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Yiyi Zhu,1 Lingling Wu,2– 5 Shuling Ye,6– 9 Yaoyang Fu,2– 5 Huimin Huang,1 Jianbo Lai,2– 5 Chuan Shi,6– 9 Shaohua Hu1– 5,10 1School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, People’s Republic of China; 5Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, People’s Republic of China; 6Peking University Sixth Hospital, Beijing, People’s Republic of China; 7Peking University Institute of Mental Health, Beijing, People’s Republic of China; 8NHC Key Laboratory of Mental Health (Peking University), Beijing, People’s Republic of China; 9National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 10Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, and MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of ChinaCorrespondence: Shaohua Hu, School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China, Email dorhushaohua@zju.edu.cn Chuan Shi, Peking University Sixth Hospital, Beijing, 100191, People’s Republic of China, Email shichuan@bjmu.edu.cnBackground: Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders.Methods: 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity.Results: A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p< 0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p< 0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p< 0.01). The differences in the ODQ scores between the patient and control groups were statistically significant.Conclusion: The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.Keywords: emotional blunting, Chinese, mood disorder, psychometrics, validation

The intricate processes of microbiota-gut-brain communication in modulating human cognition and emotion, especially in the context of mood disorders, have remained elusive. Here we performed faecal metagenomic, serum metabolomics and neuroimaging studies on a cohort of 109 unmedicated patients with depressed bipolar disorder (BD) patients and 40 healthy controls (HCs) to characterise the microbial-gut-brain axis in BD. Across over 12,000 measured metabolic features, we observed a large discrepancy (73.54%) in the serum metabolome between BD patients and HCs, spotting differentially abundant microbial-derived neuroactive metabolites including multiple B-vitamins, kynurenic acid, gamma-aminobutyric acid and short-chain fatty acids. These metabolites could be linked to the abundance of gut microbiota presented with corresponding biosynthetic potentials, including Akkermansia muciniphila, Citrobacter spp. (Citrobacter freundii and Citrobacter werkmanii), Phascolarctobacterium spp., Yersinia spp. (Yersinia frederiksenii and Yersinia aleksiciae), Enterobacter spp. (Enterobacter cloacae and Enterobacter kobei) and Flavobacterium spp. Based on functional neuroimaging, BD-related neuroactive microbes and metabolites were discovered as potential markers associated with BD-typical features of functional connectivity of brain networks, hinting at aberrant cognitive function, emotion regulation, and interoception. Our study combines gut microbiota and neuroactive metabolites with brain functional connectivity, thereby revealing potential signalling pathways from the microbiota to the gut and the brain, which may have a role in the pathophysiology of BD.

Preliminary studies have indicated metabolic dysfunction and gut dysbiosis in patients with bipolar disorder (BD). In this study, we aimed to clarify the impact of the gut microbial composition and function on metabolic dysfunction in BD patients with an acute depressive episode.Fresh fecal samples were provided from 58 patients with BD depression, including 29 with normal weight (NW) and 29 with overweight/obesity (OW), and 31 healthy controls (HCs). The hypervariable region of 16 S rRNA gene (V3-V4) sequencing was performed using IonS5TMXL platform to evaluate the bacterial communities. Differences of microbial community and correlation to clinical parameters across different groups were analyzed.Compared to NW and HCs, the OW group showed a decreased tendency in alpha diversity index. Beta diversity was markedly different among these groups (PERMANOVA: RSpecific bacterial taxa involved in pathways regulating the lipid, energy, and amino acid metabolisms may underlie the weight concerns in depressed BD patients. Potential targeting gut microbial therapy is provided for overweight/obesity patients with BD, which still need further studies in the future.

Antipsychotic-induced metabolic dysfunction (AIMD) is an intractable clinical challenge worldwide. The situation is becoming more critical as second-generation antipsychotics (SGAs), to a great extent, have replaced the role of first-generation antipsychotics in managing major psychiatric disorders. Although the exact mechanisms for developing AIMD is intricate, emerging evidence has indicated the involvement of the microbiota-gut-brain axis in AIMD. SGAs treatment may change the diversity and compositions of intestinal flora (e.g., decreased abundance of Bacteroidetes and Akkermansia muciniphila, and increased Firmicutes). Short-chain fatty acids and other metabolites derived from gut microbiota, on the one hand, can regulate the activity of intestinal endocrine cells and their secretion of satiety hormones (e.g., glucagon-like peptide 1, peptide YY, cholecystokinin and ghrelin); on the other hand, can activate the vagus nerve or transport into the brain to exert a central modulation of foraging behaviors via binding to neuropeptide receptors. Interestingly, metformin, a classical antidiabetic agent, is capable of alleviating AIMD possibly by regulating the microbiota-gut-brain axis. That is, metformin can not only partially reverse the alterations of gut microbial communities due to SGAs treatment, but also play a positive role in rectifying the disturbances of peripheral and central satiety-related neuropeptides. Current evidence has indicated a promising role for metformin on ameliorating AMID, but further verifications in well-designed clinical trials are still warranted.

Bipolar disorder (BD) is a common psychiatric illness with high prevalence and disease burden. Accumulating susceptibility genes for BD have been identified in recent years. However, the exact functions of these genes remain largely unknown. Despite its high heritability, gene and environment interaction is commonly accepted as the major contributing factor to BD pathogenesis. Intestine microbiota is increasingly recognized as a critical environmental factor for human health and diseases via the microbiota‐gut‐brain axis. BD individuals showed altered diversity and compositions in the commensal microbiota. In addition to pro‐inflammatory factors, such as interleukin‐6 and tumour necrosis factor‐α, type 1 interferon signalling pathway is also modulated by specific intestinal bacterial strains. Disruption of the microbiota‐gut‐brain axis contributes to peripheral and central nervous system inflammation, which accounts for the BD aetiology. Administration of type 1 interferon can induce the expression of TRANK1, which is associated with elevated circulating biomarkers of the impaired blood‐brain barrier in BD patients. In this review, we focus on the influence of intestine microbiota on the expression of bipolar gene TRANK1 and propose that intestine microbiota‐dependent type 1 interferon signalling is sufficient to induce the over‐expression of TRANK1, consequently causing the compromise of BBB integrity and facilitating the entrance of inflammatory mediators into the brain. Activated neuroinflammation eventually contributes to the occurrence and development of BD. This review provides a new perspective on how gut microbiota participate in the pathogenesis of BD. Future studies are needed to validate these assumptions and develop new treatment targets for BD.

Objectives To investigate the diagnostic value of serum D-dimer in patients with periprosthetic joint infection (PJI). Moreover, to provide evidence for the treatment of PJI by investigating distribution of pathogenic bacteria and antibiotic resistance situation among the patients. Methods A retrospective study of the medical records of all patients undergoing arthroplasty from the Second Xiangya Hospital of Central South University from 2014 to 2018, 40 patients with periprosthetic joint infection, 37 patients with aseptic loosening and 59 patients with extra-articular infection were selected. The results of serum D-dimer, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were collected. As well as the bacterial types and antimicrobial susceptibility test results from tissue or joint fluid samples around the prosthetic joint of the patients were collected. All the relevant data were analyzed. Results The serum D-dimer, CRP and ESR level were significantly higher in the patients with PJI. The mean D-dimer level was 2.0795 μg/mL in PJI group compared with 0.6854 μg/mL in aseptic loosening group (p = 0.000) and 0.4556 μg/mL in extra-articular infection group (p = 0.000). For diagnosing PJI, the serum D-dimer test demonstrated better sensitivity (87.50%), and better specificity (89.19%); while the serum CRP and ESR had a sensitivity of 80.00% and 82.50% and a specificity of 78.38% and 64.86%, respectively. Moreover, the sensitivity and specificity of ESR and CRP combined was 75.00% and 83.78%, respectively. In addition, 29 strains of pathogens around the prosthesis after arthroplasty were detected, including 22 strains of Gram-positive bacteria, 3 strains of Gram-negative bacteria, and 4 strains of fungi. The staphylococcus was the major pathogen showing high resistance to Cefoxitin and ampicillin. Conclusion Patients with PJI have high levels of serum D-dimer, which is a promising marker for the diagnosis of PJI. The Gram-positive bacteria are major pathogen in PJI after arthroplasty, and Staphylococcus aureus is the most common organism. Clinical efficacy is significantly improved by reasonable choice of antibiotics and effective medicine education.

To explore the changes of serum interleukin-6 (IL-6) levels in healthy pregnant women and establish reference intervals (RIs).According to the requirements for the RIs study model and the reference population screening criteria in C28-A3 document, Serum IL-6 levels were measured by electrochemiluminescence immunoassay in 480 healthy Chinese women, including 120 pregnant women in each of the first, second and third trimester and 120 non-pregnant women as the negative control. The establishment of RIs for IL-6 were defined using nonparametric percentile.The RIs for serum IL-6 levels in healthy pregnant women is 4.19 pg/ml, the RIs for serum IL-6 levels in healthy pregnant women who are in the first trimester is 3.52 pg/ml, and the RIs for serum IL-6 levels in healthy pregnant women who are in the second and third trimester is 4.40 pg/ml.Serum IL-6 level in healthy pregnant women is higher than the healthy non-pregnant women, and the level of IL-6 who are in the second and third trimester is higher than those in the first. This paper successfully established RIs for serum IL-6 levels in pregnant women, providing a reference for clinical medical staff and laboratory workers.

Butyrate is one of the most abundant short-chain fatty acids produced by intestinal bacteria. In the present study, the action of butyrate on chronic gastric mucosa lesions was investigated, as well as its underlying mechanism in mice. Male mice from the Institute of Cancer Research were randomly divided into three groups: Sham, model and butyrate groups. Butyrate was administered intragastrically for 7 days to butyrate group mice following the establishment of a gastric ulcer model. Hematoxylin and eosin staining, immunohistochemical analysis, enzyme-linked immunosorbent assay and quantitative polymerase chain reaction were used to determine the therapeutic effects and molecular mechanism of butyrate treatment. The findings demonstrated that butyrate induced a marked shift in superoxide dismutase and catalase activities, along with a decrease in malondialdehyde levels, thereby attenuating oxidative stress. Furthermore, butyrate decreased the levels of pro-inflammatory cytokines interleukin-1β, tumour necrosis factor-α and leukotriene B4, which helped combat inflammatory responses. Moreover, butyrate treatment exerted remarkable positive influences that mediate an increase in 6-keto-PGF-1α (a degradation product of prostacyclin), trefoil factor 2, MUC5AC and fibroblast growth factor-7 levels to promote gastric mucosal repair. The expression of specific receptor GPR109A for butyrate was upregulated, with no significant difference noted in the expression of GPR43 or GPR41. Overall, the present findings revealed that butyrate exerted therapeutic effects by upregulating mucosal repair factors and stimulating protective responses against oxidation and inflammation. GPR109A may be the key receptor for butyrate therapy.

The growing multidrug-resistant Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. During 2017–2018, we identified a rare multidrug-resistant (ceftriaxone and azithromycin) strain (GC250) and four strains (GC185, GC195, GC196 and GC249) with both resistance to ceftriaxone and decreased susceptibility to azithromycin. All strains belonged to NG-STAR ST1143, including the mosaic penA-60.001, which is closely related to ceftriaxone resistance. The characterization of antimicrobial resistance (AMR) determinants and phylogenetic analysis showed these five strains were closely related to internationally spreading ceftriaxone-resistant N. gonorrhoeae FC428, but with higher azithromycin MIC. Findings here demonstrated that this clone not only initiated clonal expansion in China, but acquired azithromycin resistance.