Role of arginine vasopressin in the regulation of sleep-arousal，anxiety and depression / 中风与神经疾病杂志

@#Arginine vasopressin （AVP），also known as antidiuretic hormone，is a highly conserved neuropeptide secreted by the supraoptic or paraventricular nucleus of the hypothalamus and has complex physiological functions. This article reviews the physiological properties of AVP and elaborates on the possible involvement of AVP in sleep-arousal regulation via the hypothalamic orexinergic and noradrenergic systems and the role of AVP in maintaining circadian homeostasis by facilitating intercellular coupling of suprachiasmatic nucleus neurons，as well as the potential role of AVP in the regulation of anxiety and depression.

Chinese guidelines for diagnosis and treatment of narcolepsy (2022 edition): updated interpretation / 中华神经科杂志

Chinese guidelines for diagnosis and treatment of narcolepsy (2022) as the second edition of Chinese guidelines for narcolepsy, had made important updates compared with the 2015 edition in some aspects, such as epidemiology, pathogenesis, clinical manifestations, scale assessment and laboratory examination, diagnostic criteria and treatment. This article will focus on the above updated content.

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation.

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19. Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy. Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets. Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

Impaired Parahippocampal Gyrus-Orbitofrontal Cortex Circuit Associated with Visuospatial Memory Deficit as a Potential Biomarker and Interventional Approach for Alzheimer Disease / 神经科学通报·英文版

The parahippocampal gyrus-orbitofrontal cortex (PHG-OFC) circuit in humans is homologous to the postrhinal cortex (POR)-ventral lateral orbitofrontal cortex (vlOFC) circuit in rodents. Both are associated with visuospatial malfunctions in Alzheimer's disease (AD). However, the underlying mechanisms remain to be elucidated. In this study, we explored the relationship between an impaired POR-vlOFC circuit and visuospatial memory deficits through retrograde tracing and in vivo local field potential recordings in 5XFAD mice, and investigated alterations of the PHG-OFC circuit by multi-domain magnetic resonance imaging (MRI) in patients on the AD spectrum. We demonstrated that an impaired glutamatergic POR-vlOFC circuit resulted in deficient visuospatial memory in 5XFAD mice. Moreover, MRI measurements of the PHG-OFC circuit had an accuracy of 77.33% for the classification of amnestic mild cognitive impairment converters versus non-converters. Thus, the PHG-OFC circuit explains the neuroanatomical basis of visuospatial memory deficits in AD, thereby providing a potential predictor for AD progression and a promising interventional approach for AD.

Hybrid manganese dioxide-bovine serum albumin nanostructure incorporated with doxorubicin and IR780 for enhanced breast cancer chemo-photothermal therapy.

The therapeutic outcome of chemotherapy is limited, although it is still the preferent strategy for cancer therapy. By regulation of tumor microenvironment and introduction of another therapeutic manner for combination therapy can enhance the anticancer activity of chemotherapeutics. Herein, we have constructed a hybrid nanostructure which composed of manganese dioxide (MnO2) and doxorubicin (DOX) as well as IR780 by stabilizing with BSA (BMDI) in one-pot procedure to alleviate tumor hypoxia and enhance tumor growth inhibition. The MnO2 can react with H2O2 to generate oxygen, and additionally react with GSH to realize tumor microenvironment responsive drug controlled release. And the release Mn ions further enhanced the magnetic resonance signal which made the BMDI a promising contrast agent for MRI. Moreover, the introduction of MnO2 has enhanced the anticancer activity of DOX in vitro and in vivo, and efficiently suppressed the tumor growth. By further introducing with photothermal therapy (PTT), the tumor growth was almost inhibited. It demonstrated that the BMDI hybrid nanostructure has great potential in tumor growth inhibition as therapeutics carrier.

Influence of autophagy-mediated high-intensity interval training on skeletal muscle mass and aerobic capacity of middle-aged rats / 中国组织工程研究

BACKGROUND: It is unclear whether autophagy mediates the long-term exercise adaptation of the skeletal muscle induced by high-intensity interval training (HIIT) . OBJECTIVE: To identify the influence of HIIT on skeletal muscle autophagy of middle-aged rats over time, and to understand the potential regulatory effects of autophagy on maintaining the muscle mass and improving aerobic capacity by HIIT. METHODS: Rats were randomly divided into quiet, moderate training group (50-minute running at the intensity of 60% VO2 max) and HIIT group (6 times of 3-minute running at 80% VO2 maxand 3-minute active recovery at 50% VO2 maxwith a 7-minute warm-up and a 7-minute cool-down at 60% VO2 max). All rats were tested for VO2 max, exhaustive running time and distance at baseline and after 4, 8 and 12 weeks of exercise, respectively. The soleus muscle were collected and weighted, and then the expression levels of autophagy-related protein Beclin 1, LC3 and P62 were detected by western blot assay. RESULTS AND CONCLUSION: The soleus muscle mass in the quiet group decreased at the 12thweek (P < 0.01), while the moderate training and HIIT groups improved this decline (P < 0.05). The HIIT group dramatically improved the VO2 maxfrom the 4thweek when compared with the pre-experiment and the quiet group, until the 12thweek. The expression levels of Beclin1 and LC3II in the quiet group declined at the 12thweek (P < 0.05, P < 0.001), but the expression level of LC3II and ratio of LC3II/LC3I raised from the 4thand 8thweeks till the 12thweek compared with the pre-experiment and the quiet group, and the expression level of LC3II and ratio of LC3II/LC3I point time significantly raised in the moderate training group at the 12thweek (P < 0.001, P < 0.01). In the quiet group, the content of P62 significantly increased at the 4th and 8thweeks (P < 0.05), and decreased at the 12thweek (P < 0.001), but the content of P62 remained at the low level in the moderate exercise and HIIT groups. These results imply that an equivalent or better effects on improving basic autophagy level, skeletal muscle mass and aerobic capacity of the middle aged rats,by HIIT versus moderate training,providing the theory and empirical data that highlight the role of HIIT in health promotion.

Hydrogen rich water protects against myocardial ischemia/reperfusion injury in rats / 中国组织工程研究

BACKGROUND: Increasing evidence has indicated that low-concentration hydrogen or hydrogen rich water or hydrogen saturated saline exerts a protective effect on various diseases, such as myocardial ischemia/reperfusion injury. OBJECTIVE: To explore the protective effect of hydrogen rich water on myocardial ischemia/reperfusion injury. METHODS: Forty-eight Wistar rats were equally randomized into control and hydrogen-rich groups, and then subdivided into ischemic preconditioning, ischemia, and ischemia/reperfusion groups (n=8 rats in each subgroup). The myocardial ischemia/reperfusion model was established in the heart of each rat by the following procedures: reverse perfusion for 10 minutes, room temperature for 20 minutes, and reperfusion for 20 minutes. The control rats was perfused with pre-oxygenated (95% O2plus 5% CO2) 37 ℃ K-R solution and the hydrogen-rich group was perfused with pre-oxygen-equilibrated (95% O2plus 5% CO2) 37 ℃ K-R solution plus hydrogen-rich water (0.6 mmol/L, pH=7.3). Subsequently, the heart was removed, the pathological changes of the myocardial tissues were observe by hematoxylin-eosin staining, the activities of lactic dehydrogenase and creatine kinase in the myocardial tissues were determined, and the levels of tumor necrosis factor-α and interleukin-1β were detected by ELISA. RESULTS AND CONCLUSION: In the control group, the activity of lactic dehydrogenase at the ischemic and ischemia/reperfusion stages was significantly higher than that at the ischemic preconditioning stage (P < 0.05), and the activity of creatine kinase at the ischemia/reperfusion stage was significantly higher than that at the ischemic preconditioning and ischemic stages (P < 0.05). In the hydrogen-rich group, there was no significant difference in the activities of lactic dehydrodenase and creatine kinase at each stage, but the activities of at the ischemia/reperfusion stage was significantly lower than those in the control group (P < 0.05). In the two groups, the order of the levels of tumor necrosis factor-α and interleukin-1β was as follows: the ischemia/reperfusion stage > ischemic stage > ischemic preconditioning stage (P < 0.05). The levels of above factors in the hydrogen-rich group were significantly lower than those in the control group (P < 0.05). Our findings imply that hydrogen rich water has protective effect on myocardial ischemia/reperfusion injury of the rat hearts in vitro,which may be by reducing the expression of tumor necrosis factor-α and interleukin-1β, and further alleviating the inflammatory response.

[Effects of 5-HT1A receptor antagonist on ethanol induced hypothermia and behavioral thermoregulatory response in rats].

OBJECTIVE: To observe the effects of 5-HT1Areceptor antagonist p-MPI on ethanol induced hypothermia and behavioral ther-moregulatory response in rats. METHODS: Core temperature and motor activities were monitored in undisturbed male SD rats using radioteleme-try. The behavioral thermoregulatory response and core temperature were monitored in rats using radiotelemetric temperature gradient apparatus. The rats were placed in a temperature gradient that permitted the selection of ambient temperature ranging from 15℃ to 40℃. Effect of ethanol (3 g/kg) and 5-HT1A receptor antagonist p-MPPI(1 mg/kg) on core temperature, motor activities, and the behavioral thermoregulatory re-sponse were observed in rats. RESULTS: ①Ethanol led to a rapid reduction in core temperature. The hypothermic responses were accompanied with a preference for cooler ambient temperature. ②5-HT1A receptor antagonist attenuated the hypothermia induced by ethanol, and accompa-nied with a selection for warmer ambient temperature. CONCLUSIONS: ①Behavioral thermoregulatory observations suggested that the ethanol could decrease the thermoregulatory set point,because rats treated with ethanol selected cooler ambient temperature facilitates the reduction in core temperature.②5-HT might be involved in ethanol-induced hypothermia and behavioral thermoregulatory response.

Research progress of cost estimation of community basic public health service in China / 中国卫生政策研究

Objective:To summarize the cost of basic community public health service in Chinese community for the period 2009 to 2016 and to provide suggestions for the formulation of the compensatory policy and work in-struction in each region.Methods: The literature search conducted on Chinese literature database(including CNKI, VIP, Wan Fang) from the period of 2009 to 2016.The literature was analyzed with the help of NoteExpress managing Literatures,and the relevant papers and their references were comparatively analyzed by using Microsoft excel 2007. Results:There were a total of 817 relevant articles,of which,48 were included in this study and 19 with detailed re-search results.For the 48 articles,41.7% adopted full costing method and 20.8% used activity-based costing meth-od,54.2% using six-item screener. More research of cost estimation applied to current evaluation of public health service in community,the results of cost estimation showed that the cost of basic community public health service per capita was significantly different among the studies in the period of 2009to2011 (20.9 RMB to 95 RMB).The man-power cost was the main cost of basic community public health service(between 56.59% and 74.9%).Conclusions:Further exploration and research on the cost estimation of national basic community public health service in China re-quires to be performed,and the cost estimation methods are supposed to improve in practice.

Study on chronic disease management ability and theory teaching model of undergraduates majoring in preventive medicine / 中华医学教育探索杂志

Objective Exploring theoretical teaching model of chronic diseases management of preventive medicine undergraduates,to provide feasible suggestions to improve the theoretical teaching of the chronic disease management ability of preventive medicine specialty in China so that graduates can better adapt to chronic diseases management work.Methods On the basis of reading a large number of relevant literature both at home and abroad,the research team designed questionnaires,and conducted a questionnaire survey on 190 respondents who engaged in chronic diseases management or teaching in central China.The content includes the understanding of the importance of training chronic disease management ability in undergraduate education of preventive medicine and the constitution and training mode of undergraduates' chronic disease management ability.EpiData 3.1 software was used to input survey data,SPSS 23.0 software was used for statistical description analysis,and the usage ratio and component ratio were used for statistical description analysis.Results The survey found that more than 50％ of the respondents believed that training students with chronic disease management should focus on prevention,intervention services and health promotion ability,and chronic disease modules need to be added to undergraduate courses in preventive medicine.Conclusions preventive medicine undergraduates need to be improved,and medical colleges should change teaching model to increase undergraduates' ability of chronic diseases management.

Compromised cerebral autoregulation function in patients with chronic insomnia disorder / 中华神经科杂志

Objective To analyze the cerebral autoregulation capability in patients with chronic insomnia disorder (CID).Methods Sixty CID patients (54 with generalized anxiety disorder) and 40 healthy controls were enrolled in this study.Polysomnography was done in all the participants.Noninvasive continuous cerebral blood flow velocity of bilateral middle artery and arterial blood pressure were recorded simultaneously using transcranial Doppler and a servo-controlled plethysmograph.Transfer function analysis was used to derive the autoregulatory parameters, including phase difference and coherence function.Results The phase difference values of CID patients with generalized anxiety disorder were significantly lower than that of the healthy controls ((46.89±15.39)°vs (56.00±12.05)°, t=3.439, P=0.001).In the correlation analysis, we further found that there was no correlation among phase difference values and the score of Hospital Anxiety and Depression scale.Conclusions The dynamic cerebral autoregulation was compromised in CID patients with generalized anxiety disorder regardless of the degrees of anxiety and depression.Dynamic cerebral autoregulation may be a potential therapeutic target in improving neurological symptoms in patients with CID.

Impact of apolipoprotein E gene polymorphism on cerebral blood flow in patients with mild cognitive impairment / 中华神经医学杂志

Objective To investigate whether apolipoprotein E (APOE) genotype specifically modulates cognition function and cerebral blood flow in patients with amnesic mild cognitive impairment (aMCI) by using pulsed arterial spin labeling (ASL) MR imaging.Methods Eighty-three aMCI subjects and 130 healthy controls (HCs) were recruited through heath screening in community from 2012 to 2014 in our hospital.They all underwent neuropsychological battery assessments,genetic screening and MR imaging.The aMCI subjects included 8 APOE ε2ε3 carriers,46 APOE ε3ε3 carriers and 29 APOE ε3ε4 carriers;however,in HCs,there were 35 APOE ε2ε3 carriers,46 APOE ε3ε3 carriers and 49 APOE ε3ε4/ε4ε4 carriers.Neuropsychological scale was performed in all subjects.ASL data were preprocessed by the ASLtbx toolbox.A voxel-wise two-way ANOVA was performed to examine the main effects of'disease'(MCI) and ‘genotype’ (APOE),and the disease-by-genotype interactions on regional cerebral blood flow (rCBF) maps.Multiple linear regression analysis was performed to examine the relationships between neuropsychological scale scores and rCBF values in brain areas showing significant diagnosis-by-genotype interactions.Results (1) As compared with HCs,the aMCI subjects exhibited significantly higher rCBF values primarily in the left superior and middle frontal gyrus (P＜0.05).APOE ε3ε4/ε4ε4 carriers showed significantly higher rCBF values in the right anterior and posterior cingulate cortex,right ventromedial prefrontal cortex/anterior cingutate than those of A POE ε2ε3 carriers and ε3ε3 carriers,respectively (P＜0.05).Significant disease-by-genotype interactions on rCBF were observed in the left superior frontal gyrus,right ventromedial prefrontal cortex/anterior cingutate and bilateral superior temporal gyrus;as compared with A POE ε2ε3 and A POE ε3ε3 carriers,APOE ε3ε4 carriers had significantly higher rCBF values in the above areas in the aMCI group (P＜0.05).(2) The rCBF values in the right anterior cingulate/medial prefomtal gyrus and superior temporal gyrus of APOE ε3ε4 carriers in aMCI group were negatively correlated with the similarity test scores (r=-0.453,P=0.014;r=-0.497,P=0.006).Conclusions The APOE genotype has disease-specific effects on cerebral perfusion;APOE genotype can specifically regulate cerebral blood perfusion in aMCI subjects.The carriers ofAPOE ε3ε4 genotype in aMCI subjects may maintain their overall cognitive function by increasing lateral ventricle-temporal lobe cerebral blood perfusion.

Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance.

The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes it a potential target for the treatment of type 2 diabetes and obesity. In the present study, we have designed two parental peptides and 55 modified peptides based on the structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed increased inhibitory activity in a fluorescence polarization-based assay. In the in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51 were protected against high-fat diet-induced obesity and insulin resistant. These inhibitors may potentially lead to new therapeutic alternatives for obesity and type 2 diabetes.

The relationship between interictal epileptic discharges and sleep cycle of 240 epilepsy patients / 中华神经科杂志

Objective The poor sleep quality of epileptic patients may be partly due to the occurrence epileptiform discharges (EDs).We observed the number of interictal discharges in each sleep stage and explored the associations between EDs and sleep phases in epilepsy patients.Methods Two hundred and forty epileptic patients and 213 healthy volunteers were enrolled in the current study.For all subjects,video-electroencephalogram monitoring and 24 h-night polysomnography were conducted to detect EDs and analyze the sleep structures.Results EDs were detected in 88.7％ (213/240) of epilepsy patients with the most frequent cases from the temporal lobe.The EDs detected during waking,sleeping,or both waking and non-rapid eye movement (NREM) sleep stage accounted for 20.6％ (44/213),40.4％ (86/213),and 38.9％ (83/213) of the total patients,respectively.The total sleep time and time spent in REM were similar between the epileptic patients and healthy volunteers.However,epileptic patients spent a significantly longer mean sleep time in NREM Ⅰ-Ⅱ ((304 ±39) min versus (225 ±29) min,t =3.51,P =0.000) and less in NREM Ⅲ-Ⅳ ((49 ± 7) min versus (133 ± 17) min,t =2.30,P =0.000) than healthy volunteers.Furthermore,asymmetric sleep spindles and fragmentary sleep structure as well as high inversion frequency were found in epilepsy patients,respectively.Conclusion Combination of long-term video electroencephalogram with polysomnography is a useful method to analyze associations between EDs and the sleep-wake cycle.This strategy can also help identify the nature of sleep disorders in epileptic patients,which may improve the treatment efficacy.

White matter change in diffusion tensor imaging of amnestic mild cognitive impairment / 中华神经科杂志

Objective To investigate the features of white matter impairment and its relationship with cognition in patients with amnestic mild cognitive impairment (aMCI).Methods Eighty-three cases of aMCI and 85 normal aging volunteers were scanned with diffusion tensor imaging (DTI) using MR system.All subjects completed the neuropsychological battery.We analyzed the differences between two groups using tract-based spatial statistics and the association between regions in difference and cognition using correlation analysis.Results There were significant differences between aMCI and normal control in the neuropsychological battery including the Mini-Mental State Examination(26.2 ± 2.6 vs 28.3 ± 1.3,F =43.224,P =0.000),Mattis Dementia Rating Scale-2 (131.4 ± 6.9 vs 138.0 ± 3.5,F =62.308,P =0.000),Auditory Verbal Learning Test-delayed recall(2.4 ± 1.6 vs 7.5 ± 2.0,F =324.018,P =0.000),Boston Naming Test(8.7 ± 1.4 vs 9.2 ± 1.0,F =6.821,P =0.010),Rey-Osterrich Complex Figure Test (12.1 ± 7.3 vs 18.5 ± 6.1,F =40.674,P =0.000),Symbol Digit Modulation Test (30.0 ± 10.1 vs 38.6 ± 9.8,F =30.786,P =0.000),Trail-Making Test Part B ((256.8 ± 124.5) s vs (178.1 ± 59.0) s,F =27.601,P =0.000).Significantly higher diffusivity indexes and radial diffusivity were also found in aMCI subjects compared to healthy elders in the parahippocampal,superior longitudinal fasciculus,inferior longitudinal fasciculus,superior fronto-occipital fasciculus,inferior fronto-occipital fasciculus,unciform fasciculus,corticospinal tract,corpus callosum,cingulum,corona radiate.We also found that axial diffusivity was significantly increased in the parahippocampal,superior longitudinal fasciculus,inferior longitudinal fasciculus,superior fronto-occipital fasciculus,inferior fronto-occipital fasciculus,unciform fasciculus,corticospinal tract and corpus callosum,whereas fractional anisotropy changes were not observed in aMCI.Diffusivity indexes values in bilateral frontal lobe (left r =0.67 ; right r =0.70),left cingulum (r =0.63),parietal white matter (r =0.69) and radial diffusivity values in left parietal (r =0.68) were significantly related to Trail Making Test A among aMCI (all P ＜ 0.05).Conclusions In aMCI patients,there was a wide range of white matter damage,with no brain region-specific.Executive function deficit was related to the white matter impairment in bilateral frontal lobe,left cingulate and parietal lobe.The specificity and sensitivity of four DTI parameters fordetecting white matter lesions are variant.Trial registration Clinical Research Center of Jiangsu Province (BL2013025)

Development of a fluorescence polarization based high-throughput assay to identify Casitas B-lineage lymphoma RING domain regulators.

The E3 ubiquitin protein ligase Casitas B-lineage Lymphoma (Cbl) proteins and their binding partners play an important role in regulating signal transduction pathways. It is important to utilize regulators to study the protein-protein interactions (PPIs) between these proteins. However, finding specific small-molecule regulators of PPIs remains a significant challenge due to the fact that the interfaces involved in PPIs are not well suited for effective small molecule binding. We report the development of a competitive, homogeneous, high-throughput fluorescence polarization (FP) assay to identify small molecule regulators of Cbl (RING) domain. The FP assay was used to measure binding affinities and inhibition constants of UbCH7 peptides and small molecule regulators of Cbl (RING) domains, respectively. In order to rule out promiscuous, aggregation-based inhibition, two assay conditions were developed and compared side by side. Under optimized conditions, we screened a 10,000 natural compound library in detergent-free and detergent-present (0.01% Triton X-100) systems. The results indicate that the detergent-present system is more suitable for high-throughput screens. Three potential compounds, methylprotodioscin, leonuride and catalpol, have been identified that bind to Cbl (RING) domain and interfere with the Cbl (RING)-UbCH7 protein-protein interaction.

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

A case of schizencephaly has a normal surface EEG but abnormal intracranial EEG: epilepsia partialis continua or dystonia?

Schizencephaly is a congenital malformation of the cerebral hemispheres, with communication between the lateral ventricle and the subarachnoid space. Marinelli reported that schizencephaly may be associated with continuous involuntary hand movements, such as dystonia or epilepsia partialis continua (EPC). We describe a young Chinese patient with continuous involuntary movements of the contralateral hand affected by schizencephaly. He has a normal scalp electroencephalogram (EEG) but abnormal intracranial EEG, with synchronized periodic lateralized epileptiform discharges. The results obtained from these EEG investigations and the clinical features of the involuntary movements are in favor of a diagnosis of secondary EPC.

Association between epileptiform discharges and the sleep cycle in 200 epileptic patients.

OBJECTIVE: The poor sleep quality of epileptic patients may be partly due to the occurrence epileptiform discharges (EDs). We observed the number of interictal discharges in each sleep stage and explored the associations between EDs and sleep phases in epileptic patients. METHODS: Two hundred epileptic patients and 182 healthy volunteers were enrolled in the current study. For all subjects, video electroencephalography (EEG) monitoring and 24-hr night polysomnography were conducted to detect EDs and analyze the sleep structures. RESULTS: EDs were detected in 91% of epileptic patients with the most frequent cases from the temporal lobe. The EDs detected during waking, sleeping, or both waking and nonrapid eye movement (NREM) sleep stages 1-2 accounted for 7.1%, 19.2%, and 25.3% of the total patients, respectively. EDs were rare during NREM stages 3-4 with 1.1% of total patients mainly in the central-temporal lobe. The total sleep time and time spent in REM were similar between the epileptic patients and healthy volunteers. However, epileptic patients spent a significantly longer mean sleep time in NREM stages 1-2 (293.91 ± 27.57 min vs. 223.17 ±15.28; p = .000) and less in NREM stages 3-4 (50.11 ± 12.12 min vs. 133.96 ± 10.77; p = .000) than healthy volunteers. Furthermore, asymmetric sleep spindles and fragmentary sleep structure as well as high inversion frequency were found in 26.7% and 43.3% of epileptic patients, respectively. CONCLUSION: Combination of long-term video EEG with polysomnography is a useful method to analyze associations between EDs and the sleep-wake cycle. This strategy can also help identify the nature of sleep disorders in epileptic patients, which may improve the treatment efficacy.

The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects.

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941-1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013-1.242; for dominant model: OR = 1.128, 95% CI = 1.01-1.26; for recessive model: OR = 1.151, 95% CI = 0.950-1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000-1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134-2.256; for dominant model: OR = 1.269, 95% CI = 1.134-2.256; for recessive model: OR = 1.664, 95% CI = 1.070-2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.