Progress in the study of intestinal microbiota involved in morphine tolerance.

Morphine is a widely used opioid for treatment of pain. The attendant problems including morphine tolerance and morphine dependence pose a major public health challenge. In recent years, there has been increasing interest in the gastrointestinal microbiota in many physiological and pathophysiological processes. The connectivity network between the gut microbiota and the brain is involved in multiple biological systems, and bidirectional communication between them is critical in gastrointestinal tract homeostasis, the central nervous system, and the microbial system. Many research have previously shown that morphine has a variety of effects on the gastrointestinal tract, but none have determined the function of intestinal microbiota in morphine tolerance. This study reviewed the mechanisms of morphine tolerance from the perspective of dysregulation of microbiota-gut-brain axis homeostasis, by summarizing the possible mechanisms originating from the gut that may affect morphine tolerance and the improvement of morphine tolerance through the gut microbiota.

Ketogenic diet: a potential adjunctive treatment for substance use disorders.

Substance use disorders (SUD) can lead to serious health problems, and there is a great interest in developing new treatment methods to alleviate the impact of substance abuse. In recent years, the ketogenic diet (KD) has shown therapeutic benefits as a dietary therapy in a variety of neurological disorders. Recent studies suggest that KD can compensate for the glucose metabolism disorders caused by alcohol use disorder by increasing ketone metabolism, thereby reducing withdrawal symptoms and indicating the therapeutic potential of KD in SUD. Additionally, SUD often accompanies increased sugar intake, involving neural circuits and altered neuroplasticity similar to substance addiction, which may induce cross-sensitization and increased use of other abused substances. Reducing carbohydrate intake through KD may have a positive effect on this. Finally, SUD is often associated with mitochondrial damage, oxidative stress, inflammation, glia dysfunction, and gut microbial disorders, while KD may potentially reverse these abnormalities and serve a therapeutic role. Although there is much indirect evidence that KD has a positive effect on SUD, the small number of relevant studies and the fact that KD leads to side effects such as metabolic abnormalities, increased risk of malnutrition and gastrointestinal symptoms have led to the limitation of KD in the treatment of SUD. Here, we described the organismal disorders caused by SUD and the possible positive effects of KD, aiming to provide potential therapeutic directions for SUD.

Naïve B cells with low differentiation improve the immune reconstitution of HIV-infected patients.

Incomplete immune reconstitution happens in some HIV-infected patients who have achieved persistent viral suppression under antiretroviral therapy (ART). We performed single-cell RNA sequencing for peripheral blood mononuclear cells to analyze B cell receptor (BCR) repertoire and B cell subtypes in health controls (non-HIV-infected, HCs), HIV-infected immunological responders (IRs), and immunological nonresponders (INRs). We found that the dominant usage of IGHV gene segments of naïve B cells and memory B cells were IGHV3 and IGHV4, and the diversity of BCR repertoire was decreased in INRs. Differentiation trajectory analysis showed that the low differentiation of naïve B cells was related to satisfactory immune status. The cell cycle of B cells with immune-specific genes of IgD+ B cells was degraded in INRs, which was mediated by the anaphase-promoting complex/cyclosome pathway in the phase of G2/M checkpoints. These findings provide significant insights to understand the function of B cell-mediated immune response in immune reconstitution after HIV infection.

Exercise modulates central and peripheral inflammatory responses and ameliorates methamphetamine-induced anxiety-like symptoms in mice.

Anxiety-like symptoms are common symptoms of methamphetamine (METH) users, especially in the acute withdrawal period, which is an important factor for the high relapse rate during METH acute withdrawal. Exercise has been demonstrated to relieve anxiety-like symptoms during METH withdrawal, but the underlying mechanisms of this anti-anxiety effect are still unclear. Activated microglia and abnormal neuroinflammation play an important role in the pathogenesis of anxiety-like symptoms after METH withdrawal. Moreover, peripheral immune factors were also significantly associated with anxiety symptoms. However, the effects of treadmill exercise on microglial function and neuroinflammation in the striatum and hippocampus during acute METH withdrawal have not been reported. In the current study, we found severe peripheral immune dysfunction in METH users during acute withdrawal, which may in part contribute to anxiety symptoms during METH acute withdrawal. We also showed that 2 weeks of METH exposure induced anxiety-like symptoms in the acute withdrawal period. Additionally, METH exposure resulted in increased microglial activation and proinflammatory cytokines released in the mouse striatum and hippocampus during acute withdrawal. We next evaluated the effects of treadmill exercise in countering anxiety-like symptoms induced by METH acute withdrawal. The results showed that anxiety-like symptoms induced by acute METH withdrawal were attenuated by coadministration of treadmill exercise. In addition, treadmill exercise counteracted METH-induced microglial activation in the mouse striatum and various subregions of the hippocampus. Furthermore, treadmill exercise also reversed the increase in proinflammatory cytokines induced by acute METH withdrawal in the mouse striatum, hippocampus and serum. Our findings suggest that the anti-anxiety effect of treadmill exercise may be mediated by reducing microglial activation and regulating central and peripheral inflammatory responses.

Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users.

Background: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown. Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS). Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR. Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.

Psychometric evaluation of the Chinese version of the Person-Centred Care Assessment Tool.

OBJECTIVE: This study aims to test a Chinese cross-cultural adaptation of the English version of the Person-Centred Care Assessment Tool (P-CAT) and evaluate its psychometric properties. DESIGN: P-CAT was translated/back-translated using established procedures before the psychometric evaluation of the Chinese version was made. SETTING: Two hospitals covering urban and suburban areas of Kunming in the Yunnan province of China. PARTICIPANTS: 152 female hospital staff completed the survey. MAIN OUTCOME MEASURES: Construct validity and reliability, including internal consistency and test-retest reliability, were assessed among a sample of hospital staff. RESULTS: The factor analysis resulted in a two-component solution that consisted of two subscales. The corrected item-total correlations for all of the items ranged from 0.14 to 0.44, with six items not meeting the cut-off level for item-total correlation (>0.3). The Chinese P-CAT demonstrated strong reliability, with a Cronbach's alpha of 0.91-0.94 for the scales and a test-retest reliability coefficient of 0.88 for the overall scale scores. The intraclass correlation was 0.92 (95% CI 0.90 to 0.95). CONCLUSION: P-CAT appears to be a promising measure for evaluating staff perceptions of person-centredness in Chinese hospital environments. The results show that P-CAT can be a useful tool for improving the quality of healthcare in terms of person-centred care in the Chinese context.

Psychometric evaluation of the Chinese version of the Person-centred Climate Questionnaire - Staff version (PCQ-S).

OBJECTIVES: The aim of the study was to evaluate the psychometric properties of a Chinese translation of the English version of the Person-centred Climate Questionnaire - Staff version (PCQ-S) for Chinese palliative care staff in a hospital context. DESIGN: This was a cross-sectional design. The 14-item English PCQ-S was translated and backtranslated using established procedures. Construct validity and reliability including internal consistency and test-retest reliability were assessed among hospital staff. Construct validity was tested using principal component analysis (PCA), internal consistency was assessed using Cronbach's alpha, and test-retest reliability was evaluated with the weighted kappa (Kp), Pearson correlation coefficient (r) and intra-class correlation coefficient (ICC). SETTING: This study was conducted in three hospitals in Kunming, the capital of Yunnan province in south-west China. PARTICIPANTS: A sample of hospital staff (n=163) on duty in the palliative care departments of three hospitals in Kunming consented to participate in the study. RESULTS: The 14-item Chinese PCQ-S consists of the three subscales also present in other language versions. It showed strong internal consistency, with a Cronbach's alpha of 0.94 for the total scale, 0.87 for the safety subscale, 0.90 for the everydayness subscale and 0.88 for the community subscale. The Chinese PCQ-S had high test-retest reliability as evidenced by a high Kp coefficient and a high correlation coefficient for all scales between test and retest scores, on 'a climate of safety' (Kp=0.77, r=0.88, p<0.01), 'a climate of everydayness' (Kp=0.82, r=0.91, p<0.01), 'a climate of community' (Kp=0.75, r=0.79, p<0.01), and on overall scale scores (Kp=0.85, r=0.93, p<0.01). The ICC to evaluate the test-retest reliability was 0.97 (95% CI 0.95 to 0.98). CONCLUSIONS: The Chinese version of the PCQ-S showed satisfactory reliability and validity for assessing staff perceptions of person-centred care in Chinese hospital environments.