Effect of liposomal bupivacaine for preoperative erector spinae plane block on postoperative pain following video-assisted thoracoscopic lung surgery: a protocol for a multicenter, randomized, double-blind, clinical trial.

Background: There is still a controversy about the superiority of liposomal bupivacaine (LB) over traditional local anesthetics in postoperative analgesia after thoracic surgery. This study aims to determine the effect of LB versus bupivacaine hydrochloride (HCl) for preoperative ultrasound-guided erector spinae plane block (ESPB) on postoperative acute and chronic pain in patients undergoing video-assisted thoracoscopic lung surgery. Methods: This multicenter, randomized, double-blind, controlled trial will include 272 adult patients scheduled for elective video-assisted thoracoscopic lung surgery. Patients will be randomly assigned, 1:1 and stratified by site, to the liposomal bupivacaine (LB) group or the bupivacaine (BUPI) HCl group. All patients will receive ultrasound-guided ESPB with either LB or bupivacaine HCl before surgery and patient-controlled intravenous analgesia (PCIA) as rescue analgesia after surgery. The numeric rating scale (NRS) score will be assessed after surgery. The primary outcome is the area under the curve of pain scores at rest for 0-72 h postoperatively. The secondary outcomes include the total amount of opioid rescue analgesics through 0-72 h postoperatively, time to the first press on the PCIA device as rescue analgesia, the area under the curve of pain scores on activity for 0-72 h postoperatively, NRS scores at rest and on activity at different time points during the 0-72 h postoperative period, Quality of Recovery 15 scores at 72 h after surgery, and NRS scores on activity on postsurgical day 14 and postsurgical 3 months. Adverse events after the surgery are followed up to the postsurgical day 7, including postoperative nausea and vomiting, fever, constipation, dizziness, headache, insomnia, itching, prolonged chest tube leakage, new-onset atrial fibrillation, severe ventricular arrhythmia, deep venous thrombosis, pulmonary embolism, pulmonary atelectasis, cardiac arrest, ileus, urinary retention, chylothorax, pneumothorax, and organ failure. Analyzes will be performed first according to the intention to treat principle and second with the per-protocol analysis. Discussion: We hypothesize that LB for preoperative ultrasound-guided ESPB would be more effective than bupivacaine HCl in reducing postoperative pain in video-assisted thoracoscopic lung surgery. Our results will contribute to the optimization of postoperative analgesia regimens for patients undergoing video-assisted thoracoscopic lung surgery.Clinical trial registration:http://www.chictr.org.cn, identifier ChiCTR2300074852.

Region-specific delamination strength of ascending thoracic aortic aneurysm of elderly hypertensive patients with bicuspid and tricuspid aortic valves.

Both ageing and hypertension are clinical factors that may lead to a higher propensity for dissection or rupture of ascending thoracic aortic aneurysms (ATAAs). This study sought to investigate effect of valve morphology on regional delamination strength of ATAAs in the elderly hypertensive patients. Whole fresh ATAA samples were harvested from 23 hypertensive patients (age, 71 ± 8 years) who underwent elective aortic surgery. Peeling tests were performed to measure region-specific delamination strengths of the ATAAs, which were compared between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The regional delamination strengths of the ATAAs were further correlated with patient ages and aortic diameters for BAV and TAV groups. In the anterior and right lateral regions, the longitudinal delamination strengths of the ATAAs were statistically significantly higher for BAV patients than TAV patients (33 ± 7 vs. 23 ± 8 mN/mm, p = 0.01; 30 ± 7 vs. 19 ± 9 mN/mm, p = 0.02). For both BAV and TAV patients, the left lateral region exhibited significantly higher delamination strengths in both directions than the right lateral region. Histology revealed that disruption of elastic fibers in the right lateral region of the ATAAs was more severe for the TAV patients than the BAV patients. A strong inverse correlation between longitudinal delamination strength and age was identified in the right lateral region of the ATAAs of the TAV patients. Results suggest that TAV-ATAAs are more vulnerable to aortic dissection than BAV-ATAAs for the elderly hypertensive patients. Regardless of valve morphotypes, the right lateral region may be a special quadrant which is more likely to initiate dissection when compared with other regions.

Organ-level distribution tandem mass spectrometry analysis of three structural types of brassinosteroids in rapeseed.

Background: Brassinosteroids (BRs) are a class of naturally occurring steroidal phytohormones mediating a wide range of pivotal developmental and physiological functions throughout the plant's life cycle. Therefore, it is of great significance to determine the content and the distribution of BRs in plants.Regretfully, although a large number of quantitative methods for BRs by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have been reported, the in planta distribution of BRs is still unclear because of their lower contents in plant tissues and the lack of effective ionizable groups in their chemical structures. Methods: We stablished a novel analytical method of BRs based on C18 cartridge solid-phase extraction (SPE) purification, 4-(dimethylamino)-phenylboronic acid (DMAPBA) derivatization, and online valve-switching system coupled with ultra-high performance liquid chromatography-electro spray ionization-triple quadrupole mass spectrometry (UHPLC-ESI-MS/MS). This method has been used to quantify three structural types of BRs (epibrassinolide, epicastasterone, and 6-deoxo-24-epicastaster one) in different organs of Brassica napus L. (rapeseed). Results: We obtained the contents of three structural types of BRs in various organ tissues of rapeseed. The contents of three BRs in rapeseed flowers were the highest, followed by tender pods. The levels of three BRs all decreased during the maturation of the organs. We outlined the spatial distribution maps of three BRs in rapeseed based on these results, so as to understand the spatial distribution of BRs at the visual level. Conclusions: Our results provided useful information for the precise in situ localization of BRs in plants and the metabolomic research of BRs in future work. The in planta spatial distribution of BRs at the visual level has been studied for the first time.

Targeting inhibition of TCTP could inhibit proliferation and induce apoptosis in AML cells.

Translationally controlled tumor protein (TCTP) is a highly conserved multifunctional protein, which participates in many important physiological processes. Recently, the roles of TCTP in cell proliferation and apoptosis, especially its close relationship with various tumors, have attracted widespread attention. In this study, we found that the protein level of TCTP was significantly reduced in acute promyelocytic leukemia cell line NB4 transfected with retinoic acid-induced gene G (RIG-G). The RIG-G was found in our previous work as a key mediator of anti-proliferative activity in retinoid/interferon-related pathways. Here, we tried to further explore the function of TCTP in the development of acute myeloid leukemia (AML) from different levels. Our results showed that inhibiting TCTP expression could attenuate AML cells proliferation and induce apoptosis both in AML cell lines and in xenograft of NOD-SCID mice. In addition, either compared with patients in complete remission or non-leukemia patients, we detected that the expression of TCTP was generally high in the fresh bone marrow of AML patients, suggesting that there was a certain correlation between TCTP and AML disease progression. Taken together, our study revealed the role of TCTP in AML development, and provided a potential target for AML treatment.

Barnyard Grass Stress Triggers Changes in Root Traits and Phytohormone Levels in Allelopathic and Non-Allelopathic Rice.

Despite the growing knowledge concerning allelopathic interference with barnyard grass, little is understood regarding the competitive physiological mechanisms of the interaction between allelopathic rice and herbicide-resistant barnyard grass. A hydroponic system was employed to investigate the root morphological traits and different phytohormonal changes in allelopathic and non-allelopathic rice cultivars when co-planted with quinclorac-resistant and -susceptible barnyard grass, respectively. The results show that shoot and root biomass were greater in PI. Barnyard grass stress induced an increase in shoot and root biomass in PI at 7 and 14 days of co-culturing rice and barnyard grass. Especially under the stress of quinclorac-resistant barnyard grass, the shoot biomass of PI increased by 23% and 68%, respectively, and the root biomass increased by 37% and 34%, respectively. In terms of root morphology, PI exhibited a significantly higher fine-root length, in root diameters of <0.5 mm, a greater number of root tips, and longer root tips compared to LE. The response to quinclorac-resistant barnyard grass stress was consistent in terms of the SA and JA content. The obvious accumulation of SA and JA was observed in two rice cultivars under quinclorac-resistant barnyard grass stress, with greater amounts of SA and JA in PI. The significant decrease in auxin (IAA) and abscisic acid (ABA) content in rice was detected from 7 to 14 days under co-culture stress. Additionally, highly significant and positive correlations were found between SA and JA content, and the number of root tips and root tip length at root diameters of 0-0.5 mm in rice.

Neuroinflammation-induced parvalbumin interneuron and oscillation deficits might contribute to neurobehavioral abnormities in a two-hit model of depression.

Depression is a common neuropsychiatric disorder that causes profound disability worldwide, yet the underlying mechanism remains unclear. Thus, the present study aimed to evaluate the effects of a two-hit model of depression on glial activation, parvalbumin (PV) interneuron, oscillation activity, and behavior alternations, and whether chronic fluoxetine treatment can reverse these abnormalities. Male mice were submitted to lipopolysaccharide (LPS) injection, followed by a modified chronic unpredictable stress (CUS) protocol. In our study, we showed that mice exposed to LPS and CUS exhibited reduced body weight, anhedonic-like behavior as well as cognitive and anxiety symptoms. These behavioral alternations were related to enhanced neuroinflammation, as reflected by significantly increased IL-1ß and IL-6 levels and microglia activation in the prefrontal cortex (PFC). In addition, mice exposed to LPS and CUS displayed significantly decreased PV expression and disturbance of theta and gamma oscillations in the PFC. However, chronic fluoxetine treatment reversed most of these abnormalities. In conclusion, our study suggests that neuroinflammation-induced PV interneuron and oscillation deficits might contribute to neurobehavioral abnormalities in a two-hit model of depression.

Complement C1q drives microglia-dependent synaptic loss and cognitive impairments in a mouse model of lipopolysaccharide-induced neuroinflammation.

Activated microglia and subsequent release of pro-inflammatory cytokines result in neuroinflammatory status which further damage neurological function including cognitive impairments in various neurological conditions. However, the underlying molecular mechanisms during these pathological processing remain unknown. In the current study, mice received intraperitoneal administrations of LPS (0.5 mg/kg, daily, Escherichia coli O55:B5) for seven consecutive days and their different cohorts were used for behavioral assessment with open field, Y maze, and novel object recognition test or for electrophysiology recordings of mEPSC, LFP or LTP in in vivo or ex vivo preparation. The hippocampus from some cohorts were harvested for immunostaining or Western blotting of c1q, Iba-1, CD68, PSD95 and dendritic spine density or for transcriptome and proteomics analysis. Repeated LPS injections induced an up-regulation of complement system protein c1q and distinct microglial phenotype with an enrichment of the complement-phagosome pathway. Microglial synaptic engulfment and profound synaptic loss were found. These pathological changes were accompanied with the significantly decreased excitatory synaptic transmission, disturbed theta oscillations, impaired hippocampal long-term potentiation, and cognitive impairments. Notably, neutralization of c1q signaling robustly prevented these changes. Collectively, our data provide evidence that activated microglia and complement cascade c1q signaling in the hippocampus may account for synaptic loss and cognitive impairments in a mouse model of neuroinflammation induced by repeated LPS injections. Our work implicates that complement system may be a therapeutic target for developing therapies to prevent or treat cognitive disorders related to neuroinflammation or other disease conditions including neurodegenerative disease per se.

Effect of hypertension on the delamination and tensile strength of ascending thoracic aortic aneurysm with a focus on right lateral region.

Hypertension is a major predisposing factor to initiate thoracic aortopathy. The objective of this study is to investigate effect of hypertension on delamination and tensile strength of ascending thoracic aortic aneurysms (ATAAs). A total of 35 fresh ATAA samples were harvested from 19 hypertensive and 16 non-hypertensive patients during elective aortic surgery. Peeling tests with two extension rates were performed to determine delamination strength, while uniaxial tensile (UT) tests were employed to measure failure stresses. The delamination strength and failure stresses of the ATAAs were further correlated with patient ages for hypertensive and non-hypertensive groups. The delamination strength to peel apart the ATAA tissue along the longitudinal direction was statistically significantly lower for the hypertensive patients than that of the non-hypertensive patients (35 ± 11 vs. 49 ± 9 mN/mm, p = 0.02). A higher delamination strength was measured if peeling was performed with a higher extension rate. The circumferential failure stresses were significantly lower for the hypertensive ATAAs than those of the non-hypertensive ATAAs (1.03 ± 0.27 vs. 1.43 ± 0.38 MPa, p = 0.02). Histology showed that laminar structures of elastic fibers were mainly disrupted in the hypertensive ATAAs. The longitudinal delamination strength of the ATAAs was significantly decreased and strongly correlated with ages for the hypertensive patients. Strong inverse correlations were also identified between the circumferential and longitudinal failure stresses of the ATAAs and ages for the hypertensive patients. Results suggest that the ATAAs of the elderly hypertensive patients may have a higher propensity for dissection or rupture. The dissection properties of the ATAA tissue are rate dependent.

Metabolic profiles in the xylem sap of Brassica juncea exposed to cadmium.

Metabolic profiles in xylem sap are considered a fundamental mechanism for Cadmium (Cd) detoxification in plants. However, the metabolic mechanism of Brassica juncea xylem sap in response to Cd is still unclear. Here, we investigated the effects on the metabolomics of B. juncea xylem sap treated with Cd at different times by utilizing a nontargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics method for further elucidating the response mechanism of Cd exposure. The findings indicated that 48 h and 7 days Cd exposure caused significant differences in metabolic profiles of the B. juncea xylem sap. Those differential metabolites are primarily involved in amino acids, organic acids, lipids, and carbohydrates, and most of them were downregulated, which played essential roles in response to Cd stress. Furthermore, B. juncea xylem sap resisted 48-h Cd exposure via regulation of glycerophospholipid metabolism, carbon metabolism, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism, linoleic acid metabolism, C5-branched dibasic acid metabolism, alpha-linolenic acid metabolism, cyanoamino acid metabolism, ABC transporters, biosynthesis of amino acids, and pyrimidine metabolism; whereas alpha-linolenic acid metabolism, glycerophospholipid metabolism, photosynthesis, and oxidative phosphorylation were regulated for resisting 7-day Cd exposure.

Ultramicro Interdigitated Array Electrode Chip with Optimized Construction for Detection of Ammonia Nitrogen in Water.

Ammonia nitrogen is a common contaminant in water and its determination is important for environmental protection. In this paper, an electrochemical sensor based on an ultramicro interdigitated array electrode (UIAE) chip with optimized construction was fabricated with Micro-Electro-Mechanical System (MEMS) technology and developed to realize the detection of ammonia nitrogen in water. The effects of spacing-to-width ratio and width of the working electrode on UIAE's electrochemical characteristics and its ammonia nitrogen detection performance were studied by finite element simulation and experiment. The results demonstrated that the smaller the spacing-to-width ratio, the stronger generation-collection effect, and the smaller the electrode width, the stronger the edge effect, which led to an easier steady-state reach, a higher response current, and better ammonia nitrogen determination performance. The fabricated UIAE chip with optimized construction showed the linear detection range of 0.15 mg/L~2.0 mg/L (calculated as N), the sensitivity of 0.4181 µA·L·mg-1, and good anti-interference performance, as well as a long lifetime. UIAE based on bare Pt was successfully applied to ammonia nitrogen detection in water by optimizing structure, which might broaden the methods of ammonia nitrogen detection in water.

The effects of ankle dorsiflexor fatigue on lower limb biomechanics during badminton forward forehand and backhand lunge.

Background: Local muscle fatigue may have an adverse effect on the biomechanics of the lunge movement and athletic performance. This study analyzed the biomechanical indicators of the forward lunge in badminton players before and after fatigue of the ankle dorsiflexors. Methods: Using the isometric muscular strength testing system, 15 badminton players underwent an ankle dorsiflexor fatigue test. Before and after the fatigue experiment, five lunges were done in both the forehand forward (FH) and backhand forward (BH) directions, five in each direction. A Vicon motion capture system and an AMTI force measuring station were used to record lower limb kinematic and ground reaction force (GRF). Pre-fatigue and post-fatigue variability were determined using paired-samples t-tests, Wilcoxon signed rank test, and Statistical Non-parametric Mapping (SNPM). Result: The results showed that after fatigue, the peak angle of ankle dorsiflexion was significantly reduced (p = 0.034), the range of motion (ROM) of the ankle sagittal plane (p = 0.000) and peak angle of ankle plantarflexion (p = 0.001) was significantly increased after forehand landing. After fatigue, ankle inversion was significantly increased after forehand and backhand landings (FH: p = 0.033; BH: p = 0.015). After fatigue, peak knee flexion angles increased significantly (FH: Max: p = 0.000, Min: p = 0.000; BH: Max: p = 0.017, Min: p = 0.037) during forehand and backhand landings and ROM in knee flexion and extension increased (p = 0.009) during forehand landings. Knee inversion range of motion was significantly increased after fatigue (p = 0.024) during forehand landings. Peak hip flexion angle (p = 0.000) and range of motion (p = 0.000) were significantly reduced in forehand landings after fatigue. The mean loading rate (p = 0.005) and the maximum loading rate (p = 0.001) increased significantly during backhand landings after fatigue. Post-fatigue, the center of pressure (COP) frontal offset increased significantly (FH: p = 0.000; BH: p = 0.000) in the forehand and backhand landings. Conclusion: These results indicate that when the ankle dorsiflexors are fatigued, the performance of the forehand is significantly negatively affected, and the impact force of the backhand is greater.

Insight of BaCe0.5Fe0.5O3- δ twin perovskite oxide composite for solid oxide electrochemical cells.

One-pot synthesized twin perovskite oxide composite of BaCe0.5Fe0.5O3- δ (BCF), comprising cubic and orthorhombic perovskite phases, shows triple-conducting properties for promising solid oxide electrochemical cells. Phase composition evolution of BCF under various conditions was systematically investigated, revealing that the cubic perovskite phase could be fully/partially reduced into the orthorhombic phase under certain conditions. The reduction happened between the two phases at the interface, leading to the microstructure change. As a result, the corresponding apparent conducting properties also changed due to the difference between predominant conduction properties for each phase. Based on the revealed phase composition, microstructure, and electrochemical properties changes, a deep understanding of BCF's application in different conditions (oxidizing atmospheres, reducing/oxidizing gradients, cathodic conditions, and anodic conditions) was achieved. Triple-conducting property (H+/O2-/e-), fast open-circuit voltage response (∼16-∼470 mV) for gradients change, and improved single-cell performance (∼31% lower polarization resistance at 600°C) were comprehensively demonstrated. Besides, the performance was analyzed under anodic conditions, which showed that the microstructure and phase change significantly affected the anodic behavior.

Roles of very long-chain fatty acids in compound leaf patterning in Medicago truncatula.

Plant cuticles are composed of hydrophobic cuticular waxes and cutin. Very long-chain fatty acids (VLCFAs) are components of epidermal waxes and the plasma membrane and are involved in organ morphogenesis. By screening a barrelclover (Medicago truncatula) mutant population tagged by the transposable element of tobacco (Nicotiana tabacum) cell type1 (Tnt1), we identified two types of mutants with unopened flower phenotypes, named unopened flower1 (uof1) and uof2. Both UOF1 and UOF2 encode enzymes that are involved in the biosynthesis of VLCFAs and cuticular wax. Comparative analysis of the mutants indicated that the mutation in UOF1, but not UOF2, leads to the increased number of leaflets in M. truncatula. UOF1 was specifically expressed in the outermost cell layer (L1) of the shoot apical meristem (SAM) and leaf primordia. The uof1 mutants displayed defects in VLCFA-mediated plasma membrane integrity, resulting in the disordered localization of the PIN-FORMED1 (PIN1) ortholog SMOOTH LEAF MARGIN1 (SLM1) in M. truncatula. Our work demonstrates that the UOF1-mediated biosynthesis of VLCFAs in L1 is critical for compound leaf patterning, which is associated with the polarization of the auxin efflux carrier in M. truncatula.

Integrated Proteomic and Phosphoproteomic Analysis of the Hippocampus in a Mouse Model of Early Life Inflammation.

INTRODUCTION: Inflammation in early life is a risk factor for the development of neuropsychiatric diseases later in adolescence and adulthood, yet the underlying mechanism remains elusive. In the present study, we performed an integrated proteomic and phosphoproteomic analysis of the hippocampus to identify potential molecular mechanisms of early life inflammation-induced cognitive impairment. METHODS: Both female and male mice received a single intraperitoneal injection of 100 µg/kg lipopolysaccharide (LPS) on postnatal day 10 (P10). Behavioral tests, including open field, elevated plus-maze, and Y-maze tests, were performed on P39, P40, and P41, respectively. After behavioral tests, male mice were sacrificed. The whole brain tissues and the hippocampi were harvested on P42 for proteomic, phosphoproteomic, Western blot, and Golgi staining. RESULTS: Early life LPS exposure induced cognitive impairment in male mice but not in female mice, as assessed by the Y-maze test. Therefore, following biochemical tests were conducted on male mice. By proteomic analysis, 13 proteins in LPS group exhibited differential expression. Among these, 9 proteins were upregulated and 4 proteins were downregulated. For phosphoproteomic analysis, a total of 518 phosphopeptides were identified, of which 316 phosphopeptides were upregulated and 202 phosphopeptides were downregulated in the LPS group compared with the control group. Furthermore, KEGG analysis indicated that early life LPS exposure affected the glutamatergic synapse and neuroactive ligand-receptor interaction, which were associated with synaptic function and energy metabolism. Increased level of brain protein i3 (Bri3), decreased levels of PSD-95 and mGLUR5, and dendritic spine loss after early life LPS exposure further confirmed the findings of proteomic and phosphoproteomic analysis. CONCLUSIONS: Our findings demonstrated that neuroinflammation and impaired synapse may be involved in early life inflammation-induced cognitive impairment. Future studies are required to confirm our preliminary results.

Application of Edge Computing in Structural Health Monitoring of Simply Supported PCI Girder Bridges.

This study proposes an innovative method for structural health monitoring of simply supported PCI girder bridges based on dynamic strain and edge computing. Field static and dynamic load tests were conducted on a bridge consisting of a span with newly replaced PCI girders and numerous spans with old PCI girders. Both the static and dynamic test results showed that the flexural rigidity of the old PCI girders decreased significantly due to deterioration. To improve the efficiency of on-site monitoring data transmission and data analysis, this study developed a smart dynamic strain gauge node with the function of edge computing. Continuous data with a sampling frequency of 100 Hz were computed at the sensor node. Among the computed results, only the maximum dynamic strain data caused by the passage of the heaviest vehicle within 1 min were transmitted. The on-site monitoring results indicated that under routine traffic conditions, the dynamic strain response of the new PCI girder was smaller than that of the deteriorated PCI girder. When the monitored dynamic strain response has a tendency to magnify, attention should be paid to the potential prestress loss or other deterioration behaviors of the bridge.

Toward Superb Perovskite Oxide Electrocatalysts: Engineering of Coupled Nanocomposites.

A significant issue that bedeviled the commercialization of renewable energy technologies, ranging from low-temperature water electrolyzers to high-temperature solid oxide cells, is the lack of high-performance catalysts. Among various candidates that could tackle such a challenge, perovskite oxides are rising-star materials because of their unique structural and compositional flexibility. However, single-phase perovskite oxides are challenging to satisfy all the requirements of electrocatalysts concurrently for practical applications, such as high catalytic activity, excellent stability, good ionic and electronic conductivities, and superior chemical/thermo-mechanical robustness. Impressively, perovskite oxides with coupled nanocomposites are emerging as a novel form offering multifunctionality due to their intrinsic features, including infinite interfaces with solid interaction, tunable compositions, flexible configurations, and maximum synergistic effects between assorted components. Considering this new configuration has attracted great attention owing to its promising performances in various energy-related applications, this review timely summarizes the leading-edge development of perovskite oxide-based coupled nanocomposites. Their state-of-art synthetic strategies are surveyed and highlighted, their unique structural advantages are highlighted and illustrated through the typical oxygen reduction reaction and oxygen evolution reactions in both high and low-temperature applications. Opinions on the current critical scientific issues and opportunities in this burgeoning research field are all provided.

Higher serum PGE2 is a predicative biomarker for postoperative delirium following elective orthopedic surgery in elderly patients.

BACKGROUND: Postoperative delirium (POD), one of the most common complications following major surgery, imposes a heavy burden on patients and society. The objective of this exploratory study was to conduct a secondary analysis to identify whether there exist novel and reliable serum biomarkers for the prediction of POD. METHODS: A total of 131 adult patients (≥ 65 years) undergoing lower extremity orthopedic surgery with were enrolled in this study. Cognitive function was assessed preoperatively with Mini-Mental State Examination (MMSE). Delirium was diagnosed according to the Confusion Assessment Method (CAM) criteria on preoperative day and postoperative days 1-3. The preoperative serum levels of a panel of 16 biochemical parameters were measured by ELISA. RESULTS: Thirty-five patients developed POD, with an incidence of 26.7%. Patients in POD group were older (P = 0.001) and had lower preoperative MMSE scores (P = 0.001). Preoperative serum levels of prostaglandin E2 (PGE2, P < 0.001), S100ß (P < 0.001), glial fibrillary acidic protein (P < 0.001) and neurofilament light (P = 0.002) in POD group were significantly increased. Logistic regression analysis showed that advanced age (OR = 1.144, 95%CI: 1.008 ~ 1.298, P = 0.037), higher serum neurofilament light (OR = 1.003, 95%CI: 1.000 ~ 1.005, P = 0.036) and PGE2 (OR = 1.031, 95%CI: 1.018 ~ 1.044, P < 0.001) levels were associated with the development of POD. In addition, serum level of PGE2 yielded an area under the ROC curve (AUC) of 0.897 to predict POD (P < 0.001), with a sensitivity of 80% and a specificity of 83.3%. CONCLUSIONS: Our study showed that higher preoperative serum PGE2 level might be a biomarker to predict the occurrence of POD in elderly patients undergoing elective orthopedic surgery. TRIAL REGISTRATION: NCT03792373 www. CLINICALTRIALS: gov .

IL-17A drives cognitive aging probably via inducing neuroinflammation and theta oscillation disruption in the hippocampus.

Cognitive aging is a major risk factor for neurodegenerative diseases and has a great impact on the living quality of older individuals. However, the precise mechanisms underlying cognitive aging remain elusive. Accumulating evidence has demonstrated that interleukin 17A (IL-17A) is responsible for cognitive decline in the process of various neurological diseases. Thus, we conducted this study aiming to investigate the role of IL-17A in cognitive aging. In the present study, 31 aging (65-85 years) and 25 young (18-35 years) patients scheduled for elective removal of internal fixation surgery with spinal anesthesia were included for measurements of preoperative cognitive function, serum and cerebrospinal fluid (CSF) levels of IL-17A. For animal study, RNAseq and Kyoto Encyclopedia of Genes and Genomes pathways were used to identify differentially expressed genes between young and aging mice. For the treatment groups, young (2-3 months) and aging (16-18 months) mice received intraperitoneally with IL-17A and anti-IL-17A antibody, respectively. Twenty-four hours later, neurocognitive behavioral tests were conducted. Our results suggested that differentially expressed genes between young and aging mice were mainly enriched in IL-17 pathways. Serum and CSF levels of IL-17A increased significantly in aging patients and were negatively correlated with mini-mental state examination scores. Both young mice receiving IL-17A and aging mice showed impaired memory, increased blood-brain barrier permeability, overactivated microglia and increased inflammatory mediators in the hippocampus. Additionally, aging mice showed a significantly decreased θ power in the task-related neural oscillations. Notably, intraperitoneal injection of anti-IL-17A antibody alleviated increased blood-brain barrier permeability, microglial activation, neuroinflammation, θ oscillation disruption and cognitive decline of aging mice. In conclusion, our study demonstrated that IL-17A may be an initiating factor of cognitive aging.

Increased Resting-State Functional Connectivity of the Hippocampus in Rats With Sepsis-Associated Encephalopathy.

Background: Sepsis-associated encephalopathy (SAE) has been identified as a frequent complication of sepsis, featured by an aberrant level of cognitive and affective functions. The present study is designed to explore the changes in functional connectivity (FC) of the hippocampus in rats with SAE utilizing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Sprague-Dawley rats were randomly assigned to the SAE and control groups. We acquired rs-fMRI data using a 7T MRI to evaluate hippocampal network functional differences between the two groups with a seed-based approach. Behavioral performance was assessed using the open field test and forced swimming test. Statistical analysis was undertaken to evaluate the correlation between the hippocampal FC and behavioral findings. Results: Compared with the control group, the SAE group showed increased FC between the bilateral hippocampus and thalamus, septum, bed nuclei stria terminalis (BNST), left primary forelimb somatosensory cortex (S1FL), primary motor cortex (M1), and inferior colliculus. Increased FC between the left hippocampus and thalamus, septum, BNST, left S1FL, and inferior colliculus was observed. While with the right hippocampus, FC in thalamus, septum, left S1FL and inferior colliculus was enhanced. Additionally, positive correlations were found between the hippocampal FC and the immobility time in the forced swimming test. Conclusion: Hippocampus-related brain networks have significant alterations in rats with SAE, and the elevated hippocampal resting-state FC was positively related to affective deficits. Changes in FC between the hippocampus and other brain regions could be a potential neuroimaging biomarker of cognitive or mental disorders triggered by SAE.