M1-type polarized macrophage contributes to brain damage through CXCR3.2/CXCL11 pathways after RGNNV infection in grouper.

The vertebrate central nervous system (CNS) is the most complex system of the body. The CNS, especially the brain, is generally regarded as immune-privileged. However, the specialized immune strategies in the brain and how immune cells, specifically macrophages in the brain, respond to virus invasion remain poorly understood. Therefore, this study aimed to examine the potential immune response of macrophages in the brain of orange-spotted groupers (Epinephelus coioides) following red-spotted grouper nervous necrosis virus (RGNNV) infection. We observed that RGNNV induced macrophages to produce an inflammatory response in the brain of orange-spotted grouper, and the macrophages exhibited M1-type polarization after RGNNV infection. In addition, we found RGNNV-induced macrophage M1 polarization via the CXCR3.2- CXCL11 pathway. Furthermore, we observed that RGNNV triggered M1 polarization in macrophages, resulting in substantial proinflammatory cytokine production and subsequent damage to brain tissue. These findings reveal a unique mechanism for brain macrophage polarization, emphasizing their role in contributing to nervous tissue damage following viral infection in the CNS.

Working memory deficit in schizophrenia: a systematic review and meta-analysis of fMRI studies examining frontal and parietal brain activity.

INTRODUCTION: The role of functional magnetic resonance imaging (fMRI) findings in investigation of working memory (WM) deficit in schizophrenia patients is still debatable. The aim of the study was to investigate the role of fMRI findings of the frontal and parietal brain activity in investigation of WM deficit in schizophrenia patients. MATERIAL AND METHODS: We used Medline, Embase, and the Cochrane Database to conduct a comprehensive search up to January 2023. Functional MRI findings of schizophrenia patients were compared with healthy patients in comparative studies for assessing their WM capacity in terms of dorsolateral prefrontal cortex and parietal region activation. The Cochrane Risk of Bias Assessment Tool was used to evaluate the research quality. RESULTS: Ten trials and 676 schizophrenia patients were included in our analysis. For the comparative assessment of primary outcome - alteration in dorsolateral prefrontal cortex and parietal region activity in schizophrenic patients versus healthy controls - we found the pooled odds ratio (OR) of 1.58 [95% CI: 1.09-2.29], I 2 = 61% and p = 0.01 and risk ratio (RR) was 1.27 [95% CI: 1.06-1.53], I 2 = 55% and p = 0.01. The AUC value of 0.944 indicates a favourable overall diagnostic performance of fMRI for the diagnosis of schizophrenia. CONCLUSIONS: fMRI findings showing abnormalities in the parietal and frontal regions can be used to study schizophrenia patients' WM deficits.

Different degrees of nodes behind obsessive-compulsive symptoms of schizophrenia.

Obsessive-compulsive symptoms are frequently observed in various psychiatric disorders, including obsessive-compulsive disorder, schizophrenia, depression, and anxiety. However, the underlying anatomical basis of these symptoms remains unclear. In this study, we aimed to investigate the mechanism of schizophrenia with obsessive-compulsive symptoms by using diffusion tensor imaging (DTI)-based structural brain connectivity analysis to assess the network differences between patients with obsessive-compulsive disorder (OCD), patients with schizophrenia showing obsessive-compulsive symptoms (SCH), schizophrenia patients with obsessive-compulsive symptoms due to clozapine (LDP), and healthy controls (CN). We included 21 patients with OCD, 20 patients with SCH, 12 patients with LDP, and 25 CN. All subjects underwent MRI scanning, and structural brain connections were estimated using diffusion tensor imaging for further analysis of brain connectivity. The topology and efficiency of the network and the characteristics of various brain regions were investigated. We assessed baseline YALE-BROWN OBSESSIVE COMPULSIVE SCALE (Y-BOCS), Positive and Negative Syndrome Scale (PANSS), and 24-item Hamilton Depression Scale (HAMD-24) scores. Our results showed significant differences among the SCH, OCD, and CN groups (p < 0.05) in the MRI-measured degree of the following nodes: the superior orbitofrontal gyrus (25Frontal_Med_Orb_L), lingual gyrus (47Lingual_L), postcentral gyrus (58Postcentral_R), and inferior temporal gyrus (90Temporal_Inf_R). Additionally, we found significant differences in the degree of the brain regions 02Precentral_R, 47Lingual_L, 58Postcentral_R, and 90Temporal_Inf_R between the CN, OCD, SCH, and LDP groups (p < 0.05). These findings suggest that alterations in the degree of nodes might be the mechanism behind obsessive-compulsive symptoms in schizophrenia.

The diagnostic values of multicolor melting curve analysis on drug resistance to 5 anti-tuberculosis drugs / 中国热带医学

@#Abstract: Objective To explore and analyze the diagnostic value of multicolor melting curve analysis (MMCA) for the resistance of five anti-tuberculosis drugs, so as to clarify the clinical value of MMCA in detecting drug resistance of Mycobacterium tuberculosis. Methods From April 2021 to May 2022, 200 patients with positive Mycobacterium tuberculosis admitted to the Fourth People's Hospital of Qinghai Province were selected as research objects, and sputum specimens were taken from the patients. Traditional Mycobacterium tuberculosis drug sensitivity test (modified Löwenstein-Jensen medium method) and MMCA analysis were respectively given to detect the resistance of five anti-tuberculosis drugs, including isoniazid, ethambutol, streptomycin, rifampicin and isoniazid, respectively. Those samples with inconsistent results between the two diagnosis methods were subjected to gene sequencing verification, and the diagnosis efficiency of MMCA for the five anti-tuberculosis drugs was compared. Results Using Mycobacterium tuberculosis drug sensitivity as the gold standard for drug resistance diagnosis, the sensitivity of MMCA for detecting drug resistance of rifampicin, ethambutol, streptomycin, isoniazid and levofloxacin were 95.83% (46/48), 93.75% (15/16), 100.00% (15/15), 100.00% (20/20) and 70.00% (7/10), respectively, with statistical differences between groups (P<0.05). There were no statistically significant differences in the specificity, positive predictive value, negative predictive value and accuracy of MMCA for the five anti-tuberculosis drugs (P>0.05). For the 8 samples with inconsistent results between MMCA and modified Löwenstein-Jensen medium method, gene sequencing was performed and compared with the results of gene sequencing. After comparison with gene sequencing results, it was found that the coincidence rate of MMCA and gene sequencing results was 75.00% (6/8). Conclusions In the detection of drug-resistant mutations in TB patients, multi-color probe fusion curve analysis has high diagnostic efficacy for first-line anti-tuberculosis drugs, but is not sensitive to second-line anti-tuberculosis drug levofloxacin. Therefore, for the detection of first-line anti-tuberculosis drugs, MMCA has a good clinical application prospect.

Disrupted Structural Brain Network Organization Behind Depressive Symptoms in Major Depressive Disorder.

Major depressive disorder (MDD) is a severe and devastating condition. However, the anatomical basis behind the affective symptoms, cognitive symptoms, and somatic-vegetative symptoms of MDD is still unknown. To explore the mechanism behind the depressive symptoms in MDD, we used diffusion tensor imaging (DTI)-based structural brain connectivity analysis to investigate the network difference between MDD patients and healthy controls (CN), and to explore the association between network metrics and patients' clinical symptoms. Twenty-six patients with MDD and 25 CN were included. A baseline 24-item Hamilton rating scale for depression (HAMD-24) score ≥ 21 and seven factors (anxiety/somatization, weight loss, cognitive disturbance, diurnal variation, retardation, sleep disturbance, hopelessness) scores were assessed. When compared with healthy subjects, significantly higher characteristic path length and clustering coefficient as well as significantly lower network efficiencies were observed in patients with MDD. Furthermore, MDD patients demonstrated significantly lower nodal degree and nodal efficiency in multiple brain regions including superior frontal gyrus (SFG), supplementary motor area (SMA), calcarine fissure, middle temporal gyrus (MTG), and inferior temporal gyrus (ITG). We also found that the characteristic path length of MDD patients was associated with weight loss. Moreover, significantly lower global efficiency of MDD patients was correlated with higher total HAMD score, anxiety somatization, and cognitive disturbance. The nodal degree in SFG was also found to be negatively associated with disease duration. In conclusion, our results demonstrated that MDD patients had impaired structural network features compared to CN, and disruption of optimal network architecture might be the mechanism behind the depressive symptoms and emotion disturbance in MDD patients.

Clinical characteristics of moderate-severe obsessive-compulsive disorder in children and adolescents in China.

OBJECTIVE: This study reports clinical characteristic of moderate-severe obsessive-compulsive disorder (OCD) among school students in China. METHODS: We examined 153 patients for the distribution of OCD symptoms using the Yale-Brown Obsessive Compulsive Scale Symptoms Checklist, the severity of anxiety and depression symptoms using the Hamilton Anxiety Scale and the Hamilton Depression Scale-24, respectively, and impairment in learning, family and social functions using the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire. RESULTS: The number of total OCD, obsession and compulsion symptoms was 6.71 (standard deviation [SD] = 2.25), 3.77 (SD = 1.32) and 2.94 (SD = 1.59), respectively. The incidence of moderate and severe depressive symptoms for junior high school students was significantly higher than for primary and high school students. The number of children and adolescents with OCD increased with age, reaching a peak in the senior high school stage. CONCLUSION: The most common symptoms in children and adolescent OCD patients are miscellaneous obsessions, aggressiveness, religiousness, checking, miscellaneous compulsions, cleaning-washing and repeating. These patients show a relatively high co-occurrence rate of anxiety symptoms and depressive symptoms, which impairs their learning, as well as their family and social functions.

Brain connectomic associations with traditional Chinese medicine diagnostic classification of major depressive disorder: a diffusion tensor imaging study.

BACKGROUND: Major depressive disorder (MDD) is highly heterogeneous in pathogenesis and manifestations. Further classification may help characterize its heterogeneity. We previously have shown differential metabolomic profiles of traditional Chinese medicine (TCM) diagnostic subtypes of MDD. We further determined brain connectomic associations with TCM subtypes of MDD. METHODS: In this naturalistic study, 44 medication-free patients with a recurrent depressive episode were classified into liver qi stagnation (LQS, n = 26) and Heart and Spleen Deficiency (HSD, n = 18) subtypes according to TCM diagnosis. Healthy subjects (n = 28) were included as controls. Whole-brain white matter connectivity was analyzed on diffusion tensor imaging. RESULTS: The LQS subtype showed significant differences in multiple network metrics of the angular gyrus, middle occipital gyrus, calcarine sulcus, and Heschl's gyrus compared to the other two groups. The HSD subtype had markedly greater regional connectivity of the insula, parahippocampal gyrus, and posterior cingulate gyrus than the other two groups, and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole. The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity. CONCLUSIONS: The LQS subtype is mainly characterized by aberrant connectivity of the audiovisual perception-related temporal-occipital network, whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbic-paralimbic network. Insular connectivity may serve a biomarker for TCM-based classification of depression.Trial registration Registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015.

Transcutaneous electrical acupoint stimulation for post-traumatic stress disorder: Assessor-blinded, randomized controlled study.

AIM: Transcutaneous electrical acupoint stimulation (TEAS) has the potential to alleviate post-traumatic stress disorder (PTSD). The purpose of this study was to determine whether adding TEAS to sertraline or cognitive behavioral therapy (CBT) could improve the anti-PTSD efficacy. METHODS: In this randomized controlled trial, 240 PTSD patients (60 in each group) were assigned to receive simulated TEAS combined with sertraline (group A) or with CBT (group B), active TEAS combined with CBT (group C), or active TEAS combined with CBT plus sertraline (group D) for 12 weeks. The outcomes were measured using the Clinician-Administered PTSD Scale, PTSD Check List-Civilian Version, and 17-item Hamilton Rating Scale for Depression. RESULTS: While PTSD symptoms reduced over time in all patients, groups C and D had markedly greater improvement in both PTSD and depressive measures than groups A and B in all post-baseline measurement points, with moderate to very large effect sizes of 0.484-2.244. Groups C and D also had a significantly higher rate than groups A and B on clinical response (85.0% and 95.0% vs 63.3% and 60.0%, P < 0.001) and on remission (15.0% and 25.0% vs 3.3% and 1.7%, P < 0.001). The incidence of adverse events was similar between groups A and D and between groups B and C. CONCLUSIONS: Additional TEAS augments the anti-PTSD and antidepressant efficacy of antidepressants or CBT, without increasing the incidence of adverse effects. TEAS could serve as an effective intervention for PTSD and comorbid depression. This trial was registered with www.chictr.org (no.: ChiCTR1800017255).

Blood and urinary metabolomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a highly heterogeneous disease. Further classification may characterize its heterogeneity. The purpose of this study was to examine whether metabolomic variables could differentiate traditional Chinese medicine (TCM) diagnostic subtypes of MDD. METHODS: Fifty medication-free patients who were experiencing a recurrent depressive episode were classified into Liver Qi Stagnation (LQS, n = 30) and Heart and Spleen Deficiency (HSD, n = 20) subtypes according to TCM diagnosis. Healthy volunteers (n = 28) were included as controls. Gas chromatography-mass spectrometry (GC-MS) was used to examine serum and urinary metabolomic profiles. RESULTS: Twenty-eight metabolites were identified for good separations between TCM subtypes and healthy controls in serum samples. Both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids (BCAAs) (valine, leucine, and isoleucine) and energy metabolism-related metabolites that were differentiated from healthy controls. The LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in biosynthesis of monoamine and amino acid neurotransmitters, including phenylalanine, 3-hydroxybutric acid, o-tyrosine, glycine, l-tryptophan, and N-acetyl-l-aspartic acid. Threonic acid, methionine, stearic acid, and isobutyric acid are differentially associated with the two subtypes. CONCLUSIONS: While both TCM subtypes are associated with aberrant BCAA and energy metabolism, the LQS subtype may represent an MDD subpopulation characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters and closer associations with stress-related pathophysiology. The metabolites differentially associated with the two subtypes are promising biomarkers for predicting TCM subtype-specific antidepressant response [registered at http://www.clinicaltrials.gov (NCT02346682) on January 27, 2015].

Transcutaneous electrical acupoint stimulation as an adjunct therapy for obsessive-compulsive disorder: A randomized controlled study.

BACKGROUND: Transcutaneous electrical acupoint stimulation (TEAS) is thought to have potential to treat obsessive-compulsive disorder (OCD). OBJECTIVE: The purpose of this study was to determine whether adding TEAS to cognitive behavioral therapy (CBT) and clomipramine would improve the efficacy of these conventional treatments in OCD. METHODS: In this randomized controlled trial, 360 OCD patients were assigned to receive TEAS combined with CBT plus clomipramine (Group A, n = 120), TEAS combined with CBT plus placebo (Group B, n = 120), and simulated (placebo) TEAS combined with CBT plus clomipramine (Group C, n = 120) for 12 weeks. The primary outcome was measured using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). RESULTS: OCD symptoms in all patients reduced over time, however Groups A and B had a significantly greater reduction in Y-BOCS total score and the subscale for obsession and compulsion between week 2 and week 12 compared to Group C. Groups A and B had similar scores on these measures. Both groups had significantly higher rates of clinical response than Group C (88.3% and 81.7% vs. 67.5%, respectively, p < 0.001); and higher rates of remission (30.0% and 22.5% vs. 9.2%, respectively, p < 0.001). Group B experienced fewer adverse events than the other two groups. CONCLUSIONS: TEAS enhances the efficacy of conventional OCD interventions and avoids the adverse effects associated with conventional pharmacological treatment. It can be considered as an effective adjunct intervention for OCD.

[Hypoglyceminc effect of flavonoids from Prinsepia utilis on alloxan-induced diabetic mice].

OBJECTIVE: To evaluate the hypoglycemic effect of flavonoids from Prinsepia utilis Royle in alloxan-induced diabetic mice. METHODS: The hypoglycemic effects were investigated in alloxan-induced diabetic mice after oral administration of 300 mg/kg of flavonoids from Prinsepia utilis Royle for four weeks. The blood glucose (GLU), total cholesterol (TC), triglyceride (TG), very low density lipoprotein cholesterol (VLDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and body weight of mice were determined. RESULTS: Flavonoids from Prinsepia utilis Royle had influence on body weight increasing of diabetic mice in three weeks, but had no influence in the fourth week. Flavonoids from Prinsepia utilis Royle exhibited hypoglycemic effects. Among these fractions, flavonoids from Prinsepia utilis Royle significantly reduced GLU, TG and AST level in diabetic mice compared with model control group (P<0.01), markedly reduced VLDL-C, ALT and BUN level in diabetic mice compared with model control group (P<0.05), but had little influence on TC. CONCLUSION: Flavonoids from Prinsepia utilis Royle possess significant hypoglycemic activities, they can improve hypothepatia of diabetic mice and have protective effect on renal function of diabetic mice.