Exploring adverse events of Vilazodone: evidence from the FAERS database.

OBJECTIVE: This study aims to conduct an exhaustive evaluation of Vilazodone's safety in clinical application and to unearth the potential adverse event (AE) risks associated with its utilization based on FDA Adverse Event Reporting System (FAERS) database. METHODS: This research employed data spanning from the first quarter of 2011 to the third quarter of 2023 from the FAERS database. Various signal detection methodologies, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), were utilized to ascertain the correlation between Vilazodone and specific AEs. RESULTS: The study compiled a total of 17,439,268 reports of drug AEs, out of which 5,375 were related to Vilazodone. Through signal mining, 125 Preferred Terms (PTs) encompassing 27 System Organ Classes (SOCs) were identified. The findings indicated a higher prevalence among females and patients within the 45 to 65 age bracket. The principal categories of AEs included Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders, with prevalent incidents of Diarrhoea, Nausea, and Insomnia. Moreover, the study identified robust signals of novel potential AEs, notably in areas such as sleep disturbances (Sleep paralysis, Hypnagogic hallucination, Rapid eye movements sleep abnormal, Sleep terror, Terminal insomnia, Tachyphrenia), sexual dysfunctions (Female orgasmic disorder, Orgasm abnormal, Disturbance in sexual arousal, Spontaneous penile erection, Anorgasmia, Sexual dysfunction, Ejaculation delayed), and other symptoms and injuries (Electric shock sensation, Violence-related symptom, Gun shot wound). CONCLUSION: Although Vilazodone presents a positive prospect in the management of MDD, the discovery of AEs linked to its use, particularly the newly identified potential risks such as sleep and sexual dysfunctions, necessitates heightened vigilance among clinicians.

The expression of immune related genes and potential regulatory mechanisms in schizophrenia.

OBJECTIVE: This study aimed to investigate the role of immune dysfunction in the pathogenesis of schizophrenia through single-cell transcriptome and bulk RNA data analyses. METHODS: The single-cell RNA sequencing (scRNA-seq) was selected to assess the cellular composition and gene expression profiles of the brain tissue. Further, bulk RNA sequencing data was utilized to corroborate findings from the single-cell analyses and provide additional insights into the molecular changes associated with the disease. Gene-drug interaction data was also included to identify potential therapeutic drugs targeting these dysregulated immune-related genes in schizophrenia. RESULTS: We discovered significant differences in cellular composition within schizophrenia tissue, including increased infiltration of fibroblasts, horizontal basal cells, monocytes, mesenchymal cells, and smooth muscle cells. The investigation of immune-related genes revealed significantly different expression of genes such as S100A2, CCL14, IGHA1, BPIFA1, GDF15, IL32, BPIFB2, HLA-DRA, S100A8, PTX3, TPM2, TNFRSF12A, GREM1 and others. These genes possibly contribute to the progression of schizophrenia through various pathways such as humoral immune response, IL-17 signaling pathway, adaptive immune response, antigen processing and presentation, and gut IgA production. Our findings also suggest possible transcriptional regulation in schizophrenia's immune dysfunction by transcription factors in monocytes, neutrophils, endothelial cells, and epithelial cells. Lastly, potential therapeutic drugs were identified through gene-drug interaction data, such as those targeting HLA-A and HLAB. CONCLUSION: The cellular heterogeneity and immune-related gene dysregulation play important roles in schizophrenia, which provides a foundation for understanding the pathogenesis and developing new treatment methods.

Causal relationship between schizophrenia and sex hormone binding globulin: A Mendelian randomization study.

OBJECTIVE: The underlying etiology of schizophrenia is still not fully understood, and recent studies have pointed to a potential link between hormonal factors and the risk of developing this condition. Sex Hormone-Binding Globulin (SHBG) is a protein that regulates the bioavailability of sex hormones. However, the causal relationship between SHBG levels and schizophrenia remains unclear, this study aimed to investigate the causal relationship based on two-sample Mendelian randomization (MR) analysis. METHODS: This study was based on the summary data of genome-wide association studies (GWAS) of schizophrenia and SHBG in European populations. Two-sample MR was applied, and genetic factors were used as instrumental variables, and the causal relationship between schizophrenia and SHBG was assessed. RESULTS: We selected 79 single nucleotide polymorphisms with genome-wide significance from the schizophrenia GWAS as instrumental variables. The inverse variance weighting (IVW) method results showed that there is a causal relationship and a positive correlation between schizophrenia and female SHBG, with an odds ratio (OR) of 1.024 (95%CI: 1.007-1.042, P = 0.005), and this result was further confirmed by the Weighted median odds ratio (OR) of 1.032 (95%CI: 1.016-1.048, P = 5.58E-05) and the Weighted mode of 1.035 (95%CI: 1.004-1.067, P = 0.028). Schizophrenia and male SHBG also have a causal relationship and a positive correlation, with an odds ratio (OR) of 1.027 (95%CI: 1.007-1.047, P = 0.008). CONCLUSION: This study found a positive correlation between schizophrenia and SHBG in both men and women through MR analysis, indicating that the level of SHBG may be elevated in patients with schizophrenia, regardless of gender.

Transcriptome analysis reveals tumor antigen and immune subtypes of melanoma.

Purpose: To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes. Methods: Transcriptional data (HTSEQ-FPKM) and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma (SKCM) were downloaded from the UCSC XENA website (http://xena.ucsc.edu/). Subsequently, transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus (GEO), a large global public database. All the transcriptome expression data matrices were log2 transformed for subsequent analysis. GEPIA, TIMER, and IMMPORT databases are also used for analysis. Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375. Results: Our study provides potential tumor antigens for vaccine development in melanoma patients: GZMB, GBP4, CD79A, APOBEC3F, IDO1, JCHAIN, LAG3, PLA2G2D, XCL2. In addition, we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination. In view of the unclear role of IDO1 in melanoma, we selected IDO1 for cell assay validation. Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line. After IDO1 knockdown, the activity, invasion, migration and healing ability of A375 cell lines were significantly decreased. Conclusion: Our study could provide a reference for the development of vaccines for melanoma patients.

Significance of liquid-liquid phase separation (LLPS)-related genes in breast cancer: a multi-omics analysis.

Currently, the role of liquid-liquid phase separation (LLPS) in cancer has been preliminarily explained. However, the significance of LLPS in breast cancer is unclear. In this study, single cell sequencing datasets GSE188600 and GSE198745 for breast cancer were downloaded from the GEO database. Transcriptome sequencing data for breast cancer were downloaded from UCSC database. We divided breast cancer cells into high-LLPS group and low-LLPS group by down dimension clustering analysis of single-cell sequencing data set, and obtained differentially expressed genes between the two groups. Subsequently, weighted co-expression network analysis (WGCNA) was performed on transcriptome sequencing data, and the module genes most associated with LLPS were obtained. COX regression and Lasso regression were performed and the prognostic model was constructed. Subsequently, survival analysis, principal component analysis, clinical correlation analysis, and nomogram construction were used to evaluate the significance of the prognostic model. Finally, cell experiments were used to verify the function of the model's key gene, PGAM1. We constructed a LLPS-related prognosis model consisting of nine genes: POLR3GL, PLAT, NDRG1, HMGB3, HSPH1, PSMD7, PDCD2, NONO and PGAM1. By calculating LLPS-related risk scores, breast cancer patients could be divided into high-risk and low-risk groups, with the high-risk group having a significantly worse prognosis. Cell experiments showed that the activity, proliferation, invasion and healing ability of breast cancer cell lines were significantly decreased after knockdown of the key gene PGAM1 in the model. Our study provides a new idea for prognostic stratification of breast cancer and provides a novel marker: PGAM1.

Application of "Internet +" pharmaceutical consultation services in psychiatric hospital during the epidemic.

This study explored the application value of "Internet +" pharmacy service on psychiatric hospital during the COVID-19 epidemic. During the epidemic, as of December 31, 2020, the number of online pharmacist consultations increased to 149 cases (82.78 %). At the same time, patients had various types of consultation questions, mainly involving adverse drug reactions, drug selection, usage and dosage, persistence of long-term medication, drug distribution, etc. Due to the particularity of psychiatric hospital, pharmaceutical consultation services mainly focus on nervous system drugs. The results indicated that the demand for "Internet +" pharmaceutical consultation services has increased significantly during the COVID-19 epidemic.

ADM-assisted prepectoral breast reconstruction is not associated with high complication rate as before: a Meta-analysis.

Implant-related breast reconstruction can be divided into subpectoral breast reconstruction (SPBR) and prepectoral breast reconstruction (PPBR) according to the different anatomical planes. The previous stereotype was that PPBR had a high complication rate and was not suitable for clinical use. However, with the emergence of acellular dermal matrix (ADM), the clinical effect of PPBR has been improved. To compare the outcomes difference between SPBR and PPBR, We conducted this meta-analysis. Articles on SPBR versus PPBR were searched in PubMed, Web of Sciences, Embase, and Cochrane databases, strictly following the PRISMA guidelines. According to the set criteria, we included the literature that met the requirements. Extracted data were the incidence of adverse events and the duration of drainage. Results show that SPBR has a higher incidence rate in capsular contracture, animation deformity, infection, hematoma and delayed healing wound than PPBR. There are no significant differences in skin flap necrosis, seroma, implant loss, reoperation and duration of drainage between the two groups. Hence, PPBR is no longer a high complication surgical method and can be used in the clinical practice. However, there are few large sample studies at present, so it is necessary to carry out further studies on PPBR.

Role and mechanism of ferroptosis in neurological diseases.

BACKGROUND: Ferroptosis, as a new form of cell death, is different from other cell deaths such as autophagy or senescence. Ferroptosis involves in the pathophysiological progress of several diseases, including cancers, cardiovascular diseases, nervous system diseases, and kidney damage. Since oxidative stress and iron deposition are the broad pathological features of neurological diseases, the role of ferroptosis in neurological diseases has been widely explored. SCOPE OF REVIEW: Ferroptosis is mainly characterized by changes in iron homeostasis, iron-dependent lipid peroxidation, and glutamate toxicity accumulation, of which can be specifically reversed by ferroptosis inducers or inhibitors. The ferroptosis is mainly regulated by the metabolism of iron, lipids and amino acids through System Xc-, voltage-dependent anion channels, p53, p62-Keap1-Nrf2, mevalonate and other pathways. This review also focus on the regulatory pathways of ferroptosis and its research progress in neurological diseases. MAJOR CONCLUSIONS: The current researches of ferroptosis in neurological diseases mostly focus on the key pathways of ferroptosis. At the same time, ferroptosis was found playing a bidirectional regulation role in neurological diseases. Therefore, the specific regulatory mechanisms of ferroptosis in neurological diseases still need to be further explored to provide new perspectives for the application of ferroptosis in the treatment of neurological diseases.

Establishment and application value of a novel prescription medication abuse monitoring model for psychiatric hospitals.

Objective: To construct a prescription medication abuse (PMA) monitoring model for psychiatric hospitals and to assess its applicability. Methods: A PMA monitoring working group was established to guide the formulation of a PMA monitoring system, which included three active real-time monitoring modes and one retrospective analysis monitoring mode. The effect of the established system was analyzed. Results: In 2021, 35 cases of effective PMA were reported, which was a significant increase compared to two cases identified through passive monitoring mode in the preceding year. Most of the reported cases were based on active real-time monitoring mode. Among them, 21 cases (60.00%) were identified during the diagnosis and treatment of medicine and nursing; 3 cases (8.57%) were reported based on drug concentration detection technology; and 5 cases (14.29%) were reported by the laboratory department during PMA screening. Besides, 6 cases (17.14%) were reported according to the retrospective analysis of the hospital information system. The majority of prescription medication abusers were adolescents under the age of 18 (12 cases, 34.29%). Overall, there were 27 cases of class II psychotropic prescription medications, accounting for 77.14%. Conclusion: The combined PMA monitoring model can effectively improve the quality of PMA monitoring and provide a basis for the supervision of higher-level regulatory authorities.

Database mining analysis revealed the role of the putative H+/sugar transporter solute carrier family 45 in skin cutaneous melanoma.

Metabolic reprogramming is common in various cancers. Targeting metabolism to treat tumors is a hot research topic at present. Among them, changes in glucose metabolism in cancer have been widely studied. The Warburg effect maintains a high metabolic level in the tumor, accompanied by changes in glucose transporters. The transmembrane transport of sugar was previously thought to be mediated by SGLT and GLUT. Recently, the Solute Carrier Family(SLC) 45 family may be the third sugar transporter. But the role and value of the SLC45 family in melanoma, a highly malignant skin tumor, is unclear. Our study found that the four members of the SLC45 family, SLC45A1-SLC45A4, were differentially expressed in melanoma, but only SLC45A2 and SLC45A3 had prognostic guiding values. Further analysis revealed that the co-expression patterns of SLC45A2 and SLC45A3 were enriched in multiple metabolic pathways, suggesting their potential role in melanoma. In addition, SLC45A2 and SLC45A3 are also associated with immune cell infiltration. In conclusion, SLC45A2 and SLC45A3 are good prognostic indicators for melanoma and have guiding value for the treatment of melanoma in the future.

Hypoxia induces HT-22 neuronal cell death via Orai1/CDK5 pathway-mediated Tau hyperphosphorylation.

Hypoxia and apoptosis are involved in the pathogenesis of Alzheimer's disease (AD). Hypoxia induces the formation of amyloid precursor protein in neurons, leading to the abnormal deposition of ß-amyloid protein and hyperphosphorylation of Tau. Such changes increase the risk of AD. In the present study, a cellular model of hypoxia-induced AD was established by exposing HT-22 mouse hippocampal neurons to the chemical hypoxia-mimicking agent cobalt chloride (CoCl2). It was found that hypoxia increased neuronal apoptosis. Hypoxia caused an abnormal increase in the expression of the intracellular calcium channel protein Orai1 and cyclin-dependent kinase 5 (CDK5), resulting in hyperphosphorylation of Tau. Treatment with small-interfering RNA against Orai1 (siOrai1) or an Orai1-overexpression plasmid effectively intervened the CDK5-mediated hyperphosphorylation of Tau. In summary, following hypoxic injury of neuron, the Orai1-induced expression of CDK5 leads to Tau hyperphosphorylation. Tau hyperphosphorylation is an important pathophysiological manifestation in AD patients. These results indicated that hypoxia induces HT-22 cell death by Orai1/CDK5 pathway mediated Tau hyperphosporylation. This study simulated the pathological process associated with AD and proposed that hypoxia of intravascular cells with normal blood oxygen saturation might be one of a pathogenic mechanisms of AD. Therefore, this work may provide a new theoretical basis for AD prevention and treatment.

TSNARE1 polymorphisms are associated with schizophrenia susceptibility in Han Chinese.

t-SNARE domain containing 1 gene (TSNARE1) is located at human chromosome 8q24.3, and may play a crucial role in intracellular protein transport and synaptic transmission. Recently, a large-scale meta-analysis of genome-wide association study dataset identified that rs10098073 and rs4129585, two single nucleotide polymorphisms (SNPs) within TSNARE1, were closely associated with the risk of schizophrenia in Caucasians. However, this finding has not been validated in other populations or ethnic groups thus far. In the current study, we conducted a case-control study to confirm the association of these two SNPs with the schizophrenia risk in a Han Chinese population comprising 440 schizophrenia patients and 450 control subjects. According to the genotype data of Han Chinese from Beijing in 1,000 Genomes Project database, rs10098073 and rs4129585 were located in one haplotype block and were in almost complete linkage disequilibrium (D' = 1, r (2) ≥ 0.952). Therefore, only rs10098073 was selected for the subsequent analysis. We showed for the first time that the minor allele (A) of rs10098073 was associated with a reduced risk of schizophrenia (OR = 0.753; 95 % CI 0.613-0.924; P = 0.007). Furthermore, we found that the A allele of rs10098073 reduced the schizophrenia risk through a recessive manner (A/A vs. A/C + C/C, OR = 0.563; 95 % CI 0.357-0.89; P = 0.013, P Bonferroni corrected = 0.026) rather than a dominant manner (A/A + A/C vs. C/C, OR = 0.762; 95 % CI 0.586-0.992; P = 0.043, P Bonferroni corrected = 0.086). Taken together, these findings demonstrate a significant association between TSNARE1 polymorphisms and schizophrenia risk in a Han Chinese population, suggesting TSNARE1 may represent a susceptibility gene for this disease.

rs11098403 polymorphism near NDST3 is associated with a reduced risk of schizophrenia in a Han Chinese population.

A recent genome-wide association study indicated that rs11098403, a single nucleotide polymorphism in the vicinity of NDST3, was strongly associated with the risk of schizophrenia in Caucasians. However, this relation has not been validated in other populations or ethnic groups. Herein, we conducted a case-control study to investigate the association of rs11098403 polymorphism with the schizophrenia risk in a Han Chinese population comprising 440 schizophrenia patients and 450 control subjects. For the first time, we showed that the minor allele (G) of rs11098403 is closely associated with a reduced risk of schizophrenia (OR=0.614; 95% CI: 0.453-0.833; P=0.002; Power=0.832). Meanwhile, the G allele of rs11098403 seemed to reduce the schizophrenia risk via a dominant manner (GG+AG vs. AA, OR=0.526; 95% CI: 0.374-0.74; P<0.001). Furthermore, this association was further confirmed using an independent replication sample containing 267 schizophrenia patients and 400 control subjects with a Han Chinese descent (OR=0.652; 95% CI: 0.469-0.907; P=0.011; Power=0.772). Taken together, these findings demonstrate a significant association between rs11098403 and schizophrenia risk in Han Chinese, confirming the data that previously obtained from Caucasians.