Background: Spinal cord injury (SCI) is a central nervous system (CNS) trauma involving inflammation and oxidative stress, which play important roles in this trauma’s pathogenesis. Therefore, controlling inflammation is an effective strategy for SCI treatment. As a hormone, melatonin is capable of producing antioxidation and anti-inflammation effects. In the meantime, it also causes a neuroprotective effect in various neurological diseases. Nrf2/ARE/NLRP3 is a well-known pathway in anti-inflammation and antioxidation, and Nrf2 can be positively regulated by melatonin. However, how melatonin regulates inflammation during SCI is poorly explored. Therefore, it was investigated in this study whether melatonin can inhibit the NLRP3 inflammasome through the Nrf2/ARE signaling pathway in a mouse SCI model. Methods: A model of SCI was established in C57BL/6 mice and PC12 cells. The motor function of mice was detected by performing an open field test, and Nissl staining and terminal deoxynucleotidyl transferase dUTP nick end labeling were carried out to evaluate the survival of neurons. Mitochondrial dysfunction was detected by transmission electron microscopy (TEM) and by assessing the mitochondrial membrane potential. In addition, the expression of NLRP3 inflammasome and oxidative-stress-related proteins were detected through Western blot and immunofluorescence double staining. Results: By inhibiting neuroinflammation and reducing neuronal death, melatonin promotes the recovery of neuromotor function. Besides this, melatonin is able to reduce the damage that causes neuronal mitochondrial dysfunction, reduce the level of reactive oxygen species (ROS) and malondialdehyde, and enhance the activity of superoxide dismutase and the production of glutathione peroxidase. Mechanically, melatonin inhibits the activation of NLRP3 inflammasomes and reduces the secretion of pro-inflammatory factors through the Nrf2/ARE signaling. Conclusions: In conclusion, melatonin inhibits the NLRP3 inflammasome through stimulation of the Nrf2/ARE pathway, thereby suppressing neuroinflammation, reducing mitochondrial dysfunction, and improving the recovery of nerve function after SCI.

Aims/hypothesis: The association between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA) has been reported by many observational studies in the Asian population. This study aimed to examine the bidirectional causal effects between GERD and RA by two-sample Mendelian randomization (MR) analyses using genetic evidence.Methods: Two-sample Mendelian randomization analyses were performed to determine the causal effect of GERD (129,080 cases vs. 602,604 control participants) on RA (6,236 cases vs. 147,221 control participants) and RA on GERD, respectively. The inverse-variance weighted (IVW) method was used as the primary analysis. Weighted median and MR-Egger regression were taken as supplementary analyses. Cochran’s Q test evaluated the heterogeneity. Horizontal pleiotropy was detected by estimating the intercept term of MR-Egger regression. Furthermore, multivariable MR analyses were performed to exclude the influence of confounding factors, including the years of schooling, BMI, and time spent watching television, between GERD and RA.Result: Both univariate MR (UVMR) and multivariable MR (MVMR) provided valid evidence that RA was causally and positively influenced by GERD (UVMR: OR = 1.49, 95% CI = 1.25–1.76, p = 6.18*10⁻⁶; MVMR: OR = 1.69, 95% CI = 1.24–2.31, p = 8.62*10⁻⁴), whereas GERD was not influenced by RA (UVMR: OR = 1.03, 95% CI = 1.00–1.06, p = 0.042; MVMR: OR = 1.04, 95% CI = 1.00–1.07, p = 0.0271).Conclusion: Our comprehensive bidirectional MR analysis found that for the European population, GERD can induce the occurrence of RA (OR = 1.69, p < 0.00125), whereas RA only has no significant influence on GERD. In particular, patients with GERD are suffering a 69% increased risk of RA occurrence, which means GERD is a substantial risk factor for RA.

Objective This study aimed to investigate changes in the root canal area and the cross-sectional area of the intervertebral foramen in patients with unilateral L4-L5 spinal stenosis who underwent Minimally Invasive Surgery-Transforaminal Lumbar Interbody Fusion (MIS-TLIF) and their correlation with clinical symptom improvement. Methods We selected 35 patients diagnosed and treated for unilateral L4-L5 spinal stenosis at our hospital from June 2020 to February 2022. We recorded intraoperative blood loss, operation time, and postoperative complications. The study compared changes in nerve root canal area observed in CT scans before and after MIS-TLIF surgery in spinal stenosis patients. We also assessed the nerve root canal area at different heights and the L4-L5 intervertebral foramen area. Preoperative and postoperative scores were collected for ODI (Oswestry Disability Index), NRS (Numeric Rating Scale), EQ-5D (EuroQol-5D), and GPE (Global Perceived Effect) to evaluate clinical symptoms. Correlation analyses were conducted between changes in clinical scores and changes in the above-mentioned anatomical areas. Results All patients underwent successful surgeries with an average operation time of 122.2 ± 20.33 minutes and an average intraoperative blood loss of 231.43 ± 129.53 ml. Five cases required blood transfusions, and three cases experienced postoperative cerebrospinal fluid leakage, which resolved with bed rest and fluid infusion. There were no infections, but eight cases had postoperative anemia, and no other complications, such as pulmonary embolism, occurred. Postoperative ODI and EQ-5D scores at 3 months, 6 months, and 12 months showed significant improvement compared to preoperative scores. Linear correlation analysis revealed that the cross-sectional area of the lumbar root canal was negatively correlated with ODI scores (r=-0.45, P < 0.01), positively correlated with EQ-5D scores (r = 0.46, P < 0.01), and negatively correlated with NRS-leg scores (r=-0.47, P < 0.01). Moreover, the L4-L5 intervertebral foramen area was significantly negatively correlated with ODI scores (r=-0.80, P < 0.01) and positively correlated with EQ-5D scores (r = 0.517, P < 0.01). Conclusion Identifying lumbar spinal stenosis preoperatively provides valuable guidance for effective decompression during minimally invasive surgery. However, this study has limitations, primarily due to the small sample size of patients with unilateral single-level L4-L5 symptoms. Further research with a larger sample size is warranted.