Dexmedetomidine: a real-world safety analysis based on FDA adverse event reporting system database.

Objective: Using the FDA adverse event reporting system (FAERS) database to analyze the safety profile of Dexmedetomidine and provide guidance for clinical application. Methods: Data from the FAERS database from the first quarter of 2004 to the third quarter of 2023 were collected. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), and the Bayesian confidence propagation neural network (BCPNN) were employed to detect and assess adverse events associated with Dexmedetomidine. Results: A total of 1910 reports of Dexmedetomidine as the primary suspect drug were obtained. After screening, 892 preferred terms were obtained, including 52 new preferred terms not mentioned in the drug insert. The common adverse events of Dexmedetomidine include bradycardia, cardiac arrest, hypotension, diabetes insipidus, arteriospasm coronary and agitation. Notably, cardiac disorders exhibited the highest number of reports and the highest signal intensity in the system organ class. Among the new preferred terms, those with high signal intensity include transcranial electrical motor evoked potential monitoring abnormal, acute motor axonal neuropathy, trigemino-cardiac reflex, glossoptosis, floppy iris syndrome, phaeochromocytoma crisis, postresuscitation encephalopathy and diabetes insipidus. Conclusion: This study mined and evaluated adverse events associated with Dexmedetomidine and also identified new adverse events. This could help alert clinicians to new adverse events not mentioned in the drug inserts, reducing the risk of drug.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Characterization of a germline variant TNS1 c.2999-1G > C in a hereditary cancer syndrome family.

Hereditary cancer syndromes result from the presence of inherited pathogenic variants within susceptibility genes. However, the susceptibility genes associated with hereditary cancer syndrome remain predominantly unidentified. Here, we reported a case of hereditary cancer syndrome observed in a Chinese family harboring a germline mutation in Tensin1 (TNS1). We described a 59-year-old female patient presented with Multiple myeloma and Thyroid carcinoma. The proband and her family members exhibited suspected tumor syndrome due to occurrences of other cancer cases. After oncogenetic counseling, whole-exome sequencing and Sanger sequencing were conducted and a primary driver mutation of TNS1 (NM_022648.7:c.2999-1G > C) was detected. Gene Expression Profiling Interactive Analysis revealed that TNS1 was expressed lower in different tumors when compared to normal, including Pancreatic adenocarcinoma, Breast invasive carcinoma, Thyroid carcinoma andColon adenocarcinoma cells. Despite the well-established role of TNS1 as a tumor suppressor in breast cancer and colorectal cancer, its potential utility as a marker gene for diagnosis and treatment of pancreatic cancer remains uncertain. Here, our data demonstrated that knockdown of TNS1 could promote cell proliferation and migration in Pancreatic adenocarcinoma (PDAC) cells. In addition, TNS1 regulated migration through EMT signaling pathway in PDAC cells. Our findings proposed that this variant was likely involved in cancer predisposition by disrupting the normal splicing process. In summary, we presented a genetic disease by linking an intronic mutation inTNS1. We aim to provide early detection of cancers by identifying germline variants in susceptibility genes.

A novel RBBP8(p.E281*) germline mutation is a predisposing mutation in familial hereditary cancer syndrome.

Screening tumor susceptibility genes helps in identifying powerful biomarkers for hereditary cancer monitoring, prevention, and diagnosis, providing opportunities for understanding potential molecular mechanisms and biomarkers for the precise treatment of hereditary cancer syndromes. Whole-exome sequencing of blood and bioinformatics analysis uncovered a novel RBBP8(p.E281*) germline mutation in a family with hereditary cancer syndrome, which was verified by Sanger sequencing. Cell proliferation, colony formation, cell migration, and in vivo tumorigenesis were investigated by CCK8, colony formation, Transwell, and in vivo xenograft assays. Protein localization and interaction were detected by immunofluorescence, nuclear and cytoplasmic protein extraction kits, and Co-IP. A new heterozygous germline mutation of the RBBP8(p.E281*) gene was found to be associated with familial hereditary cancer syndrome. RBBP8-WT was mainly detected in the nucleus and interacts with BRCA1. In contrast, RBBP8(p.E281*) is mainly located in the cytoplasm, with no interaction with BRCA1. RBBP8(p.E281*) variant plays an oncogenic role in the cytoplasm in addition to its loss of function in the nucleus, which promotes breast cancer proliferation, in vivo tumorigenesis, and migration. Compared with the control group, RBBP8(p.E281*) showed elevated cell death in response to cisplatin and olaparib treatment. A novel RBBP8(p.E281*) germline mutation was identified from familial hereditary cancer syndrome. RBBP8(p.E281*) is not able to enter the nucleus or interact with BRCA1 through the lost binding motif, and RBBP8(p.E281*) variant appears to promote tumorigenesis in the cytoplasm in addition to its loss of function in the nucleus. RBBP8(p.E281*) variant may promote tumor susceptibility and serve as a precision medicine biomarker in familial hereditary cancer syndrome. KEY MESSAGES: RBBP8(p.E281*) is a susceptibility gene in this familial hereditary cancer syndrome RBBP8(p.E281*) lost its ability to enter the nucleus and the BRCA1 binding motif A novel RBBP8(p.E281*) germline mutation promotes breast cancer tumorigenesis Patients with RBBP8(p.E281*) germline mutation may benefit from Olaparib, Cisplatin.

Molecular Mechanisms of Gynostemma pentaphyllum in Prevention and Treatment of Non-Small-Cell Lung Cancer.

Objective: Lung cancer represents the leading cause of cancer death on a global scale. Gynostemma pentaphyllum (G. pentaphyllum), a traditional medicinal material with a high medicinal and health value, has recently been reported for its anticancer activity. However, the pharmacological mechanism of G. pentaphyllum in non-small-cell lung cancer (NSCLC) remains to be elucidated. Methods: The active ingredients of G. pentaphyllum were obtained from the TCMSP database and known therapeutic targets of NSCLC from the GeneCards and OMIM databases. Disease-drug common targets are subjected to protein-protein interaction (PPI), GO enrichment analysis, and KEGG pathway enrichment analysis. A molecular docking strategy was performed to verify the interaction between molecules. Results: We found a total of 24 compounds of G. pentaphyllum fulfilling OB ≥ 30% concomitant with DL ≥ 0.18 and corresponding 81 target genes in the TCMSP database, with 5062 NSCLC-related genes collected in the GeneCards and OMIM databases. The network consisting of the disease-target compound was obtained, including 8 active ingredients and 69 common targets. The PPI network with 65 nodes and 645 edges was visualized. After functional enrichment analysis, it was revealed that the therapeutic effects of G. pentaphyllum on NSCLC were achieved through response to ketone, gland development, and cellular response to xenobiotic stimulus. After molecular docking analysis, it was revealed that the two active ingredients of G. pentaphyllum, quercetin and rhamnazin, bound well and stably to their targets (MYC, ESR1, and HIF1A). Conclusion: Our study, based on network pharmacology, identifies active ingredients, targets, and pathways model mechanism of G. pentaphyllum when it is used to treat NSCLC.