Fibroblast growth factor 3 contributes to neuropathic pain through Akt/mTOR signaling in mouse primary sensory neurons.

Neuropathic pain (NP), a severe chronic pain condition, remains a substantial clinical challenge due to its complex pathophysiology and limited effective treatments. An association between the members of the Fibroblast Growth Factors (FGFs), particularly Fgf3, and the development of NP has become evident. In this study, utilizing a mouse model of NP, we observed a time-dependent increase in Fgf3 expression at both mRNA and protein levels within the dorsal root ganglia (DRG). Functional studies revealed that blocking Fgf3 expression mitigated nerve injury induced nociceptive hypersensitivity, suggesting its pivotal role in pain modulation. Moreover, our findings elucidate that Fgf3 contributes to pain hypersensitivity through the activation of the Akt/mTOR signaling in injured DRG neurons. These results not only shed light on the involvement of Fgf3 in nerve injury-induced NP but also highlight its potential as a promising therapeutic target for pain management. This study thereby advances our understanding of the molecular mechanisms underlying NP and opens new avenues for the development of effective treatment strategies.

Reducing postoperative hypothermia in infants: Quality improvement in China.

BACKGROUND: Unintended postoperative hypothermia in infants is associated with increased mortality and morbidity. We noted consistent hypothermia postoperatively in more than 60% of our neonatal intensive care (NICU) babies. Therefore, we set out to determine whether a targeted quality improvement (QI) project could decrease postoperative hypothermia rates in infants. OBJECTIVES: Our SMART aim was to reduce postoperative hypothermia (<36.5°C) in infants from 60% to 40% within 6 months. METHODS: This project was approved by IRB at Guangzhou Women and Children's Medical Center, China. The QI team included multidisciplinary healthcare providers in China and QI experts from Children's Hospital of Philadelphia, USA. The plan-do-study-act (PDSA) cycles included establishing a perioperative-thermoregulation protocol, optimizing the transfer process, and staff education. The primary outcome and balancing measures were, respectively, postoperative hypothermia and hyperthermia (axillary temperature < 36.5°C, >37.5°C). Data collected was analyzed using control charts. The factors associated with a reduction in hypothermia were explored using regression analysis. RESULTS: There were 295 infants in the project. The percentage of postoperative hypothermia decreased from 60% to 37% over 26 weeks, a special cause variation below the mean on the statistical process control chart. Reduction in hypothermia was associated with an odds of 0.17 (95% CI: 0.06-0.46; p <.001) for compliance with the transport incubator and 0.24 (95% CI: 0.1-0.58; p =.002) for prewarming the OR ambient temperature to 26°C. Two infants had hyperthermia. CONCLUSIONS: Our QI project reduced postoperative hypothermia without incurring hyperthermia through multidisciplinary team collaboration with the guidance of QI experts from the USA.

Pediatric anesthesia in China.

In China, healthcare has lagged relative to its economic boom during the past 40 years. While the top tier hospitals offer pediatric perioperative care like high-income countries, lower-tier hospitals deliver lesser services of variable quality and safety related to equipment, supplies, clinician education, and availability. The national residency training program and the pediatric anesthesia fellowship program was established in 2013 and 2018 respectively. Increasing clinician workload from patient demand and a lack of consistency in quality and capability between rural and urban areas remain challenging.

Cooling treatment on the reduction of category II fetal tracings.

OBJECTIVES: Epidural-related maternal fever increases the incidence of Category II fetal tracings. To compare the effectiveness of low-flow oxygen inhalation and cooling treatment for parturients with Category II fetal tracings caused by epidural-related maternal fever. METHODS: We investigated 200 pregnant women who accepted epidural analgesia during labor and had body temperature exceeding 38 °C during labor. Among the patients, 99 and 101 were randomly allocated to receive cooling treatment group (control group) and oxygen inhalation (oxygen group), respectively. The primary outcome was the incidence of Category II fetal heart rate tracings. RESULTS: The incidence of Category II fetal heart rate tracings in the control group was significantly higher than that in the oxygen group. However, no significant differences were noted between the two groups in terms of the Apgar scores; amniotic fluid turbidity; or maternal outcomes, including cesarean section rate, forceps delivery rate, lateral resection rate, manual removal of placenta rate, the amount of intrapartum hemorrhage, and hemorrhage at postpartum 2 h. Oxygen inhalation therapy was more effective than cooling treatment in reducing the incidence of Category II tracings. CONCLUSION: Low-flow and short-term oxygen inhalation for parturients with epidural-related maternal fever reduces the incidence of Category II fetal heart rate tracings, but had no significant influence on the mode of delivery or neonatal outcomes.

Comparison of postoperative analgesia in children following ropivacaine and lidocaine surgical field infiltration with epinephrine for cleft palate repair: A double-blinded, randomized controlled trial.

STUDY OBJECTIVE: The study aimed to evaluate the efficacy of ropivacaine in providing postoperative analgesia for children undergoing cleft palate repair. METHODS: A double-blinded, randomized controlled trial was conducted on sixty-four children scheduled for cleft palate repair. The patients received either local infiltration with 1% lidocaine or 0.2% ropivacaine before incision. The primary outcome was the postoperative average pain score, and secondary outcomes included pain scores at various time points, consumption of flurbiprofen and hydromorphone, effectiveness of nurse-controlled analgesia pump, and incidence of bradycardia, vomiting, and respiratory depression. MAIN RESULTS: The results showed that the postoperative average pain score was significantly lower in the ropivacaine group compared to the lidocaine group (1.27±0.28 vs. 1.75±0.29, P<0.001). Pain scores at multiple postoperative time points were also lower in the ropivac:aine group. Additionally, consumption of flurbiprofen and hydromorphone was lower, and ineffective compressions of the nurse-controlled analgesia pump were reduced in the ropivacaine group. The incidence of vomiting, bradycardia, and respiratory depression did not show significant differences between the two groups. CONCLUSION: Local infiltration with ropivacaine effectively provided postoperative analgesia for children undergoing cleft palate repair without major side effects. It was found to be superior to lidocaine in reducing the need for additional rescue analgesia.

Bright light treatment counteracts stress-induced sleep alterations in mice, via a visual circuit related to the rostromedial tegmental nucleus.

Light in the environment greatly impacts a variety of brain functions, including sleep. Clinical evidence suggests that bright light treatment has a beneficial effect on stress-related diseases. Although stress can alter sleep patterns, the effect of bright light treatment on stress-induced sleep alterations and the underlying mechanism are poorly understood. Here, we show that bright light treatment reduces the increase in nonrapid eye movement (NREM) sleep induced by chronic stress through a di-synaptic visual circuit consisting of the thalamic ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL), lateral habenula (LHb), and rostromedial tegmental nucleus (RMTg). Specifically, chronic stress causes a marked increase in NREM sleep duration and a complementary decrease in wakefulness time in mice. Specific activation of RMTg-projecting LHb neurons or activation of RMTg neurons receiving direct LHb inputs mimics the effects of chronic stress on sleep patterns, while inhibition of RMTg-projecting LHb neurons or RMTg neurons receiving direct LHb inputs reduces the NREM sleep-promoting effects of chronic stress. Importantly, we demonstrate that bright light treatment reduces the NREM sleep-promoting effects of chronic stress through the vLGN/IGL-LHb-RMTg pathway. Together, our results provide a circuit mechanism underlying the effects of bright light treatment on sleep alterations induced by chronic stress.

Prophylactic Epidural Blood Patch or Prophylactic Epidural Infusion of Hydroxyethyl Starch in Preventing Post-Dural Puncture Headache - A Retrospective Study.

BACKGROUND: Post-dural puncture headache (PDPH) is particularly likely to happen in patients under obstetric care due to an unintentional dural puncture (UDP). There is as yet no ideal strategy for preventing UDP-induced PDPH. OBJECTIVES: The primary objective of this study was to assess whether a prophylactic epidural blood patch (EBP) or prophylactic epidural infusion of hydroxyethyl starch (HES) is effective in preventing PDPH for parturients with UDP compared with conservative treatments. STUDY DESIGN: Retrospective analysis from a single center's inpatient data. SETTING: Department of Anesthesiology at a single center. METHODS: A retrospective study was conducted of a single center's inpatient data from January 2017 through March 2020. The study included parturients with UDP during neuraxial anesthesia. The interventions of UDP included conservative treatment, prophylactic EBP, and prophylactic epidural infusion of HES. The incidence of PDPH, the use of intravenous aminophylline, therapeutic EBP, symptom onset, duration of headache, and duration of hospital stay were compared. RESULTS: A total of 85 patients were analyzed. The incidences of PDPH were 84%, 52.6% and 54.5% with conservative, prophylactic EBP, and prophylactic epidural HES treatments, respectively. Compared with the conservative treatment, prophylactic EBP and prophylactic epidural HES treatment significantly reduced the incidence of PDPH (P < 0.05). No significant difference was found between the prophylactic EBP and prophylactic epidural HES groups. Compared with the conservative treatment group, therapeutic EBP was significantly less used in the prophylactic EBP and prophylactic epidural HES groups (P < 0.05). Prophylactic EBP shortened the length of hospital stay of parturients with UDP (P < 0.05) while prophylactic epidural HES showed no statistical difference compared with conservative treatment. No severe complications, such as central nervous system and puncture site infection or nerve injury, were found in those patients. LIMITATIONS: Retrospective nature and single center data with a relatively small sample size. CONCLUSIONS: Prophylactic management with EBP and epidural infusion of HES has an effect in preventing the occurrence of PDPH; prophylactic EBP significantly shortened hospital stay length in parturients with UDP. KEY WORDS: Unintentional dural puncture, epidural blood patch, hydroxyethyl starch, post-dural puncture headache, parturient.

Altered intestinal barrier contributes to cognitive impairment in old mice with constipation after sevoflurane anesthesia.

Background: Elderly patients have a high risk of developing postoperative cognitive dysfunction (POCD). Gastrointestinal disorders, such as constipation, in the elderly population may be involved in the pathogenesis of neurological disorders by promoting inflammatory responses due to a 'leaky gut'. General anesthetic sevoflurane may impair gastrointestinal function in elderly patients to trigger neurological complications following surgery. Therefore, we hypothesized that elderly individuals with gastrointestinal dysfunction may be more vulnerable to sevoflurane and consequently develop POCD. Methods: Aged mice were randomly divided into four groups: control (CTRL), CTRL+sevoflurane (Sev), slow transit constipation (STC), and STC + Sev. Mice in the STC and STC + Sev groups were intra-gastrically administrated loperamide (3 mg/kg, twice a day for 7 days) to induce a slow transit constipation (STC) model determined with fecal water content and the time of first white fecal pellet, whereas mice in the other groups received the similar volume of saline. One week later, mice in the CTRL+Sev group and STC + Sev group received 2% sevoflurane for 2 h. The gut permeability evaluated with 4-kDa fluorescein isothiocyanate (FITC)-dextran, serum cytokines, microglia density, TLR4/NF-κB signaling expression, and POCD-like behavioral changes were determined accordingly. Results: The loperamide-induced STC mice had decreased fecal water content and prolonged time of first white fecal pellet. Sevoflurane exposure caused significantly increased gut permeability and serum cytokines, as well as the activation of microglia and the TLR4/NF-κB signaling pathway in the prefrontal cortex of the aged STC mice. Sevoflurane also caused cognitive impairment and emotional phenotype abnormality in aged STC mice. Conclusion: Aged STC mice were more vulnerable to sevoflurane anesthesia and consequently developed POCD-like behavioral changes. Our data suggest that gastrointestinal disorders including constipation may contribute to the development of POCD.

Comparison of the postoperative in-hospital versus at-home recovery quality and circadian rhythm status in preschool kids after adenotonsillectomy: a cohort and observational study.

Background: At present, minimally invasive surgery is often used in paediatric patients as a day surgery to promote rapid post-operative recovery. Obstructive Sleep Apnea Syndrome (OSAS) Patients recovery in the hospital or at home after surgery may differ in terms of recovery quality and circadian rhythm status because of sleep disruption; however, this remains unknown. Pediatric patients usually unable to explain their feelings effectively, and objective indicators to measure recovery situation in different environments are promising. This study was conducted to compare the impact of in-hospital and at-home postoperative recovery quality (primary outcome) and circadian rhythm (as measured via the salivary melatonin level) (secondary outcome) in preschool-age patients. Methods: This was a cohort, non-randomized and exploratory observational study. A total of 61 children aged 4 to 6 years who were scheduled to receive adenotonsillectomy were recruited and assigned to recover either in the hospital (Hospital group) or at home (Home group) after surgery. There were no differences in the patient characteristics and perioperative variables between the Hospital and Home groups at baseline. They received the treatment and anesthesia in the same way. The patients' preoperative and up to 28 days post-surgery OSA-18 questionnaires were harvested. Moreover, their pre- and post-surgery salivary melatonin concentrations, body temperature, three-night postoperative sleep diaries, pain scales, emergence agitation, and other adverse effects were recorded. Results: There were no significant differences in the postoperative recovery quality, as assessed by the OSA-18 questionnaire, body temperature, sleep quality, pain scales, and other adverse events (such as respiratory depression, sinus bradycardia, sinus tachycardia, hypertension, hypotension, nausea, and vomiting) between the two groups. The preoperative morning saliva melatonin secretion was decreased in both groups on the first postoperative morning (P<0.05), while a significantly greater decrease was found in the Home group on postoperative day 1 (P<0.05) and day 2 (P<0.05). Conclusions: The postoperative recovery quality of preschool kids in the hospital is as good as at home based on OSA-18 evaluation scale. However, the clinical importance of the significant decrease in morning saliva melatonin levels with at-home postoperative recovery remains unknown and warrants further study.

Safety and efficacy of esketamine for postoperative analgesia in pediatric patients with hypospadias.

Objective: To explore the safety and efficacy of the combination of continuous intravenous infusion of esketamine with sacral block for postoperative analgesia in pediatric patients undergoing surgery for hypospadias. Methods: Pediatric patients (n = 77) undergoing surgery for hypospadias were randomized into two groups: a hydromorphone group (H group, initial dose, 0.02 mg/kg; maintenance dose, 0.01 mg/kg/h) or an esketamine group (E group, initial dose, 0.3 mg/kg; maintenance dose 0.15 mg/kg/h). Caudal epidural block involved injection of 0.2% ropivacaine 1 ml/kg through the sacral hiatus. Age, weight, grade of hypospadias, intraoperative blood loss, operative time, and awaking time of patients were recorded. The Face, Legs, Activity, Cry and Consolability (FLACC) scale and Ramsay sedation scores were recorded when leaving the PACU (0 h) and at postoperative 2, 6, 12, 24, 36, and 48 h. The Pediatric Anesthesia Emergence Delirium Scale (PAED), incidence of hypotension, respiratory depression, nausea and vomiting and pruritus, and the time to first bowel movement after surgery were recorded. Results: There were no significant differences in demographic and clinical characteristics between the H group and the E group. There were no significant differences in FLACC scores at postoperative 0, 2, 6, 12, 24, 36, and 48 h in intra-group and inter-group comparisons. There were no significant differences in Ramsay sedation scores at postoperative 0, 2, 6, 12, 24, 36, and 48 h in the intra-group comparisons. Ramsay sedation scores were significantly lower at postoperative 2, 12, and 36 h in the H group compared to the E group. There were no significant differences in the PAED scale or incidence of nausea and vomiting or pruritus between the H group and the E group. The incidence of hypotension and respiratory depression was significantly lower, and the time to first bowel movement was significantly shorter in the E group compared to the H group. Urinary tryptophan, 5-hydroxytryptamine and substance P levels were significantly lower but arginine was significantly higher in the E group compared to the H group. Conclusions: The combination of continuous intravenous infusion of esketamine with sacral block provided safe and effective postoperative analgesia for pediatric patients undergoing surgery for hypospadias. Trial registration: Chinese Clinical Trial Register ChiCTR2200066967. Clinical trial registry URL: http://www.chictr.org.cn/edit.aspx?pid=185042&htm=4.

Effects of Thoracic Paravertebral Block on Postoperative Analgesia in Infants and Small Children undergoing Ultra-Fast Track Cardiac Anesthesia: A Randomized Controlled Trial.

OBJECTIVES: To assess whether a preoperative bilateral thoracic paravertebral block (TPVB) would improve postoperative analgesia in infants and small children undergoing open cardiac surgery in the protocol of an ultra-fast track cardiac anesthesia (UFTCA). DESIGN: A single-center, prospective, randomized, controlled study. SETTING: At a tertiary children's medical center. PARTICIPANTS: A total of 180 children undergoing cardiac surgery, aged 1 month to 3 years. INTERVENTIONS: Patients are allocated randomly to TPVB and parent- and/or nurse-controlled intravenous analgesia (PNCA) group (Group T) or PNCA group (Group P). MEASUREMENTS AND MAIN RESULTS: The primary outcome is the postoperative pain scores. The secondary outcome are intraoperative consumption of sufentanil, time to extubation, using of neostigmine, cumulative total and invalid PCA attempts in 24 and 48 hours after surgery, hospitalization characteristics, perioperative blood glucose, postoperative arterial oxygen partial pressure, arterial carbon dioxide partial pressure (PaCO2) and brain natriuretic peptide (BNP). The postoperative pain scores within 24 hours, intraoperative consumption of sufentanil, total, and invalid PCA attempts in 24 and 48 hours, perioperative blood glucose and BNP on the seventh day in Group T were all significantly lower than those in Group P (p < 0.001). The time to extubation, the use of neostigmine, and PaCO2 on the sixth hour, postoperatively, were significantly smaller in Group T than those in Group P (p < 0.05). There were no significant differences in the hospitalizations between the 2 groups. CONCLUSIONS: A combination of bilateral single dose TPVB and PNCA pain management is superior to a PNCA pain management alone in infants and small children undergoing open cardiac surgery and contributes to a rapid recovery with preferable perioperative outcomes in the protocol of UFTCA.

Optimizing DUS testing for Chimonanthus praecox using feature selection based on a genetic algorithm.

Chimonanthus praecox is a famous traditional flower in China with high ornamental value. It has numerous varieties, yet its classification is highly disorganized. The distinctness, uniformity, and stability (DUS) test enables the classification and nomenclature of various species; thus, it can be used to classify the Chimonanthus varieties. In this study, flower traits were quantified using an automatic system based on pattern recognition instead of traditional manual measurement to improve the efficiency of DUS testing. A total of 42 features were quantified, including 28 features in the DUS guidelines and 14 new features proposed in this study. Eight algorithms were used to classify wintersweet, and the random forest (RF) algorithm performed the best when all features were used. The classification accuracy of the outer perianth was the highest when the features of the different parts were used for classification. A genetic algorithm was used as the feature selection algorithm to select a set of 22 reduced core features and improve the accuracy and efficiency of the classification. Using the core feature set, the classification accuracy of the RF model improved to 99.13%. Finally, K-means was used to construct a pedigree cluster tree of 23 varieties of wintersweet; evidently, wintersweet was clustered into a single class, which can be the basis for further study of genetic relationships among varieties. This study provides a novel method for DUS detection, variety identification, and pedigree analysis.

Gibberellin-related genes regulate dwarfing mechanism in wintersweet.

Chimonanthus praecox (wintersweet) is an important cut flower and pot plant with a high ornamental and economic value in China. The development of dwarf wintersweet varieties has become an important research topic for the wintersweet industry. The lack of natural dwarf germplasm has hindered research into the molecular mechanisms of developing dwarf wintersweet, limiting its cultivation. After a long-term investigation and collection of germplasm resources of C. praecox, we obtained the germplasm of a dwarf C. praecox (dw). Here, the dwarf and normal C. praecox (NH) were used to identify the types of hormones regulating dw formation using phenotypic identification and endogenous hormone determination. Differentially expressed genes in the dw and NH groups were screened using transcriptome analysis. The functions of key genes in the dwarf trait were verified by heterologous expression. It was found that the internode length and cell number were significantly reduced in dw than in NH, and the thickness of the xylem and pith was significantly decreased. The dwarfness of dw could be recovered by exogenous gibberellic acid (GA) application, and endogenous GA levels showed that the GA4 content of dw was substantially lower than that of NH. Transcriptome differential gene analysis showed that the elevated expression of the CpGA2ox gene in the GA synthesis pathway and that of CpGAI gene in the signal transduction pathway might be the key mechanisms leading to dwarfing. Combined with the results of weighted gene co-expression network analysis, we selected the CpGAI gene for analysis and functional verification. These results showed that CpGAI is a nuclear transcriptional activator. Overexpression of CpGAI in Populus tomentosa Carr. showed that CpGAI could lead to the dwarfing in poplar. We analyzed the dwarfing mechanism of C. praecox, and the results provided a reference for dwarf breeding of wintersweet.

Prolonged sevoflurane exposure causes abnormal synapse development and dysregulates beta-neurexin and neuroligins in the hippocampus in neonatal rats.

BACKGROUND: The underlying molecular mechanisms of the excitatory/inhibitory (E/I) imbalance induced by sevoflurane exposure to neonates remain poorly understood. This study aimed to investigate the long-term effects of prolonged sevoflurane exposure to neonatal rats during the peak period of synaptogenesis on the changes of trans-synaptic neurexin-neuroligin interactions, synaptic ultrastructure in the hippocampus and cognition. METHODS: A total of 30 rat pups at postnatal day (P) 7 was randomly divided into two groups: the control group (exposed to 30 % oxygen balanced with nitrogen) and the sevoflurane group (exposed to 2.5 % sevoflurane plus 30 % oxygen balanced with nitrogen) for 6 h. Neurocognitive behaviors were assessed with the Open field test at P23-25 and the Morris water maze test at P26-30. The expression of ß-neurexin (ß-NRX), N-methyl-d-aspartate receptor 2 subunit (NR2A and NR2B), neuroligin-1 (NLG-1), neuroligin-2 (NLG-2), postsynaptic density protein-95 (PSD-95), α1-subunit of the γ-aminobutyric acid A receptor (GABAAα1) and gephyrin in the hippocampus at P30 were measured by Western blot. The ultrastructure of synapses was examined under electron microscope. RESULTS: Prolonged sevoflurane exposure at P7 resulted in cognitive deficiency in adolescence, as well as the downregulation of ß-NRX, NR2A, NR2B, NLG-1, and PSD-95, and the upregulation of GABAAα1, NLG-2, and gephyrin in the hippocampal CA3 region. Sevoflurane anesthesia also increased the number of symmetric synapses in the hippocampus. CONCLUSIONS: Prolonged sevoflurane exposure during the brain development leads to cognitive deficiency and disproportion of excitatory/inhibitory synapses which may be caused by dysregulated expression of synaptic adhesion molecules of ß-NRX and neuroligins.

Isoelectric Electroencephalography in Infants and Toddlers during Anesthesia for Surgery: An International Observational Study.

BACKGROUND: Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. The authors hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. METHODS: Fifteen hospitals enrolled patients age 36 months or younger for surgery using sevoflurane or propofol anesthetic. Frontal four-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life variables were analyzed for association with isoelectric events. RESULTS: Isoelectric events occurred in 32% (206 of 648) of patients, varied significantly among sites (9 to 88%), and were most prevalent during pre-incision (117 of 628; 19%) and surgical maintenance (117 of 643; 18%). Isoelectric events were more likely with infants younger than 3 months (odds ratio, 4.4; 95% CI, 2.57 to 7.4; P < 0.001), endotracheal tube use (odds ratio, 1.78; 95% CI, 1.16 to 2.73; P = 0.008), and propofol bolus for airway placement after sevoflurane induction (odds ratio, 2.92; 95% CI, 1.78 to 4.8; P < 0.001), and less likely with use of muscle relaxant for intubation (odds ratio, 0.67; 95% CI, 0.46 to 0.99; P = 0.046]. Expired sevoflurane was higher in patients with isoelectric events during preincision (mean difference, 0.2%; 95% CI, 0.1 to 0.4; P = 0.005) and surgical maintenance (mean difference, 0.2%; 95% CI, 0.1 to 0.3; P = 0.002). Isoelectric events were associated with moderate (8 of 12, 67%) and severe hypotension (11 of 18, 61%) during preincision (odds ratio, 4.6; 95% CI, 1.30 to 16.1; P = 0.018) (odds ratio, 3.54; 95% CI, 1.27 to 9.9; P = 0.015) and surgical maintenance (odds ratio, 3.64; 95% CI, 1.71 to 7.8; P = 0.001) (odds ratio, 7.1; 95% CI, 1.78 to 28.1; P = 0.005), and lower Pediatric Quality of Life scores at baseline in patients 0 to 12 months (median of differences, -3.5; 95% CI, -6.2 to -0.7; P = 0.008) and 25 to 36 months (median of differences, -6.3; 95% CI, -10.4 to -2.1; P = 0.003) and 30-day follow-up in 0 to 12 months (median of differences, -2.8; 95% CI, -4.9 to 0; P = 0.036). Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs. propofol). CONCLUSIONS: Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension.

The Prevalence of Irritable Bowel Syndrome Among Chinese University Students: A Systematic Review and Meta-Analysis.

Background: Irritable bowel syndrome (IBS) has become a common public health issue among university students, impairing their physical and mental health. This meta-analysis aimed to examine the pooled prevalence of IBS and its associated factors among Chinese university students. Methods: Databases of PubMed, EMBASE, MEDLINE (via EBSCO), CINAHL (via EBSCO), Wan Fang, CNKI and Weipu (via VIP) were systematically searched from inception date to May 31, 2021. Meta-analysis was performed using random-effects models. Meta-regression and subgroup analysis were used to detect the potential source of heterogeneity. Key Results: A total of 22 cross-sectional studies (14 were in Chinese and 8 were in English) with 33,166 Chinese university students were included. The pooled prevalence of IBS was estimated as 11.89% (95% CI = 8.06%, 16.35%). The prevalence was 10.50% (95% CI = 6.80%, 15.87%) in Rome II criteria, 12.00% (95% CI = 8.23%, 17.17%) in Rome III criteria, and 3.66% (95% CI = 2.01%, 6.60%) in Rome IV criteria. The highest prevalence of IBS was 17.66% (95% CI = 7.37%, 36.64%) in North China, and the lowest was 3.18% (95% CI = 1.28%, 7.68%) in South China. Subgroup analyses indicated that gender, major, anxiety and depression symptoms, drinking and smoking behaviors were significantly associated with the prevalence of IBS. Meta-regression analyses suggested that region influenced prevalence estimates for IBS. Conclusions and Inferences: This meta-analysis illustrated that IBS is very common in Chinese university students. Regular screening, effective prevention, and appropriate treatments should be implemented to reduce the risk of IBS in this population. More future studies should be conducted in Northeastern and Southwestern parts of China.

Programmed Intermittent Epidural Bolus in Comparison with Continuous Epidural Infusion for Uterine Contraction Pain Relief After Cesarean Section: A Randomized, Double-Blind Clinical Trial.

Purpose: Programmed intermittent epidural bolus (PIEB) was reported to provide superior maintenance of labour analgesia with better pain relief and less motor block than continuous epidural infusion (CEI). Whether this is also evident for uterine contraction pain relief after cesarean section remains unknown. Patients and Methods: Parturients scheduled for cesarean section were recruited for the study. At the end of the surgery, after a similar epidural loading dose given, patients received either PIEB (6 mL·h-1) or CEI (6 mL·h-1) of 0.1% ropivacaine. The primary outcome was the uterine contraction pain assessed with visual analog scale (VAS-U) at the postoperative 36 h. Secondary outcomes included incision pain at the rest (VAS-R) and in the movement-evoked (VAS-P), and lower extremity motor block (defined as Bromage score > 0). The whole profile of VAS scores between groups was analyzed using linear mixed model. When significant differences were found, the pairwise comparison was done with the Mann Whitney U-test followed by Bonferroni correction. Results: One hundred and twenty parturients were studied (PIEB, 60; CEI, 60). VAS-U at the postoperative 36 h in the PIEB group was lower than in the CEI group (Bonferroni-adjusted P < 0.01). The linear mixed model indicated that VAS-U, VAS-R and VAS-P were lower in the PIEB group compared with the CEI group (all P < 0.01). Motor block was higher in the CEI group than in the PIEB group during the study period except 2 h (all P < 0.05). No differences of adverse events such as hypotension and urinary retention were observed between the two groups. Conclusion: Programmed intermittent epidural bolus provides more effective uterine contraction and incision pain relief and less motor block after cesarean section than continuous epidural infusion without an increased risk of urinary retention and blood pressure instability.

Sevoflurane Induces Ferroptosis of Glioma Cells Through Activating the ATF4-CHAC1 Pathway.

Objective: To clarify the function and mechanisms of sevoflurane (Sev) on ferroptosis in glioma cells. Methods: Different concentrations of Sev were used to treat glioma cells U87 and U251. Ferroptosis inducer Erastin was used to incubate glioma cells combined with Sev and ATF4 siRNA transfection treatment. CCK-8 assay and colorimetric assay were performed to analyze cell viability and Fe+ concentration, respectively. The releases of reactive oxygen species (ROS) were determined by flow cytometry analysis. Transcriptional sequencing was used to screen the differential genes affected by Sev in U251 cells. The mRNA and protein expression of ferroptosis-associated genes was detected by qRT-PCR and Western blotting. Results: Sev could suppress cell viability, increase ROS levels and Fe+ concentration, downregulate the protein expression levels of GPX4, and upregulate transferrin, ferritin, and Beclin-1 in a dose-dependent manner in U87 and U251 cells. The expression of ferroptosis and mitophagy-related gene activating transcription factor 4 (ATF4) was identified to be enhanced by Sev analyzed by transcriptional sequencing. ChaC glutathione-specific gamma-glutamylcyclotransferase 1 (CHAC1), which is involved in ferroptosis, is a downstream gene of ATF4. Inhibition of ATF4 could interrupt the expression of CHAC1 induced by Sev in U87 and U251 cells. Ferroptosis inducer Erastin treatment obviously inhibited the cell viability, elevated the Fe2+ concentration, and promoted ROS generation in U87 and U251 cells. The protein level of ATF4 and CHAC1 was increased in Erastin-treated U87 and U251 cells. Moreover, the interruption of Sev-induced ferroptosis and CHAC1 activating induced by ATF4 suppression could be reversed by Erastin. Conclusions: In summary, this study suggested that Sev exposure-induced ferroptosis by the ATF4-CHAC1 pathway in glioma cells.

Sevoflurane Ameliorates Schizophrenia in a Mouse Model and Patients: A Pre-Clinical and Clinical Feasibility Study.

BACKGROUND: GABAergic deficits have been considered to be associated with the pathophysiology of schizophrenia, and hence, GABA receptors subtype A (GABAARs) modulators, such as commonly used volatile anesthetic sevoflurane, may have therapeutic values for schizophrenia. The present study investigates the therapeutic effectiveness of low-concentration sevoflurane in MK801-induced schizophrenia-like mice and schizophrenia patients. METHODS: Three weeks after MK801 administration (0.5 mg kg-1, i.p. twice a day for 5 days), mice were exposed to 1% sevoflurane 1hr/day for 5 days. Behavioral tests, immunohistochemical analysis, western blot assay, and electrophysiology assessments were performed 1-week post-exposure. Ten schizophrenia patients received 1% sevoflurane 5 hrs per day for 6 days and were assessed with the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18) at week 1 and week 2. RESULTS: MK801 induced hypolocomotion and social deficits, downregulated expression of NMDARs subunits and postsynaptic density protein 95 (PSD95), reduced parvalbumin - and GAD67-positive neurons, altered amplitude and frequency of mEPSCs and mIPSCs, and increased the excitation/inhibition ratio. All these changes induced by MK-801 were attenuated by sevoflurane administration. Six and eight patients achieved a response defined as a reduction of at least 30% in the PANSS total score at 1st and 2nd week after treatments. The BPRS-18 total score was found to be significantly decreased by 38% at the 2nd week (p < 0.01). CONCLUSION: Low-concentration sevoflurane effectively reversed MK801-induced schizophrenialike disease in mice and alleviated schizophrenia patients' symptoms. Our work suggests sevoflurane to be a valuable therapeutic strategy for treating schizophrenia patients.