Background Thoracic surgery with one-lung ventilation (OLV) leads to a postoperative inflammatory response. In this prospective randomized study, we compared the effect of esketamine-based anaesthesia on perioperative inflammatory cytokine levels in patients under routine anaesthesia with opioids undergoing thoracic surgery with OLV. Methods Adult patients undergoing wedge resections or total lobectomies under video-assisted thoracic surgery (VATS) were randomly assigned (1:1) to receive esketamine-based anaesthesia (Esketamine group, n = 22) or sufentanil-based anaesthesia (Sufentanil group, n = 22). Blood samples for measurement of inflammatory factors were collected from the radial artery at three time points: before anaesthesia induction (T1); 1 h after OLV (T2) and 2 h after surgery (T3). Peripheral venous blood was collected 24 hours before surgery (Preop) and 24 hours after surgery (Postop) to measure leukaemia cell lines and C-reactive protein (CRP). Results Compared with the sufentanil group, the increase in proinflammatory cytokines interleukin (IL)-6 (10.23 ± 5.60 vs. 20.97 ± 18.22 pg/ml, P = 0.029) and IL-8 secretions (4.88 ± 18.29 vs. 81.69 ± 130.34 pg/ml, P = 0.026) was significantly lower in the esketamine group 2 h after the intrathoracic procedure. CRP levels (24.36 ± 12.64 vs. 49.71 ± 29.60 mg/L, P < 0.001) and blood loss volumes (11.14 ± 4.86 ml vs. 28.18 ± 18.16 ml, P < 0.001) were significantly lower in the esketamine group than in the sufentanil group (24.36 ± 12.64 vs. 49.71 ± 29.60, P < 0.001). There was no difference in biometric data, surgical procedures, duration of surgery, OLV and mechanical ventilation, or length of hospital stay among the groups. Conclusions Our study demonstrates that esketamine possesses potent anti-inflammatory properties. Anaesthesia with esketamine may play a beneficial role in reducing both the OLV-induced systemic inflammatory response and intraoperative blood loss. Trial registration: ChiCTR2200065915. Registered on 18/11/2022.
Background. Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS). Methods. A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. Results. The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz ( P = 1.19 × 10 − 8 ). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for ( P < 1 × 10 − 5 ) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively ( P < 0.05 ). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. Conclusions. The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI.
Background Age-related hearing impairment (ARHI) has attracted increasing attention recently. It is caused by genetic and environmental factors. A number of ARHI-related genes have been found. This study aimed to detect the potential association between NR3C1 gene polymorphisms and ARHI by means of weighted allele score. Methods A total of 861 participants from Qingdao city were selected by means of cluster random sampling. We statistically evaluated the characteristics of individuals and used the Mann–Whitney U test or chi-square test for comparison. The publicly available expression quantitative trait locus (eQTL) was queried on the website of the Genotype-Tissue Expression (GTEx). We used the weighted allele score and logistic regression analysis to explore the association between NR3C1 gene polymorphisms and ARHI. Finally, the prediction model was constructed by logistic regression and receiver operating characteristic (ROC) curve. Results All individuals over 60 years of age were enrolled in this study. The allele of rs61757411, rs41423247 and rs6877893 were significantly different between the ARHI group and the normal hearing group (P < 0.01). Though eQTL analysis, rs6877893 and rs33388 might affect the occurrence of ARHI by affecting the expression of NR3C1 gene in artery aorta. Then we performed two models: one without adding any covariates into model and the other adjusting for demographic characteristic, smoking and drinking, diet and exercise, and physical conditions. In the multivariate-adjusted model 2, the odds ratio with 95% confidence interval for weighted allele score (NR3C1) was 0.841 (0.710–0.995, P = 0.043). The area under the ROC curve was 0.755, indicating that the model had good predictability. Conclusions Our study suggests that NR3C1 gene polymorphisms was significantly associated with ARHI.
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