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Biomedical subjects

Wei Han

Publications and source records attributed to Wei Han.

At least 37 records · Page 2Linked to original sources

Sex-based transmural differences in cardiac repolarization and ionic-current properties in canine left ventricles.

The female sex is associated with longer electrocardiographic QT intervals and increased proarrhythmic risks of QT-prolonging drugs. This study examined the hypothesis that sex differences in repolarization may be associated with differential transmural ion-current distribution. Whole cell patch-clamp and current-clamp were used to study ionic currents and action potentials (APs) in isolated canine left ventricular cells from epicardium, midmyocardium, and endocardium. No sex differences in AP duration (APD) were found in cells from epicardium versus endocardium. In midmyocardium, APD was significantly longer in female dogs (e.g., at 1 Hz, female vs. male: 288 +/- 21 vs. 237 +/- 8 ms; P < 0.05), resulting in greater transmural APD heterogeneity in females. No sex differences in inward rectifier K+ current (I(K1)) were observed. Transient outward K+ current (I(to)) densities in epicardium and midmyocardium also showed no sex differences. In endocardium, female dogs had significantly smaller I(to) (e.g., at +30 mV, female vs. male: 2.5 +/- 0.2 vs. 3.5 +/- 0.3 pA/pF; P < 0.05). Rapid delayed-rectifier K+ current (I(Kr)) density and activation voltage-dependence showed no sex differences. Female dogs had significantly larger slow delayed-rectifier K+ current (I(Ks)) in epicardium and endocardium (e.g., at +40 mV; tail densities, female vs. male; epicardium: 1.3 +/- 0.1 vs. 0.8 +/- 0.1 pA/pF; P < 0.001; endocardium: 1.2 +/- 0.1 vs. 0.7 +/- 0.1 pA/pF; P < 0.05), but there were no sex differences in midmyocardial I(Ks). Female dogs had larger L-type Ca2+ current (I(Ca,L)) densities in all layers than male dogs (e.g., at -20 mV, female vs. male, epicardium: -4.2 +/- 0.4 vs. -3.2 +/- 0.2 pA/pF; midmyocardium: -4.5 +/- 0.5 vs. -3.3 +/- 0.3 pA/pF; endocarium: -4.5 +/- 0.4 vs. -3.2 +/- 0.3 pA/pF; P < 0.05 for each). We conclude that there are sex-based transmural differences in ionic currents that may underlie sex differences in transmural cardiac repolarization.

Animals↗

[The pathological characters and its clinical significance of internal hemorrhoids].

OBJECTIVE: To investigate the pathological characters and the corresponding clinical significance of internal hemorrhoids tissues. METHODS: Normal anal cushion and internal haemorrhoids tissue samples were obtained after stapled haemorrhoidectomy procedure from 24 grade III hemorrhoidal patients. The macroscopically normal cushions served as own controls and the normal cushions from a patient without a history of haemorrhoids as quality control. Routine Hematoxylin-Eosin and orcein were performed for elastic fibers. RESULTS: Compared with the corresponding normal anal cushions, the subepithelial vessels especially the cavernous vessels of the hemorrhoidal tissues showed obvious structural impair, retrograde changes, and the internal elastic lamina were ruptured and discontinuous. In addition, thrombosis and subsequent ischemic changes were observed. The Trietz's muscle and the fibro-elastic tissues showed hypertrophy, distortion, rupture and tortility. Obvious mucosal injury was observed in the mucous of hemorrhoidal tissues. Venous dilatation was infrequent in the hemorrhoidal tissues. CONCLUSIONS: The anal cushions of hemorrhoids disease patients show significant pathological changes. The pathological changes include structural impair, retrograde changes of the cavernous vessels and the hypertrophy, distortion, rupture and tortility of the Trietz's muscle and the fibroelastic tissues, and mucosal injury of the mucous membranes. These pathological changes are the basis of pathogenesis and development of hemorrhoids.

Adult↗

Local signals in stem cell-based bone marrow regeneration.

The cellular basis of bone marrow (BM) tissue development and regeneration is mediated through hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Local interplays between hematopoietic cells and BM stromal cells (BMSCs) determine the reconstitution of hematopoiesis after myelosuppression. Here we review the BM local signals in control of BM regeneration after insults. Hematopoietic growth factors (HGFs) and cytokines produced by BMSCs are primary factors in regulation of BM hematopoiesis. Morphogens which are critical to early embryo development in multiple species have been added to the family of HSCs regulators, including families of Wnt proteins, Notch ligands, BMPs, and Hedgehogs. Global gene expression analysis of HSCs and BMSCs has begun to reveal signature groups of genes for both cell types. More importantly, analysis of global gene expression coupled with biochemical and biological studies of local signals during BM regeneration have strongly suggested that HGFs and cytokines may not be the primary local regulators for BM recovery, rather chemokines (SDF-1, FGF-4) and angiogenic growth factors (VEGF-A, Ang-1) play instructive roles in BM reconstitution after myelosuppression. A new direction of management of BM toxicity is emerging from the identification of BM regenerative regulators.

Bone Marrow Cells↗

Improvement of an experimental colitis in rats by lactic acid bacteria producing superoxide dismutase.

The use of superoxide dismutases (SODs) in inflammatory diseases is hampered by their short circulatory half-life. To determine whether a bacterial supply of SOD into the colon might improve an experimental colitis, the effects of oral treatment with live recombinant lactic acid bacteria producing different amounts of SOD and those of colonic infusion of SOD were compared. Wistar rats were fitted with a catheter in the proximal colon through which TNBS was administered to induce colitis. Animals received a continuous intracolonic infusion of bovine SOD (40 U per rat per day) for 4 days after TNBS or were treated orally with live recombinant Lactococcus lactis or Lactobacillus plantarum strains (10 colony-forming units (CFU)/d), producing or not producing SOD, for 4 days before and after TNBS. SOD activity of bacterial extracts was 0, 26, 74, and 624 units/10 CFU for L. plantarum, L. lactis, L. lactis SOD, and L. plantarum SOD, respectively. Four days after TNBS, macroscopic and microscopic damage, myeloperoxidase (MPO) activity, and nitrotyrosine immunostaining were evaluated. TNBS induced macroscopic and microscopic damages, an increase in MPO activity, and intense immunostaining for nitrotyrosine. Macroscopic damage and MPO activity were reduced by bovine SOD. These parameters and microscopic damages also were reduced by L. lactis, L. lactis SOD, and L. plantarum SOD, but not by L. plantarum. Nitrotyrosine immunostaining was attenuated after treatment with the 4 bacterial strains. Although not all of the anti-inflammatory effects could be attributed directly to SOD, our results suggest that SOD-producing lactic acid bacteria open a novel approach in inflammatory bowel disease treatment.

Administration, Oral↗

Family-based association analysis of hepatocyte growth factor (HGF) gene polymorphisms in high myopia.

PURPOSE: To investigate the association of high myopia with polymorphisms in the hepatocyte growth factor (HGF) gene, a potential candidate for myopia development. METHODS: Single nucleotide polymorphisms (SNPs) were screened and identified in the HGF gene region with denaturing high-performance liquid chromatography, and their linkage disequilibrium pattern was established in a Han Chinese population (n=150). Tag SNPs were selected and genotyped using restriction digestion and fluorescence polarization assays for 128 nuclear families with 133 severely myopic (mean spherical equivalent [MSE]<or=-10.0 D) offspring. A family-based association study was performed using FBAT and GenAssoc (Cambridge University, Cambridge, UK). RESULTS: Of three tag SNPs (HGF5-5b, HGFe9, and HGFe10b) selected for association study, HGF5-5b, located in the upstream region, was found to be associated with high myopia considered as a quantitative trait (MSE) in additive, dominant, and recessive models (P=0.0157, 0.0108, and 0.0108, respectively). The genotype relative risk was 2.19 for the genotype C/T, and 2.14 for T/T with reference to C/C of HGF5-5b. Significantly reduced transmission was demonstrated for the haplotypes C-A-C (HGF5-5b, HGFe9, and HGFe10b; P=0.0031) and C-A (HGF5-5b and HGFe9; P=0.0015) in the recessive model, whereas significantly increased transmission was found for haplotype T-C (HGF5-5b and HGFe10b; P=0.0040) under the dominant model. Preferential transmission of haplotypes remained significant even after correction for multiple comparisons. Analysis gave similar results, with myopia considered to be a qualitative trait. CONCLUSIONS: HGF is a potential locus associated with high myopia in the Han Chinese population. This is the first study reporting the association of an HGF gene polymorphism with high myopia.

Adult↗

Expression, refolding, and characterization of GFE peptide-fused human interferon-alpha2a in Escherichia coli.

Interferon-alpha2a (IFN-alpha2a) has been used for the treatment of various viral infections and cancers for many years. However some untolerable side effects have limited its application in some aspects. To evaluate whether or not an oligopeptide containing GFE motif can home human IFN-alpha2a to specific tissues, a fusion gene was constructed by fusing the coding sequence of GFE peptide (CGFECVRQCPERC), which was screened from phage display peptide library, to the 3' end of human IFN-alphaa gene by recombinant DNA technique. Fusion protein rhIFN-alpha2a-GFE was expressed in Escherichia coli as inclusion bodies using a T7 RNA polymerase expression system, pET-22b, refolded through dialysis and purified to homogeneity to >95% of purity by affinity chromatography. Characterization by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting demonstrated the authenticity of the fusion protein. Purified rhIFN-alpha2a-GFE was found to be functionally active in terms of its antiviral activity for about 2.5 x 108 IU/mg in vitro. Yields of the purified fusion protein were about 200 mg/L of culture medium. Tissue distribution assay in mouse showed that at 30 min IFN-alpha2a could be enriched sevenfold higher in lung in the targeted IFN group of mice than in the standard IFN group of mice, and last for a long time. At 1 h, IFN-alphaa in the targeted IFN group was still 4.02-fold higher than that in the standard group. This confirmed that GFE peptide has the ability to selectively deliver its fusion partner IFN-alpha2a to lungs. The results also showed that the IFN-alpha2a-GFE could be specifically enriched in kidney and liver. Its distribution in kidney was concordant with the finding of GFE receptor, MDP, in kidney. However, the IFN-alpha2a-GFE in liver may imply some significance in pharmacology and toxicology.

Animals↗

A human neutralizing antibody against a conformational epitope shared by oligomeric SARS S1 protein.

An antibody phage-display library was constructed from the B cells of convalescent severe acute respiratory syndrome (SARS) patients and screened using inactivated SARS coronavirus (CoV) virions as antigens. More than 80 positive clones were isolated from the library and one of them, scFv H12, was extensively characterized. scFv H12 bound to SARS-CoV with high affinity (equilibrium dissociation constant, Kd=73.5 nM), and neutralized SARS virions in vitro. The facts that scFv H12 bound to the SARS-S1 protein under non-reducing conditions and that it did not bind to monomeric S1 protein under reducing conditions strongly suggest that scFv H12 recognizes a conformational epitope shared by oligomeric S1 proteins. This study should aid in the manufacture of neutralizing antibody, provide a better understanding the immunological characteristics of SARS protein and facilitate the design of a SARS vaccine.

Amino Acid Sequence↗

[Isolation of a novel peptide that binds to BLyS from a 12-mer phage display peptide library].

A 12-mer phage display peptide library was screened for specific binders against B lymphocyte stimulator (BLyS). After 3 rounds of panning, positive phage clones were enriched. ELISAs were used to identify positive phages, and the DNA encoding the positive peptide (RHKIQLRQNIIT) was cloned and expressed as a GST fusion protein in E. coli. After purification, the identity of the fusion protein was confirmed through its specific binding to BLyS by ELISA. We have obtained a peptide that can bind to BLyS and probably act as an antagonistic peptide against the natural BLyS receptor.

B-Cell Activating Factor↗

[Protective effects of hirudin on acute experimental intracerebral hemorrhage].

OBJECTIVE: To explore the protective effects of hirudin on acute experimental intracerebral hemorrhage (ICH) by observing the changes of histologic pathology and brain water content as well as GFAP-positive cells in the perihematomal brain regions. METHOD: The models of rat ICH were made with infusion of autologous blood into the right neucleus caudatus. The rats were divided randomly into control group, intracerebral hemorrhage group and treating group with hirudin. Brain water content was measured, and pathological and GFAP changes were observed. RESULT: The pathological impairation after ICH were gradually deteriorated and peaked at the third day. Brain water content after ICH was gradually increased and obviously after one day(P < 0.05) and peaked at the third day. GFAP-positive cells were gradually increased and peaked at the seventh day after ICH. In the treating groups, the pathological impairation and brain water content as well as the GFAP-positive cells were decreased as compared to those in the intracerebral hemorrhage group and the control group. And the positive correlation between GFAP-positive cell numbers and brain water content were shown by linear regression. CONCLUSION: The local administration of hirudin, a special inhibitor of thrombin, has protective effects within the first week after ICH.

Acute Disease↗

[HSC transplantation-associated intestinal thrombotic microangiopathy: clinical pathological features, diagnosis criteria and treatment].

Thrombotic microangiopathy (TMA) is a lethal transplantation-associated complication which exactly likes acute intestinal graft-versus-host disease (GVHD) in the clinical manifestation. 373 consecutive patients with hematological diseases received family HLA matched or mismatched HCT from May, 2002 to July, 2004. To analyse the clinical and pathological characteristics of TMA, 30 patients who suffered from severe diarrhea and received colonoscopic examination and gut biopsy were retrospectively analyzed. The results indicated that 7 patients originally diagnosed as gut GVHD showed the pathological evidence of enteric TMA. The incidence of TMA was 7 out of 30 specimen (23.3%). Pathological evidence of enteric TMA shown microvascular disorder characterized by thrombus in the capillary without infiltration of lymphocytes and perivascular hemorrhages in the mucosa, swelling and focal denudation of epithelial cells. All patients with TMA were associated with cytomegalovirus (CMV) antigenemia/disease. Among these patients, 4 cases, who only showed TMA without the evidence of gut GVHD pathologically, displayed treatment-resistant bloody diarrhea, renal failure, veno-occlusive disease, hemorrhagic cystitis, hemolytic anemia as well as thrombocytopenia. But the other 3 cases, with co-existence of both TMA and GVHD pathological characteristics had better treatment response. Survival analysis indicated that 3 patients with TMA-GVHD survived for 461 to 536 days but three out of four TMA patients died from VOD with liver failure as well as multiple organ failure during 101 to 254 days after HCT. In conclusion, to better diagnose those patients with severe and refractory diarrhea following HCT, pathological examination may indicate crux evidence to identify intestinal TMA from gut GVHD. Furthermore, this primary report has first evidenced that TMA and TMA-GVHD are two pathologically well-recognized subtypes with the difference between the pathological characteristics, treatment response and clinical outcomes.

Graft vs Host Disease↗

[Inhibitory effect of dendritic cell vaccine on the growth of implanted tongue squamous cell carcinoma tumors in nude mice].

OBJECTIVE: To investigate the inhibitory effect of dendritic cells (DCs) on the growth of the implanted tongue squamous cell carcinoma (SCC) tumors in nude mice. METHODS: Being induced from human peripheral blood monocytes (PBMCs) with rhGM-CSF, rhIL-4 and rhTNF-alpha, DCs were pulsed by Tca8113 cells lysates. Those DCs and T lymphocytes were co-cultured to induce specific cytotoxic T lymphocytes (CTLs). Immunotherapy was then performed after those DCs and CTLs were implanted into the tumor-bearing nude mice. RESULTS: DCs were induced from PBMCs with multiple cytokines. Compared with the control groups, the growth of tumors was significantly inhibited in the group that had been implanted with DCs and CTLs, and tumor doubling time also increased markedly (P < 0.05). CONCLUSIONS: DCs function normally after being induced from human PBMCs with multiple cytokines; DCs pulsed with tumor cell lysates and CTLs co-cultured with those DCs have a significant anti-tumor immune activity in nude mice.

Animals↗

[A method for extracting basic rhythms of EEG via wavelet analysis].

As basic electrophysiology signals of a human being, electroencephalogram (EEG) has been widely used in researches and clinics. The paper proposes a method for extracting rhythms of EEG, based on wavelet analysis. By using Daubechies mother wavelet, raw EEG is decomposed, and then we extract basic rhythms of EEG after interference is eliminated insome scales. This method not only eliminates interference well, but also extracts rhythms perfectly.

Algorithms↗

[Donor peripheral hematopoietic stem cells infusion for prophylaxis of relapse of high risk leukemia after allogeneic hematopoietic stem cell transplantation].

OBJECTIVE: To study the effect of growth factor-primed donor hematopoietic stem cells infusion (GPBSCI) as an early adoptive immunotherapy. METHODS: Twelve patients with high-risk leukemia received prophylactic GPBSCI after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Out of the 12 patients, two were Ph(+) ALL in CR(1), one ALL in CR(2), one refractory ALL, three AML (one in relapse, one refractory disease, one in CR(3)), four CML in advanced stage and one myelodysplastic syndrome-refractory anemia with excess blast (MDS-RAEB). RESULTS: Sixteen infusions were performed in the 12 patients, including 5 infusions were performed within +90 days post-SCT. The median mononuclear cells (MNC) and CD3(+) cells infused for GPBSCI before +90 d were 1.00 (0.95 - 1.24) x 10(8)/kg and 0.53 (0.39 - 0.63) x 10(8)/kg, and after +90 d were 2.27 (1.00 - 4.30) x 10(8)/kg and 1.15 (0.55 - 2.10) x 10(8)/kg, respectively. Four patients developed grade I - II acute GVHD, and one grade III acute GVHD. Seven patients developed chronic GVHD, of which four cases were extensive. Two patients had no transfusion related GVHD. No transfusion related pancytopenia was observed. Ten patients survived disease-freely at 563 (415 - 728) days of follow-up. Two patients died of leukemia relapse after GPBSCI. CONCLUSION: Allo-HSCT with prophylactic GPBSCI could maximize graft-versus-leukemia effect with few fatal complications and might be a potentially curative strategy for hematological malignancy patients with high risk of relapse.

Adolescent↗

[Comparative study of warfarin and aspirin for stroke prevention in elderly patients with atrial fibrillation].

OBJECTIVE: To analyze current stroke prevention measures for elderly patients with atrial fibrillation. METHODS: A retrospective analysis was conducted of the clinical records of elderly patients with atrial fibrillation treated in our hospital within the recent 5 years. The distribution of high risk factors for different age levels was studied, and the incidence of stroke and complications such as hemorrhage were compared between patients treated with warfarin and aspirin therapy. RESULTS: Compared with patients of 65 to 75 years old, the incidence of complications with other high risk factors was increased in advanced age group (over 75 years). Of these patients, 19.0% were treated with warfarin and 73.4% with aspirin. Compared with the aspirin group, stroke incidence was decreased significantly in warfarin group, which had simultaneously increased nonfatal hemorrhage. CONCLUSION: Warfarin can be more effective than aspirin for stroke prevention in elderly patients with atrial fibrillation, but in clinical practice, the usage rate of warfarin still remains low with insufficient monitoring.

Aged↗

[A debate about mental disability expertise of the disability evaluation criteria of traffic accident injurious].

In recent years, mental disability estimation are more than ever in the practice of forensic psychiatric expertise. The standards about mental disability estimation in the Disability Evaluation Criteria of Traffic Accident Injury are ambiguous and difficult to operate, it cause to different understanding in one case. This article discuss some common questions through 3 aspects in mental disability expertise according to some typical cases, there are the first, we should compare the IQ score before and after injurious in intelligence estimate. The second, the mental disability estimation should be done at least one year after the end of medicine treatment. The third, mental estimate scale should be used in mental disability estimation.

Accidents, Traffic↗

[A comparative study of peripheral blood stem cell vs bone marrow transplantation from unrelated donors].

OBJECTIVE: To compare the outcomes in hematological patients receiving unrelated peripheral blood stem cell transplants (UPBSCT) with those receiving unrelated bone marrow transplants (UBMT) in a retrospective analysis. METHODS: Sixty-three patients with hematological diseases with HLA-matched (65%) or mismatched (35%) unrelated donors were receiving UPBSCT (n = 33) or UBMT (n = 30) between May 2001 and June 2005 in our institute. They all received standard conditioning regimens with Bu/Cy (n = 53) or TBI/Cy (n = 10) with the addition of ATG for 3 - 4 days (n = 58) or CD3 antibody (n = 5). There were more patients receiving rabbit ATG in the UPBSCT group than UBMT (21/33 vs 8/25, P = 0.02) and the remaining patients received pig ATG. Graft versus host disease (GVHD) prophylaxis consisting of cyclosporine, methotrexate and mycophenolate mofetil were the same. RESULTS: The two groups were matched for the following factors: gender, diagnosis, HLA-compatibility and conditioning regimens. The median age in the UPBSCT group was 29.5 (10 - 47) years and in the UBMT 21.5 (7 - 42) years (P < 0.05). The UPBSCT group consisted of 10 females and 23 males and the UBMT group 7 females and 23 males. Eleven patients in the UPBSCT and 8 patients in the UBMT group were diagnosed with as chronic myeloid leukemia (CML); 9 and 12 as acute myelocytic leukemia (AML); 11 and 10 as acute lymphatic leukemia (ALL); 2 and 0 as severe aplastic anemia (SAA). There were more patients in aggressive stage (>CR1) in the UBMT group than in the UPBSCT group (9/30 vs 3/33, P = 0.06). Median follow-up was 12 months after UPBSCT and 20 months after UBMT (P < 0.05). UPBSCT group had a higher number of infused MNC as comparison with UBMT group (6.16 x 10(8)/kg vs 2.80 x 10(8)/kg, P < 0.05). Both neutrophil and platelet recovery were faster after UPBSCT (11 days vs 17 days, 14 days vs 27.5 days, P < 0.01). Although the cumulative incidence of grades II - IV acute GVHD and severe aGVHD in the UPBSCT group were less than in the UBMT group (33.04% vs 66.69%, 7.26% vs 34.52%, P < 0.05), there was no difference after the source of ATG was counted. The incidence of chronic GVHD did not differ between the two groups (18/25 vs 14/22). Relapse including molecular relapse occurred in 6 of the 31 patients after UPBSCT and in 4 of the 30 patients after UBMT (P > 0.05). Finally, fifteen of the 30 patients died after UBMT, as compared with 8 of the 33 patients after UPBSCT. The cumulative overall survival was 62.45% after UPBSCT and 47.22% after UBMT (P = 0.114). CONCLUSION: Our results indicate that UPBSCT led to significantly faster leukocyte and platelet engraftment without increasing the incidence of aGVHD and the overall survival was comparable between the two methods of therapy.

Adolescent↗