ObjectiveTo investigate the role of CD4+ CD25+ regulatory T cells(Treg) in peripheral blood and intestinal endotoxin (ET) in liver injury of rat severe acute pancreatitis (SAP).MethodsSixty male Wistar rats were randomly allocated into sham operation group(SO group) and severe acute pancreatitis group(SAP group).The rats in SAP group recevied the injection of Sodium Taurocholate(NaTc) into their far-end of bile-pancreatic duct and were sacrificed in 3-,6-and 12-hour,serum amylase(AMY) and alanine aminotransferase(ALT) determined by full-automatic biochemistry instrument,limulus reagent method is used to determine ET content in plasma,the proportion of Treg among peripheral lymphocytes was determined by Flow Cytometry(FCM),HE stain is used to observe pathological changes in liver and pancreas,the protein of Foxp3 activity was evaluated by immunohistochemistry staining,and the relationships between these indicators were analyzed using Pearson correlation analysis test.ResultsHistopathologic examination and the level of ALT revealed the occurrence of pancreatic inflammation and pathological changes of liver in SAP group.The percentage of Treg in SAP groups significantly increased at 3 h(2.26％ ±0.32％),6 h(2.36 ％ ±0.48％)and 12 h(2.80％ ±0.35％) comparing to the SO groups(P＜0.01) ; plasma ET levels compared with the SO group was statistically significant (P＜ 0,01 ),and 12 h (0.85 ± 0.11) compared to,3 h (0.74±0.11) and 6 h (0.78-±-0.07) was no significant difference (P＞0.05).The expression of Foxp3 protein on the livers were upregulated markedly.Pearson correlation analysis teat showed that quantities of Treg were positively proportional to the levels of ET(r=0.89,P＜0.01) after liver injury of SAP.ConclusionsSAP may lead to liver injury and the high plasma levels of ET and Treg in peripheral blood may play an important role in liver injury of SAP.

The leading cause of drug withdrawal from market and clinical trials failure is drug-induced liver injury (DILI). Varying clinical, histological and laboratory features of DILI, as well as undefined underlying mechanisms, hinder patients to be diagnosed in the early-stage of the disease and receive effective treatments. Conventional indicators, like serum transaminases and bilirubin, have inevitable limitations referring to sensitive prediction and specific detection of DILI. In order to reduce the occurrence of DILI, researchers have attempted to discover potential biomarkers with higher specificity and sensitivity from blood and urine in recent years. This article aims to review recent advances in biomarkers of DILI.

In order to detect endoleaks after endovascular aneurysm repair (EVAR), we developed an implantable micro-device based on wireless power transmission to measure aortic aneurysm sac pressure. The implantable micro-device is composed of a miniature wireless pressure sensor, an energy transmitting coil, a data recorder and a data processing platform. Power transmission without interconnecting wires is performed by a transmitting coil and a receiving coil. The coupling efficiency of wireless power transmission depends on the coupling coefficient between the transmitting coil and the receiving coil. With theoretical analysis and experimental study, we optimized the geometry of the receiving coil to increase the coupling coefficient. In order to keep efficiency balance and satisfy the maximizing conditions, we designed a closed loop power transmission circuit, including a receiving voltage feedback module based on wireless communication. The closed loop improved the stability and reliability of transmission energy. The prototype of the micro-device has been developed and the experiment has been performed. The experiments showed that the micro-device was feasible and valid. For normal operation, the distance between the transmitting coil and the receiving coil is smaller than 8cm. Besides, the distance between the micro-device and the data recorder is within 50cm.
Aortic Aneurysm, Abdominal ; physiopathology ; surgery ; Blood Pressure Monitors ; Equipment Design ; Humans ; Monitoring, Ambulatory ; instrumentation ; Postoperative Care ; instrumentation ; methods ; Prostheses and Implants ; Wireless Technology ; instrumentation

Objective:To investigate the roles of T helper 17(Th17)cells and regulatory T(Treg)cells, interleukin(IL)-17 levels, and IL-6 levels in the pathogenesis of Henoch-Schonlein purpura(HSP)complicated with Helicobacter pylori(HP)infection in children. Methods:Children diagnosed with acute HSP and/or HP infection by the Department of Pediatrics, Xiamen Maternal and Child Health Care Hospital from January 2017 to December 2018 were enrolled in the study.There were 15 children with HSP complicated with HP infection(HSP-HP group), 26 children with HSP(HSP group), and 21 children with HP infection(HP group). Twenty healthy children of the same age over the same period were included in the healthy control group.The proportions of Th17 cells and Treg cells were tes-ted by flow cytometry(FCM), and concentrations of IL-17 and IL-6 in plasma were measured by enzyme linked immunosorbent assay(ELISA).Results:(1)Compared with that of the healthy control group [(1.42±0.63)%], the proportion of Th17 cells in the HSP-HP group, HSP group and HP group [(2.79±0.78)%, (2.04±0.77)%, (2.08±0.86)%] was significantly increased( F=5.271, P<0.05). The levels of IL-17 and IL-6 in the HSP-HP group [(552.16±121.13) ng/L and (12.36±6.55) ng/L], HSP group [(506.39±113.62) ng/L and(11.82±5.01) ng/L] and HP group [(483.14±121.77) ng/L and (10.19±3.87) ng/L] were significantly higher than those in the healthy control group [(302.96±82.83) ng/L and (7.81±2.04) ng/L]( F=13.113, 6.692, all P<0.01). The proportion of Treg cells in the HSP-HP group [(1.35±0.49)%], HSP group [(1.13±0.86)%] and HP group [(1.09±0.65)%] was significantly lower than that in the healthy control group [(2.31±0.83)%]( F=6.983, P<0.05). (2)The proportion of Th17 cells and the level of IL-17 in the HSP-HP group were significantly higher than those in the HSP and HP groups(all P<0.05). There was no significant difference in the proportion of Th17 cells and the level of IL-17 between the HSP group and HP group(all P>0.05). There was no significant difference in the proportion of Treg cells and the level of IL-6 among the HSP-HP group, HSP group, and HP group(all P>0.05). Conclusions:The imbalance of Th17/Treg cells in peripheral blood may contribute to the development of HSP-HP, HSP and HP infection in children.High expression of Th17 cells and their related IL-17 is more prominent in children with HSP-HP.

Objective To understand the changing resistance proifle ofProteus,Serratia,Citrobacter,Morganella andProvidencia in hospitals across China according to the data from CHINET Antimicrobial Resistance Surveillance Program 2005-2014.Methods Antimicrobial susceptibility was tested by using Kirby-Bauer method or automatic minimum inhibitory concentration determination according to a uniifed protocol.Results A total of 21 663 clinical isolates were collected from January 2005 to December 2014. The proportion ofProteus andSerratia isolates increased with time from 1.41% in 2005 to 2.09% in 2014, and from 0.99% in 2005 to 1.28% in 2014 among all the isolates. No change was found for the proportion ofCitrobacter,Morganella, orProvidencia. Less than 10% of theProteus isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, ceftazidime, cefoxitin, amikacin and tigecycline. Less than 10% of theSerratia isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, amikacin and tigecycline. Less than 20% of theCitrobacter isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, amikacin and tigecycline. Less than 10% of theMorganella isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, amikacin and tigecycline. Less than 20% of theProvidencia isolates were resistant to cefoperazone-sulbactam, piperacillin-tazobactam, cefepime, cefoxitin and tigecycline.Conclusions The antibiotic resistance ofProteus,Serratia, Citrobacter,Morganella andProvidencia isolates in hospitals across China is growing during the period from 2005 to 2014. Strengthening infection control and rational antibiotic use are effective to slow the growth of drug resistance.

Traumatic brain injury (TBI)-induced coagulopathy has increasingly been recognized as a significant risk factor for poor outcomes, but the pathogenesis remains poorly understood. In this study, we aimed to investigate the causal role of acrolein, a typical lipid peroxidation product, in TBI-induced coagulopathy, and further explore the underlying molecular mechanisms. We found that the level of plasma acrolein in TBI patients suffering from coagulopathy was higher than that in those without coagulopathy. Using a controlled cortical impact mouse model, we demonstrated that the acrolein scavenger phenelzine prevented TBI-induced coagulopathy and recombinant ADAMTS-13 prevented acrolein-induced coagulopathy by cleaving von Willebrand factor (VWF). Our results showed that acrolein may contribute to an early hypercoagulable state after TBI by regulating VWF secretion. mRNA sequencing (mRNA-seq) and transcriptome analysis indicated that acrolein over-activated autophagy, and subsequent experiments revealed that acrolein activated autophagy partly by regulating the Akt/mTOR pathway. In addition, we demonstrated that acrolein was produced in the perilesional cortex, affected endothelial cell integrity, and disrupted the blood-brain barrier. In conclusion, in this study we uncovered a novel pro-coagulant effect of acrolein that may contribute to TBI-induced coagulopathy and vascular leakage, providing an alternative therapeutic target.

Traumatic brain injury (TBI) triggers the activation of the endogenous coagulation mechanism, and a large amount of thrombin is released to curb uncontrollable bleeding through thrombin receptors, also known as protease-activated receptors (PARs). However, thrombin is one of the most critical factors in secondary brain injury. Thus, the PARs may be effective targets against hemorrhagic brain injury. Since the PAR1 antagonist has an increased bleeding risk in clinical practice, PAR4 blockade has been suggested as a more promising treatment. Here, we explored the expression pattern of PAR4 in the brain of mice after TBI, and explored the effect and possible mechanism of BMS-986120 (BMS), a novel selective and reversible PAR4 antagonist on secondary brain injury. Treatment with BMS protected against TBI in mice. mRNA-seq analysis, Western blot, and qRT-PCR verification in vitro showed that BMS significantly inhibited thrombin-induced inflammation in astrocytes, and suggested that the Tab2/ERK/NF-κB signaling pathway plays a key role in this process. Our findings provide reliable evidence that blocking PAR4 is a safe and effective intervention for TBI, and suggest that BMS has a potential clinical application in the management of TBI.

Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.

ObjectiveTo investigate the anti-convulsant activity of goat horn and its effect on the main neurotransmitters in the brain of model mice. MethodA total of 120 mice were randomly divided into a blank group，a model group，a positive drug group （estazolam， 1 mg·kg^-1）， a Saigae Tataricae Cornu （STC， 0.2 g·kg^-1） group， and low- （1.25 g·kg^-1） and high-dose （2.5 g·kg^-1） goat horn groups. Drugs were administered by gavage once at 10 mL·kg^-1. Those in the blank group and the model group were given the same volume of 0.2% sodium carboxymethyl cellulose （CMC-Na）. The mice underwent threshold electrical stimulation once 2 h after administration. Ankylosing convulsion in the hind limbs of mice was used as the index to calculate the recovery period， convulsion rate， and mortality of ankylosing convulsion. Ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） was established to analyze the changes in the content of the main neurotransmitters in the brain tissues of mice. ResultTwo hours after intragastric administration of goat horn powder to mice， the recovery period of convulsion could be shortened and the convulsion rate and mortality were reduced （P<0.05）. In terms of anti-convulsant effect， the groups were ranked as follows： high-dose goat horn group > STC group > low-dose goat horn group. UPLC-MS/MS analysis showed that compared with the results in the model group， goat horn powder and STC decreased the content of glutamic acid and aspartic acid （P<0.05） and increased the content of glycine， γ-aminobutyric acid， and 5-hydroxytryptamine （P<0.05）. ConclusionThe results showed that goat horn had a significant anti-convulsant effect on the electroshock-induced convulsion mouse model， and the underlying mechanism was presumably attributed to the improvement of the development of convulsion by regulating the changes in neurotransmitter content in brain tissues.