BACKGROUND:Although the mechanisms and pathways mediating ARDS have been studied extensively, less attention has been given to the mechanisms and pathways that counteract injury responses. This study ...found that the apelin-APJ pathway is an endogenous counterinjury mechanism that protects against ARDS. METHODS:Using a rat model of oleic acid (OA)-induced ARDS, the effects of ARDS on apelin and APJ receptor expressions and on APJ receptor binding capacity were examined. The protective effect of activating the apelin-APJ pathway against OA- or lipopolysaccharide (LPS)-induced ARDS was evaluated. RESULTS:ARDS was coupled to upregulations of the apelin and APJ receptor. Rats with OA-induced ARDS had higher lung tissue levels of apelin proprotein and APJ receptor expressions; elevated plasma, BAL fluid (BALF), and lung tissue levels of apelin-36 and apelin-12/13; and an increased apelin-APJ receptor binding capacity. Upregulation of the apelin-APJ system has important pathophysiologic function. Stimulation of the apelin-APJ signaling using receptor agonist apelin-13 alleviated, whereas inhibition of the apelin-APJ signaling using receptor antagonist Ala-apelin-13 exacerbated, OA-induced lung pathologies, extravascular lung water accumulation, capillary-alveolar leakage, and hypoxemia. The APJ receptor agonist inhibited, and the APJ receptor antagonist augmented, OA-induced lung tissue and BALF levels of tumor necrosis factor-α and monocyte chemoattractant protein-1, and plasma and lung tissue levels of malondialdehyde. Postinjury treatment with apelin-13 alleviated lung inflammation and injury and improved oxygenation in OA- and LPS-induced lung injury. CONCLUSIONS:The apelin-APJ signaling pathway is an endogenous anti-injury and organ-protective mechanism that is activated during ARDS to counteract the injury response and to prevent uncontrolled lung injury.
Background Pancreatic fistula (PF) is the most common significant complication after pancreaticoduodenectomy. Invagination and duct-to-mucosa anastomoses are anastomotic techniques that are commonly ...performed after pancreaticoduodenectomy. There are conflicting data on invagination vs duct-to-mucosa anastomoses about which is superior for minimizing the risk of PF. In addition, all previous studies involved multiple operating surgeons and failed to control for variation in surgeon expertise. Study Design This was a randomized controlled study comparing the outcomes of PD between patients who underwent invagination vs those who had duct-to-mucosa anastomoses. All 132 patients were operated on between October 2012 and March 2015 by a single surgeon experienced in both procedures. Pancreatic fistula was the main end point. Results Overall and clinically relevant rates of PF rate were 29.5% and 10.6%, respectively. Overall PF rates in the patients treated with invagination vs duct-to-mucosa anastomoses were 30.9% vs 28.5% (p = 0.729), respectively and the corresponding clinically relevant PF rates were 17.6% vs 3.1%, respectively (p = 0.004). Although the overall complication rates were similar in the 2 groups, severe complications were significantly more frequent in the patients treated with invagination (p = 0.013). Duct-to-mucosa anastomosis was also associated with shorter postoperative hospital stay (13 vs 15 days; p = 0.021). There was one perioperative death. Independent variables for the risk of PF were the diameter of the pancreatic duct (greater risk with smaller diameter), the underlying pathology, and male sex. Conclusions Both methods yield similar overall rates for PF, but the rate of clinically relevant PF is lower in patients treated with duct-to-mucosa anastomosis. Additional single-surgeon studies or multi-institution randomized trials controlling for comparable expertise in both procedures should be conducted to confirm these results.
Tubular adenoma of common bile duct (CBD) is an extremely rare benign extrahepatic bile duct adenoma. We report a case of surgery and histopathological proved CBD tubular adenoma. A 69-year-old man ...was admitted to the hospital for yellow urine for one month. Clinical, radiological and laboratory results were analyzed. Medical literature in PubMed pertaining to similar cases was reviewed. A solid mass was detected in the distant part of CBD, with dilation of the extrahepatic and intrahepatic bile duct by ultrasound, contrast enhanced ultrasound (CEUS), computer tomography (CT) and magnetic resonance imaging (MRI). It showed heterogeneous enhancement both in contrast-enhanced CT, MRI and CEUS. After operation, pathological findings indicated a tubular adenoma of CBD. Our case highlighted the fact that tubular adenoma of CBD was demonstrated as a homogeneous mass in the distant part of CBD.
Abstract Background Neuroinflammation has been proven to play a crucial role in early brain injury pathogenesis and represents a target for treatment of subarachnoid hemorrhage (SAH). Astaxanthin ...(ATX), a dietary carotenoid, has been shown to have powerful anti-inflammation property in various models of tissue injury. However, the potential effects of ATX on neuroinflammation in SAH remain uninvestigated. The goal of this study was to investigate the protective effects of ATX on neuroinflammation in a rat prechiasmatic cistern SAH model. Methods Rats were randomly distributed into multiple groups undergoing the sham surgery or SAH procedures, and ATX (25 mg/kg or 75 mg/kg) or equal volume of vehicle was given by oral gavage at 30 min after SAH. All rats were sacrificed at 24 h after SAH. Neurologic scores, brain water content, blood–brain barrier permeability, and neuronal cell death were examined. Brain inflammation was evaluated by means of expression changes in myeloperoxidase, cytokines (interleukin-1β, tumor necrosis factor-α), adhesion molecules (intercellular adhesion molecule-1), and nuclear factor kappa B DNA-binding activity. Results Our data indicated that post-SAH treatment with high dose of ATX could significantly downregulate the increased nuclear factor kappa B activity and the expression of inflammatory cytokines and intercellular adhesion molecule-1 in both messenger RNA transcription and protein synthesis. Moreover, these beneficial effects lead to the amelioration of the secondary brain injury cascades including cerebral edema, blood–brain barrier disruption, neurological dysfunction, and neuronal degeneration. Conclusions These results indicate that ATX treatment is neuroprotective against SAH, possibly through suppression of cerebral inflammation.
To investigate the role of miR-20a in hepatocellular carcinoma (HCC) cell radioresistance, which may reveal potential strategies to improve treatment.
The expression of miR-20a and PTEN were detected ...in HCC cell lines and paired primary tissues by quantitative real-time polymerase chain reaction. Cell radiation combined with colony formation assays was administrated to discover the effect of miR-20a on radiosensitivity. Bioinformatics prediction and luciferase assay were used to identify the target of miR-20a. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit phosphorylation of Akt, to verify whether miR-20a affects HCC cell radioresistance through activating the PTEN/PI3K/Akt pathway.
MiR-20a levels were increased in HCC cell lines and tissues, whereas PTEN was inversely correlated with it. Overexpression of miR-20a in Bel-7402 and SMMC-7721 cells enhances their resistance to the effect of ionizing radiation, and the inhibition of miR-20a in HCCLM3 and QGY-7701 cells sensitizes them to it. PTEN was identified as a direct functional target of miR-20a for the induction of radioresistance. Overexpression of miR-20a activated the PTEN/PI3K/Akt signaling pathway. Additionally, the kinase inhibitor LY294002 could reverse the effect of miR-20a-induced radioresistance.
MiR-20a induces HCC cell radioresistance by activating the PTEN/PI3K/Akt pathway, which suggests that miR-20a/PTEN/PI3K/Akt might represent a target of investigation for developing effective therapeutic strategies against HCC.
Abstract A prospective study was carried out to analyze the characteristics of hidden blood loss after total hip arthroplasty (THA) in a series of 1232 patients. The method of deducting the observed ...perioperative blood loss from the calculated total blood loss based on hematocrit changes was used to calculate the hidden blood loss of each patient. The reinfused and transfused bloods were also considered. We found that the amount of hidden blood loss after THA was much larger than we observed perioperatively and significantly different between differently diagnosed patients. We concluded that THA can cause a large amount of hidden blood loss, which should be monitored carefully. Retaining and repairing the articular capsule is recommended during the operation, which can significantly decrease hidden blood loss.
Objectives: To investigate the dosimetric advantages of the voluntary deep inspiration breath-hold technique assisted by optical surface monitoring system for whole breast irradiation in left breast ...cancer after breast-conserving surgery and verify the reproducibility and acceptability of this technique. Methods: Twenty patients with left breast cancer receiving whole breast irradiation after breast-conserving surgery were enrolled in this prospective phase II study. Computed tomography simulation was performed during both free breathing and voluntary deep inspiration breath-hold for all patients. Whole breast irradiation plans were designed, and the volumes and doses of the heart, left anterior descending coronary artery, and lung were compared between free breathing and voluntary deep inspiration breath-hold. Cone beam computed tomography was performed for the first 3 treatments, then weekly during voluntary deep inspiration breath-hold treatment to evaluate the accuracy of the optical surface monitoring system technique. The acceptance of this technique was evaluated with in-house questionnaires completed by patients and radiotherapists. Results: The median age was 45 (27-63) years. All patients received hypofractionated whole breast irradiation using intensity-modulated radiation therapy up to a total dose of 43.5 Gy/2.9 Gy/15f. Seventeen of the 20 patients received concomitant tumor bed boost to a total dose of 49.5 Gy/3.3 Gy/15f. Voluntary deep inspiration breath-hold showed a significant decrease in the heart mean dose (262 ± 163 cGy vs 515 ± 216 cGy, P < .001) and left anterior descending coronary artery (1191 ± 827 cGy vs 1794 ± 833 cGy, P < .001). The median delivery time of radiotherapy was 4 (1.5-11) min. The median deep breathing cycles were 4 (2-9) times. The average score for acceptance of voluntary deep inspiration breath-hold by patients and radiotherapists was 8.7 ± 0.9 (out of 12) and 10.6 ± 3.2 (out of 15), respectively, indicating good acceptance by both. Conclusions: The voluntary deep inspiration breath-hold technique for whole breast irradiation after breast-conserving surgery in patients with left breast cancer significantly reduces the cardiopulmonary dose. Optical surface monitoring system–assisted voluntary deep inspiration breath-hold is reproducible and feasible and showed good acceptance by both patients and radiotherapists.
Abstract Background Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone ...marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear. Methods In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H2 O2 was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells. Results The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H2 O2 . In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection. Conclusions These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway.
Background Bile duct microenvironment plays key roles in cholangiolithiasis occurrence. Sphincter of Oddi laxity (SOL) is associated with cholangiolithiasis, probably due to enhanced reflux of ...intestinal contents that changes the microenvironment. However, the microenvironment has not been comprehensively investigated. Study Design Patients with cholangiolithiasis were consecutively recruited and their bile was collected intraoperatively for high-throughput experiments. Pyrosequencing of 16S ribosomal RNA gene was performed to characterize the microbiota in the bile. A liquid chromatography-mass spectrometry-based method was used to profile bile composition. Clinical manifestation, microbiome, and bile composition were compared between patients with and without SOL. Results 18 patients with SOL and 27 patients without SOL were finally included. Patients with SOL showed severer inflammation. Bacteria in the bile duct were overwhelmingly aerobes and facultative anaerobes. Proteobacteria and Firmicutes were the most widespread phylotypes, especially Enterobacteriaceae . Compared with those without SOL, patients with SOL possessed more varied microbiota. In the SOL group, pathobionts, such as Bilophila and Shewanella algae had richer communities while harmless bacteria were reduced. Metabolomics analysis showed the differences in bile composition between groups were mainly distributed in lipids and bile acids. Particularly, the increased abundance of Bilophila involved in taurine metabolism was associated with reduced contents of taurine derivatives in the bile of patients with SOL. Conclusions A bile duct microenvironment with more severe bacterial infection and stronger lithogenicity was found in patients with SOL. The findings suggest a possible mechanism of cholangiolithiasis and provide the basis for future strategies for prevention of cholangiolithiasis recurrence.
To study the value of circulating microRNA 216 (miR-216) as a marker for the severity of acute pancreatitis (AP) in both murine models and patients.
Mice with AP were induced by intraperitoneal ...injection of 50μg/kg/hour cerulean either 7 times, sacrificed at 8, 9, 10, 11 or 12 hours after the first injection, or 12 times, sacrificed at 24 hours after the first injection. Plasma samples and data from patients with AP were obtained from a prospective cohort. Quantitative reverse transcription polymerase chain reaction was used to determine the miR-216a and miR-216b level.
The upregulation of miR-216a and miR-216b in the serum of mice was induced by cerulean injection in both the 7- and 12-injection groups (P < 0.05). The downregulation of miR-216a in pancreatic tissues of mice with AP was detected (P < 0.05), but no difference was observed in pancreatic miR-216b levels among any of the groups (all P > 0.05). The serum miR-216a level was positively correlated with pancreatic histopathology severity scores, and was negatively correlated with pancreatic miR-216a (r = -0.483, P = 0.009). The plasma miR-216a level was significantly upregulated in patients with severe AP (SAP) compared with patients with mild AP (MAP) or moderate severe AP (MSAP) (SAP versus MAP, P = 0.04; SAP versus MSAP, P = 0.00), but no difference was seen between patients with MAP and those with MSAP (P = 0.73).
Circulating miR-216a might be a potential biomarker for the early identification of SAP.
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