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TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2. [ABSTRACT FROM AUTHOR]

Background: Pre-operative prediction of postoperative nausea and vomiting (PONV) is primarily based on the patient's medical history. The predictive value of gastric morphological parameters observed on ultrasonography has not been comprehensively assessed., Methods: A prospective observational study was conducted to evaluate the pre-operative ultrasonographic measurement of gastric morphology for predicting PONV. The gastric antrum of the participants was assessed using ultrasound before anesthesia, and the occurrence of PONV in the first 6 hours and during the 6-24 hours after surgery was reported. The main indicators included the thickness of the muscularis propria (TMP) and the cross-sectional area of the inner side of the muscularis propria (CSA-ISMP). These were recorded and analyzed. Logistic regression analysis was applied to identify factors for PONV., Results: A total of 72 patients scheduled for elective gynecological laparoscopic surgery were investigated in the study. The pre-operative CSA-ISMP of patients with PONV in the first 6 hours was significantly greater than that of those without PONV (2.765 ± 0.865 cm² vs 2.349 ± 0.881 cm², P=0.0308), with an area under the curve of 0.648 (95% CI, 0.518 to 0.778, P=0.031). Conversely, the pre-operative TMP of patients with PONV during the 6-24 hours was significantly smaller than that of those without PONV (1.530 ± 0.473 mm vs 2.038 ± 0.707 mm, P=0.0021), with an area under the curve of 0.722 (95% CI, 0.602 to 0.842, P=0.003). Logistic regression analysis confirmed that CSA-ISMP was an independent risk factor for PONV in the first 6 hours (OR=2.986, P=0.038), and TMP was an independent protective factor for PONV during the 6-24 hours after surgery (OR=0.115, P=0.006)., Conclusion: Patients with a larger pre-operative CSA-ISMP or a thinner TMP are prone to develop PONV in the first 6 hours or during the 6-24 hours after surgery, respectively., China Clinical Trial Registration Center: http://www.chictr.org.cn (ChiCTR2100055068)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qiu, Yin, Liang, Shi, Liu, Zhang, Bai, Chen and Xiong.)

Aims: Postoperative cognitive dysfunction (POCD) is a neurological disorder associated with neuroinflammation. Connexin 43 (Cx43), an essential component of gap junction, plays a crucial role in neuroinflammation. The present study was designed to investigate the role of Cx43 in the process of POCD., Methods: POCD model was established in aged mice with internal fixation of tibial fractures. Cognitive function was examined using the Morris water maze test. Hippocampus was collected for reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence assays., Results: In the water maze test, mice undergoing surgery took longer time to reach target platform than the controls. IL-1β and TNF-α mRNA expressions in the hippocampus were significantly increased in surgery mice. Cx43 protein presence in the hippocampus was increased in the surgery group. Treatment of Gap26, a specific blocker of Cx43 hemichannel, reduced the Cx43 protein presence, decreased mRNA expressions of IL-1β and TNF-α, and improved cognitive score in the maze test., Conclusion: Internal fixation of tibial fractures in aged mice induces Cx43 hemichannels opening and enhances neuroinflammation in the hippocampus, leading to cognitive impairment. Administration of Gap26 reduces neuroinflammation in the hippocampus and improves postoperative cognitive function., Competing Interests: None.

The perioperative stress response is one of the factors leading to postoperative cognitive dysfunction (POCD). Dexmedetomidine (Dex) can reduce the stress response and hippocampus neuroapoptosis, but its mechanism of action on POCD remains unknown. This study investigated the protective effect and possible mechanism of Dex on POCD in aged rats. Ninety-six aged male rats were randomly divided into four groups (n = 24 rats per group): a non-surgical control group, a surgical (model) group, a surgical group receiving a high dose of Dex (12 μg/kg), and a surgical group receiving a low dose of Dex (3 μg/kg). Cognitive function and neuronal apoptosis were evaluated after splenectomy. Compared with the control group, the model group had significantly longer escape latencies and fewer platform crossings in the Morris water-maze test. Immunohistochemistry showed that relaxin-3 and c-fos positive neurons in the hippocampus increased on postoperative days 1 and 3. Greater downregulation of the Bcl-2 protein and upregulation of Fas, caspase-8, and caspase-9 significantly increased neuroapoptosis in the model group. Compared with the model group, rats given Dex had (1) shorter escape latencies, (2) more platform crossings, (3) fewer relaxin-3 and c-fos positive neurons in the hippocampal CA1 area, (4) upregulation of Bcl-2, (5) downregulation of Fas, caspase-8, and caspase-9 proteins, and (6) decreased neuroapoptosis in the hippocampus. Thus, our data suggest that Dex may improve cognitive functioning in aged rats by inhibiting neural over-excitability. The mechanism may operate by restraining relaxin-3 and c-fos expression.