There are two important recent advances in cardiovascular biomechanics. One is cardiovascular mechanobiology, which illustrates how mechanical factors can generate biological effects resulting in vascular remodeling. By studying signal transduction pathway in the cardiovascular system and means of mechanical control, cardiovascular mechanobiology aims to investigate the nature of cardiovascular disease at cellular and molecular level. The other is cardiovascular numerical simulation and individual design of surgery operation on the basis of clinical images. Based on fluid mechanics, clinical images as well as advanced measuring and testing methods of flow field, cardiovascular numerical simulation and quantitative analysis can be conducted. New in vivo techniques for studying cardiovascular function and the design of individual surgery system can provide biomechanical solutions for the diagnosis, therapy and prewarning of cardiovascular disease. In this special issue, seven papers on cardiovascular biomechanics are published, covering vascular cell mechanobiology and cardiovascular numerical simulation connected with the clinical problems tightly. These papers show us some recent advances in cardiovascular biomechanics in China.

OBJECTIVETo study the genome sequence of hepatitis A virus L-A-1 strain which has been applied for live attenuated vaccine production in China, to compare with other HAV strains, to understand some characteristics of L-A-1 strain, and to find the mechanism of attenuation and cell adaptation.

METHODSGenome fragments were prepared by antigen-capture PCR from infected cell (2BS), PCR products were cloned into T vector, sequenced and analyzed by using bioinformatics program.

RESULTSAnalysis of the genomic sequences(nt 25-7,418) showed that the open reading frame contains 6,675 nucleotides in length encoding 2,225 amino acids. Sequence homology comparison showed 98.00% and 94.00% homology at nucleotide level, and 98.51% and 98.65% homology at amino acid level with international strains MBB and HM 175, respectively. Through comparison with other attenuated, cell adapted and cytopathic effect (CPE) strains, L-A-1 strain had mutation at nt 152, 591, 646, 687 and insertion at nt 180-181 in 5?NTR and had mutation at nt 3,889 (aa 1 052-Val) in 2B region, these mutations and insertion are molecular basis for cell adaptation; mutation at nt 4,185 (aa 1 152-Lys) in 2C region should be attenuated marker; deletion in 3A region (nt 5,020-5,025) that caused two amino acids deletion is virus fast growth basis.

CONCLUSIONThrough analyzing L-A-1 strain genomic sequence, certain sites related to cell adaptation and attenuation were found.

Adaptation, Biological ; genetics ; Amino Acid Sequence ; Base Sequence ; Gene Deletion ; Genome, Viral ; Hepatitis A Vaccines ; genetics ; Hepatitis A virus ; genetics ; growth & development ; Mutation ; Open Reading Frames ; genetics ; Sequence Homology ; Vaccines, Attenuated ; genetics

AIMTo investigate the effect of ciliary neurotrophic factor (CNTF) on the nuclear translocation of protein kinase C (PKC) following NMDA administration in the primary cultured hippocampal neurons.

METHODS(1) PKCGAMMA or PKCepsilon- immunocytochemistry staining method was used after treating neurons with NMDA or CNTF. (2) The gray of the nucleus of the PKC-positive neurons were measured under the image pattern analysis system.

RESULTS(1) After NMDA administration of different concentration and time, Nucleus appear PKCgamma and PKCepsilon activities, especially the 100 micromol/L NMDA 30 min group. (2) The gray of nucleus in CNTF + 500 micromol/L NMDA group is similar to control group.

CONCLUSIONNMDA can induce nuclear translocation of PKC in the primary cultured hippocampal neurons, and CNTF can inhibit the translocation. It suggests that the inhibition of PKC translocation induced by NMDA is one of the important reasons for the neuro-protective effects of CNTF.

Animals ; Cells, Cultured ; Ciliary Neurotrophic Factor ; pharmacology ; Hippocampus ; cytology ; N-Methylaspartate ; pharmacology ; Neurons ; drug effects ; metabolism ; Protein Kinase C ; metabolism ; Protein Transport ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effect from different pore sizes of co culture inserts on the permeability of biomacromolecules through polyethylene terephthalate (PET) membrane so as to solve the key technology problem in mechanobiology experiment on vascular cells. Methods Inserts with 0.4 μm and 1.0 μm pores on the PET membrane were studied using flow chamber system. Low shear stress was subjected to the co-cultured system of endothelial cell (EC)/vascular smooth muscle cell (VSMC) and the concentration of platelet-derived growth factor BB (PDGF-BB) was detected by ELISA. Under the static condition, vascular cells were cultured on the plate (with no cell on PET membrane), on the outer side of PET membrane, and on the both sides of PET membrane, respectively. Then the recombinants PDGF-BB (rPDGF-BB) were added on the different sides of PET membrane. Western blotting was used to detect the change in expressions of p-ERK1/2, p-Akt and Lamin after cells were stimulated by rPGDF BB. Results After low shear stress subjection for 12 h, the concentration of PDGF-BB in the medium from VSMC side was significantly higher than that from EC-side. rPDGF-BB passed through 0.4 μm and 1.0 μm pores on the PET membrane and modulated expressions of p-ERK1/2, p-Akt and Lamin A in cells cultured on the opposite side of PET membrane and cells cultured on the plate separately. When cells were cultured on the both sides of PET membrane, rPDGF-BB only stimulated cells cultured on the same side of 0.4 μm pores on PET membrane, but had no specific effect on cells cultured on the opposite side. Conclusions PET membrane with both 0.4 μm and 1.0 μm pores was permeable to PDGF-BB, and cells cultured on the membrane could affect the permeability. The efficiency of PDGF BB passing through 0.4 μm pores was significantly repressed with cells cultured on the both sides, which was more similar to that in vivo.

OBJECTIVETo investigate the normal range of (CAG)n in spinocerebellar ataxia type 1 (SCA1) gene and spinocerebellar ataxia type 3 (SCA3/MJD) gene in 110 normal subjects of Han population in Northeastern China, to assess the genotypes for clinically diagnosed spinocerebellar ataxia(SCA) individuals including 25 patients from 8 families and 6 sporadic patients, and to make presymptomatic and prenatal diagnosis.

METHODSDNA fragments from the normal subjects and the patients were detected by fluorescence-PCR. Homozygosities were selected for DNA sequencing.

RESULTSThe normal ranges of (CAG)n of SCA1 and SCA3/MJD were 20-39 and 14-38 repeats respectively, SCA1 was found mostly to be 26 and 27 repeats, allele frequency 34.09% and 20.91%; heterozygosity was 84.55%, SCA3/MJD was found mostly to be 14 repeats, allele frequency 39.55%, heterozygosity was 78.18%.(CAG)(68) of SCA3/MJD gene of one affected individual had been found in a family but no CAG mutative expansion in related members was observed.

CONCLUSIONThe normal ranges of CAG repeats vary with areas and races. SCAs genotyping is the first choice in presymptomatic and prenatal diagnosis.

Ataxin-1 ; Ataxin-3 ; Ataxins ; China ; DNA ; chemistry ; genetics ; Family Health ; Female ; Gene Frequency ; Genotype ; Humans ; Machado-Joseph Disease ; diagnosis ; genetics ; Male ; Nerve Tissue Proteins ; genetics ; Nuclear Proteins ; genetics ; Pedigree ; Repressor Proteins ; Sequence Analysis, DNA ; Spinocerebellar Ataxias ; diagnosis ; genetics ; Trinucleotide Repeat Expansion ; genetics ; Trinucleotide Repeats ; genetics

Arteries in vivo are subjected to lumen pressure, shear flow and axial tension due to surrounding tissue tethering. The axial stress affects arterial function including its response to pressure and flow. While the effects of blood pressure and shear flow are well documented, the effects of axial tension on vascular remodeling have just gradually gained attention recently. This review summarizes the results on the observation of the axial tension in arteries and responses of arteries to elevation and reduction of the axial stress. It is concluded that the axial tension in arteries plays an important role in regulating normal arterial function and tissue remodeling and adaptation and disease development. Research on vascular remodeling under axial tension shall strengthen the understanding of normal physiological functions and pathological changes of the arteries.

Abstract：Objective To optimize the production process of inactivated vaccine of Aeromonas veronii（AV）CA07 strain. Methods The fermentation culture process of AV CA07 strain liquid was determined through the optimization of the culture time（2～16 h），medium（optimized fermentation medium，LB medium and NB medium）and fermentation conditions（in⁃ oculation amount of 1%，5%，10% and 15%；ventilation rate of 2，4，6 and 8 L／min and fermentation time of 6，8，10 and 12 h）. The optimal inactivation process was determined through the comparison of the final concentration of formalde⁃ hyde solution（0. 10%，0. 20%，0. 30% and 0. 40%），inactivation temperature（28 and 37 ℃）and inactivation time（24， 48 and 72 h）. The large⁃scale production process of inactivated vaccine of AV CA07 strain in 500 L fermentor was estab⁃ lished and the prepared vaccines were tested for safety and immunogenicity. Results The optimal inoculation amount of AV CA07 strain was 5%，ventilation rate was 4 L／min and culture time was 10 ~ 12 h. The optimal inactivation condition was adding formaldehyde solution with final concentration of 0. 30% incubating at 37 ℃ for 24 h. The number of viable bacteria in the fermentation broth of AV CA07 strain prepared in 500 L fermentor was more than 8 × 109 CFU／mL. All crucian carps immunized with the inactivated vaccine by abdomen survived. After challenge，the relative immune protection rate was more than 90%. Conclusion AV CA07 strain inactivated vaccine prepared by optimized production process showed good safety and immunogenicity.

Objective To study the role of abnormally changed migration of vascular smooth muscle cells (VSMCs) induced by low shear stress (LowSS) in vascular remodeling during atherosclerosis as well as the molecular mechanism involved in this process. Methods By using comparative proteomic analysis with two-dimensional electrophoresis combined with mass spectrometry, differential protein expression profiles of cultured vascular tissues under normal shear stress (NSS) (1.5 Pa) and LowSS (0.5 Pa) were studied. Using endothelial cells (ECs) and VSMCs co-cultured parallel plate flow chamber system, two levels of shear stress i.e. LowSS and NSS, were applied, respectively. Western blot was used to detect the protein expressions of Rab28 and phosphor-ERK. Transwell system was used to detect the migration ability of VSMCs. After using RNA interference and ERK inhibitor PD98059 to decrease the expressions of Rab28 and phosphor-ERK, respectively, the migration ability of VSMCs was observed again. Results The expression of Rab28 in the cultured rat aorta was significantly up-regulated by the LowSS (0.5 Pa) application in comparison with the NSS (1.5 Pa). The migration, expressions of Rab28, and phosphorylation of ERK in VSMCs were significantly increased by the LowSS application. Target RNA interference of Rab28 significantly decreased the migration of VSMCs, but had no specific effect on the phosphorylation of ERK. Target inhibitor of ERK, PD98059, significantly decreased both the migration and Rab28 expression in VSMCs. Conclusions The LowSS may increase the phosphorylation of ERK and then increase the expression of Rab28 in VSMCs, which subsequently modulate VSMC migration during vascular remodeling. The investigation on the role of Rab28 and its signal path in LowSS-regulated VSMCs as well as the molecular mechanism might provide a biomechanical reference for understanding the pathogenesis of vascular remodeling during atherosclerosis and finding the therapeutic target of new drugs.

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients’ baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.
Blood Component Removal* ; China* ; Colitis, Ulcerative* ; Cytokines ; Granulocytes* ; Humans ; Inflammation ; Leukocytes ; Monocytes* ; ROC Curve ; Sensitivity and Specificity ; Treatment Outcome ; Ulcer*

Blood vessels are often subjected to axial torsion (or twist) due to body movement or surgery. However, there are few studies on blood vessel under twist. This review first summarizes the clinical observation on the twist of blood vessels and then presents what we know about the mechanical behaviors of blood vessel under twist, including the constitutive models. The state of art researches on the remodeling of blood vessels under twist via ex vivo organ culture, in vivo animal experiments, and mathematical model simulations are further discussed. It is our hope that this review will draw attention for further in-depth studies on the behavior and remodeling of blood vessels under twist.