Studies on the association of maternal diabetes with autism spectrum disorders (ASDs) in offspring provide inconsistent findings; therefore an updated and comprehensive literature review and meta-analysis is necessary to perform in order to evaluate the available evidences.After searching databases systematically, we established the inclusion criteria and selected the eligible studies. In both overall and stratified analyses, the estimated effects were synthesized dependent on the presence or absence of heterogeneity.Twelve articles involving 16 studies were included and synthesized, demonstrating a significant association of maternal diabetes with ASDs among children (relative risk [RR] = 1.48). However, high heterogeneity was observed (I2 = 56.3%) and publication bias was identified. In terms of the analyses on reliable evidences from case-control studies, heterogeneity and publication bias disappeared, and the risk of ASDs was increased by 62% among diabetic mothers compared with non-diabetic mothers.Maternal diabetes, especially gestational diabetes mellitus, is associated with ASDs in offspring based on a limited number of convincing case-control studies. More large-scale population-based prospective studies are still needed to draw firm conclusions.

BackgroundWhether olanzapine/fluoxetine combination (OFC) is superior to olanzapine or fluoxetine monotherapy in patients with treatment-resistant depression (TRD) remains controversial. Thus, we conducted this meta-analysis of randomized controlled trials (RCTs) to compare the efficacy and safety of OFC with olanzapine or fluoxetine monotherapy for patients with TRD.Materials and methodsRCTs published in PubMed, Embase, Web of Science, and the ClinicalTrials.gov registry were systematically reviewed to assess the efficacy and safety of OFC. Outcomes included mean changes from baseline in Montgomery–Asberg Depression Rating Scale (MADRS), Clinical Global Impression-Severity (CGI-S), Hamilton Rating Scale for Anxiety (HAM-A), Brief Psychiatric Rating Scale (BPRS) scores, response rate, remission rate, and adverse events. Results were expressed with weighted mean difference (WMD) with 95% confidence intervals (CIs) and risk ratio (RR) with 95% CIs.ResultsA total of five RCTs with 3,020 patients met the inclusion criteria and were included in this meta-analysis. Compared with olanzapine or fluoxetine monotherapy, OFC was associated with greater changes from baseline in MADRS (WMD =−3.37, 95% CI: −4.76, −1.99; P<0.001), HAM-A (WMD =−1.82, 95% CI: −2.25, −1.40; P<0.001), CGI-S (WMD =−0.37, 95% CI: −0.45, −0.28; P<0.001), and BPRS scores (WMD =−1.46, 95% CI: −2.16, −0.76; P<0.001). Moreover, OFC had significantly higher response rate (RR =1.35, 95% CI: 1.12, 1.63; P=0.001) and remission rate (RR =1.71, 95% CI: 1.31, 2.23; P<0.001). The incidence of treatment-related adverse events was similar between the OFC and monotherapy groups (RR =1.01, 95% CI: 0.94, 1.08; P=0.834).ConclusionOFC is more effective than olanzapine or fluoxetine monotherapy in the treatment of patients with TRD. Our results provided supporting evidence for the use of OFC in TRD. However, considering the limitations in this study, more large-scale, well-designed RCTs are needed to confirm these findings.

Neuropathic pain (NP) is a complex, chronic pain condition caused by injury or dysfunction affecting the somatosensory nervous system. This study aimed to identify crucial genes and miRNAs involved in NP. Microarray data (access number GSE91396) were downloaded from the Gene Expression Omnibus (GEO). Murine RNA-seq samples from three brain regions [nucleus accumbens, (NAc); medial prefrontal cortex, (mPFC) and periaqueductal gray, (PAG)] were compared between the spared nerve injury (SNI) model and a sham surgery. After data normalization, differentially expressed RNAs were screened using the limma package and functional enrichment analysis was performed with Database for Annotation, Visualization and Integrated Discovery. The microRNA (miRNA/miR)-mRNA regulatory network and miRNA-target gene-pathway regulatory network were constructed using Cytoscape software. A total of 2,776 differentially expressed RNAs (219 miRNAs and 2,557 mRNAs) were identified in the SNI model compared with the sham surgery group. A total of two important modules (red and turquoise module) were found to be related to NP using weighed gene co-expression network analysis (WGCNA) for the 2,325 common differentially expressed RNAs in three brain regions. The differentially expressed genes (DEGs) in the miRNA-mRNA regulatory network were significantly enriched in 21 Gene Ontology terms and five pathways. A total of four important DEGs ( CXCR2 , IL12B , TNFSF8 and GRK1 ) and five miRNAs ( miR-208a-5p , miR-7688-3p , miR-344f-3p , miR-135b-3p and miR-135a-2-3p ) were revealed according to the miRNA-target gene-pathway regulatory network to be related to NP. Four important DEGs ( CXCR2 , IL12B , TNFSF8 and GRK1 ) and five miRNAs ( miR-208a-5p , miR-7688-3p , miR-344f-3p , miR-135b-3p and miR-135a-2-3p ) were differentially expressed in SNI, indicating their plausible roles in NP pathogenesis.

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