Automated three-dimensional measurement on anatomic parameters of proximal femur / 医用生物力学

ObjectiveTo automatically measure anatomic parameters of proximal femur by establishing three-dimensional (3D) coordinate system of the femur based on bony landmarks, so as to assist pre-operative planning and design of customized femoral stem. MethodsThe software named "Femeter" was independently developed for anatomic measurement of the femur, which allowed importing the femur models with STL format and manually locating the targeted anatomic landmarks. The 3D modeling of femoral medullary canal was rapidly created by semi-spherical iterative searching algorithm, and 16 key anatomic parameters of proximal femur, including femoral head radius, neck-shaft angle, anterversion were automatically calculated by least-squares fitting algorithm. ResultsBy experimenting on 30 femur STL models, the average execution time of single measurement was (0.95±0.16) seconds, and the intra-class correlation coefficient of 9 anatomic parameters was between 0.907 and 0.999, which showed high intra-rater and inter-rater reliability. ConclusionsThe automatic modeling and execution time of measuring algorithm by Femeter are fast, with satisfactory measurement repeatability and easy interaction, which is easily applicable to clinical practice. The 3D anatomic measurement of proximal femur can provide solid data for pre-operative planning of total hip arthroplasty, selection of commercialized femoral stem and design of customized femoral stem.

Frequency of T-cell FoxP3⁺ Treg and CD4⁺/CD8⁺ PD-1 expression is related to HBeAg seroconversion in hepatitis B patients on pegylated interferon / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Host immune responses against hepatitis B virus (HBV) induced by antiviral therapy play a crucial role in viral clearance. To further investigate the immune mechanisms underlying the differences between respondents and non-respondents, we analyzed myeloid dendritic cells (mDCs), plasmacytoid dendritic cells (pDCs), FoxP3(+) regulatory T cells (FoxP3(+) Treg) and programmed death 1 (PD-1) expression in CD4(+)/CD8(+) T cells in chronic hepatitis B patients undergoing pegylated interferon (PegIFN)α-2b treatment.</p><p><b>METHODS</b>Patients received PegIFNα-2b for 24 or 48 weeks, with follow-up at 24 weeks. The frequencies of mDCs, pDCs, FoxP3(+) Treg, and PD-1 expression by CD4(+)/CD8(+) T cells were evaluated by flow cytometry at baseline, weeks 4 and 12, end of treatment, and follow-up (12/24 weeks).</p><p><b>RESULTS</b>In HBeAg seroconverters (respondents), the mDC relative frequency decreased at week 4 and then rebounded at week 12. The pDC relative frequency decreased consistently. In non-HBeAg seroconverters (non-respondents), both mDC and pDC frequencies decreased slightly. The FoxP3(+) Treg relative frequency decreased during treatment and remained low during follow-up in respondents, while in non-respondents it decreased slightly during therapy but rebounded after discontinuation. In patients with HBeAg < 17.55 PEI-U/ml at week 12 and < 8.52 PEI-U/ml at week 24, the FoxP3(+) Treg frequency decreased during treatment and at follow-up. In respondents, CD4(+)PD-1 and CD8(+)PD-1 levels decreased at week 4 and remained low at week 12. In non-respondents, PD-1 expression decreased at week 4 but rebounded at week 12.</p><p><b>CONCLUSIONS</b>The results indicate that the dynamic changes in DCs, FoxP3(+) Treg frequency, and PD-1 expression by CD4(+) and CD8(+) T cells exhibit different trends in HBeAg and non-HBeAg seroconversion patients. During PegIFNα-2b treatment of chronic hepatitis B patients, these changes may be of predictive value for HBeAg seroconversion. HBsAg and HBeAg levels are related to FoxP3(+) Treg frequency.</p>

Correlation between interleukin-28B genetic polymorphisms and primary hepatocellular carcinoma / 中华预防医学杂志

<p><b>OBJECTIVE</b>To explore the correlation between single nucleotide polymorphisms (SNPs) of interleukin-28B (IL-28B) gene and the susceptibility to primary hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>A total of 300 histologically confirmed HCC cases (from November 2001 to April 2010) and 310 healthy controls with no history of chronic hepatitis B or hepatocellular carcinoma (2009-2010) were selected from a hospital in Guilin and a hospital in Beijing for this case-control study.139 HCC patients in the case group had complete clinical tracking data. All the subjects were Han Chinese, with no age or gender restrictions.2 ml peripheral blood samples were drawn from each subject with informed consent. SNP of rs12972991, rs4803223, rs8099917 and rs12979860 four loci in IL-28B gene were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF).</p><p><b>RESULTS</b>The frequencies of C allele at rs12972991, G allele at rs8099917 and G allele at rs4803223 were 6.7% (40/598), 7.9% (47/598) and 10.0% (59/588) respectively in case group; all higher than the corresponding frequencies in control group, separately 2.9% (18/618), 4.1% (25/616) and 3.6% (21/608). The differences were statistically significant (χ2=9.542, 7.858, 20.736, P values all<0.05). The above alleles could increase the risk of HCC, and the OR (95%CI) values were separately 1.67 (1.13-2.46), 1.49 (1.08-2.06) and 2.91 (1.79-4.72). The genotype frequencies of AC+CC at rs12972991, GT+GG at rs8099917, GA+GG at rs4803223 were 13.0% (39/299), 14.7% (44/299) and 19.0% (56/296) respectively in case group; while the frequencies were lower in control group, separately 5.8% (18/309), 8.1% (25/308) and 6.6% (20/304). The differences were statistically significant (χ2=9.319, 6.557, 20.948, P values all<0.05). These genotypes may increase the risk of HCC, and the adjusted OR (95%CI) values were 2.24 (1.31-3.83), 1.81 (1.14-2.88) and 2.90 (1.78-4.70), respectively. The stratified analysis of the clinical data indicated that the frequency of genotype GA+GG at rs4803223 was 50.0% (13/26) in patients of tumor thrombosis in portal vein (TTPV), higher than the frequency of genotype AA (21.1%, 23/109). The difference was statistically significant (χ2=8.965, P=0.003).</p><p><b>CONCLUSION</b>The results suggested that IL-28B gene polymorphisms was correlated to the susceptibility to HCC in Chinese Han ethnic population. Among them, GA + GG genotype at rs4803223 could increase the risk of TTPV in HCC patients.</p>

Intestinal immune barrier integrity in rats with nonalcoholic hepatic steatosis and steatohepatitis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Nonalcoholic fatty liver disease (NAFLD) has emerged as the major cause of chronic liver injury. Intestinal barrier plays an important role in the pathogenis of NAFLD. The aim of this article was to assess intestinal immune barrier function during the development of NAFLD.</p><p><b>METHODS</b>Totally 60 male Sprague-Dawley (SD) rats were divided into 2 groups: normal diet (ND) group and high-fat diet (HFD) group. NAFLD rat model was established in the HFD rat group. Portal blood endotoxin level was assessed by limulus test. The percentage of CD4+ cells and CD8+ cells in peripheral blood mononuclear cells (PBMC) and lymphocytes in Peyer's patches (PP) were analysed by flow cytometry. Intestinal secretory immunoglobulin A (SIgA) level was evaluated by enzyme-linked immunosorbent assay. Paired Student's t test was used for the statistic analysis.</p><p><b>RESULTS</b>HFD rats presented with simple steatosis at the 4th and 8th week and progressed to nonalcoholic steatohepatitis at the 12th week. Elevated lipopolysaccharides (LPS) level in HFD rats was observed at the 8th week ((1.54 ± 0.30) times of ND group, P < 0.01). CD4/CD8 ratios in PBMC and PP of HFD rats were increased at the 4th week ((1.50 ± 0.47) and (1.63 ± 0.34) times of ND group, P < 0.05) and decreased at the 8th week ((0.50 ± 0.16) and (0.61 ± 0.26) times of ND group, P < 0.05). At the 12th week, CD4/CD8 ratio ((1.47 ± 0.46) times, P < 0.05) in PP increased to levels observed in the 4th week. Intestinal SIgA expression of HFD rats was remarkably up-regulated at 12th week ((2.70 ± 1.65) times, P < 0.05).</p><p><b>CONCLUSION</b>Liver-gut axis in rats with NAFLD may mediate and improve intestinal immune function by increased CD4/CD8 ratio in PP and increased production of SIgA.</p>

The frequency, phenotypes and functions of CD4+ CD25+ regulatory T cells in hepatocellular carcinoma patients / 中华肝脏病杂志

<p><b>OBJECTIVES</b>(1) To evaluate the prevalence, phenotypes and suppressive function of CD4+CD25+ regulatory T cells (Tregs) among the in peripheral blood mononuclear cells (PBMCs) and tumor-infiltration lymphocytes (TILs) from hepatocellular carcinoma (HCC) patients and patients with chronic hepatitis B. (2) To investigate the correlation between the frequency of CD4+CD25+ Tregs and clinical characteristics of HCC patients.</p><p><b>METHODS</b>PBMCs and TILs in 18 HCC patients, 10 chronic hepatitis B (CHB) patients and 15 healthy donors were evaluated for the phenotypes of CD4+CD25+ Tregs and the proportion of CD4+CD25+ Tregs as a percentage of the total CD4+ cells, by flow cytometric analysis with three or four color staining. The relationship between the frequency of CD4+CD25+ Tregs and tumor TNM stages was analyzed. The CD4+CD25+ Tregs and CD4+CD25- T cells were isolated from PBMC of HCC patients and donors. The suppressive function of CD4+CD25+ Tregs was analyzed.</p><p><b>RESULTS</b>The percentages of CD4+CD25+ Tregs of the HCC patients (6.38% +/- 6.30%) and CHB patients (4.29% +/- 1.82%) were significantly higher than those of the healthy donors (1.58% +/- 0.55%, P less than 0.01). Among the TILs, the percentage of CD4+CD25+ Tregs was higher (t = 4.39, P < 0.01). There were significant differences in the prevalence of CD4+CD25+ Tregs in early and advanced stage HCCs (stage II vs. III, P less than 0.05; stage II vs. IV P < 0.01). The proliferative capacity of CD4+CD25- T cells was inhibited by the presence of CD4+CD25+ T cells in a dose-dependent manner where the level of suppression was correlated to the ratio of the two-cell populations.</p><p><b>CONCLUSION</b>These results suggest that the increase in frequency of CD4+CD25+ Tregs might play a role in the suppression of the immune response against HCC, which may contribute to the HCC cells that escaped from immunological surveillance.</p>

Study of phenotypes and functions of cord blood dendritic cells from fetuses whose mothers had chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the phenotypes and functions of cord blood dendritic cells of fetuses whose mothers are patients with chronic hepatitis B.</p><p><b>METHODS</b>Peripheral blood and cord blood mononuclear cells (PBMC) were isolated from whole blood by density gradient centrifugation with Ficoll-Hypaque. The adherent cells were cultured in AIM-V medium containing recombinant human IL-4, TNF-alpha and GM-CSF. On day 9, mature DCs (mDC) were harvested and used for phenotype analysis. The amounts of IL-12 which dendritic cells produced were measured. The dendritic cells that were studied and compared were from cord blood of fetuses of both CHB positive and negative mothers and from CHC adult peripheral blood.</p><p><b>RESULTS</b>The expression rate of CD80 and CD83 of chronic hepatitis B mother cord blood dendritic cells was low compared with that of the healthy cord blood, healthy adult peripheral blood, and chronic hepatitis B adult peripheral blood, P < 0.05. The amount of IL-12 produced by chronic hepatitis B mother cord blood dendritic cells was lower than that of healthy cord blood, healthy adult peripheral blood, chronic hepatitis B adult peripheral blood (P < 0.05). The T lymphocyte proliferation inducing ability of dendritic cells of healthy adult peripheral blood was higher in inducing cord blood T lymphocytes proliferation, which was greater than that of the healthy adult peripheral blood in inducing adult T lymphocytes and was greater than that of the healthy cord blood dendritic cells in inducing cord blood T lymphocytes, which was greater than that of the healthy cord blood in inducing adult T lymphocytes, which was greater than that of chronic hepatitis B mothers in inducing cord blood T lymphocytes, which was greater than that of chronic hepatitis B mother cord blood in inducing adult T lymphocytes.</p><p><b>CONCLUSION</b>The maturation and functioning of CHB mother cord blood dendritic cells were lower than those of healthy cord blood, healthy adult peripheral blood and CHB adult peripheral blood.</p>