Background: Multiple meta-analyses of diffusion tensor imaging (DTI) studies have reported impaired white matter integrity in patients with major depressive disorder (MDD). However, owing to inclusion of medicated patients in these studies, it is difficult to conclude whether these reported alterations are associated with MDD or confounded by medication effects. A meta-analysis of DTI studies on medication-free (medication-naive and medication washout) patients with MDD would therefore be necessary to disentangle MDD-specific effects. Methods: We analyzed white matter alterations between medication-free patients with MDD and healthy controls using anisotropic effect size–signed differential mapping (AES-SDM). We used DTI query software for fibre tracking. Results: Both pooled and subgroup meta-analyses in medication washout patients showed robust fractional anisotropy (FA) reductions in white matter of the right cerebellum hemispheric lobule, body of the corpus callosum (CC) and bilateral superior longitudinal fasciculus III (SLF III), whereas FA reductions in the genu of the CC and right anterior thalamic projections were seen in only medication-naive patients. Fibre tracking showed that the main tracts with observed FA reductions included the right cerebellar tracts, body of the CC, bilateral SLF III and arcuate fascicle. Limitations: The analytic techniques, patient characteristics and clinical variables of the included studies were heterogeneous; we could not exclude the effects of nondrug therapies owing to a lack of data. Conclusion: By excluding the confounding influences of current medication status, findings from the present study may provide a better understanding of the underlying neuropathology of MDD.

Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC).

To improve the response rate of immune checkpoint inhibitors such as anti-PD-L1 antibody in immunosuppressive cancers like triple-negative breast cancer (TNBC), induction of immunogenic cell death (ICD) at tumor sites can increase the antigenicity and adjuvanticity to activate the immune microenvironment so that tumors become sensitive to the intervention of immune checkpoint inhibitors. Herein, a self-amplified biomimetic nanosystem, mEHGZ, was constructed by encapsulation of epirubicin (EPI), glucose oxidase (Gox) and hemin in ZIF-8 nanoparticles and coating of the nanoparticles with calreticulin (CRT) over-expressed tumor cell membrane. EPI acts as an ICD inducer, Gox and hemin medicate the cascade generation of reactive oxygen species (ROS) to strengthen the ICD effect, and CRT-rich membrane as “eat me” signal promote presentation of the released antigens by dendritic cells (DCs) to invoke the tumor-immunity cycle. The biomimetic delivery system displays an amplified ICD effect via Gox oxidation, hydroxyl radical generation and glutathione (GSH) depletion. The induced potent ICD effect promotes DCs maturation and cytotoxic T lymphocytes (CTLs) infiltration, reversing an immunosuppressive tumor microenvironment to an immunoresponsive one. Treatment with the nanosystem in combination with anti-PD-L1 antibody results in distinctive inhibition of tumor growth and lung metastasis, supporting that a potent ICD effect can significantly boost the therapeutic efficacy of the anti-PD-L1 antibody. This self-amplified biomimetic nanoplatform offers a promising means of raising the response rate of immune checkpoint inhibitors.

Background: Brain connectome research based on graph theoretical analysis shows that small-world topological properties play an important role in the structural and functional alterations observed in patients with psychiatric disorders. However, the reported global topological alterations in small-world properties are controversial, are not consistently conceptualized according to agreed-upon criteria, and are not critically examined for consistent alterations in patients with each major psychiatric disorder. Methods: Based on a comprehensive PubMed search, we systematically reviewed studies using noninvasive neuroimaging data and graph theoretical approaches for 6 major psychiatric disorders: schizophrenia, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD), bipolar disorder (BD), obsessive–compulsive disorder (OCD) and posttraumatic stress disorder (PTSD). Here, we describe the main patterns of altered small-world properties and then systematically review the evidence for these alterations in the structural and functional connectome in patients with these disorders. Results: We selected 40 studies of schizophrenia, 33 studies of MDD, 5 studies of ADHD, 5 studies of BD, 7 studies of OCD and 5 studies of PTSD. The following 4 patterns of altered small-world properties are defined from the perspectives of segregation and integration: “regularization,” “randomization,” “stronger small-worldization” and “weaker small-worldization.” Although more differences than similarities are noted in patients with these disorders, a prominent trend is the structural regularization versus functional randomization in patients with schizophrenia. Limitations: Differences in demographic and clinical characteristics, pre-processing steps and analytical methods can produce contradictory results, increasing the difficulty of integrating results across different studies. Conclusion: Four psychoradiological patterns of altered small-world properties are proposed. The analysis of altered small-world properties may provide novel insights into the pathophysiological mechanisms underlying psychiatric disorders from a connectomic perspective. In future connectome studies, the global network measures of both segregation and integration should be calculated to fully evaluate altered small-world properties in patients with a particular disease.