Intensity-adjustable pain management with prolonged duration based on phase-transitional nanoparticles-assisted ultrasound imaging-guided nerve blockade.

BACKGROUND: The lack of a satisfactory strategy for postoperative pain management significantly impairs the quality of life for many patients. However, existing nanoplatforms cannot provide a longer duration of nerve blockage with intensity-adjustable characteristics under imaging guidance for clinical applications. RESULTS: To overcome this challenge, we proposed a biocompatible nanoplatform that enables high-definition ultrasound imaging-guided, intensity-adjustable, and long-lasting analgesia in a postoperative pain management model in awake mice. The nanoplatform was constructed by incorporating perfluoropentane and levobupivacaine with red blood cell membranes decorated liposomes. The fabricated nanoplatform can achieve gas-producing and can finely escape from immune surveillance in vivo to maximize the anesthetic effect. The analgesia effect was assessed from both motor reactions and pain-related histological markers. The findings demonstrated that the duration of intensity-adjustable analgesia in our platform is more than 20 times longer than free levobupivacaine injection with pain relief for around 3 days straight. Moreover, the pain relief was strengthened by repeatable ultrasound irradiation to effectively manage postoperative pain in an intensity-adjustable manner. No apparent systemic and local tissue injury was detected under different treatments. CONCLUSION: Our results suggest that nanoplatform can provide an effective strategy for ultrasound imaging-guided intensity-adjustable pain management with prolonged analgesia duration and show considerable transformation prospects.

[Study on modeling, simulation, and sensorless feedback control algorithm of the cavopulmonary assist device based on the subpulmonary ventricular exclusion].

The subpulmonary ventricular exclusion (Fontan) could effectively improve the living quality for the children patients with a functional single ventricle in clinical. However, postoperative Fontan circulation failure can easily occur, causing obvious limitations while clinically implementing Fontan. The cavopulmonary assist devices (CPAD) is currently an effective means to solve such limitations. Therefore, in this paper the in-silico and in-vitro experiment coupled model of Fontan circulation failure for the children patients with a single ventricle and CPAD is established to evaluate the effects of CPAD on the Fontan circulation failure. Then a sensorless feedback control algorithm is proposed to provide sufficient cardiac output and prevent vena caval suction due to CPAD constant pump speed. Based on the CPAD pump speed-an intrinsic parameter, the sensorless feedback control algorithm could accurately estimate the cavopulmonary pressure head (CPPH) using extended Kalman filter, eliminating the disadvantage for pressure sensors that cannot be used in long term. And a gain-scheduled, proportional integral (PI) controller is used to make the actual CPPH approach to the reference value. Results show that the CPAD could effectively increase physiological perfusion for the children patients and reduce the workload of a single ventricle, and the sensorless feedback control algorithm can effectively guarantee cardiac output and prevent suction. This study can provide theoretical basis and technical support for the design and optimization of CPAD, and has potential clinical application value.

A multi-component parallel-plate flow chamber system for studying the effect of exercise-induced wall shear stress on endothelial cells.

BACKGROUND: In vivo studies have demonstrated that reasonable exercise training can improve endothelial function. To confirm the key role of wall shear stress induced by exercise on endothelial cells, and to understand how wall shear stress affects the structure and the function of endothelial cells, it is crucial to design and fabricate an in vitro multi-component parallel-plate flow chamber system which can closely replicate exercise-induced wall shear stress waveforms in artery. METHODS: The in vivo wall shear stress waveforms from the common carotid artery of a healthy volunteer in resting and immediately after 30 min acute aerobic cycling exercise were first calculated by measuring the inner diameter and the center-line blood flow velocity with a color Doppler ultrasound. According to the above in vivo wall shear stress waveforms, we designed and fabricated a parallel-plate flow chamber system with appropriate components based on a lumped parameter hemodynamics model. To validate the feasibility of this system, human umbilical vein endothelial cells (HUVECs) line were cultured within the parallel-plate flow chamber under abovementioned two types of wall shear stress waveforms and the intracellular actin microfilaments and nitric oxide (NO) production level were evaluated using fluorescence microscope. RESULTS: Our results show that the trends of resting and exercise-induced wall shear stress waveforms, especially the maximal, minimal and mean wall shear stress as well as oscillatory shear index, generated by the parallel-plate flow chamber system are similar to those acquired from the common carotid artery. In addition, the cellular experiments demonstrate that the actin microfilaments and the production of NO within cells exposed to the two different wall shear stress waveforms exhibit different dynamic behaviors; there are larger numbers of actin microfilaments and higher level NO in cells exposed in exercise-induced wall shear stress condition than resting wall shear stress condition. CONCLUSION: The parallel-plate flow chamber system can well reproduce wall shear stress waveforms acquired from the common carotid artery in resting and immediately after exercise states. Furthermore, it can be used for studying the endothelial cells responses under resting and exercise-induced wall shear stress environments in vitro.

[Study on effect of aqueous extracts from aconite on "dose-time-toxicity" relationships in mice hearts].

OBJECTIVE: To study the effect of single administration of aqueous extracts from aconite on "dose-toxicity" relationship and "time-toxicity" relationship of mice hearts, through changes in electrocardiogram (ECG) and serum biochemical indexes. METHOD: Mice were grouped according to different drug doses and time points, and orally administered with water extracts from aconite for once to observe the changes of mice ECG before and after the administration, calculate visceral indexes heart, liver and kidney, and detect levels of CK, LDH, BNP and CTn-I in serum. RESULT: According to the "time-toxicity" relationship study, at 5 min after oral administration with aqueous extracts from aconite in mice, the heart rate of mice began rising, reached peak at 60 min and then slowly reduced; QRS, R amplitude, T duration and amplitude and QT interval declined at 5 min, reduced to the bottom at 60 min and then gradually elevated. The levels of CK, LDH, BNP and CTn-I in serum elevated at 5 min and reached the peak at 60 min, with no significant change in ratios of organs to body at different time points. On the basis of the "dose-toxicity" relationship, with the increase in single dose of aqueous extracts from aconite, the heart rate of mice. QRS, T duration and amplitude and QT interval declined gradually, and levels of CK, LDH, BNP and CTn-I in serum slowly elevated, with a certain dose dependence and no significant change in ratios of organs to body in mice. CONCLUSION: Single oral administration of different doses of aqueous extracts from aconite could cause different degrees of heart injury at different time points, with a certain dose dependence. Its peak time of toxicity is at 60 min after the administration of aqueous extracts from aconite.

[Evaluation on efficacy-toxicity correlation of aqueous extracts from Aconiti Lateralis Radix Praeparata on diarrheal model rats based on "warmly invigorating spleen Yang" efficacy].

The diarrheal rat model was established by orally administering senna. The preventive experiment was concurrent for 6 days. The treatment experiment modeling had lasted for 12 days. The administration started at the 7th day, and lasted for 6 days. During the experiment, efforts were made in symptom score and weighing. After the experiment, hearts, livers, spleens, kidneys, brains, adrenals and thymuses were collected and weighed, lactic dehydrogenase (LDH) and cardiac troponin-I (cTn-I) in serum were detected. The efficacy of aqueousextracts from Aconiti Lateralis Radix Praeparata in preventing and treating rats with diarrheal and its accompanying toxicity were respectively studied. The result shows that aqueous extracts from Aconiti Lateralis Radix Praeparata could improve syndromes of rats with diarrheal. The 50% effective doses (ED50) of preventive and treatment administrations were 1.420 4 g · kg(-1) and 1.048 9 g · kg(-1), respectively. Aqueous extracts from Aconiti Lateralis Radix Praeparata could decrease the ratio of heart to body weight, and increase serum LDH and cTn-I. It was concluded that aqueous extracts from Aconiti Lateralis Radix Praeparata had a specific preventive and treatment effect on rats with diarrheal caused by senna, but with specific toxicity on heart.

Artificial nano-red blood cells nanoplatform with lysosomal escape capability for ultrasound imaging-guided on-demand pain management.

Postoperative pain management would benefit significantly from an anesthetic that could take effect in an on-demand manner. An ultrasound would be an appropriate tool for such nanoplatform because it is widely used in clinical settings for ultrasound-guided anesthesia. Herein, we report a nanoplatform for postoperative on-demand pain management that can effectively enhance their analgesic time while providing ultrasonic imaging. Levobupivacaine and perfluoropentane were put into dendritic mesoporous silica and covered with red blood cell membranes to make the pain relief last longer in living organisms. The generated nanoplatform with gas-producing capability is ultrasonic responsive and can finely escape from the lysosomal in cells under ultrasound irradiation, maximizing the anesthetic effect with minimal toxicity. Using an incision pain model in vivo, levobupivacaine's sustained and controlled release gives pain reduction for approximately 3 days straight. The duration of pain relief is over 20 times greater than with a single injection of free levobupivacaine. Effective pain management was reached in vivo, and the pain reduction was enhanced by repeated ultrasonic irradiation. There was no detectable systemic or tissue injury under either of the treatments. Thus, our results suggest that nanoplatform with lysosomal escape capability can provide a practical ultrasound imaging-guided on-demand pain management strategy. STATEMENT OF SIGNIFICANCE: On-demand pain management is essential to postoperative patients. However, the traditional on-demand pain management strategy is hampered by the limited tissue penetration depth of near-infrared stimuli and the lack of proper imaging guidance. The proposed research is significant because it provides a nanoplatform for deep penetrated ultrasound controlled pain management under clinical applicable ultrasound imaging guidance. Moreover, the nanoplatform with prolonged retention time and lysosomal escape capability can provide long-term pain alleviation. Therefore, our results suggest that nanoplatform with lysosomal escape capability can provide an effective strategy for ultrasound imaging-guided on-demand pain management.

Cardiac arrest caused by coronary occlusion during transcatheter aortic valve implantation: a unique cause.

Coronary artery occlusion (CAO) is a rare but life-threatening complication of transcatheter aortic valve implantation (TAVI). The mechanism of CAO is the displacement of the native calcified valve leaflet over the coronary ostium. Here, we report on a woman who experienced sudden cardiac arrest and abrupt CAO during TAVI, which was caused by two different original obstructions, a rupture of aortic plaque or a partial tear of the aortic intima blocking the upper 2/3 of the left main trunk (LMT) ostium, and the transcatheter heart valve (THV) blocking the lower 1/3 of the LMT ostium. She was eventually successfully treated with the chimney stenting technique. Aortography other than coronary angiography was used to ascertain CAO. In patients presenting with abrupt cardiac arrest or cardiogenic shock with LMT occlusion, there must be prompt identification, and the causes of CAO may be various and rare. The identification of CAO relies not only on CAG but also on aortography, especially if the locations and origins of obstructions are special. Supportive therapy with an attempt at percutaneous revascularization is necessary. Pre-procedural assessment is crucial prior to TAVI interventions. In cases with high risk of CAO, upfront coronary artery protection can be provided.

Lingering Dynamics of Type 2 Diabetes Mellitus Red Blood Cells in Retinal Arteriolar Bifurcations.

It has been proven that the deformability of red blood cells (RBC) is reduced owing to changes in mechanical properties, such as diabetes mellitus and hypertension. To probe the effects of RBC morphological and physical parameters on the flow field in bifurcated arterioles, three types of RBC models with various degrees of biconcave shapes were built based on the in vitro experimental data. The dynamic behaviors of the RBCs in shear flow were simulated to validate the feasibility of the finite element-Arbitrary Lagrangian-Eulerian method with a moving mesh. The influences of the shear rate and viscosity ratios on RBC motions were investigated. The motion of RBCs in arteriolar bifurcations was further simulated. Abnormal variations in the morphological and physical parameters of RBCs may lead to diminished tank-tread motion and enhanced tumbling motion in shear flow. Moreover, abnormal RBC variations can result in slower RBC motion at the bifurcation with a longer transmit time and greater flow resistance, which may further cause inadequate local oxygen supply. These findings would provide useful insights into the microvascular complications in diabetes mellitus.

Moderate-Intensity Ultrasound-Triggered On-Demand Analgesia Nanoplatforms for Postoperative Pain Management.

Introduction: The restricted duration is a fundamental drawback of traditional local anesthetics during postoperative pain from a single injection. Therefore, an injectable local anesthetic that produces repeatable on-demand nerve blocks would be ideal. Methods: We offer ultrasound-triggered on-demand analgesia consisting of dendritic mesoporous silica nanoparticles (DMSN) carried with ultrasound-sensitive perfluoropentane (PFP) and levobupivacaine (DMSN-bupi-PFP) to achieve repeatable and customizable on-demand local anesthetics. Results: The vaporization of liquid PFP was triggered by ultrasound irradiation to produce a gas environment. Subsequently, the enhanced cavitation effect could improve the release of levobupivacaine to achieve pain relief under a moderate-intensity ultrasound irradiation. DMSN-bupi-PFP demonstrated a controlled-release pattern and showed a reinforced ultrasonic sensitivity compared to levobupivacaine loaded DMSN (DMSN-bupi). The sustained release of levobupivacaine produced continuous analgesia of more than 9 hours in a model of incision pain, approximately 3 times longer than a single free levobupivacaine injection (3 hours). The external ultrasound irradiation can trigger the release of levobupivacaine repeatedly, resulting in on-demand analgesia. In addition, DMSN-bupi-PFP nanoplatforms for ultrasound-enabled analgesia showed low neurotoxicity and good biocompatibility in vitro and in vivo. Conclusion: This DMSN-bupi-PFP nanoplatform can be used in pain management by providing long-lasting and on-demand pain alleviation with the help of moderate-intensity ultrasound.

Experimental Study of the Propagation Process of Dissection Using an Aortic Silicone Phantom.

BACKGROUND: The mortality of acute aortic dissection (AD) can reach 65~70%. However, it is challenging to follow the progress of AD formation. The purpose of this work was to observe the process of dissection development using a novel tear-embedded silicone phantom. METHODS: Silicone phantoms were fabricated by embedding a torn area and primary tear feature on the inner layer. CT scanning and laser lightening were conducted to observe the variations in thickness and volume of the true lumen (TL) and false lumen (FL) during development. RESULTS: The model with a larger interlayer adhesion damage required a lower pressure to trigger the development of dissection. At the initiation stage of dissection, the volume of TL increased by 25.5%, accompanied by a 19.5% enlargement of tear size. The force analysis based on the change of tear size verified the deduction of the process of interlaminar separation from the earlier studies. CONCLUSIONS: The primary tear and the weakening adhesion of the vessel layers are key factors in AD development, suggesting that some forms of primary damage to the arterial wall, in particular, the lumen morphology of vessels with straight inner lumen, should be considered as early risk predictors of AD.

[Experimental study on inhibition of retinal neovascularisation by gene transfer of extracellular 1-3 domain of VEGF receptor KDR].

OBJECTIVE: To evaluate the effect of liposome mediated plasmids KDRn3 injected into the vitreous to inhibit experimental retinal neovascularization. METHODS: One-week-old C57BL/6N mice were exposed to 75% ± 2% oxygen for 5 days, then returned to the room air to induce retinal neovascularization. Cationic liposome mediated KDRn3 comp-lex (1 µl) was injected into the vitreous in the treatment group. PBS 1µl or liposome were injected in the control group. The pEGFP-N1/KDRn3 expression was observed by using fluorescence microscope. Retinal neovascularization was evaluated by counting the number of vascular endothelial cell nuclei on the vitreal side of the inner limiting membrane of the retina and measuring the areas of non-perfusions in central retina. RESULTS: KDRn3 protein was expressed both in the ganglion layer and in the inner layer. Retinal wholemount preparation of retinal neovascular animal model showed that prominent neovascular tuft and fluorescein leakage and large areas of non-perfusions in central retina. Fewer neovascular tufts and fewer areas of non-perfusions could be seen after pEGFP-N1/KDRn3 injection. There were statistic differences between control group and pEGFP-N1/KDRn3 injecting group with the number of vascular endothelial cell nuclei on the vitreal side of the inner limiting membrane of the retina (0.20 ± 0.51, 13.58 ± 2.48, 23.05 ± 3.40, 21.70 ± 2.89; F = 1085.25, P < 0.05) and the areas of non-perfusions in central retina [(1.33 ± 0.49), (2.75 ± 0.70), (2.12 ± 0.35) mm(2); F = 17.61, P < 0.01]. CONCLUSION: pEGFP-N1/KDRn3 gene transfer can inhibit retinal neovascularisation in C57Bl/6J mice of ischaemia-induced retinal neovascularisation on some extent.

A Brush-Spin-Coating Method for Fabricating In Vitro Patient-Specific Vascular Models by Coupling 3D-Printing.

PURPOSE: In vitro patient-specific flexible vascular models are helpful for understanding the haemodynamic changes before and after endovascular treatment and for effective training of neuroendovascular interventionalists. However, it is difficult to fabricate models of overall unified or controllable thickness using existing manufacturing methods. In this study, we developed an improved and easily implemented method by combining 3D printing and brush-spin-coating processes to produce a transparent silicone model of uniform or varied thickness. METHODS: First, a water-soluble inner-skeleton model, based on clinical data, was printed on a 3D printer. The skeleton model was subsequently fixed in a single-axis-rotation machine to enable continuous coating of silicone, the thickness of which was manually controlled by adsorption and removal of excess silicone in a brush-spinning operation. After the silicone layer was solidified, the inner skeleton was further dissolved in a hot water bath, affording a transparent vascular model with real geometry. To verify the controllability of the coating thickness by using this method, a straight tube, an idealised aneurysm model, a patient-specific aortic arch model, and an abdominal aortic aneurysm model were manufactured. RESULTS: The different thicknesses of the manufactured tubes could be well controlled, with the relative standard deviations being 5.6 and 8.1% for the straight and aneurysm tubes, respectively. Despite of the diameter changing from 33 to 20 mm in the patient-specific aorta, the thickness of the fabricated aortic model remains almost the same along the longitudinal direction with a lower standard deviation of 3.1%. In the more complex patient-specific abdominal aneurysm model, varied thicknesses were realized to mimic the measured data from the CT images, where the middle of the aneurysm was with 2 mm and abdominal aorta as well as the iliac arteries had the normal thickness of 2.3 mm. CONCLUSION: Through the brush-spin-coating method, models of different sizes and complexity with prescribed thickness can be manufactured, which will be helpful for developing surgical treatment strategies or training neuroendovascular interventionalists.

Effects of a Short-Term Left Ventricular Assist Device on Hemodynamics in a Heart Failure Patient-Specific Aorta Model: A CFD Study.

Patients with heart failure (HF) or undergoing cardiogenic shock and percutaneous coronary intervention require short-term cardiac support. Short-term cardiac support using a left ventricular assist device (LVAD) alters the pressure and flows of the vasculature by enhancing perfusion and improving the hemodynamic performance for the HF patients. However, due to the position of the inflow and outflow of the LVAD, the local hemodynamics within the aorta is altered with the LVAD support. Specifically, blood velocity, wall shear stress, and pressure difference are altered within the aorta. In this study, computational fluid dynamics (CFD) was used to elucidate the effects of a short-term LVAD for hemodynamic performance in a patient-specific aorta model. The three-dimensional (3D) geometric models of a patient-specific aorta and a short-term LVAD, Impella CP, were created. Velocity, wall shear stress, and pressure difference in the patient-specific aorta model with the Impella CP assistance were calculated and compared with the baseline values of the aorta without Impella CP support. Impella CP support augmented cardiac output, blood velocity, wall shear stress, and pressure difference in the aorta. The proposed CFD study could analyze the quantitative changes in the important hemodynamic parameters while considering the effects of Impella CP, and provide a scientific basis for further predicting and assessing the effects of these hemodynamic signals on the aorta.

Inhibition of autophagy induced by proteasome inhibition increases cell death in human SHG-44 glioma cells.

AIM: The ubiquitin-proteasome system (UPS) and lysosome-dependent macroautophagy (autophagy) are two major intracellular pathways for protein degradation. Recent studies suggest that proteasome inhibitors may reduce tumor growth and activate autophagy. Due to the dual roles of autophagy in tumor cell survival and death, the effect of autophagy on the destiny of glioma cells remains unclear. In this study, we sought to investigate whether inhibition of the proteasome can induce autophagy and the effects of autophagy on the fate of human SHG-44 glioma cells. METHODS: The proteasome inhibitor MG-132 was used to induce autophagy in SHG-44 glioma cells, and the effect of autophagy on the survival of SHG-44 glioma cells was investigated using an autophagy inhibitor 3-MA. Cell viability was measured by MTT assay. Apoptosis and cell cycle were detected by flow cytometry. The expression of autophagy related proteins was determined by Western blot. RESULTS: MG-132 inhibited cell proliferation, induced cell death and cell cycle arrest at G(2)/M phase, and activated autophagy in SHG-44 glioma cells. The expression of autophagy-related Beclin-1 and LC3-I was significantly up-regulated and part of LC3-I was converted into LC3-II. However, when SHG-44 glioma cells were co-treated with MG-132 and 3-MA, the cells became less viable, but cell death and cell numbers at G(2)/M phase increased. Moreover, the accumulation of acidic vesicular organelles was decreased, the expression of Beclin-1 and LC3 was significantly down-regulated and the conversion of LC3-II from LC3-I was also inhibited. CONCLUSION: Inhibition of the proteasome can induce autophagy in human SHG-44 glioma cells, and inhibition of autophagy increases cell death. This discovery may shed new light on the effect of autophagy on modulating the fate of SHG-44 glioma cells.Acta Pharmacologica Sinica (2009) 30: 1046-1052; doi: 10.1038/aps.2009.71.

Numerical analysis of wall shear stress in ascending aorta before tearing in type A aortic dissection.

Although the incidence of many cardiovascular diseases has declined as medical treatments have improved, the prevalence of aortic dissection (AD) has increased. Compared to type B dissections, type A dissections are more severe, and most patients with type A dissections require surgical treatment. The objective of this study was to investigate the relationships between the wall shear stress (WSS) on the aortic endothelium and the frequent tearing positions using computational fluid dynamics. Five type A dissection cases and two normal aortas were included in the study. First, the structures of the aortas before the type A dissection were reconstructed on the basis of the original imaging data. Analyses of flow in the reconstructed premorbid structures reveals that the rupture positions in three of the five cases corresponded to the area of maximum elevated WSS. Moreover, the WSS at the junction of the aortic arch and descending aorta was found to be elevated, which is considered to be related to the locally disturbed helical flow. Meanwhile, the highest WSS in the patients with premorbid AD was found to be almost double that of the control group. Due to the noticeable morphological differences between the AD cases and the control group, the WSSs in the premorbid structures without vasodilation in the ascending part were estimated. The computational results revealed that the WSS was lower in the aorta without vasodilation, but the pressure drop in this situation was higher than that with vasodilation in the ascending aorta. Significant differences were seen between the AD cases and the control group in the angles of the side branches of the aortic arch and its bending degree. Dilation of the ascending aorta and alterations in the branching angles may be the key determinants of a high WSS that leads to type A dissection. Greater tortuosity of the aortic arch leads to stronger helical flow through the distal aortic arch, which may be related to tears in this region.

A single nucleotide polymorphism in hsa­miR­146a is responsible for the development of bronchial hyperresponsiveness in response to intubation during general anesthesia.

Bronchial hyperresponsiveness (BHR) is the most common clinical manifestation identified in asthmatic patients, and intubation is the major factor that stimulates the airway of patients receiving general anesthetic. In the present study, nitric oxide synthase 1 (NOS1) was identified as a target gene of micro (mi)R­146a using in silico analysis and luciferase assay. Furthermore, the regulatory role of miR­146a was demonstrated by the observation that the NOS1 expression level in pulmonary artery smooth muscle cells (PASMCs) transfected with miR­146a mimics was significantly downregulated and the NOS1 expression level in PASMCs transfected with miR­146a inhibitors was significantly upregulated. Additionally, it was identified that a polymorphism in pri­miR­146 interfered with mature processing and reduced the quantity of mature miRNA. To assess the association between the polymorphism and the development of BHR, 563 patients with basic pulmonary diseases, such as asthma, emphysema or bronchitis were enrolled in the present study. Each participant received a general anesthetic and the development of BHR was evaluated. The miR­146a rs2910164 polymorphism CC genotype was identified to be significantly associated with a decreased risk of BHR in response to intubation when compared with the GG or GC genotype (odds ratio, 0.38; confidence interval, 0.18­0.78). These findings indicate that the miR­146a rs2910164 polymorphism is associated with a decrease risk of BHR, and the CC genotype increased the level of NOS1 expression, which was physiologically inhibited by wild­type miR­146a.

A Y-Shaped Microfluidic Device to Study the Combined Effect of Wall Shear Stress and ATP Signals on Intracellular Calcium Dynamics in Vascular Endothelial Cells.

The intracellular calcium dynamics in vascular endothelial cells (VECs) in response to wall shear stress (WSS) and/or adenosine triphosphate (ATP) have been commonly regarded as an important factor in regulating VEC function and behavior including proliferation, migration and apoptosis. However, the effects of time-varying ATP signals have been usually neglected in the past investigations in the field of VEC mechanobiology. In order to investigate the combined effects of WSS and dynamic ATP signals on the intracellular calcium dynamic in VECs, a Y-shaped microfluidic device, which can provide the cultured cells on the bottom of its mixing micro-channel with stimuli of WSS signal alone and different combinations of WSS and ATP signals in one single micro-channel, is proposed. Both numerical simulation and experimental studies verify the feasibility of its application. Cellular experimental results also suggest that a combination of WSS and ATP signals rather than a WSS signal alone might play a more significant role in VEC Ca2+ signal transduction induced by blood flow.

Association of XRCC1 gene polymorphisms with susceptibility to gastric cancer in Chinese Han population.

OBJECTIVES: Gastric cancer is one of the most frequently causing cancer-related deaths worldwide. The X-ray repair complementing group 1 gene (XRCC1) is an important candidate gene for influencing gastric cancer risk. This study aimed to evaluate the associations between XRCC1 genetic variants and gastric cancer susceptibility in Chinese Han population. METHODS: Four hundred twenty-four gastric cancer patients and 430 cancer-free controls were enrolled. Two genetic variants (c.1254C>T and c.1779C>G) of XRCC1 gene were genotyped by created restriction site-polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. KEY FINDINGS: Results from this study indicated that the allele and genotype frequencies of these two genetic variants were statistically different between gastric cancer patients and cancer-free controls. The association analyses suggested that these two genetic variants were statistically associated with the increased risk of gastric cancer (for c.1254C>T, T versus C: odds ratio (OR) = 1.44, 95% confidence interval (CI) 1.17-1.77; for c.1779C>G, G versus C: OR = 1.51, 95% CI 1.22-1.86). The allele-T of c.1254C>T and allele-G c.1779C>G genetic variants may contribute to the susceptibility to gastric cancer in Chinese Han population. CONCLUSION: Our data suggest that these two genetic variants might be used as molecular markers for evaluating the susceptibility to gastric cancer.

Serum microRNA 143 and microRNA 215 as potential biomarkers for the diagnosis of chronic hepatitis and hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is regarded as one of the most common malignancies and among the leading causes of cancer death among the whole world. The most urgent needs are to find sensitive markers for early diagnosis or monitor postoperative recurrence and to give adequate treatment for HCC. MicroRNAs (miRNAs) are reported as a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of the targeted genes. This study was conducted to detect the application of miR-143 and miR-215 in the diagnosis of HCC. METHODS: A total of 340 serum samples (127 samples from controls, 118 samples from hepatitis and 95 samples from HCC patients) were collected. The levels of the two mature miRNAs (miR-143 and miR-215) were detected by probe-based stem-loop quantitative reverse-transcriptase PCR (RT-qPCR) in controls, hepatitis and HCC patients. Besides, the relationship between miR-143 and miR-215 levels and clinical and pathological factors was explored. RESULTS: We found that the expression of serum miR-215 was distinctly increased in chronic hepatitis compared with controls (mean ± SD: 6.79 ± 0.72 vs. 3.46 ± 0.37, P < 0.001 and mean ± SD: 8.38 ± 0.87 vs. 3.46 ± 0.37, P < 0.001). In addition, we conduct ROC analyses to detect the potential application of miR-143 and miR-215 in the diagnosis of chronic hepatitis and HCC. Our results showed that miR-143 and miR-215 might be a potential biomarker for the hepatitis and HCC. CONCLUSIONS: In conclusion, the expression of miR-143 and miR-215 in serum were significantly up-regulated in patients with chronic hepatitis and HCC. Due to its reasonable sensitivity and specificity for both diseases, miR-143 and miR-215 could be as potential circulating biomarkers. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1048932281272754.