ObjectiveTo investigate the expression level of mammalian sterile 20-like kinase 1 （MST1） in prostate cancer （PCa） tissues， its biological functions， and its regulatory effects on androgen receptor （AR） and vascular endothelial growth factor （VEGF） expression. MethodsImmunohistochemistry was performed to detect MST1 expression in 77 prostate cancer tissues and 34 benign prostatic hyperplasia （BPH） tissues， and the relationship between MST1 expression and clinicopathological parameters was analyzed. MST1-overexpressing C4-2 and LNCaP cell lines were constructed. CCK-8 assay， Transwell migration assay， and angiogenesis assay were conducted to evaluate the effects of MST1 on cell proliferation， migration， and angiogenesis. The expression changes of AR and VEGF were detected by qRT-PCR and Western blot. ResultsMST1 expression was significantly lower in PCa tissues compared with BPH tissues （P=0.012）. Low MST1 expression was significantly associated with tumor metastasis （P=0.033）. MST1 overexpression inhibited C4-2 cell proliferation and migration， with transmembrane migrated cells reduced by 53.6% （P<0.01）. MST1 overexpression decreased the mRNA and protein expression levels of AR and VEGF （P<0.05）. Angiogenesis assay demonstrated that the length of new vessel structure was significantly reduced （P<0.05）. ConclusionMST1 shows a low expression level in PCa tissues and is associated with tumor metastasis. MST1 exerts tumor-suppressive effects in prostate cancer by inhibiting cell proliferation， migration， and angiogenesis， as well as downregulating the expression of AR and VEGF， indicating its potential as a therapeutic target for prostate cancer.

Objective:To explore the data distribution characteristics of hydrogen and methane breath test (HMBT) in Chinese population and to evaluate its applicability for diagnosing small intestinal bacterial overgrowth (SIBO) in Chinese population.Methods:HMBT data of 18 634 individuals who underwent health check-up nationwide from March 2019 to september 2022 were retrospectively collected, which included the levels of hydrogen and methane at 0, 30, 60, and 90 min. After quality control and data cleaning, the final valid sample size was 12 654 cases, comprising 7 146 SIBO-negative cases and 5 508 SIBO-positive cases. In order to exclude confounding factors such as oral hygiene, the 12 654 cases were divided into D0 and D1 dataset, when the 0 min-value of hydrogen and methane were both lower than the 30 min-value, the 0 min-value was taken as the baseline, and induded into the D0 dataset (5 556 cases), and other situations were induded into the D1 dataset (7 098 cases). There were 2 879 SIBO-negative cases and 2 659 SIBO-positive cases in D0 dataset, and 4 249 SIBO-negative cases and 2 849 SIBO-positive cases in D1 dataset. The hydrogen and methane level at each testing time point in the SIBO-negative and SIBO-positive individuals, the difference between the peak gas level at 90 min and the baseline, and the distribution of time points at which peak level occurred were analyzed. Independent-sample t test and Mann-Whitney U test were used for statistical analysis. Results:The overall SIBO positive rate was 43.53% (5 508/12 654). In SIBO-positive cases the hydrogen level at 0, 30, 60, and 90 min were 9.41×10 -6 (5.01×10 -6, 21.90×10 -6), 11.34×10 -6 (6.13×10 -6, 22.94×10 -6), 18.16×10 -6 (11.03×10 -6, 29.37×10 -6) and 29.59×10 -6 (20.12×10 -6, 43.36×10 -6), respectively, and methane level were 9.13×10 -6 (7.12×10 -6, 12.03×10 -6), 9.23×10 -6 (8.07×10 -6, 12.03×10 -6), 10.21×10 -6 (9.02×10 -6, 13.01×10 -6), and 12.03×10 -6 (10.01×10 -6, 14.11×10 -6), respectively, which were higher than those of SIBO-negative cases (6.04×10 -6 (3.10×10 -6, 11.08×10 -6), 6.04×10 -6 (3.21×10 -6, 10.06×10 -6), 6.95×10 -6 (4.03×10 -6, 11.01×10 -6), 8.96×10 -6 (5.01×10 -6, 13.91×10 -6); 8.04×10 -6 (7.02×10 -6, 10.00×10 -6), 8.03×10 -6 (7.03×10 -6, 9.95×10 -6), 8.04×10 -6 (7.03×10 -6, 10.00×10 -6) 8.98×10 -6 (7.12×10 -6, 10.03×10 -6)], and the differences were statistically significant ( U=1.41×10 7, 1.09×10 7, 6.66×10 6, 4.14×10 6, 1.51×10 7, 1.23×10 7, 1.02×10 7, 8.86×10 6; all P<0.001). In both D0 and D1 datasets, the increase in hydrogen and methane of SIBO positive subgroup were higher than those of SIBO negative subgroup (22.39×10 -6(14.82×10 -6, 33.37×10 -6) vs. 4.82×10 -6(1.96×10 -6, 7.85×10 -6), 20.61×10 -6(7.87×10 -6, 31.44×10 -6) vs. 3.25×10 -6(0.79×10 -6, 7.88×10 -6); 3.98×10 -6(2.87×10 -6, 6.87×10 -6) vs. 1.95×10 -6(0.98×10 -6, 2.99×10 -6), 2.95×10 -6(0.98×10 -6, 4.93×10 -6) vs. 0.98×10 -6(0.00×10 -6, 1.99×10 -6)), and the differences were statistically significant( U=7.24×10 6, 9.72×10 6, 5.74×10 6, 8.27×10 6; all P<0.001). In both D0 and D1 datasets, hydrogen and methane concentrations peaked at 90 min. Conclusion:HMBT can be used for non-invasive diagnosis of SIBO in Chinese population, and the differences in hydrogen and methane concentrations at 90 min of the test have critical value for SIBO diagnosis.

Objective:To explore the data distribution characteristics of hydrogen and methane breath test (HMBT) in Chinese population and to evaluate its applicability for diagnosing small intestinal bacterial overgrowth (SIBO) in Chinese population.Methods:HMBT data of 18 634 individuals who underwent health check-up nationwide from March 2019 to september 2022 were retrospectively collected, which included the levels of hydrogen and methane at 0, 30, 60, and 90 min. After quality control and data cleaning, the final valid sample size was 12 654 cases, comprising 7 146 SIBO-negative cases and 5 508 SIBO-positive cases. In order to exclude confounding factors such as oral hygiene, the 12 654 cases were divided into D0 and D1 dataset, when the 0 min-value of hydrogen and methane were both lower than the 30 min-value, the 0 min-value was taken as the baseline, and induded into the D0 dataset (5 556 cases), and other situations were induded into the D1 dataset (7 098 cases). There were 2 879 SIBO-negative cases and 2 659 SIBO-positive cases in D0 dataset, and 4 249 SIBO-negative cases and 2 849 SIBO-positive cases in D1 dataset. The hydrogen and methane level at each testing time point in the SIBO-negative and SIBO-positive individuals, the difference between the peak gas level at 90 min and the baseline, and the distribution of time points at which peak level occurred were analyzed. Independent-sample t test and Mann-Whitney U test were used for statistical analysis. Results:The overall SIBO positive rate was 43.53% (5 508/12 654). In SIBO-positive cases the hydrogen level at 0, 30, 60, and 90 min were 9.41×10 -6 (5.01×10 -6, 21.90×10 -6), 11.34×10 -6 (6.13×10 -6, 22.94×10 -6), 18.16×10 -6 (11.03×10 -6, 29.37×10 -6) and 29.59×10 -6 (20.12×10 -6, 43.36×10 -6), respectively, and methane level were 9.13×10 -6 (7.12×10 -6, 12.03×10 -6), 9.23×10 -6 (8.07×10 -6, 12.03×10 -6), 10.21×10 -6 (9.02×10 -6, 13.01×10 -6), and 12.03×10 -6 (10.01×10 -6, 14.11×10 -6), respectively, which were higher than those of SIBO-negative cases (6.04×10 -6 (3.10×10 -6, 11.08×10 -6), 6.04×10 -6 (3.21×10 -6, 10.06×10 -6), 6.95×10 -6 (4.03×10 -6, 11.01×10 -6), 8.96×10 -6 (5.01×10 -6, 13.91×10 -6); 8.04×10 -6 (7.02×10 -6, 10.00×10 -6), 8.03×10 -6 (7.03×10 -6, 9.95×10 -6), 8.04×10 -6 (7.03×10 -6, 10.00×10 -6) 8.98×10 -6 (7.12×10 -6, 10.03×10 -6)], and the differences were statistically significant ( U=1.41×10 7, 1.09×10 7, 6.66×10 6, 4.14×10 6, 1.51×10 7, 1.23×10 7, 1.02×10 7, 8.86×10 6; all P<0.001). In both D0 and D1 datasets, the increase in hydrogen and methane of SIBO positive subgroup were higher than those of SIBO negative subgroup (22.39×10 -6(14.82×10 -6, 33.37×10 -6) vs. 4.82×10 -6(1.96×10 -6, 7.85×10 -6), 20.61×10 -6(7.87×10 -6, 31.44×10 -6) vs. 3.25×10 -6(0.79×10 -6, 7.88×10 -6); 3.98×10 -6(2.87×10 -6, 6.87×10 -6) vs. 1.95×10 -6(0.98×10 -6, 2.99×10 -6), 2.95×10 -6(0.98×10 -6, 4.93×10 -6) vs. 0.98×10 -6(0.00×10 -6, 1.99×10 -6)), and the differences were statistically significant( U=7.24×10 6, 9.72×10 6, 5.74×10 6, 8.27×10 6; all P<0.001). In both D0 and D1 datasets, hydrogen and methane concentrations peaked at 90 min. Conclusion:HMBT can be used for non-invasive diagnosis of SIBO in Chinese population, and the differences in hydrogen and methane concentrations at 90 min of the test have critical value for SIBO diagnosis.

Objective: To investigate and analyze the impact on PLT recovery of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: A retrospective analysis of Hematology Division of General Hospital of Jinan Military Command was conducted in the 85 SAA cases who treated with allo-HSCT from January 2010 to March 2017. According to the administration of medicines for platelets, 85 patients were divided into rhTPO group (n=29), rhIL-11 group (n=27) and blank group (n=29), respectively. The median time of PLT ≥20×10⁹/L, PLT ≥50×10⁹/L, and PLT ≥100×10⁹/L, the numbers of megakaryocytes in marrow smear (25±5) days after transplantation and the quantities of platelet transfusion were analyzed retrospectively. The adverse events of rhTPO and rhIL-11 groups were observed. Results: There were no significant differences in the recovery of granulocytes and PLT ≥20×10⁹/L among the three groups (P>0.05). The time of PLT ≥50×10⁹/L in rhTPO group was shorter than that in blank group [16.5 (11-39) d vs 22 (14-66) d, P<0.05], as well as the time of PLT ≥100×10⁹/L [rhTPO: 23 (12-51) d; rhIL-11: 28 (12-80) d; blank group: 35 (18-86) d, P<0.05]. Platelet transfusions were also less in rhTPO group than in rhIL-11 and blank groups [20 (10-30) U, 30 (10-50) U, 35 (10-70) U, P<0.05]. The counts of megakaryocyte in rhTPO group, rhIL-11 group and blank group were 31.5 (0-200), 12 (0-142) and 11(0-187) (P<0.05), respectively. The difference between rhTPO group and rhIL-11 group was statistically significant (P<0.05), but no difference between rhIL-11 group and blank group (P>0.05). Multivariate analysis showed that rhTPO was an independent factor for platelet recovery [HR=4.01 (95%CI 1.81-9.97), P=0.010]. The rhTPO group had no obvious adverse events. Conclusion rhTPO can promote platelet recovery of SAA patients after allo-HSCT, reduce platelet transfusion with safety.

Anemia, Aplastic ; therapy ; Hematopoietic Stem Cell Transplantation ; Humans

Objective To detect the change of CD47 on T-lymphocyte subsets marked by CD3 + CD4+ and CD3+ CD8+ in the acute graft versus host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to explore its clinical significance.Methods The peripheral blood of 30 patients was collected before and every two weeks from hematopoietic reconstitution after allo-HSCT.The expression of CD47 on T-lymphocyte subsets marked by CD3+ CD4+ and CD3+ CD8+ was detected by flow cytometry,and the relationship between their expression and the occurrence of aGVHD was analyzed.Results The percentage of CD3+ CD4+-and CD3+ CD8+-marked T-lymphocyte subsets showed no statistically significant difference between aGVHD group and non-aGVHDgroup [(38.95 ± 6.18)％ vs.(37.38 ± 4.6)％,and (22.35 ± 3.32)％ vs.(20.34 ±4.56) ％,respectively] (P＞0.05).The expression levels of CD47 on T-lymphocyte subsets marked by CD3+ CD4+ and CD3+ CD8+ was obviously increased in aGVHD group when compared to before transplantation and non-aGVHD group after transplantation,and that had no changes in non-aGVHD group when compared to before conditioning regimen after transplantation.Mean fluorescence intensity of CD47 on T-lymphocyte subsets marked by CD3+ CD4+ and CD3+ CD8+ [(93.70 ± 14.88) and (70.09 ± 12.51)] in aGVHD group significantly increased as compared with non-aGVHD group [(71.27-± 11.32) and (53.93 ± 8.35)] (P＜0.05).There was no significant difference in the expression of CD47 on T-lymphocyte subsets marked by CD3+ CD4+ and CD3+ CD8+ before and after transplantation in non-aGVHD group (P＞0.05).Moreover the expression of CD47 on T-lymphocyte subsets marked by CD3 + CD4 + and CD3 + CD8 + changed correspondingly with the outcome of aGVHD in aGVHD group.Conclusion The change of CD47 on T-lymphocyte subsets marked by CD3+ CD4+ andCD3+ CD8+ is valuable to monitor the aGVHD after allo-HSCT,which may provide a new means for the early detection of aGVHD.

Objective To investigate the effect of folic acid on the DNA methylation of tumorrelated genes promoters in healthy human peripheral blood mononuclear cells(PBMC). Methods Ten healthy volunteers were divided into two groups, and were randomized to receive either 5 mg folic acid (n=5)or placebo(n = 5) , one time per day for 3 months. The serum folic acid concentration was detected with chemiluminescence enzyme immunoassay kit before and after the intervention. The methylation statuses of five tumor-related genes promoter, including oncogenes c-myc, c-Ha-ras,tumor suppressor genes p16INK4A, E-cadherin and mismatch repair gene hMLH1 in PBMC were detected by bisufite sequencing. Results After folic acid intervention, the level of serum folic acid increased significantly in intervention group (t= -4. 739,P<0. 05) , however no significant difference in control group. After three-month folic acid intervention, the level of methylation of oncogene c-myc promoter increased from 4%, 3. 3%, 4. 1% before intervention, one week after intervention, one month after intervention respectively to 8%(t= -4. 079,P<0. 05), while no significant change in placebo taken group. Before and after the folic acid intervention, there was no significant difference of DNA methylation of other tumor-related genes promoter, including c-Ha-ras、E-cadherin、p16INK4Aand hMLH1. Conclusion Folic acid intervention can up-regulate DNA methylation of oncogene c-myc promoter, but can not affect the promoter methylation status of tumor suppressor genes E-cadherin,p16INK4Aand hMLH1.

Objective To summarize the experience of improved nonmyeloablative hematopoietic stem cell transplantation(NSCT) in the treatment of severe aplastie anemia. Methods Seventeen patients with Severe Aplastic Anemia received NSCT after a nonmyeloablative conditioning.The patients were conditioned with decreased dosage of immunosuppressive agents of CTX and anti-lymphoid cell globulin or anti-thymus gland cell globulins;CsA and MMF were used to prevent the graft-versus-host disease (GVHD) after transplantation. Results 75 % of severe aplastic anemia in patients with type Ⅰ and 60 % of severe aplastic anemia in patients with type Ⅱ achieved rapid hematopoietic reconstitution, with good prognosis and implantation rate with fewer complieations and light symptoms were observed. Conclusion NSCT is an effective treatment of severe aplastic anemia.