Bioinformatics Approach to Identify the Pathogenetic Link of Gut Microbiota-Derived Short-Chain Fatty Acids and Ischemic Stroke.

Stroke is a life-threatening condition that impairs the arteries and causes neurological impairment. The incidence of stroke is increasing year by year with the arrival of the aging population. Thus, there is an urgent need for early stroke diagnosis. Short-chain fatty acids (SCFAs) can modulate the central nervous system and directly and indirectly impact behavioral and cognitive functions. This study aimed to investigate the connection between SCFA metabolism and stroke development via bioinformatic analysis. Initially, the Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were performed based on RNA data from stroke patients to comprehend the mechanisms governing stroke pathogenesis. The functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI), was performed based on the Differentially Expressed Gene (DEG) selected by the limma package. 1220 SCFA metabolism-related genes screened from Genecards databases were intersected with 242 genes in main modules determined by Weighted Gene Co-Expression Network Analysis (WGCNA), and the final 10 SCFA key genes were obtained. GO analysis revealed that these genes were involved in immune response processes. Through lasso regression analyses, we established a stroke early diagnosis model and selected 6 genes with diagnostic value. The genes were validated by the area under curve (AUC) values and had a relatively good diagnostic performance. Finally, 4 potential therapeutic drugs targeting these genes were predicted using the Drug Signatures Database (DSigDB) via Enrichr. In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis.

A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys.

Retrograde adeno-associated viruses (AAVs) are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks. However, few retrograde AAV capsids have been shown to offer access to cortical projection neurons across different species and enable the manipulation of neural function in non-human primates (NHPs). Here, we report the development of a novel retrograde AAV capsid, AAV-DJ8R, which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques. In addition, intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations. Moreover, AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen. These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

LncRNA LINC01703 promotes the proliferation, migration, and invasion of colorectal cancer by activating PI3K/AKT pathway.

The role of LINC01703 in cancers, especially in colorectal cancer (CRC), is still largely unclear. Bioinformatics prediction, real-time quantitative polymerase chain reaction (RT-qPCR), 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, colony formation assay, Transwell assays, in vivo animal experiments, IF, luciferase reporter assay, and Western blot were carried out for the exploration of the potential involvement and underlying molecular mechanisms of LINC01703 in CRC cells. The results showed that LINC01703 appeared upregulated in CRC and was linked to poor prognosis. LINC01703 acted as an oncogene in both in vitro and in vivo CRC cell environments. LINC01703 activated the PI3K/AKT signaling pathway by mediating the miR-205-5p/E2F1 axis in CRC. In summary, LINC01703 possesses an oncogenic function and can be a possible biomarker or target to treat CRC.

Circuit-specific gene therapy reverses core symptoms in a primate Parkinson's disease model.

Parkinson's disease (PD) is a debilitating neurodegenerative disorder. Its symptoms are typically treated with levodopa or dopamine receptor agonists, but its action lacks specificity due to the wide distribution of dopamine receptors in the central nervous system and periphery. Here, we report the development of a gene therapy strategy to selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spiny neurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeutic strategy comprised of a highly efficient retrograde adeno-associated virus (AAV), promoter elements with strong D1-MSN activity, and a chemogenetic effector to enable precise D1-MSN activation after systemic ligand administration. Application of this therapeutic approach rescues locomotion, tremor, and motor skill defects in both mouse and primate models of PD, supporting the feasibility of targeted circuit modulation tools for the treatment of PD in humans.

An ultra-compact promoter drives widespread neuronal expression in mouse and monkey brains.

Promoters are essential tools for basic and translational neuroscience research. An ideal promoter should possess the shortest possible DNA sequence with cell-type selectivity. However, whether ultra-compact promoters can offer neuron-specific expression is unclear. Here, we report the development of an extremely short promoter that enables selective gene expression in neurons, but not glial cells, in the brain. The promoter sequence originates from the human CALM1 gene and is only 120 bp in size. The CALM1 promoter (pCALM1) embedded in an adeno-associated virus (AAV) genome directed broad reporter expression in excitatory and inhibitory neurons in mouse and monkey brains. Moreover, pCALM1, when inserted into an all-in-one AAV vector expressing SpCas9 and sgRNA, drives constitutive and conditional in vivo gene editing in neurons and elicits functional alterations. These data demonstrate the ability of pCALM1 to conduct restricted neuronal gene expression, illustrating the feasibility of ultra-miniature promoters for targeting brain-cell subtypes.

A comprehensive pan-cancer analysis of CDH5 in immunological response.

Background: Cadherin 5 (CDH5) functions critically in maintaining cell adhesion and integrity of endothelial and vascular cells. The expression of CDH5 is abnormal in tumor cells, which may have great potential to serve as a new immune checkpoint. The current pan-cancer analysis was performed to better understand the role of CDH5 in tumor. Methods: The clinical significance and immunological function of CDH5 in pan-cancers were comprehensively analyzed based on the correlations between CDH5 and clinicopathologic features, prognosis values, tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration and immune response genes using 33 datasets from The Cancer Genome Atlas (TCGA). We further confirmed the expression of CDH5 in bladder cancer (BCa) tissues and cell lines. The CD8+ T cells were screened from peripheral blood of healthy controls and activated. BCa cell-CD8+ T cell co-culture assay and ELISA assay were carried out to verify the immunological function of CDH5. Results: The expression of CDH5 was down-regulated in 8 types of tumors including in BCa but up-regulated in 4 types of tumors. CDH5 was significantly correlated with tumor stage in 6 types of tumors. In addition, CDH5 was positively or negatively correlated with tumor prognosis. Furthermore, CDH5 was closely associated with TMB in 15 types of tumors and with MSI in 9 types of tumors. KEGG-GSEA and Hallmarks-GSEA analyses results indicated that CDH5 was positively related to immune response in most tumor types. In many tumors, CDH5 showed a positive correlation with immune cell infiltration. Enrichment analyses demonstrated that CDH5 was significantly related to the expression of many immunomodulators and chemokines. Further experiments showed that CDH5 was low-expressed in BCa tissues and cell lines in comparison to adjacent normal tissues and normal urothelial cell line, but it was positively associated with a better prognosis of BCa patients. The results of in vitro co-culture assay and ELISA assay demonstrated that CDH5 could promote the function of CD8+ T cells in TME of BCa. Conclusion: In summary, CDH5 was positively associated with a favorable prognosis and effective immune response in tumors, showing a great potential to serve as a novel tumor biomarker and immune checkpoint.

Self-sacrifice-template epitaxial growth of hierarchical MnO2@NiCo2O4 heterojunction electrode for high-performance asymmetric supercapacitor.

Constructing three-dimensional (3D) hierarchical bimetallic pseudocapacitive materials with abundant opening channel and heterojunction structures is rather promising but still challenging for high-performance supercapacitors. Herein, a self-sacrifice-template epitaxial growth strategy was proposed for the first time to construct 3D hierarchical bimetallic pseudocapacitive material. By using this strategy, NiCo2O4 nanowires (NiCo2O4NW) arrayed randomly to form a porous shell via in-situ epitaxial growth fully enclosing a MnO2 tube core, forming multiple transport channels and nano-heterojunctions between MnO2 and NiCo2O4NW, which facilitates electron transfer, i.e. exhibiting high electronic conductivity than any single component. As a result of the self-sacrifice-template epitaxial growth method, special hollow tectorum-like 3D hierarchical structure with considerable inter-nanowire space and hollow interior space enables easy access of electrolyte to NiCo2O4NW surface and MnO2 core, thereby resulting in highly exposed redox active sites of MnO2 core and NiCo2O4NW shell for energy storage. Comprehensive evaluations confirmed MnO2@NiCo2O4NW was a supercapacitor electrode candidate, delivering a superior energy density of 106.37 Wh kg-1. Such performance can be ascribed to the synergistic coupling effect of 3D hierarchical tube and nano-heterojunction structures. The proposed self-sacrifice-template epitaxial growth strategy provides important guidance for designing high-performance energy storage materials.

LILRB4 regulates the function of decidual MDSCs via the SHP-2/STAT6 pathway during Toxoplasma gondii infection.

BACKGROUND: Toxoplasma gondii infection can cause adverse pregnancy outcomes, such as recurrent abortion, fetal growth restriction and infants with malformations, among others. Decidual myeloid-derived suppressor cells (dMDSCs) are a novel immunosuppressive cell type at the fetal-maternal interface which play an important role in sustaining normal pregnancy that is related to their high expression of the inhibitory molecule leukocyte immunoglobulin-like receptor B4 (LILRB4). It has been reported that the expression of LILRB4 is downregulated on decidual macrophages after T. gondii infection, but it remains unknown whether T. gondii infection can induce dMDSC dysfunction resulting from the change in LILRB4 expression. METHODS: LILRB4-deficient (LILRB4-/-) pregnant mice infected with T. gondii with associated adverse pregnancy outcomes, and anti-LILRB4 neutralized antibodies-treated infected human dMDSCs were used in vivo and in vitro experiments, respectively. The aim was to investigate the effect of LILRB4 expression on dMDSC dysfunction induced by T. gondii infection. RESULTS: Toxoplasma gondii infection was observed to reduce STAT3 phosphorylation, resulting in decreased LILRB4 expression on dMDSCs. The levels of the main functional molecules (arginase-1 [Arg-1], interleukin-10 [IL-10]) and main signaling molecules (phosphorylated Src-homology 2 domain-containing protein tyrosine phosphatase [p-SHP2], phosphorylated signal transducer and activator of transcription 6 [p-STAT6]) in dMDSCs were all significantly reduced in human and mouse dMDSCs due to the decrease of LILRB4 expression induced by T. gondii infection. SHP-2 was found to directly bind to STAT6 and STAT6 to bind to the promoter of the Arg-1 and IL-10 genes during T. gondii infection. CONCLUSIONS: The downregulation of LILRB4 expression on dMDSCs induced by T. gondii infection could regulate the expression of Arg-1 and IL-10 via the SHP-2/STAT6 pathway, resulting in the dysfunction of dMDSCs, which might contribute to adverse outcomes during pregnancy by T. gondii infection.

Tim-3 regulates the immunosuppressive function of decidual MDSCs via the Fyn-STAT3-C/EBPß pathway during Toxoplasma gondii infection.

Myeloid-derived suppressor cells (MDSCs) play a key role in maintaining maternal-fetal tolerance for a successful pregnancy, but the role of MDSCs in abnormal pregnancy caused by Toxoplasma gondii infection is unknown. Herein, we revealed a distinct mechanism by which T-cell immunoglobulin domain and mucin domain containing protein-3 (Tim-3), an immune checkpoint receptor that balances maternal-fetal tolerance during pregnancy, contributes to the immunosuppressive function of MDSCs during T. gondii infection. The expression of Tim-3 in decidual MDSCs was significantly downregulated following T. gondii infection. The proportion of monocytic MDSCs population, the inhibitory effect of MDSCs on T-cell proliferation, the levels of STAT3 phosphorylation, and the expression of functional molecules (Arg-1 and IL-10) in MDSCs were all decreased in T. gondii-infected pregnant Tim-3 gene knockout (Tim-3KO) mice compared with infected pregnant WT mice. After treatment with Tim-3-neutralizing Ab in vitro, the expression levels of Arg-1, IL-10, C/EBPß, and p-STAT3 were decreased, the interaction between Fyn and Tim-3 or between Fyn and STAT3 was weakened, and the binding ability of C/EBPß to the promoters of ARG1 and IL10 was decreased in human decidual MDSCs with T. gondii infection, while opposite results were observed following treatment with galectin-9 (a ligand for Tim-3). Inhibitors of Fyn and STAT3 also downregulated the expression of Arg-1 and IL-10 in decidual MDSCs and exacerbated adverse pregnancy outcomes caused by T. gondii infection in mice. Therefore, our studies discovered that the decrease of Tim-3 after T. gondii infection could downregulate the functional molecules of Arg-1 and IL-10 expression in decidual MDSCs through the Fyn-STAT3-C/EBPß signaling pathway and weaken their immunosuppressive function, which eventually contribute to the development of adverse pregnancy outcomes.

Potential of metagenomic next-generation sequencing in detecting infections of ICU patients.

BACKGROUND: Due to the limitations of traditional microbiological detection techniques in evaluating complicated infections in ICU patients, it is necessary to explore novel and effective methods to improve the clinical detection of ICU patients' infections. OBJECTIVE: This study aimed to evaluate the efficiency and specificity of mNGS in screening pathogens in the blood, deep phlegm, urine, and other sample types of ICU patients exploring an effective method for infection detection. METHODS: A total of 56 ICU patients with 131 samples were included in this study. The sample types included blood, deep phlegm, urine, drainage, anal swabs, and other types. Samples were analyzed by both conventional detection method and mNGS tests. The diagnosis efficiency and consistency of the two methods were compared. The distribution of the identified pathogens was analyzed. Moreover, the clinical features of patients with mNGS-positive or mNGS-negative results were compared. RESULTS: The positive rate of mNGS was 81.7% (107/131) including 3.1% (4/131) weakly positive, while the positive rate of traditional detection was only 30.5%, including 29 strong positive results and 11 weak positive results. Additionally, there were 41 patients chose to adjust anti-infection strategies according to the results of mNGS, which significantly saved treatment costs. The mNGS-positive patients showed a shorter ICU hospitalization and higher intention to adjust anti-infection strategies than the mNGS-negative patients. CONCLUSION: mNGS is of great potential for the pathogen detection of ICU patients, and has a higher detection rate than traditional detection methods. Further clinical application investigations can be carried out to expand the application of mNGS.

Shifts and importance of viable bacteria in treatment of DSS-induced ulcerative colitis mice with FMT.

Background and Aims: Ulcerative colitis (UC) has become a global public health concern, and is in urgent need of novel therapies. Fecal microbiota transplantation (FMT) targeting gut microbiota has recently been applied to the treatment of UC. Despite its recent successes, it is still largely unknown how FMT functionally modulates the gut microbiota and improves the disease. Methods: We prospectively collected fecal samples from the 40 mice (30 mice for dextran sulfate sodium (DSS)-induced, 10 for controls), followed by Propidium monoazide treatment for 16S rRNA gene sequencing. These 30 mice were divided equally into 3 groups, which were transplanted with original donor microbiota (DO), inactivated donor microbiota (DI) and saline, respectively. Subsequently, we used 16S rRNA gene sequencing to analyze the viable gut bacteria of ulcerative colitis (UC) mice and histological analysis to evaluate the effects of fecal microbiota transplantation (FMT) with viable microbiota. Results: We demonstrated that the community structure of viable bacteria was significantly different from fecal bacteria based on total DNA. Furthermore, the intestinal viable microbiota and colonic mucosal structure of mice were significantly changed by DSS induction. The histological analysis showed that only the mice treated with original donor microbiota group (HF) achieved a significant improvement. Compared with inactivated donor microbiota group (IF) and saline (NF), Lactobacillus and Halomonas were significantly enriched in the HF group. Conclusion: We inferred that only live bacteria from human donor reversed the histopathology and symptoms of UC in mice and altered the gut microbiota. The activity of gut microbiota in donor samples should be considered in FMT and that detailed analysis of viable microbiota is essential to understand the mechanisms by which FMT produces therapeutic effects in the future.

Effect of epidural labor analgesia on maternal and infant outcomes in parturients with gestational diabetes mellitus-A prospective cohort study.

Background: The occurrence of gestational diabetes mellitus (GDM) is caused by a variety of factors and associated with increased risks of several adverse outcomes for both mothers and infants. However, the effects of epidural labor analgesia in parturients with GDM on maternal and infant outcomes have not been characterized. Methods: According to parturients' choice, they were divided into the epidural group (n = 133) and no epidural (control) group (n = 135). Data for relative variables in the perinatal period were collected, and the potential associations of epidural labor analgesia with infant outcomes were analyzed by univariate analysis and multivariate logistic regression analyses. Results: The rate of neonatal admission to the neonatal intensive care unit (NICU) for hypoglycemia was higher in the epidural group (7.52%) than in the control group (1.48%; P < 0.05). Epidural labor analgesia and drug-based diabetes control were independent predictors of the rate of neonate transfer to the NICU for hypoglycemia. Conclusion: Epidural labor analgesia was associated with an increased risk of neonatal transfer to the NICU for hypoglycemia. Thus, monitoring of neonatal blood glucose levels after administration of epidural labor analgesia in parturients with GDM may be beneficial.Trial registration: The study was registered in the China Clinical Registration Center (Registration No. ChiCTR-OOC-17013164, Registered on 30 October 2017).

Impact of HIV-1 Infection on the Natural Progress of an Anti-HCV Positive Population in an Impoverished Village in China from 2009 to 2017.

Our study aimed to determine the impact of HIV coinfection on the natural progression of liver disease in treatment-naive HCV-infected patients. From 2009 to 2017, we tracked non-invasive markers of liver fibrosis and end-stage liver disease (ESLD)-associated mortality among HCV mono-infected and HIV/HCV coinfected patients in an impoverished village in China. The study cohort consisted of 355 HBsAg-negative and anti-HCV (+) or anti-HIV (+) patients recruited in July 2009, 164 of whom were diagnosed with HIV-1 infection. The surviving patients were re-evaluated in August 2017. During the follow-up, the disease status, liver biochemical, and non-invasive indicators of liver fibrosis (APRI and FIB-4) were measured. The transaminases ALT and AST were significantly higher in HIV-positive HCV resolvers (HIV+ HCVr) than in HIV-negative HCV resolvers (HCVr) (p = 0.019 and p < 0.0001, respectively). APRI and FIB-4 scores of HIV-positive chronic HCV carriers (HIV+ HCVc) were significantly higher than in HIV-negative chronic HCV carriers (HCVc) (p < 0.001). Similarly, APRI and FIB-4 scores were higher in the HIV+ HCVr group than in the HCVr group (ps < 0.001). From 2009 to 2017, the levels of ALT (p = 0.006), AST (p = 0.003), APRI (p = 0.015), and FIB-4 (p = 0.025) were significantly elevated in the HIV/HCV coinfected patients with CD4+ T counts below 500 cells/l. ESLD-related mortality was significantly greater in HIV/HCV-infected cases than in HCV mono-infected patients (73.3% vs. 31.3%, p = 0.009) among patients (n = 45) who died between 2009 and 2017 during follow-up. These findings suggest a higher risk of ESLD-related death and rapid progression of liver fibrosis in HIV/HCV coinfected individuals compared with HCV mono-infected patients. During HIV/HCV coinfection, HIV infection may aggravate HCV-associated liver injury.

Functional analysis of mutations endowing rAAV2-retro with retrograde tracing capacity.

Recombinant adeno-associated viruses (rAAVs) are widespread vectors in neuroscience research. However, the nearly absent retrograde access to projection neurons hampers their application in functional dissection of neural circuits and in therapeutic intervention. Recently, engineering of the AAV2 capsid has generated an AAV variant, called rAAV2-retro, with exceptional retrograde functionality. This variant comprises a 10-mer peptide insertion at residue 587 and two point mutations (LADQDYTKTA + V708I + N382D). Here, we evaluated the contribution of each mutation to retrograde transport in prefrontal cortex -striatum and amygdala-striatum pathways, respectively. Results showed that disruption of the inserted decapeptide almost completely abolishes the retrograde access to neurons projecting to striatum. Eliminating N382D has little effect on the retrograde functionality. Restoring another mutation V708I, however, even improves its performance in amygdala-striatum pathway. Parallel comparison within same animal further confirms this conflicting effect of V708I. These results demonstrate a pivotal role of decapeptide insertion in gaining the capacity of retrograde transport and highlight a neural circuit-dependent contribution of V708I. It suggests constant and custom engineering of rAAV2-retro might be required to tackle the challenge of tremendous neuronal heterogeneity.

Risk factors associated with intraoperative shivering during caesarean section: a prospective nested case-control study.

BACKGROUND: To study the incidence and risk factors of shivering in pregnant women during cesarean section. METHODS: We performed a prospective nested case-control study involving parturients scheduled for cesarean sections between July 2018 and May 2021. The overall incidence of intraoperative shivering and its potential risk factors were investigated. The potential risk factors evaluated were pain, anxiety, emergency surgery, transfer from the delivery room, epidural labor analgesia, membrane rupture, labor, and the timing of the surgery. Shivering and body temperature at different time points during the cesarean section were also recorded. The selected seven time points were: entering the operating room, post-anesthesia, post-disinfection, post-delivery, post-oxytocin, post additional hysterotonics, and before leaving the operating room. RESULTS: We analyzed 212 cesarean section parturients. The overall incidence of shivering was 89 (42.0%). Multivariate logistic regression showed that anxiety, emergency delivery, and transfer from the delivery room to the operating room increased the overall shivering incidence (odds ratio = 1.77, 2.90, and 3.83, respectively). The peak shivering incidence occurred after skin disinfection (63, 29.7%), and the lowest body temperature occurred after oxytocin treatment (36.24 ± 0.30 °C). Stratified analysis of surgery origin showed that emergency delivery was a risk factor for shivering (odds ratio = 2.99) in women transferred from the obstetric ward to the operating room. CONCLUSION: Shivering occurred frequently during cesarean sections, with the peak incidence occurring after skin disinfection. Anxiety, emergency delivery, and transfer from the delivery room to the operating room increased the risk of shivering development during cesarean sections. TRIAL REGISTRATION: The study protocol was registered online at China Clinical Registration Center (registration number: ChiCTR-ROC-17010532, Registered on 29 January 2017).

MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice.

Previous studies have shown that microRNAs (miRs), such as miR-146a play an important role in the pathogenesis of intestinal ischemia/reperfusion (I/R)-induced injury; however, the role of miR-146a in intestinal I/R-induced acute lung injury has not been elucidated. An intestinal I/R-induced injury mouse model was established in the present study by clamping the superior mesenteric artery and expression levels of miR-146a in intestinal and lung tissue samples were evaluated using reverse transcription-quantitative PCR (RT-qPCR). Intestinal and lung histopathological characteristics in mice with intestinal I/R-induced injury were assessed by hematoxylin and eosin staining, and mRNA and protein expression levels in intestinal and lung tissue samples were evaluated using RT-qPCR and western blotting, respectively. miR-146a expression was significantly downregulated in the intestinal and lung tissue samples of mice with intestinal I/R-induced injury. Intestinal I/R injury-induced histopathological changes in the lung and intestines, and pulmonary edema in mice transduced with an adenoviral miR-146a-overexpression vector (the miR-146a overexpression group) were alleviated. mRNA expression levels of TNF-α, IL-1ß, IFN-γ and TGF-ß1, and protein expression levels of TNF receptor-associated factor 6, phosphorylated-p65 NF-κB, cleaved caspase-3 and cleaved caspase-9 in lung and intestinal tissue samples were downregulated in I/R-miR-146a-overexpressing mice, compared with those from the I/R-negative control group. Thus, the present study identified that pre-treatment with the miR-146a overexpression vector alleviated intestinal I/R-induced acute lung injury in mice.

Expression level of long non-coding RNA colon adenocarcinoma hypermethylated serves as a novel prognostic biomarker in patients with thyroid carcinoma.

The present study attempts to identify the prognostic value and potential mechanism of action of colorectal adenocarcinoma hypermethylated (CAHM) in thyroid carcinoma (THCA) by using the RNA sequencing (RNA-seq) dataset from The Cancer Genome Atlas (TCGA). The functional mechanism of CAHM was explored by using RNA-seq dataset and multiple functional enrichment analysis approaches. Connectivity map (CMap) online analysis tool was also used to predict CAHM targeted drugs. Survival analysis suggests that THCA patients with high CAHM expression have lower risk of death than the low CAHM expression (log-rank P=0.022, adjusted P=0.011, HR = 0.187, 95% confidence interval (CI) = 0.051-0.685). Functional enrichment of CAHM co-expression genes suggests that CAHM may play a role in the following biological processes: DNA repair, cell adhesion, DNA replication, vascular endothelial growth factor receptor, Erb-B2 receptor tyrosine kinase 2, ErbB and thyroid hormone signaling pathways. Functional enrichment of differentially expressed genes (DEGs) between low- and high-CAHM phenotype suggests that different CAHM expression levels may have the following differences in biological processes in THCA: cell adhesion, cell proliferation, extracellular signal-regulated kinase (ERK) 1 (ERK1) and ERK2 cascade, G-protein coupled receptor, chemokine and phosphatidylinositol-3-kinase-Akt signaling pathways. Connectivity map have identified five drugs (levobunolol, NU-1025, quipazine, anisomycin and sulfathiazole) for CAHM targeted therapy in THCA. Gene set enrichment analysis (GSEA) suggest that low CAHM phenotype were notably enriched in p53, nuclear factor κB, Janus kinase-signal transducer and activators of transcription, tumor necrosis factor, epidermal growth factor receptor and other signaling pathways. In the present study, we have identified that CAHM may serve as novel prognostic biomarkers for predicting overall survival (OS) in patients with THCA.

Intrathecal dexmedetomidine improves epidural labor analgesia effects: a randomized controlled trial.

OBJECTIVE: α2­agonists and opioids have been used as intrathecal adjuvants to local anesthetics for several years, but the effect of intrathecal dexmedetomidine (Dex) or sufentanil combined with epidural ropivacaine in labor analgesia is not fully understood. METHODS: A total of 108 parturient women receiving combined spinal-epidural labor analgesia were randomly divided into three groups. Group C received l mL saline (0.9%) intrathecally, Group D received 5 µg Dex intrathecally, and Group S received 5 µg sufentanil intrathecally. All parturient women then received 0.1% epidural ropivacaine and 0.2 µg/mL sufentanil for patient-controlled epidural analgesia with standard settings. The visual analog scale score, onset time, duration of intrathecal injection, local anesthetic requirements, and side effects were recorded. RESULTS: The labor analgesia effects in Groups D and S were better than those in Group C. Groups D and S displayed significantly shorter onset times, longer durations of intrathecal injection, and reduced local anesthetic requirements compared with Group C. The incidence of shivering and pruritus in Group D was lower than that in Group S. CONCLUSION: Intrathecal administration of 5 µg Dex could improve epidural labor analgesia effects.This randomized controlled clinical trial was registered with the Chinese Clinical Registry Center (ChiCTR-1800014943, http://www.chictr.org.cn/).

Combination of sufentanil, dexmedetomidine and ropivacaine to improve epidural labor analgesia effect: A randomized controlled trial.

Opioids and α2-agonists have been used as epidural adjuvants in local anesthetics for a long time, but the effect of the combination of opioids and α2-agonists as epidural adjuvants is not completely understood. In the present study, the combination of dexmedetomidine (Dex) and sufentanil as adjuvants to ropivacaine for epidural labor analgesia was investigated. A total of 108 parturient women receiving labor epidural analgesia were randomly divided into three groups: i) Group RD received 0.1% ropivacaine + 0.5 µg/ml Dex; ii) Group RS received 0.1% ropivacaine + 0.5 µg/ml sufentanil; and iv) Group RDS received 0.1% ropivacaine + 0.25 µg/ml Dex + 0.25 µg/ml sufentanil. Patients received a 10 ml loading dose followed by a maintenance by patient controlled epidural analgesia. The visual analog scale scores, onset time, local anesthetic requirements, motor blockage and adverse effects were recorded. Group RDS displayed an improved labor analgesia effect compared with Groups RD and RS. Group RDS displayed a shorter onset time compared with Groups RD and RS, and a reduced local anesthetic requirement compared with Group RS. The motor blockage in Groups RDS and RS was significantly lower compared with Group RD, and the incidence of pruritus in Groups RDS and RD was lower compared with Group RS. In conclusion, the combined use of 0.25 µg/ml Dex and 0.25 µg/ml sufentanil as adjuvants to 0.1% ropivacaine for epidural labor analgesia displayed an improved analgesia effect compared with the use of either 0.5 µg/ml sufentanil or 0.5 µg/ml Dex alone. The present study was registered with the Chinese Clinical Trial Registry Center on 23 February, 2018 (registration no. ChiCTR-IOR-1800014943).

Epidural Labor Analgesia Is Associated with a Decreased Risk of the Edinburgh Postnatal Depression Scale in Trial of Labor after Cesarean: A Multicenter, Prospective Cohort Study.

Postpartum depression is a disabling mental disorder commonly seen in parturients under trial of labor after cesarean, which causes serious harm to the parturients. The etiology is unclear. We hypothesized that epidural labor analgesia can reduce the incidence rate of postpartum depression. Enrolled multiparas were divided into the epidural labor analgesia group (n = 263) or nonanalgesia group (n = 160) according to their own request. Edinburgh Postnatal Depression Scale was used to assess their mental status at 48 hours and 42 days after delivery. Relative perinatal variables were collected and further analyzed using univariate analysis and multivariate logistic regression analysis to assess the relation of epidural analgesia with the occurrence of postpartum depression under trial of labor after cesarean. The Edinburgh Postnatal Depression Scale score 48 hours ≥ 10 in the no epidural analgesia group was 26.42% while the epidural analgesia group was 8.49% (OR, 0.209; 95% CI, 0.096-0.429; P < 0.001). The Edinburgh Postnatal Depression Scale score 42 day ≥ 10 in the no epidural analgesia group was 25.16% while the epidural analgesia group was 6.59% (OR, 0.235; 95% CI, 0.113-0.469; P < 0.001). The incidence of postpartum depression was significantly lower in the epidural labor analgesia group at 48 hours and 42 days. There was also a significant relation between the Edinburgh Postnatal Depression Scale scores at 48 hours and 42 days after delivery. Epidural analgesia, discomfort within 42 days, and self-rating anxiety scale are independent predictors of postpartum depression for trial of labor after cesarean in 42 days. Epidural labor analgesia is associated with a decreased risk of postpartum depression. Further study with a large sample size and more centers is needed to evaluate the impact of epidural analgesia on the occurrence of postpartum depression. Chinese Clinical Trial Register, ChiCTR-ONC-17010654.