Multifunctional Filler-Free PEDOT:PSS Hydrogels with Ultrahigh Electrical Conductivity Induced by Lewis-Acid-Promoted Ion Exchange.

Highly conductive hydrogels with biotissue-like mechanical properties are of great interest in the emerging field of hydrogel bioelectronics due to their good biocompatibility, deformability, and stability. Fully polymeric hydrogels may exhibit comparable Young's modulus to biotissues. However, most of these filler-free hydrogels have a low electrical conductivity of <10 S cm-1 , which limits their wide applications of them in digital circuits or bioelectronic devices. In this work, a series of metal-halides-doped poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels with an ultrahigh electrical conductivity up to 547 S cm-1 is reported, which is 1.5 times to 104 times higher than previously reported filler-free polymeric hydrogels. Theoretical calculation demonstrated that the ion exchange between PEDOT:PSS and the metal halides played an important role to promote phase separation in the hydrogels, which thus leads to ultrahigh electrical conductivity. The high electrical conductivity resulted in multifunctional hydrogels with high performance in thermoelectrics, electromagnetic shielding, Joule heating, and sensing. Such flexible and stretchable hydrogels with ultrahigh electrical conductivity and stability upon various deformations are promising for soft bioelectronics devices and wearable electronics.

The assessment in patients with acute fatty liver of pregnancy (AFLP) treated with plasma exchange: a cohort study of 298 patients.

BACKGROUND: To assess the prevalence, risk factors, clinical characteristics of Acute fatty liver of pregnancy (AFLP) patients, and outcomes of AFLP patients treated with plasma exchange (PE). METHODS: We retrospectively reviewed the AFLP patients admitted to the First Affiliated Hospital of Xi'an Jiaotong University and Xijing Hospital of Air Force Medical University from January 2012 to May 2022. Final prediction model for death among AFLP by means of stepwise backward elimination with p value < 0.05. Patients treated with and without PE were compared by propensity-matched cohort study. RESULTS: Two hundred ninety eight patients with the diagnosis of AFLP, and finally 290 patients were enrolled in the cohort study, 50 of whom (17.2%) were dead. Compared with AFLP patients alive, the dead of patients were more likely to be combined encephalopathy (p < 0.01), postpartum hemorrhage (p < 0.01), and found significantly higher frequency of fetal distress (p = 0.04), fetal death (p < 0.01). we developed a predicted probability value and with an area under the receiver operating characteristics (ROC) curve of 0.94 (95%CI 0.87 to 1.00), indicating AFLP patients' death. The patients treated with PE had a significantly lower 60-day mortality rate (OR 0.42, 95% CI 0.29 to 2.64, p = 0.04), and significantly shorter duration of hospital-free days at day 28 (p = 0.01). CONCLUSIONS: In conclusion, our study indicated that liver function were risk factors for maternal mortality, and PE was a protective factor for maternal 60-day mortality and hospital-free days at day 28 in AFLP patients.

Loganin attenuates neuroinflammation after ischemic stroke and fracture by regulating α7nAChR-mediated microglial polarization.

Fracture in acute stage of ischemic stroke can increase inflammatory response and enhance stroke injury. Loganin alleviates the symptoms of many inflammatory diseases through its anti-inflammatory effect, but its role in ischemic stroke and fracture remains to be explored. Here, mice were handled with permanent middle cerebral artery occlusion (pMCAO) followed by tibial fracture 1 day later to establish a pMCAO+fracture model. Loganin or Methyllycaconitine (MLA, a specific a7nAchR inhibitor) were intragastrically administered 2 or 0.5 h before pMCAO, respectively. And mouse motor function and infarct volume were evaluated 3 days after pMCAO. We found that loganin alleviated the neurological deficit, cerebral infarction volume, and neuronal apoptosis (NeuN+ TUNEL+ ) in mice with pMCAO+fracture. And loganin suppressed pMCAO+fracture-induced neuroinflammation by promoting M2 microglia polarization (Iba1+ CD206+ ) and inhibiting M1 microglia polarization (Iba1+ CD11b+ ). While administration with MLA reversed the protective effect of loganin on pMCAO+fracture-induced neurological deficit and neuroinflammation. Next, LPS was used to stimulate BV2 microglia to simulate pMCAO+fracture-induced inflammatory microenvironment in vitro. Loganin facilitated the transformation of LPS-stimulated BV2 cells from M1 pro-inflammatory state (CD11b+ ) to M2 anti-inflammatory state (CD206+ ), which was antagonized by treatment with MLA. And loganin induced autophagy activation in LPS-stimulated BV2 cells by activating a7nAchR. Moreover, treatment with rapamycin (an autophagy activator) neutralized the inhibitory effect of MLA on loganin induced transformation of BV2 cells to M2 phenotype. Furthermore, BV2 cells were treated with LPS, LPS + loganin, LPS + loganin+MLA, or LPS + loganin+MLA+ rapamycin to obtain conditioned medium (CM) for stimulating primary neurons. Loganin reduced the damage of primary neurons caused by LPS-stimulated BV2 microglia through activating a7nAchR and inducing autophagy activation. In conclusion, loganin played anti-inflammatory and neuroprotective roles in pMCAO + fracture mice by activating a7nAchR, enhancing autophagy and promoting M2 polarization of microglia.

Effects of Methylprednisolone on Myocardial Function and Microcirculation in Post-resuscitation: A Rat Model.

Background: Previous studies have demonstrated that inflammation and impaired microcirculation are key factors in post-resuscitation syndromes. Here, we investigated whether methylprednisolone (MP) could improve myocardial function and microcirculation by suppressing the systemic inflammatory response following cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA). Methods: Sprague-Dawley rats were randomly assigned to (1) sham, (2) control, and (3) drug groups. Ventricular fibrillation was induced and then followed by CPR. The rats were infused with either MP or vehicle at the start of CPR. Myocardial function and microcirculation were assessed at baseline and after the restoration of spontaneous circulation. Blood samples were drawn at baseline and 60-min post-resuscitation to assess serum cytokine (TNF-α, IL-1ß, and IL-6) levels. Results: Myocardial function [estimated by the ejection fraction (EF), myocardial performance index (MPI), and cardiac output (CO)] improved post-ROSC in the MP group compared with those in the control group (p < 0.05). MP decreased the levels of the aforementioned pro-inflammatory cytokines and alleviated cerebral, sublingual, and intestinal microcirculation compared with the control (p < 0.05). A negative correlation emerged between the cytokine profile and microcirculatory blood flow. Conclusion: MP treatment reduced post-resuscitation myocardial dysfunction, inhibited pro-inflammatory cytokines, and improved microcirculation in the initial recovery phase in a CA and resuscitation animal model. Therefore, MP could be a potential clinical target for CA patients in the early phase after CPR to alleviate myocardial dysfunction and improve prognosis.

Perilipin 5 protects against oxygen-glucose deprivation/reoxygenation-elicited neuronal damage by inhibiting oxidative stress and inflammatory injury via the Akt-GSK-3ß-Nrf2 pathway.

BACKGROUND: Perilipin 5 (Plin5) acts as a pivotal mediator of oxidative stress and inflammation and is associated with the progression of relevant diseases. Cerebral ischemic stroke is a severe pathological condition that involves excess oxidative stress and inflammation. However, whether Plin5 plays a role in the progression of cerebral ischemic stroke remains unaddressed. This work focused on the investigation of Plin5 in oxygen-glucose deprivation/reoxygenation (OGD/R)-injured neurons, an in vitro model for studying cerebral ischemic stroke. METHODS: The primary neuronal cells were isolated from the hippocampus of newborn mice. Neurons were subjected to OGD/R treatment to establish an in vitro model for studying cerebral ischemic stroke. Neurons were infected with recombinant adenovirus expressing Plin5 to upregulate Plin5 expression. The mRNA levels were measured by real-time quantitative PCR (RT-qPCR). Protein levels were determined by immunoblotting. Cell viability was assessed via cell counting kit-8 (CCK-8) assay. Cell apoptosis was evaluated via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Annexin V-Allophycocyanin/7-Amino Actinomycin D (Annexin V-APC/7-AAD) apoptotic assays. Oxidative stress was monitored by dichlorofluorescein diacetate (DCFH-DA) probe. Inflammatory cytokine release was detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: A decreased level of Plin5 was observed in neurons challenged with OGD/R. Plin5 overexpression remarkably subdued OGD/R-elicited apoptosis, oxidative stress and proinflammatory response. Plin5 overexpression led to an enhancement of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway associated with regulation of the Akt-glycogen synthase kinase-3ß (GSK-3ß). The blocking of Akt was able to reverse the enhancing effect of Plin5 on Nrf2 activation. The restraining of Akt or silencing of Nrf2 diminished the protective effects of Plin5 in OGD/R-injured neurons. CONCLUSIONS: Plin5 confers neuroprotection for neurons against OGD/R damage via effects on the Nrf2-Akt-GSK-3ß pathway. This work indicates a possible role of Plin5 in cerebral ischemic stroke and the up-regulation of Plin5 is a sort of survival strategy for neurons suffering from ischemic injury.

Effectiveness of the improved B-ultrasound method for measuring the antral section to guide enteral nutrition in patients with sepsis in a randomized controlled trial.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate the application of the improved B-ultrasound method (hereafter referred to as B method) for measuring the antral section to evaluate gastric motility in guiding EN for patients with sepsis. METHODS AND STUDY DESIGN: In this single-center, non-blinded, randomized controlled trial, 64 patients with sepsis were randomly enrolled from January 2018 to December 2019. The improved B method (study group) and physicians' clinical experience (control group) were used to guide EN. The two groups patients were separated randomly both. RESULTS: Compared with the control group, the study group had a significantly shorter EN start time, faster initial rate of EN, lower incidence of EN interruption, and shorter Tmax (p<0.05,95% confidence intervals.) and exhibited lower incidences of adverse reactions (p<0.05). Kaplan-Meier survival analysis demonstrated that the study group exhibited significantly fewer adverse EN complications (p=0.029), shorter MV duration, and decreased ICU stay and in-hospital mortality (p<0.05). CONCLUSIONS: The improved B method could perform real-time monitoring of gastric function. Additionally, compared with the physician's personal clinical experience, the improved B method exhibits a better effect in guiding EN for patients with sepsis.

Mild therapeutic hypothermia improves neurological outcomes in a rat model of cardiac arrest.

Cardiac arrest (CA) is the leading cause of death in humans. Research has shown that mild therapeutic hypothermia (MTH) can reduce neurological sequelae and mortality after CA. Nevertheless, the mechanism remains unclear. This study aimed to determine whether MTH promotes neurogenesis, attenuates neuronal damage, and inhibits apoptosis of neurons in rats after CA. Sprague-Dawley rats were divided into the normothermia and mild hypothermia groups. The rats in the normothermia and hypothermia groups were exposed to 2 h of normothermia (36-37℃) and hypothermia (32-33℃), respectively, immediately after resuscitation from 5 min of asphyxial CA. Corresponding control groups not subjected to CA were included. On days 1-6, 5-bromodeoxyuridine (BrdU) 100 mg/kg/day was administered intraperitoneally. The animals were euthanized 1 week after CA. Compared with the normothermia group, the hypothermia group showed a significant increase in the number of doublecortin (DCX) immune-positive cells in the subgranular zone of the hippocampus 1 week after CA. Neurogenesis was assessed using double immunofluorescent labeling of BrdU with neuronal-specific nuclear protein (NeuN)/DCX. There was no marked change in the number of newborn mature (BrdU+-NeuN+) neurons, though there was a significant increase in the number of newborn immature (BrdU+-DCX+) neurons in the hypothermia than in the normothermia group 1 week after CA. Neuronal injury and apoptosis in the CA1 region of the hippocampus, assessed using NeuN immunofluorescence and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assays, were significantly reduced in the hypothermia group 1 week after CA. Moreover, mild hypothermia increased the expression of cold-shock protein RNA-binding motif protein 3 (RBM3) in the early stage (24 h/48 h) after CA. These results suggested that mild hypothermia promotes generation of neuronal cells, reduces neuronal injury, and inhibits apoptosis of neurons, which may be related to RBM3 expression.

Polyethylene glycol-20k reduces post-resuscitation cerebral dysfunction in a rat model of cardiac arrest and resuscitation: A potential mechanism.

Out-of-hospital cardiac arrest (CA) is a leading cause of death in the United States. Severe post-resuscitation cerebral dysfunction is a primary cause of poor outcome. Therefore, we investigate the effects of polyethylene glycol-20k (PEG-20k), a cell impermeant, on post-resuscitation cerebral function. Thirty-two male Sprague-Dawley rats were randomized into four groups: 1) Control; 2) PEG-20k; 3) Sham control; 4) Sham with PEG-20k. To investigate blood brain barrier (BBB) permeability, ten additional rats were randomized into two groups: 1) CPR+Evans Blue (EB); 2) Sham+EB. Ventricular fibrillation was induced and untreated for 8 min, followed by 8 min of CPR, and resuscitation was attempted by defibrillation. Cerebral microcirculation was visualized at baseline, 2, 4 and 6 h after return of spontaneous circulation (ROSC). Brain edema was assessed by comparing wet-to-dry weight ratios after 6 h. S-100ß, NSE and EB concentrations were analyzed to determine BBB permeability damage. For results, Post-resuscitation cerebral microcirculation was impaired compared to baseline and sham control (p < 0.05). However, dysfunction was reduced in animals treated with PEG-20k compared to control (p < 0.05). Post-resuscitation cerebral edema as measured by wet-to-dry weight ratio was lower in PEG-20k compared to control (3.23 ±â€¯0.5 vs. 3.36 ±â€¯0.4, p < 0.05). CA and CPR increased BBB permeability and damaged neuronal cell with associated elevation of S-100ß sand NSE serum levels. PEG-20k administered during CPR improved cerebral microcirculation and reducing brain edema and injury.

Oxidative α-C-C Bond Cleavage of 2° and 3° Alcohols to Aromatic Acids with O2 at Room Temperature via Iron Photocatalysis.

The selective α-C-C bond cleavage of unfunctionalized secondary (2°) and tertiary alcohols (3°) is essential for valorization of macromolecules and biopolymers. We developed a blue-light-driven iron catalysis for aerobic oxidation of 2° and 3° alcohols to acids via α-C-C bond cleavages at room temperature. The first example of oxygenation of the simple tertiary alcohols was reported. The iron catalyst and blue light play critical roles to enable the formation of highly reactive O radicals from alcohols and the consequent two α-C-C bond cleavages.

Acute pancreatitis associated with hemorrhagic fever with renal syndrome: a cohort study of 346 patients.

BACKGROUND: To assess the prevalence, risk factors, clinical characteristics, and outcomes of acute pancreatitis (AP) in patients with hemorrhagic fever with renal syndrome (HFRS). METHODS: All patients diagnosed with HFRS admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2013 to July 2020 were enrolled. Patients with and without AP were compared by two risk stratification models: (1) a multivariate regression analysis using propensity score to adjust for confounding and (2) a propensity-matched nested case-control study. RESULTS: A total of 346 patients were enrolled in the cohort study, 29 of whom (8.4%) were diagnosed as AP. There was no significant difference between patients with and without AP with regards to common risk factors and presenting signs/symptoms other than gastrointestinal symptoms (p < 0.01). The patients with AP had a significantly higher 90-day mortality rate (24.1% vs. 3.5%, OR 8.9, 95% CI 1.3 to 103.4, p = 0.045), and significantly shorter duration of therapy free-days to 28 day such as RRT and mechanical ventilation free days (p < 0.05, respectively). CONCLUSIONS: Our study indicated that AP was independently associated with higher mortality in HFRS patients. While considering the difficulty of early recognition of AP among HFRS patients with similar signs and/or symptoms, further laboratory and imaging studies might help identify these patients at risk of poor clinical prognosis.

JZL184 protects hippocampal neurons from oxygen-glucose deprivation-induced injury via activating Nrf2/ARE signaling pathway.

JZL184 is a selective inhibitor of monoacylglycerol lipase (MAGL) that has neuroprotective effect. However, the role of JZL184 in cerebral ischemia/reperfusion (I/R) injury and the exact mechanism have not been fully understood. This study was designed to elucidate the role of JZL184 in cerebral I/R injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Hippocampal neurons were pretreated with various concentrations of JZL184 for 2 h, followed by OGD for 3 h and reoxygen for 24 h. Our results showed that JZL184 improved cell viability in hippocampal neurons in response to OGD/R. JZL184 treatment significantly inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in OGD/R-induced hippocampal neurons. The increased TNF-α, IL-1ß, and IL-6 productions in OGD/R-induced hippocampal neurons were decreased after treatment with JZL184. Moreover, the OGD/R-caused intense TUNEL staining in hippocampal neurons was attenuated by JZL184. JZL184 treatment prevented OGD/R-caused increases in bax and cleaved caspase-3 expression and a decrease in bcl-2 expression. Furthermore, JZL184 treatment significantly promoted the activation of Nrf2/ARE signaling pathway in OGD/R-induced hippocampal neurons. Additionally, silencing of Nrf2 reversed the protective effect of JZL184 on hippocampal neurons under OGD/R condition. Taken together, these findings suggested that JZL184 exerted protective effect against OGD/R-induced injury in hippocampal neurons via activating Nrf2/ARE signaling pathway, which provided in vitro experimental support for the therapeutic benefit of JZL184 in cerebral ischemia.

Prognostic value of the combined variability of mean platelet volume and neutrophil percentage for short-term clinical outcomes of sepsis patients.

INTRODUCTION: In this single center retrospective cohort study, 784 patients with sepsis were enrolled and followed up for at least 30 days. The selected endpoint was an all-cause mortality event. METHOD: The relationship between MPV-CV + NEU%-CV and all-cause mortality (in-hospital and 30-day) was analyzed by categorizing the patients into four groups according to MPV-CV and NEU%-CV values. For in-hospital mortality, a significantly higher risk of mortality was observed in patients with an MPV-CV ≥ 15.00% + NEU%-CV ≥ 16.00% than in patients of the other groups (P < 0.001). After adjustment for age, sex, body mass index (BMI), infection site, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, use of vasoactive drugs, mechanical ventilation and renal replacement therapy (RRT), hematocrit, albumin, procalcitonin (PCT), and lactate, logistic regression analysis revealed that an MPV-CV ≥ 15.00% + NEU%-CV ≥ 16.00% was an independent predictive factor for in-hospital mortality [adjusted model: odds ratio (OR) = 4.48, 95% CI = 2.92-6.88, P = 0.001]. RESULTS: After adjustment for age, sex, BMI, infection site, APACHE II score, SOFA score, hematocrit, albumin, PCT, lactate, and the use of vasoactive drugs, mechanical ventilation, and RRT, Cox proportional-hazards regression model revealed that an MPV-CV ≥ 15.00% + NEU%-CV ≥ 16.00% was an independent predictive factor for 30-day mortality [adjusted model 1: hazard ratio (HR) = 7.69, 95% CI = 4.15-14.24, P < 0.001; adjusted model 2: HR = 4.07, 95% CI = 2.50-6.62, P < 0.001]. CONCLUSION: The combination of MPV-CV and NEU%-CV provides a good prognostic value and is a strong independent predictor of short-term clinical outcomes in patients with sepsis. An MPV-CV ≥ 15.00% + NEU%-CV ≥ 16.00% is significantly associated with adverse short-term clinical outcomes.Trial registration number is XJTU2AF2016LSY-04, the registration date is December 2018.

PDLIM2 protects articular chondrocytes from lipopolysaccharide-induced apoptosis, degeneration and inflammatory injury through down-regulation of nuclear factor (NF)-κB signaling.

Excessive inflammatory response-induced apoptosis and the degeneration of articular chondrocytes contribute to the development and progression of osteoarthritis. PDZ and LIM domain containing protein 2 (PDLIM2) has emerged as one of the pivotal regulators in orchestrating an inflammatory response through regulating the activity of transcription factor nuclear factor (NF)-κB. However, whether PDLIM2 participates in the articular chondrocyte-associated inflammatory response in osteoarthritis remains unknown. In the current study, we aimed to explore the biological function of PDLIM2 in lipopolysaccharide (LPS)-stimulated articular chondrocytes, an in vitro model of osteoarthritis. Herein, we found that PDLIM2 expression was significantly down-regulated in chondrocytes in response to LPS exposure. Functional experiments revealed that PDLIM2 overexpression increased the viability and decreased the apoptosis of chondrocytes following LPS treatment. Moreover, PDLIM2 overexpression attenuated LPS-induced degeneration of chondrocytes via the down-regulation of matrix metalloproteinase (MMP)-3 and MMP-13 and the up-regulation of COL2A1 and ACAN. In addition, the overexpression of PDLIM2 decreased LPS-induced production of interleukin (IL)-1ß, IL-6 and TNF-α. In contrast, depletion of PDLIM2 exhibited the opposite effect. Mechanism research elucidated that PDLIM2 repressed the activation of NF-κB signaling associated with the down-regulation of NF-κB p65 protein expression. PDLIM2 depletion-exacerbated LPS-induced injury was significantly reversed by NF-κB inhibition. Taken together, these results demonstrate that PDLIM2 overexpression attenuates LPS-induced injury of articular chondrocytes through the inactivation of NF-κB signaling.

Cannabinoid Receptor Agonist WIN55, 212-2 Adjusts Lipid Metabolism in a Rat Model of Cardiac Arrest.

The objective of this study was to investigate the effects of pharmacologically induced hypothermia with WIN55, 212-2 (WIN)on postresuscitation myocardial function, microcirculation, and metabolism-specific lipids in a rat cardiac arrest (CA) model. Ventricular fibrillation was electrically induced and untreated for 6 minutes in 24 Sprague-Dawley rats weighing 450-550 g. Cardiopulmonary resuscitation including chest compression and mechanical ventilation was then initiated and continued for 8 minutes, followed by defibrillation. At 5 minutes after restoration of spontaneous circulation (ROSC), animals were randomized into four groups: (1) normothermia with vehicle (NT); (2) physical hypothermia with vehicle (PH); (3) WIN55, 212-2 with normothermia (WN); and (4) WIN55, 212-2 with hypothermia (WH). For groups of WN and WH, WIN was administered by continuous intravenous infusion with a syringe pump for 4 hours. PH started at 5 minutes after resuscitation. NT maintained core temperature at 37°C ± 0.2°C with the aid of a heating blanket. Hypothermia groups maintained temperature at 33°C ± 0.5°C for 4 hours after ROSC. There was a significant improvement in myocardial function as measured by ejection fraction, cardiac output, and myocardial performance index in animals treated with WH and PH beginning at 1 hour after start of infusion. In the WH and PH groups, buccal microcirculation was significantly improved compared with NT and WN. Plasma at pre-CA and ROSC 4 hours was harvested for lipid metabolism. The WH group appeared to be closer to baseline than the other groups in lipid metabolism. lysophosphatidylcholine (LPC) 18:2, free fatty acid (FFA) 22:6, and ceramide (CER) (24:0) changed significantly among the lipidomic data compared with NT (p < 0.05). Postresuscitation hypothermia improved myocardial function and microcirculation. WH-mediated lipid metabolism had the best metabolic outcome to bring back the animals to normal metabolism, which may be protective to improve outcomes of CA. LPC 18:2, FFA 22:6, and CER (24:0) may be important predictors of outcomes of CA.

LncRNA RMRP accelerates hypoxia-induced injury by targeting miR-214-5p in H9c2 cells.

OBJECTIVE: To elucidate the function of lncRNA RMRP in hypoxia-induced acute myocardial infarction (AMI) in vitro and explore its underlying mechanism. METHODS: Hypoxic injury was confirmed by measurement of cell viability, LDH release, migration, invasion, and apoptosis in H9c2 cells. The interactions between RMRP and miR-214-5p as well as miR-214-5p and p53 were also investigated. RESULTS: Hypoxia treatment significantly induced cell damage in H9c2 cells, accompanied with the up-regulation of RMRP expressions. Transfection of RMRP siRNA remarkably attenuated hypoxia-induced injury by enhancing cell viability, migration and invasion, and reducing cell apoptosis and LDH release; whereas, enforced expression of RMRP aggravated hypoxia-induced injury. Furthermore, RMRP served as an endogenous sponge for miR-214-5p, and its expression was negatively regulated by RMRP. The effects of RMRP knockdown on hypoxia-induced injury were further enhanced with miR-214-5p overexpression, but significantly abrogated with miR-214-5p silence. Moreover, p53 was verified as a direct target of miR-214-5p, and functional investigation revealed that RMRP regulated hypoxia-induced injury via modulating p53 signaling pathway, which was partially mediated by miR-214-5p. CONCLUSION: Our findings demonstrated the novel molecular mechanism of RMRP/miR-214-5p/p53 axis on the regulation of hypoxia-induced myocardial injury in H9c2 cells, which might provide potential therapeutic targets for AMI treatment.

Effects of Polyethylene Glycol-20k on Postresuscitation Myocardial and Cerebral Function in a Rat Model of Cardiopulmonary Resuscitation.

OBJECTIVES: Polyethylene glycol-20k is a hybrid cell impermeant that reduces ischemia injury and improves microcirculatory flow during and following low flow states through nonenergy-dependent water transfer in the microcirculation. We investigated the effects of polyethylene glycol-20k on postresuscitation microcirculation, myocardial and cerebral function, and duration of survival in a rat model of cardiopulmonary resuscitation. DESIGN: Ventricular fibrillation was induced in 20 male Sprague Dawley rats and untreated for 6 minutes. Animals were randomized into two groups (n = 10 for each group): polyethylene glycol-20k and control. Polyethylene glycol-20k (10% solution in saline, 10% estimated blood volume) and vehicle (saline) were administered at the beginning of cardiopulmonary resuscitation by continuous IV infusion. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. SETTING: University-Affiliated Research Laboratory. SUBJECTS: Sprague Dawley Rats. INTERVENTIONS: Polyethylene glycol-20k. MEASUREMENTS AND MAIN RESULTS: Buccal microcirculation was measured at baseline, 1, 3, and 6 hours after return of spontaneous circulation using a side-stream dark-field imaging device. Myocardial function was measured by echocardiography at baseline and every hour postresuscitation for 6 hours. The animals were then returned to their cage and observed for an additional 72 hours. Neurologic Deficit Scores were recorded at 24, 48, and 72 hours after resuscitation. Postresuscitation ejection fraction, cardiac output, and myocardial performance index were significantly improved in animals treated with polyethylene glycol-20k (p < 0.05). Perfused buccal vessel density and microcirculatory flow index values were significantly higher at all time points in the polyethylene glycol-20k group compared with the control group. Postresuscitation cerebral function and survival rate were also significantly improved in animals that received polyethylene glycol-20k. CONCLUSIONS: Administration of polyethylene glycol-20k following cardiopulmonary resuscitation improves postresuscitation myocardial and cerebral function, buccal microcirculation, and survival in a rat model of cardiopulmonary resuscitation.

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.

Remote Ischemic Postconditioning Improves Myocardial Dysfunction Via the Risk and Safe Pathways in a Rat Model of Severe Hemorrhagic Shock.

INTRODUCTION: Patients who have been resuscitated after severe hemorrhagic shock still have a high mortality rate. Previously published literature has suggested that remote ischemic postconditioning (RIPostC) has a cardioprotective effect, but few studies have focused on RIPostC performed after severe hemorrhagic shock. In this study, we aim to explore the effects and mechanism of RIPostC on myocardial ischemia and reperfusion injuries after hemorrhagic shock. METHODS: Fifty male rats were randomized into four groups: sham, control, remote ischemic per-conditioning (RIPerC), and RIPostC. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume. Remote ischemic conditioning (RIC) was induced by four cycles of limb ischemia for 5 min followed by 5 min of reperfusion, during and after resuscitation for the RIPerC and RIPostC groups, respectively. Myocardial function, survival rate, IL-6, IL-10, and SOD were detected. Myocardial damage was histopathologically analyzed, and proteins related to the reperfusion injury salvage kinase (RISK) pathway (Akt, MEK, ERK1/2) and the survival activating factor enhancement (SAFE) pathway (STAT-3 and STAT5) were measured. RESULTS: Compared with the control group, the ejection fraction and myocardial performance indexes were significantly better in both RIC groups 2 h after resuscitation. Myocardial damage was attenuated and survival time increased significantly in the RIC groups. IL-6 and cardiac troponin I (cTnI) levels were notably reduced in both RIC groups. Only RIPostC had significantly increased levels of SOD and IL-10. The SAFE and RISK pathways were activated by RIPostC, whereas the effect of RIPerC was not significant. CONCLUSIONS: RIPostC attenuated myocardial dysfunction and survival outcomes via the activation of the SAFE and RISK pathways in this rat model of hemorrhagic shock. RIPerC improves myocardial dysfunction, but might not do so via the SAFE and RISK pathways.

Tumor-associated macrophages induce the expression of FOXQ1 to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells.

Gastric cancer (GC) is one of the most common malignancies, and is the second leading cause of cancer-related deaths worldwide. Macrophages infiltrated in the tumor microenvironment (TME) called tumor-associated macrophages (TAMs) are key orchestrators in TME. In GC, it has been reported that infiltration of TAMs is associated with epithelial-mesenchymal transition (EMT)-related proteins in human GC tissues, but the exactly mechanism has not been clarified. In the present study, we aimed to elucidate the underlying mechanism of TAMs on GC cells. THP-1 cells were used to investigate the effects of TAMs on GC cells. The effects of invasion and migration induced by coculture with TAMs were investigated by Transwell invasion and wound healing assays. The expression of EMT-related genes and forkhead box Q1 (FOXQ1) were examined in MKN45 and MKN74 cells after being co-cultured with TAMs. The density of TAMs and the expression of FOXQ1 were analyzed by immunohistochemistry in GC tissues. Our results revealed that, co-culture with TAMs promoted the invasion and migration of GC cells. Co-culture with TAMs induced EMT in GC cells. FOXQ1 is essential for TAM-induced EMT and metastasis in GC cells. Furthermore, silencing of FOXQ1 blocked the effect of TAM-enhanced EMT and metastasis of GC cells. High expression of CD68 was correlated with positive FOXQ1 expression (r=0.613; P<0.001) in clinical GC samples. Our data provided evidence that TAMs promote EMT, invasion and migration of GC cells via FOXQ1. Therefore, the TAM/FOXQ1 axis may represent a novel target for GC cells.