Treatment of a patient with aconitine poisoning using veno-arterial membrane oxygenation:A case report

BACKGROUND Aconitine poisoning is highly prone to causing malignant arrhythmias.The elimination of aconitine from the body takes a considerable amount of time,and during this period,patients are at a significant risk of death due to malignant arrhythmias associated with aconitine poisoning.CASE SUMMARY A 30-year-old male patient was admitted due to accidental ingestion of aconitinecontaining drugs.Upon arrival at the emergency department,the patient intermittently experienced malignant arrhythmias including ventricular tachycardia,ventricular fibrillation,ventricular premature beats,and cardiac arrest.Emergency interventions such as cardiopulmonary resuscitation and defibrillation were promptly administered.Additionally,veno-arterial extracorporeal membrane oxygenation(VA-ECMO)therapy was initiated.Successful resuscitation was achieved before ECMO placement,but upon initiation of ECMO,the patient experienced recurrent malignant arrhythmias.ECMO was utilized to maintain hemodynamics and respiration,while continuous blood purification therapy for toxin clearance,mechanical ventilation,and hypothermic brain protection therapy were concurrently administered.On the third day of VA-ECMO support,the patient’s respiratory and hemodynamic status stabilized,with only frequent ventricular premature beats observed on electrocardiographic monitoring,and echocardiography indicated recovery of cardiac contractile function.On the fourth day,a significant reduction in toxin levels was observed,along with stable hemodynamic and respiratory functions.Following a successful pump-controlled retrograde trial occlusion test,ECMO assistance was terminated.The patient gradually improved postoperatively and achieved recovery.He was discharged 11 days later.CONCLUSION VA-ECMO can serve as a bridging resuscitation technique for patients with reversible malignant arrhythmias.

Extracorporeal membrane oxygenation states basilar artery thrombectomy and left posterior cerebral artery stent thrombectomy:A case report

BACKGROUND Extracorporeal membrane oxygenation(ECMO)is a new type of extracorporeal respiratory and circulatory assistance device.It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator(membrane lung)to replace lung and heart functions in a short time.ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function.CASE SUMMARY We report a case of an 81-year-old woman who underwent whole cerebral angiography,basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO.The patient was admitted to the hospital due to myocardial infarction.Considering that the cause of the patient’s disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO,the department of Radioactive Intervention performed cerebral angiography.And the result of the angiography indicated vascular occlusion.After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain,the patency of the occlusive vessel was achieved.CONCLUSION Although the patient eventually died of circulatory failure,the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.

Effect of Xiaoyu Zhixue Tablet (消瘀止血片) on Expression ofPlatelet Membrane Glycoproteins in Patients withHemorrhagic Thrombopathy

Objective: To observe the effect of Xiaoyu Zhixue tablet (消瘀止血片,XYZXT) on the expression of platelet membrane glycoproteins in patients with hemorrhagic thrombopathy, and to explore its possible mechanism. Methods: The total of 148 patients with hemorrhagic thrombopathy were randomly divided into two groups, the traditional Chinese medicicne (TCM) group (n=98) treated with XYZXT and the Western medicine (WM) group (n=50) treated with adrenosin, vitamins C, K and P, both for 6 months. The therapeutic effect and the recovery rate of platelet aggregation in the two groups were observed. And platelet membrane glycoprotein (GP) Ⅰb/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅡb, GP Ⅲa and P-selectin were analyzed by flow cytometry in both groups before and after treatment and also in 34 normal healthy subjects. Results: The total effective rate of hemostasis was 89. 8% in TCM group and 54. 0% in the WM group (x2=45.83, P<0.01), and the recovery rate of platelet aggregation was 72.4% and 4.0% respectively (x2=62.06, P<0.01). The fluorescence intensity of GP Ⅰ b/Ⅸ, GPⅡb/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin were lower in both groups before treatment than those in the healthy subjects. Expression of above-mentioned marks was elevated in TCM group after 6 months' therapy, which was insignificantly different as compared with the healthy subjects (P>0.05) and higher than those in the WM group (P<0.05). Conclusion: One of the mechanisms in treating hemorrhagic thrombopathy with XYZXT is that it could regulate the expression of GP Ⅰb/Ⅸ, GPⅡ b/Ⅲa complexes, GPⅠb, GPⅢa and P-selectin at the level of receptor protein.

Effects of Blood Cell Membrane Disruption by Ultrasonic Technology on the Quality of Duck Blood Tofu

[Objective] The aim was to improve the quality of the duck blood tofu by ultrasonic technology. [Method] Ultrasonic technology was used to break the blood cell membrane. The optimal ultrasonic condition was determined by single factor de- sign, and the differences in sensory quality and nutritional value between the duck blood tofu treated with and without ultrasonication were studied. [Result] The optimal ultrasonic power was 400 W and the optimal ultrasonic time was 6 min. Under these conditions, the content of duck blood haemoglobin increased by 43.46%, the content of iron increased by 10.85%, and the breakage rate was 100%. The a＊ value of the duck blood tofu increased significantly under ultrasonic treatment. Both internal micro-structure and texture parameters proved that the ultrasonic contributed to the formation of gel structure. After treatment by artificial gastric juice and artifi- cial intestinal juice, the total amino acids in the digestive juice were 9.25% higher than that of the duck blood tofu without ultrasonic treatment. [Conclusion] The duck blood tofu under ultrasonic treatment would be beneficial to human body absorption, and the nutrition value would be higher as well.

Treatment of refractory giant macular hole by vitrectomy with internal limiting membrane transplantation and autologous blood

AIM：To investigate the effect of internal limiting membrane transplantation and autologous blood on treating refractory giant macular hole.METHODS：Thirty-seven eyes with giant macular hole of the smallest hole diameter 〉700 μm,the maximum diameter of the substrate 〉1000 μm and hole formation factor 〈0.6 underwent surgical treatment.The patients were randomly divided into two groups.Nineteen eyes with surgical flip of the internal limiting membrane in group A,18 eyes with internal limiting membrane transplantation in group B who underwent the tamponade of internal limiting membrane into the hole,autologous plasma was used to seal the hole.The patients were followed up for 3 mo,optical coherence tomography and best corrected visual acuity（BCVA） were recorded before and after operation,and the results were statistically analyzed.RESULTS：At 3 mo after operation,BCVA of the two groups was significantly improved compared with that before operation（tA=4.192,tB=4.374,P〈0.05）.But there was no significant difference in visual acuity between the two groups（χ^2=0.128,P〉0.05）.At 3 mo after operation,the closure rate of group A was 68.4%,and 100% in group B.（χ^2=5.628,P〈0.05）.The defect diameter of inner segment/outer segment at 3 mo after the operation was significantly lower than that before operation（tA=12.287,tB=15.481,P〈0.05）,and the difference was statistically significant（t=2.552,P〈0.05）.CONCLUSION：Internal limiting membrane transplantation combined with autologous whole blood can improve the postoperative closure rate of the refractory large aperture,and can effectively improve the postoperative visual acuity.

Expression of Platelet Membrane Glycoprotein Ib/Ⅸ/Ⅴ Complex,a Receptor of Thrombin,in Patients with Hemorrhagic Thrombopathy

To investigate the role of platelet membrane glycoprotein （GP） Ib/Ⅸ/Ⅴ complex and its subunit GP Ibα in patients with hemorrhagic thrombopathy （HT）, the expressions of GP Ib/Ⅸ/Ⅴ complex and GP Ibα,defined as mean fluorescence intensity （MFI）, were assessed by flow cytometry. The maximum aggregation of platelet was determined by turbidity method. These indicators were compared among 68 HT patients with the presenting complaint of hemorrhage, 33 well-controlled HT patients and 32 normal healthy subjects. The results showed that the MFI of GP Ib/Ⅸ /Ⅴ complex and GP Ibα was markedly lower in HT patients with current hemorrhage than that in the healthy subjects, with difference being statistically significant （P〈0.05）. There was no significant difference in the expressions of GP Ib/ Ⅸ/ Ⅴ complex and GP Ibα between well-controlled HT patients and normal healthy subjects （P〉0.05）. It was concluded that the expression of GP Ib/Ⅸ /Ⅴ complex, the receptor of thrombin and von Willebrand factor, was down-regulated in HT patients with current hemorrhage, which might result in the dysfunction of platelet aggregation and recurrence of HT.

Association of the Platelet Membrane Glycoprotein Ⅰa C807T Gene Polymorphism with Aspirin Resistance

To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein Ⅰa （GP Ⅰa） gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin （100 mg/d） for 7 days. Platelet aggregation function was detected using adenosine diphosphate （ADP） and arachidonic acid （AA） before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function： an aspirin resistant （AR） group, an aspirin semi-responder （ASR） group and an aspirin-sensitive （AS） group. Platelet GP Ⅰa gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers （PCR-SSP）. The results showed that T allelic frequency in AR group and ASR group were higher that of AS group （P〈0.005）, and the prevalence of genotypes （TT＋TC） of these two groups was significantly higher than that in AS group （P〈0.05）. Platelet GP Ⅰa T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression （OR=3.76, 95% CI： 2.87-9.58）. The results suggest that inherited platelet GP Ⅰa variations may have an important impact on aspirin resistance and the presence of GP Ⅰa T allele may be a marker of genetic susceptibility to aspirin resistance.

Vitrectomy with residual internal limiting membrane covering and autologous blood for a secondary macular hole:A case report

BACKGROUND Myopic foveoschisis(MF)is a common complication of pathological myopia.A macular hole(MH)usually results from the natural progression of MF and is a common complication of vitrectomy.Vitrectomy combined with residual internal limiting membrane(ILM)covering and autologous blood was effective for closing a secondary MH.CASE SUMMARY A 52-year-old woman presented to our clinic with a complaint of blurred vision in the right eye for 7 years.Her best corrected visual acuity(BCVA)was 20/100,axial length was 25.79 mm and standard equivalent refractive error was-10.5 dioptres.Preoperative optical coherence tomography revealed foveoschisis in the right eye.Vitrectomy with fovea-sparing ILM peeling was performed.An MH developed and gradually expanded 5 mo after the initial vitrectomy.Vitrectomy with residual ILM covering and autologous blood was performed.The MH closed 3 wk after the second vitrectomy.CONCLUSION Fovea-sparing ILM peeling can provide residual ILM for the treatment of MH secondary to vitrectomy for MF.Vitrectomy combined with residual ILM covering and autologous blood is effective for closing secondary MH and improving BCVA.

Modeling biomembranes and red blood cells by coarse-grained particle methods

In this work, the previously developed coarse-grained （CG） particle models for biomembranes and red blood cells （RBCs） are reviewed, and the advantages of the CG particle methods over the continuum and atomistic simulations for modeling biological phenomena are discussed. CG particle models can largely increase the length scale and time scale of atomistic simulations by eliminating the fast degrees of freedom while preserving the mesoscopic structures and properties of the simulated system. Moreover, CG particle models can be used to capture the microstructural alternations in diseased RBCs and simulate the topological changes of biomembranes and RBCs, which are the major challenges to the typical continuum representations of membranes and RBCs. The power and versatility of CG particle methods are demonstrated：through simulating the dynamical processes mvolving significant topological .changes e.g. lipid self-assembly vesicle fusion and membrane budding.

Redistribution of Platelet Membrane Glycoprotein IV and Release of Intracellular α-granule Thrombospondin in Patients with Chronic Myelogenous Leukemia

The redistribution of platelet membrane glycoprotein IV (GPIV) and the release of intracellular Q-granule thrombospondin (TSP) were examined and the inhibition of 5-thromboglobulin (&TG) and platelet factor 4 (PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of β-TG and PF4 in sera was conducted. GPIV in inactive platelet from CML was 36080±17010 molecules/platelet as compared with 13190±4810 from the controls (P<0,01), No abnormality was found in the distribution of platelet membrane GPIb and GPIIb/III.(P>0. 05). The GPIV redistribution on active platelet membrane induced thrombin (1U/ml) from CML and healthy donors was 44320132310 and 228001 12700 molecules/platelet respectively (P<0. 01 ). The difference in the release of intracellular Q-granule TSP between CML and the control group was not found (P>0.05). There was no direct correlation between GPIV expression and TSP binding after platelet activation. The high leveIs of β-TG and PF4 in sera inhibited release of intracellular a-granule TSP in vitro. These results indicate that the abnormality of platelet membrane GPIV is a common marker in CML, therefore the specific increase of platelet GPIV in patients with CML may be a useful tool for the diagnosis and monitoring of the platelet dysfunction. The release of interna1 TSP pools is hindered by either β-TG or PF4 in sera.

The Relationships between Erythrocyte Membrane n-6 to n-3 Polyunsaturated Fatty Acids Ratio and Blood Lipids and C-reactive Protein in Chinese Adults:An Observational Study

Objective To investigate the relationships between erythrocyte membrane n-6：n-3 PUFAs ratio and blood lipids and high sensitivity C-reactive protein （hs-CRP）. Methods The Chinese and a observational study consisted of a population-based cross-sectiona subsequent 1-year follow-up study of 171 subjects with the fasting cholesterol of 5.13-8.00 mmol/L. study of 456 plasma total Results In the cross-sectional analysis, plasma low-density lipoprotein cholesterol （LDL-c） had a significant and negative association with the erythrocyte membrane n-6：n-3 PUFAs ratio （P for trend=0.019） after adjusting for sex, age and total PUFA percentage. In the follow-up study, 171 subjects were categorized into quartiles by the changes of n-6：n-3 ratio in erythrocyte membrane （△=month 12-month 0）. In the top quartile whose ratios of n-6：n-3 increased by an average of 1.25 during the follow-up, the LDL-c-lowering extent was 3.3 times of that in the lowest quartile whose ratios of n-6：n-3 decreased by an average of 1.13 （-1.07 mmol/L v.s. -0.32 mmol/L）. The hsCRP decreased by 0.11 mg/dL in the lowest quartile while increasing by 0.10 mg/dL in the top quartile （P for difference=0.052）. Conclusion Our results suggested that the balance between n-6 and n-3 fatty acids may optimize the cardiovascular benefits from dietary PUFAs.

Membrane glycoprotein M6A promotes μ-opioid receptor endocytosis and facilitates receptor sorting into the recycling pathway

The interaction of p-opioid receptor （MOPr） with the neuronal membrane glycoprotein M6a is known to facilitate MOPr endocytosis in human embryonic kidney 293 （HEK293） cells. To further study the role of M6a in the post-endocytotic sorting of MOPr, we investigated the agonist-induced co-internalization of MOPr and M6a and protein targeting after internalization in HEK293 cells that co-expressed HA-tagged MOPr and Myc-tagged M6a. ,We found that M6a, MOPr, and Rab 11, a marker for recycling endosomes, co-localized in endocytotic vesicles, indicating that MOPr and M6a are primarily targeted to recycling endosomes after endocytosis. Furthermore, co-expression of M6a augmented the post-endocytotic sorting of 6-opioid receptors into the recycling pathway, indicating that M6a might have a more general role in opioid receptor post-endocytotic sorting. The enhanced post-endocytotic sorting of MOPr into the recycling pathway was accompanied by a decrease in agonist-induced receptor down-regulation of M6a in co-expressing cells. We tested the physiological relevance of these findings in primary cultures of cortical neurons and found that co-expression of M6a markedly increased the translocation of MOPrsfrom the plasma membrane to intracellular vesicles at steady state and significantly enhanced both constitutive and agonist-induced receptor endocytosis. In conclusion, our results strongly indicate that M6a modulates MOPr endocytosis and post-endocytotic sorting and has an important role in receptor regulation.

Hyperhomocysteinemia and Increased Oxidative Stress Levels Are Associated with Impaired Membrane Fluidity of Red Blood Cells in Hypertensive and Normotensive Men: An Electron Spin Resonance Investigation

Hyperhomocysteinemia and oxidative stress may be strongly linked to hypertension, atherosclerosis and other cardiovascular diseases. The present study was performed to investigate possible relationships among plasma total homocysteine, plasma 8-iso-prostaglandin F2α (8-isoPG F2α: an index of oxidative stress), and membrane fluidity (a reciprocal value of membrane microviscosity) in hypertension. We measured the membrane fluidity of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was significantly decreased in hypertensive men compared with normotensive men. Plasma total homocysteine levels were significantly higher in hypertensive men than in normotensive men, and correlated with plasma 8-isoPG F2α. In contrast, plasma nitric oxide (NO)-metabolites (an index of endothelial function) were lower in hypertensive men than in normotensive men. The reduced membrane fluidity of RBCs was associated with increased total homocysteine and plasma 8-isoPG F2α levels and decreased plasma NO-metabolite levels. Multivariate regression analysis showed that, after adjusting for general risk factors, plasma total homocysteine and 8-isoPG F2α were significant determinants of membrane fluidity of RBCs, respectively. These results suggest that hyperhomocysteinemia and oxidative stress with endothelial dysfunction might have a close correlation with impaired rheologic behavior of RBCs and circulatory disorders in hypertensive men.

Effect of ultraviolet blood irradiation and oxygenation on nerve function and function of the red blood cell membrane pump in patients with acute cerebral infarction

BACKGROUND： Ultraviolet blood irradiation and oxygenation （UBIO） has obtained better clinical effect in treating acute cerebral infarction, but the mechanism underlying this effect remains unclear. OBJECTIVE： To observe the effect of UBIO on the nerve function and activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase activities on the red blood cell （RBC） membrane of patients with acute cerebral infarction. DESIGN： A randomized and controlled study.SETTING： Department of Neurology, Xiangfan Central Hospital.PARTICIPANTS： From January 2000 to December 2001, excluding those above 70 years old, 58 cases of 700 patients with acute cerebral infarction admitted in the Department of Neurology, Xiangfan Central Hospital, were recruited and divided into two groups according to the random number table： UBIO treated group （n=28）, including 17 males and 11 females, aged 40-68 years; and control group （n=30）, including 20 males and 10 females, aged 44-69 years. All the patients agreed to participate in the therapeutic program and detected items. The general informations were comparable without obvious differences between the two groups （P 〉 0.05）.METHODS： ① The patients in both groups received routine treatments, besides, those in the UBIO treated group were given UBIO treatment by using the XL-200 type therapeutic apparatus produced in Shijiazhuang, whose ultraviolet wave was set at 253.7 nm with the energy density of 0.568 J/m^2 per second, UBIO treatment started from the second day after admission, once every other day, with a single course consisting of 5-7 treatments. ② In the UBIO treated group, the venous blood was sampled before and after the first, third and the completion of the treatment course respectively, the venous blood was taken at each corresponding time point in the control group. After centrifugation of the blood at 10 000 rounds per minute, the RBC membrane was separated and then the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase were detected by means of phosphorus determination.③ The nerve function was scored before and after treatment in both groups with European stroke scale, which included 13 items, the total score was 0-100 points, the higher the score, the better the nerve function. MAIN OUTCOME MEASURES ：①Score of European stroke scale before and after treatment in both groups.② Comparison of the activities of K^＋-Na^＋-ATPase and Ca2^＋-Mg2^＋-ATPase on RBC membrane between the two groups before treatment and after the first, third and the completion of the treatment. RESULTS： All the 58 patients with cerebral infarction were involved in the analysis of results.① The score of European stroke scale had no obvious difference between the two groups [（49.31±11.48）, （50.58±12.63）, P 〉 0.05], and it was obviously higher in the UBIO treated group than in the control group after treatment [84.66±13.75）, （77.05±11.17）, P 〈 0.05].②The activity of K^＋-Na^＋-ATPase on RBC membrane in the UBIO treated group was significantly increased after the first and third treatment as compared with before treatment [（31.56±19.25）, （27.64±15.83）, （17.67±13.83）, P 〈 0.01], it was still higher after the completion of the treatment than before treatment without obvious difference [（20.86±14.53）, P 〉 0.05]. After the first and third treatment, it was obviously higher in the UBIO treated group than in the control group [19.31±11.88）, （17.44±10.42）, P 〈 0.01]. ③ In the UBIO treated group, Ca2^＋-Mg2^＋-ATPase activity on RBC membrane significantly increased after the first treatment and remained higher than the pre-treatment level throughout the treatment [（27.49±14.72）, （17.41±4.82）, P 〈 0.01]. The activity of Ca2^＋-Mg2^＋-ATPase on RBC membrane was markedly higher in the UBIO treated group than in the control group after after the first, third and the completion of treatment respectively [（24.83±12.88）, （17.70±5.69）; （28.08±13.44）, （16.32±5.29）; （17.42±6.04）, P〈 0.05-0.01]. CONCLUSION： The effect of UBIO treatment against acute cerebral infarction may be mediated by the increased K^＋-Na^＋ ATPase and Ca2^＋-Mg2^＋-ATPase activities on RBC membrane, which enhances the RBC transformation ability so as to lower RBC aggregation and correct high blood viscosity.

Analysis of Mechanical Behavior of Red Blood Cell Membrane with Malaria Infection

Human red blood cells (RBCs) are responsible to transport oxygen and carbon dioxide for human bodies. The physiological functions of RBCs are greatly influenced by their mechanical properties. When RBC is infected by Malaria parasite called Plasmodium falciparum, it shows progressive changes in mechanical properties and loses its deformability. The infected red blood cells (IRBCs) develop properties of cytoadherence (stickiness) and rosetting (the binding of non-infected RBCs to parasitized RBCs). In this paper to analyze the mechanical properties and deformability of the IRBC, we applied stress-stretch ratio relation of its biomembrane .To express this constitutive relation, we proposed a mathematical model (Neo-Hookean model) based on membrane theory. On this model, we present continuous stress-stretch ratio curves for the relation derived from the model for different intracellular developmental stages of the parasite, to determine the mechanical properties of IRBC. The analytical results obtained from the mathematical model are more closed with the experimental data [1] which demonstrates the validity of the model. By restricting our attention to spherically symmetric deformation in the final schizont stage of parasite development, the pressure-extension ratio relation curve also adapted from the proposed strain energy function. The change in osmotic pressure versus volumetric ratio has been also considered for IRBC before hemolysis.

Some substrates of P-glycoprotein targeting <i>β</i>-amyloid clearance by quantitative structure-activity relationship (QSAR)/membrane-interaction (MI)-QSAR analysis

The pathogenesis of Alzheimer’s disease (AD) putatively involves a compromised blood-brain barrier (BBB). In particular, the importance of brain-to-blood transport of brain-derived metabolites across the BBB has gained increasing attention as a potential mechanism in the pathogenesis of neurodegenerative disorders such as AD, which is characterized by the aberrant polymerization and accumulation of specific misfolded proteins, particularly β-amyloid (Aβ), a neuropathological hallmark of AD. P-glycoprotein (P-gp), a major component of the BBB, plays a role in the etiology of AD through Aβ clearance from the brain. Our QSAR models on a series of purine-type and propafenone-type substrates of P-gp showed that the interaction between P-gp and its modulators depended on Molar Refractivity, LogP, and Shape Attribute of drugs it transports. Meanwhile, another model on BBB partitioning of some compounds revealed that BBB partitioning relied upon the polar surface area, LogP, Balaban Index, the strength of a molecule combined with the membrane-water complex, and the changeability of the structure of a solute-membrane-water complex. The predictive model on BBB partitioning contributes to the discovery of some molecules through BBB as potential AD therapeutic drugs. Moreover, the interaction model of P-gp and modulators for treatment of multidrug resistance (MDR) indicates the discovery of some molecules to increase Aβ clearance from the brain and reduce Aβ brain accumulation by regulating BBB P-gp in the early stages of AD. The mechanism provides a new insight into the therapeutic strategy for AD.

In situ tumor vaccination with adenovirus vectors encoding measles virus fusogenic membrane proteins and cytokines

AIM： To evaluate whether intratumoral expression of measles virus fusogenic membrane glycoproteins H and F （MV-FMG）, encoded by an adenovirus vector Ad.MV-HI F, alone or in combination with local coexpression of cytokines （IL-2, IL-12, IL-18, IL-21 or GM-CSF）, can serve as a platform for inducing tumor-specific immune responses in colon cancer.METHODS： We used confocal laser scanning microscopy and flow cytometry to analyze cell-cell fusion after expression of MV-FMG by dye colocalization. In a syngeneic bilateral subcutaneous MC38 and Colon26 colon cancer model in C57BL/6 and BALB/c mice, we assessed the effect on both the directly vector-treated tumor as well as the contralateral, not directly vector- treated tumor. We assessed the induction of a tumorspecific cytotoxic T lymphocyte （CTL） response with a lactate dehydrogenase （LDH） release assay.RESULTS： We demonstrated in vitro that transduction of MC38 and Colon26 cells with Ad.MV-H/F resulted in dye colocalization, indicative of cell-cell fusion, in addition, in the syngeneic bilateral tumor model we demonstrated a significant regression of the directly vector-inoculated tumor upon intratumoral expression of MV-FMG alone or in combination with the tested cytokines. We observed the highest anti-neoplastic efficacy with MV-FMG and lL-21 coexpression. The degree of tumor regression of the not directly vector-treated tumor correlated with the anti-neoplastic response of the directly vector-treated tumor. This regression was mediated by a tumor-specific CTL response.CONCLUSION： Our data indicate that intratumoral expression of measles virus fusogenic membrane glycoproteins is a promising tool both for direct tumor treatment as well as for tumor vaccination approaches that can be further enhanced by cytokine coexpression.

RBC Membrane Camouflaged Semiconducting Polymer Nanoparticles for Near-Infrared Photoacoustic Imaging and Photothermal Therapy

Semiconducting conjugated polymer nanoparticles(SPNs)represent an emerging class of phototheranostic materi-als with great promise for cancer treatment.In this report,low-bandgap electron donoracceptor(DA)-conjugated SPNs with sur-face cloaked by red blood cell membrane(RBCM)are developed for highly e ective photoacoustic imaging and photothermal therapy.The resulting RBCM-coated SPN(SPN@RBCM)displays remarkable near-infrared light absorption and good photosta-bility,as well as high photothermal conver-sion e ciency for photoacoustic imaging and photothermal therapy.Particularly,due to the small size(<5 nm),SPN@RBCM has the advantages of deep tumor penetration and rapid clearance from the body with no appreciable toxicity.The RBCM endows the SPNs with prolonged systematic circulation time,less reticuloendothelial system uptake and reduced immune-recognition,hence improving tumor accumulation after intravenous injection,which provides strong photoacoustic signals and exerts excellent photothermal therapeutic e ects.Thus,this work provides a valuable paradigm for safe and highly e cient tumor pho-toacoustic imaging and photothermal therapy for further clinical translation.

Preparation of antifouling ultrafiltration membranes from copolymers of polysulfone and zwitterionic poly(arylene ether sulfone)s

The past few decades have witnessed rapid gains in our demands of antifouling membranes such as water purification membranes and hemodialysis membranes.A variety of methodologies have been proposed for improving the antifouling performance and the hemocompatibility of the membranes.In this study,a series of copolymers(PSF-PESSB)containing polysulfone(PSF)and poly(arylene ether sulfone)bearing pendant zwitterionic sulfobetaine groups(PESSB)were prepared via one-pot polycondensation.Subsequently,the ultrafiltration(UF)membranes were prepared from different zwitterion-containing copolymers.The prepared membranes showed high thermal stability and mechanical properties.Besides,it also displayed attractive antifouling performance and blood compatibility.Compared with the original PSF membrane,the amount of protein absorption on the modified membrane was reduced;the flux recovery ratio and the resistance to blood cells were significantly improved.The results of this work suggest that PSF-PESSB membranes are expected to be applied in blood purification.The introduction of zwitterion-containing polymers to membranes paves ways for developing advanced hemodialysis technologies for crucial process.

The importance of laminin at the blood-brain barrier

The blood-brain barrier is a unique property of central nervous system blood vessels that protects sensitive central nervous system cells from potentially harmful blood components.The mechanistic basis of this barrier is found at multiple levels,including the adherens and tight junction proteins that tightly bind adjacent endothelial cells and the influence of neighboring pericytes,microglia,and astrocyte endfeet.In addition,extracellular matrix components of the vascular basement membrane play a critical role in establishing and maintaining blood-brain barrier integrity,not only by providing an adhesive substrate for blood-brain barrier cells to adhere to,but also by providing guidance cues that strongly influence vascular cell behavior.The extracellular matrix protein laminin is one of the most abundant components of the basement membrane,and several lines of evidence suggest that it plays a key role in directing blood-brain barrier behavior.In this review,we describe the basic structure of laminin and its receptors,the expression patterns of these molecules in central nervous system blood vessels and how they are altered in disease states,and most importantly,how genetic deletion of different laminin isoforms or their receptors reveals the contribution of these molecules to blood-brain barrier function and integrity.Finally,we discuss some of the important unanswered questions in the field and provide a“to-do”list of some of the critical outstanding experiments.