Inhibitory Effect and Mechanism upon Glucose-Insulin-Potassium Administration on Postpartum Mice with Uterine Cramping Pain.

This study aimed to explore the effect of glucose-insulin-potassium (GIK) on postpartum uterine cramping pain(UCP) in mice and the possible underlying mechanisms. Thirty full-term pregnancy C57BL/6 mice, within 6 h after spontaneous labor, the mice were randomly assigned into the following three groups: the control group (group C), the oxytocin group (group O), and the GIK plus oxytocin group (group G). Group G and group O were administered GIK and normal saline, respectively, and 10 min later, oxytocin was injected intraperitoneally; group C received normal saline twice. The pain scores of the mice were assessed after establishment of the postpartum UCP model. The differential expressions of energy metabolism and oxidized lipid metabolites in the uterus were analyzed. The behavioral scores in group G were significantly lower than those in group O (P < 0.05).When compared to group O, group G showed a significant increase in ATP levels (P = 0.046), and group G exhibited elevated levels of amino acids, including L-glutamine, L-aspartic acid, and ornithine. Additionally, phosphate compounds (2-phosphoglyceric acid and 3-phosphoglyceric acid) showed elevated levels. When compared to group O, group G exhibited a decrease in 19R-hydroxy PGF2α, an increase in 9,10-EpOME and 12,13-EpOME, and a decrease in trans-EKODE-E-Ib. Additionally, group G showed an elevation in 16,17-EpDPE and 8-HDoHE. This study confirms the analgesic effect of GIK during postpartum oxytocin infusion. Metabolomics and glycolysis product analysis suggest that GIK's alleviation of UCP is associated with its enhancement of glycolysis and the influence of phenylalanine synthesis, aspartate metabolism, and arginine synthesis pathways. Additionally, the effects of GIK appears to be linked to its influence on the linoleic acid metabolic pathway.

Predictive Role of Preoperative Nutritional Status on Early Postoperative Outcomes in Different-Aged Patients Undergoing Heart Valve Surgery.

OBJECTIVES: The authors sought to elucidate the role and predictive effects of preoperative nutritional status on postoperative outcomes across different age groups undergoing heart valve surgery. DESIGN: A retrospective study with intergroup comparison, receiver operating characteristic curve analysis, and logistic regression analysis. SETTING: A hospital affiliated with a medical university. PARTICIPANTS: Three thousand nine hundred five patients undergoing heart valve surgery between October 2016 and December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into 3 age subgroups: young (aged 18-44 years), middle-aged (aged 45-59 years), and older (aged ≥60 years) adults. The Nutritional Risk Index (NRI), Prognostic Nutritional Index, and Controlling Nutritional Status scores were evaluated. Young adults with an NRI <99 experienced a significantly higher rate of prolonged intensive care unit stay (28.3% v 4.1%, p < 0.001), with a relative risk of 4.58 (95% CI: 2.04-10.27). Similarly, young adults with an NRI <97 had a significantly increased occurrence of mortality within 30 days after surgery (6.3% v 0.2%, p < 0.001), with a relative risk of 41.11 (95% CI: 3.19-529.48). CONCLUSIONS: In patients who undergo heart valve surgery, early postoperative outcomes can be influenced by nutritional status before the surgery. In the young-adult group, NRI <99 and NRI <97 effectively could predict prolonged intensive care unit stay and 30-day mortality, respectively.

Depletion of PIEZO1 expression is accompanied by upregulating p53 signaling in mice with perioperative neurocognitive disorder.

As the common complications observed in surgical elder patients, perioperative neurocognitive disorders (PND) cause a series of serious perioperative health problems. However, there are no effective treatments, and the exact mechanisms are still largely unknown. In this study, transcriptome sequencing was performed to investigate the differentially expressed genes (DEGs) in the hippocampus of C57BL/6J aged mice with or without PND. Compared with the Mock group, the expression of 352, 395, and 772 genes changed significantly in the PND group at days 1, 7, and 21 after surgery, respectively. Gene ontology (GO) and gene set enrichment analysis (GSEA) showed that DEGs were mainly associated with p53 signaling. Moreover, GSEA revealed potentially p53-related DEGs such as leucine-rich repeat serine/threonine-protein kinase 1 (LRRK1), monooxygenase DBH-like 1 (MOXD1), and piezo type mechanosensitive ion channel component 1 (PIEZO1). Furthermore, we confirmed the decreased interaction of PIEZO1 with p53 in PND, and upregulation of PIEZO1 resulted in a decrease in p53 protein levels through increased ubiquitination of p53. In conclusion, this study contributes to the knowledge of global changes in gene expression and mechanisms during PND.

Prelimbic area to lateral hypothalamus circuit drives social aggression.

Controlling aggression is a vital skill in social species such as rodents and humans and has been associated with the medial prefrontal cortex (mPFC). In this study, we showed that during aggressive behavior, the activity of GABAergic neurons in the prelimbic area (PL) of the mPFC was significantly suppressed. Specific activation of GABAergic PL neurons significantly curbed male-to-male aggression and inhibited conditioned place preference (CPP) for aggression-paired contexts, whereas specific inhibition of GABAergic PL neurons brought about the opposite effect. Moreover, GABAergic projections from PL neurons to the lateral hypothalamus (LH) orexinergic neurons mediated aggressive behavior. Finally, directly modulated LH-orexinergic neurons influence aggressive behavior. These results suggest that GABAergic PL-orexinergic LH projection is an important control circuit for intermale aggressive behavior, both of which could be targets for curbing aggression.

Preoperative inflammatory markers predict postoperative clinical outcomes in patients undergoing heart valve surgery: A large-sample retrospective study.

Introduction: Preoperative inflammation affects the postoperative outcomes of patients undergoing heart valve surgery. This study aimed to explore the role and predictive effects of preoperative inflammation on the primary outcomes after valvular cardiac surgery. Methods: This retrospective study utilized a medical recording system to screen 5075 patients who underwent heart valve surgery. Data on the C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and neutrophil-to-lymphocyte ratio (NLR) before heart valve surgery were collected from the hospital's medical system. Postoperative hepatic insufficiency, acute kidney injury, heart failure, and myocardial damage were assessed using blood indicators. Patients with and without prolonged mechanical ventilation, extended intensive care unit stays, prolonged hospital stays, and death within 30 days after surgery (considered the primary outcome in this study) were compared. Group comparisons, receiver operating characteristic (ROC) curve analyses, and logistic analyses were performed to determine the associations between preoperative inflammation and outcomes after heart valve surgery. Results: A total of 3249 patients were included in the analysis. Significant differences in CRP level, ESR, and NLR were found between patients with and without postoperative adverse outcomes. ROC analysis showed that CRP levels >5 mg/L effectively predicted postoperative heart failure, and NLR >3.5 had a good predictive effect on all-cause mortality within 30 days after surgery. Patients with CRP levels >5 mg/L had a higher incidence of postoperative heart failure than other patients (20.7% vs. 12.6%, P<0.001), with a relative risk of 1.447 (95% confidence interval: 1.155-1.814). Patients with NLR >3.5 had a higher incidence of death within 30 days after surgery (5.3% vs. 1.2%, P<0.001), with a relative risk of 3.236 (95% confidence interval: 1.773-5.906). Conclusion: Preoperative inflammation can affect postoperative outcomes in patients undergoing heart valve surgery. CRP level >5 mg/L and NLR >3.5 can effectively predict postoperative heart failure and death within 30 days after surgery, respectively.

Laryngeal mask general anaesthesia versus spinal anaesthesia for promoting early recovery of cervical conisation: A randomised, controlled clinical study.

Background: Although both spinal and general anaesthesia provides good anaesthesia for cervical conization, spinal anaesthesia delays the return of lower limb movements and urinary function, whereas general anaesthesia requires the patient to be unconscious. It is unclear which anaesthetic technique is more conducive to early postoperative recovery in patients undergoing cervical conization. Patients and methods: 140 patients undergoing cervical conization underwent either laryngeal mask general anaesthesia (LMA, n = 70) or spinal anaesthesia (SA, n = 70). In the LMA group, an i-gel mask was used for airway management. In the SA group, spinal anaesthesia was received with 0.75% ropivacaine (15 mg) in the L3-4 interval. The quality of recovery score (QoR-15) was the primary endpoint of the study. Secondary endpoints included incidence of adverse 24-h analgesia (NRS>3); return of lower limb activity; first bed activity and feeding; and the number of catheters removed at 6, 12 and 24 h postoperatively. Result: The LMA group significantly improved QoR-15 scores (136.62 ± 11.02 vs 119.97 ± 12.75; P < 0.001); and reduced the incidence of poor analgesia (NRS >3) within 24 h postoperatively (20% vs 42.8%, P = 0.006); reduced time in bed (15.62 ± 3.83 h vs 18.27 ± 5.57 vs, P = 0.001); improved patient satisfaction (86% vs 27%; P < 0.001); and catheters removal within 24 h (70/70 vs 42/70, P < 0.001). Conclusion: LMA general anaesthesia can facilitate early postoperative recovery in patients undergoing cervical conization compared with conventional spinal anaesthesia. Trial registration: Chinese Clinical Trial Registry (ID: ChiCTR1800019384), http://www.chictr.org.cn/listbycreater.aspx (08/11/2018).

Analgesic outcomes of tramadol alone and in combination with Butorphanol or Flurbiprofen Axetil after cesarean section: a retrospective study with propensity score matching analysis.

BACKGROUND: The Society for Obstetric Anesthesia and Perinatology recommends a multimodal analgesia regimen for cesarean delivery analgesia. This study aimed to compare the analgesic effects of tramadol alone and combined with butorphanol or flurbiprofen axetil after a cesarean section. METHODS: We performed a retrospective analysis based on the electronic medical records of a teaching hospital in China from January 2018 to January 2020. We collected data on demographic characteristics, anesthesia, analgesia strategy, and pain intensity postoperatively during the first 48 hours. Inadequate postoperative analgesia during this period was defined as an NRS score ≥ 4. We also collected data regarding off-bed activity and intestinal function recovery. Participants were classified into three groups according to analgesia regimens. Groups T, TF, and TB received tramadol, a mixture of tramadol and flurbiprofen axetil, and a combination of tramadol and butorphanol, respectively. Analgesic outcomes were compared using propensity score matching analysis. RESULTS: Data from 2323 cases of caesarean section were included in the analysis, and 521 pairs were matched in each group according to their propensity score. Compared with group T, The inadequate analgesia on pain at rest and pain at movement was lower in group TF (RR: 0.42, 95% CI: 0.36-0.49, P = 0.001 and RR: 0.58, 95% CI: 0.48-0.69, P < 0.001, respectively),and the incidence of inadequate control of pain at movement was higher in group TB (RR: 1.38, 95% CI: 1.22-1.55, P < 0.001). Additionally, the percentage of off-bed activity at 2 days postoperatively was higher in group TB than in groups TF and T (78.7% vs. 68.5 and 78.7% vs. 64.9%, respectively, P < 0.001). The incidence of intestinal function recovery 2 days after cesarean delivery in group TB was higher than that in group TF (73.3% vs. 66.2%, P = 0.013). CONCLUSIONS: Combining tramadol and flurbiprofen axetil could enhance the analgesic effect and be safely used for analgesia after a cesarean section. However, combining tramadol and butorphanol may produce an antagonistic effect.

Anisocoria and mydriasis after scalp nerve block: a case report.

Strategies for the assessment of abnormal neurological findings during general anesthesia are limited. However, pupil abnormalities may represent serious neurological complications. We herein present a case of new-onset anisocoria and mydriasis that developed after scalp nerve block. The patient's signs were possibly related to increased intracranial pressure with resulting brain shift that ultimately affected the oculomotor nerves. A 45-year-old man was scheduled for left cerebellar tumor resection and ventricular drainage surgery; however, anisocoria and left pupillary mydriasis were observed after induction of general anesthesia and performance of scalp nerve block. After reducing the intracranial pressure, the right pupil showed constriction (1 mm) but the left pupil was dilated (5 mm). The pupils were of similar size postoperatively. Although pupillary dilation during general anesthesia has been previously described, this is the first case in which the mydriasis was considered to have been caused by brain shift due to increased intracranial pressure after scalp nerve block. Thus, we propose this phenomenon as a new possible cause of pupillary changes. Actively monitoring this presentation intraoperatively could enable early detection of and intervention for complications, therefore improving the prognosis.

Glucose-insulin-potassium alleviates uterine cramping pain following cesarean delivery: A randomized, controlled trial.

Objectives: To explore the effect of glucose-insulin-potassium (GIK) therapy on uterine cramping pain (UCP) following cesarean delivery (CD). Design: Single-center, randomized controlled study. Setting: Second Affiliated Hospital of Army Medical University, Chongqing, China. Participants: A total of 140 women, aged 20-40 years, who underwent CD with a transverse incision were randomly assigned to the GIK (P) or control (C) groups in a 1:1 ratio. Interventions: GIK was intravenously administered to patients in Group P. Patients in Group C received normal saline (NS). After umbilical cord clamping, oxytocin was administered intravenously. The same GIK and NS regimens were administered on postoperative days 1 and 2, followed by oxytocin 10 min later. Primary and secondary outcome measures: Following oxytocin administration, UCP was assessed using the visual analog scale (VAS), and the maximum VAS score (primary outcome) was recorded. Results: Patients in Group P had significantly lower maximum VAS scores than those in Group C on postoperative days 1 (38.4 ± 21.1 vs. 52.3 ± 20.8, p < 0.001) and 2 (10 [0,30] vs. 30.5 [8.75,50], p < 0.001). Group P patients also had shorter pain duration on postoperative day 1 (39.6 ± 19.5 min vs. 50.6 ± 18.2 min, p = 0.001). Group P patients had a lower incidence of inadequate analgesia of UCP than Group C on days 1 (45.5% vs. 74.2%, p < 0.001) and 2 (10.6% vs. 47.0%, p < 0.001); the RRs for experiencing inadequate analgesia for UCP postpartum in Group P patients was 0.612 (95% CI: 0.454-0.826, p < 0.001) on day 1 and 0.226 (95% CI: 0.107-0.476, p < 0.001) on day 2. The absolute risk reduction (ARR) was 28.7%; thus number needed to treat (NNT) was 3 after rounding up. A subgroup analysis demonstrated that Group P patients undergoing repeat CD had lower maximum VAS scores for UCP on both postoperative days 1 and 2. Conclusion: Our findings suggest that GIK can relieve UCP and shorten its duration. Our results provide information to facilitate the development of novel approaches for managing UCP.Clinical Trial Registration: This study was approved by the Medical Ethics Committee of Second Affiliated Hospital of Army Medical University (2020-109-01, 19/11/2020) and registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn, ChiCTR2100041607,01/01/2021).

A survey of current practices, attitudes and demands of anaesthesiologists regarding the depth of anaesthesia monitoring in China.

BACKGROUND: In this study, we aimed to analyse survey data to explore two different hypotheses; and for this purpose, we distributed an online survey to Chinese anaesthesiologists. The hypothetical questions in this survey include: (1) Chinese anaesthesiologists mainly use the depth of anaesthesia (DoA) monitors to prevent intraoperative awareness and (2) the accuracy of these monitors is the most crucial performance factor during the clinical daily practice of Chinese anaesthesiologists. METHODS: We collected and statistically analysed the response of a total of 12,750 anesthesiologists who were invited to participate in an anonymous online survey. The Chinese Society of Anaesthesiologists (CSA) trial group provided the email address of each anaesthesiologist, and the selection of respondents was random from the computerized system. RESULTS: The overall response rate was 32.0% (4037 respondents). Only 9.1% (95% confidence interval, 8.2-10.0%) of the respondents routinely used DoA monitors. Academic respondents (91.5, 90.3-92.7%) most frequently used DoA monitoring to prevent awareness, whereas nonacademic respondents (88.8, 87.4-90.2%) most frequently used DoA monitoring to guide the delivery of anaesthetic agents. In total, the number of respondents who did not use a DoA monitor and whose patients experienced awareness (61.7, 57.8-65.6%) was significantly greater than those who used one or several DoA monitors (51.5, 49.8-53.2%). Overall, the crucial performance factor during DoA monitoring was considered by 61.9% (60.4-63.4%) of the respondents to be accuracy. However, most respondents (95.7, 95.1-96.3%) demanded improvements in the accuracy of the monitors for DoA monitoring. In addition, broad application in patients of all ages (86.3, 85.2-87.4%), analgesia monitoring (80.4, 79.2-81.6%), and all types of anaesthetic agents (75.6, 74.3-76.9%) was reported. In total, 65.0% (63.6-66.5%) of the respondents believed that DoA monitors should be combined with EEG and vital sign monitoring, and 53.7% (52.1-55.2%) believed that advanced DoA monitors should include artificial intelligence. CONCLUSIONS: Academic anaesthesiologists primarily use DoA monitoring to prevent awareness, whereas nonacademic anaesthesiologists use DoA monitoring to guide the delivery of anaesthetics. Anaesthesiologists demand high-accuracy DoA monitors incorporating EEG signals, multiple vital signs, and antinociceptive indicators. DoA monitors with artificial intelligence may represent a new direction for future research on DoA monitoring.

Heart rate variability-derived features based on deep neural network for distinguishing different anaesthesia states.

BACKGROUND: Estimating the depth of anaesthesia (DoA) is critical in modern anaesthetic practice. Multiple DoA monitors based on electroencephalograms (EEGs) have been widely used for DoA monitoring; however, these monitors may be inaccurate under certain conditions. In this work, we hypothesize that heart rate variability (HRV)-derived features based on a deep neural network can distinguish different anaesthesia states, providing a secondary tool for DoA assessment. METHODS: A novel method of distinguishing different anaesthesia states was developed based on four HRV-derived features in the time and frequency domain combined with a deep neural network. Four features were extracted from an electrocardiogram, including the HRV high-frequency power, low-frequency power, high-to-low-frequency power ratio, and sample entropy. Next, these features were used as inputs for the deep neural network, which utilized the expert assessment of consciousness level as the reference output. Finally, the deep neural network was compared with the logistic regression, support vector machine, and decision tree models. The datasets of 23 anaesthesia patients were used to assess the proposed method. RESULTS: The accuracies of the four models, in distinguishing the anaesthesia states, were 86.2% (logistic regression), 87.5% (support vector machine), 87.2% (decision tree), and 90.1% (deep neural network). The accuracy of deep neural network was higher than those of the logistic regression (p < 0.05), support vector machine (p < 0.05), and decision tree (p < 0.05) approaches. Our method outperformed the logistic regression, support vector machine, and decision tree methods. CONCLUSIONS: The incorporation of four HRV-derived features in the time and frequency domain and a deep neural network could accurately distinguish between different anaesthesia states; however, this study is a pilot feasibility study. The proposed method-with other evaluation methods, such as EEG-is expected to assist anaesthesiologists in the accurate evaluation of the DoA.

Repeated Cesarean Delivery Predicted a Higher Risk of Inadequate Analgesia Than Primary Cesarean Delivery: A Retrospective Study with Propensity Score Match Analysis.

PURPOSE: This study aimed to compare the analgesic outcomes between primary and repeated cesarean delivery. PATIENTS AND METHODS: We performed a retrospective analysis based on the medical records of a teaching hospital in China from January 2018 to March 2019. We collected data on demographic characteristics, perioperative complications, anesthesia, and surgical factors for cesarean delivery patients. We also recorded the postoperative analgesic strategy, pain intensity (assessed by the number rating scale) during the first 48 hrs after surgery, hospital cost, and hospital stay. Postoperative inadequate analgesia was defined by a score of ≥ 4 in the number rating scale. Analgesic outcomes after cesarean delivery between primiparas and multiparas were compared using propensity score matching analysis. Moreover, subgroup logistic analysis for different age groups (≥ 35 and < 35 years) was performed to investigate the effect of the maternal category on postoperative inadequate analgesia. RESULTS: A total of 1543 patients were included in the analysis and 571 pairs (1142 patients) were matched in the primiparas and multiparaparas group according to their propensity score. In both the non-matched and matched cohort, the incidence of inadequate analgesia in the primiparas group was lower than that in the multiparas group (16.7% vs. 24.0%, P < 0.001 and 16.1% vs. 23.5%, P = 0.002; respectively). The multiparas group was identified as being at risk of inadequate analgesia after cesarean delivery in both age groups (age ≥ 35 years, odds ratio: 2.18, 95% confidence interval: 1.20-3.95; age < 35 years, odds ratio: 1.43, 95% confidence interval 1.08-1.89). CONCLUSION: Multiparas that undergo a repeat cesarean delivery had a significantly higher risk of inadequate postoperative pain treatment than primiparas. The maternal category should be considered when formulating the postoperative analgesia strategy after cesarean delivery.

Effects of Spicy Stimulation and Spicy-Food Consumption on Human Pain Sensitivity: A Healthy Volunteer Study.

Spicy-food intake has been shown to affect various human physiological systems and diseases. This study tested the analgesia effect caused by stimulation of a spicy sensation (spicy stimulation) and explored the effect of spicy-food consumption on human basal pain sensitivity. A total of 60 healthy undergraduates were included in the primary study. Placebo and sweet stimulation were used as reference interventions. Pressure and cold-pain thresholds were measured before and after taste stimulation. The frequency of spicy-food intake was also evaluated. An additional 100 subjects were recruited to validate the results. Compared to placebo stimulation, both pressure and cold-pain thresholds increased during spicy stimulation (P < .05). The increased thresholds remained, even when the taste stimulation residue was nearly eliminated (P < .05). The pressure (10.0 [2.1] vs 12.7 [3.0] kg/cm2, P < .001) and cold-pain (4.4 [1.6] vs 6.2 [2.7] seconds, P = .003) thresholds in subjects who consume spicy food ≥3 days/week were significantly lower than in those who consume it <3 days/week. In the validation population, the frequency of spicy-food intake was negatively associated with subjects' pressure (ß = -.218, P = .013) and cold-pain (ß = -.205, P = .035) thresholds. Spicy stimulation has an analgesia effect on adults that persists even after the taste stimulation stops. Conversely, a long-term spicy diet can reduce the human basal pain threshold. TRIAL REGISTRATION: The study protocol was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Army Medical University, People's Liberation Army (identification No., 2017-023-01), and it was registered on the Chinese Clinical Trial Registry at www.chictr.org.cn (No. ChiCTR1800015053). PERSPECTIVE: This study directly examined the effects of stimulation of a spicy sensation on adult pain sensitivity and was the first to explore the relationship between long-term spicy-food intake and human pain sensitivity. The results provide evidence for future clinical pain intervention and individualized pain treatment.

Neonatal exposure to propofol affects interneuron development in the piriform cortex and causes neurobehavioral deficits in adult mice.

RATIONALE: Animal studies have shown that early postnatal propofol administration is involved in neurobehavioral alterations in adults. However, the underlying mechanism is not clear. METHODS: We used c-Fos immunohistochemistry to identify activated neurons in brain regions of neonatal mice under propofol exposure and performed behavioral tests to observe the long-term consequences. RESULTS: Exposure to propofol (30g or 60 mg/kg) on P7 produced significant c-Fos expression in the deep layers of the piriform cortex on P8. Double immunofluorescence of c-Fos with interneuron markers in the piriform cortex revealed that c-Fos was specifically induced in calbindin (CB)-positive interneurons. Repeated propofol exposure from P7 to P9 induced behavioral deficits in adult mice, such as olfactory function deficit in a buried food test, decreased sociability in a three-chambered choice task, and impaired recognitive ability of learning and memory in novel object recognition tests. However, locomotor activity in the open-field test was not generally affected. Propofol treatment also significantly decreased the number of CB-positive interneurons in the piriform cortex of mice on P21 and adulthood. CONCLUSIONS: These results suggest that CB-positive interneurons in the piriform cortex are vulnerable to propofol exposure during the neonatal period, and these neurons are involved in the damage effects of propofol on behavior changes. These data provide a new target of propofol neurotoxicity and may elucidate the mechanism of neurobehavioral deficits in adulthood.

Patient-controlled intravenous tramadol versus patient-controlled intravenous hydromorphone for analgesia after secondary cesarean delivery: a randomized controlled trial to compare analgesic, anti-anxiety and anti-depression effects.

INTRODUCTION: This study aimed to compare the postoperative analgesic effects of tramadol and hydromorphone for secondary cesarean delivery (CD) as well as their anti-anxiety and anti-depression properties. METHODS: A total of 106 patients receiving secondary CD under spinal anesthesia were randomly allocated to the tramadol group (n=53) and the hydromorphone group (n=53). Each group received patient-controlled intravenous analgesia using flurbiprofen 4 mg/kg combined with tramadol (4 mg/kg) or hydromorphone (0.04 mg/kg) immediately after the surgery. Postoperative pain numerical rating scale (NRS) for incision and visceral pain, hospital anxiety and depression scale (HADS), early walking time and length of hospital stay were assessed. RESULTS: Patients in the tramadol and hydromorphone groups exhibited equivalent incision pain NRS at different time points (P>0.05). Visceral pain in the tramadol group was higher than that in the hydromorphone group at postoperative 4 hours (2.9 [1.2] vs 2.3 [1.4], P=0.011) and 8 hours (2.4 [1.1] vs 1.8 [1.1], P=0.028). One week after the surgery, the patients in the tramadol group, as compared to the hydromorphone group, had lower anxiety scores (1.9 [3.5] vs 3.6 [4.1], P=0.033) and depression scores (0.8 [1.3] vs 2.7 [4.1], P=0.023). In addition, early walking time (25.3 [7.0] hours vs 29.3 [9.6] hours, P=0.016) and length of hospital stay (2.9 [0.8] days vs 3.3 [0.8] days, P= 0.008) after the surgery in the tramadol group were less than those in the hydromorphone group. CONCLUSION: Postoperative intravenous analgesia with tramadol or hydromorphone for secondary CD provides comparable analgesic effects on incision pain. Tramadol is less effective in controlling visceral pain compared to hydromorphone. However, tramadol can help to alleviate anxiety and depression in the early postpartum period, improve patients' early mobilization and shorten their hospital stay. CLINICAL TRIAL NUMBER AND REGISTRY URL: No: ChiCTR-IIR-17011043; URL: www.chictr.org.cn.

Liver X receptor ß regulates the development of the dentate gyrus and autistic-like behavior in the mouse.

The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor ß (LXRß) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRß in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRß-null mice. In addition, LXRß deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRß in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRß-deficient mice.

Propofol Exposure in Early Life Induced Developmental Impairments in the Mouse Cerebellum.

Propofol is a widely used anesthetic in the clinic while several studies have demonstrated that propofol exposure may cause neurotoxicity in the developing brain. However, the effects of early propofol exposure on cerebellar development are not well understood. Propofol (30 or 60 mg/kg) was administered to mice on postnatal day (P)7; Purkinje cell dendritogenesis and Bergmann glial cell development were evaluated on P8, and granule neuron migration was analyzed on P10. The results indicated that exposure to propofol on P7 resulted in a significant reduction in calbindin-labeled Purkinje cells and their dendrite length. Furthermore, propofol induced impairments in Bergmann glia development, which might be involved in the delay of granule neuron migration from the external granular layer (EGL) to the internal granular layer (IGL) during P8 to P10 at the 60 mg/kg dosage, but not at the 30 mg/kg dosage. Several reports have suggested that the Notch signaling pathway plays instructive roles in the morphogenesis of Bergmann glia. Here, it was revealed that propofol treatment decreased Jagged1 and Notch1 protein levels in the cerebellum on P8. Taken together, exposure to propofol during the neonatal period impairs Bergmann glia development and may therefore lead to cerebellum development defects. Our results may aid in the understanding of the neurotoxic effects of propofol when administrated to infants.

Liver X Receptor ß Is Involved in Formalin-Induced Spontaneous Pain.

Increasing evidence indicates that the liver X receptor(LXR) ß modulates inflammatory pain. However, the molecular mechanisms through which LXRß modulates pain are unclear. Here, we found that LXRß-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXRß knockout (KO) mice compared with the WT controls. In addition, LXRß deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1ß ,TNF-α) as well as NFκB in the formalin-injected paw were elevated by the loss of LXRß. Taken together, these data indicate that LXRß is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics.

Estrogen modulation of calretinin and BDNF expression in midbrain dopaminergic neurons of ovariectomised mice.

Estrogen attenuates the loss of dopamine neurons from the substantia nigra in animal models of Parkinson's disease (PD) and excitatory amino-acid induced neurotoxicity by interactions with brain-derived neurotrophic factor (BDNF), and calretinin (CR) containing dopaminergic (DA) neurons. To examine this interaction more closely, we treated the ovariectomised (OVX) mice with estrodial for 10days, and compared these mice to those OVX mice injected with the vehicle or control mice. Estrogen treatment in OVX mice had significantly more tyrosine hydroxylase (TH) positive neurons in the substantia nigra pars compacta (SNpc). Dopamine transporter (DAT) mRNA and BDNF mRNA levels in the midbrain were also significantly increased by estrogen treatment (P<0.05). OVX markedly decreased the number of TH/CR double stained cells in the SNpc (P<0.05), a trend which could be reversed by estrogen treatment. However, the number of GFAP positive cells in the substantia nigra did not show significant changes (P >0.05) after vehicle or estrodial treatment. Furthermore, we found that estrogen treatment abrogated the OVX-induced decrease in the phosphorylated AKT (p-AKT), but not p-ERK. We hypothesize that short-term treatment with estrogen confers neuroprotection to DA neurons by increasing CR in the DA neurons and BDNF in the midbrain, which possibly related to activation of the PI3K/Akt signaling pathway.

Propofol Administration During Early Postnatal Life Suppresses Hippocampal Neurogenesis.

Propofol is currently one of the most widely used intravenous anesthetics and has been indicated to induce cognitive dysfunction in adults. Here, we investigated the effects of propofol exposure during early postnatal life on hippocampal neurogenesis. Propofol (30 or 60 mg/kg) was administered to mice on either postnatal day (P) 7 or P7-P9; cell proliferation and neurogenesis in the dentate gyrus (DG) were evaluated on P8 or P17. It showed that exposure to propofol on P7 decreased hippocampal cell proliferation as indicated by BrdU and Sox2 immunostaining at P8 in propofol treatment at the dosage of 60 mg/kg but not at the dosage of 30 mg/kg. Western blots revealed propofol treatment decreased Akt or extracellular signal-related kinase (ERK) 1/2 phosphorylation in the hippocampus at P8. Propofol treatment on P7 to P9 reduced the numbers of newly formed neurons in the DG at P17, which was accompanied by delay of granule neuron maturation and decreased the density of dendritic spines, particularly the mushroom-shaped mature spines. Furthermore, the in vitro findings indicated propofol suppressed cell proliferation and cell mitosis and activated apoptosis of C17.2 neural stem cell line in a dose-dependent manner. These findings suggest that propofol impairs cell proliferation and inhibits neurogenesis in the immature mouse brain and thus is possibly involved in the cognitive dysfunction induced by propofol anesthesia.