Risks of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis and Hyperamylasemia After Endoscopic Papillary Balloon Dilation: A Retrospective Analysis.

It is currently unclear whether endoscopic papillary balloon dilation (EPBD) is associated with increased severe postendoscopic retrograde cholangiopancreatography pancreatitis (PEP)-related morbidity owing to conflicting reports. This study aimed to investigate whether EPBD increases the risk of PEP and hyperamylasemia. Clinical data of patients with choledocholithiasis, treated at the Second Affiliated Hospital of Harbin Medical University from January 2015 to December 2016 were analyzed. Patients were divided into the EPBD group and endoscopic sphincterotomy (EST)+EPBD group, and their characteristics and PEP and hyperamylasemia incidences were compared. Incidences related to dilated balloon diameter were also analyzed. There were no significant differences in patient characteristics and the incidences of PEP (2.6% vs. 0%; P=0.257) and hyperamylasemia (4.4% vs. 5.6%; P=0.954) between the 2 groups. Results were similar even with different balloon dilatations. EPBD without endoscopic sphincterotomy did not increase the risk of PEP and hyperamylasemia. It is a safe option for choledocholithiasis patients.

Bortezomib protects against dextran sulfate sodium­induced ulcerative colitis in mice.

Bortezomib, a first­in­class proteasome inhibitor, is a standard method of treatment in multiple myeloma. In the present study, the therapeutic effect of bortezomib was evaluated in an ulcerative colitis model induced by dextran sulfate sodium (DSS) in mice, and the mechanism of action was also investigated. Mice were administered with 3% DSS drinking water for 7 consecutive days and then they were intraperitoneally treated with bortezomib (0.2, 0.6 or 1 mg/kg) for 1, 3 or 7 days. Mice in the control group and the DSS group were provided the same volume of PBS, respectively. Body weight, stool characteristics and hematochezia were observed. Serum levels of tumor necrosis factor­α (TNF­α), C­reactive protein (CRP), albumin (ALB) and colonic activity of superoxide dismutase (SOD) were evaluated using specific kits. The expression of the transcription factor nuclear factor­κB (NF­κB) p65 gene and the DNA­binding activity of NF­κB protein were also evaluated. Administration of bortezomib attenuates colonic inflammation in mice. After 3 or 7 days of treatment, Disease Activity Index (DAI) as well as histological scores and NF­κB p65 protein expression were significantly reduced in mice treated with bortezomib at a dose of 0.6 or 1 mg/kg/day. Furthermore, it was also revealed that bortezomib was able to reduce serum levels of CRP and TNF­α caused by DSS and increase the level of ALB in serum and the activity of SOD in colonic tissues. These results demonstrated that bortezomib exerts a protective effect on DSS­induced colitis, and its underlying mechanisms are associated with the NF­κB gene inhibition that mitigates colon inflammatory responses in intestinal epithelial cells.

[Effects of acute lymphoblastic leukemia children bone marrow mesenchymal stem cells on drug resistance of K562/A02 cell line].

The aim of study was to investigate the effect of acute lymphoblastic leukemia (ALL) children bone marrow mesenchymal stem cells (MSC) on resistance of K562/A02 cells and its mechanism. MSC obtained from bone marrow of AL children were cultured and identified. The co-culture of MSC and K562/A02 and the culture of K562/A02 cell suspension alone was performed, of which 2 kinds of cells were treated with same concentration of adriamycin (ADM), and the rate of apoptosis was detected by flow cytometry, bcl-2 and bax of K562/A02 were detected by RT-PCR, while mdr1 gene level was detected by FQ-PCR. The results indicated that the MSC separation and proliferation were viable and steady. The apoptosis rate of the K562/A02 cells co-cultured with MSC was 1.97 ± 0.11%, while apoptosis rate of the K562/A02 cells cultured alone was 8.38 ± 0.29%, there was significant difference (p < 0.05). As compared with the K562/A02 cells cultured alone, the bcl-2 gene expression in K562/A02 cells co-cultured with MSC obviously increased; ratio of bcl-2/bax was obviously enhanced. The mdr1 gene level in K562/A02 co-cultured with MSC was no statistical different from K562/A02 cultured alone (p > 0.05), which suggested that adhesion co-cultured with MSC did not induce mdr1 expression higher than the culture of suspension. It is concluded that the MSC of ALL children can escape the leukemia cells from proapoptotic effect of drugs, the resistance of K562/A02 to ADM may be involved in enhancement of bcl-2 gene expression of K562/A02 cells co-cultured with MSC, but not in relation to mdr1 gene in K562/A02 cells themselves.

[Change of CD4(+) CD25(+) regulatory T cells and NK Cells in peripheral blood of children with acute leukemia and its possible significance in tumor immunity].

This study was purposed to investigate the changes of CD4(+) CD25(+) regulatory T cells and NK cells in peripheral blood of acute leukemia children at different stages, the function of immune system and the possible roles of the CD4(+) CD25(+) regulatory T cells as well as NK cells in leukemia immunity. The number and proportion of CD4(+) CD25(+) regulatory T cells and NK cells were detected by flow cytometry in the peripheral blood of 53 acute leukemia children, including 25 patients in new diagnosis and 28 patients in continuous complete remission (CCR), and were compared with that of 20 normal children. The results indicated that the mean proportion of CD4(+) CD25(+) CD127(+) in CD4(+) T cells of peripheral blood in newly diagnosed patients, patients with CCR and normal children were (9.55 +/- 2.41)%, (8.54 +/- 2.51)% and (6.25 +/- 0.85)% respectively, the mean proportions of CD4(+)CD25(+)CD127(+) in newly diagnosed patients and patients with CCR were higher than that in normal children, the mean proportion of CD4(+)CD25(+)CD127(+) in newly diagnosed patients were higher than that in patients with CCR (p < 0.05). At the same time, the NK cell count in patients with acute leukaemia decreased as compared with normal control, while after achieving CCR, the NK cell count in patients were also less than that in normal control (4.11 +/- 3.87% and 10.41 +/- 7.20% vs 14.06 +/- 5.95%, p < 0.05). It is concluded that the application of CD4(+), CD25(+) and CD127(+) to detect regulatory T cells is a simple, reproductive and accurate method, and the CD4(+) CD25(+) CD127(+) T cells can better reflect the proportion of CD4(+)CD25(+) regulatory T cells. The increase of regulatory T cells and decrease of NK cells in pediatric patients with acute leukemia indicate that the function of NK cells may be depressed. Treg T cells play a role in occurrence and development of leukemia, and are involved in down-regulating NK cell function.

[Expression of human ermap gene in umbilical cord blood mononuclear cells during differentiation and development towards erythroid lineage].

The aim of study was to explore the potential of human erythroid membrane associated protein (ERMAP) gene in erythroid cell differentiation and development, mononuclear cells (MNCs) were isolated from umbilical cord blood and induced to erythroid cell differentiation by SCF, IL-3 and EPO. The cell morphology was observed by using optical microscopy, the positive rate of cells was counted by biphenylamine staining and the ratios of CD36+/CD235a-, CD36+/CD235a+, CD36-/CD235a+ cells were detected by flow cytometry, the change of human ermap gene expression level was analyzed by using fluorescent quantitative PCR (FQ-PCR). The results showed that the ermap gene expression level increased while MNCs were induced to erythroid lineage after treatment with SCF, IL-3 and EPO. It is concluded that the human ermap gene plays an important role in differentiation and development of erythroid cells.

[A study on the apoptosis of gastric carcinoma cells induced by arsenic trioxide combined with Ad-IkappaBalphaM].

OBJECTIVE: To study the activation of nuclear factor-kappaB (NF-kappaB) in gastric carcinoma SGC-7901 cells after treating with As(2)O(3) and the enhancement of the therapeutic effect of As(2)O(3) with recombinant adenovirus IkappaBalphaM. METHODS: Culture of gastric carcinoma SGC-7901 cells was carried out. The cells both uninfected and infected with Ad-IkappaBalpha but not treated with As(2)O(3) were used as control. Electrophoretic mobility shift assay (EMSA) and immunohistochemistry were used to detect the activation of NF-kappaB in the cells after treatment of As(2)O(3) and the combination with Ad-IkappaBalphaM. MTT, Hoechst staining and TUNEL were used to assay the change of apoptosis induced by As(2)O(3) after infection with Ad-IkappaBalphaM. RESULTS: The results of EMSA and immunohistochemical method showed that after the treatment of As(2)O(3) the cells showed high activity of NF-kappaB. Simultaneous infection with Ad-IkappaBalphaM can inhibit the activation of NF-kappaB; MTT method indicated that after the treatment of As(2)O(3) infected with Ad-IkappaBalphaM apoptosis rate of the cells (59.2 +/- 2.5)% was higher than that of the cells treated with As(2)O(3) and infected with Ad-IkappaBalpha but not treated with As(2)O(3) (47.5 +/- 2.3)% and these neither infected nor treated (40.0 +/- 1.2%), P < 0.01. The result of Hoechst staining method indicated that, in the group of cells treated with As(2)O(3) and infected with Ad-IkappaBalphaM, apoptosis rate is (27.7 +/- 2.6)%, which was higher than the that of the cells infected with Ad-IkappaBalpha (18.3 +/- 1.5)% but not treated with As(2)O(3) and these neither infected nor treated (11.0 +/- 1.7%), P < 0.05. Hoechst staining method was in accordance with TUNEL technique; it was shown that in the group of cells treated with As(2)O(3) and infected with Ad-IkappaBalphaM, apoptosis rate was (31.1 +/- 2.5)%, being still higher than that of cells infected with Ad-IkappaBalpha but not treated with As(2)O(3) (20.7 +/- 2.1)% and these neither infected nor treated (13.0 +/- 1.7)%, P < 0.01. Therefore, infection with Ad-IkappaBalphaM can significantly increase the apoptosis induced by As(2)O(3). CONCLUSIONS: Gastric carcinoma cells treated with As(2)O(3) show activity of NF-kappaB. It is indicated that the activity of NF-kappaB may be the mechanism of the antagonism of gastric carcinoma cells against the apoptosis induced by As(2)O(3). Infection with Ad-IkappaBalphaM can effectively inhibit the activation of NF-kappaB in gastric carcinoma cells and increase the cell apoptosis induced by As(2)O(3).

[Preliminary study on the safety and pharmacodynamic action of low dose L-asparaginase].

OBJECTIVE: To investigate the safety and therapeutic effect of low dose (1000 U/m(2)) L-asparaginase (L-Asp) in the treatment of children with acute lymphoblastic leukemia (ALL). METHODS: Six patients were treated with low dose L-Asp after previously suffered severe side effects from standard dose L-Asp (5000 - 10,000 U/m(2)). Twenty-eight blood samples were obtained randomly from 5 of them. Plasma asparagine concentration was detected by reverse phase-high performance liquid chromatography (RP-HPLC). RESULTS: All the patients treated with low dose L-Asp showed no any toxic symptoms. The plasma asparagine levels in the patients were all above 5 micromol/L except case 4 (4.91 micromol/L) before receiving L-Asp, and were all decreased below 0.5 micromol/L five days after receiving low dose L-Asp, except case 3 (3.70 micromol/L), the results being like that of receiving standard dose L-Asp. CONCLUSION: Low dose L-Asp has definite efficacy for childhood ALL, while avoids serious side effects from standard dose L-Asp.

[Research on the pharmacokinetics and pharmacodynamics of L-asparaginase during its treatment of childhood acute lymphoblastic leukemia].

OBJECTIVE: To investigate the changes in the activity of Escherichia coli asparaginase (L-asp) and the concentration of asparagines (ASN) in the plasma of the acute lymphoblastic leukemia (ALL) children receiving L-asp containing chemotherapeutic protocol to explore more reasonable usage of L-asp in the treatment of childhood ALL. METHODS: L-asp containing hemotherapy regimen of VDLP was used, in which L-asp (10,000 U/m(2)) was administered intravenously every other day for 10 doses in 15 children with ALL. A total of 340 peripheral blood samples were collected at scheduled time points during the therapy and plasma L-asp activity (by spectrophotometric assay) and asparagines concentration (by RP-HPLC) were measured. RESULTS: During the administration of L-asp, the plasma L-asp activity was increasing gradually peaked after eight doses and then decreased gradually, while the plasma concentration of asparagines maintained in complete or nearly complete depletion status. After the therapy courses finished, a plasma L-asp activity above 100 U/L with asparagines almost complete depletion status was lasting for about seven days. CONCLUSION: The current L-asp containing chemotherapeutic protocols in which L-asp was administered in a dose of 10 000/m(2) intravenously every other day, are efficient enough for the depletion of plasma ASN.