Explore the vast range of titles available.

To investigated the link between the systemic immunity-inflammation index (SII), a new inflammatory biomarker, and the risk of abnormal glucose regulation in non-diabetic population. Using data from the 2005-2016 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study on non-diabetic adults with data on SII and glucose regulation markers. We analyzed the relationship between SII and indicators of glucose regulation, including fasting plasma glucose, fasting insulin, hemoglobin A1c, oral glucose tolerance test (OGTT), and states of abnormal glucose regulation like impaired glucose tolerance (IGT), insulin resistance, and prediabetes. Adjusting for confounders, higher SII levels were significantly associated with a higher OGTT and a greater likelihood of IGT (OR = 2.673, 95% CI: 1.845, 3.873). In subgroup analysis, participants without hyperlipidemia in the highest SII quartile had a 240% higher odds of IGT compared to those in the lowest quartile (OR = 3.407, 95%CI: 1.995, 5.820), an association not observed in those with hyperlipidemia (p for interaction < 0.05). SII emerges as a useful biomarker for identifying IGT in non-diabetic individuals, specifically in those without hyperlipidemia.

Background Midlife obesity is a modifiable risk factor for Alzheimer’s disease. However, the association between childhood obesity and Alzheimer’s disease remains largely unknown. Therefore, we conducted a mendelian randomization analysis (MR) to assess the causal link between childhood obesity and Alzheimer’s disease. Methods Using summary statistics from publicly available genome-wide association studies (GWAS) database, we explored the genetic link between childhood obesity and Alzheimer’s disease through a two-sample MR. The primary analysis employed the inverse-variance weighted (IVW) method. To complement our findings, we also employed MR-Egger, weighted median, simple model, and weighted model methods for MR estimates. Furthermore, we conducted Cochrane’s Q-statistic test, Egger intercept test, and a leave-one-out sensitivity test to ensure the robustness and reliability of our results. Results The IVW analysis yielded non-significant results, indicating no significant genetic association between childhood obesity and Alzheimer’s disease (OR = 0.958, 95% CI = 0.910–1.008, p  = 0.095). Consistent with this, the results from MR-Egger, the weighted median, simple model, and weighted model approaches all supported these findings. Furthermore, we did not detect any signs of heterogeneity or pleiotropy, and our leave-one-out analysis confirmed that no single nucleotide polymorphisms had a substantial impact on the reliability of our results. Conclusions The evidence from our MR analyses suggests that there is no causal effect of childhood obesity on the risk of Alzheimer’s disease.

Background Diacylglycerol O-acyltransferase 1 (DGAT1) is crucial for triglyceride synthesis, yet its role in ischemic stroke remains unclear. This study investigated DGAT1 in ischemic stroke using middle cerebral artery occlusion (MCAO) rat models and highly differentiated PC12 cells subjected to oxygen–glucose deprivation/reoxygenation (OGD/R). Methods The therapeutic effects of DGAT1 inhibition in MCAO rats were assessed using the Zea-Longa score and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. The effects on highly differentiated PC12 cells subjected to OGD/R were evaluated using the Cell Counting Kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays. Ferroptosis-related mitochondrial damage was evaluated using transmission electron microscope. Additionally, the mechanisms by which DGAT1 inhibition regulates ferroptosis were further explored via immunohistochemistry, immunofluorescence, Western blotting, qPCR, JC-1 assay, and reactive oxygen species (ROS) detection. Results DGAT1 expression was elevated in both MCAO and OGD/R models. The DGAT1 inhibitor A 922500 improved neurological deficits, reduced infarct volume, and minimized neuronal loss in MCAO rats, while also enhancing cell viability and reducing LDH levels in OGD/R-treated PC12 cells. DGAT1 inhibition significantly alleviated ferroptosis in MCAO rats, as indicated by (i) reduced mitochondrial shortening and cristae disruption, (ii) decreased 4-HNE levels, (iii) reduced MDA and increased SOD, and (iv) lowered levels of inflammatory factors (IL-6, MCP-1, and TNF-α). Moreover, both in vivo and in vitro experiments showed that DGAT1 inhibition significantly increased Gpx4 levels, whereas lentiviral delivery of Gpx4 shRNA markedly reversed its beneficial effects. In MCAO rats, Gpx4 shRNA significantly elevated 4-HNE levels and exacerbated ferroptosis-related mitochondrial damage. In vitro, DGAT1 inhibition increased mitochondrial membrane potential and reduced ROS, whereas rotenone, a mitochondrial function inhibitor, decreased Gpx4 and impaired cell viability. Furthermore, DGAT1 inhibition significantly upregulated the key β-oxidation gene Cpt1a , whereas etomoxir, a β-oxidation inhibitor, reduced cell viability and mitochondrial membrane potential, increased ROS, and downregulated Gpx4. Conclusions Our study suggests that DGAT1 inhibition may enhance β-oxidation and mitochondrial function, thereby increasing Gpx4 levels, suppressing ferroptosis, and ultimately exerting neuroprotective effects in ischemic stroke.

Background For the patients at high-risk of aspiration, general anesthesia may increase the risk of aspiration, while local pharyngeal anesthesia may cause extreme discomfort and even failure of gastroscopy. In this study, we tested the efficacy and safety of conscious analgesia with oxycodone in these patients. Methods In this prospective, randomized, double-blind, parallel-controlled trial, the patients were randomly assigned to either the oxycodone group (group O) or the 0.9% saline group (group C). Before the gastroscope insertion, group O received oxycodone (0.05 mg/kg), while group C received an equivalent volume of 0.9% normal saline. In cases where initial gastroscope insertion failed, a rescue dose of propofol (0.5 mg/kg) was administered. The success rate of the first gastroscopy placement, the number of gastroscope insertion and rescue propofol, total consumption of propofol, duration of the procedure, patient tolerance, perioperative adverse events, the satisfaction of patients and endoscopists were compared. Results A total of 175 patients were recruited, and no patient experienced aspiration. The success rate of initial gastroscope insertion and the satisfaction of patients and endoscopists in group O were higher than those in group C ( P  < 0.001). The number of gastroscope insertion, rescue times and total consumption of propofol, duration of the procedure, the behavioral pain scale non-intubated (BPS-NI) at the time of initial gastroscope insertion, intraoperative retching, limb movement, and tachycardia in group O were significantly lower than those in group C (all P  < 0.001). Conclusion Conscious analgesia with oxycodone could help some patients at high risk of aspiration to complete the gastroscopy effectively and safely. Trial registration Registered in the Chinese Clinical Trial Registry (ChiCTR-2100053142 ) on November 13, 2021.

The objective of this study is to investigate the effect of long noncoding RNA (lncRNA) XIST on postoperative pain and inflammation of plantar incision pain (PIP) in rats and its underlying mechanisms. PIP rat models were established by plantar incision. Rats in the sham group were subjected to povidone-iodine scrubbing, and no incision was made. To explore the role of XIST/miR-340-5p/RAB1A in postoperative pain and inflammation, PIP rats were separately or simultaneously injected with lentivirus containing sh-NC, sh-XIST, mimic NC, miR-340-5p mimic, inhibitor NC, miR-340-5p inhibitor, pcDNA3.1, or pcDNA3.1-RAB1A through an intrathecal catheter. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) values of rats in each group were assessed to evaluate the pain behavior. RT-qPCR and Western blot were utilized to determine the levels of XIST, miR-340-5p, RAB1A, and NF-κB pathway-related proteins (p-IκBα, IκBα, p-p65, and p65). The concentrations of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in rat spinal dorsal horn tissues were inspected by ELISA. H and E staining was applied to observe the pathological changes of neurons in the spinal dorsal horn, TUNEL staining to detect neuronal apoptosis, and immunohistochemistry to measure RAB1A level. Plantar incision surgery caused decreased PWT and PWL values, enhanced levels of XIST, RAB1A, and inflammatory cytokines, along with an increased proportion of apoptotic neurons. The pain sensitivity and inflammation of rats were motivated after plantar incision surgery. Intrathecal injection of sh-XIST or miR-340-5p mimic ameliorated the pain and inflammation of PIP rats, while silencing of miR-340-5p or overexpression of RAB1A partly reversed the effect of sh-XIST on PIP rats. XIST targeted miR-340-5p and miR-340-5p negatively regulated RAB1A. The XIST/miR-340-5p/RAB1A axis activated the NF-κB signaling pathway. LncRNA XIST aggravates inflammatory response and postoperative pain of PIP rats by activating the NF-κB pathway via the miR-340-5p/RAB1A axis.

Propofol is widely used for sedation of hysteroscopy. It can cause injection pain, respiratory depression, and hypotension. Remimazolam is a novel ultra-short-acting benzodiazepine. Clinical practice has found that the use of remimazolam alone often leads to body movement during hysteroscopy, which decreases the safety and comfort. Here this study is to investigate whether remimazolam combined with low-dose propofol can improve the sedation effect and safety of hysteroscopy. In this prospective, randomized, parallel-controlled trial, women (18 to 60 years) undergoing hysteroscopy were randomly assigned to receive propofol (Group P), remimazolam tosylate (Group R), or remimazolam tosylate plus propofol (Group RP). Intraoperative sedation depth was kept at the bispectral index (BIS) value of 40-60. 6 μg/kg alfentanil was used for analgesic before sedation. Intraoperative low pulse oxygen saturation (SpO ), body movement, injection pain, mean arterial pressure (MAP), heart rate (HR), and postoperative recovery time, dizziness, nausea and vomiting were recorded and compared. From February to July 2022, 193 patients were recruited and randomly assigned to group P (n=64), group R (n=64), or group RP (n=65). There was no significant inter-group difference of the intraoperative BIS values. The incidence of low SpO , injection pain, hypotension, and postoperative dizziness in group RP were less than that in group P, and had no significant difference from group R. The incidence of body movement in group RP was less than that in group R, and had no significant difference from group P. Postoperative recovery time of group RP was shorter than that of the other two groups. No significant inter-group difference in bradycardia, nausea and vomiting was observed. Remimazolam tosylate combined with low dose of propofol improved sedation and safety in hysteroscopy, and may be a more ideal sedative method for hysteroscopy.

Fentanyl is a powerful opioid analgesic, and its analgesic effect is greatly different among individuals. This study was aimed at exploring the effects of multidrug resistance gene-1 (MDR1) genetic variation on postoperative fentanyl consumption. A total of 135 patients, who planned to undergo radical gastrectomy with general anesthesia, were studied. The subjects received patient-controlled analgesia (PCA) by intravenous fentanyl within 48 hours after operation and maintained a numerical rating scale (NRS) score≤3. The consumption and side effects of fentanyl were recorded within 24 hours and 48 hours after the operation. Single nucleotide polymorphisms (SNPs) of all patients with MDR1 1236C>T, 2677G>T/A, and 3435C>T were screened by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or DNA sequence analysis after PCR. There was no difference in postoperative fentanyl consumption among patients having 2677G>T/A and 3435C>T polymorphisms (all P>0.05). MDR1 1236C>T polymorphisms and haplotypes combined by three SNPs, however, significantly affected postoperative fentanyl consumption (all P<0.05). Moreover, 1236TT genotype carriers consumed more fentanyl during 24 hours (P=0.038) and 48 hours (P=0.003) postoperatively. The MDR1 TTT haplotype carriers needed more fentanyl compared with the CGC haplotype carriers during the first 48 hours after surgery (P=0.017). Nausea, vomiting, and dizziness were not found to have significant differences among the above three SNPs and their haplotypes (P>0.05). MDR1 1236C>T polymorphism and haplotypes were factors contributing to the individual variability in postoperative fentanyl consumption.

Mounting evidence shows that chronic stress can affect both the structure and function of the brain resulting in decreased synaptic plasticity and cognitive dysfunction. Although several studies have indicated that aged brains are more vulnerable to chronic stress, it remains unknown how to prevent stress-induced memory deficits in aged animals. Neuroinflammation plays an important role in the pathogenesis of chronic stress-related brain dysfunction. Receptor-interacting protein 1 (RIP1) is a key molecule that can modulate inflammation, apoptosis, and necroptosis. Here, we investigated whether inhibiting RIP1 using necrostatin-1 during chronic stress could improve chronic stress-related brain dysfunction in D-galactose-induced aging mice. The stressed mice underwent restraint stress for 14 days. Necrostatin-1 (6.25 mg/kg) or vehicle was administered intraperitoneally once every 3 days during the stress period. Locomotor activity was tested using the open field test and cognitive function was assessed using the novel object recognition and Barnes maze tests. The hippocampus was collected to assess neuroinflammation (Iba1, IL-1α, IL-1β, TNF-α, and C1q), necroptosis [RIP1, RIP3, mixed lineage kinase domain-like (MLKL), and NF-κB], neuroplasticity (doublecortin, NR1, NR2A, NR2B, GluA1, and GluA2), and the expression of glucocorticoid and mineralocorticoid receptors. Blood samples were collected to quantify the levels of corticosterone. We found that chronic stress induced obvious memory impairment and neuroinflammation, decreased neurogenesis and GluA2 expression, and increased the expression of RIP1 and NF-κB. Inhibiting RIP1 by necrostatin-1 during chronic stress rescued the memory impairment and alleviated the pathological changes induced by stress. These suggest that inhibiting RIP1 using necrostatin-1 improves chronic stress-related brain dysfunction in D-galactose-induced aging mice. The potential mechanisms include limitation of neuroinflammation and the rescue of neurogenesis and GluA2 expression.

Occurrence of postoperative cognitive dysfunction (POCD) is age-dependent and heterogenous. Factors deciding the occurrence of POCD in patients of the same age undergone same surgeries remain unclear. Here we investigated the effects of pre-existing weakness on the occurrence of POCD in mice of the same age. Pre-existing weakness of mice was induced by intraperitoneal injection of lipopolysaccharide (8mg/kg) and was evaluated by physical frailty index (by open field test), neuroinflammation level (by Iba1 immunostaining and inflammatory factors TNF-α and IL-1β), and neuronal activity (by p-CREB immunostaining). POCD was induced by partial hepatolobectomy and was evaluated by puzzle box test and Morris water maze test. The brains were collected to detect the levels of neuroinflammation, synaptophysin and NMDA receptor subunits NR2A, NR2B and NR1 (by western blot), and oxidative stress (by Dihydroethidium). Compared to the normal adult mice of the same age, LPS pretreated mice had increased physical frailty index, higher levels of neuroinflammation, and lower neuronal activity. Partial hepatolobectomy induced obvious impairments in executive function, learning and memory in LPS pretreated mice after surgery, but not in normal mice of the same age. Partial hepatolobectomy also induced heightened neuroinflammation, obvious loss of NMDA receptor subunits, strong oxidative stress in LPS pretreated mice on the 1st and 3rd postoperative day. However, the POCD-associated pathological changes didn't occur in normal mice of the same age after surgery. These results suggest that pre-existing weakness is critical for the occurrence of POCD in mice of the same age.