Publications by authors named "Song-tao Yang"

35 Publications

Endovascular Retreatment of Cerebral Aneurysms Previously Treated with Endovascular Embolization.

J Neurol Surg A Cent Eur Neurosurg 2020 May 19;81(3):207-212. Epub 2019 Nov 19.

Department of Neurosurgery, The First Hospital, Hebei Medical University, Shijiazhuang, Hebei Province, China.

Objective:  Intracranial aneurysms treated with endovascular coil embolization may recur. We investigated the factors affecting aneurysmal recurrence after embolization and effects of endovascular retreatment within 1 year.

Methods:  In 3 years, 1,335 patients with 1,385 intracranial aneurysms were treated with coil embolization. Factors affecting aneurysm recurrence and the effects of endovascular retreatment were analyzed.

Results:  Angiography immediately following embolization showed total occlusion in 1,030 aneurysms (74.4%), neck remnant in 207 (14.9%), and partial occlusion in 148 (10.7%), with a total peri-procedure complication rate of 4.2%. Overall, 145 patients with 151 aneurysms recurred within 1 year and the other 1,234 aneurysms remained occluded (89.1%). A significant ( < 0.05) difference existed in aneurysm size, rupture status, use of stent and immediate occlusion outcome between the two groups, with significantly ( < 0.05) lower recurrence rates in aneurysms with smaller sizes, no rupture and stent-assistance coiling. Neck remnant, partial occlusion, coiling without stent assistance, large and giant aneurysms were significant ( < 0.05) risk factors for aneurysm recurrence during the first year. The rate of recurrence was 4.7% (11/232) in aneurysms with total occlusion and 35.9% (23/64) in aneurysms with neck remnant and partial occlusion. Of the 34 recurrent aneurysms, 6 were re-embolized with detachable coils alone, 12 with stent-assisted coiling, 8 with balloon-assisted embolization, and the remaining 8 aneurysms with covered stents, resulting in total occlusion in 28 aneurysms and neck remnant in 6.

Conclusion:  Recurrence of previously-coiled cerebral aneurysms is significantly affected by aneurysm size, use of stent and degree of immediate occlusion. Endovascular retreatment with balloon-or stent-assisted techniques or with covered stents can be safe and effective for recurrent cerebral aneurysms.
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http://dx.doi.org/10.1055/s-0039-1685513DOI Listing
May 2020

Can we predict who will develop postoperative hyperkalaemia after parathyroidectomy in dialysis patients with secondary hyperparathyroidism?

BMC Nephrol 2019 06 20;20(1):225. Epub 2019 Jun 20.

Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, 28 Fuxing Road, Beijing, 100853, China.

Background: Hyperkalaemia occurs frequently in many maintenance haemodialysis (MHD) patients after parathyroidectomy (PTX) with secondary hyperparathyroidism (SHPT). However, the clinical risk factors that predict postoperative hyperkalaemia are uncertain.

Methods: This retrospective cohort study included 90 maintenance haemodialysis patients aged ≥18 years who underwent PTX between April 2011 and April 2016 at Aerospace Center Hospital (Peking University Aerospace School of Clinical Medicine). Pre- and post-PTX surgery venous samples were measured in quadruplicate. We examined univariate associations with demographics, dialysis characteristics, laboratory values and medications. Hyperkalaemia was defined as serum potassium >5.3 mmol/L.

Results: Out of nighty patients, twenty-two (24.4%) developed postoperative hyperkalaemia, of whom sixteen (18.1%) developed hyperkalaemia on postoperative day 3. The univariate analysis showed that weight, dialysis duration, preoperative serum potassium, alkaline phosphate, triglyceride, and postoperative alkaline phosphate were independently associated with hyperkalaemia after parathyroidectomy. The univariate logistic regression model showed that preoperative serum potassium was the only independent factor that could predict hyperkalaemia after parathyroidectomy (odds ratio, 1.59; 95% confidence interval, 1.24-2.05). The optimal cut-off for pre-operative K was 3.9 mmol/L according to the receiver operating characteristic (ROC) curve. A higher incidence of postoperative hyperkalaemia was found in male and younger patients, but the difference was not statistically significant (p>0.05).

Conclusions: Pre-operative serum potassium less than 3.9 mmol/L was associated with less hyperkalaemia post-operatively in end-stage renal disease (ESRD) patients undergoing PTX.
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http://dx.doi.org/10.1186/s12882-019-1416-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585140PMC
June 2019

Construction of Aneurysmal Models on a Curved Vascular Segment of a Carotid Siphon Model for Testing Endovascular Devices.

World Neurosurg 2019 Mar 7;123:e581-e587. Epub 2018 Dec 7.

Department of Neurosurgery, The First Hospital, Hebei Medical University, Shijiazhuang, Hebei Province, China.

Objective: To investigate construction of an aneurysm on a curved vascular segment of a carotid siphon model for testing endovascular devices.

Methods: Preshaped carotid siphon models of polytetrafluoroethylene were constructed from a human cadaver for confining canine common carotid artery (CCA). The canine right external jugular vein was isolated and harvested to make a venous pouch by suturing 1 end. The right CCA was isolated, and the venous pouch was sutured onto the right CCA to make an aneurysm. The right CCA segment containing the aneurysm was excised and guided through the preshaped polytetrafluoroethylene carotid siphon model using a guidewire with the aneurysm adjusted to protrude out of the round window of the siphon model. The siphon model together with the aneurysm was sutured end-to-end onto the left CCA to form a carotid siphon model in vivo.

Results: Five canine models were successfully constructed; the average construction time was 120 minutes. All aneurysms and siphon models remained patent 7 days and 2 weeks later. Five covered stents for intracranial use were tested for flexibility and apposition to the vascular wall in the curved segment of the carotid siphon model in vivo. All the covered stents passed the tortuous siphon model without much difficulty and were deployed successfully to cover the aneurysm orifice without endoleak.

Conclusions: The carotid siphon model in vivo can simulate well the geometry of the human carotid siphon segment and can be used to test endovascular devices for interventions.
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http://dx.doi.org/10.1016/j.wneu.2018.11.224DOI Listing
March 2019

Hemodynamic Factors Affecting Carotid Sinus Atherosclerotic Stenosis.

World Neurosurg 2019 Jan 24;121:e262-e276. Epub 2018 Sep 24.

Department of Neurosurgery, The First Hospital, Shijiazhuang, China.

Purpose: Carotid atherosclerotic plaque occurs predominantly at the outer wall of the carotid sinus, and computational fluid dynamics (CFD) plays an important role in explaining plaque formation. The present study investigated the hemodynamic factors affecting carotid atherosclerotic stenosis.

Methods: Sixteen patients with normal carotid arteries and 16 with symptomatic stenotic carotid sinus underwent 3-dimensional angiographic imaging evaluations and were studied with CFD to simulate the complete 3-dimensional blood flow and hemodynamic parameter distribution in the carotid bifurcations. The hemodynamic parameters, including wall shear stress (WSS), dynamic and total pressure, total pressure gradient, strain rate, velocity, and velocity angle, were investigated.

Results: The atherosclerosis-prone outer lateral walls of the carotid sinus and the external carotid artery at its start had significantly (P < 0.05) low dynamic pressure, WSS, strain rate, and total pressure gradient but high static pressure. The blood flow near these walls with flow separation had significantly (P < 0.05) decreased velocity and dynamic pressures but a high velocity angle. The carotid divider had significantly (P < 0.05) elevated dynamic and total pressure, WSS, strain rate, and total pressure gradient but reduced static pressure. Additional stenosis occurred at the downstream area of stenosis with significantly (P < 0.05) decreased dynamic pressure, WSS, strain rate, and total pressure gradient similar to the wall at the sinus and the start of the external carotid artery.

Conclusion: Significantly decreased vascular WSS, dynamic pressure, strain rate, and total pressure gradient are key to atherosclerotic plaque formation at the carotid sinus.
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http://dx.doi.org/10.1016/j.wneu.2018.09.091DOI Listing
January 2019

Small Tenuous Intracranial Arteries Can Well Tolerate the Deployment of 2 Stents in Y Configuration or an Overlapping Manner in Treating Intracranial Aneurysms.

World Neurosurg 2018 Aug 2;116:e1098-e1104. Epub 2018 Jun 2.

Department of Neurosurgery, The First Hospital, Hebei Medical University, Shijiazhuang, Hebei Province, China.

Objective: To investigate parent vessel response to deployment of 2 stents for treatment of cerebral aneurysms.

Methods: Fifteen patients (11 women and 4 men; age range, 25-83 years) with 18 wide-necked intracranial aneurysms were treated with 2 stents with or without subsequent coiling. The vascular diameter was measured and compared within the native parent artery, and the single stent and double stent were measured and compared before and immediately after stenting and at angiographic follow-up.

Results: Thirty stents were deployed. Before stenting, the mean vessel diameter was 3.4 ± 0.21 mm at point A, 3.06 ± 0.18 mm at point B, 3.16 ± 0.21 mm at point C, 2.67 ± 0.27 mm at point D, and 2.56 ± 0.23 mm at point E. The deployment of 2 stents resulted in statistically significant increases in both the average vascular diameter and cross-sectional area at points C (3.51 ± 0.22 mm, P = 0.0006; and 9.76 ± 1.17 mm, P = 0.001, respectively) and E (2.88 ± 0.32 mm, P = 0.01; and 7.28 ± 1.46 mm, P = 0.02, respectively) compared with prestenting. At angiographic follow-ups, compared with before stenting, significant increases were documented at point C (3.42 ± 0.22 mm and 9.42 ± 1.37 mm, respectively) at first angiographic follow-up but at points A (3.62 ± 0.45 mm and 10.51 ± 2.37 mm, respectively) and B (3.26 ± 0.24 mm and 8.47±1.26 mm, respectively) at second angiographic follow-up. No significant vascular stenosis was demonstrated at the double-stent segment compared with the single-stent or native artery segments.

Conclusions: The small tenuous cerebral arteries can well tolerate the deployment of 2 stents for the treatment of intracranial aneurysms.
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http://dx.doi.org/10.1016/j.wneu.2018.05.179DOI Listing
August 2018

Endovascular Stent Deployment in the Management of Lesions Related to Internal Carotid Artery Redundancy.

World Neurosurg 2018 Aug 28;116:e903-e912. Epub 2018 May 28.

Clinical Laboratory, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.

Objective: To investigate the endovascular treatment (stenting with or without coiling) of cervical and intracranial lesions associated with internal carotid artery (ICA) redundancy.

Methods: Nine patients harboring 12 lesions of dissections, pseudoaneurysms, and aneurysms in the presence of ICA redundancy were treated using stent deployment with or without coiling. There were 8 female and 1 male patients with an age range of 31-89 years (mean, 55 years).

Results: Two patients with ICA dissections were treated with stenting alone while all the other pseudoaneurysms and aneurysms were managed with both stenting and coiling. Fourteen stents were deployed, and the success rate of stent deployment was 100%. All the lesions were successfully occluded with subtotal occlusion in 3 lesions and total occlusions in the remaining lesions. Mean follow-up was 7.3 months (range, 3-25 months), during which time the lesions remained occluded with patent stents. No symptoms existed at follow-up.

Conclusions: Vascular lesions related to the internal carotid artery redundancy can be successfully managed endovascularly, and the redundancy can no longer represent an obstacle in modern era with advanced techniques and materials.
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http://dx.doi.org/10.1016/j.wneu.2018.05.127DOI Listing
August 2018

Comparison of surgical and endovascular approaches in the management of multiple intracranial aneurysms.

Int J Surg 2016 Aug 8;32:129-35. Epub 2016 Jul 8.

Departments of Medical Research and Neurosurgery, Shijiazhuang First Hospital, Hebei Medical University, Shijiazhuang, Hebei, PR China.

Objective: To investigate the outcomes and safety of endovascular compared with surgical clipping for multiple intracranial aneurysms.

Material And Methods: 98 patients with 260 multiple intracranial aneurysms were treated with endovascular, surgical clipping, combined treatment, and observation. Data were retrospectively studied following treatment and at follow-up.

Results: In the endovascular group, 44 aneurysms were treated with coils only and 29 aneurysms were treated with stent deployment. The complete occlusion rate was 65%, and the total complication rate was 12% with no permanent deficit. After angiographic follow-up for 1-90 (mean 62) months, the total recurrence rate was 18.3%. In the clipping group, 65 aneurysms were clipped. The complete occlusion rate was 90.8%, and the complication rate was 10.9% with 1 permanent deficit. After follow-up for 11-71 (mean 49) months, the angiographic recurrence rate was 1.5%. In the combination group, 20 aneurysms were treated endovascularly. The complete occlusion rate was 78.9%, and the complication rate was 15.8% with no permanent deficit. Twenty-eight aneurysms were treated surgically with the complete occlusion rate of 89.3%, the complication rate of 20% and 3 permanent deficits. After follow-up for 1-93 (mean 58) months, the angiographic recurrence rate was 33.3% for embolization and 3.6% for clipping. Seventy-four aneurysms for observation had 2.7% regrowth rate within 1-3 years.

Conclusion: Endovascular embolization has an accepted complication rate but no neurological deficits compared with surgical clipping and may be a better approach for multiple intracranial aneurysms than surgical clipping.
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http://dx.doi.org/10.1016/j.ijsu.2016.07.004DOI Listing
August 2016

Genetic diversity and evolutionary dynamics of Ebola virus in Sierra Leone.

Nature 2015 Aug 13;524(7563):93-6. Epub 2015 May 13.

Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun 130122, China.

A novel Ebola virus (EBOV) first identified in March 2014 has infected more than 25,000 people in West Africa, resulting in more than 10,000 deaths. Preliminary analyses of genome sequences of 81 EBOV collected from March to June 2014 from Guinea and Sierra Leone suggest that the 2014 EBOV originated from an independent transmission event from its natural reservoir followed by sustained human-to-human infections. It has been reported that the EBOV genome variation might have an effect on the efficacy of sequence-based virus detection and candidate therapeutics. However, only limited viral information has been available since July 2014, when the outbreak entered a rapid growth phase. Here we describe 175 full-length EBOV genome sequences from five severely stricken districts in Sierra Leone from 28 September to 11 November 2014. We found that the 2014 EBOV has become more phylogenetically and genetically diverse from July to November 2014, characterized by the emergence of multiple novel lineages. The substitution rate for the 2014 EBOV was estimated to be 1.23 × 10(-3) substitutions per site per year (95% highest posterior density interval, 1.04 × 10(-3) to 1.41 × 10(-3) substitutions per site per year), approximating to that observed between previous EBOV outbreaks. The sharp increase in genetic diversity of the 2014 EBOV warrants extensive EBOV surveillance in Sierra Leone, Guinea and Liberia to better understand the viral evolution and transmission dynamics of the ongoing outbreak. These data will facilitate the international efforts to develop vaccines and therapeutics.
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http://dx.doi.org/10.1038/nature14490DOI Listing
August 2015

[Photoelectric parametric test system of LED based on virtual instrument].

Guang Pu Xue Yu Guang Pu Fen Xi 2014 Nov;34(11):2912-7

The standardized measuring principle, requirements and implementations of the above parameters of LEDs were researched and analyzed in the present paper. Then a comprehensive test system involved with optics, machinery and computer was designed to accomplish data acquisition, algorithm design and interface design on virtual instrument using NI data acquisition card USB6210. And convincing results of LEDs' parameters, including peak wavelength, width of half-peak wavelength, centroid wavelength, chromaticity coordinates, purity, correlated color temperature and the forward voltage/current, were achieved with good consistency based on the measured spectrum. The system owns simple interface, reliable algorithms and stable results. Respective measurements on five kinds of color of LED result in an average error less than 3%, which show an ideal performance of the system.
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November 2014

Microcatheter looping facilitates access to both the acutely angled parent artery and cerebral aneurysms for effective embolization.

Interv Neuroradiol 2014 Dec 5;20(6):669-76. Epub 2014 Dec 5.

Department of Neurosurgery, Shijiazhuang First Hospital; Shijiazhuang, Hebei, China.

Aneurysms with an acutely angled parent artery are difficult to access for coiling. This study aimed to investigate the safety and effectiveness of microcatheter looping for embolization of cerebral aneurysms with access difficulty. Ten patients (male:female=5:5) with cerebral aneurysms treated with the microcatheter looping technique were analyzed retrospectively. The parent artery formed an acute angle with the major artery in five aneurysms. The microcatheter was looped into a "α" loop for treatment in the anterior temporal artery aneurysm and a "U" loop in the remaining nine aneurysms. All ten aneurysms were successfully treated with the microcatheter looping technique. The microcatheter tip was successfully navigated into the aneurysm sac and remained stable throughout the embolization process. All aneurysms were occluded with total occlusion in five and near-total occlusion in five, and the parent artery remained patent in all cases. No complications occurred peri-procedurally. The Glasgow Outcome Scale was 5 in all patients before discharge. Follow-up angiography six to 12 months later revealed a good occlusion status of the aneurysms. The microcatheter looping technique is effective when the conventional embolization technique fails to treat cerebral aneurysms with difficult access especially when the parent artery forming an acute angle with the major artery exacerbates difficult access to the aneurysms.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295238PMC
http://dx.doi.org/10.15274/INR-2014-10048DOI Listing
December 2014

The stent-assisted coil-jailing technique facilitates efficient embolization of tiny cerebral aneurysms.

Korean J Radiol 2014 Nov-Dec;15(6):850-7. Epub 2014 Nov 7.

Department of Neurosurgery, Shijiazhuang First Hospital, Hebei Medical University, Shijiazhuang 050011, China.

Objective: Tiny cerebral aneurysms are difficult to embolize because the aneurysm's sac is too small for a single small coil, and coils within the aneurysm may escape from the confinement of a stent. This study was performed to introduce the stent-assisted coil-jailing technique and to investigate its effect on the coil embolization of tiny intracranial aneurysms.

Materials And Methods: Sixteen patients with tiny intracranial aneurysms treated with the stent-assisted coil-jailing technique between January 2011 and December 2013 were retrospectively reviewed and followed-up.

Results: All aneurysms were successfully treated with the coil-jailing technique, and at the end of embolization, complete occlusion of the aneurysm was achieved in 9 cases (56.3%), incomplete occlusion in 6 (37.5%), and partial occlusion in 1 (6.3%). Intraprocedural complications included acute thrombosis in one case (6.3%) and re-rupture in another (6.3%). Both complications were managed appropriately with no sequela. Follow-up was performed in all patients for 3-24 months (mean, 7.7 months) after embolization. Complete occlusion was sustained in the 9 aneurysms with initial complete occlusion, progressive thrombosis to complete occlusion occurred in the 6 aneurysms with initial near-complete occlusion, and one aneurysm resulted in progressive thrombosis to complete occlusion after initial partial occlusion. No migration of stents or coils occurred at follow-up as compared with their positions immediately after embolization. At follow-up, all patients had recovered with no sequela.

Conclusion: The stent-assisted coil-jailing technique can be an efficient approach for tiny intracranial aneurysms, even though no definite conclusion regarding its safety can be drawn from the current data.
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http://dx.doi.org/10.3348/kjr.2014.15.6.850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4248643PMC
May 2015

Production and characterization of a fusion peptide derived from the rabies virus glycoprotein (RVG29).

Protein Expr Purif 2014 12 10;104:7-13. Epub 2014 Sep 10.

Military Veterinary Institute, Academy of Military Medical Sciences, Changchun 130122, Jilin Province, China. Electronic address:

Gene therapy targeting the brain holds great promise in curing nervous system degenerative diseases in clinical applications. With this in mind, in a previous study a 29 amino-acid peptide derived from the rabies virus glycoprotein (RVG29) with a nonamer stretch of arginine residues (RVG29-9R) at its carboxy-terminus was exploited as a ligand for brain-targeting gene delivery. Importantly, the report demonstrated that the RVG29-9R vector was able to cross the blood-brain barrier. RVG29-9R is currently synthesized by commercial companies with high associated costs. In this study, in order to reduce the costs of producing RVG29-9R, we have expressed and purified 6mg of a recombinant peptide (RVG29-9R-6His) from 0.4g of cultured Escherichia coli. We assessed the physiochemical properties of RVG29-9R-6His, its cytotoxicity, and the in vitro transfection efficiency in Neuro 2a cells (which express the acetylcholine receptor). Our results reveal that the RVG29-9R-6His peptide recognized Neuro 2a cells in a dose-dependent manner and it was also able to bind plasmid DNA and deliver it into the Neuro 2a cells effectively. Therefore, our study has demonstrated that the recombinant RVG29-9R-6His peptide retains the functions of RVG29-9R and so may provide an economically viable and alternative production method for the manufacture of RVG29-9R.
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http://dx.doi.org/10.1016/j.pep.2014.09.001DOI Listing
December 2014

Aptamers targeting rabies virus-infected cells inhibit street rabies virus in vivo.

Int Immunopharmacol 2014 Aug 13;21(2):432-8. Epub 2014 Apr 13.

Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun 130062, China. Electronic address:

Rabies is a viral infection of the CNS that is almost always fatal once symptoms occur. No effective treatment of the disease is available and novel antiviral strategies are urgently required. Street rabies viruses are field isolates known to be highly neurotropic. Aptamers are single-stranded oligonucleotides that bind their targets with high affinity and specificity and thus have potential for use in diagnostic and therapeutic applications. In this study, we demonstrate that the aptamers FO24 and FO21, which target RABV-infected cells, can significantly protect mice from a lethal dose of the street rabies virus FJ strain in vivo. Groups receiving preexposure prophylaxis had higher survival rates than the groups receiving postexposure prophylaxis. When mice were inoculated with aptamers (4 nmol) for 24h by intracranial or intramuscular injection prior to intramuscular inoculation with the FJ strain, approximately 60% of the mice survived. These results indicate that the FO21 and FO24 aptamers may be used to develop preventative antiviral therapy against rabies disease.
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http://dx.doi.org/10.1016/j.intimp.2014.03.020DOI Listing
August 2014

An inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice.

Virus Genes 2014 Jun 18;48(3):411-20. Epub 2014 Feb 18.

College of Veterinary Medicine, Jilin University, Changchun, 130062, China.

The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD50 than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity.
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http://dx.doi.org/10.1007/s11262-014-1049-9DOI Listing
June 2014

Selection of an aptamer against rabies virus: a new class of molecules with antiviral activity.

Virus Res 2014 May 30;184:7-13. Epub 2014 Jan 30.

Institute of Military Veterinary, Academy of Military Medical Science, Changchun 130062, China. Electronic address:

Rabies is a fatal central nervous system (CNS) disease caused by the neurotropic rabies virus (RABV). The therapeutic management of RABV infections is still problematic, and novel antiviral strategies are urgently required. We established the RVG-BHK-21 cell line, which expresses RABV glycoprotein on the cell surface, to select aptamers. Through 28 iterative rounds of selection, single-stranded DNA (ssDNA) aptamers were generated by exponential enrichment (SELEX). A virus titer assay and a real-time quantitative reverse transcription PCR (qRT-PCR) assay revealed that four aptamers could inhibit the replication of RABV in cultured baby hamster kidney (BHK)-21 cells. However, the aptamers did not inhibit the replication of other virus, e.g., canine distemper virus (CDV) and canine parvovirus (CPV). In addition, the GE54 aptamer was found to effectively protect mice against lethal RABV challenge. After inoculation with aptamers for 24h or 48h, followed by inoculation with CVS-11, approximately 25-33% of the mice survived. In summary, we selected aptamers that could significantly protect from a lethal dose of RABV in vitro and in vivo.
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http://dx.doi.org/10.1016/j.virusres.2014.01.021DOI Listing
May 2014

Canine parvovirus VP2 protein expressed in silkworm pupae self-assembles into virus-like particles with high immunogenicity.

PLoS One 2014 17;9(1):e79575. Epub 2014 Jan 17.

Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China.

The VP2 structural protein of parvovirus can produce virus-like particles (VLPs) by a self-assembly process in vitro, making VLPs attractive vaccine candidates. In this study, the VP2 protein of canine parvovirus (CPV) was expressed using a baculovirus expression system and assembled into parvovirus-like particles in insect cells and pupae. Electron micrographs of VLPs showed that they were very similar in size and morphology when compared to the wild-type parvovirus. The immunogenicity of the VLPs was investigated in mice and dogs. Mice immunized intramuscularly with purified VLPs, in the absence of an adjuvant, elicited CD4(+) and CD8(+) T cell responses and were able to elicit a neutralizing antibody response against CPV, while the oral administration of raw homogenates containing VLPs to the dogs resulted in a systemic immune response and long-lasting immunity. These results demonstrate that the CPV-VLPs stimulate both cellular and humoral immune responses, and so CPV-VLPs may be a promising candidate vaccine for the prevention of CPV-associated disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0079575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3894932PMC
September 2014

[Evaluation of optimal dosage of heparin in hemodialysis patients by thromboelastograph].

Beijing Da Xue Xue Bao Yi Xue Ban 2013 Aug;45(4):625-9

Department of Nephrology, Aerospace Central Hospital & Aerospace Clinical Medical College of Peking University, Beijing 100049, China.

Objective: To assess the blood coagulation function and investigate the appropriate dose of unfractionated heparin by thromboelastograph in maintenance hemodialysis (MHD) patients.

Methods: Thirty MHD patients were enrolled in this study and divided into two groups. The total dose of unfractionated heparin was below 80 u/kg in the low-dose group (LH, n=16), while it exceeded 80 u/kg in the high-dose group (HH, n=14). Blood routine tests and conventional coagulation examinations were measured before hemodialysis. TEG and activated partial thromboplastin time (APTT) were examined at the beginning and the end of hemodialysis at the arterial circuit, and the second hour (h 2) at the venous circuit.

Results: The initial bolus dose of unfractionated heparin for LH and HH groups were (26.6±6.2) u/kg vs. (42.3±8.2) u/kg and the repeated maintenance dose for both the groups were (13.7±5.1) u/kg/h vs. (18.2±4.3) u/kg/h. No significant difference was noticed in results from blood routine tests and conventional coagulation parameters between the two groups. In LH group, the increase of APTT at h 2 of hemodialysis was significant compared with the baseline, while it recovered partly at the end of hemodialysis. R value prolonged at h 2 and the end of hemodialysis. CI value was more negative at the end of hemodialysis. In HH group, APTT obviously prolonged at h 2 and the end of hemodialysis. R value also obviously prolonged at h 2 of hemodialysis. At the end of hemodialysis, R and K values prolonged, MA value reduced, and CI value was more negative. APTT was significantly different between the two groups at h 2 of hemodialysis. At the end of hemodialysis, APTT was still extended in HH group, but there was no significant difference. R value at h 2, and R, K, MA, CI values at the end of hemodialysis were significantly different between the two groups. R values at the end of hemodialysis had a direct correlation with the dose of unfractionated heparin (r=0.403, P=0.041), but APTT had not. There was no significant difference in transmembrane pressure, venous pressure and filter clotting between the two groups.

Conclusion: Low-dose heparin is effective and safe as anticoagulant in hemodialysis. TEG shows that the blood coagulation function is more sensitive than conventional coagulation parameters and is useful to anticoagulant therapy in MHD patients.
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August 2013

Adeno-associated viruses serotype 2-mediated RNA interference efficiently inhibits rabies virus replication in vitro and in vivo.

J Vet Med Sci 2013 Oct 14;75(10):1355-61. Epub 2013 Jul 14.

College of Veterinary Medicine, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, P. R. China.

To investigate the potential of adeno-associated viruses serotype 2 (AAV2)-mediated RNA interference (RNAi) as an antiviral agent against rabies, recombinant AAV2 vectors expressing siRNA targeting the nucleoprotein (N) gene of rabies virus (RABV) (rAAV-N796) were constructed and evaluated. When NA cells pretreated with rAAV-N796 were challenged with RABV, there was a 37.8 ± 3.4% to 55.1 ± 5.3% reduction in RABV virus titer. When cells pre-challenged with RABV were treated with rAAV-N796, there was a 4.4 ± 1.4 to 28.8 ± 3.2% reduction in RABV virus titer. Relative quantification of RABV transcripts using real-time PCR and Western blot revealed that the knockdown of RABV-N gene transcripts was based on the rAAV-N796 inoculation titer. When any NA cells were treated with rAAV-N796 before or after challenged with RABV, significant reduction in virus titer was observed in both administrations. Mice treated intracerebrally with rAAV-N796 exhibited 50 ± 5.3 and 62.5 ± 4.7% protection when challenged intracerebrally or intramuscally, respectively, with lethal RABV. When mice treated intramuscularly with rAAV-N796 were challenged intramuscularly with lethal RABV, they exhibited 37.5 ± 3.7% protection. When mice were intracerebrally and intramuscularly with rAAV-N796 24 hr after exposure to RABV infection, they exhibited 25 ± 4.1% protection The N gene mRNA levels in the brains of challenged mice with three different administrations were reduced (55, 68, 32 and 25%, respectively). These results indicated that AAV2 vector-mediated siRNA delivery in vitro in NA cells inhibited RABV multiplication, inhibited RABV multiplication in vivo in the mice brain and imparted partial protection against lethal rabies. So, it may have a potential to be used as an alternative antiviral approach against rabies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942934PMC
http://dx.doi.org/10.1292/jvms.13-0127DOI Listing
October 2013

Aptamers targeting rabies virus-infected cells inhibit viral replication both in vitro and in vivo.

Virus Res 2013 May 17;173(2):398-403. Epub 2013 Jan 17.

Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun 130062, China.

Rabies is an acute fatal encephalitis disease that affects many warm-blooded mammals. The causative agent of the disease is Rabies virus (RABV). Currently, no approved therapy is available once the clinical signs have appeared. Aptamers, oligonucleotide ligands capable of binding a variety of molecular targets with high affinity and specificity, have recently emerged as promising therapeutic agents. In this study, sixteen high-affinity single-stranded DNA (ssDNA) aptamers were generated by cell-SELEX. Viral titer assays revealed aptamers could specifically inhibit the replication of RABV in cells but did not inhibit the replication of canine distemper virus or canine parvovirus. In addition, the FO21 and FO24 aptamers, with and without PEGylation, were found to effectively protect mice against lethal RABV challenge. When mice were inoculated with aptamers for 24h prior to inoculation with CVS-11, approximately 87.5% of the mice survived. Here, we report aptamers that could significantly protect the mice from a lethal dose of RABV in vitro and in vivo, as demonstrated by the results for survival rate, weight loss and viral titers. These results indicate that FO21 and FO24 aptamers are a promising agent for specific antiviral against RABV infections.
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http://dx.doi.org/10.1016/j.virusres.2012.12.017DOI Listing
May 2013

Small interfering RNAs targeting the rabies virus nucleoprotein gene.

Virus Res 2012 Oct 3;169(1):169-74. Epub 2012 Aug 3.

Agricultural Division, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, China.

Rabies virus (RABV) infection continues to be a global threat to human and animal health, yet no curative therapy has been developed. RNA interference (RNAi) therapy, which silences expression of specific target genes, represents a promising approach for treating viral infections in mammalian hosts. We designed six small interfering (si)RNAs (N473, N580, N783, N796, N799 and N1227) that target the conserved region of the RABV challenge virus standard (CVS)-11 strain nucleoprotein (N) gene. Using a plasmid-based transient expression model, we demonstrated that N796, N580 and N799 were capable of significantly inhibiting viral replication in vitro and in vivo. These three siRNAs effectively suppressed RABV expression in infected baby hamster kidney-21 (BHK-21) cells, as evidenced by direct immunofluorescence assay, viral titer measurements, real-time PCR, and Western blotting. In addition, liposome-mediated siRNA expression plasmid delivery to RABV-infected mice significantly increased survival, compared to a non-liposome-mediated delivery method. Collectively, our results showed that the three siRNAs, N796, N580 and N799, targeting the N gene could potently inhibit RABV CVS-11 reproduction. These siRNAs have the potential to be developed into new and effective prophylactic anti-RABV drugs.
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http://dx.doi.org/10.1016/j.virusres.2012.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114411PMC
October 2012

Isolation of ssDNA aptamers that inhibit rabies virus.

Int Immunopharmacol 2012 Nov 4;14(3):341-7. Epub 2012 Jul 4.

College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, China.

Aptamers, functional nucleic acids, capable of binding a variety of molecular targets with high affinity and specificity, have emerged as promising therapeutic agents. In this study, the cell surface-systematic evolution of ligands by exponential enrichment (Cell-SELEX) strategy was used to generate DNA aptamers which targeted to the intact rabies virus-infected live cells. Through 35 iterative rounds of selection, five high-affinity single-stranded DNA (ssDNA) aptamers were generated by cell-SELEX. Virus titer assay and real-time quantitative reverse transcription PCR (qRT-PCR) assay revealed that all five aptamers could inhibit replication of rabies virus (RABV) in cultured baby hamster kidney (BHK)-21 cells; and T14 and F34 aptamers were most effective. The qRT-PCR also showed a dose-dependent inhibitory effect in BHK-21 cells. Collectively, these data show the feasibility of generating functionally effective aptamers against rabies virus-infected cells by the Cell-SELEX iterative procedure. These aptamers may prove clinically useful as therapeutic molecules with specific antiviral potential against RABV infections.
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http://dx.doi.org/10.1016/j.intimp.2012.06.019DOI Listing
November 2012

[Development of anti-influenza drug].

Bing Du Xue Bao 2011 Sep;27(5):475-80

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September 2011

Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N1.

Int Immunopharmacol 2011 Dec 18;11(12):2057-61. Epub 2011 Sep 18.

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

The H5N1 avian influenza virus (AIV) causes widespread infections in bird and human respiratory tracts, and vaccines and drug therapy are limited in their effectiveness. Recent studies of AIV structures have been published and provide new targets for designing antiviral drugs such as antisense oligonucleotides (AS ODNs), which effectively inhibit gene replication. In this study, we designed and synthesized three AS ODNs (NP267, NP628, NP749) that were specific for the RNA binding region of nucleoprotein (NP) based on AIV structure. Results showed that all three AS ODNs could inhibit viral replication in MDCK cells. The NP628 showed the best antiviral effect of all through viral titers, quantitative RT-PCR and indirect immunofluorescence (IFA) assays. In addition, the liposome mediated NP628 could partially protect the mice from a lethal H5N1 influenza virus challenge. Moreover, the NP628 group had a lower viral titer and lung index in the infected mice when compared with the viral control. Our results showed that AS ODN targeting of the AIV NP gene could potently inhibit AIV H5N1 reproduction, thus, formulating a candidate for an emergent therapeutic drug for the pathogenic H5N1 influenza virus infection.
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http://dx.doi.org/10.1016/j.intimp.2011.08.019DOI Listing
December 2011

Recombinant canine parvovirus-like particles express foreign epitopes in silkworm pupae.

Vet Microbiol 2011 Dec 1;154(1-2):49-57. Epub 2011 Jul 1.

Agricultural Division, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, China.

The capsid structural protein VP2 of canine parvovirus (CPV) can self-assemble into highly organized virus-like particles (VLPs) and retain major immunoreactivity. In this study, different recombinant baculoviruses that expressed varying fusion proteins of the CPV VP2 protein with the T cell determinant and/or the linear virus-neutralizing epitope of rabies virus (RV) were generated. Infection with these baculoviruses changed BmN cell morphology and inhibited their proliferation as well as damaged silkworms and pupae. However, infection with these baculoviruses induced high levels of recombinant protein expression in silkworms and pupae. More importantly, these fusion proteins self-assembled VLPs with properties similar to CPV virions and retained their VP2-specific immunoreactivity, but some retained their RV-specific immunoreactivity. Interestingly, only one fusion protein, T-VP2, maintained its haemagglutination activity. These data indicated that these insertions and replacements in the loop 2 of VP2 did not interfere with the formation of VLP, and silkworms and pupae could act as a low-costing bioreactor for the production of heterologous proteins. Therefore, our findings may provide a new framework for the development of subunit vaccines against RV and CPV.
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http://dx.doi.org/10.1016/j.vetmic.2011.06.022DOI Listing
December 2011

Antisense oligonucleotide inhibits avian influenza virus H5N1 replication by single chain antibody delivery system.

Vaccine 2011 Feb 5;29(8):1558-64. Epub 2011 Jan 5.

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

H5N1 avian influenza virus (AIV) causes widespread infections in poultry and wild birds, and has the potential to emerge as a pandemic threat to human. Antisense oligonucleotides (AS ODNs) are highly effective at inhibiting gene replication. Antibody-mediated delivery is a novel approach to target specific cells and tissues. In this study, we designed and synthesized three AS ODNs (PA4, PA492 and PA1203) specific for conserved region of AIV PA protein, and all the three AS ODNs could inhibit viral replication. The PA492 ODN showed the best antiviral effect by viral titers and quantitative RT-PCR in MDCK cells. The fusion protein scFv-tP was constructed as a single chain variable fragment (scFv) against AIV hemaglutinin antigen with a truncated protamine (tP). The results showed that scFv-tP fusion improved the antiviral effectiveness of PA492 in MDCK cells as measured by viral titers, quantitative RT-PCR and indirect immunofluorescence (IFA) assays. In addition, scFv-tP-delivered PA492 was also found to partially protect mice from lethal H5N1 influenza virus challenge. Using scFv-tP delivery, fluorescein isothiocyanate labeled-PA492 was found to be significantly localized in the lungs, compared to liposome-delivered PA492. Moreover, the fusion protein mediated PA492 had a lower lung index and viral titers in the infected mice as compared with the liposome method. These results provided a potential method for using anti-HA fusion protein for the targeted delivery of AS ODNs against AIV H5N1.
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http://dx.doi.org/10.1016/j.vaccine.2010.12.088DOI Listing
February 2011

Generation and characterization of a fusion protein of single-chain fragment variable antibody against hemagglutinin antigen of avian influenza virus and truncated protamine.

Vaccine 2010 May 9;28(23):3949-55. Epub 2010 Apr 9.

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

The hemagglutinin antigen (HA) of avian influenza virus (AIV) is an immunogen abundant on the surfaces of infected cells, and can be used as a target for specific antibodies to clear viral infection. Protamine has been demonstrated to deliver DNA into cells effectively. Accordingly, a fusion protein of anti-HA single-chain fragment variable (scFv) and truncated protamine (tP) may be used as a vehicle for delivering the anti-AIV siRNA into the AIV-infected cells for gene therapy. To test this hypothesis, we constructed a novel recombinant plasmid, pET28-scFv-tP, by connecting the genes for anti-H5N1 AIV HA-specific scFv with synthesized oligonucleotides encoding the 22 amino acids of human tP and a linker. Furthermore, the recombinant scFV-tP was expressed and purified, with a yield of 7-8mg of scFv-tP and a purity of >92% from 1L of bacterial culture. Characterization of its bioactivity revealed that scFv-tP recognized HA, similar to its scFv control, in a dose-dependent manner and that the scFv-tP, but not its scFv control, bound to DNA and delivered plasmid and oligonucleotide DNA into the AIV-infected MDCK cells effectively. More importantly, transfection with the mixture of the scFv-tP and plasmid for the NP-specific siRNA significantly inhibited the replication of AIV in MDCK cells, as compared with that transfection with the scFv-plasmid mixture, even with the plasmid in liposome. Our data demonstrated that the recombinant scFv-tP retained the functions of both scFv and tP, and might be potentially used for delivering genetic materials for targeting therapy of AIV infection in vivo.
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http://dx.doi.org/10.1016/j.vaccine.2010.03.045DOI Listing
May 2010

Inhibition of highly pathogenic avian influenza virus H5N1 replication by the small interfering RNA targeting polymerase A gene.

Biochem Biophys Res Commun 2009 Dec 13;390(3):421-6. Epub 2009 Sep 13.

Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.

RNA interference is a form of post-transcriptional gene silencing mediated by small interfering RNAs (siRNAs), and it provides a powerful new means to specifically inhibit viral infection. In this study, three siRNAs (ps-PA496, ps-PA1116, and ps-PA1473) targeting the polymerase A (PA) gene of highly pathogenic avian influenza virus (HPAIV) H5N1 were designed and evaluated for their abilities to inhibit HPAIV replication. Results in vitro showed that the viral replication in the siRNAs-treated cells was 78-fold lower than that of the control for ps-PA496. Real-time PCR and indirect immunofluorescence assay also showed a significant reduction of the viral RNA level and protein expression. In vivo results showed a significant decrease of lung virus titers and an increase in the survival rate of infected mice pretreated with ps-PA496. These findings suggested that siRNAs targeting PA could efficiently inhibit HPAIV replication and these conserved regions might become potential therapeutic targets against influenza virus infection.
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http://dx.doi.org/10.1016/j.bbrc.2009.09.039DOI Listing
December 2009

[Cloning and expression of single-chain Fv antibodies against H5N1 Avian influenza virus hemagglutinin].

Bing Du Xue Bao 2009 Jan;25(1):63-7

Changchun University of Science and Technology, Changchun 130022, China.

To construct Fv antibodies against H5N1 Avian influenza virus hemagglutinin,extracted mRNA from B lymphoblastoid cell lines secreting anti-HA antibodies was used and the VH and VL genes were amplified by RT-PCR and linked together by splicing overlap extension (SOE) with (Gly4 Ser)3 linker. The recombinant plasmid was then transformed to E. coli BL21(DE3) and sequence analysis indicated the total length of scFv was 714 bp and the expression of Fv was validated by PAGE and Western blot.
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January 2009

[Pathogenesis of H5N1 avian influenza virus in C57BL/6 mice].

Bing Du Xue Bao 2008 Nov;24(6):472-7

College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062.

C57BL/6 mice were inoculated intranasally (50 microl) with serial 10-fold dilution of HAB/01 H5N1 virus. Three and five days later, three mice of each group were euthanized. Lung injury was assessed by observation of lung histopathology, virus titers and MCD50 were also measured. Our data showed that H5N1 viral infection in mice resulted in mainly epithelial injury and interstitial pneumonia, featuring significant weight loss, dramatically increased lung wet weight:body weight ratio, inflammatory cellular infiltration, alveolar and interstitial edema, hemorrhage in lungs with high virus titers, and MCD50 was 10(-6.5)/ 0.05 mL. These results suggested that a mouse model of H5N1 viral infection was successfully established which may benefit study of H5N1 avian influenza virus and pathogenic mechanism of host.
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November 2008