Clinical analysis on platinum-based combined chemotherapeutical regimens for treating relapsed or refractory non-Hodgkin lymphoma / 重庆医学

Objective To evaluate the efficacy and adverse reactions of platinum-based combined chemotherapeutical regimens in treating relapsed or refractory non-Hodgkin lymphoma(NHL).Methods The clinical data of 68 patients with relapsed or refractory NHL treated with platinum-based combined chemotherapeutical regimens in the Affiliated Tumor Hospital of Guangxi Medical University from January 2008 to December 2014 were retrospectively analyzed.The curative effect of related regimens,adverse reactions and related influence factors were analyzed.Results Sixty-eight cases received 283 cycles of chemotherapy.In all cases,11 cases(16.18 ％) achieved the complete response(CR),31 cases(45.59 ％) achieved the partial response(PR),the overall response rate(ORR) was 61.76％;the median progression-free survival(PFS) was 6.51 months(95％CI:4.97-8.04 months).ORR and PFS in the cases of stage Ⅱ-Ⅲ,IPI score 0-2 and receiving only one chemotherapeutical regimen were superior to those in the cases of corresponding subgroup(P＜0.05);ORR and PFS had no statistical difference between the B cells lymphoma and Tcells lymphoma(P＞0.05).The medion PFS in the combined R group was 11.16 months,which was longer than 5.84 months in the non-combined R group(P =0.004).The major adverse events (stage Ⅱ-Ⅲ) included leukopenia (41.18 ％),thrombocytopenia (27.94％),hemoglobin decrease(11.76％),vomiting(8.82％) and diarrhea(1.47％).Conclusion The platinum-based combined chemotherapeutical regimens are effective with good safety in the treatment of relapsed or refractory NHL.

Expression and clinical significance of PAK1 and BRAF V600E mutation in papillary thyroid carcinoma / 中华普通外科杂志

Objective To investigate the expression of P-21 activated kinase 1 (PAK1) and v-raf murine sarcoma viral oncogene homolog B (BRAF) V600E mutation in papillary thyroid carcinoma (PTC)and their relationship with clinicopathological characteristics.Methods Immunohistochemistry was used to detect the expression of BRAF V600E mutation and P-21 activated kinase 1 (PAK1) in 55 PTC tissues and 25 benign thyroid tissues.The correlation between their expression and clinicopathological characteristics were analyzed.Results BRAF V600E mutation and PAK1 expressed differently between PTC and benign thyroid (respectively,x2 =12.121,9.950,all P ＜ 0.01).The expression of PAK1 and BRAF V600E mutation was positively and significantly correlated with tumor invasion,grades and lymph node metastasis(P ＜ 0.05),but it had no correlation with age,gender,tumor size,multiple tumor foci and bilateral tumor foci in PTC (P ＞ 0.05).Expression of PAK1 in BRAF V600E negative PTC was higher than that in BRAF V600E positive PTC,and expression of PAK1 and BRAF V600E mutation in PTC were negatively correlated(r =-0.284,P ＜ 0.05).Conclusion Overexpression of either BRAF V600E mutation or PAK1 predicts poor prognosis of PTC patients.

Effects of serum starvation on cell cycle synchronization in primary human umbilical vein endothelial cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the optimal starvation conditions of human umbilical vein endothelial cells (HUVECs) and establish a highly efficient and stable method for separating HUVECs.</p><p><b>METHODS</b>HUVECs harvested from human umbilical cords by digestion with 0.1% collagenase II for 15 min were cultured in endothelial culture medium (ECM) containing 5% fetal bovine serum (FBS), 1% endothelial cell growth factor (ECGS) and 1% penicillin/streptomycin solution(P/S) at 37 degrees celsius; in 5% CO2. The cells were observed for cell morphology under an inverted microscope and identified with immunofluorescence assay. The purity of HUVECs was detected using flow cytometry (FCM). The cell cycles of HUVECs cultured in the presence of 0, 0.1%, 0.5%, and 1% FBS for 0, 6, 12, 18, and 24 h were analyzed with flow cytometry.</p><p><b>RESULTS</b>s The purity of HUVECs harvested by digestion with 0.1% collagenase II reached 99.67%. The primary HUVECs showed a cobblestone or volute appearance in vitro. Immunocytochemistry showed that HUVECs highly expressed VIII-related antigen. Cell culture in the presence of different concentrations of FBS for 6 h resulted in 70% G0/G1 phase cells, which increased to 80%-90% at 12 h of cell culture, and further to around 95% at 18 and 24 h.</p><p><b>CONCLUSION</b>Digestion with 0.1% collagenase II can obtain high-purity primary HUVECs. Culturing HUVECs in serum-free medium for 12 h can result in a high purity (over 80%) of G0/G1 phase cells.</p>

Total trans-oral endoscopic thyroidectomy and cervical lymphadenectomy: a human cadavers surgery study / 中华外科杂志

<p><b>OBJECTIVE</b>To find an approach for trans-oral endoscopic thyroidectomy (TOET) and cervical lymphadenectomy using conventional endoscopic surgical instruments on frozen fresh cadavers.</p><p><b>METHODS</b>Six frozen fresh cadavers were used in three groups of trans-oral trocar installation experiments: oral vestibule installation, sublingual region installation, and combined bi-vestibular and sublingual installation. TOET (with pretrachealis method to thyroid fixation removal) and cervical lymphadenectomy were performed experiments on another 6 frozen fresh cadavers using the best access approach found in the aforementioned experiments.</p><p><b>RESULTS</b>In oral vestibule trocar installations, the trocars caused large lacerated wound and damaged air tightness. In sublingual installations, only one trocar could be installed in the sublingual area because the space in sublingual area was limited. In combined bi-vestibular and sublingual installations, no gland, vessel or nerve was damaged. Combined bi-vestibular and sublingual access were selected as the surgical approach on the basic of analysis the merits of each approach. TOET and cervical lymphadenectomy in area III, IV, VI, VII were performed without making any accessory damage through combined bi-vestibular and sublingual access approach.</p><p><b>CONCLUSIONS</b>TOET is feasible. Combined bi-vestibular and sublingual approach is available for TOET. Part of the cervical lymph nodes could be resected. Pretrachealis approach to thyroid fixation removal can still be used.</p>

Effects of soluble M-CSF receptor on differentiation of umbilical cord blood-derived myelomonocytic hematopoietic precursors in mesenchymal stem cell microenvironment / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of soluble M-CSF receptor (sMR) on proliferation and differentiation of hematopoietic precursors derived from umbilical cord blood in mesenchymal stem cell (MSC) microenvironment.</p><p><b>METHOD</b>In group of cytokine (CK) + sMR, MSCs were used as feeder cells, mononuclear cells (MNCs) from cord blood were expanded in MSC microenvironment in presence of SCF, Flt3L, TPO, IL-6 and sMR. In CK control group, no sMR was added. MNC counting and colony forming cell (CFC) culture were performed at week 1, 2, 3 and 4.</p><p><b>RESULTS</b>1) The number of MNCs increased rapidly in both group CK and group CK + sMR (108.47 -fold and 120.67 -fold, respectively, P > 0.05). 2) CFC increased, peaked at week 3(38.1 x 10(3)) and declined rapidly at week 4(18.1 x 10(3)) in group CK, but still increased in group CK + sMR at week 4 (84 x 10(3)), the total number of CFC was higher in group CK + sMR than in group CK at week 3 and week 4 (P <0.01). 3) The erythroid CFC peaked at week 1 (5891.2 and 5635.6 for groups CK and CK + sMR, respectively), then dropped rapidly and to zero at week 3, in both group CK and group CK + sMR (P > 0. 05). 4) Myeloid CFC expanded continuously and peaked at week 3 (31.5 x 10(3)), then declined at week 4 (18.3 x 10(3)) in group CK; but still increased at week 4(80.8 x 10(3)) in group CK + sMR, being higher than that in group CK at week 3 and week 4 (P <0.01).</p><p><b>CONCLUSION</b>sMR can inhibit the differentiation of cord blood hematopoietic precursors expanded in MSC microenvironment, but the inhibition exerts only on myelomonocytic but not on erythroid precursors.</p>

Effects of transforming growth factor beta1 on dendritic cells function / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of transforming growth factor beta1 (TGF-beta1) on dendritic cells (DC).</p><p><b>METHODS</b>Murine bone marrow cells were cultured with different cytokine combinations to develop immature DC (imDC, GM-CSF only) and TGFbeta-DC (GM-CSF + TGF-beta1), and their responses to lipopolysaccharide (LPS) stimulation were observed. The cell ultrastructure was observed by transmission electron microscopy and their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was assayed by mixed lymphocyte reaction (MLR) with BrdU incorporation. IL-12p70 protein was detected by ELISA and the expressions of Toll-like receptor 4 (TLR4) on DCs were analyzed with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Compared to imDC, the TGFbeta-DC had no significant alterations in ultrastructure after LPS stimulation. The expressions of CD80, CD86 were lower on TGFbeta-DC than on imDC [(4.14 +/- 0.95)% vs (13.90 +/- 7.22)%; (8.60 +/- 0.75)% vs (20.63 +/- 5.03)%, P < 0.05, both]. The TGFbeta-DC kept their immature morphology after LPS stimulation, but the expressions of I-Ab and CD80 were slightly increased. After 96 h MLR, TGFbeta-DC had weaker stimulating capacity than imDC did, especially when DC/T cells ratios were 1:4 and 1:1 (P < 0.05, both). TGFbeta-DC showed impaired IL-12p70 production and down-regulation of TLR4 expression.</p><p><b>CONCLUSIONS</b>TGF-beta1 can inhibit the expression of co-stimulatory molecules on DC. The TGFbeta-DC is resistant to maturation stimulus (LPS) and might be linked with TLR4 down-regulation.</p>

TGF ?1 inhibits the maturation of dendritic cells and down-regulates TLR4 expression / 中国病理生理杂志

AIM: To investigate the effects of transforming growth factor ?1 (TGF-?1) on murine-derived dendritic cells (DC). METHODS: Murine bone marrow cells were cultured with GM-CSF and TGF-?1 to develop TGF ?-DC. Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was measured by mixed lymphocyte reaction (MLR) using BrdU ELISA method. IL-12 p70 protein was detected by ELISA and the expressions of Toll like receptor 4 (TLR4) on DCs were measured by semi-quantitative RT-PCR and FCM. RESULTS: Compared to immature DC (imDC) cultured with GM-CSF alone, the expressions of CD_80, CD_86, I-A~b and CD_40 in TGF ?-DC were lower. The TGF ?-DC was resistant to maturation by LPS. Maturation resistance was evident from a failure to up-regulate CMs, to stimulate larger T cell proliferation and to increase secretion of IL-12 p70. Down-regulation of TLR4 expression on TGF ?-DC was also found. CONCLUSION: TGF-?1 inhibits the expression of co-stimulatory molecules on DC. It is resistant to maturation stimulus (LPS) and might be linked with TLR4 down-regulation.

Expression of sortilin gene on osteogenic and adipogenic differentiation in mesenchymal stem cells / 中国病理生理杂志

AIM: To characterize the gene expression of sortilin on adipogenic and osteogenic differentiation in mesenchymal stem cells (MSCs) in vitro and explore its significance.METHODS: MSCs derived from human bone marrow were isolated and cultured in vitro ,then were stimulated in osteogenic medium and adipogenic medium,respectively. Osteopontin and lipoprotein lipase were detected by RT-PCR. Sortilin expression was analyzed by semiquantitative RT-PCR. RESULTS: 1.MSCs displayed the potential of differentiation into osteoblast and adipocyte. 2.Sortilin was upregulated one day after osteogenic induction and remained upregulated for a week. The expression of sortilin was significant increased on day 3( P 0.05).CONCLUSION: Sortilin may be useful to modulate the osteogenic differentiation and may not be necessary for adipocyte commitment in MSCs. The regulation of sortilin expression may provide new protocal and strategy for the treatment of osteoporosis and osteopenic disease.