L-Shaped Association of Serum Chloride Level With All-Cause and Cause-Specific Mortality in American Adults: Population-Based Prospective Cohort Study.

BACKGROUND: Chloride is the most abundant anion in the human extracellular fluid and plays a crucial role in maintaining homeostasis. Previous studies have demonstrated that hypochloremia can act as an independent risk factor for adverse outcomes in various clinical settings. However, the association of variances of serum chloride with long-term mortality risk in general populations has been rarely investigated. OBJECTIVE: This study aims to assess the association of serum chloride with all-cause and cause-specific mortality in the general American adult population. METHODS: Data were collected from 10 survey cycles (1999-2018) of the National Health and Nutrition Examination Survey. All-cause mortality, cardiovascular disease (CVD) mortality, cancer mortality, and respiratory disease mortality data were obtained by linkage to the National Death Index through December 31, 2019. After adjusting for demographic factors and relevant lifestyle, laboratory items, and comorbid factors, weighted Cox proportional risk models were constructed to estimate hazard ratios and 95% CIs for all-cause and cause-specific mortality. RESULTS: A total of 51,060 adult participants were included, and during a median follow-up of 111 months, 7582 deaths were documented, 2388 of CVD, 1639 of cancer, and 567 of respiratory disease. The weighted Kaplan-Meier survival analyses showed consistent highest mortality risk in individuals with the lowest quartiles of serum chloride. The multivariate-adjusted hazard ratios from lowest to highest quartiles of serum chloride (≤101.2, 101.3-103.2, 103.2-105.0, and ≥105.1 mmol/L) were 1.00 (95% CI reference), 0.77 (95% CI 0.67-0.89), 0.72 (95% CI 0.63-0.82), and 0.77 (95% CI 0.65-0.90), respectively, for all-cause mortality (P for linear trend<.001); 1.00 (95% CI reference), 0.63 (95% CI 0.51-0.79), 0.56 (95% CI 0.43-0.73), and 0.67 (95% CI 0.50-0.89) for CVD mortality (P for linear trend=.004); 1.00 (95% CI reference), 0.67 (95% CI 0.54-0.84), 0.65 (95% CI 0.50-0.85), and 0.65 (95% CI 0.48-0.87) for cancer mortality (P for linear trend=.004); and 1.00 (95% CI reference), 0.68 (95% CI 0.41-1.13), 0.59 (95% CI 0.40-0.88), and 0.51 (95% CI 0.31-0.84) for respiratory disease mortality (P for linear trend=.004). The restricted cubic spline analyses revealed the nonlinear and L-shaped associations of serum chloride with all-cause and cause-specific mortality (all P for nonlinearity<.05), in which lower serum chloride was prominently associated with higher mortality risk. The associations of serum chloride with mortality risk were robust, and no significant additional interaction effect was detected for all-cause mortality and CVD mortality (P for interaction>.05). CONCLUSIONS: In American adults, decreased serum chloride concentrations were independently associated with increased all-cause mortality, CVD mortality, cancer mortality, and respiratory disease mortality. Our findings suggested that serum chloride may serve as a promising cost-effective health indicator in the general adult population. Further studies are warranted to explore the potential pathophysiological mechanisms underlying the association between serum chloride and mortality.

Burden of brain and other central nervous system cancer in China, 1990-2019: a systematic analysis of observational data from the global burden of disease study 2019.

OBJECTIVE: To evaluate the trends in disease burden and the epidemiological features of central nervous system (CNS) cancer in China from 1990 to 2019. DESIGN: A population-based observational study. SETTING: The incidence, prevalence, death and disability-adjusted life years (DALYs) due to CNS cancer in China, stratified by sex, age and provincial region, were collected from the Global Burden of Disease Study 2019. PARTICIPANTS: Data were publicly available and individuals were not involved. RESULTS: In 2019, the incident cases of CNS cancer in China were 347 992 (95% UI 262 084-388 896), and the age-standardised rate (ASR) of incidence was 5.69 (95% UI 4.36-6.78) per 100 000 person-years increased by 27.9% compared with that in 1990; meanwhile, CNS cancer caused 63 527 (95% UI 47 793-76 948) deaths in China in 2019, and the ASR of death was 3.5 (95% UI 2.62-4.21) per 100 000 person-years decreased by 9.6%. The ASRs of incidence and prevalence of CNS cancer in China increased more rapidly than the global average; meanwhile, the ASRs of DALYs owing to CNS cancer declined more rapidly. The burden of CNS cancer showed no significant differences between men and women, but was more pronounced in early childhood and old adulthood. The ASRs of incidence and prevalence were higher in high-income provinces, confirmed by the positive correlation with Sociodemographic Index (SDI), with correlation coefficient r of 0.322 and 0.767, respectively (both p<0.0001). However, the ASRs of death and DALYs demonstrated a negative correlation with SDI, with r of -|0.319 and -0.642, respectively (both p<0.0001). CONCLUSIONS: From a global perspective, China has been bearing a substantial burden of CNS cancer. More attention should be paid to children and elderly populations for CNS cancer. The disease burden varied significantly at the subnational level of China, which was associated with socioeconomic development.

The burden of aortic aneurysm in China from 1990 to 2019: findings from the Global Burden of Disease Study 2019.

BACKGROUND: Aortic aneurysm (AA) is a global public health concern. However, little is known about the disease burden of AA in China. METHODS: Following the general analytic strategy used in the Global Burden of Disease Study (GBD) 2019, we analyzed the mortality and years of life lost (YLLs) due to AA, stratified by sex, age, and province-level region in China from 1990 to 2019. The temporal trend of AA burden in China was analyzed and the main attributable risk factors for AA in China were also explored. RESULTS: In China, the total AA deaths were 17,038 (95% UI: 14,392-19,980) in 2019, an increase of 136.1% compared with that in 1990, with an age-standardized death rate (ASDR) of 0.93 (95% UI: 0.79-1.08) per 100,000 person-years in 2019, a decrease of 6.8%. Meanwhile AA caused 378,578 (95% UI: 315,980-450,479) YLLs in 2019, an increase of 102.6% compared with that in 1990, with a crude YLL rate of 26.6 (95% UI: 22.2-31.7) per 100,000 person-years, an increase of 68.6%. The AA mortality and YLLs were higher in males than in females. AA caused most YLLs in the 65- to 75-year-old age group. The AA mortality and YLLs varied significantly among provinces in China, and the change in ASDR showed a negative correlation with the sociodemographic index of different provinces, namely, more decline of ASDR in developed provinces. High systolic blood pressure was shown to be the most significant attributable risk factor for AA burden in both males and females, and smoking was another major attributable risk factor, especially in males. CONCLUSIONS: The disease burden of AA increased significantly from 1990 to 2019 in China, with higher mortality and YLLs in males, senior populations, and among residents of most western provinces in China. High systolic blood pressure and smoking were two major attributable risk factors for AA mortality in China.

Effect of Electroencephalography Spectral Edge Frequency (SEF) and Patient State Index (PSI)-Guided Propofol-Remifentanil Anesthesia on Delirium After Laparoscopic Surgery: The eMODIPOD Randomized Controlled Trial.

BACKGROUND: The effect of SedLine electroencephalography (EEG)-guided anesthetic care on postoperative delirium (POD) has not been studied. METHODS: This single-center randomized EEG Monitoring tO Decrease the Incidence of Post-Operative Delirium (eMODIPOD) trial involved 1560 patients aged 50 years or above undergoing laparoscopic surgery. Propofol-remifentanil anesthesia was guided either by SedLine (EEG-guided care, n=779) or not (usual care, n=781). The goal of EEG-guided care was to maintain spectral edge frequency between 10 and 15 and patient state index (PSI) between 25 and 50. The primary outcome was the incidence of POD on postoperative days 1 to 5. The secondary outcomes included emergence delirium, composite moderate-to-severe complications, length of hospital stay, intensive care unit admission, 30-day hospital readmission and all-cause mortality, and intraoperative awareness. RESULTS: Of the 1560 randomized patients, 1545 were included in the modified intention-to-treat analysis. The median propofol administered for anesthesia maintenance was 900 mg and 1000 mg in the EEG-guided and usual care groups, respectively (P=0.21). POD occurred in 1.0% (8/771) and 1.2% (9/774) of patients in the EEG-guided and usual care groups, respectively (risk ratio: 0.89; 95% confidence interval: 0.35-2.30). There were no between-group differences in all secondary outcome measures. Emergence delirium occurred in 11.8% (91/771) and 13.2% (102/774) of the EEG-guided care and usual care groups, respectively (risk ratio: 0.90; 95% confidence interval: 0.69-1.17; P=0.41). Three patients from each group reported intraoperative awareness. CONCLUSIONS: Compared with usual care, SedLine spectral edge frequency-guided and patient state index-guided propofol-remifentanil anesthetic care neither alters anesthetic delivery nor decreases the unexpected low incidence of POD in relatively young Chinese patients undergoing laparoscopic surgery.

Repeated Neonatal Isoflurane Exposure is Associated with Higher Susceptibility to Chronic Variable Stress-induced Behavioural and Neuro-inflammatory Alterations.

Numerous studies have reported that prolonged or multiple exposures to anaesthetics in early life lead to detrimental effects on brain function, most having focused on neurocognitive function, and relatively few on long term neuropsychiatric performance. The present study investigated the impact of repeated neonatal isoflurane exposure on chronic variable stress (CVS)-induced psychiatric and behavioural outcomes together with CVS-related neuronal activity and neuro-inflammatory reactivity in relevant brain circuits. In the present study, C57BL/6J mice received either three exposures to isoflurane at postnatal days 7, 8, and 9 or a control exposure. From postnatal day 45, mice were exposed to a mild, 3-week, CVS paradigm or none and the CVS-related neuropsychiatric performance was evaluated using a series of behavioural tests. The neuronal activity in relevant brain regions was measured by ΔFosB immunopositivity and CVS-related neuroinflammation was assessed by analysing levels of pro-inflammatory cytokines IL-1α, IL-1ß, IL-6, and TNF-α. In mice experiencing serial neonatal isoflurane exposure, we detected a significant enhancement in anxiety levels following CVS procedures, together with enhanced neuronal activity, and exacerbated neuroinflammation in the basolateral amygdaloid nuclei (BLA) and hippocampal dentate gyrus (DG) regions. No such change was found in control mice. These results indicate an association between early multiple isoflurane exposures in infant mice and susceptibility to a CVS-evoked anxious phenotype accompanied by enhanced neuronal activity in BLA and DG regions and high inflammatory reactivity in response to CVS.

Neonatal Lipopolysaccharide Challenge Induces Long-lasting Spatial Cognitive Impairment and Dysregulation of Hippocampal Histone Acetylation in Mice.

Neonatal inflammation induces long-term effects on brain function. We investigated the effects of systematic neonatal inflammation using lipopolysaccharide (LPS) injection at postnatal day 3 (P3) and P5 in a mouse model of spatial memory capacity measured using a Morris water maze (MWM) task in adulthood. Subsequently, we assessed histone acetylation and immediate-early response gene expression (c-Fos and brain-derived neurotrophic factor) in the hippocampus in response to MWM acquisition training. The LPS-treated mice exhibited a significant spatial cognitive impairment, which was accompanied by insufficient histone acetylation of the H4K12-specific lysine residue and repressed c-Fos gene expression immediately after acquisition training. Moreover, the enrichment of acetyl-H4K12 on the c-Fos promoter following acquisition training was decreased in LPS-treated mice. Administration of trichostatin A (TSA), a histone deacetylase inhibitor, 2 h before each MWM acquisition training session effectively enhanced hippocampal histone acetylation levels and enrichment of acetyl-H4K12 on the c-Fos promoter following acquisition training in LPS-treated mice. TSA also increased c-Fos gene expression underlying synaptic plasticity and memory formation, and consequently rescued impaired spatial cognitive function. These results indicate that the dysregulation of H4K12 acetylation during the ongoing process of memory formation plays a key role in the spatial cognitive impairment associated with a neonatal LPS challenge. The histone deacetylase inhibitor TSA exhibits therapeutic potential for treating cognitive impairment induced by neonatal inflammation, by means of improving hippocampal histone acetylation and downstream c-Fos gene expression in response to a learning task.

Sevoflurane inhibits cardiac function in pulmonary fibrosis mice through the TLR4 signaling pathway.

Pulmonary fibrosis is often concomitant with myocardial injury. We studied sevoflurane's effects on cardiac function and the expression of the TLR4/inducible nitric oxide synthase (iNOS) signaling pathway on a pulmonary fibrosis model. C57BL/6J wild-type (WT) and TLR4-deficient (TLR4-/-) mice were randomly divided into a control group and a pulmonary fibrosis group. The model of pulmonary fibrosis was induced by treatment with paraquat (PQ; 20 mg/kg). Four weeks after PQ administration, mice were tested for body weight changes, and histopathology and hydroxyproline in lung. Left ventricular function in each group of mice was measured by echocardiogram before and after sevoflurane inhalation. The expression of TLR4 and iNOS protein were analyzed. Pulmonary fibrosis mice were fed lenalidomide (50 mg/kg/day) for three days and cardiac function was assessed before and after sevoflurane inhalation. WT pulmonary fibrosis mice showed pathological damage and excessive deposition of collagen in the lung and heart. Left ventricular function decreased after four weeks of PQ exposure. TLR4-/- mice were resistant to pulmonary fibrosis like pathological damage and the effect of sevoflurane on heart rate and ejection fraction than that of WT mice. TLR4 and iNOS expression in WT pulmonary fibrosis mice increased significantly after sevoflurane inhalation. Lenalidomide treatment alleviated the effect of sevoflurane on heart rate and ejection fraction in WT pulmonary fibrosis mice. Sevoflurane inhibits cardiac function in pulmonary fibrosis mice through the TLR4/iNOS pathway. Lenalidomide attenuated the sevoflurane's effect on the cardiac function of mice with pulmonary fibrosis.

[Influential factors of cerebral oxygen saturation in pediatric cardiovascular surgery].

OBJECTIVE: To determine the intervention measures for the decrease of cerebral tissue oxygen saturation during anesthesia for the congenital heart disease in children.
 Methods: Twenty-eight children with cardiac surgery were enrolled. Anesthesia was deepened with propofol (3 mg/kg) intravenous injection. The data of cerebral tissue oxygen saturation(SctO2), mean arterial pressure (MAP), HR, bispectral index (BIS), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), hemoglobin (Hb) and middle cerebral artery (MCA) mean flow velocity (Vm) at different points were collected after intravenous injection of propofol at 3 mg/kg. The changes of SctO2 and the influential factors were analyzed.
 Results: SctO2 decreased by 4.99% after deepen anesthesia, with 95% CI 4.33% to 5.65% (P>0.05). There was no significant differince in MAP, PaO2, PaCO2, and Hb between the time points after deepen anesthesia and the baseline (P>0.05). MCA Vm decreased obviously after deepen anesthesia for 1, 5, 10 min (P<0.05). The decrease in MAP, HR, PaCO2 and MCA Vm is positively correlated with the decrease in SctO2.
 Conclusion: The decrease of MAP, HR, PaCO2, and MCA Vm is the risk factor for SctO2. To avoid the decrease, it needs to maintain the stability of SctO2 and prevent neurological complications.

Enhanced recovery after surgery pathway for patients undergoing cardiac surgery: a randomized clinical trial.

OBJECTIVES: Enhanced recovery after surgery (ERAS) pathways have not been reported in cardiac surgery. The aim of this study was to evaluate the clinical effectiveness and safety profile of ERAS pathways compared with routine care for patients undergoing cardiac valvular surgery. METHODS: A randomized clinical trial was conducted between July 2015 and November 2016. A total of 226 patients who underwent elective valvular surgery were randomly assigned to the ERAS pathway or routine care (control) group. The ERAS protocol consisted of an evidence-based systematic optimization approach for managing perioperative patients. The control group received routine care. The primary end-point was readiness for hospital discharge. The secondary outcomes were duration of intensive care unit (ICU) stay, length of postoperative vasoactive drug support, duration of mechanical ventilation, time to first bowel movement, removal of surgical drain, overall medical costs and complication rate. RESULTS: Postoperative time to readiness for discharge was significantly shorter in the ERAS group (6.0 (2.0∼14.0) days) than the control group (7.0 (4.0∼16.0) days, P = 0.01), and the duration of ICU stay and duration of mechanical ventilation were significantly shorter in the ERAS group (20.9 (13.5∼69.3) h, 7.2 (0.0∼22.3) h, respectively) than the control group (22.0 (13.4∼212.3) h, P = 0.001; 8.8 (3.7∼44.9) h, respectively; P < 0.0001). The overall treatment cost of the ERAS group (69202 (52089∼123823) CNY) was significantly lower than that of the control group (77058 (51390∼144290) CNY, P = 0.002). CONCLUSIONS: ERAS pathways reduce the length of ICU and hospital stay, postoperative complications and cost for patients undergoing cardiac surgery. Clinical trial registration: ClinicalTrials.gov: NCT02479581.

C-Type Natriuretic Peptide Ameliorates Lipopolysaccharide-Induced Cardiac Dysfunction in Rats with Pulmonary Arterial Hypertension.

Lipopolysaccharide induces rapid deterioration of cardiac function in rats with pulmonary arterial hypertension. It was desired to investigate if this cardiac dysfunction could be treated by C-type natriuretic peptide. Rat pulmonary arterial hypertension was induced by intraperitoneal injection of monocrotaline. Hemodynamics and cardiac function were measured by pressure-volume (P-V) catheter before and after the rats were treated with lipopolysaccharide and C-type natriuretic peptide. Cyclic guanosine 3',5'-monophosphate (cGMP) level was determined by enzyme-linked immunosorbent assay analysis. After the rats were injected with low-dose lipopolysaccharide, they experienced left ventricle systolic function deterioration. Administration of C-type natriuretic peptide improved hemodynamics and left ventricle systolic function. cGMP level was elevated after C-type natriuretic peptide treatment. C-type natriuretic peptide could ameliorate lipopolysaccharide-induced cardiac dysfunction and restore hemodynamic deterioration in rats with pulmonary arterial hypertension.

Lipopolysaccharide acutely suppresses right-ventricular strain in rats with pulmonary artery hypertension.

Worsening right ventricular (RV) dysfunction in the presence of pulmonary artery hypertension (PAH) increases morbidity and mortality in this patient population. Transthoracic echocardiography (TTE) is a non-invasive modality to evaluate RV function over time. Using a monocrotaline-induced PAH rat model, we evaluated the effect of acute inflammation on RV function. In this study, both PAH and control rats were injected with Escherichia coli lipopolysaccharide (LPS) to induce an acute inflammatory state. We evaluated survival curves, TTE parameters, and inflammatory markers to better understand the mechanism and impact of acute inflammation on RV function in the presence of PAH. The survival curve of the PAH rats dropped sharply within 9 h after LPS treatment. Several echocardiographic parameters including left ventricular (LV) stroke volume, RV tricuspid annular plane systolic excursion, RV longitudinal peak systolic strain, and strain rate decreased significantly in PAH rats before LPS injection and 2 h after LPS injection. The expression of phospholamban (PLB) and tumor necrosis factor-α (TNF-α) significantly increased and the expression of SERCA2a significantly decreased in PAH rats after LPS administration. LPS suppressed the RV longitudinal peak systolic strain and strain rate and cardiac function deteriorated in PAH rats. These effects may be associated with the signal pathway activity of SERCA2a/PLB.