Novel compound FLZ alleviates rotenone-induced PD mouse model by suppressing TLR4/MyD88/NF-

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ

Research progress on mechanism of botulinum toxin A in treatment of pain / 中国药理学通报

Botulinum toxin-A ( botulinum toxin-A, BTX-A) is a double chain polypeptide structure formed by 100 kDa heavy chain and 50 kDa light chain through disulfide bond. The light chain is a kind of protease, which can combine with the fusion protein at the neuromuscular junction to prevent synaptic vesicles from anchoring on cell membrane and release acetylcholine, thus interfering with the transmission of nerve impulses. In recent years, the discussion on the clinical application of BTX-A has been a hot spot. Studies have shown that Botulinum toxin A (BTX-A) can effectively treat pain, exerting the characteristics of sustainable effect without addiction, but the mechanism of action of BTX-A is still controversial. This article reviews the mechanism of BTX-A in peripheral and central nervous system.

Research progress of gut microbiota in substance dependence / 上海交通大学学报（医学版）

Substance dependence is a pervasive worldwide problem, of which the mechanism remains unclear, and there is no effective intervention. In recent years, it has been showed that the gut microbiota is closely related to substance dependence. As discussed in this review, gut microbiota is significantly affected by the substances of abuse, and may serve as an important regulator in the development of substance dependence. This article reviews the research progress of gut microbiota in the most widely used substances, in order to provide ideas for future studies on underlying mechanisms and further interventions in substance dependence.

Effects of bariatric surgery on central nervous system regulation of obesity / 中华消化外科杂志

As the incidence of obesity increases globally, treatment strategies of obesity emerge continuously. However, the weight loss effect varies between individuals without explicit explanations. In the recent years, many researchers have revealed regulation mechanisms of central nervous system on eating behavior, proposing that obese individuals exhibit brain functional abnormalities implicated in homeostatic regulation of food intake, central reward and motivation, emotion, memory, and attention system. Therefore, these scholars appeal that treating obesity cannot remain "brainless" . The most effective treatment currently available for obesity is bariatric surgery which lead to excess weight loss of 42%-67% in accompany with changes in brain activity. Functional magnetic resonance imaging showed a decreased activation in the central reward network and increased inhibitory control in the cognitive control system after bariatric surgeries. In this article, the authors introduce the central nervous system regulation of eating and investigate the effects of bariatric surgery on central nervous system.

Effects of bariatric surgery on central nervous system regulation of obesity / 中华消化外科杂志

As the incidence of obesity increases globally,treatment strategies of obesity emerge continuously.However,the weight loss effect varies between individuals without explicit explanations.In the recent years,many researchers have revealed regulation mechanisms of central nervous system on eating behavior,proposing that obese individuals exhibit brain functional abnormalities implicated in homeostatic regulation of food intake,central reward and motivation,emotion,memory,and attention system.Therefore,these scholars appeal that treating obesity cannot remain "brainless".The most effective treatment currently available for obesity is bariatric surgery which lead to excess weight loss of 42％-67％ in accompany with changes in brain activity.Functional magnetic resonance imaging showed a decreased activation in the central reward network and increased inhibitory control in the cognitive control system after bariatric surgeries.In this article,the authors introduce the central nervous system regulation of eating and investigate the effects of bariatric surgery on central nervous system.

Clinical features of central nerve system inflammatory demyelinating diseases associated with anti-myelin oligodendrocyte glycoprotein antibodies in children / 中华实用儿科临床杂志

Objective@#To describe the clinical manifestations of central nerve system inflammatory demyelinating disease associated with anti-myelin oligodendrocyte glycoprotein antibody (MOG-IDD) in children, and to explore the clinical characteristics of the children.@*Methods@#The clinical and laboratory characteristics of the patients diagnosed in Beijing Children′s Hospital, Capital Medical University, from October 2016 to August 2018 were described, and the clinical data of the patients with unipolar and recurrent diseases were compared.@*Results@#A total of 50 patients were included, among whom the ratio of male to female was 24:26, and the average age of onset was (6.7±3.1) years old (0.4-12.6 years old). There was no significant difference in the age of onset between boys and girls(t=0.712, P=0.480). The main symptoms included fever (31/50 cases), encephalopathy (26/50 cases) and optic neuritis (22/50 cases), etc.In the last follow-up, 26 patients (52.0%) had a monophasic course and 24 patients (48.0%) had a recurrent course.There were age differences in encephalopathy and ataxia in the first episode of [(5.7±2.8) years old vs.(8.1±3.0) years old, (5.0±2.5) years old vs. (7.7±3.0) years old](t=2.746, P=0.009; t=2.837, P=0.007). The average number of recurrence was (2.1±1.4) times (1-7 times), in which 17 cases (70.8%) of recurrence presented within 12 months and 20 cases (83.3%) of recurrence presented within 24 months after onset.Convulsion incidences of recurrent cases were 10 cases and 13 cases respectively in the first episode and recurrent courses, which were significantly higher than those of monophasic cases (4 cases, 4 cases)(χ2=7.912, P=0.005; χ2=8.365, P=0.004). All patients were sensitive to first-line immunotherapy.Seven patients with recu-rrence were treated with mycophenolatemofetil, and 17 patients with repeated first-line therapy.In the last follow-up, all patients were in remission and 2 patients had mild neurological dysfunction.@*Conclusions@#MOG-IDD can occur in childhood.Encephalopathy and optic neuritis are the most common symptoms.Encephalopathy and ataxia are more common in young children.Convulsions may indicate the course of recurrence.

Protective and regeneration-promoting effects of Ruyi Zhenbao Pill on nerve injury in zebrafish / 药物评价研究

Objective To observe the protective and regeneration-promoting effects of Ruyi Zhenbao Pill (RZP) on nerve injury in zebrafish.Methods The zebrafish model of central nervous injury was induced by mycophenolate mofetil,the model of peripheral motor nerve and axonal injury was induced by ethanol,and the model of myelin damage was induced by ethidium bromide.The variations of central nerve,axon and myelin sheath fluorescence intensity,and peripheral motor nerve length in zebrafish,which exposed to the different concentration (10.0,33.3,and 100.0 μ.g/mL) of RZP,were observed with fluorescence microscope.The effective protection rates of RZP on zebrafish central nerve and axone,and the regeneration-promoting effect on peripheral motor nerve and myelin sheath were analyzed and calculated with the image processing software NIDS-Element's.Results In 10.0,33.3,and 100.0 μg/mL RZP groups,the zebrafish central nervous injury protective rates were 2％,24％,and 50％ (P ＜ 0.001),respectively,the peripheral nerve regeneration promoting rates were 44％ (P ＜ 0.05),49％ (P ＜ 0.01),and 93 ％ (P ＜ 0.001),the axonal injury recovery rates were 3％,29％ and 48％ (P ＜ 0.05),and the myelin sheath regeneration promoting rates were 36％ (P ＜ 0.01),37％ (P ＜ 0.001),and 41％ (P ＜ 0.001),compared with model group.Conclusions RZP could not only protect the central nervous and axonal injury,but also promote the regeneration of peripheral nerve and myelin sheath in zebrafish.

Dynamic Expression of Nogo-A in Hippocampus of Rats after Carbon Monoxide Poisoning / 现代生物医学进展

Objective:To study the dynamic expression of Nogo-A in hippocampus of rats after carbon monoxide poisoning,and to explore the effect and influence of Nogo-A in the damage to nervous system after carbon monoxide poisoning.Methods:Thirty male SD rats were randomly divided into NC group(n=6),CO group(n=6),CO-24 h group(n=6),CO-48 h group(n=6),CO-7d group(n=6).The method of injection CO gas was used to establish the carbon monoxide poisoning model.Then immunohistochemical (IHC) and Western blot (WB) techniques were used to observe dynamic expression of Nogo-A in hippocampus of rats at several time intervals after carbon monoxide poisoning and to analyze its change law.Results:IHC results showed that the average optical density value of expression of Nogo-A in NC group,CO group,CO-24 h group,CO-48h group and CO-7d group were 0.0928± 0.0038,0.01172± 0.0042,0.1452± 0.0056,0.1271 ± 0.0057,0.1088± 0.0055.WB results showed that the expression of Nogo-A in hippocampus after carbon monoxide poisoning was significantly higher than that in NC group(P＜0.05),and reached the highest level at 24 h,then had a gradual recovery after 24h.The expression of Nogo-A decreased obviously,but still higher than that of NC group by day 7 (P＜0.05).Conclusions:In this study,the increase of expression of Nogo-A was associated with carbon monoxide poisoning.The expression of Nogo-A reached the highest level at 24h,then had a gradual recovery after 24 h.

Clinical analysis of the neurological involvement in primary Sj(o)gren's syndrome / 中华风湿病学杂志

Objective To analyze the clinical and laboratory manifestations of primary Sj(o)gren's syndrom (pSS) with neurological involvement.Methods One hundred and forty eight patients fulfilling the 2002 American-European pSS classification criteria were retrospectively analyzed.Neurological manifestations were diagnosed based on the clinical,biological,electrophysiological,and imaging findings.Biographical,clinical,and laboratory data were compared between patients with and without neurological manifestations.Statistical methods used were Mann-Whitney U test,Chi-square test and Fisher exact probability.Results The prevalence of neurological involvement in pSS was 20.3％ (30/148),and the incidence of peripheral neuropathy,the central neuropathy and combination of the central neuropathy with peripheral neuropathy were 10.1％(15/148),9.5％(14/148) and 0.7％(1/148),respectively.The clinical spectrum of peripheral neuropathies encountered in Sj(o)gren's syndrome (SS) patients varied,with the pure sensory neuropathies being the most common,followed by sensorimotor neurophathies.Motor neuron disease was the most common type of central neurophathies.Compared with those without neurological manifestations,the duration of peripheral nerve system/central nerve system (PNS/CNS)-pSS patients was relatively short [(55±76) months vs (100±108) months,Z=-2.682,P＜0.05],and the antinuclear antibody (ANA) titer and RF titer were lower [(234±248) vs (377±339),Z=-2.008,P＜0.05;(126±279) U/ml vs (359±1 445) U/ml,Z=-2.243,P＜0.05].In PNS/CNS-pSS patients,the most common clinical manifestations included numbness (50％),pain (23％),and muscle weakness (63％).Conclusion The prevalence of neurological involvement in pSS is high.The duration is relatively short and the disease activity is high,but the disease features are atypical and may be neglected by rheumatologists.

The correlation between the apolipoprotein E genetic polymorphisms and sepsis in children / 中华急诊医学杂志

Objective To study the correlation between apolipoprotein E (APOE) genetic polymorphisms and sepsis in Chinese children.Methods The inpatients suffered with sepsis were enrolled as septic group and the healthy children from child health division were enrolled as control group.The study of APOE genotypes were carried out by polymerase chain reactions followed a high-resolution melting curve analysis.SPSS 16.0 statistical software was used for data analysis.Mann-Whitney U test was used to compare the age between the groups.Hardy-Weinberg equilibrium was tested using the Pearson x2-test.The x2-test was used to compare gender and the genotype distribution between the groups.The odd ratio (OR) was calculated together with its 95％ confidence interval (CI).Potential confounding effects of variables were corrected using a multivariate unconditional logistic regression model.All statistical tests were two-sided and P ＜ 0.05 indicates statistically significance.Results Among a total of 285 children collected from March 2011 to June 2012,there were 88 patients with sepsis and 197 healthy children.In the septic group,15 septic patients were complicated with central nervous system infection.Four apolipoprotein E genotypes were identified to be ε3/ε3,ε2/ε3,ε3/ε4,and ε2/ε4.The percentage of each genotype found in patients of the septic group and the control group was 64.4％ vs.73.1％ (ε3/ε3);16.8％ vs.10.7％ (ε2/ε3);18.8％ vs.14.7％ (ε3/ε4);0％ vs.1.5％ (ε2/ε4),respectively.The number of patients with the genotype ε3/ε3 among septic patients was significantly lower than that among the control individuals (P =0.047,1-β =0.334,OR =0.585,adjusted OR =0.559).The number of patients with the genotype ε3/ε3 among the septic patients with central nervous system infection was 33.3％,which was also significantly lower than that among the septic patients without CNS infection (67.1％).(P =0.014,1-β5 =0.685,OR =0.245,adjusted OR =0.275).Conclusions Apolipoprotein E genetic polymorphisms were associated with the occurrence of sepsis and central nervous system complications in children.The susceptibility of children with genotype ε3/ε3 to sepsis and central nerve system infection complications is significantly lower than that of children with other genotypes.

Differential proteomic analysis of the zebrafish neuron protective effect of Cerebralcare granules using iTRAQ labeling coupled with 2DLC-MS/MS / 中国药学杂志

OBJECTIVE: To screen the differentially expressed proteins before and after administration of Cerebralcare granules to zebrafish central nerve injury (CNI) models and search practical markers and explore the molecular mechanism of the treatment. METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) coupled with nano liquid chromatography-tandem mass spectrometry (Nano-LC-MS/MS) were used to analyze and identify differentially expressed serum proteins in the two groups. Bioinformatics was used to analyze the identified differentially expressed proteins, and the expression of representative differential proteins was verified by Western blotting. RESULTS: With the high throughput proteomic technology of iTRAQ coupled with Nano-LC-MS/MS, 1 933 unique proteins were identified, and 130 proteins showed ≥ 1.50 or ≤ 0.70 folds of changes during differentiation. The proteins detected in the zebrafish neuroendocrine brain had roles in the biological processes of translation, metabolic process and neuronal ion channel clustering. Ef1-α (elongation factor 1-alpha) and α-6-F (Na+/K+ transporting ATPase alpha 1 polypeptide) were validated by Western blotting. The two sets of data showed a statistically significant difference (P<0.05). These RESULTS were consistent with those from quantitative mass spectrometry. CONCLUSION: A high-throughput screen for zebrafish central nerve injury proteins can be performed by a combined use of iTRAQ and Nano-LC-MS/MS, and the molecular mechanism of Cerebralcare granules treatment can thus be preliminarily explored.

Clinical analysis on 569 cases of hand, foot and mouth diseases complicated with nerve system damages / 中国基层医药

Objective To investigate the epidemiological and clinical characteristics of hand,foot and mouth disease(HFMD) complicated with central nerve system infection,in order to improve the diagnosis and treatment.Methods Total of 569 cases of HFMD complicated with central nerve system infection were enrolled.The results of pathogen detection and CSF examination were looked into,and epidemiological and clinical characteristics were analyzed retrospectively.Results HFMD of the central nervous system infections increased year by year,endanger the children's life,pathogen detection showed positive for enterovirus type 71 (640/1077,59.4％) and coxsackie virus infection in group A (158/1077,14.7％) ; Clinical manifestation:hand,foot and mouth,hips were rash (100.0％),fever(546/569,95.9.％),temperature higher than 38.5 ℃ (74.7％,425/569),there were various signs and symptoms of nervous system damage,sleepiness (187/569,32.9％),limb jitter(347/569,60.1％),easily frightened (405/569,71.2％),irritability (130/569,22.8％),convulsions (2.4％,14/569),vomiting (67/569,11.8％),choking cough (2.8 ％,16/569),irregular breathing (0.5 ％,3/569) ; Laboratory examination:the central nervous system complications in different CFPro (P =0.992),CFWBC (P =0.994) and CRP (P =0.786),no statistical difference in such aspects of brain stem encephalitis group in CFP(P =0.001),PWBC (P =0.000) and BG (P =0.000),and the differences were statistically significant; Short-term,the combination of large dose of gamma globulin and methylprednisolone had definite efficacy.Conclusion HFMD complicated with central nervous system infections have some epidemiological and clinical characteristics,early diagnosis and treatment can reduce the incidence of severe cases and mortality.

Neural Mechanisms of Acupuncture for Functional Dyspepsia / 世界科学技术-中医药现代化

Acupuncture, as one of the most distinctive traditional Chinese medicine (TCM) treatment, had a wide range of advantages in the treatment of gastrointestinal disorders with obvious clinical efficacy. The onset of functional dyspepsia had increased year by year. However, the exploration on mechanism was unclear and drug abuse showed poor clinical outcomes. Acupuncture can effectively improve gastric motility. Through a variety of ways to act on the gastrointestinal tract, gastrointestinal function was restored to improve a variety of symptoms in patients with functional dyspepsia, which provided scientific basis for the clinical selection and application of acupuncture in functional dyspepsia treatment. This paper summarized the acupuncture treatment mechanism of functional dyspepsia in recent ten years, in order to provide references for scientific basis in acupuncture treatment of functional dyspepsia. It also provided references for the development of reasonable treatment options in the clinical practice.

Research progress of oxytocin receptor ligands and its role in central nerve system and peripheral organs / 中国药理学通报

Oxytocin ( OT ) is a cyclic neuropeptide containing nine amino acids residues, in addition to the traditional roles of uterine contraction and lactation, it also plays important roles in the central nervous system and other peripheral organs, such as improving schizophrenia, autism - related psychiatric and psy-chological symptoms. Oxytocin exhibits its physiological func-tions by binding to its receptor (oxytocin receptor,OTR). Cur- rently researchers are manipulating OT system by developing new OTR ligand ( agonists and antagonists ) , hoping to prevent and treat OTR related diseases. This paper reviews the latest devel-opment of OTR agonists, antagonists and its physiological roles in central nerve system and peripheral organs.

Rapid Atypical Progression of Neuro-Behcet's Disease Involving Whole Brainstem and Bilateral Thalami

We present a case of Neuro-Behcet's disease with an unpredictable clinical course. A 47-year-old man was admitted to the neurosurgery department of our hospital with a mild headache. Three days after admission, his consciousness suddenly decreased and respiratory distress progressed rapidly. A brain MRI revealed that the previously observed abnormal signal had extended markedly to both the thalamic areas and the entire brain stem, and the surrounding brain parenchyma were compressed by cerebral edema. Based on the patient's symptoms of recurrent oral and genital ulcers, skin lesions, and uveitis, a rheumatologist made a diagnosis of Behcet's disease with CNS involvement. The patient was treated with high-dose methylprednisolone with respiratory assistance in the intensive care unit for 9 days and his neurologic symptoms improved remarkably. Neuro-Behcet's disease must be considered in the differential diagnosis in rapidly deteriorated young neurological patients along with a stroke, low-grade glioma, multiple sclerosis, and occlusive venous disease.

Dysbaric injury of rat's central nervous system: The role of microglia / 第二军医大学学报

Objective: To observe the change of microglia activity after fast decompressing and/or hyperbaric oxygenation (HBO)-induced central nervous system (CNS) damage, so as to study the role of microglia in CNS dysbaric injury and the effects of HBO on microglia. Methods: Rats were randomly divided into the following groups: normal control, safe decompressing, fast decompressing (FD) injured, and HBO treated groups. Rat models of dysbaric injury were established by FD; 6 h later the rat models were subjected to HBO treatment. The activated microglia were detected by FITC-linked Isolectin B4; TNF-α and TNF-α converting enzyme (TACE) positive cells were detected immunohistochernically; and neural apoptosis was detected by TUNEL assay. TNF-α contents in CNS tissue were determined by ELISA and the bioactivity of sTNF-α in cerebrospinal fluid (CSF) were determined by L929 cell cytotoxicity bioassay. Results: 1134 positive microglia appeared in rats' CNS 6 h after FD treatment, peaked after 24 h, and declined thereafter. The activated microglia had morphological changes. Cell apoptosis indices of CNS reached its peak 48 h after FD treatment. Activated microglia and apoptotic neurons had similar distribution. TNF-α was detected in the brain and spinal cord 6 h after FD, significantly increased after 24 h, and peaked after 48 h. The content of TNF-α was positively correlated with IB4 positive cells and apoptosis index (P<0.05). TNF-α bioactivity in CSF of FD group had a similar change to TNF-α content in CNS tissue. The IHC results showed that, TNF-α and TACE positive cells had the same morphology and distribution to those of IB4 positive cells. HBO treatment significantly decreased IB4 positive cells after 24 h, 48 h, and 72 h; reduced TNF-α content in CNS tissues and TNF-α cytotoxicity in CSF; and decreased the apoptosis index after 48 h and 72 h. Conclusion: Microglial cells are quickly activated after dysbaric-induced injury of CNS. The activated microglia play a role in secondary injury through increasing TNF-α and TACE expression. HBO therapy can protect the neurons through depressing the activation and proliferation of microglia and reducing secretion of neurotoxin.

Demyelinating encephalopathy in adult onset Still's disease / 中华神经科杂志

Objective To report clinical features,diagnosis and treatment in a case of adult onset Still's disease (AOSD) accompanied by demyelinating encephalopathy.Methods We reported a case of Stills disease with signs of encephalopathy.We also reviewed and discussed the literature on the neurological manifestations in AOSD.Results The 35-year-old patient had recurrent fever and arthralgias for 3 years,headache for 1 month and transient loss of consciousness.Laboratory tests showed non-specific immunological activity.MRI showed tumor-like lesions at left parietal and occipital lobes surrounded by sleeve-like edema.The lesion had significant occupation effect.Biopsy proved the presence of demyelinating changes.The patient recovered favorably after administration of corticosteroids and immunoglobulin.The lesions had almost disappeared on follow-up MRI 4 months later.Conclusions Demyelinating encephalopathy may develop in patient with AOSD.MRI may show tumor-like damage,which is rarely reported in the literature.Diagnosis depends on history,clinical manifestation and neuroimaging.Biopsy provides important information in making diagnosis.Treatment with corticosteroids and intravenous immunoglobulin was found to achieve good recovery.

Assessment of general and trace elements in CSF of patients with spinal cord injury / 中国康复理论与实践

@#Objective To analyze general and trace elements in cerebral spinal fluid (CSF)of patients with spinal cord injury (SCI). Methods To assess contents of general and trace elements (K, Na, Ca, Mg, Zn, Mn, Fe, Cu) in CSF of six SCI patients using ICP-AES. Results Compared with normal value, contents of Ca and Zn were significantly decreased (P<0.01), Fe and Mn were significantly increased (P<0.01), but no significant differences for Na, Mg, K and Cu in CSF of SCI patients. Conclusion The excitation of central nerve system in SCI patients may be higher than normal people indeed.

THE EXPRESSION OF REGENERATION GENE PROTEIN-2 IN THE SPINAL CORD TRAVERSE INJURY MODEL / 解剖学报

Objective To investigate the expression of regeneration gene protein-2(Reg-2) after the transection injury in rat spinal cord. Methods Forty five SD rats were randomly divided into two groups: in the injury group,the SCI was produced by complete transection of the cord at the 9(th) thoracic level,and the sham operation rats were taken as the normal control.The animals were perfused at 1h,1d,3d,7d,14d after the operation,and the spinal cord was taken out at different time points.The expressions of Reg-2 were tested by immunohistochemical analysis and Western blotting,the double staining of Reg-2 and different neural cells special markers(GFAP,Olig2,NPY,CGRP,GAP-43,et al)was done with immunofluorescence method. Results The expression of Reg-2 was found at 1h after the spinal cord injury,reached the peak on day 3 after the injury in the neurons of dorsal horn and day 7 in the neurons of ventral horn.The high expression persisted for 1 week,then decreased gradually.Conclusion Reg-2 may work as an important growth factor and participate in the regeneration and rehabilitation process after the spinal cord injury.