Investigation of singlet oxygen and superoxide radical produced from vortex-based hydrodynamic cavitation: Mechanism and its relation to cavitation intensity.

Presently, the hydroxyl radical oxidation mechanism is widely acknowledged for the degradation of organic pollutants based on hydrodynamic cavitation technology. The presence and production mechanism of other potential reactive oxygen species (ROS) in the cavitation systems are still unclear. In this paper, singlet oxygen (1O2) and superoxide radical (·O2-) were selected as the target ROS, and their generation rules and mechanism in vortex-based hydrodynamic cavitation (VBHC) were analyzed. Computational fluid dynamics (CFD) were used to simulate and analyze the intensity characteristics of VBHC, and the relationship between the generation of ROS and cavitation intensity was thoroughly revealed. The results show that the operating conditions of the device have a significant and complicated influence on the generation of 1O2 and ·O2-. When the inlet pressure reaches to 4.5 bar, it is more favorable for the generation of 1O2 and ·O2- comparing with those lower pressure. However, higher temperature (45 °C) and aeration rate (15 (L/min)/L) do not always have positive effect on the 1O2 and ·O2- productions, and their optimal parameters need to be analyzed in combination with the inlet pressure. Through quenching experiments, it is found that 1O2 is completely transformed from ·O2-, and ·O2- comes from the transformation of hydroxyl radicals and dissolved oxygen. Higher cavitation intensity is captured and shown more disperse in the vortex cavitation region, which is consistent with the larger production and stronger diffusion of 1O2 and ·O2-. This paper shed light to the generation mechanism of 1O2 and ·O2- in VBHC reactors and the relationship with cavitation intensity. The conclusion provides new ideas for the research of effective ROS in hydrodynamic cavitation process.

Rational design of a near-infrared dual-emission fluorescent probe for ratiometric imaging of glutathione in cells.

Sensors for which the output signal is an intensity change for a single-emission peak are easily disturbed by many factors, such as the stability of the instrument, intensity of the excitation light, and biological background. However, for ratiometric fluorescence sensors, the output signal is a change in the intensity ratio of two or more emission peaks. The fluorescence intensity of these emission peaks is similarly affected by external factors; thus, these sensors have the ability to self-correct, which can greatly improve the accuracy and reliability of the detection results. To accurately image glutathione (GSH) in cells, gold nanoclusters (AuNCs) with intrinsic double emission at wavelengths of 606 nm and 794 nm were synthesized from chloroauric acid. With the emission peak at 606 nm as the recognition signal and the emission peak at 794 nm as the reference signal, a near-infrared dual-emission ratio fluorescence sensing platform was constructed to accurately detect changes in the GSH concentration in cells. In vitro and in vivo analyses showed that the ratiometric fluorescent probe specifically detects GSH and enables ultrasensitive imaging, providing a new platform for the accurate detection of active small molecules.

Anesthesia management experience for pediatric day-case PDA ligation under thoracoscopy assisted by a robot: a retrospective study.

BACKGROUND: To summarize the anesthesia management experience for pediatric day-case patent ductus arteriosus (PDA) ligation under robot-assisted thoracoscopy and explore the key points of anesthesia management for this procedure. METHODS: The clinical data of 72 pediatric patients who underwent robot-assisted thoracoscopic day-case PDA ligation at the Children's Hospital, Zhejiang University School of Medicine from April 2021 to February 2023 were retrospectively analyzed. 0.3% ropivacaine local infiltration combined with S-ketamine 0.2 mg/kg intravenous injection was used for postoperative analgesia The patient's basic information and intraoperative conditions were analyzed, which included gender, age, weight, surgery time, anesthesia time, extubation time, intraoperative blood loss, MAP before pneumothorax, PaCO2 before pneumothorax, etc. Postoperative conditions were also monitored, such as PACU stay time, agitation during the recovery period, pain, and the incidence of nausea and vomiting. After discharge, the recovery status was assessed. RESULTS: A total of 70 pediatric patients who met the criteria for day-case PDA ligation were included in this study. Before the occurrence of pneumothorax, the mean arterial pressure (MAP) of these 70 patients was 69.58 ± 12.52 mmHg, and during controlled hypotension, the MAP was 54.96 ± 11.23 mmHg. Before the occurrence of pneumothorax, the partial pressure of carbon dioxide (PaCO2) was 38.69 ± 3.38 mmHg, and during controlled hypotension, the PaCO2 was 51.42 ± 4.05 mmHg. Three cases experienced agitation during the recovery period, and four cases had mild pain, but there was no moderate or severe pain, nausea, or vomiting. Only 1 case of postoperative respiratory tract infection and 1 case of postoperative pneumothorax occurred. Within 30 days after discharge, the unplanned revisit rate, unplanned readmission rate, and surgical wound infection rate were all 0. The residual shunt rate detected by echocardiography was 0 after 1 month. CONCLUSIONS: The children under the robot-assisted thoracoscopic day case PDA surgeries in this study have limited trauma, little bleeding, and little postoperative pain, though still at a risk of respiratory infection and pneumothorax.

Application of laryngeal mask airway anesthesia with preserved spontaneous breathing in children undergoing video-assisted thoracic surgery.

Purpose: To investigate the feasibility and safety of non-intubated general anesthesia with spontaneous breathing combined with paravertebral nerve blocks (PVNB) in young children undergoing video-assisted thoracic surgery (VATS) and to determine its significance for rapid recovery after pediatric thoracic surgery. Methods: The data of 46 children aged 6-36 months with an American Society of Anesthesiologists status of I-II who underwent elective VATS under general anesthesia were retrospectively analyzed. Of these patients, 25 underwent non-intubated general anesthesia with spontaneous breathing combined with PVNB (non-intubation group), and 21 received conventional intubated general anesthesia combined with local infiltration anesthesia (intubation group). The following perioperative parameters were compared between the two groups: heart rate (HR), mean arterial pressure, saturation of pulse oximetry (SpO2), partial pressure end-tidal carbon dioxide, time from the completion of the operation to extubation or removing laryngeal masks, time to first feeding after the operation, length of postoperative in-hospital stay, incidence of postoperative complications, and hospitalization expenses. Results: The operations were completed successfully in both groups. When the non-intubation group was compared with the intubation group, the minimal SpO2 level during the surgery was higher (93% vs. 88%, P < 0.001), which might indicate better oxygenation. There was no significant difference of the duration of surgery and intraoperative blood loss between two groups. Compared to the intubation group, the duration of anesthesia (P = 0.027), time from the completion of the operation to extubation (P < 0.001), time to the first feeding after surgery (P < 0.001), and length of postoperative in-hospital stay (P < 0.001) were significantly reduced in the non-intubation group. The incidence of postoperative complications was not significantly different. Conclusions: Non-intubated general anesthesia with spontaneous breathing combined with PVNB is safe and feasible in young children undergoing VATS and can promote rapid recovery in young children undergoing thoracoscopic surgery.

Gut-Derived Exosomes Induce Liver Injury After Intestinal Ischemia/Reperfusion by Promoting Hepatic Macrophage Polarization.

Liver injury induced by intestinal ischemia/reperfusion (I/R) is accompanied by the polarization of Kupffer cells, which are specialized macrophages located in the liver. However, the causes of hepatic macrophage polarization after intestinal I/R remain unknown. This study investigated whether gut-derived exosomes contribute to the pathogenesis of liver injury triggered by intestinal I/R in a murine model and explored the underlying mechanisms. Intestinal I/R models were established by temporally clamping the superior mesenteric arteries of mice. Exosomes were isolated from the intestinal tissue of mice that underwent intestinal I/R or sham surgery according to a centrifugation-based protocol. Exosomes were co-cultured with RAW 264.7 macrophages or injected intravenously in mice. Liposomal clodronate was administered intraperitoneally to deplete the macrophages. Macrophage polarization was determined by flow cytometry, immunohistochemistry, and quantitative polymerase chain reaction. Liver injury was assessed by histological morphology and increased serum aspartate aminotransferase and alanine aminotransferase levels. Exosomes from mice intestines subjected to I/R (IR-Exo) promoted macrophage activation in vitro. Intravenous injection of IR-Exo caused hepatic M1 macrophage polarization and led to liver injury in mice. Depleting macrophages ameliorated liver injury caused by intestinal I/R or the injection of IR-Exo. Furthermore, inhibiting exosome release improved intestinal injury, liver function, and survival rates of mice subjected to intestinal I/R. Our study provides evidence that gut-derived exosomes induce liver injury after intestinal I/R by promoting hepatic M1 macrophage polarization. Inhibition of exosome secretion could be a therapeutic target for preventing hepatic impairment after intestinal I/R.

Synthesis of nanocapsules blended polymeric hydrogel loaded with bupivacaine drug delivery system for local anesthetics and pain management.

Local anesthetics are used clinically for the control of postoperative pain management. This study aimed to develop chitosan (CS) with genipin (GP) hydrogels as the hydrophilic lipid shell loaded poly(ε-caprolactone) (PC) nanocapsules as the hydrophobic polymeric core composites (CS-GP/PC) to deliver bupivacaine (BPV) for the prolongation of anesthesia and pain relief. The swelling ratio, in vitro degradation, and rheological properties enhancement of CS-GP/PC polymeric hydrogel. The incorporation of PC nanocapsules into CS-GP hydrogels was confirmed by SEM, FTIR, and XRD analysis. Scanning electron microscopy results demonstrated that the CS-GP hydrogels and CS-GP/PC polymeric hydrogels have a porous structure, the pore dimensions being non-uniform with diameters between 25 and 300 µm. The in vitro drug release profile of CS-GP/PC polymeric hydrogel has been achieved 99.2 ± 1.12% of BPV drug release in 36 h. Cellular viability was evaluated using the CCK-8 test on 3T3 fibroblast cells revealed that the obtained CS-GP/PC polymeric hydrogel with BPV exhibited no obvious cytotoxicity. The CS-GP/PC polymeric hydrogel loaded with BPV showed significant improvement in pain response compared to the control group animals for at least 7 days. When compared with BPV solution, CS-GP hydrogel and CS-GP/PC polymeric hydrogel improved the skin permeation of BPV 3-fold and 5-fold in 24 h, respectively. In vitro and in vivo results pointed out PC nanocapsules loaded CS-GP hydrogel can act as effective drug carriers, thus prolonging and enhancing the anesthetic effect of BPV. Histopathological results demonstrated the excellent biodegradability and biocompatibility of the BPV-loaded CS-GP/PC polymeric hydrogel system on 7, 14, and 21 days without neurotoxicity.HIGHLIGHTSPreparation and characterization of CS-GP/PC polymeric hydrogel system.BPV-loaded CS-GP/PC exhibited prolonged in vitro release in PBS solution.Cytotoxicity of BPV-loaded CS-GP/PC polymeric hydrogel against fibroblast (3T3) cells.Development of CS-GP/PC a promising skin drug-delivery system for local anesthetic BPV.

microRNA-124-3p attenuates myocardial injury in sepsis via modulating SP1/HDAC4/HIF-1α axis.

Sepsis-induced cardiac dysfunction can lead to death in sepsis. In this case, we targeted to explore in detail the relative mechanism of microRNA (miR)-124-3p in sepsis-induced myocardial injury via the specific protein 1/histone deacetylase 4/hypoxia-inducing factor 1α (SP1/HDAC4/HIF-1α) axis. Septic rats were modeled by cecal ligation puncture while in vitro septic cardiomyocyte H9C2 were induced by lipopolysaccharide (LPS). miR-124-3p/SP1/HDAC4/HIF-1α expression levels in myocardial tissues of septic rats and LPS-treated H9C2 cells were measured. miR-124-3p overexpression and SP1 silencing assays were implemented on LPS-treated H9C2 cells to explore theirs actions in inflammation, oxidative stress and cell apoptosis. The interactions of miR-124-3p, SP1, and HDAC4 were testified. miR-124-3p was lowly expressed while SP1, HDAC4, and HIF-1α were highly expressed in sepsis. Upregulation of miR-124-3p ameliorated inflammation, oxidative stress, and apoptosis of LPS-treated H9C2 cells. Silencing SP1 improved LPS-induced damage to cardiomyocytes. miR-124-3p targeted SP1 and HDAC4 interacted with SP1. SP1 overexpression antagonized miR-124-3p upregulation-induced improvements in LPS-induced cardiomyocyte damage. This study illustrates that miR-124-3p improves myocardial injury in septic rats through targeted regulation of SP1 to mediate HDAC4/HIF-1α.

Preoperative fasting confers protection against intestinal ischaemia/reperfusion injury by modulating gut microbiota and their metabolites in a mouse model.

BACKGROUND: Intestinal ischaemia/reperfusion (I/R) injury is a grave surgical event with high morbidity and mortality. Preoperative fasting might confer protection against intestinal I/R injury by altering the composition of gut microbiota and their respective metabolites. METHODS: An intestinal I/R mouse model was established and subjected to preoperative fasting for 24 h or fed ad libitum. Intestinal I/R injury was assessed using histological examination and survival analysis. Faecal samples were collected for 16S rDNA sequencing and metabolomic analysis. Faecal transplantation of fasted and non-fasted mice and humans was conducted to evaluate the effects of gut microbiota on intestinal I/R. Murine small intestinal cells wecre subjected to oxygen and glucose deprivation/reoxygenation as an in vitro I/R model. RESULTS: Preoperative fasting protected against intestinal I/R injury and improved survival in mice (P<0.001). In addition, 16S rDNA sequencing revealed that preoperative fasting increased the diversity and restructured the composition of the gut microbiota after intestinal I/R. Mice that received microbiota from fasted mice and humans showed less intestinal damage than those that received microbiota from fed subjects. Metabolomic analysis showed that the profiles of gut microbial metabolites differed between fasted and fed groups. Specifically, the concentration of petroselinic acid was significantly higher in the fasted group (P=0.009). Treatment of intestinal I/R mice with petroselinic acid alleviated intestinal injury in vivo and decreased cell apoptosis by mediating AMP-activated protein kinase-mammalian target of rapamycin-P70S6K signaling in vitro. CONCLUSIONS: Preoperative fasting protected against intestinal I/R injury by modulating gut microbiota and petroselinic acid, suggesting a novel therapeutic strategy.

The Characteristics and Distribution of Nerve Plexuses in the Dartos Fascia From Concealed Penis Children.

The purpose of this study is to analyze the nerve plexus distribution in dartos fascia of concealed penis (CP). A total of 28 CP patients met ASA categories I and II were included, with median age of 3.5 years (8 months-5 years). During the surgery, tissue samples of dartos fascia at points 3, 6, 9, and 12 o'clock of the penile shaft were collected. Standard hematoxylin and eosin (H&E) staining and S-100 immunohistochemical staining were used to analyze the nerve plexus distribution among different positions. The number of nerve plexuses in superficial fascia collected at the 6 o'clock position of the penile shaft was the most abundant among four positions (median 7.25, range 1-24). The abundant nerve plexuses in the dartos fascia of CP patients, especially at the 6 o'clock position, indicate that the surgery on the preputial frenulum should avoid damage to the dartos fascia, as it might be related to maintain the erection and sexual function in adolescence.

Exploring the mechanism of PingTang No.5 capsule on nonalcoholic fatty liver disease through network pharmacology and experimental validation.

PingTang No.5 capsule (PT5), a modified Traditional Chinese Medicine (TCM) formula of Zexie Decoction, is used to treat patients with lipid metabolism disorders in our hospital. The present study was designed to investigate the mechanisms of PT5 in treating non-alcoholic fatty liver disease (NAFLD). PT5 information including ingredients, pharmacological properties, and potential targets was obtained from TCM databases. The candidate targets of PT5 were predicted by network pharmacological analysis, and the possible pathway and mechanism were obtained from DAVID database, followed by experimental validation in NAFLD mice model treated with PT5. Total 328 compounds were selected using the threshold oral bioactivity (OB) > 30% or drug-likeness (DL) > 0.1 of pharmacology characteristic, and 1033 candidate targets obtained to construct the network analysis. The 113 targets were selected from the intersection between candidate targets of PT5 and NAFLD relative gene. These targets were evaluated in diabetic complications, cancer, Hepatitis B, Fluid shear stress and atherosclerosis, and TNF signaling pathway. TNF-α was the important factor in protein interaction analysis of STRING and involved in the lipid regulation and oxidative stress in NAFLD. When administrated to the NAFLD mice, PT5 reduced weight, blood fatty acids, decreased the adipocyte size, and improved the metabolism. Besides, the molecular verification of lipid metabolism increased and oxidative stress reduced that interpreted the mechanism of PT5 preventing liver cell from lipid accumulation and injury of NAFLD. These results presented PT5 have the potential therapy as an alternative treatment for NAFLD.

Effect of nalbuphine on rocuronium injection pain.

Objective: Rocuronium-associated intravenous injection pain occurs frequently in children during induction of anesthesia. The aim of this study was to systematically evaluate the benefits of nalbuphine in patients with rocuronium-associated injection pain. Methods: Ninety children undergoing tonsillectomy and adenoidectomy in our hospital between October 2019 and September 2020 were randomly divided into the following groups, with 30 patients per group: control group (group C), lidocaine group (group L), and nalbuphine group (group N). Routine 0.1 mg/kg midazolam and 2 mg/kg propofol were injected intravenously. After sedation, children in group C, group L, and group N were administered an intravenous injection of saline, lidocaine (10 mg/mL), or nalbuphine hydrochloride (2 mg/mL), respectively, at a dosage of 0.1 mL/kg. Intravenous injection of rocuronium stock solution (0.6 mg/kg) was administered 2 minutes later. Pain was evaluated using Ambeshs 4-pointscale. The incidence of rocuronium injection pain was compared among the three groups, and postoperative adverse reactions, such as drowsiness, bradycardia, hypotension, and respiratory depression, were evaluated. Results: The incidence of injection pain among children in group N was significantly lower than that in group C and group L (p<0.05). The incidence of drowsiness in group N was significantly higher than that in the other groups (p<0.05). The incidences of hypotension, bradycardia, and respiratory depression were not significantly different among the three groups (p>0.05). Conclusions: Intravenous nalbuphine during induction of anesthesia effectively prevented rocuronium-associated injection pain in children. Drowsiness is a complication.

Isolation of extracellular vesicles from intestinal tissue in a mouse model of intestinal ischemia/reperfusion injury.

Extracellular vesicles (EVs) are small membranous particles that contribute to intercellular communications. Separating EVs from tissue is still a technical challenge. Here, we present a rigorous method for extracting EVs from intestinal tissue in a mouse intestinal ischemia/reperfusion (I/R) model, and for analyzing their miRNA content. The isolated EVs show a typical cup shape with a size peak of 120-130 nm in diameter, confirmed by TEM and NTA. They also express EV markers such as CD9, CD63, CD81, Tsg101 and Alix. Real-time qPCR confirmed that these pellets contain miRNAs related to I/R injury. Our study presents a practical way to isolate EVs from intestinal tissue which is suitable for downstream applications such as miRNA analysis, and provides a novel method for investigating the mechanism of intestinal I/R injury.

Recommendation about the perioperative prevention of infection to healthcare workers and the anesthesia management of children with SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely and persistently over 100 countries. New challenges have occurred in the perioperative management of airway and anesthesia in children diagnosed with SARS-CoV-2 infection. According to current publications and to our own experiences in anesthesia management for cases with SARS-CoV-2 suspected, we reviewed concerns about the perioperative prevention of SARS-CoV-2 to medical staff and the anesthesia strategy to the patient.

Danggui Sini Decoction Protected Islet Endothelial Cell Survival from Hypoxic Damage via PI3K/Akt/eNOS Pathway.

Danggui Sini decoction (DSD) is a traditional Chinese decoction, which is wildly applied and showed to be effective in ameliorating ischemia-related symptoms. However, the mechanisms of DSD action in ischemic damage remain to be fully clarified. Pancreatic islet endothelial cells are pivotal constituent of islet microvasculature, with high vulnerability to hypoxic injuries. Here, using MST1 cell, a pancreatic islet endothelial cell-line, as a model, we investigated the effects of DSD on hypoxia-stimulated endothelial cell lesions and its underlying mechanisms. We found that DSD-Containing Serum (DSD-CS), collected from DSD-treated rats, could efficiently protect MST1 survival and proliferation from Cobalt chloride (CoCl2) induced damage, including cell viability, proliferation, and tube formation. Furthermore, DSD-CS restored the activity of PI3K/Akt/eNOS signaling inhibited by CoCl2 in MST1 cells. The protective effect of DSD-CS could be blocked by the specific PI3K/Akt/eNOS inhibitor LY294002, suggesting that DSD-CS protection of MST1 cell survival from hypoxia was mediated by PI3K/Akt/eNOS pathway. In conclusion, DSD treatment protected MST1 survival from hypoxic injuries via PI3K/Akt/eNOS pathway, indicating its role in protecting microvascular endothelial cells.

Application of end-tidal carbon dioxide monitoring via distal gas samples in ventilated neonates.

BACKGROUND: Previous research has suggested correlations between the end-tidal partial pressure of carbon dioxide (PETCO2) and the partial pressure of arterial carbon dioxide (PaCO2) in mechanically ventilated patients, but both the relationship between PETCO2 and PaCO2 and whether PETCO2 accurately reflects PaCO2 in neonates and infants are still controversial. This study evaluated remote sampling of PETCO2 via an epidural catheter within an endotracheal tube to determine the procedure's clinical safety and efficacy in the perioperative management of neonates. METHODS: Abdominal surgery was performed under general anesthesia in 86 full-term newborns (age 1-30 days, weight 2.55-4.0 kg, American Society of Anesthesiologists class I or II). The infants were divided into 2 groups (n = 43 each), and carbon dioxide (CO2) gas samples were collected either from the conventional position (the proximal end) or a modified position (the distal end) of the epidural catheter. RESULTS: The PETCO2 measured with the new method was significantly higher than that measured with the traditional method, and the difference between PETCO2 and PaCO2 was also reduced. The accuracy of PETCO2 measured increased from 78.7% to 91.5% when the modified sampling method was used. The moderate correlation between PETCO2 and PaCO2 by traditional measurement was 0.596, which significantly increased to 0.960 in the modified sampling group. Thus, the PETCO2 value was closer to that of PaCO2. CONCLUSION: PETCO2 detected via modified carbon dioxide monitoring had a better accuracy and correlation with PaCO2 in neonates.

Establishment of a reference interval for high-sensitivity cardiac troponin I in healthy adults from the Sichuan area.

High-sensitivity cardiac troponin I (hs-cTnI) has been used in the diagnosis and risk stratification of acute myocardial infarction. However, there is no common consensus on an hs-cTnI reference interval for the Chinese population. The aim of this study was to describe the distribution of hs-TnI and establish the 99th percentile reference interval for hs-cTnI in healthy adults from the Sichuan area.Serum specimens were collected from 1485 healthy adults (731 men and 754 women ranging in age from 18 to 85 years) in Sichuan Provincial People's Hospital. All specimens were divided into 4 groups according to age distribution: 18 to 35 years, 36 to 50 years, 51 to 65 years, and ≥66 years. Specimens were further divided into younger/middle and older-aged groups based on a cut-off age of 50 years. The serum hs-cTnI concentration was determined using the Abbott ARCHITECT STAT hs-cTnI assay.The serum hs-cTnI concentration increased with age (P < 0.05). The 99th percentiles of hsTnI were 28.0 pg/mL among the whole population, 31.1 pg/mL among men, and 22.7 pg/mL among women. The age-dependent 99th percentiles of hs-cTnI in men and women were as follows: 28.8 versus 12.5 pg/mL for 18 to 35 years, 20.4 versus 9.2 pg/mL for 36 to 50 years, 24.2 versus 13.6 pg/mL for 51 to 65 years, and 27.9 versus 32.2 pg/mL for ≥66 years.The 99th percentile reference interval for hs-cTnI in healthy adults from the Sichuan area was similar to the manufacturer's recommendation. Men had a higher 99th percentile hs-cTnI value than women in the age range of 18 to 65 years.

Xanthohumol isolated from Humulus lupulus prevents thrombosis without increased bleeding risk by inhibiting platelet activation and mtDNA release.

AIM: As the global population has reached 7 billion and the baby boom generation reaches old age, thrombosis has become the major contributor to the global disease burden. It has been reported that, in moderate doses, beer may protect against thrombosis. Xanthohumol (XN), an antioxidant, is found at high concentrations in hop cones (Humulus lupulus L.) and is a common ingredient of beer. Here, the aim of the present work was to investigate the effects of XN on antithrombotic and antiplatelet activities, and study its mechanism. APPROACH AND RESULTS: Using ferric chloride-induced carotid artery injury, inferior vena cava ligation model, and platelet function tests, we demonstrated that XN uniquely prevents both venous and arterial thrombosis by inhibiting platelet activation. Interestingly, in tail bleeding time studies, XN did not increase bleeding risk, which is recognized as a major limitation of current antithrombotic therapies. We also demonstrated that XN induces Sirt1 expression and thereby decreases reactive oxygen species (ROS) overload, prevents mitochondrial dysfunction, and reduces activated platelet-induced mitochondrial hyperpolarization, respiratory disorders, and associated membrane damage at low concentrations. In mitochondrial function assays designed to detect amounts of extracellular mitochondrial DNA (mtDNA), we found that XN prevents mtDNA release, which induces platelet activation in a DC-SIGN-dependent manner. CONCLUSIONS: XN exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing ROS accumulation and platelet mtDNA release without incurring a bleeding risk. This study has also provided novel insights into mechanisms of thrombotic diseases with possible therapeutic implications.

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release.

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

SCCmec-associated psm-mec mRNA promotes Staphylococcus epidermidis biofilm formation.

Biofilm formation is considered the major pathogenic mechanism of Staphylococcus epidermidis-associated nosocomial infections. Reports have shown that SCCmec-associated psm-mec regulated methicillin-resistant Staphylococcus aureus virulence and biofilm formation. However, the role of psm-mec in S. epidermidis remains unclear. To this purpose, we analysed 165 clinical isolates of S. epidermidis to study the distribution, mutation and expression of psm-mec and the relationship between this gene and biofilm formation. Next, we constructed three psm-mec deletion mutants, one psm-mec transgene expression strain (p221) and two psm-mec point mutant strains (pM, pAG) to explore its effects on S. epidermidis biofilm formation. Then, the amount of biofilm formation, extracellular DNA (eDNA) and Triton X-100-induced autolysis of the constructed strains was measured. Results of psm-mec deletion and transgene expression showed that the gene regulated S. epidermidis biofilm formation. Compared with the control strains, the ability to form biofilm, Triton X-100-induced autolysis and the amount of eDNA increased in the p221 strain and the two psm-mec mutants pM and pAG expressed psm-mec mRNA without its protein, whereas no differences were observed among the three constructed strains, illustrating that psm-mec mRNA promoted S. epidermidis biofilm formation through up-regulation of bacterial autolysis and the release of eDNA. Our results reveal that acquisition of psm-mec promotes S. epidermidis biofilm formation.

Effects of Heart Bypass Surgery on Plasma Aß40 and Aß42 Levels in Infants and Young Children.

Accumulation of ß-amyloid (Aß) plaques is a pathological hallmark of Alzheimer disease. Aß levels in animals and adults were reported to be associated with postoperative cognitive dysfunction (POCD). Our goal was to determine the plasma levels of Aß in infants and young children after cardiac surgery with cardiopulmonary bypass (CPB).Forty-two infants and young children aged from 1 to 35 months undergoing cardiac surgery with general anesthetics were prospectively enrolled from January to June 2014 at a tertiary medical center. Perioperative plasma samples were obtained, and Aß42 and Aß40 levels were measured using ELISA. Other clinical characteristics of the patients were also recorded.Plasma levels of Aß42 and Aß40 decreased dramatically 2 hours after surgery and remained significantly lower 6 hours after operation. Baseline Aß42 level correlated significantly with surgical intensive care unit (SICU) length of stay (LOS) and was an independent predictor for SICU LOS on multivariate analysis.Cardiac surgery with CPB decreases plasma Aß levels. Plasma levels of Aß42 and Aß40 might be used as novel biomarkers for predicting outcomes in the patient population.