering the observed cases and by excluding the top 10% provinces regarding the missing rate of diagnostic information, respectively.@*RESULTS@#A total of 996.09 million person-years were included in this study, with 518.41 million person-years in males and 477.67 million person-years in females. The age and gender distribution of the study population was similar to that of the 2010 Chinese census data, therefore the study population was nationally representative. The prevalence of PMA in China in 2016 was 0.28 per 100 000 person-years (95%CI: 0.24-0.33), with 0.21 per 100 000 person-years (95%CI: 0.16-0.26) and 0.35 per 100 000 person-years (95%CI: 0.28-0.42) for females and males, respectively. Regional disparity existed in the Chinese PMA prevalence, with the lowest prevalence in Southwest region (0.11 per 100 000 person-years, 95%CI: 0.07-0.15) and the highest prevalence in Northwest region (3.47 per 100 000 person-years, 95%CI: 0.80-7.99). Age trend in the PMA prevalence was not obvious, but the prevalence among those aged 70 years and older was relatively higher. The age-adjusted prevalence based on 2010 Chinese census data was 0.29 per 100 000 person-years (95%CI: 0.27-0.31). The national prevalences calculated by only considering the observed cases and by excluding the top 10% provinces regar-ding the missing rate of diagnostic information were 0.17 per 100 000 person-years (95%CI: 0.14-0.20) and 0.24 per 100 000 person-years (95%CI: 0.20-0.28), respectively.@*CONCLUSION@#This study is to calculate the prevalence of PMA among adults in urban China, which can provide basic statistics for the enactment of PMA related medical policies, and clues for the studies on the mechanisms of PMA.

Diagnostic value of tremor analysis in identifying the early Parkinson's syndrome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the diagnostic value of tremor analysis in early stages of Parkinson's syndrome, when the clinical symptoms of tremor onset are not unilaterally often able for a definite diagnosis to be made.@*METHODS@#We included 70 patients with unilateral tremor, under 45 years old and disease duration within 3 years enrolled in Peking University Third Hospital from January, 2014 to December 2015. We recorded clinical features, unified Parkinson's disease rating scale (UPDRS)-III, non-motor symptom (NMS) scores. Tremor analysis and transcranial sonography were performed for all the patients. Based on the results of tremor analysis, we arbitrarily divided the patients into 3 groups: (1) The patients with classical Parkinson's syndrome manifestations on one side (25 cases); (2) The patients with classical Parkinson's syndrome manifestations on both sides (15 cases); (3) The patients with no classical Parkinson's syndrome manifestations (30 cases). The patients were monitored every 6 months to 3 years, until the final diagnosis was made.@*RESULTS@#There was no significant difference in age, gender distribution, Hamilton depression scale (HAMD) scores and H-Y scores among the three groups (P>0.05). The average UPDRS-III motor scores of the three groups were significantly different (P=0.001), with 18.23, 18.79 and 14.67, respectively. The average scores of NMS were significantly different, with 15.81, 17.07 and 9.90, respectively (P<0.001). The positive rates of transcranial sonography (TCS) in the three groups were 48.0%, 60.0% and 26.67%, with no significant difference (P=0.702). After three years of follow-up, 35 patients (50%) met the diagnostic criteria of Parkinson's disease of International Parkinson and Movement Disorder Society (MDS) in 2015, 19 patients (27.1%) met the criteria of idiopathic tremor, and 7 patients (10%) met the criteria of Parkinson's plus syndrome. The sensitivity and specificity of tremor analysis for early diagnosis of Parkinson's disease were 82.8% and 68.6%, respectively. Compared with TCS, the sensitivity and specificity of TCS were 65.7% and 62.9%. There were consistency (Kappa=0.568) and significant difference (P=0.031) between the two methods.@*CONCLUSION@#Tremor analysis is sensitive and a superior way in identifying early Parkinson's syndrome patients with tremor dominant manifestation. The combination of non-motor symptoms and transcranial sonography are also needed at diagnosis.

Management of severe internal carotid stenosis with unruptured intracranial aneurysm / 北京大学学报(医学版)

OBJECTIVE@#To investigate the safety and feasibility of endovascular treatment for severe internal carotid artery stenosis (≥70%) with unruptured intracranial aneurysms.@*METHODS@#We retrospectively reviewed 213 cases with severe stenosis or occlusion of internal carotid artery, and those patients had been treated at Peking University Third Hospital, between January 2012 and July 2015. In the study, 14 (6.6%) cases were coexistence with unruptured intracranial aneurysms. The medical records, imaging data, treatment and prognosis were analyzed.@*RESULTS@#There were 15 aneurysms (11 after the stenosis, 1 before the stenosis, and 3 in the other drainage basin) in those 14 patients with severe stenosis or occlusion of internal carotid artery. One of the 14 patients underwent carotid endarterectomy, and the 11 patients were successfully implanted with an internal carotid stent (residual stenosis 0-30%, mean 6.4%). Two patients with internal carotid artery stenosis remained untreated. One of them had complete occlusion of the initial segment of the internal carotid artery and was not possible to be treated, and the other patient refused to treat with internal carotid stenosis. The sizes of aneurysms were 1.0-7.0 mm, with an average of (2.8±1.5) mm. Three cases were treated with stenosis and aneurysms treated at the same time, and stent assisted coil embolization was performed in all the aneurysms, including 1 case that treated aneurysm before the stenosis. One patient refused surgical treatment of unruptured aneurysm, and no treatment was given to 10 patients who had small unruptured aneurysms (<5.0 mm). No perioperative complications were observed during the perioperative period. Three cases were lost with the follow-up, and the other 11 patients were followed up for 15-55 months, with a median of 37 months, and had good prognosis.@*CONCLUSION@#Our results suggest that patient coexistance with severe internal carotid stenosis and unruptured intracranial aneurysms should be treated individually according to the location and size of aneurysms. Moreover, the presence of a small intracranial aneurysm (<5.0 mm) does not seem to increase the risk of endovascular stenosis in patients with severe internal carotid stenosis.

Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study / 中华医学杂志(英文版)

Background@#Disease-modifying therapy is the standard treatment for patients with multiple sclerosis (MS) in remission. The primary objective of the current analysis was to assess the efficacy and safety of two teriflunomide doses (7 mg and 14 mg) in the subgroup of Chinese patients with relapsing MS included in the TOWER study.@*Methods@#TOWER was a multicenter, multinational, randomized, double-blind, parallel-group (three groups), placebo-controlled study. This subgroup analysis includes 148 Chinese patients randomized to receive either teriflunomide 7 mg (n = 51), teriflunomide 14 mg (n = 43), or placebo (n = 54).@*Results@#Of the 148 patients in the intent-to-treat population, adjusted annualized relapse rates were 0.63 (95% confidence interval [CI]: 0.44, 0.92) in the placebo group, 0.48 (95% CI: 0.33, 0.70) in the teriflunomide 7 mg group, and 0.18 (95% CI: 0.09, 0.36) in the teriflunomide 14 mg group; this corresponded to a significant relative risk reduction in the teriflunomide 14 mg group versus placebo (-71.2%, P = 0.0012). Teriflunomide 14 mg also tended to reduce 12-week confirmed disability worsening by 68.1% compared with placebo (hazard ratio: 0.319, P = 0.1194). There were no differences across all treatment groups in the proportion of patients with treatment-emergent adverse events (TEAEs; 72.2% in the placebo group, 74.5% in the teriflunomide 7 mg group, and 69.8% in the teriflunomide 14 mg group); corresponding proportions for serious adverse events were 11.1%, 3.9%, and 11.6%, respectively. The most frequently reported TEAEs with teriflunomide versus placebo were neutropenia, increased alanine aminotransferase, and hair thinning.@*Conclusions@#Teriflunomide was as effective and safe in the Chinese subpopulation as it was in the overall population of patients in the TOWER trial. Teriflunomide has the potential to meet unmet medical needs for MS patients in China.@*Trial Registration@#ClinicalTrials.gov, NCT00751881; https://clinicaltrials.gov/ct2/show/NCT00751881?term=NCT00751881&rank=1.

Efficacy of intravitreal injection of anti-VEGF drugs combination with other methods for Coats disease / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the effect of intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs combined with other methods in the treatment of Coats disease.METHODS:Selected 13 patients 13 eyes with Coats disease in our hospital from May 2013 to May 2016.All eyes were treated with intravitreal injection of ranibizumab and combined with scleral drainage, laser photocoagulation and so on.We observed visual acuity and retinal reattachment.RESULTS:In 13 eyes, the treatment of 4 eyes with intravitreal injection of ranibizumab and combined with scleral drainage, 3 eyes combined laser photocoagulation, 6 eyes combined vitrectomy, membrane peeling, freezing, silicone oil filling or other treatments.Eyeball retention rate was 100%.Visual acuity at 6mo after treatment significantly improved compared with before treatment (P<0.05).The visual acuity was ≥0.05-0.1, 0.01-<0.05, counting finger, light perception and hand moving before treatment in 0, 0, 38%, 38% and 23%, after treatment were 23%, 23%, 38%, 15% and 0.Complete retinal reattachment was achieved in 5 eyes, accounting for 38%;basic reset in 3 eyes, accounting for 23%;5 eyes were not reset, accounting for 38%.CONCLUSION:Intravitreal injection of anti-VEGF drugs combined with other methods for the treatment of Coats disease have a certain effect, can improve or maintain the limited visual function, avoid enucleation of eyeball due to disease progression.

Clinical Features of Isolated Bulbar Palsy of Amyotrophic Lateral Sclerosis in Chinese Population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Progressive bulbar palsy (PBP) is a classic phenotype of bulbar onset amyotrophic lateral sclerosis (ALS) with more rapid progression and worse prognosis. However, as an often under-understood variant of ALS, isolated bulbar palsy (IBP) appears to progress more slowly and has a relatively benign prognosis. This study aimed to investigate the natural course and clinical features of IBP in Chinese population and to compare them with those of PBP.</p><p><b>METHODS</b>The clinical data of patients with bulbar onset ALS were collected from January 2009 to December 2013. Revised ALS Functional Rating Scale (ALSFRS-R), forced vital capacity (FVC), and follow-up evaluation were performed, and the differences in basic clinical features, ALSFRS-R, FVC, and primary outcome measures between IBP and PBP were analyzed. The independent t-test, Chi-square test, Mann-Whitney U-test, and Kaplan-Meier analysis were used.</p><p><b>RESULTS</b>Totally 154 patients with bulbar onset ALS were categorized into two groups, 33 with IBP and 121 with PBP. In the IBP group, the male to female ratio was 0.7 to 1.0, and the mean onset age was 58.5 years. The mean duration from the onset was 16.0 months, and the mean ALSFRS-R score was 43.4 at patients' first visit to our hospital. In 14 IBP patients performing FVC examination, the mean FVC value was 90.5% and there were only two cases with abnormal FVC. In 26 IBP patients completing follow-up, 15 (58%) suffered death or tracheotomy and the mean survival time was 40.5 months. Significant differences were noted in sex ratio, onset age, ALSFRS-R score, upper motor neuron limb signs, pure lower motor neuron (LMN) bulbar signs, FVC, and survival time between IBP and PBP.</p><p><b>CONCLUSIONS</b>IBP was evidently different from PBP, which was characterized with the predominance of female, pure LMN bulbar signs, an older onset age, a relative preservation of respiratory function, and a better prognosis.</p>

Elimination Rate of Serum Lactate is Correlated with Amyotrophic Lateral Sclerosis Progression / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mitochondrial dysfunction plays an important role in the pathogenesis of amyotrophic lateral sclerosis (ALS). We aimed to demonstrate mitochondrial dysfunction in ALS using a lactate stress test and to examine the relationship between mitochondrial dysfunction with motor deterioration.</p><p><b>METHODS</b>We enrolled 116 patients and observed clinical variables, including the survival state.</p><p><b>RESULTS</b>Patients with a rapid slope of revised ALS functional rating scales (ALSFRS-r) (>20 U/year) exhibited the slowest elimination rate (median -4.67 × 10-3 mmol·L-1·min-1 , coefficient of variation, 590.15%), the shortest duration (0.63 ± 0.28 years) and the worst ALSFRS-r (32.59 ± 4.93). Patients with a moderate slope of ALSFRS-r (10-20 U/year) showed a moderate elimination rate (median -11.33 × 10-3 mmol·L-1·min-1 , coefficient of variation, 309.89%), duration (1.16 ± 0.45 years), and ALSFRS-r (34.83 ± 6.11). The slower progressing (<10 U/year group) patients exhibited a rapid elimination rate (median: -12.00 × 10-3 mmol·L-1·min-1 , coefficient of variation: 143.08%), longer duration (median: 3 years, coefficient of variation: 193.33%), and adequate ALSFRS-r values (39.58 ± 9.44). Advanced-phase ALS patients also showed slower elimination rate (ER, quartiles -17.33, -5.67, 4.00) and worse ALSFRS-r (34.88 ± 9.27), while early-phase patients showed a more rapid ER (quartiles -25.17, -11.33, -3.50) and better ALSFRS-r (39.28 ± 7.59). These differences were statistically significant. Multiple linear regression analysis revealed strong direct associations among ER, ALSFRS-r slope (standard beta = 0.33, P = 0.007), and forced vital capacity (predict %) (standard beta = -0.458, P = 0.006, adjusted for ALSFRS-r, course and onset region). However, the data obtained from 3 years of follow-up showed no statistically significant difference in the survival rates between the most rapid and slowest ER groups.</p><p><b>CONCLUSION</b>There is a potential linear relationship between ER and motor deterioration in ALS. Slower ER might be associated with faster disease progression.</p>

Association Between Rectus Abdominis Denervation and Ventilation Dysfunction in Patients with Amyotrophic Lateral Sclerosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Spontaneous potentials in electromyography (EMG) of paraspinal muscles are associated with diaphragm denervation and, therefore, poor respiratory function in amyotrophic lateral sclerosis (ALS) is understandable. EMG changes in the rectus abdominis (RA) display an effect similar to those in paraspinal muscles with respect to the function of lower motor neurons in the thoracic spinal cord. The RA denervation was examined to determine its association with ventilation dysfunction in ALS.</p><p><b>METHODS</b>We collected the clinical data of 128 patients with sporadic ALS in Department of Neurology of Peking University Third Hospital from 2009 to 2013. EMG, Revised ALS Functional Rating Scale (ALSFRS-R) and forced vital capacity (FVC) were performed in all patients and the differences in the EMG changes in RA between those with and without FVC ≥ 80% were analysed.</p><p><b>RESULTS</b>The mean FVC value was 83.4% ± 17.1% (range: 45%-131%) of the predicted value. A total of 79 patients displayed FVC ≥80%, and 49 patients displayed FVC <80%. Compared with the patients displaying a normal FVC (60/79, 75.9%), spontaneous activity in RA was significantly different among those patients displaying an FVC <80% (47/49, 95.9%). In addition, spontaneous potentials in RA were more frequently detected in patients exhibiting dyspnea (32/33, 97.0%) than in patients without dyspnea (75/95, 78.9%).</p><p><b>CONCLUSION</b>Spontaneous potentials in RA are associated with ventilation dysfunction and dyspnea in ALS patients.</p>

Clinical study on retinal nerve fiber layer thickness of children and adolescent measured by OCT / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the clinical characteristics in retinal nerve fiber layer ( RNFL) thickness of the 8~17 years old near sightedness, provide the basis for juvenile glaucoma diagnosis, to avoid missed diagnosis and misdiagnosis. METHODS:A total of 165 eyes from 99 healthy subjects ( age range 8 ~ 17 years ) were divided into low, moderate, high myopia and normal group. Cirrus HD OCT was used to measure the RNFL thickness. Each subject was performed circular scans around the optic nerve with a circle size of 3. 46mm. Total average, mean quadrant and clock - hour RNFL thicknesses were recorded and compared between the four groups. The characteristics of the RNFL thickness of myopia were observed. RESULTS: Compared myopia groups with normal group, the mean RNFL thickness decreased, there was statistically significant difference in high myopia group (PCONCLUSION: Compared adolescent myopia with normal, the Avg ( mean RNFL thickness ) , S ( superior quadrant RNFL thickness ) , I ( inferior quadrant RNFL thickness), 1:00, 5:00, 6:00 and 12:00 o'clock RNFL thickness is thinner, which is decreased with the increasing SE. While the temporal ( T) quadrant, 8:00, 9:00, 10:00 o'clock RNFL thickness is thicker, which increased with the increasing SE. Analysis of RNFL thickness in the evaluation of glaucoma should always be interpreted with reference to the refractive status, so as not to cause misdiagnosis of glaucoma. The highest diagnosis efficiency position of glaucoma is infratemporal (7:00~8:00 o'clock) and superior temporal (10:00 ~11:00 o'clock), which is not thinner in juvenile myopia, if these positions become thinner, it may be the possibility of glaucoma.

Assessing Cardiovascular Health Using Life's Simple 7 in a Chinese Population Undergoing Stroke Prevention / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The American Heart Association/American Stroke Association proposed a metric called Life's Simple 7 (LS7) to define cardiovascular health (CVH). The presence of a large number of ideal components of CVH is associated with lower cardiovascular disease and all-cause mortality. We aimed to assess CVH using LS7 in a Chinese population undergoing primary and secondary stroke prevention.</p><p><b>METHODS</b>Patients with either ischemic stroke or cardiovascular risk factors were enrolled in the study from October 2010 to July 2013. LS7 components were scored as poor (0 points), intermediate (1 point), or ideal (2 points). The overall LS7 score was categorized as inadequate (0-4), average (5-9), or optimal (10-14) CVH. The Chi-square test, Mann-Whitney U-test, and Kruskal-Wallis test were used.</p><p><b>RESULTS</b>In total, 706 patients were enrolled. (1) The distribution of the overall LS7 score (n = 255) indicated that 9.4%, 82.4%, and 8.2% of the patients had inadequate, average, and optimal CVH, respectively. The proportion of patients with optimal CVH undergoing secondary stroke prevention was lower than that for patients undergoing primary stroke prevention (3.8% vs. 12.8%, P = 0.005). The vast majority of participants (76.1%) presented with ≤2 ideal health components. (2) The proportions of patients with poor, intermediate, and ideal status, respectively, for the following LS7 components were assessed : t0 otal cholesterol (n = 275; 5.1%, 73.8%, and 21.1%), blood pressure (n = 351; 32.5%, 59.0%, and 8.5%), blood glucose (n = 280; 9.3%, 39.6%, and 51.1%), physical activity (n = 540; 90.7%, 8.7%, and 0.6%), diet (n = 524; 0.2%, 92.4%, and 7.4%), smoking (n = 619; 20.7%, 2.9%, and 76.4%), and body mass index (n = 259; 6.6%, 35.5%, and 57.9%).</p><p><b>CONCLUSIONS</b>Few Chinese patients undergoing stroke prevention had optimal CVH (determined using LS7). Additionally, fewer patients undergoing secondary prevention had optimal CVH than those undergoing primary prevention. In particular, physical activity and diet status in this population require improvement.</p>

Increased orexin expression promotes sleep/wake disturbances in the SOD1-G93A mouse model of amyotrophic lateral sclerosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Sleep/wake disturbances in patients with amyotrophic lateral sclerosis (ALS) are well-documented, however, no animal or mechanistic studies on these disturbances exist. Orexin is a crucial neurotransmitter in promoting wakefulness in sleep/wake regulation, and may play an important role in sleep disturbances in ALS. In this study, we used SOD1-G93A transgenic mice as an ALS mouse model to investigate the sleep/wake disturbances and their possible mechanisms in ALS.</p><p><b>METHODS</b>Electroencephalogram/electromyogram recordings were performed in SOD1-G93A transgenic mice and their littermate control mice at the ages of 90 and 120 days, and the samples obtained from these groups were subjected to quantitative reverse transcriptase-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>For the first time in SOD1-G93A transgenic mice, we observed significantly increased wakefulness, reduced sleep time, and up-regulated orexins (prepro-orexin, orexin A and B) at both 90 and 120 days. Correlation analysis confirmed moderate to high correlations between sleep/wake time (total sleep time, wakefulness time, rapid eye movement [REM] sleep time, non-REM sleep time, and deep sleep time) and increase in orexins (prepro-orexin, orexin A and B).</p><p><b>CONCLUSION</b>Sleep/wake disturbances occur before disease onset in this ALS mouse model. Increased orexins may promote wakefulness and result in these disturbances before and after disease onset, thus making them potential therapeutic targets for amelioration of sleep disturbances in ALS. Further studies are required to elucidate the underlying mechanisms in the future.</p>

Neurophysiological study of nerve entrapment sites in the upper limbs——evaluation value in Ginkgo leaf extract and dipyridamole injection combined with methylcobalam improving nerve conduction in diabetic peripheral neuropathy / 中华神经医学杂志

Objective To explore the effect of Ginkgo leaf extract and dipyridamole injection combined with methylcobalam on nerve conduction velocity of nerve entrapment sites in the upper limbs in patients with diabetic peripheral neuropathy (DPN).Methods Two hundred and eight type 2 diabetic patients with DPN,admitted to our hospital from January 2008 to June 2011,were selected in our study,and randomly divided into an observation group (n=103) and a control group (n=105).Dietary regulation,exercises and glucose control were conducted in both groups.In the control group,patients were given methylcobalamin at the dose of 1000 μg,three times a day.In the observation group,patients were given methylcobalamin (1000 μg,three times a day) plus Ginkgo leaf extract and dipyridamole injection of 20 mL once a day.All treatments lasted for four weeks.The sensory conduction velocity (SCV),motor conduction velocity (MCV) and sensory nerve action potential (SNAP),compound muscle action potential (CMAP) and distal motor latency (DML) of median and ulnar nerves were measured and compared before and four weeks after the treatments.Results The DML was shortened,and SCV and amplitude of median nerve were improved.Segmental MCV of above-below elbow,SCV and amplitude of ulnar nerve were significantly improved in both groups after the treatments as compared with those before treatment (P＜0.05); the total effective rate of the observation group was significantly higher than that of the control group (P＜0.05).Conclusion The nerve electrophysiological characteristics of nerve compression sites in the upper limbs is sensitive for assessing injury and treatment effect in patients with DPN; the combination of Ginkgo leaf extract and dipyfidamole injection and methylcobalam is superior than methylcobalam alone in improving the nerve conduction of diabetic patients.

Protective effect of Ifenprodil on motor neurons in in vitro amyotrophic lateral sclerosis models / 中华神经医学杂志

Objective To investigate the protective effect of Ifenprodil on motor neurons in in vitro threo-hydroxyaspartate (THA)-induced amyotrophic lateral sclerosis (ALS) models.Methods THA was added into the isolated culture of brain slices to induce chronic glutamate damage and mimic the typical changes of ALS pathology.Cultured brain slices were separated randomly to 6 different groups,including control group (without THA),THA inducement group (adding 100 μmol/L THA for one week) and THA and Ifenprodil treatment groups (adding 0.1,1,10 and 100 μmol/L of Ifenprodil 2 h before 100 μmol/L THA inducement); 6 culture dishes were employed in each group.According to PI fluorescence intensity,the most effective concentration of Ifenprodil was selected.The concentration of malonaldehyde (MDA) in supematant of cultured tissues was evaluated by MDA testing kit and the protein expression of cysteine-aspartic proteases-3 (caspase-3) in motor cortex was tested by Western blotting at different injury times.Results PI staining showed that 10 μmol/L Ifenprodil could produce prominent protective effect on motor neurons in the ALS models.Levels of MDA in supernatant and activated 17KD caspase-3 in the THA treatment group obviously increased as compared with those in the other groups (P＜0.05); 10 μmol/L Ifenprodil could block the increment of MDA and activated caspase-3 levels effectively.Conclusion Ifenprodil can effectively protect motor neurons in in vitro THA-induced ALS models by reducing oxidative stress and inhibiting caspase-3 activation.

Comparison of surgical intervention with functional treatment for acute ruptures of lateral ankle ligmant: a meta-analysis

OBJECTIVE@#To compare the effect of surgical intervention on functional treatment.@*METHODS@#By searching the MEDLINE (1966 to October 2011), EMBASE (1980 to October 2011), the Chinese Biomedical Database Databases (1980 to October 2011), a total of 9 related RCT studies comparing surgical intervention with functional treatment were included in our study. RevMan software was taken to analyze the data.@*RESULTS@#These 9 studies involved a total of 1 268 mostly young adults, including 580 patients with surgical treatment and 688 patients with functional treatment. The results showed the stability of ankle activity in surgical treatment group was better than that in functional treatment group, with the OR and 95% CI of 0.72 (0.52-0.99). No significant difference was found in the recurrence of the surgical and functional group. However, the movement disorder in the surgical treatment suggested increased risk than that in functional group, with the OR and 95% CI of 2.39 (0.98-5.85). Surgical group found more complication than the function group, such as deep vein thrombosis, deep venous thrombosis, tenderness of scar and sensory loss.@*CONCLUSIONS@#In conclusion, our finding showed that surgical treatment could gain better efficacy than functional treatment, but may bring more complication. Therefore, further large sample size RCT is warranted.

Abnormal trigeminocervical response in patients with spinal and bulbar muscular atrophy

Objective: To investigate the value of the trigeminocervical response (TCR) for revealing bulbar involvement in patients with spinal and bulbar muscular atrophy (SBMA). Methods: Thirty patients with SBMA and 30 healthy male controls were included in this study. In all of the normal controls, stimulation of the infraorbital nerve on one side produced bilateral short latency waves consisting of a positive/negative wave, p19/n31, the mean latency of which was measured. The mean square root of the ratio between the amplitude of p19/n31 and the mean rectifi ed surface electromyography (EMG) activity preceding the stimulus, the A value, was estimated. The parameters of the TCR were compared between the two groups. Results: Among the patients with SBMA, 21 (70.0%) had delayed latencies of p19/n31 (P < 0.01) and all (100%) had reduced A values (P < 0.01) relative to the normal controls. Conclusions: All parameters of the TCR were signifi cantly different between the patients with SBMA and the normal controls. T

Correlation of serum cystatin C and creatinine levels with cerebral infarction / 中华神经医学杂志

Objective To investigate the correlation of serum cystatin C and creatinine levels with cerebral infarction. Methods Eighty-four patients with cerebral infarction diagnosed by clinical manifestations, CT and (or) MRI and 76 healthy subjects were selected. Cystatin C level was tested by enzyme-linked immunosorbent assay (ELISA) and creatinine level was tested by the method of nitroxanthic acid. The correlation of cystatin C and creatinine levels with cerebral infarction was explored. Results The level of serum cystatin C in the cerebral infarction group (1.69±0.60 mg/L) was significantly lower as compared with that in the control group (2.00±0.67 mg/L) (t=-3.084, P=0.002); the level of serum creatinine in the cerebral infarction group (86.62±14.02 μmol/L) was significantly higher as compared with that in the control group (80.88±13.71 μmol/L) (t=2.611, P=0.010). Negative correlation between level of serum cystain C and cerebral infarction was noted (r=-0.238, P=0.002),while the level of serum creatinine was positively related to cerebral infarction (r=0.208, P=0.010).Conclusion A close correlation between cerebral infarction and both the levels of cystain C and creatinine exists, with cystatin C being a protective factor and creatinine being a risk factor for clinical cerebral infarction.

Clinical study of the contact heat evoked potentials / 中华神经医学杂志

Objective To search for a method to differentiate the peripherial and central part of spinothalamic tract. Methods The subjects were set on supine position. A heat-foil technology was used to elicit pain and contact heat evoked potentials (CHEP). Thermal stimuli were sent at 54.5 ℃ to three body sites: the dorsum of hand, proximal volar foratm and C7. CHEP was recorded from Cz and Pz. The main components of CHEP were watched. Nerve conduction velocity was calculated. Results Two components, Cz/N550 and Cz/P750, were found in the evoked potentials. The latency of CHEP were different when the dorsum of hand, proximal volar forarm and C, were stimulated respectively. There was no statistical difference between males and females. Nerve conduction velocity of the fiber was (12.9±7.5) m/s which was corresponded to that of AS fiber. Conclusion It is suggested that pain evoked potential could be elicited reliably,the stimulation of C7 would help differentiate the lesion of peripherial and central part of spinothalamic tract.

Linkage of modified human papillomavirus type 16 E7 to CD40 ligand enhances specific CD8+ T-lymphocyte induction and anti-tumour activity of DNA vaccine / 中国医学科学院学报

<p><b>OBJECTIVE</b>To develop human papillomavirus (HPV) 16 DNA vaccine for the treatment of HPV16 infection and its related tumors.</p><p><b>METHODS</b>HPV16 oncogene E7 was modified by combined approaches including insertion and replication of specific region of E7 gene, murine codon optimization, and point-mutation at transforming regions of the E7 protein. The resulting artificial gene, named as mE7, was obtained by gene synthesis. The mE7 gene was then genetically fused to murine CD40 ligand (CD40L) by overlapping PCR to form the mE7/CD40L fusion gene. The mE7/CD40L gene was inserted into pVR1012 plasmid and then immunized C57/BL6 mice intramuscularly. The E7-specific IFN-gamma-secreting CD8+ T cells were analyzed with EIISPOT, and E7-specific antibody was measured by indirect ELISA. FACS assays were performed to analyze the activation of E7-specific Th cells. Mice were vaccinated, followed by tumor challenged or challenged before immunization. Tumor growth was observed.</p><p><b>RESULTS</b>The mE7 DNA vaccine elicited an increased E7-specific antibody level (P < 0.01), E7-specific IFN-gamma-secreting CD8+ T (P < 0.01), and CD4+ T cells number (P < 0.05), compared with those of mice immunized with wE7 gene. Furthermore, the mE7/CD40L DNA vaccine elicited an increased number of E7-specific IFN-gamma secreting CD8+ T cell compared with that of mice immunized with mE7 gene (P < 0.01); however, no significant differences were found between mice immunized with the mE7 gene and mE7/CD40L fusion gene in the E7-specific antibody production and Th cell activation. In the preventive experiment, all mice received the mE7 or mE7/CD40L remained tumor-free 7 weeks after challenges with TC-1 tumor cells, while the wE7 group exhibited tumor growth within 2 weeks. In the therapeutic experiment, all the mice in the wE7 group exhibited tumor growth within 8 days, while among mice receiving the mE7 and mE7/CD40L, 30% and 45% of mice remained tumor-free after TC-1 challenge, respectively. HE staining of tumor tissues showed copious lymphocytes infiltration around tumor cells in mE7 and mE7/CD40L mice with regression of tumor growth.</p><p><b>CONCLUSIONS</b>The mE7 DNA vaccine increases the E7-specific humoral and cellular immune responses, and the fusion of CD40L to mE7 gene enhances the specific immune responses and anti-tumor effects against HPV16 E7-expressing murine tumors. mE7/CD40L may therefore be a suitable and promising target for HPV16 therapeutic vaccine.</p>