AbstractBackgroundNeuroimaging studies have revealed the role of the right dorsolateral prefrontal cortex (DLPFC) in the neurobiological mechanism of obsessive–compulsive disorder (OCD). However, only a few studies have examined the functional connectivity (FC) pattern of the right DLPFC at rest in OCD.ObjectiveThe aim of this research is to examine the FC patterns of the right DLPFC at rest in OCD.MethodsTwenty‐eight medication‐free patients with OCD and 20 healthy controls underwent resting‐state functional magnetic resonance imaging. Seed‐based FC and support vector machine (SVM) were used to analyze the imaging data.ResultsThe patients with OCD showed reduced FC values in the right middle temporal gyrus (MTG), right superior temporal gyrus, right ventral anterior cingulate cortex (vACC), and left Crus II. No brain regions showed a remarkable difference in FC values in patients with OCD after 8 weeks of medication treatment. The reduced right DLPFC–right MTG and right DLPFC–right vACC connectivities were correlated with the clinical symptoms of OCD. SVM results showed that reduced right DLPFC–right MTG connectivity at rest could predict the therapeutic response to OCD medication.ConclusionsThe findings highlight the important role of the right DLPFC in the pathophysiological mechanism of OCD.

BACKGROUND:Lack of comprehending key factors of schizophrenia relapse has impeded its effective treatment, indicating that the mechanism clarification and available intervention of schizophrenia relapse required further amelioration.METHOD:Based on the integration of LC-MS and 1H NMR metabolomics, a weighted correlation network was established to screen pivotal factors of accelerating schizophrenia relapse. Then, the cluster most correlated with schizophrenia relapse was explored, and the biological function of cluster was investigated. Next, the key biomarker related to schizophrenia relapse was obtained through multiple algorithms. Moreover, the Lilikoi algorithm and correlation analysis were implemented to reveal the association between key biomarker and schizophrenia relapse.RESULT:Results showed that 458 different forms of metabolites were identified for structuring the weighted correlation network. The module-trait correlation indicated that the turquoise module was the most highly correlated with schizophrenia relapse. Further, network analysis revealed that, in turquoise module, cluster 1 composed of 139 metabolites (involved in lipid metabolism and energy metabolism) was the most important subnetwork relevant to schizophrenia relapse. Finally, phenylalanylphenylalanine was recommended as the key biomarker related to schizophrenia relapse. Moreover, the correlation analysis indicated that phenylalanylphenylalanine might affect the progression of schizophrenia by intervening in energy metabolism.CONCLUSION:In summary, critical factors of schizophrenia relapse have been revealed in our research, expounding the schizophrenia progression more systemically, which could shed some light on improving the intervention of schizophrenia relapse.

Bioassay-guided isolation of the stems of Garcinia paucinervis led to one new adamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), (-)-garpauvinin A (1), and four known analogues (2-5). The structure and absolute configuration of 1 was established via spectroscopic techniques and ECD method. All the isolates displayed moderate antiproliferative activity against HL-60, PC-3 and Caco-2 human cancer cell lines with IC50 values ranging from 0.81 to 19.92 μM, and exhibited low toxicity on WPMY-1 normal human cells, showing selectivity between normal and malignant prostate cells. The biosynthetic pathways of the isolated PPAPs were proposed.

目的 通过观察黄连解毒汤(HLJDT)对淀粉样前体蛋白(APP)/早老素(PS)1双转基因小鼠海马区NOD样受体蛋白(NLRP)3表达的影响,探讨其对阿尔茨海默病(AD)的保护作用.方法 将APP/PS1双转基因小鼠随机分为对照组,模型组,HLJDT组(433 g/kg),各组连续灌胃35 d后,采用Morris水迷宫实验,检测APP/PS1小鼠的学习记忆能力,通过体重和脑、脾脏的质量,检测脏器指数变化,采用苏木素-伊红(HE)染色观察小鼠海马区神经元的结构变化,采用实时荧光定量聚合酶链式反应(RT-qPCR)检测小鼠海马区APP、β-淀粉样蛋白(Aβ)1～42和NLRP3 mRNA表达水平,Western印迹实验检测小鼠海马区APP、Aβ1～42和NLRP3蛋白表达水平.结果 与对照组比较,模型组学习记忆能力明显下降,脑和脾脏的脏器指数明显降低,神经元细胞减少,排列疏松,小鼠海马区APP、Aβ1～42和NLRP3 mRNA及蛋白表达均明显升高(均P<0.05);与模型组比较,HLJDT组能明显改善小鼠学习记忆能力(P<0.05),脑和脾脏的脏器指数明显升高,神经元细胞增多,排列较紧密,小鼠海马区APP、Aβ1～42和NLRP3 mRNA及蛋白表达均明显降低(P<0.05).结论 HLJDT可改善APP/PS1双转基因小鼠的学习记忆能力、海马神经元的结构及脏器指数,HLJDT通过抑制NLRP3的表达,使AD在一定程度上得到保护.

Background: Lack of clinically specific biomarkers has impeded the precise diagnosis of schizophrenia, mean-while, limited comprehending of pathogenesis for schizophrenia has restricted the effective treatment.& nbsp;Method: An integrated multi-omic approach, combining metabolomic platform (LC-MS and 1H NMR) and transcriptomic platform, was established to differentiate healthy subjects from schizophrenia patients. Based on filtered metabolites and genes, characteristic spectrums were further built. Then, representative metabolites and genes were screened out through Boruta algorithm. Moreover, characteristic diagnostic formulas were established via LASSO regression analysis.& nbsp;Result: As a result, 86 differential metabolites (in line with amino acid metabolism, etc.) and 189 differential expression genes (involving in amino acid metabolic process, etc.) were obtained as potential biomarkers for schizophrenia. The latent interaction between metabolites with genes, such as HMGCLL1 with energy metabolism, etc., was further studied through the analysis of pathway-based integration. Moreover, fine predictive ability was attributed to characteristic metabolomic/transcriptomic diagnostic spectrums/formulas.& nbsp;Conclusion: The functional relationships of filtered metabolites and genes were studied, which could elaborate the pathological process of schizophrenia more systemically, supplying more precise information on mechanism description and diagnostic evidence of schizophrenia.

Objective:To investigate the spontaneous neural activities and the whole-brain functional connectivity(FC) patterns at rest in patients with obsessive-compulsive disorder (OCD).Methods:40 drug-naive patients with OCD matched the diagnostic criteria of ICD-10 (OCD group), and 38 genders, age, education-matched healthy controls (controls group) underwent resting-state functional magnetic resonance imaging scan. The fractional amplitude of low-frequency fluctuations (fALFF) approach was used to explore spontaneous neural activities. The brain region with abnormal fALFF value (right orbitofrontal cortex (OFC)) was used as the interested region to carry out the whole-brain FC analysis. We analyzed the correlation of clinical symptoms with the abnormal fALFF and FC values by partial correlation analysis in patients with OCD.Results:Compared with controls group, increased fALFF were found in the right OFC and right dorsolateral prefrontal gyrus ( t=4.45, 5.25; P<0.05, GRF corrected), and increased FC were observed between the right OFC and left OFC, and left cerebellum crus Ⅱ ( t=5.39, 4.94; P<0.05, GRF corrected) in OCD group. The increased FC between right OFC and left cerebellum crus Ⅱ positively correlated with 17-Items Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale scores ( r=0.401, P=0.015; r=0.389, P=0.019; uncorrected). Conclusions:The local spontaneous neural activities and FC in the cortical-striatal-thalamic-cortical and OFC-cerebellar circuits were abnormal at rest in patients with OCD.

Background:Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear.Methods:A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier.Results:Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%.Conclusion:Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.

Disrupted functional asymmetry of cerebral hemispheres may be altered in patients with obsessive-compulsive disorder (OCD). However, little is known about whether anomalous brain asymmetries originate from inter- and/or intra-hemispheric functional connectivity (FC) at rest in OCD. In this study, resting-state functional magnetic resonance imaging was applied to 40 medication-free patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs). Data were analyzed using the parameter of asymmetry (PAS) and support vector machine methods. Patients with OCD showed significantly increased PAS in the left posterior cingulate cortex, left precentral gyrus/postcentral gyrus, and right inferior occipital gyrus and decreased PAS in the left dorsolateral prefrontal cortex (DLPFC), bilateral middle cingulate cortex (MCC), left inferior parietal lobule, and left cerebellum Crus I. A negative correlation was found between decreased PAS in the left DLPFC and Yale–Brown Obsessive-compulsive Scale compulsive behavior scores in the patients. Furthermore, decreased PAS in the bilateral MCC could be used to distinguish OCD from HCs with a sensitivity of 87.50%, an accuracy of 88.46%, and a specificity of 89.47%. These results highlighted the contribution of disrupted asymmetry of intra-hemispheric FC within and outside the cortico-striato-thalamocortical circuits at rest in the pathophysiology of OCD, and reduced intra-hemispheric FC in the bilateral MCC may serve as a potential biomarker to classify individuals with OCD from HCs.

Background Patients with obsessive-compulsive disorder (OCD) experience deficiencies in reward processing. The investigation of the reward circuit and its essential connectivity may further clarify the pathogenesis of OCD. Methods The current research was designed to analyze the nucleus accumbens (NAc) functional connectivity at rest in medicine-free patients with OCD. Forty medication-free patients and 38 gender-, education-, and age-matched healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. Seed-based functional connectivity (FC) was used to analyze the data. LIBSVM (library for support vector machines) was designed to identify whether altered FC could be applied to differentiate OCD. Results Patients with OCD showed remarkably decreased FC values between the left NAc and the bilateral orbitofrontal cortex (OFC) and bilateral medial prefrontal cortex (MPFC) and between the right NAc and the left OFC at rest in the reward circuit. Moreover, decreased left NAc-bilateral MPFC connectivity can be deemed as a potential biomarker to differentiate OCD from HCs with a sensitivity of 80.00% and a specificity of 76.32%. Conclusion The current results emphasize the importance of the reward circuit in the pathogenesis of OCD.

目的 通过观察黄连解毒汤(Huanglian Jiedutang,HLJDT)对APP/PS1双转基因小鼠行为学以及白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)表达的影响,探讨HLJDT对阿尔茨海默病(AD)的作用机制.方法 以5月龄的APP/PS1双转基因小鼠为研究对象,设为模型组、HLJDT组(433g·kg-1)处理,对照组为5月龄同背景小鼠,每组各8只.采用Morris水迷宫和新物体识别实验检测HLJDT对AD小鼠学习记忆能力的改善;采用实时荧光定量聚合酶链式反应(RT-qPCR)检测IL-1β和TNF-αmRNA表达水平.结果 HLJDT可以改善APP/PS1双转基因小鼠空间及非空间学习记忆能力,并降低IL-1β和TNF-αmRNA表达水平(P<0.05).结论 HLJDT的抗炎功效,可能是通过调控IL-1β和TNF-α的表达实现的.

Objective Decreased homotopic connectivity of brain networks such as the cortico-striato-thalamo-cortical (CSTC) circuits may contribute to the pathophysiology of obsessive-compulsive disorder (OCD). However, little is known about interhemispheric functional connectivity (FC) at rest in OCD. In this study, the voxel-mirrored homotopic connectivity (VMHC) method was applied to explore interhemispheric coordination at rest in OCD. Methods Forty medication-free patients with OCD and 38 sex-, age-, and education level-matched healthy controls (HCs) underwent a resting-state functional magnetic resonance imaging. The VMHC and support vector machine (SVM) methods were used to analyze the data. Results Patients with OCD had remarkably decreased VMHC values in the orbitofrontal cortex, thalamus, middle occipital gyrus, and precentral and postcentral gyri compared with HCs. A combination of the VMHC values in the thalamus and postcentral gyrus could optimally distinguish patients with OCD from HCs. Conclusions Our findings highlight the contribution of decreased interhemispheric FC within and outside the CSTC circuits in OCD and provide evidence to the pathophysiology of OCD.

Objective To explore the pattern of resting-state functional connectivity of bilateral amygdale in drug-naive obsessive-compulsive disorder（OCD）.Methods Forty patients with OCD matched the criteria of International Classification of Diseases-10 and 38 gender-,

目的 探讨未服药强迫症患者脑白质网络节点连接属性的特点及其与强迫症状的相关性.方法 纳入40例未服药强迫症患者,40名性别、年龄和受教育程度与之相匹配的健康对照,采用结构磁共振和基于图论的分析方法分析脑白质网络节点属性.采用耶鲁布朗强迫量表(Yale-Brown obsessive-compulsive scale,Y-BOCS)、汉密尔顿焦虑量表(Hamilton anxiety rating scale,HAMA)、17项汉密尔顿抑郁量表(17-item Hamilton rating scale for depression,HAMD-17)评估强迫思维和强迫行为、焦虑、抑郁症状.结果 与对照组相比,患者组节点局部效率在左侧眶额回、后扣带回、颞中回和右侧枕上回降低(P<0.05,FDR校正);节点聚类系数在左侧眶额回、颞中回和右侧壳核降低(P<0.05,FDR校正);节点最短路径长度在左侧脑岛增高(P<0.05,FDR校正);节点中心度在左侧海马旁回降低,在左侧脑岛增高(P<0.05,FDR校正);节点全局效率两组差异无统计学意义(P=0.66,FDR校正).患者组左侧后扣带回节点最短路径长度值与强迫思维呈负相关(r=-0.407,P<0.011,Bonferroni校正).结论 未服药强迫症患者皮质-纹状体-丘脑-皮质环路和边缘系统的大脑白质网络节点连接属性存在异常,且与强迫症状相关.

Abnormal functional connectivity (FC) within discrete brain networks is involved in the pathophysiology of obsessive-compulsive disorder (OCD) with inconsistent results. In the present study, we investigated the FC patterns of 40 drug-naive patients with OCD and 38 healthy controls (HCs) through an unbiased voxel-wise global brain FC (GFC) analysis at rest. Compared with HCs, patients with OCD showed decreased GFC within the default mode network (DMN) (i.e., left posterior cingulate cortex/lingual gyrus) and sensorimotor network (i.e., left precentral gyrus/postcentral gyrus) and increased GFC within the executive control network (ECN) (i.e., left dorsal lateral prefrontal cortex and left inferior parietal lobule). Receiver operating characteristic curve analyses further indicated that the altered GFC values within the DMN, ECN, and sensorimotor network may be used as neuroimaging markers to differentiate patients with OCD from HCs. These findings indicated the aberrant FC patterns of the DMN, ECN, and sensorimotor network associated with the pathophysiology of OCD and provided new insights into the changes in brain organization function in OCD.

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of abrupt death in patient with epilepsy. It represents 5–30% of all rapid deaths in individuals with epilepsy. Ketogenic diet (KD) has been used in clinic for treatment of epilepsy for many decades. However, the cellular and molecular mechanisms underlying the SUDEP and the relationship between KD and SUDEP remain uncertain. Kcna1-null (Kcna1−/−) mouse, an animal model of SUDEP, is frequently used to study mechanisms underlying SUDEP. The current mini-review focus on risk factors for SUDEP and their relationship with KD treatment in Kcna1−/− mice. Emerging data suggest that factors including seizure frequency, longevity, rest, age, and gender both in Kcna1−/− mice and KD treated Kcna1−/−mice are involved in SUDEP. This provides valuable prediction for clinical application of KD for treatment of SUDEP.

Objective To explore the changes of whole brain white matter ( WM) structural net-work topological property in patients with schizophrenia (SP) and the associations between WM networks to-pological efficiency and clinical variables in patients. Methods Deterministic tractography was used to con-struct the WM networks of 59 patients with SP ( patients group) and 41 age-, handedness-, and gender-matched healthy controls (HCs),and graph theoretical methods were applied to investigate abnormalities in the global and nodal properties of the WM network in these patients. Partial correlation analysis was used to analyze the relationship between global and nodal properties of the WM network and clinical variables in pa-tients with SP. Results Both the patients with SP and HCs showed small-world organization of the WM net-works. However,compared with HCs,the patients with SP exhibited significant abnormal global topology,in-cluding increased shortest path length ( t=7. 95, P=0. 0001) and decreased global efficiency ( 30. 83 ± 16. 08,8. 25±6. 13,t=-9. 81,P=0. 002),clustering coefficiency (0. 03±0. 01,0. 02±0. 01,t=-4. 48,P=0. 0003),the average clustering coefficiency (t=-8. 28,P=0. 002),the small-worldness (3. 92±0. 79,2. 79 ±0. 56,t=-7. 82,P=0. 001) of their WM structural networks(all P<0. 005,FDR corrected). Further,the patients with SP showed a reduction in nodal efficiency predominately in the cingulate gyrus ( t=-4. 11, P=0. 000),superior occipital gyrus ( t=-6. 05, P=0. 002), superior temporal gyrus ( t=-10. 46, P=0. 001),middle temporal gyrus (t=-10. 38,P=0. 000),thalamus (t=-6. 10,P=0. 000) and putamen ( t=-8. 38,P=0. 000) (P<0. 005,FDR corrected). Partial correlation results showed that there was no signifi-cant correlation between global topological properties,node efficiency and clinical symptoms in patients group (Eglob:r=-0. 14,P=0. 279;Eloc:r=-0. 06,P=0. 628;Lp:r=0. 28,P=0. 031;Cp:r=0. 27,P=0. 043;λ:r=-0. 18,P=0. 166;γ:r=-0. 29,P=0. 026;σ:r=0. 26,P=0. 048;nEglob:r=0. 36,P=0. 005;nEloc:r=0. 02,P=0. 901). Conclusions The patients with SP exhibit the abnormal of whole brain WM structural network topological property and the node efficiencies of cortico-striato-thalamo circuitry are significantly re-duced.

BACKGROUND:The simple and caged xanthones from Clusiaceae showed significant antineoplastic activity. This study aims to identify structural diverse xanthones and search for novel antitumor natural products from this family plants.METHODS:The structures of new compounds 1a and 1b were elucidated mainly through comprehensive NMR and MS spectroscopic data, and their absolute configurations were determined by the comparison of the experimental and calculated electronic circular dichroism.RESULTS:A pair of new xanthone enantiomers, (+)- and (-)-cracochinxanthone A (1a and 1b), along with thirty known analogues (2-31), were isolated from extracts of the stems and leaves of C. cochinchinense. Preliminary biological assay of some isolates against HL-60, PC-3, and MDA-MB-231 cancer cell lines.CONCLUSION:Some isolated xanthones exhibited high sensitivity against three human malignant cell lines and the structure-activity relationship study showed that the prenyl and geranyl units may play an important role in antitumor activity.

Abnormalities of the cerebellum and default-mode network (DMN) in patients with obsessive–compulsive disorder (OCD) have been widely reported. However, alterations of reciprocal functional connections between the cerebellum and DMN at rest in OCD remain unclear. Forty patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity (FC) and support vector machine (SVM) were applied to analyze the imaging data. Compared with HCs, patients with OCD exhibited increased FCs between the left Crus I–left superior medial prefrontal cortex (MPFC) and between the right Crus I–left superior MPFC, left middle MPFC, and left middle temporal gyrus (MTG). A significantly negative correlation was observed between the right Crus I–left MTG connectivity and the Yale–Brown Obsessive–Compulsive Scale compulsion subscale scores in the OCD group (r = − 0.476, p = 0.002, Bonferroni corrected). SVM classification analysis indicated that a combination of the left Crus I–left superior MPFC connectivity and the right Crus I–left middle MPFC connectivity can be used to discriminate patients with OCD from HCs with a sensitivity of 85.00%, specificity of 68.42%, and accuracy of 76.92%. Our study highlights the contribution of the cerebellar–DMN connectivity in OCD pathophysiology and provides new findings to OCD research.

BACKGROUND:Default-mode network (DMN) plays a key role in the pathophysiology of obsessive-compulsive disorder (OCD). However, the network homogeneity (NH) of DMN in OCD remains equivocal. OBJECTIVE:This study aimed to investigate abnormalities in the NH of the DMN at rest and the correlation between the NH of DMN and clinical variables in patients with OCD. METHODS:This study used the independent component analysis and unbiased hypothesis-driven NH method to analyze the resting-state functional magnetic resonance imaging data of 40 drug-naive patients with OCD and 40 age-, gender-, and education-matched healthy controls (HCs). RESULTS:Patients with OCD exhibited decreased NH values in the left ventral medial prefrontal cortex and bilateral posterior cingulate cortex (PCC)/precuneus (PCu) compared with HCs. Furthermore, analyses of receiver operating characteristic curves indicated that the decreased NH values in the right PCC/PCu may be used as a candidate neuroimaging marker to distinguish patients with OCD from HCs. CONCLUSION:These findings contribute new evidence of the participation of the altered NH of the DMN in the pathophysiology of OCD. TRIAL REGISTRATION:Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (ChiCTR-COC-17013301).

Bioassay-guided fractionation of the dichloromethane-soluble portion of the stems of Garcinia paucinervis led to the isolation of eight new xanthones, including three pairs of enantiomers, ( + ) and ( - ) paucinervins L-N (1a-3a, and 1b-3b), one optically pure compound, ( - ) paucinervin O (4), and one new analogue, paucinervin P (5), as well as thirteen known xanthones (6-18). Their structures were established by detailed analysis of extensive spectroscopic data. The absolute configurations of 1-4 were confirmed by ECD calculations. All the isolates 1-18 displayed antiproliferative effect against HL-60 with IC50 values ranging from 0.87 to 29.14 mu M, of which compound 5 was the most active. Compounds 6, and 14 exhibited potential inhibitory activity against PC-3 cells, while compounds 5-7, 14, and 16-17 displayed cytotoxic potency against Caco-2 cells. A preliminary structure-activity relationship was also discussed.