Ultrasound evaluation of gastric emptying of high-energy semifluid solid beverage in parturients during labor at term: a randomized controlled trial.

PURPOSE: What to intake during labor is controversial. The purpose of this study was to compare the gastric emptying of high-energy semifluid solid beverage (HESSB) versus that of carbohydrate (CHO) solution of equal calories and volume by evaluating the gastric antral cross-sectional area (CSA) using ultrasonography in parturients during labor at term. METHODS: The study was conducted at a maternity and infant hospital between June and October 2020. Forty parturients scheduled for epidural labor analgesia during labor at term were randomly assigned to receive HESSB (300 mL, n = 20) or CHO (300 mL, n = 20). Gastric antral CSA was measured at baseline and 5, 30, 60, 90, and 120 min after consumption of the drink. The primary outcome was gastric antral CSA at 120 min in the HESSB group and CHO group. RESULTS: The gastric antral CSA between the HESSB group and CHO group at 120 min was not statistically significant (2.73 cm2 ± 0.55 vs. 2.55 cm2 ± 0.72, P = 0.061). All patients returned to baseline at 120 min after intake of 300 mL isocaloric HESSB and CHO, confirmed by evaluation of gastric antral CSA. The visual analog scale score for satiety was higher in the HESSB group (P < 0.001), with better taste satisfaction (7[5-8] vs. 5[4-6], P < 0.001). CONCLUSION: The change of gastric antral cross-sectional area after HESSB is similar to the corresponding calories and volume of CHO and the gastric emptying of HESSB can be emptied within 2 h with better taste satisfaction and satiety in pregnant women under labor analgesia.

Spontaneous pneumothorax with pulmonary Langerhans cell histiocytosis (PLCH) in an adult heavy cigarette smoker-A case report.

Pulmonary Langerhans cell histiocytosis is a rare disease caused by the proliferation of CD1a-positive histiocyte-like cells infiltrating the lung's interstitial layer. Most cases affect young to middle-aged persons, especially adult heavy cigarette smokers. A 49-year-old male heavy smoker (40 pack-year), with non-productive cough, dyspnoea and desaturation, presented with a right-sided pneumothorax on chest x-ray with total atelectasis. Chest computed tomography (CT) revealed bilateral multiple thick-walled infiltrated cysts and multiple ground-glass nodules throughout the entire lung. Surgery with minimal invasive thoracoscopic lung biopsy and pleurodesis was performed. Pathology showed histiocyte-like cells aggregates in the pulmonary parenchyma. Immunohistochemical stain demonstrated CD1a(+), S100(+) and CD68(+). After 3 months of smoking cessation, clear improvement was evidenced with a chest CT showing bilateral multiple thin-walled rounded cysts and multiple ground-glass nodules that are smaller in size and decreased in numbers. Early minimal invasive thoracoscopic lung biopsy and pleurodesis can also be a choice if the development of secondary spontaneous pneumothorax occurs.

Accuro ultrasound-based system with computer-aided image interpretation compared to traditional palpation technique for neuraxial anesthesia placement in obese parturients undergoing cesarean delivery: a randomized controlled trial.

PURPOSE: Recently, a new handheld ultrasound-based device, called Accuro, has been commercialized with a real-time automated interpretation of lumbar ultrasound images. We hypothesized that the handheld ultrasound device would improve the efficacy and safety of combined spinal-epidural anesthesia (CSEA) for cesarean delivery in obese parturients. METHODS: Eighty parturients with a body mass index > 30 kg∙m-2 scheduled for elective cesarean delivery were randomly allocated equally (palpation group and ultrasound group). The primary outcome was the first insertion success rate. Secondary outcomes were the time taken to identify the needle puncture site, duration of CSEA procedure, the total time, the rate of parturients who require needle redirections, the number of skin punctures, changes in the intended interspace, and the incidence of complications. RESULTS: Compared to the palpation group, the first insertion success rate was significantly higher (72.5% vs. 40.0%; P = 0.003), and time taken to identify the needle puncture site was less (30 [26-36] vs. 39 [32-49] seconds; P = 0.001) in the ultrasound group. The rate of parturients who required needle redirections (40.0% vs. 72.5%; P = 0.003) and the incidence of paresthesia were both lower (7.5% vs. 45.0%; P < 0.001). The other outcomes had no significant difference between groups. The mean difference between the epidural depth measured by the handheld ultrasound and needle depth was - 0.29 cm [95% limit of agreement, - 0.52 to - 0.05]. CONCLUSIONS: Our study suggests using the Accuro ultrasound device can enhance the efficacy and safety of CSEA in obese parturients when executed by experienced anesthesiologists, and its automated estimation of epidural depth is accurate.

Acetylation of AMPA Receptors Regulates Receptor Trafficking and Rescues Memory Deficits in Alzheimer's Disease.

In Alzheimer's disease (AD), decreases in the amount and synaptic localization of AMPA receptors (AMPARs) result in weakened synaptic activity and dysfunction in synaptic plasticity, leading to impairments in cognitive functions. We have previously found that AMPARs are subject to lysine acetylation, resulting in higher AMPAR stability and protein accumulation. Here we report that AMPAR acetylation was significantly reduced in AD and neurons with Aß incubation. We identified p300 as the acetyltransferase responsible for AMPAR acetylation and found that enhancing GluA1 acetylation ameliorated Aß-induced reductions in total and cell-surface AMPARs. Importantly, expression of acetylation mimetic GluA1 (GluA1-4KQ) in APP/PS1 mice rescued impairments in synaptic plasticity and memory. These findings indicate that Aß-induced reduction in AMPAR acetylation and stability contributes to synaptopathy and memory deficiency in AD, suggesting that AMPAR acetylation may be an effective molecular target for AD therapeutics.

Revealing the synergistic mechanism of Shenfu Decoction for anti-heart failure through network pharmacology strategy.

The present study was designed to investigate the targets and synergistic mechanism of Shenfu Decoction (SFD) in the treatment of heart failure. A heart failure animal models was established to evaluate the pharmacological effects of SFD for anti-heart failure, then constructed ingredient-target interaction network by developing ingredient and target databases, the Discovery sdudio software was used for molecular docking. In addition, we validated the predicted protein targets of active ingredients in SFD by using surface plasmon resonance (SPR) technology. Our results demonstrated that SFD could enhance ejection fraction, alleviate myocardial histopathological characteristics, and reduce the level of angiotensin converting enzyme (ACE), aldosterone (ALD), atrial natriuretic polypeptide (ANP) and Renin (REN) in heart failure rat model. In addition, the ingredient database including 349 constituents and target database including 236 proteins were established, and 75 proteins were screened and identified by molecular docking strategy. 22 core target proteins were identified through network pharmacology, and the component-core target network was constructed. Finally, the affinity between the compounds and targets were verified by the SPR analysis method. The present study suggested that SFD may act on ACE 2, REN, ACE, ICAM-1, EGF, HTR2B, PARP1, NPPB and other proteins through AC, BAC, ACN, Re, Rg1, Rb1 to exert synergistic effects against heart failure.

Identification of a novel BACE1 inhibitor, timosaponin A-III, for treatment of Alzheimer's disease by a cell extraction and chemogenomics target knowledgebase-guided method.

BACKGROUND: Rhizoma Anemarrhenae (RA) has been conventionally used for treatment of Alzheimer's disease (AD) in Traditional Chinese Medicine, and thus, the active components from RA can be screened. PURPOSE: This research aimed to identify the active components of RA and their targets and further clarify the molecular mechanisms underlying its anti-AD activity. METHODS: First, the potential active compounds from RA were screened by neurocyte extraction and micro-dialysis methods. Second, the potential targets were predicted by a chemogenomics target knowledgebase and further explored by surface plasmon resonance and enzyme activity assays. Third, the pharmacological effects were evaluated by employing APP/PS1 transgenic mice and SH-SY5Y-APP cells. ELISAs and Western blot analyses were used to evaluate the expression of key molecules in the amyloidogenic and NMDAR/ERK pathways. RESULTS: Timosaponin A-III (TA-III) was screened and identified as a potential active component for the anti-AD activity, and BACE1 was proven to be a potential high-affinity target. Enzyme kinetic analysis showed that TA-III had strong noncompetitive inhibitory activity against BACE1. The in vitro and in vivo assays indicated that TA-III had pharmacological effects through improving memory impairment, reducing Aß aggregation via the amyloidogenic pathway and preventing neuronal impairment through downregulating the NMDAR/ERK signaling pathway. CONCLUSION: TA-III targets BACE1 to reduce Aß aggregation through down-regulating the NMDAR/ERK pathway for treating AD.

Optimum interval time of programmed intermittent epidural bolus of ropivacaine 0.08% with sufentanyl 0.3 µg/mL for labor analgesia: a biased-coin up-and-down sequential allocation trial.

BACKGROUND: The programmed intermittent epidural bolus (PIEB) technique is widely used in labor analgesia, but the parameter settings of PIEB have not yet been standardized. We designed a study to identify the optimal interval duration for PIEB using 10 mL of ropivacaine 0.08% and sufentanyl 0.3 µg/mL, a regimen commonly used to control labor pain in China, to provide effective analgesia in 90% of women during the first stage of labor without breakthrough pain. METHODS: We conducted a double-blind sequential allocation trial to obtain the effective interval 90% (EI90%) during the first stage of labor between April 2019 and May 2019. This study included the American Society of Anesthesiologists physical status II-III nulliparous parturients at term, who requested epidural analgesia. The bolus volume was fixed at 10 mL of ropivacaine 0.08% with sufentanyl 0.3 µg/mL. Participants were divided into four groups (groups 60, 50, 40, and 30) according to the PIEB intervals (60, 50, 40, and 30 min, respectively). The interval duration of the first parturient was set at 60 min and that of subsequent parturients varied according to a biased-coin design. The truncated Dixon and Mood method and the isotonic regression analysis method were used to estimate the EI90% and its 95% confidence intervals (CIs). RESULTS: Forty-four women were enrolled in this study. The estimated optimal interval was 44.1 min (95% CI 41.7-46.5 min) and 39.5 min (95% CI 32.5-50.0 min), using the truncated Dixon and Mood method and isotonic regression analysis, respectively. The maximum sensory block level above T6 was in nearly 20% of parturients in group 30; however, 5.3%, 0%, and 0% of the parturients presented with sensory block level above T6 in groups 40, 50, and 60, respectively. There were no cases of hypotension and only one parturient complained of motor block. CONCLUSION: With a fixed 10 mL dose of ropivacaine 0.08% with sufentanyl 0.3 µg/mL, the optimal PIEB interval is about 42 min. Further studies are warranted to define the efficacy of this regimen throughout all stages of labor. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900022199; http://www.chictr.org.cn/com/25/historyversionpuben.aspx?regno=ChiCTR1900022199.

Propofol affects mouse embryonic fibroblast survival and proliferation in vitro via ATG5- and calcium-dependent regulation of autophagy.

Propofol is a commonly used intravenous anesthetic agent, which has been found to affect cell survival and proliferation especially in early life. Our previous studies show that propofol-induced neurodegeneration and neurogenesis are closely associated with cell autophagy. In the present study we explored the roles of autophagy-related gene 5 (ATG5) in propofol-induced autophagy in mouse embryonic fibroblasts (MEF) in vitro. We showed that ATG5 was functionally related to propofol-induced cell survival and damage: propofol significantly enhanced cell survival and proliferation at a clinically relevant dose (10 µM), but caused cell death at an extremely high concentration (200 µM) in ATG5-/- MEF, but not in WT cells. The dual effects found in ATG5-/- MEF could be blocked by intracellular Ca2+ channel antagonists. We also found that propofol evoked a moderate (promote cell growth) and extremely high (cause apoptosis) cytosolic Ca2+ elevation at the concentrations of 10 µM and 200 µM, respectively, only in ATG5-/- MEF. In addition, ATG5-/- MEF themselves released more Ca2+ in cytosolic space and endoplasmic reticulum compared with WT cells, suggesting that autophagy deficiency made intracellular calcium signaling more vulnerable to external stimuli (propofol). Altogether, our results reveal that ATG5 plays a crucial role in propofol regulation of cell survival and proliferation by affecting intracellular Ca2+ homeostasis.

Cognitive Impairment and Endoplasmic Reticulum Stress Induced by Repeated Short-Term Sevoflurane Exposure in Early Life of Rats.

Sevoflurane is one of the most commonly used volatile anaesthetics for children, but the safety of prolonged or repeated clinical use of sevoflurane in infants or children is controversial. Here, we investigated the effects of sevoflurane on rats in early life and the time scale of those effects. Our behavioral results indicated that repeated short-term exposure of new-born rats to sevoflurane caused learning and memory impairment, while a single exposure of rats to sevoflurane was relatively safe. Further mechanistic investigation revealed that repeated sevoflurane exposure impaired long-term potentiation (LTP), downregulated the expression of certain synaptogenesis-related proteins (GluR1, PSD95) and upregulated proteins related to endoplasmic reticulum (ER) stress in the hippocampus. An ER stress inhibitor, tauroursodeoxycholic acid (TUDCA), reversed the changes in the levels of synaptic plasticity proteins. Our results provide new evidence for the clinical concerns regarding repeated sevoflurane anesthesia.

Cardiomyocyte differentiation induced in cardiac progenitor cells by cardiac fibroblast-conditioned medium.

Our previous study showed that after being treated with 5-azacytidine, Nkx2.5(+) human cardiac progenitor cells (CPCs) derived from embryonic heart tubes could differentiate into cardiomyocytes. Although 5-azacytidine is a classical agent that induces myogenic differentiation in various types of cells, the drug is toxic and unspecific for myogenic differentiation. To investigate the possibility of inducing CPCs to differentiate into cardiomyocytes by a specific and non-toxic method, CPCs of passage 15 and mesenchymal stem cells (MSCs) were treated with cardiac ventricular fibroblast-conditioned medium (CVF-conditioned medium). Following this treatment, the Nkx2.5(+) CPCs underwent cardiomyogenic differentiation. Phase-contrast microscopy showed that the morphology of the treated CPCs gradually changed. Ultrastructural observation confirmed that the cells contained typical sarcomeres. The expression of cardiomyocyte-associated genes, such as alpha-cardiac actin, cardiac troponin T, and beta-myosin heavy chain (MHC), was increased in the CPCs that had undergone cardiomyogenic differentiation compared with untreated cells. In contrast, the MSCs did not exhibit changes in morphology or molecular expression after being treated with CVF-conditioned medium. The results indicated that Nkx2.5(+) CPCs treated with CVF-conditioned medium were capable of differentiating into a cardiac phenotype, whereas treated MSCs did not appear to undergo cardiomyogenic differentiation. Subsequently, following the addition of Dkk1 and the blocking of Wnt signaling pathway, CVF-conditioned medium-induced morphological changes and expression of cardiomyocyte-associated genes of Nkx2.5(+) CPCs were inhibited, which indicates that CVF-conditioned medium-induced cardiomyogenic differentiation of Nkx2.5(+) CPCs is associated with Wnt signaling pathway. In addition, we also found that the activation of Wnt signaling pathway was accompanied by higher expression of GATA-4 and the blocking of the pathway inhibited the expression of GATA-4 in CVF-conditioned medium-incubated Nkx2.5(+) CPCs. This finding suggests that Wnt signaling pathway may alter GATA-4 expression and activate the cardiogenic program in the regulation of differentiation. In conclusion, Nkx2.5(+) CPCs have enormous potential for cardiomyogenic differentiation and the CVF-conditioned medium specifically induces CPCs to differentiate into a cardiac phenotype. Wnt signaling pathway is involved in CVF-conditioned medium-induced cardiomyogenic differentiation of Nkx2.5(+) CPCs.

Influence of preoperative diastolic dysfunction on hemodynamics and outcomes of patients undergoing orthotopic liver transplantation.

OBJECTIVE: Left ventricular diastolic dysfunction is receiving more attention in patients with end-stage liver diseases. The importance of diastolic dysfunction observed before orthotopic liver transplantation (OLT) and its adverse effects on hemodynamics and outcomes of OLT patients, have not been fully explored. We carried a retrospective study to investigate the influence of diastolic dysfunction on OLT patients. METHODS: Included in this retrospective study were 330 consecutive patients scheduled for cadaveric OLT over a 5-year period. According to preoperative Doppler echocardiogram (ECHO) findings, patients were divided into two groups: DD group (patients with diastolic dysfunction) and control group (patients with normal ECHO). Patient characteristics, operation variables, hemodynamic course, blood products and drug requirements, postoperative courses and outcomes were evaluated. RESULTS: 306 patients met the study entry criteria and 100 had preoperative diastolic dysfunction. Mean artery blood pressure was significantly lower in DD group after graft reperfusion than that in control group (P<0.01). More patients in DD group required epinephrine, and the mean dose of epinephrine was higher in DD group than that in control group (P<0.01). There was no significant difference in postoperative ventilation time, duration of ICU and hospital stay, renal failure and postoperative mortality between the two groups. CONCLUSION: Diastolic dysfunction is common in liver transplant recipients. Patients with diastolic dysfunction may be associated with substantial hemodynamic alterations after graft reperfusion and need more inotropic support during OLT. Diastolic dysfunction was not associated with significant adverse postoperative outcomes.

Postreperfusion syndrome during orthotopic liver transplantation: a single-center experience.

BACKGROUND: Marked hemodynamic alteration, commonly referred to as postreperfusion syndrome (PRS), often occurs after revascularization of the donor organ during orthotopic liver transplantation (OLT) and is associated with poor outcomes. This study aimed to investigate the incidence, predictive factors and clinical outcomes of PRS in Chinese patients following OLT at a liver transplantation center in China. METHODS: Over a 5-year period, 330 consecutive patients who had undergone OLT for hepatocellular carcinoma or cirrhosis were included in this retrospective study. PRS was defined as a >30% decrease in the mean arterial pressure compared with that before revascularization for more than 1 minute during the first 5 minutes of graft reperfusion. The patients were divided into 2 groups according to the development of PRS: group 1 (patients with PRS, n=56) and group 2 (patients without PRS, n=274). The demographic characteristics, operative and postoperative courses, and outcomes of the patients were analyzed using SPSS version 18.0. RESULTS: Multivariate regression analysis showed that left ventricular diastolic dysfunction determined by echocardiography and prolonged cold ischemia time were the independent risk factors for PRS. More patients in group 1 showed postoperative renal dysfunction than those in group 2 (19.23% vs 8.4%). Moreover, patients in group 1 also had higher intraoperative (7.14% vs 0%) and postoperative mortalities (26.92% vs 12.04%). CONCLUSION: Left ventricular diastolic dysfunction and prolonged cold ischemia time contribute to a high incidence of PRS, which is associated with adverse outcomes in Chinese patients following OLT.

Cardiac arrest after graft reperfusion during liver transplantation.

BACKGROUND: Cardiac arrest (CA) during orthotopic liver transplantation (OLT) is rare but it threatens the lives of patients. The cause of perioperitive CA is not fully understood. We reported the occurrence of CA in 5 patients after unclamping of the vena cava and investigated the relationship between CA and associated variables. METHODS: Five patients with CA after graft reperfusion during OLT in our unit from November 1996 to September 2003 were retrospectively reviewed. Analyzed data included donor and recipient demographic data, and recipient operative and postoperative events. RESULTS: Five (2.1%) of 240 patients undergoing OLT experienced CA 5 minutes after graft reperfusion. Two patients died of resuscitation failure. Hyperkalemia and metabolic acidosis after revascularization were observed in some patients. The five patients had hypothermia and hypocalcemia, and one had pulmonary embolism. CONCLUSIONS: CA is one of the syndromes after reperfusion. Many factors such as hyperkalemia, acidosis or pulmonary embolism combined with hypothermia and hypocalcemia during the operation seem to contribute to the occurrence of CA.

[Role of alpha-adrenergic receptors in vascular hyperreactivity in rats with high level spinal injury].

OBJECTIVE: To explore the vascular reactivity of abdominal aorta to agonists of alpha-adrenergic receptors in rat with high level transection of the spinal cord, and to quantify the expression of alpha-AR mRNA subtypes, in order to investigate relationship between alpha-AR and hyperreactivity of abdominal aorta. METHODS: Four weeks after transection of the spinal cord at the level of 4th thoracic vertebra, the rats were sacrificed, and abdominal aorta rings were adopted to assay sensitivity to phenylephrine and clonidine with isolated organ perfusion system. Alpha(1A)-AR, alpha(1B)-AR, alpha(1D)-AR, alpha(2A)-AR, alpha(2B)-AR, alpha(2C)-AR mRNA expressions were quantified by real time polymerase chain reaction (PCR). RESULTS: Compared with abdominal aorta, of rat with sham operation, reactivity of aorta of rat after transection of spinal cord to clonidine was significantly higher (P<0.05 or P<0.01), but difference of vascular reactivity to phenylephrine between them was not significant (P>0.05). Expressions of alpha(1A)-AR mRNA, alpha(1D)-AR mRNA, alpha(2A)-AR mRNA, alpha(2B)-AR mRNA, alpha(2C)-AR mRNA were significantly higher (P<0.05 or P<0.01), while the expression of alpha(1B)-AR mRNA did not vary significantly. CONCLUSION: Vascular hyperreactivity to agonist of alpha(2)-AR may be the mechanism of hyperreactivity of abdominal aorta in rat after transection of spinal cord. Although alpha(1)-AR mRNA expression is higher in aorta of rat with spinal cord injury, vascular hyperreactivity is not the result of upregulation of alpha(1)-AR sensitivity.

[Effect of high level spinal cord injury on rat heart function].

OBJECTIVE: To study the effects of high level spinal cord injury (SCI) on rat heart, and investigate the role of endothelin-1 (ET-1) in the harmful effects on heart after SCI. METHODS: Forty-eight male SD rats were randomly divided into six groups of 8 animals each: control group; 4-hour group: 4 th hour after injury to spinal cord at cervical 7 level; 12-hour group: 12 th hour after injury to 7 spinal cord at C7 level; 24-hour group with same injury; 48-hour group and 72-hour group, all with same injury. Mean arterial pressure (MAP), heart rate (HR), left ventricle systolic pressure (LVSP), and left ventricular maximum velocities of contraction (+/-dp/dt max) were recorded in each group. Lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and ET-1 contents in the myocardium. were also measured. Specimens of the myocardium were harvested for ultrastructure examination with transmission electron microscopy. RESULTS: Hemodynamics variables including HR, MAP, LVSP and+/-dp/dtmax were significantly decreased in all the injury groups compared with that of control group (P<0.05 or P<0.01). These variables in 12-hour group showed lowest values among all the groups (all P<0.01). But the values of cardiac enzymes were much higher in five injury groups compared with that of control group (P<0.05 or P<0.01). ET-1 contents in serum and cardiac tissue raised markedly after the injury was inflicted to the animals (P<0.05), reaching peak at 12 hours (P<0.01). Ultrastructural examination of the myocardial tissue demonstrated that there were mild dissolution of myocardial fibrils and vacuolation of mitochondria at 12 hours after injury. CONCLUSION: High level SCI could induce myocardial injuries and an excessive production of ET-1 in circulation and myocardial tissue might play a role in myocardial damage after injury of the spinal cord at a high level.