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Recent evidence suggests that innate and adaptive immunity play a crucial role in Parkinson’s disease (PD). However, studies regarding specific immune cell classification in the peripheral blood in PD remain lacking. Therefore, we aimed to explore the different immune status in patients with PD at different ages of onset. We included 22 patients; among them were 10 who had early-onset PD (EOPD) and 12 had late-onset PD (LOPD) and 10 young healthy controls (YHCs) and 8 elder HCs (EHCs). Mass cytometry staining technology was used to perform accurate immunotyping of cell populations in the peripheral blood. Motor symptoms and cognitive function were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) III score and Mini-mental State Examination (MMSE) score, respectively. T test and ANOVA statistical analysis were performed on the frequency of annotated cell population. Linear regression model was used to analyze the correlation between clusters and clinical symptoms. We characterized 60 cell clusters and discovered that the immune signature of PD consists of cluster changes, including decreased effector CD8+ T cells, lower cytotoxicity natural killer (NK) cells and increased activated monocytes in PD patients. In summary, we found that CD8+ T cells, NK cells, and monocytes were associated with PD. Furthermore, there may be some differences in the immune status of patients with EOPD and LOPD, suggesting differences in the pathogenesis between these groups.

ObjectiveAquaporin-4 (AQP4) facilitates a sleep-enhanced interstitial brain waste clearance system. This study was conducted to determine the clinical implication of AQP4 polymorphisms in Parkinson’s disease (PD).MethodsThree-hundred and eighty-two patients with PD and 180 healthy controls with a mean follow-up time of 66.1 months from the Parkinson’s Progression Marker Initiative study were analyzed. We examined whether AQP4 SNPs were associated with an altered rate of motor or cognitive decline using linear mixed model and Cox regression. We then investigated whether AQP4 SNPs were associated with Aβ burden as measured by 18F Florbetapir standard uptake values. Furthermore, we examined if AQP4 SNPs moderated the association between REM sleep behavior disorder (RBD) and CSF biomarkers.ResultsIn patients with PD, AQP4 rs162009 (AA/AG vs. GG) was associated with slower dementia conversion, better performance in letter-number sequencing and symbol digit modalities, lower Aβ deposition in the putamen, anterior cingulum, and frontotemporal areas. In the subgroup of high RBD screening questionnaire score, rs162009 AA/AG had a higher CSF Aβ42 level. rs162009 AA/AG also had better performance in semantic fluency in healthy controls. Besides, rs68006382 (GG/GA vs. AA) was associated with faster progression to mild cognitive impairment, worse performance in letter-number sequencing, semantic fluency, and symbol digit modalities in patients with PD.InterpretationGenetic variations of AQP4 and subsequent alterations of glymphatic efficacy might contribute to an altered rate of cognitive decline in PD. AQP4 rs162009 is likely a novel genetic prognostic marker of glymphatic function and cognitive decline in PD.

ImportanceEpidural anesthesia is a primary choice for cesarean delivery, but supplemental analgesics are often required to relieve pain during uterine traction.ObjectiveTo investigate the sedative and analgesic effects of intravenous esketamine administered before childbirth via cesarean delivery with the patient under epidural anesthesia.Design, Setting, and ParticipantsThis multicenter, double-blind randomized clinical trial assessed 903 women 18 years or older who had full-term single pregnancy and were scheduled for elective cesarean delivery with epidural anesthesia in 5 medical centers in China from September 18, 2021, to September 20, 2022.InterventionPatients were randomized to receive intravenous injection of 0.25 mg/kg of esketamine or placebo before incision.Main Outcomes and MeasuresThe coprimary outcomes included scores on the numeric rating scale of pain (an 11-point scale, with 0 indicating no pain and 10 indicating the worst pain; a difference of ≥1.65 points was clinically meaningful) and Ramsay Sedation Scale (a 6-point scale, with 1 indicating restlessness and 6 indicating deep sleep without response; a difference of ≥2 points was clinically meaningful) immediately after fetal delivery. Secondary outcomes included neonatal Apgar score assessed at 1 and 5 minutes after birth.ResultsA total of 600 women (mean [SD] age, 30.7 [4.3] years) were enrolled and randomized; all were included in the intention-to-treat analysis. Immediately after fetal delivery, the score on the numeric rating scale of pain was lower with esketamine (median [IQR], 0 [0-1]) than with placebo (median [IQR], 0 [0-2]; median difference, 0; 95% CI, 0-0; P = .001), but the difference was not clinically important. The Ramsay Sedation Scale scores were higher (sedation deeper) with esketamine (median [IQR], 4 [3-4]) than with placebo (median [IQR], 2 [2-2]; median difference, 2; 95% CI, 2-2; P < .001). The neonatal Apgar scores did not differ between the 2 groups at 1 minute (median difference, 0; 95% CI, 0-0; P = .98) and at 5 minutes (median difference, 0; 95% CI, 0-0; P = .27). Transient neurologic or mental symptoms were more common in patients given esketamine (97.7% [293 of 300]) than in those given placebo (4.7% [14 of 300]; P < .001).Conclusions and RelevanceFor women undergoing cesarean delivery under epidural anesthesia, a subanesthetic dose of esketamine administered before incision produced transient analgesia and sedation but did not induce significant neonatal depression. Mental symptoms and nystagmus were common but transient. Indications and the optimal dose of esketamine in this patient population need further clarification, but study should be limited to those who require supplemental analgesia.Trial RegistrationClinicalTrials.gov Identifier: NCT04548973

Background: Ultrasonic measurements of tongue thickness and condylar translation were recently introduced to predict difficult laryngoscopy in non-obstetric patients. We designed the present study to evaluate the performance of these two ultrasonic indicators in predicting difficult laryngoscopy in healthy parturients. Methods: The 119 parturients undergoing elective cesarean delivery were enrolled. Tongue thickness and condylar translation measured by ultrasonography, and Modified Mallampati test (MMT) score, inter-incisor distance (IID) and modified Cormack-Lehane grading system (MCLS) were measured and recorded before anesthesia. The primary outcome was difficult laryngoscopy defined as MCLS 3 or 4. The association between these variables and difficult laryngoscopy were analyzed by using multivariable logistic regression and receiver operating characteristic (ROC) curve. Results: Compared to the Easy Laryngoscopy Group, the tongue thickness was significantly higher and the condylar translation and IID were significantly lower in the Difficult Laryngoscopy Group. Tongue thickness and condylar translation but not MMT score and IID were proved to be two independent predictors for difficult laryngoscopy by multivariate logistic regression, with the odds ratios of 2.554 (95% confidence interval (CI), 1.715 to 3.802) and 0.457 (95% CI, 0.304 to 0.686). The area under the ROC curve to predict difficult laryngoscopy for tongue thickness was 0.93 (95% CI, 0.88–0.98) and for condylar translation was 0.77 (95% CI, 0.67–0.86), which were significantly higher than those for MMT score (0.67, 95% CI, 0.56–0.77) and IID (0.65, 95% CI, 0.55–0.76). Conclusions: Compared with MMT and IID, tongue thickness and condylar translation measured by ultrasonography appear to be better indicators for predicting difficult laryngoscopy in parturients. The trial was registered at the Chinese Clinical Trial Registry (ChiCTR)(www.chictr.org), registration number ChiCTR-ICR-1800019991.

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