Efficacy and safety of psychedelics for the treatment of mental disorders: A systematic review and meta-analysis.

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.

Comparison of the somatic genomic landscape between central- and peripheral-type non-small cell lung cancer.

OBJECTIVE: Lung cancer is classified into central and peripheral types based on the anatomic location. The present study aimed to explore the distinct patterns of genomic alterations between central- and peripheral-type non-small cell lung cancers (NSCLCs) with negative driver genes and identify potential driver genes and biomarkers to improve therapy strategies for NSCLC. METHODS: Whole-exome sequencing (WES) was performed with 182 tumor/control pairs of samples from 145 Chinese NSCLC patients without EGFR, ALK, or ROS1 alterations. Significantly mutated genes (SMGs) and somatic copy number alterations (SCNAs) were identified. Subsequently, tumor mutation burden (TMB), weighted genome integrity index (wGII), copy number alteration (CNA) burden, Shannon diversity index (SDI), intratumor heterogeneity (ITH), neoantigen load (NAL), and clonal variations were evaluated in central- and peripheral-type NSCLCs. Furthermore, mutational signature analysis and survival analysis were performed. RESULTS: TP53 was the most frequently mutated gene in NSCLC and more frequently mutated in central-type NSCLC. Higher wGII, ITH, and SDI were found in central-type lung adenocarcinoma (LUAD) than in peripheral-type LUAD. The NAL of central-type lung squamous cell carcinoma (LUSC) with stage III/IV was significantly higher than that of peripheral-type LUSC. Mutational signature analysis revealed that SBS10b, SBS24, and ID7 were significantly different in central- and peripheral-type NSCLCs. Furthermore, central-type NSCLC was found to evolve at a higher level with fewer clones and more subclones, particularly in central-type LUSC. Survival analysis revealed that TMB, CNA burden, NAL, subclonal driver mutations, and subclonal mutations were negatively related to the overall survival (OS) and the progression-free survival (PFS) of central-type LUAD. CONCLUSIONS: Central-type NSCLC tended to evolve at a higher level and might suggest a favorable response to immunotherapy. Our study also identified several potential driver genes and promising biomarkers for the prognosis and prediction of chemotherapy responses in NSCLC.

Identification of Novel Key Molecular Signatures in the Pathogenesis of Experimental Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a long-term major microvascular complication of uncontrolled hyperglycemia and one of the leading causes of end-stage renal disease (ESDR). The pathogenesis of DKD has not been fully elucidated, and effective therapy to completely halt DKD progression to ESDR is lacking. This study aimed to identify critical molecular signatures and develop novel therapeutic targets for DKD. This study enrolled 10 datasets consisting of 93 renal samples from the National Center of Biotechnology Information (NCBI) Gene Expression Omnibus (GEO). Networkanalyst, Enrichr, STRING, and Cytoscape were used to conduct the differentially expressed genes (DEGs) analysis, pathway enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene screening. The shared DEGs of type 1 diabetic kidney disease (T1DKD) and type 2 diabetic kidney disease (T2DKD) datasets were performed to identify the shared vital pathways and hub genes. Strepotozocin-induced Type 1 diabetes mellitus (T1DM) rat model was prepared, followed by hematoxylin & eosin (HE) staining, and Oil Red O staining to observe the lipid-related morphological changes. The quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was conducted to validate the key DEGs of interest from a meta-analysis in the T1DKD rat. Using meta-analysis, 305 shared DEGs were obtained. Among the top 5 shared DEGs, Tmem43, Mpv17l, and Slco1a1, have not been reported relevant to DKD. Ketone body metabolism ranked in the top 1 in the KEGG enrichment analysis. Coasy, Idi1, Fads2, Acsl3, Oxct1, and Bdh1, as the top 10 down-regulated hub genes, were first identified to be involved in DKD. The qRT-PCR verification results of the novel hub genes were mostly consistent with the meta-analysis. The positive Oil Red O staining showed that the steatosis appeared in tubuloepithelial cells at 6 w after DM onset. Taken together, abnormal ketone body metabolism may be the key factor in the progression of DKD. Targeting metabolic abnormalities of ketone bodies may represent a novel therapeutic strategy for DKD. These identified novel molecular signatures in DKD merit further clinical investigation.

Heparin-free adventitia pulmonary oxygenation in the treatment of trauma complicated with severe pulmonary infection: a case report.

The application of Venovenous (VV) extracorporeal membrane oxygenation (ECMO) in trauma and patients with severe bleeding tendency has been controversial. However, VV ECMO without anticoagulation contributes to reducing the risk of bleeding during ECMO maintenance. VV ECMO serves critical roles in therapy of patients with severe pulmonary infection and failure in conventional therapy. The common peripheral catheterization approach for VV ECMO is femoral vein-internal jugular vein catheterization, and bilateral femoral vein catheterization can also achieve the purpose of respiratory support for patients with limited cervical catheterization. In this case report, we described a patient with post-traumatic cervical spinal cord injury and severe pulmonary infection who was successfully treated with heparin-free intravenous ECMO.

Hypothermia prevents hippocampal oxidative stress and apoptosis via the GSK-3ß/Nrf2/HO-1 signaling pathway in a rat model of cardiac arrest-induced brain damage.

OBJECTIVES: The present study was undertaken to investigate the effects and related mechanisms of hypothermia on oxidative stress and apoptosis caused by cardiac arrest (CA)-induced brain damage in rats. METHODS: The CA/CPR model was initiated by asphyxia. Body temperature in the normothermia and hypothermia groups was maintained at 37°C ± 0.2°C and 34°C ± 0.2°C, respectively, by surface cooling with an ice pack. First, neurological deficit scores (NDSs) were assessed, and then hippocampus samples were collected at 24 and 72 h after return of spontaneous circulation (ROSC). RESULTS: The NDSs of rats were significantly reduced after CA, and hypothermia ameliorated neurological deficits. Varying degrees of changes in cellular nuclei and mitochondria were observed in the hippocampus following CA; however, morphological changes became less apparent after therapeutic hypothermia. Malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were higher in the hippocampus at 24 h after ROSC. In contrast, hypothermia did not alter MDA content, while SOD activity further increased. Furthermore, hypothermia reversed the caspase-3 enhancement observed in the normothermia group at 24 h after ROSC. CA also inhibited GSK-3ß phosphorylation, promoted Nrf2 translocation to the nucleus, and downregulated HO-1 expression. However, hypothermia significantly reversed these CA-induced changes in GSK-3ß phosphorylation, Nrf2 translocation, and HO-1 expression. CONCLUSION: Hypothermia attenuated CA-induced neurological deficits and hippocampal morphology changes in rats. The protective effect of hypothermia following CA may have been related to inhibition of oxidative stress and apoptosis, and its underlying mechanisms may have been due, at least in part, to activation of the GSK-3ß/Nrf2/HO-1 pathway.

Hypothermia protects neurons against ischemia/reperfusion-induced pyroptosis via m6A-mediated activation of PTEN and the PI3K/Akt/GSK-3ß signaling pathway.

Cerebral ischemia/reperfusion (I/R) injury often leads to irreversible neuronal injury and even death, and hypothermia is the only therapeutic method that has been proven to be effective. However, the molecular mechanisms underlying the effect of hypothermia treatment on I/R injury have not been fully elucidated. In the present study, we aimed to evaluate the neuroprotective effects and mechanisms of hypothermia against hypoxia/reoxygenation (H/R)-induced neuronal damage. Primary hippocampal neurons were exposed to H/R and were then treated with hypothermia. We observed that hypothermia significantly increased cellular viability, downregulated the expression of pyroptosis-related proteins-including NLR pyrin domain containing 3 (NLRP3), apoptotic speck-like protein containing CARD (ASC), cleaved Caspase-1, and Gasdermin-D (GsdmD) p30-and reduced secretion of the pro-inflammatory cytokines, IL-1ß and IL-18. Additionally, pretreatment with MCC950, a specific small-molecule inhibitor of the NLRP3 inflammasome, yielded a protective effect on cellular viability that was comparable to that of hypothermia treatment. Furthermore, hypothermia also significantly elevated the expression level of phosphatase and tensin homologous protein (PTEN) and activated the phosphorylation levels of protein kinase B (Akt) and glycogen synthase kinase-3ß (GSK-3ß). These protective effects of hypothermia on pyroptosis-related proteins and pro-inflammatory cytokines were partially reversed by the specific PI3K/Akt inhibitor, LY294002. Moreover, the methylated level of PTEN mRNA was elevated in hippocampal neurons upon H/R, whereas this level remained stable in the hypothermia group. Therefore, our findings suggest that hypothermia protects neurons against neuronal H/R-induced pyroptosis, and that m6A-mediated activation of PTEN and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/GSK-3ß signaling pathway may play crucial roles during this process.

RPS27, a sORF-Encoded Polypeptide, Functions Antivirally by Activating the NF-κB Pathway and Interacting With Viral Envelope Proteins in Shrimp.

A small open reading frame (smORF) or short open reading frame (sORF) encodes a polypeptide of <100 amino acids in eukaryotes (50 amino acids in prokaryotes). Studies have shown that several sORF-encoded peptides (SEPs) have important physiological functions in different organisms. Many ribosomal proteins belonging to SEPs play important roles in several cellular processes, such as DNA damage repair and apoptosis. Several studies have implicated SEPs in response to infection and innate immunity, but the mechanisms have been unclear for most of them. In this study, we identified a sORF-encoded ribosomal protein S27 (RPS27) in Marsupenaeus japonicus. The expression of MjRPS27 was significantly upregulated in shrimp infected with white spot syndrome virus (WSSV). After knockdown of MjRPS27 by RNA interference, WSSV replication increased significantly. Conversely, after MjRPS27 overexpression, WSSV replication decreased in shrimp and the survival rate of the shrimp increased significantly. These results suggested that MjRPS27 inhibited viral replication. Further study showed that, after MjRPS27 knockdown, the mRNA expression level of MjDorsal, MjRelish, and antimicrobial peptides (AMPs) decreased, and the nuclear translocation of MjDorsal and MjRelish into the nucleus also decreased. These findings indicated that MjRPS27 might activate the NF-κB pathway and regulate the expression of AMPs in shrimp after WSSV challenge, thereby inhibiting viral replication. We also found that MjRPS27 interacted with WSSV's envelope proteins, including VP19, VP24, and VP28, suggesting that MjRPS27 may inhibit WSSV proliferation by preventing virion assembly in shrimp. This study was the first to elucidate the function of the ribosomal protein MjRPS27 in the antiviral immunity of shrimp.

A Small GTPase, RhoA, Inhibits Bacterial Infection Through Integrin Mediated Phagocytosis in Invertebrates.

The Ras GTPase superfamily, including more than 100 members, plays a vital role in a number of cellular processes, such as cytoskeleton recombination, gene expression, and signaling pathway regulation. Some members of the superfamily participate in innate immunity in animals. However, there have been few studies of RhoA on this aspect. In the present study, we identified a RhoA GTPase in the shrimp Marsupenaeus japonicus and named it MjRhoA. Expression of MjRhoA was significantly upregulated in hemocytes and heart of shrimp challenged with Vibrio anguillarum. Overexpression of MjRhoA in shrimp caused the total bacterial number to decrease significantly and knockdown of MjRhoA increased the bacterial number obviously, with a consequent decline in shrimp survival. These results confirmed the antibacterial function of MjRhoA in shrimp. Further study showed that rate of phagocytosis of hemocytes was decreased in MjRhoA-knockdown shrimp. Interestingly, we observed that MjRhoA was translocated onto the hemocyte membrane at 1 h post V. anguillarum challenge. The expression levels of the ß-integrin-mediated phagocytosis markers ROCK2 and Arp2/3 declined significantly after knockdown of MjRhoA. These results suggested that the antibacterial function of MjRhoA was related to ß-integrin-mediated phagocytosis in shrimp. Our previous study identified that a C-type lectin, hFcLec4, initiated ß-integrin mediated phagocytosis after bacterial infection. Thus, knockdown of hFcLec4 and ß-integrin was performed. The results showed that the translocation of MjRhoA from the cytoplasm to membrane was inhibited and the expression level of MjRhoA was decreased, suggesting that MjRhoA participated in hFcLec4-integrin mediated phagocytosis. Therefore, our study identified a new hFcLec4-integrin-RhoA dependent phagocytosis against bacterial infection in shrimp.

Use of Platelet Indices for Determining Illness Severity and Predicting Prognosis in Critically Ill Patients.

BACKGROUND: Decreased platelet (PLT) count is one of the independent risk factors for mortality in intensive care unit (ICU) patients. This study was to investigate the relationship between PLT indices and illness severity and their performances in predicting hospital mortality. METHODS: Adult patients who admitted to ICU of Changzheng Hospital from January 2011 to September 2012 and met inclusion criteria were included in this study. Univariate analysis was used to identify potential independent risk factors for mortality. Multiple logistic regression analysis was used to calculate adjusted odds ratio for mortality in patients with normal or abnormal PLT indices. The relationship between PLT indices and illness severity were assessed by the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores or sequential organ failure assessment (SOFA) scores in patients with normal and abnormal PLT indices. The performances of PLT indices in predicting mortality were assessed by receiver operating curves and diagnostic parameters. The survival curves between patients with normal and abnormal PLT indices were compared using Kaplan-Meier method. RESULTS: From January 2011 to September 2012, 261 of 361 patients (204 survivors and 57 nonsurvivors) met the inclusion criteria. After adjustment for clinical variables, PLT count <100 × 10 12 /L (P = 0.011), plateletcrit (PCT) <0.108 (P = 0.002), mean platelet volume (MPV) >11.3 fL (P = 0.023) and platelet distribution width (PDW) percentage >17% (P = 0.009) were identified as independent risk factors for mortality. The APACHE II and SOFA scores were 14.0 (9.0-20.0) and 7.0 (5.0-10.5) in the "low PLT" tertile, 13.0 (8.0-16.0) and 7.0 (4.0-11.0) in the "low PCT" tertile, 14.0 (9.3-19.0) and 7.0 (4.0-9.8) in the "high MPV" tertile, 14.0 (10.5-20.0) and 7.0 (5.0-11.0) in the "high PDW" tertile, all of which were higher than those in patients with normal indices. Patients with decreased PLT and PCT values (all P < 0.001), or increased MPV and PDW values (P = 0.007 and 0.003, respectively) had shortened length of survival than those with normal PLT indices. CONCLUSIONS: Patients with abnormally low PLT count, high MPV value, and high PDW value were associated with more severe illness and had higher risk of death as compared to patients with normal PLT indices.

[Prognostic value of arterial lactate content combined with base excess in patients with sepsis: a retrospective study].

OBJECTIVE: To study the prognostic value of arterial lactate combined with base excess (BE) in sepsis patients. METHODS: Clinical data of patients admitted to intensive care unit (ICU) from July 2009 to December 2012 were retrospectively analyzed. Patients were divided into survivor group and non-survivor group, and the arterial blood lactate and BE concentrations were compared between groups. The receiver operating characteristic curve (ROC curve) was drawn and area under the ROC curve (AUC) was calculated to analyze the function of arterial lactate, BE and their combination in judging the prognosis of sepsis. The best cut-off values of arterial lactate and BE for sepsis prognosis were searched. RESULTS: One hundred and eighteen patients were enrolled with 75 in survivor group and 43 in non-survivor group. There were significant differences in arterial lactate [1.20(0.90) mmol/L, 2.30(1.90) mmol/L] and BE (0.44 ± 5.13 mmol/L, -4.35 ± 4.86 mmol/L) between two groups (both P=0.000). The AUC for mortality prediction was 0.805, 0.755 and 0.822 for arterial blood lactate, BE, and their combination respectively. Using arterial lactate higher than 1.7 mmol/L and BE lower than -3 mmol/L as cut-off values, a better sensitivity (79.1% and 69.8%) and positive predictive value (3.955 and 2.493) can be obtained. CONCLUSION: Combination of arterial lactate and BE can be a better indicator of prognosis in sepsis patients.