Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

contrast enhanced computed tomography and reconstruction of hepatic vascular system for transjugular intrahepatic portal systemic shunt puncture path planning

AIM: To describe a method for the transjugular intrahepatic portal systemic shunt(TIPS) placement performed with the aid of contrast-enhanced computed tomography(CECT) and three-dimensional reconstructed vascular images(3D RVIs), and to assess its safety and effectiveness. METHODS: Four hundred and ninety patients were treated with TIPS between January 2005 and December 2012. All patients underwent liver CECT and reconstruction of 3D RVIs of the right hepatic vein to portal vein(PV) prior to the operation. The 3D RVIs were carefully reviewed to plan the puncture path fromthe start to target points for needle pass through the PV in the TIPS procedure. R E S U LTS :The improved TIPS procedure was successful in 483(98.6%) of the 490 patients. The number of punctures attempted was one in 294(60%) patients, 2 to 3 in 147(30%) patients, 4 to 6 in 25(5.1%) patients and more than 6 in 17(3.5%) patients. Seven patients failed. Of the 490 patients, 12 had punctures into the artery, 15 into the bile duct, eight into the gallbladder, and 18 through the liver capsule. Analysis of the portograms from the 483 successful cases indicated that the puncture points were all located distally to the PV bifurcation on anteroposterior images, while the points were located proximally to the bifurcation in the three cases with intraabdominal bleeding. The complications included three cases of bleeding, of whom one died and two needed surgery. CONCLUSION: Use of CECT and 3D RVIs to plan the puncture path for TIPS procedure is safe, simple and effective for clinical use.

Misdiagnosis of unroofed coronary sinus syndrome as an ostium primum atrial septal defect by echocardiography:A case report

BACKGROUND Unroofed coronary sinus syndrome(UCSS)is a rare congenital heart disease,which has variable morphologic features and is strongly associated with persistent left superior vena cava(PLSVC).However,it is often difficult to visualize the left-to-right shunt pathway through the CS by transthoracic echocardiography(TTE).CASE SUMMARY A 37-year-old female was admitted to the hepatological surgery department of a hospital with complaint of subxiphoid pain that had started 1 wk prior.Physical examination revealed a grade 3/6 systolic murmur at the left margin of the sternum,between the 2nd and 3rd intercostal cartilage.The patient underwent echocardiography and was diagnosed with ostium primum atrial septal defect(ASD);thus,she was subsequently transferred to the cardiovascular surgery department.A second TTE evaluation before surgery showed type IV UCSS with secundum ASD.Right-heart contrast echocardiography(RHCE)showed that the right atrium and right ventricle were immediately filled with microbubbles,but no microbubble was observed in the CS.Meanwhile,negative filling was observed at the right atrium orifice of the CS and right atrium side of the secundum atrial septal.RHCE identified UCSS combined with secundum ASD but without PLSVC in this patient.CONCLUSION This rare case of UCSS highlights the value of TTE combined with RHCE in confirming UCSS with ASD or PLSVC.

MiR-24-3p Attenuates Doxorubicin-induced Cardiotoxicity via the Nrf2 Pathway in Mice

Objective:The nuclear factor erythroid 2(NFE2)-related factor 2(Nrf2)is associated with doxorubicin(DOX)-induced cardiac injury.It has been reported that microRNA-24-3p(miR-24-3p)may regulate the Keapl by mRNA degradation,whereas Keapl can suppress the activation of Nrf2.However,the role of miR-24-3p in DOX-related cardiotoxicity remains unclear.

Tuberous sclerosis complex-lymphangioleiomyomatosis involving several visceral organs:A case report

BACKGROUND Lymphangioleiomyomatosis(LAM)is a rare cystic lung disease characterized by the proliferation,metastasis,and infiltration of smooth muscle cells in the lung and other tissues,which can be associated with tuberous sclerosis complex(TSC).The disorder of TSC has a variable expression,and there is great phenotypic variability.CASE SUMMARY A 32-year-old Chinese woman with a history of multiple renal angioleiomyolipoma presented with a productive cough persisting for over 2 wk.Highresolution chest computed tomography revealed interstitial changes,multiple pulmonary bullae,bilateral pulmonary nodules,and multiple fat density areas of the inferior mediastinum.Conventional and contrast ultrasonography revealed multiple high echogenic masses of the liver,kidneys,retroperitoneum,and inferior mediastinum.These masses were diagnosed as angiomyolipomas.Pathology through thoracoscopic lung biopsy confirmed LAM.Furthermore,high-throughput genome sequencing of peripheral blood DNA confirmed the presence of a heterozygous mutation,c.1831C>T(p.Arg611Trp),of the TSC2 gene.The patient was diagnosed with TSC-LAM.CONCLUSION We highlight a rare case of TSC-LAM and the first report of a mediastinum lymphangioleiomyoma associated with TSC-LAM.

Emergence of Eurasian Avian-Like Swine Influenza A(H1N1) Virus from an Adult Case in Fujian Province, China

Dear Editor,As we known,pigs play a vital role as genetic mixing vessels for human and avian influenza viruses as their tracheal epitheliums possess both sialic acid a-2,6-Gal and a-2,3-Gal receptors(Ma et al.2008),and swine influenza viruses occasionally infect humans(Shinde et al.2009).The Eurasian avian-like swine influenza A(H1N1)

Double-temperature ratchet model and current reversal of coupled Brownian motors

On the basis of the transport features and experimental phenomena observed in studies of molecular motors, we propose a double-temperature ratchet model of coupled motors to reveal tile dynamical mechanism of cooperative transport of motors with two heads, where the interactions and asynchrony between two motor heads are taken into account. We investigate the collective unidirectional trans- port of coupled system and find that the direction of motion can be reversed under certain conditions. Reverse motion can be achieved by modulating the coupling strength, coupling free length, and asym- metric coefficient of the periodic potential, which is understood in terms of the effective potential theory. The dependence of the directed current on various parameters is studied systematically. Di- rected transport of coupled Brownian motors can be manipulated and optimized by adjusting the pulsation period or the phase shift of the pulsation temperature.

Ratchet motion and current motors in pulsating reversal of coupled Brownian symmetric potentials

In this study, we investigate the collective directed transport of coupled Brownian particles in spatially symmetric periodic potentials under time-periodic pulsating modulations. We find that the coupling between two particles can induce symmetry breaking and consequently collective directed motion. Moreover, the direction of motion can be reversed under certain conditions. The dependence of directed current on various parameters is systematically studied, reverse motion can be achieved by modulating the coupling free length and the phase shift of tile pulsating potential. The dynamical mechanism of these transport properties is understood in terms of the effective-potential theory and the space-time transformation invariance. The directed transport of coupled Brownian motors can be maniplflated and optimized by adjusting the coupling strength, pulsating frequency, or noise intensity.

Order parameter analysis of synchronization transitions on star networks

The collective behaviors of populations of coupled oscillators have attracted significant attention in recent years. In this paper, an order parameter approach is proposed to study the low-dimensional dynamical mechanism of collective synchronizations, by adopting the star-topology of coupled oscil- lators as a prototype system. The order parameter equation of star-linked phase oscillators can be obtained in terms of the Watanabe--Strogatz transformation, Ott--Antonsen ansatz, and the ensem- ble order parameter approach. Different solutions of the order parameter equation correspond to the diverse collective states, and different bifurcations reveal various transitions among these collective states. The properties of various transitions in the star-network model are revealed by using tools of nonlinear dynamics such as time reversibility analysis and linear stability analysis.