Network Pharmacology and Experimental Verification of Si Shen Decoction Regulating FABP4/PPARγ/NFκB Pathway in the Treatment of Collagen-induced Arthritis.

AIM: This study aimed to investigate the mechanism of SSD in rats with Collagen- Induced Arthritis (CIA). BACKGROUND: Rheumatoid arthritis (RA) is a complex immune disease characterized by bilateral symmetrical multi-joint pain and swelling. Si Shen Decoction (SSD) has shown good results in treating RA in clinical applications, but its mechanism of action remains unclear. OBJECTIVE: To investigate the mechanism of SSD in rats with Collagen-Induced Arthritis (CIA). METHODS: Bioinformatics and network pharmacology analyses were used to predict the possible treatment targets and signaling pathways. Elisa, Western blotting, and quantitative real-time polymerase chain reaction were used to verify the mechanism of SSD in the treatment of RA. RESULTS: FABP4, MMP9, and PTGS2 were the most common predicted therapeutic targets. SSD treatment significantly reduced synovitis, ankle swelling and bone erosion in CIA rats. The SSD group also significantly reduced the serum secretion of CRP, TNFα, and IL1ß, decreased mRNA levels of FABP4, IKKα, and p65 in the synovial membrane, but increased PPARγ. Western blot showed that SSD treatment could significantly reduce the expression of FABP4, IKKα, and phosphorylated p65 (p-p65) proteins in the synovium. SSD was found to inhibit the FABP4/PPARγ/NFκB signaling pathway and reduce the inflammatory response in CIA rats. The therapeutic effect of SSD was significant with the increase of dose. CONCLUSION: SSD can relieve joint symptoms in CIA rats and alleviate inflammation by inhibiting the FABP4/PPARγ/NFκB signaling pathway. The effect of high-dose SSD was more prominent.

Associations of Preoperative Nutritional Status and Sarcopenia With Mortality in Patients With Abdominal Aortic Aneurysm After Open and Endovascular Abdominal Aortic Aneurysm Repair: A Retrospective Study.

OBJECTIVE: The effect of preoperative malnutrition and sarcopenia on outcomes in patients with abdominal aortic aneurysm (AAA) after open surgical repair (OSR) and endovascular abdominal aortic aneurysm repair is undefined. The authors conducted the study to address this issue in this population. DESIGN: A retrospective observational study. SETTING: A large tertiary hospital. PARTICIPANTS: Patients with AAA who underwent OSR and endovascular aneurysm repair (EVAR). INTERVENTIONS: Evaluation of nutritional status (Nutritional Risk Screening 2002 [NRS 2002] and the Controlling Nutritional Status [CONUT] scores), muscle size (skeletal muscle index), and postoperative parameters. MEASUREMENTS AND MAIN RESULTS: A total of 199 patients were reviewed from January 2020 to December 2022. Patients weew categorized into group A (CONUT <4) and group B (CONUT ≥4) based on whether their CONUT scores were less than 4. The mortality (p = 0.004) and the incidence of Clavien-Dindo class III complications (p = 0.007) in group B were higher than those in group A. CONUT score was an independent risk factor for midterm mortality (hazard ratio 1.329; 95% CI, 1.104-1.697; p = 0.002) and Clavien-Dindo class III complications (odds ratio 1.225; 95% CI, 1.012-1.482; p = 0.037) according to univariate and multivariate analyses, whereas NRS 2002 score and sarcopenia were not. Kaplan-Meier curves showed a lower midterm survival rate in group B (log-rank p < 0.001). CONCLUSION: In patients with AAA undergoing OSR or EVAR, a CONUT score ≥4 was associated with increased Clavien-Dindo class III complications and mortality. Preoperative nutritional status should be evaluated and optimized in this high-risk population.

Effective removal of organics from Bayer liquor through combined sonolysis and ozonation: Kinetics and mechanism.

The presence of organic compounds in the waste liquor is of serious environmental concern that has plagued the development of alumina industry (Bayer Process). The present work attempts to develop a green and efficient process for removal of organics utilizing combined effect of sonolysis and ozonation (US/O3). The effects of reaction duration, ozone concentration and ultrasonic power are assessed for sonolysis (US), ozonation (O3) and combination of sonolysis and ozonation (US/O3). The optimal conditions for US/O3 treatment system is identified to be a reaction duration of 7 h, ozone concentration of 7.65 g/h, and ultrasonic power of 600 W. The total organic carbon (TOC) removal and decolorization are 60.13% and 87.1%, respectively. The process can be scaled-up to industrial scale, which could potentially serve to be a convenient, safe and sustainable alternative to the exisiting treatment technologies. Additionally, the treated waste water can be reused contributing to an improvement in the overall economics.

Investigation of the association between lens autofluorescence ratio and diabetes: a cross-sectional study.

AIMS/HYPOTHESIS: Lens autofluorescence ratio (LFR) is a novel approach to detect advanced glycation end products in a time-saving and non-invasive manner. However, its associations with glycemia and diabetes remain unclear. We conducted this study to address this issue in Chinese adults. METHODS: We enrolled a total of 4,705 participants aged 20-70 years in China between May 2020 and January 2021 in a cross-sectional study. LFR was determined by biomicroscopy (ClearPath DS-120). Diabetes was ascertained by oral glucose tolerance test, self-reported history, and/or antidiabetic medication use. Correlation and logistic regression analyses were performed. RESULTS: LFR was higher in participants with diabetes than those without (23.27 ± 6.51 vs. 19.45 ± 5.08, p < 0.001). LFR correlated with fasting plasma glucose and hemoglobin A1c in the overall and diabetes-stratified populations. The odds of diabetes was increased by 6% per one percent higher of LFR after multivariable-adjustment (odds ratio (OR) 1.06, 95% CI 1.04-1.08, p < 0.001). Participants in the highest quartile of LFR had higher odds of diabetes compared with those in the lowest quartile (OR 1.83, 95% CI 1.33-2.52, p < 0.001). Mediation analysis showed that, insulin resistance, as assessed by triglyceride-glucose index, may underline the relationship between high LFR and increased odds of diabetes. CONCLUSIONS: LFR, a non-invasive indirect measure of advanced glycation end products, appears to be associated with glycemia and the risk of developing diabetes in Chinese adults.

Impaired robust interhemispheric function integration of depressive brain from REST-meta-MDD database in China.

BACKGROUND: Recently, functional homotopy (FH) architecture, defined as robust functional connectivity (FC) between homotopic regions, has been frequently reported to be altered in MDD patients (MDDs) but with divergent locations. METHODS: In this study, we obtained resting-state functional magnetic resonance imaging (R-fMRI) data from 1004 MDDs (mean age, 33.88 years; age range, 18-60 years) and 898 matched healthy controls (HCs) from an aggregated dataset from 20 centers in China. We focused on interhemispheric function integration in MDDs and its correlation with clinical characteristics using voxel-mirrored homotopic connectivity (VMHC) devised to inquire about FH patterns. RESULTS: As compared with HCs, MDDs showed decreased VMHC in visual, motor, somatosensory, limbic, angular gyrus, and cerebellum, particularly in posterior cingulate gyrus/precuneus (PCC/PCu) (false discovery rate [FDR] q < 0.002, z = -7.07). Further analysis observed that the reduction in SMG and insula was more prominent with age, of which SMG reflected such age-related change in males instead of females. Besides, the reduction in MTG was found to be a male-special abnormal pattern in MDDs. VMHC alterations were markedly related to episode type and illness severity. The higher Hamilton Depression Rating Scale score, the more apparent VMHC reduction in the primary visual cortex. First-episode MDDs revealed stronger VMHC reduction in PCu relative to recurrent MDDs. CONCLUSIONS: We confirmed a significant VMHC reduction in MDDs in broad areas, especially in PCC/PCu. This reduction was affected by gender, age, episode type, and illness severity. These findings suggest that the depressive brain tends to disconnect information exchange across hemispheres.

Impact of depression on the quality of sleep and immune functions in patients with coronary artery disease.

Background: The risk of major depressive disorder (MDD) and insomnia is higher in patients with coronary heart disease (CHD) than in the general population. In addition, immune inflammation may be a shared aetiological factor for mental disorders and CHD. However, it is unclear whether MDD is associated with poor sleep quality and cell-mediated immune function in patients with CHD. Aims: This study investigated the impact of depression on sleep quality and cell-mediated immune functions in patients with CHD and examined discriminative factors in patients with CHD with and without MDD. Methods: This cross-sectional retrospective study was conducted at the Zhejiang University School of Medicine affiliated with Sir Run Run Shaw Hospital. The study population consisted of 84 patients with CHD assigned to two groups based on their Hamilton Depression Rating Scale (HAMD) score (CHD with MDD (HAMD score of ≥10) vs without MDD). Subjective sleep quality, systemic inflammatory response and cell-mediated immune functions were assessed in patients with CHD with (n=50) and without (n=34) MDD using the Pittsburgh Sleep Quality Index (PSQI), routine blood tests and flow cytometry. The relationships between variables were ascertained using Pearson's product-moment, and linear discriminant analysis was used to explore the discriminative factors between groups. Results: Patients with CHD with MDD had significantly poorer sleep quality than those without MDD (Z=-6.864, p<0.001). The Systemic Inflammation Index (SII) and CD4+/CD8+ T-cell ratios were higher in patients with CHD with MDD than in those without MDD (Z=-3.249, p=0.001). Patients with CHD with MDD had fewer CD3+CD8+ and CD3+ T cells (Z=3.422, p=0.001) than those without MDD (t=2.032, p=0.045). Furthermore, patients with CHD with MDD may be differentiated from those without MDD using the PSQI, SII and T-cell levels, as these variables correctly classified the depressed and non-depressed groups with an accuracy of 96.4%. Conclusions: MDD may be responsible for poor sleep quality, increased cell-mediated immunity and SII in patients with CHD, which are discriminative factors for CHD in the depressive state. Clinicians should be aware of these interactions, as treatment for depressive symptoms may also improve CHD prognosis.

Reduced Plasma Estradiol Levels are Associated with Sleep Apnea in Depressed Peri- and Post-Menopausal Women.

OBJECTIVE: This study aimed at investigating the correlation between estradiol and sleep apnea among women with major depressive disorders during the perimenopausal and postmenopausal periods. METHODS: A total of 84 perimenopausal and postmenopausal women diagnosed with depression, and who had been subjected to whole-night polysomnography (PSG) were retrospectively studied. They were assigned into two groups based on the presence of OSA (apnea-hypopnea index (AHI)≥5) (OSA vs non-OSA). The correlation between estradiol levels and apnea-hypopnea index were assessed by logistic regression models after adjusting for age, body mass index (BMI), Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), apnea frequency and progesterone. RESULTS: Among the 84 patients, 45.23% had OSA. Estradiol levels were significantly elevated in non-OSA than in OSA patients (p<0.05). Univariate analysis revealed that elevated estradiol levels are associated with reduced odds of OSA (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.875-0.966, p = 0.001). Multivariate analyses showed that low estradiol levels (OR = 0.859, 95% CI 0.826-0.991, p = 0.031), higher HAMD scores (OR = 1.212, 95% CI 1.012-1.453, p = 0.037), higher apnea frequency (OR = 2.493, 95% CI 1.389-4.473, p = 0.002) and higher BMI (OR=1.635, 95% CI 1.136-2.353, p = 0.008) are correlated with OSA. CONCLUSION: The ratio of depressed perimenopausal to postmenopausal women comorbid OSA was high. Higher BMI, low estradiol levels, high apnea frequency and high HAMD scores were correlated with OSA diagnosis and could be potential diagnostic markers for OSA in depressed perimenopausal and postmenopausal women. Reduced estradiol levels were correlated with an increased risk of OSA among depressed perimenopausal and postmenopausal women.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Disrupted hemispheric connectivity specialization in patients with major depressive disorder: Evidence from the REST-meta-MDD Project.

BACKGROUND: Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. METHODS: Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). RESULTS: Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. LIMITATIONS: Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. CONCLUSIONS: Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

[Correlation between suicidal ideation and polysomnography parameters in late-life depression patients].

OBJECTIVE: To investigate the relationship between sleep parameters and suicidal ideation in patients with late-life depression (LLD). METHODS: Seventy-seven LLD patients over 60 years old from Sir Run Run Shaw Hospital of Zhejiang University during July 2017 and July 2018 were included in the study. All patients were assessed with Hamilton Depression Rating Scale (HAMD) and polysomnography (PSG) overnight. The suicidal score of item 3 in HAMD (HAM-D3)was used to define whether there was a suicidal ideation. Participants were subsequently grouped according to endorsement of presence (HAM-D3 score ≥1, n=46) versus absence (HAM-D3 score=0, n=31) of suicidal ideation symptoms. The sleep efficiency, total sleep time, wakefulness after sleep onset, rapid eye movement percent/latency, and non-rapid eye movement sleep stages 1-3 (N1-N3) were assessed. ANOVA analyses were conducted to explore the correlation of sleep parameters with suicidal ideation between the groups with and without suicidal ideation. In model 1, the HAM-D3 constituted the independent variable in separate ANOVA tests; in model 2 the impact of depressive symptoms were assessed as a covariate with sleep parameters. RESULTS: There was less stage N3 [(55±41)min, t=-4.731, P<0.05] and the reduced percentage of N3 [(15±11)%, t=-4.194, P<0.05] in LLD patients with suicidal ideation, compared with the LLD patients without suicidal ideation [(104±49) min, (26±11)%]. Correlation analyses revealed that there was a significant correlation between the suicidal ideation and the percentage of stage N3 and sleep time of stage N3 (both P<0.05). CONCLUSIONS: Suicidal ideation is associated with less N3 sleep in LLD patients.

The association of bioimpedance analysis parameters with the outcomes of critically ill patients.

BACKGROUND: The association between bioimpedance analysis (BIA) parameters and the outcomes of critically ill patients was explored through a retrospective investigation. METHODS: The study enrolled patients in the intensive care units of our hospital who had a record of BIA measurements as well as disease severity scores assessed by Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA). The associations between clinical conditions, outcomes and BIA parameters were analysed. The relationship between individual bioimpedance values and the current frequencies fit well to a natural logarithmic function, providing a regression coefficient S value. Other parameters obtained from the BIA measurements included phase angle (PA), the ratio of bioimpedance at high and low frequencies (IR), extracellular water (ECW), intracellular water (ICW) and total body water (TBW). RESULTS: Among 201 enrolled patients, the 90-day in-hospital mortality was 35.8%. Compared to the survivors at 7-days, for the non-survivors, the IR, S value, ratio of ECW/weight and ratio of ECW/TBW were higher, and the PA was lower (P < 0.05). Compared to the survivors at 90-days, for the non-survivors, the IR, S value and ratio of ECW/weight were higher, and the PA was lower (P < 0.05). Multinomial logistic regression analysis results showed that only SAPS II and S value were independent risk factors for 7-day and 90-day death (P < 0.01). When analysed by ROC, the AUC of the S value for predicting 7-day and 90-day death was non-significantly lower than SAPS II (S vs. SAPS II, 0.729 vs. 0.747 (7-day); 0.701 vs. 0.779 (90-day), P > 0.05). Importantly, both the 7-day and the 90-day mortality in patients with S values ≤-25.5 were 0; for the others, the mortality increased with the rise of S value. For patients with SAPS II ≤33, the mortality varied minimally; and for patients with SAPS II >55, the mortality was 100%. CONCLUSIONS: The S value and SAPS II are independent risk factors for 7-day and 90-day death in critically ill patients; the former may have a greater negative predictive value, while the latter may have a greater positive predictive value.

Altered resting-state dynamic functional brain networks in major depressive disorder: Findings from the REST-meta-MDD consortium.

BACKGROUND: Major depressive disorder (MDD) is known to be characterized by altered brain functional connectivity (FC) patterns. However, whether and how the features of dynamic FC would change in patients with MDD are unclear. In this study, we aimed to characterize dynamic FC in MDD using a large multi-site sample and a novel dynamic network-based approach. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were acquired from a total of 460 MDD patients and 473 healthy controls, as a part of the REST-meta-MDD consortium. Resting-state dynamic functional brain networks were constructed for each subject by a sliding-window approach. Multiple spatio-temporal features of dynamic brain networks, including temporal variability, temporal clustering and temporal efficiency, were then compared between patients and healthy subjects at both global and local levels. RESULTS: The group of MDD patients showed significantly higher temporal variability, lower temporal correlation coefficient (indicating decreased temporal clustering) and shorter characteristic temporal path length (indicating increased temporal efficiency) compared with healthy controls (corrected p < 3.14×10-3). Corresponding local changes in MDD were mainly found in the default-mode, sensorimotor and subcortical areas. Measures of temporal variability and characteristic temporal path length were significantly correlated with depression severity in patients (corrected p < 0.05). Moreover, the observed between-group differences were robustly present in both first-episode, drug-naïve (FEDN) and non-FEDN patients. CONCLUSIONS: Our findings suggest that excessive temporal variations of brain FC, reflecting abnormal communications between large-scale bran networks over time, may underlie the neuropathology of MDD.

Reduced default mode network functional connectivity in patients with recurrent major depressive disorder.

Major depressive disorder (MDD) is common and disabling, but its neuropathophysiology remains unclear. Most studies of functional brain networks in MDD have had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Twenty-five research groups in China established the REST-meta-MDD Consortium by contributing R-fMRI data from 1,300 patients with MDD and 1,128 normal controls (NCs). Data were preprocessed locally with a standardized protocol before aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to be increased in MDD. Instead, we found decreased DMN FC when we compared 848 patients with MDD to 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naïve MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDD. Exploratory analyses also revealed alterations in FC of visual, sensory-motor, and dorsal attention networks in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates response to treatment. All R-fMRI indices of data contributed by the REST-meta-MDD consortium are being shared publicly via the R-fMRI Maps Project.

Connectome analysis of functional and structural hemispheric brain networks in major depressive disorder.

Neuroimaging studies have shown topological disruptions of both functional and structural whole-brain networks in major depressive disorder (MDD). This study examined common and specific alterations between these two types of networks and whether the alterations were differentially involved in the two hemispheres. Multimodal MRI data were collected from 35 MDD patients and 35 healthy controls, whose functional and structural hemispheric networks were constructed, characterized, and compared. We found that functional brain networks were profoundly altered at multiple levels, while structural brain networks were largely intact in patients with MDD. Specifically, the functional alterations included decreases in intra-hemispheric (left and right) and inter-hemispheric (heterotopic) functional connectivity; decreases in local, global and normalized global efficiency for both hemispheric networks; increases in normalized local efficiency for the left hemispheric networks; and decreases in intra-hemispheric integration and inter-hemispheric communication in the dorsolateral superior frontal gyrus, anterior cingulate gyrus and hippocampus. Regarding hemispheric asymmetry, largely similar patterns were observed between the functional and structural networks: the right hemisphere was over-connected and more efficient than the left hemisphere globally; the occipital and partial regions exhibited leftward asymmetry, and the frontal and temporal sites showed rightward lateralization with regard to regional connectivity profiles locally. Finally, the functional-structural coupling of intra-hemispheric connections was significantly decreased and correlated with the disease severity in the patients. Overall, this study demonstrates modality- and hemisphere-dependent and invariant network alterations in MDD, which are helpful for understanding elaborate and characteristic patterns of integrative dysfunction in this disease.

Multiple Myeloma, Misdiagnosed As Somatic Symptom Disorder: A Case Report.

Here we report on a case of a 57-year-old woman with pain and discomfort in multiple sites of upper body who was diagnosed as somatic symptom disorder after completing a partial examinations of relevant parts which turned out to be negative. Finished imageological examinations of all painful parts, she was eventually diagnosed with multiple myeloma after 6-month being misdiagnosed as somatic symptom disorder. This case highlights the importance of completing imageological examinations of all the painful parts of the patient to exclude the possibility of multiple myeloma especially when symptoms are associated with objective signs and treatment has been ineffective; and it is as well as significant to notice characteristics of symptoms and to pay excessive attention directed toward the symptoms in the diagnosis of somatic symptom disorder.

Sub-hubs of baseline functional brain networks are related to early improvement following two-week pharmacological therapy for major depressive disorder.

Accumulating evidence suggests that early improvement after two-week antidepressant treatment is predictive of later outcomes of patients with major depressive disorder (MDD); however, whether this early improvement is associated with baseline neural architecture remains largely unknown. Utilizing resting-state functional MRI data and graph-based network approaches, this study calculated voxel-wise degree centrality maps for 24 MDD patients at baseline and linked them with changes in the Hamilton Rating Scale for Depression (HAMD) scores after two weeks of medication. Six clusters exhibited significant correlations of their baseline degree centrality with treatment-induced HAMD changes for the patients, which were mainly categorized into the posterior default-mode network (i.e., the left precuneus, supramarginal gyrus, middle temporal gyrus, and right angular gyrus) and frontal regions. Receiver operating characteristic curve and logistic regression analyses convergently revealed excellent performance of these regions in discriminating the early improvement status for the patients, especially the angular gyrus (sensitivity and specificity of 100%). Moreover, the angular gyrus was identified as the optimal regressor as determined by stepwise regression. Interestingly, these regions possessed higher centrality than others in the brain (P < 10(-3)) although they were not the most highly connected hubs. Finally, we demonstrate a high reproducibility of our findings across several factors (e.g., threshold choice, anatomical distance, and temporal cutting) in our analyses. Together, these preliminary exploratory analyses demonstrate the potential of neuroimaging-based network analysis in predicting the early therapeutic improvement of MDD patients and have important implications in guiding earlier personalized therapeutic regimens for possible treatment-refractory depression.

Caspase-8 Mediates Amyloid-ß-induced Apoptosis in Differentiated PC12 Cells.

The pathogenesis of Alzheimer's disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-ß 1-40 (Aß1-40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aß-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aß1-40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aß1-40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aß1-40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aß1-40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.

Relationship between personality disorder functioning styles and the emotional states in bipolar I and II disorders.

BACKGROUND: Bipolar disorder types I (BD I) and II (BD II) behave differently in clinical manifestations, normal personality traits, responses to pharmacotherapies, biochemical backgrounds and neuroimaging activations. How the varied emotional states of BD I and II are related to the comorbid personality disorders remains to be settled. METHODS: We therefore administered the Plutchick - van Praag Depression Inventory (PVP), the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32), and the Parker Personality Measure (PERM) in 37 patients with BD I, 34 BD II, and in 76 healthy volunteers. RESULTS: Compared to the healthy volunteers, patients with BD I and II scored higher on some PERM styles, PVP, MDQ and HCL-32 scales. In BD I, the PERM Borderline style predicted the PVP scale; and Antisocial predicted HCL-32. In BD II, Borderline, Dependent, Paranoid (-) and Schizoid (-) predicted PVP; Borderline predicted MDQ; Passive-Aggressive and Schizoid (-) predicted HCL-32. In controls, Borderline and Narcissistic (-) predicted PVP; Borderline and Dependent (-) predicted MDQ. CONCLUSION: Besides confirming the different predictability of the 11 functioning styles of personality disorder to BD I and II, we found that the prediction was more common in BD II, which might underlie its higher risk of suicide and poorer treatment outcome.