Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.

Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. METHODS: Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. RESULTS: Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. CONCLUSION: This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.

Hedscandines A-C, three undescribed indole alkaloids from Hedyotis scandens with their anti-MRSA activity.

Hedscandines A-C (1-3), three undescribed indole alkaloids were isolated from Hedyotis scandens Roxb, a traditional Chinese medicine widely used in the treatment of respiratory ailments. Their structures were elucidated by extensive spectroscopic data and electronic circular dichroism calculation. Hedscandine A (1), possessed a unique carbon skeleton with a 1,4-oxazonin-2(3H)-one core system and displayed a rapid bactericidal activity against MRSA with a MIC value of 16 µg/mL. Mechanistic studies showed that compound 1 could disrupt the integrity of bacterial cell membranes and thus lead to bacterial death.

A Novel Method to Classify the Responses of Genioglossus to Negative Pressure in OSA Patients.

OBJECTIVE: This study aims to develop a novel method to classify different genioglossus (GG) responses to upper airway (UA) negative pressure in obstructive sleep apnea (OSA) patients. STUDY DESIGN: A single-center, prospective, cohort study. SETTING: Sleep Medical Center. METHODS: Patients with OSA underwent drug-induced sleep endoscopy with synchronous genioglossus electromyography (ggEMG) and UA pressure monitoring. In spontaneous obstructive apnea events, the value of epiglottis negative pressure at the end of inspiration (Pepi ) and corresponding peak phasic ggEMG were recorded as pairing data for linear regression analysis to classify GG response modes: peak phasic ggEMG-Pepi linear mode (P < .05) were classified as group 1; others (P ≥ .05) were classified as group 2. Using nasopharyngeal tube (NPT) to reopen the palatopharyngeal cavity for comparing the improvement between the OSA patients with different GG response modes. RESULTS: Sixty subjects were analyzed for GG response modes: 22 patients were in group 1 (r2 = 0.233-0.867), and 38 patients were in group 2. The proportion of partial (63.16% vs 59.09%) or complete (36.84% vs 22.73%) collapse rate of the tongue base in group 2 was significantly higher (χ2 = 7.823, P = .020). The improvement of the apnea-hypopnea index after NPT placement in group 2 was significantly lower than in group 1 (59.09% vs 31.58%, χ2 = 4.339, P = .037). CONCLUSION: This novel method is advantageous for distinguishing OSA patients with different GG response abilities to UA negative pressure, whose GG responses conforming to peak phasic ggEMG-Pepi linear mode might be more suitable for palatopharyngeal surgery.

[Chemical constituents from whole herb of Hedyotis scandens].

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 µg·mL~(-1), respectively.

Association Between Dietary and Serum Cholesterol and Cognitive Function Among the U.S. Elderly from NHANES 2011-2014.

BACKGROUND: The association between dietary or serum cholesterol and cognitive performance in older adults has not been well-established. OBJECTIVE: This study aimed to investigate the potential association between dietary or serum cholesterol and cognitive performance in the elderly population. METHODS: A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 and 2013-2014. Diet and supplement cholesterol was estimated based on two non-consecutive 24-hour dietary recalls. Cognitive function was assessed using various statistical tests. Poor cognitive performance was defined as scores below the lowest quartile within age groups. Regression models were adjusted for demographic factors, and subgroup analyses were performed for non-Hispanic White (NHW) and non-Hispanic Black (NHB) individuals. RESULTS: Among 759 participants aged 60 years and above, dietary cholesterol was only associated with dietary saturated fatty acids and serum high-density lipoprotein cholesterol. There was no evidence of an association between dietary cholesterol and cognitive function, except for NHB individuals, where dietary cholesterol showed a positive correlation with cognitive function. In the overall sample and NHW participants, there were consistent positive associations between serum total cholesterol and cognitive performance across statistical tests, while such associations were rare among NHB individuals. Although not statistically significant, NHB individuals had higher dietary/supplementary/total cholesterol intake compared with NHW individuals. CONCLUSION: Within the normal range, increasing serum cholesterol may be a potential factor to prevent or relieve cognitive dysfunction. However, ethnic differences should be taken into account when considering the association between cholesterol and cognitive performance.

Hand grip strength is inversely associated with total daily insulin dose requirement in patients with type 2 diabetes mellitus: a cross-sectional study.

Background: Short-term (2 weeks to 3 months) insulin intensive therapy using continuous subcutaneous insulin infusion (CSII) can improve islet beta cell function and prolong glycemic remission in patients with newly diagnosed type 2 diabetes mellitus (T2DM). However, the total daily insulin dose (TDD, IU/kg/d) required to achieve near-normoglycemic control with CSII still needs to be frequently adjusted based on blood glucose monitoring. Although real-time continuous glucose monitoring (rtCGM), which measures the interstitial fluid glucose concentration continuously without much difficulty, facilitates the adjustment of insulin dosage, its adoption in the T2DM population is strictly limited by insurance coverage and lack of awareness of rtCGM among clinicians. Thus, it is of clinical significance to identify easy-to-use parameters that may allow a more rapid and accurate prediction of TDD requirement. This study aimed to explore the association between hand grip strength (HGS) and TDD requirement in patients with T2DM receiving CSII therapy. Methods: A total of 180 eligible patients with T2DM were enrolled in the study and divided into three groups based on their HGS: low (L), medium (M), and high (H). The TDD requirement was calculated on day 7 or 8 of CSII treatment. Anthropometric parameters, including HGS, skeletal muscle mass, skeletal muscle index (SMI) and 6-m gait speed, and laboratory data, were collected on the morning of the second day after admission, within the first 24 h of CSII therapy. These parameters were used to identify significant predictors of TDD requirement using Pearson or Spearman correlation test, and stepwise multiple regression analysis. Results: There were no significant differences in age, duration of T2DM, waist-to-hip ratio (WHR), body mass index (BMI), blood pressure, liver function, estimated glomerular filtration rate, triglyceride, total cholesterol, glycosylated hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of beta cell function (HOMA-ß) among the groups. The H group had higher body muscle mass-to-fat ratio (BMFR), skeletal muscle mass-to-fat ratio (SMFR), SMI, 6-m gait speed, and lower TDD requirement than the M and L groups. The HGS negatively correlated with TDD requirement (r = -0.33, p < 0.001) after adjusting for sex, age, BMI, WHR, HbA1c, Ln (HOMA-ß), Ln (HOMA-IR), Ln (BMFR), Ln (SMFR), SMI, and 6-m gait speed. Multivariate stepwise regression analysis indicated that HGS was an independent predictor of TDD requirement in patients with T2DM (ß = -0.45, p < 0 001). Conclusion: Lower HGS is associated with an increased TDD requirement in T2DM patients. HGS may facilitate the prediction of TDD requirement in T2DM patients receiving CSII therapy.

Dihydroartemisinin inhibits the activation and proliferation of hepatic stellate cells by regulating miR­29b­3p.

Liver fibrosis is an early pathological feature of hepatic diseases. Hepatic stellate cell (HSC) activation and disordered proliferation are associated with liver fibrosis. The present study identified significant differences in the expression levels of microRNA (miRNA/miR)­29b­3p in clinical samples and multiple miRNA databases. Subsequently, the specific antifibrotic mechanism of miR­29b­3p was further elucidated. Reverse transcription­quantitative PCR, western blot, ELISA and immunofluorescence were used to detect the expression levels of target genes and proteins. Oil red O, Nile red and trypan blue staining were used to evaluate HSC activation and cell viability. A luciferase assay was used to detect the relationship between miR­29b­3p and VEGFA. Adhesion, wound healing, apoptosis double staining and JC­1 assays were used to detect the effects of VEGFR1 and VEGFR2 knockdown on HSCs. Immunoprecipitation and fluorescence colocalization were used to identify interactions between the proteins. Furthermore, a rat fibrosis model was constructed to investigate the effects of dihydroartemisinin (DHA) and miR­29b­3p in vivo and in vitro. The results indicated that miR­29b­3p both inhibited the activation of HSCs and limited the proliferation of activated HSCs via lipid droplet recovery and VEGF pathway regulation. VEGFA was identified as a direct target of miR­29b­3p, and knockdown of VEGFA induced cell apoptosis and autophagy. Notably, VEGFR1 and VEGFR2 knockdown both promoted apoptosis; however, VEGFR1 knockdown inhibited autophagy, whereas VEGFR2 knockdown induced autophagy. Furthermore, it was revealed that VEGFR2 regulated autophagy by mediating the PI3K/AKT/mTOR/ULK1 pathway. VEGFR2 knockdown also led to ubiquitination of heat shock protein 60, ultimately inducing mitochondrial apoptosis. Finally, DHA was identified as a natural agonist of miR­29­3p that effectively prevented liver fibrosis in vivo and in vitro. Overall, the present study determined the molecular mechanism by which DHA inhibited HSC activation and prevented liver fibrosis.

Effectiveness and safety of (adeno) tonsillectomy for pediatric obstructive sleep apnea in different age groups: A systematic review and meta-analysis.

This meta-analysis aimed to assess the effectiveness and safety of (adeno)tonsillectomy (AT) for uncomplicated pediatric obstructive sleep apnea (OSA) across different age groups. Four electronic databases were searched until April 2022, and 93 studies (9087 participants) were selected, including before-after studies, cohort studies, and randomized controlled trials. It has been suggested that age, disease severity, and length of follow-up are associated with surgical effects. Compared with older children (>7 years), patients receiving AT surgery before the age of 7 exhibited a significantly greater release of disease severity, as well as a greater decrease in hypoxemic burden, improvement in sleep quality, and better cardiovascular function. Cognitive/behavioral performance also improved after AT, although it was more related to the length of follow-up than the age at surgery. Notably, the surgical complication rate was considerably higher in patients younger than 3 years old. Overall, we suggest that the age of 3-7 years might be optimal for AT in polysomnography-diagnosed uncomplicated OSA to maximize potential benefits for both disease and comorbidities and balance the risks of surgery.

Analysis of factors that influence the occurrence of otitis media with effusion in pediatric patients with adenoid hypertrophy.

Objective: Adenoid hypertrophy (AH) and otitis media with effusion (OME) are common pediatric otolaryngological diseases and often occur concurrently. The purpose of this study was to comprehensively analyze the factors that influence the occurrence of OME pediatric patients with AH. Methods: Patients younger than 12 years with AH, who were hospitalized for treatment at Beijing Tsinghua Changgung Hospital in Beijing, China, between March 2018 and February 2022 were enrolled. The patients were divided into an AH group and an AH + OME group based on the presence of OME. The authors collected the following clinical data for univariable analysis: sex; age; body mass index (BMI); comorbid nasal congestion/rhinorrhea, recurrent tonsillitis, or allergic rhinitis (AR); adenoid and tonsil grade; tonsillar hypertrophy; food/drug allergy; history of adenoidectomy and congenital diseases; breastfeeding status; preterm birth; exposure to environmental tobacco smoke (ETS); family history of adenotonsillectomy, otitis media, and AR; main data of polysomnography and oropharyngeal conditional pathogen culture data of some patients. Univariate analysis was performed as a basis for logistic regression analysis. Results: A total of 511 children (329 boys and 182 girls) were included, their mean age was 5.37 ± 2.10 years. Of them, 407 (79.6%) were in the AH group and 104 (20.4%) in the AH + OME group. Univariate analysis revealed statistically significant differences in age, BMI, adenoid grade, AR, breastfeeding status, and ETS exposure between the two groups. Multivariate stepwise logistic regression analysis showed that age, adenoid grade, AR, breastfeeding status, and ETS influenced the occurrence of OME in pediatric patients with AH. The risk of OME decreased with increasing age. High adenoid grade, ETS exposure, and comorbid AR were risk factors for OME in pediatric patients with AH, but breastfeeding was a protective factor. The final analytical results of the oropharyngeal conditional pathogen culture data showed that Streptococcus pneumoniae positivity was associated with OME in AH. Conclusion: The pathogenesis of AH with OME is complex. Young age, high adenoid grade, ETS exposure, non-breastfed status, comorbid AR, and the presence of S. pneumoniae in the oropharynx are risk factors for OME in pediatric patients with AH.

A prediction model for difficult intubation using skeletal features in patients affected by apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) has been linked to increased risk of perioperative morbidity and mortality because of difficult intubation (DI). However, there is a lack of clinically validated tools to identify OSAHS patients who are likely to have an increased the risk of DI. METHODS: For model development, a prospective cohort study included patients with OSAHS who underwent elective surgery between September 2018 to December 2020. The outcome was DI and classified according to the Cormack-Lehane grading. Conventional airway assessment tests, skeletal features, and the severity of OSAHS were recorded, and LASSO regression was used. Validation was performed on an external sample of patients from the same hospital between January 2021 and December 2021. RESULTS: The development (prevalence of DI: 44%) and validation cohorts (prevalence of DI: 32%) included 247 and 82 patients, respectively. Based on the result of LASSO, age and four skeletal features (thyromental height, maximum mandibular protrusion, mandibulohyoid distance, and neck hypokinesis grade) were included in the final model. Discrimination and calibration of the model were satisfactory with high AUC (0.97), sensitivity (88.5%), specificity (94.6%), accuracy (92.7%), PPV (88.5%) and NPV (94.6%) from external validation. CONCLUSIONS: Our study developed and externally validated a DI prediction model using skeletal features in OSAHS patients. The final model had an NPV of nearly 95%, suggesting that a simple nomogram including only five predictors was quite helpful for ruling out the presence of difficult intubation in OSAHS patients who underwent elective surgery.

[Validation the clinical value of good outcome following attempted resuscitation scores in Chinese populations in predicting the prognosis of in-hospital cardiac arrest].

OBJECTIVE: To verify the clinical value of the good outcome following attempted resuscitation (GO-FAR) score in predicting the neurological status of patients with in-hospital cardiac arrest (IHCA) in the Chinese population. METHODS: The clinical data of patients with IHCA who were admitted to the Zigong Fourth People's Hospital from January 1 to December 31, 2020 were retrospectively analyzed. Used Glasgow-Pittsburgh cerebral performance category (CPC) score 1 point as the end point, the subjects were divided into 4 groups according to the score: ≤ 0 group, 1-8 group, 9-20 group and ≥ 21 group. Taken the group which GO-FAR score ≤ 0 as the reference group, the odds ratio (OR) of the other three groups compared with this group was calculated. The receiver operator characteristic curve (ROC curve) was performed to evaluate the predictive value of the GO-FAR score in favorable neurological outcome. A calibration curve was drawn for the Hosmer-Lemeshow test to analyze the degree of calibration of the GO-FAR score for predicting good neurological outcome. RESULTS: A total of 230 IHCA patients were enrolled in the study, including 130 males, aged 74 (65, 81) years old, and 23 case (10.0%) had good neurological prognosis. There were statistically significant differences in GO-FAR-related variables, including age, a normal neurological function on admitted, acute stroke, metastatic cancer, septicemia, medical noncardiac admission, hepatic insufficiency, hypotension, renal insufficiency or dialysis, respiratory insufficiency, pneumonia, etc (all P < 0.05). Taken the GO-FAR score ≤ 0 group as the reference group, the OR values of good neurological prognosis in the GO-FAR score 1-8 group were 0.54 [95% confidence interval (95%CI) was 0.17-1.53, P = 0.250], 9-20 group were 0.17 (95%CI was 0.02-0.67, P = 0.009) and ≥ 21 group were 0.25 (95%CI was 0.05-0.85, P = 0.025). The area under the ROC curve (AUC) of the GO-FAR score for predicting favorable neurological outcome in IHCA patients was 0.653 (95%CI was 0.529-0.777, P = 0.015) and there was no significant difference in Hosmer-Lemeshow test (P = 0.311). All these suggested that there was no significant difference between the predicted value and the actual value. CONCLUSIONS: GO-FAR score can be applied to predict neurological prognosis of IHCA patients in Chinese population. It can help clinicians to predict the prognosis of cardio-pulmonary resuscitation (CPR) and propose critical recommendations in treatment for these patients or their families.

Inhibition of ASCT2 induces hepatic stellate cell senescence with modified proinflammatory secretome through an IL-1α/NF-κB feedback pathway to inhibit liver fibrosis.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.

Identification of a 5-lncRNA-Based Signature for Immune Characteristics and Prognosis of Lung Squamous Cell Carcinoma and Verification of the Function of lncRNA SPATA41.

Lung squamous cell carcinoma (LUSC) is one of the most lethal cancers worldwide. Traditional tumor-node-metastasis (TNM) staging system has many insufficiencies in predicting immune characteristics, overall survival (OS), and prognosis of LUSC. LncRNA is currently found involved in tumor development and effectively predicts tumor prognosis. We screened potential tumor-related lncRNAs for immune characteristics and constructed a nomogram combining lncRNA and traditional clinical indicators for prognosis prediction. We obtained the large-scale gene expression profiles of samples from 492 LUSC patients in The Cancer Genome Atlas database. SPATA41, AL034550.2, AP003721.2, AC106786.1, and AC078889.1 were finally screened to construct a 5-lncRNA-based signature. The risk score of the signature divided patients into subgroups of high-risk and low-risk with significant differences in OS. Their area under the curve (AUC) reached more than 0.70 in 1, 3, and 5 years. In addition, compared with the high-risk subgroup, the low-risk subgroup exhibited a remarkably favorable prognosis and TME score, along with a higher immune infiltration score and lower TIDE score. The signature also significantly related to chemotherapy response, especially in cisplatin, vinorelbine, and paclitaxel. Importantly, the nomogram we constructed had good reliability with the assessment of the calibration chart and consistency index (c-index). GO and KEGG enrichment analysis indicated that co-expression mRNAs of the 5 lncRNAs were mainly focused on RNA splicing, DNA replication, and protein serine/threonine kinase activity. Functional assays demonstrated that SPATA41, one of the five OS-related lncRNAs, regulated invasion, migration, proliferation, and programmed death in vitro. In summary, our 5-lncRNA-based signature has a good performance in predicting immune characteristics and prognosis of LUSC patients.

Electroencephalography Theta/Beta Ratio Decreases in Patients with Severe Obstructive Sleep Apnea.

Purpose: Accumulating evidence suggests that theta/beta ratio (TBR), an electroencephalographic (EEG) frequency band parameter, might serve as an objective marker of executive cognitive control in healthy adults. Obstructive sleep apnea (OSA) has a detrimental impact on patients' behavior and cognitive performance while whether TBR is different in OSA population has not been reported. This study aimed to explore the difference in relative EEG spectral power and TBR during sleep between patients with severe OSA and non-OSA groups. Patients and Methods: 142 participants with in-laboratory nocturnal PSG recording were included, among which 100 participants suffered severe OSA (apnea hypopnea index, AHI > 30 events/hour; OSA group) and 42 participants had no OSA (AHI ≤ 5 events/h; control group). The fast Fourier transformation was used to compute the EEG power spectrum for total sleep duration within contiguous 30-second epochs of sleep. The demographic and polysomnographic characteristics, relative EEG spectral power and TBR of the two groups were compared. Results: It was found that the beta band power during NREM sleep and total sleep was significantly higher in the OSA group than controls (p < 0.001, p = 0.012, respectively), and the theta band power during NREM sleep and total sleep was significantly lower in the OSA group than controls (p = 0.019, p = 0.014, respectively). TBR during NREM sleep, REM sleep and total sleep was significantly lower in the OSA group compared to the control group (p < 0.001 for NREM sleep and total sleep, p = 0.015 for REM sleep). TBR was negatively correlated with AHI during NREM sleep (r=-0.324, p < 0.001) and total sleep (r=-0. 312, p < 0.001). Conclusion: TBR was significantly decreased in severe OSA patients compared to the controls, which was attributed to both increased beta power and decreased theta power. TBR may be a stable EEG-biomarker of OSA patients, which may accurately and reliably identify phenotype of patients.

Stroke volume variation for predicting responsiveness to fluid therapy in patients undergoing cardiac and thoracic surgery: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the reliability of stroke volume variation (SVV) for predicting responsiveness to fluid therapy in patients undergoing cardiac and thoracic surgery. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, EMBASE, Cochrane Library, Web of Science up to 9 August 2020. METHODS: Quality of included studies were assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We conducted subgroup analysis according to different anaesthesia and surgical methods with Stata V.14.0, Review Manager V.5.3 and R V.3.6.3. We used random-effects model to pool sensitivity, specificity and diagnostic odds ratio with 95% CI. The area under the curve (AUC) of receiver operating characteristic was calculated. RESULTS: Among the 20 relevant studies, 7 were conducted during thoracic surgery, 8 were conducted during cardiac surgery and the remaining 5 were conducted in intensive critical unit (ICU) after cardiac surgery. Data from 854 patients accepting mechanical ventilation were included in our systematic review. The pooled sensitivity and specificity were 0.73 (95％ CI: 0.59 to 0.83) and 0.62 (95％ CI: 0.46 to 0.76) in the thoracic surgery group, 0.71 (95％ CI: 0.65 to 0.77) and 0.76 (95％ CI: 0.69 to 0.82) in the cardiac surgery group, 0.85 (95％ CI: 0.60 to 0.96) and 0.85 (95％ CI: 0.74 to 0.92) in cardiac ICU group. The AUC was 0.73 (95% CI: 0.69 to 0.77), 0.80 (95% CI: 0.77 to 0.83) and 0.88 (95% CI: 0.86 to 0.92), respectively. Results of subgroup of FloTrac/Vigileo system (AUC=0.80, Youden index=0.38) and large tidal volume (AUC=0.81, Youden index=0.48) in thoracic surgery, colloid (AUC=0.85, Youden index=0.55) and postoperation (AUC=0.85, Youden index=0.63) in cardiac surgery, passive leg raising (AUC=0.90, Youden index=0.72) in cardiac ICU were reliable. CONCLUSION: SVV had good predictive performance in cardiac surgery or ICU after cardiac surgery and had moderate predictive performance in thoracic surgery. Nevertheless, technical and clinical variables may affect the predictive value potentially.

[Secondary metabolites of endophyte fungi Xylaria sp. from Coptis chinensis].

Two new polyketides, lasobutone A(1) and lasobutone B(2), along with three known compounds, guignardianone C(3), guignardic acid(4), and 4-hydroxy-17R-methylincisterol(5), were isolated from the endophytic fungi Xylaria sp. by silica gel, MCI, and preparative HPLC, which was separated from the Chinese medicinal material Coptis chinensis and cultivated through solid fermentation with rice. Their structures were elucidated on the basis of spectroscopic methods, such as MS, NMR, IR, UV, and ECD. Compounds 2 and 4 showed inhibitory activities against the nitric oxide(NO) production in the LPS-induced macrophage RAW264.7 with IC_(50) values of 58.7 and 42.5 µmol·L~(-1) respectively, while compound 5 exhibited cytotoxic activities against HT-29 with IC_(50) value of 14.3 µmol·L~(-1).

m6A methylation is required for dihydroartemisinin to alleviate liver fibrosis by inducing ferroptosis in hepatic stellate cells.

Activation of hepatic stellate cells (HSCs) is a central event in the development of liver fibrosis, and the elimination of activated HSCs is considered to be an effective anti-fibrotic strategy. Here, we report that dihydroartemisinin (DHA) prevented the activation of HSCs via ferroptosis pathway. Importantly, DHA treatment increased the level of autophagy in HSCs. The inhibition of autophagy by 3-MA dramatically abolished the DHA-induced ferroptosis in HSCs. Mechanistically, the up-regulated m6A modification is essential for the activation of autophagy by DHA through the reduction of fat mass and obesity-associated gene (FTO). Down-regulation of m6A modification by FTO overexpression could impair autophagy and the classical ferroptotic events. Interestingly, the m6A modification of BECN1 mRNA was evidently up-regulated compared with other autophagy-related genes. More importantly, YTHDF1 was identified as a key m6A reader protein for BECN1 mRNA stability, and knockdown of YTHDF1 could prevent DHA-induced HSC ferroptosis. Noteworthy, YTH domain was essential for YTHDF1 to prolong the half-life of BECN1 mRNA in DHA-induced HSC ferroptosis. In mice, DHA treatment alleviated liver fibrosis by triggering HSC ferroptosis. HSC-specific inhibition of m6A modification and autophagy could impair DHA-induced HSC ferroptosis in murine liver fibrosis. Overall, these results provided novel implications to reveal the molecular mechanism of DHA-induced ferroptosis, by which pointed to m6A modification-dependent ferroptosis as a potential target for the treatment of liver fibrosis.

Propofol suppresses adipose-derived stem cell progression via PI3K/AKT-Wnt signaling pathway.

Adipose-derived stem cell (ADSC) transplantation has become a prospective way to treat cardiovascular diseases and skin traumas. Propofol, a short-acting intravenous anesthetic agent, plays an important role in the induction and maintenance of general anesthesia. In this study, we investigated the effects of propofol on ADSCs. The flow cytometry results showed that ADSCs were positive for CD29, CD44, and CD90 and negative for CD31, CD34, and CD45. The results of MTT and BrdU assays demonstrated that propofol impeded the proliferation of ADSCs. The cell scratch test showed that propofol had an inhibitory effect on the migration of ADSCs. Transwell assay showed that invasive ASDC counts decreased significantly after propofol treatment. Propofol also promoted ADSC apoptosis and arrested ADSCs in the G0/G1 phase. All these effects showed in a dose-dependent manner that the higher the concentration, the stronger the effect. Western blot analysis revealed decreased levels of FAK, PI3K, AKT, and GSK3ß phosphorylation, while the phosphorylation of ß-catenin increased after 48 h of treatment with propofol. The findings above indicated that the PI3K/AKT-Wnt pathways mediated propofol-inhibited ADSC proliferation, providing new insights into the propofol application in ADSCs.

[A new polyketide of endophytic fungi Aspergillus sp. ZJ-58 from Coptis chinensis].

A new polyketide, coptaspin A(1), along with two known compounds 4-acetyl-3,4-dihydro-6,8-dihydroxy-3-methoxy-5-methylisocoumarin(2), and cytochalasin Z_(12)(3), was isolated from the endophytic fungi Aspergillus sp. ZJ-58, which was isolated from the genuine medicinal plant Coptis chinensis in Chongqing after solid-state fermentation on rice and silica gel, MCI, and HPLC-based separation. Their structures were elucidated by MS, NMR, IR, UV, and ECD. The newly isolated compound 1 showed moderate inhibitory activities against LPS-induced NO production in RAW264.7 macrophages with the IC_(50) value of 58.7 µmol·L~(-1), suggesting its potential anti-inflammatory activity.