OBJECTIVETo investigate the effect of hepatocyte growth factor (HGF) on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) after allogeneic bone marrow transplantation (allo-BMT) and related mechanism in acute lymphoblastic leukemia (ALL) mice.

METHODSTwenty nude mice were randomly divided into control (group A) and test (group B) groups for monitoring relapse, and 20 BALB/c mice into control (group C) and test (group D) groups for GVHD. HGF as injected from day 0 to day 7 after BMT for groups B and D, while PBS for A and C. CD4(+) and CD8(+) T cell were evaluated by flow cytometry. The survival of mice after BMT was recorded. The level of tumor necrosis factor-alpha (TNF-alpha) was evaluated by ELISA.

RESULTSThe median past-BMT survival were 7.00 +/- 1.58, 9.00 +/- 1.58, 11.00 +/- 3.95 and 24.00 +/- 13.44 days for groups A, B, C, D, respectively, being prolonged in group D. HGF could decrease the quantity of CD4(+) T cells [group D (10.39 +/- 1.15)% vs group C (13.50 +/- 1.80)%, P < 0.01] and increase CD8(+) T cell [group D (12.25 +/- 2.85)% vs group C (6.12 +/- 1.99)%, P < 0.01], decrease the level of TNF-alpha in transplanted ALL mice [group D (112.10 +/- 18.99) pg/ml vs group C (143.90 +/- 25.35) pg/ml, P < 0.01] and reduce the degree of GVHD.

CONCLUSIONHGF could alleviate post-allo-BMT GVHD but retain GVL effect.

Animals ; Bone Marrow Transplantation ; Disease Models, Animal ; Female ; Graft vs Host Disease ; prevention & control ; Graft vs Leukemia Effect ; drug effects ; Hepatocyte Growth Factor ; pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; surgery ; Random Allocation ; Transplantation, Homologous

OBJECTIVETo detect plasma concentrations of vascular endothelial cell growth factor (VEGF) and tissue factor (TF) in children with acute lymphoblastic leukemia (ALL) and explore their clinical significance in ALL.

METHODSThirty-three children with newly diagnosed ALL, including 18 cases of low risk, 7 cases of moderate risk and 8 cases of high risk, were enrolled in this study. Twenty-five patients received a complete remission and 8 cases were in non-remission after conventional remission induction chemotherapy. Plasma concentrations of VEGF and TF in the patients were detected using ELISA before and after treatment. Sixteen healthy children served as normal control group.

RESULTSPlasma concentrations of VEGF and TF in ALL patients before treatment were significantly higher than those in normal controls (P < 0.01). Plasma concentrations of VEGF and TF in the non-remission group before treatment were significantly higher than those in the remission group (P < 0.05) and the control group (P < 0.01). After treatment the plasma concentrations of VEGF and TF in the non-remission group were not significantly reduced and higher than those in the remission and the control groups (P < 0.01). There were significant differences in plasma concentrations of VEGF and TF among the low-risk, moderate-risk and high-risk groups before and after treatment (P < 0.05). Plasma concentrations of VEGF and TF in the high risk group were not significantly reduced after treatment and higher than those in the control group (P < 0.01). A linear correlation was noted between plasma VEGF and TF concentrations in ALL patients before treatment (r=0.50, P < 0.01).

CONCLUSIONSVEGF and TF play an important role in the development of ALL and may be useful to the evaluation of the severity and the outcome in ALL.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; etiology ; Thromboplastin ; analysis ; Vascular Endothelial Growth Factor A ; blood

To observe the effects of hepatocyte growth factor (HGF) on graft-versus-host disease (GVHD) and Th1/Th2 related cytokines in mice with acute lymphoblastic leukemia (ALL) after allogenic bone marrow transplantation (allo-BMT), BALB/c mice were conditioned by total body irradiation with 11 Gy and then were transplanted with allogeneic bone marrow after establishing ALL model. BALB/c mice were divided into groups A and B. The mice of group A were injected subcutaneously with HGF from day 0 to 7 after allo-BMT, and the mice of group B were injected subcutaneously with PBS from day 0 to 7 after allo-BMT. The symptoms of GVHD and the GVHD pathological changes of liver and small intestine and skin were observed. The serum levels of both IFN-gamma and IL-4 were determined by ELISA. The results showed that the score of GVHD in group A was lower than that in group B (P < 0.05). The levels of IFN-gamma in both groups A and B were all higher than that in normal group (P < 0.05 and P < 0.001, respectively), However, the level of IFN-gamma in group A was lower than that in group B (P < 0.01). The levels of IL-4 in both group A and B were all lower than that in normal group (P < 0.05), but the level of IL-4 in group A was higher than that in group B (P < 0.05). It is concluded that HGF can alleviates the severity of GVHD, because of its balancing the Th1/Th2-related cytokines after allo-BMT.
Animals ; Bone Marrow Transplantation ; adverse effects ; methods ; Cytokines ; blood ; Enzyme-Linked Immunosorbent Assay ; Female ; Graft vs Host Disease ; immunology ; prevention & control ; Hepatocyte Growth Factor ; pharmacology ; Interferon-gamma ; blood ; Interleukin-4 ; blood ; Male ; Mice ; Mice, Inbred BALB C ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; immunology ; surgery ; Th1 Cells ; immunology ; Th2 Cells ; immunology ; Transplantation, Homologous

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

BACKGROUND: It is of vital importance to fabricate an interface on the titanium implant surface which can promote early cell adhesion, proliferation, and differentiation, and exert better antibacterial effects with no cytotoxicity. OBJECTIVE: To prepare a TiN/Ag composite coating on the surface of pure titanium implant, and to explore its antibacterial properties and effects on MC3T3-E1 biobehaviors. METHODS: Acid etching blasting and multi-arc ion plating were adopted to prepare TiN/Ag composite coating on the smooth surface of pure titanium. Then, MC3T3-E1 cells that grew well were inoculated onto pure titanium plate, sandblasted and acid-etched titanium plate, and TiN/Ag-coated titanium plate. Twenty-four hours later, cell adhesion and viability were observed under confocal laser scanning microscope, and cell morphology was observed under scanning electron microscope. Cell counting kit-8 was used to detect cell proliferation and cytotoxicity at 24,48,72 hours after inoculation.In addition,Staphylococus aureus solution was dropped onto the smooth titanium plated, acid-etched and sandblasted titanium and TiN/Ag-coated titanium plate, and the growth of bacteria was observed by the laser confocal scanning microscope at 16 hours. RESULTS AND CONCLUSION: Under the confocal laser scanning microscope, spindle cells with bipolar or three poles were observed on the smooth titanium surface, and there was less F-actin and filopodia expression; cells on the TiN/Ag-coated titanium surface and sandblasted and acid-etched titanium surface were scattered with a large amount of interconnected filopodia that were fully stretched and adhered to the titanium surface, highly expressed F-actin was detected, and actin fibers were thickened. Under the scanning electron microscope, the cells on the smooth titanium surface were not fully adhered and stretched, and those on the TiN/Ag-coated titanium surface or the sandblasted and acid-etched titanium surface exhibited better adhesion and extension. Findings from the cell counting kit-8 showed that after 72 hours of inoculation,the cells on the smooth titanium surface grew well,with cytotoxicity level 1.In addition,Staphylococus aureus grew well on the smooth titanium surface under the confocal laser scanning microscope,while a large amount of Staphylococus aureus died on the TiN/Ag-coated titanium surface or on the sandblasted and acid-etched titanium surface. These findings indicated that TiN/Ag coating has good biocompatibility and antibacterial properties.

OBJECTIVETo study the anti-inflammatory and analgesic actions of Aike Mixture (AKM).

METHODSA total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed.

RESULTSAKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01).

CONCLUSIONAKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.

Animals ; Chronic Disease ; Disease Models, Animal ; Drug Combinations ; Male ; Mice ; Mice, Inbred ICR ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; therapeutic use ; Phytotherapy ; Prostatitis ; drug therapy ; Saponins ; pharmacology ; therapeutic use

Objective: To explore the clinical efficacy and safety of unrelated umbilical cord blood transplantation (UCBT) in the treatment of refractory and relapsed acute leukemia (AL) patients. Methods: The clinical data of 22 refractory and relapsed AL patients who were treated with UCBT as salvage therapy from November 2009 to May 2017 were retrospectively analyzed. All patients received a myeloablative conditioning regimen for prevention of graft-versus-host disease (GVHD) with cyclosporine A (CSA)/short course of mycophenolate mofetil (MMF). Results: ①Of 22 patients, 9 cases were male and 13 female. The median age was 23 (15-44) years and median weight of 52.5 (43-82) kg. All patients were transplanted with a median umbilical cord blood nucleated cells of 3.07 (1.71-5.30)×10⁷/kg (by weight), the median CD34⁺ cells was 1.60 (0.63-3.04)×10⁵/kg (by weight). ②The myeloid cumulative implantation rate was 95.5% (95%CI 45.2-99.7%) after transplantation of 42 d, with the median implantation time of 19 (13-27) d. The platelet cumulative implantation rate after transplantation of 120 d was 81.8% (95%CI 54.2-93.6%), the median implantation time of 42 (20-164) d. ③The incidence of Ⅱ-Ⅳ, Ⅲ-Ⅳ aGVHD and the 2 year cumulative incidence of cGVHD were 36.4%, 13.6% and 40.3% respectively. ④ The transplant related mortality (TRM) after transplantation of 180d was 22.7%, 2 year cumulative rate of relapse was 18.7% (95%CI 3.6-42.5%), 2 year disease-free survival rate (DFS) and overall survival rate (OS) were 53.7% and 58.1%, respectively. Conclusion: The preliminary results show that the use of UCBT is safe and effective for refractory and relapsed AL patients who fail to respond to conventional chemotherapy.
Acute Disease ; Adolescent ; Adult ; Cord Blood Stem Cell Transplantation ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia/therapy* ; Male ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies ; Transplantation Conditioning ; Young Adult

This study was purposed to detect the alloantibodies against Factor VIII (FVIII) by ELISA for estimating the incidence of the alloantibodies against Factor VIII (FVIII) in patients with hemophilia A, and to investigate the relationship between factor VIIIC domain and alloantibodies. Total of 140 patients with hemophilia A and 80 normal controls were enrolled in this study, among them plasma FVIII level of 84 patients was less than 1%, plasma FVIII level of 34 patients was between 1% and 5%, and plasma FVIII level of 22 patients was more than 5%. All patients were treated with plasma-derived FVIII concentrate or plasma before. The ELISA plate was coated with McAb (SZ-132) against FVIII prepared in our laboratory, then human recombinant FVIII concentrates were applied. After incubation in room temperature for 2 hours, diluted plasma samples and HRP-conjugated goat anti-human IgG were added successively, finally A490 was recorded. The threshold of alloantibody of patient plasma was set as mean value>3 SD more than control. The plate was coated with antibody against His, then human recombinant FVIII-C1C2 prepared in our laboratory was added. After incubation in room temperature for 2 hours, diluted plasma samples and HRP-conjugated goat anti-human IgG were added successively, finally A490 were recorded. The threshold was set as the mean value>3 SD more than control. The results showed that the alloantibodies against FVIII were found in 56 patients (40%) by ELISA, and 82.1% (46/56) of this kind of alloantibody could interact with the C domain of FVIII. It is concluded that C domain of FVIII is one of the primary binding sites for the alloantibodies against FVIII in Chinese patients with hemophilia A.
Adolescent ; Adult ; Binding Sites, Antibody ; Case-Control Studies ; Child ; Child, Preschool ; Factor VIII ; immunology ; Hemophilia A ; blood ; immunology ; Humans ; Infant ; Isoantibodies ; blood ; Male ; Middle Aged ; Protein Interaction Domains and Motifs ; Young Adult

Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.