Role of NLRP3 inflammasome in central nervous system diseases.

The central nervous system (CNS) is the most delicate system in human body, with the most complex structure and function. It is vulnerable to trauma, infection, neurodegeneration and autoimmune diseases, and activates the immune system. An appropriate inflammatory response contributes to defence against invading microbes, whereas an excessive inflammatory response can aggravate tissue damage. The NLRP3 inflammasome was the first one studied in the brain. Once primed and activated, it completes the assembly of inflammasome (sensor NLRP3, adaptor ASC, and effector caspase-1), leading to caspase-1 activation and increased release of downstream inflammatory cytokines, as well as to pyroptosis. Cumulative studies have confirmed that NLRP3 plays an important role in regulating innate immunity and autoimmune diseases, and its inhibitors have shown good efficacy in animal models of various inflammatory diseases. In this review, we will briefly discuss the biological characteristics of NLRP3 inflammasome, summarize the recent advances and clinical impact of the NLRP3 inflammasome in infectious, inflammatory, immune, degenerative, genetic, and vascular diseases of CNS, and discuss the potential and challenges of NLRP3 as a therapeutic target for CNS diseases.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. METHODS: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. RESULTS: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). CONCLUSION: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

Impaired declarative memory consolidation in children with REM sleep-related obstructive sleep apnea.

STUDY OBJECTIVES: We explored whether declarative memory consolidation is impaired in children with rapid eye movement sleep-related obstructive sleep apnea (REM-OSA) and investigated the correlation between memory consolidation and sleep-related respiratory parameters. METHODS: Participants were children with habitual snoring aged 6-14 years and control children. Participants underwent polysomnography and declarative memory testing. Participants with snoring were categorized as primary snoring (PS), non-rapid eye movement sleep-related obstructive sleep apnea (NREM-OSA), stage-independent (SI)-OSA, and REM-OSA according to obstructive apnea-hypopnea index (OAHI), OAHI in REM sleep (OAHIREM), and OAHI in NREM sleep (OAHINREM). Declarative memory consolidation level was assessed by recall and recognition rates. RESULTS: There were 34 controls and 228 children with sleep-disordered breathing: 73 PS, 48 NREM-OSA, 59 SI-OSA, and 48 REM-OSA. Total arousal index was lower in the REM-OSA group than in the NREM-OSA group. In all groups, retest scores were higher than immediate test scores. Recall consolidation in PS, SI-OSA, and REM-OSA groups was lower than for controls and lower in REM-OSA than in NREM-OSA. There were no correlations between recall consolidation or recognition consolidation and OAHI, OAHINREM, oxygen desaturation index in REM sleep, total arousal index, or REM sleep percent. Recognition consolidation was negatively correlated with OAHIREM. CONCLUSIONS: Memory consolidation is impaired in children with REM-OSA compared with NREM-OSA and controls. There was no significant correlation between memory consolidation and OAHI, and recognition consolidation was negatively correlated with OAHIREM. It is important to pay attention to the OSA subtype in children. CITATION: Tang Y, Yang C, Wang C, Wu Y, Xu Z, Ni X. Impaired declarative memory consolidation in children with REM sleep-related obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):417-425.

Aspiration and coagulation to reduce risk of delayed bleeding after gastric endoscopic submucosal dissection (with video).

OBJECTIVES: The purpose of this study was to evaluate the feasibility of a simple method named aspiration and coagulation (AC) for reducing the risk of postoperative bleeding after gastric endoscopic submucosal dissection (ESD). METHODS: Data were retrospectively reviewed and collected from the medical records and endoscopic and pathologic reports about consecutive patients who underwent ESD for early gastric cancer or precancerous lesions or gastric submucosal lesions from January 2016 to December 2021 at the Seventh Medical Center of Chinese PLA General Hospital. Enrolled patients who underwent the AC method during ESD were included in the AC group, and the others were included in the control group. Propensity score (PS) matching (1:1 match) was used to compensate for the differences that might affect post-ESD bleeding. Massive hemorrhage and overall delayed bleeding events after gastric ESD were compared between the two groups. RESULTS: Propensity score matching analysis created 242 matched pairs in the study. Characteristics of the subjects such as age and use of antithrombotic drugs were all similar between the two groups after PS matching. The rate of massive hemorrhage and overall delayed bleeding was both significantly lower in the AC group than in the control (0.4% vs. 3.3% for massive hemorrhage, P = 0.037, and 1.2% vs. 5.0% for overall delayed bleeding, P = 0.032), predominantly in mucosal lesions (0.6% vs. 4.4% for massive hemorrhage, P = 0.032, and 1.2% vs. 5.6% for overall delayed bleeding, P = 0.031). CONCLUSIONS: Our study demonstrated that the AC method effectively decreased delayed bleeding events after ESD.

Cystic Fibrosis Transmembrane Conductance Regulator Attenuates Oxidative Stress-Induced Injury in Diabetic Retinopathy Rats.

PURPOSE: To investigate the effects of cystic fibrosis transmembrane conductance regulator (CFTR) on oxidative stress-induced injury of diabetic retinopathy (DR) rats. METHODS: DR rat model was constructed treated with Ad-CFTR. Hematoxylin and Eosin (HE) staining was applied for testing the thickness of each layer of retinal tissues. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of serum inflammatory cytokines and contents of oxidative stress related genes in rats. Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining was used to detect retinal cell apoptosis, and western blotting to measure the expression of MAPK/NF-κB pathway-related proteins in retinal tissues. RESULTS: Our experiment revealed the remarkable decrease of CFTR protein in retinal tissues of DR rats. DR rats had decreased body weight and increased blood glucose level, with decreased thickness of total retinal thickness (TRT), outer nuclear layer and outer plexiform layer (ONL + OPL), inner nuclear layer (INL), and inner plexiform layer (IPL). Besides, DR rats were apparently up-regulated in the expression of pro-inflammatory cytokines, with increased malondial dehyde (MDA), p-ERK1/2/ERK1/2 and p-JNK1/2/JNK1/2 expressions, decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity in retinal tissues, as well as up-regulated p65 protein in nucleus and down-regulated p65 protein in cytoplasm. DR rats treated with Ad-CFTR were effectively improved regarding the above parameters except body weight and blood glucose. CONCLUSIONS: CFTR can inhibit MAPK/NF-κB signaling pathway to ameliorate inflammatory response and oxidative stress-induced injury of DR rats, thereby reducing retinal cell apoptosis and playing a protective role in retina.

Comparison of fully coated anti-reflux metal stenting and per-oral endoscopic myotomy in patients with achalasia: a propensity score-matched retrospective study.

BACKGROUND: Achalasia is a rare primary esophageal motility disorder disease. It is reported that the long-term effect of fully coated anti-reflux metal stent (FCARMS) implantation is satisfactory. Operated by a skilled and experienced endoscopist, the effect of per-oral endoscopic myotomy (POEM) treatment is equivalent to that of surgical myotomy. So far, there is still few evidence to prove FCARMS implantation or POEM which is better for achalasia. The choice of treatment for achalasia is still controversial. The aim of this study is to find a more suitable therapy for achalasia by comparing the efficacy of FCARMS implantation and POEM. METHODS: A propensity score (PS) matching (1:2) was used in this retrospective cohort study. Data collected from consecutive patients of Achalasia, receiving FCARMS implantation or POEM therapy at the department of gastroenterology, the Seventh Medical Center of the Chinese People's Liberation Army General Hospital from May 2007 to May 2018. According to their previous treatment, they are divided into two groups, FCARMS group and POEM group. Clinical efficacy and complications were compared between the two groups. RESULTS: A total of 166 cases were collected, including 113 cases of FCARMS and 53 cases of POEM. By PS matching, 150 patients were enrolled (100 cases of FCARMS and 50 cases of POEM). By comparison, the FCARMS group has shorter operation time, shorter fasting time and lower hospitalization costs than the POEM group (p < 0.05). Common complications in the FCARMS group are nausea, vomiting, and stent shift. Repetitions of gastroscopy in the FCARMS group was more often, which were 3.8 ± 2.4 (vs 2.1 ± 1.8 of POEM) (p = 0.00 < 0.05) The 6-month remission rates of the FCARMS combination POEM group were 89% and 94%, respectively (p = 0.39), and the 2-year remission rates were 61% and 90%, respectively (p = 0.00). CONCLUSIONS: Stent placement is a cost-effective and safe treatment option for achalasia. The short-term effect (less than 6 months) of FCARMS is similar to that of POEM, the long-term effect (more than 2 years), POEM is better than FCARMS. HRMIIis most suitable for POEM treatment. It indicate that Patients can choose treatment methods according to their own conditions.

Autonomic nervous function and low-grade inflammation in children with sleep-disordered breathing.

BACKGROUND: The objective of the study was to assess the relationship between autonomic nervous function and low-grade inflammation in children with sleep-disordered breathing. METHODS: We enrolled habitually snoring children aged 3-14 years for overnight polysomnography (PSG) and high-sensitivity C-reactive protein (hsCRP) measurement. Low-grade inflammation was defined as hsCRP >1.0 mg/L to <10.0 mg/L. An electrocardiogram recording was extracted from PSG. Heart rate variability was analyzed using time and frequency domain methods. RESULTS: In total, 190 children were included, with 61 having primary snoring (PS), 39 mild obstructive sleep apnea (OSA), and 90 moderate-to-severe OSA. The average RR interval displayed a significant decline, whereas the low frequency/high frequency (LF/HF) ratio showed an increasing tendency in children with PS, mild OSA, and moderate-to-severe OSA. Mean RR was mainly influenced by age and the apnea hypopnea index (AHI) (all P < 0.01). AHI was an independent risk factor for the altered LF/HF ratio at all sleep stages except N3 stage (all P < 0.05). In the wake stage, low-grade inflammation was an independent risk factor of altered LF/HF ratio (P = 0.014). CONCLUSIONS: Autonomic nervous function was impaired in children with OSA. The sympathetic-vagal balance was influenced by low-grade inflammation in the wake stage, whereas it was only affected by AHI when falling asleep. IMPACT: We found that autonomic nervous function was impaired in children with OSA. We found that there was a negative correlation between systemic inflammation and autonomic nervous function in children with SDB only at wake stage. A negative association between systemic inflammation and autonomic nervous function was demonstrated in children in this study. Furthermore, altered LF/HF ratio maybe a good indicator of autonomic nervous dysfunction in children as it only correlated with the SDB severity, not with age.

Clinical and PSG Characteristics of Children with Mild OSA and Respiratory Events Terminated Predominantly with Arousal.

Objective: To analyze the clinical and polysomnographic characteristics in children with mild OSA and respiratory events terminated predominantly with arousal. Methods: Children aged 3-10 yrs who had mild obstructive sleep apnea (OSA) were enrolled. All children underwent polysomnography, and patients' data were collected by using sleep-related breathing disorders (SRBD) questionnaire and OSA-18 quality of life questionnaire. Results: In total, five hundred and seventy-seven children were eligible. Children in arousal predominant group were younger and showed a lower rate of male and obesity. Compared with that of the nonarousal predominant group, the total arousal index, arousal index related to respiratory event, the percentage of NREM stage 1 (N1%), the fraction of respiratory events that were hypopnea, and the mean and minimum oxygen saturation in the arousal predominant group were significantly greater. The percentage of NREM stage 3 (N%), index of obstructive, central, mixed apnea, the fraction of respiratory events that were obstructive, and central and mixed apnea were significantly lower in arousal predominant group. Conclusion: Children with mild OSA in the arousal predominant group had specific characteristics, including younger age, lower rate of male and obesity, worse sleep architecture, higher rates of hypopnea events, and better oxygenation. This trial is registered with NCT02447614.