m6A-mediated upregulation of miRNA-193a aggravates cardiomyocyte apoptosis and inflammatory response in sepsis-induced cardiomyopathy via the METTL3/ miRNA-193a/BCL2L2 pathway.

The impact of N6-methyladenosine (m6A) modification on pri-miRNA in sepsis-induced cardiomyopathy (SICM), and its underlying regulatory mechanism, have not been fully elucidated. We successfully constructed a SICM mice model through cecal ligation and puncture (CLP). In vitro, a lipopolysaccharide (LPS)-induced HL-1 cells model was also established. The results showed that sepsis frequently resulted in excessive inflammatory response concomitant with impaired myocardial function in mice exposed to CLP, as indicated by decreases in ejection fraction (EF), fraction shortening (FS), and left ventricular end diastolic diameters (LVDd). miR-193a was enriched in CLP mice heart and in LPS-treated HL-1 cells, while overexpression of miR-193a significantly increased the expression levels of cytokines. Sepsis-induced enrichment of miR-193a significantly inhibited cardiomyocytes proliferation and enhanced apoptosis, while this was reversed by miR-193a knockdown. Furthermore, under our experimental conditions, enrichment of miR-193a in SICM could be considered excessively maturated on pri-miR-193a by enhanced m6A modification. This modification was catalyzed by sepsis-induced overexpression of methyltransferase-like 3 (METTL3). Moreover, mature miRNA-193a bound to a predictive sequence within 3'UTRs of a downstream target, BCL2L2, which was further validated by the observation that the BCL2L2-3'UTR mutant failed to decrease luciferase activity when co-transfected with miRNA-193a. The interaction between miRNA-193a and BCL2L2 resulted in BCL2L2 downregulation, subsequently activating the caspase-3 apoptotic pathway. In conclusion, sepsis-induced miR-193a enrichment via m6A modification plays an essential regulatory role in cardiomyocyte apoptosis and inflammatory response in SICM. The detrimental axis of METTL3/m6A/miR-193a/BCL2L2 is implicated in the development of SICM.

Using three-dimensional modelling of the anterior sclera to investigate the scleral profile in myopic eyes.

PURPOSE: This study used three-dimensional (3D) modelling to investigate scleral profiles in myopic eyes and compare them with emmetropic eyes. METHODS: In this prospective observational study, the eyes of 151 participants were analysed using the corneoscleral profile module (CSP) of the Pentacam HR. Non-rotationally symmetrical ellipsoids were fitted to the anterior scleral sagittal height. Three radii were analysed, namely the nasal-temporal (Rx), superior-inferior (Ry) and anterior-posterior (Rz) orientations. Additionally, the area index (AI) and aspherical parameters (Qxy, Qxz and Qyz) of the anterior sclera-fitted ellipsoid (ASFE) were quantified. RESULTS: The findings showed an increase in Rx (-0.349 mm/D), Ry (-0.373 mm/D), Rz (-1.232 mm/D) and AI (-36.165 mm2 /D) with increasing myopia. From emmetropia to high myopia, the vertical and horizontal planes of the anterior sclera became increasingly prolate (emmetropia, Qxz: 0.02, Qyz: 0.01; low myopia, Qxz: -0.28, Qyz: -0.28; high myopia, Qxz: -0.41, Qyz: -0.43). There were no significant differences in the coronal plane across the three groups (H = 2.65, p = 0.27). The anterior scleral shape of high myopes in the horizontal and vertical planes was more prolate than that of emmetropes and low myopes (Qxz, high myopes vs. low myopes: p = 0.03, high myopes vs. emmetropes: p < 0.001; Qyz, high myopes vs. low myopes: p = 0.04, high myopes vs. emmetropes: p < 0.001). CONCLUSIONS: As the degree of myopia increased, non-uniform anterior scleral enlargement was observed. These findings provide a better understanding of the anterior segment with varying degrees of myopia.

Research Progress of Natural Active Substances with Immunosuppressive Activity.

The increasing prevalence of autoimmune diseases globally has prompted extensive research and the development of immunosuppressants. Currently, immunosuppressive drugs such as cyclosporine, rapamycin, and tacrolimus have been utilized in clinical practice. However, long-term use of these drugs may lead to a series of adverse effects. Therefore, there is an urgent need to explore novel drug candidates for treating autoimmune diseases. This review aims to find potential candidate molecules for natural immunosuppressive compounds derived from plants, animals, and fungi over the past decade. These compounds include terpenoids, alkaloids, phenolic compounds, flavonoids, and others. Among them, compounds 49, 151, 173, 200, 204, and 247 have excellent activity; their IC50 were less than 1 µM. A total of 109 compounds have good immunosuppressive activity, with IC50 ranging from 1 to 10 µM. These active compounds have high medicinal potential. The names, sources, structures, immunosuppressive activity, and the structure-activity relationship were summarized and analyzed.

Salicylic acid promotes phenolic acid biosynthesis for the production of phenol acid-rich barley sprouts.

BACKGROUND: Phenolic acid exhibits a variety of well-known physiological functions. In this study, optimal germination conditions to ensure total phenolic acid enrichment in barley sprouts induced by salicylic acid treatment and its effects on sprout physiology and activity, as well as the gene expression of key enzymes for phenolic acid biosynthesis, were investigated. RESULTS: When sprouts were treated with 1 mmol L-1 salicylic acid during germination and germinated at 25 °C for 4 days, the phenolic acid content was 1.82 times that of the control, reaching 1221.54 µg g-1 fresh weight. Salicylic acid significantly increased the activity of phenylalanine aminolase and cinnamic acid-4-hydroxylase and the gene expression of phenylalanine aminolase, cinnamic acid-3-hydroxylase, cinnamic acid-4-hydroxylase, 4-coumaric acid-coenzyme A, caffeic acid O-methyltransferase, and ferulate-5-hydroxylase in barley sprouts. However, salicylic acid treatment significantly increased malondialdehyde and H2O2 content, H2O2 and O2 - fluorescence intensity, as well as significantly decreasing sprout length and fresh weight. Salicylic acid treatment markedly increased the activity of peroxidase and catalase and the gene expression of peroxidase, catalase, and ascorbate peroxidase in barley sprouts. CONCLUSION: Salicylic acid treatment during barley germination significantly promoted the enrichment of total phenolic acid by increasing the activities and gene expression levels of enzymes involved in the phenolic acid biosynthesis pathway. Salicylic acid induced the accumulation of reactive oxygen species, inhibited sprout growth, and activated the antioxidant system. This study provides a basis for the future development of functional foods using phenol acid-rich plants as raw materials. © 2024 Society of Chemical Industry.

Repeatability and Reproducibility of Corneoscleral Topography Measured With Scheimpflug Imaging in Keratoconus and Control Eyes.

OBJECTIVES: To determine and compare the repeatability and reproducibility of anterior scleral parameters measured by the corneoscleral profile (CSP) module of Pentacam in keratoconus (KC) and control eyes. METHODS: This is a prospective observational study. Thirty KC participants (30 eyes) and 24 control participants (24 eyes) were examined three times using the CSP. Sagittal height mean (SHM), sagittal height astigmatism (SHA), and mean bulbar slope (BSM) were measured in 12 mm and 16 mm chord lengths. The repeatability and reproducibility of these measurements were also assessed. Coefficients of variation (CoV), intraclass correlation coefficient (ICC), coefficient of repeatability (CoR1), and coefficient of reproducibility (CoR2) were adopted to assess the reliability. RESULTS: In the KC and control groups, SHM showed high repeatability and reproducibility (coefficients of variation [CoVs]≤0.96%, intraclass correlation coefficient [ICCs]≥0.97), and SHM of control eyes showed higher repeatability and reproducibility than that of KC eyes at 12 mm chord length (KC group, CoRs ranged from 35.56 µm to 43.52 µm, control group, ranged from 23.50 µm to 30.31 µm) and 16 mm chord length (KC group, CoRs ranged from 79.54 µm to 81.58 µm, control group, ranged from 48.25 µm to 66.10 µm). Mean bulbar slope also showed high repeatability and reproducibility (CoVs≤3.65%, CoRs≤2.64). Furthermore, the SHA of control eyes showed higher repeatability and reproducibility when compared with KC eyes (control group: CoVs≤29.95%, KC group: CoVs≥32.67%). CONCLUSIONS: Keratoconus and control eyes demonstrated high repeatability and reproducibility when using CSP measurements, which may prove helpful in fitting contact lenses.

DL-3-n-butylphthalide-induced neuroprotection in rat models of asphyxia-induced cardiac arrest followed by cardiopulmonary resuscitation.

Most patients that resuscitate successfully from cardiac arrest (CA) suffer from poor neurological prognosis. DL-3-n-butylphthalide (NBP) is known to have neuroprotective effects via multiple mechanisms. This study aimed to investigate whether NBP can decrease neurological impairment after CA. We studied the protective role of NBP in the hippocampus of a rat model of cardiac arrest induced by asphyxia. Thirty-nine rats were divided randomly into sham, control, and NBP groups. Rats in control and NBP groups underwent cardiopulmonary resuscitation (CPR) 6 min after asphyxia. NBP or vehicle (saline) was administered intravenously 10 min after the return of spontaneous circulation (ROSC). Ultrastructure of hippocampal neurons was observed under transmission electron microscope. NBP treatment improved neurological function up to 72 h after CA. The ultrastructural lesion in mitochondria recovered in the NBP-treated CA model. In conclusion, our study demonstrated multiple therapeutic benefits of NBP after CA.

Conjunctival microcirculation is associated with cerebral cortex microcirculation in post-resuscitation mild hypothermia: A rat model.

OBJECTIVE: This study aimed to compare the changes in sublingual and conjunctival microcirculation occurring with cerebral cortex microcirculation changes during mild hypothermia in a rat model of cardiac arrest. METHODS: Twenty-four rats were randomized into mild hypothermia (M) or normothermia (C) groups. Ventricular fibrillation was electrically induced and left untreated for 8 minutes, followed by 8 minutes of cardiopulmonary resuscitation. The core temperature in group M reduced to 33 ± 0.5°C at 13 minutes after restoration of spontaneous circulation and was maintained for 8 hours. In group C, the core temperature was maintained at 37 ± 0.2°C. The hemodynamics and microcirculation in the sublingual region, bulbar conjunctiva, and cerebral cortex were measured at baseline and 1, 2, 3, 4, 6, and 8 hours after restoration of spontaneous circulation. RESULTS: The M group showed significantly worse sublingual microcirculation at 6 hours post-resuscitation. However, microcirculation in the conjunctiva and cerebral cortex at 3 hours post-resuscitation were better in the M group. In the M group, microcirculation in the cerebral cortex was significantly correlated with that in the conjunctiva but not the sublingual microcirculation. CONCLUSIONS: Changes in conjunctival microcirculation are closely related to cerebral cortex microcirculation during mild hypothermia, indicating that cerebral cortex microcirculation could be monitored by measuring conjunctival microcirculation.

Cardiopulmonary resuscitation ameliorates myocardial mitochondrial dysfunction in a cardiac arrest rat model.

PURPOSE: Previous studies implicate that the mitochondrial injury may play an important role in the development of post-resuscitation myocardial dysfunction, however few of them are available regarding the ultrastructural alterations of myocardial mitochondria, mitochondrial energy producing and utilization ability in the stage of arrest time (no-low) and resuscitation time (low-flow). This study aimed to observe the dynamic changes of myocardial mitochondrial function and metabolic disorders during cardiac arrest (CA) and following cardiopulmonary resuscitation (CPR). METHODS: A total of 30 healthy male Sprague-Dawley rats were randomized into three groups: 1) VF/CPR: Ventricular fibrillation (VF) was electrically induced, and 5 min of CPR was performed after 10 min of untreated VF; 2) Untreated VF: VF was induced and untreated for 15 min; and 3) Sham: Rats were identically prepared without VF/CPR. Amplitude spectrum area (AMSA) at VF 5, 10 and 15 min were calculated from ECG signals. The rats' hearts were quickly removed at the predetermined time of 15 min after beginning the procedure to gather measurements of myocardial mitochondrial function, high-energy phosphate stores, lactate, mitochondrial ultrastructure, and myocardial glycogen. RESULTS: The mitochondrial respiratory control ratios significantly decreased after CA compared to sham group. CPR significantly increased respiratory control ratios compared with untreated VF animals. A significant decrease of myocardial glycogen was observed after CA, and a more rapid depletion of myocardial glycogen was observed in CPR animals. CPR significantly reduced the tissue lactate. The mitochondrial ultrastructure abnormalities in CPR animals were less severe than untreated VF animals. AMSA decayed during untreated VF; however, it was significantly greater in CPR group than the untreated VF group. In addition, AMSA was clearly positively correlated with ATP, but negatively correlated with myocardial glycogen. CONCLUSION: Impairment of myocardial mitochondrial function and the incapability of utilizing glycogen were observed after CA. Furthermore, optimal CPR might, in part, preserved mitochondrial function and enhanced utilization of myocardial glycogen.

Lactobacillus rhamnosus GG Ameliorates Liver Injury and Hypoxic Hepatitis in Rat Model of CLP-Induced Sepsis.

BACKGROUND: Probiotic use to prevent gastrointestinal infections in critical care has shown great promise in recent clinical trials. Although well-documented benefits of probiotic use in intestinal disorders, the potential for probiotic treatment to ameliorate liver injury and hypoxic hepatitis following sepsis has not been well explored. METHODS: In order to evaluate, if Lactobacillus rhamnosus GG (LGG) treatment in septic rats will protect against liver injury, this study used 20-22-week-old Sprague-Dawley rats which were subjected to cecal ligation and puncture to establish sepsis model and examine mRNA and protein levels of IL-1ß, NLRP3, IL-6, TNF-a, VEGF, MCP1, NF-kB and HIF-1α in the liver via real-time PCR, Elisa and Western blot. RESULTS: This study showed that LGG treatment significantly ameliorated liver injury following experimental infection and sepsis. Liver mRNA and protein levels of IL-1ß, NLRP3, IL-6, TNF-a, VEGF, MCP1, NF-kB and HIF-1α were significantly reduced in rats receiving LGG. CONCLUSIONS: Thus, our study demonstrated that LGG treatment can reduce liver injury following experimental infection and sepsis and is associated with improved hypoxic hepatitis. Probiotic therapy may be a promising intervention to ameliorate clinical liver injury and hypoxic hepatitis following systemic infection and sepsis.

Endovascular hypothermia improves post-resuscitation myocardial dysfunction by increasing mitochondrial biogenesis in a pig model of cardiac arrest.

The aim of the study was to investigate the effects of endovascular hypothermia on mitochondrial biogenesis in a pig model of prolonged cardiac arrest (CA). Ventricular fibrillation was electrically induced, and animals were left untreated for 10 min; then after 6min of cardiopulmonary resuscitation (CPR), defibrillation was attempted. 25 animals that were successfully resuscitated were randomized into three groups: Sham group (SG, 5, no CA), normal temperature group (NTG, 5 for 12 h observation and 5 for 24 h observation), and endovascular hypothermia group (EHG, 5 for 12 h observation and 5 for 24 h observation). The core temperatures (Tc) in the EHG were maintained at 34 ±â€¯0.5 °C for 6 h by an endovascular hypothermia device (Coolgard 3000), then actively increased at the speed of 0.5 °C per hour during the next 6 h to achieve a normal body temperature, while Tc were maintained at 37.5 ±â€¯0.5 °C in the NTG. Cardiac and mitochondrial functions, the quantification of myocardial mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor coactivator-1α (PGC-1α), nuclear respiratory factor (NRF)-1, and NRF-2 were examined. Results showed that myocardial and mitochondrial injury and dysfunction increased significantly at 12 h and 24 h after CA. Endovascular hypothermia offered a method to rapidly achieve the target temperature and provide stable target temperature management (TTM). Cardiac outcomes were improved and myocardial injuries were alleviated with endovascular hypothermia. Compared with NTG, endovascular hypothermia significantly increased mitochondrial activity and biogenesis by amplifying mitochondrial biogenesis factors' expressions, including PGC-1α, NRF-1, and NRF-2. In conclusions, endovascular hypothermia after CA alleviated myocardial and mitochondrial dysfunction, and was associated with increasing mitochondrial biogenesis.

Amplitude screening improves performance of AMSA method for predicting success of defibrillation in swine model.

PURPOSE: A novel amplitude screening method, termed Optimal Amplitude Spectrum Area (Opt-AMSA) with the aim of improving the performance of the Amplitude Spectrum Area (AMSA) method, was proposed to optimize the timing of defibrillation. We investigated the effects of the Opt-AMSA method on the prediction of successful defibrillation when compared with AMSA in a porcine model of ventricular fibrillation (VF). METHOD: 60 male domestic pigs were untreated in the first 10 min of VF, then received cardiopulmonary resuscitation (CPR) for 6 min. Values of Opt-AMSA and AMSA were calculated every minute before defibrillation. Linear regression was used to evaluate the correlation between Opt-AMSA and AMSA. Receiver Operating Characteristic (ROC) analysis was conducted for the two methods and to compare their predictive values. RESULTS: The values of both AMSA and Opt-AMSA gradually decreased over time during untreated VF in all animals. The values of both methods of defibrillation were slightly increased after the implementation of CPR in animals that were successfully resuscitated, while there were no significant changes in either method in those who ultimately failed to resuscitate. The significant positive correlation between Opt-AMSA and AMSA was shown by Pearson correlation analysis. ROC analysis showed that Opt-AMSA (AUC = 0.87) significantly improved the performance of AMSA (AUC = 0.77) to predict successful defibrillation (Z = 2.27, P < 0.05). CONCLUSION: Both the Opt-AMSA and AMSA methods showed high potential to predict the success of defibrillation. Moreover, the Opt-AMSA method improved the performance of the AMSA method, and may be a promising tool to optimize the timing of defibrillation.

Analyses of changes in myocardial long non-coding RNA and mRNA profiles after severe hemorrhagic shock and resuscitation via RNA sequencing in a rat model.

BACKGROUND: Ischemia-reperfusion injury has been proven to induce organ dysfunction and death, although the mechanism is not fully understood. Long non-coding RNAs (lncRNAs) have drawn wide attention with their important roles in the gene expression of some biological processes and diseases, including myocardial ischemia-reperfusion (I/R) injury. In this paper, a total of 26 Sprague-Dawley (SD) rats were randomized into two groups: sham and ischemia-reperfusion (I/R) injury. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume followed by reinfusion of shed blood. High-throughput RNA sequencing was used to analyze differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs) in the heart tissue 4 h after reperfusion. Myocardial function was also evaluated. RESULTS: After resuscitation, the decline of myocardial function of shocked animals, expressed by cardiac output, ejection fraction, and myocardial performance index (MPI), was significant (p < 0.05). DE lncRNAs and mRNAs were identified by absolute value of fold change ≥ 2 and the false discovery rate ≤ 0.001. In rats from the I/R injury group, 851 lncRNAs and 1015 mRNAs were significantly up-regulated while 1533 lncRNAs and 1702 m RNAs were significantly down-regulated when compared to the sham group. Among the DE lncRNAs, we found 12 location-associated with some known apoptosis-related protein-coding genes which were up-regulated or down-regulated accordingly, including STAT3 and Il1r1. Real time PCR assays confirmed that the expression levels of five location-associated lncRNAs (NONRATT006032.2, NONRATT006033.2, NONRATT006034.2, NONRATT006035.2 and NONRATT029969.2) and their location-associated mRNAs (STAT3 and Il1r1) in the rats from the I/R injury group were all significantly up-regulated versus the sham group. CONCLUSIONS: The DE lncRNAs (NONRATT006032.2, NONRATT006033.2, NONRATT006034.2 and NONRATT006035.2) could be compatible with their role in myocardial protection by stimulating their co-located gene (STAT3) after hemorrhagic shock and resuscitation. The final prognosis of I/R injury might be regulated by different genes, which is regarded as a complex network.

Hepatic infarction induced by HELLP syndrome: a case report and review of the literature.

BACKGROUND: HELLP syndrome is a rare disease in China, and 20% of patients with severe preeclampsia have been accompanied with HELLP syndrome, which is characterized by the presence of hemolysis, elevated liver enzymes and low platelet count. CASE PRESENTATION: In this case, we reported that a patient with preeclampsia was diagnosed with HELLP syndrome. Furthermore, hepatic infarction also was found via the computed tomographic (CT) images, which showed peripheral wedge-shaped inhomogeneous low attenuation in the right hepatic lobes via plain CT scan, and the low-density shadow and mottled appearance in the same areas where vessels were seen coursing through them via contrast-enhanced CT scan. CONCLUSIONS: Besides typical clinical manifestations of the pregnant patient with preeclampsia, the typical laboratory evidences were elevated liver enzymes and thrombocytopenia. The abdominal CT scan showed imaging features of hepatic infarction, which was helpful to identify the rare complication of HELLP syndrome. Thus, we diagnosed a patient with HELLP syndrome with hepatic infarction, though the patient had no chance to do the liver biopsy.

Mild hypothermia protects hippocampal neurons from oxygen-glucose deprivation injury through inhibiting caspase-3 activation.

Mild hypothermia (MH) is thought to be one of the most effective therapeutic methods to treat hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). However, its precise mechanisms remain unclear. In this research, hippocampal neurons were cultured and treated with mild hypothermia and Ac-DEVD-CHO after oxygen-glucose deprivation (OGD). The activity of caspase-3 was detected, in order to find the precise concentration of Ac-DEVD-CHO with the same protective role in OGD injury as MH treatment. Western blot and immunofluorescence staining were conducted to analyze the effects of MH and Ac-DEVD-CHO on the expressions of caspase-3, caspase-8, and PARP. The neuronal morphology was observed with an optical microscope. The lactic acid dehydrogenase (LDH) release rate, neuronal viability, and apoptotic rate were also detected. We found that MH (32 °C) and Ac-DEVD-CHO (5.96 µMol/L) had equal effects on blocking the activation of caspase-3 and the OGD-induced cleavage of PARP, but neither had any effect on the activation of caspase-8, which goes on to activate caspase-3 in the apoptotic pathway. Meanwhile, both MH and Ac-DEVD-CHO had similar effects in protecting cell morphology, reducing LDH release, and inhibiting OGD-induced apoptosis in neurons. They also similarly improved neuronal viability after OGD. In conclusion, caspase-3 serves as a key intervention point of the key modulation site or regulatory region in MH treatment that protects neuronal apoptosis against OGD injury. Inhibiting the expression of caspase-3 had a protective effect against OGD injury in MH treatment, and caspase-3 activation could be applied to evaluate the neuroprotective effectiveness of MH on HIE.

CPR feedback/prompt device improves the quality of hands-only CPR performed in manikin by laypersons following the 2015 AHA guidelines.

PURPOSE: We investigated the effects of a cardiopulmonary resuscitation (CPR) feedback/prompt device on the quality of chest compression (CC) during hands-only CPR following the 2015 AHA guidelines. METHODS: A total of 124 laypersons were randomly assigned into three groups. The first (n=42) followed the 2010 guidelines, the second (n=42) followed the 2015 guidelines with no feedback/prompt device, the third (n=40) followed the 2015 guidelines with a feedback/prompt device (2015F). Participants underwent manual CPR training and took a written basic life support examination, then required to perform 2min of hands-only CPR monitored by a CPR feedback/prompt device. The quality of CPR was quantified as the percentage of correct CCs (mean CC depth and rate, complete recoil and chest compression fraction (CCF)) per 20s, as recorded by the CPR feedback/prompt device. RESULTS: Significantly higher correct ratios of CC, CC depth, and rate were achieved in the 2010 group in each minute vs the 2015 group. The greater mean CC depth and rate were observed in the 2015F group vs the 2015 group. The correct ratio of CC was significantly higher in the 2015F group vs the 2015 group. CCF was also significantly higher in the 2015F group vs the 2015 group in the last 20s of CPR. CONCLUSIONS: It is difficult for a large percentage of laypersons to achieve the targets of CC depth and rate following the 2015 AHA guidelines. CPR feedback/prompt devices significantly improve the quality of hands-only CPR performance by laypersons following the standards of the 2015 AHA guidelines.

Lactate as a Potential Biomarker of Sepsis in a Rat Cecal Ligation and Puncture Model.

We attempted to investigate whether blood lactate is a useful biomarker for sepsis in a rat cecal ligation and puncture (CLP) model. Male Sprague-Dawley rats underwent approximately 75% cecum ligation and two punctures to induce high-grade sepsis. A lactate of 1.64 mmol/L (Youden score of 0.722) was selected as the best cutoff value to predict the onset of sepsis after CLP exposure; 46 of 50 rats who survived 24 hours after the CLP were divided into the L group (lactate < 1.64 mmol/L) and M group (lactate ≥ 1.64 mmol/L). In the M group, the animals had significantly higher murine sepsis scores and none survived 5 days post-CLP, and the rate of validated septic animals, serum procalcitonin, high mobility group box 1, blood urea nitrogen, alanine transaminase, cardiac troponin I, and the wet-to-dry weight ratio were significantly higher compared to the L group. Worsen PaO2/FiO2, microcirculations, and mean arterial pressure were observed in the M group. More severe damage in major organs was confirmed by histopathological scores in the M group compared with the L group. In conclusion, lactate ≥ 1.64 mmol/L might serve as a potential biomarker to identify the onset of sepsis in a rat CLP model.

Effects of Oxygen Concentrations on Postresuscitation Myocardial Oxidative Stress and Myocardial Function in a Rat Model of Cardiopulmonary Resuscitation.

OBJECTIVE: Lipid peroxidation induced by free-radical species plays a prominent role in myocardial injury following ischemia and reperfusion. However, there is a lack of data in different oxygen concentrations on myocardial lipid peroxidation during the early phase of reperfusion. In this study, we investigated whether ventilation with medium or normal concentration of oxygen would decrease the severity of myocardial lipid peroxidation and postresuscitation myocardial dysfunction. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research institution. SUBJECTS: Sixty-three healthy male Sprague-Dawley rats. INTERVENTIONS: Animals were randomized into three groups: 1) 100% group, 2) 50% group, and 3) 21% group. Ventricular fibrillation was induced and untreated for 8 minutes, and defibrillation was attempted after 8 minutes of cardiopulmonary resuscitation. Ventilation with 100%, 50%, or 21% oxygen was initiated in all groups during cardiopulmonary resuscitation and 1 hour following the return of spontaneous circulation. Normoxic ventilation was maintained thereafter. MEASUREMENTS AND MAIN RESULTS: Myocardial function, including ejection fraction and myocardial performance index, were measured at baseline, 4, or 72 hours after resuscitation. Blood samples were drawn at baseline, 15 minutes, 1, 4, or 72 hours after resuscitation for the measurements of blood gas or biomarkers. Significantly better myocardial function and longer duration of survival were observed in the 50% group. Compared with the 21% and 100% groups, a mild hyperoxia and greater oxygen extraction with lower 8-iso-prostaglandin F2α were observed in the 50% group. Pearson correlation analysis confirmed that 8-iso-prostaglandin F2α was positively correlated with myocardial performance index at 4 hours postresuscitation. CONCLUSIONS: In a rat model of cardiac arrest and resuscitation, ventilation with 50% inspired oxygen during early postischemic reperfusion phase contributed to a decreased lipid peroxidation and a better myocardial function and duration of survival.

Quality of chest compressions during compression-only CPR: a comparative analysis following the 2005 and 2010 American Heart Association guidelines.

OBJECTIVE: The latest guidelines both increased the requirements of chest compression rate and depth during cardiopulmonary resuscitation (CPR), which may make it more difficult for the rescuer to provide high-quality chest compression. In this study, we investigated the quality of chest compressions during compression-only CPR under the latest 2010 American Heart Association (AHA) guidelines (AHA 2010) and its effect on rescuer fatigue. METHODS: Eighty-six undergraduate volunteers were randomly assigned to perform CPR according to the 2005 AHA guidelines (AHA 2005) or AHA 2010. After the training course and theoretical examination of basic life support, eight min of compression-only CPR performance was assessed. The quality of chest compressions including rate and depth of compression was analyzed. The rescuer fatigue was evaluated by the changes of heart rate and blood lactate, and rating of perceived exertion. RESULTS: Thirty-nine participants in the AHA 2005 group and 42 participants in the AHA 2010 group completed the study. Significantly greater mean chest compression depth and compression rate were both achieved in the AHA 2010 group than in the AHA 2005 group. And significantly greater rescuer fatigue was observed in the AHA 2010 group. In addition, the female in the AHA 2010 group could perform the compression rate required by the guidelines, however, significantly shallower compression depth and greater rescuer fatigue were observed when compared to the male. CONCLUSIONS: The quality of chest compressions was significantly improved following the 2010 AHA guidelines, however, it's more difficult for the rescuer to meet the guidelines due to the increased fatigue of rescuer.

Methyl Jasmonate and Zinc Sulfate Induce Secondary Metabolism and Phenolic Acid Biosynthesis in Barley Seedlings.

This study aimed to reveal the impact of MeJA and ZnSO4 treatments on the physiological metabolism of barley seedlings and the content of phenolic acid. The results showed that MeJA (100 µM) and ZnSO4 (4 mM) treatments effectively increased the phenolic acid content by increasing the activities of phenylalanine ammonia-lyase and cinnamate-4-hydroxylase (PAL) and cinnamic acid 4-hydroxylase (C4H) and by up-regulating the expression of genes involved in phenolic acid synthesis. As a result of the MeJA or ZnSO4 treatment, the phenolic acid content increased by 35.3% and 30.9% at four days and by 33.8% and 34.5% at six days, respectively, compared to the control. Furthermore, MeJA and ZnSO4 treatments significantly increased the malondialdehyde content, causing cell membrane damage and decreasing the fresh weight and seedling length. Barley seedlings responded to MeJA- and ZnSO4-induced stress by increasing the activities of antioxidant enzymes and controlling their gene expression levels. Meanwhile, MeJA and ZnSO4 treatments significantly upregulated calcium-adenosine triphosphate, calmodulin-dependent protein kinase-related kinase, and calmodulin-dependent protein genes in barley seedlings. This suggested that Ca2+ may be the signaling molecule that promotes phenolic acid synthesis under MeJA and ZnSO4 treatment. This study deepens the understanding of the phenolic acid enrichment process in barley seedlings under MeJA and ZnSO4 treatments.