Safety and efficacy of botulinum toxin type A made in China for treatment of post-stroke upper limb spasticity: a randomized double-blind controlled trial / 中华神经科杂志

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191

Clinical efficacy of prophylactic cranial irradiation for patients with surgically resected small cell lung cancer / 中华放射肿瘤学杂志

Objective To evaluate the clinical efficacy of prophylactic cranial irradiation (PCI) in the treatment of surgically resected small cell lung cancer (SCLC).Methods Clinical data of SCLC patients undergoing radical resection surgery in Zhejiang Cancer Hospital from 2003 to 2015 were retrospectively analyzed.According to the treatment modality,all patients were allocated into the PCI and non-PCI groups.A total of 52 patients were finally included,including 19 patients in the PCI group (5 cases of stage Ⅰ,5 stage Ⅱ and 9 stage Ⅲ) and 33 in the non-PCI group (12 cases of stage Ⅰ,5 stage Ⅱ and 16 stage Ⅲ).Kaplan-Meier method was utilized for survival analysis.Cox proportional hazards model was adopted to analyze clinical prognosis.Results The median survival time was 32.9 months in the PCI group,and 20.4 months in the non-PCI group.The 2-year overall survival rate was 72％ in the PCI group,significantly higher than 38％ in the non-PCI group (P=0.023).The median brain metastasis-free survival (BMFS) was 32.5 months in the PCI group,and 17.1 months in the non-PCI group.In the PCI group,the 2-year BMFS rate was 89％,significantly better than 53％ in the non-PCI group (P=0.026).Subgroup analysis demonstrated that PCI could confer survival benefit to patients with p-stage Ⅲ (p=0.031) rather than p-stage Ⅰ (P=0.924) and Ⅱ (P=0.094) counterparts.Multivariate analysis revealed that PCI (HR=0.330,P=0.041) was an independent prognostic factor of the overall survival.Conclusions PCI can reduce thr risk of brain metastasis rate and improve the overall survival of patients with surgically resected SCLC.

Small RNA interference-mediated gene silencing of TREK-1 potassium channel in cultured astrocytes / 华中科技大学学报（医学）（英德文版）

This study was aimed to examine the effect of TREK-1 silencing on the function of astrocytes. Three 21-nucleotide small interfering RNA (siRNA) duplexes (siT1, siT2, siT3) targeting TREK-1 were constructed. Cy3-labeled dsRNA oligmers were used to determine the transfection efficiency in cultured astrocytes. TREK-1-specific siRNA duplexes (siT1, siT2, siT3) at the optimal concentration were transfected into cultured astrocytes, and the most efficient siRNA was identified by the method of immunocytochemical staining and Western blotting. The proliferation of astrocytes tranfected with TREK-1-targeting siRNA under hypoxia condition was measured by fluorescence-activated cell sorting (FACS). The results showed that TREK-1 was expressed in cultured astrocytes. The dsRNA oligmers targeting TREK-1 could be transfected efficiently in cultured astrocytes and down-regulate the expression of TREK-1 in astrocytes. Moreover, the down-regulation of TREK-1 in astrocytes contributed to the proliferation of astrocytes under hypoxia condition as determined by cell cycle analysis. It was concluded that siRNA is a powerful technique that can be used to knockdown the expression of TREK-1 in astrocytes, which helps further investigate the function of TREK-1 channel in astrocytes under physicological and pathological condition.

Small RNA interference-mediated gene silencing of TREK-1 potassium channel in cultured astrocytes / 华中科技大学学报（医学）（英德文版）

This study was aimed to examine the effect of TREK-1 silencing on the function of astrocytes. Three 21-nucleotide small interfering RNA (siRNA) duplexes (siT1, siT2, siT3) targeting TREK-1 were constructed. Cy3-labeled dsRNA oligmers were used to determine the transfection efficiency in cultured astrocytes. TREK-1-specific siRNA duplexes (siT1, siT2, siT3) at the optimal concentration were transfected into cultured astrocytes, and the most efficient siRNA was identified by the method of immunocytochemical staining and Western blotting. The proliferation of astrocytes tranfected with TREK-1-targeting siRNA under hypoxia condition was measured by fluorescence-activated cell sorting (FACS). The results showed that TREK-1 was expressed in cultured astrocytes. The dsRNA oligmers targeting TREK-1 could be transfected efficiently in cultured astrocytes and down-regulate the expression of TREK-1 in astrocytes. Moreover, the down-regulation of TREK-1 in astrocytes contributed to the proliferation of astrocytes under hypoxia condition as determined by cell cycle analysis. It was concluded that siRNA is a powerful technique that can be used to knockdown the expression of TREK-1 in astrocytes, which helps further investigate the function of TREK-1 channel in astrocytes under physicological and pathological condition.

The roles of thrombin and iron ions in brain jury after intracerebral hemorrhage / 国际脑血管病杂志

Intracerebral hemorrhage is a neurological emergency with high disability and mortality. Studies have demonstrated that thrombin formation,erythrocytolysis and iron ions play important roles in the brain injury after intracerebral hemorrhage. This article reviews the mechanisms of thrombin and iron ions in intracerebral hemorrhage-mediated brain injury.

Clinical analysis of 502 cases of subarachnoid hemorrhage / 中国综合临床

Objective To summarize the clinical and imaging features of subarachnoid hemorrhage(SAH) and its complications and prognosis. Methods The clinical data of 502 cases of SAH were retrospectively analyzed and summarized. Results There were 84.3 % (423/496) patients sufferring from intense headache, dizziness or vertigo (13. 1%, 66/496 ), disturbance of consciousness ( 27. 5%, 138/496 ), partial neurologic impairment (58.2% ,292/496) ,meningeal irritation sign(72.5% ,364/496). The positive rate of digital subtraction angiogra-phy was 54.1% (93/172). Aneurysm was the common reason of SAH (20. 1%, 101/496). Prognosis in most pa-tients was better,but the old patients suffered from high mortality. Conclusions The cause and clinical manifesta-tion of SAH varies,cerebral angiography often could help find the cause of SAH. Most SAH patients recover well.

Stroke Caused by Central Nervous System Vasculitis: 49 Cases Report / 中国康复理论与实践

@#Objective To explore the clinical manifestation of stroke caused by central nervous system vasculitis (CNSV). Methods 49 patients who suffered from stroke by CNSV were reviewed retrospectively. Results Among the 49 patients, 5 were intracerebral hemorrhage, 15 were ventricular hemorrhage, 7 were subarachnoid hemorrhage and 22 were cerebral infarction; the mean of age was (26.0±12.7) years old. Conclusion The clinical manifestation of stroke caused by CNSV is variform, and usually happens in young age. CNSV should be considered as the cause of stroke in adolescent.

Anterior commissure anomalies in APP/PS1 transgenic mouse models of Alzheimer's disease / 中国组织工程研究

BACKGROUND: Much research focuses on the link between β-amyloid peptide and neuron death, but there is little work about white matter alterations in the Alzheimer's disease.OBJECTIVE: To investigate the anterior commissure pathological alteration in the APP/PS1 transgenic mice which model brain amyloidosis of Alzheimer's disease.DESIGN, TIME AND SETTING: A grouping observational study based on the histology was performed in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between September 2007 and September 2008.MATERIALS: Female transgenic APP/PS1 mice [Thy1 APP751 SL (Swedish mutation KM670/671NL, London mutation V7171 introduced in human sequence APP751) × human mutation gene PS1 M146L], control animals were amyloid-deposit free female PS1 mice. A total of 28 mice were divided into young group (2 months, 8 APP/PS1, 7 PS1) and old group (24 months, 6 APP/PS1, 7 PS1).METHODS: The slides of brain tissue were stained with Congo red and antibody against amyloid beta (4G8) to detect brain amyloidosis in Alzheimer's disease transgenic model. Myelin was stained with gold chloride and axon was stained with anti-neurofilament M antibody. The anterior commissure axonal density and myelination were quantitatively analyzed with the relative optical density value of staining with densitometry.MAIN OUTCOME MEASURES: ①The staining of intracellular and extracellular amyloid beta; ②the average area of anterior commissure in the coronal brain tissue sections; ④the relative optical density value of myelin and axon staining in the anterior commissure.RESULTS: A lot of Congo red positive amyloid beta plaques were observed in the cortex, hippocampus, thalamus, and anterior commissure of aged APP/PS1 mice, while intracellular amyloid beta was only present in the cortex of young APP/PS1 mice. A prominent increase in the surface area of the anterior commissure was observed in aged PS1 mice compared with young PS1 mice and aged APP/PS1 mice. The neurofilament staining remarkably decreased, both in aged APP/PS1 and aged PS1 mice; an increase trend of myelination in the anterior commissure was observed both the forementioned groups. Different phenotype analysis demonstrated that axonal density and myelination was comparative in the young APP/PS1 and young PS1 mice; axonal density of aged APP/PS1 mice decreased remarkably compared with aged PS1 control mice, while myelination of aged APP/PS1 mice had no significant difference with aged PS1 mice.CONCLUSION: There exists an axon loss in the anterior commissure in the aged APP/PS1 mice with a complete myelin sheath. The amyloid beta shows a direct toxicity on the axon.

Advance in Biocompatibility of Biological Material for Neural Tissue Engineering(review) / 中国康复理论与实践

@#Biological scaffolds imitate the structure and function of extracellular matrix,and so good biocompatibility is essential for it.The materials in neural tissue engineering mainly include natural biomaterial and artificial biodegradable materials presently.This article has reviewed the biological function of materials mostly used in neural tissue engineering.

Current application of scaffold materials for nerve tissue engineering / 中国组织工程研究

BACKGROUND: It is a researching tendency for tissue engineering to develop compound, bionic, biological-active and intelligent materials, which are characterized by biological activity and can promote proliferation and differentiation of stem cells and tissue regeneration. OBJECTIVE: To summarize the application and development of scaffold materials for nerve tissue engineering. RETRIEVAL STRATEGY: A computer-based online search was conducted in Pubmed and V6.32 database of VIP Information Resource System for English language publications containing the key words of "nerve tissue engineering, tissue engineering, neural, neural stem cells, Schwann cell, biomedical materials, scaffold" from January 2001 to June 2007. There were 123 literatures in total. Inclusion criteria: ① articles about nerve repair with tissue engineering; ② current published literatures in the same field or in authoritative journals. Exclusion criteria: duplicated researches. LITERATURE EVALUATION: Articles are mainly derived from basic researches on scaffold materials for nerve tissue engineering, including resource, physical and chemical properties and compatibility with neural stem cells and Schwann cells. Among 36 involved literatures, there were 6 reviews, statement and lectures, and the other articles are basic researches. DATA SYNTHESIS: ① Up to now, there are no significantly researching breakthroughs about regeneration and repair after nerve injury in clinic. With the discovery of adult neural stem cells and the development of material and cell culture techniques, tissue engineering brings prospect for the treatment of nerve injury. ② Scaffold imitates the structure and function of extracellular matrix (ECM) and plays a key role in replacing extracellular matrix. It is a core for tissue engineering to look for seed cells with strong regeneration capacity and biological materials adapted to cell survival. ③ Researches demonstrate that the resource of scaffold materials for nerve tissue engineering is plentiful. Gelatine, collogen, polylactic acid hybrid materials, chitosan and acellular extracellular matrix are all considered as biocompatibility, security and stable physical and chemical characteristics. Therefore, they have a greatly applied prospect for tissue engineering. ④ There are still many difficulties of scaffold for nerve tissue engineering. It is important significance to optimise tissue construction technique and accelerate clinical application and industrial development of tissue engineering technique via further exploring basic problems, systemically elucidating formation and maturity of tissue engineering and investigating basic scientific problems and internal mechanism during prognosis in vivo. While, tissue engineering will certainly become a hot topic in the future. CONCLUSION: Researches on scaffold for nerve tissue engineering have obtained some achievements, but there are still many difficulties.

Anterior commissure anomalies in APP/PS1 transgenic mouse models of Alzheimer’s disease / 中国组织工程研究

BACKGROUND: Much research focuses on the link between ?-amyloid peptide and neuron death, but there is little work about white matter alterations in the Alzheimer’s disease. OBJECTIVE: To investigate the anterior commissure pathological alteration in the APP/PS1 transgenic mice which model brain amyloidosis of Alzheimer’s disease. DESIGN, TIME AND SETTING: A grouping observational study based on the histology was performed in the Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology between September 2007 and September 2008. MATERIALS: Female transgenic APP/PS1 mice [Thy1 APP751 SL (Swedish mutation KM670/671NL, London mutation V717I introduced in human sequence APP751) ? human mutation gene PS1 M146L], control animals were amyloid-deposit free female PS1 mice. A total of 28 mice were divided into young group (2 months, 8 APP/PS1, 7 PS1) and old group (24 months, 6 APP/PS1, 7 PS1). METHODS: The slides of brain tissue were stained with Congo red and antibody against amyloid beta (4G8) to detect brain amyloidosis in Alzheimer’s disease transgenic model. Myelin was stained with gold chloride and axon was stained with anti-neurofilament M antibody. The anterior commissure axonal density and myelination were quantitatively analyzed with the relative optical density value of staining with densitometry. MAIN OUTCOME MEASURES: The staining of intracellular and extracellular amyloid beta; ②the average area of anterior commissure in the coronal brain tissue sections; ③the relative optical density value of myelin and axon staining in the anterior commissure. RESULTS: A lot of Congo red positive amyloid beta plaques were observed in the cortex, hippocampus, thalamus, and anterior commissure of aged APP/PS1 mice, while intracellular amyloid beta was only present in the cortex of young APP/PS1 mice. A prominent increase in the surface area of the anterior commissure was observed in aged PS1 mice compared with young PS1 mice and aged APP/PS1 mice. The neurofilament staining remarkably decreased, both in aged APP/PS1 and aged PS1 mice; an increase trend of myelination in the anterior commissure was observed both the forementioned groups. Different phenotype analysis demonstrated that axonal density and myelination was comparative in the young APP/PS1 and young PS1 mice; axonal density of aged APP/PS1 mice decreased remarkably compared with aged PS1 control mice, while myelination of aged APP/PS1 mice had no significant difference with aged PS1 mice. CONCLUSION: There exists an axon loss in the anterior commissure in the aged APP/PS1 mice with a complete myelin sheath. The amyloid beta shows a direct toxicity on the axon.

Effects of collateral pathways on prognosis of cerebral infarct patients with prior transient ischemic attack / 中国医师进修杂志

Objective To investigate the effects of collateral pathways on prognosis of cerebral infarct patients with prior transient ischemic attack (TIA) and its role in neuroprotective mechanism of TIA. Methods A total of 164 cases of the first ever cerebral infarct patients were consecutively allocated into three groups: A , B and C group according to their age.Three groups were divided into two subgroups respectively based on the absence or presence of prior ipsilateral TIA: A1, A2, B1, B2, C1, C2 group. Neurological dysfunctional scores at admission and 1 month after treatment, barthel index, collateral pathways status, and cerebral infarction volume were evaluated respectively. The relationship between development of collateral pathways and prognosis was assessed at the same time. Results The neurological dysfunctional scores and cerebral infarction volume of patients in A1 group and B1 group were significantly lower than those of A2 group and B2 group (P

Clinical and neuroelectrophysiological characteristics of 32 children with poliomyelitis syndrome / 重庆医科大学学报

Objective:To analyze the clinical characteristics,neuroelectrophysiological changes and prognosis in children with Acute Flaccid Paralysis(AFP) caused by non-poliovirus(NPV) infections,and to explore it’s possible pathogenesis. Methods: Clinical observation,EV-antibody(EV-Ab) detection in blood serum,creatase detection in blood serum,cerebrospinal fluid(CSF) check-up and electrophysiologic study(EPS) were done in 32 AFP cases by NPV infections;and the result were compared. Results:(1)Children at every age were involved,mostly at age of 1~3 years;it occurred in every season,mostly in summer and autumn;Before palsy,most of them were affected by viral infections in respiratory tract or digestive tract;29 cases had AFP in one side of lower extremity with 3~4 grade muscle force,only 3 cases presented dissymmetrical AFP in both lower extremities,all cases had weakened tendon reflex,and none had sensory disorder.(2)Of 32 cases,10 presented Coxsackie virus antibody(CBV-IgM)(+) and 12 ECHOV-IgM(+) in blood serum,2 presented CBV-IgM(+) and slightly increased protein in CSF,and the rest were normal;2 cases had slightly increased CK in blood serum during climax,and presented normal in convalescent period. (3)Electrophysiologic changes included the following 29 cases had cutdowned compound muscle action potential(CMAP) wave amplitude in motor nerves,especially in the distal amplitude,even disappeared,and had normal nerve conduction velocity(NCV) in motor nerves,the present rate of F-wave was decreased,all cases had normal sensory nerve action potential(SNAP),and normal sensory nerve conduction velocity(SCV),electromyogram of 26 cases indicated neurogenic lesion,and only 3 cases had no obvious changes.(4)Majority of 32 cases recovered in two weeks,and the prognosis was good. Conclusion:The possible mechanism of AFP in children with NPV infections is that the induced immune reaction from NPV infections leaded to the motor nerve’s axonal slight degeneration,especially in its distal amplitude.

Wilson's disease and hepatic transplantation / 华中科技大学学报（医学）（英德文版）

To investigate the changes in neurological symptoms and signs, as well as serum copper, serum ceruloplasmin after hepatic transplantation in patients with Wilson's disease, neurological symptoms and signs, serum copper, serum ceruloplasmin before and after hepatic transplantation in 18 patients with Wilson's disease were observed, and those changes were followed up in 20 non-operative controls treated with penicillamine. Our results showed that the neurological symptoms and signs, serum copper and serum ceruloplasmin were improved in the operative group but deteriorated in the non-operative control group. Our study showed that hepatic transplantation is better than penicillamine in the treatment of Wilson's disease.

Study on the immunologic mechanism of myasthenia gravis / 中国病理生理杂志

AIM: To further investigate the immunologic mechanism of myasthenia gravis(MG). METHODS: Acetylcholine receptor antibodies(AchRab) and presynaptic membrane antibodies (PsMab) was determined by ELISA in 285 cases of MG patients. Tumor necrosis factor- alpha(TNF-?) and RBC-C3b receptor rosette rate(RBC-C3bRR)and RBC-IC rosette rate (RBC-ICR)was determined in 202 patients with MG. Furthermore, the peripheral blood lymphocyte subsets was examined in 104 cases MG patients. RESULTS: The positive rates of the AchRab and PsMab in MG were very significantly higher than that of control.The positive rate of PsMab in patients with negative AchRab was very significantly higher than that of patients with the positive AchRab.In 202 MG patients, the TNF-? was significantly higher, but the RBC-C3bRR was significantly lower than those of control, while the RBC-ICR has no significant change. CONCLUSION: MG is an autoimmune disease with damaged postsynaptic membrane by the AchRab, and some patients with both the AchRab and PsMab could manifest disfunction in the postsynaptic and presynaptic membrane. While the patients who just has the PsMab maybe damaged only in the presynaptic membrane. Other body fluid immune or/and cell immune mechanism may be involved in MG patients without AchRab and PsMab. [

A Preliminary Study on Cultivation Test of Protoplast Fusion Strain of Fulin (Poria cocos) / 中草药

Rcsult of field cultivation test by protoplastic fusion technique for biological cngln ering breeding of Poria cocos in Huoshan county, Anhui Province was reported for the first time. A fusion strain F1 was obtained from parents P1, P6578 by separation, fusion, marker of hypha protoplast and identification of recombinat. It was cultivated simultaneously with P1, P5778 for comparison. Results showed that the average cellal outputs were 1.73, 0.5 and 2.20kg respectively.As the output of strain F1 is intermediate between its parent P1 and P578, the result is considered to be unsatisfactory. The reason for such result was discussed.