Search

Growth arrest‐specific 5 (GAS5) is a kind of long non‐coding RNAs (lncRNAs). Previous studies showed that down‐regulation of LncRNA‐GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down‐expressed LncRNA‐GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA‐GAS5 polymorphism with SLE risk. And further explore how LncRNA‐GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5‐base pair (AGGCA/‐) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA‐GAS5 promoter region. A custom 36‐Plex SNPscan kit was used for genotyping the LncRNA‐GAS5 polymorphisms. The LncRNA‐GAS5 and miR‐21 target prediction was performed using bioinformatics software. Enzyme‐linked immunosorbent assay (ELISA) and quantitative real‐time PCR (qRT‐PCR) were performed to assess GAS5 and miR‐21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30‐0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46‐0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46‐0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53‐0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36‐0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43‐0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A‐A‐C‐G‐D haplotype (OR = 0.67, 95% CI, 0.49‐0.91, P = .010). Also, patients in the SLE group showed a down‐regulated expression of LncRNA‐GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up‐regulated expression of LncRNA‐GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR‐21 levels were considerably up‐regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR‐21 levels than the ones with the II genotype. Thus, we found that the LncRNA‐GAS5/miR‐21/PTEN signalling pathway was involved in the development of SLE, where LncRNA‐GAS5 acted as an miR‐21 target, and miR‐21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA‐GAS5 gene promoter region may be protected against SLE by up‐regulating the expression of LncRNA‐GAS5, which consecutively regulated miR‐21 and PTEN levels.

Music and instruction-guided relaxation (MIGR) is a complementary therapeutic tool used in the treatment of the major depressive disorder (MDD). However, the neural mechanism that underlies the effect of MIGR on MDD patients is not known. Twenty-three right-handed MDD patients and 23 age-, sex-, handedness-, and educational level-matched healthy controls were enrolled. Resting-state functional MRI data were acquired from patients before and after MIGR and from healthy controls. The relationships between insular subregion-based functional connectivity and Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale (HAM-A), Automatic Thoughts Questionnaire, and Ruminative Responses Scale scores were examined. One-way analysis of variance exhibited significant differences among the three groups in functional connectivity between the left dorsal anterior insula (dAI) and left superior medial frontal gyrus (SMFG), left dAI and left precuneus, left posterior insula and left gyrus rectus, right ventral anterior insula (vAI) and left posterior cingulate cortex (PCC), right vAI and right inferior frontal gyrus (R-IFG). Further comparisons in regions of interest showed that MDD patients before MIGR showed decreased functional connectivity between the left dAI and left SMFG, left dAI and left precuneus, left posterior insula, and left gyrus rectus, right vAI and left PCC, right vAI and R-IFG relative to those in healthy controls. The strength of functional connectivity between the right dAI and left putamen also exhibited a negative correlation with the HAM-A score in MDD cases before MIGR. MIGR may result in enhanced functional connectivity in insular subregions, thereby potentially increasing the regulatory influence of cognitive reappraisal.

IntroductionAfter the first episode, patients with remitted major depressive disorder (MDD) have a 60% chance of experiencing a second episode. There are currently no accepted, effective methods to prevent the recurrence of MDD in remission. Transcutaneous vagus nerve stimulation (taVNS) is a non-invasive, safe and economical approach based on the efficacy of VNS in improving clinical depression symptoms. This clinical trial will study the efficacy of taVNS in preventing MDD relapse and investigate the underlying mechanisms of this.Methods and analysisWe will conduct a multicentre, randomised, patient-blinded and evaluators double-blinded trial. We will randomise 90 eligible participants with recurrent MDD in remission in a 1:1 ratio into a real or sham taVNS group. All participants will be given six biopsychosocial assessments: proinflammatory cytokines, serum monoamine neurotransmitters, cognition, affective neuropsychology, multimodal neuroimaging and endocrinology. After the baseline measurements, all participants will be given corresponding interference for 6 months and then complete a 1-year follow-up. The assessments will be performed three times: at baseline, post-treatment and at the end of 1-year follow-up (except for multimodal MRI scanning, which will be conducted at the first two assessments only). Change in 17-item Hamilton Depression Rating Scale scores for MDD is the primary outcome parameter.Ethics and disseminationThe study protocol was approved by the Medical Ethical Committee of Beijing Hospital of Traditional Chinese Medicine on 18 January 2019 (2018BL-076). The trial results will be published in peer-reviewed journals and at conferences.Trial registration numberChiCTR1900022618.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder (MDD). It has been postulated that acupuncture may achieve its treatment effects on MDD through suppression of vagal nerve inflammatory responses. Our previous research established that taVNS significantly increases amygdala–dorsolateral prefrontal cortex connectivity, which is associated with a reduction in depression severity. However, the relationship between taVNS and the central/peripheral functional state of the immune system, as well as changes in brain neural circuits, have not as yet been elucidated. In the present paper, we outline the anatomic foundation of taVNS and emphasize that it significantly modulates the activity and connectivity of a wide range of neural networks, including the default mode network, executive network, and networks involved in emotional and reward circuits. In addition, we present the inflammatory mechanism of MDD and describe how taVNS inhibits central and peripheral inflammation, which is possibly related to the effectiveness of taVNS in reducing depression severity. Our review suggests a link between the suppression of inflammation and changes in brain regions/circuits post taVNS.

Rumination is a common symptom of major depressive disorder (MDD) and has been characterized as a vulnerability factor for the onset or recurrence of MDD. However, the neurobiological mechanisms underlying rumination and appropriate treatment strategies remain unclear. In the current study, we used resting-state functional magnetic resonance imaging to investigate the effects of body-mind relaxation meditation induction (BMRMI) intervention in MDD with rumination. To this aim, we have recruited 25 MDD and 24 healthy controls (HCs). Changes in functional connectivity (FC) of the anterior cingulate cortex (ACC) subregion and the scores of clinical measurements were examined using correlation analysis. At baseline, MDD showed stronger FC between the right dorsal ACC (dACC) and right superior frontal gyrus than did the HC group. Compared to baseline, the HC group showed a significantly enhanced FC between the right dACC and right superior frontal gyrus, and the MDD group demonstrated a significantly weaker FC between the left dACC and right middle frontal gyrus (MFG) after the intervention. Furthermore, the FC between the right dACC and right superior frontal gyrus was positively associated with rumination scores across all participants at baseline. The above results indicate that BMRMI may regulate self-referential processing and cognitive function through modulating FC of the dACC in MDD with rumination.

Major depressive disorder (MDD) is a highly prevalent mood disorder, characterized by depressed mood, reduced capabilities to concentrate, impaired cognition, as well as a high risk of relapse. Unaffected siblings who have high risks for MDD development and yet without clinical symptoms may be helpful for understanding the neural mechanisms of MDD traits.We investigated both regional fluctuation and inter-regional synchronization in 31 fully remitted MDD patients, 29 unaffected siblings and 43 age, gender, and educational level matched helathy controls (HCs) using resting-state functional magnetic resonance imaging (rs-fMRI). The 17-item HAMD and neurocognitive scales were performed. Fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) strength were investigated.Compared with healthy control group, patients with remitted MDD and unaffected siblings showed increased fALFF in the left dorsomedial prefrontal cortex (dmPFC) and increased FC between the left dmPFC and the right ventromedial prefrontal cortex (vmPFC). In addition, a negative correlation was observed between the fALFF value in the left dmPFC and the speed of Trail Making Test in the remitted MDD patients. Higher vmPFC-dmPFC FC was positively correlated with Wisconsin Card Sorting Test (WCST) total correct, and negatively correlated with WCST random errors.In the absence of clinical symptoms, individuals with remitted MDD and unaffected siblings showed increased fALFF in left dmPFC as well as the vmPFC-dmPFC connectivity. These results suggest a specific trait abnormality in the default mode network associated with vulnerability to MDD, which may have implications for developing effective therapies using this network as a target.

Major depressive disorder (MDD) is a leading cause of disability worldwide. After the first episode, patients with remitted MDD have a 60% chance of experiencing a second episode. Consideration of therapy continuation should be viewed in terms of the balance between the adverse effects of medication and the need to prevent a possible relapse. Relapse during the early stages of MDD could be prevented more efficiently by conducting individual risk assessments and providing justification for continuing therapy. Our previous work established the neuroimaging markers of relapse by comparing patients with recurrent major depressive disorder (rMDD) in depressive and remitted states. However, it is not known which of these markers are trait markers that present before initial relapse and, consequently, predict disease course. Here, we first describe how inflammation can be translated to subtype-specific clinical features and suggest how this could be used to facilitate clinical diagnosis and treatment. Next, we address the central and peripheral functional state of the immune system in patients with MDD. In addition, we emphasize the important link between the number of depressive episodes and rMDD and use neuroimaging to propose a model for the latter. Last, we address how inflammation can affect brain circuits, providing a possible mechanism for rMDD. Our review suggests a link between inflammatory processes and brain region/circuits in rMDD.

Background The Low Resistance Thought Induction Psychotherapy (TIP) is a comprehensive psychological treatment which could improve the clinical symptoms of major depressive disorder (MDD). However, the neural mechanisms for TIP treating MDD still remain unclear. This study aimed to investigate the topology of intrinsic connectivity network and the therapeutic effects of TIP in MDD on these topological properties. Methods Longitudinal study was conducted in 20 first-episode, treatment-naive MDD patients at baseline and after 6 weeks (12 sessions) of TIP treatment based on resting-state functional magnetic resonance image (rsfMRI) in conjunction with graph theoretical analysis. We constructed functional connectivity matrices and extracted the attribute features of the small-world networks in both MDD and age-, education level-, and gender-matched healthy controls (HCs). The global and local small-world network properties were explored and compared between MDD at baseline and HCs. The therapeutic effect of TIP was examined by comparing alterations in global and local network properties between MDD at baseline and after treatment. Results At baseline, MDD showed altered small-worldness and aberrant nodal properties in the frontolimbic circuit particularly in the orbital frontal gyrus, insula, precuneus and middle cingulate gyrus as compared with HCs. Following 6 weeks treatment, the abnormalities in the small-worldness and the nodal metrics were modulated, which were accompanied by a significant improvement in the clinical symptoms. Conclusions Our findings contributed to the understanding of the abnormal topological patterns in the frontolimbic systems in MDD and implicated that these disruptions may be modified by TIP treatment.

Background Metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) was aberrantly expressed in diverse diseases. Particularly in ischemic stroke (IS), the abnormal expression of MALAT1 played important roles including promotion of angiogenesis, inhibition of apoptosis and inflammation and regulation of autophagy. However, the effects of genetic variation (single nucleotide polymorphisms, SNPs) of MALAT1 on IS have rarely been explored. This study aimed to investigate whether SNPs in promoter of MALAT1 were associated with the susceptibility to IS. Methods A total of 316 IS patients and 320 age-, gender-, and ethnicity-matched controls were enrolled in this study. Four polymorphisms in the promoter of MALAT1 (i.e., rs600231, rs1194338, rs4102217, and rs591291) were genotyped by using a custom-by-design 48-Plex SNPscan kit. Results The rs1194338 C > A variant in the promoter of MALAT1 was associated with the risk of IS (AC vs. CC: adjusted OR = 0.623, 95% CI, 0.417–0.932, P = 0.021; AA vs. CC: adjusted OR = 0.474, 95% CI, 0.226–0.991, P = 0.047; Dominant model: adjusted OR = 0.596, 95% CI, 0.406–0.874, P = 0.008; A vs. C adjusted OR = 0.658, 95% CI, 0.487–0.890, P = 0.007). The haplotype analysis showed that rs600231-rs1194338-rs4102217-rs591291 (A-C-G-C) had a 1.3-fold increased risk of IS (95% CI, 1.029–1.644, P = 0.027). Logistic regression analysis identified some independent impact factors for IS including rs1194338 AC/AA, TC, TG, HDL-C, LDL-C, Apo-A1, Apo-B and NEFA (P Conclusions These results suggest that the rs1194338 AC/AA genotypes may be a protective factor for IS.

Background Insomnia is among the most prevalent of the sleep-related disorders. Insomnia disorder is associated with a brain hyperarousal state manifested by abnormal regional brain activity and resting state functional connectivity. Acupuncture improves sleep quality and modulates the hyperarousal state; however, the underlying neurobiological basis for improved sleep quality is poorly understood. The purpose of this clinical trial is to study the efficacy of acupuncture in the treatment of insomnia disorder. In addition, the neural mechanism by which acupuncture affects insomnia disorder will be explored using resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychological parameters. Methods and design A randomized, patient- and assessor-blinded trial will be conducted. We will randomize (in a 1:1 ratio) 60 eligible patients with insomnia disorder into a real acupuncture group or a sham acupuncture group. Interventions will be administered three times per week over a 4-week period, with an 8-week follow-up period. The healthy control group will consist of 30 age- and sex-matched healthy individuals who sleep well without any treatment intervention. All participants will undergo neuropsychological and rs-fMRI evaluations. The change in Pittsburgh Sleep Quality Index (PSQI) scores is the primary outcome parameter. The secondary outcome parameters include the Hyperarousal scale (HAS), rs-fMRI measurements, the Fatigue scale-14 (FS-14), the Hamilton depression scale (HAMD), the Hamilton anxiety scale (HAMA), a sleep diary, and an actigraph. Assessment of all parameters will be performed at baseline, post-treatment, and during follow-up. Analyses will be implemented based on intention-to-treat. Discussion The study results will be used to clarify the effectiveness and elucidate the mechanism by which acupuncture improves sleep quality in patients with insomnia disorder. Trial registration Chinese Clinical Trials Register, ChiCTR1800015282. Registered on 20 March 2018.

OBJECTIVE: To investigate alterations in resting-state spontaneous brain activity in patients with major depressive disorder MDD) experiencing multiple episodes. METHODS: Between May 2007 and September 2014, 24 recurrent and 22 remitted patients diagnosed with MDD with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), and 69 healthy controls matched for age, sex, and educational level participated in this study. Among them, 1 healthy control was excluded due to excessive head motion. The fractional amplitude of low-frequency fluctuation (fALFF) was assessed for all recruited subjects during the completion of resting-state functional magnetic resonance imaging. Relationships between fALFF and clinical measurements, including number of depressive episodes and illness duration, were examined. RESULTS: Compared to patients with remitted MDD and to healthy controls, patients with recurrent MDD exhibited decreased fALFF in the right posterior insula and right precuneus and increased fALFF in the left ventral anterior cingulate cortex. Decreased fALFF in the right precuneus and increased fALFF in the right middle insula were correlated with the number of depressive episodes in the recurrent MDD groups (r = -0.75, P < .01 and r = 0.78, P < .01, respectively) and remitted MDD groups (r = -0.63, P < .01 and r = 0.41, P = .03, respectively). In addition to regions in the default mode network (DMN) and salience network, the altered resting-state activity in the middle temporal and visual cortices was also identified. CONCLUSIONS: Altered resting-state activity was observed across several neural networks in patients with recurrent MDD. Consistent with the emerging theory that altered DMN activity is a risk factor for depression relapses, the association between reduced fALFF in the right precuneus and number of depressive episodes supports the role of the DMN in the pathology of recurrent depression.

Background The amygdala is a key region in emotion processing, and studies have suggested that amygdala-frontal functional connectivity deficits could be modulated by antidepressants in major depressive disorder (MDD). Transcutaneous vagus nerve stimulation (tVNS), a non-invasive, peripheral neuromodulation method at the ear, has shown promising results in treating major depressive disorder (MDD) in several pilot studies. However, the neural mechanism underlying tVNS treatment of depression has not been fully investigated. In this study, we investigated how tVNS can modulate the amygdala-lateral prefrontal network resting state functional connectivity (rsFC) in mild or moderate major depressive disorder (MDD) patients. Methods Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments for four weeks. Resting state fMRI scans were applied before and after treatments. Results After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale (HAMD) scores were reduced significantly in the tVNS group as compared with the sham tVNS group. The rsFC in the tVNS group between the right amygdala and left dorsolateral prefrontal cortex was increased compared with sham tVNS. All the rsFC increases were also associated with HAMD reduction as well as reductions in the anxiety and retardation HAMD subscales. Conclusions tVNS can significantly modulate the amygdala-lateral prefrontal rsFC of MDD patients; our results provide insights into the brain mechanism of tVNS treatment for MDD patients.

The microRNA-17-92 (miR-17-92) cluster is one of the most extensively studied miRNA clusters. Abnormal expression of the cluster has been found to play important role in different kinds of human diseases, including ischemic stroke (IS). The aim of our study was to investigate the association between three polymorphisms (rs1491034, rs9301654 and rs982873) in the promoter of the miR-17-92 cluster and risk of IS.Three hundred and ninety-eight patients with IS and 397 control subjects were included. The genotypes of the three polymorphisms were determined by Snapshot SNP genotyping assay. Relative expression of the cluster in peripheral blood mononuclear cells (PBMCs) of cases and controls were examined by quantitative real-time PCR.Significant association between rs9301654 polymorphism and risk of IS were observed basing on genotype, model and allele analyses (GA vs. AA: adjusted OR = 0.63, 95% CI: 0.41~0.97, P = 0.037; GG vs. AA: adjusted OR = 0.23, 95% CI: 0.07~0.78, P = 0.018; GA + GG vs. AA: adjusted OR = 0.57, 95% CI: 0.38~0.87, P = 0.009; GA + AA vs. GG: adjusted OR = 0.27, 95% CI: 0.08~0.89, P = 0.032; G vs. A: adjusted OR = 0.58, 95% CI: 0.40~0.83). Haplotype analysis showed that TGC and TGT haplotypes were associated with decreased risk of IS (OR = 0.59, 95% CI: 0.40~0.87, P = 0.007 for TGC haplotype; OR = 0.21, 95% CI: 0.06~0.75, P = 0.009 for TGT haplotype). Importantly, we found the expression of miR-17-5p was significant higher while miR-19a-3p was significant lower in patient with IS compared with the control group (P 0.01), and patients with rs9301654GG or GA genotype displayed lower level of miR-19a-3p compared with the AA genotype (P 0.01).Our findings indicated that rs9301654 polymorphism in the promoter of miR-17-92 cluster may be associated with susceptibility of IS in the Chinese population. However, we found that rs9301654 polymorphism and its respective gene expression did not demonstrate consistent association with IS in the Chinese population. Further studies such as gene-gene interaction are warranted to reveal the role of miR-19a and its regulatory genes in the etiology of IS.

Background Patients with major depressive disorder (MDD) can frequently develop new depressive episodes after remission. However, the neural mechanisms underlying the increased risk for depressive relapse remain unclear. Herein, we aimed to explore whether the specific changes to regional and inter-regional spontaneous brain activities within DMN are associated with the course of episodes in pooled MDD patients. Methods Resting-state functional magnetic resonance imaging was performed on patients with single-episode MDD (SEMDD, n = 30) and multiple-episode MDD (MEMDD, n = 54), and 71 age-, gender-, and educational level-matched healthy controls (HCs). We then accessed the differences in both the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity by using the right precuneus as the seed among different groups. Results Compared to the MEMDD and HC groups, the SEMDD group exhibited increased fALFF values in the right subgenual anterior cingulate cortex and right middle temporal gyrus. Decreased fALFF values in the right thalamus in the MEMDD group were also identified relative to the SEMDD and HC group. The peak values of fALFF in the right precuneus showed a negative correlation with the number of depressive episodes across the entire pool of MDD patients. No correlation was identified between functional connectivity using the right precuneus as the seed and the number of depressive episodes for the pooled MDD patients. Limitations Medication, a relatively small sample size, and hypothesis driven study. Conclusions Our neuroimaging results identified depression relapse-associated neural signatures and also indicated the role of reduced emotional appraisals in the thalamus. It is now possible to believe that the regional activity not inter-regional connectivity within the DMN may be involved in the pathology of depression relapse.

Background: The interpretation of spirometry varies on different reference values. Older people are usually underrepresented in published predictive values. This study aimed at developing spirometric reference equations for elderly Chinese in Jinan aged 60–84 years and to compare them to previous equations. Methods: The project covered all of Jinan city, and the recruitment period lasted 9 months from January 1, 2017 to September 30, 2017, 434 healthy people aged 60–84 years who had never smoked (226 females and 208 males) were recruited to undergo spirometry. Vital capacity (VC), forced VC (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, FEV1/VC, FEV6, peak expiratory flow, and forced expiratory flow at 25%, 50%, 75%, and 25–75% of FVC exhaled (FEF25%, FEF50%, FEF75%, and FEF25–75%) were analyzed. Reference equations for mean and the lower limit of normal (LLN) were derived using the lambda-mu-sigma method. Comparisons between new and previous equations were performed by paired t-test. Results: New reference equations were developed from the sample. The LLN of FEV1/FVC, FEF25–75% computed using the 2012-Global Lung Function Initiative (GLI) and 2006-Hong Kong equations were both lower than the new equations. The biggest degree of difference for FEV1/FVC was 19% (70.46% vs. 59.29%, t = 33.954, P < 0.01) and for maximal midexpiratory flow (MMEF, equals to FEF25–75%) was 22% (0.82 vs. 0.67, t = 21.303, P < 0.01). The 1990-North China and 2009-North China equations predicted higher mean values of FEV1/FVC and FEF25–75% than the present model. The biggest degrees of difference were −4% (78.31% vs. 81.27%, t = −85.359, P < 0.01) and −60% (2.11 vs. 4.68, t = −170.287, P < 0.01), respectively. Conclusions: The newly developed spirometric reference equations are applicable to elderly Chinese in Jinan. The 2012-GLI and 2006-Hong Kong equations may lead to missed diagnoses of obstructive ventilatory defects and the small airway dysfunction, while traditional linear equations for all ages may lead to overdiagnosis.

The levels of serum S100B were elevated in patients with ischemic stroke (IS), which may be a novel biomarker for diagnosing IS. The aim of this study was to investigate the association of S100B polymorphisms and serum S100B with IS risk. We genotyped the S100B polymorphisms rs9722, rs9984765, rs2839356, rs1051169 and rs2186358 in 396 IS patients and 398 controls using polymerase chain reaction-single base extension (SBE-PCR). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). Rs9722 was associated with an increased risk of IS (AA vs. GG: adjusted OR = 2.172, 95% CI, 1.175–4.014, P = 0.013; dominant: adjusted OR = 1.507, 95% CI, 1.071–2.123, P = 0.019; recessive: adjusted OR = 1.846, 95% CI, 1.025–3.323, P = 0.041; additive: adjusted OR=1.371, 95% CI, 1.109-1.694, P = 0.003). The A-C-C-C-A haplotype was associated with an increased risk of IS (OR = 1.325, 95% CI, 1.035–1.696, P = 0.025). In addition, individuals carrying the rs9722 GA/AA genotypes had a higher serum S100B compared with the rs9722 GG genotype in IS patients (P = 0.018). Our results suggest that the S100B gene rs9722 polymorphism may contribute to the susceptibility of IS, probably by promoting the expression of serum S100B.

Of major depression patients, 29-66% show only partial remission on a single antidepressant trial. Such patients are characterized by residual depressive symptoms such as anhedonia, psychic anxiety, sleep disturbance, and cognitive dysfunction. Despite having a tremendous impact on outcomes such as future relapse, morbidity, and mortality, the neural mechanisms of partially remitted depression remain unclear. Using the amplitude of low-frequency fluctuations (ALFF) approach, we investigated the intrinsic neural oscillation alterations during resting state in partially remitted depression. A total of 23 partially remitted depression patients and 68 healthy controls underwent magnetic resonance imaging for functional imaging. We compared ALFF differences between groups as well as correlations between clinical measurements and ALFF in the brain regions showing significant group differences. Compared with healthy controls, partially remitted depression patients showed increased ALFF in the left ventral anterior insula, bilateral posterior insula, and bilateral supramarginal gyrus, and decreased ALFF in the left calcarine gyrus. A trend positive correlation between the number of depressive episodes and ALFF values was found in the right posterior insula in the partially remitted depression group. In addition, the ALFF in the right supramarginal gyrus were negatively correlated with Hamilton Depression Rating Scale scores. Consistent with the emerging theory of the role of the salience network in sensing the changes of homeostasis that contributes to partially remitted depression, the current findings suggest that the increased intrinsic neural oscillation of the insula is related to the refractoriness to treatment and may be an imaging marker for predicting future depression recurrence.

The authors investigated whether male violent juvenile offenders demonstrate any differences in local functional connectivity indicative of delayed maturation of the brain that may serve as a biomarker of violence. Twenty-nine violent juvenile offenders and 28 age-matched controls were recruited. Regional homogeneity (ReHo) method was used to analyze resting-state magnetic resonance images. Violent offenders showed significantly lower ReHo values in the right caudate, right medial prefrontal cortex, and left precuneus, and higher values in the right supramarginal gyrus than the controls. These regions had both high sensitivity and specificity in distinguishing between the two groups suggesting that dysfunction in these regions can be used to correctly classify those individuals who are violent. Dysfunction in the right medial prefrontal-caudate circuit may, therefore, represent an important biomarker of violence juvenile males.

Bipolar depression (BD) is a common psychiatric illness characterized by deficits in emotional and cognitive processing. Abnormalities in the subregions of the insula are common findings in neuroanatomical studies of patients with bipolar disorder. However, the specific relationships between morphometric changes in specific insular subregions and the pathogenesis of BD are not clear. In this study, structural magnetic resonance imaging (MRI) was used to investigate gray matter volume abnormalities in the insular subregion in 27 patients with BD and in 27 age and sex-matched controls. Using DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry (VBM), we examined changes in regional gray matter volumes of the insula in patients with BD. As compared with healthy controls, the BD patients showed decreased gray matter volumes in the right posterior insula and left ventral anterior insula and increased gray matter volumes in the left dorsal anterior insula. Consistent with the emerging theory of insular interference as a contributor to emotional-cognitive dysregulation, the current findings suggest that the insular cortex may be involved in the neural substrates of BD.

Staphylococcus aureus (S. aureus) is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT), which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA), a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT) to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

Poor sleep and insomnia have been recognized to be strongly correlated with the development of depression. The exploration of the basic mechanism of sleep disturbance could provide the basis for improved understanding and treatment of insomnia and prevention of depression. In this study, 31 subjects with insomnia symptoms as measured by the Hamilton Rating Scale for Depression (HAMD-17) and 71 age- and gender-matched subjects without insomnia symptoms were recruited to participate in a clinical trial. Using resting-state functional magnetic resonance imaging (rs-fMRI), we examined the alterations in spontaneous brain activity between the two groups. Correlations between the fractional amplitude of low frequency fluctuations (fALFF) and clinical measurements (e.g., insomnia severity and Hamilton Depression Rating Scale [HAMD] scores) were also tested in all subjects. Compared to healthy participants without insomnia symptoms, participants with insomnia symptoms showed a decreased fALFF in the left ventral anterior insula, bilateral posterior insula, left thalamus, and pons but an increased fALFF in the bilateral middle occipital gyrus and right precentral gyrus. More specifically, a significant, negative correlation of fALFF in the left thalamus with early morning awakening scores and HAMD scores in the overall sample was identified. These results suggest that insomnia symptoms are associated with altered spontaneous activity in the brain regions of several important functional networks, including the insular cortex of the salience and the thalamus of the hyperarousal network. The altered fALFF in the left thalamus supports the "hyperarousal theory" of insomnia symptoms, which could serve as a biomarker for insomnia.

We examined resting state brain activity in the depressive phase of bipolar disorder (BD) by measuring the amplitude of low-frequency fluctuations (ALFF) in the functional magnetic resonance imaging (fMRI) signal. Unlike functional connectivity, the ALFF approach reflects local properties in specific regions and provides direct information about impaired foci. Groups of 26 patients with BD depression and 26 gender-, age-, and education-matched healthy subjects participated in fMRI scans. We examined group differences in ALFF findings as well as correlations between clinical measurements and ALFF in the regions showing significant group differences. Our results showed that patients with BD depression had significantly increased ALFF in the left insula, the right caudate nucleus, the temporal gyrus, the bilateral inferior frontal gyrus, and the posterior lobe of the cerebellum. They also had decreased ALFF in the left postcentral gyrus, the left parahippocampal gyrus, and the cerebellum. Moderate negative correlations were found between the Hamilton Depression Rating Scale score and ALFF in the left insular cortex in the patient group. These results support a model of BD that involves dysfunction in the prefrontal-limbic networks and associated striatal systems. We also demonstrated the feasibility of ALFF as a technique to investigate persistent cerebral dysfunction in BD. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

In the present study, we investigated differences in resting-state brain activity in patients with bipolar depression (BD) and unipolar depression (UD) by measuring the amplitude of low-frequency fluctuation (ALFF) of functional magnetic resonance imaging (fMRI) signals. Twenty-one BD and 21 gender-, age-, and education-matched UD patients participated in the fMRI analysis. We compared the differences in the ALFF between the two groups and investigated the correlation between clinical measurements and ALFF in the regions displaying significant group differences. BD subjects displayed significantly decreased ALFF in the left superior parietal lobule and the left posterior insula (l-PI). They also displayed increased ALFF in the right dorsal anterior insula (r-dAI) when compared to the UD group. Moderate negative correlations were found between the Hamilton Depression Rating Scale score (HAMD) and the ALFF in the l-PI for the BD ( r = −0.44, P = 0.02) and UD ( r = −0.45, P = 0.02) groups. Our results support the notion that insular subregions may contribute to the precise differentiation between BD and UD.

Glycosylated natural products are reliable platforms for the development of anticancer drugs, simply due to the important features added by sugar appendages to the shape and the stereoelectronic properties of natural scaffolds. Herein, we indentified D11, a novel diphyllin glycoside with acetylated D-quinovose sugar moiety, as a potent topoisomerase IIα (Topo IIα) inhibitior. This peculiar sugar moiety endows D11 an optimal conformation with a high binding affinity for Topo IIα via hydrogen bonding to the entrance of ATPase pocket, thereby helping achieve more potent Topo II inhibition activity compared to the aglycon diphyllin. Further biochemical insights manifested that D11 significantly inhibited Topo IIα ATPase-catalyzed ATP hydrolysis in an ATP-dependent, but a DNA-independent manner. All these underlie the consequent superiority of D11 in the in vitro proliferation inhibition, apoptosis induction and the in vivo remarkable antitumor potency in xenograft mouse model. Moreover, D11 treatment also displayed no obvious body weight loss and other apparent toxicities, indicative of the restricted side effects by the virtue of sugar attachment. Taken together, a defined glycosylated manipulation of diphyllin may be a promising alternative approach in the development of novel Topo II inhibitors.

Objective Anxious depression is a distinct clinical subtype of major depressive disorder (MDD) characterized by palpitations, somatic complaints, altered interoceptive awareness, high risk of suicide, and poor response to pharmacotherapy. However, the neural mechanisms of anxious depression are still not well understood. In this study we investigated changes in neural oscillation during the resting-state of patients with anxious depression by measuring differences in the amplitude of low-frequency fluctuation (ALFF). Methods Resting-state functional magnetic resonance imaging was acquired in 31 patients with anxious depression, 18 patients with remitted depression, as well as 68 gender- and age-matched healthy participants. We compared the differences both in the ALFF and fractional ALFF (fALFF) among the three groups. We also examined the correlation between the ALFF/fALFF and the severity of anxiety as well as depression. Results Anxious depression patients showed increased ALFF/fALFF in the right dorsal anterior insular cortex and decreased ALFF/fALFF in the bilateral lingual gyrus relative to remitted depression patients and healthy controls. The increased ALFF in the dorsal anterior insula was also positively correlated with stronger anxiety in the anxious depression group. Anxious depression patients also displayed increased fALFF in the right ventral anterior cingulate cortex (ACC) compared to remitted depression patients and healthy controls. Conclusions Our results suggest that alterations of the cortico-limbic networks, including the right dorsal anterior insula and right ventral ACC, may play a critical role in the physiopathology of anxious depression.

Objective Women are more prone to major depressive disorders (MDDs) and the incidence of MDD in women is almost twice that of men. Insular cortex abnormalities are a common finding in neuroanatomical studies of patients with MDD. However, it remains largely unclear whether female MDD patients at different clinical stages show morphologic changes in a specific subregion of the insular cortex. Additionally, it is not understood if any subregion changes can be used as a state or trait marker of MDD, and whether the diagnostic performance of any marker is sufficient to identify MDD. Methods Nineteen right-handed current MDD (cMDD) female patients and 19 remitted MDD (rMDD) patients, as well as 19 healthy controls matched for age and educational level, were recruited into the study. By means of voxel-based morphometry (VBM), we investigated gray matter volume abnormalities in insular subregions among the three groups and further conducted region-of-interest (ROI)-based receiver operating characteristic (ROC) analyses. The data from these investigations were correlated with clinical data to confirm the effectiveness of the identified changes in the subregions in differentiating the three groups. Results Both the cMDD and rMDD groups showed significantly decreased gray matter volumes in the left dorsal anterior insula compared to the healthy controls. The cMDD groups also showed decreased gray matter volumes in the right dorsal anterior insula relative to healthy controls. Further ROC comparisons demonstrated that the left dorsal anterior insula can effectively differentiate cMDD and rMDD groups from healthy controls. Conclusions Our findings suggest that the volume changes in the left dorsal anterior insular cortex may be a trait-related marker of vulnerability to MDD and that the right dorsal anterior insular cortex may involve pathological changes of MDD.

Medical intervention for major depressive disorder (MDD) can be more appropriately focused through the identification and characterization of neurobiological markers that are specific to the disorder, and this study aims to examine the abnormality in the fractional amplitude of low-frequency fluctuation (fALFF) and the amplitude of low-frequency fluctuation (ALFF) in currently depressed and remitted female MDD patients and to correlate these fluctuations with clinical markers of MDD. Nineteen currently depressed female patients, 19 remitted female patients, as well as 19 age- and education-matched healthy females participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the fALFF/ALFF maps among the three groups and investigated the correlation between clinical measurements and statistically significant differences in the fALFF/ALFF of various brain regions. Compared with healthy controls, both currently depressed and remitted patients showed increased fALFF/ALFF in the right putamen. Currently depressed MDD patients showed increased fALFF/ALFF in the right ventral median frontal gyrus relative to both the remitted MDD group and the healthy control group. The ALFF of the right precuneus was found to be positively correlated with the number of depressive episodes and the fALFF of the right precuneus to be positively correlated with the disease duration in currently depressed MDD patients. An abnormal fALFF/ALFF in the right ventral median frontal gyrus was found only in currently depressed patients, suggesting that such an anomaly may play a critical role in depressive symptomatology and may be a therapeutic target for MDD. An abnormal fALFF/ALFF in the right putamen is a potential candidate as a trait-related marker of vulnerability to major depression.

Natural beta-glucans extracted from plants and fungi have been used in clinical therapies since the late 20th century. However, the heterogeneity of natural beta-glucans limits their clinical applicability. We have synthesized beta-glu6, which is an analog of the lentinan basic unit, beta-(1 -> 6)-branched beta-(1 -> 3) glucohexaose, that contains an alpha-(1 -> 3)-linked bond. We have demonstrated the stimulatory effect of this molecule on the immune response, but the mechanisms by which beta-glu6 activates innate immunity have not been elucidated. In this study, murine macrophages and human PBMCs were used to evaluate the immunomodulatory effects of beta-glu6. We showed that beta-glu6 activated ERK and c-Raf phosphorylation but suppressed the AKT signaling pathway in murine macrophages. Additionally, beta-glu6 enhanced the secretion of large levels of cytokines and chemokines, including CD54, IL-1 alpha, IL-1 beta, IL-16, IL-17, IL-23, IFN-gamma, CCL1, CCL3, CCL4, CCL12, CXCL10, tissue inhibitor of metalloproteinase-1 (TIMP-1) and G-CSF in murine macrophages as well as IL-6, CCL2, CCL3, CCL5, CXCL1 and macrophage migration inhibitory factor (MIF) in human PBMCs. In summary, it demonstrates the immunomodulatory activity of beta-glu6 in innate immunity.

Objective: Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression CUD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Methods: Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. Results: We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right middle frontal gyrus, the right dorsal anterior insular, the right cerebellum posterior gyrus, and the right posterior cingulate cortex showed abnormality specific to the UD group. Conclusions: We found brain regions showing resting state ReHo differences and examined their sensitivity and specificity, suggesting a potential neuroimaging biomarker to distinguish between BD-dep and UD patients. We further clarified the pathophysiological abnormality of these regions for each of the two patient populations. (C) 2012 Elsevier Inc. All rights reserved.

Background Major depressive disorder (MDD) is a highly heritable psychiatric disease, and the existing literature is not robust enough to allow us to evaluate whether MDD-associated biomarkers are state-independent heritable endophenotypes or state markers related to depression per se. Methods Twenty two patients diagnosed with MDD, 22 siblings, as well as 26 gender-, age-, and education-matched healthy subjects, participated in the resting-state functional magnetic resonance imaging (fMRI) analysis. We compared the differences in the fractional amplitude of low-frequency fluctuation (fALFF) among the three groups and investigated the correlation between clinical measurements and fALFF in the regions displaying significant group differences. Results Both the MDD and siblings groups showed an increased fALFF in the left middle frontal gyrus (l-MFG, Brodmann Area, BA 10) compared to the healthy controls. The MDD groups demonstrated an increased fALFF in the right dorsal medial frontal gyrus (r-DMFG, BA 9) and a decreased fALFF in the bilateral lingual gyrus relative to siblings and healthy controls. Limitations Medication effects, an inability to control subjects' thoughts during imaging. Conclusions Our results suggest that the dysfunction in the l-MFG may represent an imaging endophenotype which may indicate a risk for MDD. The r-DMFG may play a critical role in depressive symptomatology and may reveal therapeutic target for MDD.

To analyse sonographical features of epididymis tuberculosis with caseous necrosis and improve the accuracy of ultrasonic diagnosis.Ultrasonic features of 12 cases with epididymis tuberculosis with caseous necrosis, confirmed by surgical pathology, was retrospectively analysed: size, location, echogenicity, degree of blood flow in the lesion.In all 12 patients, the number of purified protein derivative test (PPD) presenting the positive reached to 67%, while cases with the pulmonary tuberculosis was 42%. The epididymal tuberculosis with caseous necrosis could present images of the whole or focal epididymal enlargement and abnormal shape. The lesions internal echoes were irregular, inhomogeneous increased isoechoic echogenicity or hypoechoic, including bad-defined, irregular, homogeneous hypoechoic or anechoic. In lesional location, 4 out of 12 patients (33%) possessed richly color blood flow in Color Doppler Power Imaging(CDPI). The testicular enlargement with increased internal echoes and the testicular hydroceles were partly (58%, 7/12) observed by ultrasound. There was no varicocele, scrotal wall thickening and inguinal lymph node enlargement.The High Frequency Color Doppler images is helpful for the diagnosis and differential diagnosis of epididymis tuberculosis with caseous necrosis.

To observe the changes of serum interleukin (IL)-12, IL-13 and lung function in asthmatic patients and to evaluate the influence of glucocorticoid on them.The serum samples were obtained from (1) 25 asthmatic patients with acute asthma attack before and after one week course of oral prednisone, (2) 20 asthmatic patients in remission stage, and (3) 15 healthy volunteers. Serum IL-12 and IL-13 were determined with sandwich ELISA. Lung ventilatory function forced expiratory volume in one second (FEV(1)) and respiratory impedance airway resistance (R(5)) were measured in all patients.(1) Serum level of IL-12 in asthma attack group was significantly lower than that in asthma remission group (P0.05); both were significantly lower than that in normal control group (P0.01); in asthma attack group IL-12 level after prednisone treatment was significantly higher than that before treatment (P0.01). (2) Serum level of IL-13 in asthma attack group was significantly higher than that in asthma remission group (P0.01); both were significantly higher than that in normal control group (P0.01); in asthma attack group IL-13 level after prednisone treatment was significantly lower than that before treatment (P0.01). Correlation analysis showed that the serum level of IL-12 was positively correlated to FEV(1) and negatively correlated to R(5) and to serum level of IL-13 (r(1) = 0.458, r(2) = -0.516, and r(3) = -0.549, respectively; P0.05 and P0.01); the serum level of IL-13 was negatively correlated to FEV(1) and positively correlated to R(5) (r(1) = -0.493, and r(2) = 0.528, respectively; P0.05).The secretion of IL-12 and IL-13 was impaired in asthma with a significant increase in serum level of IL-13 and decrease in serum level of IL-12. Glucocorticoid could downregulate the serum level of IL-13 and upregulate the serum level of IL-12, redress the imbalance of IL-12/IL-13, and improve lung function in asthmatic patients.