Subsequent maternal sleep deprivation aggravates cognitive impairment by modulating hippocampal neuroinflammatory responses and synaptic function in maternal isoflurane-exposed offspring mice.

INTRODUCTION: Pregnant women may need to undergo non-obstetric surgery under general anesthesia owing to medical needs, and pregnant women frequently experience sleep disturbances during late gestation. Preclinical studies demonstrated that maternal isoflurane exposure (MISO) or maternal sleep deprivation (MSD) contributed to cognitive impairments in offspring. Research studies in mice have revealed that SD can aggravate isoflurane-induced cognitive deficits. However, it remains unclear whether MSD aggravates MISO-induced cognitive deficits in offspring. The purpose of this research was to explore the combined effects of MSD and MISO on offspring cognitive function and the role of neuroinflammation and synaptic function in the process of MSD + MISO. METHODS: Pregnant mice were exposed to 1.4% isoflurane by inhalation for 4 h on gestational day (GD) 14. Dams were then subjected to SD for 6 h (12:00-18:00 h) during GD15-21. At 3 months of age, the offspring mice were subjected to the Morris water maze test to assess cognitive function. Then the levels of inflammatory and anti-inflammatory markers and synaptic function-related proteins were assessed using molecular biology methods. RESULTS: The results of this study demonstrated that MISO led to cognitive dysfunction, an effect that was aggravated by MSD. In addition, MSD exacerbated the maternal isoflurane inhalation, leading to an enhancement in the expression levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha and a reduction in the hippocampal levels of IL-10, synaptophysin, post-synaptic density-95, growth-associated protein-43, and brain-derived neurotrophic factor. CONCLUSION: Our findings revealed that MSD aggravated the cognitive deficits induced by MISO in male offspring mice, and these results were associated with neuroinflammation and alternations in synaptic function.

Melatonin improves maternal sleep deprivation-induced learning and memory impairment, inflammation, and synaptic dysfunction in murine male adult offspring.

INTRODUCTION: Maternal sleep deprivation (MSD), which induces inflammation and synaptic dysfunction in the hippocampus, has been associated with learning and memory impairment in offspring. Melatonin (Mel) has been shown to have anti-inflammatory, antioxidant, and neuroprotective function. However, the beneficial effect of Mel on MSD-induced cognitive impairment and its mechanisms are unknown. METHODS: In the present study, adult offspring suffered from MSD were injected with Mel (20 mg/kg) once a day during postnatal days 61-88. The cognitive function was evaluated by the Morris water maze test. Levels of proinflammatory cytokines were examined by enzyme-linked immunosorbent assay. The mRNA and protein levels of synaptic plasticity associated proteins were examined using reverse transcription-polymerase chain reaction and western blotting. RESULTS: The results showed that MSD impaired learning and memory in the offspring mice. MSD increased the levels of interleukin (IL)-1creIL-6, and tumor necrosis factor-α and decreased the expression levels of brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin in the hippocampus. Furthermore, Mel attenuated cognitive impairment and restored markers of inflammation and synaptic plasticity to control levels. CONCLUSIONS: These findings indicated that Mel could ameliorate learning and memory impairment induced by MSD, and these beneficial effects were related to improvement in inflammation and synaptic dysfunction.

Establishing and Validating an Innovative Focal Adhesion-Linked Gene Signature for Enhanced Prognostic Assessment in Endometrial Cancer.

Studies have highlighted the significant role of focal adhesion signaling in cancer. Nevertheless, its specific involvement in the pathogenesis of endometrial cancer and its clinical significance remains uncertain. We analyzed TCGA-UCEC and GSE119041 datasets with corresponding clinical data to investigate focal adhesion-related gene expression and their clinical significance. A signature, "FA-riskScore," was developed using LASSO regression in the TCGA cohort and validated in the GSE dataset. The FA-riskScore was compared with four existing models in terms of their prediction performance. We employed univariate and multivariate Cox regression analyses towards FA-riskScore to assess its independent prognostic value. A prognostic evaluation nomogram based on our model and clinical indexes was established subsequently. Biological and immune differences between high- and low-risk groups were explored through functional enrichment, PPI network analysis, mutation mining, TME evaluation, and single-cell analysis. Sensitivity tests on commonly targeted drugs were performed on both groups, and Connectivity MAP identified potentially effective molecules for high-risk patients. qRT-PCR validated the expressions of FA-riskScore genes. FA-riskScore, based on FN1, RELN, PARVG, and PTEN, indicated a poorer prognosis for high-risk patients. Compared with published models, FA-riskScore achieved better and more stable performance. High-risk groups exhibited a more challenging TME and suppressive immune status. qRT-PCR showed differential expression in FN1, RELN, and PTEN. Connectivity MAP analysis suggested that BU-239, potassium-canrenoate, and tubocurarine are effective for high-risk patients. This study introduces a novel prognostic model for endometrial cancer and offers insights into focal adhesion's role in cancer pathogenesis.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice.

BACKGROUND: The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. METHODS: Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5 mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. RESULTS: SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. CONCLUSION: Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.

Enhanced Piezoelectricity of MAPbI3 by the Introduction of MXene and Its Utilization in Boosting High-Performance Photodetectors.

Recently, perovskite photodetectors (PDs) are risen to prominence due to substantial research interest. Beyond merely tweaking the composition of materials, a cutting-edge advancement lies in leveraging the innate piezoelectric polarization properties of perovskites themselves. Here, the investigation shows utilizing Ti3C2Tx, a typical MXene, as an intermediate layer for significantly boosting the piezoelectric property of MAPbI3 thin films. This improvement is primarily attributed to the enhanced polarization of the methylammonium (MA+) groups within MAPbI3, induced by the OH groups present in Ti3C2Tx. A flexible PD based on the MAPbI3/MXene heterostructure is then fabricated. The new device is sensitive to a wide range of wavelengths, displays greatly enhanced performance owing to the piezo-phototronic coupling. Moreover, the device is endowed with a greatly reduced response time, down to millisecond level, through the pyro-phototronic effect. The characterization shows applying a -1.2% compressive strain on the PD leads to a remarkable 102% increase in the common photocurrent, and a 76% increase in the pyro-phototronic current. The present work reveals how the emerging piezo-phototronic and pyro-phototronic effects can be employed to design high-performance flexible perovskite PDs.

Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus.

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro-inflammatory cytokines and Sirt1/miR-134 pathway-related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1ß, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.

Effects of sigmoidoscopy screening (including colonoscopy) on colorectal cancer: A meta-analysis based on randomized controlled trials.

Background: This study aimed to investigate the role of endoscopy screening in colorectal cancer (CRC). Methods: Up to January 2023, databases were searched for studies related to sigmoidoscopy and colonoscopy screening. The incidence of CRC, and/or CRC mortality were the main observation outcomes. Results: A total of 5 randomized controlled trials (RCTs) published from 2017 to 2022 were included. Among them, four studies used sigmoidoscopy screening and one study involved colonoscopy screening. Statistical results showed that the incidence (RR: 0.78, p < 0.001) and mortality (RR: 0.75, p < 0.001) of CRC were significantly lower in the screening group than in the control group. Further, a subgroup analysis of CRC site indicated that the incidence and mortality of CRC in the screening group were significantly lower than those in the non-screened group, regardless of distal CRC (Incidence: RR: 0.66, p < 0.001; Mortality: RR: 0.62, p < 0.001) or proximal CRC (Incidence: RR: 0.94, p = 0.038; Mortality: RR: 0.89, p = 0.038). In terms of gender, compared with the non-screening group, both males (Incidence: RR: 0.73, p < 0.001; Mortality: RR: 0.68, p < 0.001) and females (Incidence: RR: 0.85, p < 0.001; Mortality: RR: 0.85, p = 0.017), the screening group had a significant decrease in the incidence and mortality of CRC. Conclusion: This meta-analysis demonstrated that sigmoidoscopy screening (including colonoscopy) could effectively reduce the incidence and mortality of CRC.

The cardiac-related adverse events of PD-1/PD-L1 immunotherapy in advanced or metastatic lung cancer: a RCT-based meta-analysis.

BACKGROUND: This study aims to investigate the effect of PD-1/PD-L1 immunotherapy on cardiac-related adverse events in patients with advanced or metastatic lung cancer. METHODS: We conducted a detailed search in PubMed, Web of Science, Cochran, and Embase for articles on the application of immunotherapy for lung cancer and report cardiac-related adverse events with respect to myocardial ischemia, pericardial effusion, myocarditis, and electrophysiology. The dichotomous variables were assessed by relative risk (RR) and 95% confidence intervals (CI). RESULTS: A total of 7132 subjects were included in 12 phase III randomized controlled trials (RCTs). The results showed that under the fixed effects model, the probability of cardiac-related adverse events in pericardial effusion was higher in the experimental group than in the control group (RR 2.30, 95% CI 1.01-5.21, P = 0.05). Under the random effects model, there was no statistical difference between the two groups (RR 2.03, 95% CI 0.81-5.12, P = 0.13). No statistical difference is observed between the experimental group and the control group (under the fixed effects model and the random effects model) for other cardiac-related adverse events, including myocarditis, acute coronary syndrome, myocardial infarction, acute myocardial infarction, myocardial ischemia, unstable angina, ventricular tachycardia, supraventricular tachycardia, tachycardia, bradycardia, atrial flutter, atrial fibrillation, cardiac failure, cardiac arrest, cardiopulmonary failure, acute heart failure, cardiac arrest (all P > 0.05). CONCLUSIONS: PD-1/PD-L1 immunotherapy in advanced or metastatic lung cancer is generally safe for cardiac-related adverse events.

An enriched environment ameliorates maternal sleep deprivation-induced cognitive impairment in aged mice by improving mitochondrial function via the Sirt1/PGC-1α pathway.

BACKGROUND: Early life stress can cause cognitive impairment in aged offspring. Environmental enrichment (EE) is considered to be an effective non-pharmacological treatment for improving cognitive decline. The aim of this research was to evaluate the effect of EE, on cognitive impairment in aged offspring induced by maternal sleep deprivation (MSD) and the underlying mechanisms involved to investigate its potential value in clinical practice. METHODS: CD-1 damns were subjected or not to sleep deprivation during late gestation. Twenty-one days after birth, the offspring were assigned to standard or EE cages. At 18 months-old, the learning and memory function of the offspring mice was evaluated using Morris water maze. The hippocampal and prefrontal cortical levels of protein, gene, proinflammation cytokines, and oxidative stress indicators was examined by Western blot, real-time polymerase chain reaction, enzyme linked immunosorbent assay, and biochemical assays. RESULTS: Offspring in MSD group exhibited declined learning and memory abilities compared with control animals. Moreover, the hippocampal and prefrontal cortical levels of Sirtuin1 (Sirt1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), postsynaptic density protein-95, and synaptophysin were lower and those of proinflammation cytokines higher in the MSD group; meanwhile, the superoxide dismutase content was higher and the malondialdehyde and reactive oxygen species contents were lower. However, these deleterious changes were ameliorated by exposure to EE. CONCLUSIONS: EE attenuates MSD-induced cognitive impairment, oxidative stress, and neuroinflammation and reverses the reduction in synaptic protein levels in aged offspring mice via the Sirt1/PGC-1α pathway.

Long-term outcomes of endoscopic or surgical resection in T1 colorectal cancer patients: a retrospective cohort study.

BACKGROUND: The personalized treatments of T1 colorectal cancer (CRC) remains controversial. We compared the long-term outcomes of T1 CRC patients after endoscopic resection (ER) and surgery, and evaluated the risk factors for the long-term prognosis. METHODS: T1 CRCs after resection at the Cancer Hospital, Chines Academy of Medical Sciences from June 2011 to November 2021 were reviewed. High-risk factors included positive resection margin, poor differentiation, deep submucosal invasion (DSI ≥ 1000 µm), lymphovascular invasion and intermediate/high tumor budding. Comparative analyses were conducted based on three treatment methods: follow-up after ER (Group A), additional surgery after ER (Group B) and initial surgery (Group C). The primary endpoints included recurrence-free survival (RFS) and overall survival (OS). Cox proportional hazard regression models were constructed to identify risk factors for RFS and OS. RESULTS: A total of 528 patients were enrolled (173 patients in Group A, 102 patients in Group B, 253 patients in Group C). The 3-year RFS, 5-year RFS, 3-year OS, and 5-year OS rates were 96.7%, 94.7%, 99.1%, and 97.8%, respectively. In the absence of other high-risk factors, RFS (P = 0.321) and OS (P = 0.155) of patients with DSI after ER were not inferior to those after surgery. Multivariate analyses identified sex (HR 0.379; 95% CI 0.160-0.894), Charlson comorbidities index (CCI) (HR 3.330; 95% CI 1.571-7.062), margin (HR 8.212; 95% CI 2.325-29.006), and budding (HR 3.794; 95% CI 1.686-8.541) as independent predictive factors of RFS, and identified CCI (HR 10.266; 95% CI 2.856-36.899) as an independent predictive factor of OS. CONCLUSION: The long-term outcomes of ER are comparable to those of surgery in T1 CRC patients with DSI when other high-risk factors are negative. Resection margin, tumor budding, sex, and CCI may be the most important long-term prognostic factors for T1 CRC patients.

Sleep deprivation aggravates lipopolysaccharide-induced anxiety, depression and cognitive impairment: The role of pro-inflammatory cytokines and synaptic plasticity-associated proteins.

Growing evidence indicates that neuroinflammation plays a critical role in anxiety, depression, and cognitive impairment. Sleep loss disrupts the host's immune balance and increases neuroinflammation. This study explored whether chronic sleep deprivation aggravates lipopolysaccharide-induced anxiety, depression, and cognitive impairment and assessed the underlying mechanisms. Lipopolysaccharide (250 µg/kg) was administered to adult mice for 9 days, accompanied with daily intermittent sleep deprivation from 12:00 to 18:00 by using an activity wheel. Anxiety, depression, and cognitive function were evaluated using a task battery consisting of an open field, elevated plus maze, tail suspension, forced swimming, and Morris water maze tests. The levels of pro-inflammatory cytokines and synaptic plasticity-associated proteins were examined by enzyme-linked immunosorbent assay and western blot, respectively. The results showed that lipopolysaccharide increased anxiety- and depression-like behaviors, impaired cognitive function, uprelated interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and decreased brain-derived neurotrophic factor (BDNF), postsynaptic density-95 (PSD-95), and synaptophysin (SYN), which were aggravated by chronic sleep deprivation. These results suggest that chronic sleep deprivation exerted adverse effects on lipopolysaccharide-induced anxiety, depression, and cognitive impairment, which was associated with changes in pro-inflammatory cytokines and synaptic plasticity associated proteins.

A strategy combining endoscopic hand-suturing with clips for closure of rectal defects after endoscopic submucosal dissection with or without myectomy (with video).

BACKGROUND AND AIMS: Endoscopic hand-suturing (EHS) has been preliminarily demonstrated to be effective in closing defects after endoscopic submucosal dissection (ESD), but it is not easily performed. We proposed a strategy combining EHS with clips (EHS-Clips) and explored its effectiveness in closing rectal defects after ESD or ESD with myectomy (ESD-ME). METHODS: In this observational study, data from patients with rectal defects closed using EHS-Clips were reviewed. EHS-Clips refers to a strategy where defects are sutured as much as possible by EHS first, with clips being used to close the remaining parts of defects that cannot be completely sutured. The primary endpoints included complete closure rate, delayed bleeding (DB) rate, and sustained closure rate. Logistic regression analyses were performed to identify risk factors for the sustained closure. RESULTS: All 49 (100%) defects (42 ESD defects and 7 ESD-ME defects) were completely closed through the strategy of EHS-Clips, with 35 (71.4%) through EHS alone and 14 (28.6%) through EHS and additional clips. No patients experienced DB. Thirty-six (73.5%) defects remained sustained closure on postoperative days 3 to 5 (73.8% for ESD defects vs 71.4% for ESD-ME defects). The multivariate analyses identified a stitch margin of ≥5 mm (hazard ratio, 0.313; 95% confidence interval, 0.023-0.781; P = .009) as the only independent advantage factor for the sustained closure. CONCLUSIONS: EHS-Clips can be used to effectively close the rectal defects after ESD or ESD-ME and prevent DB. Complete suture with a stitch margin of ≥5 mm may achieve more reliable sustained closure.

Resveratrol ameliorates maternal immune activation-associated cognitive impairment in adult male offspring by relieving inflammation and improving synaptic dysfunction.

Maternal exposure to inflammation may represent a major risk factor for neuropsychiatric disorders with associated cognitive dysfunction in offspring in later life. Growing evidence has suggested that resveratrol exerts a beneficial effect on cognitive impairment via its anti-inflammatory and antioxidant properties and by ameliorating synaptic dysfunction. However, how resveratrol affects maternal immune activation-induced cognitive dysfunction and the underlying mechanisms are unclear. In the present study, pregnant dams were given an intraperitoneal injection of lipopolysaccharide (LPS; 50 µg/kg) on gestational day 15. Subsequently, the offspring mice were treated or not with resveratrol (40 mg/kg) from postnatal day (PND) 60 to PND 88. Male offspring were selected for the evaluation of cognitive function using the Morris water maze test. The hippocampal levels of pro-inflammatory cytokines were examined by ELISA. The mRNA and protein levels of sirtuin-1 (SIRT1), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYP) were determined by RT-qPCR and western blot, respectively. The results showed that male offspring mice exposed to LPS in utero exhibited learning and memory impairment. Additionally, the levels of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-alpha (TNF-α) were increased while those of SIRT1, BDNF, PSD-95, and SYP were decreased in male offspring of LPS-treated mothers. Treatment with resveratrol reversed cognitive impairment and attenuated the increase in the levels of pro-inflammatory cytokines induced by maternal immune activation in the offspring mice. Furthermore, resveratrol reversed the deleterious effects of maternal immune activation on SIRT1, BDNF, PSD-95, and SYP levels in the hippocampus. Collectively, our results suggested that resveratrol can effectively improve learning and memory impairment induced by maternal immune activation via the modulation of inflammation and synaptic dysfunction.

HMGB1 promotes chemoresistance in small cell lung cancer by inducing PARP1-related nucleophagy.

INTRODUCTION: Small cell lung cancer (SCLC) is prone to chemoresistance, which is closely related to genome homeostasis-related processes, such as DNA damage and repair. Nucleophagy is the elimination of specific nuclear substances by cells themselves and is responsible for maintaining genome and chromosome stability. However, the roles of nucleophagy in tumour chemoresistance have not been investigated. OBJECTIVES: The aim of this work was to elucidate the mechanism of chemoresistance in SCLC and reverse this chemoresistance. METHODS: RNA-seq data from SCLC cohorts, chemosensitive SCLC cells and the corresponding chemoresistant cells were used to discover genes associated with chemoresistance and patient prognosis. In vitro and in vivo experiments were performed to verify the effect of high-mobility group box 1 (HMGB1) knockdown or overexpression on the chemotherapeutic response in SCLC. The regulatory effect of HMGB1 on nucleophagy was then investigated by coimmunoprecipitation (co-IP) and mass spectrometry (MS), and the underlying mechanism was explored using pharmacological inhibitors and mutant proteins. RESULTS: HMGB1 is a factor indicating poor prognosis and promotes chemoresistance in SCLC. Mechanistically, HMGB1 significantly increases PARP1-LC3 binding to promote nucleophagy via PARP1 PARylation, which leads to PARP1 turnover from DNA lesions and chemoresistance. Furthermore, chemoresistance in SCLC can be attenuated by blockade of the PARP1-LC3 interaction or PARP1 inhibitor (PARPi) treatment. CONCLUSIONS: HMGB1 can induce PARP1 self-modification, which promotes the interaction of PARP1 with LC3 to promote nucleophagy and thus chemoresistance in SCLC. HMGB1 could be a predictive biomarker for the PARPi response in patients with SCLC. Combining chemotherapy with PARPi treatment is an effective therapeutic strategy for overcoming SCLC chemoresistance.

Feasibility of applying a noninvasive method for sleep monitoring based on mouse behaviors.

INTRODUCTION: Currently, electroencephalogram (EEG)/electromyogram (EMG) system is widely regarded as the "golden standard" for sleep monitoring. Imperfectly, its invasive monitoring may somehow interfere with the natural state of sleep. Up to now, noninvasive methods for sleep monitoring have developed, which could preserve the undisturbed and naïve sleep state of mice to the greatest extent, but the feasibility of their application under different conditions should be extensive validated. METHODS: Based on existing research, we verified the feasibility of a sleep monitoring system based on mouse behaviors under different conditions. The experimental mice were exposed to various stresses and placed into a combined device comprising noninvasive sleep monitoring equipment and an EEG/EMG system, and the sleep status was recorded under different physiological, pharmacological, and pathophysiological conditions. The consistency of the parameters obtained from the different systems was calculated using the Bland-Altman statistical method. RESULTS: The results demonstrated that the physiological sleep times determined by noninvasive sleep monitoring system were highly consistent with those obtained from the EEG/EMG system, and the coefficients were 94.4% and 95.1% in C57BL/6J and CD-1 mice, respectively. The noninvasive sleep monitoring system exhibited high sensitivity under the sleep-promoting effect of diazepam and caffeine-induced wakefulness, which was indicated by its ability to detect the effect of dosage on sleep times, and accurate determination of the sleep/wakeful status of mice under different pathophysiological conditions. After combining the data obtained from all the mice, the coefficient between the sleep times detected by behavior-based sleep monitoring system and those obtained from the EEG/EMG equipment was determined to .94. CONCLUSION: The results suggested that behavior-based sleep monitoring system could accurately evaluate the sleep/wakeful states of mice under different conditions.

The identification of key metabolites and mechanisms during isoniazid/rifampicin-induced neurotoxicity and hepatotoxicity in a mouse model by HPLC-TOF/MS-based untargeted urine metabolomics.

The co-administration of isoniazid (INH) and rifampicin (RIF) is associated with hepatotoxicity and neurotoxicity. To systematically investigate the mechanisms of hepatotoxicity and neurotoxicity induced by INH/RIF, we used high performance liquid chromatography-time of flight mass spectrometry (HPLC-TOF/MS)-based untargeted metabolomics to analyze urine from a mouse model and screened a range of urinary biomarkers. Mice were orally co-administered with INH (120 mg/kg) and RIF (240 mg/kg) and urine samples were collected on days 0, 7, 14 and 21. Hepatotoxicity and neurotoxicity were assessed by samples of liver, brain and kidney tissue which were harvested for histological analysis. Toxicity analysis revealed that INH/RIF caused hepatotoxicity and neurotoxicity in a time-dependent manner; compared with day 0, the levels of 35, 82 and 86 urinary metabolites were significantly different on days 7, 14 and 21, respectively. Analysis showed that by day 21, exposure to INH+RIF had caused disruption in vitamin B6 metabolism; the biosynthesis of unsaturated fatty acids; tyrosine, taurine, hypotaurine metabolism; the synthesis of ubiquinone and other terpenoid-quinones; and the metabolism of tryptophan, nicotinate and nicotinamide. Nicotinic acid, nicotinuric acid and kynurenic acid were identified as sensitive urinary biomarkers that may be useful for the diagnosis and evaluation of toxicity.

Calcium signals and potential therapy targets in ovarian cancer (Review).

Ovarian cancer (OC) is a deadly disease. The poor prognosis and high lethality of OC are attributed to its high degrees of aggressiveness, resistance to chemotherapy and recurrence rates. Calcium ion (Ca2+) signaling has received attention in recent years, as it appears to form an essential part of various aspects of cancer pathophysiology and is a potential therapeutic target for OC treatment. Disruption of normal Ca2+ signaling pathways can induce changes in cell cycle progression, apoptosis, proliferation and migration and invasion, leading to the development of the malignant phenotype of tumors. In the present review, the main roles of ion channel/receptor/pump­triggered Ca2+ signaling pathways located at the plasma membrane and organelle Ca2+ transport in OC are summarized. In addition, the potential of Ca2+ signaling as a novel target for the development of effective treatment strategies for OC was discussed. Furthering the understanding into the role of Ca2+ signaling in OC is expected to facilitated the identification of novel therapeutic targets and improved clinical outcomes for patients.

Potential role of irisin in digestive system diseases.

Digestive system diseases (DSD) are very complex conditions that severely threaten human health. Therefore, there is an urgent need to develop new pharmacological treatment strategies. Irisin, a myokine discovered in 2012, is produced by fibronectin type III domain-containing protein 5 (FNDC5), which is a transmembrane protein. Irisin is involved in promoting the browning of white adipose tissue, the regulation of energy metabolism, and the improvement of insulin resistance. Irisin is also an essential mediator of the inflammatory response, oxidative stress, and cell apoptosis. Recent studies have proved that irisin concentration is altered in DSD and exerts pivotal effects on the initiation, progression, and prognosis of these diseases through various mechanisms. Therefore, studying the expression and function of irisin may have great significance for the diagnosis and treatment of DSD. Here, we focus on irisin and explore the multiple molecular pathways targeted by irisin therapy. This review indicates that irisin can serve as a diagnostic marker or potential therapeutic agent for DSD. DATA AVAILABILITY: Not applicable.

The association between PM2.5 concentration and the severity of acute asthmatic exacerbation in hospitalized children: A retrospective study in Chongqing, China.

BACKGROUND: Ambient PM2.5 is associated with asthma exacerbation. The association between the concentration of PM2.5 and the severity of asthma exacerbation has yet to be thoroughly clarified. The study aims to explore the association between the piror 30 days average concentration of PM2.5 and the severity of acute asthma exacerbation in hospitalized children. METHODS: A total of 269 children with acute exacerbation of asthma were enrolled and divided into three groups according to the PM2.5 exposure concentrations: group 1 (PM2.5: <37.5 µg/m3 ), group 2 (PM2.5: 37.5-75 µg/m3 ), group 3 (PM2.5: ≥75 µg/m3 ), respectively. The ordered logistic regression modeling was conducted to explore the influence of daily PM2.5 concentration on the clinical severity of children's asthma exacerbation. Multiple linear regression was conducted to explore the association between the concentration of PM2.5 and the length of stay in the hospital (LOS). We also conducted a receiver operating characteristic (ROC) curve analysis to explore the cutoff value of PM2.5 to predict the children's asthma exacerbation. RESULTS: There was no statistical difference among the three groups of children in gender, age, body mass index, ethnicity, the first diagnosis of asthma, allergic history, passive smoke exposure, or family history of asthma. There was a statistically significant difference in many hospitalization characteristics (p < 0.05) among the three groups of children. Significant differences were found in terms of accessory muscles of respiration (p = 0.005), respiratory failure (p = 0.012), low respiratory tract infectious (p = 0.020), and the severity of asthma exacerbation (p < 0.001) among the three groups. PM2.5 concentration was primarily positively correlated to neutrophile inflammation. The ordered multivariate logistic regression model showed that higher PM2.5 concentrations were significantly associated with greater odds of more severe asthma exacerbation in one and two-pollutant models. The adjusted odds ratio of severe asthma exacerbation was 1.029 (1.009, 1.049) in the one-pollutant model. The most significant odds ratio of severe asthma exacerbation was 1.050 (1.027, 1.073) when controlling NO2 in the two-pollutant models. Multiple linear regression showed that PM2.5 concentration was significantly associated with longer LOS in both one-pollutant and two-pollutant models. By performing ROC analysis, the average daily concentration of 44.5 µg/m3 of PM2.5 (AUC = 0.622, p = 0.002) provided the best performance to predict severe asthma of children exacerbation with a sensitivity of 59.2% and a specificity of 63.8%. CONCLUSION: The increased prior 30 days average concentration of PM2.5 was associated with greater asthma exacerbation severity and longer length of stay in the hospital of children with asthma exacerbation.

Anesthesia management of a patient with Meigs' syndrome: A case report and literature review.

INTRODUCTION: Herein, we describe a case of Meigs' syndrome, a complex condition that poses a challenge for anesthesiologists to manage. Good anesthetic management of this syndrome is necessary to preserve the prognosis. PRESENTATION OF CASE: An 80-year-old woman was admitted to the emergency department with complaints of abdominal pain, particularly in the left lower abdomen, with aggravation after activity. The patient was unable to sleep in a supine position. Her serum carbohydrate antigen 125 level was 253.15 U/mL-1, and laboratory examinations were nonspecific. On auscultation, breath sounds were absent from the base of the right lung. Abdominal computed tomography (CT) was performed to screen for a possible tumor consisting of both solid and cystic components, but the findings were inconclusive. Chest CT showed large right pleural effusions and hiatal hernia. DISCUSSION: A multidisciplinary team conducted careful preoperative preparation, while the anesthesiology team prepared detailed peri-anesthesia management strategies to regulate acid-base and electrolyte balance and maintain respiratory and hemodynamic stability. The surgeon resected the tumor successfully. The patient was discharged after 1 week. A postoperative pathology test confirmed fibrothecomas. CONCLUSION: We provided an effective strategy for the anesthetic management of Meigs' syndrome, which remains a complex challenge for anesthesiologists. It is important that anesthesiologists perform adequate preoperative evaluation and prudent peri-anesthesia management to ensure that patients have a good prognosis and discharge healthily. A multidisciplinary team is essential when caring for patients with Meigs' syndrome.