Sex-Specific Alterations in Placental Proteomics Induced by Intrauterine Hyperglycemia.

Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both the mother and the fetus. The aim of this study was to investigate the changes in the placenta in GDM and its gender differences. In this study, we established an intrauterine hyperglycemia model using ICR mice. We collected placental specimens from mice before birth for histological observation, along with tandem mass tag (TMT)-labeled proteomic analysis, which was stratified by sex. When the analysis was not segregated by sex, the GDM group showed 208 upregulated and 225 downregulated proteins in the placenta, primarily within the extracellular matrix and mitochondria. Altered biological processes included cholesterol metabolism and oxidative stress responses. After stratification by sex, the male subgroup showed a heightened tendency for immune-related pathway alterations, whereas the female subgroup manifested changes in branched-chain amino acid metabolism. Our study suggests that the observed sex differences in placental protein expression may explain the differential impact of GDM on offspring.

Left ventricular hypertrophy and left atrial diameter are associated with mortality risk in haemodialysis patients: a retrospective cohort study.

BACKGROUND: Cardiovascular death is the main cause of death in patients with end-stage kidney disease (ESKD). Left ventricular hypertrophy (LVH) and left atrial diameter (LAD) enlargement are frequent cardiac alterations in patients with ESKD and are major risk factors for cardiovascular events. However, it remains unclear whether there is an association between combined LAD or LVH and all-cause or cardiovascular mortality in this population. METHODS: A single-centre, retrospective cohort study including 576 haemodialysis (HD) patients was conducted. Patients were evaluated by cardiac ultrasound, and the study cohort was divided into four groups according to LAD and LVH status: low LAD and non-LVH; low LAD and LVH; high LAD and non-LVH; and high LAD and LVH. We used Kaplan-Meier analysis and Cox proportional hazard regression to analyse all-cause and cardiovascular mortality after multivariate adjustment. RESULTS: LAD was associated with an increased risk of all-cause mortality (HR 2.371, 1.602-3.509; p < 0.001). No significant differences were found between LVH and the risk of all-cause mortality. Patients with high LAD and LVH had significantly greater all-cause and cardiovascular mortality than did those with low LAD and non-LVH after adjustments for numerous potential confounders (HR 3.080, 1.608-5.899; p = 0.001) (HR 4.059, 1.753-9.397; p = 0.001). CONCLUSION: Among maintenance haemodialysis (MHD) patients, LAD was more strongly associated with mortality than was LVH. A high LAD and LVH are associated with a greater risk of mortality. Our results emphasize that the occurrence of LAD and LVH in combination provides information that may be helpful in stratifying the risk of MHD patients.

Effects of low-flux and high-flux hemodialysis on the survival of elderly maintenance hemodialysis patients.

BACKGROUND: Elderly hemodialysis (HD) patients have a high risk of death. The effect of different types of HD membranes on survival is still controversial. The purpose of this study was to determine the relationship between the use of low-flux or high-flux membranes and all-cause and cardiovascular mortality in elderly hemodialysis patients. METHODS: This was a retrospective clinical study involving maintenance hemodialysis patients which were categorized into low-flux and high-flux groups according to the dialyzer they were using. Propensity score matching was used to balance the baseline data of the two groups. Survival rates were compared between the two groups, and the risk factors for death were analyzed by multivariate Cox regression. RESULTS: Kaplan-Meier survival analysis revealed no significant difference in all-cause mortality between the low-flux group and the high-flux group (log-rank test, p = 0.559). Cardiovascular mortality was significantly greater in the low-flux group than in the high-flux group (log-rank test, p = 0.049). After adjustment through three different multivariate models, we detected no significant difference in all-cause mortality. Patients in the high-flux group had a lower risk of cardiovascular death than did those in the low-flux group (HR = 0.79, 95% CI, 0.54-1.16, p = 0.222; HR = 0.58, 95% CI, 0.37-0.91, p = 0.019). CONCLUSIONS: High-flux hemodialysis was associated with a lower relative risk of cardiovascular mortality in elderly MHD patients. High-flux hemodialysis did not improve all-cause mortality rate. Differences in urea distribution volume, blood flow, and systemic differences in solute clearance by dialyzers were not further analyzed, which are the limitations of this study.

Multi working mode SPR chip laboratory for high refractive index detection.

The Fiber SPR chip laboratory has become a popular choice in biochemical detection. To meet the needs of different kinds of analytes for the detection range and number of channels of the chip, we proposed a multi-mode SPR chip laboratory based on microstructure fiber in this paper. The chip laboratory was integrated with microfluidic devices made from PDMS and detection units made of bias three-core fiber and dumbbell fiber. By injecting light into different cores of a bias three-core fiber, different detection areas of dumbbell fiber can be selected, enabling the chip laboratory to enter high refractive index detection, multi-channel detection and other working modes. In the high refractive index detection mode, the chip can detect liquid samples with a refractive index range of 1.571-1.595. In multi-channel detection mode, the chip can achieve dual parameter detection of glucose and GHK-Cu, with sensitivities of 4.16 nm/(mg/mL) and 9.729 nm/(mg/mL), respectively. Additionally, the chip can switch to temperature compensation mode. The proposed multi working mode SPR chip laboratory, based on micro structured fiber, offers a new approach for the development of portable testing equipment that can detect multiple analytes and meet multiple requirements.

Abdominal aortic calcification score can predict all-cause and cardiovascular mortality in maintenance hemodialysis patients.

Purpose: Abdominal aortic calcification (AAC) assessed by using standard lateral lumbar radiographs can be graded, and composite summary scores (range, 0-24) have been shown to be highly predictive of subsequent cardiovascular morbidity and mortality in hemodialysis (HD) patients. However, few studies have sought to determine the optimal AAC score cutoff values for the prediction of mortality among HD patients.Methods: This retrospective cohort study included 408 hemodialysis patients. AAC severity was quantified by the AAC score, which was measured by lateral lumbar radiography with complete follow-up data from January 2015 to December 2021. We used receiver operating characteristic (ROC) analysis to find the cutoff AAC value for the prediction of mortality. The Kaplan-Meier method was used to analyze all-cause and cardiovascular mortality.Results: The cutoff calcification score for the prediction of mortality was 4.5 (sensitivity, 67.3%; specificity, 70.4%). The patients with AAC scores above 4.5 had significantly higher all-cause (log-rank p < 0.001) and cardiovascular (log-rank p < 0.001) mortality rates than those with AAC scores below 4.5. In the multivariate regression analyses, an AAC score above 4.5 was a significant factor associated with all-cause mortality (HR: 2.079, p = 0.002) and cardiovascular mortality (HR: 2.610, p < 0.001).Conclusions: AAC is a reliable aortic calcification marker. HD patients with an AAC score > 4.5 have significantly elevated all-cause and cardiovascular mortality compared with those with an AAC score ≤ 4.5. AAC was a better predictor than cardiac valve calcification for mortality in HD patients.

A high platelet-to-lymphocyte ratio predicts all-cause mortality and cardiovascular mortality in maintenance hemodialysis patients.

PURPOSE: The aim of this study was to further assess whether the platelet-to-lymphocyte ratio (PLR) is independently associated with all-cause mortality and cardiovascular mortality in maintenance hemodialysis (MHD) patients. METHODS: From January 1, 2014, to December 31, 2014, patients undergoing regular hemodialysis in the Blood Purification Center of the General Hospital of Northern Theatre Command were retrospectively selected. A total of 303 MHD patients were enrolled in accordance with the inclusion and exclusion criteria. For each patient, the endpoint of follow-up was either death or December 31, 2021. The primary endpoints were all-cause and cardiovascular death. A receiver operating characteristic (ROC) curve was drawn to detect the predictive ability of PLR, and the optimal critical value of PLR was determined to be 107.57. Kaplan-Meier curves and Cox proportional analysis were used to assess the prognostic value of PLR. We used the same method to evaluate the correlation between the neutrophil-to-lymphocyte ratio (NLR) and the prognosis of MHD patients. RESULTS: At the end of follow-up, 128 MHD patients had progressed to all-cause death, and 73 MHD patients had progressed to cardiovascular death. In multivariate Cox regression, both the high PLR group and the high NLR group were independently associated with all-cause mortality (HR 2.608, 95% CI 1.579-4.306, p < .001 vs. HR 1.634, 95% CI 1.023-2.610, p = .04). Only high PLR expression was associated with cardiovascular mortality (HR 3.379, 95% CI 1.646-6.936, p = .001). CONCLUSIONS: High PLR levels can independently predict all-cause and cardiovascular mortality in MHD patients.

High sensitivity fiber cladding SPR strain sensor based on V-groove structure.

How to couple the light in the fiber core to the cladding is an urgent issue that need to be done for the fabrication of the fiber-cladding SPR sensor, and there is no report about the fiber SPR strain sensor. Hereby, we propose and demonstrate a high sensitivity fiber cladding SPR strain sensor based on V-groove structure. By CO2 laser, the V-groove is fabricated on the single-mode fiber, and the light in the fiber core is effectively coupled to the cladding. The cladding 2cm behind the V-groove is coated with sensing gold film, and a multimode fiber is spliced with the sensing probe to construct the novel fiber cladding SPR sensor. On the basis of the investigation of the effects of different V-groove depth, number and period on the performance of fiber SPR refractive index sensor, a high sensitivity strain SPR sensor is designed and fabricated by employing the characteristic that the V-groove will deform with strain. The testing results indicate that the average refractive index sensitivity of the sensor is 2896.4nm/RIU, and the strain wavelength sensitivity is 25.92pm/µÎµ which is much higher than that of the fiber interference and grating strain sensors, and the strain light intensity sensitivity is -4.4×10-4 a.u./µÎµ. The proposed fiber cladding SPR strain sensor has the advantages of simple structure and convenient manufacture, and can be used for working in a narrow space.

Multi-channel curvature sensor based on fiber bending loss wavelength and SPR.

Fiber Bragg gratings and interferometric curvature sensors are easily disturbed by axial strain and temperature, and cascaded multi-channel curvature sensing is difficult. In this letter, a curvature sensor based on fiber bending loss wavelength and the surface plasmon resonance (SPR) mechanism is proposed, which is insensitive to axial strain and temperature. In addition, fiber bending loss valley wavelength demodulation curvature improves the accuracy of bending loss intensity sensing. Experiments show that the bending loss valley of single-mode fiber with different cut-off wavelengths has different working bands which is combined with a plastic-clad multi-mode fiber SPR curvature sensor to realize a wavelength division multiplexing multi-channel curvature sensor. The bending loss valley wavelength sensitivity of single-mode fiber is 0.8474 nm/m-1, and the intensity sensitivity is 0.0036 a.u./m-1. The resonance valley wavelength sensitivity of the multi-mode fiber SPR curvature sensor is 0.3348 nm/m-1, and the intensity sensitivity is 0.0026 a.u./m-1. The proposed sensor is insensitive to temperature and strain, and the working band is controllable, which provides a new, to the best of our knowledge, solution for wavelength division multiplexing multi-channel fiber curvature sensing.

Cardiac valve calcification is associated with mortality in hemodialysis patients: a retrospective cohort study.

BACKGROUND: Cardiac valve calcification (CVC) is common in end-stage renal disease (ESRD). We investigated the effect of CVC on all-cause and cardiovascular (CV) mortality in maintenance hemodialysis (MHD) patients. METHODS: A retrospective cohort study was conducted on 434 hemodialysis patients who underwent echocardiography for qualitative assessment of valve calcification with complete follow-up data from January 1, 2014, to April 30, 2021. The baseline data between the CVC and non-CVC groups were compared. The Kaplan-Meier method was used to analyse all-cause and cardiovascular mortality. The association of CVC with all-cause and cardiovascular mortality was evaluated using multivariate Cox regression analysis. RESULTS: Overall, 27.2% of patients had mitral valve calcification (MVC), and 31.8% had aortic valve calcification (AVC) on echocardiography. Patients with CVC showed significantly higher all-cause (log-rank P < 0.001) and cardiovascular (log-rank P < 0.001) mortality rates than patients without CVC. In multivariate regression analyses, MVC (HR: 1.517, P = 0.010) and AVC (HR: 1.433, P = 0.028) were significant factors associated with all-cause mortality. MVC (HR: 2.340, P < 0.001) and AVC (HR: 2.410, P < 0.001) were also significant factors associated with cardiovascular mortality. CONCLUSIONS: MVC and AVC increased the risk of all-cause and cardiovascular mortality in MHD patients. Regular follow-up with echocardiography could be a useful method for risk stratification in MHD patients.

A Robust Regression Framework with Laplace Kernel-Induced Loss.

This work proposes a robust regression framework with nonconvex loss function. Two regression formulations are presented based on the Laplace kernel-induced loss (LK-loss). Moreover, we illustrate that the LK-loss function is a nice approximation for the zero-norm. However, nonconvexity of the LK-loss makes it difficult to optimize. A continuous optimization method is developed to solve the proposed framework. The problems are formulated as DC (difference of convex functions) programming. The corresponding DC algorithms (DCAs) converge linearly. Furthermore, the proposed algorithms are applied directly to determine the hardness of licorice seeds using near-infrared spectral data with noisy input. Experiments in eight spectral regions show that the proposed methods improve generalization compared with the traditional support vector regressions (SVR), especially in high-frequency regions. Experiments on several benchmark data sets demonstrate that the proposed methods achieve better results than the traditional regression methods in most of data sets we have considered.

Efficacy and safety of esketamine for perioperative depression in patients undergoing elective surgery: A meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and mortality in Chinese maintenance haemodialysis patients: a retrospective cohort study.

OBJECTIVE: To investigate the relationship between the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and all-cause and cardiovascular (CV) mortality in Chinese haemodialysis (HD) patients. DESIGN: Retrospective cohort study. SETTING: Patients from June 2015 to September 2016 and followed through September 2021 were categorised into quartiles according to the follow-up averaged TG/HDL-C ratio. The association between TG/HDL-C and mortality was examined by univariate and multivariate time-varying Cox regression analyses. The C-index was used to assess the predictive accuracy of the Cox regression models. PARTICIPANTS: A total of 534 maintenance HD patients were enrolled. PRIMARY AND SECONDARY OUTCOME MEASURES: The outcomes were all-cause death and CV mortality. RESULTS: During the median follow-up of 61 months, 207 patients died, with 94 (45.4%) classified as CV death. After adjusting for confounders, multivariate time-varying Cox regression analysis showed that the quartile 4 group (TG/HDL-C ≥2.64) was associated with decreased all-cause mortality (adjusted HR 0.51, 95% CI 0.33-0.77, p=0.001) and CV mortality (adjusted HR 0.31; 95% CI 0.16 to 0.62; p=0.001) in maintenance HD patients. Model 1 of all-cause mortality achieved a C-index of 0.72 (95% CI 0.68 to 0.75), and model 2 achieved a C-index of 0.77 (95% CI 0.73 to 0.82). The C-index for model 1 in CV mortality was 0.74 (95% CI 0.70 to 0.77), and the C-index for model 2 was 0.80 (95% CI 0.75 to 0.84). CONCLUSIONS: High TG/HDL-C was associated with decreased all-cause and CV mortality in HD patients.

Identification of Novel NSD1 variations in four Pediatric cases with sotos Syndrome.

OBJECTIVE: Sotos syndrome (SOTOS) is an uncommon genetic condition that manifests itself with the following distinctive features: prenatal overgrowth, facial abnormalities, and intellectual disability. This disorder is often associated with haploinsufficiency of the nuclear receptor-binding SET domain protein 1 (NSD1)gene. We investigated four pediatric cases characterized by early-onset overgrowth and developmental delay. The primary objective of this study was to achieve accurate genetic diagnoses. DESIGN&METHODS: A sequential analysis approach comprising chromosomal karyotyping, whole exome sequencing, and microarray analysis was conducted. RESULTS: All four cases exhibited variations in the NSD1 gene, with the identification of four previously unreported de novo variants, each specific to one case.Specifically, Case 1 carried the NSD1 (NM_022455): c.2686 C > T(p.Q896X) variant, Case 2 had the NSD1 (NM_022455): c.2858_2859delCT(p.S953X) variant, Case 3 displayed a chromosomal aberration, chr5: 5q35.2q35.3(176,516,604-176,639,249)×1, which encompassed the 5'-untranslated region of NSD1, and Case 4 harbored the NSD1 (NM_022455): c.6397T > G(p.C2133G) variant. CONCLUSION: This study not only provided precise diagnoses for these cases but also supplied significant evidence to facilitate informed consultations. Furthermore, our findings expanded the spectrum of mutations associated with SOTOS.

Ginsenoside Rh4 Alleviates Amyloid ß Plaque and Tau Hyperphosphorylation by Regulating Neuroinflammation and the Glycogen Synthase Kinase 3ß Signaling Pathway.

Alzheimer's disease (AD) is a primary neurodegenerative disease. It can be caused by aging and brain trauma and severely affects the abilities of cognition and memory of patients. Therefore, it seriously threatens the mental and physical health of humans worldwide. As a traditional Chinese medicine, ginsenosides have been proven to have a variety of pharmacological activities. Ginsenoside Rh4 (Rh4) is one of the rare ginsenosides with higher pharmacological activity than ordinary ginsenosides, but its effect on alleviating AD and its molecular mechanism have not been studied. Here, we investigated the anti-AD effects of Rh4 and its potential mechanisms using an AD mouse model induced by a combination of AlCl3·6H2O and d-galactose. The results showed that Rh4 could significantly improve the ability of cognizance and reduce neuronal damage in mice. Concurrently, Rh4 attenuates amyloid ß accumulation, increases the density of dendritic spines, and logically inhibits synaptic structural damage as a result of neuronal excessive apoptosis and autophagy. Rh4 can not only inhibit the inflammatory response caused by the overactivation of microglia and astrocytes, reduce the levels of pro-inflammatory factors, increase the level of antioxidant enzymes in serum, and significantly improve the activity of antioxidant enzyme SOD1 in the hippocampus but also inhibit the hyperphosphorylation of tau protein in the hippocampus of mice by regulating the Wnt2b/GSK-3ß/SMAD4 signaling pathway. Together, this study provides a theoretical basis for Rh4 in the treatment of AD and reveals that Rh4 is a potential drug for the treatment of AD.

Furazolidone-induced pulmonary toxicity in Helicobacter pylori infection: Two case reports.

BACKGROUND: Helicobacter pylori (H. pylori) infection is a global problem, causing significant morbidity and mortality. Furazolidone is recommended to eradicate H. pylori infections in China owing to the highly associated antibiotic resistance. CASE SUMMARY: This article presents two cases of lung injury caused by furazolidone treatment of H. pylori infection and the relevant literature review. Two patients developed symptoms, including fever, cough, and fatigue after receiving a course of furazolidone for H. pylori infection. Chest computed tomography showed bilateral interstitial infiltrates. Laboratory studies revealed elevated blood eosinophil count. After discontinuing furazolidone with or without the use of corticosteroids, the symptoms improved rapidly. A PubMed database literature search revealed three reported cases of lung injury suggestive of furazolidone-induced pulmonary toxicity. CONCLUSION: Clinicians should be aware of the side effects associated with the administration of furazolidone to eradicate H. pylori infection.

Wearable Fiber SPR Respiration Sensor Based on a LiBr-Doped Silk Fibroin Film.

Respiration is essential for supporting human body functions. However, a biocompatible fiber respiration sensor has rarely been discussed. In this study, we propose a wearable fiber surface plasmon resonance (SPR) respiration sensor using a LiBr-doped silk fibroin (SF) film. The SPR sensor monitors respiration by responding to airway humidity variation during inhalation and exhalation. We fabricated the SPR respiration sensor by depositing the core of a plastic-clad optical fiber with a gold film and an SF-LiBr composite film. The SF-LiBr composite film can absorb water through the interaction between water molecules and hydrogen bonds linking fibroin chains. Thus, humidity variation can change the SF-LiBr composite film's refractive index (RI), altering the phase-matching condition of the surface plasmon polaritons and shifting the SPR spectral dip. In experiments, we test the effect of the LiBr doping ratio on humidity response and confirm that the SF-22.1 wt % LiBr sensor has balanced performances. The SF-22.1 wt % LiBr sensor has a broad sensing range of 35-99% relative humidity (RH), a reasonable overall sensitivity of -6.5 nm/% RH, a fast response time of 135 ms, a quick recovery time of 150 ms, good reversibility, and good repeatability, which is capable of tracking different respiration states and patterns. Finally, we encapsulate this sensor in a conventional nasal oxygen cannula for wearable respiration monitoring, proving that the sensor is suitable for high-sensitivity, real-time, and accurate respiration monitoring.

Fiber SPR biosensor sensitized by MOFs for MUC1 protein detection.

The concentration of tumor markers is low, which needs a highly sensitive, stable and fast detection method. In this paper, we proposed and demonstrated a U-shape fiber SPR biosensor sensitized by MOFs materials. The surface of the U-shape SPR sensor was modified with MOFs materials to enhance the sensitivity, and the nucleic acid aptamer was immobilized on the sensor surface because of the biocompatibility of MOFs materials. By the high specificity of the nucleic acid aptamer, the MUC1 protein was recognized and detected. The testing results indicate that the sensor has a logarithmic linear response in the MUC1 protein concentration detection range of 1 pg/ml-100 µg/ml, its sensitivity and detection limit are 5.33 nm/log(µg/ml) and 0.16 pg/ml respectively. After being sensitized by MOFs, the detection sensitivity of the sensor can be increased by 1.62 times，the LOD can be decreased by 0.75 times. The sensor has high sensitivity and specificity, which has broad application prospects in clinical detection of tumor markers.

Detection of Novel Pathogenic Variants in Two Families with Recurrent Fetal Congenital Heart Defects.

Background: Congenital heart disease (CHD) is the most common birth defect with strong genetic heterogeneity. To date, about 400 genes have been linked to CHD, including cell signaling molecules, transcription factors, and structural proteins that are important for heart development. Genetic analysis of CHD cases is crucial for clinical management and etiological analysis. Methods: Whole-exome sequencing (WES) was performed to identify the genetic variants in two independent CHD cases with DNA samples from fetuses and their parents, followed by the exclusion of aneuploidy and large copy number variations (CNVs). The WES results were verified by Sanger sequencing. Results: In family A, a compound heterozygous variation in PLD1 gene consisting of c.1132dupA (p.I378fs) and c.1171C>T (p.R391C) was identified in the fetus. The two variants were inherited from the father (c.1132dupA) and the mother (c.1171C>T), respectively. In family B, a hemizygous variant ZIC3: c.861delG (p.G289Afs*119) was identified in the fetus, which was inherited from the heterozygous mother. We further confirmed that these variants PLD1: c.1132dupA and ZIC3: c.861delG were novel. Conclusion: The findings in our study identified novel variants to the mutation spectrum of CHD and provided reliable evidence for the recurrent risk and reproductive care options to the affected families. Our study also demonstrates that WES has considerable prospects of clinical application in prenatal diagnosis.

Effects of perioperative use of esketamine on postpartum depression risk in patients undergoing cesarean section: A randomized controlled trial.

BACKGROUND: Postpartum depression (PPD) is a prevalent public health issue. Although ketamine has prophylactic effects on PPD in women undergoing cesarean section, the effects of esketamine on PPD remain unclear. This trial aimed to evaluate the efficacy of perioperative esketamine infusion on PPD risk by assessing Edinburgh Postnatal Depression Scale (EPDS) scores and blood biomarkers. METHODS: A total of 150 participants undergoing elective cesarean section were randomly allocated to receive either esketamine or normal saline. Since 27 participants were excluded due to consent withdrawal or loss to follow-up, 123 patients were included. The primary outcome was the prevalence of PPD risk. Secondary outcomes included the prevalence of postpartum anxiety (PPA) risk, levels of biomarkers, postoperative pain intensity, and cumulative sufentanil consumption. RESULTS: The prevalence of PPD and PPA risk at 3 days, 42 days, 3 months, and 6 months postpartum did not differ between the two groups. Furthermore, EPDS scores, pain intensity at rest, and during coughing on postoperative days (POD) 1 and 2 did not differ between the two groups. Sufentanil consumption during 0-12 h, 12-24 h, 0-24 h, and 0-48 h postoperatively were significantly lower in the esketamine group compared to the control group. Blood biomarkers did not differ between the two groups on POD 3. LIMITATIONS: The sample size was small. PPD risk was simply screened, not diagnosed. CONCLUSIONS: Perioperative administration of esketamine did not decrease the incidence of PPD risk in women after elective cesarean section. However, esketamine reduced opioid consumption.

A role of GABAA receptor α1 subunit in the hippocampus for rapid-acting antidepressant-like effects of ketamine.

Ketamine can produce rapid-acting antidepressant effects in treatment-resistant patients with depression. Although alterations in glutamatergic and GABAergic neurotransmission in the brain play a role in depression, the precise molecular mechanisms in these neurotransmission underlying ketamine's antidepressant actions remain largely unknown. Mice exposed to FSS (forced swimming stress) showed depression-like behavior and decreased levels of GABA (γ-aminobutyric acid), but not glutamate, in the hippocampus. Ketamine increased GABA levels and decreased glutamate levels in the hippocampus of mice exposed to FSS. There was a correlation between GABA levels and depression-like behavior. Furthermore, ketamine increased the levels of enzymes and transporters on the GABAergic neurons (SAT1, GAD67, GAD65, VGAT and GAT1) and astrocytes (EAAT2 and GAT3), without affecting the levels of enzymes and transporters (SAT2, VGluT1 and GABAAR γ2) on glutamatergic neurons. Moreover, ketamine caused a decreased expression of GABAAR α1 subunit, which was specifically expressed on GABAergic neurons and astrocytes, an increased GABA synthesis and metabolism in GABAergic neurons, a plasticity change in astrocytes, and an increase in ATP (adenosine triphosphate) contents. Finally, GABAAR antagonist bicuculline or ATP exerted a rapid antidepressant-like effect whereas pretreatment with GABAAR agonist muscimol blocked the antidepressant-like effects of ketamine. In addition, pharmacological activation and inhibition of GABAAR modulated the synthesis and metabolism of GABA, and the plasticity of astrocytes in the hippocampus. The present data suggest that ketamine could increase GABA synthesis and astrocyte plasticity through downregulation of GABAAR α1, increases in GABA, and conversion of GABA into ATP, resulting in a rapid-acting antidepressant-like action. This article is part of the Special Issue on 'Ketamine and its Metabolites'.