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Peripheral arterial disease (PAD) affects more than 200 million people worldwide. Recent studies suggest that oxidative stress-related inflammation can lead to the initiation and progression of PAD. Ferulic acid (FA) is a natural phenolic compound and has been proven to have antioxidant and angiogenesis effects. In this study, thermosensitive chitosan-gelatin-based hydrogel was used as a delivery vehicle of FA. The effects of hydrogel encapsulating FA (FA-gel) have been demonstrated in vitro and in vivo. The results revealed that the developed hydrogel with porous structure could provide a sustained release of FA. Post-treatment of FA-gel effectively decreased the oxidative stress-induced damage in human umbilical vein endothelial cells via decreasing endogenous reactive oxygen species production, inflammation-related gene expression and apoptosis level. In the mouse hindlimb ischemia model, the results revealed that FA-gel could improve blood flow, muscle regeneration and decreases inflammation in veins. These results suggested that FA-gel may have a therapeutic potential in PAD.

BACKGROUND Patients undergoing pancreaticoduodenectomy (PD) for periampullary lesions are usually elderly with a high risk of postoperative morbidity and mortality. This retrospective cohort study investigated whether postoperative preemptive light sedation aids in recovery of elderly patients following PD. METHODS Ninety-nine geriatric patients undergoing PD at one hospital were enrolled from 2009 to 2018. Patients in the sedation group received mechanical ventilation support and preemptively light sedation with fentanyl and propofol or dexmedetomidine in the first 5 days postoperatively in the intensive care unit (ICU). Patients in the control group underwent early extubation and received morphine for pain control but no postoperative sedatives in the ordinary ward. Patients in the two groups were matched 1:1 using propensity scoring. The postoperative complication rate, surgical mortality, and postoperative hospital length of stay (LOS) were recorded. We also tested inflammation in an immortal human bronchial epithelial cell line. RESULTS After 1:1 matching, 40 patients in the sedation group were compared with 40 patients in the control group. The sedation group had a significantly lower pulmonary complication rate and fewer patients with postoperative gastroparesis. Both groups had similar postoperative hospital LOS and identical surgical mortality rates. Patients in the sedation group had significantly better postoperative quality of life, including less pain and less heartbeat variation. In vitro cell experiments supported the above clinical observations, showing that adequate use of sedatives could significantly elevate the cell viability rate, protect cells from damage, decrease interleukin-6 production, and reduce inflammation. CONCLUSION Postoperative preemptive light sedation in the ICU in geriatric patients following PD may not only reduce the rates of postoperative pulmonary complications and gastroparesis but also improve postoperative quality of life without prolonging the postoperative hospital LOS.

In this study, molecular dynamics (MD) are used to simulate the nanoimprinting behaviors of (001) Ni thin films using 3×3 array cuboid diamond punch. Different pitch of the punches was used to investigate the effect of the interaction among the forming pattern and the quality of the formed holes. Forming force was evaluated including normal and tractional force of the punch during pressing process. The dislocation behavior was also monitoring during the holes forming. The result showed that the pitch of the punch was 2w could get the best forming pattern.

BACKGROUND: Despite the availability of current therapies, including oral antidiabetic drugs and insulin, for controlling the symptoms caused by high blood glucose, it is difficult to cure diabetes mellitus, especially type 1 diabetes mellitus. AIM: Cell therapies using mesenchymal stem cells (MSCs) may be a promising option. However, the therapeutic mechanisms by which MSCs exert their effects, such as whether they can differentiate into insulin-producing cells (IPCs) before transplantation, are uncertain. METHODS: In this study, we used three types of differentiation media over 10 d to generate IPCs from human Wharton’s jelly MSCs (hWJ-MSCs). We further transplanted the undifferentiated hWJ-MSCs and differentiated IPCs derived from them into the portal vein of rats with streptozotocin-induced diabetes, and recorded the physiological and pathological changes. RESULTS: Using fluorescent staining and C-peptide enzyme-linked immunoassay, we were able to successfully induce the differentiation of hWJ-MSCs into IPCs. Transplantation of both IPCs derived from hWJ-MSCs and undifferentiated hWJ-MSCs had the therapeutic effect of ameliorating blood glucose levels and improving intraperitoneal glucose tolerance tests. The transplanted IPCs homed to the pancreas and functionally survived for at least 8 wk after transplantation, whereas the undifferentiated hWJ-MSCs were able to improve the insulitis and ameliorate the serum inflammatory cytokine in streptozotocin-induced diabetic rats. CONCLUSION: Differentiated IPCs can significantly improve blood glucose levels in diabetic rats due to the continuous secretion of insulin by transplanted cells that survive in the islets of diabetic rats. Transplantation of undifferentiated hWJ-MSCs can significantly improve insulitis and re-balance the inflammatory condition in diabetic rats with only a slight improvement in blood glucose levels.

The level of 8-hydroxy-2-deoxyguanosise (8-OHdG) is a marker of oxidative stress. The objective of this study was to evaluate the effect of enzyme replacement therapy (ERT) on the level of 8-OHdG in patients with Fabry cardiomyopathy and the clinical evolution of Fabry cardiomyopathy.We measured the serum levels of 8-OHdG in 20 healthy control and 22 patients with Fabry cardiomyopathy before and after ERT.The mean lysoGb3 and 8-OHdG levels was significantly increased in patients with Fabry cardiomyopathy compared with that of control subjects (lysoGb3, 3.6 ± 1.1 nM vs. 0.4 ± 0.1 nM, p 0.01; 8-OHdG, 4.5 ± 0.5 ng/mL vs. 3.4 ± 0.4 ng/mL, P 0.05). The mean lysoGb3 and 8-OHdG levels was significantly reduced after ERT for 14.2 months (lysoGb3, 3.6 ± 1.1 nM vs. 2.9 ± 1.1 nM, P 0.05; 8-OHdG, 4.5 ± 0.5 ng/mL to 4 ± 0.4 ng/mL, P 0.05). These changes were accompanied by decreases in LVM and LVMI.We demonstrated that the serum 8-OHdG levels is increased in patients with Fabry cardiomyopathy (FC) and that successful management of FC with ERT is associated with a decrease in this oxidative stress marker. Serum 8-OHdG levels can be used not only as a noninvasive biomarker of oxidative stress in patients with FC but also an objective and quantitative parameter in the follow-up of patients during ERT.

Aging-related oxidative stress is considered a major risk factor of cardiovascular diseases (CVD) and could be associated with mitochondrial dysfunction and reactive oxygen species (ROS) overproduction. Cisd2 is an outer mitochondrial membrane protein and plays an important role in controlling the lifespan of mammals. Ferulic acid (FA), a natural antioxidant, is able to improve cardiovascular functions and inhibit the pathogenetic CVD process. However, directly administering therapeutics with antioxidant molecules is challenging because of stability and bioavailability issues. In the present study, thermosensitive chitosan-gelatin-based hydrogel containing FA was used to treat Cisd2-deficient (Cisd2(-/-)) cardiomyocytes (CM) derived from induced pluripotent stem cells of Cisd2(-/-) murine under oxidative stress. The results revealed that the developed hydrogel could provide a sustained release of FA and increase the cell viability. Post-treatment of FA-loaded hydrogel effectively decreased the oxidative stress-induced damage in Cisd2(-/-) CM via increasing catalase activity and decreasing endogenous reactive oxygen species (ROS) production. The in vivo biocompatibility of FA-loaded hydrogel was confirmed in subcutaneously injected rabbits and intramyocardially injected Cisd2(-/-) mice. These results suggest that the thermosensitive FA-loaded hydrogel could rescue Cisd2(-/-) CM from oxidative stress-induced damage and may have potential applications in the future treatment of CVD.

Hemothorax is most commonly resulted from a closed chest trauma, while a tube thoracostomy (TT) is usually the first procedure attempted to treat it. However, TT may lead to unexpected results and complications in some cases. The advantage of thoracic ultrasound (TUS) over a physical examination combined with chest radiograph (CXR) for diagnosing hemothorax1 has been proposed previously. However, its benefits in terms of avoiding non-therapeutic TT have not yet been confirmed. Therefore, this study is aimed to evaluate the severity of hemothorax in blunt chest trauma patients by using TUS in order to avoid non-therapeutic TT in stable cases. The data from 46,036 consecutive patient visits to our trauma center over a four-year period were collected, and those with blunt chest trauma were identified. Patients who met any of the following criteria were excluded: transferred from another facility, with an abbreviated injury scale (AIS) score ≥ 2 for any region except the chest region, with a documented finding of tension pneumothorax or pneumothorax >10%, younger than 16 years old and with indications requiring any non-thoracic major operation. The decision to perform TT for those patients in the non-TUS group was made on the basis of CXR findings and clinical symptoms. The continuous data were analyzed by using the two-tailed Student’s t test, and the discrete data were analyzed by Chi-square test. A total of 84 patients met the criteria for inclusion in the final analysis, with TT having been performed on 42 (50%) of those patients. The mean volume of the drainage amount was 860 ml after TT. The TT drainage was less than 500 ml in 12 patients in the non-TUS group (40%), while none was less than 500 ml in the TUS group (p = 0.036, Fisher’s exact test). In terms of the positive rate of subsequent effective TT, the sensitivity of TUS was 90% and the specificity was 100%. There were 3 patients with delayed hemothorax: 2 of the 58 (3.6%) in the non-TUS group and 1 of 26 (4.5%) in the TUS group (p > 0.05, Fisher’s exact test). The hospital length of stay in the non-TUS group with non-therapeutic TT was significantly longer than in the TUS group without TT (8.2 vs. 5.4 days, p = 0.018). There were no other major complications or deaths in either group during the 90-day follow-up period. In the case of blunt trauma, TUS can rapidly and accurately evaluate hemothorax to avoid TT in patients who may not benefit much from it. As a result, the rate of non-therapeutic TT can be decreased, and the influence on shortening hospital length of stay may be further evaluated with prospective controlled study.

Vinorelbine (VNR), a semisynthetic vinca alkaloid acquired from vinblastine, is frequently used as the candidate for intervention of solid tumors. Nevertheless, VNR-caused endothelial injuries may lead a mitigative effect of clinical treatment efficiency. A growing body of evidence reveals that aspirin is a potent antioxidant and anti-inflammation drug. We investigated whether aspirin attenuate VNR-induced endothelial dysfunction. Human endothelial cells (EA.hy 926) were treated with VNR to cause endothelial inflammation. Western blotting, ROS assay, ELISA were used to confirm the anti-inflammatory effect of aspirin. We confirmed that VNR supresses SIRT1 expression, reduced LKB1 and AMPK phosphorylation as well as enriched PKC activation in treated endothelial cells. Furthermore, the membrane translocation assay displayed that the levels of NADPH oxidase subunits p47phox and Rac-1 in membrane fractions of endothelial cells were higher in cells that had been treated with VNR for than in untreated cells. We corroborated that treatment of Aspirin significantly diminishes VNR-repressed SIRT1, LKB1 and AMPK phosphorylation and VNR-promoted NADPH oxidase activation, however, those findings were vanished by SIRT1 and AMPK siRNAs. Our data also shown that Aspirin represses VNR-activated TGF-beta-activated kinase-1 (TAK1) activation, inhibited the interaction of TAK1/TAK-binding protein1 (TAB1), suppressed NF-kappa B activation and pro-inflammatory cytokine secretion. We demonstrated a novel connection between VNR-caused oxidative damages and endothelial dysfunction, and provide further insight into the protective effects of aspirin in VNR-caused endothelial dysfunction.

Background: We previously reported that pressure overload of the left ventricle reduced myocardial infarct (MI) size in rabbits. The threshold of pressure overload was investigated in this study. Methods: Pressure overload of the left ventricle was induced by partial snare of the ascending aorta in anesthetized, open-chest rabbits. Systolic left ventricular pressure (SLVP) was elevated 50% or 30% above baseline value by varying the degree of partial snaring. Different duration of pressure overload, including 10 minutes, 5 minutes, 3 minutes, or 2 minutes, was applied to determine the threshold of protective effects. Ischemic preconditioning was elicited by two 10-minute coronary artery occlusions and reperfusions. Ten minutes after different pretreatment, 1 hour occlusion of the left anterior descending coronary artery followed by 3 hours reperfusion was done to induce MI. The size of area at risk and MI were determined by blue dye injection and triphenyl tetrazolium chloride staining after experiments. Results: Pressure overload increase of SLVP 50% above baseline value for 10 minutes, 5 minutes, and 3 minutes significantly reduced MI size (18.5 ± 3.6%, 21.4 ± 1.9% and 21.6 ± 1.7%, respectively, vs. 26.6 ± 1.0% in the control group, mean ± standard deviation, p

Background: Myocardial infarction (MI) is a fatal disease that is increasing in incidence. The worst sequelae of MI include myocardial fibrosis and deterioration of pumping function that can lead to irreversible heart failure. This study aims to compare the therapeutic effect of undifferentiated versus TGF-β2–stimulated Wharton’s jelly mesenchymal stem cells (WJ-MSCs) in MI rats. Results: Left anterior descending (LAD) artery ligation-induced myocardial infarct rats were used to evaluate changes in left ventricular function and fibrosis following injection of PBS or 1.6 × 106 undifferentiated or TGF-β2–stimulated WJ-MSCs into the border zone myocardium. Electrocardiograph, echocardiogram, serum cardiac Troponin I level, Masson’s Trichrome staining, immunohistochemistry were used to analyze the therapeutic effects. We found that transplantation of both undifferentiated and TGF-β2 stimulated WJ-MSCs decreased serum Cardiac Troponin I levels, improved fractional shortening, ameliorated ejection fraction changes, and decreased the area of myocardial fibrosis. Moreover, some of the transplanted human WJ-MSCs survived in the myocardium. Conclusions: Transplantation of either undifferentiated or TGF-β2 stimulated WJ-MSCs improved left ventricular function after MI and increased survival. The effects were most marked using undifferentiated WJ-MSCs. These results indicate WJMSCs as a potential stem cell source for use in myocardial infarct therapy.

Background Less invasive cardiac surgery is widely adopted nowadays. Upper or lower partial sternotomy is an approach for less invasive cardiac surgery. We report results of less invasive cardiac surgery via partial sternotomy. Methods From August 1, 2009 to September 30, 2010, 35 patients underwent cardiac surgery via upper or lower partial sternotomy. The preoperative characteristics, operative variables, mortality, and morbidity were reviewed retrospectively. Results Thirty-five patients underwent cardiac surgery via partial sternotomy during the study period. Eleven patients (31%) were female. The mean age was 66 ± 11 years (range 38 to 88). Seven patients underwent aortic valve replacement via upper partial sternotomy. Simultaneous mitral valve replacement was done in one patient. Lower partial sternotomy was done in 28 patients. Sixteen patients received mitral valve replacement. Three patients underwent mitral valve repair. Concomitant tricuspid valve repair was done in eight patients. Two patients received aortic valve replacement. One patient had replacement of aortic and mitral valve replacement. One patient had repair of tricuspid valve. Two patients received LIMA anastomosis to the LAD. Two patients underwent emergent repair of the right ventricle. One patient had resection of myxoma in the left atrium. Direct cannulation of the aorta and right atrium was used for cardiopulmonary bypass in 15 patients (48%). Both antegrade and retrograde administration of cardioplegia solution was used routinely for myocardial protection. There was no mortality. Two patients developed respiratory failure. One patient suffered unstable sternum. One patient required conversion to full sternotomy. No patient suffered mediastinitis or groin wound infection. Conclusion Upper or lower partial sternotomy provides adequate exposure for various kind of cardiac surgery. Conventional cardiopulmonary bypass and cardioplegia solution administration can be used. The immediate preliminary outcome was acceptable.

Background Fabry disease (FD) causes progressive glycosphingolipid accumulation and damage in various organs, and several proinflammatory processes may be involved in this disease. Enzyme replacement therapy (ERT) can reduce the severity of Fabry cardiomyopathy (FC), but whether ERT could attenuate proinflammatory cytokines in FC remains unclear. In this study, we attempted to evaluate the efficacy of ERT on proinflammatory cytokines and vascular cell adhesion biomarkers. Methods We enrolled 25 patients with FC and administered ERT to them according to the present clinical guideline. We analyzed and compared echocardiographic and blood examination results between 25 patients with FD without left ventricular hypertrophy (LVH), 25 patients with FC with LVH who were receiving ERT, and 25 healthy age- and sex-matched controls. The parameters of cardiac function at baseline and 12 months after ERT were assessed through echocardiography, and the expression profiles of proinflammatory biomarkers were determined. Results Left ventricular mass (LVM), LVM index (LVMI), interventricular septal thickness at diastole, and serum levels of globotriaosylsphingosine (Gb3) were elevated in patients with FC. Meanwhile, several proinflammatory cytokines, including interleukin (IL)-6, IL-2, IL-1b, tumor necrosis factor-α, intercellular adhesion molecule, soluble vascular cell adhesion molecule, and monocyte chemoattractant protein-1 (MCP-1) were concomitantly increased. ERT significantly reduced these transthoracic echocardiographic parameters and lyso-Gb3 and proinflammatory cytokine levels. The changes in IL-6, MCP-1, and lyso-Gb3 levels were positively correlated with the change in LVMI. Conclusions Our study has revealed that proinflammatory biomarkers, particularly IL-6 and MCP-1, may represent effective biomarkers for evaluating ERT outcomes in patients with FC.

Background: Liver transplantation is the ultimate treatment for liver failure. However, its use is complicated by shortage of donor organs and numerous other problems. Thus, other methods for the treatment of liver failure, including cell therapy, are being considered. We have evaluated the capacity of hepatocyte-like cells differentiated from Wharton’s jelly mesenchymal stem cells (WJ-MSCs) to prevent or ameliorate acute liver failure in a rat model. Methods: WJ-MSCs were isolated from human umbilical cords and induced to differentiate into hepatocyte-like cells by incubation with a combination of liver-tissue culture medium and growth factors. The differentiated cells were evaluated with immunocytochemistry, RT-PCR, ammonia metabolism test, and glycogen storage for characteristics of functioning hepatocytes. The hepatocyte-like cells were transplanted into the portal vein of rats with acute liver failure induced by carbontetrachloride injection. Survival, serum liver function tests, and body weight of the animals were recorded. Livers of the rats 30 days after transplantation were harvested. Results: The differentiated hepatocyte-like cells had morphologic features and functional characteristics of mature hepatocytes: hepatocyte-related genes, conversion of ammonia to urea, albumin synthesis, glycogen storage, and declining values of alpha-fetoprotein. Transplantation of the hepatocyte-like cells into the rats with carbon tetrachloride-induced liver failure prevented death of the animals and prevented rising values of serum alanine transaminase (ALT), aspartate transaminase (AST), and bilirubin. Immunohistochemical study of rat liver tissues 30 days after transplantation revealed that the WJ-MSCs had survived and were producing albumin. Conclusions: WJ-MSCs of the human umbilical cord were could differentiated into hepatocyte-like cells in vitro. Transplantation of hepatocyte-like cells into the portal vein of rats with carbontetrachloride acute liver injury prevented death of the animals and irreversible liver injury. These findings may serve as a reference for future research in cell therapy of liver failure.

Nutcracker syndrome (NCS) is a rare pathology manifested by pain or hematuria in males and females alike. It can be easily overlooked, and should be considered in young men or women with symptoms of extended duration. We present a case of a 54-year-old female with chronic lower abdominal pain radiating to the left thigh of 4 years in duration. Computed tomography (CT) eventually revealed engorged left renal, gonadal, and uterine veins due to compression between the superior mesenteric artery (SMA) and the abdominal aorta, consistent with NCS. After a successful endovascular stenting and a 6-month period of antiplatelet and anticoagulant therapy, the patient returned to stable health. NCS, while rare, should be suspected in patients of both sexes with persistent pain or hematuria.

Background Emergence of daptomycin-nonsusceptible (DNS) Staphylococcus aureus is a dreadful problem in the treatment of endocarditis. Few current therapeutic agents are effective for treating infections caused by DNS S. aureus. Case presentation We describe the emergence of DNS S. aureus. in a patient with implantable cardioverter-defibrillator (ICD) device -related endocarditis who was priorily treated with daptomycin. Metastatic dissemination as osteomyelitis further complicated the management of endocarditis. The dilemma was successfully managed by surgical removal of the ICD device and combination antimicrobial therapy with high-dose daptomycin and fosfomycin. Conclusions Surgical removal of intracardiac devices remains an important adjunctive measure in the treatment of endocarditis. Our case suggests that combination therapy is more favorable than single-agent therapy for infections caused by DNS S. aureus.

Background Endovascular aneurysm repair (EVAR) has become a well-established technique in the treatment of elective surgery for abdominal aortic aneurysms (AAAs) due to proven benefits in mortality, hospital stay and operation time compared to open repair. The aim of this study was to report our experience in establishing the treatment protocol for EVAR of contained ruptured abdominal aortic aneurysms (rAAAs) and to illustrate the real impact of endovascular rAAA repair on surgical strategy. Methods Eighteen patients underwent AAA between January 2008 and October 2009. Six of them were enrolled in our study. The inclusion criteria were contained rAAA and the same anatomic consideration as in elective EVAR cases. The implant material was the Zenith AAA modular bifurcated device. Computed tomography (CT) scan was obtained in all patients pre-operatively and used as a follow-up tool. Results The mean age was 81 years (range 79–87 years). The procedural time was 259 ± 146 minutes, the maximal diameter of aneurismal sac was 8.4 ± 1.8 cm, and the pre-operative hemoglobin was 9.0 ± 1.2 mg/dL. The mean intensive care unit (ICU) stay was 10.5 ± 15 days. There was no surgical or in-hospital mortality. Complications included abdominal compartment syndrome, renal failure, wound infection and pneumonia. The mean follow-up period was 22 (range 19–29) months, with satisfactory result. Conclusion Endovascular repair of rAAAs is feasible, and short-term results are promising, especially for contained and hemodynamic subgroup patients. It is indicated for elder patients with severe underlying diseases. Good logistics and adequate training of physicians or staff in an elective setting are prerequisites for this type of treatment program.