Analysis of Factors Influencing Clinical Efficacy of Rituximab on Patients with Epstein-Barr Virus Positive Diffuse Large B-Cell Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical efficacy and safety of rituximab therapy for patients with Epstein-Barr virus (EBV) positive diffuse large B-cell lymphoma (DLBCL), and to explore the factors influencing the clinical efficacy.@*METHODS@#According to therapeutic regimen, 66 patients with EBV-positive DLBCL were divided into two groups: CHOP group (32 cases) and R-CHOP group (CHOP+ rituximab, 34 cases). The clinical efficacy and the incidence of complication were compared between two groups. The clinical risk factors for the clinical efficacy in patients with EBV-positive DLBCL were confirmed by multivariate Logistic analysis.@*RESULTS@#Compared with CHOP group, the complete remission rate, partial remission rate and the overall effective rate in R-CHOP group all were high (P＜0.05), moreover the disease progression rate in R-CHOP group were low (P＜0.05). The occurrences rate of myelotoxicity, hepatic injury and gastrointestinal reaction were not statistically significantly different between two groups (P＞0.05). Multivariate Logistic analysis showed that the Ann Arbor staging, IPI risk score and Ki-67 positive rate were independent risk factors for the clinical efficacy in patients with EBV-positive DLBCL (OR=2.689, P=0.038; OR=3.232, P=0.025; OR=2.919, P=0.023).@*CONCLUSION@#The clinical efficacy and safety of the therapy with rituximab on the patients with EBV-positive DLBCL are better. The poor Ann Arbor stage, high IPI risk score and the Ki-67 positive rate are factors affecting the clinical efficacy for the patients with EBV-positive DLBCL.

Mechanism Inducing the HL-60 Cell Differentiation by Haishengsu Tegillarca Granosa Extract via Targeting ULK1 Protein / 中国实验血液学杂志

OBJECTIVE@#To investigate the proliferation, differentiation potential and autophagic mechanism HL-60 cells via ULK1 protein targeted by Haishengsu extracted from Tegillarca granosa.@*METHODS@#The HL-60 cells were divided into five groups: Haishengsu of 10,100,1000 mg/L-treated group, all-trans retinoic acid (ATRA) 5 μmol/L-treated group and control group. The cell proliferation rates were detected by MTT after culture 12,24,48 h and 72 h. The expression of differentiation and maturation markers CD11b and CD15 were detected by flow cytometry, and the expression of autophagy molecules ULK1 and LC-3 proteins were measured by Western blot.@*RESULTS@#After cultured for 48 and 72 h the cell proliferation rates of HL-60 in Haishengsu 100 and 1000 mg/L groups were significantly lower than those of ATRA 5 μmol/L group and Haishengsu 10 mg/L group and control group (P<0.05). After 72 h, the levels of CD11b, CD15, ULK1 and LC-3 expression of HL-60 cell in Haishengsu 100 and 1000 mg/L groups were higher than those in ATRA 5 μmol/L group, Haishengsu 10 mg/L group and control group (P<0.05). While the HL-60 cells in Haishengsu 10, 100 and 1000 mg/L group were treated with ULK1 protein inhibitor and after cultured for 72 h, the proliferation rate of HL-60 cell increased, levels of CD11b and CD15 expression decreased at the same time, and the levels of ULK1 and LC-3 proteins in HL-60 cells also decreased (P<0.05).@*CONCLUSION@#Haishengsu, which extracted from Tegillarca granosa, can induce HL-60 cell proliferation and differentiation by targeting ULK1 protein in a concentration and time dependent manner, its effective mochanism may be mediating autophagic activity, promoting cell differentiation and maturation.

Feasibility of constructing a scaffold for osteochondral tissue engineering using poly(lactide-co-glycolide) alone / 中国组织工程研究

BACKGROUND: To mimic physiological and functional requirements of cartilage and subcondral bone, some recent studies have fabricated bilayered scaffolds for osteochondral tissue engineering in cartilage repair. However, in cartilage repair, and little is reported on the use of a single biomaterial instead of composite biomaterials to fabricate bilayered porous scaffolds. OBJECTIVE: To investigate the biocompatibility of an integrated bilayered porous scaffold fabricated with poly(lactic-co-glycolide) (PLGA), and then to discuss its feasibility of constructing tissue-engineered osteochondral graft. METHODS: The integrated bilayered porous scaffolds were fabricated with PLGA by changing the ultrastructure of scaffold.In vitro,bone marrow mesenchymal stem cells(BMSCs)isolated from rabbits were seeded into the bilayered porous PLGA scaffold, co-cultured for 1 week and then observed under scanning electron microscope. After co-culturing 48 hours,the cells were stained by LIVE/DEAD Kit.In vivo,the composite of DiI-labeled BMSCs and the scaffold or the scaffold alone were implanted subcutaneously into the skin of nude mice, and the implants were taken out and stained by hematoxylin-eosin and DAPI staining at 4 and 8 weeks after implantation. RESULTS AND CONCLUSION: (1) We successfully obtained the bilayered porous scaffolds with different pore sizes (the upper layer:100-200 μm and the lower layer:300-450 μm)and 85% porosity.(2)In the in vitro experiment,the LIVE/DEAD staining showed that BMSCs survived well in the scaffold, and the cells adhered well to the wall of pores in all the scaffolds and extracellular matrix deposition was found under the scanning electron microscope.(3)In the in vivo experiment, shown by the hematoxylin-eosin staining, a small amount of chondrocytes formed in the fibrous tissue in the upper layer and a large amount of trabecular bones in the lower layer were found at 8 weeks after implantation in the experimental group. The close integration between the upper layer and the lower layer appeared. BMSCs could survive for 8 weeks in vivo shown by the DAPI staining.However,in the control group,a little fibrous tissue was found without chondrocytes and apparent trabecular bone, and the scaffold was partially degraded. To conclude, the integrated bilayered porous scaffold fabricated with PLGA alone has good biocompatibility, which is feasibly used in osteochondral tissue engineering.

Inhibiting effect of letrozole combined with curcumin on xenografted endometrial carcinoma growth in nude mice / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Letrozole is an aromatase inhibitor that is used in the treatment of estrogen-sensitive tumors such as endometrial carcinoma, however, its therapeutic effect is still to be further improved. It is reported that curcumin has antitumor capability and can enhance the sensitivity of tumor cells to anticancer agents. This study was to investigate the inhibitory effect of letrozole combination with curcumin on the implanted endometrial tumor growth.</p><p><b>METHODS</b>Nude mice were implanted with endometrial carcinoma RL-952 cells. All tumor-bearing mice were randomly divided into 5 groups: control(without treatment), Let(1) (letrozole, 1 microg/d), Let(10) (letrozole, 10 microg/d), Cur [ curcumin, 300 mg/kg.d)], and Let + Cur group [10microg/d letrozole + 50mg/ (kg.d) curcumin]. The tumor growth was monitored. Tumor cells apoptosis was detected in both control and treated groups. The expressions of bcl-2 mRNA and bcl-2 protein were detected using RT-PCR and Western blot, respectively.</p><p><b>RESULTS</b>Fifty mice were successfully implanted with the endometrial tumor. Treatment with letrozole markedly inhibited tumor growth; the inhibitory effect was further enhanced by the combination of letrozole and curcumin. The inhibitory rates in Let (1), Let (10), the Cur, and the Let + Cur groups were 15.95%, 22.49%, 21.57%, and 35.89%, respectively. Treatment with curcumin inhibited the expression of bcl-2 in tumor cells at the mRNA and protein levels. The apoptosis rates in the control group and the four experimental groups mentioned above were 16.97%, 32.90%, 35.80%, 34.16%, and 47.24%, respectively. Tumor cells apoptosis were observed in mice treated with either letrozole or curcumin; however, combination of letrozole and curcumin further enhanced the inhibitory rate in tumor growth.</p><p><b>CONCLUSIONS</b>Treatment with letrozole or curcumin could inhibit the xenografted endometrial tumor growth by inducing apoptosis in tumor cells. Combination of letrozole and curcumin further enhanced the inhibitory effect of tumor growth.</p>

Overview of clinical occurrence of primary immunodeficiency disorders in children / 中华儿科杂志

<p><b>OBJECTIVE</b>More than one hundred primary immunodeficiency disorders have been discovered so far. But the incidence of these disorders in our country is still not clear, so we analyzed the clinical data of 93 children with primary immunodeficiency disorders seen in our hospital in recent 30 years to understand the occurrence of primary immunodeficiency disorders in children, to promote the clinicians to become familiar with these disorders, to improve the nationwide registry system and to establish the basis for the treatment and prevention in future.</p><p><b>METHODS</b>To analyze the constituent ratio of the 93 children with primary immunodeficiency disorders seen in our hospital from 1974 to 2003, diagnostic and classification criteria were set by taking the proposal by International Union of Immunological Societies (IUIS) PID classification committee in 2003 into account. All the data were analyzed retrospectively.</p><p><b>RESULTS</b>In the 93 children with primary immunodeficiency disorders, antibody deficiencies were the most frequent (39.8%) finding, followed by combined immunodeficiency, combined T- and B-cell disorders (22.6%), and T lymphocytic deficiencies alone (14.0%). Immunodeficiency with other major defects accounted for 12.9%, phagocytic disorders 9.7%, and complement deficiencies 1.1%. Thus, there seemed to be a tendency that the incidence increased with time. The incidence of these disorders has increased significantly as shown by 50 diagnosed cases in children with these disorders since 1996. Sixteen children died, with the highest mortality occurred with combined immunodeficiency. Seven children developed bronchiectasis. Two children suffered from persistent diarrhea while one of the two was complicated with persistent intestinal fistula. One child developed juvenile rheumatoid arthritis, another one with granulocytopenia and iridocyclitis, and the other with allergic purpura. The boys: girls ratio for all disorders was 3:1. The age of onset ranged from 10 days to 37 years of age.</p><p><b>CONCLUSIONS</b>There are vast variety of primary immunodeficiency disorders in our area and antibody deficiency is the most common abnormality. Combined immunodeficiency has early onset age and high mortality rate. With the great improvement of the diagnostic techniques, these disorders have become a group of important disorders and all the clinicians should pay great attention to these disorders.</p>

Mechanism of inhibitory effect of intravenous immunoglobulin on neonatal umbilical cord blood lymphocytes / 中华儿科杂志

<p><b>OBJECTIVE</b>The expression of CD25, CD45RA, CD45RO on umbilical cord blood mononuclear cells (CBMCs) and CD3(+) T lymphocytes was investigated to explore the mechanism of immunosuppressive effects of intravenous immunoglobulin on neonatal immune function.</p><p><b>METHODS</b>Umbilical cord blood mononuclear cells and CD3(+) T lymphocytes isolated from 8 neonates were studied. The expression of CD25, CD45RA, CD45RO on umbilical cord blood mononuclear cells (CBMCs) and CD3(+) T lymphocytes induced with various stimuli of different combinations of IVIG and phytohemagglutinin (PHA) including (1) control group, (2) PHA activation group, (3) IVIG pre-inhibition group, (4) PHA pre-activation group, (5) PHA+IVIG group was measured with four-color immunofluorescence antibodies staining-flow cytometric technique. The results were also compared with peripheral blood mononuclear cells of 8 adults (PBMCs).</p><p><b>RESULTS</b>IVIG inhibited the PHA-induced proliferation of CBMCs as reflected by the decreased expression of CD25 and CD45RO. The amounts of CD25(+) and CD4(+)CD45RO(+) CBMCs reached 77.52% +/- 2.31% and 64.29% +/- 3.09% after PHA use. But a decreased response in CD25(+) (7.66% +/- 1.20% and 7.78% +/- 1.46%) and CD4(+)CD45RO(+) CBMC (3.18% +/- 1.90% and 3.11% +/- 0.08%) was observed when IVIG was added in both IVIG pre-inhibition group and PHA+IVIG group. As compared with PBMCs, IVIG failed to induce the increase of the expression of CD45RA in CBMCs whereas CD45RA(+) PBMCs increased from 54.93% +/- 3.63% to 72.77% +/- 0.39% in IVIG pre-inhibition group. Moreover, IVIG inhibited the expression of CD25 and CD45RO on cord blood CD3(+) T lymphocytes no matter whether they were activated with PHA or not. The amounts of CD25(+) and CD4(+)CD45RO(+) CD3(+) T lymphocytes reached 97.92% +/- 2.19% and 80.41% +/- 5.57% after PHA use. But a decreased response in CD25(+) CBMCs (77.29% +/- 0.63%, 51.48% +/- 1.85% and 62.73% +/- 1.24%) and CD4(+)CD45RO(+) CD3(+) T lymphocytes (35.47% +/- 2.55%, 40.14% +/- 1.16% and 36.41% +/- 2.96%) was observed when IVIG was added in IVIG pre-inhibition group, PHA pre-activation group and PHA+IVIG group, and the degree of inhibition of IVIG on cord blood CD3(+) T lymphocytes was much lower than that of CBMCs.</p><p><b>CONCLUSIONS</b>Cord blood T lymphocytes activation was inhibited by IVIG through the inhibition of CD25(+) CBMCs expression and the prevention of transformation from CD4(+)CD45RA(+) cells into CD4(+)CD45RO(+) cells. This IVIG-mediated suppression of activation in cord blood T cells may be derived from the indirect effect of other immune cells or molecules other than the direct effects on T cells. IVIG failed to induce the increase of expression of CD45RA in CBMCs, which may be related to the fact that majority of CBMCs were CD45RA(+) cells, but this may not rule out that the immunosuppressive effect of IVIG could be accomplished by the increase of CD45RA(+) cells in adult peripheral blood mononuclear cells. The suppressive effect of IVIG on CD4(+)CD45RO(+) T lymphocytes may account for its inhibitory effect on immunoglobulin production of neonates' B cells. Considering that naïve CD45RA(+) cells dominate in neonates and IVIG can inhibit transformation from CD4(+)CD45RA(+) cells into CD4(+)CD45RO(+) cells, it is recommended that IVIG should be used properly in neonates, otherwise it may deteriorate their poor immune function especially when it is used for prophylaxis or as a treatment of neonatal non-infectious diseases, and its immunosuppressive action will increase the susceptibility of neonates to infection.</p>

Reactivity and antigenic cross-reactivity of latex in children with allergic disorders / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the relationship between latex allergen and clinical presentation as well as allergenic cross-reactivity between latex and other allergens, to know the incidence of latex allergy in Chinese children and elucidate the allergenic cross-reactivity of latex with other allergens.</p><p><b>METHODS</b>Totally 265 children with allergic disorders were assayed with 13 international standard allergen agents by means of SPT.</p><p><b>RESULTS</b>In 79 children with latex allergenic SPT position, 53 were boys and 26 were girls with an average age of 5.6 years, and 14 cases had episodes occurred in winter, 14 cases in spring, 24 cases in summer, and 27 cases in autumn. Of them, 66 cases presented as asthma, 5 cases atopic skin disorders, 1 case anaphylactoid purpura, 1 case hives and 6 cases only had mild cough. Statistical analysis showed that the positive percentage of the latex SPT had no obvious relation with sex and age, but was higher in summers and autumns than in winters and springs (P < 0.01). Children with allergic symptoms had higher positive rate in latex allergenic SPT than those without them, that is, the positive percentage of the latex SPT significantly increased among children presenting with some allergic symptoms, such as asthma, hives and atopic skin disorders (P < 0.01). All the children with latex allergenic SPT position had cross-reactivity with acarid allergen, 62.0% approximately 43.0% with animal protein allergens including milk, cats, shrimp, dogs, eggs in the order of decreasing cross-reaction rate, and 10.1% - 3.8% with mold and plant farina allergens. But the cross-reactivity between latex and mold or tree farina I were not statistically significant.</p><p><b>CONCLUSION</b>Thirty percent of the children with allergic disorders were latex allergenic SPT positive. Latex allergenic SPT positive results were significantly correlative to allergic clinical presentation and season, while were not relative to sex and age. The cross-reactivity of latex with acarid was most common, followed by animal protein allergens, while the cross-reactivity with mold and plant farina allergen was rare.</p>

Protective effect of bushen ningxin recipe on ovariectomized rabbits with atherosclerosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effects of Bushen Ningxin recipe (BNR) on atherosclerosis in ovariectomized rabbits.</p><p><b>METHODS</b>Twenty-six female New Zealand white rabbits of three months old were randomly divided into four groups, the normal group, the sham operation group, the control group (ovariectomized) and the treated group (ovariectomized and treated with BNR). All rabbits, except the normal group, were fed with high-cholesterol diet starting from two weeks after operation, and to the treated group BNR was given additionally for 3 months. Levels of blood lipid (TC, TG, LDL-C and HDL-C) and NO were measured at the end of the 12th week, and at the same time, histomorphological and pathological examination of aorta under light microscopy and scanning electron microscopy, and the ratio of atherosclerotic area of lesion/endothelium ratio (AL/AE) and thickness of endothelium/medium ratio (TE/TM) were estimated using image analyzer.</p><p><b>RESULTS</b>No significant difference was found in levels of blood lipid between groups, except those in the normal group. As compared with the control group, in the treated group, level of serum NO was higher, AL/AE and TE/TM were lower and the pathological changes of aorta was milder.</p><p><b>CONCLUSION</b>BNR could inhibit the atherosclerosis formation in ovariectomized rabbits, it showed protection on vascular endothelial cells.</p>

Comparision of the effects between estrogen and dehydroepiandrosterone on improving atherosclerosis of ovariectomized rabbits / 医学研究生学报

Objective:To compare the effects between estrogen and Prasterone(Dehydroepiandrosterone,DHEA) on improving atherosclerosis of ovariectomized rabbits. Methods: Thirty female New Zealand white rabbits of three months old were randomly divided into five groups: Group A: normal control;Group B: sham operation + high cholesterol feeding;Group C: ovariectomized + high cholesterol feeding;Group D: ovariectomized + high cholesterol feeding+ estradiol benzoate;Group E: ovariectomized + high cholesterol feeding+ DHEA.Twelve weeks later,all rabbits were sacrificed,the serum TC,TG,LDL-C,HDL-C,NO and estradiol levels were measured.The aortas and uterus were harvested for histomorphometrical evaluation with light and scanning electron microscope.The area ratios of atherosclerotic lesion to endothelium,and the thickness and area ratios of endothelium to the medium were determined by computer. Results: ①Following the treatment for 12 weeks,no significant difference was found in serum TC、LDL-C、HDL-C levels among four groups except in group A.②There were significant differences between the serum triglyceride(TC)levels of group D and group C.③The serum No levels of group D and group E were significantly higher than that of groupC.④The serum estradiol levels of group D and group E were significantly higher than that of groupC.⑤The area ratios of atherosclerotic lesion to endothelium and the thickness and area ratios of endothelium to the medium in group D and group E were significantly lower than that of group C.⑥Endometrial hyperplasia of group D was significant,while there was no such Phenomena in group E. Conclusion: Estrogen and DHEA can alleviate the early pathological changes of atherosclerosis of the ovariectomized rabbits,prevent and reduce the formation of atherosclerosis.

Changes of IL-12、 IFN-? and IL-4 in peripheral blood of postoperative gastric cancer patients vaccined with dendritic cells / 中国普通外科杂志

Objective To investigate effects of dendritic cells (DC) vaccine on immune function in postoperative gastric cancer patients Methods DCs were extracted and pulsed with self tumor antigens in vitro Fifty patients with gastric cancer were divided into 2 groups randomly Four times of DC vaccinations were administered at 7 days intervals to the postoperative patients in treatment group after they underwent chemotherapy The control group were treated with chemotherapy only The level of IL 12 、 IFN ? and IL 4 in peripheral blood were analysed Results In DCs group, the levels of IL 12 were 37?4、 68?6、 96?12 and 59?9 pg/ml, the levels of IFN ? were 61?12、 134?19、 145?20 and 111?15 pg/ml, and levels of IL 4 were 55?7、 49?6、 46?5 and 50?8 pg/ml before and 2, 4 and 8 weeks after vaccination, respectively In control group, the levels of IL 12 were 39?7、 45?9、 44?10 and 44?6 pg/ml, the levels of IFN ? were 63?10、 61?13、 62?11、 61?7 pg/ml, and levels of IL 4 were 52?11、 55?9、 53?10、 55?8 pg/ml before and 2, 4 and 8 weeks after vaccination, respectively The levels of IL 12 and IFN ? increased significantly in DCs group No severe side effects were found during treatment Conclusion DC vaccine improves immune function of posroprative patients with gastric cancer

Effects of the Bushen Ningxin Chinese herb-containing serum on the adherence of human monocytes to endothelial cells / 中国病理生理杂志

AIM: To study effect of the Bushen Ningxin decoction, a Chinese medicine, on the adherence of monocytes to endothelial cells and its mechanism. METHODS: Using cultured human umbilical vein endothelial cells (HUVECs) as target cells, oxidized low density lipoprotein (ox-LDL) was added to the endothelial cell culture to prepare the model of human endothelial cell injury. The serum of rabbits having been treated with Bushen Ningxin decoction was added to trial architecture, the adherence of monocyte-like cell line U937 to HUVECs was analyzed using Rose Bengal staining. In addition, the expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1(VCAM-1) and E-selectin in HUVECs was measured by flow cytometry. RESULTS: Treatment of HUVEC with ox-LDL (100 mg/L) for 24 hours significantly increased adhesion of U937 to HUVECs. If serum of the animal treated with Bushen Ningxin decoction was added to trial architecture, the adhesion decreased significantly. The flow cytometry analysis showed that ox-LDL could induce the expression of ICAM-1, VCAM-1 and E-selectin in HUVECs. Serum of the animal treated with Bushen Ningxin decoction significantly decreased the expression of ICAM-1, VCAM-1 and E-selectin in HUVECs. CONCLUSION: The Bushen Ningxin Chinese herb-containing serum has an inhibitory effect on the adherence of monocytes to endothelial cells, probably by way of down-regulating the expression of ICAM-1, VCAM-1 and E -selectin in endothelial cells.

Screening the differentially expressed genes of immature and LPS-induced mature dendritic cells using cDNA microarray / 解放军医学杂志

Objective To study the changes in gene expression profiles of dendritic cells(DCs) during their maturation processes using cDNA microarray.Method DCs were generated from human peripheral blood monocytes induced by GM-CSF and IL-4,and lipopolysaccharide(LPS) was used to induce the maturation of DCs.After inducing for 48h,cells were collected to extract the general RNA.Genes expressions of mature DCs(maDC) and immature DCs(imDC) were analyzed using cDNA microarray,and immature DCs without induction served as control.Results DCs expressed highly surface markers of mature DCs after LPS induction.The studied data showed that among those 165 target genes,a total of 50 genes(30.3%) exhibited differential levels of expression in LPS-induced mature DCs.Thirty-five genes were up-regulated and fifteen genes were down-regulated.Maturation-dependent up-regulation,defined by a differential expression ratio of ≥2,included twelve cytokine and chemokine genes,ten antigen uptake and presentation genes and thirteen signal transduction molecule genes.Reciprocally,maturation-dependent down-regulation,defined by a differential expression ratio of ≤0.5,occurred with two cytokine,five antigen uptake and presentation genes and eight signal transduction molecule genes.Semi-quantitative reverse transcription polymerase chain reaction(RT-PCR) was employed to further confirm the results of cDNA microarray.Conclusion It is suggested that LPS has significant influence on many genes of DCs in their maturing processes.Those changed genes include cytokines,chemokines and their receptors,antigen uptake and presentation molecules and signal transduction molecules.Analysis on these differentially expressed genes is helpful in understanding the maturing processes of DCs.