Importance: Postpartum depression (PPD) is one of the most common mental health conditions during the perinatal and postpartum periods, which can have adverse effects on both mother and infant.Objective: To investigate the efficacy of perioperative adjunctive esketamine administration after cesarean deliveries in the prevention of PPD.Design, Setting, and Participants: A single-center, double-blind, placebo-controlled, randomized clinical trial was conducted from January 1, 2022, to January 1, 2023, at Fujian Provincial Hospital among 298 women aged 18 to 40 years, with an American Society of Anesthesiologists grade I to III classification and singleton full-term pregnancies who were scheduled for elective cesarean deliveries. Primary analyses were performed on a modified intention-to-treat basis.Interventions: Patients were randomly assigned to the esketamine (n = 148) and control (n = 150) groups. Those in the esketamine group received a single intravenous injection of 0.25 mg/kg of esketamine immediately after fetal delivery, followed by 50 mg of esketamine as an adjuvant in patient-controlled intravenous analgesia for 48 hours after surgery. Saline was given to the control group of patients.Main Outcomes and Measures: The primary outcome was assessments of PPD symptoms by using the Edinburgh Postnatal Depression Scale (EPDS) at postpartum day 7. Positive screening for PPD was defined as a score of 10 or more points on the EPDS. In addition, the EPDS was analyzed as a continuous variable to evaluate depressive symptoms. Secondary outcomes included the Numeric Rating Scale (NRS) of postoperative pain, along with safety evaluations including adverse events and clinical assessments at postpartum days 14, 28, and 42.Results: A total of 298 pregnant women were included, with 150 in the control group (median age, 31.0 years [IQR, 29.0-34.0 years]) and 148 in the esketamine group (median age, 31.0 years [IQR, 28.0-34.0 years]). The prevalence of depression symptoms was significantly lower among patients given esketamine compared with controls (23.0% [34 of 148] vs 35.3% [53 of 150]; odds ratio, 0.55; 95% CI, 0.33-0.91; P = .02) on postpartum day 7. In addition, the esketamine group also showed a significantly lower change in EPDS scores (difference of least-squares means [SE], −1.17 [0.44]; 95% CI, −2.04 to −0.31; effect size, 0.74; P = .008). However, there were no differences between the groups in the incidence of positive screening results for PPD or in changes from the baseline EPDS scores at postpartum days 14, 28, and 42. There were no differences in NRS scores at rest and on movement except on movement at 72 hours postoperatively, when scores were significantly lower in the esketamine group (median, 3.0 [IQR, 2.0-3.0] vs 3.0 [IQR, 3.0-3.5]; median difference, 0 [95% CI, 0-0]; P = .03).Conclusions and Relevance: These results suggest that intravenous administration of esketamine during the perioperative period of elective cesarean delivery can improve depression symptoms during the early postpartum period. However, this antidepression effect may not be universally applicable to patients with low EPDS scores.Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100054199

Introduction Postoperative impaired sleep quality and pain are associated with adverse outcomes. Stellate ganglion block (SGB) has shown promising results in enhancing sleep quality and alleviating neuropathic pain. This study aimed to investigate the effects of ultrasound-guided SGB on postoperative sleep quality and pain in patients undergoing breast cancer surgery. Methods This study is a parallel-group randomized controlled clinical trial with two groups: SGB and control. Fifty female patients undergoing breast cancer surgery were randomized in a 1:1 ratio to receive preoperative ultrasound-guided single-injection SGB (SGB group) or just an ultrasound scan (control group). All participants were blinded to the group assignment. The primary outcome was postoperative sleep quality, assessed by the St. Mary’s Hospital Sleep Questionnaire and actigraphy 2 days postoperatively. The secondary outcome was postoperative pain, measured by the visual analog scale. Results A total of 48 patients completed the study, with 23 patients in the control group and 25 in the SGB group. The postoperative St. Mary’s Hospital Sleep Questionnaire scores were significantly higher in the SGB group than in the control group on 1 day postoperative (30.88 ± 2.44 versus 27.35 ± 4.12 points, P = 0.001). The SGB also increased the total sleep time and sleep efficiency (main actigraphy indicators) during the first two postoperative nights. Compared with the control group, preoperative SGB reduced postoperative pain and the incidence of breast cancer-related lymphedema (20% versus 52.2%, P = 0.02, odds ratio 0.229, 95% confidence interval 0.064–0.821). There were no adverse events related to SGB. Conclusion Preoperative ultrasound-guided SGB improves postoperative sleep quality and analgesia in patients undergoing breast cancer surgery. SGB may be a safe and practical treatment to enhance the postoperative quality of life in patients with breast cancer. Trial Registration The study was registered in the Chinese Clinical Trial Registry (ChiCTR2100046620, principal investigator: Kai Zeng, date of registration: 23 May 2021).

Background: Sepsis associated encephalopathy (SAE) is prevalent among elderly patients in the ICU and significantly affects patient prognosis. Due to the symptom similarity with other neurological disorders and the absence of specific biomarkers, early clinical diagnosis remains challenging. This study aimed to develop a predictive model for SAE in elderly ICU patients.Methods: The data of elderly sepsis patients were extracted from the MIMIC IV database (version 3.1) and divided into training and test sets in a 7:3 ratio. Feature variables were selected using the LASSO-Boruta combined algorithm, and five machine learning (ML) models, including Extreme Gradient Boosting (XGBoost), Categorical Boosting (CatBoost),Light Gradient Boosting Machine(LGBM), Multilayer Perceptron (MLP), and Support Vector Machines (SVM), were subsequently developed using these variables. A comprehensive set of performance metrics was used to assess the predictive accuracy, calibration, and clinical applicability of these models. For the machine learning model with the best performance, we employed the SHapley Additive Explanations(SHAP) method to visualize the model.Results: Based on strict inclusion and exclusion criteria, a total of 3,156 elderly sepsis patients were enrolled in the study, with an SAE incidence rate of 48.7%. The mortality rate of elderly sepsis patients who developed SAE was significantly higher than that of patients in the non-SAE group (28.78% vs. 12.59%, P < 0.001). A total of 18 feature variables were selected for the construction of the ML model using the LASSO-Boruta combined algorithm. Compared to the other four models and traditional scoring systems, the XGBoost model demonstrated the best overall predictive performance, with Area Under the Curve(AUC)=0.898, accuracy=0.830, recall=0.819, F1-Score=0.820, specificity=0.840, and Precision=0.821. Furthermore, the results from the Decision Curve Analysis (DCA) and calibration curves demonstrated that the XGBoost model has significant clinical value and stable predictive performance. The ten-fold cross-validation method further confirmed the robustness and generalizability of the model. In addition, we simplified the model based on the SHAP feature importance ranking, and the results indicated that the simplified XGBoost model retains excellent predictive ability (AUC=0.858).Conclusions: The XGBoost model effectively predicts SAE in elderly ICU patients and may serve as a reliable tool for clinicians to identify high-risk patients.

Background: Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats. Methods: Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels. Results: Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1β and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased. Conclusions: The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation.

Sepsis is a severe systemic inflammatory response commonly occurring in infectious diseases, caused by infection with virulent pathogens. In the pathogenesis of sepsis, the cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator of interferon genes (cGAS-STING) signaling pathway serves a crucial role as a fundamental immunoregulatory mechanism. This signaling pathway activates STING upon recognizing intracellular DNA damage and pathogen-derived DNA, subsequently inducing the production of numerous inflammatory mediators, including interferon and inflammatory cytokines, which in turn trigger an inflammatory response. The aim of this paper is to explore the activation mechanism of the cGAS-STING signaling pathway in sepsis and its impact on inflammatory regulation. By delving into the mechanism of action of the cGAS-STING signaling pathway in sepsis, we aim to identify new therapeutic strategies for the treatment and prevention of sepsis.

Nonalcoholic steatohepatitis (NASH) is a prevalent chronic disease, yet its exact mechanisms and effective treatments remain elusive. Nuclear receptor subfamily 5 group A member 2 (NR5A2), a transcription factor closely associated with cholesterol metabolism in the liver, has been hindered from comprehensive investigation due to the lethality of NR5A2 loss in cell lines and animal models. To elucidate the role of NR5A2 in NASH, we generated hepatocyte-specific knockout mice for Nr5a2 (Nr5a2^HKO) and examined their liver morphology across different age groups under a regular diet. Furthermore, we established cell lines expressing haploid levels of NR5A2 and subsequently reintroduced various isoforms of NR5A2. In the liver of Nr5a2^HKO mice, inflammation and fibrosis spontaneously emerged from an early age, independent of lipid accumulation. Pyroptosis occurred in NR5A2-deficient cell lines, and different isoforms of NR5A2 reversed this form of cell death. Our findings unveiled that inhibition of NR5A2 triggers pyroptosis, a proinflammatory mode of cell death primarily mediated by the activation of the NF-κB pathway induced by reactive oxygen species (ROS). As a transcriptionally regulated molecule of NR5A2, aldehyde dehydrogenase 1 family member B1 (ALDH1B1) participates in pyroptosis through modulation of ROS level. In conclusion, the diverse isoforms of NR5A2 exert hepatoprotective effects against NASH by maintaining a finely tuned balance of ROS, which is contingent upon the activity of ALDH1B1.