Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in major depressive disorder patients.

BACKGROUND: The microbiota-gut-brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients. METHODS: We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD. RESULTS: The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890. CONCLUSIONS: The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.

Study protocol for a parallel-group, double-blinded, randomized, controlled, noninferiority trial: the effect and safety of hybrid electroconvulsive therapy (Hybrid-ECT) compared with routine electroconvulsive therapy in patients with depression.

BACKGROUND: Electroconvulsive therapy (ECT) is the most rapid and effective treatment for patients with depression, ECT can achieve remarkable antidepressant effects in the initial 3-4 sessions, but significant side effects limit its use. However, recent low-charge electrotherapy (LCE) studies have demonstrated antidepressant or antipsychotic effects with significantly fewer side effects. The aim of this study is to propose a novel two-step charge set strategy for ECT treatment, referred to as Hybrid-ECT, to decrease side effects by using a low charge while preserving treatment efficacy. METHODS/DESIGN: A randomized, double-blinded, standard-controlled, parallel-group design will be carried out. We plan to enroll 112 inpatients diagnosed with depression (unipolar or bipolar) and randomly assign them to conventional ECT (control group) or to Hybrid-ECT (treatment group, 3 ECT sessions followed by LCE sessions (approximately 2.8 joules per session)). We will evaluate participants across a wide variety of domains including clinical symptoms, cognitive, psychological and functional metrics. We will also perform magnetic resonance imaging (MRI) and event-related potential (ERPs) assessments during treatment to explore brain function differences between ECT and LCE. DISCUSSION: This research proposes a simple but completely novel ECT strategy that aims to rapidly relieve depressive symptoms and minimize side effects. The mechanism of ECT and LCE will be further discussed. TRIAL REGISTRATION: Chinese Clinical Trial Registry, Number: ChiCTR1900022905 (Registration date: April 30, 2019).

Effect of bone morphogenetic protein 7 on differentiation of adipose derived mesenchymal stem cells into brown adipocytes in rats.

OBJECTIVE: To evaluate the effect of bone morphogenetic protein(BMP7)on the differentiation of adipose derived mesenchymal stem cells(AD-MSCs)isolated from different adipose tissues into brown adipocytes in rats. METHODS: Primary AD-MSCs were isolated from rate interscapular brown adipose tissue(iBAT),inguinal subcutaneous white adipose tissue(sWAT),and epididymal white adipose tissue(eWAT),respectively,and then cultivated in vitro. Differentiation of AD-MSCs into brown adipocytes was induced by BMP7. The characteristics of brown adipocytes were detected by immunofluorescence staining and oil red staining of cells. The expression levels of brown adipocyte-related genes were detected by polymerase chain reaction. RESULTS: AD-MSCs from iBAT and sWAT were differentiated into cluster multilocular cells,which were stained red by oil red "O"staining and showed uncoupling protein 1-positive by immunofluorescent staining method. AD-MSCs from eWAT had a small number of scattered multilocular cells and showed uncoupling protein 1-negative. The results of reverse transcription-polymerase chain reaction showed that the uncoupling protein 1 gene was highly expressed in the iBAT group and sWAT group but was negative in the eWAT group. CONCLUSION: AD-MSCs isolated from different adipose tissues in rats have different gene expression profiles and differentiation potentials.

[Preparation of and study on magnetic resonance imaging performance of metal porphyrin modified by low molecular weight chitosan].

The functional complex Mn-TCPP-CS20 as a potential magnetic resonance imaging (MRI) contrast agent was synthesized through tetra(4-carboxyphenyl) Mn(II)-porphyrin (Mn-TCPP) modified by CS20, which was low degree of polymerization and narrow distribution. The results showed that Mn-TCPP-CS20 had good water-solubility and structural stability. The chemical structures of the products were characterized with Fourier transform infrared spectra (FTIR), UV-Vis spectra, mass spectrum (MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES). The results showed that Mn-TCPP was successfully linked to CS20 by an amide function. The relaxation properties in vitro of the functional complex Mn-TCPP-CS20 as the potential MRI contrast agent were preliminarily studied. It was found that the longitudinal relaxivity (r1) of the synthesized Mn-TCPP-CS20 (6.11 mmol(-1) x L x s(-1)) was higher than that of the commercial contrast agent Gd-DTPA (r1 = 3.59 mmol(-1) x L x s(-1)). Besides, the imaging effect of Mn-TCPP-CS20 was superior to that of Gd-DTPA in the same condition. These studies suggested that Mn-TCPP-CS20 has the advantage of becoming a potential tissue-targeting contrast agent.

Shotgun metagenomics reveals both taxonomic and tryptophan pathway differences of gut microbiota in bipolar disorder with current major depressive episode patients.

BACKGROUND: The microbiome-gut-brain axis, especially the microbial tryptophan biosynthesis and metabolism pathway (MiTBamp), is closely connected to bipolar disorder with current major depressive episode (BPD). METHODS: We performed shotgun metagenomics sequencing (SMS) of faecal samples from 25 BPD patients and 28 healthy controls (HCs). Except for the microbiota taxa and MiTBamp analyses, we also built a classification model using the Random Forests (RF) and Boruta algorithm to find the microbial biomarkers for BPD. RESULTS: Compared to HCs, the phylum Bacteroidetes abundance was significantly reduced, whereas that of the Actinobacteria and Firmicutes were significantly increased in BPD patients. We also identified 38 species increased and 6 species decreased significantly in the BPD group. In the MiTBamp, we identified that two Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K00658 and K00837) were significantly lower in the BPD, and five KOs (K01696, K00382, K00626, K01667, and K03781) were significantly higher in the BPD group. We also identified significant genera and species which were closely related to these KOs. Finally, RF classification based on gut microbiota at the genus level can achieve an area under the receiver operating characteristic curve of 0.997. LIMITATIONS: The features of cross-sectional design, limited sample size, the heterogeneity of bipolar disorders, and a lack of serum/plasma tryptophan concentration measurements. CONCLUSIONS: The present findings enable a better understanding of changes in gastrointestinal microbiome and MiTBamp in BPD. Alterations of microbes may have potential as biomarkers for distinguishing the BPD patients form HCs.

Low-charge electrotherapy for patients with schizophrenia: A double-blind, randomised controlled pilot clinical trial.

A double-blind, randomised controlled pilot clinical trial was conducted to assess the potential effectiveness and safety of low-charge electrotherapy (LCE) for patients with schizophrenia. Bitemporal LCE (approximately 2.8 Joules) was administered three times a week. The Positive and Negative Syndrome Scale score was set as the outcome measure. Any adverse event (AE) was recorded. Three visits occurred at baseline, post-treatment, and after one month of follow-up. Twelve patients were randomised to the electroconvulsive therapy (ECT) group or LCE group (6 patients in each group). No patient withdrew during the study. The LCE group did not experience seizures during the trial. Patients in both groups showed significant improvements in clinical measures after treatment, and the reduction of all scale scores between the two groups was nonsignificant. The LCE group experienced significantly fewer AEs than the ECT group. Compared with ECT, LCE exerts similar antipsychotic effects while causing fewer AEs. Thus, LCE has the potential to be a safe and effective treatment for patients with schizophrenia, but further research is needed.

Trends in prevalence, awareness, treatment, and control of diabetes mellitus in mainland china from 1979 to 2012.

Diabetes mellitus (DM) is one of the primary causes of premature death and disability worldwide. We performed a systematic review and meta-analysis of the published literature regarding the trends in prevalence, awareness, treatment, and control of diabetes mellitus in mainland China. PUBMED, EMBASE, Chinese Biomedical Database, China National Infrastructure database, Chinese Wan Fang database, and Chongqing VIP database were searched. Fifty-six eligible studies were included. Increasing trends in the prevalence, treatment, and control of diabetes in mainland China from 1979 to 2012 were observed. The pooled prevalence, awareness, treatment, and control of diabetes mellitus were 6.41%, 45.81%, 42.54%, and 20.87%, respectively. A higher prevalence of diabetes mellitus was found in urban (7.48%, 95%CI = 5.45~9.50) than rural (6.53%, 95%CI = 4.30~8.76) areas. Furthermore, an increasing chronological tendency was shown in different subgroups of age with regard to the prevalence of diabetes. A higher awareness of DM was found in urban (44.25%, 95%CI = 32.60~55.90) than rural (34.27%, 95%CI = 21.00~47.54) populations, and no significant differences were found in the treatment, and control of diabetes among the subgroups stratified by gender and location. From 1979 to 2012, the prevalence, treatment, and control of diabetes mellitus increased; nevertheless, there was no obvious improvement in the awareness of diabetes.