Neurodynamic models that simulate how micro-level alterations propagate upward to impact macroscopic neural circuits and overall brain function may offer valuable insights into the pathological mechanisms of schizophrenia (SCZ). In this study, we integrated a neurodynamic model with the classical Contrastive Variational Autoencoder (CVAE) to extract and evaluate macro-scale SCZ-specific features, including subject-level, region-level parameters, and time-varying states. Firstly, we demonstrated the robust fitting of the model within our multi-site dataset. Subsequently, by employing representational similarity analysis and a deep learning classifier, we confirmed the specificity and disorder-related information capturing ability of SCZ-specific features. Moreover, analysis of the attractor characteristics of the neurodynamic system revealed significant differences in attractor space patterns between SCZ-specific states and shared states. Finally, we utilized Partial Least Squares (PLS) regression to examine the multivariate mapping relationship between SCZ-specific features and symptoms, identifying two sets of correlated modes implicating unique molecular mechanisms: one mode corresponding to negative and general symptoms, and another mode corresponding to positive symptoms. Our results provide valuable insights into disorder-specific neurodynamic features and states associated with SCZ, laying the foundation for understanding the intricate pathophysiology of this disorder.

The global burden of major depressive disorder (MDD) is increasing. Preclinical and clinical studies have indicated a close association between levels of trace elements and the incidence of MDD. However, little is known about the association between selenium levels and MDD. Methionine sulfoxide reductase B1 (MSRB1) is a selenoprotein regulated by dietary selenium levels that can indirectly clear reactive oxygen species (ROS). Here we show that supplementing the diet with L-selenomethionine, the most common organic selenium compound in organisms, effectively reduces the susceptibility of mice to depressive-like behavior induced by unpredictable chronic mild stress (CUMS). Furthermore, by knocking down MSRB1 in primary astrocytes and mouse hippocampi, we demonstrate that L-selenomethionine exerts its protective effect by increasing MSRB1 levels in hippocampal astrocytes. MSRB1 reduces ROS-induced neuroinflammation in astrocytes by indirectly clearing ROS. Our findings not only reveal a role for dietary selenium in regulating the susceptibility of mice to CUMS-induced depressive-like behaviors but also further identify the specific selenoprotein mediating this effect. These findings provide a potential dietary approach for preventing MDD in clinical practice and the motivation for further preclinical studies.

Background: Pregnancy is a very complex and highly stressful time in women. Despite the high prevalence of postpartum depression, more than 50 % of mothers are undiagnosed or untreated, showing an urgent need to explore an effective preventive strategy. Regular physical activity has been suggested to be associated with an increased quality of life in pregnant and postpartum women. The purpose of this study was to determine whether perinatal running training can affect maternal care stress-related anxiety, depressive-like behavior, and cognitive changes in postpartum dams and to explore the possible underlying mechanism. Methods: 40 female C57BL/6J mice were divided into four groups: prenatal control (NC) and running training (EX) group (NC+EX), prenatal control and nonrunning training (RE) group (NC+RE), prenatal subchronic variable stress (SCVS) and running training group (SCVS+EX) and prenatal SCVS and non-running training group (SCVS+RE). Mice in prenatal stress groups were subjected to SCVS after pregnancy confirmed. Mice in running training groups subjected to running training throughout pregnancy and lactation. Then after the delivery, maternal behavior, cognitive changes, anxiety and depressive-like behaviors were tested. Then we measured the serum prolactin (PRL), hypothalamic-pituitary adrenal (HPA) axis activity, and adult hippocampus neurogenesis (AHN) in dams. Results: Compared to NC+RE, prenatal SCVS caused cognitive impairments, the decrease in maternal behavior, and anxiety and depressive-like behavior in SCVS+RE dams, accompanying increase in HPA axis activity and decreased the PRL levels and AHN in postpartum period. Then compared to SCVS+RE, perinatal running training mitigates cognitive impairments, increased maternal behavior, and alleviates anxiety and depressive-like behavior in SCVS+EX dams, accompanying the decreased HPA axis activity, and the increased PRL levels and AHN in postpartum period. Conclusion: Overall, this study suggests that perinatal running training might improve maternal care and reverse prenatal stress-related cognitive impairment and anxiety and depressive-like behavior in postpartum dams.

Background Resting-state functional magnetic resonance imaging (fMRI) studies have shown altered brain activity in major depressive disorder (MDD) and schizophrenia (SZ). Despite differing diagnoses, SZ and MDD share similar features. However, functional brain activity similarities and differences between SZ and MDD remain unclear. Methods Participants with MDD, SZ, and normal controls (n=36 each) underwent resting-state fMRI scans. Amplitude of low-frequency fluctuations (ALFF) was used to analyze the preprocessed rs-fMRI data. One-way ANOVAs and post hoc analyses compared ALFF values in different brain regions. Pearson correlation analysis examined associations with clinical symptoms. Results Comparison among the three groups revealed significant differences in ALFF values within the left superior parietal cortex (L-SPC) and bilateral striatum. Through pairwise comparisons, patients with SZ but not patients with MDD were found to exhibit increased striatum ALFF values relative to NC individuals, but decreased in MDD. Meanwhile, L-SPC ALFF values were significantly increased in patients with SZ relative to both normal control individuals and patients with MDD, while no differences in these values were observed between the normal control and MDD groups. The Pearson correlation analyses showed significant positive correlations between ALFF in the striatum and PANSS positive score, but no significant correlation with other symptom severity in SZ and MDD. Conclusion These findings support the hypothesis of alterations in brain functional activity as a fundamental component of the pathogenesis of MDD and SZ. The observed differences in functional brain activity in the superior parietal cortex and striatum between MDD and SZ provide a neuroimaging basis that can contribute to the differential diagnosis of these debilitating conditions.

The neuroinflammatory state may contribute to the pathogenesis of many mental disorders including schizophrenia. Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for activation of proteins involved in mitochondria quality control, such as Sirtuin3 (SIRT3). Our previous study has found that NAD+ supplement could rescue early life stress (ELS)-induced neuroinflammation and down-regulation of SIRT3 in adult offspring. However, it is unclear whether SIRT3 is the key to the neuroprotective effects of NAD+ supplement in this animal model of schizophrenia. The present study used 24 h maternal separation (MS) as ELS to Wistar rat pups on the postnatal day (PND) 9. Schizophrenia-like behaviors and memory impairments were detected by behavioral tests. Microglial activation, pro-inflammatory cytokine expression, and NAD+/SIRT3 expression were detected in the prefrontal cortex and hippocampus. Meanwhile, NAM (a precursor of NAD+), and the SIRT3 activator Honokiol (HNK), and the SIRT3 inhibitor 3-TYP were used as an intervention in vivo. Our results showed that ELS could induce schizophrenia-like behaviors and M1 microglial activation, NAD+ decline, lower expression of SIRT3, and increased acetylated superoxide dismutase 2 expression at the adult stage. NAD+ supplement or HNK administration could block this process and normalize the behavioral alterations of the MS animals. 3-TYP administration in the control group and the NAM-treated MS rats caused M1 microglial activation and cognitive deficits. Our results demonstrated that SIRT3 mediated the stabilizing effect of NAD+ on normalizing M1 microglial activation and behavioral phenotypes in MS rats.

Schizophrenia is characterized by the distributed dysconnectivity of resting-state multiple brain networks. However, the abnormalities of intra- and inter-network functional connectivity (FC) in schizophrenia and its relationship to symptoms remain unknown. The aim of the present study is to compare the intra- and inter-connectivity of the intrinsic networks between a large sample of patients with schizophrenia and healthy controls. Using the Region of interest (ROI) to ROI FC analyses, the intra- and inter-network FC of the eight resting state networks [default mode network (DMN); salience network (SN); frontoparietal network (FPN); dorsal attention network (DAN); language network (LN); visual network (VN); sensorimotor network (SMN); and cerebellar network (CN)] were investigated in 196 schizophrenia and 169-healthy controls. Compared to the healthy control group, the schizophrenia group exhibited increased intra-network FC in the DMN and decreased intra-network FC in the CN. Additionally, the schizophrenia group showed the decreased inter-network FC mainly involved the SN-DMN, SN-LN and SN-CN while increased inter-network FC in the SN-SMN and SN-DAN (p < 0.05, FDR-corrected). Our study suggests widespread intra- and inter-network dysconnectivity among large-scale RSNs in schizophrenia, mainly involving the DMN, SN and SMN, which may further contribute to the dysconnectivity hypothesis of schizophrenia.

Background: There is a high correlation between the risk of major depressive disorder (MDD) and adverse childhood experiences (ACEs) such as adverse parenting (AP). While there appears to be an association between ACEs and changes in brain structure and function, there have yet to be multimodal neuroimaging studies of associations between parenting style and brain developmental changes in MDD patients. To explore the effect of AP on brain structure and function. Methods: In this cross-sectional study, 125 MDD outpatients were included in the study and divided into the AP group and the optimal parenting (OP) group. Participants completed self-rating scales to assess depressive severity, symptoms, and their parents' styles. They also completed magnetic resonance imaging within one week of filling out the instruments. The differences between groups of gender, educational level, and medications were analyzed using the chi-squared test and those of age, duration of illness, and scores on scales using the independent samples t-test. Differences in gray matter volume (GMV) and resting-state functional connectivity (RS-FC) were assessed between groups. Results: AP was associated with a significant increase in GMV in the right superior parietal lobule (SPL) and FC between the right SPL and the bilateral medial superior frontal cortex in MDD patients. Limitations: The cross-cultural characteristics of AP will result in the lack of generalizability of the findings. Conclusions: The results support the hypothesis that AP during childhood may imprint the brain and affect depressive symptoms in adulthood. Parents should pay attention to the parenting style and avoid a style that lacks warmth.

Early life stress (ELS) is associated with the later development of schizophrenia. In the rodent model, the maternal separation (MS) stress may induce neuronal apoptosis and schizophrenia-like behavior. Although the TRPV1 agonist capsaicin (CAP) has been reported to reduce apoptosis in the central nervous system, its effect in MS models is unclear. Twenty-four hours of MS of Wistar rat pups on postnatal day (PND9) was used as an ELS. Male rats in the adult stage were the subjects of the study. CAP (1 mg/kg/day) intraperitoneal injection pretreatment was undertaken before behavioral tests for 1 week and continued during the tests. Behavioral tests included open field, novel object recognition, Barnes maze test, and pre-pulse inhibition (PPI) test. MS rats showed behavioral deficits and cognitive impairments mimicking symptoms of schizophrenia compared with controls. MS decreased the expression of TRPV1 in the frontal association cortex (FrA) and in the hippocampal CA1, CA3, and dentate gyrus (DG) regions compared with the control group resulting in the increase of pro-apoptotic proteins (BAX, Caspase3, Cleaved-Caspase3) and the decrease of anti-apoptotic proteins (Bcl-2). The number of NeuN++TUNEL+ cells increased in the MS group in the FrA, CA1, CA3, and DG compared with the control group. Neuronal and behavioral impairments of MS were reversed by treatment with CAP. Exposure to ELS may lead to increased neuronal apoptosis and impaired cognitive function with decreased TRPV1 expression in the prefrontal cortex and hippocampus in adulthood. Sustained low-dose administration of CAP improved neuronal apoptosis and cognitive function. Our results provide evidence for future clinical trials of chili peppers or CAP as dietary supplements for the reversal treatment of schizophrenia.

产后抑郁症是抑郁症中常见的一种类型,指分娩后4周内出现重度抑郁发作.产后抑郁症损害产妇心理、生理、社会功能等,该疾病诊断及治疗因多方面因素有较大困难,故产后抑郁的预防环节应得到重视.预防措施之一—运动,受到广泛关注,但预防机制仍在探索过程中,本文回顾运动对产后抑郁的作用,以及对运动对产后抑郁预防作用的潜在生物学机制进行汇总.

BACKGROUND:The mechanism by which synaptic plasticity mediates the occurrence of depression is unknown. Low-density lipoprotein receptor-related protein 1 (LRP1) affects axon growth and neurogenesis in the brain, but its role in depressive-like behaviors is poorly understood. METHODS:Adeno-associated virus-mediated small interfering RNA was injected into the bilateral hippocampus 14 days before chronic unpredicted mild stress (CUMS). Behavior performance was assessed for depressive-like behaviors. Western blot was conducted to detect levels of LRP1, neurogenesis-related proteins, synaptic markers, microtubule system molecules and Akt/GSK-3β signaling-related proteins. Immunohistochemical staining was performed for LRP1 protein, immunofluorescence staining was conducted to determine the Sox2 protein, Nissl's staining and transmission electron microscope staining were used to observe hippocampal morphological features. RESULTS:The expression of hippocampal LRP1 was positively correlated with depressive-like behaviors. Treatment with iAAV-LRP1 exerted protective effects on depressive-like behaviors. LRP1 Knockdown relieved the inhibition of synaptic plasticity induced by CUMS. Expression of Sox2, GluR2 and SYP was significantly increased in iAAV-LRP1 CUMS rats. LRP1 knockdown reduced the p-tau (Ser262 and Thr404) and Acet-tubule levels in depressed rats. Finally, we found that LRP1 knockdown activated the PI3K/Akt pathway and inhibited GSK-3β signal transduction. LIMITATIONS:More neurogenesis markers would be considered, and stereotactic injection into hippocampal DG region could be performed to investigate the effects of LRP1. CONCLUSIONS:These findings indicated that hippocampal LRP1 deficiency in stressed rats plays an important protective role in depressive-like behavior by increasing synaptic plasticity mediated by microtubule dynamic and activating Akt/GSK-3β signaling pathway. Therefore, LRP1 may represent a potential therapeutic target for depression.

Background Inter-hemispheric disconnection is a primary pathological finding in schizophrenia. However, given the inherent complexity of this disease and its development, it remains unclear as to whether associated inter-hemispheric changes play an important role in auditory verbal hallucination (AVH) development. As such, this study was developed to explore inter-hemispheric connectivity in the context of schizophrenia with AVH while excluding positive symptoms and other factors with the potential to confound these results. Method In total, resting-state functional magnetic resonance imaging (fMRI) was used to assess 42 patients with AVH (APG), 26 without AVH (NPG), and 82 normal control (NC) individuals. Inter-hemispheric connectivity in these subjects was then assessed through the use of voxel-mirrored homotopic connectivity (VMHC) and Pearson correlation analyses. Result Relative to HC and NPG subjects, APG individuals exhibited a decrease in VMHC in the superior temporal gyrus (STG) extending into Heschl's gyrus, the insula, and the Rolandic operculum as well as in the fusiform gyrus extending into the para-hippocampus (Corrected p < 0.005, cluster size = 52). Among APG individuals, these observed impairments of inter-hemispheric connectivity were negatively correlated with Hoffman auditory hallucination scores. Conclusion These results support the schizophrenia hemitropic disconnection hypothesis, and provide novel evidence suggesting that there may be a relationship between reductions in inter-hemispheric connectivity in auditory and memory-related networks and the pathogenesis of AVH in patients with schizophrenia following the exclusion of confounding factors from other positive symptoms.

Depression is a prevalent psychiatric disorder with a significant health impact and economic burden worldwide. Unfortunately, the exact pathogenesis of depression is not well understood. Neuroinflammation and microglial activation play an essential role in the pathogenesis of depression. Previous studies have shown that polydatin has anti-inflammatory and antioxidant properties. However, the link between polydatin and depression remains unclear. Therefore, the objective of this study was to investigate the antidepressant effect of polydatin in lipopolysaccharide (LPS)-induced depression in mice and its possible mechanism. Adult male C57BL/6 J mice were used in this study. The polydatin and LPS were injected intraperitoneally daily for 5 days. In addition, the EX527, an inhibitor of Sirt1, was injected intraperitoneally daily and 1 h before the polydatin injection. The behavior tests were performed to elucidate the depression-like behaviors. The Sirt1/HMGB1/NF-κB pathway expression was detected by western blot, ELISA, and immunofluorescence staining. Polydatin can significantly improve LPS-induced depression-like behavior in mice. Treatment with polydatin increased the expression of the Sirt1 but decreased the expression of the HMGB1, p-NF-κB, IL-1b, and TNF-α in the LPS-induced depression mice. In addition, the EX527 abolished the anti-depressive effects of the polydatin and the levels of Sirt1 protein. These findings suggested that the polydatin reversed the depressive effects through the Sirt1/HMGB1/NF-κB signaling in the LPS-induced depression mice. Therefore, polydatin can be used in the treatment of depression.

目的 探讨立体定向辅助下双侧内囊前肢毁损术(ALIC-RSF)治疗难治性精神分裂症(SCZ)伴发的攻击行为的疗效.方法 回顾性分析2019年6月至2021年1月立体定向辅助下ALIC-RSF治疗的35例伴攻击行为的难治性SCZ的临床资料.术前、术后3个月、术后1年,使用外显攻击量表(MOAS)、阳性及阴性症状量表(PANSS)、蒙特利尔认知评估量表(MoCA)、社会功能缺陷筛选量表(SDSS)评估疗效.使用R软件,采用LASSO回归分析检验PANSS评分与术后12个月MOAS评分的相关性.结果 术后3、12个月,MOAS评分、PANSS评分、SDSS评分均显著改善(P＜0.05),而MoCA评分无明显变化(P＞0.05).手术相关并发症大多在术后2周恢复,2例术后1年表现轻度行为懒散、兴趣缺乏的症状.术后12个月MOAS评分改善率与PANSS阳性评分改善率、术前PANSS子项被害评分呈明显正相关(P＜0.05),而与PANSS子项交谈缺乏自发性和流畅性评分、不合作评分以及年龄呈明显负相关(P＜0.05).结论 ALIC-RSF对难治性SCZ的攻击行为有确切疗效,可明显提高病人的社会功能和生活质量.

目的:探讨首发精神分裂症患者和复发精神分裂症患者急性发作时血浆细胞因子水平及其与临床症状的关系.方法:本研究纳入首发精神分裂症急性期患者33例(首发组)、复发精神分裂症急性发作期患者35例(复发组)及健康对照组32例(对照组).采用流式免疫技术检测被试者血浆中炎性因子水平,采用阳性与阴性症状量表(PANSS)评估患者临床症状严重程度.比较各组以上指标水平的差异,同时分析炎性因子水平与精神分裂症患者临床症状严重程度的关系.结果:与对照组相比,首发组和复发组血浆中白细胞介素-2(IL-2)、白细胞介素-4(1L-4)、白细胞介素-6(IL-6)水平均显著升高(P＜0.01)且复发组IL-6较首发组升高更明显(P＜0.01),各组白细胞介素-10(IL-10),肿瘤坏死因子-α(TNF-α),干扰素-γ(IFN-γ)水平差异无统计意义(P＞0.05).另外,首发组和复发组血浆中IL-2与PANSS总分、阳性症状量表、一般精神病理症状量表评分呈正相关(r=0.26,P＜0.05;r=0.25,P＜0.05;r=0.35,P＜0.01);IL-10与阴性症状量表呈正相关(r=0.29,P＜0.05).结论:首发和复发精神分裂症患者急性发作期均存在促炎性和抗炎性因子失衡,精神症状的严重程度与这种免疫功能异常相关.

目的:观察培元抗癌汤通过调节癌相关成纤维细胞(CAFs)抑制H22肝癌细胞增殖、诱导H22肝癌细胞凋亡,以及对CAFs细胞MMP-2、MMP-9及CXCL1、CXCL2表达的调节作用.方法:原代CAFs细胞分离、培养并鉴定,分为模型组、中药组,药物干预后收集CAFs细胞培养上清,并加入对数生长期的H22细胞中培养24 h.CCK8法检测H22细胞的增殖情况,流式细胞学检测H22细胞的凋亡情况;ELISA法检测CAFs细胞上清中CXCL1、CXCL2水平,PCR检测CAFs细胞中MMP-2、MMP-9 mRNA表达,Western Blot检测CAFs细胞中MMP-2、MMP-9蛋白质表达.结果:与模型组相比,中药组H22细胞增殖抑制、细胞凋亡增加,差异具有统计学意义(P<0.05).与模型组比较,中药组CAFs细胞上清中CXCL1、CXCL2含量减少,中药组CAFs细胞MMP-2、MMP-9 mRNA和蛋白质表达明显降低,差异具有统计学意义(P<0.05).结论:培元抗癌汤在体外能抑制H22细胞肝癌细增殖、诱导其凋亡,其机制可能是调节肿瘤微环境中CAFs,抑制MMP-2、MMP-9与CXCL1、CXCL2,进而抑制肿瘤生长、发展.

目的 观察培元抗癌汤对Lewis肺癌小鼠肿瘤生长及肿瘤肺转移的抑制作用,探讨培元抗癌汤对自噬及PI3K-AKT-mTOR信号通路的影响.方法 Lewis肺癌细胞接种在C57BL/6小鼠右腋皮下,制成Lewis肺癌荷瘤小鼠模型.将荷瘤小鼠随机分为模型组、顺铂组、培元抗癌汤组、培元抗癌汤-顺铂组,分别给予中药灌胃、顺铂腹腔注射,进行药物干预后,观察各组小鼠生存质量;观察肺转移灶、计算肺转移抑制率;称取各组荷瘤小鼠肿瘤的质量、计算抑瘤率;透射电镜观察自噬泡的形成;Western blot法检测肿瘤组织中自噬因子LC3 Ⅰ及LC3 Ⅱ蛋白的表达,检测肿瘤组织中PI3K、p-PI3 K、AKT、p-AKT、mTOR、p-mTOR表达.结果 模型组、顺铂组小鼠生存质量差,小鼠有聚集、毛发脱落、反应迟缓等现象,培元抗癌汤组、培元抗癌汤-顺铂组小鼠生存质量较好.与模型组比较,培元抗癌汤组、培元抗癌汤-顺铂组能明显抑制肺转移(P＜0.05),顺铂组有抑制肺转移趋势,但差异无统计学意义(P＞0.05);培元抗癌汤-顺铂组肺转移抑制率则明显高于培元抗癌汤组.与模型组比较,顺铂组、培元抗癌汤组、培元抗癌汤-顺铂组能明显抑制肿瘤生长,差异有统计学意义(P＜0.05),顺铂组高于培元抗癌汤组(P＜0.05),培元抗癌汤-顺铂组明显高于培元抗癌汤组和顺铂组.与模型相比,顺铂组、培元抗癌汤组、培元抗癌汤-顺铂组自噬泡明显增多,提示自噬增强.各用药组肿瘤组织中LC3Ⅱ/LC3 Ⅰ均明显高于模型组(P＜0.05);与培元抗癌汤组比较,顺铂组、培元抗癌汤-顺铂组的LC3 Ⅱ/LC3 Ⅰ表达更高(P＜0.05),而培元抗癌汤-顺铂组的LC3 Ⅱ/LC3 Ⅰ表达最高.与模型组比较,各用药组肿瘤组织中PI3K、AKT、mTOR的表达无明显差异(P＞0.05),各用药组肿瘤组织中p-PI3K、p-AKT、p-mTOR表达均明显低于模型组(P＜0.05);与培元抗癌汤组比较,顺铂组、培元抗癌汤-顺铂组的p-PI3K、p-AKT、p-mTOR表达更低(P＜0.05),而培元抗癌汤-顺铂组的p-PI3K、p-AKT、p-mTOR表达最低.结论 培元抗癌汤能明显改善小鼠生存质量及抑制肿瘤生长及转移,其机制可能是抑制PI3K-AKT-mTOR信号通路,增强肿瘤自噬.

目的:了解精神分裂症(SCZ)患者的脑白质损害的特点及其与临床症状、认知功能损害之间的关系.方法:招募精神分裂症患者(SCZ组)及健康对照(HC组)各30例,对2组进行磁共振扩散张量成像(DTI)扫描,及临床症状评定、SCZ认知功能简明评测量表(BACS)测评;采用优化的空间统计方法(TBSS)对DTI数据进行分析,分析两组之间DTI扫描结果的差异及其与临床症状、BACS得分的相关性.结果:SCZ组全脑多处纤维束FA值低于对照组(P<0.05);左侧小脑上脚FA值与符号编码得分呈正相关(r=0.384,P=0.039).结论:SCZ患者存在全脑多处白质纤维损害,且部分重要白质纤维损害与认知障碍存在相关性.

Objective:To compare and explore the characteristics of striatum functional connectivity in major depression and schizophrenic.Methods:Thirty-six patients with major depressive disorder (MDD), schizophrenia, and health controls were recruited in this study. All subjects underwent rest-stating functional magnetic resonance imaging (rs-fMRI). Routine preprocessing of rs-fMRI data was performed. The regional homogeneity (ReHo), and fractional amplitude of low frequency fluctuation (fALFF) values of the three groups were calculated, separately. Based on the results of one-way analysis of covariance, different brain areas were superimposed to obtain the overlapping regions (the left striatum). Next, the superimposed brain region (the left striatum) was used as the region of interest (ROI), and the customized ROI method was used for the whole-brain functional connectivity analysis. Finally, Pearson correlation analysis was performed between the functional connectivity of the brain regions and clinical features of MDD and schizophrenia.Result:Among the three groups, left striatum extending to the insula and Rolland′s insula showed significant differences of the ReHo values ( P<0.001, AlphaSim correction, voxel number >99);while left superior parietal areas and bilateral insula extending to lentiform nucleus showed significant differences of fALFF values (AlphaSim correction, P<0.001, voxel number >90). The left striatum were superimposed and revealed significant ReHo and fALFF values. The ROI analysis showed that the brain area with different functional connections in the three groups was left inferior temporal gyrus (AlphaSim correction, P<0.001, volume element number>42). The pairwise comparative analysis showed that compared with healthy controls (0.24±0.03), patients with MDD (0.15±0.02) and schizophrenia (0.09±0.01) showed decreased functional connections between the left striatum and the inferior temporal gyrus, and the decline was more significant in patients with schizophrenia. The functional connectivity value of left inferior temporal gyrus was not correlated with HAMD score in MDD( r=-0.02, P=0.93). The functional connectivity value of left inferior temporal gyrus was positively correlated with PANSS positive score in patients with schizophrenia ( r=-0.40, P=0.02). Conclusion:Both MDD and schizophrenia patients may have abnormal function connections of the striatum and the abnormal function connection with the left temporal inferior gyrus may closely related to clinical symptoms of schizophrenia. The brain function activity of striatum and its abnormal connection with the left temporal inferior gyrus may play an important role in the neuropathology of schizophrenia and MDD.

目的 观察培元抗癌汤联合替加氟对MMP2、MMP9及CXCL1、CXCL2调节作用及对H22肝癌细胞转移能力影响.方法 用H22肿瘤细胞悬液,注入小鼠尾静脉中造模后进行药物干预.解剖小鼠,取出肺组织,镜下观察肺部转移结节数目并记录,计算肺转移抑制率.免疫组化法检测转移瘤中MMP2、MMP9蛋白表达水平,ELISA检测小鼠血中CXCL1、CXCL2的水平.结果 空白组与荷瘤组、替加氟组、中西医组结节数比较有统计学意义(P＜0.05),替加氟组与中西医组比较有统计学意义(P＜0.05).西药组、中西医组转移抑制率分别为11％、49％,中西医组疗效优于单药组.MMP2、MMP9在空白组呈弱阳性,在荷瘤组呈强阳性,在替加氟组、中西医组呈阳性,且中西医组表达更少.中西医组对肺转移癌外周血中CXCL1有抑制作用,替加氟组无抑制作用.西药组、中西医组均对肺转移癌外周血中CXCL2有抑制作用,两组数据均表明中西医组疗效优于单药组.结论 培元抗癌汤联合替加氟在体内能抑制H22细胞肝癌细胞转移能力,其机制可能是调节肿瘤微环境中的MMP2、MMP9及CXCL1、CXCL2.

目的:研究双相情感障碍患者CYP2C19基因多态性与丙戊酸盐(VPA)所致肝功能变化的关系.方法:本研究收集2016年至2019年在武汉大学人民医院精神卫生中心住院的双相情感障碍患者122例:非VPA治疗对照组35例、500 mg/d治疗组20例、750 mg/d治疗组32例、1 000 mg/d治疗组35例,检测CYP2C19基因多态性,将各剂量组再分为代谢亚组(快代谢亚组、中代谢亚组),VPA持续给药2周后检测肝功能和血药浓度.结果:①各处理组间肝功能ALT、AST和ALT/AST存在差异(P＜0.05).②500 mg/d组和750 mg/d组代谢亚组间肝功能指标均无统计学差异(P＞0.05),1 000 mg/d组代谢亚组间ALT和AST存在统计学差异(P＜0.05).③各处理组间血药浓度存在统计学差异,只有1 000 mg/d组的CYP2C19中代谢亚组血药浓度高于快代谢亚组(P＜0.01).结论:在双相情感障碍患者中,CYP2C19基因多态性与高剂量VPA血药浓度及其所致肝功能变化有关.