Determining of 18 amino acids in plasma of pregnant women with sleep disorders by UHPLC-MS/MS.

Many pregnant women experience sleep disorders, and amino acid levels could play a crucial role in affecting maternal sleep. To explore this potential relationship, an accurate and effective UHPLC-MS/MS method has been developed to monitor 18 amino acids in the plasma samples of pregnant women. This method aims to assess how plasma amino acid levels might be linked to sleep disorders during pregnancy. Plasma samples were precipitated with acetonitrile containing 0.2% formic acid. We used 5% seralbumin as the surrogate matrix to establish quantitative curves for amino acid determination in human plasma. The method was validated in both the surrogate matrix and human plasma. The optimized UHPLC-MS/MS method was validated, showing that that the analytes had comparable recovery and negligible matrix effects in both 5% seralbumin and human plasma. The linearity, lower limit of quantification, precision, accuracy, and stability all met the acceptance criteria. The validated method was successfully applied to determination of the plasma levels of 18 amino acids in pregnant women with or without sleep disorders, indicating that alanine, lysine, tryptophan, glutamic acid, and phenylalanine levels had significant changes which may be related to sleep disorders during early pregnancy. An accurate, reliable, and efficient UHPLC-MS/MS method was successfully developed and support to find the specific amino acids as potential biomarkers for sleep disorders in pregnant women.

The positive impact of smoking on poor sleep quality is moderated by IGF1 levels in cerebrospinal fluid: a case-control study among Chinese adults.

Objective: Previous research indicates associations between cigarette smoking, insulin-like growth factor-1 (IGF1), and sleep disturbances. This study aimed to examine the association between smoking and sleep quality and investigate the moderating role of IGF1. Methods: This case-control study involved 146 Chinese adult males (53 active smokers and 93 non-smokers) from September 2014 to January 2016. Sleep quality and disturbances were evaluated using the Pittsburgh Sleep Quality Index (PSQI), which includes seven scales. Pearson correlation analysis and logistic regression analysis were utilized to examine the link between IGF1 levels in cerebrospinal fluid (CSF) and PSQI scores. The effect of IGF1 was assessed using the moderation effect and simple slope analysis, with adjustments made for potential confounders. Results: Active smokers exhibited significantly higher global PSQI scores and lower IGF1 levels in CSF compared to non-smokers. A significant negative correlation was observed between IGF1 and PSQI scores (â = -0.28, P < 0.001), with a stronger association in non-smokers (Pearson r = -0.30) compared to smokers (Pearson r = -0.01). Smoking was associated with higher global PSQI scores (â = 0.282, P < 0.001), and this association was moderated by IGF1 levels in CSF (â = 0.145, P < 0.05), with a stronger effect at high IGF1 levels (Bsimple = 0.402, p < 0.001) compared to low IGF1 levels (Bsimple = 0.112, p = 0.268). Four subgroup analysis revealed similar results for sleep disturbances (Bsimple = 0.628, P < 0.001), with a marginal moderation effect observed on subjective sleep quality (Bsimple = 0.150, P = 0.070). However, independent associations rather than moderating effects were observed between IGF1 and sleep efficiency and daytime disturbance. Conclusion: We provided evidence to demonstrate the moderation effect of IGF1 on the relationship between smoking and sleep in CSF among Chinese adult males.

Association of impulsive behavior and cerebrospinal fluid/plasma oxidation and antioxidation ratio in Chinese men.

OBJECTIVES: Impulsive behavior is the precursor of many psychiatric and neurological conditions. High levels of impulsive behavior will increase health risk behavior and related injuries. Impulsive behavior is produced and regulated by central and peripheral biological factors, and oxidative stress (OS) can aggravate it. However, previous studies only showed that impulsive behavior was related to the level of the peripheral OS. Therefore, this study aims to clarify the relationship between OS and impulsive behavior in the brain and peripheral blood. METHODS: We recruited 64 Chinese men. We measured superoxide dismutase (SOD) (including copper, zinc and manganese) and nitric oxide synthase (NOS) (including total, inducible and constitutive) in cerebrospinal fluid (CSF) and plasma. The Barratt Impulsiveness Scale version 11 (BIS-11) was used to evaluate impulsive behavior. The relationship between OS and impulsive behavior was evaluated by partial correlation analysis and stepwise multiple regression analysis. RESULTS: Partial correlation analysis showed that the ratio of total NOS-to-MnSOD and iNOS-to-MnSOD in CSF were negatively correlated with the BIS-11 motor scores (r = -0.431, p = -0.001; r = -0.434, p = -0.001). Stepwise multiple regression analysis showed that the ratio of CSF iNOS-to-MnSOD was the most influential variable on the BIS-11 motor scores(ß = -0.434, t = -3.433, 95 %CI(-0.374, -0.098), p = 0.001). CONCLUSIONS AND RELEVANCE: The imbalance of central oxidation and antioxidation is related to impulsive behavior, which broadens our understanding of the correlation between impulsive behavior and OS.

Association of cigarette smoking with cerebrospinal fluid biomarkers of insulin sensitivity and neurodegeneration.

INTRODUCTION: Cigarette smoking increases both the risk for insulin resistance and amyloid-ß (Aß) aggregation, and impaired brain insulin/insulin-like growth factor 1 (IGF1) signaling might increase risk factors for Alzheimer's disease (AD). We aimed to investigate the association among cerebrospinal fluid (CSF) insulin sensitivity/IGF1, glucose/lactate, and Aß42 and further explore whether insulin sensitivity contributed to the risk for AD in active smokers. METHODS: In this cross-sectional study, levels of insulin, IGF1, and lactate/glucose of 75 active smokers and 78 nonsmokers in CSF were measured. Three polymorphisms regulating IGF1 were genotyped. Analysis of variance was used to compare differences of variables between groups. Partial correlation was performed to test the relationship between CSF biomarkers and smoking status. General linear models were applied to test the interaction of the effect of single nucleotide polymorphisms and cigarette smoking on CSF IGF1 levels. RESULTS: In the CSF from active smokers, IGF1 and lactate levels were significantly lower (p = .016 and p = .010, respectively), whereas Aß42 (derived from our earlier research) and insulin levels were significantly higher (p < .001 and p = .022, respectively) as compared to the CSF from nonsmokers. The AG + GG genotype of rs6218 in active smokers had a significant effect on lower CSF IGF1 levels (p = .004) and lower CSF insulin levels in nonsmokers (p = .016). CONCLUSIONS: Cigarette smoking as the "at-risk" factor for AD might be due to lower cerebral insulin sensitivity in CSF, and the subjects with rs6218G allele seem to be more susceptible to the neurodegenerative risks for cigarette smoking.

The low ratio of ghrelin in plasma and cerebrospinal fluid might be beneficial to sleep.

OBJECTIVE: Ghrelin is physiologically important for maintaining sleep rhythm. Cigarette smoking has been demonstrated to significantly increase the risk of insufficient sleep by regulating ghrelin at the central and peripheral levels. No research has been published to study the relationship between active smoking and sleep via ghrelin level in cerebrospinal fluid (CSF). METHODS: A total of 139 Chinese males were recruited and divided into active smokers (n = 77) and non-smokers (n = 62). The levels of CSF and plasma ghrelin were measured. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep. RESULTS: Non-smokers had lower PSQI scores (1.71 ± 1.93) than active smokers (3.70 ± 1.78). Non-smokers have significantly lower plasma ghrelin levels and lower plasma/CSF ghrelin ratio but higher CSF ghrelin than active smokers. Among non-smokers, plasma ghrelin levels were not correlated with PSQI scores (all p > 0.05), CSF ghrelin levels were positively correlated with PSQI scores (r = 0.309, p = 0.019), and the plasma/CSF ghrelin ratio was negatively correlated with PSQI scores (r = -0.346, p = 0.008). CONCLUSIONS: This study is the first to reveal the relationship between cigarette smoking, high CSF ghrelin levels and insufficient sleep, suggesting that maintaining a normal plasma/CSF ghrelin ratio may be the physiological mechanism of healthy sleep, and the insufficient sleep population must quit smoking.

Comparison of chronic gastrointestinal and genitourinary toxicities between brachytherapy and external beam radiotherapy for patients with prostate cancer: A systematic review and meta-analysis.

BACKGROUND: 125I BT is an effective radiotherapy for prostate cancer. However, comparison data of GI and GU toxicities between BT, BT + EBRT, and EBRT-alone patient groups is limited. OBJECTIVE: To define the GI and GU toxicities in prostate cancer to prevent adverse events after treatment. METHODS: We searched published studies in PubMed, Cochrane, and Embase databases up to December 31, 2022. The endpoints were the RRs of GI and GU toxicities. Pooled data were assessed using a random-effects model. RESULTS: Fifteen eligible studies were included into this analysis. LDR-BT had significantly lower RRs than LDR-BT + EBRT for acute GI (2.13; 95% CI, 1.22-3.69; P= 0.007) and late GI toxicities (3.96; 95% CI, 1.23-12.70; P= 0.02). Moreover, EBRT had significantly higher RRs than LDR-BT for acute GU (2.32; 95% CI, 1.29-4.15; P= 0.005) and late GU toxicities (2.38; 95% CI, 1.27-4.44; P= 0.007). HDR-BT had significantly higher RRs for acute GU toxicities than LDR-BT alone (0.30; 95% CI, 0.23-0.40; P< 0.00001). CONCLUSION: The results implied that BT with and without EBRT can result in both GI and GU toxicities in patients with prostate cancer, with LDR-BT leading to a poorer urinary function than EBRT.

Clinical study of multifunctional laryngeal mask in airway interventional therapy.

OBJECTIVE: This study is conducted to evaluate the efficacy and safety of using multifunctional intubation laryngeal masks with normal frequency jet ventilation in airway interventional therapy. METHODS: A total of 200 patients receiving airway interventional therapy were enrolled in this retrospective study and were divided into 2 groups (group M and group P) by doctors in our hospital to compare the effect of different laryngeal masks. Group M used common laryngeal masks and an anesthesia machine for positive pressure ventilation while group P took multifunctional intubation laryngeal masks and used a jet ventilator for normal frequency jet ventilation. The patients' mean arterial pressure, heart rate, arterial oxygen partial pressure (PaO2) and arterial carbon dioxide partial pressure (PaCO2), and the operation time, recovery score and the patients' and doctors' satisfaction levels were compared between the 2 groups. RESULTS: Both groups were hemodynamically stable, and their PaO2 levels were significantly higher before the operation than that during and after the operation (P < .05). Compared with group M, the PaCO2 level of group P was more stable both during and after the operation, and this difference was statistically significant (P < .05). There was no statistically significant difference in terms of the 2 group's operating time, recovery score, and patients' satisfaction levels (P > .05). However, the satisfaction levels of doctors in group P were higher than that in group M, and this difference was statistically significant (P < .05). CONCLUSION: As statistics show, the intraoperative hemodynamics and PaO2 and PaCO2 levels were stable, and patients, surgeons and anesthesia operators were satisfied. Therefore, it is feasible to apply multifunctional intubation laryngeal masks with normal frequency jet ventilation in airway interventional therapy and it is a safe and ideal way to ensure ventilation.

Risks of Digestive System Side-Effects of Selective Serotonin Reuptake Inhibitors in Patients with Depression: A Network Meta-Analysis.

Purpose: Selective serotonin reuptake inhibitors (SSRIs) are the preferred treatments for depression. The most common adverse drug reactions are symptoms involving the digestive system, leading to low compliance in patients with depression. Therefore, it is important to assess the safety of SSRIs with respect to the digestive system. Several meta-analyses have compared the risks of digestive side effects of SSRIs and other antidepressants. We aimed to compare the risks of various SSRIs (fluoxetine, escitalopram, citalopram, paroxetine, and sertraline) for adverse reactions of the digestive system. Methods: Systematic searches returned 30 randomized controlled trials (n = 5004) of five antidepressants and placebos. Results: Fluoxetine had the lowest probability of digestive side effects, ranking fifth at 0.548. Sertraline had the highest probability of digestive side effects, with a probability of 0.611. For gastrointestinal tolerability, escitalopram was better than paroxetine (odds ratio [OR] =0.62, 95% confidence interval [CI] 0.43-0.87) and sertraline (OR=0.56, 95% CI 0.32-0.99). Conclusion: Fluoxetine exhibited distinct advantages compared to other SSRIs, while sertraline had the greatest likelihood of digestive system side effects. These findings will help doctors understand the relative advantages of various antidepressants.

Association of Fatigue With Sleep Duration and Bedtime During the Third Trimester.

Purpose: To investigate the association between fatigue and sleep habits of pregnant women to further explore the effect of sleep duration and bedtime on fatigue during the third trimester. Materials and Methods: A total of 465 Chinese Han pregnant women in the third trimester (after 28 weeks) with a singleton gestation were recruited. Sleep habits (such as bedtime, sleep onset latency, and night sleep duration) and the 14-item Fatigue Scale scores (FS-14, used to assess fatigue) were collected. Results: The effects of sleep duration and bedtime on FS-14 physical and total scores were significant. FS-14 physical scores and total scores of the participants in the group of sleep before 23 o'clock (SBC) of short sleep duration (<7 h) were significantly higher as compared to the participants in the group of SBC of normal sleep duration, and those of the participants in the group of SBC of normal sleep duration were significantly lower than the participants in the group of sleep after 23 o'clock of normal sleep duration. There were negative correlations of sleep duration with FS-14 physical score and total score in the SBC of short sleep duration group. Conclusion: Sleep less than 7 h or bedtime after 23 o'clock was associated with increased fatigue levels of pregnant women in the third trimester. Therefore, it is necessary to develop good sleep habits (enough sleep duration and early bedtime) to keep fatigue at a low level for pregnant women in the third trimester.

Efficacy of nondrug interventions in perinatal depression: A meta-analysis.

Perinatal depression causes significant harm to mothers and unborn infants. Nondrug intervention is a common and acceptable method for reducing perinatal depression in pregnant women; however, it lacks an evidence-based basis. This study aimed to evaluate the effectiveness of nondrug interventions, such as cognitive behavioral therapy (CBT), interpersonal psychotherapy (IPT), and yoga, in reducing perinatal depression. Randomized controlled trials (RCTs) of CBT, IPT, and yoga for improving perinatal depression were searched in the Cochrane Library, PubMed, Web of Science, Embase, ProQuest, ScienceDirect, ClinicalKey, Wanfang Data (Chinese database), and China Knowledge Resource Integrated Database. The retrieval time limit was set from the establishment of the database to December 2021. Twenty-one studies involving a total of 1981 participants were included.The present meta-analysis showed that CBT and IPT could effectively alleviate depressive symptoms in perinatal women, and the curative effect of IPT was better than that of CBT. There was no significant difference in the improvement effect of yoga on participants with depressive symptoms compared with that in the controls.This study was registered with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022307675).

Association of Cigarette Smoking With Male Cognitive Impairment and Metal Ions in Cerebrospinal Fluid.

Objective: Cigarette smoking might accelerate cognitive impairment; however, this has never been investigated using human cerebrospinal fluid (CSF). We conducted this study to investigate the association between cigarette smoking and cognitive impairment through metal ions in CSF. Methods: We obtained 5-ml CSF samples from routine lumbar puncture procedures in patients undergoing anterior cruciate ligament reconstruction before surgery in China. A total of 180 Chinese males were recruited (80 active smokers and 100 non-smokers). We measured specific cigarette-related neurotoxic metal ions in CSF, including iron, copper, zinc, lead, aluminum, and manganese. Sociodemographic data and history of smoking were obtained. The Montreal Cognitive Assessment (MoCA) was applied. Results: Active smokers had fewer years of education (11.83 ± 3.13 vs. 13.17 ± 2.60, p = 0.01), and higher age (33.70 ± 10.20 vs. 29.76 ± 9.58, p = 0.01) and body mass index (25.84 ± 3.52 vs. 24.98 ± 4.06, p =0.03) than non-smokers. Compared to non-smokers, active smokers had significantly higher CSF levels of iron, zinc, lead, and aluminum and lower MoCA scores (all p < 0.05). Average daily numbers of cigarettes smoked negatively correlated with the MoCA scores (r = -0.244, p = 0.048). In young smokers, CSF manganese levels negatively correlated with MoCA scores (r = -0.373, p = 0.009). Conclusions and Relevance: Cigarette smoking might be associated with male cognitive impairment, as shown by lower MoCA scores and higher levels of CSF iron, zinc, lead, and aluminum in active smokers. This might be early evidence of cigarette smoking accelerating male cognitive impairment.

Association of Acute Postoperative Pain and Cigarette Smoking With Cerebrospinal Fluid Levels of Beta-Endorphin and Substance P.

Objectives: Cigarette smoking is associated with postoperative pain perception, which might be mediated by beta-endorphin and substance P. These effects on postoperative pain perception have never been investigated in human cerebrospinal fluid (CSF), which reflects biochemical alterations in the brain. Therefore, we investigated the associations among cigarette smoking, postoperative pain, and levels of beta-endorphin and substance P in human CSF. Methods: We recruited 160 Chinese men (80 active smokers and 80 nonsmokers) who underwent lumbar puncture before anterior cruciate ligament reconstruction, and 5-ml CSF samples were collected. Pain visual analog scale (VAS) scores, post-anesthetic recovery duration (PARD), and smoking variables were obtained. CSF levels of beta-endorphin and substance P were measured. Results: Compared to non-smokers, active smokers had significantly higher pain VAS (2.40 ± 0.67 vs. 1.70 ± 0.86, p < 0.001) and PARD scores (9.13 ± 2.11 vs. 7.27 ± 1.35, p = 0.001), lower CSF beta-endorphin (33.76 ± 1.77 vs. 35.66 ± 2.20, p = 0.001) and higher CSF substance P (2,124.46 ± 217.34 vs. 1,817.65 ± 302.14, p < 0.001) levels. Pain VAS scores correlated with PARD in active smokers (r = 0.443, p = 0.001). Conclusions: Cigarette smoking is associated with increased postoperative pain intensity, shown by delayed pain perception, higher pain VAS scores, and lower beta-endorphin and higher substance P levels in the CSF of active smokers. The more extended postoperative pain perception is delayed, the more pain intensity increases.

miRNAs may regulate GABAergic transmission associated genes in aged rats with anesthetics-induced recognition and working memory dysfunction.

BACKGROUND: Isoflurane and sevoflurane are widely used anesthetics in surgery and administration of these anesthetics could lead to postoperative cognitive dysfunction (POCD). However, the mechanisms remain unclear. METHODS: Aged Wistar rats were exposed to isoflurane and sevoflurane for 2 or 4h. Recognition memory and spatial working memory were measured using Novel object recognition (NOR) and Y-maze test, respectively. Apoptotic cells were detected by TUNEL staining. miRNA expression was measured by Real-time PCR while protein expression was measured by Western blot. Dual-Luciferase reporter assay was used to establish the direct relationship between miRNAs and Gabra5 and gephyrin gene expression. RESULTS: Exposure to isoflurane and sevoflurane for 2 or 4h significantly decreased the NOR index in the NOR test and spontaneous alternations in arm entries in the Y-maze test in aged rats. TUNEL staining showed that isoflurane and sevoflurane administration significantly induced apoptosis in the mPFC and hippocampus. The protein level of α5 GABAA receptor (α5GABAAR), gephyrin, and dystrophin were significantly increased, whereas the expression of miR-30a, miR-31, miR-190a, and miR-190b was significantly decreased in the hippocampus and mPFC in aged rats exposed to isoflurane and sevoflurane compared to control rats. The protein levels of α5GABAAR, gephyrin, and dystrophin protein in the hippocampus and the mPFC significantly correlated with NOR index and spontaneous alternations. Dual-Luciferase reporter assay showed that miR-30a and miR-190a/b mimics significantly inhibited Gabra5 and gephyrin gene expression, respectively. CONCLUSION: There might be a miRNAs-GABAergic transmission pathway which may be involved in the pathophysiological alteration in anesthetics-induced POCD.

A New DEM Generalization Method Based on Watershed and Tree Structure.

The DEM generalization is the basis of multi-dimensional observation, the basis of expressing and analyzing the terrain. DEM is also the core of building the Multi-Scale Geographic Database. Thus, many researchers have studied both the theory and the method of DEM generalization. This paper proposed a new method of generalizing terrain, which extracts feature points based on the tree model construction which considering the nested relationship of watershed characteristics. The paper used the 5 m resolution DEM of the Jiuyuan gully watersheds in the Loess Plateau as the original data and extracted the feature points in every single watershed to reconstruct the DEM. The paper has achieved generalization from 1:10000 DEM to 1:50000 DEM by computing the best threshold. The best threshold is 0.06. In the last part of the paper, the height accuracy of the generalized DEM is analyzed by comparing it with some other classic methods, such as aggregation, resample, and VIP based on the original 1:50000 DEM. The outcome shows that the method performed well. The method can choose the best threshold according to the target generalization scale to decide the density of the feature points in the watershed. Meanwhile, this method can reserve the skeleton of the terrain, which can meet the needs of different levels of generalization. Additionally, through overlapped contour contrast, elevation statistical parameters and slope and aspect analysis, we found out that the W8D algorithm performed well and effectively in terrain representation.